251 research outputs found

    Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

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    With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/

    Lorentz Covariant Theory of Light Propagation in Gravitational Fields of Arbitrary-Moving Bodies

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    The Lorentz covariant theory of propagation of light in the (weak) gravitational fields of N-body systems consisting of arbitrarily moving point-like bodies with constant masses is constructed. The theory is based on the Lienard-Wiechert presentation of the metric tensor. A new approach for integrating the equations of motion of light particles depending on the retarded time argument is applied. In an approximation which is linear with respect to the universal gravitational constant, G, the equations of light propagation are integrated by quadratures and, moreover, an expression for the tangent vector to the perturbed trajectory of light ray is found in terms of instanteneous functions of the retarded time. General expressions for the relativistic time delay, the angle of light deflection, and gravitational red shift are derived. They generalize previously known results for the case of static or uniformly moving bodies. The most important applications of the theory are given. They include a discussion of the velocity dependent terms in the gravitational lens equation, the Shapiro time delay in binary pulsars, and a precise theoretical formulation of the general relativistic algorithm of data processing of radio and optical astrometric measurements in the non-stationary gravitational field of the solar system. Finally, proposals for future theoretical work being important for astrophysical applications are formulated.Comment: 77 pages, 7 figures, list of references is updated, to be published in Phys. Rev. D6

    The role of species charisma in biological invasions

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    Commonly used in the literature to refer to the "attractiveness", "appeal", or "beauty" of a species, charisma can be defined as a set of characteristics - and the perception thereof - that affect people's attitudes and behaviors toward a species. It is a highly relevant concept for invasion science, with implications across all stages of the invasion process. However, the concept of invasive alien species (IAS) charisma has not yet been systematically investigated. We discuss this concept in detail, provide a set of recommendations for further research, and highlight management implications. We review how charisma affects the processes associated with biological invasions andIASmanagement, including species introductions and spread, media portrayals, public perceptions of species management, research attention, and active public involvement in research and management. Explicit consideration ofIAScharisma is critical for understanding the factors that shape people's attitudes toward particular species, planning management measures and strategies, and implementing a combination of education programs, awareness raising, and public involvement campaigns.Peer reviewe

    Population density and group size effects on reproductive behavior in a simultaneous hermaphrodite

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    <p>Abstract</p> <p>Background</p> <p>Despite growing evidence that population dynamic processes can have substantial effects on mating system evolution, little is known about their effect on mating rates in simultaneous hermaphrodites. According to theory, mating rate is expected to increase with mate availability because mating activity is primarily controlled by the male sexual function. A different scenario appears plausible in the hermaphroditic opisthobranch <it>Chelidonura sandrana</it>. Here, field mating rates are close to the female fitness optimum, suggesting that mating activity remains unresponsive to variation in mate availability.</p> <p>Results</p> <p>Applying an experimental design that aims at independent experimental manipulation of density and social group size, we find substantial increases in mate encounter rate with both factors, but no statistically detectable effects on mating rate in <it>C. sandrana</it>. Instead, mating rate remained close to the earlier determined female fitness optimum.</p> <p>Conclusions</p> <p>We demonstrate that mating rate in <it>C. sandrana </it>is largely unresponsive to variation in mate availability and is maintained close to the female fitness optimum. These findings challenge the prevailing notion of male driven mating rates in simultaneous hermaphrodites and call for complementary investigations of mating rate effects on fitness through the male sexual function.</p

    Coding Early Naturalists' Accounts into Long-Term Fish Community Changes in the Adriatic Sea (1800–2000)

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    The understanding of fish communities' changes over the past centuries has important implications for conservation policy and marine resource management. However, reconstructing these changes is difficult because information on marine communities before the second half of the 20th century is, in most cases, anecdotal and merely qualitative. Therefore, historical qualitative records and modern quantitative data are not directly comparable, and their integration for long-term analyses is not straightforward. We developed a methodology that allows the coding of qualitative information provided by early naturalists into semi-quantitative information through an intercalibration with landing proportions. This approach allowed us to reconstruct and quantitatively analyze a 200-year-long time series of fish community structure indicators in the Northern Adriatic Sea (Mediterranean Sea). Our analysis provides evidence of long-term changes in fish community structure, including the decline of Chondrichthyes, large-sized and late-maturing species. This work highlights the importance of broadening the time-frame through which we look at marine ecosystem changes and provides a methodology to exploit, in a quantitative framework, historical qualitative sources. To the purpose, naturalists' eyewitness accounts proved to be useful for extending the analysis on fish community back in the past, well before the onset of field-based monitoring programs

    Sexual Display and Mate Choice in an Energetically Costly Environment

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    Sexual displays and mate choice often take place under the same set of environmental conditions and, as a consequence, may be exposed to the same set of environmental constraints. Surprisingly, however, very few studies consider the effects of environmental costs on sexual displays and mate choice simultaneously. We conducted an experiment, manipulating water flow in large flume tanks, to examine how an energetically costly environment might affect the sexual display and mate choice behavior of male and female guppies, Poecilia reticulata. We found that male guppies performed fewer sexual displays and became less choosy, with respect to female size, in the presence of a water current compared to those tested in still water. In contrast to males, female responsive to male displays did not differ between the water current treatments and females exhibited no mate preferences with respect to male size or coloration in either treatment. The results of our study underscore the importance of considering the simultaneous effects of environmental costs on the sexual behaviors of both sexes

    Determination of Therapeutic Equivalence of Generic Products of Gentamicin in the Neutropenic Mouse Thigh Infection Model

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    Background: Drug regulatory agencies (DRA) support prescription of generic products of intravenous antibiotics assuming therapeutic equivalence from pharmaceutical equivalence. Recent reports of deaths associated with generic heparin and metoprolol have raised concerns about the efficacy and safety of DRA-approved drugs. Methodology/Principal Findings: To challenge the assumption that pharmaceutical equivalence predicts therapeutic equivalence, we determined in vitro and in vivo the efficacy of the innovator product and 20 pharmaceutically equivalent generics of gentamicin. The data showed that, while only 1 generic product failed in vitro (MIC = 45.3 vs. 0.7 mg/L, P,0.05), 10 products (including gentamicin reference powder) failed in vivo against E. coli due to significantly inferior efficacy (E max = 4.81 to 5.32 vs. 5.99 log 10 CFU/g, P#0.043). Although the design lacked power to detect differences in survival after thigh infection with P. aeruginosa, dissemination to vital organs was significantly higher in animals treated with generic gentamicin despite 4 days of maximally effective treatment. Conclusion: Pharmaceutical equivalence does not predict therapeutic equivalence of generic gentamicin. Stricter criteri

    Phenology of Scramble Polygyny in a Wild Population of Chrysolemid Beetles: The Opportunity for and the Strength of Sexual Selection

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    Recent debate has highlighted the importance of estimating both the strength of sexual selection on phenotypic traits, and the opportunity for sexual selection. We describe seasonal fluctuations in mating dynamics of Leptinotarsa undecimlineata (Coleoptera: Chrysomelidae). We compared several estimates of the opportunity for, and the strength of, sexual selection and male precopulatory competition over the reproductive season. First, using a null model, we suggest that the ratio between observed values of the opportunity for sexual selections and their expected value under random mating results in unbiased estimates of the actual nonrandom mating behavior of the population. Second, we found that estimates for the whole reproductive season often misrepresent the actual value at any given time period. Third, mating differentials on male size and mobility, frequency of male fighting and three estimates of the opportunity for sexual selection provide contrasting but complementary information. More intense sexual selection associated to male mobility, but not to male size, was observed in periods with high opportunity for sexual selection and high frequency of male fights. Fourth, based on parameters of spatial and temporal aggregation of female receptivity, we describe the mating system of L. undecimlineata as a scramble mating polygyny in which the opportunity for sexual selection varies widely throughout the season, but the strength of sexual selection on male size remains fairly weak, while male mobility inversely covaries with mating success. We suggest that different estimates for the opportunity for, and intensity of, sexual selection should be applied in order to discriminate how different behavioral and demographic factors shape the reproductive dynamic of populations

    Specialized Learning in Antlions (Neuroptera: Myrmeleontidae), Pit-Digging Predators, Shortens Vulnerable Larval Stage

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    Unique in the insect world for their extremely sedentary predatory behavior, pit-dwelling larval antlions dig pits, and then sit at the bottom and wait, sometimes for months, for prey to fall inside. This sedentary predation strategy, combined with their seemingly innate ability to detect approaching prey, make antlions unlikely candidates for learning. That is, although scientists have demonstrated that many species of insects possess the capacity to learn, each of these species, which together represent multiple families from every major insect order, utilizes this ability as a means of navigating the environment, using learned cues to guide an active search for food and hosts, or to avoid noxious events. Nonetheless, we demonstrate not only that sedentary antlions can learn, but also, more importantly, that learning provides an important fitness benefit, namely decreasing the time to pupate, a benefit not yet demonstrated in any other species. Compared to a control group in which an environmental cue was presented randomly vis-à-vis daily prey arrival, antlions given the opportunity to associate the cue with prey were able to make more efficient use of prey and pupate significantly sooner, thus shortening their long, highly vulnerable larval stage. Whereas “median survival time,” the point at which half of the animals in each group had pupated, was 46 days for antlions receiving the Learning treatment, that point never was reached in antlions receiving the Random treatment, even by the end of the experiment on Day 70. In addition, we demonstrate a novel manifestation of antlions' learned response to cues predicting prey arrival, behavior that does not match the typical “learning curve” but which is well-adapted to their sedentary predation strategy. Finally, we suggest that what has long appeared to be instinctive predatory behavior is likely to be highly modified and shaped by learning
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