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    <title>DSpace Collection:</title>
    <link>http://hdl.handle.net/10023/46</link>
    <description />
    <pubDate>Thu, 20 Jun 2013 07:02:23 GMT</pubDate>
    <dc:date>2013-06-20T07:02:23Z</dc:date>
    <image>
      <title>DSpace Collection:</title>
      <url>http://research-repository.st-andrews.ac.uk:80/retrieve/12246/school of biology.gif</url>
      <link>http://hdl.handle.net/10023/46</link>
    </image>
    <item>
      <title>Root traits for infertile soils</title>
      <link>http://hdl.handle.net/10023/3692</link>
      <description>Abstract: Crop production is often restricted by the availability of essential mineral elements. For example, the availability of N, P, K, and S limits low-input agriculture, the phytoavailability of Fe, Zn, and Cu limits crop production on alkaline and calcareous soils, and P, Mo, Mg, Ca,and K deficiencies, together with proton, Al and Mn toxicities, limit crop production on acid soils. Since essential mineral elements are acquired by the root system, the development of crop genotypes with root traits increasing their acquisition should increase yields on infertile soils. This paper examines root traits likely to improve the acquisition of these elements and observes that, although the efficient acquisition of a particular element requires a specific set of root traits, suites of traits can be identified that benefit the acquisition of a group of mineral elements. Elements can be divided into three Groups based on common trait requirements. Group 1 comprises N, S, K, B, and P. Group 2 comprises Fe, Zn, Cu, Mn, and Ni. Group 3 contains mineral elements that rarely affect crop production. It is argued that breeding for a limited number of distinct root ideotypes,addressing particular combinations of mineral imbalances, should be pursued.</description>
      <pubDate>Tue, 11 Jun 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3692</guid>
      <dc:date>2013-06-11T00:00:00Z</dc:date>
      <dc:creator>White, Philip</dc:creator>
      <dc:creator>George, Timothy</dc:creator>
      <dc:creator>Dupuy, Lionel</dc:creator>
      <dc:creator>Karley, Alison</dc:creator>
      <dc:creator>Valentine, Tracy</dc:creator>
      <dc:creator>Wiesel, Lea</dc:creator>
      <dc:creator>Wishart, Jane</dc:creator>
      <dc:description>Crop production is often restricted by the availability of essential mineral elements. For example, the availability of N, P, K, and S limits low-input agriculture, the phytoavailability of Fe, Zn, and Cu limits crop production on alkaline and calcareous soils, and P, Mo, Mg, Ca,and K deficiencies, together with proton, Al and Mn toxicities, limit crop production on acid soils. Since essential mineral elements are acquired by the root system, the development of crop genotypes with root traits increasing their acquisition should increase yields on infertile soils. This paper examines root traits likely to improve the acquisition of these elements and observes that, although the efficient acquisition of a particular element requires a specific set of root traits, suites of traits can be identified that benefit the acquisition of a group of mineral elements. Elements can be divided into three Groups based on common trait requirements. Group 1 comprises N, S, K, B, and P. Group 2 comprises Fe, Zn, Cu, Mn, and Ni. Group 3 contains mineral elements that rarely affect crop production. It is argued that breeding for a limited number of distinct root ideotypes,addressing particular combinations of mineral imbalances, should be pursued.</dc:description>
    </item>
    <item>
      <title>Ecological causes of morphological evolution in the three-spined stickleback</title>
      <link>http://hdl.handle.net/10023/3574</link>
      <description>Abstract: The central assumption of evolutionary theory is that natural selection drives the adaptation of populations to local environmental conditions, resulting in the evolution of adaptive phenotypes. The three-spined stickleback (Gasterosteus aculeatus) displays remarkable phenotypic variation, offering an unusually tractable model for understanding the ecological mechanisms underpinning adaptive evolutionary change. Using populations on North Uist, Scotland we investigated the role of predation pressure and calcium limitation on the adaptive evolution of stickleback morphology and behavior. Dissolved calcium was a significant predictor of plate and spine morph, while predator abundance was not. Stickleback latency to emerge from a refuge varied with morph, with populations with highly reduced plates and spines and high predation risk less bold. Our findings support strong directional selection in three-spined stickleback evolution, driven by multiple selective agents.</description>
      <pubDate>Tue, 01 Jan 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3574</guid>
      <dc:date>2013-01-01T00:00:00Z</dc:date>
      <dc:creator>Spence, Rowena Grace Alison</dc:creator>
      <dc:creator>Wootton, Robert</dc:creator>
      <dc:creator>Barber, Iain</dc:creator>
      <dc:creator>Przybylski, Mirosław</dc:creator>
      <dc:creator>Smith, Carl</dc:creator>
      <dc:description>The central assumption of evolutionary theory is that natural selection drives the adaptation of populations to local environmental conditions, resulting in the evolution of adaptive phenotypes. The three-spined stickleback (Gasterosteus aculeatus) displays remarkable phenotypic variation, offering an unusually tractable model for understanding the ecological mechanisms underpinning adaptive evolutionary change. Using populations on North Uist, Scotland we investigated the role of predation pressure and calcium limitation on the adaptive evolution of stickleback morphology and behavior. Dissolved calcium was a significant predictor of plate and spine morph, while predator abundance was not. Stickleback latency to emerge from a refuge varied with morph, with populations with highly reduced plates and spines and high predation risk less bold. Our findings support strong directional selection in three-spined stickleback evolution, driven by multiple selective agents.</dc:description>
    </item>
    <item>
      <title>Unravelling the structure of viral replication complexes at super-resolution</title>
      <link>http://hdl.handle.net/10023/3573</link>
      <description>Abstract: During infection, many RNA viruses produce characteristic inclusion bodies that contain both viral and host components. These structures were first described over a century ago and originally termed “X-bodies,” as their function was not immediately appreciated. Whilst some inclusion bodies may represent cytopathic by-products of viral protein over-accumulation, X-bodies have emerged as virus “factories,” quasi-organelles that coordinate diverse viral infection processes such as replication, protein expression, evasion of host defenses, virion assembly, and intercellular transport. Accordingly, they are now generally referred to as viral replication complexes (VRCs). We previously used confocal fluorescence microscopy to unravel the complex structure of X-bodies produced by Potato virus X (PVX). Here we used 3D-structured illumination (3D-SIM) super-resolution microscopy to map the PVX X-body at a finer scale. We identify a previously unrecognized membrane structure induced by the PVX “triple gene block” (TGB) proteins, providing new insights into the complex interplay between virus and host within the X-body.</description>
      <pubDate>Thu, 31 Jan 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3573</guid>
      <dc:date>2013-01-31T00:00:00Z</dc:date>
      <dc:creator>Linnik, Olga</dc:creator>
      <dc:creator>Liesche, Johannes</dc:creator>
      <dc:creator>Tilsner, Jens</dc:creator>
      <dc:creator>Oparka, Karl J.</dc:creator>
      <dc:description>During infection, many RNA viruses produce characteristic inclusion bodies that contain both viral and host components. These structures were first described over a century ago and originally termed “X-bodies,” as their function was not immediately appreciated. Whilst some inclusion bodies may represent cytopathic by-products of viral protein over-accumulation, X-bodies have emerged as virus “factories,” quasi-organelles that coordinate diverse viral infection processes such as replication, protein expression, evasion of host defenses, virion assembly, and intercellular transport. Accordingly, they are now generally referred to as viral replication complexes (VRCs). We previously used confocal fluorescence microscopy to unravel the complex structure of X-bodies produced by Potato virus X (PVX). Here we used 3D-structured illumination (3D-SIM) super-resolution microscopy to map the PVX X-body at a finer scale. We identify a previously unrecognized membrane structure induced by the PVX “triple gene block” (TGB) proteins, providing new insights into the complex interplay between virus and host within the X-body.</dc:description>
    </item>
    <item>
      <title>Auditory same/different concept learning and generalization in black-capped chickadees (Poecile atricapillus)</title>
      <link>http://hdl.handle.net/10023/3570</link>
      <description>Abstract: Abstract concept learning was thought to be uniquely human, but has since been observed in many other species. Discriminating same from different is one abstract relation that has been studied frequently. In the current experiment, using operant conditioning, we tested whether black-capped chickadees (Poecile atricapillus) could discriminate sets of auditory stimuli based on whether all the sounds within a sequence were the same or different from one another. The chickadees were successful at solving this same/different relational task, and transferred their learning to same/different sequences involving novel combinations of training notes and novel notes within the range of pitches experienced during training. The chickadees showed limited transfer to pitches that was not used in training, suggesting that the processing of absolute pitch may constrain their relational performance. Our results indicate, for the first time, that black-capped chickadees readily form relational auditory same and different categories, adding to the list of perceptual, behavioural, and cognitive abilities that make this species an important comparative model for human language and cognition.</description>
      <pubDate>Mon, 15 Oct 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3570</guid>
      <dc:date>2012-10-15T00:00:00Z</dc:date>
      <dc:creator>Hoeschele, Marisa</dc:creator>
      <dc:creator>Cook, Robert</dc:creator>
      <dc:creator>Guillette, Lauren</dc:creator>
      <dc:creator>Hahn, Allison</dc:creator>
      <dc:creator>Sturdy, Christopher</dc:creator>
      <dc:description>Abstract concept learning was thought to be uniquely human, but has since been observed in many other species. Discriminating same from different is one abstract relation that has been studied frequently. In the current experiment, using operant conditioning, we tested whether black-capped chickadees (Poecile atricapillus) could discriminate sets of auditory stimuli based on whether all the sounds within a sequence were the same or different from one another. The chickadees were successful at solving this same/different relational task, and transferred their learning to same/different sequences involving novel combinations of training notes and novel notes within the range of pitches experienced during training. The chickadees showed limited transfer to pitches that was not used in training, suggesting that the processing of absolute pitch may constrain their relational performance. Our results indicate, for the first time, that black-capped chickadees readily form relational auditory same and different categories, adding to the list of perceptual, behavioural, and cognitive abilities that make this species an important comparative model for human language and cognition.</dc:description>
    </item>
    <item>
      <title>Associative learning in insects : evolutionary models, mushroom bodies, and a neuroscientific conundrum</title>
      <link>http://hdl.handle.net/10023/3568</link>
      <description>Abstract: Environmental predictability has for many years been posited to be a key variable in whether learning is expected to evolve in particular species, a claim revisited in two recent papers. However, amongst many researchers, especially neuroscientists, consensus is building for a very different view, namely that learning ability may be an emergent property of nervous systems and, thus, all animals with nervous systems should be able to learn. Here we explore these differing views, sample research on associative learning in insects, and review our own work demonstrating learning in larval antlions (Neuroptera: Myrmeleontidae), a highly unlikely insect candidate. We conclude by asserting that the capacity for associative learning is the default condition favored by neuroscientists: Whenever selection pressures favor evolution of nervous systems, the capacity for associative learning follows ipso facto. Nonetheless, to reconcile these disparate views, we suggest that (a) models for the evolution of learning may instead be models for conditions overriding behavioral plasticity; and, (b) costs of learning in insects may be, in fact, costs associated with more complex cognitive skills, skills that are just beginning to be discovered, rather than simple associative learning.</description>
      <pubDate>Sat, 01 Jan 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3568</guid>
      <dc:date>2011-01-01T00:00:00Z</dc:date>
      <dc:creator>Hollis, Karen</dc:creator>
      <dc:creator>Guillette, Lauren</dc:creator>
      <dc:description>Environmental predictability has for many years been posited to be a key variable in whether learning is expected to evolve in particular species, a claim revisited in two recent papers. However, amongst many researchers, especially neuroscientists, consensus is building for a very different view, namely that learning ability may be an emergent property of nervous systems and, thus, all animals with nervous systems should be able to learn. Here we explore these differing views, sample research on associative learning in insects, and review our own work demonstrating learning in larval antlions (Neuroptera: Myrmeleontidae), a highly unlikely insect candidate. We conclude by asserting that the capacity for associative learning is the default condition favored by neuroscientists: Whenever selection pressures favor evolution of nervous systems, the capacity for associative learning follows ipso facto. Nonetheless, to reconcile these disparate views, we suggest that (a) models for the evolution of learning may instead be models for conditions overriding behavioral plasticity; and, (b) costs of learning in insects may be, in fact, costs associated with more complex cognitive skills, skills that are just beginning to be discovered, rather than simple associative learning.</dc:description>
    </item>
    <item>
      <title>What hummingbirds can tell us about cognition in the wild.</title>
      <link>http://hdl.handle.net/10023/3567</link>
      <description>Abstract: Here we review around 20 years of experimental data that we have collected during tests of cognitive abilities of free-living, wild rufous hummingbirds Selasphorus rufus at their breeding grounds in southwestern Alberta. Because these birds are readily trained to feed from artificial flowers they have proved a useful system for testing cognitive abilities of an animal outside the box wherein animal cognitive abilities are so often tested in the laboratory. And, although these data all come from a single species in a single location, the long-term aim of this work is to make a contribution to our understanding of the evolution of cognitive abilities, by examining the relationship between the ecological demands these birds face and their cognitive abilities. Testing predictions based on our knowledge of their ecology we have found that, while these birds aggressively defend a territory and display to females during the time we train and test them, they can learn and remember the locations of rewarded flowers, what those flowers look like, and when they are likely to contain food. Small-brained though they may be, these 3g hummingbirds appear to have cognitive capabilities that are not only well matched to their ecological demands, they are in at least some instances better (more capacious) than those of animals tested in the laboratory.</description>
      <pubDate>Tue, 01 Jan 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3567</guid>
      <dc:date>2013-01-01T00:00:00Z</dc:date>
      <dc:creator>Healy, Susan Denise</dc:creator>
      <dc:creator>Hurly, T. Andrew</dc:creator>
      <dc:description>Here we review around 20 years of experimental data that we have collected during tests of cognitive abilities of free-living, wild rufous hummingbirds Selasphorus rufus at their breeding grounds in southwestern Alberta. Because these birds are readily trained to feed from artificial flowers they have proved a useful system for testing cognitive abilities of an animal outside the box wherein animal cognitive abilities are so often tested in the laboratory. And, although these data all come from a single species in a single location, the long-term aim of this work is to make a contribution to our understanding of the evolution of cognitive abilities, by examining the relationship between the ecological demands these birds face and their cognitive abilities. Testing predictions based on our knowledge of their ecology we have found that, while these birds aggressively defend a territory and display to females during the time we train and test them, they can learn and remember the locations of rewarded flowers, what those flowers look like, and when they are likely to contain food. Small-brained though they may be, these 3g hummingbirds appear to have cognitive capabilities that are not only well matched to their ecological demands, they are in at least some instances better (more capacious) than those of animals tested in the laboratory.</dc:description>
    </item>
    <item>
      <title>Acoustic mechanisms of a species-based discrimination of the chick-a-dee call in sympatric black-capped (Poecile atricapillus) and mountain chickadees (P. gambeli)</title>
      <link>http://hdl.handle.net/10023/3566</link>
      <description>Abstract: Previous perceptual research with black-capped and mountain chickadees has demonstrated that these species treat each other’s namesake chick-a-dee calls as belonging to separate, open-ended categories. Further, the terminal dee portion of the call has been implicated as the most prominent species marker. However, statistical classification using acoustic summary features suggests that all note-types contained within the chick-a-dee call should be sufficient for species classification. The current study seeks to better understand the note-type based mechanisms underlying species-based classification of the chick-a-dee call by black-capped and mountain chickadees. In two, complementary, operant discrimination experiments, both species were trained to discriminate the species of the signaler using either entire chick-a-dee calls, or individual note-types from chick-a-dee calls. In agreement with previous perceptual work we find that the D note had significant stimulus control over species-based discrimination. However, in line with statistical classifications, we find that all note-types carry species information. We discuss reasons why the most easily discriminated note-types are likely candidates to carry species-based cues.</description>
      <pubDate>Fri, 01 Jan 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3566</guid>
      <dc:date>2010-01-01T00:00:00Z</dc:date>
      <dc:creator>Guillette, Lauren</dc:creator>
      <dc:creator>Farrell, Tara</dc:creator>
      <dc:creator>Hoeschele, Marisa</dc:creator>
      <dc:creator>Sturdy, Christopher</dc:creator>
      <dc:description>Previous perceptual research with black-capped and mountain chickadees has demonstrated that these species treat each other’s namesake chick-a-dee calls as belonging to separate, open-ended categories. Further, the terminal dee portion of the call has been implicated as the most prominent species marker. However, statistical classification using acoustic summary features suggests that all note-types contained within the chick-a-dee call should be sufficient for species classification. The current study seeks to better understand the note-type based mechanisms underlying species-based classification of the chick-a-dee call by black-capped and mountain chickadees. In two, complementary, operant discrimination experiments, both species were trained to discriminate the species of the signaler using either entire chick-a-dee calls, or individual note-types from chick-a-dee calls. In agreement with previous perceptual work we find that the D note had significant stimulus control over species-based discrimination. However, in line with statistical classifications, we find that all note-types carry species information. We discuss reasons why the most easily discriminated note-types are likely candidates to carry species-based cues.</dc:description>
    </item>
    <item>
      <title>Specialized learning in antlions (Neuroptera: Myrmeleontidae), pit-digging predators, shortens vulnerable larval stage</title>
      <link>http://hdl.handle.net/10023/3565</link>
      <description>Abstract: Unique in the insect world for their extremely sedentary predatory behavior, pit-dwelling larval antlions dig pits, and then sit at the bottom and wait, sometimes for months, for prey to fall inside. This sedentary predation strategy, combined with their seemingly innate ability to detect approaching prey, make antlions unlikely candidates for learning. That is, although scientists have demonstrated that many species of insects possess the capacity to learn, each of these species, which together represent multiple families from every major insect order, utilizes this ability as a means of navigating the environment, using learned cues to guide an active search for food and hosts, or to avoid noxious events. Nonetheless, we demonstrate not only that sedentary antlions can learn, but also, more importantly, that learning provides an important fitness benefit, namely decreasing the time to pupate, a benefit not yet demonstrated in any other species. Compared to a control group in which an environmental cue was presented randomly vis-à-vis daily prey arrival, antlions given the opportunity to associate the cue with prey were able to make more efficient use of prey and pupate significantly sooner, thus shortening their long, highly vulnerable larval stage. Whereas ‘‘median survival time,’’ the point at which half of the animals in each group had pupated, was 46 days for antlions receiving the Learning treatment, that point never was reached in antlions receiving the Random treatment, even by the end of the experiment on Day 70. In addition, we demonstrate a novel manifestation of antlions’ learned response to cues predicting prey arrival, behavior that does not match the typical ‘‘learning curve’’ but which is well-adapted to their sedentary predation strategy. Finally, we suggest that what has long appeared to be instinctive predatory behavior is likely to be highly modified and shaped by learning.
Description: Formal Correction: This article has been formally corrected to address the following errors. Figures 2 and 3 were switched in production. The image listed as Figure 3 is actually Figure 2, and the image listed as Figure 2 is actually Figure 3. The legends are correct.</description>
      <pubDate>Tue, 29 Mar 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3565</guid>
      <dc:date>2011-03-29T00:00:00Z</dc:date>
      <dc:creator>Hollis, Karen</dc:creator>
      <dc:creator>Cogswell, Heather</dc:creator>
      <dc:creator>Snyder, Kenzie</dc:creator>
      <dc:creator>Guillette, Lauren</dc:creator>
      <dc:creator>Nowbahari, Elise</dc:creator>
      <dc:description>Unique in the insect world for their extremely sedentary predatory behavior, pit-dwelling larval antlions dig pits, and then sit at the bottom and wait, sometimes for months, for prey to fall inside. This sedentary predation strategy, combined with their seemingly innate ability to detect approaching prey, make antlions unlikely candidates for learning. That is, although scientists have demonstrated that many species of insects possess the capacity to learn, each of these species, which together represent multiple families from every major insect order, utilizes this ability as a means of navigating the environment, using learned cues to guide an active search for food and hosts, or to avoid noxious events. Nonetheless, we demonstrate not only that sedentary antlions can learn, but also, more importantly, that learning provides an important fitness benefit, namely decreasing the time to pupate, a benefit not yet demonstrated in any other species. Compared to a control group in which an environmental cue was presented randomly vis-à-vis daily prey arrival, antlions given the opportunity to associate the cue with prey were able to make more efficient use of prey and pupate significantly sooner, thus shortening their long, highly vulnerable larval stage. Whereas ‘‘median survival time,’’ the point at which half of the animals in each group had pupated, was 46 days for antlions receiving the Learning treatment, that point never was reached in antlions receiving the Random treatment, even by the end of the experiment on Day 70. In addition, we demonstrate a novel manifestation of antlions’ learned response to cues predicting prey arrival, behavior that does not match the typical ‘‘learning curve’’ but which is well-adapted to their sedentary predation strategy. Finally, we suggest that what has long appeared to be instinctive predatory behavior is likely to be highly modified and shaped by learning.</dc:description>
    </item>
    <item>
      <title>Structure of the archaeal Cascade subunit Csa5 : Relating the small subunits of CRISPR effector complexes</title>
      <link>http://hdl.handle.net/10023/3550</link>
      <description>Abstract: The Cascade complex for CRISPR-mediated antiviral immunity uses CRISPR RNA (crRNA) to target invading DNA species from mobile elements such as viruses, leading to their destruction. The core of the Cascade effector complex consists of the Cas5 and Cas7 subunits, which are widely conserved in prokaryotes. Cas7 binds crRNA and forms the helical backbone of Cascade. Many archaea encode a version of the Cascade complex (denoted Type I-A) that includes a Csa5 (or small) subunit, which interacts weakly with the core proteins. Here, we report the crystal structure of the Csa5 protein from Sulfolobus solfataricus. Csa5 comprises a conserved α-helical domain with a small insertion consisting of a weakly conserved β-strand domain. In the crystal, the Csa5 monomers have multimerized into infinite helical threads. At each interface is a strictly conserved intersubunit salt bridge, deletion of which disrupts multimerization. Structural analysis indicates a shared evolutionary history among the small subunits of the CRISPR effector complexes. The same α-helical domain is found in the C-terminal domain of Cse2 (from Type I-E Cascade), while the N-terminal domain of Cse2 is found in Cmr5 of the CMR (Type III-B) effector complex. As Cmr5 shares no match with Csa5, two possibilities present themselves: selective domain loss from an ancestral Cse2 to create two new subfamilies or domain fusion of two separate families to create a new Cse2 family. A definitive answer awaits structural studies of further small subunits from other CRISPR effector complexes.
Description: This work was funded by a grant from the Biotechnology and Biological Sciences Research Council (BBSRC) (REF: BB/G011400/1) to M.F.W. and J.H.N. and a BBSRC-funded studentship to J.R.</description>
      <pubDate>Wed, 01 May 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3550</guid>
      <dc:date>2013-05-01T00:00:00Z</dc:date>
      <dc:creator>Reeks, Judith Anne</dc:creator>
      <dc:creator>Graham, Shirley</dc:creator>
      <dc:creator>Liu, Huanting</dc:creator>
      <dc:creator>White, Malcolm F</dc:creator>
      <dc:creator>Naismith, Jim</dc:creator>
      <dc:description>The Cascade complex for CRISPR-mediated antiviral immunity uses CRISPR RNA (crRNA) to target invading DNA species from mobile elements such as viruses, leading to their destruction. The core of the Cascade effector complex consists of the Cas5 and Cas7 subunits, which are widely conserved in prokaryotes. Cas7 binds crRNA and forms the helical backbone of Cascade. Many archaea encode a version of the Cascade complex (denoted Type I-A) that includes a Csa5 (or small) subunit, which interacts weakly with the core proteins. Here, we report the crystal structure of the Csa5 protein from Sulfolobus solfataricus. Csa5 comprises a conserved α-helical domain with a small insertion consisting of a weakly conserved β-strand domain. In the crystal, the Csa5 monomers have multimerized into infinite helical threads. At each interface is a strictly conserved intersubunit salt bridge, deletion of which disrupts multimerization. Structural analysis indicates a shared evolutionary history among the small subunits of the CRISPR effector complexes. The same α-helical domain is found in the C-terminal domain of Cse2 (from Type I-E Cascade), while the N-terminal domain of Cse2 is found in Cmr5 of the CMR (Type III-B) effector complex. As Cmr5 shares no match with Csa5, two possibilities present themselves: selective domain loss from an ancestral Cse2 to create two new subfamilies or domain fusion of two separate families to create a new Cse2 family. A definitive answer awaits structural studies of further small subunits from other CRISPR effector complexes.</dc:description>
    </item>
    <item>
      <title>Structural insights into the mechanism and inhibition of the beta-Hydroxydecanoyl-Acyl carrier protein dehydratase from pseudomonas aeruginosa</title>
      <link>http://hdl.handle.net/10023/3510</link>
      <description>Abstract: Fatty acid biosynthesis is an essential component of metabolism in both eukaryotes and prokaryotes. The fatty acid biosynthetic pathway of Gram-negative bacteria is an established therapeutic target. Two homologous enzymes FabA and FabZ catalyze a key step in fatty acid biosynthesis; both dehydrate hydroxyacyl fatty acids that are coupled via a phosphopantetheine to an acyl carrier protein (ACP). The resulting trans-2-enoyl-ACP is further polymerized in a processive manner. FabA, however, carries out a second reaction involving isomerization of trans-2-enoyl fatty acid to cis-3-enoyl fatty acid. We have solved the structure of Pseudomonas aeruginosa FabA with a substrate allowing detailed molecular insight into the interactions of the active site. This has allowed a detailed examination of the factors governing the second catalytic step. We have also determined the structure of FabA in complex with small molecules (so-called fragments). These small molecules occupy distinct regions of the active site and form the basis for a rational inhibitor design program. (C) 2012 Elsevier Ltd. All rights reserved.</description>
      <pubDate>Wed, 23 Jan 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3510</guid>
      <dc:date>2013-01-23T00:00:00Z</dc:date>
      <dc:creator>Moynie, Lucile</dc:creator>
      <dc:creator>Leckie, Stuart M.</dc:creator>
      <dc:creator>McMahon, Stephen A.</dc:creator>
      <dc:creator>Duthie, Fraser G.</dc:creator>
      <dc:creator>Koehnke, Alessa</dc:creator>
      <dc:creator>Taylor, James W.</dc:creator>
      <dc:creator>Alphey, Magnus S.</dc:creator>
      <dc:creator>Brenk, Ruth</dc:creator>
      <dc:creator>Smith, Andrew D.</dc:creator>
      <dc:creator>Naismith, James H.</dc:creator>
      <dc:description>Fatty acid biosynthesis is an essential component of metabolism in both eukaryotes and prokaryotes. The fatty acid biosynthetic pathway of Gram-negative bacteria is an established therapeutic target. Two homologous enzymes FabA and FabZ catalyze a key step in fatty acid biosynthesis; both dehydrate hydroxyacyl fatty acids that are coupled via a phosphopantetheine to an acyl carrier protein (ACP). The resulting trans-2-enoyl-ACP is further polymerized in a processive manner. FabA, however, carries out a second reaction involving isomerization of trans-2-enoyl fatty acid to cis-3-enoyl fatty acid. We have solved the structure of Pseudomonas aeruginosa FabA with a substrate allowing detailed molecular insight into the interactions of the active site. This has allowed a detailed examination of the factors governing the second catalytic step. We have also determined the structure of FabA in complex with small molecules (so-called fragments). These small molecules occupy distinct regions of the active site and form the basis for a rational inhibitor design program. (C) 2012 Elsevier Ltd. All rights reserved.</dc:description>
    </item>
    <item>
      <title>Models incorporating chromatin modification data identify functionally important p53 binding sites</title>
      <link>http://hdl.handle.net/10023/3504</link>
      <description>Abstract: Genome-wide prediction of transcription factor binding sites is notoriously difficult. We have developed and applied a logistic regression approach for prediction of binding sites for the p53 transcription factor that incorporates sequence information and chromatin modification data. We tested this by comparison of predicted sites with known binding sites defined by chromatin immunoprecipitation (ChIP), by the location of predictions relative to genes, by the function of nearby genes and by analysis of gene expression data after p53 activation. We compared the predictions made by our novel model with predictions based only on matches to a sequence position weight matrix (PWM). In whole genome assays, the fraction of known sites identified by the two models was similar, suggesting that there was little to be gained from including chromatin modification data. In contrast, there were highly significant and biologically relevant differences between the two models in the location of the predicted binding sites relative to genes, in the function of nearby genes and in the responsiveness of nearby genes to p53 activation. We propose that these contradictory results can be explained by PWM and ChIP data reflecting primarily biophysical properties of protein–DNA interactions, whereas chromatin modification data capture biologically important functional information.</description>
      <pubDate>Tue, 01 Jan 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3504</guid>
      <dc:date>2013-01-01T00:00:00Z</dc:date>
      <dc:creator>Lim, Ji-Hyun</dc:creator>
      <dc:creator>Iggo, Richard D</dc:creator>
      <dc:creator>Barker, Daniel</dc:creator>
      <dc:description>Genome-wide prediction of transcription factor binding sites is notoriously difficult. We have developed and applied a logistic regression approach for prediction of binding sites for the p53 transcription factor that incorporates sequence information and chromatin modification data. We tested this by comparison of predicted sites with known binding sites defined by chromatin immunoprecipitation (ChIP), by the location of predictions relative to genes, by the function of nearby genes and by analysis of gene expression data after p53 activation. We compared the predictions made by our novel model with predictions based only on matches to a sequence position weight matrix (PWM). In whole genome assays, the fraction of known sites identified by the two models was similar, suggesting that there was little to be gained from including chromatin modification data. In contrast, there were highly significant and biologically relevant differences between the two models in the location of the predicted binding sites relative to genes, in the function of nearby genes and in the responsiveness of nearby genes to p53 activation. We propose that these contradictory results can be explained by PWM and ChIP data reflecting primarily biophysical properties of protein–DNA interactions, whereas chromatin modification data capture biologically important functional information.</dc:description>
    </item>
    <item>
      <title>Stressed but stable : Canopy loss decreased species synchrony and metabolic variability in an intertidal hard-bottom community</title>
      <link>http://hdl.handle.net/10023/3501</link>
      <description>Abstract: The temporal stability of aggregate community properties depends on the dynamics of the component species. Since species growth can compensate for the decline of other species, synchronous species dynamics can maintain stability (i.e. invariability) in aggregate properties such as community abundance and metabolism. In field experiments we tested the separate and interactive effects of two stressors associated with storminess–loss of a canopy-forming species and mechanical disturbances–on species synchrony and community respiration of intertidal hard-bottom communities on Helgoland Island, NE Atlantic. Treatments consisted of regular removal of the canopy-forming seaweed Fucus serratus and a mechanical disturbance applied once at the onset of the experiment in March 2006. The level of synchrony in species abundances was assessed from estimates of species percentage cover every three months until September 2007. Experiments at two sites consistently showed that canopy loss significantly reduced species synchrony. Mechanical disturbance had neither separate nor interactive effects on species synchrony. Accordingly, in situ measurements of CO2-fluxes showed that canopy loss, but not mechanical disturbances, significantly reduced net primary productivity and temporal variation in community respiration during emersion periods. Our results support the idea that compensatory dynamics may stabilise aggregate properties. They further suggest that the ecological consequences of the loss of a single structurally important species may be stronger than those derived from smaller-scale mechanical disturbances in natural ecosystems.</description>
      <pubDate>Fri, 04 May 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3501</guid>
      <dc:date>2012-05-04T00:00:00Z</dc:date>
      <dc:creator>Valdivia, Nelson</dc:creator>
      <dc:creator>Gollety, Claire</dc:creator>
      <dc:creator>Migne, Aline</dc:creator>
      <dc:creator>Davoult, Dominique</dc:creator>
      <dc:creator>Molis, Marcus</dc:creator>
      <dc:description>The temporal stability of aggregate community properties depends on the dynamics of the component species. Since species growth can compensate for the decline of other species, synchronous species dynamics can maintain stability (i.e. invariability) in aggregate properties such as community abundance and metabolism. In field experiments we tested the separate and interactive effects of two stressors associated with storminess–loss of a canopy-forming species and mechanical disturbances–on species synchrony and community respiration of intertidal hard-bottom communities on Helgoland Island, NE Atlantic. Treatments consisted of regular removal of the canopy-forming seaweed Fucus serratus and a mechanical disturbance applied once at the onset of the experiment in March 2006. The level of synchrony in species abundances was assessed from estimates of species percentage cover every three months until September 2007. Experiments at two sites consistently showed that canopy loss significantly reduced species synchrony. Mechanical disturbance had neither separate nor interactive effects on species synchrony. Accordingly, in situ measurements of CO2-fluxes showed that canopy loss, but not mechanical disturbances, significantly reduced net primary productivity and temporal variation in community respiration during emersion periods. Our results support the idea that compensatory dynamics may stabilise aggregate properties. They further suggest that the ecological consequences of the loss of a single structurally important species may be stronger than those derived from smaller-scale mechanical disturbances in natural ecosystems.</dc:description>
    </item>
    <item>
      <title>Estimating animal population density using passive acoustics</title>
      <link>http://hdl.handle.net/10023/3496</link>
      <description>Abstract: Reliable estimation of the size or density of wild animal populations is very important for effective wildlife management, conservation and ecology. Currently, the most widely used methods for obtaining such estimates involve either sighting animals from transect lines or some form of capture-recapture on marked or uniquely identifiable individuals. However, many species are difficult to sight, and cannot be easily marked or recaptured. Some of these species produce readily identifiable sounds, providing an opportunity to use passive acoustic data to estimate animal density. In addition, even for species for which other visually based methods are feasible, passive acoustic methods offer the potential for greater detection ranges in some environments (e.g. underwater or in dense forest), and hence potentially better precision. Automated data collection means that surveys can take place at times and in places where it would be too expensive or dangerous to send human observers. Here, we present an overview of animal density estimation using passive acoustic data, a relatively new and fast-developing field. We review the types of data and methodological approaches currently available to researchers and we provide a framework for acoustics-based density estimation, illustrated with examples from real-world case studies. We mention moving sensor platforms (e.g. towed acoustics), but then focus on methods involving sensors at fixed locations, particularly hydrophones to survey marine mammals, as acoustic-based density estimation research to date has been concentrated in this area. Primary among these are methods based on distance sampling and spatially explicit capture-recapture. The methods are also applicable to other aquatic and terrestrial sound-producing taxa. We conclude that, despite being in its infancy, density estimation based on passive acoustic data likely will become an important method for surveying a number of diverse taxa, such as sea mammals, fish, birds, amphibians, and insects, especially in situations where inferences are required over long periods of time. There is considerable work ahead, with several potentially fruitful research areas, including the development of (i) hardware and software for data acquisition, (ii) efficient, calibrated, automated detection and classification systems, and (iii) statistical approaches optimized for this application. Further, survey design will need to be developed, and research is needed on the acoustic behaviour of target species. Fundamental research on vocalization rates and group sizes, and the relation between these and other factors such as season or behaviour state, is critical. Evaluation of the methods under known density scenarios will be important for empirically validating the approaches presented here</description>
      <pubDate>Wed, 01 May 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3496</guid>
      <dc:date>2013-05-01T00:00:00Z</dc:date>
      <dc:creator>Marques, Tiago A.</dc:creator>
      <dc:creator>Thomas, Len</dc:creator>
      <dc:creator>Martin, Stephen</dc:creator>
      <dc:creator>Mellinger, David</dc:creator>
      <dc:creator>Ward, Jessica</dc:creator>
      <dc:creator>Moretti, David</dc:creator>
      <dc:creator>Harris, Danielle Veronica</dc:creator>
      <dc:creator>Tyack, Peter Lloyd</dc:creator>
      <dc:description>Reliable estimation of the size or density of wild animal populations is very important for effective wildlife management, conservation and ecology. Currently, the most widely used methods for obtaining such estimates involve either sighting animals from transect lines or some form of capture-recapture on marked or uniquely identifiable individuals. However, many species are difficult to sight, and cannot be easily marked or recaptured. Some of these species produce readily identifiable sounds, providing an opportunity to use passive acoustic data to estimate animal density. In addition, even for species for which other visually based methods are feasible, passive acoustic methods offer the potential for greater detection ranges in some environments (e.g. underwater or in dense forest), and hence potentially better precision. Automated data collection means that surveys can take place at times and in places where it would be too expensive or dangerous to send human observers. Here, we present an overview of animal density estimation using passive acoustic data, a relatively new and fast-developing field. We review the types of data and methodological approaches currently available to researchers and we provide a framework for acoustics-based density estimation, illustrated with examples from real-world case studies. We mention moving sensor platforms (e.g. towed acoustics), but then focus on methods involving sensors at fixed locations, particularly hydrophones to survey marine mammals, as acoustic-based density estimation research to date has been concentrated in this area. Primary among these are methods based on distance sampling and spatially explicit capture-recapture. The methods are also applicable to other aquatic and terrestrial sound-producing taxa. We conclude that, despite being in its infancy, density estimation based on passive acoustic data likely will become an important method for surveying a number of diverse taxa, such as sea mammals, fish, birds, amphibians, and insects, especially in situations where inferences are required over long periods of time. There is considerable work ahead, with several potentially fruitful research areas, including the development of (i) hardware and software for data acquisition, (ii) efficient, calibrated, automated detection and classification systems, and (iii) statistical approaches optimized for this application. Further, survey design will need to be developed, and research is needed on the acoustic behaviour of target species. Fundamental research on vocalization rates and group sizes, and the relation between these and other factors such as season or behaviour state, is critical. Evaluation of the methods under known density scenarios will be important for empirically validating the approaches presented here</dc:description>
    </item>
    <item>
      <title>Variation in sexual dimorphism and assortative mating do not predict genetic divergence in the sexually dimorphic Goodeid fish Girardinichthys multiradiatus</title>
      <link>http://hdl.handle.net/10023/3483</link>
      <description>Abstract: Sexual dimorphism is often used as a proxy for the intensity of sexual selection in comparative studies of sexual selection and diversification. The Mexican Goodeinae are a group of livebearing freshwater fishes with large variation between species in sexual dimorphism in body shape. Previously we found an association between variation in morphological sexual dimorphism between species and the amount of gene flow within populations in the Goodeinae. Here we have examined if morphological differentiation within a single dimorphic species is related to assortative mating or gene flow between populations. In the Amarillo fish Girardinichthys multiradiatus studies have shown that exaggerated male fins are targets of female preferences. We find that populations of the species differ in the level of sexual dimorphism displayed due to faster evolution of differences in male than female morphology. However, this does not predict variation in assortative mating tests in the laboratory; in fact differences in male morphology are negatively correlated with assortative mating. Microsatellite markers reveal significant genetic differences between populations. However, gene flow is not predicted by either morphological differences or assortative mating. Rather, it demonstrates a pattern of isolation by distance with greater differentiation between watersheds. We discuss the caveats of predicting behavioural and genetic divergence from so-called proxies of sexual selection [Current Zoology 58 (3): 440-452, 2012].</description>
      <pubDate>Sun, 01 Jan 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3483</guid>
      <dc:date>2012-01-01T00:00:00Z</dc:date>
      <dc:creator>Macias Garcia, C.</dc:creator>
      <dc:creator>Smith, G.</dc:creator>
      <dc:creator>Gonzalez Zuarth, C.</dc:creator>
      <dc:creator>Graves, J. A.</dc:creator>
      <dc:creator>Ritchie, M. G.</dc:creator>
      <dc:description>Sexual dimorphism is often used as a proxy for the intensity of sexual selection in comparative studies of sexual selection and diversification. The Mexican Goodeinae are a group of livebearing freshwater fishes with large variation between species in sexual dimorphism in body shape. Previously we found an association between variation in morphological sexual dimorphism between species and the amount of gene flow within populations in the Goodeinae. Here we have examined if morphological differentiation within a single dimorphic species is related to assortative mating or gene flow between populations. In the Amarillo fish Girardinichthys multiradiatus studies have shown that exaggerated male fins are targets of female preferences. We find that populations of the species differ in the level of sexual dimorphism displayed due to faster evolution of differences in male than female morphology. However, this does not predict variation in assortative mating tests in the laboratory; in fact differences in male morphology are negatively correlated with assortative mating. Microsatellite markers reveal significant genetic differences between populations. However, gene flow is not predicted by either morphological differences or assortative mating. Rather, it demonstrates a pattern of isolation by distance with greater differentiation between watersheds. We discuss the caveats of predicting behavioural and genetic divergence from so-called proxies of sexual selection [Current Zoology 58 (3): 440-452, 2012].</dc:description>
    </item>
    <item>
      <title>Willin, an upstream component of the Hippo signaling pathway, orchestrates mammalian peripheral nerve fibroblasts</title>
      <link>http://hdl.handle.net/10023/3474</link>
      <description>Abstract: Willin/FRMD6 was first identified in the rat sciatic nerve, which is composed of neurons, Schwann cells, and fibroblasts. Willin is an upstream component of the Hippo signaling pathway, which results in the inactivation of the transcriptional coactivator YAP through Ser127 phosphorylation. This in turn suppresses the expression of genes involved in cell growth, proliferation and cancer development ensuring the control of organ size, cell contact inhibition and apoptosis. Here we show that in the mammalian sciatic nerve, Willin is predominantly expressed in fibroblasts and that Willin expression activates the Hippo signaling cascade and induces YAP translocation from the nucleus to the cytoplasm. In addition within these cells, although it inhibits cellular proliferation, Willin expression induces a quicker directional migration towards scratch closure and an increased expression of factors linked to nerve regeneration. These results show that Willin modulates sciatic nerve fibroblast activity indicating that Willin may have a potential role in the regeneration of the peripheral nervous system.</description>
      <pubDate>Mon, 08 Apr 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3474</guid>
      <dc:date>2013-04-08T00:00:00Z</dc:date>
      <dc:creator>Moleirinho, Susan</dc:creator>
      <dc:creator>Patrick, Calum</dc:creator>
      <dc:creator>Tilston-Lunel, Andrew Martin</dc:creator>
      <dc:creator>Higginson, JR</dc:creator>
      <dc:creator>Angus, Liselotte</dc:creator>
      <dc:creator>Antkowiak, Maciej</dc:creator>
      <dc:creator>Barnett, Susan</dc:creator>
      <dc:creator>Prystowsky, Michael</dc:creator>
      <dc:creator>Reynolds, Paul Andrew</dc:creator>
      <dc:creator>Gunn-Moore, Frank J</dc:creator>
      <dc:description>Willin/FRMD6 was first identified in the rat sciatic nerve, which is composed of neurons, Schwann cells, and fibroblasts. Willin is an upstream component of the Hippo signaling pathway, which results in the inactivation of the transcriptional coactivator YAP through Ser127 phosphorylation. This in turn suppresses the expression of genes involved in cell growth, proliferation and cancer development ensuring the control of organ size, cell contact inhibition and apoptosis. Here we show that in the mammalian sciatic nerve, Willin is predominantly expressed in fibroblasts and that Willin expression activates the Hippo signaling cascade and induces YAP translocation from the nucleus to the cytoplasm. In addition within these cells, although it inhibits cellular proliferation, Willin expression induces a quicker directional migration towards scratch closure and an increased expression of factors linked to nerve regeneration. These results show that Willin modulates sciatic nerve fibroblast activity indicating that Willin may have a potential role in the regeneration of the peripheral nervous system.</dc:description>
    </item>
    <item>
      <title>Development of a contact call in black-capped chickadees (Poecile atricapillus) hand-reared in different acoustic environments</title>
      <link>http://hdl.handle.net/10023/3472</link>
      <description>Abstract: The tseet contact call, common to black-capped (Poecile atricapillus) and mountain chickadees (P. gambeli), is the most frequently produced vocalization of each species. Previous work has characterized the tseet call of black-capped and mountain chickadees from different geographic locations in terms of nine acoustic features. In the current study, using similar methods, the tseet call of black-capped chickadees that were hand reared with either conspecifics, heterospecifics (mountain chickadees), or in isolation from adult chickadees are described. Analysis of call features examined which acoustic features were most affected by rearing environment, and revealed that starting frequency and the slope of the descending portion of the tseet call differed between black-capped chickadees reared with either conspecific or heterospecific adults. Birds reared in isolation from adults differed from the other hand-reared groups on almost every acoustic feature. Chickadee tseet calls are more individualized when they are reared with adult conspecifics or heterospecifics compared to chickadees that are reared in isolation from adults. The current results suggest a role of learning in this commonly used contact call.</description>
      <pubDate>Sat, 01 Jan 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3472</guid>
      <dc:date>2011-01-01T00:00:00Z</dc:date>
      <dc:creator>Guillette, Lauren</dc:creator>
      <dc:creator>Bloomfiled, Laurie</dc:creator>
      <dc:creator>Batty, Emily</dc:creator>
      <dc:creator>Dawson, Michael</dc:creator>
      <dc:creator>Sturdy, Chris</dc:creator>
      <dc:description>The tseet contact call, common to black-capped (Poecile atricapillus) and mountain chickadees (P. gambeli), is the most frequently produced vocalization of each species. Previous work has characterized the tseet call of black-capped and mountain chickadees from different geographic locations in terms of nine acoustic features. In the current study, using similar methods, the tseet call of black-capped chickadees that were hand reared with either conspecifics, heterospecifics (mountain chickadees), or in isolation from adult chickadees are described. Analysis of call features examined which acoustic features were most affected by rearing environment, and revealed that starting frequency and the slope of the descending portion of the tseet call differed between black-capped chickadees reared with either conspecific or heterospecific adults. Birds reared in isolation from adults differed from the other hand-reared groups on almost every acoustic feature. Chickadee tseet calls are more individualized when they are reared with adult conspecifics or heterospecifics compared to chickadees that are reared in isolation from adults. The current results suggest a role of learning in this commonly used contact call.</dc:description>
    </item>
    <item>
      <title>Competing conservation objectives for predators and prey : estimating killer whale prey requirements for Chinook salmon</title>
      <link>http://hdl.handle.net/10023/3456</link>
      <description>Abstract: Ecosystem-based management (EBM) of marine resources attempts to conserve interacting species. In contrast to single-species fisheries management, EBM aims to identify and resolve conflicting objectives for different species. Such a conflict may be emerging in the northeastern Pacific for southern resident killer whales (Orcinus orca) and their primary prey, Chinook salmon (Oncorhynchus tshawytscha). Both species have at-risk conservation status and transboundary (Canada–US) ranges. We modeled individual killer whale prey requirements from feeding and growth records of captive killer whales and morphometric data from historic live-capture fishery and whaling records worldwide. The models, combined with caloric value of salmon, and demographic and diet data for wild killer whales, allow us to predict salmon quantities needed to maintain and recover this killer whale population, which numbered 87 individuals in 2009. Our analyses provide new information on cost of lactation and new parameter estimates for other killer whale populations globally. Prey requirements of southern resident killer whales are difficult to reconcile with fisheries and conservation objectives for Chinook salmon, because the number of fish required is large relative to annual returns and fishery catches. For instance, a U.S. recovery goal (2.3% annual population growth of killer whales over 28 years) implies a 75% increase in energetic requirements. Reducing salmon fisheries may serve as a temporary mitigation measure to allow time for management actions to improve salmon productivity to take effect. As ecosystem-based fishery management becomes more prevalent, trade-offs between conservation objectives for predators and prey will become increasingly necessary. Our approach offers scenarios to compare relative influence of various sources of uncertainty on the resulting consumption estimates to prioritise future research efforts, and a general approach for assessing the extent of conflict between conservation objectives for threatened or protected wildlife where the interaction between affected species can be quantified.</description>
      <pubDate>Wed, 09 Nov 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3456</guid>
      <dc:date>2011-11-09T00:00:00Z</dc:date>
      <dc:creator>Williams, Robert</dc:creator>
      <dc:creator>Krkošek, Martin</dc:creator>
      <dc:creator>Ashe, Erin</dc:creator>
      <dc:creator>Branch, Trevor A</dc:creator>
      <dc:creator>Clark, Stephen</dc:creator>
      <dc:creator>Hammond, Philip Steven</dc:creator>
      <dc:creator>Hoyt, Eric</dc:creator>
      <dc:creator>Noren, Dawn P</dc:creator>
      <dc:creator>Rosen, David</dc:creator>
      <dc:creator>Winship, Arliss</dc:creator>
      <dc:description>Ecosystem-based management (EBM) of marine resources attempts to conserve interacting species. In contrast to single-species fisheries management, EBM aims to identify and resolve conflicting objectives for different species. Such a conflict may be emerging in the northeastern Pacific for southern resident killer whales (Orcinus orca) and their primary prey, Chinook salmon (Oncorhynchus tshawytscha). Both species have at-risk conservation status and transboundary (Canada–US) ranges. We modeled individual killer whale prey requirements from feeding and growth records of captive killer whales and morphometric data from historic live-capture fishery and whaling records worldwide. The models, combined with caloric value of salmon, and demographic and diet data for wild killer whales, allow us to predict salmon quantities needed to maintain and recover this killer whale population, which numbered 87 individuals in 2009. Our analyses provide new information on cost of lactation and new parameter estimates for other killer whale populations globally. Prey requirements of southern resident killer whales are difficult to reconcile with fisheries and conservation objectives for Chinook salmon, because the number of fish required is large relative to annual returns and fishery catches. For instance, a U.S. recovery goal (2.3% annual population growth of killer whales over 28 years) implies a 75% increase in energetic requirements. Reducing salmon fisheries may serve as a temporary mitigation measure to allow time for management actions to improve salmon productivity to take effect. As ecosystem-based fishery management becomes more prevalent, trade-offs between conservation objectives for predators and prey will become increasingly necessary. Our approach offers scenarios to compare relative influence of various sources of uncertainty on the resulting consumption estimates to prioritise future research efforts, and a general approach for assessing the extent of conflict between conservation objectives for threatened or protected wildlife where the interaction between affected species can be quantified.</dc:description>
    </item>
    <item>
      <title>Estimating seasonal abundance of a central place forager using counts and telemetry data</title>
      <link>http://hdl.handle.net/10023/3454</link>
      <description>Abstract: Obtaining population estimates of species that are not easily observed directly can be problematic. However, central place foragers can often be observed some of the time, e.g. when seals are hauled out. In these instances, population estimates can be derived from counts, combined with information on the proportion of time that animals can be observed. We present a modelling framework to estimate seasonal absolute abundance using counts and information from satellite telemetry data. The method was tested on a harbour seal population in an area of southeast Scotland. Counts were made monthly, between November 2001 and June 2003, when seals were hauled out on land and were corrected for the proportion of time the seals were at sea using satellite telemetry. Harbour seals (n=25) were tagged with satellite relay data loggers between November 2001 and March 2003. To estimate the proportion of time spent hauled out, time at sea on foraging trips was modelled separately from haul-out behaviour close to haul-out sites because of the different factors affecting these processes. A generalised linear mixed model framework was developed to capture the longitudinal nature of the data and the repeated measures across individuals. Despite seasonal variability in the number of seals counted at haul-out sites, the model generated estimates of abundance, with an overall mean of 846 (95% CI: 767 to 979). The methodology shows the value of using count and telemetry data collected concurrently for estimating absolute abundance, information that is essential to assess interactions between predators, fish stocks and fisheries.
Description: R.J.S. was supported by a Natural Environment Research Council studentship.</description>
      <pubDate>Thu, 01 Jan 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3454</guid>
      <dc:date>2009-01-01T00:00:00Z</dc:date>
      <dc:creator>Sharples, RJ</dc:creator>
      <dc:creator>MacKenzie, Monique Lea</dc:creator>
      <dc:creator>Hammond, Philip Steven</dc:creator>
      <dc:description>Obtaining population estimates of species that are not easily observed directly can be problematic. However, central place foragers can often be observed some of the time, e.g. when seals are hauled out. In these instances, population estimates can be derived from counts, combined with information on the proportion of time that animals can be observed. We present a modelling framework to estimate seasonal absolute abundance using counts and information from satellite telemetry data. The method was tested on a harbour seal population in an area of southeast Scotland. Counts were made monthly, between November 2001 and June 2003, when seals were hauled out on land and were corrected for the proportion of time the seals were at sea using satellite telemetry. Harbour seals (n=25) were tagged with satellite relay data loggers between November 2001 and March 2003. To estimate the proportion of time spent hauled out, time at sea on foraging trips was modelled separately from haul-out behaviour close to haul-out sites because of the different factors affecting these processes. A generalised linear mixed model framework was developed to capture the longitudinal nature of the data and the repeated measures across individuals. Despite seasonal variability in the number of seals counted at haul-out sites, the model generated estimates of abundance, with an overall mean of 846 (95% CI: 767 to 979). The methodology shows the value of using count and telemetry data collected concurrently for estimating absolute abundance, information that is essential to assess interactions between predators, fish stocks and fisheries.</dc:description>
    </item>
    <item>
      <title>Photo-grammetric measurements of swimming speed and body length of basking sharks observed around the Hebrides, Scotland</title>
      <link>http://hdl.handle.net/10023/3445</link>
      <description>Abstract: Photo-grammetric techniques developed for measuring body length and small scale movement patterns of cetaceans were applied to surface swimming basking sharks off the west coast of Scotland. These methods removed the need for close approaches, reducing the likelihood of disturbing the focal animal. Average swimming speed was calculated from the total path length between shark locations measured at approximately one minute intervals. These average speeds varied from 0.49 to 0.73 ms−1 for tracks of between 30 and 170 minutes' duration. Body length measurements ranged between 2.35 and 6.43 m. For ten sharks where body length and swimming speed were measured there was a significant correlation between body length (L) and swimming speed (V) expressed as V = 0.36L033.</description>
      <pubDate>Mon, 01 Mar 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3445</guid>
      <dc:date>2010-03-01T00:00:00Z</dc:date>
      <dc:creator>Lacey, Claire</dc:creator>
      <dc:creator>Leaper, Russell</dc:creator>
      <dc:creator>Moscrop, Anna</dc:creator>
      <dc:creator>Gillespie, Douglas Michael</dc:creator>
      <dc:creator>McLanaghan, Richard</dc:creator>
      <dc:creator>Brown, Steve</dc:creator>
      <dc:description>Photo-grammetric techniques developed for measuring body length and small scale movement patterns of cetaceans were applied to surface swimming basking sharks off the west coast of Scotland. These methods removed the need for close approaches, reducing the likelihood of disturbing the focal animal. Average swimming speed was calculated from the total path length between shark locations measured at approximately one minute intervals. These average speeds varied from 0.49 to 0.73 ms−1 for tracks of between 30 and 170 minutes' duration. Body length measurements ranged between 2.35 and 6.43 m. For ten sharks where body length and swimming speed were measured there was a significant correlation between body length (L) and swimming speed (V) expressed as V = 0.36L033.</dc:description>
    </item>
    <item>
      <title>Crenarchaeal chromatin proteins Cren7 and Sul7 compact DNA by inducing rigid bends</title>
      <link>http://hdl.handle.net/10023/3440</link>
      <description>Abstract: Archaeal chromatin proteins share molecular and functional similarities with both bacterial and eukaryotic chromatin proteins. These proteins play an important role in functionally organizing the genomic DNA into a compact nucleoid. Cren7 and Sul7 are two crenarchaeal nucleoid-associated proteins, which are structurally homologous, but not conserved at the sequence level. Co-crystal structures have shown that these two proteins induce a sharp bend on binding to DNA. In this study, we have investigated the architectural properties of these proteins using atomic force microscopy, molecular dynamics simulations and magnetic tweezers. We demonstrate that Cren7 and Sul7 both compact DNA molecules to a similar extent. Using a theoretical model, we quantify the number of individual proteins bound to the DNA as a function of protein concentration and show that forces up to 3.5 pN do not affect this binding. Moreover, we investigate the flexibility of the bending angle induced by Cren7 and Sul7 and show that the protein-DNA complexes differ in flexibility from analogous bacterial and eukaryotic DNA-bending proteins.</description>
      <pubDate>Tue, 01 Jan 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3440</guid>
      <dc:date>2013-01-01T00:00:00Z</dc:date>
      <dc:creator>Driessen, Rosalie P. C.</dc:creator>
      <dc:creator>Meng, He</dc:creator>
      <dc:creator>Suresh, Gorle</dc:creator>
      <dc:creator>Shahapure, Rajesh</dc:creator>
      <dc:creator>Lanzani, Giovanni</dc:creator>
      <dc:creator>Priyakumar, U. Deva</dc:creator>
      <dc:creator>White, Malcolm F.</dc:creator>
      <dc:creator>Schiessel, Helmut</dc:creator>
      <dc:creator>van Noort, John</dc:creator>
      <dc:creator>Dame, Remus Th</dc:creator>
      <dc:description>Archaeal chromatin proteins share molecular and functional similarities with both bacterial and eukaryotic chromatin proteins. These proteins play an important role in functionally organizing the genomic DNA into a compact nucleoid. Cren7 and Sul7 are two crenarchaeal nucleoid-associated proteins, which are structurally homologous, but not conserved at the sequence level. Co-crystal structures have shown that these two proteins induce a sharp bend on binding to DNA. In this study, we have investigated the architectural properties of these proteins using atomic force microscopy, molecular dynamics simulations and magnetic tweezers. We demonstrate that Cren7 and Sul7 both compact DNA molecules to a similar extent. Using a theoretical model, we quantify the number of individual proteins bound to the DNA as a function of protein concentration and show that forces up to 3.5 pN do not affect this binding. Moreover, we investigate the flexibility of the bending angle induced by Cren7 and Sul7 and show that the protein-DNA complexes differ in flexibility from analogous bacterial and eukaryotic DNA-bending proteins.</dc:description>
    </item>
    <item>
      <title>hSSB1 interacts directly with the MRN complex stimulating its recruitment to DNA double-strand breaks and its endo-nuclease activity</title>
      <link>http://hdl.handle.net/10023/3439</link>
      <description>Abstract: hSSB1 is a recently discovered single-stranded DNA binding protein that is essential for efficient repair of DNA double-strand breaks (DSBs) by the homologous recombination pathway. hSSB1 is required for the efficient recruitment of the MRN complex to sites of DSBs and for the efficient initiation of ATM dependent signalling. Here we explore the interplay between hSSB1 and MRN. We demonstrate that hSSB1 binds directly to NBS1, a component of the MRN complex, in a DNA damage independent manner. Consistent with the direct interaction, we observe that hSSB1 greatly stimulates the endo-nuclease activity of the MRN complex, a process that requires the C-terminal tail of hSSB1. Interestingly, analysis of two point mutations in NBS1, associated with Nijmegen breakage syndrome, revealed weaker binding to hSSB1, suggesting a possible disease mechanism.</description>
      <pubDate>Sun, 01 May 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3439</guid>
      <dc:date>2011-05-01T00:00:00Z</dc:date>
      <dc:creator>Richard, Derek J.</dc:creator>
      <dc:creator>Cubeddu, Liza</dc:creator>
      <dc:creator>Urquhart, Aaron J.</dc:creator>
      <dc:creator>Bain, Amanda</dc:creator>
      <dc:creator>Bolderson, Emma</dc:creator>
      <dc:creator>Menon, Dinoop</dc:creator>
      <dc:creator>White, Malcolm F.</dc:creator>
      <dc:creator>Khanna, Kum Kum</dc:creator>
      <dc:description>hSSB1 is a recently discovered single-stranded DNA binding protein that is essential for efficient repair of DNA double-strand breaks (DSBs) by the homologous recombination pathway. hSSB1 is required for the efficient recruitment of the MRN complex to sites of DSBs and for the efficient initiation of ATM dependent signalling. Here we explore the interplay between hSSB1 and MRN. We demonstrate that hSSB1 binds directly to NBS1, a component of the MRN complex, in a DNA damage independent manner. Consistent with the direct interaction, we observe that hSSB1 greatly stimulates the endo-nuclease activity of the MRN complex, a process that requires the C-terminal tail of hSSB1. Interestingly, analysis of two point mutations in NBS1, associated with Nijmegen breakage syndrome, revealed weaker binding to hSSB1, suggesting a possible disease mechanism.</dc:description>
    </item>
    <item>
      <title>hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex</title>
      <link>http://hdl.handle.net/10023/3438</link>
      <description>Abstract: hSSB1 is a newly discovered single-stranded DNA (ssDNA)-binding protein that is essential for efficient DNA double-strand break signalling through ATM. However, the mechanism by which hSSB1 functions to allow efficient signalling is unknown. Here, we show that hSSB1 is recruited rapidly to sites of double-strand DNA breaks (DSBs) in all interphase cells (G1, S and G2) independently of, CtIP, MDC1 and the MRN complex (Rad50, Mre11, NBS1). However expansion of hSSB1 from the DSB site requires the function of MRN. Strikingly, silencing of hSSB1 prevents foci formation as well as recruitment of MRN to sites of DSBs and leads to a subsequent defect in resection of DSBs as evident by defective RPA and ssDNA generation. Our data suggests that hSSB1 functions upstream of MRN to promote its recruitment at DSBs and is required for efficient resection of DSBs. These findings, together with previous work establish essential roles of hSSB1 in controlling ATM activation and activity, and subsequent DSB resection and homologous recombination (HR).</description>
      <pubDate>Tue, 01 Mar 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3438</guid>
      <dc:date>2011-03-01T00:00:00Z</dc:date>
      <dc:creator>Richard, Derek J.</dc:creator>
      <dc:creator>Savage, Kienan</dc:creator>
      <dc:creator>Bolderson, Emma</dc:creator>
      <dc:creator>Cubeddu, Liza</dc:creator>
      <dc:creator>So, Sairei</dc:creator>
      <dc:creator>Ghita, Mihaela</dc:creator>
      <dc:creator>Chen, David J.</dc:creator>
      <dc:creator>White, Malcolm F.</dc:creator>
      <dc:creator>Richard, Kerry</dc:creator>
      <dc:creator>Prise, Kevin M.</dc:creator>
      <dc:creator>Schettino, Giuseppe</dc:creator>
      <dc:creator>Khanna, Kum Kum</dc:creator>
      <dc:description>hSSB1 is a newly discovered single-stranded DNA (ssDNA)-binding protein that is essential for efficient DNA double-strand break signalling through ATM. However, the mechanism by which hSSB1 functions to allow efficient signalling is unknown. Here, we show that hSSB1 is recruited rapidly to sites of double-strand DNA breaks (DSBs) in all interphase cells (G1, S and G2) independently of, CtIP, MDC1 and the MRN complex (Rad50, Mre11, NBS1). However expansion of hSSB1 from the DSB site requires the function of MRN. Strikingly, silencing of hSSB1 prevents foci formation as well as recruitment of MRN to sites of DSBs and leads to a subsequent defect in resection of DSBs as evident by defective RPA and ssDNA generation. Our data suggests that hSSB1 functions upstream of MRN to promote its recruitment at DSBs and is required for efficient resection of DSBs. These findings, together with previous work establish essential roles of hSSB1 in controlling ATM activation and activity, and subsequent DSB resection and homologous recombination (HR).</dc:description>
    </item>
    <item>
      <title>Crystallization of Ranasmurfin, a blue coloured protein from Polypedates leucomystax</title>
      <link>http://hdl.handle.net/10023/3437</link>
      <description>Abstract: Ranasmurfin, a previously uncharacterized similar to 13 kDa blue protein found in the nests of the frog Polypedates leucomystax, has been purified and crystallized. The crystals are an intense blue colour and diffract to 1.51 angstrom with P2(1) symmetry and unit-cell parameters a = 40.9, b = 59.9, c = 45.0 angstrom, beta = 93.3 degrees. Self-rotation function analysis indicates the presence of a dimer in the asymmetric unit. Biochemical data suggest that the blue colour of the protein is related to dimer formation. Sequence data for the protein are incomplete, but thus far have identified no model for molecular replacement. A fluorescence scan shows a peak at 9.676 keV, indicating that the protein binds zinc and suggesting a route for structure solution.</description>
      <pubDate>Wed, 01 Nov 2006 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3437</guid>
      <dc:date>2006-11-01T00:00:00Z</dc:date>
      <dc:creator>McMahon, Stephen</dc:creator>
      <dc:creator>Walsh, MA</dc:creator>
      <dc:creator>Ching, RTY</dc:creator>
      <dc:creator>Carter, Lester</dc:creator>
      <dc:creator>Dorward, M</dc:creator>
      <dc:creator>Johnson, Kenneth Alan</dc:creator>
      <dc:creator>Liu, Huanting</dc:creator>
      <dc:creator>Oke, Muse</dc:creator>
      <dc:creator>Block Jr, C</dc:creator>
      <dc:creator>Kennedy, MW</dc:creator>
      <dc:creator>Latiff, AA</dc:creator>
      <dc:creator>Cooper, A</dc:creator>
      <dc:creator>Taylor, Garry Lindsay</dc:creator>
      <dc:creator>White, Malcolm Frederick</dc:creator>
      <dc:creator>Naismith, James Henderson</dc:creator>
      <dc:description>Ranasmurfin, a previously uncharacterized similar to 13 kDa blue protein found in the nests of the frog Polypedates leucomystax, has been purified and crystallized. The crystals are an intense blue colour and diffract to 1.51 angstrom with P2(1) symmetry and unit-cell parameters a = 40.9, b = 59.9, c = 45.0 angstrom, beta = 93.3 degrees. Self-rotation function analysis indicates the presence of a dimer in the asymmetric unit. Biochemical data suggest that the blue colour of the protein is related to dimer formation. Sequence data for the protein are incomplete, but thus far have identified no model for molecular replacement. A fluorescence scan shows a peak at 9.676 keV, indicating that the protein binds zinc and suggesting a route for structure solution.</dc:description>
    </item>
    <item>
      <title>Runaway sexual selection without genetic correlations : social environments and flexible mate choice initiate and enhance the Fisher process</title>
      <link>http://hdl.handle.net/10023/3429</link>
      <description>Abstract: Female mating preferences are often flexible, reflecting the social environment in which they are expressed. Associated indirect genetic effects (IGEs) can affect the rate and direction of evolutionary change, but sexual selection models do not capture these dynamics. We incorporate IGEs into quantitative genetic models to explore how variation in social environments and mate choice flexibility influence Fisherian sexual selection. The importance of IGEs is that runaway sexual selection can occur in the absence of a genetic correlation between male traits and female preferences. Social influences can facilitate the initiation of the runaway process and increase the rate of trait elaboration. Incorporating costs to choice do not alter the main findings. Our model provides testable predictions: (1) genetic covariances between male traits and female preferences may not exist, (2) social flexibility in female choice will be common in populations experiencing strong sexual selection, (3) variation in social environments should be associated with rapid sexual trait divergence, and (4) secondary sexual traits will be more elaborate than previously predicted. Allowing feedback from the social environment resolves discrepancies between theoretical predictions and empirical data, such as why indirect selection on female preferences, theoretically weak, might be sufficient for preferences to become elaborated.</description>
      <pubDate>Sat, 01 Sep 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3429</guid>
      <dc:date>2012-09-01T00:00:00Z</dc:date>
      <dc:creator>Bailey, Nathan William</dc:creator>
      <dc:creator>Moore, Allen J.</dc:creator>
      <dc:description>Female mating preferences are often flexible, reflecting the social environment in which they are expressed. Associated indirect genetic effects (IGEs) can affect the rate and direction of evolutionary change, but sexual selection models do not capture these dynamics. We incorporate IGEs into quantitative genetic models to explore how variation in social environments and mate choice flexibility influence Fisherian sexual selection. The importance of IGEs is that runaway sexual selection can occur in the absence of a genetic correlation between male traits and female preferences. Social influences can facilitate the initiation of the runaway process and increase the rate of trait elaboration. Incorporating costs to choice do not alter the main findings. Our model provides testable predictions: (1) genetic covariances between male traits and female preferences may not exist, (2) social flexibility in female choice will be common in populations experiencing strong sexual selection, (3) variation in social environments should be associated with rapid sexual trait divergence, and (4) secondary sexual traits will be more elaborate than previously predicted. Allowing feedback from the social environment resolves discrepancies between theoretical predictions and empirical data, such as why indirect selection on female preferences, theoretically weak, might be sufficient for preferences to become elaborated.</dc:description>
    </item>
    <item>
      <title>Iso-seco-tanapartholides : isolation, synthesis and biological evaluation</title>
      <link>http://hdl.handle.net/10023/3420</link>
      <description>Abstract: The isolation, identification and total synthesis of two plant-derived inhibitors of the NF-kappa B signaling pathway from the iso-seco-tanapartholide family of natural products is described. A key step in the efficient reaction sequence is a late-stage oxidative cleavage reaction that was carried out in the absence of protecting groups to give the natural products directly. A detailed comparison of the synthetic material with samples of the natural products proved informative. Biological studies on synthetic material confirmed that these compounds act late in the NF-kappa B signaling pathway. ((C) Wiley-VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)</description>
      <pubDate>Sun, 01 Nov 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3420</guid>
      <dc:date>2009-11-01T00:00:00Z</dc:date>
      <dc:creator>Makiyi, Edward F.</dc:creator>
      <dc:creator>Frade, Raquel F. M.</dc:creator>
      <dc:creator>Lebl, Tomas</dc:creator>
      <dc:creator>Jaffray, Ellis G.</dc:creator>
      <dc:creator>Cobb, Susan E.</dc:creator>
      <dc:creator>Harvey, Alan L.</dc:creator>
      <dc:creator>Slawin, Alexandra M. Z.</dc:creator>
      <dc:creator>Hay, Ronald T.</dc:creator>
      <dc:creator>Westwood, Nicholas J.</dc:creator>
      <dc:description>The isolation, identification and total synthesis of two plant-derived inhibitors of the NF-kappa B signaling pathway from the iso-seco-tanapartholide family of natural products is described. A key step in the efficient reaction sequence is a late-stage oxidative cleavage reaction that was carried out in the absence of protecting groups to give the natural products directly. A detailed comparison of the synthetic material with samples of the natural products proved informative. Biological studies on synthetic material confirmed that these compounds act late in the NF-kappa B signaling pathway. ((C) Wiley-VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)</dc:description>
    </item>
    <item>
      <title>To ping or not to ping : the use of active acoustic devices in mitigating interactions between small cetaceans and gillnet fisheries</title>
      <link>http://hdl.handle.net/10023/3394</link>
      <description>Abstract: Active sound emitters (‘pingers’) are used in several gillnet fisheries to reduce bycatch of small cetaceans, and/or to reduce depredation by dolphins. Here, we review studies conducted to determine how effective these devices may be as management tools. Significant reductions in bycatch of harbour porpoise Phocoena phocoena, franciscana Pontoporia blainvillei, common Delphinus delphis and striped dolphin Stenella coeruleoalba, and beaked whales as a group have been demonstrated. For harbour porpoise this result has been replicated in 14 controlled experiments in North America and Europe, and appears to be due to porpoises avoiding the area ensonified by pingers. Two gillnet fisheries (California-Oregon driftnet fishery for swordfish; New England groundfish fishery) with mandatory pinger use have been studied for over a decade. Bycatch rates of dolphins/porpoises have fallen by 50 to 60%, and there is no evidence of bycatch increasing over time due to habituation. In both fisheries, bycatch rates were significantly higher in nets sparsely equipped with pingers or in which pingers had failed, than in nets without any pingers at all. Studies of pinger use to reduce depredation by bottlenose dolphins Tursiops truncatus generally show small and inconsistent improvements in fish catches and somewhat reduced net damage. Dolphin bycatch in these fisheries is rare, but still occurs in nets with pingers. Taken together, these studies suggest that the most promising candidates for bycatch reduction via pinger use will be gillnet fisheries in developed countries in which the bycaught cetaceans are generally neophobic species with large home ranges. We offer a set of lessons learned from the last decade of bycatch management.</description>
      <pubDate>Tue, 01 Jan 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3394</guid>
      <dc:date>2013-01-01T00:00:00Z</dc:date>
      <dc:creator>Dawson, Steve</dc:creator>
      <dc:creator>Northridge, Simon Patrick</dc:creator>
      <dc:creator>Waples, Danielle</dc:creator>
      <dc:creator>Read, Andrew</dc:creator>
      <dc:description>Active sound emitters (‘pingers’) are used in several gillnet fisheries to reduce bycatch of small cetaceans, and/or to reduce depredation by dolphins. Here, we review studies conducted to determine how effective these devices may be as management tools. Significant reductions in bycatch of harbour porpoise Phocoena phocoena, franciscana Pontoporia blainvillei, common Delphinus delphis and striped dolphin Stenella coeruleoalba, and beaked whales as a group have been demonstrated. For harbour porpoise this result has been replicated in 14 controlled experiments in North America and Europe, and appears to be due to porpoises avoiding the area ensonified by pingers. Two gillnet fisheries (California-Oregon driftnet fishery for swordfish; New England groundfish fishery) with mandatory pinger use have been studied for over a decade. Bycatch rates of dolphins/porpoises have fallen by 50 to 60%, and there is no evidence of bycatch increasing over time due to habituation. In both fisheries, bycatch rates were significantly higher in nets sparsely equipped with pingers or in which pingers had failed, than in nets without any pingers at all. Studies of pinger use to reduce depredation by bottlenose dolphins Tursiops truncatus generally show small and inconsistent improvements in fish catches and somewhat reduced net damage. Dolphin bycatch in these fisheries is rare, but still occurs in nets with pingers. Taken together, these studies suggest that the most promising candidates for bycatch reduction via pinger use will be gillnet fisheries in developed countries in which the bycaught cetaceans are generally neophobic species with large home ranges. We offer a set of lessons learned from the last decade of bycatch management.</dc:description>
    </item>
    <item>
      <title>Tissue-specific transcriptomics in the field cricket Teleogryllus oceanicus</title>
      <link>http://hdl.handle.net/10023/3391</link>
      <description>Abstract: Field crickets (family Gryllidae) frequently are used in studies of behavioral genetics, sexual selection, and sexual conflict, but there have been no studies of transcriptomic differences among different tissue types. We evaluated transcriptome variation among testis, accessory gland, and the remaining whole-body preparations from males of the field cricket, Teleogryllus oceanicus. Non-normalized cDNA libraries from each tissue were sequenced on the Roche 454 platform, and a master assembly was constructed using testis, accessory gland, and whole-body preparations. A total of 940,200 reads were assembled into 41,962 contigs, to which 36,856 singletons (reads not assembled into a contig) were added to provide a total of 78,818 sequences used in annotation analysis. A total of 59,072 sequences (75%) were unique to one of the three tissues. Testis tissue had the greatest proportion of tissue-specific sequences (62.6%), followed by general body (56.43%) and accessory gland tissue (44.16%). We tested the hypothesis that tissues expressing gene products expected to evolve rapidly as a result of sexual selection—testis and accessory gland—would yield a smaller proportion of BLASTx matches to homologous genes in the model organism Drosophila melanogaster compared with whole-body tissue. Uniquely expressed sequences in both testis and accessory gland showed a significantly lower rate of matching to annotated D. melanogaster genes compared with those from general body tissue. These results correspond with empirical evidence that genes expressed in testis and accessory gland tissue are rapidly evolving targets of selection.
Description: This work was supported by a Natural Environment Research Council Junior Postdoctoral Fellowship (NE/G014906/1) and Pacific Rim Foundation funding (08-T-PRRP-05-0029) to N.W.B.</description>
      <pubDate>Fri, 01 Feb 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3391</guid>
      <dc:date>2013-02-01T00:00:00Z</dc:date>
      <dc:creator>Bailey, Nathan William</dc:creator>
      <dc:creator>Veltsos, Paris</dc:creator>
      <dc:creator>Tan, Yew-Foon</dc:creator>
      <dc:creator>Millar, A. Harvey</dc:creator>
      <dc:creator>Ritchie, Michael Gordon</dc:creator>
      <dc:creator>Simmons, Leigh W.</dc:creator>
      <dc:description>Field crickets (family Gryllidae) frequently are used in studies of behavioral genetics, sexual selection, and sexual conflict, but there have been no studies of transcriptomic differences among different tissue types. We evaluated transcriptome variation among testis, accessory gland, and the remaining whole-body preparations from males of the field cricket, Teleogryllus oceanicus. Non-normalized cDNA libraries from each tissue were sequenced on the Roche 454 platform, and a master assembly was constructed using testis, accessory gland, and whole-body preparations. A total of 940,200 reads were assembled into 41,962 contigs, to which 36,856 singletons (reads not assembled into a contig) were added to provide a total of 78,818 sequences used in annotation analysis. A total of 59,072 sequences (75%) were unique to one of the three tissues. Testis tissue had the greatest proportion of tissue-specific sequences (62.6%), followed by general body (56.43%) and accessory gland tissue (44.16%). We tested the hypothesis that tissues expressing gene products expected to evolve rapidly as a result of sexual selection—testis and accessory gland—would yield a smaller proportion of BLASTx matches to homologous genes in the model organism Drosophila melanogaster compared with whole-body tissue. Uniquely expressed sequences in both testis and accessory gland showed a significantly lower rate of matching to annotated D. melanogaster genes compared with those from general body tissue. These results correspond with empirical evidence that genes expressed in testis and accessory gland tissue are rapidly evolving targets of selection.</dc:description>
    </item>
    <item>
      <title>Dimer-dimer stacking interactions are important for nucleic acid binding by the archaeal chromatin protein Alba</title>
      <link>http://hdl.handle.net/10023/3374</link>
      <description>Abstract: Archaea use a variety of small basic proteins to package their DNA. One of the most widespread and highly conserved is the Alba (Sso10b) protein. Alba interacts with both DNA and RNA in vitro, and we show in the present study that it binds more tightly to dsDNA (double-stranded DNA) than to either ssDNA (single-stranded DNA) or RNA. The Alba protein is dimeric in solution, and forms distinct ordered complexes with DNA that have been visualized by electron microscopy studies; these studies suggest that, on binding dsDNA, the protein forms extended helical protein fibres. An end-to-end association of consecutive Alba dimers is suggested by the presence of a dimer-dimer interface in crystal structures of Alba from several species, and by the strong conservation of the interface residues, centred on Are and Phe(60). In the present study we map perturbation of the polypeptide backbone of Alba upon binding to DNA and RNA by NMR, and demonstrate the central role of Phe(60) in forming the dimer dimer interface. Site-directed spin labelling and pulsed ESR are used to confirm that an end-to-end, dimer dimer interaction forms in the presence of dsDNA.</description>
      <pubDate>Thu, 01 Apr 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3374</guid>
      <dc:date>2010-04-01T00:00:00Z</dc:date>
      <dc:creator>Jelinska, Clare</dc:creator>
      <dc:creator>Petrovic-Stojanovska, Biljana</dc:creator>
      <dc:creator>Ingledew, W John</dc:creator>
      <dc:creator>White, Malcolm F.</dc:creator>
      <dc:description>Archaea use a variety of small basic proteins to package their DNA. One of the most widespread and highly conserved is the Alba (Sso10b) protein. Alba interacts with both DNA and RNA in vitro, and we show in the present study that it binds more tightly to dsDNA (double-stranded DNA) than to either ssDNA (single-stranded DNA) or RNA. The Alba protein is dimeric in solution, and forms distinct ordered complexes with DNA that have been visualized by electron microscopy studies; these studies suggest that, on binding dsDNA, the protein forms extended helical protein fibres. An end-to-end association of consecutive Alba dimers is suggested by the presence of a dimer-dimer interface in crystal structures of Alba from several species, and by the strong conservation of the interface residues, centred on Are and Phe(60). In the present study we map perturbation of the polypeptide backbone of Alba upon binding to DNA and RNA by NMR, and demonstrate the central role of Phe(60) in forming the dimer dimer interface. Site-directed spin labelling and pulsed ESR are used to confirm that an end-to-end, dimer dimer interaction forms in the presence of dsDNA.</dc:description>
    </item>
    <item>
      <title>Seasonal inflow of warm water onto the southern Weddell Sea continental shelf, Antarctica</title>
      <link>http://hdl.handle.net/10023/3370</link>
      <description>Abstract: To capture the austral summer to winter transition in water mass properties over the southern Weddell Sea continental shelf and slope region Weddell seals were tagged with miniaturized conductivity–temperature–depth sensors in February 2011. During the following 8 months the instruments yielded about 9000 temperature–salinity profiles from a previously undersampled area. This allows, for the first time, a description of the seasonality of warm water intrusions onto the shelf. A temperature section across the Filchner Depression and eastern shelf shows a pronounced decrease in warm water inflow from summer to winter, further supported by an almost 3–year long time series from a shelf–break mooring. The seasonal variability is related to the surface wind stress and an associated deepening of the off–shore core of Warm Deep Water.</description>
      <pubDate>Sat, 01 Sep 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3370</guid>
      <dc:date>2012-09-01T00:00:00Z</dc:date>
      <dc:creator>Arthun, Marius</dc:creator>
      <dc:creator>Nicholls, Keith</dc:creator>
      <dc:creator>Makinson, Keith</dc:creator>
      <dc:creator>Fedak, Mike</dc:creator>
      <dc:creator>Boehme, Lars</dc:creator>
      <dc:description>To capture the austral summer to winter transition in water mass properties over the southern Weddell Sea continental shelf and slope region Weddell seals were tagged with miniaturized conductivity–temperature–depth sensors in February 2011. During the following 8 months the instruments yielded about 9000 temperature–salinity profiles from a previously undersampled area. This allows, for the first time, a description of the seasonality of warm water intrusions onto the shelf. A temperature section across the Filchner Depression and eastern shelf shows a pronounced decrease in warm water inflow from summer to winter, further supported by an almost 3–year long time series from a shelf–break mooring. The seasonal variability is related to the surface wind stress and an associated deepening of the off–shore core of Warm Deep Water.</dc:description>
    </item>
    <item>
      <title>Genetic analysis of life-history constraint and evolution in a wild ungulate population</title>
      <link>http://hdl.handle.net/10023/3363</link>
      <description>Abstract: Trade-offs among life-history traits are central to evolutionary theory. In quantitative genetic terms, trade-offs may be manifested as negative genetic covariances relative to the direction of selection on phenotypic traits. Although the expression and selection of ecologically important phenotypic variation are fundamentally multivariate phenomena, the in situ quantification of genetic covariances is challenging. Even for life-history traits, where well-developed theory exists with which to relate phenotypic variation to fitness variation, little evidence exists from in situ studies that negative genetic covariances are an important aspect of the genetic architecture of life-history traits. In fact, the majority of reported estimates of genetic covariances among life-history traits are positive. Here we apply theory of the genetics and selection of life histories in organisms with complex life cycles to provide a framework for quantifying the contribution of multivariate genetically based relationships among traits to evolutionary constraint. We use a Bayesian framework to link pedigree-based inference of the genetic basis of variation in life-history traits to evolutionary demography theory regarding how life histories are selected. Our results suggest that genetic covariances may be acting to constrain the evolution of female life-history traits in a wild population of red deer Cervus elaphus: genetic covariances are estimated to reduce the rate of adaptation by about 40%, relative to predicted evolutionary change in the absence of genetic covariances. Furthermore, multivariate phenotypic (rather than genetic) relationships among female life-history traits do not reveal this constraint.</description>
      <pubDate>Sun, 01 Apr 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3363</guid>
      <dc:date>2012-04-01T00:00:00Z</dc:date>
      <dc:creator>Morrissey, Michael Blair</dc:creator>
      <dc:creator>Walling, Craig</dc:creator>
      <dc:creator>Wilson, Alastair</dc:creator>
      <dc:creator>Pemberton, Josephine</dc:creator>
      <dc:creator>Clutton-Brock, Tim</dc:creator>
      <dc:creator>Kruuk, Loeske</dc:creator>
      <dc:description>Trade-offs among life-history traits are central to evolutionary theory. In quantitative genetic terms, trade-offs may be manifested as negative genetic covariances relative to the direction of selection on phenotypic traits. Although the expression and selection of ecologically important phenotypic variation are fundamentally multivariate phenomena, the in situ quantification of genetic covariances is challenging. Even for life-history traits, where well-developed theory exists with which to relate phenotypic variation to fitness variation, little evidence exists from in situ studies that negative genetic covariances are an important aspect of the genetic architecture of life-history traits. In fact, the majority of reported estimates of genetic covariances among life-history traits are positive. Here we apply theory of the genetics and selection of life histories in organisms with complex life cycles to provide a framework for quantifying the contribution of multivariate genetically based relationships among traits to evolutionary constraint. We use a Bayesian framework to link pedigree-based inference of the genetic basis of variation in life-history traits to evolutionary demography theory regarding how life histories are selected. Our results suggest that genetic covariances may be acting to constrain the evolution of female life-history traits in a wild population of red deer Cervus elaphus: genetic covariances are estimated to reduce the rate of adaptation by about 40%, relative to predicted evolutionary change in the absence of genetic covariances. Furthermore, multivariate phenotypic (rather than genetic) relationships among female life-history traits do not reveal this constraint.</dc:description>
    </item>
    <item>
      <title>Vocal copying of individually distinctive signature whistles in bottlenose dolphins</title>
      <link>http://hdl.handle.net/10023/3361</link>
      <description>Abstract: Vocal learning is relatively common in birds but less so in mammals. Sexual selection and individual or group recognition have been identified as major forces in its evolution. While important in the development of vocal displays, vocal learning also allows signal copying in social interactions. Such copying can function in addressing or labelling selected conspecifics. Most examples of addressing in non-humans come from bird song, where matching occurs in an aggressive context. However, in other animals, addressing with learned signals is very much an affiliative signal. We studied the function of vocal copying in a mammal that shows vocal learning as well as complex cognitive and social behaviour, the bottlenose dolphin (Tursiops truncatus). Copying occurred almost exclusively between close associates such as mother–calf pairs and male alliances during separation and was not followed by aggression. All copies were clearly recognizable as such because copiers consistently modified some acoustic parameters of a signal when copying it. We found no evidence for the use of copying in aggression or deception. This use of vocal copying is similar to its use in human language, where the maintenance of social bonds appears to be more important than the immediate defence of resources.</description>
      <pubDate>Mon, 22 Apr 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3361</guid>
      <dc:date>2013-04-22T00:00:00Z</dc:date>
      <dc:creator>King, Stephanie Laura</dc:creator>
      <dc:creator>Sayigh, Laela</dc:creator>
      <dc:creator>Wells, Randall</dc:creator>
      <dc:creator>Fellner, Wendi</dc:creator>
      <dc:creator>Janik, Vincent M.</dc:creator>
      <dc:description>Vocal learning is relatively common in birds but less so in mammals. Sexual selection and individual or group recognition have been identified as major forces in its evolution. While important in the development of vocal displays, vocal learning also allows signal copying in social interactions. Such copying can function in addressing or labelling selected conspecifics. Most examples of addressing in non-humans come from bird song, where matching occurs in an aggressive context. However, in other animals, addressing with learned signals is very much an affiliative signal. We studied the function of vocal copying in a mammal that shows vocal learning as well as complex cognitive and social behaviour, the bottlenose dolphin (Tursiops truncatus). Copying occurred almost exclusively between close associates such as mother–calf pairs and male alliances during separation and was not followed by aggression. All copies were clearly recognizable as such because copiers consistently modified some acoustic parameters of a signal when copying it. We found no evidence for the use of copying in aggression or deception. This use of vocal copying is similar to its use in human language, where the maintenance of social bonds appears to be more important than the immediate defence of resources.</dc:description>
    </item>
    <item>
      <title>A class of 5-nitro-2-furancarboxylamides with potent trypanocidal activity against Trypanosoma brucei in vitro</title>
      <link>http://hdl.handle.net/10023/3359</link>
      <description>Abstract: Recently, the World Health Organization approved the nifurtimox–eflornithine combination therapy for the treatment of human African trypanosomiasis, renewing interest in nitroheterocycle therapies for this and associated diseases. In this study, we have synthesized a series of novel 5-nitro-2-furancarboxylamides that show potent trypanocidal activity, 1000-fold more potent than nifurtimox against in vitro Trypanosoma brucei with very low cytotoxicity against human HeLa cells. More importantly, the most potent analogue showed very limited cross-resistance to nifurtimox-resistant cells and vice versa. This implies that our novel, relatively easy to synthesize and therefore cheap, 5-nitro-2-furancarboxylamides are targeting a different, but still essential, biochemical process to those targeted by nifurtimox or its metabolites in the parasites. The significant increase in potency (smaller dose probably required) has the potential for greatly reducing unwanted side effects and also reducing the likelihood of drug resistance. Collectively, these findings have important implications for the future therapeutic treatment of African sleeping sickness.</description>
      <pubDate>Thu, 14 Feb 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3359</guid>
      <dc:date>2013-02-14T00:00:00Z</dc:date>
      <dc:creator>Zhou, Linna</dc:creator>
      <dc:creator>Stewart, Gavin</dc:creator>
      <dc:creator>Rideau, Emeline</dc:creator>
      <dc:creator>Westwood, Nicholas James</dc:creator>
      <dc:creator>Smith, Terry K</dc:creator>
      <dc:description>Recently, the World Health Organization approved the nifurtimox–eflornithine combination therapy for the treatment of human African trypanosomiasis, renewing interest in nitroheterocycle therapies for this and associated diseases. In this study, we have synthesized a series of novel 5-nitro-2-furancarboxylamides that show potent trypanocidal activity, 1000-fold more potent than nifurtimox against in vitro Trypanosoma brucei with very low cytotoxicity against human HeLa cells. More importantly, the most potent analogue showed very limited cross-resistance to nifurtimox-resistant cells and vice versa. This implies that our novel, relatively easy to synthesize and therefore cheap, 5-nitro-2-furancarboxylamides are targeting a different, but still essential, biochemical process to those targeted by nifurtimox or its metabolites in the parasites. The significant increase in potency (smaller dose probably required) has the potential for greatly reducing unwanted side effects and also reducing the likelihood of drug resistance. Collectively, these findings have important implications for the future therapeutic treatment of African sleeping sickness.</dc:description>
    </item>
    <item>
      <title>Fast silencing reveals a lost role for reciprocal inhibition in locomotion</title>
      <link>http://hdl.handle.net/10023/3357</link>
      <description>Abstract: Summary Alternating contractions of antagonistic muscle groups during locomotion are generated by spinal “half-center” networks coupled in antiphase by reciprocal inhibition. It is widely thought that reciprocal inhibition only coordinates the activity of these muscles. We have devised two methods to rapidly and selectively silence neurons on just one side of Xenopus tadpole spinal cord and hindbrain, which generate swimming rhythms. Silencing activity on one side led to rapid cessation of activity on the other side. Analyses reveal that this resulted from the depression of reciprocal inhibition connecting the two sides. Although critical neurons in intact tadpoles are capable of pacemaker firing individually, an effect that could support motor rhythms without inhibition, the swimming network itself requires ∼23 min to regain rhythmic activity after blocking inhibition pharmacologically, implying some homeostatic changes. We conclude therefore that reciprocal inhibition is critical for the generation of normal locomotor rhythm.</description>
      <pubDate>Wed, 09 Jan 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3357</guid>
      <dc:date>2013-01-09T00:00:00Z</dc:date>
      <dc:creator>Moult, Peter Robert</dc:creator>
      <dc:creator>Cottrell, Glen Alfred</dc:creator>
      <dc:creator>Li, Wenchang</dc:creator>
      <dc:description>Summary Alternating contractions of antagonistic muscle groups during locomotion are generated by spinal “half-center” networks coupled in antiphase by reciprocal inhibition. It is widely thought that reciprocal inhibition only coordinates the activity of these muscles. We have devised two methods to rapidly and selectively silence neurons on just one side of Xenopus tadpole spinal cord and hindbrain, which generate swimming rhythms. Silencing activity on one side led to rapid cessation of activity on the other side. Analyses reveal that this resulted from the depression of reciprocal inhibition connecting the two sides. Although critical neurons in intact tadpoles are capable of pacemaker firing individually, an effect that could support motor rhythms without inhibition, the swimming network itself requires ∼23 min to regain rhythmic activity after blocking inhibition pharmacologically, implying some homeostatic changes. We conclude therefore that reciprocal inhibition is critical for the generation of normal locomotor rhythm.</dc:description>
    </item>
    <item>
      <title>The role of endosymbionts in the evolution of haploid-male genetic systems in scale insects (Coccoidea)</title>
      <link>http://hdl.handle.net/10023/3355</link>
      <description>Abstract: There is an extraordinary diversity in genetic systems across species, but this variation remains poorly understood. In part, this is because the mechanisms responsible for transitions between systems are often unknown. A recent hypothesis has suggested that conflict between hosts and endosymbiotic microorganisms over transmission could drive the transition from diplodiploidy to systems with male haploidy (haplodiploidy, including arrhenotoky and paternal genome elimination [PGE]). Here, we present the first formal test of this idea with a comparative analysis across scale insects (Hemiptera: Coccoidea). Scale insects are renowned for their large variation in genetic systems, and multiple transitions between diplodiploidy and haplodiploidy have taken place within this group. Additionally, most species rely on endosymbiotic microorganisms to provide them with essential nutrients lacking in their diet. We show that species harboring endosymbionts are indeed more likely to have a genetic system with male haploidy, which supports the hypothesis that endosymbionts might have played a role in the transition to haplodiploidy. We also extend our analysis to consider the relationship between endosymbiont presence and transitions to parthenogenesis. Although in scale insects there is no such overall association, species harboring eukaryote endosymbionts were more likely to be parthenogenetic than those with bacterial symbionts. These results support the idea that intergenomic conflict can drive the evolution of novel genetic systems and affect host reproduction.</description>
      <pubDate>Tue, 01 May 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3355</guid>
      <dc:date>2012-05-01T00:00:00Z</dc:date>
      <dc:creator>Ross, Laura</dc:creator>
      <dc:creator>Shuker, David M.</dc:creator>
      <dc:creator>Normark, Benjamin B.</dc:creator>
      <dc:creator>Pen, Ido</dc:creator>
      <dc:description>There is an extraordinary diversity in genetic systems across species, but this variation remains poorly understood. In part, this is because the mechanisms responsible for transitions between systems are often unknown. A recent hypothesis has suggested that conflict between hosts and endosymbiotic microorganisms over transmission could drive the transition from diplodiploidy to systems with male haploidy (haplodiploidy, including arrhenotoky and paternal genome elimination [PGE]). Here, we present the first formal test of this idea with a comparative analysis across scale insects (Hemiptera: Coccoidea). Scale insects are renowned for their large variation in genetic systems, and multiple transitions between diplodiploidy and haplodiploidy have taken place within this group. Additionally, most species rely on endosymbiotic microorganisms to provide them with essential nutrients lacking in their diet. We show that species harboring endosymbionts are indeed more likely to have a genetic system with male haploidy, which supports the hypothesis that endosymbionts might have played a role in the transition to haplodiploidy. We also extend our analysis to consider the relationship between endosymbiont presence and transitions to parthenogenesis. Although in scale insects there is no such overall association, species harboring eukaryote endosymbionts were more likely to be parthenogenetic than those with bacterial symbionts. These results support the idea that intergenomic conflict can drive the evolution of novel genetic systems and affect host reproduction.</dc:description>
    </item>
    <item>
      <title>Functional analysis of Leishmania cyclopropane fatty acid synthetase</title>
      <link>http://hdl.handle.net/10023/3354</link>
      <description>Abstract: The single gene encoding cyclopropane fatty acid synthetase (CFAS) is present in Leishmania infantum, L. mexicana and L. braziliensis but absent from L. major, a causative agent of cutaneous leishmaniasis. In L. infantum, usually causative agent of visceral leishmaniasis, the CFAS gene is transcribed in both insect (extracellular) and host (intracellular) stages of the parasite life cycle. Tagged CFAS protein is stably detected in intracellular L. infantum but only during the early log phase of extracellular growth, when it shows partial localisation to the endoplasmic reticulum. Lipid analyses of L. infantum wild type, CFAS null and complemented parasites detect a low abundance CFAS-dependent C19 Delta fatty acid, characteristic of a cyclopropanated species, in wild type and add-back cells. Sub-cellular fractionation studies locate the C19 Delta fatty acid to both ER and plasma membrane-enriched fractions. This fatty acid is not detectable in wild type L. major, although expression of the L. infantum CFAS gene in L. major generates cyclopropanated fatty acids, indicating that the substrate for this modification is present in L. major, despite the absence of the modifying enzyme. Loss of the L. infantum CFAS gene does not affect extracellular parasite growth, phagocytosis or early survival in macrophages. However, while endocytosis is also unaffected in the extracellular CFAS nulls, membrane transporter activity is defective and the null parasites are more resistant to oxidative stress. Following infection in vivo, L. infantum CFAS nulls exhibit lower parasite burdens in both the liver and spleen of susceptible hosts but it has not been possible to complement this phenotype, suggesting that loss of C19 Delta fatty acid may lead to irreversible changes in cell physiology that cannot be rescued by re-expression. Aberrant cyclopropanation in L. major decreases parasite virulence but does not influence parasite tissue tropism.</description>
      <pubDate>Mon, 10 Dec 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3354</guid>
      <dc:date>2012-12-10T00:00:00Z</dc:date>
      <dc:creator>Oyola, Samuel O.</dc:creator>
      <dc:creator>Evans, Krystal J.</dc:creator>
      <dc:creator>Smith, Terry K.</dc:creator>
      <dc:creator>Smith, Barbara A.</dc:creator>
      <dc:creator>Hilley, James D.</dc:creator>
      <dc:creator>Mottram, Jeremy C.</dc:creator>
      <dc:creator>Kaye, Paul M.</dc:creator>
      <dc:creator>Smith, Deborah F.</dc:creator>
      <dc:description>The single gene encoding cyclopropane fatty acid synthetase (CFAS) is present in Leishmania infantum, L. mexicana and L. braziliensis but absent from L. major, a causative agent of cutaneous leishmaniasis. In L. infantum, usually causative agent of visceral leishmaniasis, the CFAS gene is transcribed in both insect (extracellular) and host (intracellular) stages of the parasite life cycle. Tagged CFAS protein is stably detected in intracellular L. infantum but only during the early log phase of extracellular growth, when it shows partial localisation to the endoplasmic reticulum. Lipid analyses of L. infantum wild type, CFAS null and complemented parasites detect a low abundance CFAS-dependent C19 Delta fatty acid, characteristic of a cyclopropanated species, in wild type and add-back cells. Sub-cellular fractionation studies locate the C19 Delta fatty acid to both ER and plasma membrane-enriched fractions. This fatty acid is not detectable in wild type L. major, although expression of the L. infantum CFAS gene in L. major generates cyclopropanated fatty acids, indicating that the substrate for this modification is present in L. major, despite the absence of the modifying enzyme. Loss of the L. infantum CFAS gene does not affect extracellular parasite growth, phagocytosis or early survival in macrophages. However, while endocytosis is also unaffected in the extracellular CFAS nulls, membrane transporter activity is defective and the null parasites are more resistant to oxidative stress. Following infection in vivo, L. infantum CFAS nulls exhibit lower parasite burdens in both the liver and spleen of susceptible hosts but it has not been possible to complement this phenotype, suggesting that loss of C19 Delta fatty acid may lead to irreversible changes in cell physiology that cannot be rescued by re-expression. Aberrant cyclopropanation in L. major decreases parasite virulence but does not influence parasite tissue tropism.</dc:description>
    </item>
    <item>
      <title>The AEROPATH project targeting Pseudomonas aeruginosa : crystallographic studies for assessment of potential targets in early-stage drug discovery</title>
      <link>http://hdl.handle.net/10023/3352</link>
      <description>Abstract: Bacterial infections are increasingly difficult to treat owing to the spread of antibiotic resistance. A major concern is Gram-negative bacteria, for which the discovery of new antimicrobial drugs has been particularly scarce. In an effort to accelerate early steps in drug discovery, the EU-funded AEROPATH project aims to identify novel targets in the opportunistic pathogen Pseudomonas aeruginosa by applying a multidisciplinary approach encompassing target validation, structural characterization, assay development and hit identification from small-molecule libraries. Here, the strategies used for target selection are described and progress in protein production and structure analysis is reported. Of the 102 selected targets, 84 could be produced in soluble form and the de novo structures of 39 proteins have been determined. The crystal structures of eight of these targets, ranging from hypothetical unknown proteins to metabolic enzymes from different functional classes (PA1645, PA1648, PA2169, PA3770, PA4098, PA4485, PA4992 and PA5259), are reported here. The structural information is expected to provide a firm basis for the improvement of hit compounds identified from fragment-based and high-throughput screening campaigns.</description>
      <pubDate>Tue, 01 Jan 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3352</guid>
      <dc:date>2013-01-01T00:00:00Z</dc:date>
      <dc:creator>Moynie, Lucile</dc:creator>
      <dc:creator>Schnell, Robert</dc:creator>
      <dc:creator>McMahon, Stephen A.</dc:creator>
      <dc:creator>Sandalova, Tatyana</dc:creator>
      <dc:creator>Abdelli Boulkeroua, Wassila</dc:creator>
      <dc:creator>Schmidberger, Jason W.</dc:creator>
      <dc:creator>Alphey, Magnus</dc:creator>
      <dc:creator>Cukier, Cyprian</dc:creator>
      <dc:creator>Duthie, Fraser</dc:creator>
      <dc:creator>Kopec, Jolanta</dc:creator>
      <dc:creator>Liu, Huanting</dc:creator>
      <dc:creator>Jacewicz, Agata</dc:creator>
      <dc:creator>Hunter, William N.</dc:creator>
      <dc:creator>Naismith, James H.</dc:creator>
      <dc:creator>Schneider, Gunter</dc:creator>
      <dc:description>Bacterial infections are increasingly difficult to treat owing to the spread of antibiotic resistance. A major concern is Gram-negative bacteria, for which the discovery of new antimicrobial drugs has been particularly scarce. In an effort to accelerate early steps in drug discovery, the EU-funded AEROPATH project aims to identify novel targets in the opportunistic pathogen Pseudomonas aeruginosa by applying a multidisciplinary approach encompassing target validation, structural characterization, assay development and hit identification from small-molecule libraries. Here, the strategies used for target selection are described and progress in protein production and structure analysis is reported. Of the 102 selected targets, 84 could be produced in soluble form and the de novo structures of 39 proteins have been determined. The crystal structures of eight of these targets, ranging from hypothetical unknown proteins to metabolic enzymes from different functional classes (PA1645, PA1648, PA2169, PA3770, PA4098, PA4485, PA4992 and PA5259), are reported here. The structural information is expected to provide a firm basis for the improvement of hit compounds identified from fragment-based and high-throughput screening campaigns.</dc:description>
    </item>
    <item>
      <title>Estimating demographic parameters for capture-recapture data in the presence of multiple mark types</title>
      <link>http://hdl.handle.net/10023/3344</link>
      <description>Abstract: In mark-recapture studies, various techniques can be used to uniquely identify individual animals, such as ringing, tagging or photo-identification using natural markings. In some long-term studies more than one type of marking procedure may be implemented during the study period. In these circumstances, ignoring the different mark types can produce biased survival estimates since the assumption that the different mark types are equally catchable (homogeneous capture probability across mark types) may be incorrect.We implement an integrated approach where we simultaneously analyse data obtained using three different marking techniques, assuming that animals can be cross-classified across the different mark types. We discriminate between competing models using the AIC statistic. This technique also allows us to estimate both relative mark-loss probabilities and relative recapture efficiency rates for the different marking methods.We initially perform a simulation study to explore the different biases that can be introduced if we assume a homogeneous recapture probability over mark type, before applying the method to a real dataset. We make use of data obtained from an intensive long-term observational study of UK female grey seals (Halichoerus grypus) at a single breeding colony, where three different methods are used to identify individuals within a single study: branding, tagging and photo-identification based on seal coat pattern or pelage.</description>
      <pubDate>Wed, 01 Jun 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3344</guid>
      <dc:date>2011-06-01T00:00:00Z</dc:date>
      <dc:creator>Smout, Sophie Caroline</dc:creator>
      <dc:creator>King, Ruth</dc:creator>
      <dc:creator>Pomeroy, Patrick</dc:creator>
      <dc:description>In mark-recapture studies, various techniques can be used to uniquely identify individual animals, such as ringing, tagging or photo-identification using natural markings. In some long-term studies more than one type of marking procedure may be implemented during the study period. In these circumstances, ignoring the different mark types can produce biased survival estimates since the assumption that the different mark types are equally catchable (homogeneous capture probability across mark types) may be incorrect.We implement an integrated approach where we simultaneously analyse data obtained using three different marking techniques, assuming that animals can be cross-classified across the different mark types. We discriminate between competing models using the AIC statistic. This technique also allows us to estimate both relative mark-loss probabilities and relative recapture efficiency rates for the different marking methods.We initially perform a simulation study to explore the different biases that can be introduced if we assume a homogeneous recapture probability over mark type, before applying the method to a real dataset. We make use of data obtained from an intensive long-term observational study of UK female grey seals (Halichoerus grypus) at a single breeding colony, where three different methods are used to identify individuals within a single study: branding, tagging and photo-identification based on seal coat pattern or pelage.</dc:description>
    </item>
    <item>
      <title>Evolution of ancient functions in the vertebrate insulin-like growth factor system uncovered by study of duplicated salmonid fish genomes</title>
      <link>http://hdl.handle.net/10023/3343</link>
      <description>Abstract: Whole genome duplication (WGD) was experienced twice by the vertebrate ancestor (2 rounds; 2R), again by the teleost fish ancestor (3R) and most recently in certain teleost lineages (4R). Consequently, vertebrate gene families are often expanded in 3R and 4R genomes. Arguably, many types of ‘functional divergence’ present across 2R gene families will exceed that between 3R/4R paralogues of genes comprising 2R families. Accordingly, 4R offers a form of replication of 2R. Examining if this concept has implications for molecular evolutionary research, we studied insulin-like growth factor (IGF) binding proteins (IGFBPs), whose six 2R family members carry IGF hormones and regulate interactions between IGFs and IGF1-receptors (IGF1Rs). Using phylogenomic approaches, we resolved the complete IGFBP repertoire of 4R-derived salmonid fishes (nineteen genes; thirteen more than human) and established evolutionary relationships/nomenclature with respect to WGDs. Traits central to IGFBP action were determined for all genes, including atomic interactions in IGFBP-IGF1/IGF2 complexes regulating IGF-IGF1R binding. Using statistical methods, we demonstrate that attributes of these protein interfaces are overwhelming a product of 2R IGFBP family membership, explain 49-68% of variation in IGFBP mRNA concentration in several different tissues and strongly predict the strength and direction of IGFBP transcriptional regulation under differing nutritional-states. The results support a model where vertebrate IGFBP family members evolved divergent structural attributes to provide distinct competition for IGFs with IGF1Rs, pre-disposing different functions in the regulation of IGF-signaling. Evolution of gene expression acted to ensure the appropriate physiological production of IGFBPs according to their structural specializations, leading to optimal IGF-signaling according to nutritional-status and the endocrine/local mode of action. This study demonstrates that relatively recent gene family expansion can facilitate inference of functional evolution within ancient genetic systems.
Description: This work was supported by the Marine Alliance for Science and Technology for Scotland pooling initiative, funded by the Scottish Funding Council (grant number HR09011) and contributing institutions.</description>
      <pubDate>Tue, 01 Jan 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3343</guid>
      <dc:date>2013-01-01T00:00:00Z</dc:date>
      <dc:creator>MacQueen, Daniel John</dc:creator>
      <dc:creator>Garcia de la Serrana Castillo, Daniel</dc:creator>
      <dc:creator>Johnston, Ian Alistair</dc:creator>
      <dc:description>Whole genome duplication (WGD) was experienced twice by the vertebrate ancestor (2 rounds; 2R), again by the teleost fish ancestor (3R) and most recently in certain teleost lineages (4R). Consequently, vertebrate gene families are often expanded in 3R and 4R genomes. Arguably, many types of ‘functional divergence’ present across 2R gene families will exceed that between 3R/4R paralogues of genes comprising 2R families. Accordingly, 4R offers a form of replication of 2R. Examining if this concept has implications for molecular evolutionary research, we studied insulin-like growth factor (IGF) binding proteins (IGFBPs), whose six 2R family members carry IGF hormones and regulate interactions between IGFs and IGF1-receptors (IGF1Rs). Using phylogenomic approaches, we resolved the complete IGFBP repertoire of 4R-derived salmonid fishes (nineteen genes; thirteen more than human) and established evolutionary relationships/nomenclature with respect to WGDs. Traits central to IGFBP action were determined for all genes, including atomic interactions in IGFBP-IGF1/IGF2 complexes regulating IGF-IGF1R binding. Using statistical methods, we demonstrate that attributes of these protein interfaces are overwhelming a product of 2R IGFBP family membership, explain 49-68% of variation in IGFBP mRNA concentration in several different tissues and strongly predict the strength and direction of IGFBP transcriptional regulation under differing nutritional-states. The results support a model where vertebrate IGFBP family members evolved divergent structural attributes to provide distinct competition for IGFs with IGF1Rs, pre-disposing different functions in the regulation of IGF-signaling. Evolution of gene expression acted to ensure the appropriate physiological production of IGFBPs according to their structural specializations, leading to optimal IGF-signaling according to nutritional-status and the endocrine/local mode of action. This study demonstrates that relatively recent gene family expansion can facilitate inference of functional evolution within ancient genetic systems.</dc:description>
    </item>
    <item>
      <title>Development temperature has persistent effects on muscle growth responses in gilthead sea bream</title>
      <link>http://hdl.handle.net/10023/3334</link>
      <description>Abstract: Initially we characterised growth responses to altered nutritional input at the transcriptional and tissue levels in the fast skeletal muscle of juvenile gilthead sea bream. Fish reared at 21–22°C (range) were fed a commercial diet at 3% body mass d−1 (non-satiation feeding, NSF) for 4 weeks, fasted for 4d (F) and then fed to satiation (SF) for 21d. 13 out of 34 genes investigated showed consistent patterns of regulation between nutritional states. Fasting was associated with a 20-fold increase in MAFbx, and a 5-fold increase in Six1 and WASp expression, which returned to NSF levels within 16h of SF. Refeeding to satiation was associated with a rapid (&lt;24 h) 12 to 17-fold increase in UNC45, Hsp70 and Hsp90α transcripts coding for molecular chaperones associated with unfolded protein response pathways. The growth factors FGF6 and IGF1 increased 6.0 and 4.5-fold within 16 h and 24 h of refeeding respectively. The average growth in diameter of fast muscle fibres was checked with fasting and significant fibre hypertrophy was only observed after 13d and 21d SF. To investigate developmental plasticity in growth responses we used the same experimental protocol with fish reared at either 17.5–18.5°C (range) (LT) or 21–22°C (range) (HT) to metamorphosis and then transferred to 21–22°C. There were persistent effects of development temperature on muscle growth patterns with 20% more fibres of lower average diameter in LT than HT group of similar body size. Altering the nutritional input to the muscle to stimulate growth revealed cryptic changes in the expression of UNC45 and Hsp90α with higher transcript abundance in the LT than HT groups, whereas there were no differences in the expression of MAFbx and Six1. It was concluded that myogenesis and gene expression patterns during growth are not fixed, but can be modified by temperature during the early stages of the life cycle.</description>
      <pubDate>Mon, 17 Dec 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3334</guid>
      <dc:date>2012-12-17T00:00:00Z</dc:date>
      <dc:creator>Garcia de la Serrana Castillo, Daniel</dc:creator>
      <dc:creator>Vieira-Johnston, Vera Lucia Almeida</dc:creator>
      <dc:creator>Andree, Karl B</dc:creator>
      <dc:creator>Darias, Maria</dc:creator>
      <dc:creator>Estévez, Alicia</dc:creator>
      <dc:creator>Gisbert, Enric</dc:creator>
      <dc:creator>Johnston, Ian Alistair</dc:creator>
      <dc:description>Initially we characterised growth responses to altered nutritional input at the transcriptional and tissue levels in the fast skeletal muscle of juvenile gilthead sea bream. Fish reared at 21–22°C (range) were fed a commercial diet at 3% body mass d−1 (non-satiation feeding, NSF) for 4 weeks, fasted for 4d (F) and then fed to satiation (SF) for 21d. 13 out of 34 genes investigated showed consistent patterns of regulation between nutritional states. Fasting was associated with a 20-fold increase in MAFbx, and a 5-fold increase in Six1 and WASp expression, which returned to NSF levels within 16h of SF. Refeeding to satiation was associated with a rapid (&lt;24 h) 12 to 17-fold increase in UNC45, Hsp70 and Hsp90α transcripts coding for molecular chaperones associated with unfolded protein response pathways. The growth factors FGF6 and IGF1 increased 6.0 and 4.5-fold within 16 h and 24 h of refeeding respectively. The average growth in diameter of fast muscle fibres was checked with fasting and significant fibre hypertrophy was only observed after 13d and 21d SF. To investigate developmental plasticity in growth responses we used the same experimental protocol with fish reared at either 17.5–18.5°C (range) (LT) or 21–22°C (range) (HT) to metamorphosis and then transferred to 21–22°C. There were persistent effects of development temperature on muscle growth patterns with 20% more fibres of lower average diameter in LT than HT group of similar body size. Altering the nutritional input to the muscle to stimulate growth revealed cryptic changes in the expression of UNC45 and Hsp90α with higher transcript abundance in the LT than HT groups, whereas there were no differences in the expression of MAFbx and Six1. It was concluded that myogenesis and gene expression patterns during growth are not fixed, but can be modified by temperature during the early stages of the life cycle.</dc:description>
    </item>
    <item>
      <title>Unusual features of pomoviral RNA movement</title>
      <link>http://hdl.handle.net/10023/3329</link>
      <description>Abstract: Potato mop-top pomovirus (PMTV) is one of a few viruses that can move systemically in plants in the absence of the capsid protein (CP). Pomoviruses encode the triple gene block genetic module of movement proteins (TGB 1, 2, and 3) and recent research suggests that PMTV RNA is transported either as ribonucleoprotein (RNP) complexes containing TGB1 or encapsidated in virions containing TGB1. Furthermore, there are different requirements for local or systemic (long-distance) movement. Research suggests that nucleolar passage of TGB1 may be important for the long-distance movement of both RNP and virions. Moreover, and uniquely, the long-distance movement of the CP-encoding RNA requires expression of both major and minor CP subunits and is inhibited when only the major CP sub unit is expressed. This paper reviews pomovirus research and presents a current model for RNA movement.</description>
      <pubDate>Thu, 22 Dec 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3329</guid>
      <dc:date>2011-12-22T00:00:00Z</dc:date>
      <dc:creator>Torrance, Lesley</dc:creator>
      <dc:creator>Wright, Kathryn M</dc:creator>
      <dc:creator>Crutzen, Francois</dc:creator>
      <dc:creator>Cowan, Graham H</dc:creator>
      <dc:creator>Lukhovitskaya, Nina I</dc:creator>
      <dc:creator>Bragard, Claude</dc:creator>
      <dc:creator>Savenkov, Eugene I</dc:creator>
      <dc:description>Potato mop-top pomovirus (PMTV) is one of a few viruses that can move systemically in plants in the absence of the capsid protein (CP). Pomoviruses encode the triple gene block genetic module of movement proteins (TGB 1, 2, and 3) and recent research suggests that PMTV RNA is transported either as ribonucleoprotein (RNP) complexes containing TGB1 or encapsidated in virions containing TGB1. Furthermore, there are different requirements for local or systemic (long-distance) movement. Research suggests that nucleolar passage of TGB1 may be important for the long-distance movement of both RNP and virions. Moreover, and uniquely, the long-distance movement of the CP-encoding RNA requires expression of both major and minor CP subunits and is inhibited when only the major CP sub unit is expressed. This paper reviews pomovirus research and presents a current model for RNA movement.</dc:description>
    </item>
    <item>
      <title>Phasing of muscle gene expression with fasting-induced recovery growth in Atlantic salmon</title>
      <link>http://hdl.handle.net/10023/3328</link>
      <description>Abstract: Background: Many fish species experience long periods of fasting in nature often associated with seasonal reductions in water temperature and prey availability or spawning migrations. During periods of nutrient restriction, changes in metabolism occur to provide cellular energy via catabolic processes. Muscle is particularly affected by prolonged fasting as myofibrillar proteins act as a major energy source. To investigate the mechanisms of metabolic reorganisation with fasting and refeeding in a saltwater stage of Atlantic salmon (Salmo salar L.) we analysed the expression of genes involved in myogenesis, growth signalling, lipid biosynthesis and myofibrillar protein degradation and synthesis pathways using qPCR. Results: Hierarchical clustering of gene expression data revealed three clusters. The first cluster comprised genes involved in lipid metabolism and triacylglycerol synthesis (ALDOB, DGAT1 and LPL) which had peak expression 3-14d after refeeding. The second cluster comprised ADIPOQ, MLC2, IGF-I and TALDO1, with peak expression 14-32d after refeeding. Cluster III contained genes strongly down regulated as an initial response to feeding and included the ubiquitin ligases MuRF1 and MAFbx, myogenic regulatory factors and some metabolic genes. Conclusion: Early responses to refeeding in fasted salmon included the synthesis of triacylglycerols and activation of the adipogenic differentiation program. Inhibition of MuRF1 and MAFbx respectively may result in decreased degradation and concomitant increased production of myofibrillar proteins. Both of these processes preceded any increase in expression of myogenic regulatory factors and IGF-I. These responses could be a necessary strategy for an animal adapted to long periods of food deprivation whereby energy reserves are replenished prior to the resumption of myogenesis.</description>
      <pubDate>Mon, 24 Aug 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3328</guid>
      <dc:date>2009-08-24T00:00:00Z</dc:date>
      <dc:creator>Bower, Neil I.</dc:creator>
      <dc:creator>Taylor, Richard G.</dc:creator>
      <dc:creator>Johnston, Ian A.</dc:creator>
      <dc:description>Background: Many fish species experience long periods of fasting in nature often associated with seasonal reductions in water temperature and prey availability or spawning migrations. During periods of nutrient restriction, changes in metabolism occur to provide cellular energy via catabolic processes. Muscle is particularly affected by prolonged fasting as myofibrillar proteins act as a major energy source. To investigate the mechanisms of metabolic reorganisation with fasting and refeeding in a saltwater stage of Atlantic salmon (Salmo salar L.) we analysed the expression of genes involved in myogenesis, growth signalling, lipid biosynthesis and myofibrillar protein degradation and synthesis pathways using qPCR. Results: Hierarchical clustering of gene expression data revealed three clusters. The first cluster comprised genes involved in lipid metabolism and triacylglycerol synthesis (ALDOB, DGAT1 and LPL) which had peak expression 3-14d after refeeding. The second cluster comprised ADIPOQ, MLC2, IGF-I and TALDO1, with peak expression 14-32d after refeeding. Cluster III contained genes strongly down regulated as an initial response to feeding and included the ubiquitin ligases MuRF1 and MAFbx, myogenic regulatory factors and some metabolic genes. Conclusion: Early responses to refeeding in fasted salmon included the synthesis of triacylglycerols and activation of the adipogenic differentiation program. Inhibition of MuRF1 and MAFbx respectively may result in decreased degradation and concomitant increased production of myofibrillar proteins. Both of these processes preceded any increase in expression of myogenic regulatory factors and IGF-I. These responses could be a necessary strategy for an animal adapted to long periods of food deprivation whereby energy reserves are replenished prior to the resumption of myogenesis.</dc:description>
    </item>
    <item>
      <title>Mechanisms of gene duplication and translocation and progress towards understanding their relative contributions to animal genome evolution</title>
      <link>http://hdl.handle.net/10023/3316</link>
      <description>Abstract: Duplication of genetic material is clearly a major route to genetic change, with consequences for both evolution and disease. A variety of forms and mechanisms of duplication are recognised, operating across the scales of a few base pairs upto entire genomes. With the ever-increasing amounts of gene and genome sequence data that are becoming available, our understanding of the extent of duplication is greatly improving, both in terms of the scales of duplication events as well as their rates of occurrence. An accurate understanding of these processes is vital if we are to properly understand important events in evolution as well as mechanisms operating at the level of genome organisation. Here we will focus on duplication in animal genomes and how the duplicated sequences are distributed, with the aim of maintaining a focus on principles of evolution and organisation that are most directly applicable to the shaping of our own genome.</description>
      <pubDate>Sun, 01 Jan 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3316</guid>
      <dc:date>2012-01-01T00:00:00Z</dc:date>
      <dc:creator>Mendivil Ramos, Olivia</dc:creator>
      <dc:creator>Ferrier, David Ellard Keith</dc:creator>
      <dc:description>Duplication of genetic material is clearly a major route to genetic change, with consequences for both evolution and disease. A variety of forms and mechanisms of duplication are recognised, operating across the scales of a few base pairs upto entire genomes. With the ever-increasing amounts of gene and genome sequence data that are becoming available, our understanding of the extent of duplication is greatly improving, both in terms of the scales of duplication events as well as their rates of occurrence. An accurate understanding of these processes is vital if we are to properly understand important events in evolution as well as mechanisms operating at the level of genome organisation. Here we will focus on duplication in animal genomes and how the duplicated sequences are distributed, with the aim of maintaining a focus on principles of evolution and organisation that are most directly applicable to the shaping of our own genome.</dc:description>
    </item>
    <item>
      <title>How many seals were there? The global shelf loss during the Last Glacial Maximum and its effect on the size and distribution of grey seal populations</title>
      <link>http://hdl.handle.net/10023/3315</link>
      <description>Abstract: Predicting how marine mammal populations act to habitat changes will be essential for developing conservation management strategies by marine mammal ecologists in the 21st century. Responses to previous environmental change may be informative in the development of predictive models. Here we describe the likely effects of the last ice age on grey seal population size and distribution. We use satellite telemetry data to define grey seal foraging habitat in terms of the temperature and depth ranges exploited by the contemporary populations. We estimate the available extent of such habitat in the North Atlantic at present and at the last glacial maximum (LGM); taking account of glacial and seasonal sea-ice coverage, estimated reductions of sea-level (123m) and seawater temperature hind-casts from GLAMAP-2000. Most of the extensive continental shelf waters (North Sea, Baltic Sea and Scotian Shelf), currently supporting &gt;95% of grey seals, were unavailable at the LGM. A combination of lower sea-level and extensive ice-sheets, massively increased seasonal sea-ice coverage and southerly extent of cold water would have pushed grey seals into areas with no significant shelf waters. The habitat during the LGM might have been as small as 4%, when compared to today’s extent and grey seal populations may have fallen to similarly. An alternative scenario involving a major change to a pelagic/bathy-pelagic foraging niche cannot be discounted. However, hooded seals that appear to out-compete and effectively exclude grey seals from such habitat currently dominate that niche. If as seems likely, the grey seal population fell to very low levels it would have remained low for several thousand years before expanding into current habitats over the last 12000 years or so.</description>
      <pubDate>Wed, 26 Dec 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3315</guid>
      <dc:date>2012-12-26T00:00:00Z</dc:date>
      <dc:creator>Boehme, Lars</dc:creator>
      <dc:creator>Thompson, David</dc:creator>
      <dc:creator>Fedak, Mike</dc:creator>
      <dc:creator>Bowen, Don</dc:creator>
      <dc:creator>Hammill, Mike</dc:creator>
      <dc:creator>Stenson, Gary</dc:creator>
      <dc:description>Predicting how marine mammal populations act to habitat changes will be essential for developing conservation management strategies by marine mammal ecologists in the 21st century. Responses to previous environmental change may be informative in the development of predictive models. Here we describe the likely effects of the last ice age on grey seal population size and distribution. We use satellite telemetry data to define grey seal foraging habitat in terms of the temperature and depth ranges exploited by the contemporary populations. We estimate the available extent of such habitat in the North Atlantic at present and at the last glacial maximum (LGM); taking account of glacial and seasonal sea-ice coverage, estimated reductions of sea-level (123m) and seawater temperature hind-casts from GLAMAP-2000. Most of the extensive continental shelf waters (North Sea, Baltic Sea and Scotian Shelf), currently supporting &gt;95% of grey seals, were unavailable at the LGM. A combination of lower sea-level and extensive ice-sheets, massively increased seasonal sea-ice coverage and southerly extent of cold water would have pushed grey seals into areas with no significant shelf waters. The habitat during the LGM might have been as small as 4%, when compared to today’s extent and grey seal populations may have fallen to similarly. An alternative scenario involving a major change to a pelagic/bathy-pelagic foraging niche cannot be discounted. However, hooded seals that appear to out-compete and effectively exclude grey seals from such habitat currently dominate that niche. If as seems likely, the grey seal population fell to very low levels it would have remained low for several thousand years before expanding into current habitats over the last 12000 years or so.</dc:description>
    </item>
    <item>
      <title>Variation in female grey seal (Halichoerus grypus) reproductive performance correlates to proactive-reactive behavioural types</title>
      <link>http://hdl.handle.net/10023/3314</link>
      <description>Abstract: Consistent individual differences (CIDs) in behaviour, indicative of behavioural types or personalities, have been shown in taxa ranging from Cnidaria to Mammalia. However, despite numerous theoretical explanations there remains limited empirical evidence for selective mechanisms that maintain such variation within natural populations. We examined behavioural types and fitness proxies in wild female grey seals at the North Rona breeding colony. Experiments in 2009 and 2010 employed a remotely-controlled vehicle to deliver a novel auditory stimulus to females to elicit changes in pup-checking behaviour. Mothers tested twice during lactation exhibited highly repeatable individual pup-checking rates within and across breeding seasons. Observations of undisturbed mothers (i.e. experiencing no disturbance from conspecifics or experimental test) also revealed CIDs in pup-checking behaviour. However, there was no correlation between an individuals’ pup-checking rate during undisturbed observations with the rate in response to the auditory test, indicating plasticity across situations. The extent to which individuals changed rates of pup-checking from undisturbed to disturbed conditions revealed a continuum of behavioural types from proactive females, who maintained a similar rate throughout, to reactive females, who increased pup-checking markedly in response to the test. Variation in maternal expenditure (daily mass loss rate) was greater among more reactive mothers than proactive mothers. Consequently pups of more reactive mothers had more varied growth rates centred around the long-term population mean. These patterns could not be accounted for by other measured covariates as behavioural type was unrelated to a mother’s prior experience, degree of inter-annual site fidelity, physical characteristics of their pupping habitat, pup sex or pup activity. These findings are consistent with the hypothesis that variation in behavioural types is maintained by spatial and temporal environmental variation combined with limits to phenotype-environment matching.</description>
      <pubDate>Fri, 16 Nov 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3314</guid>
      <dc:date>2012-11-16T00:00:00Z</dc:date>
      <dc:creator>Twiss, Sean D</dc:creator>
      <dc:creator>Cairns, Charlotte</dc:creator>
      <dc:creator>Culloch, Ross</dc:creator>
      <dc:creator>Richards, Shane A</dc:creator>
      <dc:creator>Pomeroy, Patrick</dc:creator>
      <dc:description>Consistent individual differences (CIDs) in behaviour, indicative of behavioural types or personalities, have been shown in taxa ranging from Cnidaria to Mammalia. However, despite numerous theoretical explanations there remains limited empirical evidence for selective mechanisms that maintain such variation within natural populations. We examined behavioural types and fitness proxies in wild female grey seals at the North Rona breeding colony. Experiments in 2009 and 2010 employed a remotely-controlled vehicle to deliver a novel auditory stimulus to females to elicit changes in pup-checking behaviour. Mothers tested twice during lactation exhibited highly repeatable individual pup-checking rates within and across breeding seasons. Observations of undisturbed mothers (i.e. experiencing no disturbance from conspecifics or experimental test) also revealed CIDs in pup-checking behaviour. However, there was no correlation between an individuals’ pup-checking rate during undisturbed observations with the rate in response to the auditory test, indicating plasticity across situations. The extent to which individuals changed rates of pup-checking from undisturbed to disturbed conditions revealed a continuum of behavioural types from proactive females, who maintained a similar rate throughout, to reactive females, who increased pup-checking markedly in response to the test. Variation in maternal expenditure (daily mass loss rate) was greater among more reactive mothers than proactive mothers. Consequently pups of more reactive mothers had more varied growth rates centred around the long-term population mean. These patterns could not be accounted for by other measured covariates as behavioural type was unrelated to a mother’s prior experience, degree of inter-annual site fidelity, physical characteristics of their pupping habitat, pup sex or pup activity. These findings are consistent with the hypothesis that variation in behavioural types is maintained by spatial and temporal environmental variation combined with limits to phenotype-environment matching.</dc:description>
    </item>
    <item>
      <title>What is biodiversity?</title>
      <link>http://hdl.handle.net/10023/3311</link>
      <pubDate>Wed, 15 Dec 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3311</guid>
      <dc:date>2010-12-15T00:00:00Z</dc:date>
      <dc:creator>Magurran, Anne E.</dc:creator>
    </item>
    <item>
      <title>The geometric mean of relative abundance indices : a biodiversity measure with a difference</title>
      <link>http://hdl.handle.net/10023/3310</link>
      <description>Abstract: The 2010 Biodiversity Target of the Convention on Biological Diversity (CBD), set in 2002, which stated that there should be ‘a significant reduction of the current rate of biodiversity loss' by 2010, highlighted the need for informative and tractable metrics that can be used to evaluate change in biological diversity. While the subsequent Aichi 2020 targets are more wide-ranging, they also seek to reduce the rate of biodiversity loss. The geometric mean of relative abundance indices, G, is increasingly being used to examine trends in biological diversity and to assess whether biodiversity targets are being met. Here, we explore the mathematical and statistical properties of G that make it useful for judging temporal change in biological diversity, and we discuss its advantages and limitations relative to other measures. We demonstrate that the index reflects trends in both abundance and evenness, and that it is not prone to bias when detectability of individuals varies by species. We note that it allows data from different surveys to be combined to generate a composite index. However, the index exhibits high variance and unstable behaviour when rarely-recorded species are included in the analyses. Read More: http://www.esajournals.org/doi/abs/10.1890/ES11-00186.1</description>
      <pubDate>Fri, 02 Sep 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3310</guid>
      <dc:date>2011-09-02T00:00:00Z</dc:date>
      <dc:creator>Buckland, Stephen Terrence</dc:creator>
      <dc:creator>Studeny, Angelika Caroline</dc:creator>
      <dc:creator>Magurran, Anne</dc:creator>
      <dc:creator>Illian, Janine Baerbel</dc:creator>
      <dc:creator>Newson, Stuart</dc:creator>
      <dc:description>The 2010 Biodiversity Target of the Convention on Biological Diversity (CBD), set in 2002, which stated that there should be ‘a significant reduction of the current rate of biodiversity loss' by 2010, highlighted the need for informative and tractable metrics that can be used to evaluate change in biological diversity. While the subsequent Aichi 2020 targets are more wide-ranging, they also seek to reduce the rate of biodiversity loss. The geometric mean of relative abundance indices, G, is increasingly being used to examine trends in biological diversity and to assess whether biodiversity targets are being met. Here, we explore the mathematical and statistical properties of G that make it useful for judging temporal change in biological diversity, and we discuss its advantages and limitations relative to other measures. We demonstrate that the index reflects trends in both abundance and evenness, and that it is not prone to bias when detectability of individuals varies by species. We note that it allows data from different surveys to be combined to generate a composite index. However, the index exhibits high variance and unstable behaviour when rarely-recorded species are included in the analyses. Read More: http://www.esajournals.org/doi/abs/10.1890/ES11-00186.1</dc:description>
    </item>
    <item>
      <title>Local and regional rarity in a diverse tropical fish assemblage</title>
      <link>http://hdl.handle.net/10023/3309</link>
      <description>Abstract: Because most species in an ecological assemblage are rare, much of the species richness we value is due to taxa with few individuals or a restricted distribution. It has been apparent since the time of ecological pioneers such as Bates and Darwin that tropical systems have disproportionately large numbers of rare species, yet the distribution and abundance patterns of these species remain largely unknown. Here, we examine the diversity of freshwater fish in a series of lakes in the Amazonian várzea, and relate relative abundance, both as numbers of individuals and as biomass, to the occurrence of species in space and time. We find a bimodal relationship of occurrence that distinguishes temporally and spatially persistent species from those that are infrequent in both space and time. Logistic regression reveals that information on occurrence helps distinguish those species that are rare in this locality but abundant elsewhere, from those that are rare throughout the region. These results form a link between different approaches used to evaluate commonness and rarity. In doing so, they provide a tool for identifying species of high conservation priority in poorly documented but species rich localities.</description>
      <pubDate>Tue, 01 Jan 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3309</guid>
      <dc:date>2013-01-01T00:00:00Z</dc:date>
      <dc:creator>Hercos, A</dc:creator>
      <dc:creator>Sobansky, M</dc:creator>
      <dc:creator>Queiroz, H</dc:creator>
      <dc:creator>Magurran, Anne</dc:creator>
      <dc:description>Because most species in an ecological assemblage are rare, much of the species richness we value is due to taxa with few individuals or a restricted distribution. It has been apparent since the time of ecological pioneers such as Bates and Darwin that tropical systems have disproportionately large numbers of rare species, yet the distribution and abundance patterns of these species remain largely unknown. Here, we examine the diversity of freshwater fish in a series of lakes in the Amazonian várzea, and relate relative abundance, both as numbers of individuals and as biomass, to the occurrence of species in space and time. We find a bimodal relationship of occurrence that distinguishes temporally and spatially persistent species from those that are infrequent in both space and time. Logistic regression reveals that information on occurrence helps distinguish those species that are rare in this locality but abundant elsewhere, from those that are rare throughout the region. These results form a link between different approaches used to evaluate commonness and rarity. In doing so, they provide a tool for identifying species of high conservation priority in poorly documented but species rich localities.</dc:description>
    </item>
    <item>
      <title>A model for 3-methyladenine recognition by 3-methyladenine DNA glycosylase I (TAG) from Staphylococcus aureus</title>
      <link>http://hdl.handle.net/10023/3302</link>
      <description>Abstract: The removal of chemically damaged DNA bases such as 3-methyladenine (3-MeA) is an essential process in all living organisms and is catalyzed by the enzyme 3-MeA DNA glycosylase I. A key question is how the enzyme selectively recognizes the alkylated 3-MeA over the much more abundant adenine. The crystal structures of native and Y16F-mutant 3-MeA DNA glycosylase I from Staphylococcus aureus in complex with 3-MeA are reported to 1.8 and 2.2 angstrom resolution, respectively. Isothermal titration calorimetry shows that protonation of 3-MeA decreases its binding affinity, confirming previous fluorescence studies that show that chargecharge recognition is not critical for the selection of 3-MeA over adenine. It is hypothesized that the hydrogen-bonding pattern of Glu38 and Tyr16 of 3-MeA DNA glycosylase I with a particular tautomer unique to 3-MeA contributes to recognition and selection.</description>
      <pubDate>Fri, 01 Jun 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3302</guid>
      <dc:date>2012-06-01T00:00:00Z</dc:date>
      <dc:creator>Zhu, Xiaofeng</dc:creator>
      <dc:creator>Yan, Xuan</dc:creator>
      <dc:creator>Carter, Lester G.</dc:creator>
      <dc:creator>Liu, Huanting</dc:creator>
      <dc:creator>Graham, Shirley</dc:creator>
      <dc:creator>Coote, Peter J.</dc:creator>
      <dc:creator>Naismith, James</dc:creator>
      <dc:description>The removal of chemically damaged DNA bases such as 3-methyladenine (3-MeA) is an essential process in all living organisms and is catalyzed by the enzyme 3-MeA DNA glycosylase I. A key question is how the enzyme selectively recognizes the alkylated 3-MeA over the much more abundant adenine. The crystal structures of native and Y16F-mutant 3-MeA DNA glycosylase I from Staphylococcus aureus in complex with 3-MeA are reported to 1.8 and 2.2 angstrom resolution, respectively. Isothermal titration calorimetry shows that protonation of 3-MeA decreases its binding affinity, confirming previous fluorescence studies that show that chargecharge recognition is not critical for the selection of 3-MeA over adenine. It is hypothesized that the hydrogen-bonding pattern of Glu38 and Tyr16 of 3-MeA DNA glycosylase I with a particular tautomer unique to 3-MeA contributes to recognition and selection.</dc:description>
    </item>
    <item>
      <title>Estimated tissue and blood N2 levels and risk of in vivo bubble formation in deep-, intermediate- and shallow diving toothed whales during exposure to naval sonar.</title>
      <link>http://hdl.handle.net/10023/3301</link>
      <description>Abstract: Naval sonar has been accused of causing whale stranding by a mechanism which increases formation of tissue N2 gas bubbles. Increased tissue and blood N2 levels, and thereby increased risk of decompression sickness (DCS), is thought to result from changes in behavior or physiological responses during diving. Previous theoretical studies have used hypothetical sonar-induced changes in both behavior and physiology to model blood and tissue N2 tension PN2, but this is the first attempt to estimate the changes during actual behavioral responses to sonar. We used an existing mathematical model to estimate blood and tissue N2 tension PN2 from dive data recorded from sperm, killer, long-finned pilot, Blainville’s beaked, and Cuvier’s beaked whales before and during exposure to Low- (1–2 kHz) and Mid- (2–7 kHz) frequency active sonar. Our objectives were: (1) to determine if differences in dive behavior affects risk of bubble formation, and if (2) behavioral- or (3) physiological responses to sonar are plausible risk factors. Our results suggest that all species have natural high N2 levels, with deep diving generally resulting in higher end-dive PN2 as compared with shallow diving. Sonar exposure caused some changes in dive behavior in both killer whales, pilot whales and beaked whales, but this did not lead to any increased risk of DCS. However, in three of eight exposure session with sperm whales, the animal changed to shallower diving, and in all these cases this seem to result in an increased risk of DCS, although risk was still within the normal risk range of this species. When a hypothetical removal of the normal dive response (bradycardia and peripheral vasoconstriction), was added to the behavioral response during model simulations, this led to an increased variance in the estimated end-dive N2 levels, but no consistent change of risk. In conclusion, we cannot rule out the possibility that a combination of behavioral and physiological responses to sonar have the potential to alter the blood and tissue end-dive N2 tension to levels which could cause DCS and formation of in vivo bubbles, but the actually observed behavioral responses of cetaceans to sonar in our study, do not imply any significantly increased risk of DCS.</description>
      <pubDate>Thu, 10 May 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3301</guid>
      <dc:date>2012-05-10T00:00:00Z</dc:date>
      <dc:creator>Kvadsheim, Petter H</dc:creator>
      <dc:creator>Miller, Patrick</dc:creator>
      <dc:creator>Tyack, Peter Lloyd</dc:creator>
      <dc:creator>Sivle, Lise D</dc:creator>
      <dc:creator>Lam, Frans Peter</dc:creator>
      <dc:creator>Fahlman, Andreas</dc:creator>
      <dc:description>Naval sonar has been accused of causing whale stranding by a mechanism which increases formation of tissue N2 gas bubbles. Increased tissue and blood N2 levels, and thereby increased risk of decompression sickness (DCS), is thought to result from changes in behavior or physiological responses during diving. Previous theoretical studies have used hypothetical sonar-induced changes in both behavior and physiology to model blood and tissue N2 tension PN2, but this is the first attempt to estimate the changes during actual behavioral responses to sonar. We used an existing mathematical model to estimate blood and tissue N2 tension PN2 from dive data recorded from sperm, killer, long-finned pilot, Blainville’s beaked, and Cuvier’s beaked whales before and during exposure to Low- (1–2 kHz) and Mid- (2–7 kHz) frequency active sonar. Our objectives were: (1) to determine if differences in dive behavior affects risk of bubble formation, and if (2) behavioral- or (3) physiological responses to sonar are plausible risk factors. Our results suggest that all species have natural high N2 levels, with deep diving generally resulting in higher end-dive PN2 as compared with shallow diving. Sonar exposure caused some changes in dive behavior in both killer whales, pilot whales and beaked whales, but this did not lead to any increased risk of DCS. However, in three of eight exposure session with sperm whales, the animal changed to shallower diving, and in all these cases this seem to result in an increased risk of DCS, although risk was still within the normal risk range of this species. When a hypothetical removal of the normal dive response (bradycardia and peripheral vasoconstriction), was added to the behavioral response during model simulations, this led to an increased variance in the estimated end-dive N2 levels, but no consistent change of risk. In conclusion, we cannot rule out the possibility that a combination of behavioral and physiological responses to sonar have the potential to alter the blood and tissue end-dive N2 tension to levels which could cause DCS and formation of in vivo bubbles, but the actually observed behavioral responses of cetaceans to sonar in our study, do not imply any significantly increased risk of DCS.</dc:description>
    </item>
    <item>
      <title>Conventional and unconventional antimicrobials from fish, marine invertebrates and micro-algae</title>
      <link>http://hdl.handle.net/10023/3300</link>
      <description>Abstract: All eukaryotic organisms, single-celled or multi-cellular, produce a diverse array of natural anti-infective agents that, in addition to conventional antimicrobial peptides, also include proteins and other molecules often not regarded as part of the innate defences. Examples range from histones, fatty acids, and other structural components of cells to pigments and regulatory proteins. These probably represent very ancient defence factors that have been re-used in new ways during evolution. This review discusses the nature, biological role in host protection and potential biotechnological uses of some of these compounds, focusing on those from fish, marine invertebrates and marine micro-algae.</description>
      <pubDate>Wed, 14 Apr 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3300</guid>
      <dc:date>2010-04-14T00:00:00Z</dc:date>
      <dc:creator>Smith, Valerie Jane</dc:creator>
      <dc:creator>Desbois, Andrew Paul</dc:creator>
      <dc:creator>Dyrynda, Elisabeth</dc:creator>
      <dc:description>All eukaryotic organisms, single-celled or multi-cellular, produce a diverse array of natural anti-infective agents that, in addition to conventional antimicrobial peptides, also include proteins and other molecules often not regarded as part of the innate defences. Examples range from histones, fatty acids, and other structural components of cells to pigments and regulatory proteins. These probably represent very ancient defence factors that have been re-used in new ways during evolution. This review discusses the nature, biological role in host protection and potential biotechnological uses of some of these compounds, focusing on those from fish, marine invertebrates and marine micro-algae.</dc:description>
    </item>
    <item>
      <title>Discovery and validation of SIRT2 inhibitors based on tenovin-6 : use of a H-1-NMR method to assess deacetylase activity</title>
      <link>http://hdl.handle.net/10023/3293</link>
      <description>Abstract: The search for potent and selective sirtuin inhibitors continues as chemical tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. These studies identify a sub-micromolar inhibitor that has increased selectivity for SIRT2 over SIRT1 compared to tenovin-6. In addition, a H-1-NMR-based method is developed and used to validate further this class of sirtuin inhibitors. A thermal shift analysis of SIRT2 in the presence of tenovin-6, -43, a control tenovin and the known SIRT2 inhibitor AGK2 is also presented.</description>
      <pubDate>Mon, 01 Oct 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3293</guid>
      <dc:date>2012-10-01T00:00:00Z</dc:date>
      <dc:creator>Pirrie, Lisa</dc:creator>
      <dc:creator>McCarthy, Anna R.</dc:creator>
      <dc:creator>Major, Louise L.</dc:creator>
      <dc:creator>Morkunaite, Vaida</dc:creator>
      <dc:creator>Zubriene, Asta</dc:creator>
      <dc:creator>Matulis, Daumantas</dc:creator>
      <dc:creator>Lain, Sonia</dc:creator>
      <dc:creator>Lebl, Tomas</dc:creator>
      <dc:creator>Westwood, Nicholas J.</dc:creator>
      <dc:description>The search for potent and selective sirtuin inhibitors continues as chemical tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. These studies identify a sub-micromolar inhibitor that has increased selectivity for SIRT2 over SIRT1 compared to tenovin-6. In addition, a H-1-NMR-based method is developed and used to validate further this class of sirtuin inhibitors. A thermal shift analysis of SIRT2 in the presence of tenovin-6, -43, a control tenovin and the known SIRT2 inhibitor AGK2 is also presented.</dc:description>
    </item>
    <item>
      <title>Protein-induced changes in DNA structure and dynamics observed with noncovalent site-directed spin-labeling and PELDOR</title>
      <link>http://hdl.handle.net/10023/3286</link>
      <description>Abstract: Site-directed spin labeling and pulsed electron–electron double resonance (PELDOR or DEER) have previously been applied successfully to study the structure and dynamics of nucleic acids. Spin labeling nucleic acids at specific sites requires the covalent attachment of spin labels, which involves rather complicated and laborious chemical synthesis. Here, we use a noncovalent label strategy that bypasses the covalent labeling chemistry and show that the binding specificity and efficiency are large enough to enable PELDOR or DEER measurements in DNA duplexes and a DNA duplex bound to the Lac repressor protein. In addition, the rigidity of the label not only allows resolution of the structure and dynamics of oligonucleotides but also the determination of label orientation and protein-induced conformational changes. The results prove that this labeling strategy in combination with PELDOR has a great potential for studying both structure and dynamics of oligonucleotides and their complexes with various ligands.</description>
      <pubDate>Tue, 01 Jan 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3286</guid>
      <dc:date>2013-01-01T00:00:00Z</dc:date>
      <dc:creator>Reginsson, Gunnar Widtfeldt</dc:creator>
      <dc:creator>Shelke, Sandip</dc:creator>
      <dc:creator>Rouillon, Christophe</dc:creator>
      <dc:creator>White, Malcolm F</dc:creator>
      <dc:creator>Sigurdsson, Snorri T</dc:creator>
      <dc:creator>Schiemann, Olav</dc:creator>
      <dc:description>Site-directed spin labeling and pulsed electron–electron double resonance (PELDOR or DEER) have previously been applied successfully to study the structure and dynamics of nucleic acids. Spin labeling nucleic acids at specific sites requires the covalent attachment of spin labels, which involves rather complicated and laborious chemical synthesis. Here, we use a noncovalent label strategy that bypasses the covalent labeling chemistry and show that the binding specificity and efficiency are large enough to enable PELDOR or DEER measurements in DNA duplexes and a DNA duplex bound to the Lac repressor protein. In addition, the rigidity of the label not only allows resolution of the structure and dynamics of oligonucleotides but also the determination of label orientation and protein-induced conformational changes. The results prove that this labeling strategy in combination with PELDOR has a great potential for studying both structure and dynamics of oligonucleotides and their complexes with various ligands.</dc:description>
    </item>
    <item>
      <title>Quantifying temporal change in biodiversity : challenges and opportunities</title>
      <link>http://hdl.handle.net/10023/3284</link>
      <description>Abstract: Growing concern about biodiversity loss underscores the need to quantify and understand temporal change. Here, we review the opportunities presented by biodiversity time series, and address three related issues: (i) recognizing the characteristics of temporal data; (ii) selecting appropriate statistical procedures for analysing temporal data; and (iii) inferring and forecasting biodiversity change. With regard to the first issue, we draw attention to defining characteristics of biodiversity time series—lack of physical boundaries, uni-dimensionality, autocorrelation and directionality—that inform the choice of analytic methods. Second, we explore methods of quantifying change in biodiversity at different timescales, noting that autocorrelation can be viewed as a feature that sheds light on the underlying structure of temporal change. Finally, we address the transition from inferring to forecasting biodiversity change, highlighting potential pitfalls associated with phase-shifts and novel conditions.</description>
      <pubDate>Tue, 01 Jan 2013 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3284</guid>
      <dc:date>2013-01-01T00:00:00Z</dc:date>
      <dc:creator>Dornelas, Maria</dc:creator>
      <dc:creator>Magurran, Anne</dc:creator>
      <dc:creator>Buckland, Stephen Terrence</dc:creator>
      <dc:creator>Chao, Anne</dc:creator>
      <dc:creator>Chazdon, Robin L</dc:creator>
      <dc:creator>Colwell, Robert K</dc:creator>
      <dc:creator>Curtis, Tom</dc:creator>
      <dc:creator>Gaston, Kevin J</dc:creator>
      <dc:creator>Gotelli, Nicolas J</dc:creator>
      <dc:creator>Kosnik, Matthew A</dc:creator>
      <dc:creator>McGill, Brian</dc:creator>
      <dc:creator>McCune, Jenny L</dc:creator>
      <dc:creator>Morlon, Hélène</dc:creator>
      <dc:creator>Mumby, Peter J</dc:creator>
      <dc:creator>Øvreås, Lise</dc:creator>
      <dc:creator>Studeny, Angelika</dc:creator>
      <dc:creator>Vellend, Mark</dc:creator>
      <dc:description>Growing concern about biodiversity loss underscores the need to quantify and understand temporal change. Here, we review the opportunities presented by biodiversity time series, and address three related issues: (i) recognizing the characteristics of temporal data; (ii) selecting appropriate statistical procedures for analysing temporal data; and (iii) inferring and forecasting biodiversity change. With regard to the first issue, we draw attention to defining characteristics of biodiversity time series—lack of physical boundaries, uni-dimensionality, autocorrelation and directionality—that inform the choice of analytic methods. Second, we explore methods of quantifying change in biodiversity at different timescales, noting that autocorrelation can be viewed as a feature that sheds light on the underlying structure of temporal change. Finally, we address the transition from inferring to forecasting biodiversity change, highlighting potential pitfalls associated with phase-shifts and novel conditions.</dc:description>
    </item>
    <item>
      <title>Reasons for the invasive success of a guppy (Poecilia reticulata) population in Trinidad</title>
      <link>http://hdl.handle.net/10023/3283</link>
      <description>Abstract: The introduction of non-native species into new habitats poses a major threat to native populations. Of particular interest, though often overlooked, are introductions of populations that are not fully reproductively isolated from native individuals and can hybridize with them. To address this important topic we used different approaches in a multi-pronged study, combining the effects of mate choice, shoaling behaviour and genetics. Here we present evidence that behavioural traits such as shoaling and mate choice can promote population mixing if individuals do not distinguish between native and foreign conspecifics. We examined this in the context of two guppy (Poecilia reticulata) populations that have been subject to an introduction and subsequent population mixing event in Trinidad. The introduction of Guanapo River guppies into the Turure River more than 50 years ago led to a marked reduction of the original genotype. In our experiments, female guppies did not distinguish between shoaling partners when given the choice between native and foreign individuals. Introduced fish are therefore likely to benefit from the protection of a shoal and will improve their survival chances as a result. The additional finding that male guppies do not discriminate between females on the basis of origin will further increase the process of population mixing, especially if males encounter mixed shoals. In a mesocosm experiment, in which the native and foreign populations were allowed to mate freely, we found, as expected on the basis of these behavioural interactions, that the distribution of offspring genotypes could be predicted from the proportions of the two types of founding fish. This result suggests that stochastic and environmental processes have reinforced the biological ones to bring about the genetic dominance of the invading population in the Turure River. Re-sampling the Turure for genetic analysis using SNP markers confirmed the population mixing process and showed that it is an on-going process in this river and has led to the nearly complete disappearance of the original genotype.</description>
      <pubDate>Thu, 31 May 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3283</guid>
      <dc:date>2012-05-31T00:00:00Z</dc:date>
      <dc:creator>Sievers, Caya</dc:creator>
      <dc:creator>Willing, Eva-Maria</dc:creator>
      <dc:creator>Hoffmann, Margarete</dc:creator>
      <dc:creator>Dreyer, Christine</dc:creator>
      <dc:creator>Ramnarine, Indar</dc:creator>
      <dc:creator>Magurran, Anne</dc:creator>
      <dc:description>The introduction of non-native species into new habitats poses a major threat to native populations. Of particular interest, though often overlooked, are introductions of populations that are not fully reproductively isolated from native individuals and can hybridize with them. To address this important topic we used different approaches in a multi-pronged study, combining the effects of mate choice, shoaling behaviour and genetics. Here we present evidence that behavioural traits such as shoaling and mate choice can promote population mixing if individuals do not distinguish between native and foreign conspecifics. We examined this in the context of two guppy (Poecilia reticulata) populations that have been subject to an introduction and subsequent population mixing event in Trinidad. The introduction of Guanapo River guppies into the Turure River more than 50 years ago led to a marked reduction of the original genotype. In our experiments, female guppies did not distinguish between shoaling partners when given the choice between native and foreign individuals. Introduced fish are therefore likely to benefit from the protection of a shoal and will improve their survival chances as a result. The additional finding that male guppies do not discriminate between females on the basis of origin will further increase the process of population mixing, especially if males encounter mixed shoals. In a mesocosm experiment, in which the native and foreign populations were allowed to mate freely, we found, as expected on the basis of these behavioural interactions, that the distribution of offspring genotypes could be predicted from the proportions of the two types of founding fish. This result suggests that stochastic and environmental processes have reinforced the biological ones to bring about the genetic dominance of the invading population in the Turure River. Re-sampling the Turure for genetic analysis using SNP markers confirmed the population mixing process and showed that it is an on-going process in this river and has led to the nearly complete disappearance of the original genotype.</dc:description>
    </item>
    <item>
      <title>Role of Bunyamwera orthobunyavirus NSs protein in infection of mosquito cells</title>
      <link>http://hdl.handle.net/10023/3280</link>
      <description>Abstract: Background: Bunyamwera orthobunyavirus is both the prototype and study model of the Bunyaviridae family. The viral NSs protein seems to contribute to the different outcomes of infection in mammalian and mosquito cell lines. However, only limited information is available on the growth of Bunyamwera virus in cultured mosquito cells other than the Aedes albopictus C6/36 line. Methodology and Principal Findings: To determine potential functions of the NSs protein in mosquito cells, replication of wild-type virus and a recombinant NSs deletion mutant was compared in Ae. albopictus C6/36, C7-10 and U4.4 cells, and in Ae. aegypti Ae cells by monitoring N protein production and virus yields at various times post infection. Both viruses established persistent infections, with the exception of NSs deletion mutant in U4.4 cells. The NSs protein was nonessential for growth in C6/36 and C7-10 cells, but was important for productive replication in U4.4 and Ae cells. Fluorescence microscopy studies using recombinant viruses expressing green fluorescent protein allowed observation of three stages of infection, early, acute and late, during which infected cells underwent morphological changes. In the absence of NSs, these changes were less pronounced. An RNAi response efficiently reduced virus replication in U4.4 cells transfected with virus specific dsRNA, but not in C6/36 or C7/10 cells. Lastly, Ae. aegypti mosquitoes were exposed to blood-meal containing either wild-type or NSs deletion virus, and at various times post-feeding, infection and disseminated infection rates were measured. Compared to wild-type virus, infection rates by the mutant virus were lower and more variable. If the NSs deletion virus was able to establish infection, it was detected in salivary glands at 6 days post-infection, 3 days later than wild-type virus. Conclusions/Significance: Bunyamwera virus NSs is required for efficient replication in certain mosquito cell lines and in Ae. aegypti mosquitoes.</description>
      <pubDate>Sat, 01 Sep 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3280</guid>
      <dc:date>2012-09-01T00:00:00Z</dc:date>
      <dc:creator>Szemiel, Agnieszka M.</dc:creator>
      <dc:creator>Failloux, Anna-Bella</dc:creator>
      <dc:creator>Elliott, Richard M.</dc:creator>
      <dc:description>Background: Bunyamwera orthobunyavirus is both the prototype and study model of the Bunyaviridae family. The viral NSs protein seems to contribute to the different outcomes of infection in mammalian and mosquito cell lines. However, only limited information is available on the growth of Bunyamwera virus in cultured mosquito cells other than the Aedes albopictus C6/36 line. Methodology and Principal Findings: To determine potential functions of the NSs protein in mosquito cells, replication of wild-type virus and a recombinant NSs deletion mutant was compared in Ae. albopictus C6/36, C7-10 and U4.4 cells, and in Ae. aegypti Ae cells by monitoring N protein production and virus yields at various times post infection. Both viruses established persistent infections, with the exception of NSs deletion mutant in U4.4 cells. The NSs protein was nonessential for growth in C6/36 and C7-10 cells, but was important for productive replication in U4.4 and Ae cells. Fluorescence microscopy studies using recombinant viruses expressing green fluorescent protein allowed observation of three stages of infection, early, acute and late, during which infected cells underwent morphological changes. In the absence of NSs, these changes were less pronounced. An RNAi response efficiently reduced virus replication in U4.4 cells transfected with virus specific dsRNA, but not in C6/36 or C7/10 cells. Lastly, Ae. aegypti mosquitoes were exposed to blood-meal containing either wild-type or NSs deletion virus, and at various times post-feeding, infection and disseminated infection rates were measured. Compared to wild-type virus, infection rates by the mutant virus were lower and more variable. If the NSs deletion virus was able to establish infection, it was detected in salivary glands at 6 days post-infection, 3 days later than wild-type virus. Conclusions/Significance: Bunyamwera virus NSs is required for efficient replication in certain mosquito cell lines and in Ae. aegypti mosquitoes.</dc:description>
    </item>
    <item>
      <title>Photoacclimation, growth and distribution of massive coral species in clear and turbid waters</title>
      <link>http://hdl.handle.net/10023/3276</link>
      <description>Abstract: ABSTRACT: Massive coral species play a key role in coral reef ecosystems, adding significantly to physical integrity, long term stability and reef biodiversity. This study coupled the assessment of the distribution and abundance of 4 dominant massive coral species, Diploastrea heliopora, Favia speciosa, F. matthaii and Porites lutea, with investigations into species-specific photoacclimatory responses within the Wakatobi Marine National Park of southeast Sulawesi, Indonesia, to determine the potential of photoacclimation to be a driver of biological success. For this, rapid light curves using pulse amplitude modulated (PAM) chlorophyll a fluorescence techniques were employed with additional manipulations to circumvent differences of light quality and absorption between species and across environmental gradients. P. lutea was examined over a range of depths and sites to determine patterns of photoacclimation, and all 4 species were assessed at a single depth between sites for which long-term data for coral community structure and growth existed. Light availability was more highly constrained with depth than between sites; consequently, photoacclimation patterns for P. lutea appeared greater with depth than across environmental gradients. All 4 species were found to differentially modify the extent of non-photochemical quenching to maintain a constant photochemical operating efficiency (qP). Therefore, our results suggest that these massive corals photoacclimate to ensure a constant light-dependent rate of reduction of the plastoquinone pool across growth environments.</description>
      <pubDate>Mon, 13 Oct 2008 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3276</guid>
      <dc:date>2008-10-13T00:00:00Z</dc:date>
      <dc:creator>Hennige, S.J.</dc:creator>
      <dc:creator>Smith, D.J.</dc:creator>
      <dc:creator>Perkins, R.</dc:creator>
      <dc:creator>Consalvey, M</dc:creator>
      <dc:creator>Paterson, David Maxwell</dc:creator>
      <dc:creator>Suggett, D.J.</dc:creator>
      <dc:description>ABSTRACT: Massive coral species play a key role in coral reef ecosystems, adding significantly to physical integrity, long term stability and reef biodiversity. This study coupled the assessment of the distribution and abundance of 4 dominant massive coral species, Diploastrea heliopora, Favia speciosa, F. matthaii and Porites lutea, with investigations into species-specific photoacclimatory responses within the Wakatobi Marine National Park of southeast Sulawesi, Indonesia, to determine the potential of photoacclimation to be a driver of biological success. For this, rapid light curves using pulse amplitude modulated (PAM) chlorophyll a fluorescence techniques were employed with additional manipulations to circumvent differences of light quality and absorption between species and across environmental gradients. P. lutea was examined over a range of depths and sites to determine patterns of photoacclimation, and all 4 species were assessed at a single depth between sites for which long-term data for coral community structure and growth existed. Light availability was more highly constrained with depth than between sites; consequently, photoacclimation patterns for P. lutea appeared greater with depth than across environmental gradients. All 4 species were found to differentially modify the extent of non-photochemical quenching to maintain a constant photochemical operating efficiency (qP). Therefore, our results suggest that these massive corals photoacclimate to ensure a constant light-dependent rate of reduction of the plastoquinone pool across growth environments.</dc:description>
    </item>
    <item>
      <title>Evolution of the multifaceted eukaryotic akirin gene family</title>
      <link>http://hdl.handle.net/10023/3275</link>
      <description>Abstract: Background: Akirins are nuclear proteins that form part of an innate immune response pathway conserved in Drosophila and mice. This studies aim was to characterise the evolution of akirin gene structure and protein function in the eukaryotes. Results: akirin genes are present throughout the metazoa and arose before the separation of animal, plant and fungi lineages. Using comprehensive phylogenetic analysis, coupled with comparisons of conserved synteny and genomic organisation, we show that the intron-exon structure of metazoan akirin genes was established prior to the bilateria and that a single proto-orthologue duplicated in the vertebrates, before the gnathostome-agnathan separation, producing akirin1 and akirin2. Phylogenetic analyses of seven vertebrate gene families with members in chromosomal proximity to both akirin1 and akirin2 were compatible with a common duplication event affecting the genomic neighbourhood of the akirin proto-orthologue. A further duplication of akirins occurred in the teleost lineage and was followed by lineage-specific patterns of paralogue loss. Remarkably, akirins have been independently characterised by five research groups under different aliases and a comparison of the available literature revealed diverse functions, generally in regulating gene expression. For example, akirin was characterised in arthropods as subolesin, an important growth factor and in Drosophila as bhringi, which has an essential myogenic role. In vertebrates, akirin1 was named mighty in mice and was shown to regulate myogenesis, whereas akirin2 was characterised as FB11 in rats and promoted carcinogenesis, acting as a transcriptional repressor when bound to a 14-3-3 protein. Both vertebrate Akirins have evolved under comparably strict constraints of purifying selection, although a likelihood ratio test predicted that functional divergence has occurred between paralogues. Bayesian and maximum likelihood tests identified amino-acid positions where the rate of evolution had shifted significantly between paralogues. Interestingly, the highest scoring position was within a conserved, validated binding-site for 14-3-3 proteins. Conclusion: This work offers an evolutionary framework to facilitate future studies of eukaryotic akirins and provides insight into their multifaceted and conserved biochemical functions.</description>
      <pubDate>Fri, 06 Feb 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3275</guid>
      <dc:date>2009-02-06T00:00:00Z</dc:date>
      <dc:creator>Macqueen, Daniel J.</dc:creator>
      <dc:creator>Johnston, Ian A.</dc:creator>
      <dc:description>Background: Akirins are nuclear proteins that form part of an innate immune response pathway conserved in Drosophila and mice. This studies aim was to characterise the evolution of akirin gene structure and protein function in the eukaryotes. Results: akirin genes are present throughout the metazoa and arose before the separation of animal, plant and fungi lineages. Using comprehensive phylogenetic analysis, coupled with comparisons of conserved synteny and genomic organisation, we show that the intron-exon structure of metazoan akirin genes was established prior to the bilateria and that a single proto-orthologue duplicated in the vertebrates, before the gnathostome-agnathan separation, producing akirin1 and akirin2. Phylogenetic analyses of seven vertebrate gene families with members in chromosomal proximity to both akirin1 and akirin2 were compatible with a common duplication event affecting the genomic neighbourhood of the akirin proto-orthologue. A further duplication of akirins occurred in the teleost lineage and was followed by lineage-specific patterns of paralogue loss. Remarkably, akirins have been independently characterised by five research groups under different aliases and a comparison of the available literature revealed diverse functions, generally in regulating gene expression. For example, akirin was characterised in arthropods as subolesin, an important growth factor and in Drosophila as bhringi, which has an essential myogenic role. In vertebrates, akirin1 was named mighty in mice and was shown to regulate myogenesis, whereas akirin2 was characterised as FB11 in rats and promoted carcinogenesis, acting as a transcriptional repressor when bound to a 14-3-3 protein. Both vertebrate Akirins have evolved under comparably strict constraints of purifying selection, although a likelihood ratio test predicted that functional divergence has occurred between paralogues. Bayesian and maximum likelihood tests identified amino-acid positions where the rate of evolution had shifted significantly between paralogues. Interestingly, the highest scoring position was within a conserved, validated binding-site for 14-3-3 proteins. Conclusion: This work offers an evolutionary framework to facilitate future studies of eukaryotic akirins and provides insight into their multifaceted and conserved biochemical functions.</dc:description>
    </item>
    <item>
      <title>Evolution of a complex locus : exon gain, loss and divergence at the Gr39a locus in Drosophila</title>
      <link>http://hdl.handle.net/10023/3274</link>
      <description>Abstract: Background. Gene families typically evolve by gene duplication followed by the adoption of new or altered gene functions. A different way to evolve new but related functions is alternative splicing of existing exons of a complex gene. The chemosensory gene families of animals are characterised by numerous loci of related function. Alternative splicing has only rarely been reported in chemosensory loci, for example in 5 out of around 120 loci in Drosophila melanogaster. The gustatory receptor gene Gr39a has four large exons that are alternatively spliced with three small conserved exons. Recently the genome sequences of eleven additional species of Drosophila have become available allowing us to examine variation in the structure of the Gr39a locus across a wide phylogenetic range of fly species. Methodology/Principal Findings. We describe a fifth exon and show that the locus has a complex evolutionary history with several duplications, pseudogenisations and losses of exons. PAML analyses suggested that the whole gene has a history of purifying selection, although this was less strong in exons which underwent duplication. Conclusions/Significance. Estimates of functional divergence between exons were similar in magnitude to functional divergence between duplicated genes, suggesting that exon divergence is broadly equivalent to gene duplication.</description>
      <pubDate>Wed, 30 Jan 2008 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3274</guid>
      <dc:date>2008-01-30T00:00:00Z</dc:date>
      <dc:creator>Gardiner, Anastasia</dc:creator>
      <dc:creator>Barker, Daniel</dc:creator>
      <dc:creator>Butlin, Roger K.</dc:creator>
      <dc:creator>Jordan, William C.</dc:creator>
      <dc:creator>Ritchie, Michael G.</dc:creator>
      <dc:description>Background. Gene families typically evolve by gene duplication followed by the adoption of new or altered gene functions. A different way to evolve new but related functions is alternative splicing of existing exons of a complex gene. The chemosensory gene families of animals are characterised by numerous loci of related function. Alternative splicing has only rarely been reported in chemosensory loci, for example in 5 out of around 120 loci in Drosophila melanogaster. The gustatory receptor gene Gr39a has four large exons that are alternatively spliced with three small conserved exons. Recently the genome sequences of eleven additional species of Drosophila have become available allowing us to examine variation in the structure of the Gr39a locus across a wide phylogenetic range of fly species. Methodology/Principal Findings. We describe a fifth exon and show that the locus has a complex evolutionary history with several duplications, pseudogenisations and losses of exons. PAML analyses suggested that the whole gene has a history of purifying selection, although this was less strong in exons which underwent duplication. Conclusions/Significance. Estimates of functional divergence between exons were similar in magnitude to functional divergence between duplicated genes, suggesting that exon divergence is broadly equivalent to gene duplication.</dc:description>
    </item>
    <item>
      <title>An update on MyoD evolution in teleosts and a proposed consensus nomenclature to accommodate the tetraploidization of different vertebrate genomes</title>
      <link>http://hdl.handle.net/10023/3273</link>
      <description>Abstract: Background: MyoD is a muscle specific transcription factor that is essential for vertebrate myogenesis. In several teleost species, including representatives of the Salmonidae and Acanthopterygii, but not zebrafish, two or more MyoD paralogues are conserved that are thought to have arisen from distinct, possibly lineage-specific duplication events. Additionally, two MyoD paralogues have been characterised in the allotetraploid frog, Xenopus laevis. This has lead to a confusing nomenclature since MyoD paralogues have been named outside of an appropriate phylogenetic framework. Methods and Principal Findings: Here we initially show that directly depicting the evolutionary relationships of teleost MyoD orthologues and paralogues is hindered by the asymmetric evolutionary rate of Acanthopterygian MyoD2 relative to other MyoD proteins. Thus our aim was to confidently position the event from which teleost paralogues arose in different lineages by a comparative investigation of genes neighbouring myod across the vertebrates. To this end, we show that genes on the single myod-containing chromosome of mammals and birds are retained in both zebrafish and Acanthopterygian teleosts in a striking pattern of double conserved synteny. Further, phylogenetic reconstruction of these neighbouring genes using Bayesian and maximum likelihood methods supported a common origin for teleost paralogues following the split of the Actinopterygii and Sarcopterygii. Conclusion: Our results strongly suggest that myod was duplicated during the basal teleost whole genome duplication event, but was subsequently lost in the Ostariophysi ( zebrafish) and Protacanthopterygii lineages. We propose a sensible consensus nomenclature for vertebrate myod genes that accommodates polyploidization events in teleost and tetrapod lineages and is justified from a phylogenetic perspective.
Description: DJM was supported by a Natural Environment Research Council studentship (NERC/S/A/2004/12435).</description>
      <pubDate>Wed, 06 Feb 2008 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3273</guid>
      <dc:date>2008-02-06T00:00:00Z</dc:date>
      <dc:creator>Macqueen, Daniel J.</dc:creator>
      <dc:creator>Johnston, Ian A.</dc:creator>
      <dc:description>Background: MyoD is a muscle specific transcription factor that is essential for vertebrate myogenesis. In several teleost species, including representatives of the Salmonidae and Acanthopterygii, but not zebrafish, two or more MyoD paralogues are conserved that are thought to have arisen from distinct, possibly lineage-specific duplication events. Additionally, two MyoD paralogues have been characterised in the allotetraploid frog, Xenopus laevis. This has lead to a confusing nomenclature since MyoD paralogues have been named outside of an appropriate phylogenetic framework. Methods and Principal Findings: Here we initially show that directly depicting the evolutionary relationships of teleost MyoD orthologues and paralogues is hindered by the asymmetric evolutionary rate of Acanthopterygian MyoD2 relative to other MyoD proteins. Thus our aim was to confidently position the event from which teleost paralogues arose in different lineages by a comparative investigation of genes neighbouring myod across the vertebrates. To this end, we show that genes on the single myod-containing chromosome of mammals and birds are retained in both zebrafish and Acanthopterygian teleosts in a striking pattern of double conserved synteny. Further, phylogenetic reconstruction of these neighbouring genes using Bayesian and maximum likelihood methods supported a common origin for teleost paralogues following the split of the Actinopterygii and Sarcopterygii. Conclusion: Our results strongly suggest that myod was duplicated during the basal teleost whole genome duplication event, but was subsequently lost in the Ostariophysi ( zebrafish) and Protacanthopterygii lineages. We propose a sensible consensus nomenclature for vertebrate myod genes that accommodates polyploidization events in teleost and tetrapod lineages and is justified from a phylogenetic perspective.</dc:description>
    </item>
    <item>
      <title>The CRISPR associated protein Cas4 Is a 5' to 3' DNA exonuclease with an iron-sulfur cluster</title>
      <link>http://hdl.handle.net/10023/3270</link>
      <description>Abstract: The Cas4 protein is one of the core CRISPR-associated (Cas) proteins implicated in the prokaryotic CRISPR system for antiviral defence. Cas4 is thought to play a role in the capture of new viral DNA sequences for incorporation into the host genome. No biochemical activity has been reported for Cas4, but it is predicted to include a RecB nuclease domain. We show here that Cas4 family proteins from the archaeon Sulfolobus solfataricus utilise four conserved cysteine residues to bind an iron-sulfur cluster in an arrangement reminiscent of the AddB nuclease of Bacillus subtilis. The Cas4 family protein Sso0001 is a 5' to 3' single stranded DNA exonuclease in vitro that is stalled by extrahelical DNA adducts. A role for Cas4 in DNA duplex strand resectioning to generate recombinogenic 3' single stranded DNA overhangs is proposed. Comparison of the AddB structure with that of a related bacterial nuclease from Eubacterium rectales reveals that the iron-sulfur cluster can be replaced by a zinc ion without disrupting the protein structure, with implications for the evolution of iron-sulfur binding proteins.</description>
      <pubDate>Mon, 08 Oct 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3270</guid>
      <dc:date>2012-10-08T00:00:00Z</dc:date>
      <dc:creator>Zhang, Jing</dc:creator>
      <dc:creator>Kasciukovic, Taciana</dc:creator>
      <dc:creator>White, Malcolm F.</dc:creator>
      <dc:description>The Cas4 protein is one of the core CRISPR-associated (Cas) proteins implicated in the prokaryotic CRISPR system for antiviral defence. Cas4 is thought to play a role in the capture of new viral DNA sequences for incorporation into the host genome. No biochemical activity has been reported for Cas4, but it is predicted to include a RecB nuclease domain. We show here that Cas4 family proteins from the archaeon Sulfolobus solfataricus utilise four conserved cysteine residues to bind an iron-sulfur cluster in an arrangement reminiscent of the AddB nuclease of Bacillus subtilis. The Cas4 family protein Sso0001 is a 5' to 3' single stranded DNA exonuclease in vitro that is stalled by extrahelical DNA adducts. A role for Cas4 in DNA duplex strand resectioning to generate recombinogenic 3' single stranded DNA overhangs is proposed. Comparison of the AddB structure with that of a related bacterial nuclease from Eubacterium rectales reveals that the iron-sulfur cluster can be replaced by a zinc ion without disrupting the protein structure, with implications for the evolution of iron-sulfur binding proteins.</dc:description>
    </item>
    <item>
      <title>The functional response of a generalist predator</title>
      <link>http://hdl.handle.net/10023/3269</link>
      <description>Abstract: Background: Predators can have profound impacts on the dynamics of their prey that depend on how predator consumption is affected by prey density (the predator's functional response). Consumption by a generalist predator is expected to depend on the densities of all its major prey species (its multispecies functional response, or MSFR), but most studies of generalists have focussed on their functional response to only one prey species. Methodology and principal findings: Using Bayesian methods, we fit an MSFR to field data from an avian predator (the hen harrier Circus cyaneus) feeding on three different prey species. We use a simple graphical approach to show that ignoring the effects of alternative prey can give a misleading impression of the predator's effect on the prey of interest. For example, in our system, a “predator pit” for one prey species only occurs when the availability of other prey species is low. Conclusions and significance: The Bayesian approach is effective in fitting the MSFR model to field data. It allows flexibility in modelling over-dispersion, incorporates additional biological information into the parameter priors, and generates estimates of uncertainty in the model's predictions. These features of robustness and data efficiency make our approach ideal for the study of long-lived predators, for which data may be sparse and management/conservation priorities pressing.</description>
      <pubDate>Thu, 27 May 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3269</guid>
      <dc:date>2010-05-27T00:00:00Z</dc:date>
      <dc:creator>Smout, Sophie Caroline</dc:creator>
      <dc:creator>Asseburg, C</dc:creator>
      <dc:creator>Matthiopoulos, Jason</dc:creator>
      <dc:creator>Fernández, Carmen</dc:creator>
      <dc:creator>Redpath, S</dc:creator>
      <dc:creator>Thirgood, S</dc:creator>
      <dc:creator>Harwood, John</dc:creator>
      <dc:description>Background: Predators can have profound impacts on the dynamics of their prey that depend on how predator consumption is affected by prey density (the predator's functional response). Consumption by a generalist predator is expected to depend on the densities of all its major prey species (its multispecies functional response, or MSFR), but most studies of generalists have focussed on their functional response to only one prey species. Methodology and principal findings: Using Bayesian methods, we fit an MSFR to field data from an avian predator (the hen harrier Circus cyaneus) feeding on three different prey species. We use a simple graphical approach to show that ignoring the effects of alternative prey can give a misleading impression of the predator's effect on the prey of interest. For example, in our system, a “predator pit” for one prey species only occurs when the availability of other prey species is low. Conclusions and significance: The Bayesian approach is effective in fitting the MSFR model to field data. It allows flexibility in modelling over-dispersion, incorporates additional biological information into the parameter priors, and generates estimates of uncertainty in the model's predictions. These features of robustness and data efficiency make our approach ideal for the study of long-lived predators, for which data may be sparse and management/conservation priorities pressing.</dc:description>
    </item>
    <item>
      <title>Repeated elicitation of the acoustic startle reflex leads to sensitisation in subsequent avoidance behaviour and induces fear conditioning</title>
      <link>http://hdl.handle.net/10023/3267</link>
      <description>Abstract: Background: Autonomous reflexes enable animals to respond quickly to potential threats, prevent injury and mediate fight or flight responses. Intense acoustic stimuli with sudden onsets elicit a startle reflex while stimuli of similar intensity but with longer rise times only cause a cardiac defence response. In laboratory settings, habituation appears to affect all of these reflexes so that the response amplitude generally decreases with repeated exposure to the stimulus. The startle reflex has become a model system for the study of the neural basis of simple learning processes and emotional processing and is often used as a diagnostic tool in medical applications. However, previous studies did not allow animals to avoid the stimulus and the evolutionary function and long-term behavioural consequences of repeated startling remain speculative. In this study we investigate the follow-up behaviour associated with the startle reflex in wild-captured animals using an experimental setup that allows individuals to exhibit avoidance behaviour. Results: We present evidence that repeated elicitation of the acoustic startle reflex leads to rapid and pronounced sensitisation of sustained spatial avoidance behaviour in grey seals (Halichoerus grypus). Animals developed rapid flight responses, left the exposure pool and showed clear signs of fear conditioning. Once sensitised, seals even avoided a known food source that was close to the sound source. In contrast, animals exposed to non-startling (long rise time) stimuli of the same maximum sound pressure habituated and flight responses waned or were absent from the beginning. The startle threshold of grey seals expressed in units of sensation levels was comparable to thresholds reported for other mammals (93 dB). Conclusions: Our results demonstrate that the acoustic startle reflex plays a crucial role in mediating flight responses and strongly influences the motivational state of an animal beyond a short-term muscular response by mediating long-term avoidance. The reflex is therefore not only a measure of emotional state but also influences emotional processing. The biological function of the startle reflex is most likely associated with mediating rapid flight responses. The data indicate that repeated startling by anthropogenic noise sources might have severe effects on long-term behaviour. Future, studies are needed to investigate whether such effects can be associated with reduced individual fitness or even longevity of individuals.</description>
      <pubDate>Sat, 01 Jan 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3267</guid>
      <dc:date>2011-01-01T00:00:00Z</dc:date>
      <dc:creator>Gotz, Thomas</dc:creator>
      <dc:creator>Janik, Vincent M.</dc:creator>
      <dc:description>Background: Autonomous reflexes enable animals to respond quickly to potential threats, prevent injury and mediate fight or flight responses. Intense acoustic stimuli with sudden onsets elicit a startle reflex while stimuli of similar intensity but with longer rise times only cause a cardiac defence response. In laboratory settings, habituation appears to affect all of these reflexes so that the response amplitude generally decreases with repeated exposure to the stimulus. The startle reflex has become a model system for the study of the neural basis of simple learning processes and emotional processing and is often used as a diagnostic tool in medical applications. However, previous studies did not allow animals to avoid the stimulus and the evolutionary function and long-term behavioural consequences of repeated startling remain speculative. In this study we investigate the follow-up behaviour associated with the startle reflex in wild-captured animals using an experimental setup that allows individuals to exhibit avoidance behaviour. Results: We present evidence that repeated elicitation of the acoustic startle reflex leads to rapid and pronounced sensitisation of sustained spatial avoidance behaviour in grey seals (Halichoerus grypus). Animals developed rapid flight responses, left the exposure pool and showed clear signs of fear conditioning. Once sensitised, seals even avoided a known food source that was close to the sound source. In contrast, animals exposed to non-startling (long rise time) stimuli of the same maximum sound pressure habituated and flight responses waned or were absent from the beginning. The startle threshold of grey seals expressed in units of sensation levels was comparable to thresholds reported for other mammals (93 dB). Conclusions: Our results demonstrate that the acoustic startle reflex plays a crucial role in mediating flight responses and strongly influences the motivational state of an animal beyond a short-term muscular response by mediating long-term avoidance. The reflex is therefore not only a measure of emotional state but also influences emotional processing. The biological function of the startle reflex is most likely associated with mediating rapid flight responses. The data indicate that repeated startling by anthropogenic noise sources might have severe effects on long-term behaviour. Future, studies are needed to investigate whether such effects can be associated with reduced individual fitness or even longevity of individuals.</dc:description>
    </item>
    <item>
      <title>Models of cultural niche construction with selection and assortative mating</title>
      <link>http://hdl.handle.net/10023/3262</link>
      <description>Abstract: Niche construction is a process through which organisms modify their environment and, as a result, alter the selection pressures on themselves and other species. In cultural niche construction, one or more cultural traits can influence the evolution of other cultural or biological traits by affecting the social environment in which the latter traits may evolve. Cultural niche construction may include either gene-culture or culture-culture interactions. Here we develop a model of this process and suggest some applications of this model. We examine the interactions between cultural transmission, selection, and assorting, paying particular attention to the complexities that arise when selection and assorting are both present, in which case stable polymorphisms of all cultural phenotypes are possible. We compare our model to a recent model for the joint evolution of religion and fertility and discuss other potential applications of cultural niche construction theory, including the evolution and maintenance of large-scale human conflict and the relationship between sex ratio bias and marriage customs. The evolutionary framework we introduce begins to address complexities that arise in the quantitative analysis of multiple interacting cultural traits.</description>
      <pubDate>Tue, 14 Aug 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3262</guid>
      <dc:date>2012-08-14T00:00:00Z</dc:date>
      <dc:creator>Creanza, Nicole</dc:creator>
      <dc:creator>Fogarty, Laurel</dc:creator>
      <dc:creator>Feldman, Marcus W.</dc:creator>
      <dc:description>Niche construction is a process through which organisms modify their environment and, as a result, alter the selection pressures on themselves and other species. In cultural niche construction, one or more cultural traits can influence the evolution of other cultural or biological traits by affecting the social environment in which the latter traits may evolve. Cultural niche construction may include either gene-culture or culture-culture interactions. Here we develop a model of this process and suggest some applications of this model. We examine the interactions between cultural transmission, selection, and assorting, paying particular attention to the complexities that arise when selection and assorting are both present, in which case stable polymorphisms of all cultural phenotypes are possible. We compare our model to a recent model for the joint evolution of religion and fertility and discuss other potential applications of cultural niche construction theory, including the evolution and maintenance of large-scale human conflict and the relationship between sex ratio bias and marriage customs. The evolutionary framework we introduce begins to address complexities that arise in the quantitative analysis of multiple interacting cultural traits.</dc:description>
    </item>
    <item>
      <title>Motion dazzle and camouflage as distinct anti-predator defenses</title>
      <link>http://hdl.handle.net/10023/3253</link>
      <description>Abstract: Background: Camouflage patterns that hinder detection and/or recognition by antagonists are widely studied in both human and animal contexts. Patterns of contrasting stripes that purportedly degrade an observer's ability to judge the speed and direction of moving prey ('motion dazzle') are, however, rarely investigated. This is despite motion dazzle having been fundamental to the appearance of warships in both world wars and often postulated as the selective agent leading to repeated patterns on many animals (such as zebra and many fish, snake, and invertebrate species). Such patterns often appear conspicuous, suggesting that protection while moving by motion dazzle might impair camouflage when stationary. However, the relationship between motion dazzle and camouflage is unclear because disruptive camouflage relies on high-contrast markings. In this study, we used a computer game with human subjects detecting and capturing either moving or stationary targets with different patterns, in order to provide the first empirical exploration of the interaction of these two protective coloration mechanisms. Results: Moving targets with stripes were caught significantly less often and missed more often than targets with camouflage patterns. However, when stationary, targets with camouflage markings were captured less often and caused more false detections than those with striped patterns, which were readily detected. Conclusions: Our study provides the clearest evidence to date that some patterns inhibit the capture of moving targets, but that camouflage and motion dazzle are not complementary strategies. Therefore, the specific coloration that evolves in animals will depend on how the life history and ontogeny of each species influence the trade-off between the costs and benefits of motion dazzle and camouflage.</description>
      <pubDate>Fri, 25 Nov 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3253</guid>
      <dc:date>2011-11-25T00:00:00Z</dc:date>
      <dc:creator>Stevens, Martin</dc:creator>
      <dc:creator>Searle, W. Tom L.</dc:creator>
      <dc:creator>Seymour, Jenny E.</dc:creator>
      <dc:creator>Marshall, Kate L. A.</dc:creator>
      <dc:creator>Ruxton, Graeme D.</dc:creator>
      <dc:description>Background: Camouflage patterns that hinder detection and/or recognition by antagonists are widely studied in both human and animal contexts. Patterns of contrasting stripes that purportedly degrade an observer's ability to judge the speed and direction of moving prey ('motion dazzle') are, however, rarely investigated. This is despite motion dazzle having been fundamental to the appearance of warships in both world wars and often postulated as the selective agent leading to repeated patterns on many animals (such as zebra and many fish, snake, and invertebrate species). Such patterns often appear conspicuous, suggesting that protection while moving by motion dazzle might impair camouflage when stationary. However, the relationship between motion dazzle and camouflage is unclear because disruptive camouflage relies on high-contrast markings. In this study, we used a computer game with human subjects detecting and capturing either moving or stationary targets with different patterns, in order to provide the first empirical exploration of the interaction of these two protective coloration mechanisms. Results: Moving targets with stripes were caught significantly less often and missed more often than targets with camouflage patterns. However, when stationary, targets with camouflage markings were captured less often and caused more false detections than those with striped patterns, which were readily detected. Conclusions: Our study provides the clearest evidence to date that some patterns inhibit the capture of moving targets, but that camouflage and motion dazzle are not complementary strategies. Therefore, the specific coloration that evolves in animals will depend on how the life history and ontogeny of each species influence the trade-off between the costs and benefits of motion dazzle and camouflage.</dc:description>
    </item>
    <item>
      <title>Features of the ancestral bilaterian inferred from Platynereis dumerilii ParaHox genes</title>
      <link>http://hdl.handle.net/10023/3252</link>
      <description>Abstract: Background The ParaHox gene cluster is the evolutionary sister to the Hox cluster. Whilst the role of the Hox cluster in patterning the anterior-posterior axis of bilaterian animals is well established, and the organisation of vertebrate Hox clusters is intimately linked to gene regulation, much less is known about the more recently discovered ParaHox cluster. ParaHox gene clustering, and its relationship to expression, has only been described in deuterostomes. Conventional protostome models (Drosophila melanogaster and Caenorhabditis elegans) are secondarily derived with respect to ParaHox genes, suffering gene loss and cluster break-up. Results We provide the first evidence for ParaHox gene clustering from a less-derived protostome animal, the annelid Platynereis dumerilii. Clustering of these genes is thus not a sole preserve of the deuterostome lineage within Bilateria. This protostome ParaHox cluster is not entirely intact however, with Pdu-Cdx being on the opposite end of the same chromosome arm from Pdu-Gsx and Pdu-Xlox. From the genomic sequence around the P. dumerilii ParaHox genes the neighbouring genes are identified, compared with other taxa, and the ancestral arrangement deduced. Conclusion We relate the organisation of the ParaHox genes to their expression, and from comparisons with other taxa hypothesise that a relatively complex pattern of ParaHox gene expression existed in the protostome-deuterostome ancestor, which was secondarily simplified along several invertebrate lineages. Detailed comparisons of the gene content around the ParaHox genes enables the reconstruction of the genome surrounding the ParaHox cluster of the protostome-deuterostome ancestor, which existed over 550 million years ago.</description>
      <pubDate>Thu, 23 Jul 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3252</guid>
      <dc:date>2009-07-23T00:00:00Z</dc:date>
      <dc:creator>Hui, JHL</dc:creator>
      <dc:creator>Raible, F</dc:creator>
      <dc:creator>Korchagina, N</dc:creator>
      <dc:creator>Dray, N</dc:creator>
      <dc:creator>Samain, S</dc:creator>
      <dc:creator>Magdelenat, G</dc:creator>
      <dc:creator>Jubin, C</dc:creator>
      <dc:creator>Segurens, B</dc:creator>
      <dc:creator>Balavoine, G</dc:creator>
      <dc:creator>Arendt, D</dc:creator>
      <dc:creator>Ferrier, David Ellard Keith</dc:creator>
      <dc:description>Background The ParaHox gene cluster is the evolutionary sister to the Hox cluster. Whilst the role of the Hox cluster in patterning the anterior-posterior axis of bilaterian animals is well established, and the organisation of vertebrate Hox clusters is intimately linked to gene regulation, much less is known about the more recently discovered ParaHox cluster. ParaHox gene clustering, and its relationship to expression, has only been described in deuterostomes. Conventional protostome models (Drosophila melanogaster and Caenorhabditis elegans) are secondarily derived with respect to ParaHox genes, suffering gene loss and cluster break-up. Results We provide the first evidence for ParaHox gene clustering from a less-derived protostome animal, the annelid Platynereis dumerilii. Clustering of these genes is thus not a sole preserve of the deuterostome lineage within Bilateria. This protostome ParaHox cluster is not entirely intact however, with Pdu-Cdx being on the opposite end of the same chromosome arm from Pdu-Gsx and Pdu-Xlox. From the genomic sequence around the P. dumerilii ParaHox genes the neighbouring genes are identified, compared with other taxa, and the ancestral arrangement deduced. Conclusion We relate the organisation of the ParaHox genes to their expression, and from comparisons with other taxa hypothesise that a relatively complex pattern of ParaHox gene expression existed in the protostome-deuterostome ancestor, which was secondarily simplified along several invertebrate lineages. Detailed comparisons of the gene content around the ParaHox genes enables the reconstruction of the genome surrounding the ParaHox cluster of the protostome-deuterostome ancestor, which existed over 550 million years ago.</dc:description>
    </item>
    <item>
      <title>Tunicates push the limits of animal evo-devo</title>
      <link>http://hdl.handle.net/10023/3250</link>
      <description>Abstract: The phylum to which humans belong, Chordata, takes its name from one of the major shared derived features of the group, the notochord. All chordates have a notochord, at least during embryogenesis, and there is little doubt about notochord homology at the morphological level. A study in BMC Evolutionary Biology now shows that there is greater variability in the molecular genetics underlying notochord development than previously appreciated.</description>
      <pubDate>Thu, 20 Jan 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3250</guid>
      <dc:date>2011-01-20T00:00:00Z</dc:date>
      <dc:creator>Ferrier, David Ellard Keith</dc:creator>
      <dc:description>The phylum to which humans belong, Chordata, takes its name from one of the major shared derived features of the group, the notochord. All chordates have a notochord, at least during embryogenesis, and there is little doubt about notochord homology at the morphological level. A study in BMC Evolutionary Biology now shows that there is greater variability in the molecular genetics underlying notochord development than previously appreciated.</dc:description>
    </item>
    <item>
      <title>Sexual and postmating reproductive isolation between allopatric Drosophila montana populations suggest speciation potential</title>
      <link>http://hdl.handle.net/10023/3249</link>
      <description>Abstract: Background: Widely distributed species with populations adapted to different environmental conditions can provide valuable opportunities for tracing the onset of reproductive incompatibilities and their role in the speciation process. Drosophila montana, a D. virilis group species found in high latitude boreal forests in Nearctic and Palearctic regions around the globe, could be an excellent model system for studying the early stages of speciation, as a wealth of information concerning this species' ecology, mating system, life history, genetics and phylogeography is available. However, reproductive barriers between populations have hereto not been investigated. Results: We report both pre- and postmating barriers to reproduction between flies from European (Finnish) and North American (Canadian) populations of Drosophila montana. Using a series of mate-choice designs, we show that flies from these two populations mate assortatively (i.e., exhibit significant sexual isolation) while emphasizing the importance of experimental design in these kinds of studies. We also assessed potential postmating isolation by quantifying egg and progeny production in intra-and interpopulation crosses and show a significant one-way reduction in progeny production, affecting both male and female offspring equally. Conclusion: We provide evidence that allopatric D. montana populations exhibit reproductive isolation and we discuss the potential mechanisms involved. Our data emphasize the importance of experimental design in studies on premating isolation between recently diverged taxa and suggest that postmating barriers may be due to postcopulatory-prezygotic mechanisms. D. montana populations seem to be evolving multiple barriers to gene flow in allopatry and our study lays the groundwork for future investigations of the genetic and phenotypic mechanisms underlying these barriers.</description>
      <pubDate>Mon, 14 Mar 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3249</guid>
      <dc:date>2011-03-14T00:00:00Z</dc:date>
      <dc:creator>Jennings, Jackson H.</dc:creator>
      <dc:creator>Mazzi, Dominique</dc:creator>
      <dc:creator>Ritchie, Michael G.</dc:creator>
      <dc:creator>Hoikkala, Anneli</dc:creator>
      <dc:description>Background: Widely distributed species with populations adapted to different environmental conditions can provide valuable opportunities for tracing the onset of reproductive incompatibilities and their role in the speciation process. Drosophila montana, a D. virilis group species found in high latitude boreal forests in Nearctic and Palearctic regions around the globe, could be an excellent model system for studying the early stages of speciation, as a wealth of information concerning this species' ecology, mating system, life history, genetics and phylogeography is available. However, reproductive barriers between populations have hereto not been investigated. Results: We report both pre- and postmating barriers to reproduction between flies from European (Finnish) and North American (Canadian) populations of Drosophila montana. Using a series of mate-choice designs, we show that flies from these two populations mate assortatively (i.e., exhibit significant sexual isolation) while emphasizing the importance of experimental design in these kinds of studies. We also assessed potential postmating isolation by quantifying egg and progeny production in intra-and interpopulation crosses and show a significant one-way reduction in progeny production, affecting both male and female offspring equally. Conclusion: We provide evidence that allopatric D. montana populations exhibit reproductive isolation and we discuss the potential mechanisms involved. Our data emphasize the importance of experimental design in studies on premating isolation between recently diverged taxa and suggest that postmating barriers may be due to postcopulatory-prezygotic mechanisms. D. montana populations seem to be evolving multiple barriers to gene flow in allopatry and our study lays the groundwork for future investigations of the genetic and phenotypic mechanisms underlying these barriers.</dc:description>
    </item>
    <item>
      <title>Fitness consequences of female multiple mating : A direct test of indirect benefits</title>
      <link>http://hdl.handle.net/10023/3248</link>
      <description>Abstract: Background The observation that females mate multiply when males provide nothing but sperm - which sexual selection theory suggests is unlikely to be limiting - continues to puzzle evolutionary biologists. Here we test the hypothesis that multiple mating is prevalent under such circumstances because it enhances female fitness. We do this by allowing female Trinidadian guppies to mate with either a single male or with multiple males, and then tracking the consequences of these matings across two generations. Results Overall, multiply mated females produced 67% more F2 grand-offspring than singly mated females. These offspring, however, did not grow or mature faster, nor were they larger at birth, than F2 grand-offspring of singly mated females. Our results, however, show that multiple mating yields benefits to females in the form of an increase in the production of F1. The higher fecundity among multiply mated mothers was driven by greater production of sons but not daughters. However, contrary to expectation, individually, the offspring of multiply mated females do not grow at different rates than offspring of singly mated females, nor do any indirect fitness benefits or costs accrue to second-generation offspring. Conclusions The study provides strong evidence that multiple mating is advantageous to females, even when males contribute only sperm. This benefit is achieved through an increase in fecundity in the first generation, rather than through other fitness correlates such as size at birth, growth rate, time to sexual maturation and survival. Considered alongside previous work that female guppies can choose to mate with multiple partners, our results provide compelling evidence that direct fitness benefits underpin these mating decisions.</description>
      <pubDate>Sat, 15 Sep 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3248</guid>
      <dc:date>2012-09-15T00:00:00Z</dc:date>
      <dc:creator>Barbosa, Miguel</dc:creator>
      <dc:creator>Connolly, Sean R</dc:creator>
      <dc:creator>Hisano, Mizue</dc:creator>
      <dc:creator>Dornelas, Maria</dc:creator>
      <dc:creator>Magurran, Anne</dc:creator>
      <dc:description>Background The observation that females mate multiply when males provide nothing but sperm - which sexual selection theory suggests is unlikely to be limiting - continues to puzzle evolutionary biologists. Here we test the hypothesis that multiple mating is prevalent under such circumstances because it enhances female fitness. We do this by allowing female Trinidadian guppies to mate with either a single male or with multiple males, and then tracking the consequences of these matings across two generations. Results Overall, multiply mated females produced 67% more F2 grand-offspring than singly mated females. These offspring, however, did not grow or mature faster, nor were they larger at birth, than F2 grand-offspring of singly mated females. Our results, however, show that multiple mating yields benefits to females in the form of an increase in the production of F1. The higher fecundity among multiply mated mothers was driven by greater production of sons but not daughters. However, contrary to expectation, individually, the offspring of multiply mated females do not grow at different rates than offspring of singly mated females, nor do any indirect fitness benefits or costs accrue to second-generation offspring. Conclusions The study provides strong evidence that multiple mating is advantageous to females, even when males contribute only sperm. This benefit is achieved through an increase in fecundity in the first generation, rather than through other fitness correlates such as size at birth, growth rate, time to sexual maturation and survival. Considered alongside previous work that female guppies can choose to mate with multiple partners, our results provide compelling evidence that direct fitness benefits underpin these mating decisions.</dc:description>
    </item>
    <item>
      <title>Why do adaptive immune responses cross-react?</title>
      <link>http://hdl.handle.net/10023/3247</link>
      <description>Abstract: Antigen specificity of adaptive immune responses is often in the host's best interests, but with important and as yet unpredictable exceptions. For example, antibodies that bind to multiple flaviviral or malarial species can provide hosts with simultaneous protection against many parasite genotypes. Vaccinology often aims to harness such imprecision, because cross-reactive antibodies might provide broad-spectrum protection in the face of antigenic variation by parasites. However, the causes of cross-reactivity among immune responses are not always known, and here, we explore potential proximate and evolutionary explanations for cross-reactivity. We particularly consider whether cross-reactivity is the result of constraints on the ability of the immune system to process information about the world of antigens, or whether an intermediate level of cross-reactivity may instead represent an evolutionary optimum. We conclude with a series of open questions for future interdisciplinary research, including the suggestion that the evolutionary ecology of information processing might benefit from close examination of immunological data.</description>
      <pubDate>Sun, 01 Feb 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3247</guid>
      <dc:date>2009-02-01T00:00:00Z</dc:date>
      <dc:creator>Fairlie-Clarke, KJ</dc:creator>
      <dc:creator>Shuker, David Michael</dc:creator>
      <dc:creator>Graham, AL</dc:creator>
      <dc:description>Antigen specificity of adaptive immune responses is often in the host's best interests, but with important and as yet unpredictable exceptions. For example, antibodies that bind to multiple flaviviral or malarial species can provide hosts with simultaneous protection against many parasite genotypes. Vaccinology often aims to harness such imprecision, because cross-reactive antibodies might provide broad-spectrum protection in the face of antigenic variation by parasites. However, the causes of cross-reactivity among immune responses are not always known, and here, we explore potential proximate and evolutionary explanations for cross-reactivity. We particularly consider whether cross-reactivity is the result of constraints on the ability of the immune system to process information about the world of antigens, or whether an intermediate level of cross-reactivity may instead represent an evolutionary optimum. We conclude with a series of open questions for future interdisciplinary research, including the suggestion that the evolutionary ecology of information processing might benefit from close examination of immunological data.</dc:description>
    </item>
    <item>
      <title>MtsslWizard : in silico spin-labelling and generation of distance distributions in PyMOL</title>
      <link>http://hdl.handle.net/10023/3160</link>
      <description>Abstract: MtsslWizard is a computer program, which operates as a plugin for the PyMOL molecular graphics system. MtsslWizard estimates distances between spin labels on proteins quickly with user configurable options through a simple graphical interface. The program searches for ensembles of possible MTSSL conformations that do not clash with a static model of the protein. Options include restricting the search procedure to published rotamer libraries of MTSSL or scoring for contacts with protein. Once conformations are assigned, distance distributions between two or more sites are calculated, displayed and can be exported to other software. The program's use is evaluated in a number of challenging test cases and its performance discussed. The strength of the program is its accuracy and simplicity.</description>
      <pubDate>Sun, 01 Apr 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3160</guid>
      <dc:date>2012-04-01T00:00:00Z</dc:date>
      <dc:creator>Hageluken, Gregor</dc:creator>
      <dc:creator>Ward, Richard James</dc:creator>
      <dc:creator>Naismith, Jim</dc:creator>
      <dc:creator>Schiemann, Olav</dc:creator>
      <dc:description>MtsslWizard is a computer program, which operates as a plugin for the PyMOL molecular graphics system. MtsslWizard estimates distances between spin labels on proteins quickly with user configurable options through a simple graphical interface. The program searches for ensembles of possible MTSSL conformations that do not clash with a static model of the protein. Options include restricting the search procedure to published rotamer libraries of MTSSL or scoring for contacts with protein. Once conformations are assigned, distance distributions between two or more sites are calculated, displayed and can be exported to other software. The program's use is evaluated in a number of challenging test cases and its performance discussed. The strength of the program is its accuracy and simplicity.</dc:description>
    </item>
    <item>
      <title>Identification of learning mechanisms in a wild meerkat population</title>
      <link>http://hdl.handle.net/10023/3082</link>
      <description>Abstract: Vigorous debates as to the evolutionary origins of culture remain unresolved due to an absence of methods for identifying learning mechanisms in natural populations. While laboratory experiments on captive animals have revealed evidence for a number of mechanisms, these may not necessarily reflect the processes typically operating in nature. We developed a novel method that allows social and asocial learning mechanisms to be determined in animal groups from the patterns of interaction with, and solving of, a task. We deployed it to analyse learning in groups of wild meerkats (Suricata suricatta) presented with a novel foraging apparatus. We identify nine separate learning processes underlying the meerkats' foraging behaviour, in each case precisely quantifying their strength and duration, including local enhancement, emulation, and a hitherto unrecognized form of social learning, which we term `observational perseverance'. Our analysis suggests a key factor underlying the stability of behavioural traditions is a high ratio of specific to generalized social learning effects. The approach has widespread potential as an ecologically valid tool to investigate learning mechanisms in natural groups of animals, including humans.</description>
      <pubDate>Wed, 08 Aug 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3082</guid>
      <dc:date>2012-08-08T00:00:00Z</dc:date>
      <dc:creator>Hoppitt, William John Edward</dc:creator>
      <dc:creator>Samson, Jamie</dc:creator>
      <dc:creator>Laland, Kevin N.</dc:creator>
      <dc:creator>Thornton, Alex</dc:creator>
      <dc:description>Vigorous debates as to the evolutionary origins of culture remain unresolved due to an absence of methods for identifying learning mechanisms in natural populations. While laboratory experiments on captive animals have revealed evidence for a number of mechanisms, these may not necessarily reflect the processes typically operating in nature. We developed a novel method that allows social and asocial learning mechanisms to be determined in animal groups from the patterns of interaction with, and solving of, a task. We deployed it to analyse learning in groups of wild meerkats (Suricata suricatta) presented with a novel foraging apparatus. We identify nine separate learning processes underlying the meerkats' foraging behaviour, in each case precisely quantifying their strength and duration, including local enhancement, emulation, and a hitherto unrecognized form of social learning, which we term `observational perseverance'. Our analysis suggests a key factor underlying the stability of behavioural traditions is a high ratio of specific to generalized social learning effects. The approach has widespread potential as an ecologically valid tool to investigate learning mechanisms in natural groups of animals, including humans.</dc:description>
    </item>
    <item>
      <title>Vessel noise affects beaked whale behavior : Results of a dedicated acoustic response study</title>
      <link>http://hdl.handle.net/10023/3078</link>
      <description>Abstract: Some beaked whale species are susceptible to the detrimental effects of anthropogenic noise. Most studies have concentrated on the effects of military sonar, but other forms of acoustic disturbance (e.g. shipping noise) may disrupt behavior. An experiment involving the exposure of target whale groups to intense vessel-generated noise tested how these exposures influenced the foraging behavior of Blainville’s beaked whales (Mesoplodon densirostris) in the Tongue of the Ocean (Bahamas). A military array of bottom-mounted hydrophones was used to measure the response based upon changes in the spatial and temporal pattern of vocalizations. The archived acoustic data were used to compute metrics the echolocation-based foraging behavior for 16 targeted groups, 10 groups further away on the range, and 26 nonexposed groups. The duration of foraging bouts was not significantly affected by the exposure. Changes in the hydrophone over which the group was most frequently detected occurred as the animals moved around within a foraging bout, and their number was significantly less the closer the whales were to the sound source. Non-exposed groups also had significantly more changes in the primary hydrophone than exposed groups irrespective of distance. Our results suggested that broadband ship noise caused a significant change in beaked whale behavior up to at least 5.2 kilometers away from the vessel. The observed change could potentially correspond to a restriction in the movement of groups, a period of more directional travel, a reduction in the number of individuals clicking within the group, or a response to changes in prey movement.</description>
      <pubDate>Fri, 03 Aug 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3078</guid>
      <dc:date>2012-08-03T00:00:00Z</dc:date>
      <dc:creator>Pirotta, Enrico</dc:creator>
      <dc:creator>Milor, Rachel</dc:creator>
      <dc:creator>Quick, Nicola Jane</dc:creator>
      <dc:creator>Moretti, David</dc:creator>
      <dc:creator>Dimarzio, Nancy</dc:creator>
      <dc:creator>Tyack, Peter Lloyd</dc:creator>
      <dc:creator>Boyd, Ian</dc:creator>
      <dc:creator>Hastie, Gordon Drummond</dc:creator>
      <dc:description>Some beaked whale species are susceptible to the detrimental effects of anthropogenic noise. Most studies have concentrated on the effects of military sonar, but other forms of acoustic disturbance (e.g. shipping noise) may disrupt behavior. An experiment involving the exposure of target whale groups to intense vessel-generated noise tested how these exposures influenced the foraging behavior of Blainville’s beaked whales (Mesoplodon densirostris) in the Tongue of the Ocean (Bahamas). A military array of bottom-mounted hydrophones was used to measure the response based upon changes in the spatial and temporal pattern of vocalizations. The archived acoustic data were used to compute metrics the echolocation-based foraging behavior for 16 targeted groups, 10 groups further away on the range, and 26 nonexposed groups. The duration of foraging bouts was not significantly affected by the exposure. Changes in the hydrophone over which the group was most frequently detected occurred as the animals moved around within a foraging bout, and their number was significantly less the closer the whales were to the sound source. Non-exposed groups also had significantly more changes in the primary hydrophone than exposed groups irrespective of distance. Our results suggested that broadband ship noise caused a significant change in beaked whale behavior up to at least 5.2 kilometers away from the vessel. The observed change could potentially correspond to a restriction in the movement of groups, a period of more directional travel, a reduction in the number of individuals clicking within the group, or a response to changes in prey movement.</dc:description>
    </item>
    <item>
      <title>Spatial variation in foraging behaviour of a marine top predator (Phoca vitulina) determined by a large-scale satellite tagging program</title>
      <link>http://hdl.handle.net/10023/3076</link>
      <description>Abstract: The harbour seal (Phoca vitulina) is a widespread marine predator in Northern Hemisphere waters. British populations have been subject to rapid declines in recent years. Food supply or inter-specific competition may be implicated but basic ecological data are lacking and there are few studies of harbour seal foraging distribution and habits. In this study, satellite tagging conducted at the major seal haul outs around the British Isles showed both that seal movements were highly variable among individuals and that foraging strategy appears to be specialized within particular regions. We investigated whether these apparent differences could be explained by individual level factors: by modelling measures of trip duration and distance travelled as a function of size, sex and body condition. However, these were not found to be good predictors of foraging trip duration or distance, which instead was best predicted by tagging region, time of year and inter-trip duration. Therefore, we propose that local habitat conditions and the constraints they impose are the major determinants of foraging movements. Specifically the distance to profitable feeding grounds from suitable haul-out locations may dictate foraging strategy and behaviour. Accounting for proximity to productive foraging resources is likely to be an important component of understanding population processes. Despite more extensive offshore movements than expected, there was also marked fidelity to the local haul-out region with limited connectivity between study regions. These empirical observations of regional exchange at short time scales demonstrates the value of large scale electronic tagging programs for robust characterization of at-sea foraging behaviour at a wide spatial scale.</description>
      <pubDate>Mon, 21 May 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3076</guid>
      <dc:date>2012-05-21T00:00:00Z</dc:date>
      <dc:creator>Sharples, Ruth Jemma</dc:creator>
      <dc:creator>Moss, Simon E</dc:creator>
      <dc:creator>Patterson, Toby A</dc:creator>
      <dc:creator>Hammond, Philip Steven</dc:creator>
      <dc:description>The harbour seal (Phoca vitulina) is a widespread marine predator in Northern Hemisphere waters. British populations have been subject to rapid declines in recent years. Food supply or inter-specific competition may be implicated but basic ecological data are lacking and there are few studies of harbour seal foraging distribution and habits. In this study, satellite tagging conducted at the major seal haul outs around the British Isles showed both that seal movements were highly variable among individuals and that foraging strategy appears to be specialized within particular regions. We investigated whether these apparent differences could be explained by individual level factors: by modelling measures of trip duration and distance travelled as a function of size, sex and body condition. However, these were not found to be good predictors of foraging trip duration or distance, which instead was best predicted by tagging region, time of year and inter-trip duration. Therefore, we propose that local habitat conditions and the constraints they impose are the major determinants of foraging movements. Specifically the distance to profitable feeding grounds from suitable haul-out locations may dictate foraging strategy and behaviour. Accounting for proximity to productive foraging resources is likely to be an important component of understanding population processes. Despite more extensive offshore movements than expected, there was also marked fidelity to the local haul-out region with limited connectivity between study regions. These empirical observations of regional exchange at short time scales demonstrates the value of large scale electronic tagging programs for robust characterization of at-sea foraging behaviour at a wide spatial scale.</dc:description>
    </item>
    <item>
      <title>Global coverage of cetacean line-transect surveys : status quo, data gaps and future challenges</title>
      <link>http://hdl.handle.net/10023/3074</link>
      <description>Abstract: Knowledge of abundance, trends and distribution of cetacean populations is needed to inform marine conservation efforts, ecosystem models and spatial planning. We compiled a geo-spatial database of published data on cetacean abundance from dedicated visual line-transect surveys and encoded &gt;1100 abundance estimates for 47 species from 430 surveys conducted worldwide from 1975-2005. Our subsequent analyses revealed large spatial, temporal and taxonomic variability and gaps in survey coverage. With the exception of Antarctic waters, survey coverage was biased toward the northern hemisphere, especially US and northern European waters. Overall, &lt;25% of the world’s ocean surface was surveyed and only 6% had been covered frequently enough (≥ 5 times) to allow trend estimation. Almost half the global survey effort, defined as total area (km2) covered by all survey study areas across time, was concentrated in the Eastern Tropical Pacific (ETP). Neither the number of surveys conducted nor the survey effort had increased in recent years. Across species, an average of 10% of a species’ predicted range had been covered by at least one survey, but there was considerable variation among species. With the exception of three delphinid species, &lt;1% of all species’ ranges had been covered frequently enough for trend analysis. We use a data-rich species, sperm whale, as an example to illustrate the challenges of using available data from line-transect surveys for the detection of trends or for spatial planning. Finally, we propose and contrast several field and analytical methods to fill in data gaps to improve future cetacean conservation management efforts.</description>
      <pubDate>Wed, 12 Sep 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3074</guid>
      <dc:date>2012-09-12T00:00:00Z</dc:date>
      <dc:creator>Kaschner, Kristin</dc:creator>
      <dc:creator>Quick, Nicola Jane</dc:creator>
      <dc:creator>Jewell, Rebecca Lucy</dc:creator>
      <dc:creator>Williams, Robert</dc:creator>
      <dc:creator>Harris, Catriona M</dc:creator>
      <dc:description>Knowledge of abundance, trends and distribution of cetacean populations is needed to inform marine conservation efforts, ecosystem models and spatial planning. We compiled a geo-spatial database of published data on cetacean abundance from dedicated visual line-transect surveys and encoded &gt;1100 abundance estimates for 47 species from 430 surveys conducted worldwide from 1975-2005. Our subsequent analyses revealed large spatial, temporal and taxonomic variability and gaps in survey coverage. With the exception of Antarctic waters, survey coverage was biased toward the northern hemisphere, especially US and northern European waters. Overall, &lt;25% of the world’s ocean surface was surveyed and only 6% had been covered frequently enough (≥ 5 times) to allow trend estimation. Almost half the global survey effort, defined as total area (km2) covered by all survey study areas across time, was concentrated in the Eastern Tropical Pacific (ETP). Neither the number of surveys conducted nor the survey effort had increased in recent years. Across species, an average of 10% of a species’ predicted range had been covered by at least one survey, but there was considerable variation among species. With the exception of three delphinid species, &lt;1% of all species’ ranges had been covered frequently enough for trend analysis. We use a data-rich species, sperm whale, as an example to illustrate the challenges of using available data from line-transect surveys for the detection of trends or for spatial planning. Finally, we propose and contrast several field and analytical methods to fill in data gaps to improve future cetacean conservation management efforts.</dc:description>
    </item>
    <item>
      <title>ATG5 Is Essential for ATG8-Dependent Autophagy and Mitochondrial Homeostasis in Leishmania major</title>
      <link>http://hdl.handle.net/10023/3051</link>
      <description>Abstract: Macroautophagy has been shown to be important for the cellular remodelling required for Leishmania differentiation. We now demonstrate that L. major contains a functional ATG12-ATG5 conjugation system, which is required for ATG8-dependent autophagosome formation. Nascent autophagosomes were found commonly associated with the mitochondrion. L. major mutants lacking ATG5 (Δatg5) were viable as promastigotes but were unable to form autophagosomes, had morphological abnormalities including a much reduced flagellum, were less able to differentiate and had greatly reduced virulence to macrophages and mice. Analyses of the lipid metabolome of Δatg5 revealed marked elevation of phosphatidylethanolamines (PE) in comparison to wild type parasites. The Δatg5 mutants also had increased mitochondrial mass but reduced mitochondrial membrane potential and higher levels of reactive oxygen species. These findings indicate that the lack of ATG5 and autophagy leads to perturbation of the phospholipid balance in the mitochondrion, possibly through ablation of membrane use and conjugation of mitochondrial PE to ATG8 for autophagosome biogenesis, resulting in a dysfunctional mitochondrion with impaired oxidative ability and energy generation. The overall result of this is reduced virulence.</description>
      <pubDate>Thu, 17 May 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3051</guid>
      <dc:date>2012-05-17T00:00:00Z</dc:date>
      <dc:creator>Williams, Roderick A. M.</dc:creator>
      <dc:creator>Smith, Terry K.</dc:creator>
      <dc:creator>Cull, Benjamin</dc:creator>
      <dc:creator>Mottram, Jeremy C.</dc:creator>
      <dc:creator>Coombs, Graham H.</dc:creator>
      <dc:description>Macroautophagy has been shown to be important for the cellular remodelling required for Leishmania differentiation. We now demonstrate that L. major contains a functional ATG12-ATG5 conjugation system, which is required for ATG8-dependent autophagosome formation. Nascent autophagosomes were found commonly associated with the mitochondrion. L. major mutants lacking ATG5 (Δatg5) were viable as promastigotes but were unable to form autophagosomes, had morphological abnormalities including a much reduced flagellum, were less able to differentiate and had greatly reduced virulence to macrophages and mice. Analyses of the lipid metabolome of Δatg5 revealed marked elevation of phosphatidylethanolamines (PE) in comparison to wild type parasites. The Δatg5 mutants also had increased mitochondrial mass but reduced mitochondrial membrane potential and higher levels of reactive oxygen species. These findings indicate that the lack of ATG5 and autophagy leads to perturbation of the phospholipid balance in the mitochondrion, possibly through ablation of membrane use and conjugation of mitochondrial PE to ATG8 for autophagosome biogenesis, resulting in a dysfunctional mitochondrion with impaired oxidative ability and energy generation. The overall result of this is reduced virulence.</dc:description>
    </item>
    <item>
      <title>Fast skeletal muscle transcriptome of the Gilthead sea bream (Sparus aurata) determined by next generation sequencing</title>
      <link>http://hdl.handle.net/10023/3046</link>
      <description>Abstract: Background: The gilthead sea bream (Sparus aurata L.) occurs around the Mediterranean and along Eastern Atlantic coasts from Great Britain to Senegal. It is tolerant of a wide range of temperatures and salinities and is often found in brackish coastal lagoons and estuarine areas, particularly early in its life cycle. Gilthead sea bream are extensively cultivated in the Mediterranean with an annual production of 125,000 metric tonnes. Here we present a de novo assembly of the fast skeletal muscle transcriptome of gilthead sea bream using 454 reads and identify gene paralogues, splice variants and microsatellite repeats. An annotated transcriptome of the skeletal muscle will facilitate understanding of the genetic and molecular basis of traits linked to production in this economically important species. Results: Around 2.7 million reads of mRNA sequence data were generated from the fast myotomal of adult fish (~2 kg) and juvenile fish (~0.09 kg) that had been either fed to satiation, fasted for 3-5d or transferred to low (11°C) or high (33°C) temperatures for 3-5d. Newbler v2.5 assembly resulted in 43,461 isotigs &gt;100 bp. The number of sequences annotated by searching protein and gene ontology databases was 10,465. The average coverage of the annotated isotigs was x40 containing 5655 unique gene IDs and 785 full-length cDNAs coding for proteins containing 58–1536 amino acids. The v2.5 assembly was found to be of good quality based on validation using 200 full-length cDNAs from GenBank. Annotated isotigs from the reference transcriptome were attributable to 344 KEGG pathway maps. We identified 26 gene paralogues (20 of them teleost-specific) and 43 splice variants, of which 12 had functional domains missing that were likely to affect their biological function. Many key transcription factors, signaling molecules and structural proteins necessary for myogenesis and muscle growth have been identified. Physiological status affected the number of reads that mapped to isotigs, reflecting changes in gene expression between treatments. Conclusions: We have produced a comprehensive fast skeletal muscle transcriptome for the gilthead sea bream, which will provide a resource for SNP discovery in genes with a large effect on production traits of commercial interest and for expression studies of growth and adaptation.</description>
      <pubDate>Fri, 11 May 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3046</guid>
      <dc:date>2012-05-11T00:00:00Z</dc:date>
      <dc:creator>Garcia de la Serrana Castillo, Daniel</dc:creator>
      <dc:creator>Estevez, Alicia</dc:creator>
      <dc:creator>Andree, Karl</dc:creator>
      <dc:creator>Johnston, Ian Alistair</dc:creator>
      <dc:description>Background: The gilthead sea bream (Sparus aurata L.) occurs around the Mediterranean and along Eastern Atlantic coasts from Great Britain to Senegal. It is tolerant of a wide range of temperatures and salinities and is often found in brackish coastal lagoons and estuarine areas, particularly early in its life cycle. Gilthead sea bream are extensively cultivated in the Mediterranean with an annual production of 125,000 metric tonnes. Here we present a de novo assembly of the fast skeletal muscle transcriptome of gilthead sea bream using 454 reads and identify gene paralogues, splice variants and microsatellite repeats. An annotated transcriptome of the skeletal muscle will facilitate understanding of the genetic and molecular basis of traits linked to production in this economically important species. Results: Around 2.7 million reads of mRNA sequence data were generated from the fast myotomal of adult fish (~2 kg) and juvenile fish (~0.09 kg) that had been either fed to satiation, fasted for 3-5d or transferred to low (11°C) or high (33°C) temperatures for 3-5d. Newbler v2.5 assembly resulted in 43,461 isotigs &gt;100 bp. The number of sequences annotated by searching protein and gene ontology databases was 10,465. The average coverage of the annotated isotigs was x40 containing 5655 unique gene IDs and 785 full-length cDNAs coding for proteins containing 58–1536 amino acids. The v2.5 assembly was found to be of good quality based on validation using 200 full-length cDNAs from GenBank. Annotated isotigs from the reference transcriptome were attributable to 344 KEGG pathway maps. We identified 26 gene paralogues (20 of them teleost-specific) and 43 splice variants, of which 12 had functional domains missing that were likely to affect their biological function. Many key transcription factors, signaling molecules and structural proteins necessary for myogenesis and muscle growth have been identified. Physiological status affected the number of reads that mapped to isotigs, reflecting changes in gene expression between treatments. Conclusions: We have produced a comprehensive fast skeletal muscle transcriptome for the gilthead sea bream, which will provide a resource for SNP discovery in genes with a large effect on production traits of commercial interest and for expression studies of growth and adaptation.</dc:description>
    </item>
    <item>
      <title>ALDH2 mediates 5-nitrofuran activity in multiple species</title>
      <link>http://hdl.handle.net/10023/3043</link>
      <description>Abstract: Understanding how drugs work in vivo is critical for drug design and for maximizing the potential of currently available drugs. 5-nitrofurans are a class of pro-drugs widely used to treat bacterial and trypanosome infections, but despite relative specificity 5-nitrofurans often cause serious toxic side-effects in people. Here, we use yeast, zebrafish and human in vitro systems to assess the biological activity of 5-nitrofurans, and identify a conserved interaction between aldehyde dehydrogenase (ALDH) 2 and 5-nitrofurans across these species. In addition, we show that the activity of nifurtimox, a 5-nitrofuran anti-trypanosome pro-drug, is dependent on zebrafish Aldh2 and that nifurtimox is a substrate for human ALDH2. This study reveals a conserved and biologically relevant ALDH2-5-nitrofuran interaction that may have important implications for managing the toxicity of 5nitrofuran treatment.</description>
      <pubDate>Fri, 27 Jul 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3043</guid>
      <dc:date>2012-07-27T00:00:00Z</dc:date>
      <dc:creator>Zhou, Linna</dc:creator>
      <dc:creator>Ishizaki, Hironori</dc:creator>
      <dc:creator>Spitzer, Michaela</dc:creator>
      <dc:creator>Taylor, Kerrie</dc:creator>
      <dc:creator>Temperley, Nicholas</dc:creator>
      <dc:creator>Johnson, Stephen</dc:creator>
      <dc:creator>Brear, Paul</dc:creator>
      <dc:creator>Gautier, Philippe</dc:creator>
      <dc:creator>Zeng, Zhiqiang</dc:creator>
      <dc:creator>Mitchell, Amy</dc:creator>
      <dc:creator>Narayan, Vikram</dc:creator>
      <dc:creator>McNeil, Ewan</dc:creator>
      <dc:creator>Melton, David</dc:creator>
      <dc:creator>Smith, Terry K</dc:creator>
      <dc:creator>Tyers, Mike</dc:creator>
      <dc:creator>Westwood, Nicholas James</dc:creator>
      <dc:creator>Patton, Elizabeth</dc:creator>
      <dc:description>Understanding how drugs work in vivo is critical for drug design and for maximizing the potential of currently available drugs. 5-nitrofurans are a class of pro-drugs widely used to treat bacterial and trypanosome infections, but despite relative specificity 5-nitrofurans often cause serious toxic side-effects in people. Here, we use yeast, zebrafish and human in vitro systems to assess the biological activity of 5-nitrofurans, and identify a conserved interaction between aldehyde dehydrogenase (ALDH) 2 and 5-nitrofurans across these species. In addition, we show that the activity of nifurtimox, a 5-nitrofuran anti-trypanosome pro-drug, is dependent on zebrafish Aldh2 and that nifurtimox is a substrate for human ALDH2. This study reveals a conserved and biologically relevant ALDH2-5-nitrofuran interaction that may have important implications for managing the toxicity of 5nitrofuran treatment.</dc:description>
    </item>
    <item>
      <title>In and out of Madagascar : dispersal to peripheral islands, insular speciation and diversification of Indian Ocean daisy trees (Psiadia, Asteraceae)</title>
      <link>http://hdl.handle.net/10023/3042</link>
      <description>Abstract: Madagascar is surrounded by archipelagos varying widely in origin, age and structure. Although small and geologically young, these archipelagos have accumulated disproportionate numbers of unique lineages in comparison to Madagascar, highlighting the role of waif-dispersal and rapid in situ diversification processes in generating endemic biodiversity. We reconstruct the evolutionary and biogeographical history of the genus Psiadia (Asteraceae), a plant genus with near equal numbers of species in Madagascar and surrounding islands. Analyzing patterns and processes of diversification, we explain species accumulation on peripheral islands and aim to offer new insights on the origin and potential causes for diversification in the Madagascar and Indian Ocean Islands biodiversity hotspot. Our results provide support for an African origin of the group, with strong support for non-monophyly. Colonization of the Mascarenes took place by two evolutionary distinct lineages from Madagascar, via two independent dispersal events, each unique for their spatial and temporal properties. Significant shifts in diversification rate followed regional expansion, resulting in co-occurring and phenotypically convergent species on high-elevation volcanic slopes. Like other endemic island lineages, Psiadia have been highly successful in dispersing to and radiating on isolated oceanic islands, typified by high habitat diversity and dynamic ecosystems fuelled by continued geological activity. Results stress the important biogeographical role for Rodrigues in serving as an outlying stepping stone from which regional colonization took place. We discuss how isolated volcanic islands contribute to regional diversity by generating substantial numbers of endemic species on short temporal scales. Factors pertaining to the mode and tempo of archipelago formation and its geographical isolation strongly govern evolutionary pathways available for species diversification, and the potential for successful diversification of dispersed lineages, therefore, appears highly dependent on the timing of arrival, as habitat and resource properties change dramatically over the course of oceanic island evolution.</description>
      <pubDate>Fri, 10 Aug 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3042</guid>
      <dc:date>2012-08-10T00:00:00Z</dc:date>
      <dc:creator>Strijk, Joeri S</dc:creator>
      <dc:creator>Noyes, Richard D</dc:creator>
      <dc:creator>Strasberg, Dominique</dc:creator>
      <dc:creator>Cruaud, Corinne</dc:creator>
      <dc:creator>Gavory, Frederic</dc:creator>
      <dc:creator>Chase, Mark W</dc:creator>
      <dc:creator>Abbott, Richard John</dc:creator>
      <dc:creator>Thebaud, Christophe</dc:creator>
      <dc:description>Madagascar is surrounded by archipelagos varying widely in origin, age and structure. Although small and geologically young, these archipelagos have accumulated disproportionate numbers of unique lineages in comparison to Madagascar, highlighting the role of waif-dispersal and rapid in situ diversification processes in generating endemic biodiversity. We reconstruct the evolutionary and biogeographical history of the genus Psiadia (Asteraceae), a plant genus with near equal numbers of species in Madagascar and surrounding islands. Analyzing patterns and processes of diversification, we explain species accumulation on peripheral islands and aim to offer new insights on the origin and potential causes for diversification in the Madagascar and Indian Ocean Islands biodiversity hotspot. Our results provide support for an African origin of the group, with strong support for non-monophyly. Colonization of the Mascarenes took place by two evolutionary distinct lineages from Madagascar, via two independent dispersal events, each unique for their spatial and temporal properties. Significant shifts in diversification rate followed regional expansion, resulting in co-occurring and phenotypically convergent species on high-elevation volcanic slopes. Like other endemic island lineages, Psiadia have been highly successful in dispersing to and radiating on isolated oceanic islands, typified by high habitat diversity and dynamic ecosystems fuelled by continued geological activity. Results stress the important biogeographical role for Rodrigues in serving as an outlying stepping stone from which regional colonization took place. We discuss how isolated volcanic islands contribute to regional diversity by generating substantial numbers of endemic species on short temporal scales. Factors pertaining to the mode and tempo of archipelago formation and its geographical isolation strongly govern evolutionary pathways available for species diversification, and the potential for successful diversification of dispersed lineages, therefore, appears highly dependent on the timing of arrival, as habitat and resource properties change dramatically over the course of oceanic island evolution.</dc:description>
    </item>
    <item>
      <title>How selection structures species abundance distributions</title>
      <link>http://hdl.handle.net/10023/3030</link>
      <description>Abstract: How do species divide resources to produce the characteristic species abundance distributions seen in nature? One way to resolve this problem is to examine how the biomass (or capacity) of the spatial guilds that combine to produce an abundance distribution is allocated among species. Here we argue that selection on body size varies across guilds occupying spatially distinct habitats. Using an exceptionally well-characterized estuarine fish community, we show that biomass is concentrated in large bodied species in guilds where habitat structure provides protection from predators, but not in those guilds associated with open habitats and where safety in numbers is a mechanism for reducing predation risk. We further demonstrate that while there is temporal turnover in the abundances and identities of species that comprise these guilds, guild rank order is conserved across our 30-year time series. These results demonstrate that ecological communities are not randomly assembled but can be decomposed into guilds where capacity is predictably allocated among species.</description>
      <pubDate>Sat, 22 Sep 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3030</guid>
      <dc:date>2012-09-22T00:00:00Z</dc:date>
      <dc:creator>Magurran, Anne E.</dc:creator>
      <dc:creator>Henderson, Peter A.</dc:creator>
      <dc:description>How do species divide resources to produce the characteristic species abundance distributions seen in nature? One way to resolve this problem is to examine how the biomass (or capacity) of the spatial guilds that combine to produce an abundance distribution is allocated among species. Here we argue that selection on body size varies across guilds occupying spatially distinct habitats. Using an exceptionally well-characterized estuarine fish community, we show that biomass is concentrated in large bodied species in guilds where habitat structure provides protection from predators, but not in those guilds associated with open habitats and where safety in numbers is a mechanism for reducing predation risk. We further demonstrate that while there is temporal turnover in the abundances and identities of species that comprise these guilds, guild rank order is conserved across our 30-year time series. These results demonstrate that ecological communities are not randomly assembled but can be decomposed into guilds where capacity is predictably allocated among species.</dc:description>
    </item>
    <item>
      <title>Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebrates</title>
      <link>http://hdl.handle.net/10023/3022</link>
      <description>Abstract: 14-3-3 proteins regulate cellular responses to stimuli by docking onto pairs of phosphorylated residues on target proteins. The present study shows that the human 14-3-3-binding phosphoproteome is highly enriched in 2R-ohnologues, which are proteins in families of two to four members that were generated by two rounds of whole genome duplication at the origin of the vertebrates. We identify 2R-ohnologue families whose members share a ‘lynchpin’, defined as a 14-3-3-binding phosphosite that is conserved across members of a given family, and aligns with a Ser/Thr residue in pro-orthologues from the invertebrate chordates. For example, the human receptor expression enhancing protein (REEP) 1–4 family has the commonest type of lynchpin motif in current datasets, with a phosphorylatable serine in the –2 position relative to the 14-3-3-binding phosphosite. In contrast, the second 14-3-3-binding sites of REEPs 1–4 differ and are phosphorylated by different kinases, and hence the REEPs display different affinities for 14-3-3 dimers. We suggest a conceptual model for intracellular regulation involving protein families whose evolution into signal multiplexing systems was facilitated by 14-3-3 dimer binding to lynchpins, which gave freedom for other regulatory sites to evolve. While increased signalling complexity was needed for vertebrate life, these systems also generate vulnerability to genetic disorders.</description>
      <pubDate>Sun, 01 Jul 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3022</guid>
      <dc:date>2012-07-01T00:00:00Z</dc:date>
      <dc:creator>Tinti, Michele</dc:creator>
      <dc:creator>Johnson, Catherine</dc:creator>
      <dc:creator>Toth, Rachel</dc:creator>
      <dc:creator>Ferrier, David Ellard Keith</dc:creator>
      <dc:creator>MacKintosh, Carol</dc:creator>
      <dc:description>14-3-3 proteins regulate cellular responses to stimuli by docking onto pairs of phosphorylated residues on target proteins. The present study shows that the human 14-3-3-binding phosphoproteome is highly enriched in 2R-ohnologues, which are proteins in families of two to four members that were generated by two rounds of whole genome duplication at the origin of the vertebrates. We identify 2R-ohnologue families whose members share a ‘lynchpin’, defined as a 14-3-3-binding phosphosite that is conserved across members of a given family, and aligns with a Ser/Thr residue in pro-orthologues from the invertebrate chordates. For example, the human receptor expression enhancing protein (REEP) 1–4 family has the commonest type of lynchpin motif in current datasets, with a phosphorylatable serine in the –2 position relative to the 14-3-3-binding phosphosite. In contrast, the second 14-3-3-binding sites of REEPs 1–4 differ and are phosphorylated by different kinases, and hence the REEPs display different affinities for 14-3-3 dimers. We suggest a conceptual model for intracellular regulation involving protein families whose evolution into signal multiplexing systems was facilitated by 14-3-3 dimer binding to lynchpins, which gave freedom for other regulatory sites to evolve. While increased signalling complexity was needed for vertebrate life, these systems also generate vulnerability to genetic disorders.</dc:description>
    </item>
    <item>
      <title>Incipient speciation in Drosophila melanogaster involves chemical signals</title>
      <link>http://hdl.handle.net/10023/3011</link>
      <description>Abstract: The sensory and genetic bases of incipient speciation between strains of Drosophila melanogaster from Zimbabwe and those from elsewhere are unknown. We studied mating behaviour between eight strains - six from Zimbabwe, together with two cosmopolitan strains. The Zimbabwe strains showed significant sexual isolation when paired with cosmopolitan males, due to Zimbabwe females discriminating against these males. Our results show that flies' cuticular hydrocarbons (CHs) were involved in this sexual isolation, but that visual and acoustic signals were not. The mating frequency of Zimbabwe females was highly significantly negatively correlated with the male's relative amount of 7-tricosene (%7-T), while the mating of cosmopolitan females was positively correlated with %7-T. Variation in transcription levels of two hydrocarbon-determining genes, desat1 and desat2, did not correlate with the observed mating patterns. Our study represents a step forward in our understanding of the sensory processes involved in this classic case of incipient speciation.</description>
      <pubDate>Thu, 19 Jan 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3011</guid>
      <dc:date>2012-01-19T00:00:00Z</dc:date>
      <dc:creator>Grillet, Micheline</dc:creator>
      <dc:creator>Everaerts, Claude</dc:creator>
      <dc:creator>Houot, Benjamin</dc:creator>
      <dc:creator>Ritchie, Michael G.</dc:creator>
      <dc:creator>Cobb, Matthew</dc:creator>
      <dc:creator>Ferveur, Jean-Francois</dc:creator>
      <dc:description>The sensory and genetic bases of incipient speciation between strains of Drosophila melanogaster from Zimbabwe and those from elsewhere are unknown. We studied mating behaviour between eight strains - six from Zimbabwe, together with two cosmopolitan strains. The Zimbabwe strains showed significant sexual isolation when paired with cosmopolitan males, due to Zimbabwe females discriminating against these males. Our results show that flies' cuticular hydrocarbons (CHs) were involved in this sexual isolation, but that visual and acoustic signals were not. The mating frequency of Zimbabwe females was highly significantly negatively correlated with the male's relative amount of 7-tricosene (%7-T), while the mating of cosmopolitan females was positively correlated with %7-T. Variation in transcription levels of two hydrocarbon-determining genes, desat1 and desat2, did not correlate with the observed mating patterns. Our study represents a step forward in our understanding of the sensory processes involved in this classic case of incipient speciation.</dc:description>
    </item>
    <item>
      <title>Temperature, age of mating and starvation determine the role of maternal effects on sex allocation in the mealybug Planococcus citri</title>
      <link>http://hdl.handle.net/10023/3007</link>
      <description>Abstract: Environmental effects on sex allocation are common, yet the evolutionary significance of these effects remains poorly understood. Environmental effects might influence parents, such that their condition directly influences sex allocation by altering the relative benefits of producing sons versus daughters. Alternatively, the environment might influence the offspring themselves, such that the conditions they find themselves in influence their contribution to parental fitness. In both cases, parents might be selected to bias their sex ratio according to the prevailing environmental conditions. Here, we consider sex allocation in the citrus mealybug Planococcus citri, a species with an unusual genetic system in which paternal genes are lost from the germline in males. We test environmental factors that may influence either female condition directly (rearing temperature and food restriction) or that may be used as cues of the future environment (age at mating). Using cytological techniques to obtain primary sex ratios, we show that high temperature, older age at mating and starvation all affect sex allocation, resulting in female-biased sex ratios. However, the effect of temperature is rather weak, and food restriction appears to be strongly associated with reduced longevity and a truncation of the usual schedule of male and offspring production across a female's reproductive lifetime. Instead, facultative sex allocation seems most convincingly affected by age at mating, supporting previous work that suggests that social interactions experienced by adult P. citri females are used when allocating sex. Our results highlight that, even within one species, different aspects of the environment may have conflicting effects on sex allocation.</description>
      <pubDate>Sun, 01 May 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3007</guid>
      <dc:date>2011-05-01T00:00:00Z</dc:date>
      <dc:creator>Ross, Laura</dc:creator>
      <dc:creator>Dealey, Elizabeth J.</dc:creator>
      <dc:creator>Beukeboom, Leo W.</dc:creator>
      <dc:creator>Shuker, David M.</dc:creator>
      <dc:description>Environmental effects on sex allocation are common, yet the evolutionary significance of these effects remains poorly understood. Environmental effects might influence parents, such that their condition directly influences sex allocation by altering the relative benefits of producing sons versus daughters. Alternatively, the environment might influence the offspring themselves, such that the conditions they find themselves in influence their contribution to parental fitness. In both cases, parents might be selected to bias their sex ratio according to the prevailing environmental conditions. Here, we consider sex allocation in the citrus mealybug Planococcus citri, a species with an unusual genetic system in which paternal genes are lost from the germline in males. We test environmental factors that may influence either female condition directly (rearing temperature and food restriction) or that may be used as cues of the future environment (age at mating). Using cytological techniques to obtain primary sex ratios, we show that high temperature, older age at mating and starvation all affect sex allocation, resulting in female-biased sex ratios. However, the effect of temperature is rather weak, and food restriction appears to be strongly associated with reduced longevity and a truncation of the usual schedule of male and offspring production across a female's reproductive lifetime. Instead, facultative sex allocation seems most convincingly affected by age at mating, supporting previous work that suggests that social interactions experienced by adult P. citri females are used when allocating sex. Our results highlight that, even within one species, different aspects of the environment may have conflicting effects on sex allocation.</dc:description>
    </item>
    <item>
      <title>How reproductive ecology contributes to the spread of a globally invasive fish</title>
      <link>http://hdl.handle.net/10023/3006</link>
      <description>Abstract: Invasive freshwater fish represent a major threat to biodiversity. Here, we first demonstrate the dramatic, human-mediated range expansion of the Trinidadian guppy (Poecilia reticulata), an invasive fish with a reputation for negatively impacting native freshwater communities. Next, we explore possible mechanisms that might explain successful global establishment of this species. Guppies, along with some other notable invasive fish species such as mosquitofish (Gambusia spp.), have reproductive adaptations to ephemeral habitats that may enable introductions of very small numbers of founders to succeed. The remarkable ability of single pregnant guppies to routinely establish viable populations is demonstrated using a replicated mesocosm set up. In 86% of cases, these populations persisted for two years (the duration of the experiment). Establishment success was independent of founder origin (high and low predation habitats), and there was no loss of behavioural performance amongst mesocosm juveniles. Behavioural "signatures" of the founding locality were, however, evident in mesocosm fish. Our results demonstrate that introductions consisting of a single individual can lead to thriving populations of this invasive fish and suggest that particular caution should be exercised when introducing this species, or other livebearers, to natural water bodies.
Description: The work was funded by Natural Environment Research Council (NERC) (UK) and the European Research Council.</description>
      <pubDate>Mon, 19 Sep 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3006</guid>
      <dc:date>2011-09-19T00:00:00Z</dc:date>
      <dc:creator>Deacon, Amy E.</dc:creator>
      <dc:creator>Ramnarine, Indar W.</dc:creator>
      <dc:creator>Magurran, Anne E.</dc:creator>
      <dc:description>Invasive freshwater fish represent a major threat to biodiversity. Here, we first demonstrate the dramatic, human-mediated range expansion of the Trinidadian guppy (Poecilia reticulata), an invasive fish with a reputation for negatively impacting native freshwater communities. Next, we explore possible mechanisms that might explain successful global establishment of this species. Guppies, along with some other notable invasive fish species such as mosquitofish (Gambusia spp.), have reproductive adaptations to ephemeral habitats that may enable introductions of very small numbers of founders to succeed. The remarkable ability of single pregnant guppies to routinely establish viable populations is demonstrated using a replicated mesocosm set up. In 86% of cases, these populations persisted for two years (the duration of the experiment). Establishment success was independent of founder origin (high and low predation habitats), and there was no loss of behavioural performance amongst mesocosm juveniles. Behavioural "signatures" of the founding locality were, however, evident in mesocosm fish. Our results demonstrate that introductions consisting of a single individual can lead to thriving populations of this invasive fish and suggest that particular caution should be exercised when introducing this species, or other livebearers, to natural water bodies.</dc:description>
    </item>
    <item>
      <title>The quantitative genetic basis of sex ratio variation in Nasonia vitripennis : a QTL study</title>
      <link>http://hdl.handle.net/10023/3005</link>
      <description>Abstract: Our understanding of how natural selection should shape sex allocation is perhaps more developed than for any other trait. However, this understanding is not matched by our knowledge of the genetic basis of sex allocation. Here, we examine the genetic basis of sex ratio variation in the parasitoid wasp Nasonia vitripennis, a species well known for its response to local mate competition (LMC). We identified a quantitative trait locus (QTL) for sex ratio on chromosome 2 and three weaker QTL on chromosomes 3 and 5. We tested predictions that genes associated with sex ratio should be pleiotropic for other traits by seeing if sex ratio QTL co-occurred with clutch size QTL. We found one clutch size QTL on chromosome 1, and six weaker QTL across chromosomes 2, 3 and 5, with some overlap to regions associated with sex ratio. The results suggest rather limited scope for pleiotropy between these traits.</description>
      <pubDate>Sat, 01 Jan 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3005</guid>
      <dc:date>2011-01-01T00:00:00Z</dc:date>
      <dc:creator>Pannebakker, B. A.</dc:creator>
      <dc:creator>Watt, R.</dc:creator>
      <dc:creator>Knott, S. A.</dc:creator>
      <dc:creator>West, S. A.</dc:creator>
      <dc:creator>Shuker, D. M.</dc:creator>
      <dc:description>Our understanding of how natural selection should shape sex allocation is perhaps more developed than for any other trait. However, this understanding is not matched by our knowledge of the genetic basis of sex allocation. Here, we examine the genetic basis of sex ratio variation in the parasitoid wasp Nasonia vitripennis, a species well known for its response to local mate competition (LMC). We identified a quantitative trait locus (QTL) for sex ratio on chromosome 2 and three weaker QTL on chromosomes 3 and 5. We tested predictions that genes associated with sex ratio should be pleiotropic for other traits by seeing if sex ratio QTL co-occurred with clutch size QTL. We found one clutch size QTL on chromosome 1, and six weaker QTL across chromosomes 2, 3 and 5, with some overlap to regions associated with sex ratio. The results suggest rather limited scope for pleiotropy between these traits.</dc:description>
    </item>
    <item>
      <title>Phocid seal leptin : tertiary structure and hydrophobic receptor binding site preservation during distinct leptin gene evolution</title>
      <link>http://hdl.handle.net/10023/3003</link>
      <description>Abstract: The cytokine hormone leptin is a key signalling molecule in many pathways that control physiological functions. Although leptin demonstrates structural conservation in mammals, there is evidence of positive selection in primates, lagomorphs and chiropterans. We previously reported that the leptin genes of the grey and harbour seals (phocids) have significantly diverged from other mammals. Therefore we further investigated the diversification of leptin in phocids, other marine mammals and terrestrial taxa by sequencing the leptin genes of representative species. Phylogenetic reconstruction revealed that leptin diversification was pronounced within the phocid seals with a high dN/dS ratio of 2.8, indicating positive selection. We found significant evidence of positive selection along the branch leading to the phocids, within the phocid clade, but not over the dataset as a whole. Structural predictions indicate that the individual residues under selection are away from the leptin receptor (LEPR) binding site. Predictions of the surface electrostatic potential indicate that phocid seal leptin is notably different to other mammalian leptins, including the otariids. Cloning the grey seal leptin binding domain of LEPR confirmed that this was structurally conserved. These data, viewed in toto, support a hypothesis that phocid leptin divergence is unlikely to have arisen by random mutation. Based upon these phylogenetic and structural assessments, and considering the comparative physiology and varying life histories among species, we postulate that the unique phocid diving behaviour has produced this selection pressure. The Phocidae includes some of the deepest diving species, yet have the least modified lung structure to cope with pressure and volume changes experienced at depth. Therefore, greater surfactant production is required to facilitate rapid lung re-inflation upon surfacing, while maintaining patent airways. We suggest that this additional surfactant requirement is met by the leptin pulmonary surfactant production pathway which normally appears only to function in the mammalian foetus.</description>
      <pubDate>Thu, 19 Apr 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3003</guid>
      <dc:date>2012-04-19T00:00:00Z</dc:date>
      <dc:creator>Hammond, John Anthony</dc:creator>
      <dc:creator>Hauton, Chris</dc:creator>
      <dc:creator>Bennett, Kimberley A.</dc:creator>
      <dc:creator>Hall, Ailsa Jane</dc:creator>
      <dc:description>The cytokine hormone leptin is a key signalling molecule in many pathways that control physiological functions. Although leptin demonstrates structural conservation in mammals, there is evidence of positive selection in primates, lagomorphs and chiropterans. We previously reported that the leptin genes of the grey and harbour seals (phocids) have significantly diverged from other mammals. Therefore we further investigated the diversification of leptin in phocids, other marine mammals and terrestrial taxa by sequencing the leptin genes of representative species. Phylogenetic reconstruction revealed that leptin diversification was pronounced within the phocid seals with a high dN/dS ratio of 2.8, indicating positive selection. We found significant evidence of positive selection along the branch leading to the phocids, within the phocid clade, but not over the dataset as a whole. Structural predictions indicate that the individual residues under selection are away from the leptin receptor (LEPR) binding site. Predictions of the surface electrostatic potential indicate that phocid seal leptin is notably different to other mammalian leptins, including the otariids. Cloning the grey seal leptin binding domain of LEPR confirmed that this was structurally conserved. These data, viewed in toto, support a hypothesis that phocid leptin divergence is unlikely to have arisen by random mutation. Based upon these phylogenetic and structural assessments, and considering the comparative physiology and varying life histories among species, we postulate that the unique phocid diving behaviour has produced this selection pressure. The Phocidae includes some of the deepest diving species, yet have the least modified lung structure to cope with pressure and volume changes experienced at depth. Therefore, greater surfactant production is required to facilitate rapid lung re-inflation upon surfacing, while maintaining patent airways. We suggest that this additional surfactant requirement is met by the leptin pulmonary surfactant production pathway which normally appears only to function in the mammalian foetus.</dc:description>
    </item>
    <item>
      <title>The multifunctional NS1 protein of influenza virus</title>
      <link>http://hdl.handle.net/10023/3001</link>
      <description>Abstract: The non-structural (NS1) protein of influenza A viruses is a non-essential virulence factor that has multiple accessory functions during viral infection. In recent years, the major role ascribed to NS1 has been its inhibition of host immune responses, especially the limitation of both interferon (IFN) production and the antiviral effects of IFN-induced proteins, such as dsRNA-dependent protein kinase R (PKR) and 2'5'-oligoadenylate synthetase (OAS)/RNase L. However, it is clear that NS1 also acts directly to modulate other important aspects of the virus replication cycle, including viral RNA replication, viral protein synthesis, and general host-cell physiology. Here, we review the current literature on this remarkably multifunctional viral protein. In the first part of this article, we summarize the basic biochemistry of NS1, in particular its synthesis, structure, and intracellular localization. We then discuss the various roles NS1 has in regulating viral replication mechanisms, host innate/adaptive immune responses, and cellular signalling pathways. We focus on the NS1-RNA and NS1-protein interactions that are fundamental to these processes, and highlight apparent strain-specific ways in which different NS1 proteins may act. In this regard, the contributions of certain NS1 functions to the pathogenicity of human and animal influenza A viruses are also discussed. Finally, we outline practical applications that future studies on NS1 may lead to, including the rational design and manufacture of influenza vaccines, the development of novel antiviral drugs, and the use of oncolytic influenza A viruses as potential anti-cancer agents.</description>
      <pubDate>Wed, 01 Oct 2008 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/3001</guid>
      <dc:date>2008-10-01T00:00:00Z</dc:date>
      <dc:creator>Hale, Benjamin Geoffrey</dc:creator>
      <dc:creator>Randall, Richard Edward</dc:creator>
      <dc:creator>Ortin, J</dc:creator>
      <dc:creator>Jackson, David</dc:creator>
      <dc:description>The non-structural (NS1) protein of influenza A viruses is a non-essential virulence factor that has multiple accessory functions during viral infection. In recent years, the major role ascribed to NS1 has been its inhibition of host immune responses, especially the limitation of both interferon (IFN) production and the antiviral effects of IFN-induced proteins, such as dsRNA-dependent protein kinase R (PKR) and 2'5'-oligoadenylate synthetase (OAS)/RNase L. However, it is clear that NS1 also acts directly to modulate other important aspects of the virus replication cycle, including viral RNA replication, viral protein synthesis, and general host-cell physiology. Here, we review the current literature on this remarkably multifunctional viral protein. In the first part of this article, we summarize the basic biochemistry of NS1, in particular its synthesis, structure, and intracellular localization. We then discuss the various roles NS1 has in regulating viral replication mechanisms, host innate/adaptive immune responses, and cellular signalling pathways. We focus on the NS1-RNA and NS1-protein interactions that are fundamental to these processes, and highlight apparent strain-specific ways in which different NS1 proteins may act. In this regard, the contributions of certain NS1 functions to the pathogenicity of human and animal influenza A viruses are also discussed. Finally, we outline practical applications that future studies on NS1 may lead to, including the rational design and manufacture of influenza vaccines, the development of novel antiviral drugs, and the use of oncolytic influenza A viruses as potential anti-cancer agents.</dc:description>
    </item>
    <item>
      <title>Clasp-mediated microtubule bundling regulates persistent motility and contact repulsion in Drosophila macrophages in vivo</title>
      <link>http://hdl.handle.net/10023/2999</link>
      <description>Abstract: Drosophila melanogaster macrophages are highly migratory cells that lend themselves beautifully to high resolution in vivo imaging experiments. By expressing fluorescent probes to reveal actin and microtubules, we can observe the dynamic interplay of these two cytoskeletal networks as macrophages migrate and interact with one another within a living organism. We show that before an episode of persistent motility, whether responding to developmental guidance or wound cues, macrophages assemble a polarized array of microtubules that bundle into a compass-like arm that appears to anticipate the direction of migration. Whenever cells collide with one another, their microtubule arms transiently align just before cell–cell repulsion, and we show that forcing depolymerization of microtubules by expression of Spastin leads to their defective polarity and failure to contact inhibit from one another. The same is true in orbit/clasp mutants, indicating a pivotal role for this microtubule-binding protein in the assembly and/or functioning of the microtubule arm during polarized migration and contact repulsion.
Description: P. Martin and W. Wood contributed equally to this paper</description>
      <pubDate>Mon, 17 May 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2999</guid>
      <dc:date>2010-05-17T00:00:00Z</dc:date>
      <dc:creator>Stramer, Brian</dc:creator>
      <dc:creator>Moreira, Severina</dc:creator>
      <dc:creator>Millard, Tom</dc:creator>
      <dc:creator>Evans, Iwan</dc:creator>
      <dc:creator>Huang, Chieh-Yin</dc:creator>
      <dc:creator>Sabet, Ola</dc:creator>
      <dc:creator>Milner, Martin John</dc:creator>
      <dc:creator>Dunn, Graham</dc:creator>
      <dc:creator>Martin, Paul</dc:creator>
      <dc:creator>Wood, Will</dc:creator>
      <dc:description>Drosophila melanogaster macrophages are highly migratory cells that lend themselves beautifully to high resolution in vivo imaging experiments. By expressing fluorescent probes to reveal actin and microtubules, we can observe the dynamic interplay of these two cytoskeletal networks as macrophages migrate and interact with one another within a living organism. We show that before an episode of persistent motility, whether responding to developmental guidance or wound cues, macrophages assemble a polarized array of microtubules that bundle into a compass-like arm that appears to anticipate the direction of migration. Whenever cells collide with one another, their microtubule arms transiently align just before cell–cell repulsion, and we show that forcing depolymerization of microtubules by expression of Spastin leads to their defective polarity and failure to contact inhibit from one another. The same is true in orbit/clasp mutants, indicating a pivotal role for this microtubule-binding protein in the assembly and/or functioning of the microtubule arm during polarized migration and contact repulsion.</dc:description>
    </item>
    <item>
      <title>Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase</title>
      <link>http://hdl.handle.net/10023/2997</link>
      <description>Abstract: Influenza virus sialidase has an essential role in the virus’ life cycle. Two distinct groups of influenza A virus sialidases have been established, that differ in the flexibility of the ‘150-loop’, providing a more open active site in the apo form of the group-1 compared to group-2 enzymes. In this study we show, through a multidisciplinary approach, that novel sialic acid-based derivatives can exploit this structural difference and selectively inhibit the activity of group-1 sialidases. We also demonstrate that group-1 sialidases from drug-resistant mutant influenza viruses are sensitive to these designed compounds. Moreover, we have determined, by protein X-ray crystallography, that these inhibitors lock open the group-1 sialidase flexible 150-loop, in agreement with our molecular modelling prediction. This is the first direct proof that compounds may be developed to selectively target the pandemic A/H1N1, avian A/H5N1 and other group-1 sialidase-containing viruses, based on an open 150-loop conformation of the enzyme.
Description: This work was supported by the Medical Research Council and the Scottish Funding Council.</description>
      <pubDate>Tue, 16 Nov 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2997</guid>
      <dc:date>2010-11-16T00:00:00Z</dc:date>
      <dc:creator>Rudrawar, S</dc:creator>
      <dc:creator>Dyason, JC</dc:creator>
      <dc:creator>Rameix-Welti, MA</dc:creator>
      <dc:creator>Rose, FJ</dc:creator>
      <dc:creator>Kerry, Philip Stephen</dc:creator>
      <dc:creator>Russell, Rupert James Martin</dc:creator>
      <dc:creator>van der Werf, S</dc:creator>
      <dc:creator>Thomson, RJ</dc:creator>
      <dc:creator>Naffakh, N</dc:creator>
      <dc:creator>von Itzstein, M</dc:creator>
      <dc:description>Influenza virus sialidase has an essential role in the virus’ life cycle. Two distinct groups of influenza A virus sialidases have been established, that differ in the flexibility of the ‘150-loop’, providing a more open active site in the apo form of the group-1 compared to group-2 enzymes. In this study we show, through a multidisciplinary approach, that novel sialic acid-based derivatives can exploit this structural difference and selectively inhibit the activity of group-1 sialidases. We also demonstrate that group-1 sialidases from drug-resistant mutant influenza viruses are sensitive to these designed compounds. Moreover, we have determined, by protein X-ray crystallography, that these inhibitors lock open the group-1 sialidase flexible 150-loop, in agreement with our molecular modelling prediction. This is the first direct proof that compounds may be developed to selectively target the pandemic A/H1N1, avian A/H5N1 and other group-1 sialidase-containing viruses, based on an open 150-loop conformation of the enzyme.</dc:description>
    </item>
    <item>
      <title>Conservation of a crystallographic interface suggests a role for beta-sheet augmentation in influenza virus NS1 multifunctionality</title>
      <link>http://hdl.handle.net/10023/2996</link>
      <description>Abstract: The effector domain (ED) of the influenza virus virulence factor NS1 is capable of interaction with a variety of cellular and viral targets, although regulation of these events is poorly understood. Introduction of a W187A mutation into the ED abolishes dimer formation; however, strand-strand interactions between mutant NS1 ED monomers have been observed in two previous crystal forms. A new condition for crystallization of this protein [0.1 M Bis-Tris pH 6.0, 0.2 M NaCl, 22%(w/v) PEG 3350, 20 mM xylitol] was discovered using the hanging-drop vapour-diffusion method. Diffraction data extending to 1.8 Å resolution were collected from a crystal grown in the presence of 40 mM thieno[2,3-b]pyridin-2-ylmethanol. It was observed that there is conservation of the strand-strand interface in crystals of this monomeric NS1 ED in three different space groups. This observation, coupled with conformational changes in the interface region, suggests a potential role for [beta]-sheet augmentation in NS1 function.
Description: This research was supported by grants from the Medical Research Council (MRC) and the Scottish Funding Council (SFC).</description>
      <pubDate>Mon, 01 Aug 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2996</guid>
      <dc:date>2011-08-01T00:00:00Z</dc:date>
      <dc:creator>Kerry, Philip Stephen</dc:creator>
      <dc:creator>Long, E</dc:creator>
      <dc:creator>Taylor, Margaret Alexandra</dc:creator>
      <dc:creator>Russell, Rupert James Martin</dc:creator>
      <dc:description>The effector domain (ED) of the influenza virus virulence factor NS1 is capable of interaction with a variety of cellular and viral targets, although regulation of these events is poorly understood. Introduction of a W187A mutation into the ED abolishes dimer formation; however, strand-strand interactions between mutant NS1 ED monomers have been observed in two previous crystal forms. A new condition for crystallization of this protein [0.1 M Bis-Tris pH 6.0, 0.2 M NaCl, 22%(w/v) PEG 3350, 20 mM xylitol] was discovered using the hanging-drop vapour-diffusion method. Diffraction data extending to 1.8 Å resolution were collected from a crystal grown in the presence of 40 mM thieno[2,3-b]pyridin-2-ylmethanol. It was observed that there is conservation of the strand-strand interface in crystals of this monomeric NS1 ED in three different space groups. This observation, coupled with conformational changes in the interface region, suggests a potential role for [beta]-sheet augmentation in NS1 function.</dc:description>
    </item>
    <item>
      <title>The small genome segment of Bunyamwera orthobunyavirus harbours a single transcription-termination signal</title>
      <link>http://hdl.handle.net/10023/2884</link>
      <description>Abstract: Transcription termination of the mRNA produced from the small (S) genome segment of Bunyamwera orthobunyavirus (BUNV) has previously been mapped to two cis-acting sequences located within the 5′ UTR using a virus-free replication assay. The ability of these sequences to terminate transcription was attributed to the shared pentanucleotide motif 3′-UGUCG-5′. Taking advantage of our plasmid-based rescue system to generate recombinant viruses, we re-evaluated the importance of both pentanucleotide motifs as well as that of two other conserved sequences in transcription termination in vivo. Analysis of the 3′ ends of positive-stranded viral RNAs derived from the S segment revealed that only the region around the upstream pentanucleotide motif mediated transcription termination in cells infected with wild-type BUNV, leading to mRNAs that were about 100 nt shorter than antigenome RNA. Furthermore, the downstream motif was not recognized in recombinant viruses in which the upstream signal has been disrupted. Our results suggest that in the context of virus infection transcription termination of the BUNV S genome segment mRNA is exclusively directed by the upstream-termination signal. Interestingly, within this region we identified a motif similar to a transcription-termination sequence used by Rift Valley fever phlebovirus.</description>
      <pubDate>Sun, 01 Jul 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2884</guid>
      <dc:date>2012-07-01T00:00:00Z</dc:date>
      <dc:creator>Blakqori, Gjon</dc:creator>
      <dc:creator>Lowen, Anice C.</dc:creator>
      <dc:creator>Elliott, Richard Michael</dc:creator>
      <dc:description>Transcription termination of the mRNA produced from the small (S) genome segment of Bunyamwera orthobunyavirus (BUNV) has previously been mapped to two cis-acting sequences located within the 5′ UTR using a virus-free replication assay. The ability of these sequences to terminate transcription was attributed to the shared pentanucleotide motif 3′-UGUCG-5′. Taking advantage of our plasmid-based rescue system to generate recombinant viruses, we re-evaluated the importance of both pentanucleotide motifs as well as that of two other conserved sequences in transcription termination in vivo. Analysis of the 3′ ends of positive-stranded viral RNAs derived from the S segment revealed that only the region around the upstream pentanucleotide motif mediated transcription termination in cells infected with wild-type BUNV, leading to mRNAs that were about 100 nt shorter than antigenome RNA. Furthermore, the downstream motif was not recognized in recombinant viruses in which the upstream signal has been disrupted. Our results suggest that in the context of virus infection transcription termination of the BUNV S genome segment mRNA is exclusively directed by the upstream-termination signal. Interestingly, within this region we identified a motif similar to a transcription-termination sequence used by Rift Valley fever phlebovirus.</dc:description>
    </item>
    <item>
      <title>Bunyaviruses and the type I interferon system</title>
      <link>http://hdl.handle.net/10023/2882</link>
      <description>Abstract: The family Bunyaviridae contains more than 350 viruses that are distributed throughout the world. Most members of the family are transmitted by arthopods, and several cause disease in man, domesticated animals and crop plants. Despite being recognized as an emerging threat, details of the virulence mechanisms employed by bunyaviruses are scant. In this article we summarise the information currently available on how these viruses are able to establish infection when confronted with a powerful antiviral interferon system.</description>
      <pubDate>Mon, 23 Nov 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2882</guid>
      <dc:date>2009-11-23T00:00:00Z</dc:date>
      <dc:creator>Elliott, Richard Michael</dc:creator>
      <dc:creator>Weber, F</dc:creator>
      <dc:description>The family Bunyaviridae contains more than 350 viruses that are distributed throughout the world. Most members of the family are transmitted by arthopods, and several cause disease in man, domesticated animals and crop plants. Despite being recognized as an emerging threat, details of the virulence mechanisms employed by bunyaviruses are scant. In this article we summarise the information currently available on how these viruses are able to establish infection when confronted with a powerful antiviral interferon system.</dc:description>
    </item>
    <item>
      <title>Modeling distribution and abundance of Antarctic baleen whales using ships of opportunity</title>
      <link>http://hdl.handle.net/10023/2857</link>
      <description>Abstract: Information on animal abundance and distribution is at the cornerstone of many wildlife and conservation strategies. However, these data can be difficult and costly to obtain for cetacean species. The expense of sufficient ship time to conduct design-unbiased line transect surveys may be simply out of reach for researchers in many countries, which nonetheless grapple with problems of conservation of endangered species, by-catch of small cetaceans in commercial fisheries, and progression toward ecosystem-based fisheries management. Recently developed spatial modeling techniques show promise for estimating wildlife abundance using non-randomized surveys, but have yet to receive much field-testing in areas where designed surveys have also been conducted. Effort and sightings data were collected along 9 650 km of transects aboard ships of opportunity in the Southern Ocean during the austral summers of 2000 - 2001 and 2001 - 2002. Generalized additive models with generalized cross-validation were used to express heterogeneity of cetacean sightings as functions of spatial covariates. Models were used to map predicted densities and to estimate abundance of humpback, minke, and fin whales in the Drake Passage and along the Antarctic Peninsula. All species' distribution maps showed strong density gradients, which were robust to jackknife resampling when each of 14 trips was removed sequentially with replacement. Looped animations of model predictions of whale density illustrate uncertainty in distribution estimates in a way that is informative to non-scientists. The best abundance estimate for humpback whales was 1 829 (95% CI: 978- 3 422). Abundance of fin whales was 4 487 ( 95% CI: 1 326 - 15 179) and minke whales was 1,544 ( 95% CI: 1,221 - 1,953). These estimates agreed roughly with those reported from a designed survey conducted in the region during the previous austral summer. These estimates assumed that all animals on the trackline were detected, but preliminary results suggest that any negative bias due to violation of this assumption was likely small. Similarly, current methodological limitations prohibit inclusion of all known sources of uncertainty in the favored variance estimator. Meanwhile, our approach can be seen generally as an inexpensive pilot study to identify areas of predicted high density that could be targeted to: inform stratified designs for future line transect surveys, making them less expensive and more precise; increase efficiency of future photo-identification or biopsy studies; identify candidate time-area fisheries closures to minimize by-catch; or direct ecotourism activities. The techniques are likely to apply to areas where funding is limiting, where cetacean studies or wilderness-based tourism are just beginning, or in regions where even a very rough estimate of animal abundance is needed for conservation or management purposes.</description>
      <pubDate>Thu, 01 Jun 2006 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2857</guid>
      <dc:date>2006-06-01T00:00:00Z</dc:date>
      <dc:creator>Williams, Robert</dc:creator>
      <dc:creator>Hedley, Sharon L.</dc:creator>
      <dc:creator>Hammond, Philip S.</dc:creator>
      <dc:description>Information on animal abundance and distribution is at the cornerstone of many wildlife and conservation strategies. However, these data can be difficult and costly to obtain for cetacean species. The expense of sufficient ship time to conduct design-unbiased line transect surveys may be simply out of reach for researchers in many countries, which nonetheless grapple with problems of conservation of endangered species, by-catch of small cetaceans in commercial fisheries, and progression toward ecosystem-based fisheries management. Recently developed spatial modeling techniques show promise for estimating wildlife abundance using non-randomized surveys, but have yet to receive much field-testing in areas where designed surveys have also been conducted. Effort and sightings data were collected along 9 650 km of transects aboard ships of opportunity in the Southern Ocean during the austral summers of 2000 - 2001 and 2001 - 2002. Generalized additive models with generalized cross-validation were used to express heterogeneity of cetacean sightings as functions of spatial covariates. Models were used to map predicted densities and to estimate abundance of humpback, minke, and fin whales in the Drake Passage and along the Antarctic Peninsula. All species' distribution maps showed strong density gradients, which were robust to jackknife resampling when each of 14 trips was removed sequentially with replacement. Looped animations of model predictions of whale density illustrate uncertainty in distribution estimates in a way that is informative to non-scientists. The best abundance estimate for humpback whales was 1 829 (95% CI: 978- 3 422). Abundance of fin whales was 4 487 ( 95% CI: 1 326 - 15 179) and minke whales was 1,544 ( 95% CI: 1,221 - 1,953). These estimates agreed roughly with those reported from a designed survey conducted in the region during the previous austral summer. These estimates assumed that all animals on the trackline were detected, but preliminary results suggest that any negative bias due to violation of this assumption was likely small. Similarly, current methodological limitations prohibit inclusion of all known sources of uncertainty in the favored variance estimator. Meanwhile, our approach can be seen generally as an inexpensive pilot study to identify areas of predicted high density that could be targeted to: inform stratified designs for future line transect surveys, making them less expensive and more precise; increase efficiency of future photo-identification or biopsy studies; identify candidate time-area fisheries closures to minimize by-catch; or direct ecotourism activities. The techniques are likely to apply to areas where funding is limiting, where cetacean studies or wilderness-based tourism are just beginning, or in regions where even a very rough estimate of animal abundance is needed for conservation or management purposes.</dc:description>
    </item>
    <item>
      <title>Methods for investigating measurement error in cetacean line-transect surveys</title>
      <link>http://hdl.handle.net/10023/2856</link>
      <description>Abstract: Line-transect estimates of abundance generally assume that distances and angles to animals are measured without error. Biased distance measurements will lead to corresponding bias in abundance estimates. Efforts to address this have been made, but measuring distance to cetaceans at sea remains problematic. Four distance-estimation experiments were conducted to explore relationships between estimated and measured distance, Heteroscedasticity was found in all four cases. Preliminary evidence suggested that an observer differed in the ability to judge distance to fixed, continuously-visible cues and ephemeral, cetacean cues, which calls into the question the common practice of using marker buoys as cetacean proxies in distance-estimation experiments. Two studies found visual estimates to be positively biased, and two studies found reticule measurements to be negatively biased. Suitable correction factors were developed to address systematic bias from visual estimates, but these varied widely among observers and were sometimes non-linear. Errors in three studies showed positive skew, suggesting that ranges were overestimated to a larger degree than they were underestimated. if reticule and photogrammetric measurements yield log-normally distributed errors generally, then a least-squares regression will always overstimate the correction factor, underestimate range, and overestimate abundance. Photogrammetric methods to measure range to cetaceans performed well, and their use is encouraged. When measurements cannot be made to all sightings, however, it is recommended that experiements be conducted that generate sufficient sample size (of the target species, across typical survey conditions, and beyond the maximum range that most estimates will be made during the survey) to assess error distributions, examine evidence for non-linearity, and to consider inter-observer differences. Distance experiments, and training on survey protocols, and be conducted using ships of opportunity prior to the beginning of a dedicated survey, which would improve observer efficiency while reducing the costs of dedicated vessel time.</description>
      <pubDate>Mon, 26 Feb 2007 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2856</guid>
      <dc:date>2007-02-26T00:00:00Z</dc:date>
      <dc:creator>Williams, Robert</dc:creator>
      <dc:creator>Leaper, R</dc:creator>
      <dc:creator>Zerbini, AN</dc:creator>
      <dc:creator>Hammond, Philip Steven</dc:creator>
      <dc:description>Line-transect estimates of abundance generally assume that distances and angles to animals are measured without error. Biased distance measurements will lead to corresponding bias in abundance estimates. Efforts to address this have been made, but measuring distance to cetaceans at sea remains problematic. Four distance-estimation experiments were conducted to explore relationships between estimated and measured distance, Heteroscedasticity was found in all four cases. Preliminary evidence suggested that an observer differed in the ability to judge distance to fixed, continuously-visible cues and ephemeral, cetacean cues, which calls into the question the common practice of using marker buoys as cetacean proxies in distance-estimation experiments. Two studies found visual estimates to be positively biased, and two studies found reticule measurements to be negatively biased. Suitable correction factors were developed to address systematic bias from visual estimates, but these varied widely among observers and were sometimes non-linear. Errors in three studies showed positive skew, suggesting that ranges were overestimated to a larger degree than they were underestimated. if reticule and photogrammetric measurements yield log-normally distributed errors generally, then a least-squares regression will always overstimate the correction factor, underestimate range, and overestimate abundance. Photogrammetric methods to measure range to cetaceans performed well, and their use is encouraged. When measurements cannot be made to all sightings, however, it is recommended that experiements be conducted that generate sufficient sample size (of the target species, across typical survey conditions, and beyond the maximum range that most estimates will be made during the survey) to assess error distributions, examine evidence for non-linearity, and to consider inter-observer differences. Distance experiments, and training on survey protocols, and be conducted using ships of opportunity prior to the beginning of a dedicated survey, which would improve observer efficiency while reducing the costs of dedicated vessel time.</dc:description>
    </item>
    <item>
      <title>Global analysis of cetacean line-transect surveys : detecting trends in cetacean density</title>
      <link>http://hdl.handle.net/10023/2747</link>
      <description>Abstract: Measuring the effect of anthropogenic change on cetacean populations is hampered by our lack of understanding about population status and a lack of power in the available data to detect trends in abundance. Often long-term data from repeated surveys are lacking, and alternative approaches to trend detection must be considered. We utilised an existing database of line transect survey records to determine whether temporal trends could be detected when survey effort from around the world was combined. We extracted density estimates for 25 species and fitted generalised additive models (GAMs) to investigate whether taxonomic, spatial or methodological differences among systematic line-transect surveys affect estimates of density and whether we can identify temporal trends in the data once these factors are accounted for. The selected GAM consisted of 2 parts: an intercept term that was a complex interaction of taxonomic, spatial and methodological factors and a smooth temporal term with trends varying by family and ocean basin. We discuss the trends found and assess the suitability of published density estimates for detecting temporal trends using retrospective power analysis. In conclusion, increasing sample size through combining survey effort across a global scale does not necessarily result in sufficient power to detect trends because of the extent of variability across surveys, species and oceans. Instead, results from repeated dedicated surveys designed specifically for the species and geographical region of interest should be used to inform conservation and management.</description>
      <pubDate>Mon, 07 May 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2747</guid>
      <dc:date>2012-05-07T00:00:00Z</dc:date>
      <dc:creator>Jewell, Rebecca Lucy</dc:creator>
      <dc:creator>Thomas, Len</dc:creator>
      <dc:creator>Harris, Catriona M</dc:creator>
      <dc:creator>Kaschner, Kristin</dc:creator>
      <dc:creator>Wiff, Rodrigo Alexis</dc:creator>
      <dc:creator>Hammond, Philip Steven</dc:creator>
      <dc:creator>Quick, Nicola Jane</dc:creator>
      <dc:description>Measuring the effect of anthropogenic change on cetacean populations is hampered by our lack of understanding about population status and a lack of power in the available data to detect trends in abundance. Often long-term data from repeated surveys are lacking, and alternative approaches to trend detection must be considered. We utilised an existing database of line transect survey records to determine whether temporal trends could be detected when survey effort from around the world was combined. We extracted density estimates for 25 species and fitted generalised additive models (GAMs) to investigate whether taxonomic, spatial or methodological differences among systematic line-transect surveys affect estimates of density and whether we can identify temporal trends in the data once these factors are accounted for. The selected GAM consisted of 2 parts: an intercept term that was a complex interaction of taxonomic, spatial and methodological factors and a smooth temporal term with trends varying by family and ocean basin. We discuss the trends found and assess the suitability of published density estimates for detecting temporal trends using retrospective power analysis. In conclusion, increasing sample size through combining survey effort across a global scale does not necessarily result in sufficient power to detect trends because of the extent of variability across surveys, species and oceans. Instead, results from repeated dedicated surveys designed specifically for the species and geographical region of interest should be used to inform conservation and management.</dc:description>
    </item>
    <item>
      <title>Changes in intra-nuclear mobility of mature snRNPs provide a mechanism for splicing defects in Spinal Muscular Atrophy</title>
      <link>http://hdl.handle.net/10023/2743</link>
      <description>Abstract: It is becoming increasingly clear that defects in RNA metabolism can lead to disease. Spinal Muscular Atrophy (SMA), a leading genetic cause of infant mortality, results from insufficient amounts of survival motor neuron (SMN) protein. SMN is required for the biogenesis of snRNPs: essential components of the spliceosome. Splicing abnormalities have been detected in models of SMA but it is unclear how lowered SMN affects the fidelity of pre-mRNA splicing. We have examined the dynamics of mature snRNPs in cells depleted of SMN and demonstrated that SMN depletion increases the mobility of mature snRNPs within the nucleus. To dissect the molecular mechanism by which SMN deficiency affects intra-nuclear snRNP mobility, we employed a panel of inhibitors of different stages of pre-mRNA processing. This in vivo modeling demonstrates that snRNP mobility is altered directly as a result of impaired snRNP maturation. Current models of nuclear dynamics predict that sub-nuclear structures, including the spliceosome, form by self-organization mediated by stochastic interactions between their molecular components. Thus, alteration of the intra-nuclear mobility of snRNPs provides a molecular mechanism for splicing defects in SMA.
Description: This work was funded by the Wellcome Trust (grant ID WT078810MA)</description>
      <pubDate>Sun, 01 Apr 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2743</guid>
      <dc:date>2012-04-01T00:00:00Z</dc:date>
      <dc:creator>Clelland, Allyson Kara</dc:creator>
      <dc:creator>Bales, Alexandra Beatrice Elizabeth</dc:creator>
      <dc:creator>Sleeman, Judith Elizabeth</dc:creator>
      <dc:description>It is becoming increasingly clear that defects in RNA metabolism can lead to disease. Spinal Muscular Atrophy (SMA), a leading genetic cause of infant mortality, results from insufficient amounts of survival motor neuron (SMN) protein. SMN is required for the biogenesis of snRNPs: essential components of the spliceosome. Splicing abnormalities have been detected in models of SMA but it is unclear how lowered SMN affects the fidelity of pre-mRNA splicing. We have examined the dynamics of mature snRNPs in cells depleted of SMN and demonstrated that SMN depletion increases the mobility of mature snRNPs within the nucleus. To dissect the molecular mechanism by which SMN deficiency affects intra-nuclear snRNP mobility, we employed a panel of inhibitors of different stages of pre-mRNA processing. This in vivo modeling demonstrates that snRNP mobility is altered directly as a result of impaired snRNP maturation. Current models of nuclear dynamics predict that sub-nuclear structures, including the spliceosome, form by self-organization mediated by stochastic interactions between their molecular components. Thus, alteration of the intra-nuclear mobility of snRNPs provides a molecular mechanism for splicing defects in SMA.</dc:description>
    </item>
    <item>
      <title>Inbreeding and selection on sex ratio in the bark beetle Xylosandrus germanus</title>
      <link>http://hdl.handle.net/10023/2606</link>
      <description>Abstract: Background: Local Mate Competition (LMC) theory predicts a female should produce a more female-biased sex ratio if her sons compete with each other for mates. Because it provides quantitative predictions that can be experimentally tested, LMC is a textbook example of the predictive power of evolutionary theory. A limitation of many earlier studies in the field is that the population structure and mating system of the studied species are often estimated only indirectly. Here we use microsatellites to characterize the levels of inbreeding of the bark beetle Xylosandrus germanus, a species where the level of LMC is expected to be high. Results: For three populations studied, genetic variation for our genetic markers was very low, indicative of an extremely high level of inbreeding (F-IS = 0.88). There was also strong linkage disequilibrium between microsatellite loci and a very strong genetic differentiation between populations. The data suggest that matings among non-siblings are very rare (3%), although sex ratios from X. germanus in both the field and the laboratory have suggested more matings between non-sibs, and so less intense LMC. Conclusions: Our results confirm that caution is needed when inferring mating systems from sex ratio data, especially when a lack of biological detail means the use of overly simple forms of the model of interest.</description>
      <pubDate>Tue, 13 Dec 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2606</guid>
      <dc:date>2011-12-13T00:00:00Z</dc:date>
      <dc:creator>Keller, Laurent</dc:creator>
      <dc:creator>Peer, Katharina</dc:creator>
      <dc:creator>Bernasconi, Christian</dc:creator>
      <dc:creator>Taborsky, Michael</dc:creator>
      <dc:creator>Shuker, David M.</dc:creator>
      <dc:description>Background: Local Mate Competition (LMC) theory predicts a female should produce a more female-biased sex ratio if her sons compete with each other for mates. Because it provides quantitative predictions that can be experimentally tested, LMC is a textbook example of the predictive power of evolutionary theory. A limitation of many earlier studies in the field is that the population structure and mating system of the studied species are often estimated only indirectly. Here we use microsatellites to characterize the levels of inbreeding of the bark beetle Xylosandrus germanus, a species where the level of LMC is expected to be high. Results: For three populations studied, genetic variation for our genetic markers was very low, indicative of an extremely high level of inbreeding (F-IS = 0.88). There was also strong linkage disequilibrium between microsatellite loci and a very strong genetic differentiation between populations. The data suggest that matings among non-siblings are very rare (3%), although sex ratios from X. germanus in both the field and the laboratory have suggested more matings between non-sibs, and so less intense LMC. Conclusions: Our results confirm that caution is needed when inferring mating systems from sex ratio data, especially when a lack of biological detail means the use of overly simple forms of the model of interest.</dc:description>
    </item>
    <item>
      <title>A general discrete-time modeling framework for animal movement using multi-state random walks</title>
      <link>http://hdl.handle.net/10023/2605</link>
      <description>Abstract: Recent developments in animal tracking technology have permitted the collection of detailed data on the movement paths of individuals from many species. However, analysis methods for these data have not developed at a similar pace, largely due to a lack of suitable candidate models, coupled with the technical difficulties of fitting such models to data. To facilitate a general modeling framework, we propose that complex movement paths can be conceived as a series of movement strategies among which animals transition as they are affected by changes in their internal and external environment. We synthesize previously existing and novel methodologies to develop a general suite of mechanistic models based on biased and correlated random walks that allow different behavioral states for directed (e.g., migration), exploratory (e.g., dispersal), area-restricted (e.g., foraging), and other types of movement. Using this “tool-box” of nested model components, multi-state movement models may be custom-built for a wide variety of species and applications. As a unified state-space modeling framework, it allows the simultaneous investigation of numerous hypotheses about animal movement from imperfectly observed data, including time allocations to different movement behavior states, transitions between states, the use of memory or navigation, and strengths of attraction (or repulsion) to specific locations. The inclusion of covariate information permits further investigation of specific hypotheses related to factors driving different types of movement behavior. Using reversible jump Markov chain Monte Carlo methods to facilitate Bayesian model selection and multi-model inference, we apply the proposed methodology to real data by adapting it to the natural history of the grey seal (Halichoerus grypus) in the North Sea. Although previous grey seal studies tended to focus on correlated movements, we found overwhelming evidence that bias towards haul-out or foraging locations better explained seal movement than simple or correlated random walks. Posterior model probabilities also provided evidence that seals transition among directed, area-restricted, and exploratory movements associated with haul-out, foraging, and other behaviors. With this intuitive framework for modeling and interpreting animal movement, we believe the development and application of bespoke movement models will become more accessible to ecologists and non-statisticians.</description>
      <pubDate>Sun, 01 Jan 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2605</guid>
      <dc:date>2012-01-01T00:00:00Z</dc:date>
      <dc:creator>McClintock, Brett Thomas</dc:creator>
      <dc:creator>King, Ruth</dc:creator>
      <dc:creator>Thomas, Len</dc:creator>
      <dc:creator>Matthiopoulos, Jason</dc:creator>
      <dc:creator>McConnell, Bernie J</dc:creator>
      <dc:creator>Morales, Juan</dc:creator>
      <dc:description>Recent developments in animal tracking technology have permitted the collection of detailed data on the movement paths of individuals from many species. However, analysis methods for these data have not developed at a similar pace, largely due to a lack of suitable candidate models, coupled with the technical difficulties of fitting such models to data. To facilitate a general modeling framework, we propose that complex movement paths can be conceived as a series of movement strategies among which animals transition as they are affected by changes in their internal and external environment. We synthesize previously existing and novel methodologies to develop a general suite of mechanistic models based on biased and correlated random walks that allow different behavioral states for directed (e.g., migration), exploratory (e.g., dispersal), area-restricted (e.g., foraging), and other types of movement. Using this “tool-box” of nested model components, multi-state movement models may be custom-built for a wide variety of species and applications. As a unified state-space modeling framework, it allows the simultaneous investigation of numerous hypotheses about animal movement from imperfectly observed data, including time allocations to different movement behavior states, transitions between states, the use of memory or navigation, and strengths of attraction (or repulsion) to specific locations. The inclusion of covariate information permits further investigation of specific hypotheses related to factors driving different types of movement behavior. Using reversible jump Markov chain Monte Carlo methods to facilitate Bayesian model selection and multi-model inference, we apply the proposed methodology to real data by adapting it to the natural history of the grey seal (Halichoerus grypus) in the North Sea. Although previous grey seal studies tended to focus on correlated movements, we found overwhelming evidence that bias towards haul-out or foraging locations better explained seal movement than simple or correlated random walks. Posterior model probabilities also provided evidence that seals transition among directed, area-restricted, and exploratory movements associated with haul-out, foraging, and other behaviors. With this intuitive framework for modeling and interpreting animal movement, we believe the development and application of bespoke movement models will become more accessible to ecologists and non-statisticians.</dc:description>
    </item>
    <item>
      <title>The influence of the freshwater environment and the biological characteristics of Atlantic salmon smolts on their subsequent marine survival</title>
      <link>http://hdl.handle.net/10023/2603</link>
      <description>Abstract: Atlantic salmon have declined markedly in the past 20-30 years throughout their range. Much of the focus for this decline has been on increased mortality during the marine phase of the life cycle. However, marine mortality does not operate independently of factors acting in freshwater and the biological characteristics of smolts migrating to sea. Over recent decades, juvenile salmon in many rivers have grown faster and migrated to sea at a younger age, and thus typically smaller. This has shortened the generation time for many individuals, and may dampen the impact of increased marine mortality, assuming expected higher in-river survival prior to smolting is not outweighed by increased mortality of smaller smolts at sea. Over the same period, smolt run-timing across the geographic range has been occurring earlier, at a rate of almost three days per decade, on average. This has given rise to growing concerns about smolts potentially missing the optimum environmental migration “window”, the timing of which may also be changing. Contaminants and other factors operating in freshwater also impact on smolt quality with adverse consequences for their physiological readiness for life at sea. Given that managers have very limited ability to influence the broad scale factors limiting salmon survival at sea, it is vital that freshwater habitats are managed to both maximise smolt output and to minimise the impact of factors acting in freshwater which may compromise salmon once they migrate to sea.</description>
      <pubDate>Sun, 01 Jan 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2603</guid>
      <dc:date>2012-01-01T00:00:00Z</dc:date>
      <dc:creator>Russell, Ian</dc:creator>
      <dc:creator>Aprahamian, Miran</dc:creator>
      <dc:creator>Barry, Jon</dc:creator>
      <dc:creator>Davidson, Ian</dc:creator>
      <dc:creator>Fiske, Peder</dc:creator>
      <dc:creator>Ibbotson, Anton</dc:creator>
      <dc:creator>Kennedy, Richard</dc:creator>
      <dc:creator>Maclean, Julian</dc:creator>
      <dc:creator>Moore, Andrew</dc:creator>
      <dc:creator>Otero, Jaime</dc:creator>
      <dc:creator>Potter, Ted</dc:creator>
      <dc:creator>Todd, Christopher David</dc:creator>
      <dc:description>Atlantic salmon have declined markedly in the past 20-30 years throughout their range. Much of the focus for this decline has been on increased mortality during the marine phase of the life cycle. However, marine mortality does not operate independently of factors acting in freshwater and the biological characteristics of smolts migrating to sea. Over recent decades, juvenile salmon in many rivers have grown faster and migrated to sea at a younger age, and thus typically smaller. This has shortened the generation time for many individuals, and may dampen the impact of increased marine mortality, assuming expected higher in-river survival prior to smolting is not outweighed by increased mortality of smaller smolts at sea. Over the same period, smolt run-timing across the geographic range has been occurring earlier, at a rate of almost three days per decade, on average. This has given rise to growing concerns about smolts potentially missing the optimum environmental migration “window”, the timing of which may also be changing. Contaminants and other factors operating in freshwater also impact on smolt quality with adverse consequences for their physiological readiness for life at sea. Given that managers have very limited ability to influence the broad scale factors limiting salmon survival at sea, it is vital that freshwater habitats are managed to both maximise smolt output and to minimise the impact of factors acting in freshwater which may compromise salmon once they migrate to sea.</dc:description>
    </item>
    <item>
      <title>Biosonar performance of foraging beaked whales (Mesoplodon densirostris)</title>
      <link>http://hdl.handle.net/10023/2598</link>
      <description>Abstract: Toothed whales (Cetacea, odontoceti) emit sound pulses to probe their surroundings by active echolocation. Noninvasive, acoustic Dtags were placed on deep-diving Blainville's beaked whales (Mesoplodon densirostris) to record their ultrasonic clicks and the returning echoes from prey items, providing a unique view on how a whale operates its biosonar during foraging in the wild. The process of echolocation during prey capture in this species can be divided into search, approach and terminal phases, as in echolocating bats. The approach phase, defined by the onset of detectable echoes recorded on the tag for click sequences terminated by a buzz, has interclick intervals (ICI) of 300-400 ms. These ICIs are more than a magnitude longer than the decreasing two-way travel time to the targets, showing that ICIs are not given by the two-way-travel times plus a fixed, short lag time. During the approach phase, the received echo energy increases by 10.4((+/-)2) dB when the target range is halved, demonstrating that the whales do not employ range compensating gain control of the transmitter, as has been implicated for some bats and dolphins. The terminal/buzz phase with ICIs of around 10 ms is initiated when one or more targets are within approximately a body length of the whale (2-5 m), so that strong echo returns in the approach phase are traded for rapid updates in the terminal phase. It is suggested that stable ICIs in the search and approach phases facilitate auditory scene analysis in a complex multi-target environment, and that a concomitant low click rate allows the whales to maintain high sound pressure outputs for prey detection and discrimination with a pneumatically driven, bi-modal sound generator. demonstrating that the whales do not employ range-compensating gain control of the transmitter, as has been implicated for some bats and dolphins. The terminal/buzz phase with ICIs of around 10 ms is initiated when one or more targets are within approximately a body length of the whale (2-5 m), so that strong echo returns in the approach phase are traded for rapid updates in the terminal phase. It is suggested that stable ICIs in the search and approach phases facilitate auditory scene analysis in a complex multi-target environment, and that a concomitant low click rate allows the whales to maintain high sound pressure outputs for prey detection and discrimination with a pneumatically driven, bi-modal sound generator.</description>
      <pubDate>Sat, 15 Jan 2005 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2598</guid>
      <dc:date>2005-01-15T00:00:00Z</dc:date>
      <dc:creator>Madsen, P T</dc:creator>
      <dc:creator>Johnson, M</dc:creator>
      <dc:creator>de Soto, N A</dc:creator>
      <dc:creator>Zimmer, W M X</dc:creator>
      <dc:creator>Tyack, P</dc:creator>
      <dc:description>Toothed whales (Cetacea, odontoceti) emit sound pulses to probe their surroundings by active echolocation. Noninvasive, acoustic Dtags were placed on deep-diving Blainville's beaked whales (Mesoplodon densirostris) to record their ultrasonic clicks and the returning echoes from prey items, providing a unique view on how a whale operates its biosonar during foraging in the wild. The process of echolocation during prey capture in this species can be divided into search, approach and terminal phases, as in echolocating bats. The approach phase, defined by the onset of detectable echoes recorded on the tag for click sequences terminated by a buzz, has interclick intervals (ICI) of 300-400 ms. These ICIs are more than a magnitude longer than the decreasing two-way travel time to the targets, showing that ICIs are not given by the two-way-travel times plus a fixed, short lag time. During the approach phase, the received echo energy increases by 10.4((+/-)2) dB when the target range is halved, demonstrating that the whales do not employ range compensating gain control of the transmitter, as has been implicated for some bats and dolphins. The terminal/buzz phase with ICIs of around 10 ms is initiated when one or more targets are within approximately a body length of the whale (2-5 m), so that strong echo returns in the approach phase are traded for rapid updates in the terminal phase. It is suggested that stable ICIs in the search and approach phases facilitate auditory scene analysis in a complex multi-target environment, and that a concomitant low click rate allows the whales to maintain high sound pressure outputs for prey detection and discrimination with a pneumatically driven, bi-modal sound generator. demonstrating that the whales do not employ range-compensating gain control of the transmitter, as has been implicated for some bats and dolphins. The terminal/buzz phase with ICIs of around 10 ms is initiated when one or more targets are within approximately a body length of the whale (2-5 m), so that strong echo returns in the approach phase are traded for rapid updates in the terminal phase. It is suggested that stable ICIs in the search and approach phases facilitate auditory scene analysis in a complex multi-target environment, and that a concomitant low click rate allows the whales to maintain high sound pressure outputs for prey detection and discrimination with a pneumatically driven, bi-modal sound generator.</dc:description>
    </item>
    <item>
      <title>A digital acoustic recording tag for measuring the response of wild marine mammals to sound</title>
      <link>http://hdl.handle.net/10023/2594</link>
      <description>Abstract: Definitive studies on the response of marine mammals to anthropogenic sound are hampered by the short surface time and deep-diving lifestyle of many species. A novel archival tag, called the DTAG, has been developed to monitor the behavior of marine mammals, and their response to sound, continuously throughout the dive cycle. The tag contains a large array of solid-state memory and records continuously from a built-in hydrophone and suite of sensors. The sensors sample the orientation of the animal in three dimensions with sufficient speed and resolution to capture individual fluke strokes. Audio and sensor recording is synchronous so the relative timing of sounds and motion can be determined precisely. The DTAG has been attached to more than 30 northern right whales (Eubalaena glacialis) and 20 sperm whales (Physeter macrocephalus) with recording duration of up to 12 h per deployment. Several deployments have included sound playbacks to the tagged whale and a transient response to at least one playback is evident in the tag data.</description>
      <pubDate>Wed, 01 Jan 2003 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2594</guid>
      <dc:date>2003-01-01T00:00:00Z</dc:date>
      <dc:creator>Johnson, Mark</dc:creator>
      <dc:creator>Tyack, P L</dc:creator>
      <dc:description>Definitive studies on the response of marine mammals to anthropogenic sound are hampered by the short surface time and deep-diving lifestyle of many species. A novel archival tag, called the DTAG, has been developed to monitor the behavior of marine mammals, and their response to sound, continuously throughout the dive cycle. The tag contains a large array of solid-state memory and records continuously from a built-in hydrophone and suite of sensors. The sensors sample the orientation of the animal in three dimensions with sufficient speed and resolution to capture individual fluke strokes. Audio and sensor recording is synchronous so the relative timing of sounds and motion can be determined precisely. The DTAG has been attached to more than 30 northern right whales (Eubalaena glacialis) and 20 sperm whales (Physeter macrocephalus) with recording duration of up to 12 h per deployment. Several deployments have included sound playbacks to the tagged whale and a transient response to at least one playback is evident in the tag data.</dc:description>
    </item>
    <item>
      <title>The maintenance of genetic variation due to asymmetric gene flow in dendritic metapopulations</title>
      <link>http://hdl.handle.net/10023/2591</link>
      <description>Abstract: Dendritic landscapes can have ecological properties that differ importantly from simpler spatial arrangements of habitats. Most dendritic landscapes are structured by elevation, and therefore, migration is likely to be directionally biased. While the population‐genetic consequences of both dendritic landscape arrangements and asymmetric migration have begun to be studied, these processes have not been considered together. Simple conceptual models predict that if migration into branch (headwater) populations is limited, such populations can act as reservoirs for potentially unique alleles. As a consequence of the fact that dendritic landscapes have, by definition, more branches than internal habitat patches, this process may lead to the maintenance of higher overall genetic diversities in metapopulations inhabiting dendritic networks where migration is directionally biased. Here we begin to address the generality of these simple predictions using genetic models and a review of empirical literature. We show, for a range of demographic parameters, that dendritic systems with asymmetric migration can maintain levels of genetic variation that are very different, sometimes very elevated, compared with more classical models of geographical population structure. Furthermore, predicted patterns of genetic variation within metapopulations—that is, stepwise increases in genetic diversity at nodes—do occur in some empirical data.</description>
      <pubDate>Tue, 01 Dec 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2591</guid>
      <dc:date>2009-12-01T00:00:00Z</dc:date>
      <dc:creator>Morrissey, Michael Blair</dc:creator>
      <dc:creator>de Kerckhove, Derrick</dc:creator>
      <dc:description>Dendritic landscapes can have ecological properties that differ importantly from simpler spatial arrangements of habitats. Most dendritic landscapes are structured by elevation, and therefore, migration is likely to be directionally biased. While the population‐genetic consequences of both dendritic landscape arrangements and asymmetric migration have begun to be studied, these processes have not been considered together. Simple conceptual models predict that if migration into branch (headwater) populations is limited, such populations can act as reservoirs for potentially unique alleles. As a consequence of the fact that dendritic landscapes have, by definition, more branches than internal habitat patches, this process may lead to the maintenance of higher overall genetic diversities in metapopulations inhabiting dendritic networks where migration is directionally biased. Here we begin to address the generality of these simple predictions using genetic models and a review of empirical literature. We show, for a range of demographic parameters, that dendritic systems with asymmetric migration can maintain levels of genetic variation that are very different, sometimes very elevated, compared with more classical models of geographical population structure. Furthermore, predicted patterns of genetic variation within metapopulations—that is, stepwise increases in genetic diversity at nodes—do occur in some empirical data.</dc:description>
    </item>
    <item>
      <title>Deadly diving? Physiological and behavioural management of decompression stress in diving mammals</title>
      <link>http://hdl.handle.net/10023/2475</link>
      <description>Abstract: Decompression sickness (DCS; 'the bends') is a disease associated with gas uptake at pressure. The basic pathology and cause are relatively well known to human divers. Breath-hold diving marine mammals were thought to be relatively immune to DCS owing to multiple anatomical, physiological and behavioural adaptations that reduce nitrogen gas (N-2) loading during dives. However, recent observations have shown that gas bubbles may form and tissue injury may occur in marine mammals under certain circumstances. Gas kinetic models based on measured time-depth profiles further suggest the potential occurrence of high blood and tissue N-2 tensions. We review evidence for gas-bubble incidence in marine mammal tissues and discuss the theory behind gas loading and bubble formation. We suggest that diving mammals vary their physiological responses according to multiple stressors, and that the perspective on marine mammal diving physiology should change from simply minimizing N-2 loading to management of the N-2 load. This suggests several avenues for further study, ranging from the effects of gas bubbles at molecular, cellular and organ function levels, to comparative studies relating the presence/absence of gas bubbles to diving behaviour. Technological advances in imaging and remote instrumentation are likely to advance this field in coming years.</description>
      <pubDate>Thu, 22 Mar 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2475</guid>
      <dc:date>2012-03-22T00:00:00Z</dc:date>
      <dc:creator>Hooker, S. K.</dc:creator>
      <dc:creator>Fahlman, A.</dc:creator>
      <dc:creator>Moore, M. J.</dc:creator>
      <dc:creator>Aguilar de Soto, N.</dc:creator>
      <dc:creator>Bernaldo de Quiros, Y.</dc:creator>
      <dc:creator>Brubakk, A. O.</dc:creator>
      <dc:creator>Costa, D. P.</dc:creator>
      <dc:creator>Costidis, A. M.</dc:creator>
      <dc:creator>Dennison, S.</dc:creator>
      <dc:creator>Falke, K. J.</dc:creator>
      <dc:creator>Fernandez, A.</dc:creator>
      <dc:creator>Ferrigno, M.</dc:creator>
      <dc:creator>Fitz-Clarke, J. R.</dc:creator>
      <dc:creator>Garner, M. M.</dc:creator>
      <dc:creator>Houser, D. S.</dc:creator>
      <dc:creator>Jepson, P. D.</dc:creator>
      <dc:creator>Ketten, D. R.</dc:creator>
      <dc:creator>Kvadsheim, P. H.</dc:creator>
      <dc:creator>Madsen, P. T.</dc:creator>
      <dc:creator>Pollock, N. W.</dc:creator>
      <dc:creator>Rotstein, D. S.</dc:creator>
      <dc:creator>Rowles, T. K.</dc:creator>
      <dc:creator>Simmons, S. E.</dc:creator>
      <dc:creator>Van Bonn, W.</dc:creator>
      <dc:creator>Weathersby, P. K.</dc:creator>
      <dc:creator>Weise, M. J.</dc:creator>
      <dc:creator>Williams, T. M.</dc:creator>
      <dc:creator>Tyack, P. L.</dc:creator>
      <dc:description>Decompression sickness (DCS; 'the bends') is a disease associated with gas uptake at pressure. The basic pathology and cause are relatively well known to human divers. Breath-hold diving marine mammals were thought to be relatively immune to DCS owing to multiple anatomical, physiological and behavioural adaptations that reduce nitrogen gas (N-2) loading during dives. However, recent observations have shown that gas bubbles may form and tissue injury may occur in marine mammals under certain circumstances. Gas kinetic models based on measured time-depth profiles further suggest the potential occurrence of high blood and tissue N-2 tensions. We review evidence for gas-bubble incidence in marine mammal tissues and discuss the theory behind gas loading and bubble formation. We suggest that diving mammals vary their physiological responses according to multiple stressors, and that the perspective on marine mammal diving physiology should change from simply minimizing N-2 loading to management of the N-2 load. This suggests several avenues for further study, ranging from the effects of gas bubbles at molecular, cellular and organ function levels, to comparative studies relating the presence/absence of gas bubbles to diving behaviour. Technological advances in imaging and remote instrumentation are likely to advance this field in coming years.</dc:description>
    </item>
    <item>
      <title>Temporal turnover and the maintenance of diversity in ecological assemblages</title>
      <link>http://hdl.handle.net/10023/2474</link>
      <description>Abstract: Temporal variation in species abundances occurs in all ecological communities. Here, we explore the role that this temporal turnover plays in maintaining assemblage diversity. We investigate a three-decade time series of estuarine fishes and show that the abundances of the individual species fluctuate asynchronously around their mean levels. We then use a time-series modelling approach to examine the consequences of different patterns of turnover, by asking how the correlation between the abundance of a species in a given year and its abundance in the previous year influences the structure of the overall assemblage. Classical diversity measures that ignore species identities reveal that the observed assemblage structure will persist under all but the most extreme conditions. However, metrics that track species identities indicate a narrower set of turnover scenarios under which the predicted assemblage resembles the natural one. Our study suggests that species diversity metrics are insensitive to change and that measures that track species ranks may provide better early warning that an assemblage is being perturbed. It also highlights the need to incorporate temporal turnover in investigations of assemblage structure and function.</description>
      <pubDate>Sat, 27 Nov 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2474</guid>
      <dc:date>2010-11-27T00:00:00Z</dc:date>
      <dc:creator>Magurran, Anne E.</dc:creator>
      <dc:creator>Henderson, Peter A.</dc:creator>
      <dc:description>Temporal variation in species abundances occurs in all ecological communities. Here, we explore the role that this temporal turnover plays in maintaining assemblage diversity. We investigate a three-decade time series of estuarine fishes and show that the abundances of the individual species fluctuate asynchronously around their mean levels. We then use a time-series modelling approach to examine the consequences of different patterns of turnover, by asking how the correlation between the abundance of a species in a given year and its abundance in the previous year influences the structure of the overall assemblage. Classical diversity measures that ignore species identities reveal that the observed assemblage structure will persist under all but the most extreme conditions. However, metrics that track species identities indicate a narrower set of turnover scenarios under which the predicted assemblage resembles the natural one. Our study suggests that species diversity metrics are insensitive to change and that measures that track species ranks may provide better early warning that an assemblage is being perturbed. It also highlights the need to incorporate temporal turnover in investigations of assemblage structure and function.</dc:description>
    </item>
    <item>
      <title>Ancient homeobox gene loss and the evolution of chordate brain and pharynx development : deductions from amphioxus gene expression</title>
      <link>http://hdl.handle.net/10023/2473</link>
      <description>Abstract: Homeobox genes encode a large superclass of transcription factors with widespread roles in animal development. Within chordates there are over 100 homeobox genes in the invertebrate cephalochordate amphioxus and over 200 in humans. Set against this general trend of increasing gene number in vertebrate evolution, some ancient homeobox genes that were present in the last common ancestor of chordates have been lost from vertebrates. Here, we describe the embryonic expression of four amphioxus descendants of these genes—AmphiNedxa, AmphiNedxb, AmphiMsxlx and AmphiNKx7. All four genes are expressed with a striking asymmetry about the left–right axis in the pharyngeal region of neurula embryos, mirroring the pronounced asymmetry of amphioxus embryogenesis. AmphiMsxlx and AmphiNKx7 are also transiently expressed in an anterior neural tube region destined to become the cerebral vesicle. These findings suggest significant rewiring of developmental gene regulatory networks occurred during chordate evolution, coincident with homeobox gene loss. We propose that loss of otherwise widely conserved genes is possible when these genes function in a confined role in development that is subsequently lost or significantly modified during evolution. In the case of these homeobox genes, we propose that this has occurred in relation to the evolution of the chordate pharynx and brain.</description>
      <pubDate>Mon, 22 Nov 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2473</guid>
      <dc:date>2010-11-22T00:00:00Z</dc:date>
      <dc:creator>Butts, Thomas</dc:creator>
      <dc:creator>Holland, Peter W.H.</dc:creator>
      <dc:creator>Ferrier, David Ellard Keith</dc:creator>
      <dc:description>Homeobox genes encode a large superclass of transcription factors with widespread roles in animal development. Within chordates there are over 100 homeobox genes in the invertebrate cephalochordate amphioxus and over 200 in humans. Set against this general trend of increasing gene number in vertebrate evolution, some ancient homeobox genes that were present in the last common ancestor of chordates have been lost from vertebrates. Here, we describe the embryonic expression of four amphioxus descendants of these genes—AmphiNedxa, AmphiNedxb, AmphiMsxlx and AmphiNKx7. All four genes are expressed with a striking asymmetry about the left–right axis in the pharyngeal region of neurula embryos, mirroring the pronounced asymmetry of amphioxus embryogenesis. AmphiMsxlx and AmphiNKx7 are also transiently expressed in an anterior neural tube region destined to become the cerebral vesicle. These findings suggest significant rewiring of developmental gene regulatory networks occurred during chordate evolution, coincident with homeobox gene loss. We propose that loss of otherwise widely conserved genes is possible when these genes function in a confined role in development that is subsequently lost or significantly modified during evolution. In the case of these homeobox genes, we propose that this has occurred in relation to the evolution of the chordate pharynx and brain.</dc:description>
    </item>
    <item>
      <title>Sexual selection on song and cuticular hydrocarbons in two distinct populations of Drosophila montana</title>
      <link>http://hdl.handle.net/10023/2459</link>
      <description>Abstract: Sexual selection has the potential to contribute to population divergence and speciation. Most studies of sexual selection in Drosophila have concentrated on a single signaling modality, usually either courtship song or cuticular hydrocarbons (CHCs), which can act as contact pheromones. We have examined the relationship between both signal types and reproductive success using F1–3 offspring of wild- collected flies, raised in the lab. We used two populations of the Holarctic species Drosophila montana that represent different phylogeographic clades that have been separate for ca. 0.5 million years (MY), and differ to some extent in both traits. Here, we characterize the nature and identify the targets of sexual selection on song, CHCs, and both traits combined within the populations. Three measures of courtship outcome were used as fitness proxies. They were the probability of mating, mating latency, and the production of rejection song by females, and showed patterns of association with different traits that included both linear and quadratic selection. Courtship song predicted courtship outcome better than CHCs and the signal modalities acted in an additive rather than synergistic manner. Selection was generally consistent in direction and strength between the two populations and favored males that sang more vigorously. Sexual selection differed in the extent, strength, and nature on some of the traits between populations. However, the differences in the directionality of selection detected were not a good predictor of population differences. In addition, a character previously shown to be important for species recognition, interpulse interval, was found to be under sexual selection. Our results highlight the complexity of understanding the relationship between within-population sexual selection and population differences. Sexual selection alone cannot predict differences between populations.</description>
      <pubDate>Sun, 01 Jan 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2459</guid>
      <dc:date>2012-01-01T00:00:00Z</dc:date>
      <dc:creator>Veltsos, Paris</dc:creator>
      <dc:creator>Wicker-Thomas, Claude</dc:creator>
      <dc:creator>Butlin, Roger</dc:creator>
      <dc:creator>Hoikkala, Anneli</dc:creator>
      <dc:creator>Ritchie, Michael Gordon</dc:creator>
      <dc:description>Sexual selection has the potential to contribute to population divergence and speciation. Most studies of sexual selection in Drosophila have concentrated on a single signaling modality, usually either courtship song or cuticular hydrocarbons (CHCs), which can act as contact pheromones. We have examined the relationship between both signal types and reproductive success using F1–3 offspring of wild- collected flies, raised in the lab. We used two populations of the Holarctic species Drosophila montana that represent different phylogeographic clades that have been separate for ca. 0.5 million years (MY), and differ to some extent in both traits. Here, we characterize the nature and identify the targets of sexual selection on song, CHCs, and both traits combined within the populations. Three measures of courtship outcome were used as fitness proxies. They were the probability of mating, mating latency, and the production of rejection song by females, and showed patterns of association with different traits that included both linear and quadratic selection. Courtship song predicted courtship outcome better than CHCs and the signal modalities acted in an additive rather than synergistic manner. Selection was generally consistent in direction and strength between the two populations and favored males that sang more vigorously. Sexual selection differed in the extent, strength, and nature on some of the traits between populations. However, the differences in the directionality of selection detected were not a good predictor of population differences. In addition, a character previously shown to be important for species recognition, interpulse interval, was found to be under sexual selection. Our results highlight the complexity of understanding the relationship between within-population sexual selection and population differences. Sexual selection alone cannot predict differences between populations.</dc:description>
    </item>
    <item>
      <title>Beaked whales respond to simulated and actual navy sonar</title>
      <link>http://hdl.handle.net/10023/2458</link>
      <description>Abstract: Beaked whales have mass stranded during some naval sonar exercises, but the cause is unknown. They are difficult to sight but can reliably be detected by listening for echolocation clicks produced during deep foraging dives. Listening for these clicks, we documented Blainville's beaked whales, Mesoplodon densirostris, in a naval underwater range where sonars are in regular use near Andros Island, Bahamas. An array of bottom-mounted hydrophones can detect beaked whales when they click anywhere within the range. We used two complementary methods to investigate behavioral responses of beaked whales to sonar: an opportunistic approach that monitored whale responses to multi-day naval exercises involving tactical mid-frequency sonars, and an experimental approach using playbacks of simulated sonar and control sounds to whales tagged with a device that records sound, movement, and orientation. Here we show that in both exposure conditions beaked whales stopped echolocating during deep foraging dives and moved away. During actual sonar exercises, beaked whales were primarily detected near the periphery of the range, on average 16 km away from the sonar transmissions. Once the exercise stopped, beaked whales gradually filled in the center of the range over 2-3 days. A satellite tagged whale moved outside the range during an exercise, returning over 2-3 days post-exercise. The experimental approach used tags to measure acoustic exposure and behavioral reactions of beaked whales to one controlled exposure each of simulated military sonar, killer whale calls, and band-limited noise. The beaked whales reacted to these three sound playbacks at sound pressure levels below 142 dB re 1 mu Pa by stopping echolocation followed by unusually long and slow ascents from their foraging dives. The combined results indicate similar disruption of foraging behavior and avoidance by beaked whales in the two different contexts, at exposures well below those used by regulators to define disturbance.</description>
      <pubDate>Mon, 14 Mar 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2458</guid>
      <dc:date>2011-03-14T00:00:00Z</dc:date>
      <dc:creator>Tyack, Peter L.</dc:creator>
      <dc:creator>Zimmer, Walter M. X.</dc:creator>
      <dc:creator>Moretti, David</dc:creator>
      <dc:creator>Southall, Brandon L.</dc:creator>
      <dc:creator>Claridge, Diane E.</dc:creator>
      <dc:creator>Durban, John W.</dc:creator>
      <dc:creator>Clark, Christopher W.</dc:creator>
      <dc:creator>D'Amico, Angela</dc:creator>
      <dc:creator>DiMarzio, Nancy</dc:creator>
      <dc:creator>Jarvis, Susan</dc:creator>
      <dc:creator>McCarthy, Elena</dc:creator>
      <dc:creator>Morrissey, Ronald</dc:creator>
      <dc:creator>Ward, Jessica</dc:creator>
      <dc:creator>Boyd, Ian L.</dc:creator>
      <dc:description>Beaked whales have mass stranded during some naval sonar exercises, but the cause is unknown. They are difficult to sight but can reliably be detected by listening for echolocation clicks produced during deep foraging dives. Listening for these clicks, we documented Blainville's beaked whales, Mesoplodon densirostris, in a naval underwater range where sonars are in regular use near Andros Island, Bahamas. An array of bottom-mounted hydrophones can detect beaked whales when they click anywhere within the range. We used two complementary methods to investigate behavioral responses of beaked whales to sonar: an opportunistic approach that monitored whale responses to multi-day naval exercises involving tactical mid-frequency sonars, and an experimental approach using playbacks of simulated sonar and control sounds to whales tagged with a device that records sound, movement, and orientation. Here we show that in both exposure conditions beaked whales stopped echolocating during deep foraging dives and moved away. During actual sonar exercises, beaked whales were primarily detected near the periphery of the range, on average 16 km away from the sonar transmissions. Once the exercise stopped, beaked whales gradually filled in the center of the range over 2-3 days. A satellite tagged whale moved outside the range during an exercise, returning over 2-3 days post-exercise. The experimental approach used tags to measure acoustic exposure and behavioral reactions of beaked whales to one controlled exposure each of simulated military sonar, killer whale calls, and band-limited noise. The beaked whales reacted to these three sound playbacks at sound pressure levels below 142 dB re 1 mu Pa by stopping echolocation followed by unusually long and slow ascents from their foraging dives. The combined results indicate similar disruption of foraging behavior and avoidance by beaked whales in the two different contexts, at exposures well below those used by regulators to define disturbance.</dc:description>
    </item>
    <item>
      <title>Activation of the beta interferon promoter by paramyxoviruses in the absence of virus protein synthesis</title>
      <link>http://hdl.handle.net/10023/2451</link>
      <description>Abstract: Conflicting reports exist regarding the requirement for virus replication in interferon (IFN) induction by paramyxoviruses. Our previous work has demonstrated that pathogen-associated molecular patterns capable of activating the IFN-induction cascade are not normally generated during virus replication, but are associated instead with the presence of defective interfering (DI) viruses. We demonstrate here that DIs of paramyxoviruses, including parainfluenza virus 5, mumps virus and Sendai virus, can activate the IFN-induction cascade and the IFN-beta promoter in the absence of virus protein synthesis. As virus protein synthesis is an absolute requirement for paramyxovirus genome replication, our results indicate that these DI viruses do not require replication to activate the IFN-induction cascade.</description>
      <pubDate>Wed, 01 Feb 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2451</guid>
      <dc:date>2012-02-01T00:00:00Z</dc:date>
      <dc:creator>Killip, M. J.</dc:creator>
      <dc:creator>Young, D. F.</dc:creator>
      <dc:creator>Precious, B. L.</dc:creator>
      <dc:creator>Goodbourn, S.</dc:creator>
      <dc:creator>Randall, R. E.</dc:creator>
      <dc:description>Conflicting reports exist regarding the requirement for virus replication in interferon (IFN) induction by paramyxoviruses. Our previous work has demonstrated that pathogen-associated molecular patterns capable of activating the IFN-induction cascade are not normally generated during virus replication, but are associated instead with the presence of defective interfering (DI) viruses. We demonstrate here that DIs of paramyxoviruses, including parainfluenza virus 5, mumps virus and Sendai virus, can activate the IFN-induction cascade and the IFN-beta promoter in the absence of virus protein synthesis. As virus protein synthesis is an absolute requirement for paramyxovirus genome replication, our results indicate that these DI viruses do not require replication to activate the IFN-induction cascade.</dc:description>
    </item>
    <item>
      <title>Identification of essential and non-essential single-stranded DNA-binding proteins in a model archaeal organism</title>
      <link>http://hdl.handle.net/10023/2414</link>
      <description>Abstract: Single-stranded DNA-binding proteins (SSBs) play vital roles in all aspects of DNA metabolism in all three domains of life and are characterized by the presence of one or more OB fold ssDNA-binding domains. Here, using the genetically tractable euryarchaeon Haloferax volcanii as a model, we present the first genetic analysis of SSB function in the archaea. We show that genes encoding the OB fold and zinc finger-containing RpaA1 and RpaB1 proteins are individually non-essential for cell viability but share an essential function, whereas the gene encoding the triple OB fold RpaC protein is essential. Loss of RpaC function can however be rescued by elevated expression of RpaB, indicative of functional overlap between the two classes of haloarchaeal SSB. Deletion analysis is used to demonstrate important roles for individual OB folds in RpaC and to show that conserved N- and C-terminal domains are required for efficient repair of DNA damage. Consistent with a role for RpaC in DNA repair, elevated expression of this protein leads to enhanced resistance to DNA damage. Taken together, our results offer important insights into archaeal SSB function and establish the haloarchaea as a valuable model for further studies.</description>
      <pubDate>Wed, 01 Feb 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2414</guid>
      <dc:date>2012-02-01T00:00:00Z</dc:date>
      <dc:creator>Skowyra, Agnieszka</dc:creator>
      <dc:creator>MacNeill, Stuart</dc:creator>
      <dc:description>Single-stranded DNA-binding proteins (SSBs) play vital roles in all aspects of DNA metabolism in all three domains of life and are characterized by the presence of one or more OB fold ssDNA-binding domains. Here, using the genetically tractable euryarchaeon Haloferax volcanii as a model, we present the first genetic analysis of SSB function in the archaea. We show that genes encoding the OB fold and zinc finger-containing RpaA1 and RpaB1 proteins are individually non-essential for cell viability but share an essential function, whereas the gene encoding the triple OB fold RpaC protein is essential. Loss of RpaC function can however be rescued by elevated expression of RpaB, indicative of functional overlap between the two classes of haloarchaeal SSB. Deletion analysis is used to demonstrate important roles for individual OB folds in RpaC and to show that conserved N- and C-terminal domains are required for efficient repair of DNA damage. Consistent with a role for RpaC in DNA repair, elevated expression of this protein leads to enhanced resistance to DNA damage. Taken together, our results offer important insights into archaeal SSB function and establish the haloarchaea as a valuable model for further studies.</dc:description>
    </item>
    <item>
      <title>Sphingolipid and ceramide homeostasis : potential therapeutic targets</title>
      <link>http://hdl.handle.net/10023/2412</link>
      <description>Abstract: Sphingolipids are ubiquitous in eukaryotic cells where they have been attributed a plethora of functions from the formation of structural domains to polarized cellular trafficking and signal transduction. Recent research has identified and characterised many of the key enzymes involved in sphingolipid metabolism and this has lead to a heightened interest in the possibility of targeting these processes for therapies against cancers, Alzheimer’s disease and numerous important human pathogens. In this review we outline the major pathways in eukaryotic sphingolipid metabolism and discuss these in relation to disease and therapy for both chronic and infectious conditions.</description>
      <pubDate>Sun, 01 Jan 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2412</guid>
      <dc:date>2012-01-01T00:00:00Z</dc:date>
      <dc:creator>Young, Simon</dc:creator>
      <dc:creator>Mina, John</dc:creator>
      <dc:creator>Denny, Paul</dc:creator>
      <dc:creator>Smith, Terry</dc:creator>
      <dc:description>Sphingolipids are ubiquitous in eukaryotic cells where they have been attributed a plethora of functions from the formation of structural domains to polarized cellular trafficking and signal transduction. Recent research has identified and characterised many of the key enzymes involved in sphingolipid metabolism and this has lead to a heightened interest in the possibility of targeting these processes for therapies against cancers, Alzheimer’s disease and numerous important human pathogens. In this review we outline the major pathways in eukaryotic sphingolipid metabolism and discuss these in relation to disease and therapy for both chronic and infectious conditions.</dc:description>
    </item>
    <item>
      <title>Mitochondrial β-amyloid in Alzheimer's disease</title>
      <link>http://hdl.handle.net/10023/2250</link>
      <description>Abstract: It is well established that the intracellular accumulation of beta-amyloid is associated with Alzheimer’s disease and that this accumulation is toxic to neurons. The precise mechanism by which this toxicity occurs is not well understood, however, identifying the causes of this toxicity is an essential step in developing treatments for Alzheimer’s disease. One intracellular location where the accumulation of beta-amyloid can have a major effect is within mitochondria has identified mitochondrial proteins that act as binding sites for beta-amyloid and when binding occurs a toxic response results. For one of these identified sites, an enzyme known as ‘ABAD’, we have identified the changes in gene expression in the brain cortex following beta-amyloid accumulation within mitochondria. Specifically, we have identified two proteins that are upregulated in the brains of transgenic animal models for Alzheimer’s disease but also human sufferers. The increased expression of these proteins demonstrates the complex and counter-acting pathways that are activated in Alzheimer’s disease. Previous studies have identified the approximate contact sites between ABAD and beta-amyloid, and based on these observations we have shown that using a modified peptide approach, it is possible to reverse the expression of these two proteins in living transgenic animals and also recover both mitochondrial and behavioural deficits. This indicates that the ABAD-beta-amyloid interaction is potentially an interesting target for therapeutic intervention. To explore this further we used a fluorescing substrate mimic to measure the activity of ABAD within living cells, and in addition we have identified chemical fragments that bind to ABAD, by using a thermal shift assay.
Description: This research is supported by Alzheimer's Research UK, the Wellcome Trust and the Biotechnology and Biological Sciences Research Council.</description>
      <pubDate>Mon, 01 Aug 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2250</guid>
      <dc:date>2011-08-01T00:00:00Z</dc:date>
      <dc:creator>Borger, Eva</dc:creator>
      <dc:creator>Aitken, Laura</dc:creator>
      <dc:creator>Muirhead, Kirsty Elizabeth Adair</dc:creator>
      <dc:creator>Allen, Zoe Eleanor</dc:creator>
      <dc:creator>Ainge, James Alexander</dc:creator>
      <dc:creator>Conway, Stuart</dc:creator>
      <dc:creator>Gunn-Moore, Frank J</dc:creator>
      <dc:description>It is well established that the intracellular accumulation of beta-amyloid is associated with Alzheimer’s disease and that this accumulation is toxic to neurons. The precise mechanism by which this toxicity occurs is not well understood, however, identifying the causes of this toxicity is an essential step in developing treatments for Alzheimer’s disease. One intracellular location where the accumulation of beta-amyloid can have a major effect is within mitochondria has identified mitochondrial proteins that act as binding sites for beta-amyloid and when binding occurs a toxic response results. For one of these identified sites, an enzyme known as ‘ABAD’, we have identified the changes in gene expression in the brain cortex following beta-amyloid accumulation within mitochondria. Specifically, we have identified two proteins that are upregulated in the brains of transgenic animal models for Alzheimer’s disease but also human sufferers. The increased expression of these proteins demonstrates the complex and counter-acting pathways that are activated in Alzheimer’s disease. Previous studies have identified the approximate contact sites between ABAD and beta-amyloid, and based on these observations we have shown that using a modified peptide approach, it is possible to reverse the expression of these two proteins in living transgenic animals and also recover both mitochondrial and behavioural deficits. This indicates that the ABAD-beta-amyloid interaction is potentially an interesting target for therapeutic intervention. To explore this further we used a fluorescing substrate mimic to measure the activity of ABAD within living cells, and in addition we have identified chemical fragments that bind to ABAD, by using a thermal shift assay.</dc:description>
    </item>
    <item>
      <title>A critical review of the literature on population modelling</title>
      <link>http://hdl.handle.net/10023/2241</link>
      <description>Abstract: The 2005 report of the National Research Council’s ‘Committee on Characterizing Biologically Significant Marine Mammal Behavior’ proposed a framework, which they called PCAD - Population Consequences of Acoustic Disturbance, that uses a series of transfer functions to link behavioural responses to sound with life functions, vital rates, and population change. The Committee suggested that the best understood transfer functions are those linking vital rates to population change. One of the main aims of this report is to document that understanding. However, we also show how the existing frameworks for modelling the dynamics of marine mammal populations can be extended to include the effects of behavioural responses on vital rates. In Chapter 1 we introduce the central concept of the rate of increase (lambda) of a population, which we believe is the most useful measure of the effects of behavioural responses on the dynamics of a population. If the value of lambda exceeds one, then thepopulation will increase over time; if it is less than one it will decrease. We show how changes in lambda provide a measure of the impact of human activities (such as exploitation, conservation, or disturbance) on a population. We also introduce structured population models, which take account of the fact that all individuals in a population are not identical, and show how the dynamics of different parts of a population can be modelled using a population projection matrix. The mathematical properties of this projection matrix can be used to determine the sensitivity of lambda to small changes in vital rates. Finally, we provide a very brief introduction to the concept of stochasticity, and the use of lambda to predict when (and if) a population might be driven to extinction. Chapter 2 describes how lambda also provides a measure of the Darwinian fitness of the individual members of a population. An individual’s fitness, the contribution it will make to future generations, depends to a large extent on its body condition and on the risks of mortality to which it is exposed. Both of these could be affected by behaviour responses to sound. We also explain current theories about the relationship between an individual’s feeding behaviour and the abundance and distribution of prey, and how this can affect body condition. Chapter 3 provides a more detailed description of how elasticity analysis can be used to investigate the impact of changes in vital rates on lambda . Elasticity analysis is a useful tool for detecting which vital rates are most important in determining the dynamics of a population. However, its value is limited because it does not take account of random variations (stochasticity) and, in theory, it can only predict the effect of small changes in vital rates. Chapter 4 describes the fundamental concept of density dependence: the way in which vital rates change with population size or the availability of resources, such as prey. Not only is density dependence an essential prerequisite for population stability and sustainable use, but the form it takes will also determine how a population responds to behavioural changes. This is because behaviour, and particularly the effect of behavioural change on body condition, plays a central role in many of the mechanistic models of density dependence. Chapters 5 and 6 explore the way in which additional complexities, such as social structure and the way in which populations are distributed in space, can affect the dynamics of populations. Models that account for these complexities behave in a much less predictable way than the relatively simple structured models that form the core of Chapters 1-4. So far, the models of population dynamics that we have reviewed have been deterministic. That is, they have assumed that the only way in which vital rates can vary is in response to a change in abundance, via density dependent mechanisms. In Chapters 7 and 8 we investigate the effect of random variation (stochasticity) on population dynamics. We distinguish the effects of demographic stochasticity, chance variations in the number of animals that die or give birth in a time interval that occur even if vital rates do not vary over time, and environmental stochasticity, which is the result of variations in vital rates across years. Variation in abundance may also occur as a result of environmental change and changes in the ecological community of which a population is a part. The effect of all these sources of variation is to reduce the realised growth rate of a population, and therefore its risk of extinction. In Chapter 9 we consider how the basic population modelling framework described in Chapters 1-8 might be extended to take account of the life functions identified by the NRC Committee. We suggest that these life functions are useful for defining the context in which behavioural responses might affect vital rates, but that they do not need to be modelled explicitly. Removing vital functions from the PCAD framework results in a much simpler structure, which is compatible with existing population modelling frameworks. However, these will have to be extended to allow population states, like body condition, that vary continuously to be modelled. Chapter 10 describes how changes in lambda can be detected. The simple analytical frameworks that are available for this are all vulnerable to the effects of variability that we introduced in Chapter 7. However, there is a framework (state-space and hidden Markov process modelling) that can account for the effects of this variability, and we recommend its use for detecting trends. The additional benefit of this approach is that its use results in a detailed model of the dynamics of the population that is under investigation. Chapter 11 reviews the different model structures that can be used to describe the dynamics of a population, and explains when different forms of population models (e.g. discrete vs. continuous time, deterministic vs. stochastic) are most appropriate. We also discuss how these different frameworks can be extended to account for continuous population states, as recommended in Chapter 8. The final focus is on how state-space models can be fitted to time series of abundance estimates and information on vital rates. Chapter 12 looks at the relevance of the different modelling approaches described in the previous chapters for analysing the potential effects of behavioural responses to sound on population dynamics, particularly the kinds of sounds that may be generated by the oil and gas industry. We conclude that lambda , the population rate of increase, and its variation provides a useful measure of these effects. We also believe that the models used for this purpose will certainly have to account for the effects of variability and density dependence. They will probably also have to account for the effects of social structure and the way in which populations use space. The state-space modelling framework outlined in Chapter 11 can, in principle, be extended to capture all of these features although work on this is still in its infancy.
Description: Final Report to the Joint Industry Project of the International Association of Oil &amp; Gas Producers on contract JIP22 07_20</description>
      <pubDate>Thu, 01 Jan 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2241</guid>
      <dc:date>2009-01-01T00:00:00Z</dc:date>
      <dc:creator>Cabrelli, Abigail</dc:creator>
      <dc:creator>Harwood, John</dc:creator>
      <dc:creator>Matthiopoulos, Jason</dc:creator>
      <dc:creator>New, Leslie Frances</dc:creator>
      <dc:creator>Thomas, Len</dc:creator>
      <dc:description>The 2005 report of the National Research Council’s ‘Committee on Characterizing Biologically Significant Marine Mammal Behavior’ proposed a framework, which they called PCAD - Population Consequences of Acoustic Disturbance, that uses a series of transfer functions to link behavioural responses to sound with life functions, vital rates, and population change. The Committee suggested that the best understood transfer functions are those linking vital rates to population change. One of the main aims of this report is to document that understanding. However, we also show how the existing frameworks for modelling the dynamics of marine mammal populations can be extended to include the effects of behavioural responses on vital rates. In Chapter 1 we introduce the central concept of the rate of increase (lambda) of a population, which we believe is the most useful measure of the effects of behavioural responses on the dynamics of a population. If the value of lambda exceeds one, then thepopulation will increase over time; if it is less than one it will decrease. We show how changes in lambda provide a measure of the impact of human activities (such as exploitation, conservation, or disturbance) on a population. We also introduce structured population models, which take account of the fact that all individuals in a population are not identical, and show how the dynamics of different parts of a population can be modelled using a population projection matrix. The mathematical properties of this projection matrix can be used to determine the sensitivity of lambda to small changes in vital rates. Finally, we provide a very brief introduction to the concept of stochasticity, and the use of lambda to predict when (and if) a population might be driven to extinction. Chapter 2 describes how lambda also provides a measure of the Darwinian fitness of the individual members of a population. An individual’s fitness, the contribution it will make to future generations, depends to a large extent on its body condition and on the risks of mortality to which it is exposed. Both of these could be affected by behaviour responses to sound. We also explain current theories about the relationship between an individual’s feeding behaviour and the abundance and distribution of prey, and how this can affect body condition. Chapter 3 provides a more detailed description of how elasticity analysis can be used to investigate the impact of changes in vital rates on lambda . Elasticity analysis is a useful tool for detecting which vital rates are most important in determining the dynamics of a population. However, its value is limited because it does not take account of random variations (stochasticity) and, in theory, it can only predict the effect of small changes in vital rates. Chapter 4 describes the fundamental concept of density dependence: the way in which vital rates change with population size or the availability of resources, such as prey. Not only is density dependence an essential prerequisite for population stability and sustainable use, but the form it takes will also determine how a population responds to behavioural changes. This is because behaviour, and particularly the effect of behavioural change on body condition, plays a central role in many of the mechanistic models of density dependence. Chapters 5 and 6 explore the way in which additional complexities, such as social structure and the way in which populations are distributed in space, can affect the dynamics of populations. Models that account for these complexities behave in a much less predictable way than the relatively simple structured models that form the core of Chapters 1-4. So far, the models of population dynamics that we have reviewed have been deterministic. That is, they have assumed that the only way in which vital rates can vary is in response to a change in abundance, via density dependent mechanisms. In Chapters 7 and 8 we investigate the effect of random variation (stochasticity) on population dynamics. We distinguish the effects of demographic stochasticity, chance variations in the number of animals that die or give birth in a time interval that occur even if vital rates do not vary over time, and environmental stochasticity, which is the result of variations in vital rates across years. Variation in abundance may also occur as a result of environmental change and changes in the ecological community of which a population is a part. The effect of all these sources of variation is to reduce the realised growth rate of a population, and therefore its risk of extinction. In Chapter 9 we consider how the basic population modelling framework described in Chapters 1-8 might be extended to take account of the life functions identified by the NRC Committee. We suggest that these life functions are useful for defining the context in which behavioural responses might affect vital rates, but that they do not need to be modelled explicitly. Removing vital functions from the PCAD framework results in a much simpler structure, which is compatible with existing population modelling frameworks. However, these will have to be extended to allow population states, like body condition, that vary continuously to be modelled. Chapter 10 describes how changes in lambda can be detected. The simple analytical frameworks that are available for this are all vulnerable to the effects of variability that we introduced in Chapter 7. However, there is a framework (state-space and hidden Markov process modelling) that can account for the effects of this variability, and we recommend its use for detecting trends. The additional benefit of this approach is that its use results in a detailed model of the dynamics of the population that is under investigation. Chapter 11 reviews the different model structures that can be used to describe the dynamics of a population, and explains when different forms of population models (e.g. discrete vs. continuous time, deterministic vs. stochastic) are most appropriate. We also discuss how these different frameworks can be extended to account for continuous population states, as recommended in Chapter 8. The final focus is on how state-space models can be fitted to time series of abundance estimates and information on vital rates. Chapter 12 looks at the relevance of the different modelling approaches described in the previous chapters for analysing the potential effects of behavioural responses to sound on population dynamics, particularly the kinds of sounds that may be generated by the oil and gas industry. We conclude that lambda , the population rate of increase, and its variation provides a useful measure of these effects. We also believe that the models used for this purpose will certainly have to account for the effects of variability and density dependence. They will probably also have to account for the effects of social structure and the way in which populations use space. The state-space modelling framework outlined in Chapter 11 can, in principle, be extended to capture all of these features although work on this is still in its infancy.</dc:description>
    </item>
    <item>
      <title>2A peptides provide distinct solutions to driving stop-carry on translational recoding</title>
      <link>http://hdl.handle.net/10023/2227</link>
      <description>Abstract: Expression of viral proteins frequently includes non-canonical decoding events (‘recoding’) during translation. ‘2A’ oligopeptides drive one such event, termed ‘stop-carry on’ recoding. Nascent 2A peptides interact with the ribosomal exit tunnel to dictate an unusual stop codon-independent termination of translation at the final Pro codon of 2A. Subsequently, translation ‘reinitiates’ on the same codon, two individual proteins being generated from one open reading frame. Many 2A peptides have been identified, and they have a conserved C-terminal motif. Little similarity is present in the N-terminal portions of these peptides, which might suggest that these amino acids are not important in the 2A reaction. However, mutagenesis indicates that identity of the amino acid at nearly all positions of a single 2A peptide is important for activity. Each 2A may then represent a specific solution for positioning the conserved C-terminus within the peptidyl-transferase centre to promote recoding. Nascent 2A peptide:ribosome interactions are suggested to alter ribosomal fine structure to discriminate against prolyl-tRNAPro and promote termination in the absence of a stop codon. Such structural modifications may account for our observation that replacement of the final Pro codon of 2A with any stop codon both stalls ribosome processivity and inhibits nascent chain release.</description>
      <pubDate>Sun, 01 Jan 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2227</guid>
      <dc:date>2012-01-01T00:00:00Z</dc:date>
      <dc:creator>Sharma, P</dc:creator>
      <dc:creator>Yan, F</dc:creator>
      <dc:creator>Doronina, V</dc:creator>
      <dc:creator>Escuin-Ordinas, Helena</dc:creator>
      <dc:creator>Ryan, Martin Denis</dc:creator>
      <dc:creator>Brown, Jeremy</dc:creator>
      <dc:description>Expression of viral proteins frequently includes non-canonical decoding events (‘recoding’) during translation. ‘2A’ oligopeptides drive one such event, termed ‘stop-carry on’ recoding. Nascent 2A peptides interact with the ribosomal exit tunnel to dictate an unusual stop codon-independent termination of translation at the final Pro codon of 2A. Subsequently, translation ‘reinitiates’ on the same codon, two individual proteins being generated from one open reading frame. Many 2A peptides have been identified, and they have a conserved C-terminal motif. Little similarity is present in the N-terminal portions of these peptides, which might suggest that these amino acids are not important in the 2A reaction. However, mutagenesis indicates that identity of the amino acid at nearly all positions of a single 2A peptide is important for activity. Each 2A may then represent a specific solution for positioning the conserved C-terminus within the peptidyl-transferase centre to promote recoding. Nascent 2A peptide:ribosome interactions are suggested to alter ribosomal fine structure to discriminate against prolyl-tRNAPro and promote termination in the absence of a stop codon. Such structural modifications may account for our observation that replacement of the final Pro codon of 2A with any stop codon both stalls ribosome processivity and inhibits nascent chain release.</dc:description>
    </item>
    <item>
      <title>Generation and characterization of a recombinant Rift Valley fever virus expressing a V5 epitope-tagged RNA-dependent RNA polymerase</title>
      <link>http://hdl.handle.net/10023/2191</link>
      <description>Abstract: The viral RNA-dependent RNA polymerase (RdRp; L protein) of Rift Valley fever virus (RVFV; family Bunyaviridae) is a 238 kDa protein that is crucial for the life cycle of the virus, as it catalyses both transcription of viral mRNAs and replication of the tripartite genome. Despite its importance, little is known about the intracellular distribution of the polymerase or its other roles during infection, primarily because of lack of specific antibodies that recognize L protein. To begin to address these questions we investigated whether the RVFV (MP12 strain) polymerase could tolerate insertion of the V5 epitope, as has been previously demonstrated for the Bunyamwera virus L protein. Insertion of the 14 aa epitope into the polymerase sequence at aa 1852 resulted in a polymerase that retained functionality in a minigenome assay, and we were able to rescue recombinant viruses that expressed the modified L protein by reverse genetics. The L protein could be detected in infected cells by Western blotting with anti-V5 antibodies. Examination of recombinant virus-infected cells by immunofluorescence revealed a punctate perinuclear or cytoplasmic distribution of the polymerase that co-localized with the nucleocapsid protein. The generation of RVFV expressing a tagged RdRp will allow detailed examination of the role of the viral polymerase in the virus life cycle.</description>
      <pubDate>Thu, 01 Dec 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2191</guid>
      <dc:date>2011-12-01T00:00:00Z</dc:date>
      <dc:creator>Brennan, Benjamin</dc:creator>
      <dc:creator>Li, Ping</dc:creator>
      <dc:creator>Elliott, Richard M.</dc:creator>
      <dc:description>The viral RNA-dependent RNA polymerase (RdRp; L protein) of Rift Valley fever virus (RVFV; family Bunyaviridae) is a 238 kDa protein that is crucial for the life cycle of the virus, as it catalyses both transcription of viral mRNAs and replication of the tripartite genome. Despite its importance, little is known about the intracellular distribution of the polymerase or its other roles during infection, primarily because of lack of specific antibodies that recognize L protein. To begin to address these questions we investigated whether the RVFV (MP12 strain) polymerase could tolerate insertion of the V5 epitope, as has been previously demonstrated for the Bunyamwera virus L protein. Insertion of the 14 aa epitope into the polymerase sequence at aa 1852 resulted in a polymerase that retained functionality in a minigenome assay, and we were able to rescue recombinant viruses that expressed the modified L protein by reverse genetics. The L protein could be detected in infected cells by Western blotting with anti-V5 antibodies. Examination of recombinant virus-infected cells by immunofluorescence revealed a punctate perinuclear or cytoplasmic distribution of the polymerase that co-localized with the nucleocapsid protein. The generation of RVFV expressing a tagged RdRp will allow detailed examination of the role of the viral polymerase in the virus life cycle.</dc:description>
    </item>
    <item>
      <title>Innate sensing of HIV-infected cells</title>
      <link>http://hdl.handle.net/10023/2178</link>
      <description>Abstract: Cell-free HIV-1 virions are poor stimulators of type I interferon (IFN) production. We examined here how HIV-infected cells are recognized by plasmacytoid dendritic cells (pDCs) and by other cells. We show that infected lymphocytes are more potent inducers of IFN than virions. There are target cell-type differences in the recognition of infected lymphocytes. In primary pDCs and pDC-like cells, recognition occurs in large part through TLR7, as demonstrated by the use of inhibitors and by TLR7 silencing. Donor cells expressing replication-defective viruses, carrying mutated reverse transcriptase, integrase or nucleocapsid proteins induced IFN production by target cells as potently as wild-type virus. In contrast, Env-deleted or fusion defective HIV-1 mutants were less efficient, suggesting that in addition to TLR7, cytoplasmic cellular sensors may also mediate sensing of infected cells. Furthermore, in a model of TLR7-negative cells, we demonstrate that the IRF3 pathway, through a process requiring access of incoming viral material to the cytoplasm, allows sensing of HIV-infected lymphocytes. Therefore, detection of HIV-infected lymphocytes occurs through both endosomal and cytoplasmic pathways. Characterization of the mechanisms of innate recognition of HIV-infected cells allows a better understanding of the pathogenic and exacerbated immunologic events associated with HIV infection.</description>
      <pubDate>Tue, 01 Feb 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2178</guid>
      <dc:date>2011-02-01T00:00:00Z</dc:date>
      <dc:creator>Lepelley, Alice</dc:creator>
      <dc:creator>Louis, Stephanie</dc:creator>
      <dc:creator>Sourisseau, Marion</dc:creator>
      <dc:creator>Law, Helen K. W.</dc:creator>
      <dc:creator>Pothlichet, Julien</dc:creator>
      <dc:creator>Schilte, Clementine</dc:creator>
      <dc:creator>Chaperot, Laurence</dc:creator>
      <dc:creator>Plumas, Joel</dc:creator>
      <dc:creator>Randall, Richard E.</dc:creator>
      <dc:creator>Si-Tahar, Mustapha</dc:creator>
      <dc:creator>Mammano, Fabrizio</dc:creator>
      <dc:creator>Albert, Matthew L.</dc:creator>
      <dc:creator>Schwartz, Olivier</dc:creator>
      <dc:description>Cell-free HIV-1 virions are poor stimulators of type I interferon (IFN) production. We examined here how HIV-infected cells are recognized by plasmacytoid dendritic cells (pDCs) and by other cells. We show that infected lymphocytes are more potent inducers of IFN than virions. There are target cell-type differences in the recognition of infected lymphocytes. In primary pDCs and pDC-like cells, recognition occurs in large part through TLR7, as demonstrated by the use of inhibitors and by TLR7 silencing. Donor cells expressing replication-defective viruses, carrying mutated reverse transcriptase, integrase or nucleocapsid proteins induced IFN production by target cells as potently as wild-type virus. In contrast, Env-deleted or fusion defective HIV-1 mutants were less efficient, suggesting that in addition to TLR7, cytoplasmic cellular sensors may also mediate sensing of infected cells. Furthermore, in a model of TLR7-negative cells, we demonstrate that the IRF3 pathway, through a process requiring access of incoming viral material to the cytoplasm, allows sensing of HIV-infected lymphocytes. Therefore, detection of HIV-infected lymphocytes occurs through both endosomal and cytoplasmic pathways. Characterization of the mechanisms of innate recognition of HIV-infected cells allows a better understanding of the pathogenic and exacerbated immunologic events associated with HIV infection.</dc:description>
    </item>
    <item>
      <title>A transient homotypic interaction model for the influenza A virus NS1 protein effector domain</title>
      <link>http://hdl.handle.net/10023/2177</link>
      <description>Abstract: Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins.
Description: Work in St. Andrews was supported by the Medical Research Council, UK (RER and RJR), and the Scottish Funding Council (RJR).</description>
      <pubDate>Mon, 28 Mar 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2177</guid>
      <dc:date>2011-03-28T00:00:00Z</dc:date>
      <dc:creator>Kerry, Philip S.</dc:creator>
      <dc:creator>Ayllon, Juan</dc:creator>
      <dc:creator>Taylor, Margaret A.</dc:creator>
      <dc:creator>Hass, Claudia</dc:creator>
      <dc:creator>Lewis, Andrew</dc:creator>
      <dc:creator>Garcia-Sastre, Adolfo</dc:creator>
      <dc:creator>Randall, Richard E.</dc:creator>
      <dc:creator>Hale, Benjamin G.</dc:creator>
      <dc:creator>Russell, Rupert J.</dc:creator>
      <dc:description>Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins.</dc:description>
    </item>
    <item>
      <title>Universal scaling rules predict evolutionary patterns of myogenesis in species with indeterminate growth</title>
      <link>http://hdl.handle.net/10023/2170</link>
      <description>Abstract: Intraspecific phenotypic variation is ubiquitous and often associated with resource exploitation in emerging habitats. For example, reduced body size has evolved repeatedly in Arctic charr (Salvelinus alpinus L.) and threespine stickleback (Gasterosteus aculeatus L.) across post-glacial habitats of the Northern Hemisphere. Exploiting these models, we examined how body size and myogenesis evolve with respect to the 'optimum fibre size hypothesis', which predicts that selection acts to minimize energetic costs associated with ionic homeostasis by optimizing muscle fibre production during development. In eight dwarf Icelandic Arctic charr populations, the ultimate production of fast-twitch muscle fibres (FN(max)) was only 39.5 and 15.5 per cent of that in large-bodied natural and aquaculture populations, respectively. Consequently, average fibre diameter (FD) scaled with a mass exponent of 0.19, paralleling the relaxation of diffusional constraints associated with mass-specific metabolic rate scaling. Similar reductions in FN(max) were observed for stickleback, including a small-bodied Alaskan population derived from a larger-bodied oceanic stock over a decadal timescale. The results suggest that in species showing indeterminate growth, body size evolution is accompanied by strong selection for fibre size optimization, theoretically allowing resources saved from ionic homeostasis to be allocated to other traits affecting fitness, including reproduction. Gene flow between small- and large-bodied populations residing in sympatry may counteract the evolution of this trait.</description>
      <pubDate>Thu, 07 Jun 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2170</guid>
      <dc:date>2012-06-07T00:00:00Z</dc:date>
      <dc:creator>Johnston, Ian Alistair</dc:creator>
      <dc:creator>Kristjansson, Bjarni K.</dc:creator>
      <dc:creator>Paxton, Charles G. M.</dc:creator>
      <dc:creator>Vieira-Johnston, Vera Lucia Almeida</dc:creator>
      <dc:creator>MacQueen, Daniel John</dc:creator>
      <dc:creator>Bell, Michael A.</dc:creator>
      <dc:description>Intraspecific phenotypic variation is ubiquitous and often associated with resource exploitation in emerging habitats. For example, reduced body size has evolved repeatedly in Arctic charr (Salvelinus alpinus L.) and threespine stickleback (Gasterosteus aculeatus L.) across post-glacial habitats of the Northern Hemisphere. Exploiting these models, we examined how body size and myogenesis evolve with respect to the 'optimum fibre size hypothesis', which predicts that selection acts to minimize energetic costs associated with ionic homeostasis by optimizing muscle fibre production during development. In eight dwarf Icelandic Arctic charr populations, the ultimate production of fast-twitch muscle fibres (FN(max)) was only 39.5 and 15.5 per cent of that in large-bodied natural and aquaculture populations, respectively. Consequently, average fibre diameter (FD) scaled with a mass exponent of 0.19, paralleling the relaxation of diffusional constraints associated with mass-specific metabolic rate scaling. Similar reductions in FN(max) were observed for stickleback, including a small-bodied Alaskan population derived from a larger-bodied oceanic stock over a decadal timescale. The results suggest that in species showing indeterminate growth, body size evolution is accompanied by strong selection for fibre size optimization, theoretically allowing resources saved from ionic homeostasis to be allocated to other traits affecting fitness, including reproduction. Gene flow between small- and large-bodied populations residing in sympatry may counteract the evolution of this trait.</dc:description>
    </item>
    <item>
      <title>Sex differences in impulsivity : a meta-analysis</title>
      <link>http://hdl.handle.net/10023/2161</link>
      <description>Abstract: Men are overrepresented in socially problematic behaviors, such as aggression and criminal behavior, which have been linked to impulsivity. Our review of impulsivity is organized around the tripartite theoretical distinction between reward hypersensitivity, punishment hyposensitivity, and inadequate effortful control. Drawing on evolution try, criminological, developmental, and personality theories, we predicted that sex differences would be most pronounced in risky activities with men demonstrating greater sensation seeking, greater reward sensitivity, and lower punishment sensitivity. We predicted a small female advantage in effortful control. We analyzed 741 effect sizes from 277 studies, including psychometric and behavioral measures. Women were consistently more punishment sensitive (d = -0.33), but men did not show greater reward sensitivity (d = 0.01). Men showed significantly higher sensation seeking on questionnaire mea lures (d = 0.41) and on a behavioral risk-taking task (d = 0.36). Questionnaire measures of deficits in effortful control showed a very modest effect size in the male direction (d = 0.08). Sex differences were not found on delay discounting or executive function tasks. The results indicate a stronger sex difference in motivational rather than effortful or executive forms of behavior control. Specifically, they support evolutionary and biological theories of risk taking predicated on sex differences in punishment sensitivity. A clearer understanding of sex differences in impulsivity depends upon recognizing important distinctions between sensation seeking and impulsivity, between executive and effortful forms of control, and between impulsivity as a deficit and as a trait.
Description: Supplemental materials: http://dx.doi.org/10.1037/a0021591.supp</description>
      <pubDate>Sat, 01 Jan 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2161</guid>
      <dc:date>2011-01-01T00:00:00Z</dc:date>
      <dc:creator>Cross, Catharine P.</dc:creator>
      <dc:creator>Copping, Lee T.</dc:creator>
      <dc:creator>Campbell, Anne</dc:creator>
      <dc:description>Men are overrepresented in socially problematic behaviors, such as aggression and criminal behavior, which have been linked to impulsivity. Our review of impulsivity is organized around the tripartite theoretical distinction between reward hypersensitivity, punishment hyposensitivity, and inadequate effortful control. Drawing on evolution try, criminological, developmental, and personality theories, we predicted that sex differences would be most pronounced in risky activities with men demonstrating greater sensation seeking, greater reward sensitivity, and lower punishment sensitivity. We predicted a small female advantage in effortful control. We analyzed 741 effect sizes from 277 studies, including psychometric and behavioral measures. Women were consistently more punishment sensitive (d = -0.33), but men did not show greater reward sensitivity (d = 0.01). Men showed significantly higher sensation seeking on questionnaire mea lures (d = 0.41) and on a behavioral risk-taking task (d = 0.36). Questionnaire measures of deficits in effortful control showed a very modest effect size in the male direction (d = 0.08). Sex differences were not found on delay discounting or executive function tasks. The results indicate a stronger sex difference in motivational rather than effortful or executive forms of behavior control. Specifically, they support evolutionary and biological theories of risk taking predicated on sex differences in punishment sensitivity. A clearer understanding of sex differences in impulsivity depends upon recognizing important distinctions between sensation seeking and impulsivity, between executive and effortful forms of control, and between impulsivity as a deficit and as a trait.</dc:description>
    </item>
    <item>
      <title>Lipidomic analysis of bloodstream and procyclic form Trypanosoma brucei</title>
      <link>http://hdl.handle.net/10023/2117</link>
      <description>Abstract: The biological membranes of Trypanosonza brucei contain a complex array of phospholipids that are synthesized de novo from precursors obtained either directly from the host, or as catabolised endocytosed lipids. This paper describes the use of nanoflow electrospray tandem mass spectrometry and high resolution mass spectrometry in both positive and negative ion modes, allowing the identification of similar to 500 individual molecular phospholipids species from total lipid extracts of cultured bloodstream and procyclic form T. brucei. Various molecular species of all of the major subclasses of glycerophospholipids were identified including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol as well as phosphatidic acid, phosphatidylglycerol and cardolipin, and the sphingolipids sphingomyelin, inositol phosphoceramide and ethanolamine phosphoceramide. The lipidomic data obtained in this study will aid future biochemical phenotyping of either genetically or chemically manipulated commonly used bloodstream and procyclic strains of Trypanosoma brucei. Hopefully this will allow a greater understanding of the bizarre world of lipids in this important human pathogen.</description>
      <pubDate>Sun, 01 Aug 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2117</guid>
      <dc:date>2010-08-01T00:00:00Z</dc:date>
      <dc:creator>Richmond, Gregory S.</dc:creator>
      <dc:creator>Gibellini, Federica</dc:creator>
      <dc:creator>Young, Simon A.</dc:creator>
      <dc:creator>Major, Louise</dc:creator>
      <dc:creator>Denton, Helen</dc:creator>
      <dc:creator>Lilley, Alison</dc:creator>
      <dc:creator>Smith, Terry K</dc:creator>
      <dc:description>The biological membranes of Trypanosonza brucei contain a complex array of phospholipids that are synthesized de novo from precursors obtained either directly from the host, or as catabolised endocytosed lipids. This paper describes the use of nanoflow electrospray tandem mass spectrometry and high resolution mass spectrometry in both positive and negative ion modes, allowing the identification of similar to 500 individual molecular phospholipids species from total lipid extracts of cultured bloodstream and procyclic form T. brucei. Various molecular species of all of the major subclasses of glycerophospholipids were identified including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol as well as phosphatidic acid, phosphatidylglycerol and cardolipin, and the sphingolipids sphingomyelin, inositol phosphoceramide and ethanolamine phosphoceramide. The lipidomic data obtained in this study will aid future biochemical phenotyping of either genetically or chemically manipulated commonly used bloodstream and procyclic strains of Trypanosoma brucei. Hopefully this will allow a greater understanding of the bizarre world of lipids in this important human pathogen.</dc:description>
    </item>
    <item>
      <title>Displacement of the canonical single-stranded DNA-binding protein in the Thermoproteales</title>
      <link>http://hdl.handle.net/10023/2108</link>
      <description>Abstract: Single-stranded DNA binding proteins (SSBs) based on the OB-fold are considered ubiquitous in nature and play a central role in many DNA transactions including replication, recombination and repair. We demonstrate that the thermoproteales, a clade of hyperthermophilic crenarchaea, lack a canonical SSB. Instead, they encode a distinct ssDNA-binding protein that we term "ThermoDBP", exemplified by protein Ttx1576 from Thermoproteus tenax. ThermoDBP binds specifically to ssDNA with low sequence specificity. The crystal structure of Ttx1576 reveals a unique fold and mechanism for ssDNA binding, consisting of an extended cleft lined with hydrophobic phenylalanine residues and flanked by basic amino acids. Two ssDNA-binding domains are linked by a coiled-coil leucine zipper. ThermoDBP appears to have displaced the canonical SSB during the diversification of the thermoproteales – a highly unusual example where a “ubiquitous” protein has been lost in evolution.</description>
      <pubDate>Tue, 14 Feb 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2108</guid>
      <dc:date>2012-02-14T00:00:00Z</dc:date>
      <dc:creator>Paytubi, Sonia</dc:creator>
      <dc:creator>McMahon, Stephen</dc:creator>
      <dc:creator>Graham, Shirley</dc:creator>
      <dc:creator>Liu, Huanting</dc:creator>
      <dc:creator>Botting, Catherine Helen</dc:creator>
      <dc:creator>Makarova, Kira S.</dc:creator>
      <dc:creator>Kroonin, Eugene V.</dc:creator>
      <dc:creator>Naismith, Jim</dc:creator>
      <dc:creator>White, Malcolm F</dc:creator>
      <dc:description>Single-stranded DNA binding proteins (SSBs) based on the OB-fold are considered ubiquitous in nature and play a central role in many DNA transactions including replication, recombination and repair. We demonstrate that the thermoproteales, a clade of hyperthermophilic crenarchaea, lack a canonical SSB. Instead, they encode a distinct ssDNA-binding protein that we term "ThermoDBP", exemplified by protein Ttx1576 from Thermoproteus tenax. ThermoDBP binds specifically to ssDNA with low sequence specificity. The crystal structure of Ttx1576 reveals a unique fold and mechanism for ssDNA binding, consisting of an extended cleft lined with hydrophobic phenylalanine residues and flanked by basic amino acids. Two ssDNA-binding domains are linked by a coiled-coil leucine zipper. ThermoDBP appears to have displaced the canonical SSB during the diversification of the thermoproteales – a highly unusual example where a “ubiquitous” protein has been lost in evolution.</dc:description>
    </item>
    <item>
      <title>PCNA stimulates catalysis by structure-specific nuclease using two distinct mechanisms : substrate targeting and catalytic step</title>
      <link>http://hdl.handle.net/10023/2103</link>
      <description>Abstract: The sliding clamp Proliferating Cell Nuclear Antigen (PCNA) functions as a recruiter and organizer of a wide variety of DNA modifying enzymes including nucleases, helicases, polymerases and glycosylases. The 5-flap endonuclease Fen-1 is essential for Okazaki fragment processing in eukaryotes and archaea, and is targeted to the replication fork by PCNA. Crenarchaeal XPF, a 3-flap endonuclease, is also stimulated by PCNA in vitro. Using a novel continuous fluorimetric assay, we demonstrate that PCNA activates these two nucleases by fundamentally different mechanisms. PCNA stimulates Fen-1 by increasing the enzymes binding affinity for substrates, as suggested previously. However, PCNA activates XPF by increasing the catalytic rate constant by four orders of magnitude without affecting the K-M. PCNA may function as a platform upon which XPF exerts force to distort DNA substrates, destabilizing the substrate and/or stabilizing the transition state structure. This suggests that PCNA can function directly in supporting catalysis as an essential cofactor in some circumstances, a new role for a protein that is generally assumed to perform a passive targeting and organizing function in molecular biology. This could provide a mechanism for the exquisite control of nuclease activity targeted to specific circumstances, such as replication forks or damaged DNA with pre-loaded PCNA.
Description: This work was supported by the Biotechnology and Biological Sciences Research Council [grants BBD0014391 and BBE0146741]</description>
      <pubDate>Mon, 01 Dec 2008 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2103</guid>
      <dc:date>2008-12-01T00:00:00Z</dc:date>
      <dc:creator>Hutton, R D</dc:creator>
      <dc:creator>Roberts, J A</dc:creator>
      <dc:creator>Penedo, Carlos</dc:creator>
      <dc:creator>White, Malcolm Frederick</dc:creator>
      <dc:description>The sliding clamp Proliferating Cell Nuclear Antigen (PCNA) functions as a recruiter and organizer of a wide variety of DNA modifying enzymes including nucleases, helicases, polymerases and glycosylases. The 5-flap endonuclease Fen-1 is essential for Okazaki fragment processing in eukaryotes and archaea, and is targeted to the replication fork by PCNA. Crenarchaeal XPF, a 3-flap endonuclease, is also stimulated by PCNA in vitro. Using a novel continuous fluorimetric assay, we demonstrate that PCNA activates these two nucleases by fundamentally different mechanisms. PCNA stimulates Fen-1 by increasing the enzymes binding affinity for substrates, as suggested previously. However, PCNA activates XPF by increasing the catalytic rate constant by four orders of magnitude without affecting the K-M. PCNA may function as a platform upon which XPF exerts force to distort DNA substrates, destabilizing the substrate and/or stabilizing the transition state structure. This suggests that PCNA can function directly in supporting catalysis as an essential cofactor in some circumstances, a new role for a protein that is generally assumed to perform a passive targeting and organizing function in molecular biology. This could provide a mechanism for the exquisite control of nuclease activity targeted to specific circumstances, such as replication forks or damaged DNA with pre-loaded PCNA.</dc:description>
    </item>
    <item>
      <title>Selection of reference genes for expression studies with fish myogenic cell cultures</title>
      <link>http://hdl.handle.net/10023/2093</link>
      <description>Abstract: Background: Relatively few studies have used cell culture systems to investigate gene expression and the regulation of myogenesis in fish. To produce robust data from quantitative real-time PCR mRNA levels need to be normalised using internal reference genes which have stable expression across all experimental samples. We have investigated the expression of eight candidate genes to identify suitable reference genes for use in primary myogenic cell cultures from Atlantic salmon (Salmo salar L.). The software analysis packages geNorm, Normfinder and Best keeper were used to rank genes according to their stability across 42 samples during the course of myogenic differentiation. Results: Initial results showed several of the candidate genes exhibited stable expression throughout myogenic culture while Sdha was identified as the least stable gene. Further analysis with geNorm, Normfinder and Bestkeeper identified Ef1 alpha, Hprt1, Ppia and RNApolII as stably expressed. Comparison of data normalised with the geometric average obtained from combinations of any three of these genes showed no significant differences, indicating that any combination of these genes is valid. Conclusion: The geometric average of any three of Hprt1, Ef1 a, Ppia and RNApolII is suitable for normalisation of gene expression data in primary myogenic cultures from Atlantic salmon.</description>
      <pubDate>Mon, 10 Aug 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2093</guid>
      <dc:date>2009-08-10T00:00:00Z</dc:date>
      <dc:creator>Bower, Neil I.</dc:creator>
      <dc:creator>Johnston, Ian A.</dc:creator>
      <dc:description>Background: Relatively few studies have used cell culture systems to investigate gene expression and the regulation of myogenesis in fish. To produce robust data from quantitative real-time PCR mRNA levels need to be normalised using internal reference genes which have stable expression across all experimental samples. We have investigated the expression of eight candidate genes to identify suitable reference genes for use in primary myogenic cell cultures from Atlantic salmon (Salmo salar L.). The software analysis packages geNorm, Normfinder and Best keeper were used to rank genes according to their stability across 42 samples during the course of myogenic differentiation. Results: Initial results showed several of the candidate genes exhibited stable expression throughout myogenic culture while Sdha was identified as the least stable gene. Further analysis with geNorm, Normfinder and Bestkeeper identified Ef1 alpha, Hprt1, Ppia and RNApolII as stably expressed. Comparison of data normalised with the geometric average obtained from combinations of any three of these genes showed no significant differences, indicating that any combination of these genes is valid. Conclusion: The geometric average of any three of Hprt1, Ef1 a, Ppia and RNApolII is suitable for normalisation of gene expression data in primary myogenic cultures from Atlantic salmon.</dc:description>
    </item>
    <item>
      <title>Transcriptional regulation of the IGF signaling pathway by amino acids and insulin-like growth factors during myogenesis in Atlantic salmon</title>
      <link>http://hdl.handle.net/10023/2092</link>
      <description>Abstract: The insulin-like growth factor signalling pathway is an important regulator of skeletal muscle growth. We examined the mRNA expression of components of the insulin-like growth factor (IGF) signalling pathway as well as Fibroblast Growth Factor 2 (FGF2) during maturation of myotubes in primary cell cultures isolated from fast myotomal muscle of Atlantic salmon (Salmo salar). The transcriptional regulation of IGFs and IGFBP expression by amino acids and insulin-like growth factors was also investigated. Proliferation of cells was 15% d(-1) at days 2 and 3 of the culture, increasing to 66% d(-1) at day 6. Three clusters of elevated gene expression were observed during the maturation of the culture associated with mono-nucleic cells (IGFBP5.1 and 5.2, IGFBP-6, IGFBP-rP1, IGFBP-2.2 and IGF-II), the initial proliferation phase (IGF-I, IGFBP-4, FGF2 and IGF-IRb) and terminal differentiation and myotube production (IGF2R, IGF-IRa). In cells starved of amino acids and serum for 72 h, IGF-I mRNA decreased 10-fold which was reversed by amino acid replacement. Addition of IGF-I and amino acids to starved cells resulted in an 18-fold increase in IGF-I mRNA indicating synergistic effects and the activation of additional pathway(s) leading to IGF-I production via a positive feedback mechanism. IGF-II, IGFBP-5.1 and IGFBP-5.2 expression was unchanged in starved cells, but increased with amino acid replacement. Synergistic increases in expression of IGFBP5.2 and IGFBP-4, but not IGFBP5.1 were observed with addition of IGF-I, IGF-II or insulin and amino acids to the medium. IGF-I and IGF-II directly stimulated IGFBP-6 expression, but not when amino acids were present. These findings indicate that amino acids alone are sufficient to stimulate myogenesis in myoblasts and that IGF-I production is controlled by both endocrine and paracrine pathways. A model depicting the transcriptional regulation of the IGF pathway in Atlantic salmon muscle following feeding is proposed.</description>
      <pubDate>Mon, 14 Jun 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2092</guid>
      <dc:date>2010-06-14T00:00:00Z</dc:date>
      <dc:creator>Bower, Neil I.</dc:creator>
      <dc:creator>Johnston, Ian A.</dc:creator>
      <dc:description>The insulin-like growth factor signalling pathway is an important regulator of skeletal muscle growth. We examined the mRNA expression of components of the insulin-like growth factor (IGF) signalling pathway as well as Fibroblast Growth Factor 2 (FGF2) during maturation of myotubes in primary cell cultures isolated from fast myotomal muscle of Atlantic salmon (Salmo salar). The transcriptional regulation of IGFs and IGFBP expression by amino acids and insulin-like growth factors was also investigated. Proliferation of cells was 15% d(-1) at days 2 and 3 of the culture, increasing to 66% d(-1) at day 6. Three clusters of elevated gene expression were observed during the maturation of the culture associated with mono-nucleic cells (IGFBP5.1 and 5.2, IGFBP-6, IGFBP-rP1, IGFBP-2.2 and IGF-II), the initial proliferation phase (IGF-I, IGFBP-4, FGF2 and IGF-IRb) and terminal differentiation and myotube production (IGF2R, IGF-IRa). In cells starved of amino acids and serum for 72 h, IGF-I mRNA decreased 10-fold which was reversed by amino acid replacement. Addition of IGF-I and amino acids to starved cells resulted in an 18-fold increase in IGF-I mRNA indicating synergistic effects and the activation of additional pathway(s) leading to IGF-I production via a positive feedback mechanism. IGF-II, IGFBP-5.1 and IGFBP-5.2 expression was unchanged in starved cells, but increased with amino acid replacement. Synergistic increases in expression of IGFBP5.2 and IGFBP-4, but not IGFBP5.1 were observed with addition of IGF-I, IGF-II or insulin and amino acids to the medium. IGF-I and IGF-II directly stimulated IGFBP-6 expression, but not when amino acids were present. These findings indicate that amino acids alone are sufficient to stimulate myogenesis in myoblasts and that IGF-I production is controlled by both endocrine and paracrine pathways. A model depicting the transcriptional regulation of the IGF pathway in Atlantic salmon muscle following feeding is proposed.</dc:description>
    </item>
    <item>
      <title>Targeted rapid amplification of cDNA ends (T-RACE)-an improved RACE reaction through degradation of non-target sequences</title>
      <link>http://hdl.handle.net/10023/2090</link>
      <description>Abstract: Amplification of the 5' ends of cDNA, although simple in theory, can often be difficult to achieve. We describe a novel method for the specific amplification of cDNA ends. An oligo-dT adapter incorporating a dUTP-containing PCR primer primes first-strand cDNA synthesis incorporating dUTP. Using the Cap finder approach, another distinct dUTP containing adapter is added to the 3' end of the newly synthesized cDNA. Second-strand synthesis incorporating dUTP is achieved by PCR, using dUTP-containing primers complimentary to the adapter sequences incorporated in the cDNA ends. The double-stranded cDNA-containing dUTP serves as a universal template for the specific amplification of the 3' or 5' end of any gene. To amplify the ends of cDNA, asymmetric PCR is performed using a single gene-specific primer and standard dNTPs. The asymmetric PCR product is purified and non-target transcripts containing dUTP degraded by Uracil DNA glycosylase, leaving only those transcripts produced during the asymmetric PCR. Subsequent PCR using a nested gene-specific primer and the 3' or 5' T-RACE primer results in specific amplification of cDNA ends. This method can be used to specifically amplify the 3' and 5' ends of numerous cDNAs from a single cDNA synthesis reaction.</description>
      <pubDate>Mon, 01 Nov 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2090</guid>
      <dc:date>2010-11-01T00:00:00Z</dc:date>
      <dc:creator>Bower, Neil I.</dc:creator>
      <dc:creator>Johnston, Ian A.</dc:creator>
      <dc:description>Amplification of the 5' ends of cDNA, although simple in theory, can often be difficult to achieve. We describe a novel method for the specific amplification of cDNA ends. An oligo-dT adapter incorporating a dUTP-containing PCR primer primes first-strand cDNA synthesis incorporating dUTP. Using the Cap finder approach, another distinct dUTP containing adapter is added to the 3' end of the newly synthesized cDNA. Second-strand synthesis incorporating dUTP is achieved by PCR, using dUTP-containing primers complimentary to the adapter sequences incorporated in the cDNA ends. The double-stranded cDNA-containing dUTP serves as a universal template for the specific amplification of the 3' or 5' end of any gene. To amplify the ends of cDNA, asymmetric PCR is performed using a single gene-specific primer and standard dNTPs. The asymmetric PCR product is purified and non-target transcripts containing dUTP degraded by Uracil DNA glycosylase, leaving only those transcripts produced during the asymmetric PCR. Subsequent PCR using a nested gene-specific primer and the 3' or 5' T-RACE primer results in specific amplification of cDNA ends. This method can be used to specifically amplify the 3' and 5' ends of numerous cDNAs from a single cDNA synthesis reaction.</dc:description>
    </item>
    <item>
      <title>PCNA and XPF cooperate to distort DNA substrates</title>
      <link>http://hdl.handle.net/10023/2089</link>
      <description>Abstract: XPF is a structure-specific endonuclease that preferentially cleaves 3' DNA flaps during a variety of repair processes. The crystal structure of a crenarchaeal XPF protein bound to a DNA duplex yielded insights into how XPF might recognise branched DNA structures, and recent kinetic data have demonstrated that the sliding clamp PCNA acts as an essential cofactor, possibly by allowing XPF to distort the DNA structure into a proper conformation for efficient cleavage to occur. Here, we investigate the solution structure of the 3'-flap substrate bound to XPF in the presence and absence of PCNA using intramolecular Forster resonance energy transfer (FRET). We demonstrate that recognition of the flap substrate by XPF involves major conformational changes of the DNA, including a 90 degrees kink of the DNA duplex and organization of the single-stranded flap. In the presence of PCNA, there is a further substantial reorganization of the flap substrate bound to XPF, providing a structural basis for the observation that PCNA has an essential catalytic role in this system. The wider implications of these observations for the plethora of PCNA-dependent enzymes are discussed.</description>
      <pubDate>Mon, 01 Mar 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2089</guid>
      <dc:date>2010-03-01T00:00:00Z</dc:date>
      <dc:creator>Hutton, Richard D.</dc:creator>
      <dc:creator>Craggs, Timothy D.</dc:creator>
      <dc:creator>White, Malcolm F</dc:creator>
      <dc:creator>Penedo, J. Carlos</dc:creator>
      <dc:description>XPF is a structure-specific endonuclease that preferentially cleaves 3' DNA flaps during a variety of repair processes. The crystal structure of a crenarchaeal XPF protein bound to a DNA duplex yielded insights into how XPF might recognise branched DNA structures, and recent kinetic data have demonstrated that the sliding clamp PCNA acts as an essential cofactor, possibly by allowing XPF to distort the DNA structure into a proper conformation for efficient cleavage to occur. Here, we investigate the solution structure of the 3'-flap substrate bound to XPF in the presence and absence of PCNA using intramolecular Forster resonance energy transfer (FRET). We demonstrate that recognition of the flap substrate by XPF involves major conformational changes of the DNA, including a 90 degrees kink of the DNA duplex and organization of the single-stranded flap. In the presence of PCNA, there is a further substantial reorganization of the flap substrate bound to XPF, providing a structural basis for the observation that PCNA has an essential catalytic role in this system. The wider implications of these observations for the plethora of PCNA-dependent enzymes are discussed.</dc:description>
    </item>
    <item>
      <title>Genome-wide expression profiling of in vivo-derived bloodstream parasite stages and dynamic analysis of mRNA alterations during synchronous differentiation in Trypanosoma brucei</title>
      <link>http://hdl.handle.net/10023/2087</link>
      <description>Abstract: Background: Trypanosomes undergo extensive developmental changes during their complex life cycle. Crucial among these is the transition between slender and stumpy bloodstream forms and, thereafter, the differentiation from stumpy to tsetse-midgut procyclic forms. These developmental events are highly regulated, temporally reproducible and accompanied by expression changes mediated almost exclusively at the post-transcriptional level. Results: In this study we have examined, by whole-genome microarray analysis, the mRNA abundance of genes in slender and stumpy forms of T. brucei AnTat1.1 cells, and also during their synchronous differentiation to procyclic forms. In total, five biological replicates representing the differentiation of matched parasite populations derived from five individual mouse infections were assayed, with RNAs being derived at key biological time points during the time course of their synchronous differentiation to procyclic forms. Importantly, the biological context of these mRNA profiles was established by assaying the coincident cellular events in each population (surface antigen exchange, morphological restructuring, cell cycle re-entry), thereby linking the observed gene expression changes to the well-established framework of trypanosome differentiation. Conclusion: Using stringent statistical analysis and validation of the derived profiles against experimentally-predicted gene expression and phenotypic changes, we have established the profile of regulated gene expression during these important life-cycle transitions. The highly synchronous nature of differentiation between stumpy and procyclic forms also means that these studies of mRNA profiles are directly relevant to the changes in mRNA abundance within individual cells during this well-characterised developmental transition.</description>
      <pubDate>Fri, 11 Sep 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2087</guid>
      <dc:date>2009-09-11T00:00:00Z</dc:date>
      <dc:creator>Kabani, Sarah</dc:creator>
      <dc:creator>Fenn, Katelyn</dc:creator>
      <dc:creator>Ross, Alan</dc:creator>
      <dc:creator>Ivens, Al</dc:creator>
      <dc:creator>Smith, Terry K.</dc:creator>
      <dc:creator>Ghazal, Peter</dc:creator>
      <dc:creator>Matthews, Keith</dc:creator>
      <dc:description>Background: Trypanosomes undergo extensive developmental changes during their complex life cycle. Crucial among these is the transition between slender and stumpy bloodstream forms and, thereafter, the differentiation from stumpy to tsetse-midgut procyclic forms. These developmental events are highly regulated, temporally reproducible and accompanied by expression changes mediated almost exclusively at the post-transcriptional level. Results: In this study we have examined, by whole-genome microarray analysis, the mRNA abundance of genes in slender and stumpy forms of T. brucei AnTat1.1 cells, and also during their synchronous differentiation to procyclic forms. In total, five biological replicates representing the differentiation of matched parasite populations derived from five individual mouse infections were assayed, with RNAs being derived at key biological time points during the time course of their synchronous differentiation to procyclic forms. Importantly, the biological context of these mRNA profiles was established by assaying the coincident cellular events in each population (surface antigen exchange, morphological restructuring, cell cycle re-entry), thereby linking the observed gene expression changes to the well-established framework of trypanosome differentiation. Conclusion: Using stringent statistical analysis and validation of the derived profiles against experimentally-predicted gene expression and phenotypic changes, we have established the profile of regulated gene expression during these important life-cycle transitions. The highly synchronous nature of differentiation between stumpy and procyclic forms also means that these studies of mRNA profiles are directly relevant to the changes in mRNA abundance within individual cells during this well-characterised developmental transition.</dc:description>
    </item>
    <item>
      <title>Biochemical characterization of the initial steps of the Kennedy pathway in Trypanosoma brucei : the ethanolamine and choline kinases</title>
      <link>http://hdl.handle.net/10023/2086</link>
      <description>Abstract: Ethanolamine and choline are major components of the trypanosome membrane phospholipids, in the form of GPEtn (glycero-phosphoethanolamine) and GPCho (glycerophosphocholine). Ethanolamine is also found as an integral component of the GPI (glycosylpliosphatidylinositol) anchor that is required for membrane attachment of cell-surface proteins, most notably the variant-surface glycoproteins. The de novo synthesis of GPEtn and GPCho starts with the generation of phosphoethanolamine and phosphocholine by ethanolamine and choline kinases via the Kennedy pathway. Database mining revealed two putative C/EKs (choline/ethanolamine kinases) in the Trypanosoma brucei genome, which were cloned, overexpressed, purified and characterized. TbEK 1 (T brucei ethanolamine kinase 1) was shown to be catalytically active as an ethanolamine-specific kinase, i.e. it had no choline kinase activity. The K values for ethanolamine and ATP were found to be 18.4 +/- 0.9 and 219 29 mu M respectively. TbC/EK2 (T brucei choline/ethanolamine kinase 2), on the other hand, was found to be able to phosphorylate both ethanolamine and choline, even though choline was the preferred substrate, with a K-m 80 times lower than that of ethanolamine. The K. values for choline, ethanolamine and ATP were 31.4 +/- 2.6 mu M, 2.56 +/- 0.31 mu M and 20.6 +/- 1.96 mu M respectively. Further substrate specificity analysis revealed that both TbEK1 and TbC/EK2 were able to tolerate various modifications at the amino group, with the exception of a quaternary amine for TbEK1 (choline) and a primary amine for TbC/EK2 (ethanolamine). Both enzymes recognized analogues with substituents oil C-2, but substitutions oil C-1 and elongations of the carbon chain were not well tolerated.</description>
      <pubDate>Wed, 01 Oct 2008 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2086</guid>
      <dc:date>2008-10-01T00:00:00Z</dc:date>
      <dc:creator>Gibellini, Federica</dc:creator>
      <dc:creator>Hunter, William N.</dc:creator>
      <dc:creator>Smith, Terry K.</dc:creator>
      <dc:description>Ethanolamine and choline are major components of the trypanosome membrane phospholipids, in the form of GPEtn (glycero-phosphoethanolamine) and GPCho (glycerophosphocholine). Ethanolamine is also found as an integral component of the GPI (glycosylpliosphatidylinositol) anchor that is required for membrane attachment of cell-surface proteins, most notably the variant-surface glycoproteins. The de novo synthesis of GPEtn and GPCho starts with the generation of phosphoethanolamine and phosphocholine by ethanolamine and choline kinases via the Kennedy pathway. Database mining revealed two putative C/EKs (choline/ethanolamine kinases) in the Trypanosoma brucei genome, which were cloned, overexpressed, purified and characterized. TbEK 1 (T brucei ethanolamine kinase 1) was shown to be catalytically active as an ethanolamine-specific kinase, i.e. it had no choline kinase activity. The K values for ethanolamine and ATP were found to be 18.4 +/- 0.9 and 219 29 mu M respectively. TbC/EK2 (T brucei choline/ethanolamine kinase 2), on the other hand, was found to be able to phosphorylate both ethanolamine and choline, even though choline was the preferred substrate, with a K-m 80 times lower than that of ethanolamine. The K. values for choline, ethanolamine and ATP were 31.4 +/- 2.6 mu M, 2.56 +/- 0.31 mu M and 20.6 +/- 1.96 mu M respectively. Further substrate specificity analysis revealed that both TbEK1 and TbC/EK2 were able to tolerate various modifications at the amino group, with the exception of a quaternary amine for TbEK1 (choline) and a primary amine for TbC/EK2 (ethanolamine). Both enzymes recognized analogues with substituents oil C-2, but substitutions oil C-1 and elongations of the carbon chain were not well tolerated.</dc:description>
    </item>
    <item>
      <title>Identifying social learning in animal populations : A new ‘option-bias’ method</title>
      <link>http://hdl.handle.net/10023/2085</link>
      <description>Abstract: Studies of natural animal populations reveal widespread evidence for the diffusion of novel behaviour patterns, and for intra- and inter-population variation in behaviour. However, claims that these are manifestations of animal ‘culture’ remain controversial because alternative explanations to social learning remain difficult to refute. This inability to identify social learning in social settings has also contributed to the failure to test evolutionary hypotheses concerning the social learning strategies that animals deploy. We present a solution to this problem, in the form of a new means of identifying social learning in animal populations. The method is based on the assumption that social learning will generate greater homogeneity in behaviour between animals than expected in its absence. Our procedure compares the observed level of homogeneity to a bootstrapped sampling distribution utilizing randomization and other procedures. We illustrate the method on data from groups of monkeys provided with novel two-option extractive foraging tasks, demonstrating that social learning can indeed be distinguished from unlearned processes and asocial learning, and revealing that the monkeys only employed social learning for the more difficult tasks. The method is further validated against published datasets and through simulation, and exhibits higher statistical power than conventional inferential statistics.</description>
      <pubDate>Sat, 01 Aug 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2085</guid>
      <dc:date>2009-08-01T00:00:00Z</dc:date>
      <dc:creator>Kendal, R L</dc:creator>
      <dc:creator>Kendal, J R</dc:creator>
      <dc:creator>Hoppitt, William John Edward</dc:creator>
      <dc:creator>Laland, Kevin Neville</dc:creator>
      <dc:description>Studies of natural animal populations reveal widespread evidence for the diffusion of novel behaviour patterns, and for intra- and inter-population variation in behaviour. However, claims that these are manifestations of animal ‘culture’ remain controversial because alternative explanations to social learning remain difficult to refute. This inability to identify social learning in social settings has also contributed to the failure to test evolutionary hypotheses concerning the social learning strategies that animals deploy. We present a solution to this problem, in the form of a new means of identifying social learning in animal populations. The method is based on the assumption that social learning will generate greater homogeneity in behaviour between animals than expected in its absence. Our procedure compares the observed level of homogeneity to a bootstrapped sampling distribution utilizing randomization and other procedures. We illustrate the method on data from groups of monkeys provided with novel two-option extractive foraging tasks, demonstrating that social learning can indeed be distinguished from unlearned processes and asocial learning, and revealing that the monkeys only employed social learning for the more difficult tasks. The method is further validated against published datasets and through simulation, and exhibits higher statistical power than conventional inferential statistics.</dc:description>
    </item>
    <item>
      <title>Complex Region Spatial Smoother (CReSS)</title>
      <link>http://hdl.handle.net/10023/2048</link>
      <description>Abstract: Conventional smoothing over complicated coastal and island regions may result in errors across boundaries, due to the use of Euclidean distances to represent inter-point similarity. The new Complex Region Spatial Smoother (CReSS) method presented here, uses estimated geodesic distances, model averaging and a local radial basis function to provide improved smoothing over complex domains. CReSS is compared, via simulation, to recent related smoothing techniques, Thin Plate Splines (TPS, Harder and Desmarais, 1972), geodesic low rank TPS [Wang and Ranalli, 2007] and the Soap film smoother [Wood et al., 2008]. The GLTPS method cannot be used in areas with islands and SOAP can be hard to parameterize. CReSS is comparable with, if not better than, all considered methods on a range of simulations. Supplementary materials for this article are available online.</description>
      <pubDate>Sat, 01 Jan 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2048</guid>
      <dc:date>2011-01-01T00:00:00Z</dc:date>
      <dc:creator>Scott Hayward, Lindesay Alexandra Sarah</dc:creator>
      <dc:creator>MacKenzie, Monique Lea</dc:creator>
      <dc:creator>Donovan, Carl Robert</dc:creator>
      <dc:creator>Walker, Cameron</dc:creator>
      <dc:creator>Ashe, Erin</dc:creator>
      <dc:description>Conventional smoothing over complicated coastal and island regions may result in errors across boundaries, due to the use of Euclidean distances to represent inter-point similarity. The new Complex Region Spatial Smoother (CReSS) method presented here, uses estimated geodesic distances, model averaging and a local radial basis function to provide improved smoothing over complex domains. CReSS is compared, via simulation, to recent related smoothing techniques, Thin Plate Splines (TPS, Harder and Desmarais, 1972), geodesic low rank TPS [Wang and Ranalli, 2007] and the Soap film smoother [Wood et al., 2008]. The GLTPS method cannot be used in areas with islands and SOAP can be hard to parameterize. CReSS is comparable with, if not better than, all considered methods on a range of simulations. Supplementary materials for this article are available online.</dc:description>
    </item>
    <item>
      <title>Bird species richness and diversity at montane Important Bird Area (IBA) sites in south-eastern Nigeria</title>
      <link>http://hdl.handle.net/10023/2043</link>
      <description>Abstract: The mountains of south-eastern Nigeria are a western extension of the Cameroon mountain range, which is classified as an endemic bird area (EBA). Unlike its eastern extension in Cameroon, most of the ornithological surveys in the western extension of the Cameroon highlands in Nigeria have produced only limited checklists and inventories. There is a clear need for quantitative baseline data so that conservation problems can be identified. Twenty line transects covering a total transect length of 28.8 km were used to survey five sites (Afi Mountain Wildlife Sanctuary, Oban and Okwangwo Division of Cross River National Park, Sankwala Mountains and Mbe Mountains) in the westernmost extension of the Cameroon Mountains EBA in south western Nigeria. Vegetation measurements were taken to control for the potential confounding effect of variation in vegetation density and structure on detectability of birds between sites. The 193 bird species recorded in Afi, 158 in Sankwala, 124 in Oban, 100 in Mbe and 73 in Okwangwo Division included most of the Cameroon highlands restricted range species. The results show that the mountains of south-eastern Nigeria are important parts of the Cameroon EBA, particularly the Afi Mountain Wildlife Sanctuary. However these sites are threatened by fire and livestock grazing on the hilltops, shifting agriculture on the hillsides and lowlands, and logging for timber in some parts, as well as wildlife hunting for bush meat.</description>
      <pubDate>Wed, 01 Sep 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2043</guid>
      <dc:date>2010-09-01T00:00:00Z</dc:date>
      <dc:creator>Manu, S</dc:creator>
      <dc:creator>Imong, I. S.</dc:creator>
      <dc:creator>Cresswell, Will</dc:creator>
      <dc:description>The mountains of south-eastern Nigeria are a western extension of the Cameroon mountain range, which is classified as an endemic bird area (EBA). Unlike its eastern extension in Cameroon, most of the ornithological surveys in the western extension of the Cameroon highlands in Nigeria have produced only limited checklists and inventories. There is a clear need for quantitative baseline data so that conservation problems can be identified. Twenty line transects covering a total transect length of 28.8 km were used to survey five sites (Afi Mountain Wildlife Sanctuary, Oban and Okwangwo Division of Cross River National Park, Sankwala Mountains and Mbe Mountains) in the westernmost extension of the Cameroon Mountains EBA in south western Nigeria. Vegetation measurements were taken to control for the potential confounding effect of variation in vegetation density and structure on detectability of birds between sites. The 193 bird species recorded in Afi, 158 in Sankwala, 124 in Oban, 100 in Mbe and 73 in Okwangwo Division included most of the Cameroon highlands restricted range species. The results show that the mountains of south-eastern Nigeria are important parts of the Cameroon EBA, particularly the Afi Mountain Wildlife Sanctuary. However these sites are threatened by fire and livestock grazing on the hilltops, shifting agriculture on the hillsides and lowlands, and logging for timber in some parts, as well as wildlife hunting for bush meat.</dc:description>
    </item>
    <item>
      <title>Characteristics of the Ascophyllum nodosum stands and their associated diversity along the coast of Brittany, France</title>
      <link>http://hdl.handle.net/10023/2042</link>
      <description>Abstract: The present study aimed at estimating the characteristics of the Ascophyllum nodosum stands along the coast of Brittany, France. Although both an ecologically and economically important macroalga on sheltered rocky shores of the North Atlantic, no study has simultaneously dealt with the variability of the densities, lengths and biomasses of A. nodosum together with a description of its associated algal and animal diversity. There were significant differences in mean lengths and variations in the length–population structures between sites. However, the biomasses and densities showed no significant differences. The biomasses are amongst the highest ones estimated over the entire species distribution. The algal and animal assemblages were typical of A. nodosum zones, but only the identity composition of the algal communities seemed to reflect site differences in environmental forces. The biomasses measured in the present study should help improve future macroalgae biomass and metabolism estimates on regional or global scales. Finally, the data will provide a reference state for future studies on the responses of fucoid canopies to environmental changes.</description>
      <pubDate>Sun, 01 May 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2042</guid>
      <dc:date>2011-05-01T00:00:00Z</dc:date>
      <dc:creator>Gollety, Claire</dc:creator>
      <dc:creator>Thiébaut, Eric</dc:creator>
      <dc:creator>Davoult, Dominique</dc:creator>
      <dc:description>The present study aimed at estimating the characteristics of the Ascophyllum nodosum stands along the coast of Brittany, France. Although both an ecologically and economically important macroalga on sheltered rocky shores of the North Atlantic, no study has simultaneously dealt with the variability of the densities, lengths and biomasses of A. nodosum together with a description of its associated algal and animal diversity. There were significant differences in mean lengths and variations in the length–population structures between sites. However, the biomasses and densities showed no significant differences. The biomasses are amongst the highest ones estimated over the entire species distribution. The algal and animal assemblages were typical of A. nodosum zones, but only the identity composition of the algal communities seemed to reflect site differences in environmental forces. The biomasses measured in the present study should help improve future macroalgae biomass and metabolism estimates on regional or global scales. Finally, the data will provide a reference state for future studies on the responses of fucoid canopies to environmental changes.</dc:description>
    </item>
    <item>
      <title>Technical Note: Animal-borne CTD-Satellite Relay Data Loggers for real-time oceanographic data collection</title>
      <link>http://hdl.handle.net/10023/2039</link>
      <description>Abstract: The increasing need for continuous monitoring of the world oceans has stimulated the development of a range of autonomous sampling platforms. One novel addition to these approaches is a small, relatively inexpensive data-relaying device that can be deployed on marine mammals to provide vertical oceanographic profiles throughout the upper 2000 m of the water column. When an animal dives, the CTD-Satellite Relay Data Logger (CTD-SRDL) records vertical profiles of temperature, conductivity and pressure. Data are compressed once the animal returns to the surface where it is located by, and relays data to, the Argos satellite system. The technical challenges met in the design of the CTD-SRDL are the maximising of energy efficiency and minimising size, whilst simultaneously maintaining the reliability of an instrument that cannot be recovered and is required to survive its lifetime attached to a marine mammal. The CTD-SRDLs record temperature and salinity with an accuracy of better than 0.005 degrees C and 0.02 respectively. However, due to the limited availability of reference data, real-time data from remote places are often associated with slightly higher errors. The potential to collect large numbers of profiles cost-effectively makes data collection using CTD-SRDL technology particularly beneficial in regions where traditional oceanographic measurements are scarce or even absent. Depending on the CTD-SRDL configuration, it is possible to sample and transmit hydrographic profiles on a daily basis, providing valuable and often unique information for a real-time ocean observing system.
Description: Funded by NERC grants NE/E018289/1 and NER/D/S/2002/00426</description>
      <pubDate>Tue, 15 Dec 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2039</guid>
      <dc:date>2009-12-15T00:00:00Z</dc:date>
      <dc:creator>Boehme, L.</dc:creator>
      <dc:creator>Lovell, P.</dc:creator>
      <dc:creator>Biuw, M.</dc:creator>
      <dc:creator>Roquet, F.</dc:creator>
      <dc:creator>Nicholson, J.</dc:creator>
      <dc:creator>Thorpe, S. E.</dc:creator>
      <dc:creator>Meredith, M. P.</dc:creator>
      <dc:creator>Fedak, M.</dc:creator>
      <dc:description>The increasing need for continuous monitoring of the world oceans has stimulated the development of a range of autonomous sampling platforms. One novel addition to these approaches is a small, relatively inexpensive data-relaying device that can be deployed on marine mammals to provide vertical oceanographic profiles throughout the upper 2000 m of the water column. When an animal dives, the CTD-Satellite Relay Data Logger (CTD-SRDL) records vertical profiles of temperature, conductivity and pressure. Data are compressed once the animal returns to the surface where it is located by, and relays data to, the Argos satellite system. The technical challenges met in the design of the CTD-SRDL are the maximising of energy efficiency and minimising size, whilst simultaneously maintaining the reliability of an instrument that cannot be recovered and is required to survive its lifetime attached to a marine mammal. The CTD-SRDLs record temperature and salinity with an accuracy of better than 0.005 degrees C and 0.02 respectively. However, due to the limited availability of reference data, real-time data from remote places are often associated with slightly higher errors. The potential to collect large numbers of profiles cost-effectively makes data collection using CTD-SRDL technology particularly beneficial in regions where traditional oceanographic measurements are scarce or even absent. Depending on the CTD-SRDL configuration, it is possible to sample and transmit hydrographic profiles on a daily basis, providing valuable and often unique information for a real-time ocean observing system.</dc:description>
    </item>
    <item>
      <title>Integrated holographic system for all-optical manipulation of developing embryos</title>
      <link>http://hdl.handle.net/10023/2007</link>
      <description>Abstract: We demonstrate a system for the combined optical injection and trapping of developing embryos. A Ti:sapphire femtosecond laser in tandem with a spatial light modulator, is used to perform fast and accurate beam-steering and multiplexing. We show successful intracellular delivery of a range of impermeable molecules into individual blastomeres of the annelid Pomatoceros lamarckii embryo by optoinjection, even when the embryo is still enclosed in a chorion. We also demonstrate the ability of the femtosecond laser optoinjection to deliver materials into inner layers of cells in a well-developed embryo. By switching to the continuous wave mode of the Ti:sapphire laser, the same system can be employed to optically trap and orient the 60 μm sized P. lamarckii embryo whilst maintaining its viability. Hence, a complete all-optical manipulation platform is demonstrated paving the way towards single-cell genetic modification and cell lineage mapping in emerging developmental biology model species.</description>
      <pubDate>Wed, 01 Jun 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2007</guid>
      <dc:date>2011-06-01T00:00:00Z</dc:date>
      <dc:creator>Torres, Maria Leilani</dc:creator>
      <dc:creator>Antkowiak, Maciej</dc:creator>
      <dc:creator>Cizmarova, Hana</dc:creator>
      <dc:creator>Ferrier, David Ellard Keith</dc:creator>
      <dc:creator>Dholakia, Kishan</dc:creator>
      <dc:creator>Gunn-Moore, Frank J</dc:creator>
      <dc:description>We demonstrate a system for the combined optical injection and trapping of developing embryos. A Ti:sapphire femtosecond laser in tandem with a spatial light modulator, is used to perform fast and accurate beam-steering and multiplexing. We show successful intracellular delivery of a range of impermeable molecules into individual blastomeres of the annelid Pomatoceros lamarckii embryo by optoinjection, even when the embryo is still enclosed in a chorion. We also demonstrate the ability of the femtosecond laser optoinjection to deliver materials into inner layers of cells in a well-developed embryo. By switching to the continuous wave mode of the Ti:sapphire laser, the same system can be employed to optically trap and orient the 60 μm sized P. lamarckii embryo whilst maintaining its viability. Hence, a complete all-optical manipulation platform is demonstrated paving the way towards single-cell genetic modification and cell lineage mapping in emerging developmental biology model species.</dc:description>
    </item>
    <item>
      <title>Inhibition of Amyloid-beta (A beta) peptide-binding alcohol dehydrogenase-A beta interaction reduces A beta accumulation and improves mitochondrial function in a mouse model of Alzheimer's disease</title>
      <link>http://hdl.handle.net/10023/2006</link>
      <description>Abstract: Amyloid- beta (A beta) peptide-binding alcohol dehydrogenase (ABAD), an enzyme present in neuronal mitochondria, exacerbates A beta-induced cell stress. The interaction of ABAD with A beta exacerbates A beta-induced mitochondrial and neuronal dysfunction. Here, we show that inhibition of the ABAD-A beta interaction, using a decoy peptide (DP) in vitro and in vivo, protects against aberrant mitochondrial and neuronal function and improves spatial learning/memory. Intraperitoneal administration of ABAD-DP [fused to the transduction of human immunodeficiency virus 1-transactivator (Tat) protein and linked to the mitochondrial targeting sequence (Mito) (TAT-mito-DP) to transgenic APP mice (Tg mAPP)] blocked formation of ABAD-A beta complex in mitochondria, increased oxygen consumption and enzyme activity associated with the mitochondrial respiratory chain, attenuated mitochondrial oxidative stress, and improved spatial memory. Similar protective effects were observed in Tg mAPP mice overexpressing neuronal ABAD decoy peptide (Tg mAPP/mito-ABAD). Notably, inhibition of the ABAD-A beta interaction significantly reduced mitochondrial A beta accumulation. In parallel, the activity of mitochondrial A beta-degrading enzyme PreP (presequence peptidase) was enhanced in Tg mAPP mitochondria expressing the ABAD decoy peptide. These data indicate that segregating ABAD from A beta protects mitochondria/neurons from A beta toxicity; thus, ABAD-A beta interaction is an important mechanism underlying A beta-mediated mitochondrial and neuronal perturbation. Inhibitors of ABAD-A beta interaction may hold promise as targets for the prevention and treatment of Alzheimer's disease.</description>
      <pubDate>Wed, 09 Feb 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/2006</guid>
      <dc:date>2011-02-09T00:00:00Z</dc:date>
      <dc:creator>Yao, Jun</dc:creator>
      <dc:creator>Du, Heng</dc:creator>
      <dc:creator>Yan, Shiqiang</dc:creator>
      <dc:creator>Fang, Fang</dc:creator>
      <dc:creator>Wang, Chaodong</dc:creator>
      <dc:creator>Lue, Lih-Fen</dc:creator>
      <dc:creator>Guo, Lan</dc:creator>
      <dc:creator>Chen, Doris</dc:creator>
      <dc:creator>Stern, David M.</dc:creator>
      <dc:creator>Gunn-Moore, Frank J.</dc:creator>
      <dc:creator>Chen, John Xi</dc:creator>
      <dc:creator>Arancio, Ottavio</dc:creator>
      <dc:creator>Yan, Shirley ShiDu</dc:creator>
      <dc:description>Amyloid- beta (A beta) peptide-binding alcohol dehydrogenase (ABAD), an enzyme present in neuronal mitochondria, exacerbates A beta-induced cell stress. The interaction of ABAD with A beta exacerbates A beta-induced mitochondrial and neuronal dysfunction. Here, we show that inhibition of the ABAD-A beta interaction, using a decoy peptide (DP) in vitro and in vivo, protects against aberrant mitochondrial and neuronal function and improves spatial learning/memory. Intraperitoneal administration of ABAD-DP [fused to the transduction of human immunodeficiency virus 1-transactivator (Tat) protein and linked to the mitochondrial targeting sequence (Mito) (TAT-mito-DP) to transgenic APP mice (Tg mAPP)] blocked formation of ABAD-A beta complex in mitochondria, increased oxygen consumption and enzyme activity associated with the mitochondrial respiratory chain, attenuated mitochondrial oxidative stress, and improved spatial memory. Similar protective effects were observed in Tg mAPP mice overexpressing neuronal ABAD decoy peptide (Tg mAPP/mito-ABAD). Notably, inhibition of the ABAD-A beta interaction significantly reduced mitochondrial A beta accumulation. In parallel, the activity of mitochondrial A beta-degrading enzyme PreP (presequence peptidase) was enhanced in Tg mAPP mitochondria expressing the ABAD decoy peptide. These data indicate that segregating ABAD from A beta protects mitochondria/neurons from A beta toxicity; thus, ABAD-A beta interaction is an important mechanism underlying A beta-mediated mitochondrial and neuronal perturbation. Inhibitors of ABAD-A beta interaction may hold promise as targets for the prevention and treatment of Alzheimer's disease.</dc:description>
    </item>
    <item>
      <title>Darwin in mind : new opportunities for evolutionary psychology</title>
      <link>http://hdl.handle.net/10023/1990</link>
      <description>Abstract: Evolutionary Psychology (EP) views the human mind as organized into many modules, each underpinned by psychological adaptations designed to solve problems faced by our Pleistocene ancestors. We argue that the key tenets of the established EP paradigm require modification in the light of recent findings from a number of disciplines, including human genetics, evolutionary biology, cognitive neuroscience, developmental psychology, and paleoecology. For instance, many human genes have been subject to recent selective sweeps; humans play an active, constructive role in co-directing their own development and evolution; and experimental evidence often favours a general process, rather than a modular account, of cognition. A redefined EP could use the theoretical insights of modern evolutionary biology as a rich source of hypotheses concerning the human mind, and could exploit novel methods from a variety of adjacent research fields.</description>
      <pubDate>Tue, 19 Jul 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1990</guid>
      <dc:date>2011-07-19T00:00:00Z</dc:date>
      <dc:creator>Bolhuis, Johan</dc:creator>
      <dc:creator>Brown, Gillian Ruth</dc:creator>
      <dc:creator>Richardson, Robert</dc:creator>
      <dc:creator>Laland, Kevin Neville</dc:creator>
      <dc:description>Evolutionary Psychology (EP) views the human mind as organized into many modules, each underpinned by psychological adaptations designed to solve problems faced by our Pleistocene ancestors. We argue that the key tenets of the established EP paradigm require modification in the light of recent findings from a number of disciplines, including human genetics, evolutionary biology, cognitive neuroscience, developmental psychology, and paleoecology. For instance, many human genes have been subject to recent selective sweeps; humans play an active, constructive role in co-directing their own development and evolution; and experimental evidence often favours a general process, rather than a modular account, of cognition. A redefined EP could use the theoretical insights of modern evolutionary biology as a rich source of hypotheses concerning the human mind, and could exploit novel methods from a variety of adjacent research fields.</dc:description>
    </item>
    <item>
      <title>Annelid Distal-less/Dlx duplications reveal varied post-duplication fates</title>
      <link>http://hdl.handle.net/10023/1989</link>
      <description>Abstract: Background: Dlx (Distal-less) genes have various developmental roles and are widespread throughout the animal kingdom, usually occurring as single copy genes in non-chordates and as multiple copies in most chordate genomes. While the genomic arrangement and function of these genes is well known in vertebrates and arthropods, information about Dlx genes in other organisms is scarce. We investigate the presence of Dlx genes in several annelid species and examine Dlx gene expression in the polychaete Pomatoceros lamarckii. Results: Two Dlx genes are present in P. lamarckii, Capitella teleta and Helobdella robusta. The C. teleta Dlx genes are closely linked in an inverted tail-to-tail orientation, reminiscent of the arrangement of vertebrate Dlx pairs, and gene conversion appears to have had a role in their evolution. The H. robusta Dlx genes, however, are not on the same genomic scaffold and display divergent sequences, while, if the P. lamarckii genes are linked in a tail-to-tail orientation they are a minimum of 41 kilobases apart and show no sign of gene conversion. No expression in P. lamarckii appendage development has been observed, which conflicts with the supposed conserved role of these genes in animal appendage development. These Dlx duplications do not appear to be annelid-wide, as the polychaete Platynereis dumerilii likely possesses only one Dlx gene. Conclusions: On the basis of the currently accepted annelid phylogeny, we hypothesise that one Dlx duplication occurred in the annelid lineage after the divergence of P. dumerilii from the other lineages and these duplicates then had varied evolutionary fates in different species. We also propose that the ancestral role of Dlx genes is not related to appendage development.
Description: Additional files can be viewed at http://www.biomedcentral.com/1471-2148/11/241/additional/</description>
      <pubDate>Tue, 16 Aug 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1989</guid>
      <dc:date>2011-08-16T00:00:00Z</dc:date>
      <dc:creator>McDougall, Carmel</dc:creator>
      <dc:creator>Korchagina, Natalia</dc:creator>
      <dc:creator>Tobin, Johnathan</dc:creator>
      <dc:creator>Ferrier, David Ellard Keith</dc:creator>
      <dc:description>Background: Dlx (Distal-less) genes have various developmental roles and are widespread throughout the animal kingdom, usually occurring as single copy genes in non-chordates and as multiple copies in most chordate genomes. While the genomic arrangement and function of these genes is well known in vertebrates and arthropods, information about Dlx genes in other organisms is scarce. We investigate the presence of Dlx genes in several annelid species and examine Dlx gene expression in the polychaete Pomatoceros lamarckii. Results: Two Dlx genes are present in P. lamarckii, Capitella teleta and Helobdella robusta. The C. teleta Dlx genes are closely linked in an inverted tail-to-tail orientation, reminiscent of the arrangement of vertebrate Dlx pairs, and gene conversion appears to have had a role in their evolution. The H. robusta Dlx genes, however, are not on the same genomic scaffold and display divergent sequences, while, if the P. lamarckii genes are linked in a tail-to-tail orientation they are a minimum of 41 kilobases apart and show no sign of gene conversion. No expression in P. lamarckii appendage development has been observed, which conflicts with the supposed conserved role of these genes in animal appendage development. These Dlx duplications do not appear to be annelid-wide, as the polychaete Platynereis dumerilii likely possesses only one Dlx gene. Conclusions: On the basis of the currently accepted annelid phylogeny, we hypothesise that one Dlx duplication occurred in the annelid lineage after the divergence of P. dumerilii from the other lineages and these duplicates then had varied evolutionary fates in different species. We also propose that the ancestral role of Dlx genes is not related to appendage development.</dc:description>
    </item>
    <item>
      <title>Education research as a route to collaborative work practice in HE</title>
      <link>http://hdl.handle.net/10023/1970</link>
      <pubDate>Mon, 01 Aug 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1970</guid>
      <dc:date>2011-08-01T00:00:00Z</dc:date>
      <dc:creator>Sibbett, Lorna Rosemary</dc:creator>
    </item>
    <item>
      <title>Habitat-specific morphological variation among threespine sticklebacks (Gasterosteus aculeatus) within a drainage basin</title>
      <link>http://hdl.handle.net/10023/1958</link>
      <description>Abstract: Habitat-specific morphological variation, often corresponding to resource specialization, is well documented in freshwater fishes. In this study we used landmark based morphometric analyses to investigate morphological variation among threespine sticklebacks (Gasterosteus aculeatus L.) from four interconnected habitat types within a single lowland drainage basin in eastern England. These included the upper and lower reaches of the river, the estuary, a connected ditch network and a coastal salt marsh. We found significant habitat-specific differences in morphology, with three axes of variation describing differences in orbit diameter, body depth, caudal peduncle shape and pectoral fin positioning as well as variation in relative dorsal and pelvic spine size. Interestingly, the ditch system, an artificial and heavily managed habitat, is populated by sticklebacks with a characteristic morphology, suggesting that human management of habitats can in some circumstances lead to morphological variation among the animals that inhabit them. We discuss the mechanisms that conceivably underlie the observed morphological variation and the further work necessary to identify them. Finally, we consider the implications of habitat-specific body shape variation for the behavioural ecology of this ecologically generalist species.</description>
      <pubDate>Wed, 15 Jun 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1958</guid>
      <dc:date>2011-06-15T00:00:00Z</dc:date>
      <dc:creator>Webster, Mike M.</dc:creator>
      <dc:creator>Atton, Nicola</dc:creator>
      <dc:creator>Hart, Paul J. B.</dc:creator>
      <dc:creator>Ward, Ashley J. W.</dc:creator>
      <dc:description>Habitat-specific morphological variation, often corresponding to resource specialization, is well documented in freshwater fishes. In this study we used landmark based morphometric analyses to investigate morphological variation among threespine sticklebacks (Gasterosteus aculeatus L.) from four interconnected habitat types within a single lowland drainage basin in eastern England. These included the upper and lower reaches of the river, the estuary, a connected ditch network and a coastal salt marsh. We found significant habitat-specific differences in morphology, with three axes of variation describing differences in orbit diameter, body depth, caudal peduncle shape and pectoral fin positioning as well as variation in relative dorsal and pelvic spine size. Interestingly, the ditch system, an artificial and heavily managed habitat, is populated by sticklebacks with a characteristic morphology, suggesting that human management of habitats can in some circumstances lead to morphological variation among the animals that inhabit them. We discuss the mechanisms that conceivably underlie the observed morphological variation and the further work necessary to identify them. Finally, we consider the implications of habitat-specific body shape variation for the behavioural ecology of this ecologically generalist species.</dc:description>
    </item>
    <item>
      <title>Ensuring each student reaches their potential : (2) transferability issues</title>
      <link>http://hdl.handle.net/10023/1913</link>
      <description>Abstract: Isolation of knowledge within disciplines, or for students, within the confines of single taught modules, diminishes the learner’s richness of understanding. Whilst flexible degree programmes are attractive to prospective students, there is a need to ensure that such programmes do not situate understanding within narrow contexts. The curriculum must provide both incentive and structure for students to develop transferability in their knowledge and skills. Transferability of skills is dependent upon transfer of both principles and dispositions. Teaching to maximise the former requires active development of student understanding of generalisable principles, this being a minimum aim of any educator. However, transfer of dispositions, for example towards critical thinking, is more problematic, particularly within the higher education (HE) sector where individual students are exposed to varied tutors and lecturers, each of whom has built a career upon arguing the uniqueness of their thoughts and approaches. In the University of St Andrews School of Biology, introduction of core skills teaching has facilitated and integrated learning across modules and from co-curricular activities. This structure has been successful in establishing transfer of both principles and dispositions. This reflexive analysis reviews the strategies and successes of this programme in relation to transfer conditions.</description>
      <pubDate>Mon, 15 Nov 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1913</guid>
      <dc:date>2010-11-15T00:00:00Z</dc:date>
      <dc:creator>Sibbett, Lorna Rosemary</dc:creator>
      <dc:description>Isolation of knowledge within disciplines, or for students, within the confines of single taught modules, diminishes the learner’s richness of understanding. Whilst flexible degree programmes are attractive to prospective students, there is a need to ensure that such programmes do not situate understanding within narrow contexts. The curriculum must provide both incentive and structure for students to develop transferability in their knowledge and skills. Transferability of skills is dependent upon transfer of both principles and dispositions. Teaching to maximise the former requires active development of student understanding of generalisable principles, this being a minimum aim of any educator. However, transfer of dispositions, for example towards critical thinking, is more problematic, particularly within the higher education (HE) sector where individual students are exposed to varied tutors and lecturers, each of whom has built a career upon arguing the uniqueness of their thoughts and approaches. In the University of St Andrews School of Biology, introduction of core skills teaching has facilitated and integrated learning across modules and from co-curricular activities. This structure has been successful in establishing transfer of both principles and dispositions. This reflexive analysis reviews the strategies and successes of this programme in relation to transfer conditions.</dc:description>
    </item>
    <item>
      <title>What do students in higher education do and what do they value?</title>
      <link>http://hdl.handle.net/10023/1912</link>
      <description>Abstract: A survey of undergraduate biology students at the University of St Andrews provides evidence that both formal and informal learning are valued by students, but there are differences in the extent to which such value is manifest in student activities. Comparisons between students with with different entry qualifications, indicated that those with "A" Levels spent more hours in attending classes; private study and social engagement via volunteer groups; sports societies and creative arts. Those with Scottish Highers spent longer hours on online social networks. As we are a Scottish university, these outcomes might be expected due to the nature of students electing to study at greater distance from their home. Such data do not provide evidence of weakness in the Scottish Education System. Our survey highlighted one point for concern: level of study is positively correlated with the number of hours spent in earning. Whilst earning can be essential, and is itself an opportunity for learning, authors such as Callender (2008) provide evidence that employment has a negative impact on achievement. When class hours are reduced in favour of individual pursuit of literature and opportunities for project collaboration, students use the hours gained to increase hours in employment; they do not increase their hours in private study.</description>
      <pubDate>Tue, 09 Dec 2008 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1912</guid>
      <dc:date>2008-12-09T00:00:00Z</dc:date>
      <dc:creator>Sibbett, Lorna Rosemary</dc:creator>
      <dc:description>A survey of undergraduate biology students at the University of St Andrews provides evidence that both formal and informal learning are valued by students, but there are differences in the extent to which such value is manifest in student activities. Comparisons between students with with different entry qualifications, indicated that those with "A" Levels spent more hours in attending classes; private study and social engagement via volunteer groups; sports societies and creative arts. Those with Scottish Highers spent longer hours on online social networks. As we are a Scottish university, these outcomes might be expected due to the nature of students electing to study at greater distance from their home. Such data do not provide evidence of weakness in the Scottish Education System. Our survey highlighted one point for concern: level of study is positively correlated with the number of hours spent in earning. Whilst earning can be essential, and is itself an opportunity for learning, authors such as Callender (2008) provide evidence that employment has a negative impact on achievement. When class hours are reduced in favour of individual pursuit of literature and opportunities for project collaboration, students use the hours gained to increase hours in employment; they do not increase their hours in private study.</dc:description>
    </item>
    <item>
      <title>Global network analysis of drug tolerance, mode of action and virulence in methicillin-resistant S. aureus</title>
      <link>http://hdl.handle.net/10023/1911</link>
      <description>Abstract: Background: Staphylococcus aureus is a major human pathogen and strains resistant to existing treatments continue to emerge. Development of novel treatments is therefore important. Antimicrobial peptides represent a source of potential novel antibiotics to combat resistant bacteria such as Methicillin-Resistant Staphylococcus aureus (MRSA). A promising antimicrobial peptide is ranalexin, which has potent activity against Gram-positive bacteria, and particularly S. aureus. Understanding mode of action is a key component of drug discovery and network biology approaches enable a global, integrated view of microbial physiology, including mechanisms of antibiotic killing. We developed a systems-wide functional association network approach to integrate proteome and transcriptome profiles, enabling study of drug resistance and mode of action. Results: The functional association network was constructed by Bayesian logistic regression, providing a framework for identification of antimicrobial peptide (ranalexin) response modules from S. aureus MRSA-252 transcriptome and proteome profiling. These signatures of ranalexin treatment revealed multiple killing mechanisms, including cell wall activity. Cell wall effects were supported by gene disruption and osmotic fragility experiments. Furthermore, twenty-two novel virulence factors were inferred, while the VraRS two-component system and PhoU-mediated persister formation were implicated in MRSA tolerance to cationic antimicrobial peptides. Conclusions: This work demonstrates a powerful integrative approach to study drug resistance and mode of action. Our findings are informative to the development of novel therapeutic strategies against Staphylococcus aureus and particularly MRSA.</description>
      <pubDate>Thu, 12 May 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1911</guid>
      <dc:date>2011-05-12T00:00:00Z</dc:date>
      <dc:creator>Overton, Ian M.</dc:creator>
      <dc:creator>Graham, Shirley</dc:creator>
      <dc:creator>Gould, Katherine A.</dc:creator>
      <dc:creator>Hinds, Jason</dc:creator>
      <dc:creator>Botting, Catherine H.</dc:creator>
      <dc:creator>Shirran, Sally</dc:creator>
      <dc:creator>Barton, Geoffrey J.</dc:creator>
      <dc:creator>Coote, Peter J.</dc:creator>
      <dc:description>Background: Staphylococcus aureus is a major human pathogen and strains resistant to existing treatments continue to emerge. Development of novel treatments is therefore important. Antimicrobial peptides represent a source of potential novel antibiotics to combat resistant bacteria such as Methicillin-Resistant Staphylococcus aureus (MRSA). A promising antimicrobial peptide is ranalexin, which has potent activity against Gram-positive bacteria, and particularly S. aureus. Understanding mode of action is a key component of drug discovery and network biology approaches enable a global, integrated view of microbial physiology, including mechanisms of antibiotic killing. We developed a systems-wide functional association network approach to integrate proteome and transcriptome profiles, enabling study of drug resistance and mode of action. Results: The functional association network was constructed by Bayesian logistic regression, providing a framework for identification of antimicrobial peptide (ranalexin) response modules from S. aureus MRSA-252 transcriptome and proteome profiling. These signatures of ranalexin treatment revealed multiple killing mechanisms, including cell wall activity. Cell wall effects were supported by gene disruption and osmotic fragility experiments. Furthermore, twenty-two novel virulence factors were inferred, while the VraRS two-component system and PhoU-mediated persister formation were implicated in MRSA tolerance to cationic antimicrobial peptides. Conclusions: This work demonstrates a powerful integrative approach to study drug resistance and mode of action. Our findings are informative to the development of novel therapeutic strategies against Staphylococcus aureus and particularly MRSA.</dc:description>
    </item>
    <item>
      <title>An International Quiet Ocean Experiment</title>
      <link>http://hdl.handle.net/10023/1909</link>
      <description>Abstract: The effect of noise on marine life is one of the big unknowns of current marine science. Considerable evidence exists that the human contribution to ocean noise has increased during the past few decades: human noise has become the dominant component of marine noise in some regions, and noise is directly correlated with the increasing industrialization of the ocean. Sound is an important factor in the lives of many marine organisms, and theory and increasing observations suggest that human noise could be approaching levels at which negative effects on marine life may be occurring. Certain species already show symptoms of the effects of sound. Although some of these effects are acute and rare, chronic sublethal effects may be more prevalent, but are difficult to measure. We need to identify the thresholds of such effects for different species and be in a position to predict how increasing anthropogenic sound will add to the effects. To achieve such predictive capabilities, the Scientific Committee on Oceanic Research (SCOR) and the Partnership for Observation of the Global Oceans (POGO) are developing an International Quiet Ocean Experiment (IQOE), with the objective of coordinating the international research community to both quantify the ocean soundscape and examine the functional relationship between sound and the viability of key marine organisms. SCOR and POGO will convene an open science meeting to gather community input on the important research, observations, and modeling activities that should be included in IQOE.</description>
      <pubDate>Wed, 01 Jun 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1909</guid>
      <dc:date>2011-06-01T00:00:00Z</dc:date>
      <dc:creator>Boyd, Ian L.</dc:creator>
      <dc:creator>Frisk, George</dc:creator>
      <dc:creator>Urban, Ed</dc:creator>
      <dc:creator>Tyack, Peter</dc:creator>
      <dc:creator>Ausubel, Jesse</dc:creator>
      <dc:creator>Seeyave, Sophie</dc:creator>
      <dc:creator>Cato, Doug</dc:creator>
      <dc:creator>Southall, Brandon</dc:creator>
      <dc:creator>Weise, Michael</dc:creator>
      <dc:creator>Andrew, Rex</dc:creator>
      <dc:creator>Akamatsu, Tomonari</dc:creator>
      <dc:creator>Dekeling, Rene</dc:creator>
      <dc:creator>Erbe, Christine</dc:creator>
      <dc:creator>Farmer, David</dc:creator>
      <dc:creator>Gentry, Roger</dc:creator>
      <dc:creator>Gross, Tom</dc:creator>
      <dc:creator>Hawkins, Anthony</dc:creator>
      <dc:creator>Li, Fenghua</dc:creator>
      <dc:creator>Metcalf, Kathy</dc:creator>
      <dc:creator>Miller, James H.</dc:creator>
      <dc:creator>Moretti, David</dc:creator>
      <dc:creator>Rodrigo, Cristian</dc:creator>
      <dc:creator>Shinke, Tomio</dc:creator>
      <dc:description>The effect of noise on marine life is one of the big unknowns of current marine science. Considerable evidence exists that the human contribution to ocean noise has increased during the past few decades: human noise has become the dominant component of marine noise in some regions, and noise is directly correlated with the increasing industrialization of the ocean. Sound is an important factor in the lives of many marine organisms, and theory and increasing observations suggest that human noise could be approaching levels at which negative effects on marine life may be occurring. Certain species already show symptoms of the effects of sound. Although some of these effects are acute and rare, chronic sublethal effects may be more prevalent, but are difficult to measure. We need to identify the thresholds of such effects for different species and be in a position to predict how increasing anthropogenic sound will add to the effects. To achieve such predictive capabilities, the Scientific Committee on Oceanic Research (SCOR) and the Partnership for Observation of the Global Oceans (POGO) are developing an International Quiet Ocean Experiment (IQOE), with the objective of coordinating the international research community to both quantify the ocean soundscape and examine the functional relationship between sound and the viability of key marine organisms. SCOR and POGO will convene an open science meeting to gather community input on the important research, observations, and modeling activities that should be included in IQOE.</dc:description>
    </item>
    <item>
      <title>Impact of biodiversity-climate futures on primary production and metabolism in a model benthic estuarine system</title>
      <link>http://hdl.handle.net/10023/1813</link>
      <description>Abstract: Understanding the effects of anthropogenically-driven changes in global temperature, atmospheric carbon dioxide and biodiversity on the functionality of marine ecosystems is crucial for predicting and managing the associated impacts. Coastal ecosystems are important sources of carbon (primary production) to shelf waters and play a vital role in global nutrient cycling. These systems are especially vulnerable to the effects of human activities and will be the first areas impacted by rising sea levels. Within these coastal ecosystems, microalgal assemblages (microphytobenthos: MPB) are vital for autochthonous carbon fixation. The level of in situ production by MPB mediates the net carbon cycling of transitional ecosystems between net heterotrophic or autotrophic metabolism. In this study, we examine the interactive effects of elevated atmospheric CO2 concentrations (370, 600, and 1000 ppmv), temperature (6°C, 12°C, and 18°C) and invertebrate biodiversity on MPB biomass in experimental systems. We assembled communities of three common grazing invertebrates (Hydrobia ulvae, Corophium volutator and Hediste diversicolor) in monoculture and in all possible multispecies combinations. This experimental design specifically addresses interactions between the selected climate change variables and any ecological consequences caused by changes in species composition or richness.
Description: All work was supported by NERC grant NE/E006795/1</description>
      <pubDate>Sat, 01 Jan 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1813</guid>
      <dc:date>2011-01-01T00:00:00Z</dc:date>
      <dc:creator>Hicks, Natalie</dc:creator>
      <dc:creator>Bulling, Mark</dc:creator>
      <dc:creator>Solan, Martin</dc:creator>
      <dc:creator>Raffaelli, David</dc:creator>
      <dc:creator>White, Piran</dc:creator>
      <dc:creator>Paterson, David Maxwell</dc:creator>
      <dc:description>Understanding the effects of anthropogenically-driven changes in global temperature, atmospheric carbon dioxide and biodiversity on the functionality of marine ecosystems is crucial for predicting and managing the associated impacts. Coastal ecosystems are important sources of carbon (primary production) to shelf waters and play a vital role in global nutrient cycling. These systems are especially vulnerable to the effects of human activities and will be the first areas impacted by rising sea levels. Within these coastal ecosystems, microalgal assemblages (microphytobenthos: MPB) are vital for autochthonous carbon fixation. The level of in situ production by MPB mediates the net carbon cycling of transitional ecosystems between net heterotrophic or autotrophic metabolism. In this study, we examine the interactive effects of elevated atmospheric CO2 concentrations (370, 600, and 1000 ppmv), temperature (6°C, 12°C, and 18°C) and invertebrate biodiversity on MPB biomass in experimental systems. We assembled communities of three common grazing invertebrates (Hydrobia ulvae, Corophium volutator and Hediste diversicolor) in monoculture and in all possible multispecies combinations. This experimental design specifically addresses interactions between the selected climate change variables and any ecological consequences caused by changes in species composition or richness.</dc:description>
    </item>
    <item>
      <title>Automated chemical crystallography</title>
      <link>http://hdl.handle.net/10023/1769</link>
      <description>Abstract: The first fully automated small-molecule robotic X-ray diffractometer is described. After demonstrating the utility of the instrument using multiple samples of ammonium bitartrate, we investigated the conformational chirality of diphenyl dichalcogenide (E2Ph2, where E = S, Se, or Te). Structural and computational studies suggest that the two enantiomers are energetically indistinguishable. Therefore, it was unsurprising that we found (in 35 suitable data collections) the proportion 0.51:0.49 of M-S2Ph2 to P-S2Ph2 in the bulk sample. Interestingly, after 65 data collections of Te2Ph2, (46 provided suitable data sets), we found the proportion 0.72 +/- 0.13 of M-Te2Ph2, suggesting there could be a statistically significant preference for the M-enantiomer in the sample examined here. We found that Se2Ph2 underwent homochiral crystallization, with all 24 crystals being M. Our experiments may represent a salutary lesson in statistical analysis.</description>
      <pubDate>Wed, 28 Apr 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1769</guid>
      <dc:date>2010-04-28T00:00:00Z</dc:date>
      <dc:creator>Fuller, Amy</dc:creator>
      <dc:creator>Scott-Hayward, Lindesay Alexandra Sarah</dc:creator>
      <dc:creator>Li, Yang</dc:creator>
      <dc:creator>Buehl, Michael</dc:creator>
      <dc:creator>Slawin, Alexandra Martha Zoya</dc:creator>
      <dc:creator>Woollins, J Derek</dc:creator>
      <dc:description>The first fully automated small-molecule robotic X-ray diffractometer is described. After demonstrating the utility of the instrument using multiple samples of ammonium bitartrate, we investigated the conformational chirality of diphenyl dichalcogenide (E2Ph2, where E = S, Se, or Te). Structural and computational studies suggest that the two enantiomers are energetically indistinguishable. Therefore, it was unsurprising that we found (in 35 suitable data collections) the proportion 0.51:0.49 of M-S2Ph2 to P-S2Ph2 in the bulk sample. Interestingly, after 65 data collections of Te2Ph2, (46 provided suitable data sets), we found the proportion 0.72 +/- 0.13 of M-Te2Ph2, suggesting there could be a statistically significant preference for the M-enantiomer in the sample examined here. We found that Se2Ph2 underwent homochiral crystallization, with all 24 crystals being M. Our experiments may represent a salutary lesson in statistical analysis.</dc:description>
    </item>
    <item>
      <title>Phospholipases A1</title>
      <link>http://hdl.handle.net/10023/1708</link>
      <description>Abstract: Phospholipase A1 (PLA1) is an enzyme that hydrolyzes phospholipids and produces 2-acyl-lysophospholipids and fatty acids. This lipolytic activity is conserved in a wide range of organisms but is carried out by a diverse set of PLA1 enzymes. Where their function is known, PLA1s have been shown to act as digestive enzymes, possess central roles in membrane maintenance and remodeling, or regulate important cellular mechanisms by the production of various lysophospholipid mediators, such as lysophosphatidylserine and lysophosphatidic acid, which in turn have multiple biological functions.
Description: Research in the author's laboratory is supported in part by a Wellcome Trust Senior Research Fellowship (067441), and Wellcome Trust project grants (086658 and 093228) and a Wellcome Trust Prize Studentship (G.S.R).</description>
      <pubDate>Sat, 01 Jan 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1708</guid>
      <dc:date>2011-01-01T00:00:00Z</dc:date>
      <dc:creator>Richmond, Gregory S.</dc:creator>
      <dc:creator>Smith, Terry K.</dc:creator>
      <dc:description>Phospholipase A1 (PLA1) is an enzyme that hydrolyzes phospholipids and produces 2-acyl-lysophospholipids and fatty acids. This lipolytic activity is conserved in a wide range of organisms but is carried out by a diverse set of PLA1 enzymes. Where their function is known, PLA1s have been shown to act as digestive enzymes, possess central roles in membrane maintenance and remodeling, or regulate important cellular mechanisms by the production of various lysophospholipid mediators, such as lysophosphatidylserine and lysophosphatidic acid, which in turn have multiple biological functions.</dc:description>
    </item>
    <item>
      <title>Synthesis and stereochemical assignment of (+)-chamuvarinin</title>
      <link>http://hdl.handle.net/10023/1685</link>
      <description>Abstract: A stereocontrolled total synthesis of (+)-chamuvarinin, isolated from the root extract of Uvaria Chamae, utilizes a convergent modular strategy to construct the adjacently linked C15−C28 ether array, followed by a late-stage Julia−Kocienski olefination to append the butenolide motif. This constitutes the first total synthesis of (+)-chamuvarinin, defining the relative and absolute configuration of this unique annonaceous acetogenin.
Description: Supported by grants from EPSRC (EP/F011458/1) and The Wellcome Trust (086658).</description>
      <pubDate>Fri, 04 Feb 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1685</guid>
      <dc:date>2011-02-04T00:00:00Z</dc:date>
      <dc:creator>Florence, Gordon John</dc:creator>
      <dc:creator>Morris, Joanne Charleen</dc:creator>
      <dc:creator>Murray, Ross George</dc:creator>
      <dc:creator>Osler, Jonathan</dc:creator>
      <dc:creator>Reddy, Vanga R.</dc:creator>
      <dc:creator>Smith, Terry K</dc:creator>
      <dc:description>A stereocontrolled total synthesis of (+)-chamuvarinin, isolated from the root extract of Uvaria Chamae, utilizes a convergent modular strategy to construct the adjacently linked C15−C28 ether array, followed by a late-stage Julia−Kocienski olefination to append the butenolide motif. This constitutes the first total synthesis of (+)-chamuvarinin, defining the relative and absolute configuration of this unique annonaceous acetogenin.</dc:description>
    </item>
    <item>
      <title>The essential neutral sphingomyelinase is involved in the trafficking of the variant surface glycoprotein in the bloodstream form of Trypanosoma brucei</title>
      <link>http://hdl.handle.net/10023/1641</link>
      <description>Abstract: Sphingomyelin is the main sphingolipid in Trypanosoma brucei, the causative agent of African sleeping sickness. In vitro and in vivo characterization of the T. brucei neutral sphingomyelinase demonstrates that it is directly involved in sphingomyelin catabolism. Gene knockout studies in the bloodstream form of the parasite indicate that the neutral sphingomyelinase is essential for growth and survival, thus highlighting that the de novo biosynthesis of ceramide is unable to compensate for the loss of sphingomyelin catabolism. The phenotype of the conditional knockout has given new insights into the highly active endocytic and exocytic pathways in the bloodstream form of T. brucei. Hence, the formation of ceramide in the endoplasmic reticulum affects post-Golgi sorting and rate of deposition of newly synthesized GPI-anchored variant surface glycoprotein on the cell surface. This directly influences the corresponding rate of endocytosis, via the recycling endosomes, of pre-existing cell surface variant surface glycoprotein. The trypanosomes use this coupled endocytic and exocytic mechanism to maintain the cell density of its crucial variant surface glycoprotein protective coat. TbnSMase is therefore genetically validated as a drug target against African trypanosomes, and suggests that interfering with the endocytic transport of variant surface glycoprotein is a highly desirable strategy for drug development against African trypanosomasis.</description>
      <pubDate>Tue, 01 Jun 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1641</guid>
      <dc:date>2010-06-01T00:00:00Z</dc:date>
      <dc:creator>Young, Simon A.</dc:creator>
      <dc:creator>Smith, Terry K.</dc:creator>
      <dc:description>Sphingomyelin is the main sphingolipid in Trypanosoma brucei, the causative agent of African sleeping sickness. In vitro and in vivo characterization of the T. brucei neutral sphingomyelinase demonstrates that it is directly involved in sphingomyelin catabolism. Gene knockout studies in the bloodstream form of the parasite indicate that the neutral sphingomyelinase is essential for growth and survival, thus highlighting that the de novo biosynthesis of ceramide is unable to compensate for the loss of sphingomyelin catabolism. The phenotype of the conditional knockout has given new insights into the highly active endocytic and exocytic pathways in the bloodstream form of T. brucei. Hence, the formation of ceramide in the endoplasmic reticulum affects post-Golgi sorting and rate of deposition of newly synthesized GPI-anchored variant surface glycoprotein on the cell surface. This directly influences the corresponding rate of endocytosis, via the recycling endosomes, of pre-existing cell surface variant surface glycoprotein. The trypanosomes use this coupled endocytic and exocytic mechanism to maintain the cell density of its crucial variant surface glycoprotein protective coat. TbnSMase is therefore genetically validated as a drug target against African trypanosomes, and suggests that interfering with the endocytic transport of variant surface glycoprotein is a highly desirable strategy for drug development against African trypanosomasis.</dc:description>
    </item>
    <item>
      <title>Mumps virus Enders strain is sensitive to interferon (IFN) despite encoding a functional IFN antagonist</title>
      <link>http://hdl.handle.net/10023/1640</link>
      <description>Abstract: Although the Enders strain of mumps virus (MuV) encodes a functional V protein that acts as an interferon (IFN) antagonist, in multi-cycle growth assays MuV Enders grew poorly in naive ('IFN-competent' Hep2) cells but grew to high titres in 'IFN-compromised' Hep2 cells. Even so, the growth rate of MuV Enders was significantly slower in 'IFN-compromised' Hep2 cells when compared with its replication rate in Vero cells and with the replication rate of parainfluenza virus type 5 (a closely related paramyxovirus) in both naive and 'IFN-compromised' Hep2 cells. This suggests that a consequence of slower growth is that the IFN system of naive Hep2 cells can respond quickly enough to control the growth of MuV Enders. This is supported by the finding that rapidly growing variants of MuV Enders that were selected on 'IFN-compromised' Hep2 cells (i.e. in the absence of any selection pressure exerted by the IFN response) also grew to high titres on naive Hep2 cells. Sequencing of the complete genome of one of these variants identified a single point mutation that resulted in a substitution of a conserved asparagine by histidine at position 498 of the haemagglutinin-neuraminidase protein, although this mutation was not present in all rapidly growing variants. These results support the concept that there is a race between the ability of a cell to detect and respond to virus infection and the ability of a virus to block the IFN response. Importantly, this emphasizes that factors other than viral IFN antagonists influence the sensitivity of viruses to IFN.</description>
      <pubDate>Sun, 01 Nov 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1640</guid>
      <dc:date>2009-11-01T00:00:00Z</dc:date>
      <dc:creator>Young, D F</dc:creator>
      <dc:creator>Galiano, M</dc:creator>
      <dc:creator>Lemon, K</dc:creator>
      <dc:creator>Chen, Y-H</dc:creator>
      <dc:creator>Andrejeva, Jelena</dc:creator>
      <dc:creator>Duprex, P</dc:creator>
      <dc:creator>Rima, B K</dc:creator>
      <dc:creator>Randall, Richard Edward</dc:creator>
      <dc:description>Although the Enders strain of mumps virus (MuV) encodes a functional V protein that acts as an interferon (IFN) antagonist, in multi-cycle growth assays MuV Enders grew poorly in naive ('IFN-competent' Hep2) cells but grew to high titres in 'IFN-compromised' Hep2 cells. Even so, the growth rate of MuV Enders was significantly slower in 'IFN-compromised' Hep2 cells when compared with its replication rate in Vero cells and with the replication rate of parainfluenza virus type 5 (a closely related paramyxovirus) in both naive and 'IFN-compromised' Hep2 cells. This suggests that a consequence of slower growth is that the IFN system of naive Hep2 cells can respond quickly enough to control the growth of MuV Enders. This is supported by the finding that rapidly growing variants of MuV Enders that were selected on 'IFN-compromised' Hep2 cells (i.e. in the absence of any selection pressure exerted by the IFN response) also grew to high titres on naive Hep2 cells. Sequencing of the complete genome of one of these variants identified a single point mutation that resulted in a substitution of a conserved asparagine by histidine at position 498 of the haemagglutinin-neuraminidase protein, although this mutation was not present in all rapidly growing variants. These results support the concept that there is a race between the ability of a cell to detect and respond to virus infection and the ability of a virus to block the IFN response. Importantly, this emphasizes that factors other than viral IFN antagonists influence the sensitivity of viruses to IFN.</dc:description>
    </item>
    <item>
      <title>Predicting functional gene links from phylogenetic-statistical analyses of whole genomes</title>
      <link>http://hdl.handle.net/10023/1588</link>
      <description>Abstract: An important element of the developing field of proteomics is to understand protein-protein interactions and other functional links amongst genes. Across-species correlation methods for detecting functional links work on the premise that functionally linked proteins will tend to show a common pattern of presence and absence across a range of genomes. We describe a maximum likelihood statistical model for predicting functional gene linkages. The method detects independent instances of the correlated gain or loss of pairs of proteins on phylogenetic trees, reducing the high rates of false positives observed in conventional across-species methods that do not explicitly incorporate a phylogeny. We show, in a dataset of 10,551 protein pairs, that the phylogenetic method improves by up to 35% on across-species analyses at identifying known functionally linked proteins. The method shows that protein pairs with at least two to three correlated events of gain or loss are almost certainly functionally linked. Contingent evolution, in which one gene's presence or absence depends upon the presence of another, can also be detected phylogenetically, and may identify genes whose functional significance depends upon its interaction with other genes. Incorporating phylogenetic information improves the prediction of functional linkages. The improvement derives from having a lower rate of false positives and from detecting trends that across-species analyses miss. Phylogenetic methods can easily be incorporated into the screening of large-scale bioinformatics datasets to identify sets of protein links and to characterise gene networks.</description>
      <pubDate>Wed, 01 Jun 2005 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1588</guid>
      <dc:date>2005-06-01T00:00:00Z</dc:date>
      <dc:creator>Barker, Daniel</dc:creator>
      <dc:creator>Pagel, M</dc:creator>
      <dc:description>An important element of the developing field of proteomics is to understand protein-protein interactions and other functional links amongst genes. Across-species correlation methods for detecting functional links work on the premise that functionally linked proteins will tend to show a common pattern of presence and absence across a range of genomes. We describe a maximum likelihood statistical model for predicting functional gene linkages. The method detects independent instances of the correlated gain or loss of pairs of proteins on phylogenetic trees, reducing the high rates of false positives observed in conventional across-species methods that do not explicitly incorporate a phylogeny. We show, in a dataset of 10,551 protein pairs, that the phylogenetic method improves by up to 35% on across-species analyses at identifying known functionally linked proteins. The method shows that protein pairs with at least two to three correlated events of gain or loss are almost certainly functionally linked. Contingent evolution, in which one gene's presence or absence depends upon the presence of another, can also be detected phylogenetically, and may identify genes whose functional significance depends upon its interaction with other genes. Incorporating phylogenetic information improves the prediction of functional linkages. The improvement derives from having a lower rate of false positives and from detecting trends that across-species analyses miss. Phylogenetic methods can easily be incorporated into the screening of large-scale bioinformatics datasets to identify sets of protein links and to characterise gene networks.</dc:description>
    </item>
    <item>
      <title>Computational inference of neural information flow networks</title>
      <link>http://hdl.handle.net/10023/1586</link>
      <description>Abstract: Determining how information flows along anatomical brain pathways is a fundamental requirement for understanding how animals perceive their environments, learn, and behave. Attempts to reveal such neural information flow have been made using linear computational methods, but neural interactions are known to be nonlinear. Here, we demonstrate that a dynamic Bayesian network (DBN) inference algorithm we originally developed to infer nonlinear transcriptional regulatory networks from gene expression data collected with microarrays is also successful at inferring nonlinear neural information flow networks from electrophysiology data collected with microelectrode arrays. The inferred networks we recover from the songbird auditory pathway are correctly restricted to a subset of known anatomical paths, are consistent with timing of the system, and reveal both the importance of reciprocal feedback in auditory processing and greater information flow to higher-order auditory areas when birds hear natural as opposed to synthetic sounds. A linear method applied to the same data incorrectly produces networks with information flow to non-neural tissue and over paths known not to exist. To our knowledge, this study represents the first biologically validated demonstration of an algorithm to successfully infer neural information flow networks.</description>
      <pubDate>Wed, 01 Nov 2006 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1586</guid>
      <dc:date>2006-11-01T00:00:00Z</dc:date>
      <dc:creator>Smith, Victoria Anne</dc:creator>
      <dc:creator>Yu, Jing</dc:creator>
      <dc:creator>Smulders, Tom V</dc:creator>
      <dc:creator>Hartemink, Alex J</dc:creator>
      <dc:creator>Jarvis, Erich D</dc:creator>
      <dc:description>Determining how information flows along anatomical brain pathways is a fundamental requirement for understanding how animals perceive their environments, learn, and behave. Attempts to reveal such neural information flow have been made using linear computational methods, but neural interactions are known to be nonlinear. Here, we demonstrate that a dynamic Bayesian network (DBN) inference algorithm we originally developed to infer nonlinear transcriptional regulatory networks from gene expression data collected with microarrays is also successful at inferring nonlinear neural information flow networks from electrophysiology data collected with microelectrode arrays. The inferred networks we recover from the songbird auditory pathway are correctly restricted to a subset of known anatomical paths, are consistent with timing of the system, and reveal both the importance of reciprocal feedback in auditory processing and greater information flow to higher-order auditory areas when birds hear natural as opposed to synthetic sounds. A linear method applied to the same data incorrectly produces networks with information flow to non-neural tissue and over paths known not to exist. To our knowledge, this study represents the first biologically validated demonstration of an algorithm to successfully infer neural information flow networks.</dc:description>
    </item>
    <item>
      <title>Phylogeography and allopatric divergence in cypress species (Cupressus L.) in the Qinghai-Tibetan Plateau and adjacent regions</title>
      <link>http://hdl.handle.net/10023/1438</link>
      <description>Abstract: Background Although allopatric speciation is viewed as the most common way in which species originate, allopatric divergence among a group of closely related species has rarely been examined at the population level through phylogeographic analysis. Here we report such a case study on eight putative cypress (Cupressus) species, which each have a mainly allopatric distribution in the Qinghai-Tibetan Plateau (QTP) and adjacent regions. The analysis involved sequencing three plastid DNA fragments (trnD-trnT, trnS-trnG and trnL-trnF) in 371 individuals sampled from populations at 66 localities. Results Both phylogenetic and network analyses showed that most DNA haplotypes recovered or haplotype-clustered lineages resolved were largely species-specific. Across all species, significant phylogeographic structure (NST &gt; GST, P &lt; 0.05) implied a high correlation between haplotypes/lineages and geographic distribution. Two species, C. duclouxiana and C. chengiana, which are distributed in the eastern QTP region, contained more haplotypes and higher diversity than five species with restricted distributions in the western highlands of the QTP. The remaining species, C. funebris, is widely cultivated and contained very little cpDNA diversity. Conclusions It is concluded that the formation of high mountain barriers separating deep valleys in the QTP and adjacent regions caused by various uplifts of the plateau since the early Miocene most likely promoted allopatric divergence in Cupressus by restricting gene flow and fixing local, species-specific haplotypes in geographically isolated populations. The low levels of intraspecific diversity present in most species might stem from population bottlenecks brought about by recurrent periods of unfavorable climate and more recently by the negative impacts of human activities on species' distributions. Our findings shed new light on the importance of geographical isolation caused by the uplift of the QTP on the development of high plant species diversity in the QTP biodiversity hotspot.
Description: Additional files can be found at http://www.biomedcentral.com/1471-2148/10/194</description>
      <pubDate>Tue, 01 Jun 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1438</guid>
      <dc:date>2010-06-01T00:00:00Z</dc:date>
      <dc:creator>Xu, Ting-Ting</dc:creator>
      <dc:creator>Abbott, Richard John</dc:creator>
      <dc:creator>Milne, Richard I</dc:creator>
      <dc:creator>Mao, Kang-Shan</dc:creator>
      <dc:creator>Du, Fang K</dc:creator>
      <dc:creator>Wu, Gui-Li</dc:creator>
      <dc:creator>Ciren, Zhaxi</dc:creator>
      <dc:creator>Miehe, Georg</dc:creator>
      <dc:creator>Liu, Jian-Quan</dc:creator>
      <dc:description>Background Although allopatric speciation is viewed as the most common way in which species originate, allopatric divergence among a group of closely related species has rarely been examined at the population level through phylogeographic analysis. Here we report such a case study on eight putative cypress (Cupressus) species, which each have a mainly allopatric distribution in the Qinghai-Tibetan Plateau (QTP) and adjacent regions. The analysis involved sequencing three plastid DNA fragments (trnD-trnT, trnS-trnG and trnL-trnF) in 371 individuals sampled from populations at 66 localities. Results Both phylogenetic and network analyses showed that most DNA haplotypes recovered or haplotype-clustered lineages resolved were largely species-specific. Across all species, significant phylogeographic structure (NST &gt; GST, P &lt; 0.05) implied a high correlation between haplotypes/lineages and geographic distribution. Two species, C. duclouxiana and C. chengiana, which are distributed in the eastern QTP region, contained more haplotypes and higher diversity than five species with restricted distributions in the western highlands of the QTP. The remaining species, C. funebris, is widely cultivated and contained very little cpDNA diversity. Conclusions It is concluded that the formation of high mountain barriers separating deep valleys in the QTP and adjacent regions caused by various uplifts of the plateau since the early Miocene most likely promoted allopatric divergence in Cupressus by restricting gene flow and fixing local, species-specific haplotypes in geographically isolated populations. The low levels of intraspecific diversity present in most species might stem from population bottlenecks brought about by recurrent periods of unfavorable climate and more recently by the negative impacts of human activities on species' distributions. Our findings shed new light on the importance of geographical isolation caused by the uplift of the QTP on the development of high plant species diversity in the QTP biodiversity hotspot.</dc:description>
    </item>
    <item>
      <title>The SMN protein is a key regulator of nuclear architecture in differentiating neuroblastoma cells</title>
      <link>http://hdl.handle.net/10023/1195</link>
      <description>Abstract: The cell nucleus contains two closely related structures, Cajal bodies (CBs) and gems. CBs are the first site of accumulation of newly assembled splicing snRNPs (small nuclear ribonucleoproteins) following their import into the nucleus, before they form their steady-state localization in nuclear splicing speckles. Gems are the nuclear site of accumulation of survival motor neurons (SMNs), an insufficiency of which leads to the inherited neurodegenerative condition, spinal muscular atrophy (SMA). SMN is required in the cytoplasm for the addition of core, Sm, proteins to new snRNPs and is believed to accompany snRNPs to the CB. In most cell lines, gems are indistinguishable from CBs, although the structures are often separate in vivo. The relationship between CBs and gems is not fully understood, but there is evidence that symmetrical dimethylation of arginine residues in the CB protein coilin brings them together in HeLa cells. During neuronal differentiation of the human neuroblastoma cell line SH-SY5Y, CBs and gems increase their colocalization, mimicking changes seen during foetal development. This does not result from alterations in the methylation of coilin, but from increased levels of SMN. Expression of exogenous SMN results in an increased efficiency of snRNP transport to nuclear speckles. This suggests different mechanisms are present in different cell types and in vivo that may be significant for the tissue-specific pathology of SMA.</description>
      <pubDate>Sun, 01 Nov 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1195</guid>
      <dc:date>2009-11-01T00:00:00Z</dc:date>
      <dc:creator>Clelland, Allyson K.</dc:creator>
      <dc:creator>Kinnear, Nicholas P.</dc:creator>
      <dc:creator>Oram, Lisa</dc:creator>
      <dc:creator>Burza, Julie</dc:creator>
      <dc:creator>Sleeman, Judith Elizabeth</dc:creator>
      <dc:description>The cell nucleus contains two closely related structures, Cajal bodies (CBs) and gems. CBs are the first site of accumulation of newly assembled splicing snRNPs (small nuclear ribonucleoproteins) following their import into the nucleus, before they form their steady-state localization in nuclear splicing speckles. Gems are the nuclear site of accumulation of survival motor neurons (SMNs), an insufficiency of which leads to the inherited neurodegenerative condition, spinal muscular atrophy (SMA). SMN is required in the cytoplasm for the addition of core, Sm, proteins to new snRNPs and is believed to accompany snRNPs to the CB. In most cell lines, gems are indistinguishable from CBs, although the structures are often separate in vivo. The relationship between CBs and gems is not fully understood, but there is evidence that symmetrical dimethylation of arginine residues in the CB protein coilin brings them together in HeLa cells. During neuronal differentiation of the human neuroblastoma cell line SH-SY5Y, CBs and gems increase their colocalization, mimicking changes seen during foetal development. This does not result from alterations in the methylation of coilin, but from increased levels of SMN. Expression of exogenous SMN results in an increased efficiency of snRNP transport to nuclear speckles. This suggests different mechanisms are present in different cell types and in vivo that may be significant for the tissue-specific pathology of SMA.</dc:description>
    </item>
    <item>
      <title>The regulation of type I interferon production by paramyxoviruses</title>
      <link>http://hdl.handle.net/10023/1194</link>
      <description>Abstract: Experimentally, paramyxoviruses are conventionally considered good inducers of type I interferons (IFN-alpha/beta), and have been used as agents in the commercial production of human IFN-alpha. However, in the last few years it has become clear that viruses in general mount a major challenge to the IFN system, and paramyxoviruses are no exception. Indeed, most paramyxoviruses encode mechanisms to inhibit both the production of, and response to, type I IFN. Here we review our knowledge of the type I IFN-inducing signals (by so-called pathogen-associated molecular patterns, or PAMPs) produced during paramyxovirus infections, and discuss how paramyxoviruses limit the production of PAMPs and inhibit the cellular responses to PAMPs by interfering with the activities of the pattern recognition receptors (PRRs), mda-5, and RIG-I, as well as downstream components in the type I IFN induction cascades.
Description: Research supported by The Wellcome Trust (087751/A/08/Z)</description>
      <pubDate>Tue, 01 Sep 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1194</guid>
      <dc:date>2009-09-01T00:00:00Z</dc:date>
      <dc:creator>Goodbourn, S</dc:creator>
      <dc:creator>Randall, Richard Edward</dc:creator>
      <dc:description>Experimentally, paramyxoviruses are conventionally considered good inducers of type I interferons (IFN-alpha/beta), and have been used as agents in the commercial production of human IFN-alpha. However, in the last few years it has become clear that viruses in general mount a major challenge to the IFN system, and paramyxoviruses are no exception. Indeed, most paramyxoviruses encode mechanisms to inhibit both the production of, and response to, type I IFN. Here we review our knowledge of the type I IFN-inducing signals (by so-called pathogen-associated molecular patterns, or PAMPs) produced during paramyxovirus infections, and discuss how paramyxoviruses limit the production of PAMPs and inhibit the cellular responses to PAMPs by interfering with the activities of the pattern recognition receptors (PRRs), mda-5, and RIG-I, as well as downstream components in the type I IFN induction cascades.</dc:description>
    </item>
    <item>
      <title>Antibacterial free fatty acids : activities, mechanisms of action and biotechnological potential</title>
      <link>http://hdl.handle.net/10023/1193</link>
      <description>Abstract: Amongst the diverse and potent biological activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. Whilst their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy production, FFA action may also result from the inhibition of enzyme activity, impairment of nutrient uptake, generation of peroxidation and auto-oxidation degradation products or direct lysis of bacterial cells. Their broad spectrum of activity, non-specific mode of action and safety makes them attractive as antibacterial agents for various applications in medicine, agriculture and food preservation, especially where the use of conventional antibiotics is undesirable or prohibited. Moreover, the evolution of inducible FFA-resistant phenotypes is less problematic than with conventional antibiotics. The potential for commercial or biomedical exploitation of antibacterial FFAs, especially for those from natural sources, is discussed.</description>
      <pubDate>Mon, 01 Feb 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1193</guid>
      <dc:date>2010-02-01T00:00:00Z</dc:date>
      <dc:creator>Desbois, Andrew Paul</dc:creator>
      <dc:creator>Smith, Valerie Jane</dc:creator>
      <dc:description>Amongst the diverse and potent biological activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. Whilst their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy production, FFA action may also result from the inhibition of enzyme activity, impairment of nutrient uptake, generation of peroxidation and auto-oxidation degradation products or direct lysis of bacterial cells. Their broad spectrum of activity, non-specific mode of action and safety makes them attractive as antibacterial agents for various applications in medicine, agriculture and food preservation, especially where the use of conventional antibiotics is undesirable or prohibited. Moreover, the evolution of inducible FFA-resistant phenotypes is less problematic than with conventional antibiotics. The potential for commercial or biomedical exploitation of antibacterial FFAs, especially for those from natural sources, is discussed.</dc:description>
    </item>
    <item>
      <title>Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain</title>
      <link>http://hdl.handle.net/10023/1192</link>
      <description>Abstract: Background: IPS-1/MAVS/VISA/Cardif is an adaptor protein that plays a crucial role in the induction of interferons in response to viral infection. In the initial stage of the intracellular antiviral response two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-association gene 5 (MDA5), are independently able to bind viral RNA in the cytoplasm. The 62 kDa protein IPS-1/MAVS/VISA/Cardif contains an N-terminal caspase activation and recruitment (CARD) domain that associates with the CARD regions of RIG-I and MDA5, ultimately leading to the induction of type I interferons. As a first step towards understanding the molecular basis of this important adaptor protein we have undertaken structural studies of the IPS-1 MAVS/VISA/Cardif CARD region. Results: The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1 angstrom resolution. The protein was expressed and crystallized as a maltose-binding protein (MBP) fusion protein. The MBP and IPS-1 components each form a distinct domain within the structure. IPS-1/MAVS/VISA/Cardif CARD adopts a characteristic six-helix bundle with a Greek-key topology and, in common with a number of other known CARD structures, contains two major polar surfaces on opposite sides of the molecule. One face has a surface-exposed, disordered tryptophan residue that may explain the poor solubility of untagged expression constructs. Conclusion: The IPS-1/MAVS/VISA/Cardif CARD domain adopts the classic CARD fold with an asymmetric surface charge distribution that is typical of CARD domains involved in homotypic protein-protein interactions. The location of the two polar areas on IPS-1/MAVS/VISA/Cardif CARD suggest possible types of associations that this domain makes with the two CARD domains of MDA5 or RIG-I. The N-terminal CARD domains of RIG-I and MDA5 share greatest sequence similarity with IPS-1/MAVS/VISA/Cardif CARD and this has allowed modelling of their structures. These models show a very different charge profile for the equivalent surfaces compared to IPS-1/MAVS/VISA/Cardif CARD.</description>
      <pubDate>Thu, 28 Feb 2008 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1192</guid>
      <dc:date>2008-02-28T00:00:00Z</dc:date>
      <dc:creator>Potter, Jane A.</dc:creator>
      <dc:creator>Randall, Richard Edward</dc:creator>
      <dc:creator>Taylor, Garry L.</dc:creator>
      <dc:description>Background: IPS-1/MAVS/VISA/Cardif is an adaptor protein that plays a crucial role in the induction of interferons in response to viral infection. In the initial stage of the intracellular antiviral response two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-association gene 5 (MDA5), are independently able to bind viral RNA in the cytoplasm. The 62 kDa protein IPS-1/MAVS/VISA/Cardif contains an N-terminal caspase activation and recruitment (CARD) domain that associates with the CARD regions of RIG-I and MDA5, ultimately leading to the induction of type I interferons. As a first step towards understanding the molecular basis of this important adaptor protein we have undertaken structural studies of the IPS-1 MAVS/VISA/Cardif CARD region. Results: The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1 angstrom resolution. The protein was expressed and crystallized as a maltose-binding protein (MBP) fusion protein. The MBP and IPS-1 components each form a distinct domain within the structure. IPS-1/MAVS/VISA/Cardif CARD adopts a characteristic six-helix bundle with a Greek-key topology and, in common with a number of other known CARD structures, contains two major polar surfaces on opposite sides of the molecule. One face has a surface-exposed, disordered tryptophan residue that may explain the poor solubility of untagged expression constructs. Conclusion: The IPS-1/MAVS/VISA/Cardif CARD domain adopts the classic CARD fold with an asymmetric surface charge distribution that is typical of CARD domains involved in homotypic protein-protein interactions. The location of the two polar areas on IPS-1/MAVS/VISA/Cardif CARD suggest possible types of associations that this domain makes with the two CARD domains of MDA5 or RIG-I. The N-terminal CARD domains of RIG-I and MDA5 share greatest sequence similarity with IPS-1/MAVS/VISA/Cardif CARD and this has allowed modelling of their structures. These models show a very different charge profile for the equivalent surfaces compared to IPS-1/MAVS/VISA/Cardif CARD.</dc:description>
    </item>
    <item>
      <title>Optineurin negatively regulates the induction of IFNβ in response to RNA virus infection</title>
      <link>http://hdl.handle.net/10023/1191</link>
      <description>Abstract: The innate immune response provides a critical defense against microbial infections, including viruses. These are recognised by pattern recognition receptors including Toll-like receptors (TLRs) and RIG-I like helicases (RLHs). Detection of virus triggers signalling cascades that induce transcription of type I interferons including IFNb, which are pivotal for the initiation of an anti-viral state. Despite the essential role of IFNb in the anti-viral response, there is an incomplete understanding of the negative regulation of IFNb induction. Here we provide evidence that expression of the Nemo-related protein, optineurin (NRP/FIP2), has a role in the inhibition of virus-triggered IFNb induction. Over-expression of optineurin inhibited Sendaivirus (SeV) and dsRNA triggered induction of IFNb, whereas depletion of optineurin with siRNA promoted virus-induced IFNb production and decreased RNA virus replication. Immunoprecipitation and immunofluorescence studies identified optineurin in a protein complex containing the antiviral protein kinase TBK1 and the ubiquitin ligase TRAF3. Furthermore, mutagenesis studies determined that binding of ubiquitin was essential for both the correct sub-cellular localisation and the inhibitory function of optineurin. This work identifies optineurin as a critical regulator of antiviral signalling and potential target for future antiviral therapy.
Description: Work in RME laboratories is funded by the Wellcome Trust [079810/Z/06/Z].</description>
      <pubDate>Mon, 01 Feb 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1191</guid>
      <dc:date>2010-02-01T00:00:00Z</dc:date>
      <dc:creator>Mankouri, J</dc:creator>
      <dc:creator>Fragkoudis, R</dc:creator>
      <dc:creator>Richards, K</dc:creator>
      <dc:creator>Wetherill, L</dc:creator>
      <dc:creator>Harris, M</dc:creator>
      <dc:creator>Kohl, A</dc:creator>
      <dc:creator>Elliott, Richard Michael</dc:creator>
      <dc:creator>MacDonald, A</dc:creator>
      <dc:description>The innate immune response provides a critical defense against microbial infections, including viruses. These are recognised by pattern recognition receptors including Toll-like receptors (TLRs) and RIG-I like helicases (RLHs). Detection of virus triggers signalling cascades that induce transcription of type I interferons including IFNb, which are pivotal for the initiation of an anti-viral state. Despite the essential role of IFNb in the anti-viral response, there is an incomplete understanding of the negative regulation of IFNb induction. Here we provide evidence that expression of the Nemo-related protein, optineurin (NRP/FIP2), has a role in the inhibition of virus-triggered IFNb induction. Over-expression of optineurin inhibited Sendaivirus (SeV) and dsRNA triggered induction of IFNb, whereas depletion of optineurin with siRNA promoted virus-induced IFNb production and decreased RNA virus replication. Immunoprecipitation and immunofluorescence studies identified optineurin in a protein complex containing the antiviral protein kinase TBK1 and the ubiquitin ligase TRAF3. Furthermore, mutagenesis studies determined that binding of ubiquitin was essential for both the correct sub-cellular localisation and the inhibitory function of optineurin. This work identifies optineurin as a critical regulator of antiviral signalling and potential target for future antiviral therapy.</dc:description>
    </item>
    <item>
      <title>The N-terminus of Bunyamwera orthobunyavirus NSs protein is essential for interferon antagonism</title>
      <link>http://hdl.handle.net/10023/1148</link>
      <description>Abstract: Bunyamwera virus NSs protein is involved in the inhibition of cellular transcription and the interferon (IFN) response, and it interacts with the Med8 component of Mediator. A spontaneous mutant of a recombinant NSs-deleted Bunyamwera virus (rBUNdelNSs2) was identified and characterized. This mutant virus, termed mBUNNSs22, expresses a 21 aa N-terminally truncated form of NSs. Like rBUNdelNSs2, mBUNNSs22 is attenuated in IFN-deficient cells, and to a greater extent in IFN-competent cells. Both rBUNdelNSs2 and mBUNNSs22 are potent IFN inducers and their growth can be rescued by depleting cellular IRF3. Strikingly, despite encoding an NSs protein that contains the Med8 interaction domain, mBUNNSs22 fails to block RNA polymerase II activity during infection. Overall, our data suggest that both the interaction of NSs with Med8 and a novel unidentified function of the NSs N-terminus, seem necessary for Bunyamwera virus to counteract host antiviral responses.</description>
      <pubDate>Thu, 01 Apr 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1148</guid>
      <dc:date>2010-04-01T00:00:00Z</dc:date>
      <dc:creator>Van Knippenberg, Ingeborg Christine</dc:creator>
      <dc:creator>Carlton-Smith, Charles</dc:creator>
      <dc:creator>Elliott, Richard Michael</dc:creator>
      <dc:description>Bunyamwera virus NSs protein is involved in the inhibition of cellular transcription and the interferon (IFN) response, and it interacts with the Med8 component of Mediator. A spontaneous mutant of a recombinant NSs-deleted Bunyamwera virus (rBUNdelNSs2) was identified and characterized. This mutant virus, termed mBUNNSs22, expresses a 21 aa N-terminally truncated form of NSs. Like rBUNdelNSs2, mBUNNSs22 is attenuated in IFN-deficient cells, and to a greater extent in IFN-competent cells. Both rBUNdelNSs2 and mBUNNSs22 are potent IFN inducers and their growth can be rescued by depleting cellular IRF3. Strikingly, despite encoding an NSs protein that contains the Med8 interaction domain, mBUNNSs22 fails to block RNA polymerase II activity during infection. Overall, our data suggest that both the interaction of NSs with Med8 and a novel unidentified function of the NSs N-terminus, seem necessary for Bunyamwera virus to counteract host antiviral responses.</dc:description>
    </item>
    <item>
      <title>Functional analysis of the Bunyamwera orthobunyavirus Gc glycoprotein</title>
      <link>http://hdl.handle.net/10023/1147</link>
      <description>Abstract: The virion glycoproteins Gn and Gc of Bunyamwera orthobunyavirus (BUNV, family Bunyaviridae) are encoded by the M RNA genome segment and have roles in both viral attachment and membrane fusion. To investigate further the structure and function of the Gc protein in viral replication we generated twelve mutants that contain truncations from the N-terminus. The effects of these deletions were analysed with regard to Golgi targeting, low-pH dependent membrane fusion, infectious virus-like particle (VLP) formation and virus infectivity. Our results showed that the N-terminal half (453 residues) of the Gc ectodomain (909 residues in total) is dispensable for Golgi trafficking and cell fusion. However, deletions in this region resulted in significant reduction in VLP formation. Four mutant viruses that contain N-terminal deletions in their Gc proteins were rescued, and found to be attenuated to different degrees in BHK-21 cells. Taken together, our data indicate that the N-terminal half of the Gc ectodomain is dispensable for replication in cell culture, whereas the C-terminal half is required to mediate cell fusion. A model for the domain structure of the Gc ectodomain is proposed.</description>
      <pubDate>Thu, 01 Oct 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1147</guid>
      <dc:date>2009-10-01T00:00:00Z</dc:date>
      <dc:creator>Shi, Xiaohong</dc:creator>
      <dc:creator>Goli, Josthna</dc:creator>
      <dc:creator>Clark, Gordon</dc:creator>
      <dc:creator>Brauburger, Kristina</dc:creator>
      <dc:creator>Elliott, Richard Michael</dc:creator>
      <dc:description>The virion glycoproteins Gn and Gc of Bunyamwera orthobunyavirus (BUNV, family Bunyaviridae) are encoded by the M RNA genome segment and have roles in both viral attachment and membrane fusion. To investigate further the structure and function of the Gc protein in viral replication we generated twelve mutants that contain truncations from the N-terminus. The effects of these deletions were analysed with regard to Golgi targeting, low-pH dependent membrane fusion, infectious virus-like particle (VLP) formation and virus infectivity. Our results showed that the N-terminal half (453 residues) of the Gc ectodomain (909 residues in total) is dispensable for Golgi trafficking and cell fusion. However, deletions in this region resulted in significant reduction in VLP formation. Four mutant viruses that contain N-terminal deletions in their Gc proteins were rescued, and found to be attenuated to different degrees in BHK-21 cells. Taken together, our data indicate that the N-terminal half of the Gc ectodomain is dispensable for replication in cell culture, whereas the C-terminal half is required to mediate cell fusion. A model for the domain structure of the Gc ectodomain is proposed.</dc:description>
    </item>
    <item>
      <title>Evaluating the influence of epidemiological parameters and host ecology on the spread of phocine distemper virus through populations of harbour seals</title>
      <link>http://hdl.handle.net/10023/1112</link>
      <description>Abstract: Background: Outbreaks of phocine distemper virus (PDV) in Europe during 1988 and 2002 were responsible for the death of around 23,000 and 30,000 harbour seals, respectively. These epidemics, particularly the one in 2002, provided an unusual opportunity to estimate epidemic parameters for a wildlife disease. There were marked regional differences in the values of some parameters both within and between epidemics. Methodology and Principal Findings: We used an individual-based model of seal movement that allowed us to incorporate realistic representations of space, time and animal behaviour into a traditional epidemiological modelling framework. We explored the potential influence of a range of ecological (foraging trip duration, time of epidemic onset, population size) and epidemiological (length of infectious period, contact rate between infectious and susceptible individuals, case mortality) parameters on four readily-measurable epidemic characteristics (number of dead individuals, duration of epidemic, peak mortality date and prevalence) and on the probability that an epidemic would occur in a particular region. We analysed the outputs as if they were the results of a series of virtual experiments, using Generalised Linear Modelling. All six variables had a significant effect on the probability that an epidemic would be recognised as an unusual mortality event by human observers. Conclusions: Regional and temporal variation in contact rate was the most likely cause of the observed differences between the two epidemics. This variation could be a consequence of differences in the way individuals divide their time between land and sea at different times of the year.</description>
      <pubDate>Tue, 01 Jul 2008 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1112</guid>
      <dc:date>2008-07-01T00:00:00Z</dc:date>
      <dc:creator>Harris, Catriona M</dc:creator>
      <dc:creator>Travis, J.M.J</dc:creator>
      <dc:creator>Harwood, John</dc:creator>
      <dc:description>Background: Outbreaks of phocine distemper virus (PDV) in Europe during 1988 and 2002 were responsible for the death of around 23,000 and 30,000 harbour seals, respectively. These epidemics, particularly the one in 2002, provided an unusual opportunity to estimate epidemic parameters for a wildlife disease. There were marked regional differences in the values of some parameters both within and between epidemics. Methodology and Principal Findings: We used an individual-based model of seal movement that allowed us to incorporate realistic representations of space, time and animal behaviour into a traditional epidemiological modelling framework. We explored the potential influence of a range of ecological (foraging trip duration, time of epidemic onset, population size) and epidemiological (length of infectious period, contact rate between infectious and susceptible individuals, case mortality) parameters on four readily-measurable epidemic characteristics (number of dead individuals, duration of epidemic, peak mortality date and prevalence) and on the probability that an epidemic would occur in a particular region. We analysed the outputs as if they were the results of a series of virtual experiments, using Generalised Linear Modelling. All six variables had a significant effect on the probability that an epidemic would be recognised as an unusual mortality event by human observers. Conclusions: Regional and temporal variation in contact rate was the most likely cause of the observed differences between the two epidemics. This variation could be a consequence of differences in the way individuals divide their time between land and sea at different times of the year.</dc:description>
    </item>
    <item>
      <title>Influence of the physical environment and conspecific aggression on the spatial arrangement of breeding grey seals</title>
      <link>http://hdl.handle.net/10023/1082</link>
      <description>Abstract: Understanding the habitat requirements of a species for breeding is essential for its conservation, particularly if the availability of suitable habitat is a limiting factor for population growth. This is postulated to be the case for grey seals, one of the more abundant marine apex predators in northern European waters. In common with similar studies that have investigated the habitat preferences of breeding grey seals, we use abiotic (topographical, climatological) attributes but, unlike previous work, we also incorporate behavioural variables, particularly the occurrence of aggressive interactions between females and the presence of neighbouring seals. We used two Generalized Additive Models (GAM) in a sequential and iterative fashion. The first model links the occurrence of aggression at particular points in the colony to local topography derived from a Geographical Information System (GIS), presence of neighbouring seal pups and the day of the breeding season. The output of this GAM is used as one of the explanatory variables in a GAM of daily variation in the spatial distribution of births. Although proximity of a birth site to a water source and the presence of neighbouring seal pups both had significant influences on the distribution of newborn pups over time and space, at the scale of the study site it was found that simple rules could predict pup distribution more efficiently than a complex individual-based simulation model. (c) 2007 Elsevier B.V. All rights reserved.</description>
      <pubDate>Sat, 01 Dec 2007 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1082</guid>
      <dc:date>2007-12-01T00:00:00Z</dc:date>
      <dc:creator>Harris, Catriona M</dc:creator>
      <dc:creator>Matthiopoulos, Jason</dc:creator>
      <dc:creator>Harwood, John</dc:creator>
      <dc:description>Understanding the habitat requirements of a species for breeding is essential for its conservation, particularly if the availability of suitable habitat is a limiting factor for population growth. This is postulated to be the case for grey seals, one of the more abundant marine apex predators in northern European waters. In common with similar studies that have investigated the habitat preferences of breeding grey seals, we use abiotic (topographical, climatological) attributes but, unlike previous work, we also incorporate behavioural variables, particularly the occurrence of aggressive interactions between females and the presence of neighbouring seals. We used two Generalized Additive Models (GAM) in a sequential and iterative fashion. The first model links the occurrence of aggression at particular points in the colony to local topography derived from a Geographical Information System (GIS), presence of neighbouring seal pups and the day of the breeding season. The output of this GAM is used as one of the explanatory variables in a GAM of daily variation in the spatial distribution of births. Although proximity of a birth site to a water source and the presence of neighbouring seal pups both had significant influences on the distribution of newborn pups over time and space, at the scale of the study site it was found that simple rules could predict pup distribution more efficiently than a complex individual-based simulation model. (c) 2007 Elsevier B.V. All rights reserved.</dc:description>
    </item>
    <item>
      <title>Light-dependant biostabilisation of sediments by stromatolite assemblages</title>
      <link>http://hdl.handle.net/10023/1063</link>
      <description>Abstract: For the first time we have investigated the natural ecosystem engineering capacity of stromatolitic microbial assemblages. Stromatolites are laminated sedimentary structures formed by microbial activity and are considered to have dominated the shallows of the Precambrian oceans. Their fossilised remains are the most ancient unambiguous record of early life on earth. Stromatolites can therefore be considered as the first recognisable ecosystems on the planet. However, while many discussions have taken place over their structure and form, we have very little information on their functional ecology and how such assemblages persisted despite strong eternal forcing from wind and waves. The capture and binding of sediment is clearly a critical feature for the formation and persistence of stromatolite assemblages. Here, we investigated the ecosystem engineering capacity of stromatolitic microbial assemblages with respect to their ability to stabilise sediment using material from one of the few remaining living stromatolite systems (Highborne Cay, Bahamas). It was shown that the most effective assemblages could produce a rapid (12-24h) and significant increase in sediment stability that continued in a linear fashion over the period of the experimentation (228h). Importantly, it was also found that light was required for the assemblages to produce this stabilisation effect and that removal of assemblage into darkness could lead to a partial reversal of the stabilisation. This was attributed to the breakdown of extracellular polymeric substances under anaerobic conditions. These data were supported by microelectrode profiling of oxygen and calcium. The structure of the assemblages as they formed was visualised by low-temperature scanning electron microscopy and confocal laser microscopy. These results have implications for the understanding of early stromatolite development and highlight the potential importance of the evolution of photosynthesis in the mat forming process. The evolution of photosynthesis may have provided an important advance for the niche construction activity of microbial systems and the formation and persistence of the stromatolites which came to dominate shallow coastal environments for 80% of the biotic history of the earth.</description>
      <pubDate>Tue, 01 Jan 2008 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1063</guid>
      <dc:date>2008-01-01T00:00:00Z</dc:date>
      <dc:creator>Paterson, David Maxwell</dc:creator>
      <dc:creator>Aspden, R J</dc:creator>
      <dc:creator>Visscher, P T</dc:creator>
      <dc:creator>Consalvey, M</dc:creator>
      <dc:creator>Andres, M</dc:creator>
      <dc:creator>Decho, A W</dc:creator>
      <dc:creator>Stolz, J</dc:creator>
      <dc:creator>Reid, P R</dc:creator>
      <dc:description>For the first time we have investigated the natural ecosystem engineering capacity of stromatolitic microbial assemblages. Stromatolites are laminated sedimentary structures formed by microbial activity and are considered to have dominated the shallows of the Precambrian oceans. Their fossilised remains are the most ancient unambiguous record of early life on earth. Stromatolites can therefore be considered as the first recognisable ecosystems on the planet. However, while many discussions have taken place over their structure and form, we have very little information on their functional ecology and how such assemblages persisted despite strong eternal forcing from wind and waves. The capture and binding of sediment is clearly a critical feature for the formation and persistence of stromatolite assemblages. Here, we investigated the ecosystem engineering capacity of stromatolitic microbial assemblages with respect to their ability to stabilise sediment using material from one of the few remaining living stromatolite systems (Highborne Cay, Bahamas). It was shown that the most effective assemblages could produce a rapid (12-24h) and significant increase in sediment stability that continued in a linear fashion over the period of the experimentation (228h). Importantly, it was also found that light was required for the assemblages to produce this stabilisation effect and that removal of assemblage into darkness could lead to a partial reversal of the stabilisation. This was attributed to the breakdown of extracellular polymeric substances under anaerobic conditions. These data were supported by microelectrode profiling of oxygen and calcium. The structure of the assemblages as they formed was visualised by low-temperature scanning electron microscopy and confocal laser microscopy. These results have implications for the understanding of early stromatolite development and highlight the potential importance of the evolution of photosynthesis in the mat forming process. The evolution of photosynthesis may have provided an important advance for the niche construction activity of microbial systems and the formation and persistence of the stromatolites which came to dominate shallow coastal environments for 80% of the biotic history of the earth.</dc:description>
    </item>
    <item>
      <title>The helicase XPD unwinds bubble structures and is not stalled by DNA lesions removed by the nucleotide excision repair pathway</title>
      <link>http://hdl.handle.net/10023/1048</link>
      <description>Abstract: Xeroderma pigmentosum factor D (XPD) is a 5'-3' superfamily 2 helicase and the founding member of a family of DNA helicases with iron-sulphur cluster domains. As a component of transcription factor II H (TFIIH), XPD is involved in DNA unwinding during nucleotide excision repair (NER). Archaeal XPD is closely related in sequence to the eukaryal enzyme and the crystal structure of the archaeal enzyme has provided a molecular understanding of mutations causing xeroderma pigmentosum and trichothiodystrophy in humans. Consistent with a role in NER, we show that archaeal XPD can initiate unwinding from a DNA bubble structure, differentiating it from the related helicases FancJ and DinG. XPD was not stalled by substrates containing extrahelical fluorescein adducts, abasic sites nor a cyclobutane pyrimidine dimer, regardless of whether these modifications were placed on either the displaced or translocated strands. This suggests that DNA lesions repaired by NER may not present a barrier to XPD translocation in vivo, in contrast to some predictions. Preferential binding of a fluorescein-adducted oligonucleotide was observed, and XPD helicase activity was readily inhibited by both single- and double-stranded DNA binding proteins. These observations have several implications for the current understanding of the NER pathway.</description>
      <pubDate>Fri, 01 Jan 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1048</guid>
      <dc:date>2010-01-01T00:00:00Z</dc:date>
      <dc:creator>Rudolf, Jana</dc:creator>
      <dc:creator>Rouillon, Christophe</dc:creator>
      <dc:creator>Schwarz-Linek, Ulrich</dc:creator>
      <dc:creator>White, Malcolm F</dc:creator>
      <dc:description>Xeroderma pigmentosum factor D (XPD) is a 5'-3' superfamily 2 helicase and the founding member of a family of DNA helicases with iron-sulphur cluster domains. As a component of transcription factor II H (TFIIH), XPD is involved in DNA unwinding during nucleotide excision repair (NER). Archaeal XPD is closely related in sequence to the eukaryal enzyme and the crystal structure of the archaeal enzyme has provided a molecular understanding of mutations causing xeroderma pigmentosum and trichothiodystrophy in humans. Consistent with a role in NER, we show that archaeal XPD can initiate unwinding from a DNA bubble structure, differentiating it from the related helicases FancJ and DinG. XPD was not stalled by substrates containing extrahelical fluorescein adducts, abasic sites nor a cyclobutane pyrimidine dimer, regardless of whether these modifications were placed on either the displaced or translocated strands. This suggests that DNA lesions repaired by NER may not present a barrier to XPD translocation in vivo, in contrast to some predictions. Preferential binding of a fluorescein-adducted oligonucleotide was observed, and XPD helicase activity was readily inhibited by both single- and double-stranded DNA binding proteins. These observations have several implications for the current understanding of the NER pathway.</dc:description>
    </item>
    <item>
      <title>The archaeo-eukaryotic GINS proteins and the archaeal primase catalytic subunit PriS share a common domain</title>
      <link>http://hdl.handle.net/10023/1047</link>
      <description>Abstract: Primase and GINS are essential factors for chromosomal DNA replication in eukaryotic and archaeal cells. Here we describe a previously undetected relationship between the C-terminal domain of the catalytic subunit (PriS) of archaeal primase and the B-domains of the archaeo-eukaryotic GINS proteins in the form of a conserved structural domain comprising a three-stranded antiparallel beta-sheet adjacent to an alpha-helix and a two-stranded beta-sheet or hairpin. The presence of a shared domain in archaeal PriS and GINS proteins, the genes for which are often found adjacent on the chromosome, suggests simple mechanisms for the evolution of these proteins.</description>
      <pubDate>Mon, 12 Apr 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1047</guid>
      <dc:date>2010-04-12T00:00:00Z</dc:date>
      <dc:creator>Swiatek, Agnieszka</dc:creator>
      <dc:creator>MacNeill, Stuart Andrew</dc:creator>
      <dc:description>Primase and GINS are essential factors for chromosomal DNA replication in eukaryotic and archaeal cells. Here we describe a previously undetected relationship between the C-terminal domain of the catalytic subunit (PriS) of archaeal primase and the B-domains of the archaeo-eukaryotic GINS proteins in the form of a conserved structural domain comprising a three-stranded antiparallel beta-sheet adjacent to an alpha-helix and a two-stranded beta-sheet or hairpin. The presence of a shared domain in archaeal PriS and GINS proteins, the genes for which are often found adjacent on the chromosome, suggests simple mechanisms for the evolution of these proteins.</dc:description>
    </item>
    <item>
      <title>Assessing the effectiveness of conservation measures : resolving the "wicked" problem of the Steller sea lion</title>
      <link>http://hdl.handle.net/10023/1034</link>
      <description>Abstract: “Wicked” problems are those that are complex and that change when solutions are applied. Many conflicts in conservation fall in to this category. The study approached the problem of how to constrain the apparent wickedness of a problem in the conservation management of a species by using simple empirical indicators to carry out iterative assessment of the risk to a population and to document how this risk evolves in relation to the addition of new data and the implementation of management actions. Effects of high levels of uncertainty within data and also concerning population structure were examined through stochastic simulation and by exploration of scenarios. Historical trends in the example used, the Steller sea lion, showed rapid declines in abundance in some regions during the 1980s. The current total population is 130,000-150,000 Steller sea lions through Alaska and British Columbia and this number has been stable since about 1990 in spite of regional differences in population dynamics. Regional differences in the sequence of changes in the number of pups and non-pups, suggested that an internal re-distribution of juveniles could have happened between 1980 and 1990. Current productivity also appears close to the long term mean. Stochastic population projection using various scenarios showed that, based upon this history, the risk of extinction for the population has declined and is below reasonable thresholds for considering the population to be endangered.</description>
      <pubDate>Thu, 01 Jul 2010 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1034</guid>
      <dc:date>2010-07-01T00:00:00Z</dc:date>
      <dc:creator>Boyd, Ian Lamont</dc:creator>
      <dc:description>“Wicked” problems are those that are complex and that change when solutions are applied. Many conflicts in conservation fall in to this category. The study approached the problem of how to constrain the apparent wickedness of a problem in the conservation management of a species by using simple empirical indicators to carry out iterative assessment of the risk to a population and to document how this risk evolves in relation to the addition of new data and the implementation of management actions. Effects of high levels of uncertainty within data and also concerning population structure were examined through stochastic simulation and by exploration of scenarios. Historical trends in the example used, the Steller sea lion, showed rapid declines in abundance in some regions during the 1980s. The current total population is 130,000-150,000 Steller sea lions through Alaska and British Columbia and this number has been stable since about 1990 in spite of regional differences in population dynamics. Regional differences in the sequence of changes in the number of pups and non-pups, suggested that an internal re-distribution of juveniles could have happened between 1980 and 1990. Current productivity also appears close to the long term mean. Stochastic population projection using various scenarios showed that, based upon this history, the risk of extinction for the population has declined and is below reasonable thresholds for considering the population to be endangered.</dc:description>
    </item>
    <item>
      <title>Invasive species control : Incorporating demographic data and seed dispersal into a management model for Rhododendron ponticum</title>
      <link>http://hdl.handle.net/10023/1033</link>
      <description>Abstract: Rhododendron ponticum is a serious invasive alien plant in the British Isles and is of significant conservation and economic concern. Here, we integrate information on both the demographics and spatial dynamics of this species within an individual-based, spatially-explicit model and investigate the effectiveness of different control strategies. Importantly, we simulate seed movement and dispersal using a mechanistic seed dispersal model. We investigate the effectiveness of initiating control at the edge versus the core of the infestation, with and without returning each year to remove seedlings. We compare these results to an age-dependent strategy whereby the oldest plants are removed each year. Age-dependent control, in which the oldest plants were removed first, was the most effective strategy investigated, both in terms of the probability of successful eradication and the number of years taken to control. We demonstrate that this is because the older (and taller) plants towards the core produce more seeds that, on average, travel further. Indeed, our results suggest that the expansion of the invading front is actually driven as much by seeds that disperse long distances from these larger plants as by the seed rain from recently matured plants located much closer to the front. Finally, we investigate the potential use of ‘quarantine lines’ — corridors of unsuitable habitat that are sufficiently wide to contain an infestation, preventing spread to vulnerable areas. This study has provided generic insights into best practice for management based on the current understanding of the biology and ecology of this pernicious, invasive plant.</description>
      <pubDate>Tue, 01 Sep 2009 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1033</guid>
      <dc:date>2009-09-01T00:00:00Z</dc:date>
      <dc:creator>Harris, Catriona M</dc:creator>
      <dc:creator>Park, K.J.</dc:creator>
      <dc:creator>Atkinson, R.</dc:creator>
      <dc:creator>Edwards, C.</dc:creator>
      <dc:creator>Travis, J.M.J.</dc:creator>
      <dc:description>Rhododendron ponticum is a serious invasive alien plant in the British Isles and is of significant conservation and economic concern. Here, we integrate information on both the demographics and spatial dynamics of this species within an individual-based, spatially-explicit model and investigate the effectiveness of different control strategies. Importantly, we simulate seed movement and dispersal using a mechanistic seed dispersal model. We investigate the effectiveness of initiating control at the edge versus the core of the infestation, with and without returning each year to remove seedlings. We compare these results to an age-dependent strategy whereby the oldest plants are removed each year. Age-dependent control, in which the oldest plants were removed first, was the most effective strategy investigated, both in terms of the probability of successful eradication and the number of years taken to control. We demonstrate that this is because the older (and taller) plants towards the core produce more seeds that, on average, travel further. Indeed, our results suggest that the expansion of the invading front is actually driven as much by seeds that disperse long distances from these larger plants as by the seed rain from recently matured plants located much closer to the front. Finally, we investigate the potential use of ‘quarantine lines’ — corridors of unsuitable habitat that are sufficiently wide to contain an infestation, preventing spread to vulnerable areas. This study has provided generic insights into best practice for management based on the current understanding of the biology and ecology of this pernicious, invasive plant.</dc:description>
    </item>
    <item>
      <title>Responses of hyperthermophilic crenarchaea to UV irradiation</title>
      <link>http://hdl.handle.net/10023/1029</link>
      <description>Abstract: Background: DNA damage leads to cellular responses that include the increased expression of DNA repair genes, repression of DNA replication and alterations in cellular metabolism. Archaeal information processing pathways resemble those in eukaryotes, but archaeal damage response pathways remain poorly understood. Results: We analyzed the transcriptional response to UV irradiation in two related crenarchaea, Sulfolobus solfataricus and Sulfolobus acidocaldarius. Sulfolobus species encounter high levels of DNA damage in nature, as they inhabit high temperature, aerobic environments and are exposed to sunlight. No increase in expression of DNA repair genes following UV irradiation was observed. There was, however, a clear transcriptional response, including repression of DNA replication and chromatin proteins. Differential effects on the expression of the three transcription factor B ( tfb) genes hint at a mechanism for the modulation of transcriptional patterns in response to DNA damage. TFB3, which is strongly induced following UV irradiation, competes with TFB1 for binding to RNA polymerase in vitro, and may act as a repressor of transcription or an alternative transcription factor for certain promoters. Conclusion: A clear response to DNA damage was observed, with down-regulation of the DNA replication machinery, changes in transcriptional regulatory proteins, and up-regulation of the biosynthetic enzymes for beta-carotene, which has UV protective properties, and proteins that detoxify reactive oxygen species. However, unlike eukaryotes and bacteria, there was no induction of DNA repair proteins in response to DNA damage, probably because these are expressed constitutively to deal with increased damage arising due to high growth temperatures.
Description: This work was supported by a dedicated functional genomics grant from the Swedish Research Council and the Swedish Graduate Research School in Genomics and Bioinformatics to RB, and by grants from the Wellcome Trust and BBSRC to MFW.</description>
      <pubDate>Mon, 01 Jan 2007 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1029</guid>
      <dc:date>2007-01-01T00:00:00Z</dc:date>
      <dc:creator>Gotz, Dorothee</dc:creator>
      <dc:creator>Paytubi, Sonia</dc:creator>
      <dc:creator>Munro, Stacey</dc:creator>
      <dc:creator>Lundgren, Magnus</dc:creator>
      <dc:creator>Bernander, Rolf</dc:creator>
      <dc:creator>White, Malcolm F.</dc:creator>
      <dc:description>Background: DNA damage leads to cellular responses that include the increased expression of DNA repair genes, repression of DNA replication and alterations in cellular metabolism. Archaeal information processing pathways resemble those in eukaryotes, but archaeal damage response pathways remain poorly understood. Results: We analyzed the transcriptional response to UV irradiation in two related crenarchaea, Sulfolobus solfataricus and Sulfolobus acidocaldarius. Sulfolobus species encounter high levels of DNA damage in nature, as they inhabit high temperature, aerobic environments and are exposed to sunlight. No increase in expression of DNA repair genes following UV irradiation was observed. There was, however, a clear transcriptional response, including repression of DNA replication and chromatin proteins. Differential effects on the expression of the three transcription factor B ( tfb) genes hint at a mechanism for the modulation of transcriptional patterns in response to DNA damage. TFB3, which is strongly induced following UV irradiation, competes with TFB1 for binding to RNA polymerase in vitro, and may act as a repressor of transcription or an alternative transcription factor for certain promoters. Conclusion: A clear response to DNA damage was observed, with down-regulation of the DNA replication machinery, changes in transcriptional regulatory proteins, and up-regulation of the biosynthetic enzymes for beta-carotene, which has UV protective properties, and proteins that detoxify reactive oxygen species. However, unlike eukaryotes and bacteria, there was no induction of DNA repair proteins in response to DNA damage, probably because these are expressed constitutively to deal with increased damage arising due to high growth temperatures.</dc:description>
    </item>
    <item>
      <title>TarO : a target optimisation system for structural biology</title>
      <link>http://hdl.handle.net/10023/1028</link>
      <description>Abstract: TarO (http://www.compbio.dundee.ac.uk/taro) offers a single point of reference for key bioinformatics analyses relevant to selecting proteins or domains for study by structural biology techniques. The protein sequence is analysed by 17 algorithms and compared to 8 databases. TarO gathers putative homologues, including orthologues, and then obtains predictions of properties for these sequences including crystallisation propensity, protein disorder and post-translational modifications. Analyses are run on a high-performance computing cluster, the results integrated, stored in a database and accessed through a web-based user interface. Output is in tabulated format and in the form of an annotated multiple sequence alignment (MSA) that may be edited interactively in the program Jalview. TarO also simplifies the gathering of additional annotations via the Distributed Annotation System, both from the MSA in Jalview and through links to Dasty2. Routes to other information gateways are included, for example to relevant pages from UniProt, COG and the Conserved Domains Database. Open access to TarO is available from a guest account with private accounts for academic use available on request. Future development of TarO will include further analysis steps and integration with the Protein Information Management System (PIMS), a sister project in the BBSRC Structural Proteomics of Rational Targets initiative.
Description: This work was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC) Structural Proteomics of Rational Targets (SPoRT) initiative, (Grant BBS/B/14434). Funding to pay the Open Access publication charges for this article was provided by BBSRC.</description>
      <pubDate>Tue, 01 Jul 2008 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1028</guid>
      <dc:date>2008-07-01T00:00:00Z</dc:date>
      <dc:creator>Overton, I M</dc:creator>
      <dc:creator>van Niekerk, C A</dc:creator>
      <dc:creator>Carter, L G</dc:creator>
      <dc:creator>Dawson, A</dc:creator>
      <dc:creator>Martin, D M</dc:creator>
      <dc:creator>Cameron, S</dc:creator>
      <dc:creator>McMahon, S A</dc:creator>
      <dc:creator>White, Malcolm Frederick</dc:creator>
      <dc:creator>Hunter, W N</dc:creator>
      <dc:creator>Naismith, James Henderson</dc:creator>
      <dc:creator>Barton, G J</dc:creator>
      <dc:description>TarO (http://www.compbio.dundee.ac.uk/taro) offers a single point of reference for key bioinformatics analyses relevant to selecting proteins or domains for study by structural biology techniques. The protein sequence is analysed by 17 algorithms and compared to 8 databases. TarO gathers putative homologues, including orthologues, and then obtains predictions of properties for these sequences including crystallisation propensity, protein disorder and post-translational modifications. Analyses are run on a high-performance computing cluster, the results integrated, stored in a database and accessed through a web-based user interface. Output is in tabulated format and in the form of an annotated multiple sequence alignment (MSA) that may be edited interactively in the program Jalview. TarO also simplifies the gathering of additional annotations via the Distributed Annotation System, both from the MSA in Jalview and through links to Dasty2. Routes to other information gateways are included, for example to relevant pages from UniProt, COG and the Conserved Domains Database. Open access to TarO is available from a guest account with private accounts for academic use available on request. Future development of TarO will include further analysis steps and integration with the Protein Information Management System (PIMS), a sister project in the BBSRC Structural Proteomics of Rational Targets initiative.</dc:description>
    </item>
    <item>
      <title>The Mre11 protein interacts with both Rad50 and the HerA bipolar helicase and is recruited to DNA following gamma irradiation in the archaeon Sulfolobus acidocaldarius</title>
      <link>http://hdl.handle.net/10023/1027</link>
      <description>Abstract: Background: The ubiquitous Rad50 and Mre11 proteins play a key role in many processes involved in the maintenance of genome integrity in Bacteria and Eucarya, but their function in the Archaea is presently unknown. We showed previously that in most hyperthermophilic archaea, rad50-mre11 genes are linked to nurA encoding both a single-strand endonuclease and a 5' to 3' exonuclease, and herA, encoding a bipolar DNA helicase which suggests the involvement of the four proteins in common molecular pathway(s). Since genetic tools for hyperthermophilic archaea are just emerging, we utilized immuno-detection approaches to get the first in vivo data on the role(s) of these proteins in the hyperthermophilic crenarchaeon Sulfolobus acidocaldarius. Results: We first showed that S. acidocaldarius can repair DNA damage induced by high doses of gamma rays, and we performed a time course analysis of the total levels and sub-cellular partitioning of Rad50, Mre11, HerA and NurA along with the RadA recombinase in both control and irradiated cells. We found that during the exponential phase, all proteins are synthesized and display constant levels, but that all of them exhibit a different sub-cellular partitioning. Following gamma irradiation, both Mre11 and RadA are immediately recruited to DNA and remain DNA-bound in the course of DNA repair. Furthermore, we show by immuno-precipitation assays that Rad50, Mre11 and the HerA helicase interact altogether. Conclusion: Our analyses strongly support that in Sulfolobus acidocaldarius, the Mre11 protein and the RadA recombinase might play an active role in the repair of DNA damage introduced by gamma rays and/or may act as DNA damage sensors. Moreover, our results demonstrate the functional interaction between Mre11, Rad50 and the HerA helicase and suggest that each protein play different roles when acting on its own or in association with its partners. This report provides the first in vivo evidence supporting the implication of the Mre11 protein in DNA repair processes in the Archaea and showing its interaction with both Rad50 and the HerA bipolar helicase. Further studies on the functional interactions between these proteins, the NurA nuclease and the RadA recombinase, will allow us to define their roles and mechanism of action.</description>
      <pubDate>Fri, 22 Feb 2008 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/1027</guid>
      <dc:date>2008-02-22T00:00:00Z</dc:date>
      <dc:creator>Quaiser, Achim</dc:creator>
      <dc:creator>Constantinesco, Florence</dc:creator>
      <dc:creator>White, Malcolm F.</dc:creator>
      <dc:creator>Forterre, Patrick</dc:creator>
      <dc:creator>Elie, Christiane</dc:creator>
      <dc:description>Background: The ubiquitous Rad50 and Mre11 proteins play a key role in many processes involved in the maintenance of genome integrity in Bacteria and Eucarya, but their function in the Archaea is presently unknown. We showed previously that in most hyperthermophilic archaea, rad50-mre11 genes are linked to nurA encoding both a single-strand endonuclease and a 5' to 3' exonuclease, and herA, encoding a bipolar DNA helicase which suggests the involvement of the four proteins in common molecular pathway(s). Since genetic tools for hyperthermophilic archaea are just emerging, we utilized immuno-detection approaches to get the first in vivo data on the role(s) of these proteins in the hyperthermophilic crenarchaeon Sulfolobus acidocaldarius. Results: We first showed that S. acidocaldarius can repair DNA damage induced by high doses of gamma rays, and we performed a time course analysis of the total levels and sub-cellular partitioning of Rad50, Mre11, HerA and NurA along with the RadA recombinase in both control and irradiated cells. We found that during the exponential phase, all proteins are synthesized and display constant levels, but that all of them exhibit a different sub-cellular partitioning. Following gamma irradiation, both Mre11 and RadA are immediately recruited to DNA and remain DNA-bound in the course of DNA repair. Furthermore, we show by immuno-precipitation assays that Rad50, Mre11 and the HerA helicase interact altogether. Conclusion: Our analyses strongly support that in Sulfolobus acidocaldarius, the Mre11 protein and the RadA recombinase might play an active role in the repair of DNA damage introduced by gamma rays and/or may act as DNA damage sensors. Moreover, our results demonstrate the functional interaction between Mre11, Rad50 and the HerA helicase and suggest that each protein play different roles when acting on its own or in association with its partners. This report provides the first in vivo evidence supporting the implication of the Mre11 protein in DNA repair processes in the Archaea and showing its interaction with both Rad50 and the HerA bipolar helicase. Further studies on the functional interactions between these proteins, the NurA nuclease and the RadA recombinase, will allow us to define their roles and mechanism of action.</dc:description>
    </item>
    <item>
      <title>Is all learning innovation?</title>
      <link>http://hdl.handle.net/10023/644</link>
      <description>Abstract: Research on animal innovation is an underdeveloped field, and for this reason we welcome the efforts Ramsey and colleagues have made to stimulate its study in wild populations. However, we feel that in attempting to find an operational definition the authors have overstretched the idea of what we should consider innovation in some areas and over-restricted it in others.
Description: Open peer commentary on "Animal innovation defined and operationalized" Grant Ramsey, Meredith L. Bastian and Carel van Schaik&#xD;
Behavioral and Brain Sciences , Volume 30, Issue 04, August 2007, pp 393-407</description>
      <pubDate>Mon, 01 Jan 2007 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/644</guid>
      <dc:date>2007-01-01T00:00:00Z</dc:date>
      <dc:creator>Rendell, L</dc:creator>
      <dc:creator>Hoppitt, W</dc:creator>
      <dc:creator>Kendal, J</dc:creator>
      <dc:description>Research on animal innovation is an underdeveloped field, and for this reason we welcome the efforts Ramsey and colleagues have made to stimulate its study in wild populations. However, we feel that in attempting to find an operational definition the authors have overstretched the idea of what we should consider innovation in some areas and over-restricted it in others.</dc:description>
    </item>
    <item>
      <title>Coda vocalizations recorded in breeding areas are almost entirely produced by mature female sperm whales (Physeter macrocephalus)</title>
      <link>http://hdl.handle.net/10023/491</link>
      <description>Abstract: We investigated the use and function of coda communication by sperm whales (Physeter macrocephalus L., 1758 (=Physeter Catodon L., 1758)) Codas are stereotyped patterns of clicks often made by sperm whales in social contexts. We used the pulsed structure of coda clicks recorded from socializing female/immature groups to estimate the bodylength distribution of the animals producing the codas. Ninety-five percent of the 10653 codas that we measured were produced by whales measuring from 9 to 11 m. This size range corresponds to the length of mature females. We compared these data to a length distribution calculated from photographic measurements of individuals from the same groups encountered during the same studies.  There were more whales shorter than 8.5 m (10.0%)and longer than 12.5 m (2.7%) in the photographic length distribution than in that of the coda producers (0.30% and 0.08% respectively). Since males leave their natal group when they are shorter than 9 m and return to breeding areas when they measure 13 m or more, our data shows that the codas were produced almost entirely by mature females. We suggest that coda communication serves several functions, including social bonding.</description>
      <pubDate>Sun, 01 Jan 2006 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://hdl.handle.net/10023/491</guid>
      <dc:date>2006-01-01T00:00:00Z</dc:date>
      <dc:creator>Marcoux, M</dc:creator>
      <dc:creator>Whitehead, H</dc:creator>
      <dc:creator>Rendell, L</dc:creator>
      <dc:description>We investigated the use and function of coda communication by sperm whales (Physeter macrocephalus L., 1758 (=Physeter Catodon L., 1758)) Codas are stereotyped patterns of clicks often made by sperm whales in social contexts. We used the pulsed structure of coda clicks recorded from socializing female/immature groups to estimate the bodylength distribution of the animals producing the codas. Ninety-five percent of the 10653 codas that we measured were produced by whales measuring from 9 to 11 m. This size range corresponds to the length of mature females. We compared these data to a length distribution calculated from photographic measurements of individuals from the same groups encountered during the same studies.  There were more whales shorter than 8.5 m (10.0%)and longer than 12.5 m (2.7%) in the photographic length distribution than in that of the coda producers (0.30% and 0.08% respectively). Since males leave their natal group when they are shorter than 9 m and return to breeding areas when they measure 13 m or more, our data shows that the codas were produced almost entirely by mature females. We suggest that coda communication serves several functions, including social bonding.</dc:description>
    </item>
  </channel>
</rss>

