bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Pain in my heart”: Understanding perinatal depression among women living with HIV in Malawi
Authors: LeMasters Katherine , Dussault Josée , Barrington Clare , Bengtson Angela , Gaynes Bradley , Go Vivian , Hosseinipour Mina C. , Kulisewa Kazione , Kutengule Anna , Meltzer-Brody Samantha , Midiani Dalitso , Mphonda Steve , Udedi Michael , Pence Brian 
Published: January 2020

AbstractBackgroundPerinatal depression (PND) can interfere with HIV care engagement and outcomes. We examined experiences of PND among women living with HIV (WLWH) in Malawi.MethodsWe screened 73 WLWH presenting for perinatal care in Lilongwe, Malawi using the Edinburgh Postnatal Depression Scale (EPDS). We conducted interviews with 24 women experiencing PND and analyzed data using inductive and deductive coding and narrative analysis.ResultsWomen experienced a double burden of physical and mental illness, expressed as pain in one’s heart. Receiving an HIV diagnosis unexpectedly during antenatal care was a key contributor to developing PND. This development was influenced by stigmatization and social support.ConclusionsThese findings highlight the need to recognize the mental health implications of routine screening for HIV and to routinely screen and treat PND among WLWH. Culturally appropriate mental health interventions are needed in settings with a high HIV burden.
Lumbar corticospinal tract in rodents modulates sensory inputs but does not convey motor command
Authors: Moreno-Lopez Yunuen , Bichara Charlotte , Delbecq Gilles , Isope Philippe , Cordero-Erausquin Matilde 
Published: January 2020

AbstractIt is generally assumed that the main function of the corticospinal tract (CST) is to convey motor commands to bulbar or spinal motoneurons. Yet the CST has also been shown to modulate sensory signals at their entry point in the spinal cord, through presynaptic inhibition. By sequentially investigating different routes of corticofugal pathways through electrophysiological recordings and an intersectional viral strategy, we here demonstrate that motor and sensory modulation commands in mice belong to segregated paths within the CST. Sensory modulation is excuted exclusively by the CST via a population of lumbar interneurons located in the deep dorsal horn. In contrast, the cortex conveys the motor command via a relay in the upper spinal cord or supraspinal motor centers. At lumbar level, the main role of the CST is thus the modulation of sensory inputs, which is an essential component of the selective tuning of sensory feedback, to ensure well-coordinated and skilled movement.Impact statementWhile the corticospinal tract is often considered exclusively as a motor path, this study demonstrates that, in the mouse lumbar cord, its main role is the modulation of sensory inputs.
Genome-wide comparison of DNA methylation between life cycle stages ofDrosophila melanogasterusing high-throughput sequencing techniques
Authors: Deshmukh Saniya , Abhyankar Varada , Vellarikkal Shamsudheen Karuthedath , Sivasubbu Sridhar , Scaria Vinod , Deobagkar Deepti 
Published: January 2020

ABSTRACTDrosophila melanogasterundergoes holometabolous development, has very low levels of DNA methylation, and is known to possess a single known methyltransferase, dDNMT2. This study compares the DNA methylation patterns between the two life cycle stages ofD. melanogasterusing a combination of DNA immunoprecipitation and high throughput sequencing techniques.Our results indicate, a change in the chromosomal distribution of the sparse DNA methylation concerning genes and natural transposable elements between in the embryo and the adult stages ofD. melanogaster. The differentially methylated regions localised on genes involved in the regulation of cell cycle processes of mitotic cell divisions and chromosomal segregation. dDNMT2 knockout flies exhibited altered patterns of DNA methylation. The observed differences in DNA methylation were in genes involved in cellular communication and cytoskeletal functions. The variation in DNA methylation between the two life cycle stages is indicative that it could have a role in regulatory processes during development and, dDNMT2 may have a role as a co-factor for the hitherto undiscovered DNA methyltransferase inD. melanogaster.
barCoder: a tool to generate unique, orthogonal genetic tags for qPCR detection
Authors: Bernhards Casey B. , Lux Matthew W. , Katoski Sarah E. , Goralski Tyler D. P. , Liem Alvin T. , Gibbons Henry S. 
Published: January 2020

AbstractBackgroundTracking dispersal of microbial populations in the environment requires specific detection methods that discriminate between the target strain and all potential natural and artificial interferents, including previously utilized tester strains. Recent work has shown that genomic insertion of short identification tags, called “barcodes” here, allows detection of chromosomally tagged strains by real-time PCR. Manual design of these barcodes is feasible for small sets, but expansion of the technique to larger pools of distinct and well-functioning assays would be significantly aided by software-guided design.ResultsHere we introduce barCoder, a bioinformatics tool that facilitates the process of creating sets of uniquely identifiable barcoded strains. barCoder utilizes the genomic sequence of the target strain and a set of user-specified PCR parameters to generate a list of suggested barcode “modules” that consist of binding sites for primers and probes and appropriate spacer sequences. Each module is designed to yield optimal PCR amplification and unique identification. Optimal amplification includes metrics such as ideal Tmand G+C-content, appropriate spacing, and minimal stem-loop formation; unique identification includes low BLAST hits against the target organism, previously generated barcode modules, and databases, such as NCBI. We tested the ability of our algorithm to suggest appropriate barcodes by generating 12 modules forBacillus thuringiensisserovarkurstaki, a simulant for the potential biowarfare agentBacillus anthracis, and three each for other potential target organisms with variable G+C content. Real-time PCR detection assays directed at barcodes were specific and yielded minimal cross-reactivity with a panel of near-neighbor and potential contaminant materials.ConclusionsThe barCoder algorithm facilitates the generation of barcoded biological simulants by (a) eliminating the task of creating modules by hand, (b) minimizing optimization of PCR assays, and (c) reducing effort wasted on non-unique barcode modules.
Hybridization capture of larch (LarixMill) chloroplast genomes from sedimentary ancient DNA reveals past changes of Siberian forests
Authors: Schulte Luise , Bernhardt Nadine , Stoof-Leichsenring Kathleen R. , Zimmermann Heike H. , Pestryakova Luidmila A. , Epp Laura S. , Herzschuh Ulrike 
Published: January 2020

AbstractSiberian larch (LarixMill.) forests dominate vast areas of northern Russia and contribute important ecosystem services to the world. It is important to understand the past dynamics of larches, in order to predict their likely response to a changing climate in the future. Sedimentary ancient DNA extracted from lake sediment cores can serve as archives to study past vegetation. However, the traditional method of studying sedimentary ancient DNA – metabarcoding – focuses on small fragments which cannot resolveLarixto species level nor allow the detailed study of population dynamics. Here we use shotgun sequencing and hybridization capture with long-range PCR-generated baits covering the completeLarixchloroplast genome to studyLarixpopulations from a sediment core reaching back up to 6700 years in age from the Taymyr region in northern Siberia. In comparison to shotgun sequencing, hybridization capture results in an increase of taxonomically classified reads by several orders of magnitude and the recovery of near-complete chloroplast genomes ofLarix. Variation in the chloroplast reads corroborate an invasion ofLarix gmeliniiinto the range ofLarix sibiricabefore 6700 years ago. Since then, both species have been present at the site, although larch populations have decreased with only a few trees remaining in what was once a forested area. This study demonstrates for the first time that hybridization capture applied to ancient DNA from lake sediments can provide genome-scale information and is a viable tool for studying past changes of a specific taxon.
Single-cell epigenomic identification of inherited risk loci in Alzheimer’s and Parkinson’s disease
Authors: Corces M. Ryan , Shcherbina Anna , Kundu Soumya , Gloudemans Michael J. , Frésard Laure , Granja Jeffrey M. , Louie Bryan H. , Shams Shadi , Bagdatli S. Tansu , Mumbach Maxwell R. , Liu Bosh , Montine Kathleen S. , Greenleaf William J. , Kundaje Anshul , Montgomery Stephen B. , Chang Howard Y. , Montine Thomas J. 
Published: January 2020

ABSTRACTGenome-wide association studies (GWAS) have identified thousands of variants associated with disease phenotypes. However, the majority of these variants do not alter coding sequences, making it difficult to assign their function. To this end, we present a multi-omic epigenetic atlas of the adult human brain through profiling of the chromatin accessibility landscapes and three-dimensional chromatin interactions of seven brain regions across a cohort of 39 cognitively healthy individuals. Single-cell chromatin accessibility profiling of 70,631 cells from six of these brain regions identifies 24 distinct cell clusters and 359,022 cell type-specific regulatory elements, capturing the regulatory diversity of the adult brain. We develop a machine learning classifier to integrate this multi-omic framework and predict dozens of functional single nucleotide polymorphisms (SNPs), nominating gene and cellular targets for previously orphaned GWAS loci. These predictions both inform well-studied disease-relevant genes, such asBIN1in microglia for Alzheimer’s disease (AD) and reveal novel gene-disease associations, such asSTAB1in microglia andMALin oligodendrocytes for Parkinson’s disease (PD). Moreover, we dissect the complex inverted haplotype of theMAPT(encoding tau) PD risk locus, identifying ectopic enhancer-gene contacts in neurons that increaseMAPTexpression and may mediate this disease association. This work greatly expands our understanding of inherited variation in AD and PD and provides a roadmap for the epigenomic dissection of noncoding regulatory variation in disease.
A comprehensive and comparative study on the action of pentacyclic triterpenoids onVibrio choleraebiofilms
Authors: Bhattacharya Sudipta Paul , Bhattacharya Arijit , Sen Aparna 
Published: January 2020

AbstractWhile serving as environmental reservoir forV. choleraeinfection, biofilms are also crucial for intestinal colonization of the pathogen. Triterpenoids, a group of bioactive phytochemicals, have been tested for antibiofilm activity against model biofilm forming bacteria in recent times. In this context, glycyrrhetinic acid (GRA), ursolic acid (UA) and betulinic acid (BA), representing three categorically distinct groups of pentacyclic triterpenoids, are targeted for profiling their impact onVibrio choleraeC6709 biofilms. The triterpenoids substantially affected biofilm associated attributes like formation, substratum adherence and dispersion from preformed biofilms. Though at variable degree, the compounds decreased cell surface hydrophobicity and composition in terms of macromolecular content. Not only EPS-associated extracellular enzyme activities were estimated to be reduced by triterpenoid exposure, ultra structural analysis also revealed that GRA, UA and BA can affect extracellular polymeric substance (EPS) content. Albeit total extracellular proteolytic activity remained unaffected by the triterpenoids, GRA treatment resulted in considerable reduction of extracellular gelatinase activity. Molecular docking analysis indicated potential interaction with cyclic di-GMP sensor VpsT, autoinducer-2 sensor kinase LuxP-LuxQ and transcriptional activator HapR, component of complex quorum sensing networks modulating biofilm formation. Comprehensive analysis of antibiotic action revealed accentuation of cephalosporin antibiotics with GRA and UA while BA potentiated action of fluoroquinolones, widening the scope of combinatorial therapeutic strategy.
Overexpression ofThalassiosira pseudonanaviolaxanthin de-epoxidase-like 2 (VDL2) increases fucoxanthin while stoichiometrically reducing diadinoxanthin cycle pigment abundance
Authors: Gaidarenko Olga , Mills Dylan W. , Vernet Maria , Hildebrand Mark 
Published: January 2020

ABSTRACTDespite the ubiquity and ecological importance of diatoms, much remains to be understood about their physiology and metabolism, including their carotenoid biosynthesis pathway. Early carotenoid biosynthesis steps are well-conserved, while the identity of the enzymes that catalyze the later steps and their order remain unclear. Those steps lead to the biosynthesis of the final pathway products: the main accessory light-harvesting pigment fucoxanthin (Fx) and the main photoprotective pigment pool comprised of diadinoxanthin (Ddx) and its reversibly de-epoxidized form diatoxanthin (Dtx). We used sequence comparison to known carotenoid biosynthesis enzymes to identify novel candidates in the diatomThalassiosira pseudonana. Microarray and RNA-seq data was used to select candidates with transcriptomic responses similar to known carotenoid biosynthesis genes and to create full-length gene models, and we focused on those that encode proteins predicted to be chloroplast-localized. We identified a violaxanthin de-epoxidase-like gene (Thaps3_11707, VDL2) that when overexpressed results in increased Fx abundance while stoichiometrically reducing Ddx+Dtx. Based on transcriptomics, we hypothesize that Thaps3_10233 may also contribute to Fx biosynthesis, in addition to VDL2. Separately using antisense RNA to target VDL2, VDL1, and both LUT1-like copies (hypothesized to catalyze an earlier step in the pathway) simultaneously, reduced the overall cellular photosynthetic pigment content, including chlorophylls, suggesting destabilization of light-harvesting complexes by Fx deficiency. Based on transcriptomic and physiological data, we hypothesize that the two predictedT. pseudonanazeaxanthin epoxidases have distinct functions and that different copies of phytoene synthase and phytoene desaturase may serve to initiate carotenoid biosynthesis in response to different cellular needs. Finally, nine carotene cis/trans isomerase (CRTISO) candidates identified based on sequence identity to known CRTISO proteins were narrowed to two most likely to be part of theT. pseudonanacarotenoid biosynthesis pathway based on transcriptomic responses and predicted chloroplast targeting.
Dysregulation of excitatory neural firing replicates physiological and functional changes in aging visual cortex
Authors: Talyansky Seth , Brinkman Braden A. W. 
Published: January 2020

AbstractThe mammalian visual system has been the focus of countless experimental and theoretical studies designed to elucidate principles of neural computation and sensory coding. Most theoretical work has focused on networks intended to reflect developing or mature neural circuitry, in both health and disease. Few computational studies have attempted to model changes that occur in neural circuitry as an organism ages non-pathologically. In this work we contribute to closing this gap, studying how physiological changes correlated with advanced age impact the computational performance of a spiking network model of primary visual cortex (V1). Our results demonstrate that deterioration of homeostatic regulation of excitatory firing, coupled with long-term synaptic plasticity, is a sufficient mechanism to reproduce features of observed physiological and functional changes in neural activity data, specifically declines in inhibition and in selectivity to oriented stimuli. This suggests a potential causality between dysregulation of neuron firing and age-induced changes in brain physiology and performance. While this does not rule out deeper underlying causes or other mechanisms that could give rise to these changes, our approach opens new avenues for exploring these underlying mechanisms in greater depth and making predictions for future experiments.
Simulation of the Gαq /Phospholipase Cβ1 Signaling Pathway Returns Differentiated PC12 Cells to a Stem-like State
Authors: Garwain Osama , Pearce Katherine M. , Jackson Lela , Carley Samuel , Rosati Barbara , Scarlata Suzanne 
Published: January 2020

ABSTRACTPhospholipase Cβ1 is activated by Gαq to generate calcium signals in response to hormones and neurotransmitters, and is found at high levels in mammalian neuronal tissue. Besides carrying out this key plasma membrane function, PLCβ1 has a cytosolic population that helps, in part, to drive the differentiation of PC12 cells by inhibiting a nuclease that promotes RNA-induced silencing (C3PO). Here, we show that down-regulating PLCβ1 or reducing its cytosolic population by activating Gαq to drive it to the plasma membrane, returns differentiated PC12 cells to an undifferentiated state. In this state, the cells return to a spherical morphology, resume proliferation and express the stem cell transcription factors nanog and Oct4. Similar changes are seen with C3PO down-regulation. This return to a stem-like state is accompanied by shifts in multiple miR populations, such as increased levels of rno-miR-21 and rno-miR-26a. Surprisingly, we find that de-differentiation can also be induced by extended stimulation of the Gαq. In this case, the neurites completely retract over a 10-minute period, and while levels of nanog remain unchanged, the levels of some miRs begin to return to their undifferentiated values. In complementary studies, we followed the real time hydrolysis of a fluorescent-tagged miR in cells where PLCβ1 or C3PO were down-regulated. These samples showed substantial differences in miR processing in cells both the undifferentiated and differentiated states. Taken together, our studies suggest that PLCβ1, through its ability to regulate C3PO and endogenous miR populations, plays a key role in mediating PC12 cell differentiation.
Structural basis for catalysis and substrate specificity of human ACAT1
Authors: Qian Hongwu , Zhao Xin , Yan Renhong , Gao Shuai , Sun Xue , Wong Catherine C. L. , Yan Nieng 
Published: January 2020

SummaryAcyl-coenzyme A: cholesterol acyltransferases (ACATs) catalyze acyl transfer from acyl-coenzyme A (CoA) to cholesterol to generate cholesteryl ester, which is the primary form for cellular storage and plasma transport of cholesterol. Because of their close relationship with cholesterol metabolism, ACATs represent potential drug target for the treatment of atherosclerosis and other cholesterol-related disorders. Here we present the cryo-EM structure of human ACAT1 at 3.3 Å resolution for dimer of dimers and 3.0 Å for a dimer. Each protomer consists of nine transmembrane segments that enclose a cytosolic (C) and a transmembrane (T) tunnel. The tunnels, each accommodating an elongated density, converge at the predicted catalytic site. Structure-guided mutational analyses suggest the cytosolic and lateral entry for acyl-CoA and cholesterol, respectively. Our structural, biochemical, and mass spectrometric characterizations reveal the catalytic mechanism and substrate preference for unsaturated acyl chain by ACAT1.
Long-term warming weakens stabilizing effects of biodiversity in aquatic ecosystems
Authors: Chang Chun-Wei , Ye Hao , Miki Takeshi , Deyle Ethan R. , Souissi Sami , Anneville Orlane , Adrian Rita , Chiang Yin-Ru , Ichise Satoshi , Kumagai Michio , Matsuzaki Shin-ichiro S. , Shiah Fuh-Kwo , Wu Jiunn-Tzong , Hsieh Chih-hao , Sugihara George 
Published: January 2020

AbstractDespite the consensus that warming will affect biodiversity, alter physicochemical environments, and disrupt biological interactions, the relative importance of these key processes and how they interact to determine overall ecosystem function is poorly understood. Here, we analyze long-term (16∼39 years) time series data from ten aquatic ecosystems and use convergent cross mapping (CCM) to quantify the hidden causal network linking species diversity, ecosystem function, and physicochemical factors. We observe that aquatic ecosystems subject to stronger warming exhibit decreased stability (larger fluctuations in phytoplankton biomass). We further show that this effect can be attributed to a weakening of stabilizing causal pathways between biodiversity, nutrient cycling, and phytoplankton biomass. Thus, rather than thinking in terms of separate factors, a more holistic view, that causally links biodiversity and the other ecosystem components, is required to understand and predict climate impacts on the temporal stability of aquatic ecosystems.
Whole genome comparisons of Staphylococcus agnetis isolates from cattle and chickens
Authors: Shwani Abdulkarim , Adkins Pamela R. F. , Ekesi Nnamdi S. , Alrubaye Adnan , Calcutt Michael J. , Middleton John R. , Rhoads Douglas D. 
Published: January 2020

AbstractS. agnetis has been previously associated with subclinical or clinically mild cases of mastitis in dairy cattle and is one of several Staphylococcal species that have been isolated from the bone and blood of lame broilers. We were the first to report that S. agnetis could be obtained frequently from bacterial chondronecrosis with osteomyelitis (BCO) lesions of lame broilers. Further, we showed that a particular isolate of S. agnetis, chicken isolate 908, can induce lameness in over 50% of exposed chickens, far exceeding normal BCO incidences in broiler operations. We have previously reported the assembly and annotation of the genome of isolate 908. To better understand the relationship between dairy cattle and broiler isolates, we assembled 11 additional genomes for S. agnetis isolates, including an additional chicken BCO strain, and ten isolates from milk, mammary gland secretions or udder skin, from the collection at the University of Missouri. To trace phylogenetic relationships, we constructed phylogenetic trees based on multi-locus sequence typing, and Genome-to-Genome Distance Comparisons. Chicken isolate 908 clustered with two of the cattle isolates along with three isolates from chickens in Denmark and an isolate of S. agnetis we isolated from a BCO lesion on a commercial broiler farm in Arkansas. We used a number of BLAST tools to compare the chicken isolates to those from cattle and identified 98 coding sequences distinguishing isolate 908 from the cattle isolates. None of the identified genes explain the differences in host or tissue tropism. These analyses are critical to understanding how Staphylococci colonize and infect different hosts and potentially how they can transition to alternative niches (bone vs dermis).ImportanceStaphylococcus agnetis has been recently recognized as associated with disease in dairy cattle and meat type chickens. The infections appear to be limited in cattle and systemic in broilers. This report details the molecular relationships between cattle and chicken isolates in order to understand how this recently recognized species infects different hosts with different disease manifestations. The data show the chicken and cattle isolates are very closely related but the chicken isolates all cluster together suggesting a single jump from cattle to chickens.