bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergence and the spread of the F200Y benzimidazole resistance mutation in Haemonchus contortus and Haemonchus placei from buffalo and cattle
Authors: Ali Qasim , Rashid Imran , Shabbir Muhammad Zubair , Aziz-Ul-Rahman  , Shahzad Kashif , Ashraf Kamran , Sargison Neil D. , Chaudhry Umer 
Published: September 2018

AbstractBenzimidazoles have been intensively used in the livestock sector, particularly in small ruminants for over 40 years. This has been led to the widespread emergence of resistance in a number of small ruminant parasite species, in particular Haemonchus contortus. In many counties benzimidazole resistance in the small ruminants H. contortus has become severely compromising its control; but there is a little information on benzimidazole resistance in H. contortus infecting buffalo and cattle. Resistance to benzimidazoles have also been reported in the large ruminant parasite, Haemonchus placei, but again there is relatively little information on its prevalence. Hence it is extremely important to understand how resistance-conferring mutations emerge and spread in both parasites in the buffalo and cattle host in order to develop the approaches for the recognition of the problem at an early stage of its development. The present study suggests that the F200Y (TAC) mutation is common in H. contortus, being detected in 5/7 populations at frequencies between 7 to 57%. Furthermore, 6/10 H. placei populations contained the F200Y (TAC) mutation, albeit at low frequencies of between 0.4 to 5%. The phylogenetic analysis suggests that the F200Y (TAC) mutation in H. contortus has emerged on multiple occasions in the region, with at least three independent emergence of resistance alleles across the populations. In contrast, the F200Y (TAC) resistance-conferring mutation in H. placei is only seen on a single haplotype. A high level of haplotype frequency of the susceptible alleles in the region, suggests that the unique resistance conferring-mutation has spread from a single emergence; likely by anthropogenic animal movement. Overall, these results provide the first clear genetic evidence for the spread of benzimidazoles resistance-conferring mutations to multiple different locations from a single emergence in H. placei; while supporting previous small ruminant-based observations of multiple emergence of resistance mutations in H. contortus.
Phospholipid-Cellulose Interactions: Insight from Atomistic Computer Simulations for Understanding the Impact of Cellulose-Based Materials on Plasma Membranes
Authors: Gurtovenko Andrey A. , Mukhamadiarov Evgenii I. , Kostritskii Andrei Yu. , Karttunen Mikko 
Published: September 2018

AbstractCellulose is an important biocompatible and nontoxic polymer widely used in numerous biomedical applications. The impact of cellulose-based materials on cells and, more specifically, on plasma membranes that surround cells, however, remains poorly understood. To this end, here we performed atomic-scale molecular dynamics (MD) simulations of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) bilayers interacting with the surface of a cellulose crystal. Both biased umbrella sampling and unbiased simulations clearly show the existence of strong attractive interactions between phospholipids and cellulose: the free energy of the cellulose-bilayer binding was found to be −1.89 and −1.96 kJ/mol per cellulose dimer for PC and PE bilayers, respectively. Although the values are similar, there is a pronounced difference between PC and PE bilayers. The driving force in both cases is the formation of hydrogen bonds. There are two distinct types of hydrogen bonds: 1) between the lipid head groups and the hydroxyl (hydroxymethyl) groups of cellulose, and 2) lipid-water and cellulose-water bonds. The former is the dominant component for PE systems whereas the latter dominates in PC systems. This suggests that achieving controlled binding via new cellulose modifications must pay close attention to the lipid head groups involved. The observed attractive phospholipid-cellulose interactions have a significant impact on bilayer properties: a cellulose crystal induces noticeable structural perturbations on the bilayer leaflet next to the crystal. Given that such perturbations can be undesirable when it comes to the interactions of cellulose-based materials with cell membranes, our computational studies suggest that the impact of cellulose could be reduced through chemical modification of the cellulose surface which prevents cellulose-phospholipid hydrogen bonding.
Lasting effects of repeated Δ9-tetrahydrocannabinol (THC) vapor inhalation during adolescence in male and female rats
Authors: Nguyen Jacques D. , Creehan K. M. , Kerr Tony M. , Taffe Michael A. 
Published: September 2018

AbstractAdolescents are regularly exposed to Δ9-tetrahydrocannabinol (THC) via smoking, and, more recently, vaping, cannabis / extracts. Growing legalization of cannabis for medical and recreational purposes, combined with decreasing perceptions of harm, makes it increasingly important to determine the consequences of frequent adolescent exposure for motivated behavior and lasting tolerance in response to THC. Male and female rats inhaled THC vapor, or that from the propylene glycol (PG) vehicle, twice daily for 30 minutes from postnatal day (PND) 35-39 and PND 42-45 using an e-cigarette system. Thermoregulatory responses to vapor inhalation were assessed by radio-telemetry during adolescence and from PND 86-94; chow intake was assessed in adulthood. Blood samples were obtained from additional adolescent groups following initial THC inhalation and after four days of twice daily exposure. Additional groups exposed repeatedly to THC or PG during adolescence were evaluated for intravenous self-administration of oxycodone as adults. Female, not male, adolescents developed tolerance to the hypothermic effects of THC inhalation in the first week of repeated exposure despite similar plasma THC levels. Each sex exhibited tolerance to THC hypothermia in adulthood after repeated adolescent THC with THC greater potency exhibited in females. Repeated-THC male rats consumed more food than their PG treated control group, in the absence of a significant bodyweight difference. Adolescent THC did not alter oxycodone self-administration in either sex, but increased fentanyl self-administration in females. Repeated THC vapor inhalation in adolescent rats results in lasting consequences observable in adulthood.AbbreviationsPG, propylene glycol; THC, Δ9tetrahydrocannabinol;
Reduced representation characterization of genetic and epigenetic differentiation to oil pollution in the foundation plant Spartina alterniflora
Authors: Alvarez Mariano , Robertson Marta , van Gurp Thomas , Wagemaker Niels , Giraud Delphine , Ainouche Malika L. , Salmon Armel , Verhoeven Koen J. F. , Richards Christina L. 
Published: September 2018

AbstractTheory predicts that environmental challenges can shape the composition of populations, which is manifest at the molecular level. Previously, we demonstrated that oil pollution affected gene expression patterns and altered genetic variation in natural populations of the foundation salt marsh grass, Spartina alterniflora. Here, we used a reduced representation bisulfite sequencing approach, epigenotyping by sequencing (epiGBS), to examine relationships among DNA sequence, DNA methylation, gene expression, and exposure to oil pollution. We documented genetic and methylation differentiation between oil-exposed and unexposed populations, suggesting that the Deepwater Horizon oil spill may have selected on genetic variation, and either selected on epigenetic variation or induced particular epigenotypes and expression patterns in exposed compared to unexposed populations. In support of the potential for differential response to the Deepwater Horizon oil spill, we demonstrate genotypic differences in response to oil under controlled conditions. Overall, these findings demonstrate genetic variation, epigenetic variation and gene expression are correlated to exposure to oil pollution, which may all contribute to the response to environmental stress.
ICTD: A semi-supervised cell type identification and deconvolution method for multi-omics data
Authors: Chang Wennan , Wan Changlin , Lu Xiaoyu , Tu Szu-wei , Sun Yifan , Zhang Xinna , Zang Yong , Zhang Anru , Huang Kun , Liu Yunlong , Lu Xiongbin , Cao Sha , Zhang Chi 
Published: September 2018

AbstractWe developed a novel deconvolution method, namely Inference of Cell Types and Deconvolution (ICTD) that addresses the fundamental issue of identifiability and robustness in current tissue data deconvolution problem. ICTD provides substantially new capabilities for omics data based characterization of a tissue microenvironment, including (1) maximizing the resolution in identifying resident cell and sub types that truly exists in a tissue, (2) identifying the most reliable marker genes for each cell type, which are tissue and data set specific, (3) handling the stability problem with co-linear cell types, (4) co-deconvoluting with available matched multi-omics data, and (5) inferring functional variations specific to one or several cell types. ICTD is empowered by (i) rigorously derived mathematical conditions of identifiable cell type and cell type specific functions in tissue transcriptomics data and (ii) a semi supervised approach to maximize the knowledge transfer of cell type and functional marker genes identified in single cell or bulk cell data in the analysis of tissue data, and (iii) a novel unsupervised approach to minimize the bias brought by training data. Application of ICTD on real and single cell simulated tissue data validated that the method has consistently good performance for tissue data coming from different species, tissue microenvironments, and experimental platforms. Other than the new capabilities, ICTD outperformed other state-of-the-art devolution methods on prediction accuracy, the resolution of identifiable cell, detection of unknown sub cell types, and assessment of cell type specific functions. The premise of ICTD also lies in characterizing cell-cell interactions and discovering cell types and prognostic markers that are predictive of clinical outcomes.
Population-scale study of eRNA transcription reveals bipartite functional enhancer architecture
Authors: Kristjánsdóttir Katla , Kwak Yeonui , Tippens Nathaniel D. , Lis John T. , Min Kang Hyun , Kwak Hojoong 
Published: September 2018

AbstractEnhancer RNAs (eRNA) are non-coding RNAs transcribed bidirectionally from active regulatory sequences. Their expression levels correlate with the activating potentials of the enhancers, but due to their instability, eRNAs have proven difficult to quantify in large scale. To overcome this, we use capped-nascent-RNA sequencing to efficiently capture the bidirectional initiation of eRNAs. We apply this in large scale to the human lymphoblastoid cell lines from the Yoruban population, and detected nearly 75,000 eRNA transcription sites with high sensitivity and specificity. We identify genetic variants significantly associated with overall eRNA initiation levels, as well as the transcription directionality between the two divergent eRNA pairs, namely the transcription initiation and directional initiation quantitative trait loci (tiQTLs and diQTLs) respectively. High-resolution analyses of these two types of eRNA QTLs reveal distinct positions of enrichment not only at the central transcription factor (TF) binding regions but also at the flanking eRNA initiation regions, both of which are equivalently associated with mRNA expression QTLs. These two regions - the central TF binding footprint and the eRNA initiation cores - define the bipartite architecture and the function of enhancers, and may provide further insights into interpreting the significance of non-coding regulatory variants.
Leveraging single cell RNA sequencing experiments to model intra-tumor heterogeneity
Authors: Ferrall-Fairbanks Meghan C. , Ball Markus , Padron Eric , Altrock Philipp M. 
Published: September 2018

ABSTRACTPURPOSEMany cancers can be treated with targeted therapy. Almost inevitably, tumors develop resistance to targeted therapy, either from preexistence or by evolving new genotypes and traits. Intra-tumor heterogeneity serves as a reservoir for resistance, which often occurs due to selection of minor cellular sub-clones. On the level of gene expression, the ‘clonal’ heterogeneity can only be revealed by high-dimensional single cell methods. We propose to use a general diversity index (GDI) to quantify heterogeneity on multiple scales and relate it to disease evolution.METHODSWe focused on individual patient samples probed with single cell RNA sequencing to describe heterogeneity. We developed a pipeline to analyze single cell data, via sample normalization, clustering and mathematical interpretation using a generalized diversity measure, and exemplify the utility of this platform using single cell data.RESULTSWe focused on three sources of RNA sequencing data: two healthy bone marrow (BM) samples, two acute myeloid leukemia (AML) patients, each sampled before and after BM transplant (BMT), four samples of pre-sorted lineages, and six lung carcinoma patients with multi-region sampling. While healthy/normal samples scored low in diversity overall, GDI further quantified in which respect these samples differed. While a widely used Shannon diversity index sometimes reveals less differences, GDI exhibits differences in the number of potential key drivers or clonal richness. Comparing pre and post BMT AML samples did not reveal differences in heterogeneity, although they can be very different biologically.CONCLUSIONGDI can quantify cellular heterogeneity changes across a wide spectrum, even when standard measures, such as the Shannon index, do not. Our approach offers wide applications to quantify heterogeneity across samples and conditions.
Mechanisms of integrin αVβ5 clustering in flat clathrin lattices
Authors: Zuidema Alba , Wang Wei , Kreft Maaike , Molder Lisa te , Hoekman Liesbeth , Bleijerveld Onno B. , Nahidiaza Leila , Janssen Hans , Sonnenberg Arnoud 
Published: September 2018

Summary statementThis article highlights several molecular mechanisms that result in the assembly of integrin αVβ5-containing flat clathrin lattices in human keratinocytes.AbstractThe family of integrin transmembrane receptors is essential for the normal function of multicellular organisms by facilitating cell-extracellular matrix adhesion. The vitronectin-binding integrin αVβ5 localizes to focal adhesions (FAs) as well as poorly characterized flat clathrin lattices (FCLs). Here we show that in human keratinocytes αVβ5 is predominant found in FCLs and that formation of the αVβ5-containing FCLs requires the presence of vitronectin as ligand, calcium, and the clathrin adaptor proteins ARH, Numb, and EPS15/EPS15L1. Integrin chimeras, containing the extracellular and transmembrane domains of β5 and the cytoplasmic domains of β1 or β3, almost exclusively localize in FAs. Interestingly, lowering actomyosin-mediated contractility promotes integrin redistribution to FLCs in an integrin tail-dependent manner, while increasing cellular tension favors αVβ5 clustering in FAs. Our findings strongly indicate that clustering of integrin αVβ5 in FCLs is dictated by the β5 subunit cytoplasmic domain, cellular tension, and recruitment of specific adaptor proteins to the β5 subunit cytoplasmic domains.
Trait-based approach to bacterial growth efficiency
Authors: Muscarella Mario E. , Howey Xia Meng , Lennon Jay T. 
Published: September 2018

AbstractBacterial growth efficiency (BGE) is the proportion of assimilated carbon that is converted into biomass and reflects the balance between growth and energetic demands. Often measured as an aggregate property of the community, BGE is highly variable within and across ecosystems. To understand this variation, we first identified how species identity and resource type affect BGE using 20 bacterial isolates belonging to the phylum Proteobacteria that were enriched from north temperate lakes. Using a trait-based approach that incorporated genomic and phenotypic information, we characterized the metabolism of each isolate and tested for predicted trade-offs between growth rate and efficiency. A substantial amount of variation in BGE could be explained at both broad (i.e., order, 20 %) and fine (i.e., strain, 58 %) taxonomic levels. While resource type was a relatively weak predictor across species, it explained > 60 % of the variation in BGE within a given species. Furthermore, a metabolic trade-off (between maximum growth rate and efficiency) and genomic features revealed that BGE is a predictable metabolic feature. Our study suggests that genomic and phylogenetic information may help predict aggregate microbial community functions like BGE and the fate of carbon in ecosystems.Originality and SignificanceBacterial growth efficiency (BGE) is an important yet notoriously variable measure of metabolism that has proven difficult to predict. To better understand how assimilated carbon is allocated, we explored growth efficiency across a collection of bacteria strains using a trait-based approach. Specifically, we measured respiration and biomass formation rates for populations grown in minimal media containing one of three carbon resources. In addition, we collected a suite of physiological traits to describe each strain, and we sequenced the genome of each organism. Our results suggest that species identity and resource type may contribute to growth efficiency when measured as an aggregate property of a natural community. In addition, we identified genomic pathways that are associated with elevated BGE. The findings have implications for integrating microbial metabolism from the cellular to ecosystem scale.
Wound-induced polyploidization is driven by Myc and supports tissue repair in the presence of DNA damage
Authors: Grendler Janelle , Lowgren Sara , Mills Monique , Losick Vicki P. 
Published: September 2018

AbstractTissue repair requires either polyploid cell growth or cell division, but the molecular mechanism promoting polyploidy and limiting proliferation remains poorly understood. Here we find that injury to the adultDrosophilaepithelium causes cells to enter the endocycle through the activation of Yorkie dependent genes (myc,e2f1, orcycE). Myc is even sufficient to induce the endocycle in the post-mitotic epithelium. As result, epithelial cells enter S phase but mitosis is blocked by inhibition of mitotic gene expression. The mitotic cell cycle program can be activated by simultaneously expressing the mitotic activator,Stg, while genetically depletingfzr. However, forcing cells to undergo mitosis is detrimental to wound repair as the adult fly epithelium accumulates DNA damage and mitotic errors ensue when cells are forced to proliferate. In conclusion, we find that wound-induced polyploidization enables tissue repair when cell division is not a viable option.
Pixel: a content management platform for quantitative omics data
Authors: Denecker Thomas , Durand William , Maupetit Julien , Hébert Charles , Camadro Jean-Michel , Poulain Pierre , Lelandais Gaëlle 
Published: September 2018

ABSTRACTBackgroundIn biology, high-throughput experimental technologies, also referred as “omics” technologies, are increasingly used in research laboratories. Several thousands of gene expression measurements can be obtained in a single experiment. Researchers are routinely facing the challenge to annotate, store, explore and mine all the biological information they have at their disposal. We present here the Pixel web application (Pixel Web App), an original content management platform to help people involved in a multi-omics biological project.MethodsThe Pixel Web App is built with open source technologies and hosted on the collaborative development platform GitHub (https://github.com/Candihub/pixel). It is written in Python using the Django framework and stores all the data in a PostgreSQL database. It is developed in the open and licensed under the BSD 3-clause license. The Pixel Web App is also heavily tested with both unit and functional tests, a strong code coverage and continuous integration provided by CircleCI. To ease the development and the deployment of the Pixel Web App, Docker and Docker Compose are used to bundle the application as well as its dependencies.ResultsThe Pixel Web App offers researchers an intuitive way to annotate, store, explore and mine their multi-omics results. It can be installed on a personal computer or on a server to fit the needs of many users. In addition, anyone can enhance the application to better suit their needs, either by contributing directly on GitHub (encouraged) or by extending Pixel on their own. The Pixel Web App does not provide any computational programs to analyze the data. Still, it helps to rapidly explore and mine existing results and holds a strategic position in the management of research data.
Isolation of cancer stem cells by selection for miR-302 expressing cells
Authors: Rahimi Karim , Füchtbauer Annette C. , Fathi Fardin , Mowla Seyed Javad , Füchtbauer Ernst-Martin 
Published: September 2018

AbstractCancer stem cells receive increasing interest because they are believed to be a major reason for long-term therapy failure. The reason for the therapy resistance of cancer stem cells lies partially in their multi-drug resistance and partially in the ability to rest mitotically inactive in the hypoxic center of tumors. Due to their variable number and their often low proliferation rate, cancer stem cells are difficult to purify in decent quantities and to grow in cell culture systems, where they are easily outcompeted by faster growing more ‘differentiated’, i.e. less stem cell-like tumor cells. Here we present a proof of principle study based on the idea to select cancer stem cells by means of the expression of a stem cell-specific gene. We inserted a selectableegfp-neocoding sequence in the last exon of the non-coding murinemiR-302host gene. As a stem cell specific regulatory element, we used 2.1 kb of the genomic region immediately upstream of themiR-302host gene transcription start. Stable transgenic CJ7 embryonic stem cells were used to induce teratomas. After three weeks, tumors were removed for analysis and primary cultures were established. Stem-like cells were selected from these culture based on G418 selection. When the selection was removed, stem cell morphology andmiR-302expression were rapidly lost, indicating that it were not the original ES cells that have been isolated. In conclusion, we show the possibility to use drug resistance expressed from a regulatory sequence of a stem cell-specific marker, to isolate and propagate cancer stem cells that otherwise might be hidden in the majority of tumor cells.