bluuebunny/crossref_metadata_2025_split huggingface dataset:
New microsatellite marker tools for genotype identification and analyses of genetic relationships in two ornamentals, the popular common lilac (Syringa vulgaris) and the invasive garden escapee Himalayan balsam (Impatiens glandulifera)
Authors: Korpelainen Helena , Pietiläinen Maria 
Published: March 2020

ABSTRACTNowadays, high-throughput sequencing technologies are widely available. Yet, it is practical to have an access to simpler and cheaper, yet effective low-throughput analyses as well. For that purpose, species-specific microsatellites, also called simple sequence repeats (SSR), are valuable, multi-purpose types of markers. In the present study, we introduce new sets of SSR markers for two ornamental plant species, the popular common lilac (Syringa vulgarisL.) (16 markers) and the invasive garden escapee Himalayan balsam (Impatiens glanduliferaRoyle) (259 markers). The markers were developed as a by-product of a genotyping-by-sequencing project producing a large amount of DNA sequence data. Both the frequency of SSRs and the success rate for marker development were considerably greater inI. glanduliferawhen compared toS. vulgaris. The new markers will contribute to the characterization of germplasm and to other types of genetic analyses on these two species.
Rerouting of ribosomal proteins into splicing in plant organelles
Authors: Wang Chuande , Fourdin Rachel , Quadrado Martine , Dargel-Graffin Céline , Tolleter Dimitri , Macherel David , Mireau Hakim 
Published: March 2020

AbstractProduction and expression of RNAs requires the action of multiple RNA-binding proteins (RBPs). New RBPs are most often created by novel combinations of dedicated RNA binding modules. However, recruiting existing genes to create new RBPs is also an important evolutionary strategy. In this report, we analysed the 8-member uL18 ribosomal protein family in Arabidopsis. uL18 proteins share a short structurally conserved domain that binds the 5S rRNA and allow its incorporation into ribosomes. Our results indicate that Arabidopsis uL18-like proteins are targeted to either mitochondria or chloroplasts. While two members of the family are found in organelle ribosomes, we reveal that two uL18-type proteins correspond to splicing factors that are necessary for the elimination of certain mitochondrial and plastid group II introns. These two proteins do not co-sediment with mitochondrial or plastid ribosomes but associate with the introns whose splicing they promote. Our study thus reveals that the RNA binding capacity of uL18 ribosomal proteins has been detoured to create factors facilitating the elimination of organellar introns.
Extended amygdala-parabrachial circuits alter threat assessment to regulate feeding
Authors: Bhatti Dionnet L. , Luskin Andrew T. , Pedersen Christian E. , Mulvey Bernard , Oden-Brunson Hannah , Kimbell Kate , Sawyer Abbie , Gereau Robert W. , Dougherty Joseph D. , Bruchas Michael R. 
Published: March 2020

AbstractAn animal’s evolutionary success depends on the ability to seek and consume foods while avoiding environmental threats. However, how evolutionarily conserved threat detection circuits modulate feeding is unknown. In mammals, feeding and threat assessment are strongly influenced by the parabrachial nucleus (PBN), a structure that responds to threats and inhibits feeding. Here, we report that the PBN receives dense inputs from the bed nucleus of the stria terminalis (BNST), an extended amygdala structure that encodes affective information. Using a series of complementary approaches, we identify opposing BNST-PBN circuits that modulate a genetically-defined population of PBN neurons to control feeding. This previously unrecognized neural circuit integrates threat assessment with the intrinsic drive to eat.
High-throughput cell-based assays for the preclinical development of DsbA inhibitors as antivirulence therapeutics
Authors: Verderosa Anthony D. , Dhouib Rabeb , Hong Yaoqin , Heras Begoña , Totsika Makrina 
Published: March 2020

AbstractAntibiotics are failing fast, and the development pipeline is alarmingly dry. New drug research and development is being urged by world health officials, with new antibacterials against multidrug-resistant Gram-negative pathogens as the highest priority. Antivirulence drugs, which are inhibitors of bacterial pathogenicity factors, are a class of promising antibacterials, however, their development is often stifled by lack of standardised preclinical testing akin to what guides antibiotic development. The lack of established target-specific microbiological assays amenable to high-throughput, often means that cell-based testing of virulence inhibitors is absent from the discovery (hit-to-lead) phase, only to be employed at later-stages of lead optimization. Here, we address this by establishing a pipeline of bacterial cell-based assays developed for the identification and early preclinical evaluation of DsbA inhibitors. Inhibitors of DsbA block bacterial oxidative protein folding and were previously identified by biophysical and biochemical assays. Here we use existingEscherichia coliDsbA inhibitors and uropathogenicE. coli(UPEC) as a model pathogen, to demonstrate that a combination of a cell-based AssT sulfotransferase assay and the UPEC motility assay, modified for a higher throughput format, can provide a robust and target-specific platform for the evaluation of DsbA inhibitors. Our pipeline could also be used in fragment and compound screening for the identification of new DsbA inhibitor classes or hits with a broad spectrum of activity. In conclusion, the establishment of accurate, high-throughput microbiological assays for antivirulence drug identification and early preclinical development, is a significant first step towards their translation into effective therapeutics.ImportanceThe safety net of last resort antibiotics is quickly vanishing as bacteria become increasingly resistant to most available drugs. If no action is taken, we will likely enter a post-antibiotic era, where common infections and minor injuries are once again lethal. The paucity in new antibiotic discovery of the past decades has compounded the problem of increasing antibiotic resistance, to the point that it now constitutes a global health crisis that demands global action. There is currently an urgent need for new antibacterial drugs with new targets and modes of action. To address this, research and development efforts into antivirulence drugs, such as DsbA inhibitors, have been ramping up globally. However, the development of microbiological assays as tools for effectively identifying and evaluating antivirulence drugs is lagging behind. Here, we present a high-throughput cell-based screening and evaluation pipeline, which could significantly advance development of DsbA inhibitor as antivirulence therapeutics.
Non-CG methylation is superior to CG methylation in genome regulation
Authors: Domb Katherine , Katz Aviva , Yaari Rafael , Kaisler Efrat , Nguyen Vu Hoang , Hong Uyen Vu Thuy , Griess Ofir , Heskiau Karina Gitin , Ohad Nir , Zemach Assaf 
Published: March 2020

AbstractDNA methylation in plants occurs in CG, CHG, and CHH sites. While depletion of CG methylation in transposons is associated with ample transcriptional activation, it was mainly studied in species with limited non-CG methylation that is linked to CG methylation. Here we profiled transcription in the moss plant,Physcomitrella patens, that has robust non-CG methylation with similar symmetrical CG and CHG methylation levels. Separated contextual methylation mechanisms inPhyscomitrella patensenabled generation of numerous context-specific hypomethylated mutants. Our transcriptome data show that specific elimination of CG methylation is fully complemented by non-CG methylation. Conversely, exclusive removal of non-CG methylation massively dysregulated genes and transposons. Moreover, CHG methylation silenced transposons stronger than CG methylation. Lastly, we found non-CG methylation as crucial for silencing CG-depleted transposons. These results demonstrate the potency of non-CG methylation in genome regulation and suggest that it evolved due to moderate silencing and/or rapid mutability of methylated CGs.
Systematic prioritization of candidate genes in disease loci identifies TRAFD1 as a master regulator of IFNγ signalling in celiac disease
Authors: van der Graaf Adriaan , Zorro Maria , Claringbould Annique , Vosa Urmo , Aguirre-Gamboa Raul , Li Chan , Mooiweer Joram , Ricano-Ponce Isis , Borek Zuzanna , Koning Frits , Kooy-Winkelaar Yvonne , Sollid Ludvig , Qiao Shuo-Wang ,   BIOS consortium, Kumar Vinod , Li Yang , Franke Lude , Withoff Sebo , Wijmenga Cisca , Sanna Serena , Jonkers Iris 
Published: March 2020

AbstractBackgroundCeliac disease (CeD) is a complex T cell–mediated enteropathy induced by gluten. Although genome-wide association studies have identified numerous genomic regions associated with CeD, it is difficult to accurately pinpoint which genes in these loci are most likely to cause CeD.ResultsWe used four different in silico approaches – Mendelian Randomization inverse variance weighting, COLOC, LD overlap and DEPICT – to integrate information gathered from a large transcriptomics dataset. This identified 118 prioritized genes across 50 CeD-associated regions. Co-expression and pathway analysis of these genes indicated an association with adaptive and innate cytokine signalling and T cell activation pathways. 51 of these genes are targets of known drug compounds and likely druggable genes, suggesting that our methods can be used to pinpoint potential therapeutic targets. In addition, we detected 172 gene-combinations that were affected by our CeD-prioritized genes in trans. Notably, 41 of these trans-mediated genes appear to be under control of one master regulator, TRAFD1, and were found to be involved in IFNγ signalling and MHC I antigen processing/presentation. Finally, we performed in vitro experiments that validated the role of TRAFD1 as an immune regulator acting in trans.ConclusionsOur strategy has confirmed the role of adaptive immunity in CeD and revealed a genetic link between CeD and the IFNγ signalling and MHC I antigen processing pathways, both major players of immune activation and CeD pathogenesis.
Great Expectations: A Critical Review of and Recommendations for the study of Reward Processing as a Cause and Predictor of Depression
Authors: Nielson Dylan M. , Keren Hanna , O’Callaghan Georgia , Jackson Sarah M. , Douka Ioanna , Zheng Charles Y. , Vidal-Ribas Pablo , Pornpattananangkul Narun , Camp Christopher C. , Gorham Lisa S. , Wei Christine , Kirwan Stuart , Stringaris Argyris 
Published: March 2020

AbstractBoth human and animal studies support the relationship between depression and reward processing abnormalities, giving rise to the expectation that neural signals of these processes may serve as biomarkers or mechanistic treatment targets. Given the great promise of this research line, we scrutinize those findings and the theoretical claims that underlie them. To achieve this, we apply the framework provided by classical work on causality as well as contemporary approaches to prediction. We identify a number of conceptual, practical, and analytical challenges to this line of research, and use a pre-registered meta-analysis to quantify the longitudinal associations between reward processing aberrations and depression. We also investigate the impact of measurement error on reported data. We find that reward processing abnormalities do not reach levels that would be useful for clinical prediction, yet the evidence thus far does not exclude their possible causal role in depression.
Public broadly neutralizing antibodies against hepatitis B virus in individuals with elite serologic activity
Authors: Wang Qiao , Michailidis Eleftherios , Yu Yingpu , Wang Zijun , Hurley Arlene M. , Oren Deena A. , Mayer Christian T. , Gazumyan Anna , Liu Zhenmi , Zhou Yunjiao , Schoofs Till , Yao Kai-hui , Nieke Jan P. , Wu Jianbo , Jiang Qingling , Zou Chenhui , Kabbani Mohanmmad , Quirk Corrine , Oliveira Thiago , Chhosphel Kalsang , Zhang Qianqian , Schneider William M. , Jahan Cyprien , Ying Tianlei , Horowitz Jill , Caskey Marina , Jankovic Mila , Robbiani Davide F. , Wen Yumei , de Jong Ype P. , Rice Charles M. , Nussenzweig Michel C. 
Published: March 2020

SUMMARYAlthough there is no effective cure for chronic hepatitis B virus (HBV) infection, antibodies are protective and constitute clinical correlates of recovery from infection. To examine the human neutralizing antibody response to HBV in elite neutralizers we screened 144 individuals. The top individuals produced shared clones of broadly neutralizing antibodies (bNAbs) that targeted 3 non-overlapping epitopes on the HBV S antigen (HBsAg). Single bNAbs protected humanized mice against infection, but selected for resistance mutations in mice with established infection. In contrast, infection was controlled by a combination of bNAbs targeting non-overlapping epitopes with complementary sensitivity to mutations that commonly emerge during human infection. The co-crystal structure of one of the bNAbs with a peptide epitope containing residues frequently mutated in human immune escape variants revealed a loop anchored by oppositely charged residues. The structure provides a molecular explanation for why immunotherapy for HBV infection may require combinations of complementary bNAbs.
Prediction of Protein-Protein Interactions Based on L1-Regularized Logistic Regression and Gradient Tree Boosting
Authors: Yu Bin , Chen Cheng , Zhou Hongyan , Liu Bingqiang , Ma Qin 
Published: March 2020

AbstractProtein-protein interactions (PPIs) are of great importance to understand genetic mechanisms, disease pathogenesis, and guide drug design. With the increase of PPIs sequence data and development of machine learning, the prediction and identification of PPIs have become a research hotspot in proteomics. In this paper, we propose a new prediction pipeline for PPIs based on gradient tree boosting (GTB). First, the initial feature vector is extracted by fusing pseudo amino acid composition (PseAAC), pseudo-position-specific scoring matrix (PsePSSM), reduced sequence and index-vectors (RSIV) and autocorrelation descriptor (AD). Second, to remove redundancy and noise, we employ L1-regularized logistic regression to select an optimal feature subset. Finally, GTB-PPI model based on GTB is constructed. Five-fold cross-validation showed GTB-PPI achieved the accuracies of 95.15% and 90.47% onSaccharomyces cerevisiaeandHelicobacter pylori, respectively. In addition, GTB-PPI could be applied to predictCaenorhabditis elegans,Escherichia coli,Homo sapiens,andMus musculusindependent test sets, the one-core PPIs network for CD9, and the crossover PPIs network. The results show that GTB-PPI can significantly improve prediction accuracy of PPIs. The code and datasets of GTB-PPI can be downloaded fromhttps://github.com/QUST-AIBBDRC/GTB-PPI/.
Molecular Ecology of Coral Reef Microorganisms in the Western Indian Ocean coast of Kenya
Authors: Wambua Sammy , Gourlé Hadrien , de Villiers Etienne , Karlsson Oskar , Wambiji Nina , Macdonald Angus , Bongcam-Rudloff Erik , de Villiers Santie 
Published: March 2020

AbstractCoral reefs face increased environmental threats from anthropomorphic climate change and pollution, from agriculture, industries and tourism. They are economically vital for many people worldwide, and harbour a fantastically diverse ecosystem, being the home for many species of fish and algae. Surprisingly little is known about the microbial communities living in and in the surrounding of coral reefs. Here we employ high throughput sequencing for investigating the bacteria living in the water column and upper sediment layer in close proximity to coral reefs on the Kenyan coast of the West Indian Ocean. We show that while the read-level taxonomic distribution of bacteria is similar with ones obtained from 16S metabarcoding, whole metagenome sequencing provides valuable functional insights not available with 16S metabarcoding. We find evidence of pollution, marked by the presence ofVibrioand more importantly the presence of antibiotic resistance notably to vancomycin, that we attribute to the use of avoparcin in agriculture. Additionally, 175 bacterial genomes not previously sequenced were discovered.Our study is the first whole-metagenome study from the West Indian Ocean, provides a much-needed baseline to study microbes surrounding coral reefs under different conditions as well as the microbiome of coral reefs.
The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones
Authors: Shemesh Netta , Jubran Juman , Abu-Qarn Mehtap , Simonovky Eyal , Basha Omer , Hekselman Idan , Dror Shiran , Vinogradov Ekaterina , Carra Serena , Ben-Zvi Anat , Yeger-Lotem Esti 
Published: March 2020

AbstractThe sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, the organization of the chaperone system across physiological human tissues has received little attention. Here, we used human tissue RNA-sequencing profiles to analyze the expression and organization of chaperones across 29 main tissues. We found that relative to protein-coding genes, chaperones were significantly more ubiquitously and highly expressed across all tissues. Nevertheless, differential expression analysis revealed that most chaperones were up- or down-regulated in certain tissues, suggesting that they have tissue-specific roles. In agreement, chaperones that were upregulated in skeletal muscle were highly enriched in mouse myoblasts and in nematode’s muscle tissue, and overlapped significantly with chaperones that are causal for muscle diseases. We also identified a distinct subset of chaperones that formed a uniformly-expressed, cross-family core group conducting basic cellular functions that was significantly more essential for cell survival. Altogether, this suggests a layered architecture of chaperones across tissues that is composed of shared core elements that are complemented by variable elements which give rise to tissue-specific functions and sensitivities, thereby contributing to the tissue-specificity of protein misfolding diseases.Significance StatementProtein misfolding diseases, such as neurodegenerative disorders and myopathies, are often manifested in a specific tissue or even a specific cell type. Enigmatically, however, they are typically caused by mutations in widely expressed proteins. Here we focused on chaperones, the main and basic components of the protein-folding machinery of cells. Computational analyses of large scale tissue transcriptomes unveils that the chaperone system is composed of core essential elements that are uniformly expressed across tissues, and of variable elements that are differentially expressed in a tissue-specific manner. This organization allows each tissue to fit the quality control system to its specific requirements and illuminates the mechanisms that underlie a tissue’s susceptibility to protein-misfolding diseases.
Leaky severe combined immunodeficiency in mice lacking non-homologous end joining factors XLF and MRI
Authors: Castañeda-Zegarra Sergio , Zhang Qindong , Alirezaylavasani Amin , Fernandez-Berrocal Marion , Yao Rouan , Oksenych Valentyn 
Published: March 2020

AbstractNon-homologous end-joining (NHEJ) is a DNA repair pathway required to detect, process, and ligate DNA double-stranded breaks (DSBs) throughout the cell cycle. The NHEJ pathway is necessary for V(D)J recombination in developing B and T lymphocytes. During NHEJ, Ku70 and Ku80 form a heterodimer that recognizes DSBs and promotes recruitment and function of downstream factors PAXX, MRI, DNA-PKcs, Artemis, XLF, XRCC4, and LIG4. Mutations in several known NHEJ genes result in severe combined immunodeficiency (SCID). Inactivation ofMri, PaxxorXlfin mice results in normal or mild phenotype, while combined inactivation ofXlf/Mri, Xlf/Paxx, orXlf/Dna-pkcsleads to late embryonic lethality. Here, we describe three new mouse models. We demonstrate that deletion ofTrp53rescues embryonic lethality in mice with combined deficiencies ofXlfandMri. Furthermore,Xlf-/-Mri-/-Trp53+/-andXlf-/-Paxx-/-Trp53+/-mice possess reduced body weight, severely reduced mature lymphocyte counts, and accumulation of progenitor B cells. We also report that combined inactivation ofMri/Paxxresults in live-born mice with modest phenotype, and combined inactivation ofMri/Dna-pkcsresults in embryonic lethality. Therefore, we conclude that XLF is functionally redundant with MRI and PAXX during lymphocyte developmentin vivo. Moreover,Mrigenetically interacts withDna-pkcsandPaxx.
Gradients of functional connectivity in the mouse cortex reflect neocortical evolution
Authors: Huntenburg Julia M. , Yeow Ling Yun , Mandino Francesca , Grandjean Joanes 
Published: March 2020

AbstractUnderstanding cortical organization is a fundamental goal of neuroscience that requires comparisons across species and modalities. Large-scale connectivity gradients have recently been introduced as a data-driven representation of the intrinsic organization of the cortex. We studied resting-state functional connectivity gradients in the mouse cortex and found robust spatial patterns across four data sets. The principal gradient of functional connectivity shows a striking overlap with an axis of neocortical evolution from two primordial origins. Additional gradients reflect sensory specialization and aspects of a sensory-to-transmodal hierarchy, and are associated with transcriptomic features. While some of these gradients strongly resemble observations in the human cortex, the overall pattern in the mouse cortex emphasizes the specialization of sensory areas over a global functional hierarchy.HighlightsThe principal gradient of functional connectivity in the mouse cortex recapitulates an axis of neocortical evolution from archicortex and paleocortex.Additional gradients highlight sensory specialization and reflect aspects of a sensory-to-transmodal hierarchy.Functional connectivity gradients partly align with gene expression patterns.Mouse cortical gradients are stable across data sets.
Pheno-RNA, a method to identify genes linked to a specific phenotype: application to cellular transformation
Authors: Darwiche Rabih , Struhl Kevin 
Published: March 2020

ABSTRACTCellular transformation is associated with dramatic changes in gene expression, but it is difficult to determine which regulated genes are oncogenically relevant. Here, we describe Pheno-RNA, a general approach to identify candidate genes associated with a specific phenotype. Specifically, we generate a “phenotypic series” by treating a non-transformed breast cell line with a wide variety of molecules that induce cellular transformation to various extents. By performing transcriptional profiling across this phenotypic series, the expression profile of every gene can be correlated with the transformed phenotype. We identify ~200 genes whose expression profiles are very highly correlated with the transformation phenotype, strongly suggesting their importance in transformation. Within biological categories linked to cancer, some genes show high correlations with the transformed phenotype, but others do not. Many genes whose expression profiles are highly correlated with transformation have never been linked to cancer, suggesting the involvement of heretofore unknown genes in cancer.