bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contrasting genome dynamics between domesticated and wild yeasts
Authors: Yue Jia-Xing , Li Jing , Aigrain Louise , Hallin Johan , Persson Karl , Oliver Karen , Bergström Anders , Coupland Paul , Warringer Jonas , Consentino Lagomarsino Marco , Fischer Gilles , Durbin Richard , Liti Gianni 
Published: September 2016

AbstractStructural rearrangements have long been recognized as an important source of genetic variation with implications in phenotypic diversity and disease, yet their evolutionary dynamics are difficult to characterize with short-read sequencing. Here, we report long-read sequencing for 12 strains representing major subpopulations of the partially domesticated yeastSaccharomyces cerevisiaeand its wild relativeSaccharomyces paradoxus. Complete genome assemblies and annotations generate population-level reference genomes and allow for the first explicit definition of chromosome partitioning into cores, subtelomeres and chromosome-ends. High-resolution view of structural dynamics uncovers that, in chromosomal cores,S. paradoxusexhibits higher accumulation rate of balanced structural rearrangements (inversions, translocations and transpositions) whereasS. cerevisiaeaccumulates unbalanced rearrangements (large insertions, deletions and duplications) more rapidly. In subtelomeres, recurrent interchromosomal reshuffling was found in both species, with higher rate inS. cerevisiae. Such striking contrasts between wild and domesticated yeasts reveal the influence of human activities on structural genome evolution.
Genetic indicators of drug resistance in the highly repetitive genomes ofTrichomonas vaginalisand other trichomonads
Authors: Bradic Martina , Warring Sally D. , Tooley Grace E. , Scheid Paul , Secor William E. , Land Kirkwood M. , Huang Po-Jung , Chen Ting-Wen , Lee Chi-Ching , Tang Petrus , Sullivan Steven A. , Carlton Jane M. 
Published: September 2016

AbstractBackgroundTrichomonas vaginalis, the most common non-viral sexually transmitted parasite, causes ~283 million trichomoniasis infections annually and is associated with complications during pregnancy and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but has lead to widespread drug resistance. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance.ResultsReduced representation genome sequencings of more than 100T. vaginalisclinical isolates identified 3,923 SNP markers and presence of a bipartite population structure. Linkage disequilibrium decays rapidly, suggesting genome-wide recombination and the feasibility of genetic association studies in the parasite. We identified 72 SNPs associated with metronidazole resistance, and a comparison of SNPs within several lab-derived resistant lines revealed an overlap with the clinically resistant isolates. We identified SNPs in sets of genes for which no function has yet been assigned, as well as in functionally-characterized genes highly relevant to drug resistance (e.g., pyruvate:ferredoxin oxidoreductase(PFO)). Transcription profiling of these and other genes served as proxy for testing the functional consequences of multiple identified SNPs. Transcription profiles of lab-derived drug resistance strain as well as clinically resistant strain depict common regulation changes in carbohydrate metabolism and oxygen detoxification pathways correlated with Mz resistance. Finally, we identified convergent genetic changes in lab-derived resistant lines ofTritrichomonas foetus, a distantly-related species that causes venereal disease in cattle.ConclusionsOur observation of shared genetic changes within and betweenT. vaginalisandTr. foetusparasites suggests conservation of the pathways through which adaptation has occurred. These findings extend our knowledge of drug resistance in the parasite, providing a panel of markers that can be used as a diagnostic tool.
Inferring recent demography from isolation by distance of long shared sequence blocks
Authors: Ringbauer Harald , Coop Graham , Barton Nick 
Published: September 2016

ABSTRACTRecently it has become feasible to detect long blocks of almost identical sequence shared between pairs of genomes. These so called IBD-blocks are direct traces of recent coalescence events, and as such contain ample signal for inferring recent demography. Here, we examine sharing of such blocks in two-dimensional populations with local migration. Using a diffusion approximation to trace genetic ancestry back in time, we derive analytical formulas for patterns of isolation by distance of long IBD-blocks, which can also incorporate recent population density changes. As a main result, we introduce an inference scheme that uses a composite likelihood approach to fit observed block sharing to these formulas. We assess our inference method on simulated block sharing data under several standard population genetics models. We first validate the diffusion approximation by showing that the theoretical results closely match simulated block sharing patterns. We then show that our inference scheme rather accurately and robustly recovers estimates of the dispersal rate and effective density, as well as bounds on recent dynamics of population density. To demonstrate an application, we use our estimation scheme to explore the fit of a diffusion model to Eastern European samples in the POPRES data set. We show that ancestry diffusing with a rate ofduring the last centuries, combined with accelerating population growth, can explain the observed exponential decay of block sharing with pairwise sample distance.
Early inflammation, immunopathology and aging
Authors: Khan Imroze , Agashe Deepa , Rolff Jens 
Published: September 2016

ABSTRACTAge-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetleTenebrio molitoras a study organism. We hypothesized that phenoloxidase (PO), an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage, in turn accelerating aging. In support of this hypothesis, we found that RNAi knockdown of PO transcripts in young adults reduced inflammation-induced autoreactive tissue damage to Malpighian tubules, and increased adult lifespan. Our work thus provides empirical evidence for a causative link between immunopathological costs of early life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, they displayed exacerbated immunopathological costs and higher post-infection mortality. RNAi-mediated knockdown of PO response reduced immunopathology in older beetles and increased their lifespan after infection. This is the first demonstration of a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of immunopathology under diverse contexts of aging and immune response.
Temporal probabilistic modeling of bacterial compositions derived from 16S rRNA sequencing
Authors: Äijö Tarmo , Müller Christian L. , Bonneau Richard 
Published: September 2016

AbstractThe number of microbial and metagenomic studies has increased drastically due to advance-ments in next-generation sequencing-based measurement techniques. Statistical analysis and the validity of conclusions drawn from (time series) 16S rRNA and other metagenomic sequencing data is hampered by the presence of significant amount of noise and missing data (sampling zeros). Accounting uncertainty in microbiome data is often challenging due to the difficulty of obtaining biological replicates. Additionally, the compositional nature of current amplicon and metagenomic data differs from many other biological data types adding another challenge to the data analysis.To address these challenges in human microbiome research, we introduce a novel probabilistic approach to explicitly model overdispersion and sampling zeros by considering the temporal correlation between nearby time points using Gaussian Processes. The proposed Temporal Gaussian Process Model for Compositional Data Analysis (TGP-CODA) shows superior modeling performance compared to commonly used Dirichlet-multinomial, multinomial, and non-parametric regression models on real and synthetic data. We demonstrate that the nonreplicative nature of human gut microbiota studies can be partially overcome by our method with proper experimental design of dense temporal sampling. We also show that different modeling ap-proaches have a strong impact on ecological interpretation of the data, such as stationarity, persistence, and environmental noise models.A Stan implementation of the proposed method is available under MIT license athttps://github.com/tare/GPMicrobiome.
Analyzing whole genome bisulfite sequencing data from highly divergent genotypes
Authors: Wulfridge Phillip , Langmead Ben , Feinberg Andrew P. , Hansen Kasper D. 
Published: September 2016

AbstractIn the study of DNA methylation, genetic variation between species, strains, or individuals can result in CpG sites that are exclusive to a subset of samples, and insertions and deletions can rearrange the spatial distribution of CpGs. How to account for this variation in an analysis of the interplay between sequence variation and DNA methylation is not well understood, especially when the number of CpG differences between samples is large. Here we use whole-genome bisulfite sequencing data on two highly divergent inbred mouse strains to study this problem. We find that while the large number of strain-specific CpGs necessitates considerations regarding the reference genomes used during alignment, properties such as CpG density are surprisingly conserved across the genome. We introduce a method for including strain-specific CpGs in differential analysis, and show that accounting for strain-specific CpGs increases the power to find differentially methylated regions between the strains. Our method uses smoothing to impute methylation levels at strain-specific sites, thereby allowing strain-specific CpGs to contribute to the analysis, and also allowing us to account for differences in the spatial occurrences of CpGs. Our results have implications for analysis of genetic variation and DNA methylation using bisulfite-converted DNA.
PEMapper / PECaller: A simplified approach to whole-genome sequencing
Authors: Johnston H Richard , Chopra Pankaj , Wingo Thomas S , Patel Viren ,   Internation Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome, Epstein Michael P , Mulle Jennifer , Warren Stephen T , Zwick Michael E , Cutler David J. 
Published: September 2016

ABSTRACTThe analysis of human whole-genome sequencing data presents significant computational challenges. The sheer size of datasets places an enormous burden on computational, disk array, and network resources. Here we present an integrated computational package, PEMapper/PECaller, that was designed specifically to minimize the burden on networks and disk arrays, create output files that are minimal in size, and run in a highly computationally efficient way, with the single goal of enabling whole-genome sequencing at scale. In addition to improved computational efficiency, we implement a novel statistical framework that allows for a base-by-base error model, allowing this package to perform as well or better than the widely used Genome Analysis Toolkit (GATK) in all key measures of performance on human whole-genome sequences.
Interaction of multiple courses of wave‐induced fluid flow in layered porous media
Authors: Cao Chenghao , Zhang Hongbing , Pan Yixin 
Published: September 2016

ABSTRACTDifferent theoretical and laboratory studies on the propagation of elastic waves in layered hydrocarbon reservoir have shown characteristic velocity dispersion and attenuation of seismic waves. The wave‐induced fluid flow between mesoscopic‐scale heterogeneities (larger than the pore size but smaller than the predominant wavelengths) is the most important cause of attenuation for frequencies below 1 kHz. Most studies on mesoscopic wave‐induced fluid flow in the seismic frequency band are based on the representative elementary volume, which does not consider interaction of fluid flow due to the symmetrical structure of representative elementary volume. However, in strongly heterogeneous media with unsymmetrical structures, different courses of wave‐induced fluid flow may lead to the interaction of the fluid flux in the seismic band; this has not yet been explored. This paper analyses the interaction of different courses of wave‐induced fluid flow in layered porous media. We apply a one‐dimensional finite‐element numerical creep test based on Biot's theory of consolidation to obtain the fluid flux in the frequency domain. The characteristic frequency of the fluid flux and the strain rate tensor are introduced to characterise the interaction of different courses of fluid flux. We also compare the behaviours of characteristic frequencies and the strain rate tensor on two scales: the local scale and the global scale. It is shown that, at the local scale, the interaction between different courses of fluid flux is a dynamic process, and the weak fluid flux and corresponding characteristic frequencies contain detailed information about the interaction of the fluid flux. At the global scale, the averaged strain rate tensor can facilitate the identification of the interaction degree of the fluid flux for the porous medium with a random distribution of mesoscopic heterogeneities, and the characteristic frequency of the fluid flux is potentially related to that of the peak attenuation. The results are helpful for the prediction of the distribution of oil–gas patches based on the statistical properties of phase velocities and attenuation in layered porous media with random disorder.
Arctangent function‐based third derivative attribute for characterisation of faults
Authors: Yu Jingbo , Li Zhong 
Published: September 2016

ABSTRACTUsing seismic attributes such as coherence and curvature to characterise faults not only can improve the efficiency of seismic interpretation but also can expand the capability to detect faults. The coherence and curvature have been widely applied to characterising faults for years. These two methods detect faults based on the similarity of seismic waveforms and shapes of the reflectors, respectively, and they are complementary to each other and both have advantages and disadvantages in fault characterisation. A recent development in fault characterisation based on reflector shapes has been the use of the rate of change of curvature. Through an application to the seismic data from Western Tazhong of the Tarim Basin, China, it was demonstrated that the rate of change of curvature is more capable of detecting subtle faults having quite small throws and heaves. However, there often exist multiple extreme values indicating the same fault when applying the rate of change of curvature, which significantly degrades the signal‐to‐noise ratio of the computation result for multiple extrema interfering with each other. To resolve this problem, we propose the use of a linear combination of arctangent and proportional functions as the directrix of a cylindrical surface to fit the fault model and calculate its third derivative, which can then be used to characterise the fault. Through an application to the 3D seismic data from Western Tazhong of the Tarim Basin, the results show that the proposed method not only retains the same capability to detect subtle faults having small throws as the curvature change rate but also greatly improves the signal‐to‐noise ratio of the calculated result.
Role of VR1 in the differentiation of bone marrow‐derived mesenchymal stem cells into cardiomyocytes associated with Wnt/β‐catenin signaling
Authors: Ren Mingming , Wang Tao , Huang Lei , Ye Xiaoqiang , Xv Zhifeng , Ouyang Chun , Han Zhen 
Published: September 2016

SummaryAimAccumulating evidence showed that transient receptor potential channels play an important role in the regulation of cardiomyocyte differentiation. The vanilloid receptor 1 (VR1) is a member of the transient receptor channel super family and is expressed in cardiomyocytes. However, its function in cardiomyocytes remains unclear.MethodsHerein, the aim of this study was to investigate the functional role of VR1 in the cardiomyocyte differentiation of bone marrow‐derived mesenchymal stem cells (BMSCs) and to elucidate the potential molecular mechanisms.ResultsImmunofluorescence assay showed that cardiomyocyte marker cardiac troponin T (cTnT) was found significantly elevated in differentiated BMSCs induced by 5‐azacytidine compared with control. Similarly, VR1 expression was also found significantly increased in induced BMSCs differentiation. Additionally, we examined the role of VR1 in BMSC differentiation processes through VR1 siRNAs. We found that the expression of cardiomyocyte marker genes, such as alpha‐myosin heavy chain (α‐MHC), α‐cardiac actin, and Nkx2.5 (cardiac‐specific transcription factor), was significantly decreased when VR1 was silenced. Furthermore, we found that inhibition of VR1 expression is associated with downregulation of Wnt/β‐catenin signaling.ConclusionsTo summarize, our data demonstrate important role of VR1 in BMSCs differentiation into cardiomyocytes in conjunction of Wnt/β‐catenin signaling.
Impact of stent diameter and length on in‐stent restenosis after DES vs BMS implantation in patients needing large coronary stents—A clinical and health‐economic evaluation
Authors: Zbinden Rainer , von Felten Stefanie , Wein Bastian , Tueller David , Kurz David J. , Reho Ivano , Galatius Soren , Alber Hannes , Conen David , Pfisterer Matthias , Kaiser Christoph , Eberli Franz R. 
Published: September 2016

SummaryAimsThe British National Institute of Clinical Excellence (NICE) guidelines recommend to use drug‐eluting stents (DES) instead of bare‐metal stents (BMS) only in lesions >15 mm in length or in vessels <3 mm in diameter. We analyzed the impact of stent length and stent diameter on in‐stent restenosis (ISR) in the BASKET‐PROVE study population and evaluated the cost‐effectiveness of DES compared to BMS.Methods/ResultsThe BASKET‐PROVE trial compared DES vs BMS in large coronary arteries (≥3 mm). We calculated incremental cost‐effectiveness ratios (ICERs) and cost‐effectiveness acceptability curves with regard to quality‐adjusted life years (QALYs) gained and target lesion revascularizations (TLRs) avoided.A total of 2278 patients were included in the analysis. A total of 74 ISR in 63 patients were observed. In‐stent restenosis was significantly more frequent in segments treated with a BMS compared to segments treated with a DES (5.4% vs 0.76%; P<.001). The benefit of a DES compared to a BMS regarding ISR was consistent among the subgroups of stent length >15 mm and ≤15 mm, respectively. With the use of DES in short lesions, there was only a minimal gain of 0.005 in QALYs. At a threshold of 10 000 CHF per TLR avoided, DES had a high probability of being cost‐effective.ConclusionIn the BASKET‐PROVE study population, the strongest predictor of ISR is the use of a BMS, even in patients in need of stents ≥3.0 mm and ≤15 mm lesion length and DES were cost‐effective. This should prompt the NICE to reevaluate its recommendation to use DES instead of BMS only in vessels <3.0 mm and lesions >15 mm length.
Activated monocytes resist elimination by retinal pigment epithelium and downregulate their OTX2 expression via TNF‐α
Authors: Mathis Thibaud , Housset Michael , Eandi Chiara , Beguier Fanny , Touhami Sara , Reichman Sacha , Augustin Sebastien , Gondouin Pauline , Sahel José‐Alain , Kodjikian Laurent , Goureau Olivier , Guillonneau Xavier , Sennlaub Florian 
Published: September 2016

SummaryOrthodenticle homeobox 2 (OTX2) controls essential, homeostatic retinal pigment epithelial (RPE) genes in the adult. Using cocultures of human CD14+ blood monocytes (Mos) and primary porcine RPE cells and a fully humanized system using human‐induced pluripotent stem cell‐derived RPE cells, we show that activated Mos markedly inhibit RPEOTX2 expression and resist elimination in contact with the immunosuppressive RPE. Mechanistically, we demonstrate that TNF‐α, secreted from activated Mos, mediates the downregulation of OTX2 and essential RPE genes of the visual cycle among others. Our data show how subretinal, chronic inflammation and in particular TNF‐α can affect RPE function, which might contribute to the visual dysfunctions in diseases such as age‐related macular degeneration (AMD) where subretinal macrophages are observed. Our findings provide important mechanistic insights into the regulation of OTX2 under inflammatory conditions. Therapeutic restoration of OTX2 expression might help revive RPE and visual function in retinal diseases such as AMD.
Effect of a randomised exclusive breastfeeding counselling intervention nested into the MINIMat prenatal nutrition trial in Bangladesh
Authors: Khan Ashraful Islam , Kabir Iqbal , Eneroth Hanna , El Arifeen Shams , Ekström Eva‐Charlotte , Frongillo Edward A. , Persson Lars Åke 
Published: September 2016

AbstractAimIt is unknown whether maternal malnutrition reduces the effect of counselling on exclusive breastfeeding. This study evaluated the effect of breastfeeding counselling on the duration of exclusive breastfeeding, and whether the timing of prenatal food and different micronutrient supplements further prolonged this duration.MethodsPregnant women in Matlab, Bangladesh, were randomised to receive daily food supplements of 600 kcal at nine weeks of gestation or at the standard 20 weeks. They also were allocated to either 30 mg of iron and 400 μg folic acid, or the standard programme 60 mg of iron and folic acid or multiple micronutrients. At 30 weeks of gestation, 3188 women were randomised to receive either eight breastfeeding counselling sessions or the usual health messages.ResultsThe median duration of exclusive breastfeeding was 135 days in the counselling group and 75 days in the usual health message group (p < 0.001). Prenatal supplements did not modify the effects of counselling. Women in the usual health message group who were randomised to multiple micronutrients exclusively breastfed for 12 days longer than mothers receiving the standard iron–folate combination (p = 0.003).ConclusionBreastfeeding counselling increased the duration of exclusive breastfeeding by 60 days. This duration was not influenced by the supplements.