bluuebunny/crossref_metadata_2025_split huggingface dataset:
New insights into the ORF2 capsid protein, a key player of the hepatitis E virus lifecycle
Authors: Ankavay Maliki , Montpellier Claire , Sayed Ibrahim M. , Saliou Jean-Michel , Wychowski Czeslaw , Saas Laure , Duvet Sandrine , Aliouat-Denis Cécile-Marie , Farhat Rayan , de Masson d’Autume Valentin , Meuleman Philip , Dubuisson Jean , Cocquerel Laurence 
Published: October 2018

AbstractHepatitis E Virus (HEV) genome encodes three proteins including the ORF2 protein that is the viral capsid protein. Recently, we developed an efficient HEV cell culture system and demonstrated that this virus produces three different forms of its capsid protein: (i) the ORF2i form (infectious/intracellular) which is the form associated with the infectious particles, (ii) the ORF2g (glycosylated ORF2) and ORF2c (cleaved ORF2) forms that are massively secreted glycoproteins not associated with infectious particles, but are the major antigens present in HEV-infected patient sera. The ORF2 protein sequence contains three highly conserved potential N-glycosylation sites (N1, N2 and N3). Although ORF2 protein is the most characterized viral protein, its glycosylation status and the biological relevance of this post-translational modification is still unclear. In the present study, we constructed and extensively characterized a series of ORF2 mutants in which the three N-glycosylation sites were mutated individually or in combination. We demonstrated that the ORF2g/c protein is N-glycosylated on N1 and N3 sites but not on the N2 site. We showed that N-glycosylation of ORF2 protein does not play any role in replication and assembly of infectious HEV particles. We found that glycosylated ORF2g/c forms are very stable proteins which are targeted by patient antibodies. During our study, we also demonstrated that the ORF2i protein is translocated into the nucleus of infected cells. In conclusion, our study led to new insights into the molecular mechanisms of ORF2 expression.
Establishment of murinein vitroblood-brain barrier models using immortalized cell lines: co-cultures of brain endothelial cells, astrocytes, and neurons
Authors: Idris Fakhriedzwan , Hanna Muharram Siti , Zaini Zainun , Diah Suwarni 
Published: October 2018

AbstractBlood-brain barrier (BBB) is a selective barrier formed by the endothelial cells that line cerebral microvessels. It serves as a physical barrier due to the presence of complex tight junctions between adjacent endothelial cells which limits the paracellular movement of most molecules across the BBB. Manyin vitromodels of the BBB have been established to mimic thesein vivoproperties with limited success. In this study, we described the properties of a cell-based murinein vitroBBB model in five configurations constructed using immortalized cell lines in a 12-well format Transwell system: murine brain endothelial cells (bEnd.3) grown in a monoculture, or as co-culture in contact with astrocytes, or without contact with astrocytes or neurons, and triple co-culture combining the three cell lines. We found that only contact and triple co-culture model closely mimic thein vivoBBB tightness as evaluated by apparent permeability (Papp) of sucrose and albumin producing the lowest Papp values of 0.56 ± 0.16 × 10−6cms−1and 3.30 ± 0.51 × 10−6cms−1, respectively, obtained in triple co-culture model. Co-culturing of bEnd.3 with astrocytes increased the expression of occludin as shown by western blot analysis, and immunohistochemistry showed an increase in peripheral localization of occludin and claudin-5. In addition, we found conditioned media were able to increasein vitroBBB model tightness through the modulation of tight junction proteins localization. We conclude that the presence of astrocytes and neurons in close proximity to brain endothelial cells is essential to produce a tightin vitroBBB model.
Integrating Vectors for Genetic Studies in the Rare ActinomyceteAmycolatopsis marina
Authors: Gao Hong , Murugesan Buvani , Hoßbach Janina , Evans Stephanie K. , Stark W. Marshall , Smith Margaret C.M. 
Published: October 2018

AbstractFew natural product pathways from rare Actinomycetes have been studied due to the difficulty in applying molecular approaches in these genetically intractable organisms. In this study, we sought to identify integrating vectors, derived using phageint/attPloci, that would efficiently integrate site-specifically in the rare Actinomycete,Amycolatopsis marinaDSM45569. Analysis of the genome of A.marinaDSM45569 indicated the presence ofattB-like sequences for TG1 and R4 integrases. The TG1 and R4attBswere active inin vitrorecombination assays with their cognate purified integrases andattPloci. Integrating vectors containing either the TG1 or R4int/attPloci yielded exconjugants in conjugation assays fromE. colitoA. marinaDSM45569. Site-specific recombination of the plasmids into the host TG1 or R4attBsites was confirmed by sequencing. The presence of homologous TG1 and R4attBsites in other species of this genus indicates that vectors based on TG1 and R4 integrases could be widely applicable.ImportanceRare Actinomycetes have the same potential of natural product discovery as Streptomyces, but the potential has not been fully explored due to the lack of efficient molecular biology tools. In this study, we identified two serine integrases, TG1 and R4, which could be used in the rare Actinomycetes species,Amycolatopsis marina, as tools for genome integration. The high level of conservation between theattBsites for TG1 and R4 in a number of Amycolatopsis species suggested that plasmids with the integration systems from these phages should be widely useful in this genus.
Comprehensive in silico Analysis of IKBKAP gene that could potentially cause Familial dysautonomia
Authors: Mustafa Mujahed I. , Osman Enas A. , Abdelmoneiom Abdelrahman H. , Hassn Dania M. , Yousif Hadeel M. , Mahgoub Inshrah K. , Badawi Razan M. , Albushra Kutuf A. , Abdelhameed Tebyan A , Hassan Mohamed A. 
Published: October 2018

AbstractBackgroundFamilial dysautonomia (FD) is a rare neurodevelopmental genetic disorder within the larger classification of hereditary sensory and autonomic neuropathies. We aimed to identify the pathogenic SNPs in IKBKAP gene by computational analysis software’s, and to determine the structure, function and regulation of their respective proteins.Materials and MethodsWe carried out in silico analysis of structural effect of each SNP using different bioinformatics tools to predict SNPs influence on protein structure and function.Result41 novel mutations out of 973 nsSNPs that are found be deleterious effect on the IKBKAP structure and function.ConclusionThis is the first in silico analysis in IKBKAP gene to prioritize SNPs for further genetic studies.
Comparison of DNA metabarcoding and morphological identification for stream macroinvertebrate biodiversity assessment and monitoring
Authors: Serrana Joeselle M. , Miyake Yo , Gamboa Maribet , Watanabe Kozo 
Published: October 2018

AbstractConventional morphology-based identification is commonly used for routine assessment of freshwater ecosystems. However, cost and time efficient techniques such as high-throughput sequencing (HTS) based approaches may resolve the constraints encountered in conducting morphology-based surveys. Here, we characterized stream macroinvertebrate species diversity and community composition via metabarcoding and morphological analysis from environmental samples collected from the Shigenobu River Basin in Ehime Prefecture, Japan. We compared diversity metrics and assessed both approaches’ ability to evaluate the relationship between macroinvertebrate community and environmental variables. In total, we morphologically identified 45 taxa (3 families, six subfamilies, 31 genera, and five species) from 8,276 collected individuals from ten study sites. We detected 44 species by metabarcoding, with 35 species collapsed into 11 groups matching the morphologically identified taxa. A significant positive correlation between logged depth (number of HTS reads) and abundance of morphological taxa was observed, which implied that quantitative data can be used for subsequent analyses. Relatively higher estimates of alpha diversity were calculated from the metabarcoding data in comparison to morphology-based data. However, beta diversity estimates between metabarcoding and morphology data based on both incidence and abundance-based matrices were correlated proving that community differences between sampling sites were preserved in the molecular data. Also, both models were significant, but metabarcoding data (93%) explained a relatively higher percentage of variation in the relationship between community composition and the environmental variables than morphological data (91%). Overall, we present both the feasibility and limitations of HTS-driven estimations of taxonomic richness, community composition, and diversity metrics, and that metabarcoding was proven comparable and more sensitive against morphology-based analysis for stream macroinvertebrate biodiversity assessment and environmental monitoring.
A role for the VPS retromer inBrucellaintracellular replication revealed by genome-wide siRNA screening
Authors: Casanova Alain , Low Shyan Huey , Québatte Maxime , Sedzicki Jaroslaw , Tschon Therese , Ketterer Maren , Smith Kevin , Emmenlauer Mario , Ben-Tekaya Houchaima , Dehio Christoph 
Published: October 2018

AbstractBrucella,the causing agent of brucellosis, is a major zoonotic pathogen with worldwide distribution.Brucellaresides and replicates inside infected host cells in membrane-bound compartments called BCVs (Brucella-containing vacuoles). Following uptake,Brucellaresides in eBCVs (endosomal BCVs) that gradually mature from early to late endosomal features. Through a poorly understood process that is key to the intracellular lifestyle ofBrucella,the eBCV escapes fusion with lysosomes by transitioning to the rBCV (replicative BCV), a replicative niche directly connected to the endoplasmic reticulum (ER). Despite the notion that this complex intracellular lifestyle must depend on a multitude of host factors, a holistic view on which of these components controlBrucellacell entry, trafficking and replication is still missing. Here we used a systematic cell-based siRNA knockdown screen in HeLa cells infected withBrucella abortusand identified 425 components of the human infectome forBrucellainfection. These include multiple components of pathways involved in central processes such as cell cycle, actin cytoskeleton dynamics or vesicular trafficking. Using assays for pathogen entry, knockdown complementation and co-localization at single-cell resolution, we identified the requirement of the VPS retromer forBrucellato escape the lysosomal degradative pathway and to establish its intracellular replicative niche. We thus validated a component of the VPS retromer as novel host factor critical forBrucellaintracellular trafficking. Further, our genome-wide data shed light on the interplay between central host processes and the biogenesis of theBrucellareplicative niche.ImportanceWith >300,000 new cases of human brucellosis annually,Brucellais regarded as one of the most important zoonotic bacterial pathogen worldwide. The causing agent of brucellosis resides inside host cells within vacuoles termedBrucellacontaining vacuoles (BCVs). Although few host components required to escape the degradative lysosomal pathway and to establish the ER-derived replicative BCV (rBCV) have already been identified, the global understanding of this highly coordinated process is still partial and many factors remain unknown. To gain a deeper insight into these fundamental questions we performed a genome-wide RNA interference (RNAi) screen aiming at discovering novel host factors involved in theBrucellaintracellular cycle. We identified 425 host proteins that contribute toBrucellacellular entry, intracellular trafficking, and replication. Together, this study sheds light on previously unknown host pathways required for theBrucellainfection cycle and highlights the VPS retromer components as critical factors for the establishment of theBrucellaintracellular replicative niche.
Insights into the structure-driven protein interactivity of RNA molecules
Authors: de Groot Natalia Sanchez , Armaos Alexandros , Montes Ricardo Graña , Alriquet Marion , Calloni Giulia , Vabulas R. Martin , Tartaglia Gian Gaetano 
Published: October 2018

ABSTRACTThe combination of high-throughput sequencing and in vivo crosslinking approaches leads to the progressive uncovering of the complex interdependence between cellular transcriptome and proteome. Yet the molecular determinants that govern interactions in protein-RNA networks are poorly known at present. Here we used the most recent experimental data to investigate the relationship between RNA structure and protein interactions. Our results show that, independently of the particular technique, the amount of structure in RNA molecules correlates with the capacity of binding to proteins in vitro and in vivo. To validate this observation, we generated an in vitro network that mimics the composition of phase-separated RNA granules. We observed that RNA, when structured, competes with protein binding and can rearrange the interaction network. The simplicity of the principle bears great potential to boost the understanding and modelling of cellular processes involving RNA-protein interactions.
Would conserving natural land cover in landscapes conserve biodiversity?
Authors: De Camargo Rafael X. , Currie David J. 
Published: October 2018

ABSTRACTIt is generally accepted that protecting natural land cover would protect biodiversity. This would only be true as a general statement if the relationship between richness and natural land cover were monotonic positive and scale- and method-independent. Assertions about habitat loss causing species losses often come from broad-scale assessment of richness (e.g., from range maps) combined with patterns of natural habitat conversion. Yet, the evidence about species loss following habitat loss or fragmentation typically comes from fine-scale experiments. Here, we test whether broad-extent relationships between avian species richness and natural land cover are independent of: 1) whether species distribution data come from systematic censuses (atlases) versus range maps, and 2) the grain size of the analysis. We regressed census-based and range map-based avian species richness against the proportion of natural land cover and temperature. Censused richness at the landscape level was obtained from Breeding Bird Atlases of Ontario and New York State. Range-map richness derived from BirdLife International range maps. Comparisons were made across different spatial grains: 25-km2, 100-km2, and 900-km2. Over regional extents, range-map richness relates strongly to temperature, irrespective of spatial grain. Censused species richness relates to temperature less strongly. Range-map richness is a negative function of the proportion of natural land cover, while realized richness is a peaked function. The two measures of richness are not monotonically related to each other. In conclusion, the data do not indicate that, in practice, landscapes with greater natural land cover in southern Ontario or in New York State have higher species richness. Moreover, different data types can lead to dramatically different relationships between richness and natural land cover. We argue that the argument that habitat loss is the main driver of species loss has become a panchreston. It may be misguiding conservation biology strategies by focusing on a threat that is too general to be usefully predictive.
Drinking motives and alcohol use among college students with the alcohol flush reaction
Authors: Oh Sarah Soyeon , Ju Yeong Jun , Lee San , Jang Sung-in , Park Eun-Cheol 
Published: October 2018

ABSTRACTBackgroundThis study investigated the relationship between drinking motives and alcohol use among a nationally representative sample of college students with the alcohol flush reaction (AFR). We surveyed and analyzed the data of 2,245 male and 2,326 female college students in a nationally representative sample of 82 colleges in South Korea.MethodsOf our study population, 725 males (32.3%) and 812 females (34.9%) reported to currently suffering from AFR. Multiple regression analysis was used to identify the association between drinking motives and drinking behavior, measured via the AUDIT.ResultsRelative to drinking because of peer pressure, students drinking for pleasure (males: β = 2.622,p<.0001; females β = 2.769,p<.0001) or stress/depression (males: β = 2.479,p<.0001; females β = 2.489,p<.0001) had higher AUDIT scores. Among students drinking because of stress/depression, seniors (males: β = 3.603,p<.0001; females: β = 3.791,p= 0.000), smokers (males: β = 1.564,p= 0.000; females β = 1.816,p= 0.007) and/or liberal arts students (males: β = 6.1136,p<.0001; females β = 4.2105,p<.0001) consumed more alcohol than their peers. Relative to conformity motives, enhancement and coping motives were found to have a greater influence on alcohol intake among college students with alcohol flush reaction.ConclusionConsidering that the flush reaction can occur in AFR individuals after just one sip of wine, our results show that educators and policymakers must take action to deal with this problem.
CLEESE: An open-source audio-transformation toolbox for data-driven experiments in speech and music cognition
Authors: Burred Juan José , Ponsot Emmanuel , Goupil Louise , Liuni Marco , Aucouturier JJ 
Published: October 2018

AbstractOver the past few years, the field of visual social cognition and face processing has been dramatically impacted by a series of data-driven studies employing computer-graphics tools to synthesize arbitrary meaningful facial expressions. In the auditory modality, reverse correlation is traditionally used to characterize sensory processing at the level of spectral or spectro-temporal stimulus properties, but not higher-level cognitive processing of e.g. words, sentences or music, by lack of tools able to manipulate the stimulus dimensions that are relevant for these processes. Here, we present an open-source audio-transformation toolbox, called CLEESE, able to systematically randomize the prosody/melody of existing speech and music recordings. CLEESE works by cutting recordings in small successive time segments (e.g. every successive 100 milliseconds in a spoken utterance), and applying a random parametric transformation of each segment’s pitch, duration or amplitude, using a new Python-language implementation of the phase-vocoder digital audio technique. We present here two applications of the tool to generate stimuli for studying intonation processing of interrogative vs declarative speech, and rhythm processing of sung melodies.
Rabies prevention and control practice and associated factors among dog owners in Aksum town and Laelay-Machew district, north Ethiopia: community based comparative cross-sectional study
Authors: Gebrezgiher Letebrhan , Berhe Gebretsadik , Belay Aregawi Gebreyesus , Adisu Alefech 
Published: October 2018

AbstractBackgroundRabies is nearly 100% fatal zoonotic disease. One thousand seven hundred suspected rabies exposures reported in north Ethiopia, Tigray region in 2017, which has the highest rabies prevalence from Ethiopia. Almost half of them were from Central zone only. Of these 38% were in Aksum town and Laelay-Machew. Though Rabies exposure is prevalent in Tigray, there is scanty information on rabies prevention and control practices among dog owners. Thus, this deals with rabies prevention and control practice and associated factors among dog owners.Methods and materialsComparative community based cross-sectional study was conducted in Aksum town and Laelay-Machew district from March 01 to 20, 2018. A multi stage sampling was employed to recruit 558 households. Data were collected via structured and pretested questionnaire. Data were entered into Epi_info_7 and then exported to SPSS_20 for analysis. Both descriptive and inferential analysis was done with 95% confidence intervals at p value of 5% for the final model.ResultThe overall prevalence of poor rabies prevention and control practice was 56% [95%CI (50, 61.9)] in urban and 62% [95% CI (57.2, 67.7)] in rural dog owners. In urban; being government employee [AOR (95%CI) = 0.35 (0.13, 0.94)], private employee [AOR (95%CI) =0.39(0.16, 0.97)] and having poor attitude [(AOR (95%CI) =1.84 (1.04, 3.25)] were significantly associated with outcome variable. Whereas in rural dwellers; having no formal education [AOR (95%CI)=6.41(1.1,38.6)], poor attitude [AOR (95%CI)= 2.19 (1.18,4.05)], having one dog [AOR (95%CI)=3.31(1.34,8.15)], travel ≥30 minute to get vaccine [AOR (95%CI)= 4.26 (2.14,8.47]), no history of dog bite exposure [AOR (95%CI)= 4.16(1.49,11.6)] and neighbors as their source of information [AOR (95%CI) =3.64 (1.31,10.1)] have statistical significance with the outcome variable.Conclusion and RecommendationThe prevalence of poor rabies prevention and control practice was higher among rural dog owners. Thus; interventions should be implemented both to urban and rural residents based on the identified findings so as to promote effective rabies prevention and control activities.
Evidence for strong fixation bias at 4-fold degenerate sites across genes in the great tit genome
Authors: Gossmann Toni I. , Bockwoldt Mathias , Diringer Lilith , Schwarz Friedrich , Schumann Vic-Fabienne 
Published: October 2018

ABSTRACTIt is well established that GC content varies across the genome in many species and that GC biased gene conversion, one form of meiotic recombination, is likely to contribute to this heterogeneity. Bird genomes provide an extraordinary system to study the impact of GC biased gene conversion owed to their specific genomic features. They are characterised by a high karyotype conservation with substantial heterogeneity in chromosome sizes, with up to a dozen large macrochromosomes and many smaller microchromosomes common across all bird species. This heterogeneity in chromosome morphology is also reflected by other genomic features, such as smaller chromosomes being gene denser, more compact and more GC rich relative to their macrochromosomal counterparts - illustrating that the intensity of GC biased gene conversion varies across the genome. Here we study whether it is possible to infer heterogeneity in GC biased gene conversion rates across the genome using a recently published method that accounts for GC biased gene conversion when estimating branch lengths in a phylogenetic context. To infer the strength of GC biased gene conversion we contrast branch length estimates across the genome both taking and not taking non-stationary GC composition into account. Using simulations we show that this approach works well when GC fixation bias is strong and note that the number of substitutions along a branch is consistently overestimated when GC biased gene conversion is not accounted for. We use this predictable feature to infer the strength of GC dynamics across the great tit genome by applying our new test statistic to data at 4-fold degenerate sites from three bird species - great tit, zebra finch and chicken - three species that are among the best annotated bird genomes to date. We show that using a simple one-dimensional binning we fail to capture a signal of fixation bias as observed in our simulations. However, using a multidimensional binning strategy, we find evidence for heterogeneity in the strength of fixation bias, including AT fixation bias. This highlights the difficulties when combining sequence data across different regions in the genome.