1,586 research outputs found

    Rapid changes in phenotype distribution during range expansion in a migratory bird

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    The capacity of species to track changing environmental conditions is a key component of population and range changes in response to environmental change. High levels of local adaptation may constrain expansion into new locations, while the relative fitness of dispersing individuals will influence subsequent population growth. However, opportunities to explore such processes are rare, particularly at scales relevant to species-based conservation strategies. Icelandic black-tailed godwits, Limosa limosa islandica, have expanded their range throughout Iceland over the last century. We show that current male morphology varies strongly in relation to the timing of colonization across Iceland, with small males being absent from recently occupied areas. Smaller males are also proportionately more abundant on habitats and sites with higher breeding success and relative abundance of females. This population-wide spatial structuring of male morphology is most likely to result from female preferences for small males and better-quality habitats increasing both small-male fitness and the dispersal probability of larger males into poorer-quality habitats. Such eco-evolutionary feedbacks may be a key driver of rates of population growth and range expansion and contraction

    Faster subsequence recognition in compressed strings

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    Computation on compressed strings is one of the key approaches to processing massive data sets. We consider local subsequence recognition problems on strings compressed by straight-line programs (SLP), which is closely related to Lempel--Ziv compression. For an SLP-compressed text of length mˉ\bar m, and an uncompressed pattern of length nn, C{\'e}gielski et al. gave an algorithm for local subsequence recognition running in time O(mˉn2logn)O(\bar mn^2 \log n). We improve the running time to O(mˉn1.5)O(\bar mn^{1.5}). Our algorithm can also be used to compute the longest common subsequence between a compressed text and an uncompressed pattern in time O(mˉn1.5)O(\bar mn^{1.5}); the same problem with a compressed pattern is known to be NP-hard

    Single-cell profiling of MC1R-inhibited melanocytes

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    The human red hair color (RHC) trait is caused by increased pheomelanin (red-yellow) and reduced eumelanin (black-brown) pigment in skin and hair due to diminished melanocortin 1 receptor (MC1R) function. In addition, individuals harboring the RHC trait are predisposed to melanoma development. While MC1R variants have been established as causative of RHC and are a well-defined risk factor for melanoma, it remains unclear mechanistically why decreased MC1R signaling alters pigmentation and increases melanoma susceptibility. Here, we use single-cell RNA sequencing (scRNA-seq) of melanocytes isolated from RHC mouse models to define a MC1R-inhibited Gene Signature (MiGS) comprising a large set of previously unidentified genes which may be implicated in melanogenesis and oncogenic transformation. We show that one of the candidate MiGS genes, TBX3, a well-known anti-senescence transcription factor implicated in melanoma progression, binds both E-box and T-box elements to regulate genes associated with melanogenesis and senescence bypass. Our results provide key insights into further mechanisms by which melanocytes with reduced MC1R signaling may regulate pigmentation and offer new candidates of study toward understanding how individuals with the RHC phenotype are predisposed to melanoma.This research was supported by the National Human Genome Research Institute (NHGRI) Intramural Research Program at the National Institutes of Health (NIH) (1ZIAHG000068-15), the Intramural Research Program of the National Cancer Institute (NCI) at the National Institutes of Health (NIH) (1ZIACP010201), and the Ludwig Institute for Cancer Research. H.M.B. is supported by an NHGRI Intramural Research Training Award, the NIH Oxford-Cambridge Scholars Program, and the NIH Medical Research Scholars Program, a public–private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, Genentech, the American Association for Dental Research, and the Colgate-Palmolive Company. Additionally, P.M.A. would like to thank H2020-WIDESPREAD-2018-951921-ImmunoHUB for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Regional variation of total sodium concentration in the healthy human brain

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    Two Component Systems: Physiological Effect of a Third Component

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    Signal transduction systems mediate the response and adaptation of organisms to environmental changes. In prokaryotes, this signal transduction is often done through Two Component Systems (TCS). These TCS are phosphotransfer protein cascades, and in their prototypical form they are composed by a kinase that senses the environmental signals (SK) and by a response regulator (RR) that regulates the cellular response. This basic motif can be modified by the addition of a third protein that interacts either with the SK or the RR in a way that could change the dynamic response of the TCS module. In this work we aim at understanding the effect of such an additional protein (which we call “third component”) on the functional properties of a prototypical TCS. To do so we build mathematical models of TCS with alternative designs for their interaction with that third component. These mathematical models are analyzed in order to identify the differences in dynamic behavior inherent to each design, with respect to functionally relevant properties such as sensitivity to changes in either the parameter values or the molecular concentrations, temporal responsiveness, possibility of multiple steady states, or stochastic fluctuations in the system. The differences are then correlated to the physiological requirements that impinge on the functioning of the TCS. This analysis sheds light on both, the dynamic behavior of synthetically designed TCS, and the conditions under which natural selection might favor each of the designs. We find that a third component that modulates SK activity increases the parameter space where a bistable response of the TCS module to signals is possible, if SK is monofunctional, but decreases it when the SK is bifunctional. The presence of a third component that modulates RR activity decreases the parameter space where a bistable response of the TCS module to signals is possible

    Rotation of planet-harbouring stars

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    The rotation rate of a star has important implications for the detectability, characterisation and stability of any planets that may be orbiting it. This chapter gives a brief overview of stellar rotation before describing the methods used to measure the rotation periods of planet host stars, the factors affecting the evolution of a star's rotation rate, stellar age estimates based on rotation, and an overview of the observed trends in the rotation properties of stars with planets.Comment: 16 pages, 4 figures: Invited review to appear in 'Handbook of Exoplanets', Springer Reference Works, edited by Hans J. Deeg and Juan Antonio Belmont

    Ensemble Models of Neutrophil Trafficking in Severe Sepsis

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    A hallmark of severe sepsis is systemic inflammation which activates leukocytes and can result in their misdirection. This leads to both impaired migration to the locus of infection and increased infiltration into healthy tissues. In order to better understand the pathophysiologic mechanisms involved, we developed a coarse-grained phenomenological model of the acute inflammatory response in CLP (cecal ligation and puncture)-induced sepsis in rats. This model incorporates distinct neutrophil kinetic responses to the inflammatory stimulus and the dynamic interactions between components of a compartmentalized inflammatory response. Ensembles of model parameter sets consistent with experimental observations were statistically generated using a Markov-Chain Monte Carlo sampling. Prediction uncertainty in the model states was quantified over the resulting ensemble parameter sets. Forward simulation of the parameter ensembles successfully captured experimental features and predicted that systemically activated circulating neutrophils display impaired migration to the tissue and neutrophil sequestration in the lung, consequently contributing to tissue damage and mortality. Principal component and multiple regression analyses of the parameter ensembles estimated from survivor and non-survivor cohorts provide insight into pathologic mechanisms dictating outcome in sepsis. Furthermore, the model was extended to incorporate hypothetical mechanisms by which immune modulation using extracorporeal blood purification results in improved outcome in septic rats. Simulations identified a sub-population (about of the treated population) that benefited from blood purification. Survivors displayed enhanced neutrophil migration to tissue and reduced sequestration of lung neutrophils, contributing to improved outcome. The model ensemble presented herein provides a platform for generating and testing hypotheses in silico, as well as motivating further experimental studies to advance understanding of the complex biological response to severe infection, a problem of growing magnitude in humans
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