bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zoonotic tuberculosis in India: looking beyondMycobacterium bovis
Authors: Duffy Shannon C , Srinivasan Sreenidhi , Schilling Megan A , Stuber Tod , Danchuk Sarah N , Michael Joy S , Venkatesan Manigandan , Bansal Nitish , Maan Sushila , Jindal Naresh , Chaudhary Deepika , Dandapat Premanshu , Katani Robab , Chothe Shubhada , Veerasami Maroudam , Robbe-Austerman Suelee , Juleff Nicholas , Kapur Vivek , Behr Marcel A 
Published: November 2019

AbstractBackgroundZoonotic tuberculosis (zTB) is the transmission ofMycobacterium tuberculosiscomplex (MTBC) subspecies from animals to humans. zTB is generally quantified by determining the proportion of human isolates that areMycobacterium bovis. Although India has the world’s largest number of human TB cases and the largest cattle population, where bovine TB is endemic, the burden of zTB is unknown.MethodsTo obtain estimates of zTB in India, a PCR-based approach was applied to sub-speciate positive MGIT® cultures from 940 patients (548 pulmonary, 392 extrapulmonary disease) at a large referral hospital in India. Twenty-five isolates of interest were subject to whole genome sequencing (WGS) and compared with 715 publicly available MTBC sequences from South Asia.FindingsA conclusive identification was obtained for 939 samples; wildtypeM. boviswas not identified (95% CI: 0 – 0.4%). There were 912M. tuberculosis sensu stricto(97.0%, 95% CI: 95.7 – 98.0), 7M. orygis(95% CI: 0.3 – 1.5%); 5M. bovisBCG, and 15 non-tuberculous mycobacteria. WGS analysis of 715 MTBC sequences again identified noM. bovis(95% CI: 0 – 0.4%). Human and cattle MTBC isolates were interspersed within theM. orgyisandM. tuberculosis sensu strictolineages.InterpretationM. bovisprevalence in humans is an inadequate proxy of zTB in India. The recovery ofM. orygisfrom humans, together with the finding ofM. tuberculosisin cattle, underscores the need for One Health investigations to assess the burden of zTB in countries with endemic bovine TB.FundingBill & Melinda Gates Foundation, Canadian Institutes for Health Research
Comparative metatranscriptomics of periodontitis supports a common polymicrobial shift in metabolic function and identifies novel putative disease-associated ncRNAs
Authors: Ram-Mohan Nikhil , Meyer Michelle M. 
Published: November 2019

AbstractPeriodontitis is an inflammatory disease that deteriorates bone supporting teeth afflicting ∼743 million people worldwide. Bacterial communities associated with disease have been classified into red, orange, purple, blue, green, and yellow complexes based on their roles in the periodontal pocket. Previous metagenomic and metatranscriptomics analyses suggest a common shift in metabolic signatures in disease vs. healthy communities with up-regulated processes including pyruvate fermentation, histidine degradation, amino acid metabolism, TonB-dependent receptors. In this work, we examine existing metatranscriptome datasets to identify the commonly differentially expressed transcripts and potential underlying RNA regulatory mechanisms behind the metabolic shifts. Raw RNA-seq reads from three studies (including 49 healthy and 48 periodontitis samples) were assembled into transcripts de novo. Analyses revealed 859 differentially expressed (DE) transcripts, 675 more- and 174 less-expressed. Only ∼20% of the DE transcripts originate from the pathogenic red/orange complexes, and ∼50% originate from organisms unaffiliated with a complex. Comparison of expression profiles revealed variations among disease samples; while specific metabolic processes are commonly up-regulated, the underlying organisms are diverse both within and across disease associated communities. Surveying DE transcripts for known ncRNAs from the Rfam database identified a large number of tRNAs and tmRNAs as well as riboswitches (FMN, glycine, lysine, and SAM) in more prevalent transcripts and the cobalamin riboswitch in both more and less prevalent transcripts. In silico discovery identified many putative ncRNAs in DE transcripts. We report 15 such putative ncRNAs having promising covariation in the predicted secondary structure and interesting genomic context. Seven of these are antisense of ribosomal proteins that are novel and may involve maintaining ribosomal protein stoichiometry during the disease associated metabolic shift. Our findings describe the role of organisms previously unaffiliated with disease and identify the commonality in progression of disease across three metatranscriptomic studies. We find that although the communities are diverse between individuals, the switch in metabolic signatures characteristic of disease is typically achieved through the contributions of several community members. Furthermore, we identify many ncRNAs (both known and putative) which may facilitate the metabolic shifts associated with periodontitis.
Testes of DAZL null sheep lack spermatogonia and maintain normal somatic cells
Authors: McLean Zachariah , Appleby Sarah Jane , Wei Jingwei , Snell Russell Grant , Oback Björn 
Published: November 2019

AbstractMultiplying the germline would increase the number of offspring that can be produced from selected animals, accelerating genetic improvement for livestock breeding. This could be achieved by producing multiple chimaeric animals, each carrying a mix of donor and host germ cells in their gonads. However, such chimaeric germlines would produce offspring from both donor and host genotypes, limiting the rate of genetic improvement. To resolve this problem and produce chimaeras with absolute donor germline transmission, we have disrupted the RNA-binding protein DAZL and generated germ cell-deficient host animals. Using Cas9 mediated homology-directed repair (HDR), we introduced a DAZL loss-of-function mutation in male ovine fetal fibroblasts. Following manual single-cell isolation, 4/48 (8.3%) of donor cell strains were homozygously HDR-edited. Sequence-validated strains were used as nuclear donors for somatic cell cloning to generate three lambs, which died at birth. All DAZL-null male neonatal sheep lacked germ cells. Somatic cells within their testes were morphologically intact and expressed normal levels of somatic cell-specific marker genes, indicating that the germ cell niche remained intact. This extends the DAZL-mutant phenotype beyond mice into agriculturally relevant ruminants, providing a pathway for using absolute transmitters in rapid livestock improvement.
Mitochondrial DNA Copy Number and Incident Atrial Fibrillation
Authors: Zhao Di , Bartz Traci M. , Sotoodehnia Nona , Post Wendy S. , Heckbert Susan R. , Alonso Alvaro , Longchamps Ryan J. , Castellani Christina A. , Hong Yun Soo , Rotter Jerome I. , Lin Henry J. , O’Rourke Brian , Pankratz Nathan , Lane John A , Yang Stephanie Y. , Guallar Eliseo , Arking Dan E. 
Published: November 2019

AbstractBackgroundMechanistic studies suggests that mitochondria DNA (mtDNA) dysfunction may be associated with increased risk of atrial fibrillation (AF). The association between mtDNA copy number (mtDNA-CN) and incident AF in the general population, however, remains unknown.MethodsWe conducted prospective analyses of 19,709 participants from the Atherosclerosis Risk in Communities Study (ARIC), the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS). mtDNA-CN from peripheral blood was calculated from probe intensities on the Affymetrix Genome-Wide Human single nucleotide polymorphisms (SNP) Array 6.0 in ARIC and MESA, and from multiplexed real time quantitative polymerase chain reaction (qPCR) in CHS. Incident AF cases were identified through electrocardiograms, review of hospital discharge codes, Medicare claims, and death certificates.ResultsThe median follow-up time was 21.4 years in ARIC, 12.9 years in MESA and 11.0 years in CHS, during which 4,021 participants developed incident atrial fibrillation (1,761 in ARIC, 790 in MESA, and 1,470 in CHS). The fully-adjusted pooled hazard ratio for incident atrial fibrillation comparing the 1st to the 5th quintile of mitochondria DNA copy number was 1.13 (1.01, 1.27). The fully-adjusted pooled hazard ratio comparing the 10th vs the 90th percentile of mitochondria DNA copy number was 1.13 (1.04, 1.24). Dose-response spline analysis also showed an inverse association between mitochondria DNA copy number and hazard for atrial fibrillation for all three cohorts. These associations were consistent across subgroups.ConclusionsMitochondria DNA copy number was inversely associated with the risk of AF independent of traditional cardiovascular risk factors. These findings implicate mitochondria DNA copy number as a novel risk factor for atrial fibrillation. Further research is warranted to understand the underlying mechanisms and to evaluate the role of mitochondria DNA copy number in the management of atrial fibrillation risk.
Restriction of essential amino acids dictates the systemic response to dietary protein dilution
Authors: Yap Yann W. , Rusu Patricia M. , Chan Andrea Y. , Fam Barbara C. , Jungmann Andreas , Solon-Biet Samantha M. , Barlow Christopher K. , Creek Darren J. , Huang Cheng , Schittenhelm Ralf B. , Morgan Bruce , Schmoll Dieter , Kiens Bente , Piper Matthew D.W. , Heikenwälder Mathias , Simpson Stephen J. , Bröer Stefan , Andrikopoulos Sofianos , Müller Oliver J. , Rose Adam J. 
Published: November 2019

AbstractDietary protein dilution (DPD) promotes metabolic remodelling and health but the precise nutritional components driving this response remain elusive. Here we demonstrate that dietary amino acids (AA) are sufficient and necessary to drive the response to DPD. In particular, the restriction of dietary essential AA (EAA) supply, but not non-EAA, drives the systemic metabolic response to total AA deprivation. Furthermore, systemic deprivation of Thr and Trp, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction. Thr is also potentially limiting in low-protein diet fed humans, and dietary Thr restriction (DTR) retarded the development of obesity-associated metabolic dysfunction in mice. Liver-derived fibroblast growth factor 21 was required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of Thr biosynthetic capacity reversed the systemic response to DTR. Taken together, our studies demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD.
FUSgene is dual-coding with both proteins united in FUS-mediated toxicity
Authors: Brunet Marie A. , Jacques Jean-Francois , Nassari Sonya , Tyzack Giulia E. , McGoldrick Philip , Zinman Lorne , Jean Steve , Robertson Janice , Patani Rickie , Roucou Xavier 
Published: November 2019

ABSTRACTNovel functional coding sequences (altORFs) are camouflaged within annotated ones (CDS) in a different reading frame. We discovered an altORF nested in the FUS CDS encoding a conserved 169 amino acid protein, altFUS. AltFUS is endogenously expressed in human tissues, notably in the motor cortex and motor neurons. Overexpression of wild-type FUS and/or amyotrophic lateral sclerosis-linked FUS mutants is known to trigger toxic mechanisms in different models. These include an inhibition of autophagy, loss of mitochondrial potential, and accumulation of cytoplasmic aggregates. We show here that altFUS, not FUS, is responsible for the inhibition of autophagy. AltFUS is also pivotal in the mechanisms leading to the mitochondrial potential loss and accumulation of cytoplasmic aggregates. Suppression of altFUS expression in aDrosophilamodel ofFUS-related toxicity protects against neurodegeneration. Some mutations found in ALS patients are overlooked because of their synonymous effect on the FUS protein. Yet we showed they exert a deleterious effect via their missense consequence on the overlapping altFUS protein. These findings demonstrate thatFUSis a bicistronic gene and suggest that both proteins, FUS and altFUS, cooperate in toxic mechanisms.
Characterisation of the ERF102 to ERF105 genes of Arabidopsis thaliana and their role in the response to cold stress
Authors: Illgen Sylvia , Zintl Stefanie , Zuther Ellen , Hincha Dirk K. , Schmülling Thomas 
Published: November 2019

AbstractThe ETHYLENE RESPONSE FACTOR (ERF) genes of Arabidopsis thaliana form a large family encoding plant-specific transcription factors. Here, we characterise the four phylogenetically closely related ERF102/ERF5, ERF103/ERF6, ERF104 and ERF105 genes. Expression analyses revealed that these four genes are similarly regulated by different hormones and abiotic stresses. Analyses of tissue-specific expression using promoter:GUS reporter lines revealed their predominant expression in root tissues including the root meristem (ERF103), the quiescent center (ERF104) and the root vasculature (all). All GFP-ERF fusion proteins were nuclear-localised. The analysis of insertional mutants, amiRNA lines and 35S:ERF overexpressing transgenic lines indicated that ERF102 to ERF105 have only a limited impact on regulating shoot and root growth. Previous work had shown a role for ERF105 in the cold stress response. Here, measurement of electrolyte leakage to determine leaf freezing tolerance and expression analyses of cold-responsive genes revealed that the combined activity of ERF102 and ERF103 is also required for a full cold acclimation response likely involving the CBF regulon. Together, these results suggest a common function of these ERF genes in regulating root architecture and the response to cold stress.
The effect of anteroposterior perturbations on the control of the center of mass during treadmill walking
Authors: van den Bogaart Maud , Bruijn Sjoerd M. , van Dieën Jaap H. , Meyns Pieter 
Published: November 2019

AbstractShifts of the center of pressure (CoP) through modulation of foot placement and ankle moments (CoP-mechanism) cause accelerations of the center of mass (CoM) that can be used to stabilize gait. An additional mechanism that can be used to stabilize gait, is the counter-rotation mechanism, i.e., changing the angular momentum of segments around the CoM to change the direction of the ground reaction force. The relative contribution of these mechanisms to the control of the CoM is unknown. Therefore, we aimed to determine the relative contribution of these mechanisms to control the CoM in the anteroposterior (AP) direction during a normal step and the first recovery step after perturbation in healthy adults. Nineteen healthy subjects walked on a split-belt treadmill and received unexpected belt acceleration perturbations of various magnitudes applied immediately after right heel-strike. Full-body kinematic and force plate data were obtained to calculate the contributions of the CoP-mechanism and the counter-rotation mechanism to control the CoM. We found that the CoP-mechanism contributed to corrections of the CoM acceleration after the AP perturbations, while the counter-rotation mechanism actually contributed to CoM acceleration in the direction of the perturbation, but only in the initial phases of the first step after the perturbation. The counter-rotation mechanism appeared to prevent interference with the gait pattern, rather than using it to control the CoM after the perturbation. Understanding the mechanisms used to stabilize gait may have implications for the design of therapeutic interventions that aim to decrease fall incidence.Summary statementUnderstanding the mechanisms used to stabilize gait during unperturbed and perturbed walking may have implications for the design of therapeutic interventions that aim to decrease fall incidence.
Combining Focused Identification of Germplasm and Core Collection Strategies to Identify Genebank Accessions for Central European Soybean Breeding
Authors: Haupt Max , Schmid Karl 
Published: November 2019

ABSTRACTEnvironmental adaptation of crops is essential for reliable agricultural production and an important breeding objectives. Genbanks provide genetic variation for the improvement of modern varieties, but the selection of suitable germplasm is frequently impeded by incomplete phenotypic data. We address this bottleneck by combining aFocused Identification of Germplasm Strategy(FIGS) with core collection methodology to select soybean (Glycine max) germplasm for Central European breeding from a collection of >17,000 accessions. By focussing on environmental adaptation to high-latitude cold regions, we selected an ‘environmental precore’ of 3,663 accessions using environmental data and compared the Donor Population of Environments (DPE) in Asia and the Target Population of Environments (TPE) in Central Europe in the present and in 2070. Using SNP genotypes we reduced the precore into two diverse core collections of 183 and 366 of accessions as diversity panels for evaluation in high-latitude cold regions. Tests of genetic differentiation between precore and core collections revealed differentiation signatures in genomic regions that control maturity, and novel candidate loci for environmental adaptation demonstrating the potential of diversity panels for studying environmental adaptation. Objective-driven core collections increase germplasm utilization for abiotic adaptation by breeding for a rapidly changing climate, orde novoadaptation of crop species to expand cultivation ranges.
Adiponectin Receptor Fragmentation in Mouse Models of Type 1 and Type 2 Diabetes
Authors: Frabutt Dylan , Stull Natalie , Pineros Annie R. , Tersey Sarah A. , Scheuner Donalyn , Mastracci Teresa L. , Pugia Michael J. 
Published: November 2019

AbstractThe protein hormone adiponectin regulates glucose and fatty acid metabolism by binding to two PAQR-family receptors (AdipoR1 and AdipoR2). Both receptors feature a C-terminal segment which is released by proteolysis to form a freely-circulating C-terminal fragment (CTF) found in the plasma of normal individuals but not in some undefined diabetes patients. The AdipoR1-CTF344-376 is a competitive inhibitor of tumor necrosis factor α cleavage enzyme (TACE) but it contains a shorter peptide domain (AdipoR1 CTF351-362) that is a strong non-competitive inhibitor of insulin-degrading enzyme (IDE). The link between adiponectin receptor fragmentation and diabetes pathology is unclear but could lead to new therapeutic strategies. We therefore investigated physiological variations in the concentrations of CTF in non-obese diabetic (NOD/ShiLtJ) mice and C57BL/6 mice with diet-induced obesity (DIO) as models of diabetes types 1 and 2, respectively. We tested for changes in adiponectin receptor signaling, immune responses, disease progression, and the abundance of neutralizing autoantibodies. Finally, we administered exogenous AdipoR1-CTF peptides either containing or lacking the IDE-binding domain. We observed the more pronounced CTF shedding in the TACE-active NOD mice, which represents an inflammatory autoimmune phenotype, but fragmentation was also observed to a lesser extent in the DIO model. Autoantibodies to CTF were detected in both models. Neither exogenous CTF peptide affected IgG-CTF plasma levels, body weight or the conversion of NOD mice to diabetes. The pattern of AdipoR1 fragmentation and autoantibody production under physiological conditions of aging, DIO, and autoimmune diabetes therefore provides insight into the association adiponectin biology and diabetes.
Interneuron dysfunction in a new knock-in mouse model of SCN1A GEFS+
Authors: Das Antara , Zhu Bingyao , Xie Yunyao , Zeng Lisha , Pham An T. , Neumann Jonathan C. , MacGregor Grant R. , Schutte Soleil , Hunt Robert F. , O’Dowd Diane K. 
Published: November 2019

AbstractAdvances in genome sequencing have identified over 1300 mutations in the SCN1A sodium channel gene that result in genetic epilepsies. However, how individual mutations within SCN1A produce seizures remains elusive for most mutations. Previous work from our lab has shown that the K1270T (KT) mutation, which is linked to GEFS+ (Genetic Epilepsy with Febrile Seizure plus) in humans, causes reduced firing of GABAergic neurons in a Drosophila knock-in model. To examine the effect of this mutation in mammals, we introduced the equivalent KT mutation into the mouse Scn1a (Scn1aKT) gene using CRISPR/Cas9. Mouse lines carrying this mutation were examined in two widely used genetic backgrounds, C57BL/6NJ and 129×1/SvJ. In both backgrounds, homozygous mutants had spontaneous seizures and died by postnatal day 23. There was no difference in the lifespan of mice heterozygous for the mutation in either background when compared to wild-type littermates up to 6 months. Heterozygous mutants had heat-induced seizures at ~42 deg. Celsius, a temperature that did not induce seizures in wild-type littermates. In acute hippocampal slices, current-clamp recordings revealed a significant depolarized shift in action potential threshold and reduced action potential amplitude in parvalbumin-expressing inhibitory interneurons in Scn1aKT/+ mice. There was no change in the firing properties of excitatory CA1 pyramidal neurons. Our results indicate that Scn1aKT/+ mice develop seizures, and impaired action potential firing of inhibitory interneurons in Scn1aKT/+ mice may produce hyperexcitability in the hippocampus.
Genomic Characterization of SiGRFs in Foxtail Millet and SiGRF1-overexpression in Arabidopsis thaliana Promotes Plant to Avoid Salt Stress
Authors: Liu Jiaming , Jiang Chengyao , Kang Lu , Zhang Chongchang , Song Yu , Zheng Weijun 
Published: November 2019

AbstractIn plants, 14-3-3 proteins are recognized as mediators of signal transduction and function in both development and stress response. However, their functions have not been reported in the C4 crop foxtail millet. Here, phylogenetic analysis categorized foxtail millet 14-3-3s (SiGRFs) into ten discrete groups (Clusters I to □). Transcriptome and qPCR analyses showed that all the SiGRFs responded to at least one abiotic stress. All but one SiGRF-overexpressing (OE) Arabidopsis thaliana line (SiGRF1) exhibited insensitivity to abiotic stresses during seed germination and seedling growth. Compared with the Col-0 wild-type, SiGRF1-OEs had slightly lower germination rates and smaller leaves. However, flowering time of SiGRF1-OEs occurred earlier than that of Col-0 under high-salt stress. Interaction of SiGRF1 with a foxtail millet E3 ubiquitin-protein ligase (SiRNF1/2) indicates that the proteinase system might hydrolyse SiGRF1. Further investigation showed that SiGRF1 localized in the cytoplasm, and its gene was ubiquitously expressed in various tissues throughout various developmental stages. Additionally, flowering-related genes, WRKY71, FLOWERING LOCUS T, LEAFY and FRUITFULL, in SiGRF1-OEs exhibited considerably higher expression levels than those in Col-0 under salinity-stressed conditions. Results suggest that SiGRF1 hastens flowering, thereby providing a means for foxtail millet to complete its life cycle and avoid further salt stress.HighlightSiGRFs in foxtail millet: SiGRF1 hastens flowering in transgenic Arabidopsis thaliana exposed to salt stress