bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide selection inference at short tandem repeats
Authors: Huang Bonnie , Durvasula Arun , Mousavi Nima , Ziaei-Jam Helyaneh , Maksimov Mikhail , Lohmueller Kirk E. , Gymrek Melissa 
Published: May 2022

AbstractShort tandem repeats (STRs) comprising repeated sequences of 1-6 bp are one of the largest sources of genetic variation in humans. STRs are known to contribute to a variety of disorders, including Mendelian diseases, complex traits, and cancer. Based on their functional importance, mutations at some STRs are likely to introduce negative effects on reproductive fitness over evolutionary time. We previously developed SISTR (Selection Inference at STRs), a population genetics framework to measure negative selection against individual STR alleles. Here, we extend SISTR to enable joint estimation of the distribution of selection coefficients across a set of STRs. This method (SISTR2) allows for more accurate analysis of a broader range of STRs, including loci with low mutation rates. We apply SISTR2 to explore the range of feasible mutation parameters and demonstrate substantial variation in mutation and selection parameters across different classes of STRs. Finally, we show that de novo STR mutations tend to confer a greater selective burden compared to standing STR variation in the population and measure the relative burden of STRs vs. single nucleotide variants in a typical genome. Overall, we anticipate that the evolutionary insights gained from this study will be important for future studies of variation at STRs and their role in evolution and disease.
Photoperiod and vernalization alleles and their combinations greatly affected phenological and agronomic traits in bread wheat under autumn and spring sowing conditions
Authors: Amo Aduragbemi , Serikbay Dauren , Song Luxing , Chen Liang , Hu Yin-Gang 
Published: May 2022

AbstractThe responses to temperature (vernalization) and day length (photoperiod) in wheat (Triticum aestivum L.) are entirely defined by allelic differences at the respective VRN-1 and PPD-1 loci. These two physiological factor greatly affect wheat phenology. Using molecular markers, a panel of 61 diverse bread wheat varieties were genotyped for VRN-1 and PPD-1 alleles, and the traits were evaluated under autumn and spring sowing conditions to investigate the impact of the alleles and their combinations on phenological stage, morphological traits, and yield traits. The results revealed that the earlier heading (HD), and flowering (FD) conferred by insensitive alleles for VRN-1 and PPD-1 genes was consistent regardless of the variation under the two sowing conditions. The effects of a single dominant allele of VRN-1 were similar, with an additive effects when combined. The effects of a single PPD-1 insensitive allele differed, with Ppd-D1a stronger than Ppd-B1a, and Ppd-A1a was the least, with an additive effects when combined. Secondly, varieties sown under spring condition recorded a larger flag leaf area when compared to those sown under autumn condition regardless of the single and combined influence at the VRN-1 and PPD-1 loci. When compared to other genes, PPD-D1 had a consistent and significant effect on flag leaf area, spike length, and plant height across both sowing conditions. Furthermore, the sensitive allele Ppd-D1b had larger biomass across both sowing conditions, but this did not translate into increased yield because the Ppd-D1a insensitive allele recorded higher yield. The impact of PPD-D1 gene on grain yield was evident across both sowing conditions. Overall, according to the findings of this study, VRN-1 and PPD-1 genes impact in modulating phenology stages, morphological, spike and yield traits was dependent on the sowing conditions and also on genetic background with the spring and insensitive alleles poised to be favored for selection.
Environmental selection, rather than neutral processes, best explain patterns of diversity in a tropical rainforest fish
Authors: Gates Katie , Sandoval-Castillo Jonathan , Brauer Chris J. , Unmack Peter J. , Laporte Martin , Bernatchez Louis , Beheregaray Luciano B. 
Published: May 2022

AbstractTo conserve the high functional and genetic variation in hotspots such as tropical rainforests, it is essential to understand the forces driving and maintaining biodiversity. We asked to what extent environmental gradients and terrain structure affect morphological and genomic variation across the wet tropical distribution of an Australian rainbowfish, Melanotaenia splendida splendida. We used an integrative riverscape genomics and morphometrics framework to assess the influence of these factors on both putative adaptive and non-adaptive spatial divergence. We found that neutral genetic population structure was largely explainable by restricted gene flow among drainages. However, environmental associations revealed that ecological variables had a similar power to explain overall genetic variation, and greater power to explain body shape variation, than the included neutral covariables. Hydrological and thermal variables were the best environmental predictors and were correlated with traits previously linked to heritable habitat-associated dimorphism in rainbowfishes. Additionally, climate-associated genetic variation was significantly associated with morphology, supporting heritability of shape variation. These results support the inference of evolved functional differences among localities, and the importance of hydroclimate in early stages of diversification. We expect that substantial evolutionary responses will be required in tropical rainforest endemics to mitigate local fitness losses due to changing climates.
Detection of Borrelia garinii in the USA
Authors: Rudenko Natalie , Golovchenko Maryna , Horak Ales , Grubhoffer Libor , Mongodin Emmanuel F. , Fraser Claire M. , Qiu Weigang , Luft Benjamin J. , Morgan Richard G. , Casjens Sherwood R. , Schutzer Steven E. 
Published: May 2022

AbstractBorrelia garinii, is a cause of Lyme disease in Europe and Asia. For the first time, we report it in the southeastern United States in rodents. Whole genome sequencing and phylogenetic analysis revealed that USA-located B. garinii is part of a clade consisting primarily of few European and majority of Far Eastern strains. Continued surveillance of wildlife hosts and ticks is necessary to assess the ecological status and public health risks of B. garinii in southeastern US.
Ecological Drivers of Community Cohesion
Authors: Gokhale Chaitanya S. , Velasque Mariana , Denton Jai A. 
Published: May 2022

AbstractFrom protocellular to societal, networks of living systems are complex and multi-scale. The assembly of these intricate interdependencies, under ecological pressures, can be nearly impossible to understand using pairwise methods. We develop a mathematical and computational model based on a four-strain Saccharomyces cerevisiae synthetic inter-dependent system. Our system leverages transiently structured ecologies for achieving community cohesion. We show how ecological interventions could reverse or slow the extinction rate of a cohesive community. An interconnected system first needs to persist long enough to be a subject of natural selection. Our emulation of Darwin’s warm little ponds’ with an ecology governed by transient compartmentalisation provides the necessary persistence. Our results find utility across scales of organisation, stressing the importance of cyclic processes in major evolutionary transitions engineering of synthetic microbial consortia and conservation biology.
3D Chromatin Structure in Chondrocytes Identifies Putative Osteoarthritis Risk Genes
Authors: Thulson Eliza , Davis Eric S. , D’Costa Susan , Coryell Philip R. , Kramer Nicole E. , Mohlke Karen L. , Loeser Richard F. , Diekman Brian O. , Phanstiel Douglas H. 
Published: May 2022

ABSTRACTGenome-wide association studies (GWAS) have identified over 100 loci associated with osteoarthrtis (OA) risk, but the majority of OA risk variants are non-coding, making it difficult to identify the impacted genes for further study and therapeutic development. To address this need, we used a multi-omic approach and genome editing to identify and functionally characterize potential OA risk genes. Computational analysis of GWAS and ChIP-seq data revealed that chondrocyte regulatory loci are enriched for OA risk variants. We constructed a chondrocyte specific regulatory network by mapping 3D chromatin structure and active enhancers in human chondrocytes. We then intersected these data with our previously collected RNA-seq dataset of chondrocytes responding to fibronectin fragment (FN-f), a known OA trigger. Integration of the three genomic datasets with recently reported OA GWAS variants revealed a refined set of putative causal OA variants and their potential target genes. One of the novel putative target genes identified wasSOCS2, which was connected to a putative causal variant by a 170 Kb loop and is differentially regulated in response to FN-f. CRISPR-Cas9-mediated deletion ofSOCS2in primary human chondrocytes from three independent donors led to heightened expression of inflammatory markers after FN-f treatment. These data suggest thatSOCS2plays a role in resolving inflammation in response to cartilage matrix damage and provides a possible mechanistic explanation for its influence on OA risk. In total, we identified 56 unique putative OA risk genes for further research and potential therapeutic development.
Whole-brain computation of cognitive versus acoustic errors in music
Authors: Bonetti L. , Carlomagno F. , Kliuchko M. , Gold B.P. , Palva S. , Haumann N.T. , Tervaniemi M. , Huotilainen M. , Vuust P. , Brattico E. 
Published: May 2022

ABSTRACTPrevious studies have evidenced how the local prediction of physical stimulus features may affect the neural processing of incoming stimuli. Less known are the effects of cognitive priors on predictive processes, and how the brain computes local versus cognitive predictions and their errors. Here, we determined the differential brain mechanisms underlying prediction errors related to high-level, cognitive priors for melody (rhythm, contour) versus low-level, local acoustic priors (tuning, timbre). We measured with magnetoencephalography the mismatch negativity (MMN) prediction error signal in 104 adults having varying levels of musical expertise. We discovered that the brain regions involved in predictive processes for local priors were primary and secondary auditory cortex and insula, whereas cognitive brain regions such as cingulate and orbitofrontal cortices were recruited for melodic errors in cognitive priors. The involvement of higher-level brain regions for computing cognitive errors was enhanced in musicians, especially in cingulate cortex, inferior frontal gyri, and supplementary motor area. Overall, the findings expand knowledge on whole-brain mechanisms of predictive processing and the related MMN generators, previously mainly confined to the auditory cortex, to a frontal network that strictly depends on the type of priors that are to be computed by the brain.
Genetic diversity varies with species traits and latitude in predatory soil arthropods (Myriapoda: Chilopoda)
Authors: Bharti D. K. , Pawar Pooja Yashwant , Edgecombe Gregory D. , Joshi Jahnavi 
Published: May 2022

AbstractAimTo investigate the drivers of intra-specific genetic diversity in centipedes, a group of ancient predatory soil arthropods.LocationGlobalTime periodPresentMajor taxa studiedCentipedes (Class: Chilopoda)MethodsWe assembled a database of over 1200 mitochondrial cytochrome c oxidase subunit I sequences representing 120 centipede species from all five orders of Chilopoda. We used this sequence dataset to estimate genetic diversity for centipede species and compared its distribution with estimates from other arthropod groups. We studied the variation in centipede genetic diversity with species traits and biogeography using a beta regression framework, controlling for the effect of shared evolutionary history within a family.ResultsWe observed a wide variation in genetic diversity across centipede species (0 to 0.1713), which falls towards the higher end of values among arthropods. Overall, 21.51% of the variation in mitochondrial COI genetic diversity in centipedes was explained by a combination of predictors related to life history and biogeography. Genetic diversity decreased with body size and latitudinal position of sampled localities, was greater in species showing maternal care and increased with geographic distance among conspecifics.Main conclusionsCentipedes fall towards the higher end of genetic diversity among arthropods, which may be related to their long evolutionary history and low dispersal ability. In centipedes, the negative association of body size with genetic diversity may be mediated by its influence on local abundance or the influence of ecological strategy on long-term population history. Species with maternal care had higher genetic diversity, which goes against our expectations and needs further scrutiny. Hemispheric differences in genetic diversity can be due to historic climatic stability and lower seasonality in the southern hemisphere. Overall, we find that despite the differences in mean genetic diversity among animals, similar processes related to life history strategy and biogeography shape the variation within them.
Myeloid cell evolution uncovered by shrimp immune cell analysis at single-cell resolution
Authors: Yang Peng , Chen Yaohui , Huang Zhiqi , Xia Huidan , Cheng Ling , Wu Hao , Zhang Yueling , Wang Fan 
Published: May 2022

AbstractHow myeloid cells evolved from invertebrate to vertebrate is still a mystery. Here we collected circulating hemocytes from a marine invertebrate-Penaeus vannamei via gradient centrifugation and identified prohemocyte, monocytic hemocyte and granulocyte as three major types of cells in shrimp hemolymph by single-cell mRNA sequencing. Additional pseudotime trajectory analysis revealed that shrimp monocytic hemocytes and granulocytes were differentiated from a common progenitor which was similar with that of human myeloid cells. More interestingly, we identified that MH2, a terminal differentiated monocytic hemocyte, was a macrophage-like phagocytic cell which could engulf fluorescein labelled Vibrio parahaemolyticus and shared nine marker genes including inflammasome components Nlrp3 and Casp1 with human macrophage. After that, we compared our classification with traditional shrimp hemocytes classification and found that hyalinocyte included both prohemocyte and monocytic hemocyte while semi-granulocyte included both monocytic hemocyte and granulocyte. In general, our results redefine shrimp hemocyte classification based on functional marker genes and unveil evolutionary trace of myeloid cells in marine invertebrate.
Stronger sexual dimorphism in fruit flies may be favored when congeners are present and females actively search for mates
Authors: Hippee Alaine C. , Beer Marc A. , Norrbom Allen L. , Forbes Andrew A. 
Published: May 2022

AbstractWhy are some species sexually dimorphic while other closely related species are not? When the degree of sexual dimorphism varies within a genus, an integrative phylogenetic approach may help reveal underlying patterns favoring the evolution of dimorphism. While all female flies in genus Strauzia – a genus of true fruit flies – share a multiply-banded wing pattern, males of four species have patterns wherein bands have “coalesced” into a continuous dark streak across much of the wing. We find that the origin of coalesced male wing patterns and pronounced differences in male wing shape correlate with the presumed origin of host plant sharing in this genus. A survey of North American Tephritidae finds just three other genera with specialist species that share host plants. Each has one or more congeners with wing patterns unusual for that genus, and just one genus, Eutreta, has those unusual wing patterns only in the male sex. Eutreta is also the only other genus among this subset wherein, like Strauzia, males hold territories while females search for mates. Sharing the same hosts may result in reproductive character displacement, and when coupled with a biology wherein females actively search for males, may specifically favor sexually dimorphic wing patterns.
MCell4 with BioNetGen: A Monte Carlo Simulator of Rule-Based Reaction-Diffusion Systems with Python Interface
Authors: Husar Adam , Ordyan Mariam , Garcia Guadalupe C. , Yancey Joel G. , Saglam Ali S. , Faeder James R. , Bartol Thomas M. , Kennedy Mary B. , Sejnowski Terrence J. 
Published: May 2022

AbstractBiochemical signaling pathways in living cells are often highly organized into spatially segregated volumes, membranes, scaffolds, subcellular compartments, and organelles comprising small numbers of interacting molecules. At this level of granularity stochastic behavior dominates, well-mixed continuum approximations based on concentrations break down and a particle-based approach is more accurate and more efficient. We describe and validate a new version of the open-source MCell simulation program (MCell4), which supports generalized 3D Monte Carlo modeling of diffusion and chemical reaction of discrete molecules and macromolecular complexes in solution, on surfaces representing membranes, and combinations thereof. The main improvements in MCell4 compared to the previous versions, MCell3 and MCell3-R, include a Python interface and native BioNetGen reaction language (BNGL) support. MCell4’s Python interface opens up completely new possibilities for interfacing with external simulators to allow creation of sophisticated event-driven multiscale/multiphysics simulations. The native BNGL support, implemented through a new open-source library libBNG (also introduced in this paper), provides the capability to run a given BNGL model spatially resolved in MCell4 and, with appropriate simplifying assumptions, also in the BioNetGen simulation environment, greatly accelerating and simplifying model validation and comparison.
Between heuristics and optimality: Flexible integration of cost and evidence during information sampling
Authors: Hsiung Abigail , Pearson John M. , Poh Jia-Hou , Hakimi Shabnam , Adcock R. Alison , Huettel Scott A. 
Published: May 2022

AbstractEffective decision making in an uncertain world requires balancing the benefits of acquiring relevant information with the costs of delaying choice. Optimal strategies for information sampling can be accurate but computationally expensive, whereas heuristic strategies are often computationally simple but rigid. To characterize the computations that underlie information sampling, we examined choice processes in human participants who sampled sequences of images (e.g. indoor and outdoor scenes) and attempted to infer the majority category (e.g. indoor or outdoor) under two reward conditions. We examined how behavior maps onto potential information sampling strategies. We found that choices were best described by a flexible function that lay between optimality and heuristics; integrating the magnitude of evidence favoring each category and the number of samples collected thus far. Integration of these criteria resulted in a trade-off between evidence and samples collected, in which the strength of evidence needed to stop sampling decreased linearly as the number of samples accumulated over the course of a trial. This non-optimal trade-off best accounted for choice behavior even under high reward contexts. Our results demonstrate that unlike the optimal strategy, humans are performing simple accumulations instead of computing expected values, and that unlike a simple heuristic strategy, humans are dynamically integrating multiple sources of information in lieu of using only one source. This evidence-by-costs tradeoff illustrates a computationally efficient strategy that balances competing motivations for accuracy and cost minimization.
A dynamic HIF1α- PPARγ circuit controls a paradoxical adipocyte regulatory landscape
Authors: Kudo Takamasa , Zhao Michael L. , Kovary Kyle , LaGory Edward L. , Covert Markus W. , Teruel Mary N. 
Published: May 2022

AbstractHypoxia-induced upregulation of HIF1α triggers adipose tissue dysfunction and insulin resistance in obese patients. HIF1α closely interacts with PPARγ, the master regulator of adipocyte differentiation and lipid accumulation, but there are conflicting results how this co-regulation controls the excessive lipid accumulation that drives adipocyte dysfunction. Using single-cell imaging and modeling, we find that, surprisingly, HIF1α both promotes and represses lipid accumulation during adipogenesis. We show that the opposing roles of HIF1α are isolated from each other and depend on when HIF1α increases relative to the positive-feedback mediated upregulation of PPARγ that drives adipocyte differentiation. A theoretical model incorporating our findings resolves conflicting prior results and suggests that three network nodes before and after the isolation step have to be synergistically targeted in therapeutic strategies to revert hypoxia-mediated adipose tissue dysfunction in obesity.TeaserA systems biology approach detangles the effect of hypoxic and adipogenic regulators on lipid accumulation in adipocytes.
Trait-dependent diversification in angiosperms: patterns, models and data
Authors: Helmstetter Andrew J. , Zenil-Ferguson Rosana , Sauquet Hervé , Otto Sarah P. , Méndez Marcos , Vallejo-Marin Mario , Schönenberger Jürg , Burgarella Concetta , Anderson Bruce , de Boer Hugo , Glémin Sylvain , Käfer Jos 
Published: May 2022

AbstractVariation in species richness across the tree of life, accompanied by the incredible variety of ecological and morphological characteristics found in nature, has inspired many studies to link traits with species diversification. Angiosperms are a highly diverse group that has fundamentally shaped life on earth since the Cretaceous, and illustrate how species diversification affects ecosystem functioning. Numerous traits and processes have been linked to differences in species richness within this group, but we know little about how these interact and their relative importance. Here, we synthesized data from 152 studies that used state-dependent speciation and extinction (SSE) models on angiosperm clades. Intrinsic traits related to reproduction and morphology were often linked to diversification but a set of universal drivers did not emerge as traits did not have consistent effects across clades. Importantly, dataset properties were correlated to SSE model results - trees that were larger, older, or less well-sampled tended to yield trait-dependent outcomes. We compared these properties to recommendations for SSE model use and provide a set of best practices to follow when designing studies and reporting results. Finally, we argue that SSE model inferences should be considered in a larger context incorporating species’ ecology, demography and genetics.