bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut Microbiome Functional and Taxonomic Diversity within an Amazonian semi-nomadic hunter-gatherer group
Authors: Conteville LC , Oliveira-Ferreira J , Vicente AC 
Published: March 2019

AbstractBackgroundHuman gut microbiome profiles have been associated with human health and disease. These profiles have been defined based on microbes’ taxonomy and more recently, on their functionality. Human groups that still maintain traditional modes of subsistence (hunter-gatherers and rural agriculturalists) represent the groups non-impacted by urban-industrialized lifestyles, and therefore study them provide the basis for understanding the human microbiome evolution. The Yanomami is the largest semi-nomadic hunter-gatherer group of the Americas, exploring different niches of the Amazon rainforest in Brazil and Venezuela. In order to extend the analysis of this unique and diverse group, we focused on the gut microbiome of the Yanomami from Brazil and compared with those from Venezuela, and also with other traditional groups from the Amazon, considering taxonomic and functional profiles.ResultsA diversity of taxonomic biomarkers were identified to each South American traditional group studied, including the two Yanomami groups, despite their overall similarity in the taxonomic gut microbiome profiles. Broader levels of functional categories poorly discriminated traditional and urban-industrialized groups. Interestingly, a diversity was observed with the stratification of these categories, clearly segregating those groups. The Yanomami/Brazil gut microbiome presented unique functional features, such as a higher abundance of gene families involved in regulation/cell signaling, motility/chemotaxis, and virulence, contrasting with the microbiomes from the Yanomami/Venezuela and other groups.ConclusionsOur study revealed biomarkers, taxonomic and functional differences between the gut microbiome of Yanomami/Brazil and Yanomami/Venezuela individuals. This intra-Yanomami group diversity was accessed due to the increase number of individuals and group studied. These differences may reflect their semi-nomadic behavior, as well as, the local and seasonal diversity of the vast rainforest niche they explore, despite their shared cultural and genetic background. Overall, their microbiome profiles are shared with South American and African traditional groups, probably due to their lifestyle. The unique features identified within the Yanomami highlight the bias imposed by underrepresented sampling, and factors such as variations over space and time (seasonality) that impact, mainly, the hunter-gatherers. Therefore, to reach knowledge about human microbiome variations and their implications in human health, it is essential to enlarge data concerning the number of individuals, as well as the groups representing different lifestyles.
Quantitative assessment of anti-gravity reflexes to evaluate vestibular dysfunction in rats
Authors: Martins-Lopes Vanessa , Bellmunt Anna , Greguske Erin A. , Maroto Alberto F. , Boadas-Vaello Pere , Llorens Jordi 
Published: March 2019

AbstractThe tail-lift reflex and the air-righting reflex are anti-gravity reflexes in rats that depend on vestibular function. To obtain objective and quantitative measures of performance, we recorded these reflexes with slow motion video in two experiments. In the first experiment, vestibular dysfunction was elicited by acute exposure to 0 (control), 400, 600 or 1000 mg/kg of 3,3’-iminodipropionitrile (IDPN), which causes dose-dependent hair cell degeneration. In the second, rats were exposed to sub-chronic IDPN in the drinking water for 0 (control), 4 or 8 weeks; this causes reversible or irreversible loss of vestibular function depending on exposure time. In the tail-lift test, we obtained the minimum angle defined during the lift and descent maneuver by the nose, the back of the neck and the base of the tail. In the air-righting test, we obtained the time to right the head. We also obtained Vestibular Dysfunction Ratings (VDRs) using a previously validated behavioral test battery. Each measure, VDR, tail-lift angle and air-righting time, demonstrated dose-dependent loss of vestibular function after acute IDPN, and time-dependent loss of vestibular function after sub-chronic IDPN. All measures showed high correlations between each other, and maximal correlation coefficients were found between VDRs and tail-lift angles. In scanning electron microscopy evaluation of the vestibular sensory epithelia, the utricle and the saccule showed diverse pathological outcomes, suggesting that they have a different role in these reflexes. We conclude that these anti-gravity reflexes provide useful objective and quantitative measures of vestibular function in rats that are open to further development.
The structure of an injectisome export gate demonstrates conservation of architecture in the core export gate between flagellar and virulence type three secretion systems
Authors: Johnson Steven , Kuhlen Lucas , Deme Justin C. , Abrusci Patrizia , Lea Susan M. 
Published: March 2019

AbstractExport of proteins through type three secretion systems (T3SS) is critical for motility and virulence of many major bacterial pathogens. Proteins are exported though a genetically defined export gate complex consisting of three proteins. We have recently shown at 4.2 Å that the flagellar complex of these three putative membrane proteins (FliPQR in flagellar systems, SctRST in virulence systems) assemble into an extra-membrane helical assembly that likely seeds correct assembly of the rod above. Here we present the structure of an equivalent complex from the more fragile Shigella virulence system at 3.5 Å by cryo-electron microscopy. This higher resolution structure reveals further detail and confirms the prediction of structural conservation in this core complex. Analysis of particle heterogeneity also reveals details of how the SctS/FliQ subunits sequentially assemble in the complex.
High-throughput Phenotyping with Temporal Sequences
Authors: Estiri Hossein , Strasser Zachary H , Murphy Shawn N. 
Published: March 2019

ABSTRACTObjectiveHigh-throughput electronic phenotyping algorithms can accelerate translational research using data from electronic health record (EHR) systems. The temporal information buried in EHRs are often underutilized in developing computational phenotypic definitions. The objective of this study is to develop a high-throughput phenotyping method, leveraging temporal sequential patterns of discrete events from electronic health records.Materials and MethodsWe develop a representation mining algorithm to extract five classes of representations from EHR diagnosis and medication records: the aggregated vector of the records (AVR), the traditional immediate sequential patterns (SPM), the transitive sequential patterns (tSPM), as well as two hybrid classes of SPM+AVR and tSPM+AVR. A final small set of representations were selected from each class using the MSMR dimensionality reduction algorithm. Using EHR data on 10 phenotypes from Mass General Brigham Biobank, we trained regularized logistic regression algorithms, which we validated using labeled data.ResultsPhenotyping with temporal sequences resulted in a superior classification performance across all 10 phenotypes compared with the AVR representations that are conventionally used in electronic phenotyping. Although this study only utilizes the diagnosis and medication records, the high-throughput algorithm’s classification performance was superior or similar to the performance of previously published electronic phenotyping algorithms. We characterize and evaluate the top transitive sequences of diagnosis records paired with the records of risk factors, symptoms, complications, medications, or vaccinations.DiscussionThe proposed high-throughput phenotyping approach enables seamless discovery of sequential record combinations that may be difficult to assume from raw EHR data. A transitive sequence can offer a more accurate characterization of the phenotype, compared with its individual components. Additionally, the identified transitive sequences of a given phenotype reflect the actual lived experiences of the patients with that particular disease.ConclusionSequential data representations provide a precise mechanism for incorporating raw EHR records into downstream Machine Learning.
NatB modulates Rb mutant cell death and tumor growth by regulating EGFR/MAPK signaling through the N-end rule pathways
Authors: Sheng Zhentao , Du Wei 
Published: March 2019

AbstractDespite the prevalence of N-terminal acetylation (Nt-acetylation), little is known of its biological functions. In this study, we show that NatB regulates Rb mutant cell survival, EGFR/MAPK signaling activity, and EGFR signaling-dependent tumor growth. We identify Grb2/Drk, MAPK, and PP2AC as the key NatB targets of EGFR pathway. Surprisingly, NatB activity increases the levels of positive pathway components Grb2/Drk and MAPK while decreases the levels of negative pathway component PP2AC despite these proteins have the same first two amino acids that are recognized by NatB and N-end rule pathways. Mechanistically, we show that NatB regulates Grb2/Drk protein stability through its N-terminal sequences and that Grb2/Drk and MAPK are selectively degraded by the Arg/N-end rule E3 ubiquitin ligase Ubr4, which targets proteins with free N-terminus. In contrast, PP2AC is selectively degraded by the Ac/N-end rule pathway E3 ubiquitin ligase Cnot4 that targets proteins with acetylated N-terminus. These results reveal a novel mechanism by which NatB-mediated Nt-acetylation and N-end rule pathways modulate EGFR/MAPK signaling by inversely regulating the levels of positive and negative components. Since mutation or overexpression that deregulate the EGFR/Ras signaling pathway are common in human cancers and NatB subunits are significant unfavorable prognostic markers, this study can potentially lead to the development of novel therapeutic approaches.Significance StatementNt-acetylation is often regarded as a constitutive, irreversible, and static modification that is not suited to serve regulatory functions. Our observation that Nt-acetylation by NatB coordinately regulate the levels of positive and negative components of the EGFR/MAPK pathway show that Nt-acetylation and N-end rule pathways can play important roles regulating important signaling pathways. As Acetyl-CoA level, which is influenced by cell metabolism, can be rate limiting for Nt-acetylation, our results also suggest a potentially new mechanism by which cellular metabolic status can regulate growth factor signaling.
Unique Trophoblast Chromatin Environment Mediated by the PcG Protein SFMBT2
Authors: Tang Priscilla , Miri Kamelia , Varmuza Susannah 
Published: March 2019

ABSTRACTStem/progenitor cells are maintained by a chromatin environment, mediated in part by Polycomb group (PcG) proteins, that depresses differentiation. The trophoblast-specific PcG protein SFMBT2 is known to be required for maintenance of trophoblast progenitors. Rather than binding to trophoblast specific genes repressed in TSC, SFMBT2 is concentrated at chromocenters and regions rich in repetitive elements, specifically LINE sequences and major satellites, suggesting that it is involved in higher order organization of the trophoblast genome. It is also found enriched at a subset of ncRNAs. Comparison of ChIP-seq data sets for other chromatin proteins reveals several stereotypical distribution patterns, suggesting that SFMBT2 interacts with several different types of chromatin complexes specific to the trophoblast lineage.
Online sensory feedback during active search improves tactile localization
Authors: Fuchs Xaver , Wulff Dirk U. , Heed Tobias 
Published: March 2019

AbstractMany natural behaviors involve closed feedback loops in which ongoing sensory input refines motor behavior. Previous research on tactile localization, however, has implemented localization as open-loop behavior. For instance, participants indicate a touched position on a silhouette shape of the body or on an occluding board mounted above the hand. Such studies have suggested that humans often make large errors when localizing touch on the skin, or that “perceptual body representations” are distorted. However, by artificially preventing tactile feedback from the target body area, the natural action-perception loop is interrupted. Therefore, these localization approaches may underestimate individuals’ localization ability and draw erroneous conclusions about the role and precision of body representations. Here, we tested tactile localization in a natural setting, in which participants first received brief touches on their left forearm and then searched for the target location by moving the right index finger across the skin. Tactile search reduced localization error when the searching finger was far from, but not when it was near the target, resulting in a remaining error of 1-2 cm. Error reduction was absent when participants searched on an acrylic barrier mounted above the arm, suggesting that availability of tactile feedback on the target arm but not proprioceptive and motor signals of the searching arm determined precision, thus confirming the pivotal role of closed-loop sensory feedback for tactile localization. We suggest that actively produced online tactile feedback routinely refines coarse spatial body representations, similar to the refinement of sparse spatial representations in visual memory through consecutive saccades.
Orchestrating Single-Cell Analysis with Bioconductor
Authors: Amezquita Robert A. , Carey Vince J. , Carpp Lindsay N. , Geistlinger Ludwig , Lun Aaron T. L. , Marini Federico , Rue-Albrecht Kevin , Risso Davide , Soneson Charlotte , Waldron Levi , Pagès Hervé , Smith Mike , Huber Wolfgang , Morgan Martin , Gottardo Raphael , Hicks Stephanie C. 
Published: March 2019

AbstractRecent developments in experimental technologies such as single-cell RNA sequencing have enabled the profiling a high-dimensional number of genome-wide features in individual cells, inspiring the formation of large-scale data generation projects quantifying unprecedented levels of biological variation at the single-cell level. The data generated in such projects exhibits unique characteristics, including increased sparsity and scale, in terms of both the number of features and the number of samples. Due to these unique characteristics, specialized statistical methods are required along with fast and efficient software implementations in order to successfully derive biological insights. Bioconductor - an open-source, open-development software project based on the R programming language - has pioneered the analysis of such high-throughput, high-dimensional biological data, leveraging a rich history of software and methods development that has spanned the era of sequencing. Featuring state-of-the-art computational methods, standardized data infrastructure, and interactive data visualization tools that are all easily accessible as software packages, Bioconductor has made it possible for a diverse audience to analyze data derived from cutting-edge single-cell assays. Here, we present an overview of single-cell RNA sequencing analysis for prospective users and contributors, highlighting the contributions towards this effort made by Bioconductor.
A triple-hybrid cross reveals a new hybrid incompatibility locus betweenD. melanogaster and D. sechellia
Authors: Cooper Jacob C. , Guo Ping , Bladen Jackson , Phadnis Nitin 
Published: March 2019

AbstractHybrid incompatibilities are the result of deleterious interactions between diverged genes in the progeny of two species. InDrosophila, crosses between femaleD. melanogasterand males from theD. simulansclade (D. simulans,D. mauritiana,D. sechellia) fail to produce hybrid F1 males. When attempting to rescue hybrid F1 males by depleting the incompatible allele of a previously identified hybrid incompatibility gene, we observed robust rescue in crosses ofD. melanogastertoD. simulansorD. mauritiana, but no rescue in crosses toD. sechellia. To investigate the genetic basis ofD. sechelliaresistance to hybrid rescue, we designed a triple-hybrid cross to generate recombinantD. sechellia/D. simulansgenotypes. We tested the ability of those genotypes to rescue hybrid males withD. melanogaster, and used whole genome sequencing to measure theD. sechellia/D. simulansallele frequency of viable F1 males. We found that recombinant genotypes were rescued when they contained two specific loci fromD. simulans– a region containing previously identifiedLethal hybrid rescue (Lhr), and an unknown region of chromosome 3L which we nameSechellia aversion to hybrid rescue (Satyr). Our results show that the genetic basis for the recent evolution of this hybrid incompatibility is simple rather than a highly dispersed effect. Further, these data suggest that fixation of differences atLhrafter the split of theD. simulansclade strengthened the hybrid incompatibility betweenD. sechelliaandD. melanogaster.
A conserved acidic cluster motif in SERINC5 confers resistance to antagonism by HIV-1 Nef
Authors: Stoneham Charlotte A. , Ramirez Peter W. , Singh Rajendra , Suarez Marissa , Debray Andrew , Lim Christopher , Jia Xiaofei , Xiong Yong , Guatelli John 
Published: March 2019

AbstractThe cellular protein SERINC5 inhibits the infectivity of diverse retroviruses and is counteracted by the glycoGag protein of MLV, the S2 protein of EIAV, and the Nef protein of HIV-1. Determining regions within SERINC5 that provide restrictive activity or Nef-sensitivity should inform mechanistic models of the SERINC5/HIV-1 relationship. Here, we report that deletion of the highly conserved sequence EDTEE, which is located within a cytoplasmic loop of SERINC5 and is reminiscent of an acidic cluster membrane trafficking signal, increases the sensitivity of SERINC5 to antagonism by Nef while having no effect on the intrinsic activity of the protein as an inhibitor of infectivity. The effects on infectivity correlated with enhanced removal of the ΔEDTEE mutant relative to wild type SERINC5 from the cell surface and with enhanced exclusion of the mutant protein from virions by Nef. Mutational analysis revealed that the acidic residues, but not the threonine, within the EDTEE motif are important for the relative resistance to Nef. Deletion of the EDTEE sequence did not increase the sensitivity of SERINC5 to antagonism by the glycoGag protein of MLV, suggesting that its virologic role is Nef-specific. These results are consistent with the reported mapping of the cytoplasmic loop that contains the EDTEE sequence as a general determinant of Nef-responsiveness, but they further indicate that sequences inhibitory to as well as supportive of Nef-activity reside in this region. We speculate that the EDTEE motif might have evolved to mediate resistance against retroviruses that use Nef-like proteins to antagonize SERINC5.ImportanceCellular membrane proteins in the SERINC family, especially SERINC5, inhibit the infectivity of retroviral virions. This inhibition is counteracted by retroviral proteins, specifically HIV-1 Nef, MLV glycoGag, and EIAV S2. One consequence of such a host-pathogen “arms race” is compensatory change in the host antiviral protein as it evolves to escape the effects of the viral antagonist. This is often reflected in a genetic signature, positive selection, which is conspicuously missing inSERINC5. Here we show that despite this lack of genetic evidence, a sequence in SERINC5 nonetheless provides relative resistance to antagonism by HIV-1 Nef.
CoBATCH for high-throughput single-cell epigenomic profiling
Authors: Wang Qianhao , Xiong Haiqing , Ai Shanshan , Yu Xianhong , Liu Yaxi , Zhang Jiejie , He Aibin 
Published: March 2019

ABSTRACTAn efficient, generalizable method for genome-wide mapping of single-cell histone modifications or chromatin-binding proteins is so far lacking. Here we develop CoBATCH,combinatorialbarcodingandtargetedchromatin release, for single-cell profiling of genomic distribution of chromatin-binding proteins in cell culture and tissue. Protein A in fusion to Tn5 transposase is enriched through specific antibodies to genomic regions and Tn5 generates indexed chromatin fragments ready for the library preparation and sequencing. Importantly, through a combinatorial barcoding strategy, we are able to measure epigenomic features up to tens of thousands single cells per experiment. CoBATCH produces not only high signal-to-noise features, but also ~10,000 reads per cells, allowing for efficiently deciphering epigenetic heterogeneity of cell populations and subtypes and inferring developmental histories. Thus, obviating specialized device, CoBATCH is easily deployable for any laboratories in life science and medicine.
Integrating detection of copy neutral chromosomal losses in a clinical setting in leukemia and lymphoma by means of allelic imbalance and read depth ratio comparison
Authors: Hansen Marcus C. , Cédile Oriane , Ludvigsen Maja , Kjeldsen Eigil , Møller Peter L. , Abildgaard Niels , Hokland Peter , Nyvold Charlotte G. 
Published: March 2019

AbstractChromosomal aberrations are common features of hematological malignancies, with several recurrent aberrations recognized as important diagnostic or prognostic molecular markers. While genome-wide genotyping and genomic hybridization microarray analyses have been implemented in clinical laboratories for several years the usage of next generation sequencing for detection of acquired copy number alterations has not yet reached full clinical integration. One evident problem is the identification of copy neutral loss of heterozygosity (CN-LoH), which is not detectable by sequencing read depth correlation or the analogous microarray CGH. We selected 23 paired samples of hematological disorders from 14 individuals, focusing on leukemia and lymphomas, and tested whether a low complexity approach, relying on Fisher’s exact test or χ2, is efficient for the analysis of variant allele frequencies with read-depth ratio correlations in order to resolve both copy-altering and neutral chromosomal aberrations. This combination helped to identify 69 altered chromosomes and offered mutual confirmation. Moreover, six CN-LoHs (>1% AF shifts, p<0.01) were found with one additional suspected low frequency deletion (~10-15% burden) in a case of CLL. We conclude that this simple method is directly clinically applicable for the detection of copy neutral chromosomal loss of single genes from WES with intermediate coverage.AvailabilityMentioned plot software is available at Harvard Dataverse http://doi.org/10.7910/DVN/KFMGNYContactMarcus.celik.hansen@rsyd.dk or marcus@clin.au.dkSupplementary informationSupplementary plots are available