bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optogenetic inhibition of colon epithelium reduces hypersensitivity in a mouse model of inflammatory bowel disease
Authors: Najjar Sarah A. , Ejoh Lindsay L. , Loeza-Alcocer Emanuel , Edwards Brian S. , Smith-Edwards Kristen M. , Epouhe Ariel Y. , Gold Michael S. , Davis Brian M. , Albers Kathryn M. 
Published: May 2020

ABSTRACTVisceral pain is a prevalent symptom of inflammatory bowel disease (IBD) that can be difficult to treat. Pain and hypersensitivity are mediated by extrinsic primary afferent neurons (ExPANs) that innervate the colon. Recent studies indicate that the colon epithelium contributes to initiating ExPAN firing and nociceptive responses. Based on these findings we hypothesized that the epithelium contributes to inflammation-induced hypersensitivity. A key prediction of this hypothesis is that inhibition of the epithelium would attenuate nociceptive signaling and inflammatory hypersensitivity. To test this hypothesis, the inhibitory yellow light activated protein archaerhodopsin was targeted to the intestinal epithelium (villin-Arch) or the ExPANs (TRPV1-Arch) that innervate the colon. Visceral sensitivity was assessed by measuring the visceromotor response (VMR) to colorectal distension (CRD), with and without yellow light illumination of the colon lumen. Inhibition of the colon epithelium in healthy villin-Arch mice significantly diminished the CRD-induced VMR. Direct inhibition of ExPANs during CRD using TRPV1-Arch mice showed that ExPAN and epithelial inhibition were similarly effective in reducing the VMR to CRD. We then investigated the effect of epithelial and ExPAN inhibition in the dextran sulfate sodium (DSS) model of inflammatory bowel disease (IBD). Inhibition of the colon epithelium significantly decreased DSS-induced hypersensitivity and was comparable to inhibition of ExPANS. Together these results reveal the potential of targeting the colon epithelium for treatment of pain.
Cold-induced hyperphagia requires AgRP neuron activation in mice
Authors: Deem Jennifer D. , Faber Chelsea L. , Pedersen Christian , Phan Bao Anh , Larsen Sarah A. , Ogimoto Kayoko , Nelson Jarrell T. , Damian Vincent , Tran Megan A. , Palmiter Richard D. , Kaiyala Karl J. , Scarlett Jarrad M. , Bruchas Michael R. , Schwartz Michael W. , Morton Gregory J. 
Published: May 2020

ABSTRACTTo maintain energy homeostasis during cold exposure, the increased energy demands of thermogenesis must be counterbalanced by increased energy intake. To investigate the neurobiological mechanisms underlying this cold-induced hyperphagia, we asked whether agouti-related peptide (AgRP) neurons are activated when animals are placed in a cold environment and, if so, whether this response is required for the associated hyperphagia. We report that AgRP-neuron activation occurs rapidly upon acute cold exposure, as do increases of both energy expenditure and energy intake, suggesting the mere perception of cold is sufficient to engage each of these responses. We further report that silencing of AgRP neurons selectively blocks the effect of cold exposure to increase food intake. Together, these findings establish a physiologically important role for AgRP neurons in the hyperphagic response to cold exposure.
Proliferation is a requirement for differentiation of oligodendrocyte progenitor cells during CNS remyelination
Authors: Foerster Sarah , Neumann Björn , McClain Crystal , Di Canio Ludovica , Chen Civia Z , Reich Daniel S , Simons Benjamin D , Franklin Robin JM 
Published: May 2020

SummaryOligodendrocytes that generate new myelin sheaths around demyelinated axons in the regenerative process of remyelination are generally derived from oligodendrocyte progenitor cells (OPCs). During this process, OPCs become activated, populate the area of myelin loss, and finally differentiate. Although much is known about the individual stages of remyelination, the exact sequence of events and whether a dependency of each individual stage on each other exists is unknown. Understanding the biology behind these questions is important for the development of remyelination therapies to overcome the age-related decline in remyelination efficiency observed in the chronic phase of multiple sclerosis (MS). Here we show that, following toxin-induced demyelination, all re-populating OPCs first migrate into the site of damage, undergo relatively few rounds of division and eventually differentiate. We further show that OPC proliferation is a requirement for differentiation. Together, our results reveal an unexpected link between OPC proliferation and differentiation, and opens up the possibility of novel regenerative strategies in MS focussing on stimulating OPC proliferation.
Whole genome analysis of four Bangladeshi individuals
Authors: Khan Salim , Akter Shahina , Goswami Barna , Habib Ahashan , Banu Tanjina Akhtar , Barton Carl , Osman Eshrar , Samir Samiruzzaman , Arjuman Farida , Hasan Saam , Hossain Maqsud 
Published: May 2020

AbstractWhole-genome sequencing (WGS) is a comprehensive method for analysing entire genomes and this has been instrumental in characterizing the single nucleotide polymorphisms associated with different diseases including cancer, diabetes, cardiovascular diseases and many others. In this paper we undertake a pilot study for sequencing four Bangladeshi individuals and profiling their single nucleotide variants. Our findings shed possible light on specific biological pathways effected by such variants in this population.
Development of a genetic evaluation for hair shedding in American Angus cattle to improve thermotolerance
Authors: Durbin Harly J. , Lu Duc , Yampara-Iquise Helen , Miller Stephen P. , Decker Jared E. 
Published: May 2020

AbstractBackgroundHeat stress and fescue toxicosis caused by ingesting tall fescue infected with the endophytic fungus Epichloë coenophiala represent two of the most prevalent stressors to beef cattle in the United States, costing the beef industry millions of dollars each year. The rate at which a beef cow sheds her winter coat early in the summer is an indicator of adaptation to heat and an economically relevant trait in many parts of the U.S. Further, research suggests that early-summer hair shedding may be reflective of tolerance to fescue toxicosis, as vasoconstriction induced by fescue toxicosis limits the ability of an animal to shed its winter coat. Here, we developed parameters for routine genetic evaluation of hair shedding score in American Angus cattle and identified genomic loci associated with variation in hair shedding score via genome-wide association analysis (GWAA).ResultsHair shedding score was found to be moderately heritable (h2 = 0.34 to 0.40), with differing repeatability estimates between cattle grazing versus not grazing endophyte-infected tall fescue. Our results suggest modestly negative genetic and phenotypic correlations between a dam’s hair shedding score (lower score is earlier shedding) and the weaning weight of her calf, one metric of performance. Together, these results indicate that economic gains can be made via the use of hair shedding score breeding values to select for heat tolerant cattle. GWAA identified 176 variants significant at FDR < 0.05. Functional enrichment analyses using genes within 50 Kb of these variants identified pathways involved in keratin formation, prolactin signaling, host-virus interaction, and other biological processes.ConclusionsThis work contributes to a continuing trend in the development of genetic evaluations for environmental adaptation. The results of this work will aid beef cattle producers in selecting more sustainable and climate-adapted cattle, as well as enable the development of similar routine genetic evaluations in other breeds.
Performance and impact of disposable and reusable respirators for healthcare workers during pandemic respiratory disease: a rapid evidence review
Authors: Burton Chris , Coles Briana , Adisesh Anil , Smith Simon , Toomey Elaine , Chan Xin Hui , Ross Lawrence , Greenhalgh Trisha 
Published: May 2020

AbstractObjectivesIn the context of the Covid-19 pandemic, to identify the range of filtering respirators that can be used in patient care and synthesise evidence to guide the selection and use of different respirator types.DesignComparative analysis of international standards for filtering respirators and rapid review of their performance and impact in healthcare.Data sourcesWebsites of international standards organisations, Medline and EMBASE (final search 11thMay 2020), with hand-searching of references and citations.Study selectionGuided by the SPIDER tool, we included studies whose sample was healthcare workers (including students). The phenomenon of interest was respirators, including disposable and reusable types. Study designs including cross-sectional, observational cohort, simulation, interview and focus group. Evaluation approaches included test of respirator performance, test of clinician performance or adherence, self-reported comfort and impact, and perceptions of use. Research types included quantitative, qualitative and mixed methods. We excluded studies comparing the effectiveness of respirators with other forms of protective equipment.Data extraction, analysis and synthesisTwo reviewers extracted data using a template. Suitability for inclusion in the analysis was judged by two reviewers. We synthesised standards by tabulating data according to key criteria. For the empirical studies, we coded data thematically followed by narrative synthesis.ResultsWe included relevant standards from 8 authorities across Europe, North and South America, Asia and Australasia. 39 research studies met our inclusion criteria. There were no instances of comparable publications suitable for quantitative comparison. There were four main findings. First, international standards for respirators apply across workplace settings and are broadly comparable across jurisdictions. Second, effective and safe respirator use depends on proper fitting and fit-testing. Third, all respirator types carry a burden to the user of discomfort and interference with communication which may limit their safe use over long periods; studies suggest that they have little impact on specific clinical skills in the short term but there is limited evidence on the impact of prolonged wearing. Finally, some clinical activities, particularly chest compressions, reduce the performance of filtering facepiece respirators.ConclusionA wide range of respirator types and models is available for use in patient care during respiratory pandemics. Careful consideration of performance and impact of respirators is needed to maximise protection of healthcare workers and minimise disruption to the delivery of care.
Comparison of renin–angiotensin–aldosterone system inhibitors with other antihypertensives in association with coronavirus disease-19 clinical outcomes: systematic review and meta-analysis
Authors: Bezabih Yihienew M. , Bezabih Alemayehu , Aalamneh Endalkachew , Peterson Gregory M. , Bezabhe Woldesellassie M. 
Published: May 2020

AbstractIntroductionThe effects of renin–angiotensin–aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting in different studies. This meta-analysis was undertaken to provide more conclusive evidence.MethodsA systematic search for published articles was performed in PubMed and EMBASE from January 5 2020 till May 5 2020. Studies that reported the clinical outcomes of patients with COVID-19, stratified by the class of concomitant antihypertensive drug therapy, were included. The Mantel-Haenszel random effects model was used to estimate pooled odds ratio (OR).ResultsA total of 6,997 patients with COVID-19 were included, and all of them had hypertension. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR=0.84, 95% CI: [0.73, 0.96]; P=0.017) compared with those receiving non-RAAS inhibitor antihypertensives. Patients taking angiotensin-I-converting enzyme inhibitors (ACEIs) were less likely to experience poor clinical outcomes (OR=0.73, 95% CI: [0.58-0.92]; P=0.01) compared with those receiving angiotensin-II receptor blockers (ARBs). In addition, comparison of ACEIs to the rest of non-ACEI antihypertensives gave a consistently decreased risk of poor COVID-19 outcome (OR=0.77, 95% CI: [0.63-0.93]; P=0.002). However, ARBs did not decrease the risk of poor COVID-19 outcomes compared to all other non-ARB antihypertensives (OR=1.13, 95% CI: [0.95-1.35]).ConclusionThe risk of developing severe illness or death from COVID-19 was lower in patients who received RAAS inhibitors compared with those who took non-RAAS inhibitors. ACEIs might be better in decreasing the severity and mortality of COVID-19 than ARBs.
SARS-CoV-2 infection in London, England: Impact of lockdown on community point-prevalence, March-May 2020
Authors: Edelstein Michael , Obi Chinelo , Chand Meera , Hopkins Susan , Brown Kevin , Ramsay Mary 
Published: May 2020

AbstractCOVID-19 point prevalence PCR community testing allows disease burden estimation. In a sample of London residents, point prevalence decreased from 2.2% (95%CI 1.4;3.5) in early April (reflecting infection around lockdown implementation) to 0.2% (95%CI 0.03-1.6) in early May (reflecting infection 3-5 weeks into lockdown). Extrapolation from reports of confirmed cases suggest that 5-7.6% of total infections were confirmed by testing during this period. These data complement seroprevalence surveys improving the understanding of transmission in London.
Standardization of enzyme-linked immunosorbent assays for serosurveys of the SARS-CoV-2 pandemic using clinical and at-home blood sampling
Authors: Klumpp-Thomas Carleen , Kalish Heather , Drew Matthew , Hunsberger Sally , Snead Kelly , Fay Michael P , Mehalko Jennifer , Shunmugavel Anandakumar , Wall Vanessa , Frank Peter , Denson John-Paul , Hong Min , Gulten Gulcin , Messing Simon , Hicks Jennifer , Michael Sam , Gillette William , Hall Matthew D , Memoli Matthew , Esposito Dominic , Sadtler Kaitlyn 
Published: May 2020

ABSTRACTThe extent of SARS-CoV-2 infection throughout the United States population is currently unknown. High quality serology is a key tool to understanding the spread of infection, immunity against the virus, and correlates of protection. Limited validation and testing of serology assays used for serosurveys can lead to unreliable or misleading data, and clinical testing using such unvalidated assays can lead to medically costly diagnostic errors and improperly informed public health decisions. Estimating prevalence and clinical decision making is highly dependent on specificity. Here, we present an optimized ELISA-based serology protocol from antigen production to data analysis. This protocol defines thresholds for IgG and IgM for determination of seropositivity with estimated specificity well above 99%. Validation was performed using both traditionally collected serum and dried blood on mail-in blood sampling kits, using archival (pre-2019) negative controls and known PCR-diagnosed positive patient controls. Minimal cross-reactivity was observed for the spike proteins of MERS, SARS1, OC43 and HKU1 viruses and no cross reactivity was observed with anti-influenza A H1N1 HAI titer during validation. This strategy is highly specific and is designed to provide good estimates of seroprevalence of SARS-CoV-2 seropositivity in a population, providing specific and reliable data from serosurveys and clinical testing which can be used to better evaluate and understand SARS-CoV-2 immunity and correlates of protection.
COVID-19 Confirmed Case Incidence Age Shift to Young Persons Age 0-19 and 20-39 Years Over Time: Washington State March - April 2020
Authors: Malmgren Judith , Guo Boya , Kaplan Henry G. 
Published: May 2020

AbstractBackgroundAs the coronavirus (COVID-19) epidemic passes the peak infection rate in some states and counties a phased re-opening with changes of stay-at-home restrictions and social distancing recommendations may lead to an increase of nonessential work, social activities and gathering, especially among younger persons.MethodsA longitudinal cohort analysis of Washington State Department of Health COVID-19 confirmed case age distribution March 1-April 19 2020 for proportional change over time using chi square tests for significance (N = 13,934).ResultsFrom March 1st to April 19, 2020 age distribution shifted with a 10% decline in cases age 60 years and older and a 20% increase in age 0-19/20-39 years (chi-square = 223.10, p <.001). Number of cases over the eight-week analysis period were 0-19 years n = 515, 20-39 years n = 4078, 40-59 years n =4788, 60-79 years n = 3221, 80+ years n = 1332. New cases increased steadily among 0-19 and 20-39-year olds. After the peak (March 22, 2020), there was no decline among age 0-19 and a lesser decline among age 20-39 than older groups. As incidence declined in older age groups, the combined percentage of cases age 0-19 and 20-39 increased from 20% to 40% of total cases.ConclusionsIncreased COVID-19 infection among children and young adults is not without serious morbidity and mortality risk to them and others they may come in contact with, indicating a targeted approach for awareness and safety measures is advisable to reduce incidence among the supposedly less vulnerable but more mobile young population age 0-19 and 20-39 years.
Decreased miR-24-3p potentiates DNA damage responses and increases susceptibility to COPD
Authors: Nouws Jessica , Wan Feng , Finnemore Eric , Roque Willy , Kim Sojin , Bazan Isabel , Li Chuan-xing , Magnus Skold C. , Yan Xiting , Neumeister Veronique , Britto Clemente J. , Sweasy Joann , Bindra Ranjit , Wheelock Åsa M. , Gomez-Villalobos Jose , Kaminski Naftali , Lee Patty J. , Sauler Maor 
Published: May 2020

ABSTRACTActivation of the DNA damage response (DDR) due to chronic exposure to cigarette smoke (CS) is implicated in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). However, not all smokers develop COPD and the pathologic consequences of CS exposure are heterogenous. Cellular mechanisms that regulate the DDR and contribute to disease progression in susceptible individuals are poorly understood. Because microRNAs are well known regulators of the DDR, we evaluated microRNA expression arrays performed on lung samples from 172 subjects with and without COPD. We identified miR-24-3p as the microRNA best correlated with radiographic emphysema (ρ=-0.353, P=1.3e-04) and validated this finding in multiple cohorts. In a CS-exposure mouse model, miR-24-3p inhibition increased emphysema severity. In human airway epithelial cells, miR-24-3p suppressed apoptosis through the BH3-only protein BIM and suppressed homology-directed DNA repair and the DNA repair protein BRCA1. Finally, we found BIM and BRCA1 were increased in COPD lung tissue and inversely correlated with miR-24-3p expression. We concluded that decreased miR-24-3p expression increases COPD susceptibility and potentiates the DDR through BIM and BRCA1.
Spatiotemporal structure of sensory-evoked and spontaneous activity revealed by mesoscale imaging in anesthetized and awake mice
Authors: Afrashteh Navvab , Inayat Samsoon , Contreras Edgar Bermudez , Luczak Artur , McNaughton Bruce L. , Mohajerani Majid H. 
Published: May 2020

AbstractBrain activity propagates across the cortex in diverse spatiotemporal patterns, both as a response to sensory stimulation and during spontaneous activity. Despite been extensively studied, the relationship between the characteristics of such patterns during spontaneous and evoked activity is not completely understood. To investigate this relationship, we compared visual, auditory, and tactile evoked activity patterns elicited with different stimulus strengths and spontaneous activity motifs in lightly anesthetized and awake mice using mesoscale wide-field voltage-sensitive dye and glutamate imaging respectively. The characteristics of cortical activity that we compared include amplitude, speed, direction, and complexity of propagation trajectories in spontaneous and evoked activity patterns. We found that the complexity of the propagation trajectories of spontaneous activity, quantified as their fractal dimension, is higher than the one from sensory evoked responses. Moreover, the speed and direction of propagation, are modulated by the amplitude during both, spontaneous and evoked activity. Finally, we found that spontaneous activity had similar amplitude and speed when compared to evoked activity elicited with low stimulus strengths. However, this similarity gradually decreased when the strength of stimuli eliciting evoked responses increased. Altogether, these findings are consistent with the fact that even primary sensory areas receive widespread inputs from other cortical regions, and that, during rest, the cortex tends to reactivate traces of complex, multi-sensory experiences that may have occurred in a range of different behavioural contexts.
Reevaluation of theToxoplasma gondiiandNeospora caninumgenomes reveals misassembly, karyotype differences and chromosomal rearrangements
Authors: Berna Luisa , Marquez Pablo , Cabrera Andrés , Greif Gonzalo , Francia María E. , Robello Carlos 
Published: May 2020

ABSTRACTNeospora caninumprimarily infects cattle causing abortions with an estimated impact of a billion dollars on worldwide economy, annually. However, the study of its biology has been unheeded by the established paradigm that it is virtually identical to its close relative, the widely studied human pathogen,Toxoplasma gondii. By revisiting the genome sequence, assembly and annotation using third generation sequencing technologies, here we show that theN. caninumgenome was originally incorrectly assembled under the presumption of synteny withT. gondii. We show that major chromosomal rearrangements have occurred between these species. Importantly, we show that chromosomes originally annotated as ChrVIIb and VIII are indeed fused, reducing the karyotype of bothN. caninumandT. gondiito 13 chromosomes. We reannotate theN. caninumgenome, revealing over 500 new genes. We sequence and annotate the non-photosynthetic plastid and mitochondrial genomes, and show that while apicoplast genomes are virtually identical, high levels of gene fragmentation and reshuffling exists between species and strains. Our results correct assembly artifacts that are currently widely distributed in the genome database ofN. caninumandT. gondii, but more importantly, highlight the mitochondria as a previously oversighted source of variability and pave the way for a change in the paradigm of synteny, encouraging rethinking the genome as basis of the comparative unique biology of these pathogens.