bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interference hypothesis for recombination suppression in chromosomal inversion heterozygotes: A formal genetics analysis inDrosophila melanogaster
Authors: Koury Spencer A. 
Published: April 2018

ABSTRACTSuppressed recombination in chromosomal inversion heterozygotes is a well-known but poorly understood phenomenon. Recombination suppression is the result of at least four different regional effects of inversion heterozygosity; surprisingly, this includes areas outside inversions where there are no barriers to normal pairing, synapsis, double strand break formation, or recovery of crossover products. The interference hypothesis of recombination suppression proposes heterozygous inversion breakpoints possess chiasma-like properties such that recombination suppression extends from breakpoints in a process analogous to crossover interference. This hypothesis is qualitatively consistent with chromosome-wide patterns of recombination suppression, unifying the various regional effects under a single mechanism. The present study generates quantitative predictions for this hypothesis using a probabilistic model of crossover interference as a stationary renewal point process with gamma-distributed interarrival distances. These predictions were tested with formal genetic data (>40,000 meioses) on crossing-over in intervals external and adjacent to four cosmopolitan inversions ofDrosophila melanogaster. The decay of recombination suppression differs for each of the four cosmopolitan inversions, with a strong dependence on proximity to the centromere. Counterintuitively, greater than expected recombination was observed in centromeric regions for the most proximally placed inversions. Structural features of chromosomes are discussed as potentially confounding variables in modelling recombination suppression. The true form of the decay function is not currently known and will require high-resolution mapping of rare crossover events in regions immediately adjacent to inversion breakpoints. A simple extension of the present experimental system can be conducted as a genetic screen for those rare crossover events.
Introduced populations of ragweed show as much evolutionary potential as native populations
Authors: McGoey Brechann V. , Stinchcombe John R. 
Published: April 2018

AbstractInvasive species are a global economic and ecological problem. They also offer an opportunity to understand evolutionary processes in a colonizing context. The impacts of evolutionary factors, such as genetic variation, on the invasion process are increasingly appreciated but there remain gaps in the empirical literature. The adaptive potential of populations can be quantified using genetic variance-covariance matrices(G), which encapsulate the heritable genetic variance in a population. Here, we use a multivariate, Bayesian approach to assess the adaptive potential of introduced populations of ragweed,Ambrosia artemisiifolia, a serious allergen and agricultural weed. We compared several aspects of genetic architecture and the structure of G matrices between three native and three introduced populations, based on data collected in the field in a common garden experiment. We find moderate differences in the quantitative genetic architecture among populations, but we do not find that introduced populations suffer from a limited adaptive potential compared to native populations. Ragweed has an annual life history, is an obligate outcrosser, and produces billions of seeds and pollen grains per. These characteristics, combined with the significant additive genetic variance documented here, suggest ragweed will be able to respond quickly to selection pressures in both its native and introduced ranges.
LCA robustly reveals subtle diversity in large-scale single-cell RNA-seq data
Authors: Cheng Changde , Easton John , Rosencrance Celeste , Li Yan , Ju Bensheng , Williams Justin , Mulder Heather L , Chen Wenan , Chen Xiang 
Published: April 2018

AbstractSingle-cell RNA sequencing has emerged as a powerful tool for characterizing the cell-to-cell variation and dynamics. We present Latent Cellular Analysis (LCA), a machine learning– based analytical pipeline that features a dual-space model search with inference of latent cellular states, control of technical variations, cosine similarity measurement, and spectral clustering. LCA has proved to be robust, accurate, scalable, and powerful in revealing subtle diversity in cell populations.
Sub-2 Å Ewald Curvature Corrected Single-Particle Cryo-EM
Authors: Tan Yong Zi , Aiyer Sriram , Mietzsch Mario , Hull Joshua A. , McKenna Robert , Grieger Joshua , Samulski R. Jude , Baker Timothy S. , Agbandje-McKenna Mavis , Lyumkis Dmitry 
Published: April 2018

AbstractSingle-particle cryogenic electron microscopy (cryo-EM) provides a powerful methodology for structural biologists, but the resolutions typically attained with experimentally determined structures have lagged behind microscope capabilities. Here, we have exploited several technical solutions to improve resolution, including sub-Angstrom pixelation, per-particle CTF refinement, and most notably a correction for Ewald sphere curvature. The application of these methods on micrographs recorded on a base model Titan Krios enabled structure determination at ∼1.86-Å resolution of an adeno-associated virus serotype 2 variant (AAV2), an important gene-delivery vehicle.
Spatial distribution of private gene mutations in clear cell renal cell carcinoma
Authors: Moore Ariane L. , Batavia Aashil A. , Kuipers Jack , Singer Jochen , Burcklen Elodie , Schraml Peter , Beisel Christian , Moch Holger , Beerenwinkel Niko 
Published: April 2018

AbstractIntra-tumour heterogeneity is the molecular hallmark of renal cancer, and the molecular tumour composition determines the treatment outcome of renal cancer patients. In renal cancer tumourigenesis, in general, different tumour clones evolve over time. We analysed intra-tumour heterogeneity and subclonal mutation patterns in 178 tumour samples obtained from 89 clear cell renal cell carcinoma patients. In an initial discovery phase, whole-exome and transcriptome sequencing data from paired tumour biopsies from 16 ccRCC patients were used to design a gene panel for follow-up analysis. In this second phase, 826 selected genes were targeted at deep coverage in an extended cohort of 89 patients for a detailed analysis of tumour heterogeneity. On average, we found 22 mutations per patient. Pairwise comparison of the two biopsies from the same tumour revealed that on average 62% of the mutations in a patient were detected in one of the two samples. In addition to commonly mutated genes (VHL,PBRM1,SETD2andBAP1),frequent subclonal mutations with low variant allele frequency (<10%) were observed inTP53and in mucin coding genesMUC6,MUC16, andMUC3A. Of the 89 ccRCC tumours, 87 (~98%) harboured private mutations, occurring in only one of the paired tumour samples. Clonally exclusive pathway pairs were identified using the WES data set from 16 ccRCC patients. Our findings imply that shared and private mutations significantly contribute to the complexity of differential gene expression and pathway interaction, and might explain clonal evolution of different molecular renal cancer subgroups. Multi-regional sequencing is central for the identification of subclones within ccRCC.
Rethomics: an R framework to analyse high-throughput behavioural data
Authors: Geissmann Quentin , Rodriguez Luis Garcia , Beckwith Esteban J. , Gilestro Giorgio F. 
Published: April 2018

AbstractThe recent development of automatised methods to score various behaviours on a large number of animals provides biologists with an unprecedented set of tools to decipher these complex phenotypes. Analysing such data comes with several challenges that are largely shared across acquisition platform and paradigms. Here, we presentrethomics, a set ofRpackages that unifies the analysis of behavioural datasets in an efficient and flexible manner.rethomicsoffers a computational solution to storing, manipulating and visualising large amounts of behavioural data. We propose it as a tool to bridge the gap between behavioural biology and data sciences, thus connecting computational and behavioural scientists.rethomicscomes with a extensive documentation as well as a set of both practical and theoretical tutorials (available athttps://rethomics.github.io).
Elevated O-GlcNAcylation Enhances Pro-Inflammatory Th17 Function by Altering the Lipid Microenvironment
Authors: Machacek Miranda , Zhang Zhen , Tan Ee Phie , Li Jibiao , Li Tiangang , Villar Maria T. , Artigues Antonio , Lydic Todd , Slawson Chad , Fields Patrick 
Published: April 2018

SUMMARYChronic, low-grade inflammation increases the risk of atherosclerosis, cancer, and autoimmunity in diseases like obesity and diabetes. Here, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc (O-linked β-N-acetylglucosamine) are present in naïve CD4+ T cells from a diet-induced obesity murine model, and elevation in O-GlcNAc leads to increased pro-inflammatory IL-17A production. Importantly, CD4+ T helper 17 (Th17) cells, which secrete IL-17A, are increased in obesity and contribute to the inflammatory milieu. We found increased binding of the Th17 master transcription factor, RORγt, at the IL-17 locus and significant alterations in the lipid microenvironment, leading to increased ligands capable of increasing RORγt transcriptional activity. Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl CoA carboxylase 1 (ACC1), is necessary for production of these RORγt activating ligands and is O-GlcNAcylated. Thus, we have identified O-GlcNAc as a critical link between excess nutrients and pathological inflammation.
In Silico Analysis Reveals a Shared Immune Signature in CASP8-Mutated Carcinomas with Varying Correlations to Prognosis
Authors: Ghanekar Yashoda , Sadasivam Subhashini 
Published: April 2018

AbstractBackgroundSequencing studies across multiple cancers continue to reveal the spectrum of mutations and genes involved in the pathobiology of these cancers. Exome sequencing of oral cancers, a subset of Head and Neck Squamous cell Carcinomas (HNSCs) common among tobacco-chewing populations, revealed that ~34% of the affected patients harbor mutations in the CASP8 gene. Uterine Corpus Endometrial Carcinoma (UCEC) is another cancer type where about 10% cases harbor CASP8 mutations. Caspase-8, the protease encoded by CASP8 gene, plays a dual role in programmed cell death, which in turn has an important role in tumor cell death and drug resistance. CASP8 is a protease required for the extrinsic pathway of apoptosis and is also a negative regulator of necroptosis. Using bioinformatics approaches to mine data in The Cancer Genome Atlas, we compared the molecular features and survival of these carcinomas with and without CASP8 mutations.ResultsOur in silico analyses showed that HNSCs with CASP8 mutations displayed a prominent signature of genes involved in immune response and inflammation, and were rich in immune cell infiltrates. However, in contrast to Human Papilloma Virus-positive HNSCs, a subtype that exhibits high immune cell infiltration and better overall survival, HNSC patients with mutant-CASP8 tumors did not display any survival advantage. A similar bioinformatic analyses in UCECs revealed that while UCECs with CASP8 mutations also displayed an immune signature, they had better overall survival, in contrast to the HNSC scenario. On further examination, we found that there was significant up-regulation of neutrophils as well as the cytokine, IL33 in mutant-CASP8 HNSCs, both of which were not observed in mutant-CASP8 UCECs.ConclusionsThese results suggested that carcinomas with mutant CASP8 have broadly similar immune signatures albeit with different effects on survival. We hypothesize that subtle tissue-dependent differences could influence survival by modifying the micro-environment of mutant-CASP8 carcinomas. High neutrophil numbers, which is a well-known negative prognosticator in HNSCs, and/or high IL33 levels may be some of the factors affecting survival of mutant-CASP8 cases.
Loop-mediated isothermal amplification assay forEnterococcus sp., E. coliandS. aureusin chicken
Authors: Song HyeSoon , Bae YouChan , Kwon HyukMan , Kwon YongKuk , Joh SeongJoon 
Published: April 2018

ABSTRACTBacterial chondronecrosis with osteomyelitis (BCO) is a major cause of lameness in broiler chicken, and results in serious economic losses worldwide. Although the pathogenesis mechanism leading to lameness is not entirely understood, some strains ofEnterococcus sp., avian pathogenicEscherichia coli, orStaphylococcus aureushave been long recognized as important causative pathogens. To prevent the progression ofEnterococcus sp., avian pathogenicE. coli, orS. aureusinfections, we developed rapid, sensitive, and convenient diagnostic assays using loop-mediated isothermal amplification (LAMP). Entero-Common-LAMP assays were developed for a simultaneous detection of eightEnterococcusspecies. To target specific microorganisms, seven Entero-Specific-LAMP assays forE. faecalis, E. faecium, E. hirae, E. gallinarum, E. avium, E. duransandE. cecorum, andE. coli-LAMP andS. aureus-LAMP assays, were developed. Considering the prevalence and economic impact ofEnterococcus sp., E. coli, andS. aureus, the developed ten different LAMP assays have a considerable potential as routine diagnostic methods in the field or in resource-limited environments.
Trend and pattern of antimicrobial resistance in molluscanVibriospecies sourced to Canadian estuaries
Authors: Banerjee Swapan K. , Farber Jeffrey M. 
Published: April 2018

ABSTRACTEmergence of antimicrobial resistance (AMR) in foodborne bacteria is a growing concern worldwide. AMR surveillance is a key element in understanding the implications resulting from the use of antibiotics for therapeutic as well as prophylactic needs. The emergence and spread of AMR in foodborne human pathogens is an indirect health hazard. This surveillance study reports the trend and pattern of AMR detected inVibriospecies isolated from molluscs harvested in Canada, between 2006 and 2012, against 19 commonly used antibiotics. Five common antibiotics, ampicillin, cephalothin, erythromycin, kanamycin and streptomycin, predominantly contributed to AMR including multi-drug resistance (MDR) in the molluscanVibriospp. isolated in 2006. A prospective follow-up analysis of these drugs showed a declining trend in the frequency of MDR/AMR-Vibriospp. in subsequent years until 2012. The observed decline appears to have been influenced by the specific downturn in resistance to the aminoglycosides, kanamycin and streptomycin. Frequently observed MDR/AMR-Vibriospp. in seafood is a potential health concern associated with seafood consumption. Our surveillance study provided an indication of the antibiotics that challenged the marine bacteria, sourced to Canadian estuaries, during and/or prior to the study period.
Staphylococcal superantigen-like protein 13 activates neutrophils via Formyl Peptide Receptor 2
Authors: Zhao Yuxi , van Kessel Kok P. M. , de Haas Carla J. C. , Rogers Malbert R. C. , van Strijp Jos A. G. , Haas Pieter-Jan A. 
Published: April 2018

AbstractStaphylococcal Superantigen-Like (SSL) proteins, one of major virulence factor families produced byStaphylococcus aureus, were previously demonstrated to be immune evasion molecules that interfere with a variety of innate immune defenses. However, in contrast to these characterized SSLs, that inhibit immune functions, we show that SSL13 is a strong activator of neutrophils via the formyl-peptide receptor 2 (FPR2). Moreover, our data show that SSL13 acts as a chemoattractant, induces degranulation and oxidative burst in neutrophils. As with many other staphylococcal immune evasion proteins, SSL13 shows a high degree of human specificity. SSL13 is not able to efficiently activate mouse neutrophils, hamperingin vivoexperiments.In conclusion, SSL13 is a neutrophil chemoattractant and activator that acts via the FPR2. Therefore, SSL13 is a unique SSL member that does not belong to the immune evasion class, but is a pathogen alarming molecule.
ARKS: chromosome-scale scaffolding of human genome drafts with linked read kmers
Authors: Coombe Lauren , Zhang Jessica , Vandervalk Benjamin P , Chu Justin , Jackman Shaun D , Birol Inanc , Warren René L 
Published: April 2018

AbstractBackgroundThe long-range sequencing information captured by linked reads, such as those available from 10x Genomics (10xG), helps resolve genome sequence repeats, and yields accurate and contiguous draft genome assemblies. We introduce ARKS, an alignment-free linked read genome scaffolding methodology that uses linked reads to organize genome assemblies further into contiguous drafts. Our approach departs from other read alignment-dependent linked read scaffolders, including our own (ARCS), and uses a kmer-based mapping approach. The kmer mapping strategy has several advantages over read alignment methods, including better usability and faster processing, as it precludes the need for input sequence formatting and draft sequence assembly indexing. The reliance on kmers instead of read alignments for pairing sequences relaxes the workflow requirements, and drastically reduces the run time.ResultsHere, we show how linked reads, when used in conjunction with Hi-C data for scaffolding, improve a draft human genome assembly of PacBio long-read data five-fold (baseline vs. ARKS NG50=4.6 vs. 23.1 Mbp, respectively). We also demonstrate how the method provides further improvements of a megabase-scale Supernova human genome assembly, which itself exclusively uses linked read data for assembly, with an execution speed six to nine times faster than competitive linked read scaffolders. Following ARKS scaffolding of a human genome 10xG Supernova assembly (of cell line NA12878), fewer than 9 scaffolds cover each chromosome, except the largest (chromosome 1, n=13).ConclusionsARKS uses a kmer mapping strategy instead of linked read alignments to record and associate the barcode information needed to order and orient draft assembly sequences. The simplified workflow, when compared to that of our initial implementation, ARCS, markedly improves run time performances on experimental human genome datasets. Furthermore, ARKS utilizes barcoding information from linked reads to estimate gap size. It accomplishes this by modeling the relationship between known distances of a region within contigs and calculating associated Jaccard indices. ARKS has the potential to provide correct, chromosome-scale, genome assemblies, promptly. We expect ARKS to have broad utility in helping refine draft genomes.
Multi-target visual search organisation across the lifespan: Cancellation task performance in a large and demographically stratified sample of healthy adults
Authors: Benjamins Jeroen S. , Dalmaijer Edwin S. , Brink Antonia F. Ten , Nijboer Tanja C.W. , Stigchel Stefan Van der 
Published: April 2018

Highlights-Cancellation tasks are useful clinical tools that probe many cognitive modules-We used cancellation tests on 523 participants of different ages, sex, and education-We provide cancellation task norm scores for indices computed from a big sample-Cancellation indices include attention bias, processing speed and search organisation-About a quarter of the healthy population shows relatively disorganised searchAbstractIt is important that accurate tests exist to assess cognition in various groups of individuals. One popular test of attention and executive functioning is the cancellation task, in which participants perform multi-target visual search to find and ‘cancel’ targets among distractors. Although cancellation tasks have been used extensively with neurological patients, it is only partly clear whether performance is affected by demographic variables such as age and education, which can vary wildly among patients. Here, we describe performance in a sample of 523 healthy participants who participated in a web-based cancellation task. Specifically, we examined indices of spatial bias, processing speed, perseveration and revisiting behaviour, and search organisation. In this sample, age, sex, and level of education did not affect cancellation performance. A cluster analysis identified four cognitive profiles: Participants who make many omissions (N=18), who make many revisits (N=18), who have relatively poor search organisation (N=125), and who have relatively good search organisation (N=362). We advise neurologists and neuropsychologists to exercise caution when interpreting scores pertaining to search organisation in patients: Given the large proportion of healthy individuals with poor search organisation, disorganised search in patients might be pre-existing rather than disorder-related. Finally, we include norm scores for indices of spatial bias, perseverations and revisits, processing speed, and search organisation for a popular cancellation task.
Effective population sizes and adaptive genetic variation in a captive bird population
Authors: Athrey Giridhar , Faust Nikolas , Charlotte Hieke Anne-Sophie , Brisbin I. Lehr 
Published: April 2018

AbstractCaptive populations are considered a key component of ex situ conservation programs. Research on multiple taxa have shown the differential success of maintaining demographic versus genetic stability and viability in captive populations. In typical captive populations, usually founded by few or related individuals, genetic diversity can be lost and inbreeding can accumulate rapidly, calling into question their ultimate utility for release into the wild. Furthermore, domestication selection for survival in captive conditions is another concern. Therefore, it is crucial to understand the dynamics of population sizes, particularly the effective population size, and genetic diversity at non-neutral, at adaptive loci in captive populations.In this study, we assessed effective population sizes and genetic variation at both neutral microsatellite markers, as well as SNP variants from the MHC-B locus of a captive Red Junglefowl population. This population is represents a rare instance of a population with a well-documented history in captivity, following a realistic scenario of chain-of-custody, unlike captive lab populations. Our analysis, which included 27 individuals comprising the entirety of one captive population show very low neutral and adaptive genetic variation, as well as low effective sizes, which are surprising in spite of the known demographic history. Finally, our study also shows the divergent impacts of small effective size and inbreeding in captive populations on microsatellite versus adaptive genetic variation in the MHC-B locus. Our study provides insights into the difficulties of maintaining adaptive genetic variation in small captive populations.