bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic modelling of hepatitis C transmission among people who inject drugs: A tool to support WHO elimination targets
Authors: Stocks Theresa , Martin Leah J. , Kühlmann-Berenzon Sharon , Britton Tom 
Published: November 2018

AbstractTo reach the WHO goal of hepatitis C elimination, it is essential to identify the number of people unaware of their hepatitis C virus (HCV) infection and to investigate the effect of interventions on the disease transmission dynamics. In many middle- and high-income countries, one of the primary routes of HCV transmission is via contaminated needles shared by people who inject drugs (PWIDs). However, substantial underreporting combined with high uncertainty regarding the size of this difficult to reach population, makes it challenging to estimate the core indicators recommended by the WHO. To help enable countries to monitor their progress towards the elimination goal, we present a novel multi-layered dynamic transmission model for HCV transmission within a PWID population. The model explicitly accounts for disease stage (acute and chronic), injection drug use status (active and former PWIDs), status of diagnosis (diagnosed and undiagnosed) and country of disease acquisition (domestic or abroad). First, based on this model, and using routine surveillance data, we estimate the number of undiagnosed PWIDs, the true incidence, the average time until diagnosis, the reproduction numbers and associated uncertainties. Second, we examine the impact of two interventions on disease dynamics: 1) direct-acting antiviral drug treatment, and 2) needle exchange programs. To make the model accessible to relevant users and to support communication of our results to public health decision makers, the model and its output are made available through a Shiny app. As a proof of concept, we illustrate our results for a specific data set; however, through the app our model can be easily adapted to other high-income countries with similar transmission patterns among PWIDs where the disease is endemic.
Efficient GFP-labeling and analysis of spermatogenic cells using the IRG transgene and flow cytometry
Authors: Zagore Leah L. , Akesson Cydni C. , Licatalosi Donny D. 
Published: November 2018

AbstractSpermatogenesis is a highly ordered developmental program that produces haploid male germ cells. The study of male germ cell development in the mouse has provided unique perspectives into the molecular mechanisms that control cell development and differentiation in mammals, including tissue-specific gene regulatory programs. An intrinsic challenge in spermatogenesis research is the heterogeneity of germ and somatic cell types present in the testis. Techniques to separate and isolate distinct mouse spermatogenic cell types have great potential to shed light on molecular mechanisms controlling mammalian cell development, while also providing new insights into cellular events important for human reproductive health. Here, we detail a versatile strategy that combines Cre-lox technology to fluorescently label germ cells, with flow cytometry to discriminate and isolate germ cells in different stages of development for cellular and molecular analyses.
A Two-Player Iterated Survival Game
Authors: Wakeley John , Nowak Martin 
Published: November 2018

AbstractWe describe an iterated game between two players, in which the payoff is to survive a number of steps. Expected payoffs are probabilities of survival. A key feature of the game is that individuals have to survive on their own if their partner dies. We consider individuals with hardwired, unconditional behaviors or strategies. When both players are present, each step is a symmetric two-player game. The overall survival of the two individuals forms a Markov chain. As the number of iterations tends to infinity, all probabilities of survival decrease to zero. We obtain general, analytical results for n-step payoffs and use these to describe how the game changes as n increases. In order to predict changes in the frequency of a cooperative strategy over time, we embed the survival game in three different models of a large, well-mixed population. Two of these models are deterministic and one is stochastic. Offspring receive their parent’s type without modification and fitnesses are determined by the game. Increasing the number of iterations changes the prospects for cooperation. All models become neutral in the limit (n → ∞). Further, if pairs of cooperative individuals survive together with high probability, specifically higher than for any other pair and for either type when it is alone, then cooperation becomes favored if the number of iterations is large enough. This holds regardless of the structure of pairwise interactions in a single step. Even if the single-step interaction is a Prisoner’s Dilemma, the cooperative type becomes favored. Enhanced survival is crucial in these iterated evolutionary games: if players in pairs start the game with a fitness deficit relative to lone individuals, the prospects for cooperation can become even worse than in the case of a single-step game.
Unitization modulates recognition of within-domain and cross-domain associations: Evidence from event related potentials
Authors: Li Bingcan , Han Meng , Guo Chunyan , Tibon Roni 
Published: November 2018

AbstractAlthough it is often assumed that memory of episodic associations requires recollection, it has been suggested that when stimuli are experienced as a unit, familiarity processes might contribute to their subsequent associative recognition. We investigated the effects of associative relations and perceptual domain during episodic encoding on retrieval of associative information. During study, participants encoded compound and non-compound words-pairs, presented either to the same sensory modality (visual presentation) or to different sensory modalities (audio-visual presentation). At test, they discriminated between old, rearranged, and new pairs while event related potentials (ERPs) were recorded. In an early ERP component, generally associated with familiarity processes, differences related to associative memory only emerged for compounds, regardless their encoding modality. In contrast, in a later ERP component associated with recollection, differences related to associative memory emerged in all encoding conditions. These findings may indicate that episodic retrieval of compound words can be supported by familiarity-related processes, regardless of whether both words were presented to the same or different sensory modalities.
Bile acid metabolites control Th17 and Treg cell differentiation
Authors: Hang Saiyu , Paik Donggi , Devlin A. Sloan , Jamma Trinath , Lu Jingping , Ha Soyoung , Nelson Brandon N. , Kelly Samantha P. , Wu Lin , Zheng Ye , Rastinejad Fraydoon , Krout Michael R. , Fischbach Michael A. , Littman Dan R. , Huh Jun R. 
Published: November 2018

AbstractBile acids are abundantly present in the mammalian gut, where they undergo bacteria-mediated transformation, generating a large pool of bioactive molecules. While they have been shown to affect host metabolism, cancer progression and innate immunity, it is unknown whether bile acids affect the function of adaptive immune cells such as T cells expressing IL-17a (Th17 cells) and regulatory T cells (Tregs) that mediate inflammatory and anti-inflammatory responses, respectively. By screening a small-molecule library primarily composed of bile acid metabolites, we identified two distinct derivatives of lithocholic acid (LCA), 3-oxoLCA and isoalloLCA, as specific regulators of Th17 and Treg cells. While 3-oxoLCA inhibited Th17 cell differentiation by directly binding to its key transcription factor RORγt (retinoid-related orphan receptor γ t), isoalloLCA enhanced differentiation of Tregs through mitochondrial-dependent metabolic changes, leading to an increased expression of Foxp3. IsoalloLCA-dependent Treg enhancement required an intronic Foxp3 enhancer, the conserved noncoding sequence 3 (CNS3), which acts as an epigenetic switch that confers a poised state to the Foxp3 promoter. Lastly, oral administration of 3-oxoLCA and isoalloLCA to mice led to reduced Th17 and increased Treg cell differentiation in the intestinal lamina propria. Altogether, our data suggest novel mechanisms by which bile acid metabolites control host immune responses by directly modulating the Th17 and Treg balance.
Desiccation Does Not Drastically Increase the Accessibility of Foreign DNA to the Nuclear Genomes: Evidence from the Frequency of Endosymbiotic DNA Transfer
Authors: Li Xi-Xi , Fang Cheng , Zhao Jun-Peng , Zhou Xiao-Yu , Ni Zhihua , Niu Deng-Ke 
Published: November 2018

AbstractHorizontal gene transfer (HGT) is a widely accepted force in the evolution of prokaryotic genomes. However, in eukaryotes, it is still in hot debate. Some bdelloid rotifers that are resistant to extreme desiccation and radiation were reported to have a very high level of HGTs. However, a similar report in another resistant invertebrate, tardigrades, has been mired in controversy. The DNA double-strand breaks (DSBs) induced by prolonged desiccation have been postulated to open the gateway of nuclear genome for foreign DNA integration and thus facilitate the HGT process. If so, the rate of endosymbiotic DNA transfer should also be enhanced. We first surveyed the abundance of nuclear mitochondrial DNAs (NUMTs) and nuclear plastid DNAs (NUPTs) in three groups of eukaryotes that are extremely resistant to desiccation, bdelloid rotifers, A. vaga and A. ricciae, tardigrades, H. dujardini and R. varieornatus, and the resurrection plants, D. hygrometricum and S. tamariscina. Excessive NUMTs or NUPTs have not been detected. Furthermore, we compared nine groups of desiccation-tolerant organisms with their desiccation-sensitive relatives but did not find significant difference in the NUMT/NUPT contents. Desiccation could induce DSBs, but it unlikely dramatically increase the frequency of foreign sequence integration in most eukaryotes. Only in the nuclear genomes enriched in repetitive sequences, the DSBs are predominantly repaired by non-homologous end joining (NHEJ) and desiccation-induced DSBs is possible to enhance the integration of foreign sequences into nuclear genome for some degree.
GLaMST: Grow Lineages along Minimum Spanning Tree for B Cell Receptor Sequencing Data
Authors: Yang Xingyu , Tipton Christopher M. , Woodruff Matthew C. , Zhou Enlu , Lee F. Eun-Hyung , Sanz Inãki , Qiu Peng 
Published: November 2018

AbstractB cell affinity maturation enables B cells to generate high-affinity antibodies. This process involves somatic hypermutation of B cell immunoglobulin receptor (BCR) genes and selection by their ability to bind antigens. Lineage trees are used to describe this microevolution of B cell immunoglobulin genes. In a lineage tree, each node is one BCR sequence that mutated from the germinal center and each directed edge represents a single base mutation, insertion or deletion. In BCR sequencing data, the observed data only contains a subset of BCR sequences in this microevolution process. Therefore, reconstructing the lineage tree from experimental data requires algorithms to build the tree based on partially observed tree nodes. We developed a new algorithm named Grow Lineages along Minimum Spanning Tree (GLaMST), which efficiently reconstruct the lineage tree given observed BCR sequences that correspond to a subset of the tree nodes. GLaMST constructs the minimum-spanning-tree (MST) to approximate the landscape of how observed BCR sequences are related, uses the MST to guide the interpolation of the closest unobserved sequence, updates the MST for the interpolation of additional unobserved sequences, and iterates until a full lineage tree is completed, where all observed sequences are connected by interpolated unobserved sequences and single base operations of mutations, insertions and deletions. Through comparison using simulated and real data, GLaMST outperforms existing algorithms in simulations with high rates of mutation, insertion and deletion, and generates lineage trees with smaller size and closer to ground truth according to tree features that highly correlated with selection pressure.
A missense mutation of Ip3r1 in Dp2 mice leads to short-term mydriasis and unfolded protein response in the iris constrictor muscles
Authors: Chen Bing , Qi Chongyang , Chen Li , Dai Mengjun , Miao Yayou , Chen Rui , Wei Wane , Yang Shun , Wang Hongling , Duan Xiaoge , Gong Minwei , Yi Wang , Xue Zhengfeng 
Published: November 2018

ABSTRACTIp3r1 encodes an inositol 1,4,5-triphosphate-responsive calcium channel. Mutations in the Ip3r1 gene in humans may cause Gillespie syndrome (GS) typically presents as fixed dilated pupils in affected infants, which was referred to as iris hypoplasia. However, there is no report of mice with Ip3r1 heterozygous mutations showing dilated pupils. Here, we report a new Ip3r1 allele (dilated pupil 2; Dp2) with short-term dilated pupil phenotype derived from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. This allele carries a G5927A transition mutation, which is predicted to result in a C1976Y amino acid change in the open reading frame. Histology and pharmacological tests show that the dilated pupil phenotype is a mydriasis caused by the functional defect in the iris constrictor muscles in Dp2. The dilated pupil phenotype in Dp2 was referred to as mydriasis and excluding iris hypoplasia. IHC analysis revealed increased expression of BIP protein, the master regulator of unfolded protein response (UPR) signaling, in Dp2 mice that did not recover. Apart from the dilated pupil phenotype (mydriasis), there are no other abnormal phenotypes including Ip3r1-related ataxia that may be found. This study is the first report of an Ip3r1 mutation being associated with the mydriasis phenotype. Dp2 mice represent a valuable self-healing model that may be used to study the therapeutic approach for Ip3r1-related diseases or diseases caused by similar pathomechanisms.
No-Go Decay mRNA cleavage in the ribosome exit tunnel produces 5’-OH ends phosphorylated by Trl1
Authors: Navickas Albertas , Chamois Sébastien , Saint-Fort Rénette , Henri Julien , Torchet Claire , Benard Lionel 
Published: November 2018

AbstractThe No-Go Decay (NGD) mRNA surveillance pathway degrades mRNAs containing stacks of stalled ribosomes. Although an endoribonuclease has been proposed to initiate cleavages upstream of the stall sequence, the production of two RNA fragments resulting from a unique cleavage has never been demonstrated. We have used mRNAs expressing a 3’-ribozyme to produce truncated transcriptsin vivoto mimic naturally occurring truncated mRNAs known to trigger NGD. This technique allows us to analyse endonucleolytic cleavage events at single-nucleotide resolution starting at the third collided ribosome, which we show to be Hel2-dependent. These cleavages map precisely in the mRNA exit tunnel of the ribosome, 8 nucleotides upstream of the first P-site residue and release 5’-hydroxylated RNA fragments requiring 5’-phosphorylation prior to digestion by the exoribonuclease Xrn1, or alternatively by Dxo1. Finally, we identify the RNA kinase Trl1, alias Rlg1, as an essential player in the degradation of NGD RNAs.
GenGraph: a python module for the simple generation and manipulation of genome graphs
Authors: Ambler Jon Mitchell , Mulaudzi Shandukani , Mulder Nicola 
Published: November 2018

AbstractBackgroundAs sequencing technology improves, the concept of a single reference genome is becoming increasingly restricting. In the case of Mycobacterium tuberculosis, one must often choose between using a genome that is closely related to the isolate, or one that is annotated in detail. One promising solution to this problem is through the graph based representation of collections of genomes as a single genome graph. Though there are currently a handful of tools that can create genome graphs and have demonstrated the advantages of this new paradigm, there still exists a need for flexible tools that can be used by researchers to overcome challenges in genomics studies.ResultsWe present the GenGraph toolkit, a tool that uses existing multiple sequence alignment tools to create genome graphs. It is written in Python, one of the most popular coding languages for the biological sciences, and creates the genome graphs as Python NetworkX graph objects. The conceptual model is highly intuitive, and as much as possible represents the biological relationship between the genomes. This design means that users will quickly be able to start creating genome graphs and using them in their own projects.We outline the methods used in the generation of the graphs, and give some examples of how the created graphs may be used. GenGraph utilises existing file formats and methods in the generation of these graphs, allowing graphs to be visualised and imported with widely used applications, including Cytoscape, R, and Java Script.ConclusionGenGraph provides a set of tools for generating graph based representations of sets of sequences with a simple conceptual model in a widely used coding language. It is publicly available on Github (https://github.com/jambler24/GenGraph).
Protein synthesis rates and ribosome occupancies reveal determinants of translation elongation rates
Authors: Riba Andrea , Nanni Noemi Di , Mittal Nitish , Arhné Erik , Schmidt Alexander , Zavolan Mihaela 
Published: November 2018

AbstractAlthough protein synthesis dynamics has been studied both with theoretical models and by profiling ribosome footprints, the determinants of ribosome flux along open reading frames (ORFs) are not fully understood. Combining measurements of protein synthesis rate with ribosome footprinting data, we here inferred translation initiation and elongation rates for over a thousand ORFs in exponentially-growing wildtype yeast cells. We found that the amino acid composition of synthesized proteins is as important a determinant of translation elongation rate as parameters related to codon and tRNA adaptation. We did not find evidence of ribosome collisions curbing the protein output of yeast transcripts, either in high translation conditions associated with exponential growth, or in strains in which deletion of individual ribosomal protein genes leads to globally increased or decreased translation. Slow translation elongation is characteristic of RP-encoding transcripts, which have markedly lower protein output than other transcripts with equally high ribosome densities.Significance StatementAlthough sequencing of ribosome footprints has uncovered new aspects of mRNA translation, the determinants of ribosome flux remain incompletely understood. Combining ribosome footprint data with measurements of protein synthesis rates, we here inferred translation initiation and elongation rates for over a thousand ORFs in yeast strains with varying translation capacity. We found that the translation elongation rate varies up to ~20-fold among yeast transcripts, and is significantly correlated with the rate of translation initiation. Furthermore, the amino acid composition of synthesized proteins impacts the rate of translation elongation to the same extent as measures of codon and tRNA adaptation. Transcripts encoding ribosomal proteins are translated especially slow, having markedly lower protein output than other transcripts with equally high ribosome densities.
Improved spatial ecological sampling using open data and standardization: an example from malaria mosquito surveillance
Authors: Sedda Luigi , Lucas Eric R. , Djogbénou Luc S. , Edi Ako V.C. , Egyir-Yawson Alexander , Kabula Bilali I. , Midega Janet , Ochomo Eric , Weetman David , Donnelly Martin J. 
Published: November 2018

AbstractVector-borne disease control relies on efficient vector surveillance, mostly carried out using traps whose number and locations are often determined by expert opinion rather than a rigorous quantitative sampling design. In this work we first propose a framework for ecological sampling design which in its preliminary stages can take into account environmental conditions obtained from open data (i.e. remote sensing and meteorological stations). These environmental data are used to delimit the area into ecologically homogenous strata. By employing a model-based sampling design, the traps are deployed among the strata using a mixture of random and grid locations which allows balancing predictions and fitting accuracies. Sample sizes and the effect of ecological strata on sample sizes are estimated from previous sampling campaigns. Notably, we found that a configuration of 30 locations with 4 households each (120 traps) will have a similar accuracy in the estimates of mosquito abundance as 300 random samples. In addition, we show that random sampling independently from ecological strata, produces biased estimates of the mosquito abundance. Finally, we propose standardizing reporting of sampling designs to allow transparency and repetition / re-use in subsequent sampling campaigns.
Ancestry-agnostic estimation of DNA sample contamination from sequence reads
Authors: Zhang Fan , Flickinger Matthew ,   InPSYght Psychiatric Genetics Consortium
Published: November 2018

AbstractDetecting and estimating DNA sample contamination are important steps to ensure high quality genotype calls and reliable downstream analysis. Existing methods rely on population allele frequency information for accurate estimation of contamination rates. Correctly specifying population allele frequencies for each individual in early stage of sequence analysis is impractical or even impossible for large-scale sequencing centers that simultaneously process samples from multiple studies across diverse populations. On the other hand, incorrectly specified allele frequencies may result in substantial bias in estimated contamination rates. For example, we observed that existing methods often fail to identify 10% contaminated samples at a typical 3% contamination exclusion threshold when genetic ancestry is misspecified. Such an incomplete screening of contaminated samples substantially inflates the estimated rate of genotyping errors even in deeply sequenced genomes and exomes.We propose a robust statistical method that accurately estimates DNA contamination and is agnostic to genetic ancestry of the intended or contaminating sample. Our method integrates the estimation of genetic ancestry and DNA contamination in a unified likelihood framework by leveraging individual-specific allele-frequencies projected from reference genotypes onto principal component coordinates. We demonstrate this method robustly and accurately estimates contamination rates across different populations and contamination rates. We further demonstrate that in the presence contamination, quantitative estimates of genetic ancestry (e.g. principal component coordinates) can be substantially biased if contamination is ignored, and that our proposed method corrects for this bias. Our method is publicly available at http://github.com/Griffan/verifyBamID