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Willin, an upstream component of the Hippo signaling pathway, orchestrates mammalian peripheral nerve fibroblasts

Moleirinho, Susana — 2013-04-08T00:00:00Z

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.

Estimating whale abundance using sparse hydrophone arrays

Harris, Danielle V. — 2012-06-20T00:00:00Z

Abstract: Passive acoustic monitoring has been used to investigate many aspects of marine mammal ecology, although methods to estimate absolute abundance and density using acoustic data have only been developed in recent years. The instrument configuration in an acoustic survey determines which abundance estimation methods can be used. Sparsely distributed arrays of instruments are useful because wide geographic areas can be covered. However, instrument spacing in sparse arrays is such that the same vocalisation will not be detected on multiple instruments, excluding the use of some abundance estimation methods. The aim of this thesis was to explore cetacean abundance and density estimation using novel sparse array datasets, applying existing methods where possible, or developing new approaches. The wealth of data collected by sparse arrays was demonstrated by analysing a 10-year dataset collected by the U.S. Navy’s Sound Surveillance System in the north-east Atlantic. Spatial and temporal patterns of blue (Balaenoptera musculus) and fin whale (Balaenoptera physalus) vocal activity were investigated using generalised additive models. Distance sampling-based methods were applied to fin whale calls recorded by an array of Ocean Bottom Seismometers in the north-east Atlantic. Estimated call density was 993 calls/1000 km².hr⁻¹ (CV: 0.39). Animal density could not be estimated because the call rate was unknown. Further development of the call localisation method is required so the current density estimate may be biased. Furthermore, analysing a single day of data resulted in a high variance estimate. Finally, a new simulation-based method developed to estimate density from single hydrophones was applied to blue whale calls recorded in the northern Indian Ocean. Estimated call density was 3 calls/1000 km².hr⁻¹ (CV: 0.17). Again, density of whales could not be estimated as the vocalisation rate was unknown. Lack of biological knowledge poses the greatest limitation to abundance and density estimation using acoustic data.

Concepts in context

Onofri, Andrea — 2013-01-01T00:00:00Z

Abstract: My thesis discusses two related problems that have taken center stage in the recent literature on concepts: 1) What are the individuation conditions of concepts? Under what conditions is a concept C₁ the same concept as a concept C₂? 2) What are the possession conditions of concepts? What conditions must be satisfied for a thinker to have a concept C? The thesis defends a novel account of concepts, which I call “pluralist-contextualist”: 1) Pluralism: Different concepts have different kinds of individuation and possession conditions: some concepts are individuated more “coarsely”, have less demanding possession conditions and are widely shared, while other concepts are individuated more “finely” and not shared. 2) Contextualism: When a speaker ascribes a propositional attitude to a subject S, or uses his ascription to explain/predict S’s behavior, the speaker’s intentions in the relevant context determine the correct individuation conditions for the concepts involved in his report. In chapters 1-3 I defend a contextualist, non-Millian theory of propositional attitude ascriptions. Then, I show how contextualism can be used to offer a novel perspective on the problem of concept individuation/possession. More specifically, I employ contextualism to provide a new, more effective argument for Fodor’s “publicity principle”: if contextualism is true, then certain specific concepts must be shared in order for interpersonally applicable psychological generalizations to be possible. In chapters 4-5 I raise a tension between publicity and another widely endorsed principle, the “Fregean constraint” (FC): subjects who are unaware of certain identity facts and find themselves in so-called “Frege cases” must have distinct concepts for the relevant object x. For instance: the ancient astronomers had distinct concepts (HESPERUS/PHOSPHORUS) for the same object (the planet Venus). First, I examine some leading theories of concepts and argue that they cannot meet both of our constraints at the same time. Then, I offer principled reasons to think that no theory can satisfy (FC) while also respecting publicity. (FC) appears to require a form of holism, on which a concept is individuated by its global inferential role in a subject S and can thus only be shared by someone who has exactly the same inferential dispositions as S. This explains the tension between publicity and (FC), since holism is clearly incompatible with concept shareability. To solve the tension, I suggest adopting my pluralist-contextualist proposal: concepts involved in Frege cases are holistically individuated and not public, while other concepts are more coarsely individuated and widely shared; given this “plurality” of concepts, we will then need contextual factors (speakers’ intentions) to “select” the specific concepts to be employed in our intentional generalizations in the relevant contexts. In chapter 6 I develop the view further by contrasting it with some rival accounts. First, I examine a very different kind of pluralism about concepts, which has been recently defended by Daniel Weiskopf, and argue that it is insufficiently radical. Then, I consider the inferentialist accounts defended by authors like Peacocke, Rey and Jackson. Such views, I argue, are committed to an implausible picture of reference determination, on which our inferential dispositions fix the reference of our concepts: this leads to wrong predictions in all those cases of scientific disagreement where two parties have very different inferential dispositions and yet seem to refer to the same natural kind.

Lateral entorhinal cortex is critical for novel object-context recognition

Wilson, David Ian Greig — 2013-01-01T00:00:00Z

Abstract: Episodic memory incorporates information about specific events or occasions including spatial locations and the contextual features of the environment in which the event took place. It has been modeled in rats using spontaneous exploration of novel configurations of objects, their locations, and the contexts in which they are presented. While we have a detailed understanding of how spatial location is processed in the brain relatively little is known about where the nonspatial contextual components of episodic memory are processed. Initial experiments measured c-fos expression during an object-context recognition (OCR) task to examine which networks within the brain process contextual features of an event. Increased c-fos expression was found in the lateral entorhinal cortex (LEC; a major hippocampal afferent) during OCR relative to control conditions. In a subsequent experiment it was demonstrated that rats with lesions of LEC were unable to recognize object-context associations yet showed normal object recognition and normal context recognition. These data suggest that contextual features of the environment are integrated with object identity in LEC and demonstrate that recognition of such object-context associations requires the LEC. This is consistent with the suggestion that contextual features of an event are processed in LEC and that this information is combined with spatial information from medial entorhinal cortex to form episodic memory in the hippocampus. © 2013 Wiley Periodicals, Inc.

Competing conservation objectives for predators and prey : estimating killer whale prey requirements for Chinook salmon

Williams, Robert — 2011-11-09T00:00:00Z

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.

Estimating seasonal abundance of a central place forager using counts and telemetry data

Sharples, RJ — 2009-01-01T00:00:00Z

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.

Male mating tactics in the rose bitterling (Rhodeus ocellatus) and European bitterling (Rhodeus amarus)

Casalini, Mara — 2013-06-26T00:00:00Z

Abstract: The aim of this study was to investigate the basis to male mating decisions in two related species of bitterling: Rhodeus ocellatus and R. amarus. Bitterling have a resource-based mating system; females lay eggs in the gills of live freshwater mussels and males fertilize the eggs by releasing sperm into the inhalant syphon of the mussel. Male bitterling perform courtship behaviour and aggressively defend mussels in a territory from which they exclude other males. Using laboratory and field experiments it was shown that male aggressive behaviour is inherited through additive maternal genes. Male aggression is also influenced by the number of conspecific males encountered in competition for a mussel, and by the degree of clustering of mussels. Limited availability of mussels results in stronger selection on traits males use in mating context: hence they are more aggressive, larger and more colourful. The differences in mating behaviours in different environments may indicate a conflict between male dominance and female choice, but have not led to reproductive isolation. Resource availability during ontogenesis and male density during embryogenesis, however, do not exert an effect on male aggressive behaviour. Red carotenoid-based nuptial coloration functions as an inter- and intra-sexual signal and undergoes rapid variation in response to changes in mating context. Male bitterling do not modulate their courtship and aggressive behaviour in response to variation in female size, and their choice of mussel species is influenced by, and consistent with, female oviposition choice.

Photo-grammetric measurements of swimming speed and body length of basking sharks observed around the Hebrides, Scotland

Lacey, Claire — 2010-03-01T00:00:00Z

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.

Synthesis of phosphonate and phostone analogues of ribose-1-phosphates

Nasomjai, Pitak — 2009-07-27T00:00:00Z

Abstract: The synthesis of phosphonate analogues of ribose-1-phosphate and 5-fluoro-5-deoxyribose-1-phosphate is described. Preparations of both the alpha- and beta-phosphonate anomers are reported for the ribose and 5-fluoro-5-deoxyribose series and a synthesis of the corresponding cyclic phostones of each alpha-ribose is also reported. These compounds have been prepared as tools to probe the details of fluorometabolism in S. cattleya.

Three step synthesis of single diastereoisomers of the vicinal trifluoro motif

Brunet, Vincent A. — 2009-11-05T00:00:00Z

Abstract: A three step route to single diastereoisomers of the vicinal trifluoromethyl motif is described. The route starts from either syn- or anti-alpha,beta-epoxy alcohols and takes a direct approach in that each of the three steps introduces a fluorine atom in a regio- and stereospecific manner. Starting from either the syn- or the anti-alpha,beta-epoxy alcohol, stereospecific reactions generate two separate diastereoisomeric series of this motif. The route is a significant improvement on an earlier six step strategy.

Crenarchaeal chromatin proteins Cren7 and Sul7 compact DNA by inducing rigid bends

Driessen, Rosalie P. C. — 2013-01-01T00:00:00Z

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.

hSSB1 interacts directly with the MRN complex stimulating its recruitment to DNA double-strand breaks and its endo-nuclease activity

Richard, Derek J. — 2011-05-01T00:00:00Z

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.

hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex

Richard, Derek J. — 2011-03-01T00:00:00Z

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).

Crystallization of Ranasmurfin, a blue coloured protein from Polypedates leucomystax

McMahon, Stephen — 2006-11-01T00:00:00Z

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.

Facial skin coloration affects perceived health of human faces

Stephen, Ian David — 2009-12-01T00:00:00Z

Abstract: Numerous researchers have examined the effects of skin condition, including texture and color, on the perception of health, age, and attractiveness in human faces. They have focused on facial color distribution, homogeneity of pigmentation, or skin quality. We here investigate the role of overall skin color in determining perceptions of health from faces by allowing participants to manipulate the skin portions of color-calibrated Caucasian face photographs along CIELab color axes. To enhance healthy appearance, participants increased skin redness (a*), providing additional support for previous findings that skin blood color enhances the healthy appearance of faces. Participants also increased skin yellowness (b*) and lightness (L*), suggesting a role for high carotenoid and low melanin coloration in the healthy appearance of faces. The color preferences described here resemble the red and yellow color cues to health displayed by many species of nonhuman animals. Description: I stephen was funded by a BBSRC Studentship. M Stirrat was funded by an EPSRC Studentship.

Skin blood perfusion and oxygenation colour affect affect perceived human health

Stephen, Ian David — 2009-04-01T00:00:00Z

Abstract: Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice. Description: I Stephen was funded by a BBSRC Studentship.

You are what you eat : Within-subject increases in fruit and vegetable consumption confer beneficial skin-color changes

Whitehead, Ross — 2012-03-07T00:00:00Z

Abstract: Background: Fruit and vegetable consumption and ingestion of carotenoids have been found to be associated with human skin-color (yellowness) in a recent cross-sectional study. This carotenoid-based coloration contributes beneficially to the appearance of health in humans and is held to be a sexually selected cue of condition in other species. Methodology and Principal Findings: Here we investigate the effects of fruit and vegetable consumption on skin-color longitudinally to determine the magnitude and duration of diet change required to change skin-color perceptibly. Diet and skin-color were recorded at baseline and after three and six weeks, in a group of 35 individuals who were without makeup, self-tanning agents and/or recent intensive UV exposure. Six-week changes in fruit and vegetable consumption were significantly correlated with changes in skin redness and yellowness over this period, and diet-linked skin reflectance changes were significantly associated with the spectral absorption of carotenoids and not melanin. We also used psychophysical methods to investigate the minimum color change required to confer perceptibly healthier and more attractive skin-coloration. Modest dietary changes are required to enhance apparent health (2.91 portions per day) and attractiveness (3.30 portions). Conclusions: Increased fruit and vegetable consumption confers measurable and perceptibly beneficial effects on Caucasian skin appearance within six weeks. This effect could potentially be used as a motivational tool in dietary intervention. Description: R Whitehead was funded by an ESRC Studentship.

Single-molecule chemical denaturation of riboswitches

Dalgarno, Paul Allan — 2013-01-01T00:00:00Z

Abstract: To date, single-molecule RNA science has been developed almost exclusively around the effect of metal ions as folding promoters and stabilizers of the RNA structure. Here, we introduce a novel strategy that combines single-molecule Förster resonance energy transfer (FRET) and chemical denaturation to observe and manipulate RNA dynamics. We demonstrate that the competing interplay between metal ions and denaturant agents provides a platform to extract information that otherwise will remain hidden with current methods. Using the adenine-sensing riboswitch aptamer as a model, we provide strong evidence for a rate-limiting folding step of the aptamer domain being modulated through ligand binding, a feature that is important for regulation of the controlled gene. In the absence of ligand, the rate-determining step is dominated by the formation of long-range key tertiary contacts between peripheral stem-loop elements. In contrast, when the adenine ligand interacts with partially folded messenger RNAs, the aptamer requires specifically bound Mg2+ ions, as those observed in the crystal structure, to progress further towards the native form. Moreover, despite that the ligand-free and ligand-bound states are indistinguishable by FRET, their different stability against urea-induced denaturation allowed us to discriminate them, even when they coexist within a single FRET trajectory; a feature not accessible by existing methods.

Iso-seco-tanapartholides : isolation, synthesis and biological evaluation

Makiyi, Edward F. — 2009-11-01T00:00:00Z

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 & Co. KGaA, 69451 Weinheim, Germany, 2009)

Quantifying biodiversity trends in time and space

Studeny, Angelika C. — 2012-11-30T00:00:00Z

Abstract: The global loss of biodiversity calls for robust large-scale diversity assessment. Biological diversity is a multi-faceted concept; defined as the “variety of life”, answering questions such as “How much is there?” or more precisely “Have we succeeded in reducing the rate of its decline?” is not straightforward. While various aspects of biodiversity give rise to numerous ways of quantification, we focus on temporal (and spatial) trends and their changes in species diversity. Traditional diversity indices summarise information contained in the species abundance distribution, i.e. each species' proportional contribution to total abundance. Estimated from data, these indices can be biased if variation in detection probability is ignored. We discuss differences between diversity indices and demonstrate possible adjustments for detectability. Additionally, most indices focus on the most abundant species in ecological communities. We introduce a new set of diversity measures, based on a family of goodness-of-fit statistics. A function of a free parameter, this family allows us to vary the sensitivity of these measures to dominance and rarity of species. Their performance is studied by assessing temporal trends in diversity for five communities of British breeding birds based on 14 years of survey data, where they are applied alongside the current headline index, a geometric mean of relative abundances. Revealing the contributions of both rare and common species to biodiversity trends, these "goodness-of-fit" measures provide novel insights into how ecological communities change over time. Biodiversity is not only subject to temporal changes, but it also varies across space. We take first steps towards estimating spatial diversity trends. Finally, processes maintaining biodiversity act locally, at specific spatial scales. Contrary to abundance-based summary statistics, spatial characteristics of ecological communities may distinguish these processes. We suggest a generalisation to a spatial summary, the cross-pair overlap distribution, to render it more flexible to spatial scale.

Locations of envy : an ethnography of Aguabuena potters

Castellanos Montes, Daniela — 2012-12-04T00:00:00Z

Abstract: This thesis is an anthropological exploration of the envy of Aguabuena people, a small rural community of potters in the village of Ráquira, in the Boyacá region of Andean Colombia. Based on long-term ethnographic fieldwork among these potters, I propose an understanding of envy in Aguabuena as an existential experience, shaping relationships between the self and others in the world, crosscutting metaphysical and physical spheres, and balancing between corrosive and more empathetic ways of co-existence. Disclosing the multipresence of envy in Aguabuena’s world, its effects on people (including the ethnographer), and the way envy is embodied, performed, reciprocated and circumvented by the potters, I locate envy in various contexts where it is said to be manifested. Furthermore, I discuss the complex spectrum of envy and its multivalent meanings, or oscillations, in the life of Aguabuena people. I also present interactions with people surrounding potters, such as Augustinian monks, crafts middlemen, and municipal authorities, all of whom recount the envy of potters. My research challenges previous anthropological interpretations on envy and provides an alternative reading of this phenomenon. Moving away from labelling and regulatory explanations of envy, performative models, or pathological interpretations of the subject, I analyse the lived experience of envy and how it encompasses different realms of experience as well as flows of social relations. While focusing on the tensions and entanglements that envy brings to potters, as it constrains social life but also activates and reinforces social bonds, I examine the channels through which envy circulates and how it is put into motion by potters. Additionally, my thesis intends to contribute to anthropological studies of rural pottery communities in Andean Colombia. I present my unfolding understanding of envy by using both the potters’ concept and material detail, punto, location, referring to a spot from where Aguabuena people enter different vistas of the world, or denoting a precise time when things or materials change their physical qualities. Through this device, I disclose realms of envy, while seeking to immerse the reader in the lived experience of envy.

Sharp global nonlinear stability for a fluid overlying a highly porous material

Hill, Antony A. — 2010-01-08T00:00:00Z

Abstract: The stability of convection in a two-layer system in which a layer of fluid with a temperature-dependent viscosity overlies and saturates a highly porous material is studied. Owing to the difficulties associated with incorporating the nonlinear advection term in the Navier-Stokes equations into a stability analysis, previous literature on fluid/porous thermal convection has modelled the fluid using the linear Stokes equations. This paper derives global stability for the full nonlinear system, by utilizing a model proposed by Ladyzhenskaya. The nonlinear stability boundaries are shown to be sharp when compared with the linear instability thresholds.

Nonlinear stability of the one-domain approach to modelling convection in superposed fluid and porous layers

Hill, A A — 2010-09-01T00:00:00Z

Abstract: Studies of the nonlinear stability of fluid/porous systems have been developed very recently. A two-domain modelling approach has been adopted in previous works, but was restricted to specific configurations. The extension to the more general case of a Navier–Stokes modelled fluid over a porous material was not achieved for the two-domain approach owing to the difficulties associated with handling the interfacial boundary conditions. This paper addresses this issue by adopting a one-domain approach, where the governing equations for both regions are combined into a unique set of equations that are valid for the entire domain. It is shown that the nonlinear stability bound, in the one-domain approach, is very sharp and hence excludes the possibility of subcritical instabilities. Moreover, the one-domain approach is compared with an equivalent two-domain approach, and excellent agreement is found between the two.

Instability in internal solitary waves with trapped cores

Carr, Magda — 2012-01-01T00:00:00Z

Abstract: A numerical method that employs a combination of contour advection and pseudo-spectral techniques is used to investigate instability in internal solitary waves with trapped cores. A three-layer configuration for the background stratification in which the top two layers are linearly stratified and the lower layer is homogeneous is considered throughout. The strength of the stratification in the very top layer is chosen to be sufficient so that waves of depression with trapped cores can be generated. The flow is assumed to satisfy the Dubriel-Jacotin-Long equation both inside and outside of the core region. The Brunt-Vaisala frequency is modelled such that it varies from a constant value outside of the core to zero inside the core over a sharp but continuous transition length. This results in a stagnant core in which the vorticity is zero and the density is homogeneous and approximately equal to that at the core boundary. The time dependent simulations show that instability occurs on the boundary of the core. The instability takes the form of Kelvin-Helmholtz billows. If the instability in the vorticity field is energetic enough, disturbance in the buoyancy field is also seen and fluid exchange takes place across the core boundary. Occurrence of the Kelvin-Helmholtz billows is attributed to the sharp change in the vorticity field at the boundary between the core and the pycnocline. The numerical scheme is not limited by small Richardson number unlike the other alternatives currently available in the literature which appear to be.

Shear induced breaking of large amplitude internal solitary waves

Fructus, D — 2009-02-01T00:00:00Z

Convectively induced shear instability in large amplitude internal solitary waves

Carr, Magda — 2008-12-01T00:00:00Z

Abstract: Laboratory study has been carried out to investigate the instability of an internal solitary wave of depression in a shallow stratified fluid system. The experimental campaign has been supported by theoretical computations and has focused on a two layered stratification consisting of a homogeneous dense layer below a linearly stratified top layer. The initial background stratification has been varied and it is found that the onset and intensity of breaking are affected dramatically by changes in the background stratification. Manifestations of a combination of shear and convective instability are seen on the leading face of the wave. It is shown that there is an interplay between the two instability types and convective instability induces shear by enhancing isopycnal compression. Variation in the upper boundary condition is also found to have an effect on stability. In particular, the implications for convective instability are shown to be profound and a dramatic increase in wave amplitude is seen for a fixed (as opposed to free) upper boundary condition.

To ping or not to ping : the use of active acoustic devices in mitigating interactions between small cetaceans and gillnet fisheries

Dawson, Steve — 2013-01-01T00:00:00Z

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.

Tissue-specific transcriptomics in the field cricket Teleogryllus oceanicus

Bailey, Nathan William — 2013-02-01T00:00:00Z

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.

Mg structural state in coral aragonite and implications for the paleoenvironmental proxy

Finch, Adrian A. — 2008-04-19T00:00:00Z

Abstract: Thermodynamic calculations and inorganic precipitation experiments indicate a relationship between aragonite Mg/Ca and water temperature. This offers a route to reconstruct seawater temperatures from fossil corals. Fundamental to this is the assumption that Mg2+ exchanges for Ca2+ within carbonate. We present X-ray Absorption Fine Structure (XAFS) data to indicate the structural state of Mg in modern Porites coral skeletons. We show Mg is not in aragonite, but hosted by a disordered Mg-bearing material. Mg may be predominantly hosted in organic materials or as a highly disordered inorganic phase, e. g., a nanoparticulate form of Mg carbonate or hydroxide. Reported correlations between seawater temperature and coral Mg/Ca are unlikely to be consistent between corals and hence analysis of Mg/Ca in fossils is unlikely to produce accurate climate reconstructions. We anticipate XAFS will be applied widely to environmental proxies and become an important tool in identifying those that reconstruct accurate climates.

Dimer-dimer stacking interactions are important for nucleic acid binding by the archaeal chromatin protein Alba

Jelinska, Clare — 2010-04-01T00:00:00Z

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.

Seasonal inflow of warm water onto the southern Weddell Sea continental shelf, Antarctica

Arthun, Marius — 2012-09-01T00:00:00Z

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.

Fitting complex ecological point process models with integrated nested Laplace approximation

Illian, Janine Baerbel — 2013-01-01T00:00:00Z

Abstract: Summary 1. We highlight an emerging statistical method, integrated nested Laplace approximation (INLA), which is ideally suited for fitting complex models to many of the rich spatial data sets that ecologists wish to analyse. 2. INLA is an approximation method that nevertheless provides very exact estimates. In this article, we describe the INLA methodology highlighting where it offers opportunities for drawing inference from (spatial) ecological data that would previously have been too complex to make practical model fitting feasible. 3. We use INLA to fit a complex joint model to the spatial pattern formed by a plant species, Thymus carnosus, as well as to the health status of each individual. 4. The key ecological result revealed by our spatial analysis of these data, relates to the distance-to-water covariate. We find that T. carnosus plants are generally healthier when they are further away from the water. 5. We suggest that this may be the result of a combination of (1) plants having alternative rooting strategies depending on how close to water they grow and (2) the rooting strategy determining how well the plants were able to tolerate an unusually dry summer. 6. We anticipate INLA becoming widely used within spatial ecological analysis over the next decade and suggest that both ecologists and statisticians will benefit greatly from working collaboratively to further develop and apply these emerging statistical methods.

Vocal copying of individually distinctive signature whistles in bottlenose dolphins

King, Stephanie Laura — 2013-04-22T00:00:00Z

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.

A class of 5-nitro-2-furancarboxylamides with potent trypanocidal activity against Trypanosoma brucei in vitro

Zhou, Linna — 2013-02-14T00:00:00Z

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.

Fast silencing reveals a lost role for reciprocal inhibition in locomotion

Moult, Peter Robert — 2013-01-09T00:00:00Z

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.

The role of endosymbionts in the evolution of haploid-male genetic systems in scale insects (Coccoidea)

Ross, Laura — 2012-05-01T00:00:00Z

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.

Functional analysis of Leishmania cyclopropane fatty acid synthetase

Oyola, Samuel O. — 2012-12-10T00:00:00Z

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.

The AEROPATH project targeting Pseudomonas aeruginosa : crystallographic studies for assessment of potential targets in early-stage drug discovery

Moynie, Lucile — 2013-01-01T00:00:00Z

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.

A small-molecule inhibitor of T. gondii motility induces the posttranslational modification of myosin light chain-1 and inhibits myosin motor activity

Heaslip, Aoife T. — 2010-01-15T00:00:00Z

Abstract: Toxoplasma gondii is an obligate intracellular parasite that enters cells by a process of active penetration. Host cell penetration and parasite motility are driven by a myosin motor complex consisting of four known proteins: TgMyoA, an unconventional Class XIV myosin; TgMLC1, a myosin light chain; and two membrane-associated proteins, TgGAP45 and TgGAP50. Little is known about how the activity of the myosin motor complex is regulated. Here, we show that treatment of parasites with a recently identified small-molecule inhibitor of invasion and motility results in a rapid and irreversible change in the electrophoretic mobility of TgMLC1. While the precise nature of the TgMLC1 modification has not yet been established, it was mapped to the peptide Val46-Arg59. To determine if the TgMLC1 modification is responsible for the motility defect observed in parasites after compound treatment, the activity of myosin motor complexes from control and compound-treated parasites was compared in an in vitro motility assay. TgMyoA motor complexes containing the modified TgMLC1 showed significantly decreased motor activity compared to control complexes. This change in motor activity likely accounts for the motility defects seen in the parasites after compound treatment and provides the first evidence, in any species, that the mechanical activity of Class XIV myosins can be modulated by posttranslational modifications to their associated light chains.

A family of spatial biodiversity measures based on graphs

Rajala, T — 2012-12-01T00:00:00Z

Abstract: While much research in ecology has focused on spatially explicit modelling as well as on measures of biodiversity, the concept of spatial (or local) biodiversity has been discussed very little. This paper generalises existing measures of spatial biodiversity and introduces a family of spatial biodiversity measures by flexibly defining the notion of the individuals’ neighbourhood within the framework of graphs associated to a spatial point pattern. We consider two non-independent aspects of spatial biodiversity, scattering, i.e. the spatial arrangement of the individuals in the study area and exposure, the local diversity in an individual’s neighbourhood. A simulation study reveals that measures based on the most commonly used neigh-bourhood defined by the geometric graph do not distinguish well between scattering and exposure. This problem is much less pronounced when other graphs are used. In an analysis of the spatial diversity in a rainforest, the results based on the geometric graph have been shown to spuriously indicate a decrease in spatial biodiversity when no such trend was detected by the other types of neighbourhoods. We also show that the choice neighbourhood markedly impacts on the classification of species according to how strongly and in what way different species spatially structure species diversity. Clearly, in an analysis of spatial or local diversity an appropriate choice of local neighbourhood is crucial in particular in terms of the biological interpretation of the results. Due to its general definition, the approach discussed here offers the necessary flexibility that allows suitable and varying neighbourhood structures to be chosen.

Public information use in ninespine sticklebacks (Pungitius pungitius) : isolating the mechanisms using computer-animated stimuli

Chouinard-Thuly, Laura — 2012-01-01T00:00:00Z

Abstract: Many studies demonstrated the use, and strategies of use, of public information -or the ability of an observer to assess a resource’s quality by watching inadvertent behavioural cues- in the ninespine stickleback (Pungitius pungitius) presented with a foraging patch assessment problem. Many aspects of behaviour were seen to vary with an increased feeding rate and identifying the one responsible for transmission of information is difficult with live demonstrators. This project created and utilized computer-animated ninespine sticklebacks to isolate behaviours and test which ones are used by observers to gain information. We predicted and found that out of six different behaviours associated with an increase in feeding rate, strike rate is the one used to assess foraging patches’ quality. Observer ninespine sticklebacks preferred to associate with sides that were formerly associated with an animated shoal of conspecifics different only in the amount of strikes per demonstration period, in a ratio of six versus two.

Multispecies functional response of the minke whale Balaenoptera acutorostrata based on small-scale foraging studies

Smout, Sophie Caroline — 2007-07-01T00:00:00Z

Abstract: Atlantic minke whales are important predators in the Barents Sea ecosystem; capelin Mallotus villosus, krill Thysanoessa sp. and Meganyctephanes norvegica and herring Clupea harengus are their major prey. Their consumption of commercial species may present an economic problem for the local fishery. In order to estimate this consumption and understand the potential consequences for prey dynamics, it is essential to determine the multispecies functional response of the whales. The parameterisation of a functional response requires measurements of consumption rates and prey availability. In this localised study, undigested stomach contents were used to assess the amount of each prey that had been consumed immediately prior to capture. To determine the availability of prey to the whales, standard acoustic surveys were run in the same area within 2 d of the capture of the whales. The spatial distribution of prey was modelled using generalised additive models (GAMs). In order to generate a measure of prey availability and the uncertainty in this value, a simple model was assumed for whale movement, and prey abundance was sampled over space according to a Gaussian kernel. A multispecies functional response (MSFR) model was then fitted to the consumption and prey availability data using Bayesian methods. Simple simulations, based on the fitted MSFR, indicate that minke whales may deplete local capelin aggregations at small spatial scales. This is the first time that a multispecies functional response has been fitted for a cetacean predator, and the methods outlined here may prove useful for modelling marine mammal-fish interactions in other systems.

Estimating demographic parameters for capture-recapture data in the presence of multiple mark types

Smout, Sophie Caroline — 2011-06-01T00:00:00Z

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.

Evolution of ancient functions in the vertebrate insulin-like growth factor system uncovered by study of duplicated salmonid fish genomes

MacQueen, Daniel John — 2013-01-01T00:00:00Z

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.

The influence of a fluid-porous interface on solar pond stability

Hill, A. A — 2013-02-01T00:00:00Z

Abstract: The linear instability of the gradient zone of a solar pond containing a fluidporous interface is investigated. It is found that the gradient zone can retain the same stability for lower values of the solute Rayleigh number with the introduction of a porous material compared with a purely fluid layer, whilst maintaining the same lower convective zone temperature. Interestingly, it is also shown that for certain parameter values the penetration of a porous medium into the gradient zone can cause the temperature of the lower convective zone to rise. However, for certain parameter ranges, when the fluid-porous interface is towards the top of the gradient zone, the solar pond can become highly unstable.

Development temperature has persistent effects on muscle growth responses in gilthead sea bream

Garcia de la Serrana Castillo, Daniel — 2012-12-17T00:00:00Z

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 (<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.

Prins fluorination cyclisations : Preparation of 4-fluoro-pyran and -piperidine heterocycles

Launay, Guillaume G. — 2010-04-26T00:00:00Z

Abstract: The Prins reaction was investigated using BF3 center dot OEt2 as a Lewis acid. It has been recently demonstrated, that if BF3 center dot OEt2 is used in stoichiometric amounts then these reactions generate fluorinated products where the BF3 center dot OEt2 contributes fluoride ion to quench the intermediate carbocations. In this study oxa- and aza-Prins reactions for the synthesis of 4-fluoro-pyrans and -piperidines were investigated. The products were obtained in good yields, but only with moderate diastereoselectivity. These Prins fluorination reactions can be accelerated under microwave conditions. The study extends the Prins fluorination methodology for the generation of the C-F bond in heterocycles.

Living history with Open Virtual Worlds : Reconstructing St Andrews Cathedral as a stage for historic narrative

Kennedy, Sarah — 2012-12-01T00:00:00Z

Abstract: St Andrews Cathedral is located on the East Coast of Scotland, construction started in 1160 and spanned Romanesque and Gothic architectural styles. It was consecrated in 1318, four years after the battle of Bannockburn in the presence of King Robert the Bruce. For several hundred years, the Cathedral was one of the most important religious buildings in Europe and the centre of religious life in Scotland. During the Scottish Reformation, John Knox lead reformers in divesting the Cathedral of much of its finery. Thereafter it fell into disuse and decline. Today the impressive remains only hint at the former glory of this important building. Cultural Heritage encompasses physical aspects such as architecture and artifacts along with less tangible culture such as music, songs and stories. Open virtual worlds offer an extensible collaborative environment for developing historic scenes against the background of which material and ephemeral aspects of cultural heritage associated with a site may be explored through engagement with historic narratives. They offer the potential to reconstruct within a 3D computer environment both the physical structures of the past and important aspects of the light, music and life that once filled those structures. Virtual reconstructions enable scenarios to be created where individual pieces of art can be located and appreciated within the audio, visual and spacial contexts for which they were originally created. Bringing together architecture, sculpture, illumination, stained-glass, music, procession and lighting into a scene which can be explored from multiple spatial perspectives enables holistic experience and appreciation. Historic reconstructions may be created upon virtual stages allowing new and engaging Cultural Heritage perspectives to be accessible to diverse audiences. Through the example of St Andrews Cathedral reconstruction this paper presents an example of Open Virtual Worlds as a technology for supporting the creation and use of virtual reconstructions as a platform that promotes understanding of and engagement with Cultural Heritage. The use contexts discussed range from research based exploration of 3D spaces, to primary schools students using the reconstructions as a backdrop for tag. The digital literacies of the audience and goals of the use case impact on the appropriateness of the user interface. A range of interfaces are explored including games controllers, touch screens, tablets that provide location aware views into the model and hands free gesture control systems.

Phasing of muscle gene expression with fasting-induced recovery growth in Atlantic salmon

Bower, Neil I. — 2009-08-24T00:00:00Z

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.

Ontogeny of neural circuits underlying spatial memory in the rat

Ainge, James A. — 2012-03-01T00:00:00Z

Abstract: Spatial memory is a well-characterized psychological function in both humans and rodents. The combined computations of a network of systems including place cells in the hippocampus, grid cells in the medial entorhinal cortex and head direction cells found in numerous structures in the brain have been suggested to form the neural instantiation of the cognitive map as first described by Tolman in 1948. However, while our understanding of the neural mechanisms underlying spatial representations in adults is relatively sophisticated, we know substantially less about how this network develops in young animals. In this article we briefly review studies examining the developmental time scale that these systems follow. Electrophysiological recordings from very young rats show that directional information is at adult levels at the outset of navigational experience. The systems supporting allocentric memory, however, take longer to mature. This is consistent with behavioral studies of young rats which show that spatial memory based on head direction develops very early but that allocentric spatial memory takes longer to mature. We go on to report new data demonstrating that memory for associations between objects and their spatial locations is slower to develop than memory for objects alone. This is again consistent with previous reports suggesting that adult like spatial representations have a protracted development in rats and also suggests that the systems involved in processing non-spatial stimuli come online earlier.

Aberrant NF-kappaB expression in autism spectrum condition : a mechanism for neuroinflammation

Young, Adam — 2011-05-13T00:00:00Z

Abstract: Autism spectrum condition (ASC) is recognized as having an inflammatory component. Post-mortem brain samples from patients with ASC display neuroglial activation and inflammatory markers in cerebrospinal fluid, although little is known about the underlying molecular mechanisms. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein found in almost all cell types and mediates regulation of immune response by inducing the expression of inflammatory cytokines and chemokines, establishing a feedback mechanism that can produce chronic or excessive inflammation. This article describes immunodetection and immunofluorescence measurements of NF-κB in human post-mortem samples of orbitofrontal cortex tissue donated to two independent centers: London Brain Bank, Kings College London, UK (ASC: n = 3, controls: n = 4) and Autism Tissue Program, Harvard Brain Bank, USA (ASC: n = 6, controls: n = 5). The hypothesis was that concentrations of NF-κB would be elevated, especially in activated microglia in ASC, and pH would be concomitantly reduced (i.e., acidification). Neurons, astrocytes, and microglia all demonstrated increased extranuclear and nuclear translocated NF-κB p65 expression in brain tissue from ASC donors relative to samples from matched controls. These between-groups differences were increased in astrocytes and microglia relative to neurons, but particularly pronounced for highly mature microglia. Measurement of pH in homogenized samples demonstrated a 0.98-unit difference in means and a strong (F = 98.3; p = 0.00018) linear relationship to the expression of nuclear translocated NF-κB in mature microglia. Acridine orange staining localized pH reductions to lysosomal compartments. In summary, NF-κB is aberrantly expressed in orbitofrontal cortex in patients with ASC, as part of a putative molecular cascade leading to inflammation, especially of resident immune cells in brain regions associated with the behavioral and clinical symptoms of ASC.

Two independent mechanisms for motion-in-depth perception : evidence from individual differences

Nefs, Harold — 2010-10-12T00:00:00Z

Abstract: Our forward-facing eyes allow us the advantage of binocular visual information: using the tiny differences between right and left eye views to learn about depth and location in three dimensions. Our visual systems also contain specialized mechanisms to detect motion-in-depth from binocular vision, but the nature of these mechanisms remains controversial. Binocular motion-in-depth perception could theoretically be based on first detecting binocular disparity and then monitoring how it changes over time. The alternative is to monitor the motion in the right and left eye separately and then compare these motion signals. Here we used an individual differences approach to test whether the two sources of information are processed via dissociated mechanisms, and to measure the relative importance of those mechanisms. Our results suggest the existence of two distinct mechanisms, each contributing to the perception of motion-in-depth in most observers. Additionally, for the first time, we demonstrate the relative prevalence of the two mechanisms within a normal population. In general, visual systems appear to rely mostly on the mechanism sensitive to changing binocular disparity, but perception of motion-in-depth is augmented by the presence of a less sensitive mechanism that uses interocular velocity differences. Occasionally, we find observers with the opposite pattern of sensitivity. More generally this work showcases the power of the individual differences approach in studying the functional organization of cognitive systems.

Mechanisms of gene duplication and translocation and progress towards understanding their relative contributions to animal genome evolution

Mendivil Ramos, Olivia — 2012-01-01T00:00:00Z

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.

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

Boehme, Lars — 2012-12-26T00:00:00Z

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 >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.

Variation in female grey seal (Halichoerus grypus) reproductive performance correlates to proactive-reactive behavioural types

Twiss, Sean D — 2012-11-16T00:00:00Z

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.

What is biodiversity?

Magurran, Anne E. — 2010-12-15T00:00:00Z

The geometric mean of relative abundance indices : a biodiversity measure with a difference

Buckland, Stephen Terrence — 2011-09-02T00:00:00Z

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

Local and regional rarity in a diverse tropical fish assemblage

Hercos, A — 2013-01-01T00:00:00Z

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.

Using INLA to fit a complex point process model with temporally varying effects – a case study

Illian, Janine Baerbel — 2012-07-01T00:00:00Z

Abstract: Integrated nested Laplace approximation (INLA) provides a fast and yet quite exact approach to fitting complex latent Gaussian models which comprise many statistical models in a Bayesian context, including log Gaussian Cox processes. This paper discusses how a joint log Gaussian Cox process model may be fitted to independent replicated point patterns. We illustrate the approach by fitting a model to data on the locations of muskoxen (Ovibos moschatus) herds in Zackenberg valley, Northeast Greenland and by detailing how this model is specified within the R-interface R-INLA. The paper strongly focuses on practical problems involved in the modelling process, including issues of spatial scale, edge effects and prior choices, and finishes with a discussion on models with varying boundary conditions.

A Bayesian approach to fitting Gibbs processes with temporal random effects

King, Ruth — 2012-12-01T00:00:00Z

Abstract: We consider spatial point pattern data that have been observed repeatedly over a period of time in an inhomogeneous environment. Each spatial point pattern can be regarded as a “snapshot” of the underlying point process at a series of times. Thus, the number of points and corresponding locations of points differ for each snapshot. Each snapshot can be analyzed independently, but in many cases there may be little information in the data relating to model parameters, particularly parameters relating to the interaction between points. Thus, we develop an integrated approach, simultaneously analyzing all snapshots within a single robust and consistent analysis. We assume that sufficient time has passed between observation dates so that the spatial point patterns can be regarded as independent replicates, given spatial covariates. We develop a joint mixed effects Gibbs point process model for the replicates of spatial point patterns by considering environmental covariates in the analysis as fixed effects, to model the heterogeneous environment, with a random effects (or hierarchical) component to account for the different observation days for the intensity function. We demonstrate how the model can be fitted within a Bayesian framework using an auxiliary variable approach to deal with the issue of the random effects component. We apply the methods to a data set of musk oxen herds and demonstrate the increased precision of the parameter estimates when considering all available data within a single integrated analysis.

Electron microscopic studies of growth of nanoscale catalysts and soot particles in a candle flame

Zhou, Wuzong — 2012-09-01T00:00:00Z

Abstract: Scanning electron microscopy and high-resolution transmission electron microscopy have been used to investigate non-classic crystal growth of catalytic nanoparticles, such as zeolites, perovskites, metal and alloy particles. Growth mechanisms of some crystals with novel morphologies, for example, BiOBr flower-like particles and ZnO twin-crystals, have also been studied. A development of sampling method for soot particles inside a candle flame allows us to reveal all four well-known carbon forms, amorphous, graphitic, fullerenic and nanodiamond particles. This article demonstrates that electron microscopy is a powerful tool to study the microstructures of small particles, giving us more freedom to develop new materials.

A model for 3-methyladenine recognition by 3-methyladenine DNA glycosylase I (TAG) from Staphylococcus aureus

Zhu, Xiaofeng — 2012-06-01T00:00:00Z

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.

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.

Kvadsheim, Petter H — 2012-05-10T00:00:00Z

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.

Conventional and unconventional antimicrobials from fish, marine invertebrates and micro-algae

Smith, Valerie Jane — 2010-04-14T00:00:00Z

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.

Crystallization, dehydration and experimental phasing of WbdD, a bifunctional kinase and methyltransferase from Escherichia coli O9a

Hagelueken, Gregor — 2012-10-01T00:00:00Z

Abstract: WbdD is a bifunctional kinase/methyltransferase that is responsible for regulation of lipopolysaccharide O antigen polysaccharide chain length in Escherichia coli serotype O9a. Solving the crystal structure of this protein proved to be a challenge because the available crystals belonging to space group I23 only diffracted to low resolution (>95% of the crystals diffracted to resolution lower than 4 angstrom and most only to 8 angstrom) and were non-isomorphous, with changes in unit-cell dimensions of greater than 10%. Data from a serendipitously found single native crystal that diffracted to 3.0 angstrom resolution were non-isomorphous with a lower (3.5 angstrom) resolution selenomethionine data set. Here, a strategy for improving poor (3.5 angstrom resolution) initial phases by density modification and cross-crystal averaging with an additional 4.2 angstrom resolution data set to build a crude model of WbdD is desribed. Using this crude model as a mask to cut out the 3.5 angstrom resolution electron density yielded a successful molecular-replacement solution of the 3.0 angstrom resolution data set. The resulting map was used to build a complete model of WbdD. The hydration status of individual crystals appears to underpin the variable diffraction quality of WbdD crystals. After the initial structure had been solved, methods to control the hydration status of WbdD were developed and it was thus possible to routinely obtain high-resolution diffraction (to better than 2.5 angstrom resolution). This novel and facile crystal-dehydration protocol may be useful for similar challenging situations.

PRC1 and PRC2 are not required for targeting of H2A.Z to developmental genes in embryonic stem cells

Illingworth, Robert S. — 2012-04-09T00:00:00Z

Abstract: The essential histone variant H2A.Z localises to both active and silent chromatin sites. In embryonic stem cells (ESCs), H2A.Z is also reported to co-localise with polycomb repressive complex 2 (PRC2) at developmentally silenced genes. The mechanism of H2A.Z targeting is not clear, but a role for the PRC2 component Suz12 has been suggested. Given this association, we wished to determine if polycomb functionally directs H2A.Z incorporation in ESCs. We demonstrate that the PRC1 component Ring1B interacts with multiple complexes in ESCs. Moreover, we show that although the genomic distribution of H2A.Z co-localises with PRC2, Ring1B and with the presence of CpG islands, H2A.Z still blankets polycomb target loci in the absence of Suz12, Eed (PRC2) or Ring1B (PRC1). Therefore we conclude that H2A.Z accumulates at developmentally silenced genes in ESCs in a polycomb independent manner.

Discovery and validation of SIRT2 inhibitors based on tenovin-6 : use of a H-1-NMR method to assess deacetylase activity

Pirrie, Lisa — 2012-10-01T00:00:00Z

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.

Structure of WbdD : a bifunctional kinase and methyltransferase that regulates the chain length of the O antigen in Escherichia coli O9a

Hagelueken, Gregor — 2012-11-01T00:00:00Z

Abstract: The Escherichia coli serotype O9a O-antigen polysaccharide (O-PS) is a model for glycan biosynthesis and export by the ATP-binding cassette transporter-dependent pathway. The polymannose O9a O-PS is synthesized as a polyprenol-linked glycan by mannosyltransferase enzymes located at the cytoplasmic membrane. The chain length of the O9a O-PS is tightly regulated by the WbdD enzyme. WbdD first phosphorylates the terminal non-reducing mannose of the O-PS and then methylates the phosphate, stopping polymerization. The 2.2?angstrom resolution structure of WbdD reveals a bacterial methyltransferase domain joined to a eukaryotic kinase domain. The kinase domain is again fused to an extended C-terminal coiled-coil domain reminiscent of eukaryotic DMPK (Myotonic Dystrophy Protein Kinase) family kinases such as Rho-associated protein kinase (ROCK). WbdD phosphorylates 2-a-d-mannosyl-d-mannose (2a-MB), a short mimic of the O9a polymer. Mutagenesis identifies those residues important in catalysis and substrate recognition and the in vivo phenotypes of these mutants are used to dissect the termination reaction. We have determined the structures of co-complexes of WbdD with two known eukaryotic protein kinase inhibitors. Although these are potent inhibitors in vitro, they do not show any in vivo activity. The structures reveal new insight into O-PS chain-length regulation in this important model system.

Routine use of microbial whole genome sequencing in diagnostic and public health microbiology

Koeser, Claudio U. — 2012-08-02T00:00:00Z

Abstract: Whole genome sequencing (WGS) promises to be transformative for the practice of clinical microbiology, and the rapidly falling cost and turnaround time mean that this will become a viable technology in diagnostic and reference laboratories in the near future. The objective of this article is to consider at a very practical level where, in the context of a modern diagnostic microbiology laboratory, WGS might be cost-effective compared to current alternatives. We propose that molecular epidemiology performed for surveillance and outbreak investigation and genotypic antimicrobial susceptibility testing for microbes that are difficult to grow represent the most immediate areas for application of WGS, and discuss the technical and infrastructure requirements for this to be implemented.

Protein-induced changes in DNA structure and dynamics observed with noncovalent site-directed spin-labeling and PELDOR

Reginsson, Gunnar Widtfeldt — 2013-01-01T00:00:00Z

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.

Quantifying temporal change in biodiversity : challenges and opportunities

Dornelas, Maria — 2013-01-01T00:00:00Z

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.

Reasons for the invasive success of a guppy (Poecilia reticulata) population in Trinidad

Sievers, Caya — 2012-05-31T00:00:00Z

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.

Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification

Ballester, Pedro — 2012-12-07T00:00:00Z

Abstract: One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated Ki ranging from 4 to 250 μM (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification.

Role of Bunyamwera orthobunyavirus NSs protein in infection of mosquito cells

Szemiel, Agnieszka M. — 2012-09-01T00:00:00Z

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.

Photoacclimation, growth and distribution of massive coral species in clear and turbid waters

Hennige, S.J. — 2008-10-13T00:00:00Z

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.

Evolution of the multifaceted eukaryotic akirin gene family

Macqueen, Daniel J. — 2009-02-06T00:00:00Z

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.

Evolution of a complex locus : exon gain, loss and divergence at the Gr39a locus in Drosophila

Gardiner, Anastasia — 2008-01-30T00:00:00Z

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.

An update on MyoD evolution in teleosts and a proposed consensus nomenclature to accommodate the tetraploidization of different vertebrate genomes

Macqueen, Daniel J. — 2008-02-06T00:00:00Z

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).

Growing the use of Virtual Worlds in education : an OpenSim perspective

Allison, Colin — 2012-11-25T00:00:00Z

Abstract: The growth in the range of disciplines that Virtual Worlds support for educational purposes is evidenced by recent applications in the fields of cultural heritage, humanitarian aid, space exploration, virtual laboratories in the physical sciences, archaeology, computer science and coastal geography. This growth is due in part to the flexibility of OpenSim, the open source virtual world platform which by adopting Second Life protocols and norms has created a de facto standard for open virtual worlds that is supported by a growing number of third party open source viewers. Yet while this diversity of use-cases is impressive and Virtual Worlds for open learning are highly popular with lecturers and learners alike immersive education remains an essentially niche activity. This paper identifies functional challenges in terms of Management, Network Infrastructure, the Immersive 3D Web and Programmability that must be addressed to enable the wider adoption of Open Virtual Worlds as a routine learning technology platform. We refer to specific use-cases based on OpenSim and abstract generic requirements which should be met to enable the growth in use of Open Virtual Worlds as a mainstream educational facility. A case study of a deployment to support a formal education curriculum and associated informal learning is used to illustrate key points.

African perceptions of female attractiveness

Coetzee, Vinet — 2012-10-29T00:00:00Z

Abstract: Little is known about mate choice preferences outside Western, educated, industrialised, rich and democratic societies, even though these Western populations may be particularly unrepresentative of human populations. To our knowledge, this is the first study to test which facial cues contribute to African perceptions of African female attractiveness and also the first study to test the combined role of facial adiposity, skin colour (lightness, yellowness and redness), skin homogeneity and youthfulness in the facial attractiveness preferences of any population. Results show that youthfulness, skin colour, skin homogeneity and facial adiposity significantly and independently predict attractiveness in female African faces. Younger, thinner women with a lighter, yellower skin colour and a more homogenous skin tone are considered more attractive. These findings provide a more global perspective on human mate choice and point to a universal role for these four facial cues in female facial attractiveness.

The CRISPR associated protein Cas4 Is a 5' to 3' DNA exonuclease with an iron-sulfur cluster

Zhang, Jing — 2012-10-08T00:00:00Z

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.

The functional response of a generalist predator

Smout, Sophie Caroline — 2010-05-27T00:00:00Z

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.

Oxygenated-blood colour change thresholds for perceived facial redness, health, and attractiveness

Re, Daniel E. — 2011-03-23T00:00:00Z

Abstract: Blood oxygenation level is associated with cardiovascular fitness, and raising oxygenated blood colouration in human faces increases perceived health. The current study used a two-alternative forced choice (2AFC) psychophysics design to quantify the oxygenated blood colour (redness) change threshold required to affect perception of facial colour, health and attractiveness. Detection thresholds for colour judgments were lower than those for health and attractiveness, which did not differ. The results suggest redness preferences do not reflect a sensory bias, rather preferences may be based on accurate indications of health status. Furthermore, results suggest perceived health and attractiveness may be perceptually equivalent when they are assessed based on facial redness. Appearance-based motivation for lifestyle change can be effective; thus future studies could assess the degree to which cardiovascular fitness increases face redness and could quantify changes in aerobic exercise needed to increase facial attractiveness.

Repeated elicitation of the acoustic startle reflex leads to sensitisation in subsequent avoidance behaviour and induces fear conditioning

Gotz, Thomas — 2011-01-01T00:00:00Z

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.

Redness enhances perceived aggression, dominance and attractiveness in men's faces

Stephen, Ian D. — 2012-01-01T00:00:00Z

Abstract: In a range of non-human primate, bird and fish species, the intensity of red coloration in males is associated with social dominance, testosterone levels and mate selection. In humans too, skin redness is associated with health, but it is not known whether - as in non-human species - it is also associated with dominance and links to attractiveness have not been thoroughly investigated. Here we allow female participants to manipulate the CIELab a* value (red-green axis) of skin to maximize the perceived aggression, dominance and attractiveness of photographs of men's faces, and make two findings. First, participants increased a* (increasing redness) to enhance each attribute, suggesting that facial redness is perceived as conveying similar information about a male's qualities in humans as it does in non-human species. Second, there were significant differences between trial types: the highest levels of red were associated with aggression, an intermediate level with dominance, and the least with attractiveness. These differences may reflect a trade-off between the benefits of selecting a healthy, dominant partner and the negative consequences of aggression.

Participation in mass gatherings can benefit well-being : longitudinal and control data from a North Indian Hindu pilgrimage event

Tewari, Shruti — 2012-10-17T00:00:00Z

Abstract: How does participation in a long-duration mass gathering (such as a pilgrimage event) impact well-being? There are good reasons to believe such collective events pose risks to health. There are risks associated with communicable diseases. Moreover, the physical conditions at such events (noise, crowding, harsh conditions) are often detrimental to well-being. Yet, at the same time, social psychological research suggests participation in group-related activities can impact well-being positively, and we therefore investigated if participating in a long-duration mass gathering can actually bring such benefits. In our research we studied one of the world's largest collective events – a demanding month-long Hindu religious festival in North India. Participants (comprising 416 pilgrims who attended the gathering for the whole month of its duration, and 127 controls who did not) completed measures of self-assessed well-being and symptoms of ill-health at two time points. The first was a month before the gathering commenced, the second was a month after it finished. We found that those participating in this collective event reported a longitudinal increase in well-being relative to those who did not participate. Our data therefore imply we should reconceptualise how mass gatherings impact individuals. Although such gatherings can entail significant health risks, the benefits for well-being also need recognition. Indeed, an exclusive focus on risk is misleading and limits our understanding of why such events may be so attractive. More importantly, as our research is longitudinal and includes a control group, our work adds robust evidence to the social psychological literature concerning the relationship between participation in social group activities and well-being.

The preferred conformation of erythro- and threo-1,2-difluorocyclododecanes

Wang, Yi — 2012-08-10T00:00:00Z

Abstract: Cyclododecane adopts a square-like structure with corner and edge CH2 groups. In this study erythro- and threo-1,2-difluorocyclododecanes were prepared to explore whether the two vicinal C-F bonds, with different relative configurations, preferably locate at corner/edge or edge/edge locations. Conformational analysis comparing the diastereoisomers was explored by using a combination of F-19{H-1} NMR spectroscopy, computational studies and, in the case of the threo isomer, X-ray structural analysis. In the lowest energy conformers for both diastereoisomers the vicinal C-F bonds are located corner/edge, rather than edge/edge. These structures avoid placing a C-F bond endo into the ring, and appear to benefit from C-CHF-C angle widening, which relaxes 1,4-H, H transannular interactions.

A non-technical overview of spatially explicit capture-recapture models

Borchers, David — 2012-02-01T00:00:00Z

Abstract: Most capture-recapture studies are inherently spatial in nature, with capture probabilities depending on the location of traps relative to animals. The spatial component of the studies has until recently, however, not been incorporated in statistical capture-recapture models. This paper reviews capture-recapture models that do include an explicit spatial component. This is done in a non-technical way, omitting much of the algebraic detail and focussing on the model formulation rather than on the estimation methods (which include inverse prediction, maximum likelihood and Bayesian methods). One can view spatially explicit capture-recapture (SECR) models as an endpoint of a series of spatial sampling models, starting with circular plot survey models and moving through conventional distance sampling models, with and without measurement errors, through mark-recapture distance sampling (MRDS) models. This paper attempts a synthesis of these models in what I hope is a style accessible to non-specialists, placing SECR models in the context of other spatial sampling models.

Tunicates push the limits of animal evo-devo

Ferrier, David Ellard Keith — 2011-01-20T00:00:00Z

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.

Sexual and postmating reproductive isolation between allopatric Drosophila montana populations suggest speciation potential

Jennings, Jackson H. — 2011-03-14T00:00:00Z

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.

Fitness consequences of female multiple mating : A direct test of indirect benefits

Barbosa, Miguel — 2012-09-15T00:00:00Z

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.

Why do adaptive immune responses cross-react?

Fairlie-Clarke, KJ — 2009-02-01T00:00:00Z

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.

Towards a guideline for person-centered research in clinical communication : lessons learned from three countries

van Dulmen, Sandra — 2012-04-01T00:00:00Z

Abstract: The delivery of quality health care is dependent to a large degree on the success of the interaction between health care provider and patient. The ability to research this interaction has improved with the development of recording technology, storage and data coding. In addition, familiarity with recording of doctor-patient communication has increased encouraging researchers to embark on developing this data-rich resource. Factors that are pertinent to the collection of this material are outlined from the experience of researchers from three countries: The Netherlands, Norway and the UK. The conclusion stresses the need to attend closely to the issues listed to increase the likelihood of obtaining a research platform for investigating health care encounters in some depth. The article presents a first step in the production of a practical, person-centered guideline for this important research endeavour.

Attenuation of bunyavirus replication by modification of genomic untranslated regions

Mazel-Sanchez, Beryl — 2012-11-30T00:00:00Z

Abstract: Bunyamwera orthobunyavirus (BUNV) is the prototype for the family Bunyaviridae. BUNV has a tripartite RNA genome of negative polarity composed of the large(L),medium (M)and small(S)segments. Each segment contains an open reading frame (ORF) flanked by untranslated regions (UTRs). The eleven terminal nucleotides are conserved between the three segments while the internal regions are unique. The UTRs play an important role in the virus life cycle by promoting transcription, replication and encapsidation of the viral genome.The work presented in this thesis explores UTRs plasticity and examines ways to engineere attenuated viruses by modifying only their UTRs. Using reverse genetics, mainly two ways of attenuation were explored: rescue of viruses either carrying deletions within their 3’ and/or 5’ UTRs in all three segments, or of viruses carrying one segment bearing heterologous UTRs. Both approaches resulted in virus attenuation in tissue culture, with viruses producing smaller plaques or even no plaques, and growing to lower titres than wild-type BUNV. Through serial passage, viruses were shown to regain some level of fitness while the mutations introduced in the UTRs proved to be stable. Thus, to investigate the mechanism behind fitness recovery, the nucleotide sequence of the entire genome of viruses with deletions in their UTRs was determined. Amino acid changes were observed in the viral polymerase (L protein) of most mutant viruses and the vast majority of the amino acid changes occured in the C-terminal region. The function of this domain is unclear to date, however data obtained using a mini-replicon assay suggest that the C-terminal domain of the L protein might be involved in UTR recognition. Full genome sequencing also allowed the identification of an amino acid mutation within the polymerase that resulted in a temperature sensitive phenotype when introduced in an otherwise wild-type BUNV. Thus, it was shown that mutations introduced within the UTR regions of the genome were stable through serial passage and resulted in attenuation. Such a strategy could be used in combination with mutations of the ORF to design live-attenuated vaccines against serious pathogens within the family Bunyaviridae.

The influence of mid-ocean ridges on euphausiid and pelagic ecology

Letessier, Tom Bech — 2012-06-19T00:00:00Z

Abstract: 1 & 2. Euphausiids comprise a major component of ecosystems in the pelagic realm, the world’s largest habitat, but basin scale drivers of euphausiids diversity and abundance are poorly understood. Mid-Ocean Ridges are the largest topographical feature in the pelagic realm and their benthic and pelagic fauna have only just recently become the focus of research. This thesis present new analyses on the drivers of euphausiids species richness in the Atlantic and the Pacific, giving specific attention to the influence of Mid- Ocean Ridges. New information is given on the biogeography of euphausiids and pelagic food-web trophology of the Mid-Atlantic Ridge, and on the biogeography of pelagic decapods on the South-West Indian Ocean ridge. 3. A Generalized Additive Model framework was used to explore spatial patterns of variability in euphausiid species richness (from recognized areas of occurrence) and in numerical abundance (from the Continuous Plankton Recorder survey) in conjunction with variability in a suite of biological, physical and environmental parameters on, and at either side of, the Mid-Atlantic Ridge. Euphausiid species richness peaked in midlatitudes and was significantly higher on the ridge than in adjacent waters, but the ridge did not influence numerical abundance in the top 10 m significantly. Sea surface temperature (SST) was the most important single factor influencing both euphausiid numerical abundance (-76.7%) and species richness (34.44%). Dissolved silicate concentration, a proxy for diatom abundance, significantly increased species richness (29.46%). Increases in sea surface height variance, a proxy for mixing, increased the numerical abundance of euphausiids. GAM predictions of variability in species richness as a function of SST and depth of the mixed layer were consistent with present theories, which suggest that pelagic niche-availability is related to the thermal structure of the near surface water. 4. Using a Generalized Additive Model in the Pacific, the main drivers of species richness, in order of decreasing importance, were found to be sea surface temperature (explaining 29.53% in species variability), salinity (20.29%), longitude (-15.01%, species richness decreased from West to East), distance to coast (10.99%), and dissolved silicate concentration (9.03%). An additional linear model poorly predicted numerical abundance. The practical differences in drivers of species richness in the Atlantic and Pacific Ocean were compared. Predictions of future species richness changes in the Pacific and Atlantic were made using projected environmental change from the IPCC A1B climate scenario, suggesting an increase in species richness in temperature latitudes (30° to 60° N and S) and little to no change in low latitudes (20° N to 20° S). 5. New baseline information is presented on biogeography, abundance and vertical distribution of euphausiids along the Mid-Atlantic Ridge (40° to 62° N). 18 species were recorded, with Euphausia krohni and Thysanoessa longicaudata being most abundant. Eight species had not been recorded in the area previously. The Subpolar Front is a northern boundary to some southern species, but not a southern boundary to northern ubiquitous species that show submergence. Four major species assemblages were identified and characterised in terms of spatial distribution and species composition. Numerical abundance was highly variable but decreased by orders of magnitude with depth. The Mid-Atlantic Ridge showed only a marginal effect on euphausiid distribution and abundance patterns. 6. Zooplankton and micronektic invertebrate epi- and mesopelagic (0-200 and 200- 800m) vertical distribution (e.g. Euphausiacea, Decapoda, Amphipoda, Thecosomata, Lophogastrida) on either side of the Subpolar Front of the Mid-Atlantic Ridge is described. Dietary relationships are explored, using stable isotope ratios and fatty acid trophic marker (FATM) composition. An increase in trophic level with size was observed. Individuals from southern stations were higher in dinoflagellate Fatty Acid Trophic Markers (FATM) (22:6(n-3)) and individuals from northern stations were higher in Calanus spp and storage FATMs (20:1(n-9) and 22:1(n-9)) reflecting primary production patterns in the two survey sectors. Observations on the geographical and vertical variability in trophodynamics are discussed. 7. New baseline information is presented on the biogeography, abundance, and vertical distribution of mesopelagic (200-1000 m), crustacean micronekton on- and offseamounts of the South-West Indian Ocean Ridge (26° to 42° S). Species richness and numerical abundance were typically higher near seamounts and lower over the abyssal plains, with several species being caught uniquely on seamounts. Observations suggest that the ‘oasis effect’ of seamounts conventionally associated with higher trophic levels is also applicable to pelagic micronektic crustaceans at lower trophic levels. Biophysical coupling of micronekton to seamounts may be an important factor controlling benthopelagic coupling in seamount food-webs. 8. Euphausiid and pelagic diversity is driven primarily by geographical variability in temperature, by longitudinal patterns in upwellings, and by variability in nutrient concentration. Mid-Ocean Ridges modify pelagic ecology, by raising the seafloor and by bringing in proximity true pelagic and bathypelagic predators associated with the seabed. The increase in specialized fauna and biomass associated with ridges and seamounts serves to deplete zooplankton in the near bottom layer (0-200 m) and affect systems in and above the benthic boundary layer (<200 m from the seafloor), and the benthopelagic faunal layer. Mid-Ocean Ridges may serve to structure pelagic faunal distribution, and increase the overall diversity of the world ocean. The influence of ridges in the ocean basin may be comparable to that of hedges in a farmland; whilst delimiting the extent of crops (or zooplankton assemblages), hedges serve as local hotspots of mammal and avian diversity.

Examining the response of top marine predators to ecological change using stable isotope proxies

Hanson, Nora N. — 2012-11-30T00:00:00Z

Abstract: Monitoring the response of upper trophic level animals to ecological change is important to understanding the state and stability of ecosystems. Marine predators integrate information over large geographical scales and are relatively long-lived; furthermore, many of these organisms are restricted to terrestrial or freshwater habitats at certain times during their life history and are accessible to researchers. This thesis investigated the response of marine predators to ecological change at a variety of spatial and temporal scales using stable isotope ratio methods with the aims of developing meaningful proxies, or indices, of variability in marine ecosystems. The first study explored the intrinsic (i.e. ontogenetic) and extrinsic (i.e. environmental) factors important to modulating variation in the stable isotope ratios of C and N in tooth dentin of male Antarctic fur seals (Arctocephalus gazella) in the Southern Ocean. In the second study, long-term records of variation in δ15N δ13C values of Atlantic salmon (Salmo salar) scales and grey seal (Halichoerus grypus) tooth dentin provided evidence for large-scale climate forcing across the eastern North Atlantic. In the following study, a more detailed examination of intra- and inter-individual stable isotope variation in Atlantic salmon within a single year was undertaken in an attempt to better understand recent declines in somatic condition of these fish. The last two studies were concerned with the development of high resolution sampling of fish otoliths using secondary mass spectrometry (SIMS) and the application of this technique to reconstructing the thermal and metabolic histories of individual Atlantic salmon from intra-otolith δ13C and δ18O values. Stable isotope proxies can be used to document shifts in trophic dynamics and animal movement that may be associated with ecological change. Using multiple tissues, elements and species, such studies provide unique monitoring tools at a range of spatial and temporal scales.

Workshop on new developments in cetacean survey methods

Borchers, David Louis — 2011-01-01T00:00:00Z

Abstract: This report contains the slides from a workshop on New Developments in Cetacean Survey Methods held on 27th November 2011 at the 19th Biennial Conference on the Biology of Marine Mammals, Tampa, Florida. Review talks were given on Passive Acoustic Density Estimation (Len Thomas); Dealing with g(0)<1: Perception Bias (Stephen Buckland); Dealing with g(0)<1: Availability Bias (Hans Skaug); Dealing with Measurement Error (David Borchers); and Density Surface Modelling (Jay Barlow). The sessions were followed by a discussion, and this is summarized at the end of the report.

Spontaneous emergence, imitation and spread of alternative foraging techniques among groups of vervet monkeys

van de Waal, Erica — 2012-10-10T00:00:00Z

Abstract: Animal social learning has become a subject of broad interest, but demonstrations of bodily imitation in animals remain rare. Based on Voelkl and Huber's study of imitation by marmosets, we tested four groups of semi-captive vervet monkeys presented with food in modified film canisters (“aethipops’). One individual was trained to take the tops off canisters in each group and demonstrated five openings to them. In three groups these models used their mouth to remove the lid, but in one of the groups the model also spontaneously pulled ropes on a canister to open it. In the last group the model preferred to remove the lid with her hands. Following these spontaneous differentiations of foraging techniques in the models, we observed the techniques used by the other group members to open the canisters. We found that mouth opening was the most common technique overall, but the rope and hands methods were used significantly more in groups they were demonstrated in than in groups where they were not. Our results show bodily matching that is conventionally described as imitation. We discuss the relevance of these findings to discoveries about mirror neurons, and implications of the identity of the model for social transmission.

MtsslWizard : in silico spin-labelling and generation of distance distributions in PyMOL

Hageluken, Gregor — 2012-04-01T00:00:00Z

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.

Impact of environmental change on primary production in model marine coastal ecosystems

Hicks, Natalie — 2011-01-01T00:00:00Z

Abstract: Coastal ecosystems, including estuaries, provide a range of services to humans, mediated by the species within these ecosystems. Microphytobenthos (MPB) play a vital role in many key processes within estuarine ecosystems, and provide a food source for higher trophic levels. Anthropogenic activity is already causing changes to ecosystems, through pollution, overexploitation and, more recently, climate change. Increasing temperature and carbon dioxide levels, and altered biodiversity, are likely to affect species, and their interactions, within these ecosystems. Much ecological research has focused on the effects of a single stressor on specific species or ecosystems, with relatively little work examining the effects of multiple stressors. The research in this thesis investigates the effects of altered environmental variables (light, tidal regime, temperature and carbon dioxide) and different macrofaunal diversity on primary production (MPB biomass) through a series of manipulative lab-based mesocosm experiments. This work also examines the temporal variability of environmental stressors on species across two trophic levels. Results demonstrate how multiple environmental stressors interact in a complex and non-additive way to determine an ecosystem response (MPB biomass, nutrient concentration), and the effects of altered biodiversity were underpinned by strong species effects. Temporal variation of stressors had a strong effect on ecosystem response. In marine coastal ecosystems, environmental changes through ocean acidification will have economic and social repercussions, directly impacting the human services and livelihoods that these systems provide. As such, future research should be focused on identifying and mitigating the inevitable multiple effects that future global change may have on coastal ecosystems.

Identification of learning mechanisms in a wild meerkat population

Hoppitt, William John Edward — 2012-08-08T00:00:00Z

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.

Vessel noise affects beaked whale behavior : Results of a dedicated acoustic response study

Pirotta, Enrico — 2012-08-03T00:00:00Z

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.

Learning to use illumination gradients as an unambiguous cue to three dimensional shape

Harding, Glen — 2012-04-30T00:00:00Z

Abstract: The luminance and colour gradients across an image are the result of complex interactions between object shape, material and illumination. Using such variations to infer object shape or surface colour is therefore a difficult problem for the visual system. We know that changes to the shape of an object can affect its perceived colour, and that shading gradients confer a sense of shape. Here we investigate if the visual system is able to effectively utilise these gradients as a cue to shape perception, even when additional cues are not available. We tested shape perception of a folded card object that contained illumination gradients in the form of shading and more subtle effects such as inter-reflections. Our results suggest that observers are able to use the gradients to make consistent shape judgements. In order to do this, observers must be given the opportunity to learn suitable assumptions about the lighting and scene. Using a variety of different training conditions, we demonstrate that learning can occur quickly and requires only coarse information. We also establish that learning does not deliver a trivial mapping between gradient and shape; rather learning leads to the acquisition of assumptions about lighting and scene parameters that subsequently allow for gradients to be used as a shape cue. The perceived shape is shown to be consistent for convex and concave versions of the object that exhibit very different shading, and also similar to that delivered by outline, a largely unrelated cue to shape. Overall our results indicate that, although gradients are less reliable than some other cues, the relationship between gradients and shape can be quickly assessed and the gradients therefore used effectively as a visual shape cue.

Spatial variation in foraging behaviour of a marine top predator (Phoca vitulina) determined by a large-scale satellite tagging program

Sharples, Ruth Jemma — 2012-05-21T00:00:00Z

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.

Global coverage of cetacean line-transect surveys : status quo, data gaps and future challenges

Kaschner, Kristin — 2012-09-12T00:00:00Z

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 >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, <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, <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.

Defining and evaluating the impact of cross-disciplinary conservation research

Evely, Anna C. — 2010-12-01T00:00:00Z

Abstract: Cross-disciplinary research is advocated as a way of improving understanding of the complexity of environmental problems; cross-disciplinary projects, centres and academic institutes have increased. However, there is confusion over the nature of cross-disciplinary research. Through review of papers defining themselves as cross-disciplinary that aim to address conservation problems, and by standardizing the definition of cross-disciplinary research, it is possible to evaluate the potential research impact on peers and practitioners. When papers were reclassified by authors, those reclassified as transdisciplinary were perceived to have a greater impact on practitioners, and those reclassified as non cross-disciplinary had the greatest impact on colleagues. Having clear definitions for types of cross-disciplinary research would help establish a firm foundation, not only for improving research quality, but also for evaluating research impact. While the number of cross-disciplinary studies is increasing, cross-disciplinary research falls short of integrating disciplinary methods in much depth and does not have much impact on participants outside of academia.

Requirements for educational support tools in Virtual Worlds

Duncan, Ishbel Mary Macdonald — 2012-04-18T00:00:00Z

Abstract: Virtual Worlds have been used for online gaming, socialising, business advertising and education. As the educational uses become more sophisticated from early information advertising and teaching resources to simulated laboratory and scenarios, it is necessary to determine requirements for tools and virtual systems to achieve the optimal support possible. This paper discusses the current educational uses of Virtual Worlds and applies this to a set of support requirements derived for an evaluated support tool for learning to program. The result is a layered approach, or checklist, to support learning and evaluation for effective and adaptive online educational support tools including virtual world educational systems. Description: Paper number 65

Numerical simulation of shear-induced instabilities in internal solitary waves

Carr, Magda — 2011-09-25T00:00:00Z

Abstract: A numerical method that employs a combination of contour advection and pseudo-spectral techniques is used to simulate shear-induced instabilities in an internal solitary wave (ISW). A three-layer configuration for the background stratification, in which a linearly stratified intermediate layer is sandwiched between two homogeneous ones, is considered throughout. The flow is assumed to satisfy the inviscid, incompressible, Oberbeck–Boussinesq equations in two dimensions. Simulations are initialized by fully nonlinear, steady-state, ISWs. The results of the simulations show that the instability takes place in the pycnocline and manifests itself as Kelvin–Helmholtz billows. The billows form near the trough of the wave, subsequently grow and disturb the tail. Both the critical Richardson number (Ric) and the critical amplitude required for instability are found to be functions of the ratio of the undisturbed layer thicknesses. It is shown, therefore, that the constant, critical bound for instability in ISWs given in Barad & Fringer (J. Fluid Mech., vol. 644, 2010, pp. 61–95), namely Ric = 0.1 ± 0.01 , is not a sufficient condition for instability. It is also shown that the critical value of Lx/λ required for instability, where Lx is the length of the region in a wave in which Ri < 1/4 and λ is the half-width of the wave, is sensitive to the ratio of the layer thicknesses. Similarly, a linear stability analysis reveals that δiTw (where δi is the growth rate of the instability averaged over Tw, the period in which parcels of fluid are subjected to Ri < 1/4) is very sensitive to the transition between the undisturbed pycnocline and the homogeneous layers, and the amplitude of the wave. Therefore, the alternative tests for instability presented in Fructus et al. (J. Fluid Mech., vol. 620, 2009, pp. 1–29) and Barad & Fringer (J. Fluid Mech., vol. 644, 2010, pp. 61–95), respectively, namely Lx/λ ≥ 0.86 and δiTw > 5 , are shown to be valid only for a limited parameter range. Description: This work was supported by the UK Engineering and Physical Sciences Research Council [grant number EP/F030622/1]

"For the salvation of my soul": women and wills in medieval and early modern France

2012-01-01T00:00:00Z

Abstract: This volume seeks to investigate the testamentary practices of women in medieval and early modern France, examining the experience of a cross-section of the population, from artisans to the elite, in Aix-en-Provence, Avignon, Marseille, Montpellier, La Rochelle, Brittany, and Burgundy. The making of a will was perhaps the single most prominent moment in women’s lives for the assertion of agency. Though constrained to some degree by customary practice and the increasing influence of Roman law, women demonstrated remarkable initiative in the formulation of their last wishes. Wills permitted women to reward friendship and loyalty, to designate universal heirs as major beneficiaries, to stipulate conditions of inheritance so that last wishes were carried out, and, perhaps most importantly, to make pious donations to the Church for the salvation of the testators’ souls. They chose their burial sites and arranged for funeral processions, and they endowed anniversary masses for their souls in perpetuity. Individual testamentary decisions differed, as did spousal strategies, but the reinforcement of family ties, even the assertion of relationship, was possible in wills.

ATG5 Is Essential for ATG8-Dependent Autophagy and Mitochondrial Homeostasis in Leishmania major

Williams, Roderick A. M. — 2012-05-17T00:00:00Z

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.

Fast skeletal muscle transcriptome of the Gilthead sea bream (Sparus aurata) determined by next generation sequencing

Garcia de la Serrana Castillo, Daniel — 2012-05-11T00:00:00Z

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 >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.

ALDH2 mediates 5-nitrofuran activity in multiple species

Zhou, Linna — 2012-07-27T00:00:00Z

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.

In and out of Madagascar : dispersal to peripheral islands, insular speciation and diversification of Indian Ocean daisy trees (Psiadia, Asteraceae)

Strijk, Joeri S — 2012-08-10T00:00:00Z

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.

How selection structures species abundance distributions

Magurran, Anne E. — 2012-09-22T00:00:00Z

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.

Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebrates

Tinti, Michele — 2012-07-01T00:00:00Z

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.

Social learning of vocal structure in a nonhuman primate?

Lemasson, Alban — 2011-12-16T00:00:00Z

Abstract: Background: Non-human primate communication is thought to be fundamentally different from human speech, mainly due to vast differences in vocal control. The lack of these abilities in non-human primates is especially striking if compared to some marine mammals and bird species, which has generated somewhat of an evolutionary conundrum. What are the biological roots and underlying evolutionary pressures of the human ability to voluntarily control sound production and learn the vocal utterances of others? One hypothesis is that this capacity has evolved gradually in humans from an ancestral stage that resembled the vocal behavior of modern primates. Support for this has come from studies that have documented limited vocal flexibility and convergence in different primate species, typically in calls used during social interactions. The mechanisms underlying these patterns, however, are currently unknown. Specifically, it has been difficult to rule out explanations based on genetic relatedness, suggesting that such vocal flexibility may not be the result of social learning. Results: To address this point, we compared the degree of acoustic similarity of contact calls in free-ranging Campbell's monkeys as a function of their social bonds and genetic relatedness. We calculated three different indices to compare the similarities between the calls' frequency contours, the duration of grooming interactions and the microsatellite-based genetic relatedness between partners. We found a significantly positive relation between bond strength and acoustic similarity that was independent of genetic relatedness. Conclusion: Genetic factors determine the general species-specific call repertoire of a primate species, while social factors can influence the fine structure of some the call types. The finding is in line with the more general hypothesis that human speech has evolved gradually from earlier primate-like vocal communication.

Polarities of difference : how Wapichannao negotiate identities within a creole state

Hope, Stacy A. A. — 2011-01-01T00:00:00Z

Abstract: This thesis is an ethnographic account of how the Wapichannao, who are situated in the Rupununi of Guyana perceive themselves within the nation-state. This is also an account of how non-Amerindian Guyanese envisage Amerindians as ‘past’ peoples. Hence, distinctions are made between Amerindian and non-Amerindian—us vs. them—where both identities become placed as opposite poles within a continuum. Emphasis is placed on the shifting relationships between these poles, but more specifically, the cultural paradigm through which these relationships are made possible. This paradigm, I suggest, may be understood in terms of polarities of difference, with regard to which Amerindians are constantly ambiguating/negotiating, disjoining, and resignifying notions of ‘who they are’. This thesis evidences this paradigm through an ethnography of some of those aspects of Wapichannao culture—village work, the shop, joking activity, culture shows—that are considered to be traditional on the one hand, and modern on the other. In doing so, an incongruous trend emerges, on which makes the classic imagery of Amerindian ontological homogeneity much more complex. Therefore, this thesis moves from the more traditional aspects of Wapichannao culture towards the nation-state, in order to take into account aspects of Amerindian experience absent from classic ethnographic accounts.

Laser chemosensor with rapid responsivity and inherent memory based on a polymer of intrinsic microporosity

Wang, Yue — 2011-03-01T00:00:00Z

Abstract: This work explores the use of a polymer of intrinsic microporosity (PIM-1) as the active layer within a laser sensor to detect nitroaromatic-based explosive vapors. We show successful detection of dinitrobenzene (DNB) by monitoring the real-time photoluminescence. We also show that PIM-1 has an inherent memory, so that it accumulates the analyte during exposure. In addition, the optical gain and refractive index of the polymer were studied by amplified spontaneous emission and variable-angle ellipsometry, respectively. A second-order distributed feedback PIM-1 laser sensor was fabricated and found to show an increase in laser threshold of 2.5 times and a reduction of the laser slope efficiency by 4.4 times after a 5-min exposure to the DNB vapor. For pumping at 2 times threshold, the lasing action was stopped within 30 s indicating that PIM-1 has a very fast responsivity and as such has a potential sensing ability for ultra-low-concentration explosives.

Assessing asthma control in UK primary care : Use of routinely collected prospective observational consultation data to determine appropriateness of a variety of control assessment models

Hoskins, Gaylor — 2011-09-29T00:00:00Z

Abstract: Background: Assessing asthma control using standardised questionnaires is recommended as good clinical practice but there is little evidence validating their use within primary care. There is however, strong empirical evidence to indicate that age, weight, gender, smoking, symptom pattern, medication use, health service resource use, geographical location, deprivation, and organisational issues, are factors strongly associated with asthma control. A good control measure is therefore one whose variation is most explained by these factors. Method: Eight binary (Yes = poor control, No = good control) models of asthma control were constructed from a large UK primary care dataset: the Royal College of Physicians 3-Questions (RCP-3Qs); the Jones Morbidity Index; three composite measures; three single component models. Accounting for practice clustering of patients, we investigated the effects of each model for assessing control. The binary models were assessed for goodness-of-fit statistics using Pseudo R-squared and Akaikes Information Criteria (AIC), and for performance using Area Under the Receiver Operator Characteristic (AUROC). In addition, an expanded RCP-3Q control scale (0-9) was derived and assessed with linear modelling. The analysis identified which model was best explained by the independent variables and thus could be considered a good model of control assessment. Results: 1,205 practices provided information on 64,929 patients aged 13+ years. The RCP-3Q model provided the best fit statistically, with a Pseudo R-squared of 18%, and an AUROC of 0.79. By contrast, the composite model based on the GINA definition of controlled asthma had a higher AIC, an AUROC of 0.72, and only 10% variability explained. In addition, although the Peak Expiratory Flow Rate (PEFR) model had the lowest AIC, it had an AUROC of 71% and only 6% of variability explained. However, compared with the RCP-3Qs binary model, the linear RCP-3Q Total Score Model (Scale 0-9), was found to be a more robust 'tool' for assessing asthma control with a lower AIC (28,6163) and an R-squared of 33%. Conclusion: In the absence of a gold standard for assessing asthma control in primary care, the results indicate that the RCP-3Qs is an effective control assessment tool but, for maximum effect, the expanded scoring model should be used.

Community-specific evaluation of tool affordances in wild chimpanzees

Gruber, Thibaud — 2011-11-03T00:00:00Z

Abstract: The notion of animal culture, defined as socially transmitted community-specific behaviour patterns, remains controversial, notably because the definition relies on surface behaviours without addressing underlying cognitive processes. In contrast, human cultures are the product of socially acquired ideas that shape how individuals interact with their environment. We conducted field experiments with two culturally distinct chimpanzee communities in Uganda, which revealed significant differences in how individuals considered the affording parts of an experimentally provided tool to extract honey from a standardised cavity. Firstly, individuals of the two communities found different functional parts of the tool salient, suggesting that they experienced a cultural bias in their cognition. Secondly, when the alternative function was made more salient, chimpanzees were unable to learn it, suggesting that prior cultural background can interfere with new learning. Culture appears to shape how chimpanzees see the world, suggesting that a cognitive component underlies the observed behavioural patterns.

Communication during sex among female bonobos : effects of dominance, solicitation and audience

Clay, Zanna — 2012-03-01T00:00:00Z

Abstract: Bonobo females frequently form close bonds, which give them social power over other group members. One potential mechanism to facilitate female bonding is the performance of sexual interactions. Using naturalistic observations and experiments, we found various patterns that determined female-female sexual interactions. First, while low-ranked females interacted with all females, sexual interactions between high-ranked females were rare. Second, during genital contacts, females sometimes produced 'copulation calls', which were significantly affected by the rank of the caller and partner, as well as the solicitation direction. Third, there was a significant effect of the alpha female as a bystander, while variables relating to physical experience had no effects. Overall, results highlight the importance of sexual interactions for bonobo female social relations. Copulation calls are an important tool during this process, suggesting that they have become ritualised, beyond their reproductive function, to serve as broader social signals in flexible and potentially strategic ways.

Incipient speciation in Drosophila melanogaster involves chemical signals

Grillet, Micheline — 2012-01-19T00:00:00Z

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.

Deficits in facial, body movement and vocal emotional processing in autism spectrum disorders

Philip, R. C. M. — 2010-11-01T00:00:00Z

Abstract: Background. Previous behavioural and neuroimaging studies of emotion processing in autistic spectrum disorder (ASD) have focused on the use of facial stimuli. To date, however, no studies have examined emotion processing in autism across a broad range of social signals. Method. This study addressed this issue by investigating emotion processing in a group of 23 adults with ASD and 23 age-and gender-matched controls. Recognition of basic emotions ('happiness ', 'sadness', 'anger', disgust' and 'fear') was assessed from facial, body movement and vocal stimuli. The ability to make social judgements (such as approachability) from facial stimuli was also investigated. Results. Significant deficits in emotion recognition were found in the ASD group relative to the control group across all stimulus domains (faces, body movements and voices). These deficits were seen across a range of emotions. The ASD group were also impaired in making social judgements compared to the control group and this correlated with impairments in basic emotion recognition. Conclusions. This study demonstrates that there are significant and broad-ranging deficits in emotion processing in ASD present across a range of stimulus domains and in the auditory and visual modality; they cannot therefore be accounted for simply in terms of impairments in face processing or in the visual modality alone. These results identify a core deficit affecting the processing of a wide range of emotional information in ASD, which contributes to the impairments in social function seen in people with this condition.

Temperature, age of mating and starvation determine the role of maternal effects on sex allocation in the mealybug Planococcus citri

Ross, Laura — 2011-05-01T00:00:00Z

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.

How reproductive ecology contributes to the spread of a globally invasive fish

Deacon, Amy E. — 2011-09-19T00:00:00Z

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.

The quantitative genetic basis of sex ratio variation in Nasonia vitripennis : a QTL study

Pannebakker, B. A. — 2011-01-01T00:00:00Z

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.

Phocid seal leptin : tertiary structure and hydrophobic receptor binding site preservation during distinct leptin gene evolution

Hammond, John Anthony — 2012-04-19T00:00:00Z

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.

The multifunctional NS1 protein of influenza virus

Hale, Benjamin Geoffrey — 2008-10-01T00:00:00Z

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.

Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase

Rudrawar, S — 2010-11-16T00:00:00Z

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.

Conservation of a crystallographic interface suggests a role for beta-sheet augmentation in influenza virus NS1 multifunctionality

Kerry, Philip Stephen — 2011-08-01T00:00:00Z

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).

Regional susceptibility to TNF-alpha induction of murine brain inflammation via classical IKK/NF-kappa B signalling

Young, Adam M. H. — 2012-06-11T00:00:00Z

Abstract: It is becoming clear that inflammation plays a significant role in a number of neurological and psychiatric conditions. Post mortem brain samples in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, schizophrenia and most recently autism spectrum condition, all exhibit neuroglial activation and inflammatory markers within the CSF. Many questions remain about the underlying molecular mechanisms. By adding the pro-inflammatory cytokine, TNF-alpha, to mouse brain tissue we demonstrated that the frontal lobes and temporal region, areas involved in higher functions such as memory and learning, are most susceptible to cytokine-induced inflammation via the NF-kappa B signalling pathway. We observed direct correlations between the volumetric increase and molecular expression indicating that therapeutic targets in these lobes may require different approaches when treating conditions with a central neuroinflammatory component.

Production and perception rules underlying visual patterns : effects of symmetry and hierarchy

Westphal, Gesche — 2012-07-19T00:00:00Z

Abstract: Formal language theory has been extended to two-dimensional patterns, but little is known about two-dimensional pattern perception. We first examined spontaneous two-dimensional visual pattern production by humans, gathered using a novel touch screen approach. Both spontaneous creative production and subsequent aesthetic ratings show that humans prefer ordered, symmetrical patterns over random patterns. We then further explored pattern-parsing abilities in different human groups, and compared them with pigeons. We generated visual plane patterns based on rules varying in complexity. All human groups tested, including children and individuals diagnosed with autism spectrum disorder (ASD), were able to detect violations of all production rules tested. Our ASD participants detected pattern violations with the same speed and accuracy as matched controls. Children's ability to detect violations of a relatively complex rotational rule correlated with age, whereas their ability to detect violations of a simple translational rule did not. By contrast, even with extensive training, pigeons were unable to detect orientation-based structural violations, suggesting that, unlike humans, they did not learn the underlying structural rules. Visual two-dimensional patterns offer a promising new formally-grounded way to investigate pattern production and perception in general, widely applicable across species and age groups.

Neural events underlying escape swimming behaviour in the squat lobster 'Galathea strigosa' (Crustacea, Anomura)

Sillar, Keith Thomas — 1984-01-01T00:00:00Z

Abstract: 1. The anatomy and physiology of escape swimming behaviour in the squat lobster, Galathea strigosa, have been investigated and the results discussed in the context of comparative mechanisms of escape in rela~ed species. 2. In contrast to many other decapods, G. strigosa, does not possess a giant-fibre system which underlies escape. 3. In terms of the number, size and position of neuronal somata, the fast flexor motorneuron pools in Galathea and crayfish are homologous. 4. A neuron, homologous with the crayfish MeG, has been studied. Unlike the crayfish neuron, MoGH is a typical, unspecialized fast flexor motorneuron. 5. The anatomy of afferent and efferent neurons involved in abdominal extension has been investigated. The extensor motorneuron and accessory neuron pools in crayfish and Galathea are largely homologous. 6. A small degree of intersegmental and interspecific variation in abdominal flexor and extensor motorneuron pools is reported. 7. The anatomy and physiology of the abdominal MRO's has been examined. These are found to be homologous in structure and function with other decapod MRO's. 8. The considerable differences between the phasic and tonic MRO sensory dendrites may account for their different response characteristics. 9. The MRO's excite both extensor motorneurons and the flexor inhibitor motorneuron via an apparently monosynaptic pathway. Similar input properties have been described for the crayfish MHO's . 10. The MRO's, which are shown to fire in response to abdominal flexion, produce EPSP's in extensor motorneurons which both summate and facilitate. This feature has not been decribed previously and may be important in the reflex function of the MHO's during escape swimming behaviour. 11. The relative roles of proprioceptive and exteroceptive feedback on the generation of the swimming rhythm have been studied using a variety of preparations involving restraint and deafferenta- tion. 12. Sensory feedback both excites and inhibits swimming. It is deduced that proprioceptive feedback has excitatory effects and extero- ceptive feedback inhibits swimming behaviour. 13. It is suggested that the MHO's may playa role in exciting the neural circuits underlying swimming bewvbur via both direct connections with the thoracic nervous system and a restricted portion of the abdominal motorneuron pool. 14. A deafferented preparation has been used to analyse the motor programme underlying swimming behaviour. The ability to record swimming activity, identical with that recorded in the intact animal, in the absence of sensory feedback from the abdomen, suggests that swimming behaviour is controlled by a central pattern generator (CPG). 15. A method of inducing swimming activity by high frequency electrical- stimulation of abdominal sensori-motor roots is described. 16. The CPG for swimming behaviour is shown to be most likely to reside in the suboesophageal or thoracic ganglion. 17. The activity of flexor and extensor motorneurons in abdominal ganglia has been analysed at the cellular level using both extra- cellular and intracellular recording techniques. 18. Fast flexor motorneurons are driven by a combination of brief unitary synaptic potentials and a large underlying oscillatory slow wave depolarization. 19. Current injection into the somata of fast flexor motorneurons during swimming has dramatic effects on slow wave amplitude and suggests that motorneuron drive results from powerful periodic excitation via chemical synapses. 20. In contrast to the fast flexor motorneurons, fast extensor motorneurons are driven by only brief unitary synaptic potentials and not by an underlying slow wave depolarization. The contrasting mechanisms for excitation in antagonistic sets of motorneurons is documented and a possible explanation presented. 21. Among the fast extensor motorneurons there is an apparent gradation in spike thresholds which can be correlated with a gradation in soma diameter. The largest of the available pool of extensor motorneurons has the highest spike threshold. 22. The activity of the phasic inhibitors of the extensor and flexor muscles has been analysed. The extensor inhibitor, which fires in antiphase with other extensor motorneurons during the flexion phase of the swim cycle, appears to receive the same slow wave depolarization as fast flexor motorneurons. The extensor inibitor motorneuron burst is terminated by a high frequency barrage of IPSP's superimposed upon the membrane slow wave. The flexor inhibitor motorneuron receives complex excitation and inhibition during swimming, involving both unitary events and membrane waves. 23. The coordination of segmented limb structures during swimming has been investigated. The walking legs are physically protracted during flexion while the unmodified male swimmerets are flicked posteriorly. 24. Swimmeret retraction during swimming is controlled by the activity of a single swimmeret motorneuron which appears to be part of the swimming circuit and which may also be a primitive homologue of the Segmental Giant neuron in crayfish. 25. It is concluded that escape swimming behaviour is homologous with non-giant backwards swimming in crayfish and may also be homologous with swimming in certain sand crab species. The evolutionary relationships of a number of decapods is discussed on the basis of escape circuitry and it is suggested that Galathea may represent an ancestral type of swimming decapod.

Physical, biological and cultural factors influencing the formation, stabilisation and protection of archaeological deposits in U.K. coastal waters

Ferrari, Ben — 1995-01-01T00:00:00Z

Abstract: A considerable corpus of information regarding the formation of terrestrial archaeological deposits exists which is not matched by studies of deposit formation in coastal waters. Similarly, there is a disjunction between strident calls for minimal disturbance investigation, with conservation in situ, and knowledge of how this might actually be achieved in the marine environment. The manner in which the investigation of deposit formation can complement the study of in situ conservation is considered An approach is proposed which combines selected elements of Schiffer's Transformation Theory with a method of studying changes to deposits outlined by Wildesen. It is suggested that, although sufficient regularities can be detected in the influence of formation processes to allow their influence to be recognised and inference refined accordingly, there are case specific limitations on the extent to which the precise influence of each process can be described and evaluated. A case study is presented which investigates casual depredation as a formation process. Commercial fishing activity and marine burrowing activity are the subject of detailed consideration. New insights into these processes result from this study and specific recommendations concerning in situ conservation of deposits subject to their influence are made. The need to consider fishing practice as well as the mechanical properties of fishing gear in the study of deposit formation and protection is emphasised. The excavation of a 16th century wreck in Studland Bay, Dorset, is used to demonstrate the pervasive influence of burrowing activity and the problems associated with mitigation of this process. Recommendations are made regarding future study of formation processes and the development of policy related to the management of the submerged archaeological resource.

A taste of movement : an exploration of the social ethics of the Tsimanes of lowland Bolivia

Ellis, Rebecca — 1997-01-01T00:00:00Z

Abstract: This thesis explores Tsimane understandings and creations of varying forms of sociality. Each chapter addresses different but related issues concerning sociality. Fieldwork was carried out in three riverine settlements over the period from December 1991 to August 1994. The thesis shows that sociality is created and perpetuated by individuals as a processual endeavour, and does not amount to a tangible structure predicated upon fixed social relationships. Community in a physically bound sense is not found amongst the Tsimanes. Given forms of sociality are shown to rest more upon an appropriateness or inappropriateness of mood or affectivity. These are created and effected by subtle details of each individual’s presence amongst others. Social presence is understood by the Tsimanes as both potentially nurturant and predatory. Tsimanes are explicit about their ideas of preferred and abhorred social presence and behaviour of human and non-human others. This thesis explores ways in which such ideas are articulated to create a discourse on social ethics. A Tsimane aesthetics of social living carries with it practical implications for creating and perpetuating forms of sociality. An underlying theme of the thesis is one of mobility and the oscillating nature of Tsimane movements between different groups of kin and affines, and between moods and forms of sociality. I demonstrate that the high value placed by the Tsimanes upon movement, and the enjoyment they experience from it, most efficiently enable the achievement of correct social existence. A lack of knowledge and intention, ultimately resulting in illness and death, are principally deemed to occur as a result of immobility.

MACiE (Mechanism, Annotation and Classification in Enzymes) : novel tools for searching catalytic mechanisms

Holliday, Gemma L. — 2007-01-01T00:00:00Z

Abstract: MACiE (Mechanism, Annotation and Classification in Enzymes) is a database of enzyme reaction mechanisms, and is publicly available as a web-based data resource. This paper presents the first release of a web-based search tool to explore enzyme reaction mechanisms in MACiE. We also present Version 2 of MACiE, which doubles the dataset available (from Version 1). MACiE can be accessed from http://www.ebi.ac.uk/thornton-srv/databases/MACIE/.

The small genome segment of Bunyamwera orthobunyavirus harbours a single transcription-termination signal

Blakqori, Gjon — 2012-07-01T00:00:00Z

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.

Is EC class predictable from reaction mechanism?

Nath, Neetika — 2012-04-24T00:00:00Z

Abstract: Background: We investigate the relationships between the EC (Enzyme Commission) class, the associated chemical reaction, and the reaction mechanism by building predictive models using Support Vector Machine (SVM), Random Forest (RF) and k-Nearest Neighbours (kNN). We consider two ways of encoding the reaction mechanism in descriptors, and also three approaches that encode only the overall chemical reaction. Both cross-validation and also an external test set are used. Results: The three descriptor sets encoding overall chemical transformation perform better than the two descriptions of mechanism. SVM and RF models perform comparably well; kNN is less successful. Oxidoreductases and hydrolases are relatively well predicted by all types of descriptor; isomerases are well predicted by overall reaction descriptors but not by mechanistic ones. Conclusions: Our results suggest that pairs of similar enzyme reactions tend to proceed by different mechanisms. Oxidoreductases, hydrolases, and to some extent isomerases and ligases, have clear chemical signatures, making them easier to predict than transferases and lyases. We find evidence that isomerases as a class are notably mechanistically diverse and that their one shared property, of substrate and product being isomers, can arise in various unrelated ways. The performance of the different machine learning algorithms is in line with many cheminformatics applications, with SVM and RF being roughly equally effective. kNN is less successful, given the role that non-local information plays in successful classification. We note also that, despite a lack of clarity in the literature, EC number prediction is not a single problem; the challenge of predicting protein function from available sequence data is quite different from assigning an EC classification from a cheminformatics representation of a reaction.

Bunyaviruses and the type I interferon system

Elliott, Richard Michael — 2009-11-23T00:00:00Z

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.

Structure and functional analysis of LptC, a conserved membrane protein involved in the lipopolysaccharide export pathway in Escherichia coli

Tran, An X. — 2010-10-22T00:00:00Z

Abstract: LptC is a conserved bitopic inner membrane protein from Escherichia coli involved in the export of lipopolysaccharide from its site of synthesis in the cytoplasmic membrane to the outer membrane. LptC forms a complex with the ATP-binding cassette transporter, LptBFG, which is thought to facilitate the extraction of lipopolysaccharide from the inner membrane and release it into a translocation pathway that includes the putative periplasmic chaperone LptA. Cysteine modification experiments established that the catalytic domain of LptC is oriented toward the periplasm. The structure of the periplasmic domain is described at a resolution of 2.2-angstrom from x-ray crystallographic data. The periplasmic domain of LptC consists of a twisted boat structure with two beta-sheets in apposition to each other. The beta-sheets contain seven and eight antiparallel beta-strands, respectively. This structure bears a high degree of resemblance to the crystal structure of LptA. Like LptA, LptC binds lipopolysaccharide in vitro. In vitro, LptA can displace lipopolysaccharide from LptC (but not vice versa), consistent with their locations and their proposed placement in a unidirectional export pathway. Description: This work is supported by a Wellcome Trust Career Development Fellowship to C.D.

Space, time and harmony : symbolic aspects of language in Andean textiles with special reference to those from Bolivar Province (Cochabamba, Bolivia).

Crickmay, Lindsey — 1992-01-01T00:00:00Z

Abstract: The thesis investigates how the designs woven in Andean textiles make up a symbolic language which both communicates information about those who wear them and demonstrates their desire to balance the opposing forces which are believed to govern their world. All textile elements share this communicative function and the thesis examines the significance of spin, colour and layout in the textile as a whole and in the individual designs. Textile terminology is drawn from fieldwork, the literature and from early Aymara and Quechua lexicons. The contemporary designs examined were personally observed in Bolivar in 1982/3 and 1986; the thesis suggests their derivation from colonial designs and discusses their possible iconographic content. Part one shows the significance of clothing as a statement of identity and describes briefly the weaving techniques and figures typical of the Bolivar area. Part two shows how cloth is seen as a vital, three-dimensional object and how in weaving as in the other plastic arts designs are encoded with abstract concepts fundamental to the traditions of a social group. Part three examines how certain colour combinations represent social, political or cosmic tensions and how their arrangement attempts to manipulate and control the energy generated by them. In particular it investigates how colour represents the circulation of suerte, or fortune, many of the names of which are also terms for colour combinations similar to those used in textiles. It also shows how specific elements such as stripes and figured designs act as metaphors through which the textile becomes a map or record of social, ritual and cosmic space.

The implications of manioc cultivation in the culture and mythology of the Machiguenga of South Eastern Peru

Lewington, Anna — 1986-01-01T00:00:00Z

Abstract: The aim of this thesis is to effect an introduction to the place of manioc (Manihot esculenta Crantz) in the culture of the Machiguenga Indians of the Peruvian rain forest. The main substance of my work finds its focus in a myth, the narrative of which was recorded during fieldwork on location in the Urubamba region of south east Peru. My thesis will attempt to examine the role of manioc and the justification of its description as a ‘sacred plant’ to the Machiguenga. The evidence I put forward to demonstrate the significance of manioc comes under the following headings: a) manioc cultivation and dietary uses, b) manioc plant taxonomy, c) the manioc myth itself, which I have transcribed and translated from my recordings. Whilst the anthropological structures of the myth are examined, no attempt will be made to deal in detail with the vocabulary and morphology of the Machiguenga language. Whilst conceding that it is vital to show the connection between the material use of manioc and the belief structure surrounding it, material already collected would suggest a more ambitious piece of work than a Master of Philosophy degree would allow, and I hope in the future to undertake full-scale investigation into this largely untouched aspect of Machiguenga social and religious organization. The present work aims only at an introduction to the people and their use of manioc, and the presentation of the manioc myth.

Scoring functions and enrichment : a case study on Hsp90

Konstantinou-Kirtay, Chrysi — 2007-01-26T00:00:00Z

Abstract: Background: The need for fast and accurate scoring functions has been driven by the increased use of in silico virtual screening twinned with high-throughput screening as a method to rapidly identify potential candidates in the early stages of drug development. We examine the ability of some the most common scoring functions (GOLD, ChemScore, DOCK, PMF, BLEEP and Consensus) to discriminate correctly and efficiently between active and non-active compounds among a library of similar to 3,600 diverse decoy compounds in a virtual screening experiment against heat shock protein 90 (Hsp90). Results: Firstly, we investigated two ranking methodologies, GOLD(rank) and BestScore(rank). GOLD(rank) is based on ranks generated using GOLD. The various scoring functions, GOLD, ChemScore, DOCK, PMF, BLEEP and Consensus, are applied to the pose ranked number one by GOLD for that ligand. BestScore(rank) uses multiple poses for each ligand and independently chooses the best ranked pose of the ligand according to each different scoring function. Secondly, we considered the effect of introducing the Thr184 hydrogen bond tether to guide the docking process towards a particular solution, and its effect on enrichment. Thirdly, we considered normalisation to account for the known bias of scoring functions to select larger molecules. All the scoring functions gave fairly similar enrichments, with the exception of PMF which was consistently the poorest performer. In most cases, GOLD was marginally the best performing individual function; the Consensus score usually performed similarly to the best single scoring function. Our best results were obtained using the Thr184 tether in combination with the BestScore(rank) protocol and normalisation for molecular weight. For that particular combination, DOCK was the best individual function; DOCK recovered 90% of the actives in the top 10% of the ranked list; Consensus similarly recovered 89% of the actives in its top 10%. Conclusion: Overall, we demonstrate the validity of virtual screening as a method for identifying new leads from a pool of ligands with similar physicochemical properties and we believe that the outcome of this study provides useful insight into the setting up of a suitable docking and scoring protocol, resulting in enrichment of 'target active' compounds. Description: This work was funded by the EPSRC, InsightFaraday (now part of the Chemistry Innovation Knowledge Transfer Network), Arrow Therapeutics Ltd and Unilever plc.

Quantitative comparison of catalytic mechanisms and overall reactions in convergently evolved enzymes : implications for classification of enzyme function

Almonacid, Daniel E. — 2010-03-12T00:00:00Z

Abstract: Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation. Description: The authors thank the National Institutes of Health (NIH R01 GM60595 to PCB) and the Scottish Universities Life Sciences Alliance (SULSA to JBOM) for funding.

A novel hybrid ultrafast shape descriptor method for use in virtual screening

Cannon, EO — 2008-02-18T00:00:00Z

Abstract: Background We have introduced a new Hybrid descriptor composed of the MACCS key descriptor encoding topological information and Ballester and Richards' Ultrafast Shape Recognition (USR) descriptor. The latter one is calculated from the moments of the distribution of the interatomic distances, and in this work we also included higher moments than in the original implementation. Results The performance of this Hybrid descriptor is assessed using Random Forest and a dataset of 116,476 molecules. Our dataset includes 5,245 molecules in ten classes from the 2005 World Anti-Doping Agency (WADA) dataset and 111,231 molecules from the National Cancer Institute (NCI) database. In a 10-fold Monte Carlo cross-validation this dataset was partitioned into three distinct parts for training, optimisation of an internal threshold that we introduced, and validation of the resulting model. The standard errors obtained were used to assess statistical significance of observed improvements in performance of our new descriptor. Conclusion The Hybrid descriptor was compared to the MACCS key descriptor, USR with the first three (USR), four (UF4) and five (UF5) moments, and a combination of MACCS with USR (three moments). The MACCS key descriptor was not combined with UF5, due to similar performance of UF5 and UF4. Superior performance in terms of all figures of merit was found for the MACCS/UF4 Hybrid descriptor with respect to all other descriptors examined. These figures of merit include recall in the top 1% and top 5% of the ranked validation sets, precision, F-measure, area under the Receiver Operating Characteristic curve and Matthews Correlation Coefficient. Description: The authors thank the EPSRC and Unilever plc for funding.

Simultaneous feature selection and parameter optimisation using an artificial ant colony : case study of melting point prediction

O'Boyle, NM — 2008-10-29T00:00:00Z

Abstract: Background We present a novel feature selection algorithm, Winnowing Artificial Ant Colony (WAAC), that performs simultaneous feature selection and model parameter optimisation for the development of predictive quantitative structure-property relationship (QSPR) models. The WAAC algorithm is an extension of the modified ant colony algorithm of Shen et al. (J Chem Inf Model 2005, 45: 1024–1029). We test the ability of the algorithm to develop a predictive partial least squares model for the Karthikeyan dataset (J Chem Inf Model 2005, 45: 581–590) of melting point values. We also test its ability to perform feature selection on a support vector machine model for the same dataset. Results Starting from an initial set of 203 descriptors, the WAAC algorithm selected a PLS model with 68 descriptors which has an RMSE on an external test set of 46.6°C and R2 of 0.51. The number of components chosen for the model was 49, which was close to optimal for this feature selection. The selected SVM model has 28 descriptors (cost of 5, ε of 0.21) and an RMSE of 45.1°C and R2 of 0.54. This model outperforms a kNN model (RMSE of 48.3°C, R2 of 0.47) for the same data and has similar performance to a Random Forest model (RMSE of 44.5°C, R2 of 0.55). However it is much less prone to bias at the extremes of the range of melting points as shown by the slope of the line through the residuals: -0.43 for WAAC/SVM, -0.53 for Random Forest. Conclusion With a careful choice of objective function, the WAAC algorithm can be used to optimise machine learning and regression models that suffer from overfitting. Where model parameters also need to be tuned, as is the case with support vector machine and partial least squares models, it can optimise these simultaneously. The moving probabilities used by the algorithm are easily interpreted in terms of the best and current models of the ants, and the winnowing procedure promotes the removal of irrelevant descriptors. Description: The authors thank the BBSRC (NMOB and JBOM – grant BB/C51320X/1), Pfizer (DSP and JBOM – through the Pfizer Institute for Pharmaceutical Materials Science), and Unilever for funding FN and JBOM and for supporting the Centre for Molecular Science Informatics.

CMLSnap : Animated reaction mechanisms

Holliday, G L — 2004-10-26T00:00:00Z

Abstract: Reactions with many steps can be represented by a single XML-based table of the atoms, bonds and electrons. For each step the complete Chemical Markup Language 1 representation of all components is obtained and a snapshot representing the end point of the step is generated. These snapshots can then be combined to give an animated description of the complete reaction, both in "2D" chemical structure diagrams and in three dimensions. Here we demonstrate the method's power with enzymatic reactions. It should be noted that readers of this paper will benefit from having an SVG (Scalable Vector Graphics) viewer plugin. Description: The authors thank the EPSRC for financial support of this project and Unilever for their support of the Centre for Molecular Science Informatics.

Chemistry in Bioinformatics

Murray-Rust, P — 2005-06-07T00:00:00Z

Abstract: Chemical information is now seen as critical for most areas of life sciences. But unlike Bioinformatics, where data is openly available and freely re-usable, most chemical information is closed and cannot be re-distributed without permission. This has led to a failure to adopt modern informatics and software techniques and therefore paucity of chemistry in bioinformatics. New technology, however, offers the hope of making chemical data (compounds and properties) free during the authoring process. We argue that the technology is already available; we require a collective agreement to enhance publication protocols.

Communication and re-use of chemical information in bioscience

Murray-Rust, P — 2005-07-18T00:00:00Z

Abstract: The current methods of publishing chemical information in bioscience articles are analysed. Using 3 papers as use-cases, it is shown that conventional methods using human procedures, including cut-and-paste are time-consuming and introduce errors. The meaning of chemical terms and the identity of compounds is often ambiguous. valuable experimental data such as spectra and computational results are almost always omitted. We describe an Open XML architecture at proof-of-concept which addresses these concerns. Compounds are identified through explicit connection tables or links to persistent Open resources such as PubChem. It is argued that if publishers adopt these tools and protocols, then the quality and quantity of chemical information available to bioscientists will increase and the authors, publishers and readers will find the process cost-effective.

Modeling distribution and abundance of Antarctic baleen whales using ships of opportunity

Williams, Robert — 2006-06-01T00:00:00Z

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.

Methods for investigating measurement error in cetacean line-transect surveys

Williams, Robert — 2007-02-26T00:00:00Z

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.

Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator

Lain, Sonia — 2008-05-06T00:00:00Z

Abstract: We have carried out a cell-based screen aimed at discovering small molecules that activate p53 and have the potential to decrease tumor growth. Here, we describe one of our hit compounds, tenovin-1, along with a more water-soluble analog, tenovin-6. Via a yeast genetic screen, biochemical assays, and target validation studies in mammalian cells, we show that tenovins act through inhibition of the protein-deacetylating activities of SirT1 and SirT2, two important members of the sirtuin family. Tenovins are active on mammalian cells at one-digit micromolar concentrations and decrease tumor growth in vivo as single agents. This underscores the utility of these compounds as biological tools for the study of sirtuin function as well as their potential therapeutic interest.

Perception of relative depth interval : Systematic biases in perceived depth

Harris, Julie — 2012-01-01T00:00:00Z

Abstract: Given an estimate of the binocular disparity between a pair of points and an estimate of the viewing distance, or knowledge of eye position, it should be possible to obtain an estimate of their depth separation. Here we show that, when points are arranged in different vertical geometric configurations across two intervals, many observers find this task difficult. Those who can do the task tend to perceive the depth interval in one configuration as very different from depth in the other configuration. We explore two plausible explanations for this effect. The first is the tilt of the empirical vertical horopter: Points perceived along an apparently vertical line correspond to a physical line of points tilted backwards in space. Second, the eyes can rotate in response to a particular stimulus. Without compensation for this rotation, biases in depth perception would result. We measured cyclovergence indirectly, using a standard psychophysical task, while observers viewed our depth configuration. Biases predicted from error due either to cyclovergence or to the tilted vertical horopter were not consistent with the depth configuration results. Our data suggest that, even for the simplest scenes, we do not have ready access to metric depth from binocular disparity.

Global analysis of cetacean line-transect surveys : detecting trends in cetacean density

Jewell, Rebecca Lucy — 2012-05-07T00:00:00Z

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.

What visual information is used for stereoscopic depth displacement discrimination.

Nefs, Harold — 2010-01-01T00:00:00Z

Abstract: There are two ways to detect a displacement in stereoscopic depth, namely by monitoring the change in disparity over time (CDOT) or by monitoring the inter-ocular velocity difference (IOVD). Though previous studies have attempted to understand which cue is most significant for the visual system, none have designed stimuli that provide a comparison in terms of relative efficiency between them. Here we used two-frame motion and random dot noise to deliver equivalent strengths of CDOT and IOVD information to the visual system. Using three kinds of random dot stimuli, we were able to isolate CDOT or IOVD or deliver both simultaneously. The proportion of dots delivering CDOT or IOVD signals could be varied, and we defined discrimination threshold as the proportion needed to detect the direction of displacement (towards or away)1. Thresholds were similar for stimuli containing CDOT only, and containing both CDOT and IOVD, but only one participant was able to consistently perceive the displacement for stimuli containing only IOVD. We also investigated the effect of disparity pedestals on discrimination. Performance was best when the displacement crossed the reference plane, but was not significantly different for stimuli containing CDOT only, or containing both CDOT and IOVD. When stimuli are specifically designed to provide equivalent two-frame motion or disparity-change, few participants can reliably detect displacement when IOVD is the only cue. This challenges the notion that IOVD is involved in the discrimination of direction of displacement in two-frame motion displays.

Changes in intra-nuclear mobility of mature snRNPs provide a mechanism for splicing defects in Spinal Muscular Atrophy

Clelland, Allyson Kara — 2012-04-01T00:00:00Z

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)

Pictures and interpretations : towards an applied semiotics

Boot, Katie — 1994-01-01T00:00:00Z

Abstract: This is a study about the ways in which pictures can be interpreted and the ways in which they are interpreted; the latter, specifically, in a relatively remote part of Peru. Chapter II reviews an assortment of picture tests which bring to light differences in the ways pictures are perceived. Chapter III examines the specific cultural context in which a fairly informal picture test was administered. Chapter IV presents some results and asks what cultural and situational factors may have contributed to the variety in interpretations evident. The drawing of firm conclusions is precluded by the absence of any systematic approach to the interpretations or to the pictures themselves, and it is this which the second half of the study attempts to remedy; by providing a theoretical framework for the assessment of verbalized responses to pictures. Chapter V offers a definition of "picture" and locates it within a typology of indices. It also examines the notion of "visual resemblance", eventually adopting the view that any picture is infinitely ambiguous. Chapter VI introduces two methodological necessities consequent on this ambiguity: a stipulation as to the identity and the taxonomic specificity of any signified object; and a stipulation as to the spatial extension of its signifier. No other methodological content is presented. Chapter VII classifies types of verbalized responses in terms of their visual motivation, and the degree to which they interrelate the stipulated pictorial units. Chapter VIII acknowledges that signification may continue beyond the representational level. Further, postrepresentational, types of responses are classified in terms of the nature of the link maintained with the representational signified.

Mongoose : throughput redistributing virtual world

Oliver, Iain Angus — 2012-08-30T00:00:00Z

Abstract: Metaverses provide a framework for developing distributed 3D Internet applications where users gain presence through the proxy of an avatar. They offer much of the engagement of on line 3D games but support heterogeneous applications. From the network perspective metaverses are similar to games in that timeliness is important but differ in that their traffic is less regular and requires more bandwidth. The motivation for our study flows from using virtual worlds to support experiential learning and to promote cultural heritage; the applicability of the results is wider. The responsiveness of the system is effected by interactions between avatar activity, application traffic regulation and network conditions. Through measurement and analysis current virtual world traffic regulation is evaluated and compared with Transmission Control Protocol fair rate. The measurement study motivates the design of Mongoose, which adds measurement based packet regulation to open virtual world clients and servers. Mongoose combines isolating distinct functional components with efficient use of network esources and fairness to other traffic.

Inbreeding and selection on sex ratio in the bark beetle Xylosandrus germanus

Keller, Laurent — 2011-12-13T00:00:00Z

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.

A general discrete-time modeling framework for animal movement using multi-state random walks

McClintock, Brett Thomas — 2012-01-01T00:00:00Z

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.

The influence of the freshwater environment and the biological characteristics of Atlantic salmon smolts on their subsequent marine survival

Russell, Ian — 2012-01-01T00:00:00Z

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.

The use of active sonar to study cetaceans

Bernasconi, Matteo — 2012-06-01T00:00:00Z

Abstract: Cetacean species face serious challenges worldwide due to the increasing noise pollution brought to their environment by human activities such as seismic exploration. Regulation of these activities is vaguely defined and uncoordinated. Visual observations and passive listening devices, aimed at preventing conflicts between human wealth and cetaceans’ health have some fundamental limitations and may consequently fail their mitigation purposes. Active sonar technology could be the optimal solution to implement mitigation of such human activities. In my thesis, the proper sonar unit was used to test the feasibility to detect cetaceans in situ. Omnidirectional sonars could be the optimal solution to monitor the presence of cetaceans in the proximity of potential danger areas. To use this class of sonar in a quantitative manner, the first step was to develop a calibration method. This thesis links in situ measurements of target strength (TS) with variation trends linked to the behavior, morphology and physiology of cetacean. The butterfly effect of a cetacean’s body was described for a fin whale insonified from different angles. A relationship between whale respiration and TS energy peaks was tested through a simple prediction model which seems very promising for further implementation. The effect of lung compression on cetacean TS due to increasing depth was tested through a basic mathematical model. The model fit the in situ TS measurements. TS measurements at depth of a humpback whale, when post-processed, correspond to TS measurements recorded at the surface. Sonar technology is clearly capable of detecting whale foot prints around an operating vessel. Sonar frequency response shows that frequencies between 18 and 38 kHz should be employed. This work has established a baseline and raised new questions so that active sonar can be developed and employed in the best interest for the whales involved in potentially harmful conflicts with man.

Replication of Bunyamwera virus in mosquito cells

Szemiel, Agnieszka M. — 2011-01-01T00:00:00Z

The Bernese disputations of 1532 and 1538 : a historical and theological analysis

Eccher, Stephen Brett — 2011-11-01T00:00:00Z

Abstract: Given the relative paucity of treatments relating to both the 1532 and 1538 Bern Gespräche, alongside a growing historiography which has offered a clearer understanding of the backdrop around which these two debates were held, the focus of this research project will be to provide a comparative analysis of the recorded dialogues from the debates at Bern. This ecclesiologically focused comparison aims to discern whether the debate relating to the nature of the church at the 1538 session was merely a redundant exercise and continuation of the earlier 1532 disputation or whether the latter debate offered anything substantively new to the ongoing religious dialogue between these two groups. Furthermore, all of the respective views on the nature of the church manifest in these debates will be examined in light of the preceding Anabaptist/Reformed dialogue of the period to determine their place contextually. Having embarked upon the aforementioned goals several conclusions may be definitively drawn. First, the major ecclesiological suppositions expressed by both the Anabaptist and Reformed participants at the 1538 debate were, in fact, retained using the same core theological elements employed by their predecessors at the 1532 debate. Yet, despite this striking similarity, the independent nature of these debates must also be acknowledged. This may primarily be found in that both groups expressed their retained ecclesiologies with notable variation in things such as language, argumentative content, biblical corroboration, and illustrative evidence. Finally, both the similar and independent nature of these events will be shown to have been largely derived from the Anabaptist/Reformed dialogue already begun as the Swiss Brethren movement emerged from under Zwingli’s reform efforts in Zürich. Each of these conclusions should help to paint a more accurate portrait of not only what was accomplished through these debates, but where each stands contextually during the period.

Assessing public engagement with science in a university primate research centre in a national zoo

Bowler, Mark Timothy — 2012-04-04T00:00:00Z

Abstract: Recent years have seen increasing encouragement by research institutions and funding bodies for scientists to actively engage with the public, who ultimately finance their work. Animal behaviour as a discipline possesses several features, including its inherent accessibility and appeal to the public, that may help it occupy a particularly successful niche within these developments. It has also established a repertoire of quantitative behavioural methodologies that can be used to document the public's responses to engagement initiatives. This kind of assessment is becoming increasingly important considering the enormous effort now being put into public engagement projects, whose effects are more often assumed than demonstrated. Here we report our first attempts to quantify relevant aspects of the behaviour of a sample of the hundreds of thousands of visitors who pass through the ‘Living Links to Human Evolution Research Centre’ in Edinburgh Zoo. This University research centre actively encourages the public to view ongoing primate research and associated science engagement activities. Focal follows of visitors and scan sampling showed substantial ‘dwell times’ in the Centre by common zoo standards and the addition of new engagement elements in a second year was accompanied by significantly increased overall dwell times, tripling for the most committed two thirds of visitors. Larger groups of visitors were found to spend more time in the Centre than smaller ones. Viewing live, active science was the most effective activity, shown to be enhanced by novel presentations of carefully constructed explanatory materials. The findings emphasise the importance and potential of zoos as public engagement centres for the biological sciences.

Evidence for weak or linear conformity but not for hyper-conformity in an everyday social learning context

Claidiere, Nicolas — 2012-02-20T00:00:00Z

Abstract: Conformity is thought to be an important force in cultural evolution because it has the potential to stabilize cooperation in large groups, potentiate group selection and thus explain uniquely human behaviors. However, the effects of such conformity on cultural and biological evolution will depend much on the way individuals are influenced by the frequency of alternative behavioral options witnessed. Theoretical modeling has suggested that only what we refer to as ‘hyper-conformity’, an exaggerated tendency to perform the most frequent behavior witnessed in other individuals, is able to increase within-group homogeneity and between-group diversity, for instance. Empirically however, few experiments have addressed how the frequency of behavior witnessed affects behavior. Accordingly we performed an experiment to test for the presence of conformity in a natural situation with humans. Visitors to a Zoo exhibit were invited to write or draw answers to questions on A5 cards and potentially win a small prize. We manipulated the proportion of existing writings versus drawings visible to visitors and measured the proportion of written cards submitted. We found a strong and significant effect of the proportion of text displayed on the proportion of text in the answers, thus demonstrating social learning. We show that this effect is approximately linear, with potentially a small, weak-conformist component but no hyper-conformist one. The present experiment therefore provides evidence for linear conformity in humans in a very natural context.

Status assessment of the Critically Endangered Azores Bullfinch Pyrrhula murina

Ceia, Ricardo S. — 2011-01-01T00:00:00Z

Abstract: The Azores Bullfinch is endemic to the island of São Miguel (Azores, Portugal). Its status was uplisted to Critically Endangered in 2005 on the basis of an extremely small and declining population that was considered to be restricted to a very small mountain range (43 km2), in a single location, within which the spread of invasive plants constituted a threat to habitat quality. Nevertheless, information was mostly inferred, or the product of, non-systematic studies. In order to carry out a complete assessment of the conservation status we analysed: (i) population trend, calculated from annual monitoring 1991–2008, (ii) population size, and (iii) range size, obtaining estimates in a single morning study in 2008 involving the simultaneous participation of 48 observers. Contrary to previous inferences, the population is no longer decreasing, although quality of laurel forest habitat continues to decline due to the persistent threat of invasive species. Population size (mean ± SE) was estimated at 1,064 ± 304 individuals using distance sampling methods, although the estimate was very sensitive to the survey method used. Range size estimates (extent of occurrence and area of occupancy) were 144 km2 and 83 km2 respectively. Given the present information, we propose the downlisting of Azores Bullfinch to Endangered on the IUCN Red List.

Deadly diving? Physiological and behavioural management of decompression stress in diving mammals

Hooker, S. K. — 2012-03-22T00:00:00Z

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.

Temporal turnover and the maintenance of diversity in ecological assemblages

Magurran, Anne E. — 2010-11-27T00:00:00Z

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.

Ancient homeobox gene loss and the evolution of chordate brain and pharynx development : deductions from amphioxus gene expression

Butts, Thomas — 2010-11-22T00:00:00Z

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.

Targeting mitotic chromosomes : a conserved mechanism to ensure viral genome persistence

Feeney, Katherine Martha — 2009-05-07T00:00:00Z

Abstract: Viruses that maintain their genomes as extrachromosomal circular DNA molecules and establish infection in actively dividing cells must ensure retention of their genomes within the nuclear envelope in order to prevent genome loss. The loss of nuclear membrane integrity during mitosis dictates that paired host cell chromosomes are captured and organized by the mitotic spindle apparatus before segregation to daughter cells. This prevents inaccurate chromosomal segregation and loss of genetic material. A similar mechanism may also exist for the nuclear retention of extrachromosomal viral genomes or episomes during mitosis, particularly for genomes maintained at a low copy number in latent infections. It has been heavily debated whether such a mechanism exists and to what extent this mechanism is conserved among diverse viruses. Research over the last two decades has provided a wealth of information regarding the mechanisms by which specific tumour viruses evade mitotic and DNA damage checkpoints. Here, we discuss the similarities and differences in how specific viruses tether episomal genomes to host cell chromosomes during mitosis to ensure long-term persistence.

Predicting the mechanism of phospholipidosis

Lowe, Robert — 2012-01-26T00:00:00Z

Abstract: The mechanism of phospholipidosis is still not well understood. Numerous different mechanisms have been proposed, varying from direct inhibition of the breakdown of phospholipids to the binding of a drug compound to the phospholipid, preventing breakdown. We have used a probabilistic method, the Parzen-Rosenblatt Window approach, to build a model from the ChEMBL dataset which can predict from a compound's structure both its primary pharmaceutical target and other targets with which it forms off-target, usually weaker, interactions. Using a small dataset of 182 phospholipidosis-inducing and non-inducing compounds, we predict their off-target activity against targets which could relate to phospholipidosis as a side-effect of a drug. We link these targets to specific mechanisms of inducing this lysosomal build-up of phospholipids in cells. Thus, we show that the induction of phospholipidosis is likely to occur by separate mechanisms when triggered by different cationic amphiphilic drugs. We find that both inhibition of phospholipase activity and enhanced cholesterol biosynthesis are likely to be important mechanisms. Furthermore, we provide evidence suggesting four specific protein targets. Sphingomyelin phosphodiesterase, phospholipase A2 and lysosomal phospholipase A1 are shown to be likely targets for the induction of phospholipidosis by inhibition of phospholipase activity, while lanosterol synthase is predicted to be associated with phospholipidosis being induced by enhanced cholesterol biosynthesis. This analysis provides the impetus for further experimental tests of these hypotheses.

Sexual selection on song and cuticular hydrocarbons in two distinct populations of Drosophila montana

Veltsos, Paris — 2012-01-01T00:00:00Z

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.

Beaked whales respond to simulated and actual navy sonar

Tyack, Peter L. — 2011-03-14T00:00:00Z

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.

An efficient one-step site-directed deletion, insertion, single and multiple-site plasmid mutagenesis protocol

Liu, Huanting — 2008-12-04T00:00:00Z

Abstract: Background: Mutagenesis plays an essential role in molecular biology and biochemistry. It has also been used in enzymology and protein science to generate proteins which are more tractable for biophysical techniques. The ability to quickly and specifically mutate a residue(s) in protein is important for mechanistic and functional studies. Although many site-directed mutagenesis methods have been developed, a simple, quick and multi-applicable method is still desirable. Results: We have developed a site-directed plasmid mutagenesis protocol that preserved the simple one step procedure of the QuikChange (TM) site-directed mutagenesis but enhanced its efficiency and extended its capability for multi-site mutagenesis. This modified protocol used a new primer design that promoted primer-template annealing by eliminating primer dimerization and also permitted the newly synthesized DNA to be used as the template in subsequent amplification cycles. These two factors we believe are the main reasons for the enhanced amplification efficiency and for its applications in multi-site mutagenesis. Conclusion: Our modified protocol significantly increased the efficiency of single mutation and also allowed facile large single insertions, deletions/truncations and multiple mutations in a single experiment, an option incompatible with the standard QuikChange (TM). Furthermore the new protocol required significantly less parental DNA which facilitated the DpnI digestion after the PCR amplification and enhanced the overall efficiency and reliability. Using our protocol, we generated single site, multiple single-site mutations and a combined insertion/deletion mutations. The results demonstrated that this new protocol imposed no additional reagent costs (beyond basic QuikChange T) but increased the overall success rates.

Activation of the beta interferon promoter by paramyxoviruses in the absence of virus protein synthesis

Killip, M. J. — 2012-02-01T00:00:00Z

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.

Altered antibiotic transport in OmpC mutants isolated from a series of clinical strains of multi-drug resistant E. coli

Lou, Hubing — 2011-10-28T00:00:00Z

Abstract: Antibiotic-resistant bacteria, particularly Gram negative species, present significant health care challenges. The permeation of antibiotics through the outer membrane is largely effected by the porin superfamily, changes in which contribute to antibiotic resistance. A series of antibiotic resistant E. coli isolates were obtained from a patient during serial treatment with various antibiotics. The sequence of OmpC changed at three positions during treatment giving rise to a total of four OmpC variants (denoted OmpC20, OmpC26, OmpC28 and OmpC33, in which OmpC20 was derived from the first clinical isolate). We demonstrate that expression of the OmpC K12 porin in the clinical isolates lowers the MIC, consistent with modified porin function contributing to drug resistance. By a range of assays we have established that the three mutations that occur between OmpC20 and OmpC33 modify transport of both small molecules and antibiotics across the outer membrane. This results in the modulation of resistance to antibiotics, particularly cefotaxime. Small ion unitary conductance measurements of the isolated porins do not show significant differences between isolates. Thus, resistance does not appear to arise from major changes in pore size. Crystal structures of all four OmpC clinical mutants and molecular dynamics simulations also show that the pore size is essentially unchanged. Molecular dynamics simulations suggest that perturbation of the transverse electrostatic field at the constriction zone reduces cefotaxime passage through the pore, consistent with laboratory and clinical data. This subtle modification of the transverse electric field is a very different source of resistance than occlusion of the pore or wholesale destruction of the transverse field and points to a new mechanism by which porins may modulate antibiotic passage through the outer membrane.

Miller, Bradwardine and the Truth

Read, Stephen — 2011-06-01T00:00:00Z

Abstract: In his article "Verdades antiguas y modernas" (in the same issue, pp. 207-27), David Miller criticised Thomas Bradwardine’s theory of truth and signification and my defence of Bradwardine’s application of it to the semantic paradoxes. Much of Miller’s criticism is sympathetic and helpful in gaining a better understanding of the relationship between Bradwardine’s proposed solution to the paradoxes and Alfred Tarski’s. But some of Miller’s criticisms betray a misunderstanding of crucial aspects of Bradwardine’s account of truth and signification.

Female chimpanzees use copulation calls flexibly to prevent social competition

Townsend, Simon W. — 2008-06-18T00:00:00Z

Abstract: The adaptive function of copulation calls in female primates has been debated for years. One influential idea is that copulation calls are a sexually selected trait, which enables females to advertise their receptive state to males. Male-male competition ensues and females benefit by getting better mating partners and higher quality offspring. We analysed the copulation calling behaviour of wild female chimpanzees (Pan troglodytes schweinfurthii) at Budongo Forest, Uganda, but found no support for the male-male competition hypothesis. Hormone analysis showed that the calling behaviour of copulating females was unrelated to their fertile period and likelihood of conception. Instead, females called significantly more while with high-ranking males, but suppressed their calls if high-ranking females were nearby. Copulation calling may therefore be one potential strategy employed by female chimpanzees to advertise receptivity to high-ranked males, confuse paternity and secure future support from these socially important individuals. Competition between females can be dangerously high in wild chimpanzees, and our results indicate that females use their copulation calls strategically to minimise the risks associated with such competition.

Identification of essential and non-essential single-stranded DNA-binding proteins in a model archaeal organism

Skowyra, Agnieszka — 2012-02-01T00:00:00Z

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.

Sphingolipid and ceramide homeostasis : potential therapeutic targets

Young, Simon — 2012-01-01T00:00:00Z

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.

The first animals : ca. 760-million-year-old sponge-like fossils from Namibia

Brain, C. K. 'Bob' — 2012-01-01T00:00:00Z

Abstract: One of the most profound events in biospheric evolution was the emergence of animals, which is thought to have occurred some 600-650 Ma. Here we report on the discovery of phosphatised body fossils that we interpret as ancient sponge-like fossils and term them Otavia antiqua gen. et sp. nov. The fossils are found in Namibia in rocks that range in age between about 760 Ma and 550 Ma. This age places the advent of animals some 100 to 150 million years earlier than proposed, and prior to the extreme climatic changes and postulated stepwise increases in oxygen levels of Ediacaran time. These findings support the predictions based on genetic sequencing and inferences drawn from biomarkers that the first animals were sponges. Further, the deposition and burial of Otavia as sedimentary particles may have driven the large positive C-isotopic excursions and increases in oxygen levels that have been inferred for Neoproterozoic time.

Mitochondrial β-amyloid in Alzheimer's disease

Borger, Eva — 2011-08-01T00:00:00Z

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.

A critical review of the literature on population modelling

Cabrelli, Abigail — 2009-01-01T00:00:00Z

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 & Gas Producers on contract JIP22 07_20

2A peptides provide distinct solutions to driving stop-carry on translational recoding

Sharma, P — 2012-01-01T00:00:00Z

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.

Generation and characterization of a recombinant Rift Valley fever virus expressing a V5 epitope-tagged RNA-dependent RNA polymerase

Brennan, Benjamin — 2011-12-01T00:00:00Z

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.

Innate sensing of HIV-infected cells

Lepelley, Alice — 2011-02-01T00:00:00Z

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.

A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Kerry, Philip S. — 2011-03-28T00:00:00Z

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).

Universal scaling rules predict evolutionary patterns of myogenesis in species with indeterminate growth

Johnston, Ian Alistair — 2012-06-07T00:00:00Z

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.

Revisiting Geneva: Robert Kingdon and the coming of the French Wars of Religion

2012-01-01T00:00:00Z

Abstract: The late Robert Kingdon’s Geneva and the Coming of the Wars of Religion in France, 1555-1563 (1956) was not merely an engaging and challenging piece of scholarship, it came to dominate the study of Genevan Protestantism and the city’s relationship with other Reformed communities, particularly those in France. Based on the rich archival records in Geneva, Kingdon’s work would inspire many subsequent scholars to investigate the questions he first raised in the 1950s. This volume is testament to the breadth of material he first covered, and demonstrates the variety of fields in which he came to have influence, including printing history, the role of the nobility in the Reformation, the functioning of the Consistory and the lives of pastors. Born out of a conference celebrating the fiftieth anniversary of his original book, this volume now stands as a memorial to a life of exemplary scholarship.

An update to the methods in Endangered Species Research 2011 paper "Estimating North Pacific right whale Eubalaena japonica density using passive acoustic cue counting"

Marques, Tiago A. — 2012-01-01T00:00:00Z

A toolbox for fitting complex spatial point process models using integrated nested Laplace approximation (INLA)

Illian, Janine Baerbel — 2012-12-01T00:00:00Z

Abstract: This paper develops methodology that provides a toolbox for routinely fitting complex models to realistic spatial point pattern data. We consider models that are based on log-Gaussian Cox processes and include local interaction in these by considering constructed covariates. This enables us to use integrated nested Laplace approximation and to considerably speed up the inferential task. In addition, methods for model comparison and model assessment facilitate the modelling process. The performance of the approach is assessed in a simulation study. To demonstrate the versatility of the approach, models are tted to two rather dierent examples, a large rainforest data set with covariates and a point pattern with multiple marks.

Obesity and the ageing brain : could leptin play a role in neurodegeneration?

Doherty, Gayle Helane — 2011-01-01T00:00:00Z

Abstract: Obesity and ageing are both characteristics of the human population that are on the increase across the globe. It has long been established that ageing is the major risk factor for neurodegenerative conditions such as Alzheimer’s disease, and it is becoming increasingly evident that obesity is another such factor. Leptin resistance or insensitivity has been uncovered as a cause of obesity, and in addition the leptin signalling system is less potent in the elderly. Taken together, these findings reveal that this molecule may be a link between neurodegeneration and obesity or ageing. It is now known that leptin has beneficial effects on both the survival and neurophysiology of the neurons that are lost in Alzheimer’s disease suggesting that it may be an important research target in the quest for strategies to prevent, halt or cure this condition.

Lipidomic analysis of bloodstream and procyclic form Trypanosoma brucei

Richmond, Gregory S. — 2010-08-01T00:00:00Z

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.

Developing Fife Interprofessional Clinical Skills Model of Education for student clinical placements

O'Carroll, Veronica — 2011-12-01T00:00:00Z

Abstract: End of pilot report for FICSME, an ACT funded initiative. Description: Funding of the pilot was provided by ACT from both NHS Fife and NHS Tayside.

Kametsa asaiki : the pursuit of the 'good life' in an Ashaninka village (Peruvian Amazonia)

Sarmiento Barletti, Juan Pablo — 2011-01-01T00:00:00Z

Abstract: This thesis is an ethnographic study of the pursuit of kametsa asaiki (‘the good life’) in an Ashaninka village by the Bajo Urubamba River (Peruvian Amazonia). My study centres on Ashaninka social organization in a context made difficult by the wake of the Peruvian Internal War, the activities of extractive industries, and a series of despotic decrees that have been passed by the Peruvian government. This is all framed by a change in their social organization from living in small, separated family-based settlements to one of living in villages. This shift presents them with great problems when internal conflicts arise. Whilst in the past settlements would have fissioned in order to avoid conflict, today there are two related groups of reasons that lead them to want to live in centralised communities. The first is their great desire for their children to go to school and the importance they place on long-term cash-crops. The second is the encroachment of the Peruvian State and private companies on their territory and lives which forces them to stay together in order to resist and protect their territory and way of life. I suggest that this change in organisation changes the rules of the game of sociality. Contemporary Ashaninka life is centred on the pursuit of kametsa asaiki, a philosophy of life they believe to have inherited from their ancestors that teaches emotional restraint and the sharing of food in order to create the right type of Ashaninka person. Yet, at present it also has new factors they believe allow them to become ‘civilised’: school education, new forms of leadership and conflict resolution, money, new forms of conflict resolution, intercultural health, and a strong political federation to defend their right to pursue kametsa asaiki. My thesis is an anthropological analysis of the 'audacious innovations' they have developed to retake the pursuit of kametsa asaiki in the aftermath of the war. I show that this ethos of living is not solely a communal project of conviviality but it has become a symbol of resistance in their fight for the right to have rights in Peru.

Displacement of the canonical single-stranded DNA-binding protein in the Thermoproteales

Paytubi, Sonia — 2012-02-14T00:00:00Z

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.

PCNA stimulates catalysis by structure-specific nuclease using two distinct mechanisms : substrate targeting and catalytic step

Hutton, R D — 2008-12-01T00:00:00Z

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]

The dramatising of theology : humanity’s participation in God’s drama with particular reference to the theologies of Hans Urs von Balthasar and Karl Barth

Farlow, Matthew S. — 2011-11-30T00:00:00Z

Abstract: The aim of this project is to investigate the proper response of theology to the Christian God who, as revealed through revelation, is Being-in-act. This project takes seriously the idea posited by Shakespeare, that totus mundus agit histrionem, and upon this stage ‘all the men and women merely players: They have their exits and their entrances; and one man in his time plays many parts.’ If, then, God’s Being is in act, and as so many have deduced, life and death are enveloped within the drama of everyday, then, might it be possible that our theological endeavours would prosper through a dramatic rendering? In light of this, the project seeks to illumine that it is beneficial for both the Church and society, to realise how drama can be, and is, fruitful for our theological endeavours. God is Being-in-act, and through His revelation, He invites humanity to enter into and participate in His action. In light of the aforementioned, then, theology must contend with the implications for its practices, which, as is being argued, are benefited most through a full embrace of the dramatising of theology. The thesis is situated in the recent movement of our theological endeavours that recognise the profundity of the dramatic and its ability to illuminate God’s action and call to action from theology, the Church and society. Moving forward from the seminal work of Hans Urs von Balthasar, and set forth in the context of the theologies of Balthasar and Karl Barth, this project argues that it is through the dramatising of theology that theology is best equipped to illumine God’s desire for humanity’s participation in His Theo-drama. The dramatising of theology is a natural response to God’s Being-in-act; it is the natural movement of theology’s response to God’s action which calls for an active response on our part. Current examples of today’s theological movement towards the dramatic can be seen in such authors as Max Harris, Trevor Hart, Stanley Hauerwas, Michael Horton, Todd Johnson and Dale Savidge, Ben Quash, Kevin Vanhoozer, Samuel Wells and N.T. Wright. This project hopes to contribute to the movement towards the dramatising of theology.

Selection of reference genes for expression studies with fish myogenic cell cultures

Bower, Neil I. — 2009-08-10T00:00:00Z

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.