bluuebunny/crossref_metadata_2025_split huggingface dataset:
Climate change vulnerability for species – assessing the assessments
Authors: Wheatley Christopher J. , Beale Colin M. , Bradbury Richard B. , Pearce-Higgins James W. , Critchlow Rob , Thomas Chris D. 
Published: July 2016

AbstractClimate change vulnerability assessments are commonly used to identify species at risk from global climate change, but the wide range of methodologies available makes it difficult for end users, such as conservation practitioners or policy makers, to decide which method to use as a basis for decision-making. Here, we compare the outputs of 12 such climate change vulnerability assessment methodologies, using both real and simulated species, and we test the methods using historic data for British birds and butterflies (i.e., using historical data to assign risks, and more recent data for validation). Our results highlight considerable inconsistencies in species risk assignment across all the approaches considered and suggest the majority of the frameworks are poor predictors of risk under climate change – two methods performed worse than random. Methods that incorporated historic trend data were the only ones to have any validity at predicting distributional trends in subsequent time periods.
An RNA editing/binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer
Authors: Qi Lihua , Song Yangyang , Chan Tim Hon Man , Yang Henry , Lin Chi Ho , Tay Daryl Jin Tai , Hong HuiQi , Lin Jaymie Siqi , Ng Vanessa Hui En , Maury Julien Jean Pierre , Tenen Daniel G. , Chen Leilei 
Published: July 2016

AbstractAdenosine-to-inosine (A-to-I) editing, catalysed by Adenosine DeAminases acting on double-stranded RNA (dsRNA) (ADAR), occurs predominantly in the 3’ untranslated regions (3’UTRs). Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) and the expression of target genes undergoing extensive 3’UTR editing. UsingMETTL7A(Methyltransferase Like 7A), a novel tumor suppressor as an exemplary target gene, we demonstrate that its expression could be repressed by ADARs beyond their RNA editing and dsRNA binding functions. ADARs interact with Dicer to augment the processing of pre-miR-27a to mature miR-27a. Consequently, mature miR-27a targets theMETTL7A3’UTR to repress its expression level. In sum, our study unveils that the extensive 3’UTR editing is merely a footprint of ADAR binding, and is dispensable for the regulation of at least a subset of target genes. Instead, ADARs contribute to cancer progression by regulating cancer-related gene expression through their non-canonical functions independent of RNA editing and dsRNA binding. The functional significance of ADARs is much more diverse than previously appreciated and this gene regulatory function of ADARs is most likely to be of higher importance than the best-studied editing function. This novel non-editing side of ADARs opens another door to target cancer. This study is timely and represents a major break-through in the field of ADAR gene regulation and cancer biology.
Rett syndrome – biological pathways leading from MECP2 to disorder phenotypes
Authors: Ehrhart Friederike , Coort Susan L.M. , Cirillo Elisa , Smeets Eric , Evelo Chris T. , Curfs Leopold M. 
Published: July 2016

AbstractRett syndrome (RTT) is a rare disease but still one of the most abundant causes for intellectual disability in females. Typical symptoms are onset at month 6-18 after normal pre-and postnatal development, loss of acquired skills and severe intellectual disability. The type and severity of symptoms are individually highly different. A single mutation in one gene, coding for methyl-CpG-binding protein 2 (MECP2), is responsible for the disease. The most important action of MECP2 is regulating epigenetic imprinting and chromatin condensation, but MECP2 influences many different biological pathways on multiple levels. In this review the known changes in metabolite levels, gene expression and biological pathways in RTT are summarized. It is discussed how they are leading to some characteristic RTT phenotypes and identifies the gaps of knowledge, namely which phenotypes have currently no mechanistic explanation leading back to MECP2 related pathways. As a result of this review the visualization of the biologic pathways showing MECP2 up-and downstream regulation was developed and published onWikiPathways.
Inbreeding parents should invest more resources in fewer offspring
Authors: Duthie A. Bradley , Lee Aline M. , Reid Jane M. 
Published: July 2016

AbstractInbreeding increases parent-offspring relatedness and commonly reduces offspring viability, shaping selection on reproductive interactions involving relatives and associated parental investment (PI). Nevertheless, theories predicting selection for inbreeding versus inbreeding avoidance and selection for optimal PI have only been considered separately, precluding prediction of optimal PI and associated reproductive strategy given inbreeding. We unify inbreeding and PI theory, demonstrating that optimal PI increases when a female's inbreeding decreases the viability of her offspring. Inbreeding females should therefore produce fewer offspring due to the fundamental trade-off between offspring number and PI. Accordingly, selection for inbreeding versus inbreeding avoidance changes when females can adjust PI with the degree that they inbreed. In contrast, optimal PI does not depend on whether a focal female is herself inbred. However, inbreeding causes optimal PI to increase given strict monogamy and associated biparental investment compared to female-only investment. Our model implies that understanding evolutionary dynamics of inbreeding strategy, inbreeding depression, and PI requires joint consideration of the expression of each in relation to the other. Overall, we demonstrate that existing PI and inbreeding theories represent special cases of a more general theory, implying that intrinsic links between inbreeding and PI affect evolution of behaviour and intra-familial conflict.
Foxc1controls cell fate decisions during transforming growth factor β induced epithelial to mesenchymal transition through the regulation of fibroblast growth factor receptor 1 expression
Authors: Hopkins Alex , Coatham Mackenzie L. , Berry Fred B. 
Published: July 2016

ABSTRACTEpithelial to mesenchymal transition (EMT) is an important physiological process that drives tissue formation during development but also contributes to disease pathogenesis including fibrosis and cancer metastasis. The forkhead box transcription factor gene FOXC1 is an important developmental regulator in the generation of mesenchymal cells necessary in the formation of the anterior segment of the eye, the craniofacial skeleton and the meninges. Recently elevated expression ofFOXC1has been detected in several metastatic cancers that have undergone EMT events. We sought to determine the role of FOXC1 in the initiation of EMT events using NMuMG cells treated with TFGβ1. We found that although Foxc1 expression was increased following TFGβ1 induced EMT, Foxc1 was not required for this induction. Instead we propose that Foxc1 is required for the specification of the mesenchyme cell type, promoting an activated fibroblast phenotype over a myofibroblast phenotype following the initiation of EMT. This cells type specification was achieved through the regulation of Fibroblast growth factor (Fgfr) 1 expression. Using an RNA sequencing approach, we determined that levels of Fgfr1 normally activated upon TFGβ1 treatment were reduced in Foxc1-knockdown cells. Through chromatin immunoprecipitation experiments we determined that FOXC1 could bind to an Fgfr1 upstream regulatory region. Furthermore, expression of the myofibroblast marker α-smooth muscle actin (αSMA) was elevated in Foxc1 knockdown cells. Finally we determined that FGF2 mediated three dimensional migratory ability was greatly impaired in Foxc1-knockdown cells. Together these results define a role for Foxc1 in specifying a mesenchymal cell type following TFGβ1 mediated EMT events.
Do Dams Also Stop Frogs? Assessing Population Connectivity of Coastal Tailed Frogs (Ascaphus truei) in the North Cascades National Park Service Complex
Authors: Grummer Jared A. , Leaché Adam D. 
Published: July 2016

AbstractWe investigated the effects of three hydroelectric dams and their associated lakes on the population structure and connectivity of the coastal tailed frog, Ascaphus truei, in the North Cascades National Park Service Complex. Three dams were erected on the Skagit River in northern-central Washington state between 1924 and 1953 and subsequently changed the natural shape and movement of the Skagit River and its tributaries. We collected 183 individuals from 13 tributaries and generated a dataset of >2,500 loci (unlinked SNPs) using double digestion restriction site-associated DNA sequencing (ddRADseq). An analysis of molecular variance (AMOVA) identified ~99% of the genetic variation within groups, and the remaining variation among groups separated by dams, or the Skagit River. All populations exhibited low FSTvalues with a maximum of 0.03474. A ‘de novo’ discriminant analysis of principal components revealed two populations with no geographic cohesiveness. However, testing groups that were partitioneda prioriby the dams revealed distinctiveness of populations down-river of the lowest dam. Coalescent-based analyses of recent migration suggest that up to 17.3% of each population is composed of migrants from other populations, and an estimation of effective migration rates revealed high levels of migration heterogeneity and population connectivity in this area. Our results suggest that although the populations down-river from the lowest dam are distinguishable, a high level ofA.trueipopulation connectivity exists throughout the North Cascades National Park Service Complex.
Coral life history differences determine the refugium potential of a remote Caribbean reef
Authors: Davies Sarah W. , Strader Marie E. , Kool Johnathan T. , Kenkel Carly D. , Matz Mikhail V. 
Published: July 2016

AbstractRemote populations can influence connectivity and may serve as refugia from climate change. Here, we investigated two reef-building corals (Pseudodiploria strigosaandOrbicella franksi) from the Flower Garden Banks (FGB) – the most isolated, high-latitude Caribbean reef system that retains high coral cover. We characterized coral size frequency distributions, quantified larval mortality rates and onset of competence, estimated larval production, and created detailed biophysical models incorporating these parameters to evaluate source-sink dynamics from 2009 to 2012. Mortality rates were similar across species but competency differed dramatically:P. strigosawas capable of metamorphosis within 2.5 days post fertilization (dpf), whileO. franksiwere not competent until >20dpf and remained competent up to 120dpf Despite these differences, models demonstrated that larvae of both types were similarly successful in reseeding the FGB. Nevertheless, corals with shorter pelagic larval durations (PLD), such asP. strigosa, were highly isolated from the rest of the Caribbean, while long PLD corals, such asO. franksi, could export larvae to distant northern Caribbean reefs. These results suggest that FGB coral populations are self-sustaining and highlight the potential of long PLD corals, such as endangeredOrbicella, to act as larval sources for other degraded Caribbean reefs.
Batch effects and the effective design of single-cell gene expression studies
Authors: Tung Po-Yuan , Blischak John D. , Hsiao Chiaowen Joyce , Knowles David A. , Burnett Jonathan E. , Pritchard Jonathan K. , Gilad Yoav 
Published: July 2016

AbstractSingle cell RNA sequencing (scRNA-seq) can be used to characterize variation in gene expression levels at high resolution. However, the sources of experimental noise in scRNA-seq are not yet well understood. We investigated the technical variation associated with sample processing using the single cell Fluidigm C1 platform. To do so, we processed three C1 replicates from three human induced pluripotent stem cell (iPSC) lines. We added unique molecular identifiers (UMIs) to all samples, to account for amplification bias. We found that the major source of variation in the gene expression data was driven by genotype, but we also observed substantial variation between the technical replicates. We observed that the conversion of reads to molecules using the UMIs was impacted by both biological and technical variation, indicating that UMI counts are not an unbiased estimator of gene expression levels. Based on our results, we suggest a framework for effective scRNA-seq studies.
Coding translational rates: the hidden genetic code
Authors: Diambra Luis 
Published: July 2016

ABSTRACTIn this paper we propose that translational rate is modulated by pairs of consecutive codons or bicodons. By a statistical analysis of coding sequences, associated with low or with high abundant proteins, we found some bicodons with significant preference usage for either of these sets. These usage preferences cannot be explained by the frequency usage of the single codons. We compute a pause propensity measure of all bicodons in nine organisms, which reveals that in many cases bicodon preference is shared between related organisms. We found that bicodons associated with sequences encoding low abundant proteins are involved in translational attenuation reported in SufIprotein inE. coli.Furthermore, we observe that the misfolding in the drug-transport protein, encoded byMDR1gene, is better explained by a big change in the pause propensity due to the synonymous bicodon variant, rather than by a relatively small change in the codon usage. These findings suggest that bicodon usage can be a more powerful framework to understand translational speed, protein folding efficiency, and to improve protocols to optimize heterologous gene expression.
VarMatch: robust matching of small variant datasets using flexible scoring schemes
Authors: Sun Chen , Medvedev Paul 
Published: July 2016

ABSTRACTMotivationSmall variant calling is an important component of many analyses, and, in many instances, it is important to determine the set of variants which appear in multiple callsets. Variant matching is complicated by variants that have multiple equivalent representations. Normalization and decomposition algorithms have been proposed, but are not robust to different representation of complex variants. Variant matching is also usually done to maximize the number of matches, as opposed to other optimization criteria.ResultsWe present the VarMatch algorithm for the variant matching problem. Our algorithm is based on a theoretical result which allows us to partition the input into smaller subproblems without sacrificing accuracy VarMatch is robust to different representation of complex variants and is particularly effective in low complexity regions or those dense in variants. VarMatch is able to detect more matches than either the normalization or decomposition algorithms on tested datasets. It also implements different optimization criteria, such as edit distance, that can improve robustness to different variant representations. Finally the VarMatch software provides summary statistics, annotations, and visualizations that are useful for understanding callers’ performance.AvailabilityVarMatch is freely available at:https://github.com/medvedevgroup/varmatchContactchensun@cse.psu.edu
Genome-wide Variants of Eurasian Facial Shape Differentiation and a prospective model of DNA based Face Prediction
Authors: Qiao Lu , Yang Yajun , Fu Pengcheng , Hu Sile , Zhou Hang , Peng Shouneng , Tan Jingze , Lu Yan , Lou Haiyi , Lu Dongsheng , Wu Sijie , Guo Jing , Jin Li , Guan Yaqun , Wang Sijia , Xu Shuhua , Tang Kun 
Published: July 2016

AbstractIt is a long standing question as to which genes define the characteristic facial features among different ethnic groups. In this study, we use Uyghurs, an ancient admixed population to query the genetic bases why Europeans and Han Chinese look different. Facial traits were analyzed based on high-dense 3D facial images; numerous biometric spaces were examined for divergent facial features between European and Han Chinese, ranging from inter-landmark distances to dense shape geometrics. Genome-wide association analyses were conducted on a discovery panel of Uyghurs. Six significant loci were identified four of which, rs1868752, rs118078182, rs60159418 at or near UBASH3B, COL23A1, PCDH7 and rs17868256 were replicated in independent cohorts of Uyghurs or Southern Han Chinese. A prospective model was also developed to predict 3D faces based on top GWAS signals, and tested in hypothetic forensic scenarios.
A nonsense mutation in theCOL7A1gene causes epidermolysis bullosa in Vorderwald cattle
Authors: Pausch Hubert , Ammermüller Simon , Wurmser Christine , Hamann Henning , Tetens Jens , Drögemüller Cord , Fries Ruedi 
Published: July 2016

AbstractBackgroundThe widespread use of individual sires for artificial insemination promotes the propagation of recessive conditions. Inadvertent matings between unnoticed carriers of deleterious alleles may result in the manifestation of fatal phenotypes in their progeny. Breeding consultants and farmers reported on Vorderwald calves with a congenital skin disease. The clinical findings in affected calves were compatible with epidermolysis bullosa.ResultsPedigree analysis indicated autosomal recessive inheritance of epidermolysis bullosa in Vorderwald cattle. We genotyped two diseased and 41 healthy animals at 41,436 single nucleotide polymorphisms and performed whole-genome haplotype-based association testing, which allowed us to map the locus responsible for the skin disease to the distal end of bovine chromosome 22 (P=8.0×10−14). The analysis of whole-genome re-sequencing data of one diseased calf, three obligate mutation carriers and 1682 healthy animals from various bovine breeds revealed a nonsense mutation (rs876174537, p.Arg1588X) in theCOL7A1gene that segregates with the disease. The same mutation was previously detected in three calves with dystrophic epidermolysis bullosa from the Rotes Hӧehenvieh cattle breed. We show that diseased animals from Vorderwald and Rotes Hӧehenvieh cattle are identical by descent for an 8.72 Mb haplotype encompassing rs876174537 indicating they inherited the deleterious allele from a recent common ancestor.ConclusionsAutosomal recessive epidermolysis bullosa in Vorderwald and Rotes Hӧehenvieh cattle is caused by a nonsense mutation in theCOL7A1gene. Our findings demonstrate that recessive deleterious alleles may segregate across cattle populations without apparent admixture. The identification of the causal mutation now enables the reliable detection of carriers of the defective allele. Genome-based mating strategies can avoid inadvertent matings of carrier animals thereby preventing the birth of homozygous calves that suffer from a painful skin disease.
Competition between continuously evolving lineages in asexual populations
Authors: Ribeck Noah , Mulka Joseph S. , Zaman Luis , Connelly Brian D. , Lenski Richard E. 
Published: July 2016

ABSTRACTIn an asexual population, the fate of a beneficial mutation depends on how its lineage competes against other mutant lineages in the population. With high beneficial mutation rates or large population sizes, competition between contending mutations is strong, and successful lineages can accumulate multiple mutations before any single one achieves fixation. Most current theory about asexual population dynamics either neglects this multiple-mutations regime or introduces simplifying assumptions that may not apply. Here, we develop a theoretical framework that describes the dynamics of adaptation and substitution over all mutation-rate regimes by conceptualizing the population as a collection of continuously adapting lineages. This model of “lineage interference” shows that each new mutant’s advantage over the rest of the population must be above a critical threshold in order to likely achieve fixation, and we derive a simple expression for that threshold. We apply this framework to examine the role of beneficial mutations with different effect sizes across the transition to the multiple-mutations regime.
Functional Connectivity Patterns Underlying the Experience of Auditory Verbal Hallucinations in Patients with Schizophrenia
Authors: Pravesh Parekh , John John P. , Menon Sangeetha , Halahalli Harsha N. , Kutty Bindu M. 
Published: July 2016

AbstractSchizophrenia is characterized by functional connectivity aberrations between brain regions that mediate different cognitive processes. The characteristic symptoms of schizophrenia such as delusions, hallucinations, passivity experiences etc. are suggested to reflect a disordered self-awareness. In the present study, we used a novel fMRI paradigm, the ‘Hallucination Attentional Modulation Task (HAMT)”, to examine the functional connectivity patterns underlying the experience of auditory verbal hallucinations in contrast to the patterns associated with processing of visual stimuli. We found that there was substantial overlap amongst healthy (n=8) and schizophrenia (n=6) subjects with respect to the functional connectivity patterns during the ‘free attention’ and ‘visual attention’ conditions of the paradigm. In patients with schizophrenia having continuous auditory verbal hallucinations, the connectivity between the bilateral superior parietal lobules and bilateral thalami were stronger during the ‘hallucination attention’ condition. These results provide preliminary leads that link auditory verbal hallucinations to an underlying disorder of self-agency.
Past climate changes, population dynamics and the origin of Bison in Europe
Authors: Massilani Diyendo , Guimaraes Silvia , Brugal Jean-Philip , Bennett E. Andrew , Tokarska Malgorzata , Arbogast Rose-Marie , Baryshnikov Gennady , Boeskorov Gennady , Castel Jean-Christophe , Davydov Sergey , Madelaine Stephane , Putelat Olivier , Spasskaya Natalia , Uerpmann Hans-Peter , Grange Thierry , Geigl Eva-Maria 
Published: July 2016

AbstractClimatic and environmental fluctuations as well as anthropogenic pressure have led to the extinction of much of Europe’s megafauna. Here we show that the emblematic European bison has experienced several waves of population expansion, contraction and extinction during the last 50,000 years in Europe, culminating in a major reduction of genetic diversity during the Holocene. Fifty-seven complete and partial ancient mitogenomes from throughout Europe, the Caucausus and Siberia reveal that three populations of wisent (Bison bonasus) and steppe bison (B. priscus) alternated in Western Europe correlating with climate-induced environmental changes. The Late Pleistocene European steppe bison originated from northern Eurasia whereas the modern wisent population emerged from a refuge in the southern Caucasus after the last glacial maximum. A population overlap in a transition period is reflected in ca. 36,000 year-old paintings in the French Chauvet cave. Bayesian analyses of these complete ancient mitogenomes yielded new dates of the various branching events during the evolution of Bison and its radiation with Bos that lead us to propose that the genetic affiliation between the wisent and cattle mitogenomes result from incomplete lineage sorting rather than post-speciation gene flow.SignificanceClimatic fluctuations during the Pleistocene had a major impact on the environment and led to multiple megafaunal extinctions. Through ancient DNA analyses we decipher these processes for one of the largest megafauna of Eurasia, the bison. We show that Western Europe was successively populated during the Late Pleistocene by three different bison clades or species originating from the Caucasus and North-Eastern Europe that can be correlated to major climatic fluctuations and environmental changes. Aurignacian cave artists were witnesses to the first replacement of bison species ~35,000 years ago. All of these populations went extinct except for one that survived into the Holocene where it experienced severe reductions of its genetic diversity due to anthropogenic pressure.