bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single molecule structure sequencing reveals RNA structural dependencies, breathing and ensembles
Authors: Bizuayehu Teshome Tilahun , Labun Kornel , Jakubec Martin , Jefimov Kirill , Niazi Adnan , Valen Eivind 
Published: May 2020

AbstractRNA molecules can form secondary and tertiary structures that can regulate their localization and function. Using enzymatic or chemical probing together with high-throughput sequencing, secondary structure can be mapped across the entire transcriptome. However, a limiting factor is that only population averages can be obtained since each read is an independent measurement. Although long-read sequencing has recently been used to determine RNA structure, these methods still used aggregate signals across the strands to detect structure. Averaging across the population also means that only limited information about structural heterogeneity across molecules or dependencies within each molecule can be obtained. Here, we present Single-Molecule Structure sequencing (SMS-seq) that combines structural probing with native RNA sequencing to provide non-amplified, structural profiles of individual molecules with novel analysis methods. Our new approach using mutual information enabled single molecule structural interrogation. Each RNA is probed at numerous bases enabling the discovery of dependencies and heterogeneity of structural features. We also show that SMS-seq can capture tertiary interactions, dynamics of riboswitch ligand binding, and mRNA structural features.
A meta-analytic approach to mapping co-occurrent grey matter volume increases and decreases in psychiatric disorders
Authors: Mancuso Lorenzo , Fornito Alex , Costa Tommaso , Ficco Linda , Liloia Donato , Manuello Jordi , Duca Sergio , Cauda Franco 
Published: May 2020

AbstractNumerous studies have investigated gray matter (GM) volume changes in diverse patient groups. Reports of disorder-related GM reductions are common in such work, but many studies also report evidence for GM volume increases in patients. It is unclear whether these GM increases and decreases independent or related in some way. Here, we address this question using a novel meta-analytic network mapping approach. We used a coordinate-based meta-analysis of 64 voxel-based morphometry studies of psychiatric disorders to calculate the probability of finding a GM increase or decrease in one region given an observed change in the opposite direction in another region. Estimating this co-occurrence probability for every pair of brain regions allowed us to build a network of concurrent GM changes of opposing polarity. Our analysis revealed that disorder-related GM increases and decreases are not independent; instead, a GM change in one area is often statistically related to a change of opposite polarity in other areas, highlighting distributed yet coordinated changes in GM volume as a function of brain pathology. Most regions showing GM changes linked to an opposite change in a distal area were located in salience, executive-control and default mode networks, as well as the thalamus and basal ganglia. Moreover, pairs of regions showing coupled changes of opposite polarity were more likely to belong to different canonical networks than to the same one. Our results suggest that regional GM alterations in psychiatric disorders are often accompanied by opposing changes in distal regions that belong to distinct functional networks.
Multidimensional Chromatin Regulation of Cell Lineage Differentiation in a Metazoan Embryo
Authors: Zhao Zhiguang , Fan Rong , Xu Weina , Wang Yangyang , Ma Xuehua , Du Zhuo 
Published: May 2020

SUMMARYHow chromatin dictates cell differentiation is an intriguing question in developmental biology. Here, a reporter gene integrated throughout the genome was used as a sensor to map the chromatin activity landscape in lineage-resolved cells duringC. elegansembryogenesis. Single-cell analysis of chromatin dynamics across critical dimensions of cell differentiation was performed, including lineage, tissue, and symmetry. During lineage progression, chromatin gradually diversifies in general and exhibits switch-like changes following specific cell division, which is predictive of anterior-posterior fate asymmetry. Upon tissue differentiation, chromatin of cells from distinct lineages converge to tissue-specific states but retain “memory” of each cell’s lineage history, which contributes to intra-tissue heterogeneity. However, cells with a morphologically left-right symmetric organization utilize a predetermination chromatin strategy to program analogous regulatory states in early progenitor cells. Additionally, chromatin co-regulation drives the functional coordination of the genome. Collectively, this work reveals the role of multidimensional chromatin regulation in cell differentiation.
Whole-Brain High-Resolution Metabolite Mapping with 3D Compressed-Sensing-SENSE-LowRank1H FID-MRSI
Authors: Klauser Antoine , Klauser Paul , Grouiller Frédéric , Courvoisier Sebastien , Lazeyras Francois 
Published: May 2020

AbstractThere is a growing interest in the neuroscience community to map the distribution of brain metabolites in vivo. Magnetic resonance spectroscopic imaging (MRSI) is often limited by either a poor spatial resolution and/or a long acquisition time which severely limits its applications for clinical or research purposes. Building on a recently developed technique of acquisition-reconstruction for 2D MRSI, we combined fast Cartesian1H-FID-MRSI acquisition sequence, compressed-sensing acceleration, and low-rank total-generalized-variation constrained reconstruction to produce 3D high-resolution whole-brain MRSI with a significant acquisition time reduction. We first evaluated the acceleration performance using retrospective undersampling of a fully-sampled dataset. Second, a 20 min accelerated MRSI acquisition was performed on the brain of three healthy volunteers resulting in metabolite maps with 5 mm isotropic resolution. The metabolite maps exhibited the detailed neurochemical composition of all brain regions and revealed parts of the underlying brain anatomy. The latter assessment used previous reported knowledge and a brain atlas-based analysis to show consistency of the concentration contrasts and ratio across all brain regions. These results acquired on a clinical 3 Tesla MRI successful combinae of the 3D1H-FID-MRSI with a constrained reconstruction to produce detailed mapping of metabolite concentrations at high-resolution over the whole brain, with an acquisition time suitable for clinical or research settings.
Resistance to pirimiphos-methyl in West AfricanAnophelesis spreading via duplication and introgression of theAce1locus
Authors: Grau-Bové Xavier , Lucas Eric , Pipini Dimitra , Rippon Emily , van’t Hof Arjèn , Constant Edi , Dadzie Samuel , Egyir-Yawson Alexander , Essandoh John , Chabi Joseph , Djogbénou Luc , Harding Nicholas J. , Miles Alistair , Kwiatkowski Dominic , Donnelly Martin J. , Weetman David ,   The Anopheles gambiae 1000 Genomes Consortium
Published: May 2020

AbstractVector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverseAnophelesgenomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectorsAnopheles gambiaeandA. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene,Ace1, provides the key resistance diagnostic in anA. coluzziipopulation from Côte d’Ivoire that we used for sequence-based association mapping, with replication in other West African populations. TheAce1and substitution and duplications occur on a unique resistance haplotype that evolved inA. gambiaeand introgressed intoA. coluzzii, and is now common in West Africa probably due to cross-resistance with previously used insecticides. Our findings highlight the phenotypic value of this complex resistance haplotype and clarify its evolutionary history, providing tools to understand the current and future effectiveness of pirimiphos-methyl based interventions.
Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice
Authors: Nguyen-Tu Marie-Sophie , Martinez-Sanchez Aida , Leclerc Isabelle , Rutter Guy A. , da Silva Xavier Gabriela 
Published: May 2020

AbstractTranscription factor 7-like 2 (TCF7L2) is a downstream effector of the Wnt/beta-catenin signalling pathway and its expression is critical for adipocyte development. The precise role of TCF7L2 in glucose and lipid metabolism in adult adipocytes remains to be defined. Here, we aim to investigate how changes in TCF7L2 expression in mature adipocytes affect glucose homeostasis.Tcf7l2was selectively ablated from mature adipocytes in C57BL/6J mice using an adiponectin promoter-drivenCrerecombinase to recombine alleles floxed at exon 1 of theTcf7l2gene. Mice lackingTcf7l2in mature adipocytes displayed normal body weight. Male mice exhibited normal glucose homeostasis at eight weeks of age. Male heterozygote knockout mice (aTCF7L2het) exhibited impaired glucose tolerance (AUC increased 1.14 ± 0.04 -fold, p=0.03), as assessed by intraperitoneal glucose tolerance test, and changes in fat mass at 16 weeks (increased by 1.4 ± 0.09-fold, p=0.007). Homozygote knockout mice exhibited impaired oral glucose tolerance at 16 weeks of age (AUC increased 2.15 ± 0.15-fold, p=0.0001). Islets of Langerhans exhibited impaired glucose-stimulated insulin secretionin vitro(decreased 0.54 ± 0.13-fold aTCF7L2KO vs control, p=0.02), but no changes inin vivoglucose-stimulated insulin secretion. Female mice in which one or two alleles of theTcf7l2gene was knocked out in adipocytes displayed no changes in glucose tolerance, insulin sensitivity or insulin secretion. Plasma levels of glucagon-like peptide-1 and gastric inhibitory polypeptide were lowered in knockout mice (decreased 0.57 ± 0.03-fold and 0.41 ± 0.12-fold, p=0.04 and p=0.002, respectively), whilst plasma free fatty acids and Fatty Acid Binding Protein 4 circulating levels were increased by 1.27 ± 0.07 and 1.78 ± 0.32-fold, respectively (p=0.05 and p=0.03). Mice with biallelicTcf7l2deletion exposed to high fat diet for 9 weeks exhibited impaired glucose tolerance (p=0.003 at 15 min after glucose injection) which was associated with reducedin vivoglucose-stimulated insulin secretion (decreased 0.51 ± 0.03-fold, p=0.02). Thus, our data indicate that loss ofTcf7l2gene expression in adipocytes leads to impairments on metabolic responses which are dependent on gender, age and nutritional status. Our findings further illuminate the role of TCF7L2 in the maintenance of glucose homeostasis.
Skeletal muscle DNMT3A plays a necessary role in endurance exercise by regulating oxidative capacity of red muscles
Authors: Villivalam Sneha Damal , You Dongjoo , Ebert Scott M. , Kim Jinse , Xiao Han , Palacios Hector H. , Adams Christopher M. , Kang Sona 
Published: May 2020

AbstractExercise interventions alter the DNA methylation profile in skeletal muscle, yet little is known about the role of the DNA methylation machinery in exercise capacity. In this study, we found that in oxidative red muscle, DNMT3A expression increases greatly following a bout of endurance exercise. Mice lackingDnmt3ain skeletal muscle fibers had reduced tolerance to endurance exercise, accompanied by reduced oxidative capacity and reduced mitochondrial counts. Moreover, during exercise, the knockout muscles overproduced reactive oxygen species (ROS), which are major contributors to muscle dysfunction. In mechanistic terms, we demonstrated thatAldh1l1is a key target of repression by DNMT3A in red muscles. DNMT3A directly regulated the Aldh1l1 transcription by binding to theAldh1l1promoter region and altering DNA methylation and histone modification. Enforcing ALDH1L1 expression, leading to elevated NADPH, led to overproduction of ROS by the NADPH oxidase complex (NOX) in myotubes, ultimately resulting in mitochondrial defects. Moreover, both genetic inhibition of ALDH1L1 and pharmacological inhibition of NOX rescued oxidative stress and mitochondrial decline inDnmt3a-deficient myotubes, confirming the essential role of ALDH1L1-dependent ROS generation as a downstream effector of DNMT3A loss of function. Together, our results reveal that DNMT3A in skeletal muscle plays a pivotal role in endurance exercise by controlling intracellular oxidative stress.
Monitoring the microbiome for food safety and quality using deep shotgun sequencing
Authors: Beck Kristen L. , Haiminen Niina , Chambliss David , Edlund Stefan , Kunitomi Mark , Huang B. Carol , Kong Nguyet , Ganesan Balasubramanian , Baker Robert , Markwell Peter , Kawas Ban , Davis Matthew , Prill Robert J. , Krishnareddy Harsha , Seabolt Ed , Marlowe Carl H. , Pierre Sophie , Quintanar André , Parida Laxmi , Dubois Geraud , Kaufman James , Weimer Bart C. 
Published: May 2020

ABSTRACTIn this work, we hypothesized that shifts in the food microbiome can be used as an indicator of unexpected contaminants or environmental changes. To test this hypothesis, we sequenced total RNA of 31 high protein powder (HPP) samples of poultry meal pet food ingredients. We developed a microbiome analysis pipeline employing a key eukaryotic matrix filtering step that improved microbe detection specificity to >99.96% duringin silicovalidation. The pipeline identified 119 microbial genera per HPP sample on average with 65 genera present in all samples. The most abundant of these wereBacteroides, Clostridium, Lactococcus, Aeromonas, andCitrobacter.We also observed shifts in the microbial community corresponding to ingredient composition differences. When comparing culture-based results forSalmonellawith total RNA sequencing, we found thatSalmonellagrowth did not correlate with multiple sequence analyses. We conclude that microbiome sequencing is useful to characterize complex food microbial communities, while additional work is required for predicting specific species’ viability from total RNA sequencing.
Lipid Droplet Is an Ancient and Inheritable Organelle in Bacteria
Authors: Chi Xiang , Ogunsade Ololade Omolara , Zhou Ziyun , Li Zemin , Li Xuehan , Zhang Mengwei , Song Fuhang , Wang Jun , Hammad Mirza Ahmed , Zhang Xuelin , Zhang Shuyan , Wan Xia , Zhang Lixin , Zhang Congyan , Liu Pingsheng 
Published: May 2020

AbstractLipid droplet (LD) is a monolayer phospholipid membrane-bound organelle found in all eukaryotes and several prokaryotes which plays key roles in cellular lipid homeostasis and human health. The origin and evolution of the organelle remains unknown. Here, we report that through screening over 660 bacteria using biophysical and biochemical methods, plus LD isolation and proteomic tool, LDs were identified in most of these microbes, affiliated with five main bacterial phyla. Moreover, LDs were also identified in E. coli overexpressing lipid synthesis enzymes, indicating that bacteria without detectable LDs possessed the ability of LD biogenesis. The similarity of isolated LDs from representative strains and evolutionary analysis of LD major protein PspA demonstrate that LDs were conserved in bacteria. Furthermore, time-lapse imaging revealed that LDs were inheritable accompanying with bacterial growth and division. Finally, a common ancestor of LD-containing bacteria was predicted to originate 3.19 billion years ago by a phylogenetic analysis. Our findings suggest that LD is a widespread and inheritable organelle from an ancient common ancestor.
Antiviral activity of Glucosylceramide synthase inhibitors against SARS-CoV-2 and other RNA virus infections
Authors: Vitner Einat. B. , Avraham Roy , Achdout Hagit , Tamir Hadas , Agami Avi , Cherry Lilach , Yahalom-Ronen Yfat , Politi Boaz , Erez Noam , Melamed Sharon , Paran Nir , Israely Tomer 
Published: May 2020

AbstractThe need for antiviral drugs is real and relevant. Broad spectrum antiviral drugs have a particular advantage when dealing with rapid disease outbreaks, such as the current COVID-19 pandemic. Since viruses are completely dependent on internal cell mechanisms, they must cross cell membranes during their lifecycle, creating a dependence on processes involving membrane dynamics. Thus, in this study we examined whether the synthesis of glycosphingolipids, biologically active components of cell membranes, can serve as an antiviral therapeutic target. We examined the antiviral effect of two specific inhibitors of GlucosylCeramide synthase (GCS); (i) Genz-123346, an analogue of the FDA-approved drug Cerdelga®, (ii) GENZ-667161, an analogue of venglustat which is currently under phase III clinical trials. We found that both GCS inhibitors inhibit the replication of four different enveloped RNA viruses of different genus, organ-target and transmission route: (i) Neuroinvasive Sindbis virus (SVNI), (ii) West Nile virus (WNV), (iii) Influenza A virus, and (iv) SARS-CoV-2. Moreover, GCS inhibitors significantly increase the survival rate of SVNI-infected mice. Our data suggest that GCS inhibitors can potentially serve as a broad-spectrum antiviral therapy and should be further examined in preclinical and clinical trial. Analogues of the specific compounds tested have already been studied clinically, implying they can be fast-tracked for public use. With the current COVID-19 pandemic, this may be particularly relevant to SARS-CoV-2 infection.One Sentence SummaryAn analogue of Cerdelga®, an FDA-approved drug, is effective against a broad range of RNA-viruses including the newly emerging SARS-CoV-2.
Cytotoxic effects of tRNA-derived fragments and tRNA halves from non-pathogenicEscherichia colistrain on colorectal cancer cells
Authors: Cao Kai-Yue , Pan Yu , Yan Tong-Meng , Tao Peng , Xiao Yi , Jiang Zhi-Hong 
Published: May 2020

ABSTRACTTransfer RNAs (tRNAs) purified from non-pathogenicE. colistrain (NPECS) possess cytotoxic properties on colorectal cancer cells. In the present study, the bioactivity of tRNA halves and tRNA fragments (tRFs) derived from NPECS are investigated for their anticancer potential. Both tRNA halves and tRF mimics studied exhibited significant cytotoxicity on colorectal cancer cells, with the latter being more effective suggesting that tRFs may be important contributors to the bioactivities of tRNAs derived from gut microbiota. Through high-throughput screening, EC83 mimic, a double-strand RNA with a 22 nt 5’-tRF derived from tRNA-Leu(CAA) as antisense chain, was identified as one with the highest potency (IC50=52 nM). Structure-activity investigations revealed that 2’-O-methylation of the ribose of guanosine may enhance the cytotoxic effects of EC83 mimicviaincreasing the stability of its tertiary structure. Consistently, 4-thiouridine substitution reversed this increased stability and the enhanced cytotoxic effects. This provides the first evidence that the bioactivity of tRF mimics would be impacted by chemical modifications. Furthermore, the present study provides the first evidence to suggest that novel tRNA fragments derived from the gut microbiota may possess anti-cancer properties and have the potential to be potent and selective therapeutic molecules.IMPORTANCEWhile the gut microbiota has been increasingly recognized to be of vital importance to human health and disease, the current literature shows that there is a lack of attention given on the non-pathogenicEscherichia colistrain. Moreover, the biological activities of tRNA fragments (tRFs) derived from bacteria have rarely been investigated. The findings from this study revealed tRFs as a new class of bioactive constituents derived from gut microorganisms, suggesting that studies on biological functional molecules in intestinal microbiota should not neglect tRFs. The research of tRFs would play an important role in biological research of gut microorganisms, including bacteria-bacteria interaction, gut-brain axis, gut-liver axis, etc. Furthermore, the guidance on the rational design of tRF therapeutics provided in this study indicates that further investigations should pay more attention to these therapeutics from probiotics. The innovative drug research of tRFs as potent druggable RNA molecules derived from intestinal microorganisms would open a new area in biomedical sciences.
Depression and loneliness during COVID-19 restrictions in the United States, and their associations with frequency of social and sexual connections
Authors: Rosenberg Molly , Luetke Maya , Hensel Devon , Kianersi Sina , Fu Tsung-chieh , Herbenick Debby 
Published: May 2020

ABSTRACTPurposeTo estimate the prevalence of depression and loneliness during the US COVID-19 response, and examine their associations with frequency of social and sexual connections.MethodsWe conducted an online cross-sectional survey of a nationally representative sample of American adults (n=1010), aged 18-94, running from April 10-20, 2020. We assessed depressive symptoms (CES-D-10 scale), loneliness (UCLA 3-Item Loneliness scale), and frequency of in-person and remote social connections (4 items, e.g. hugging family member, video chats) and sexual connections (4 items, e.g. partnered sexual activity, dating app use).ResultsOne-third of participants (32%) reported depressive symptoms, and loneliness was high [mean (SD): 4.4 (1.7)]. Those with depressive symptoms were more likely to be women, age 20-29, unmarried, and low-income. Frequent in-person connections were associated with lower depression and loneliness; frequent remote connections were not.ConclusionsDepression and loneliness were elevated during the early US COVID-19 response. Those who maintained frequent in-person, but not remote, social and sexual connections had better mental health outcomes. While COVID-19 social restrictions remain necessary, it will be critical to expand mental health services to serve those most at-risk and identify effective ways of maintaining social and sexual connections from a distance.
Prediction of protein subcellular localization using deep learning and data augmentation
Authors: Eftekhar Majid Ghorbani 
Published: May 2020

AbstractIdentifying subcellular localization of protein is significant for understanding its molecular function. It provides valuable insights that can be of tremendous help to protein’s function research and the detection of potential cell surface/secreted drug targets. The prediction of protein subcellular localization using bioinformatics methods is an inexpensive option to experimentally approaches. Many computational tools have been built during the past two decades, however, producing reliable prediction has always been the challenge. In this study, a Deep learning (DL) technique is proposed to enhance the precision of the analytical engine of one of these tools called PSORTb v3.0. Its conventional SVM machine learning model was replaced by the state-of-the-art DL method (BiLSTM) and a Data augmentation measure (SeqGAN). As a result, the combination of BiLSTM and SeqGAN outperformed SVM by improving its precision from 57.4% to 75%. This method was applied on a dataset containing 8230 protein sequences, which was experimentally derived by Brinkman Lab. The presented model provides promising outcomes for the future research. The source code of the model is available athttps://github.com/mgetech/SubLoc.