bluuebunny/crossref_metadata_2025_split huggingface dataset:
The predictability of genomic changes underlying a recent host shift in Melissa blue butterflies
Authors: Chaturvedi Samridhi , Lucas Lauren K. , Nice Chris C. , Fordyce James A. , Forister Matthew L. , Gompert Zachariah 
Published: November 2017

AbstractDespite accumulating evidence that evolution can be predictable, studies quantifying the predictability of evolution remain rare. Here, we measured the predictability of genome-wide evolutionary changes associated with a recent host shift in the Melissa blue butterfly (Lycaeides melissa). We asked whether and to what extent genome-wide patterns of evolutionary change in nature could be predicted (1) by comparisons among instances of repeated evolution, and (2) from SNP × performance associations in a lab experiment. We delineated the genetic loci (SNPs) most strongly associated with host use in twoL. melissalineages that colonized alfalfa. Whereas most SNPs were strongly associated with host use in none or one of these lineages, we detected a ~two-fold excess of SNPs associated with host use in both lineages. Similarly, we found that host-associated SNPs in nature could also be partially predicted from SNP × performance (survival and weight) associations in a lab rearing experiment. But the extent of overlap, and thus degree of predictability, was somewhat reduced. Although we were able to predict (to a modest extent) the SNPs most strongly associated with host use in nature (in terms of parallelism and from the experiment), we had little to no ability to predict the direction of evolutionary change during the colonization of alfalfa. Our results show that different aspects of evolution associated with recent adaptation can be more or less predictable, and highlight how stochastic and deterministic processes interact to drive patterns of genome-wide evolutionary change.
What can an evolutionary perspective on women’s health provide to the current public health paradigm? A case study on redefining thyroid cancer as a reproductive cancer
Authors: Fraser Abby 
Published: November 2017

AbstractIncidence rates of non-communicable diseases in women are increasing worldwide and now contributing more to mortality and morbidity than reproductive health. Despite this universal trend, there is no recognition by the WHO of this phenomenon in women’s health. Additionally, thyroid cancer is considered a non-sex specific cancer despite female incidence rates being triple those of males. To understand why there are such conceptual limitations to women’s health, biomedicine - and its prevalence in western public health authorities - will be analysed from an anthropological perspective. In mind of these conceptual limitations, insights from evolutionary perspectives on health are introduced as well as how they may alleviate the conceptual barriers in the current biomedical paradigm. Using the example of breast cancer, the difference between a reproductive cancer in women, and cancer located in the reproductive tract will be explored. From this, the possibility that a cancer outside the reproductive tract can be directly influenced by reproductive function is explored in the specific case of thyroid cancer. Thyroid cancer and current public health approaches to preventing malignancies of the thyroid are examined to show the limitations of their scope. Furthermore, evidence supporting the direct link between thyroid function and reproductive function is presented. Current academic studies into the link between thyroid cancer and women’s reproductive function are analysed to show they are subject to the same conceptual limitations of women’s reproductive function as found previously in biomedicine. To conclude, I will introduce a new hypothesis for exploring the impact of women’s reproductive function on thyroid cancer incidence rates. This hypothesis will allow women’s health to be viewed holistically, and allows reproductive function to be investigated beyond parity. Thus, the conceptual limitations of women’s health in the public health paradigm will be alleviated.
Recovery of gene haplotypes from a metagenome
Authors: Nicholls Samuel M. , Aubrey Wayne , Edwards Arwyn , Grave Kurt de , Huws Sharon , Schietgat Leander , Soares André , Creevey Christopher J. , Clare Amanda 
Published: November 2017

AbstractElucidation of population-level diversity of microbiomes is a significant step towards a complete understanding of the evolutionary, ecological and functional importance of microbial communities. Characterizing this diversity requires the recovery of the exact DNA sequence (haplotype) of each gene isoform from every individual present in the community. To address this, we present Hansel and Gretel: a freely-available data structure and algorithm, providing a software package that reconstructs the most likely haplotypes from metagenomes. We demonstrate recovery of haplotypes from short-read Illumina data for a bovine rumen microbiome, and verify our predictions are 100% accurate with long-read PacBio CCS sequencing. We show that Gretel’s haplotypes can be analyzed to determine a significant difference in mutation rates between core and accessory gene families in an ovine rumen microbiome. All tools, documentation and data for evaluation are open source and available via our repository: https://github.com/samstudio8/gretel
Genomic insights into the domestication of the chocolate tree,Theobroma cacaoL
Authors: Cornejo Omar E. , Yee Muh-Ching , Dominguez Victor , Andrews Mary , Sockell Alexandra , Strandberg Erika , Livingstone Donald , Stack Conrad , Romero Alberto , Umaharan Pathmanathan , Royaert Stefan , Tawari Nilesh R. , Pauline Ng , Schnell Ray , Phillips Wilbert , Mockaitis Keithanne , Bustamante Carlos D. , Motamayor Juan C. 
Published: November 2017

AbstractDomestication has had a strong impact on the development of modern societies. We sequenced 200 genomes of the chocolate plantTheobroma cacaoL. to show for the first time that a single population underwent strong domestication approximately 3,600 years (95% CI: 2481 – 10,903 years ago) ago, the Criollo population. We also show that during the process of domestication, there was strong selection for genes involved in the metabolism of the colored protectants anthocyanins and the stimulant theobromine, as well as disease resistance genes. Our analyses show that domesticated populations ofT. cacao(Criollo) maintain a higher proportion of high frequency deleterious mutations. We also show for the first time the negative consequences the increase accumulation of deleterious mutations during domestication on the fitness of individuals (significant negative correlation between Criollo ancestry and Kg of beans per hectare per year, P = 0.000425).
Epigenome-wide association in adipose tissue from the METSIM cohort
Authors: Orozco Luz D. , Farrell Colin , Hale Christopher , Rbi Liudmilla , Rinaldi Arturo , Civelek Mete , Pan Calvin , Lam Larry , Montoya Dennis , Edillor Chantle , Seldin Marcus , Mohlke Karen L , Jacobsen Steve , Kuusisto Johanna , Laakso Markku , Lusis Aldons J , Pellegrinil Matteo 
Published: November 2017

ABSTRACTMost epigenome-wide association studies to date have been conducted in blood. However, metabolic syndrome is mediated by a dysregulation of adiposity and therefore it is critical to study adipose tissue in order to understand the effects of this syndrome on epigenomes. To determine if natural variation in DNA methylation was associated with metabolic syndrome traits, we profiled global methylation levels in subcutaneous abdominal adipose tissue. We measured association between 32 clinical traits related to diabetes and obesity in 201 people from the Metabolic Syndrome In Men cohort. We performed epigenome-wide association studies between DNA methylation levels and traits, and identified associations for 13 clinical traits in 21 loci. We prioritized candidate genes in these loci using eQTL, and identified 18 high confidence candidate genes, including known and novel genes associated with diabetes and obesity traits. Using methylation deconvolution, we examined which cell types may be mediating the associations, and concluded that most of the loci we identified were specific to adipocytes. We determined whether the abundance of cell types varies with metabolic traits, and found that macrophages increased in abundance with the severity of metabolic syndrome traits. Finally, we developed a DNA methylation based biomarker to assess type II diabetes risk in adipose tissue. In conclusion, our results demonstrate that profiling DNA methylation in adipose tissue is a powerful tool for understanding the molecular effects of metabolic syndrome on adipose tissue, and can be used in conjunction with traditional genetic analyses to further characterize this disorder.
Genome-wide detection of genes under positive selection in worldwide populations of the barley scald pathogen
Authors: Mohd-Assaad Norfarhan , McDonald Bruce A. , Croll Daniel 
Published: November 2017

AbstractThe coevolution between hosts and pathogens generates strong selection pressures to maintain resistance and infectivity, respectively. Genomes of plant pathogens often encode major effect loci for the ability to successfully infect a specific host. Hence, heterogeneity in the host genotypes and abiotic factors leads to locally adapted pathogen populations. However, the genetic basis of local adaptation is poorly understood. We analyzed global field populations of Rhynchosporium commune, the pathogen causing barley scald disease, to identify candidate genes for local adaptation. Whole genome sequencing data generated for 125 isolates showed that the pathogen is subdivided into three genetic clusters associated with distinct geographic and climatic regions. Using haplotype-based selection scans applied independently to each genetic cluster, we found strong evidence for selective sweeps throughout the genome. Comparisons of loci under selection among clusters revealed little overlap, suggesting that ecological differences associated with each cluster led to variable selection regimes. The strongest signals of selection were found predominantly in the two clusters composed of isolates from Central Europe and Ethiopia. The strongest selective sweep regions encoded proteins with functions related to both biotic and abiotic stresses. We found that selective sweep regions were enriched in genes encoding functions in cellular localization, protein transport activity, and DNA damage responses. In contrast to the prevailing view that a small number of gene-for-gene interactions govern plant pathogen evolution, our analyses suggest that the evolutionary trajectory is largely determined by spatially heterogeneous biotic and abiotic selection pressures.
Developing a low-cost milliliter-scale chemostat array for precise control of cellular growth
Authors: Skelding David , Hart Sam , Vidyasagar Thejas , Pozhitkov Alexander E. , Shou Wenying 
Published: November 2017

AbstractMultiplexed milliliter-scale chemostats are useful for measuring cell physiology under various degrees of nutrient limitation and for experimental evolution. In each chemostat, fresh medium containing a growth rate-limiting metabolite is pumped into the culturing chamber at a constant rate, while culture effluent exits at an equal rate. Although such devices have been developed by various labs, key parameters - the accuracy and precision of flow rate and the operational range - are not explicitly characterized. Here we report the development of multiplexed milliliter-scale chemostats where flow rates for eight chambers can be independently controlled to vary within a wide range, corresponding to population doubling times of 3~ 13 hours. Importantly, flow rates are precise and accurate without the use of expensive feedback systems. Among the eight chambers, the maximal coefficient of variation in flow rate is less than 3%, and average flow rates are only slightly below targets,i.e., 3-6% for 13-hour and 0.6-1.0% for 3-hour doubling times. This deficit is largely due to evaporation and should be correctable. We experimentally demonstrate that our device allows accurate and precise quantification of population phenotypes.
Architecture of human interphase chromosome determines the spatiotemporal dynamics of chromatin loci
Authors: Liu Lei , Shi Guang , Thirumalai D. , Hyeon Changbong 
Published: November 2017

By incorporating the information of human chromosome inferred from Hi-C experiments into a heteropolymer model of chromatin chain, we generate a conformational ensemble to investigate its spatiotemporal dynamics. The heterogeneous loci interactions result in hierarchical organization of chromatin chain, which obeys compact space-filling (SF) statistics at intermediate length scale. Remarkably, the higher order architecture of the chromatin, characterized by the single universal Flory exponent (ν= 1/3) for condensed homopolymers, provides quantitative account of the dynamical properties of the chromosome. The local chromosome structures, exemplified by topologically associated domains (~ 0.1 − 1 Mb), display dynamics with fast relaxation time (≲ 50 sec), whereas the long-range spatial reorganization of the entire chromatinoccurs on a much longer time scale (≳ hour), suggestive of glass-like behavior. This key finding provides the dynamic basis of cell-to-cell variability. Active forces, modeled using stronger isotropic white noises, accelerate the relaxation dynamics of chromatin domain described by the low frequency modes. Surprisingly, they do not significantly change the local scale dynamics from those under passive condition. By linking the spatiotemporal dynamics of chromosome with its organization, our study highlights the importance of physical constraints in chromosome architecture on the sluggish dynamics.Significance StatementChromosomes are giant chain molecules made of hundreds of megabase-long DNA intercalated with proteins. Structure and dynamics of interphase chromatin in space and time hold the key to understanding the cell type-dependent gene regulation. In this study, we establish that the crumpled and space-filling organization of chromatin fiber in the chromosome territory, characterized by a single universal exponent used to describe polymer sizes, is sufficient to explain the complex spatiotemporal hierarchy in chromatin dynamics as well as the subdiffusive motion of the chromatin loci. While seemingly a daunting problem at a first glance, our study shows that relatively simple principles, rooted in polymer physics, can be used to grasp the essence of dynamical properties of the interphase chromatin.
BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous cell carcinoma
Authors: Lazarus Kyren A. , Hadi Fazal , Zambon Elisabetta , Bach Karsten , Santolla Maria-Francesca , Watson Julie K. , Correia Lucia L. , Das Madhumita , Ugur Rosemary , Pensa Sara , Becker Lukas , Campos Lia S. , Ladds Graham , Liu Pentao , Evan Gerard , McCaughan Frank , Le Quesne John , Lee Joo-Hyeon , Calado Dinis , Khaled Walid T. 
Published: November 2017

AbstractPatients diagnosed with lung squamous cell carcinoma (LUSC) have limited targeted therapeutic options. We report here the identification and characterisation of the transcriptional regulator,BCL11A, as a LUSC oncogene. Analysis of cancer genomics datasets revealedBCL11Ato be upregulated in LUSC but not lung adenocarcinoma (LUAD). We demonstrated that knockdown ofBCL11Ain LUSC cell lines abolished xenograft tumour growth and its overexpressionin vivoled to lung airway hyperplasia and the development of reserve cell hyperplastic lesions. In addition, deletion ofBcl11ain the tracheal basal cells abolished the development of tracheosphere organoids while its overexpression led to solid tracheospheres with a squamous phenotype. At the molecular level we foundBCL11Ato be a target of SOX2 and we show that it is required for the oncogenic role of SOX2 in LUSC. Furthermore, we showed thatBCL11Aand SOX2 interact at the protein level and that together they co-regulated the expression of several transcription factors. We demonstrate that pharmacological inhibition of SETD8, a gene co-regulated by BCL11A and SOX2, alone or in combination with cisplatin treatment, shows significant selectivity to LUSC in comparison to LUAD cells. Collectively, these results indicate that the disruption of the BCL11A-SOX2 transcriptional program provides a future framework for the development of targeted therapeutic intervention for LUSC patients.
Evaluation of anti insulin receptor antibodies as potential novel therapies for human insulin receptoropathy
Authors: Brierley Gemma. V. , Siddle Kenneth. , Semple Robert. K. 
Published: November 2017

AbstractBiallelic loss-of-function mutations in the insulin receptor (INSR) commonly cause extreme insulin resistance and early mortality. Therapeutic options are limited, but anti-INSR antibodies have previously been shown to activate two mutant receptors. This study evaluated four murine anti-INSR monoclonal antibodies, each capable of stimulating wildtype INSR signaling, against ten known pathogenic INSR mutants and one novel mutation, F248C. All the mutant INSR bound antibody. Eight mutants showed antibody-induced autophosphorylation while co-treatment with antibody and insulin increased maximal phosphorylation. After simultaneous knockdown of mouse Insr and expression of mutant INSR in 3T3-L1 adipocytes two antibodies activated signalingviaAKT preferentially over signaling via ERK1/2 for seven mutants. Two antibodies (83-7 and 83-14) stimulated glucose uptakeviaP193L, S323L, F382V, and D707A mutant INSR, with antibody response greater than insulin response for D707A. These findings suggest that selected monoclonal anti-INSR antibodies elicit sufficient signaling by some mutated INSR to be clinically significant.One sentence summaryAnti-insulin receptor monoclonal antibodies can activate selected naturally occurring mutated human insulin receptors, raising the prospect of novel therapy for lethal recessive insulin resistance.
Magnetic resonance imaging for characterisation of a chick embryo model of cancer cell metastases
Authors: Herrmann Anne , Taylor Arthur , Murray Patricia , Poptani Harish , Sée Violaine 
Published: November 2017

ABSTRACTBackgroundMetastasis is the most common cause of death for cancer patients, hence its study has rapidly expanded over the past few years. To fully understand all the steps involved in metastatic dissemination,in vivomodels are required, of which murine ones are the most common. Therefore pre-clinical imaging methods have mainly been developed for small mammals. However, the potential of preclinical imaging techniques such as magnetic resonance imaging (MRI) to monitor cancer growth and metastasis in non-mammalianin vivomodels is not commonly used. We have here used MRI to measure primary neuroblastoma tumour size and presence of metastatic dissemination in a chick embryo model. We compared its sensitivity and accuracy to end-point fluorescence detection.MethodsHuman neuroblastoma cells were labelled with GFP and micron-sized iron particles (MPIOs) and implanted on the extraembryonic chorioallantoic membrane of the chick embryo at E7. T2 RARE, T2 weighted FLASH as well as time-of-flight MR angiography imaging was applied at E14. Primary tumours as well as metastatic deposits in the chick embryo were dissected post imaging to compare with MRI results.ResultsMPIO labelling of neuroblastoma cells allowedin ovoobservation of the primary tumour and tumour volume measurement non-invasively over time. Moreover, T2weighted and FLASH imaging permitted the detection of very small metastatic deposits in the chick embryo.ConclusionsThe use of contrast agents enabled the detection of metastatic deposits of neuroblastoma cells in a chick embryo model, thereby reinforcing the potential of this cost efficient and convenient, 3R compliant,in vivomodel for cancer research.
Nextstrain: real-time tracking of pathogen evolution
Authors: Hadfield James , Megill Colin , Bell Sidney M. , Huddleston John , Potter Barney , Callender Charlton , Sagulenko Pavel , Bedford Trevor , Neher Richard A. 
Published: November 2017

AbstractSummaryUnderstanding the spread and evolution of pathogens is important for effective public health measures and surveillance. Nextstrain consists of a database of viral genomes, a bioinformatics pipeline for phylodynamics analysis, and an interactive visualisation platform. Together these present a real-time view into the evolution and spread of a range of viral pathogens of high public health importance. The visualization integrates sequence data with other data types such as geographic information, serology, or host species. Nextstrain compiles our current understanding into a single accessible location, publicly available for use by health professionals, epidemiologists, virologists and the public alike.Availability and implementationAll code (predominantly JavaScript and Python) is freely available from github.com/nextstrain and the web-application is available at nextstrain.org.
Modelling the Dynamics of Biological Systems with the Geometric Hidden Markov Model
Authors: Vangelov Borislav , Barahona Mauricio 
Published: November 2017

ABSTRACTMany biological processes can be described geometrically in a simple way: stem cell differentiation can be represented as a branching tree and cell division can be depicted as a cycle. In this paper we introduce the geometric hidden Markov model (GHMM), a dynamical model whose goal is to capture the low-dimensional characteristics of biological processes from multivariate time series data. The framework integrates a graph-theoretical algorithm for dimensionality reduction with a latent variable model for sequential data. We analyzed time series data generated by an in silico model of a biomolecular circuit, the represillator. The trained model has a simple structure: the latent Markov chain corresponds to a two-dimensional lattice. We show that the short-term and long-term predictions of the GHMM reflect the oscillatory behaviour of the genetic circuit. Analysis of the inferred model with a community detection methods leads to a coarse-grained representation of the process.
Empirical test of crab-clam predator-prey model predictions: storm-driven phase shift to a low-density steady state
Authors: Glaspie Cassandra N. , Seitz Rochelle D. , Lipcius Romuald N. 
Published: November 2017

ABSTRACTA dynamic systems approach can predict steady states in predator-prey interactions, but there are very few empirical tests of predictions from predator-prey models. Here, we examine the empirical evidence for the low-density steady state predicted by a Lotka-Volterra model of a crab-clam predator-prey system using data from long-term monitoring, a field survey, and a field experiment. We show that Tropical Storm Agnes in 1972 likely resulted in a phase shift to a low-density state for the soft-shell clamMya arenaria, which was once a biomass dominant in Chesapeake Bay. This storm altered predator-prey dynamics betweenM. arenariaand the blue crabCallinectes sapidus, shifting from a system controlled from the bottom-up by prey resources, to a system controlled from the top-down by predation pressure on bivalves. Predator-prey models with these two species alone were capable of reproducing observations of clam densities and mortality rates, consistent with the idea thatC. sapidusare a major driver ofM. arenariapopulation dynamics. Over 40 y post-storm,M. arenariadensities hover near a low-density steady state predicted from the predator-prey model. Relatively simple models can predict phase shifts and identify alternative stable states, as shown by agreement between model predictions and field data in this system. The preponderance of multispecies interactions exhibiting nonlinear dynamics indicates that this may be a general phenomenon.