bluuebunny/crossref_metadata_2025_split huggingface dataset:
Desert lizard diversity worldwide: effects of environment, time, and evolutionary rate
Authors: Tejero-Cicuéndez Héctor , Tarroso Pedro , Carranza Salvador , Rabosky Daniel 
Published: February 2021

ABSTRACTAimBiodiversity is not uniformly distributed across the Earth’s surface, even among physiographically comparable biomes in different biogeographic regions. For lizards, the world’s large desert regions are characterized by extreme heterogeneity in species richness, spanning some of the most species-rich (arid Australia) and species-poor (central Asia) biomes overall. Regional differences in species diversity may arise as a consequence of the interplay of several factors (e.g., evolutionary time, diversification rate, environment), but their relative importance for biogeographic patterns remains poorly known. Here we use distributional and phylogenetic data to assess the evolutionary and ecological drivers of large-scale variation in desert lizard diversity.LocationDeserts worldwide.Major taxa studiedLizards (non-snake squamates).MethodsWe specifically test whether diversity patterns are best explained by differences in the ages of arid-adapted lineages (evolutionary time hypothesis), by regional variation in speciation rate, by geographic area of the arid systems, and by spatial variation related to environment (climate, topography, and productivity).ResultsWe found no effect of recent speciation rate and geographic area on differences in desert lizard diversity. We demonstrate that the extreme species richness of the Australian deserts cannot be explained by greater evolutionary time, because species began accumulating more recently there than in more species-poor arid regions. We found limited support for relationships between regional lizard richness and environmental variables, but these effects were inconsistent across deserts, showing a differential role of the environment in shaping the lizard diversity in different arid regions.Main conclusionsOur results provide evidence against several classic hypotheses for interregional variation in species richness, but also highlight the complexity of processes underlying vertebrate community richness in the world’s great arid systems.
Fluctuations in TCR and pMHC interactions regulate T cell activation
Authors: Egan Joseph R. , Abu-Shah Enas , Dushek Omer , Elliott Tim , MacArthur Ben D. 
Published: February 2021

ABSTRACTAdaptive immune responses depend on interactions between T cell receptors (TCRs) and peptide major-histocompatibility complex (pMHC) ligands located on the surface of T cells and antigen presenting cells (APCs) respectively. As TCRs and pMHCs are often only present at low copy-numbers their interactions are inherently stochastic, yet the role of stochastic fluctuations on T cell function is unclear. Here we introduce a minimal stochastic model of T cell activation that accounts for serial TCR-pMHC engagement, reversible TCR conformational change and TCR aggregation. Analysis of this model indicates that it is not the strength of binding between the T cell and the APC cellper sethat elicits an immune response, but rather the information imparted to the T cell from the encounter, as assessed by the entropy rate of the TCR-pMHC binding dynamics. This view provides an information-theoretic interpretation of T cell activation that explains a range of experimental observations. Based on this analysis we propose that effective T cell therapeutics may be enhanced by optimizing the inherent stochasticity of TCR-pMHC binding dynamics.
Emergent Oscillation Induced by Nutrient-Modulating Growth Feedback
Authors: Melendez-Alvarez Juan , He Changhan , Zhang Rong , Kuang Yang , Tian Xiao-Jun 
Published: February 2021

AbstractGrowth feedback, the inherent coupling between the synthetic gene circuit and the host cell growth, could significantly change the circuit behaviors. Previously, a diverse array of emerged behaviors, such as growth bistability, enhanced ultrasensitivity, and topology-dependent memory loss, were reported to be induced by growth feedback. However, the influence of the growth feedback on the circuit functions remains underexplored. Here, we reported an unexpected oscillatory behavior of a self-activation gene circuit induced by nutrient-modulating growth feedback. Specifically, after dilution of the activated self-activation switch into the fresh medium with moderate nutrient, its gene expression first decreases as the cell grows and then shows a significant overshoot before it reaches the steady states, leading to oscillation dynamics. Fitting the data with a coarse-grained model suggests a nonmonotonic growth-rate regulation on gene production rate. The underlying mechanism of the oscillation was demonstrated by a molecular mathematical model, which includes the ribosome allocation towards gene production, cell growth, and cell maintenance. Interestingly, the model predicted a counterintuitive dependence of oscillation amplitude on the nutrition level, where the highest peak was found in the medium with a moderate nutrient but was not observed in rich nutrient. We experimentally verified this prediction by tuning the nutrient level in the culture medium. We did not observe significant oscillatory behavior for toggle switch, suggesting that the emergence of oscillatory behavior depends on circuit network topology. Our results demonstrated a new nonlinear emergent behavior mediated by growth feedback, which depends on the ribosome allocation between gene circuit and cell growth.
Sequence neighborhoods enable reliable prediction of pathogenic mutations in cancer genomes
Authors: Banerjee Shayantan , Raman Karthik , Ravindran Balaraman 
Published: February 2021

AbstractIdentifying cancer-causing mutations from sequenced cancer genomes hold much promise for targeted therapy and precision medicine. “Driver” mutations are primarily responsible for cancer progression, while “passengers” are functionally neutral. Although several computational approaches have been developed for distinguishing between driver and passenger mutations, very few have concentrated on utilizing the raw nucleotide sequences surrounding a particular mutation as potential features for building predictive models. Using experimentally validated cancer mutation data in this study, we explored various string-based feature representation techniques to incorporate information on the neighborhood bases immediately 5’ and 3’ from each mutated position. Density estimation methods showed significant distributional differences between the neighborhood bases surrounding driver and passenger mutations. Binary classification models derived using repeated cross-validation experiments gave comparable performances across all window sizes. Integrating sequence features derived from raw nucleotide sequences with other genomic, structural and evolutionary features resulted in the development of a pan-cancer mutation effect prediction tool, NBDriver, which was highly efficient in identifying pathogenic variants from five independent validation datasets. An ensemble predictor obtained by combining the predictions from NBDriver with two other commonly used driver prediction tools (CONDEL and Mutation Taster) outperformed existing pan-cancer models in prioritizing a literature-curated list of driver and passenger mutations. Using the list of true positive mutation predictions derived from NBDriver, we identified a list of 138 known driver genes with functional evidence from various sources. Overall, our study underscores the efficacy of utilizing raw nucleotide sequences as features to distinguish between driver and passenger mutations from sequenced cancer genomes.
Validating a high-throughput tracking system: ATLAS as a regional-scale alternative to GPS
Authors: Beardsworth Christine E. , Gobbens Evy , van Maarseveen Frank , Denissen Bas , Dekinga Anne , Nathan Ran , Toledo Sivan , Bijleveld Allert I. 
Published: February 2021

AbstractFine-scale tracking of animal movement is important to understand the proximate mechanisms of animal behaviour. While GPS tracking is an excellent tool for measuring animal movement, trade-offs between tag weight, cost and lifespan limit its application to relatively large species, a small number of individuals or short tracking durations, respectively. The reverse-GPS system – ATLAS – uses lighter, cheaper tags compared to GPS tags, that can also last long periods of time at high sampling frequencies. Six systems are now operational worldwide and have successfully tracked over 50 species in various landscape types. This growing use of ATLAS to track animal movement motivates further refinement of best-practice application and an assessment of its accuracy.Here, we test the accuracy and precision of the largest ATLAS system, located in the Dutch Wadden Sea using concurrent GPS measurements as a reference. This large-scale ATLAS system consists of 26 receivers and covers 1326 km2of intertidal region, with almost no physical obstacles for radio signals, providing a useful baseline for other systems. To measure accuracy, we calculated the distance between ATLAS and GPS location estimates for a route (mobile test) and 16 fixed locations (stationary test) on the Griend mudflat.ATLAS-derived location estimates differed on average 4.2 m from GPS-estimated stationary test sites and 5.7 m from GPS tracks taken whilst moving between them. Signals that were collected by more receiver stations were more accurate, although even 3-receiver localisations were comparable with GPS localisations (∼10 m difference). Higher receiver stations detected the tag at longer distances.Future ATLAS users should consider the height of receivers, their spatial arrangement, density and the movement mode of the study species (e.g., ground-dwelling or flying). In conclusion, ATLAS provides an accurate, regional-scale alternative to global GPS-based tracking with which hundreds of relatively small-bodied species can be tracked simultaneously for long periods of time. Our study shows that ATLAS is a valid alternative, providing comparable location estimates to GPS.
The seasonal dynamics of bud dormancy in grapevine suggest a regulated checkpoint prior to acclimation
Authors: Velappan Yazhini , Chabikwa Tinashe G , Considine John A , Agudelo-Romero Patricia , Foyer Christine H , Signorelli Santiago , Considine Michael J 
Published: February 2021

ABSTRACTGrapevine (Vitis viniferaL.) displays wide plasticity to climate and seasonality, ranging from strongly deciduous to evergreen. Understanding the physiology of decisions to grow or quiesce is critical for improved crop management, prediction, and the adaptability of production to alternative climate scenarios. The perenniating bud (N+2) is a major economic unit and focus of study. Here we investigated the physiology and transcriptome of cv. Merlot buds grown in a temperate maritime climate from summer to spring in two consecutive years. The changes in bud respiration, hydration and internal tissue oxygen data were consistent with the transcriptome data. ABA-responsive gene processes prevailed upon the transition to a deep metabolic and cellular quiescence in the bud during autumn. Light, together with hypoxia and redox signalling presided over the resumption of nuclear and cellular growth in the transition to spring. Comparisons with transcriptome data from bud burst studies revealed a number of regulatory candidates for the orderly resumption of growth in spring, including components that may integrate light and temperature signalling. Importantly however, the bud burst forcing data, which is widely used as a measure of bud dormancy, were not consistent with the physiological and transcription data. We hypothesise the existence of a physiological checkpoint following bud set in summer, which if not met results in extreme quiescence. Collectively this is the most integrated developmental dataset of the latent bud of cultivated grapevine, and establishes a platform for systems approaches to study seasonal plasticity.One sentence summaryPhysiology and transcriptome data provide strong evidence of a regulatory checkpoint prior to acclimation and dormancy in latent grapevine buds.
New multiscale characterisation methodology for effective determination of isolation-structure-function relationship of extracellular vesicles
Authors: Phan Thanh Huyen , Divakarla Shiva Kamini , Yeo Jia Hao , Lei Qingyu , Tharkar Priyanka , Pansani Taisa Nogueira , Leslie Kathryn G. , Tong Maggie , Coleman Victoria A. , Jämting Åsa , Du Plessis Mar-Dean , New Elizabeth J. , Kalionis Bill , Demokritou Philip , Woo Hyun-Kyung , Cho Yoon-Kyoung , Chrzanowski Wojciech 
Published: February 2021

AbstractExtracellular vesicles (EVs) have been lauded as next generation medicines, but very few EV-based therapeutics have progressed to clinical use. Limited clinical translation is largely due to technical barriers that hamper our ability to mass-produce EVs,i.e.to isolate, purify and characterise them effectively. Technical limitations in comprehensive characterisation of EVs leads to unpredicted biological effects of EVs. Here, using a range of optical and non-optical techniques, we showed that the differences in molecular composition of EVs isolated using two isolation methods correlated with the differences in their biological function. Our results demonstrated that the isolation method determines the composition of isolated EVs at single and sub-population levels. Besides the composition, we measured for the first time the dry mass and predicted sedimentation of EVs. These parameters were shown to correlate well with the biological and functional effects of EVs on single cell and cell cultures. We anticipate that our new multiscale characterisation approach, which goes beyond traditional experimental methodology, will support fundamental understanding of EVs as well as elucidate the functional effects of EVs inin vitroandin vivostudies. Our findings and methodology will be pivotal for developing optimal isolation methods and establishing EVs as mainstream therapeutics and diagnostics. This innovative approach is applicable to a wide range of sectors including biopharma and biotechnology as well as to regulatory agencies.
Genome-wide prediction and integrative functional characterization of Alzheimer’s disease-associated genes
Authors: Lin Cui-Xiang , Li Hong-Dong , Deng Chao , Liu Weisheng , Erhardt Shannon , Wu Fang-Xiang , Zhao Xing-Ming , Wang Jun , Wang Daifeng , Hu Bin , Wang Jianxin 
Published: February 2021

AbstractThe mechanism of Alzheimer’s disease (AD) remains elusive, partly due to the incomplete identification of risk genes. We developed an approach to predict AD-associated genes by learning the functional pattern of curated AD-associated genes from brain gene networks. We created a pipeline to evaluate disease-gene association by interrogating heterogeneous biological networks at different molecular levels. Our analysis showed that top-ranked genes were functionally related to AD. We identified gene modules associated with AD pathways, and found that top-ranked genes were correlated with both neuropathological and clinical phenotypes of AD on independent datasets. We also identified potential causal variants for genes such asFYNandPRKAR1Aby integrating brain eQTL and ATAC-seq data. Lastly, we created the ALZLINK web interface, enabling users to exploit the functional relevance of predicted genes to AD. The predictions and pipeline could become a valuable resource to advance the identification of therapeutic targets for AD.
The biogenesis and function of nucleosome arrays
Authors: Singh Ashish Kumar , Schauer Tamás , Pfaller Lena , Straub Tobias , Mueller-Planitz Felix 
Published: February 2021

AbstractNumerous chromatin remodeling enzymes position nucleosomes in eukaryotic cells. Aside from these factors, transcription, DNA sequence, and statistical positioning of nucleosomes also shapes the nucleosome landscape. Precise contributions of these processes remain unclear due to their functional redundancyin vivo. By incisive genome engineering, we radically decreased their redundancy inSaccharomyces cerevisiae. The transcriptional machinery is strongly disruptive of evenly spaced nucleosomes, and proper nucleosome density and DNA sequence critical for their biogenesis. The INO80 remodeling complex spaces nucleosomesin vivoand positions the first nucleosome over genes in an H2A.Z-independent fashion. INO80 requires its Arp8 subunit but unexpectedly not the Nhp10 module for spacing. Spaced nucleosomes prevent cryptic transcription and protect cells against genotoxic stress such as DNA damage, recombination and transpositions. We derive a unifying model of the biogenesis of the nucleosome landscape and suggest that it evolved not only to regulate but also to protect the genome.
Spinal premotor interneurons controlling antagonistic muscles are spatially intermingled
Authors: Ronzano Remi , Skarlatou Sophie , Barriga Bianca K. , Bannatyne B. Anne , Bhumbra Gardave S. , Foster Joshua D. , Moore Jeffrey D. , Lancelin Camille , Pocratsky Amanda , Özyurt Mustafa Görkem , Smith Calvin C. , Todd Andrew J. , Maxwell David J. , Murray Andrew J. , Pfaff Samuel L. , Brownstone Robert M. , Zampieri Niccolò , Beato Marco 
Published: February 2021

AbstractElaborate behaviours are produced by tightly controlled flexor-extensor motor neuron activation patterns. Motor neurons are regulated by a network of interneurons within the spinal cord, but the computational processes involved in motor control are not fully understood. The neuroanatomical arrangement of motor and premotor neurons into topographic patterns related to their controlled muscles is thought to facilitate how information is processed by spinal circuits. Rabies retrograde monosynaptic tracing has been used to label premotor interneurons innervating specific motor neuron pools, with previous studies reporting topographic mediolateral positional biases in flexor and extensor premotor interneurons. To more precisely define how premotor interneurons contacting specific motor pools are organized we used multiple complementary viral-tracing approaches to minimize systematic biases associated with each method. Contrary to expectations, we found that premotor interneurons contacting motor pools controlling flexion and extension of the ankle are highly intermingled rather than segregated into specific domains like motor neurons. Thus, premotor spinal neurons controlling different muscles process motor instructions in the absence of clear spatial patterns among the flexor-extensor circuit components.The paper can be downloaded in executable format as a MATLAB live script fromhttps://github.com/marcobeato/Spinal_premotor_interneurons_controlling_antagonistic_muscles_are_spatially_intermingled, where all the data are available An R version of the executable paper is available athttps://mybinder.org/v2/gh/rronzano/Spinal_premotor_interneurons_controlling_antagonistic_muscles_are_spatially_intermingled.git/HEAD?urlpath=rstudio
Rapid genomic convergent evolution in experimental populations of Trinidadian guppies (Poecilia reticulata)
Authors: van der Zee Mijke J. , Whiting James R. , Paris Josephine R. , Bassar Ron D. , Travis Joseph , Weigel Detlef , Reznick David N. , Fraser Bonnie A. 
Published: February 2021

ABSTRACTIt is now accepted that phenotypic evolution can occur quickly but the genetic basis of rapid adaptation to natural environments is largely unknown in multicellular organisms. Population genomic studies of experimental populations of Trinidadian guppies (Poecilia reticulata) provide a unique opportunity to study this phenomenon. Guppy populations that were transplanted from high-predation (HP) to low-predation (LP) environments have been shown to mimic naturally-colonised LP populations phenotypically in as few as 8 generations. The new phenotypes persist in subsequent generations in lab environments, indicating their high heritability. Here, we compared whole genome variation in four populations recently introduced into LP sites along with the corresponding HP source population. We examined genome-wide patterns of genetic variation to estimate past demography, and uncovered signatures of selection with a combination of genome scans and a novel multivariate approach based on allele frequency change vectors. We were able to identify a limited number of candidate loci for convergent evolution across the genome. In particular, we found a region on chromosome 15 under strong selection in three of the four populations, with our multivariate approach revealing subtle parallel changes in allele frequency in all four populations across this region. Investigating patterns of genome-wide selection in this uniquely replicated experiment offers remarkable insight into the mechanisms underlying rapid adaptation, providing a basis for comparison with other species and populations experiencing rapidly changing environments.IMPACT STATEMENTThe genetic basis of rapid adaptation to new environments is largely unknown. Here we take advantage of a unique replicated experiment in the wild, where guppies from a high predation source were introduced into four low predation localities. Previous reports document census size fluctuations and rapid phenotypic evolution in these populations. We used genome-wide sequencing to understand past demography and selection. We detected clear signals of population growth and bottlenecks at the genome-wide level matching known census population data changes. We then identified candidate regions of selection across the genome, some of which were shared between populations. In particular, using a novel multivariate method, we identified parallel allele frequency change at a strong candidate locus for adaptation to low predation. These results and methods will be of use to those studying evolution at a recent, ecological timescale.
Cutevariant: a GUI-based desktop application to explore genetics variations
Authors: Schutz Sacha , Marijon Pierre , Montier Tristan , Genin Emmanuelle 
Published: February 2021

AbstractCutevariant is a user-friendly GUI based desktop application for genomic research designed to search for variations in DNA samples collected in annotated files and encoded in the Variant Calling Format. The application imports data into a local relational database wherefrom complex filter-queries can be built either from the intuitive GUI or using a Domain Specific Language (DSL). Cutevariant provides more features than any existing applications without compromising on performance. The plugin based architecture provides highly customizable features. Cutevariant is distributed as a multiplatform client-side software under an open source licence and is available athttps://github.com/labsquare/Cutevariant. It has been designed from the beginning to be easily adopted by IT-agnostic end-users.