bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure of Rats to Permethrin, Pyridostigmine or Diethyl‐M‐Toluamide (DEET) Attenuates Skeletal Muscle Function.
Authors: Navarrrete Viridiana , Rodriguez Antonio , Galera Leonor , Garate Elva Alejandra , villarreal Francisco , Ramirez-Sanchez Israel 
Published: April 2020

BackgroundGulf War Illness (GWI) is a chronic multi‐symptom disorder experienced by as many as a third of the veterans of the 1991 Gulf War. GWI mainly affects nervous and skeletal muscle (SkM) systems yielding cognitive deficit, depression, muscle pain, weakness, intolerance to exercise and fatigue. Military personnel was exposed to toxic substances such as insecticides and repellents like permetrim (PM), N;N‐diethyl‐m‐toluamide (DEET), and pyridostigmine (PB) provided as a prophylactic for a nerve gas attack.MethodsThree months old male Wistar rats were used for all experiments (n=50). Control group (n=10) were provided water (oral), 70% ethanol (applied to back skin). The PB group (n=10) were given pyridostigmine 1.3 mg/kg/day by oral gavage. The PM group (n=10) were dosed at 0.13 mg/kg/day (back of shaved skin in 70% ethanol). The DEET group (n=10) were dosed at 40 mg/kg/day (back skin in ethanol). A physically restrained group (n=10) was also included with animals being restrained for 5 min/day (in rat plexiglass holders). Treatments were provided daily for 3 weeks. At 6 weeks, animals were subjected to treadmill and front limb strength testing followed by euthanasia and SkM (gastrocnemius) muscles collected for histological and biochemical analysis.ResultsAnimals exposed to chemicals did not evidence changes in body weight or food intake. The front limb strength of the animals was recorded weekly. Significant strength increases were recorded in control, PM, DEET and restricted groups. However, in the PB group strength increases were not detected showing ~ 35% decrease vs. contros. At the end of the treatment phase, overall physical endurance was evaluated on a treadmill. This evaluation demonstrated that the groups administered with the different chemical agents (PM, PB and DEET) significantly blunted the fatigue resistance time (on average 12 minutes) vs. controls (18 min). The gastrocnemius mass (weight) of animals exposed to PB, PM and DEET were significantly decreased by ~15% vs. controls. Gastrocnemius myofiber cross area measurements (CSA) were measured and results demonstrate that in the PB, PM and DEET groups it is significantly decreased by ~13% vs. controls. Oxidative stress levels were assessed in muscles and we observed that groups administered with DEET, PM and PB increased carbonyl protein content (average >40 nmol/ml) vs. controls (25 nmol/ml). The plasma levels of the pro‐inflammatory cytokines IL‐1b, TNF‐a, and IFN‐g were elevated only in the PB group (vs. controls) with no differences noted with the other chemical agents.ConclusionsExposure of rodents to equivalent human doses of associated GWI chemicals leads to a loss of muscle mass and strength and/or function. These effects are likely related to increases in oxidative stress and/or pro‐inflammatory cytokines.
The role of D‐loop synthesis and progression in trinucleotide repeat stability via a break induced replication (BIR) model.
Authors: Sanders Emma A. , Polleys Erica J. , Freudenreich Catherine H. 
Published: April 2020

Homologous recombination (HR) is a complex, multi‐step process, that has been linked to increasing instability of trinucleotide repeats in Saccharomyces cerevisiae. One step of HR, formation and progression of the D‐loop, involves the invasion of ssDNA into a homologous sequence in the genome. Due to the involvement of a variety of polymerases and accessory factors during D‐loop synthesis and progression, it is possible to hypothesize that there is a high risk of slippage and stalling which could lead to changes in length (instability) of a CAG repeat. Break induced replication (BIR) is a genomic repair process that involves the progression of a D‐loop over long tracts of DNA, and thus is a good model to analyze this structure. In this project an assay system, involving a galactose inducible HO double strand break, results in the formation of a D‐loop due to homology to the URA3 gene on both the left and right arms of chromosome V. Repair through this tract of DNA on the right arm of chromosome V has been characterized through measures of viability, PCR of trinucleotide repeat tract, as well as Southern and Western blots. The characterization of this repair currently leads to the ultimate goal of discerning the impact of different DNA repair mutants on tract length changes within the assay system.Support or Funding InformationTufts University, Freudenreich Lab
Gastric Distension‐induced Nodose Ganglionic Cell Responses Using a High‐throughput Multi‐electrode Array in the Ferret
Authors: Harms Jonathan E. , Miller Derek , Shulgach Jonathan A. , Nanivadekar Ameya C. , Fulton Stephanie , Sciullo Michael , Fisher Lee E. , Yates Bill J. , Horn Charles C. 
Published: April 2020

The nodose ganglion (NG) contains cell bodies of gastrointestinal afferents, which play critical roles in metabolic and feeding disorders and gastrointestinal and inflammatory diseases. To further understand the population coding of nodose ganglionic signals, we used a 32‐chan multi‐electrode array (MEA; 4×8, 400 μm pitch; Blackrock Microsystems) to record single‐unit responses with 3 main objectives: (1) determine the stability of multiple single‐unit responses during several hours of in vivo electrophysiological recording; (2) measure the activation patterns of these neurons to prototypical stimulation, such as gastric distension; and (3) investigate the phenotypes of nodose neurons using mechanical probing and vagus nerve electrical stimulation to determine conduction velocities. Acute experiments were performed in anesthetized ferrets using inhalational isoflurane (~2.5%) anesthesia. MEAs were inserted in the nodose ganglion using a pneumatic inserter, and a balloon‐catheter was advanced into the stomach through a small incision on the lateral edge of the gastric fundus. Two volumes of saline, 10 and 20 ml, were infused into the balloon to provide distension. Nerve cuff electrodes were placed on the abdominal vagus trunk to determine conduction velocity. Ganglionic single‐unit activity was successfully recorded from the NG for up to 5.3 h. In our preliminary analysis using spike sorting on each channel (MKsort, https://github.com/ripple‐neuro/mksort; Matlab), we were able to identify a total of 233 units in 6 animals (16 to 55 units per animal). Gastric balloon distension produced >20% increase in neuronal activity in an average of 48% of units to 10 ml inflation and 56% of units to 20 ml inflation. These results demonstrate the feasibility to record multiple single‐unit responses from the ferret NG to provide insight into gastric‐related population coding. Future effort could focus on delineating the physiological roles of these gastric neurons for the design of neuromodulation devices, which could be used to treat diseases involving vagal sensory input such as obesity and the chronic nausea associated with gastroparesis.Support or Funding InformationThis research was supported by funding from the NIH SPARC Common Fund Program (award #U18TR002205).
Repressor Activator Protein 1 Worsens Cardiomyopathy in Diet‐induced Type 2 Diabetic Mice
Authors: WANG LIN , LIU Hao , CAI Yin , ZHANG Liangqing , Irwin Michael G , XIA Zhengyuan 
Published: April 2020

BackgroundDiabetic cardiomyopathy is defined by the structural and functional abnormalities of the myocardium in the absence of other cardiac risk factors in diabetic patients. In diabetes, the increment of fatty acid metabolism and subsequently cardiac inefficiency and myocardial lipid accumulation may underlie the pathology of diabetic cardiomyopathy. The telomeric protein repressor activator protein 1 (Rap1) is an identified regulator that regulates gene transcription by binding to non‐telomeric sites. In particular, Rap1 can bind to nuclear PPARα (an important transcriptional regulator of lipid metabolism) loci, and regulate transcription of PPARα and its target genes, including CD36 (fatty acid transporter). However, the effects of Rap1 on diabetic cardiomyopathy are largely unknown. Thus, the present study investigated if Rap1 deficiency protects against diabetic cardiomyopathy and explored the underlying mechanisms.Methods and ResultsHigh fat diet feeding is a widely used protocol to induce type 2 diabetes in mice. Upon high fat feeding (60% fat) for 12 weeks, male Rap1 knockout (KO) mice displayed significantly reduced body weight gain compared with their wild type (WT) littermates. The glucose tolerance test and insulin tolerance test showed that Rap1 deficiency in the high fat diet fed‐mice led to improved glucose intolerance and insulin action. Furthermore, Rap1 deficiency attenuates high fat diet‐induced cardiac structural remodeling and dysfunction in mice, as evidenced by significantly reduction in left ventricular internal dimension in systole (LVIDs), left ventricular mass, increment in ejection fraction (EF) and fractional shortening (FS), as well as improving of myocardial performance index (MPI). These changes were associated with remarkable reductions in the mRNA and protein expression of PPARα and CD36 in the myocardium of high fat fed‐Rap1 KO mice, indicating that Rap1 deficiency may protect against diabetic cardiomyopathy via the suppression of PPARα/CD36 signaling.ConclusionIn summary, these results suggest that Rap1 impairment has cardioprotective consequences in the high fat diet‐induced diabetes model, identifying a new dimension in the roles of endogenous Rap1.Support or Funding InformationThe authors’ work was supported by The General Research Fund (17117217M, 17123718M, Research Grants Council of Hong Kong) and The National Natural Science Foundation of China (No. 81800245).
Early prediction of mortality risk among severe COVID-19 patients using machine learning
Authors: Hu Chuanyu , Liu Zhenqiu , Jiang Yanfeng , Zhang Xin , Shi Oumin , Xu Kelin , Suo Chen , Wang Qin , Song Yujing , Yu Kangkang , Mao Xianhua , Wu Xuefu , Wu Mingshan , Shi Tingting , Jiang Wei , Mu Lina , Tully Damien C , Xu Lei , Jin Li , Li Shusheng , Tao Xuejin , Zhang Tiejun , Chen Xingdong 
Published: April 2020

AbstractBackgroundCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading globally. The number of deaths has increased with the increase in the number of infected patients. We aimed to develop a clinical model to predict the outcome of severe COVID-19 patients early.MethodsEpidemiological, clinical, and first laboratory findings after admission of 183 severe COVID-19 patients (115 survivors and 68 nonsurvivors) from the Sino-French New City Branch of Tongji Hospital were used to develop the predictive models. Five machine learning approaches (logistic regression, partial least squares regression, elastic net, random forest, and bagged flexible discriminant analysis) were used to select the features and predict the patients’ outcomes. The area under the receiver operating characteristic curve (AUROC) was applied to compare the models’ performance. Sixty-four severe COVID-19 patients from the Optical Valley Branch of Tongji Hospital were used to externally validate the final predictive model.ResultsThe baseline characteristics and laboratory tests were significantly different between the survivors and nonsurvivors. Four variables (age, high-sensitivity C-reactive protein level, lymphocyte count, and d-dimer level) were selected by all five models. Given the similar performance among the models, the logistic regression model was selected as the final predictive model because of its simplicity and interpretability. The AUROCs of the derivation and external validation sets were 0.895 and 0.881, respectively. The sensitivity and specificity were 0.892 and 0.687 for the derivation set and 0.839 and 0.794 for the validation set, respectively, when using a probability of death of 50% as the cutoff. The individual risk score based on the four selected variables and the corresponding probability of death can serve as indexes to assess the mortality risk of COVID-19 patients. The predictive model is freely available at https://phenomics.fudan.edu.cn/risk_scores/.ConclusionsAge, high-sensitivity C-reactive protein level, lymphocyte count, and d-dimer level of COVID-19 patients at admission are informative for the patients’ outcomes.
Proteome-wide analysis of differentially-expressed SARS-CoV-2 antibodies in early COVID-19 infection
Authors: Zhang Xiaomei , Wu Xian , Wang Dan , Lu Minya , Hou Xin , Wang Hongye , Liang Te , Dai Jiayu , Duan Hu , Xu Yingchun , Li Yongzhe , Yu Xiaobo 
Published: April 2020

AbstractRapid and accurate tests that detect IgM and IgG antibodies to SARS-CoV-2 proteins are essential in slowing the spread of COVID-19 by identifying patients who are infected with COVID-19. Using a SARS-CoV-2 proteome microarray developed in our lab, we comprehensively profiled both IgM and IgG antibodies in forty patients with early-stage COVID-19, influenza, or non-influenza who had similar symptoms. The results revealed that the SARS-CoV-2 N protein is not an ideal biomarker for COVID-19 diagnosis because of its low immunogenicity, thus tests that rely on this marker alone will have a high false negative rate. Our data further suggest that the S protein subunit 1 receptor binding domain (S1-RBD) might be the optimal antigen for IgM antibody detection, while the S protein extracellular domain (S1+S2ECD) would be the optimal antigen for both IgM and IgG antibody detection. Notably, the combination of all IgM and IgG biomarkers can identify 87% and 73.3% COVID-19 patients, respectively. Finally, the COVID-19-specific antibodies are significantly correlated with the clinical indices of viral infection and acute myocardial injury (p≤0.05). Our data may help understand the function of anti-SARS-CoV-2 antibodies and improve serology tests for rapid COVID-19 screening.
Health Education for Parents During the COVID-19 Outbreak Public Health Education for Parents During the Outbreak of COVID-19: A Rapid Review
Authors: Li Weiguo , Liao Jing , Li Qinyuan , Baskota Muna , Wang Xingmei , Tang Yuyi , Zhou Qi , Wang Xiaoqing , Luo Xufei , Ma Yanfang , Fukuoka Toshio , Ahn Hyeong Sik , Lee Myeong Soo , Chen Yaolong , Luo Zhengxiu , Liu Enmei 
Published: April 2020

AbstractBackgroundIt is well-known that public health education plays a crucial role in the prevention and control of emerging infectious diseases, but how health providers should advise families and parents to obtain health education information is a challenging question. With COVID-19 (Coronavirus disease 2019) spreading around the world, this rapid review aims to answer that question and thus to promote evidence-based decision making in health education policy and practice.MethodsWe systematically searched the literature on health education during COVID-19, SARS (severe acute respiratory syndrome) and MERS (middle east respiratory syndrome) epidemics in Medline (via PubMed), Cochrane Library, EMBASE, Web of Science, CBM (China Biology Medicine disc), CNKI (China National Knowledge Infrastructure), and Wanfang Data from their inception until March 31, 2020. The potential bias of the studies was assessed by Joanna Briggs Institute Prevalence Critical Appraisal Tool.ResultsOf 1067 papers found, 24 cross-sectional studies with a total of 35,967 participants were included in this review. The general public lacked good knowledge of SARS and MERS at the early stage of epidemics. Some people’s knowledge, attitude and practice (KAP) of COVID-19 had been improved, but the health behaviors of some special groups including children and their parents need to be strengthened. Negative emotions including fear and stigmatization occurred during the outbreaks. Reliable health information was needed to improve public awareness and mental health for infectious diseases. Health information from nonprofit, government and academic websites was more accurate than privately owned commercial websites and media websites.ConclusionsFor educating and cultivating children, parents should obtain information from the official websites of authorities such as the World Health Organization (WHO) and national Centers for Disease Control, or from other sources endorsed by these authorities, rather than from a general search of the internet or social media.
The Effect of Selenium on Hashimoto’s Thyroiditis; Systemic Review and Metaanalysis
Authors: Alijani Ehsan 
Published: April 2020

AbstractBackgroundSelenium forms a significant component of seleno-proteins in the body. Seleno-methionine is integrated into proteins instead of methionine and acts as a storage pool. In proteins, the active form of Selenium is seleno-cysteine.in this review we aim to prevail the results of selenium effect on thyroid status in recent clinical trials. The systemic review aims to find out the correlation between supplementation of Selenium and anti-TPO antibodies and T4 levels in Hashimoto’s Thyroiditis. Selenium supplementation decreases the level of anti-TPO antibodies. The supplementation of Selenium increases the level of T4 levels.MethodsThe mean and standard deviation (SD) of all 8 studies was were calculated. One of the researches had all the information in figures, and only the levels of anti-TPO antibodies and FT4 were obtained. Heterogenicity was estimated using I2.ResultsThe p-value calculated for Anti-TPO by SPSS of the eight groups had a p-value of 0.142. The p-value calculated for T4 levels by SPSS of the five groups had a p-value of 0.239. The heterogenicity test was zero after the I2 test. The studies that were included in the systematic review were assessed by Prisma diagram and selected among the articles resulted from search keywords selenium and anti tpo and hashimotho thyroiditis on different data sources. All the participants were evaluated by sex, ages, duration of the study and the levels of anti tpo ab and thyroxin (t4) and then using SPSS software to deploy metanalysis in the systematic review.Conclusionin 6 of 8 studies it was a relation of selenium and thyroid status, whereas 2 studies were not. As We ran meta analysis on the data we realized that there is not significant desired effect from selenium on thyroid antibodies against previous metanalysis done by other researchers.
ProtTox: Toxin identification from Protein Sequences
Authors: Muthiah Sathappan , Datta Debanjan , Islam Mohammad Raihanul , Butler Patrick , Warren Andrew , Ramakrishnan Naren 
Published: April 2020

AbstractToxin classification of protein sequences is a challenging task with real world applications in healthcare and synthetic biology. Due to an ever expanding database of proteins and the inordinate cost of manual annotation, automated machine learning based approaches are crucial. Approaches need to overcome challenges of homology, multi-functionality, and structural diversity among proteins in this task. We propose a novel deep learning based method ProtTox, that aims to address some of the shortcomings of previous approaches in classifying proteins as toxins or not. Our method achieves a performance of 0.812 F1-score which is about 5% higher than the closest performing baseline.
Mediodorsal thalamus contributes to the timing of instrumental actions
Authors: Lusk Nicholas , Meck Warren H. , Yin Henry H. 
Published: April 2020

AbstractThe perception of time is critical to adaptive behavior. While prefrontal cortex and basal ganglia have been implicated in interval timing in the seconds to minutes range, little is known about the role of the mediodorsal thalamus (MD), which is a key component of the limbic cortico-basal ganglia-thalamocortical loop. In this study we tested the role of the MD in timing, using an operant temporal production task in male mice. In this task, the expected timing of available rewards is indicated by lever pressing. Inactivation of the MD with muscimol produced rightward shifts in peak pressing on probe trials as well as increases in peak spread, thus significantly altering both temporal accuracy and precision. Optogenetic inhibition of glutamatergic projection neurons in the MD also resulted in similar changes in timing. The observed effects were found to be independent of significant changes in movement. Our findings suggest that the MD is a critical component of the neural circuit for interval timing, without playing a direct role in regulating ongoing performance.Significance StatementThe mediodorsal nucleus of the thalamus (MD) is strongly connected with the prefrontal cortex and basal ganglia, areas which have been implicated in interval timing. Previous work has shown that the MD contributes to working memory and learning of action-outcome contingencies, but its role in behavioral timing is poorly understood. Using an operant temporal production task, we showed that inactivation of the MD significantly impaired timing behavior.
Transcriptome Comparison of organ of Corti in mice, chick and zebrafish
Authors: Guo Sen , Hu Zhengqing 
Published: April 2020

DisclaimerThis manuscript has been withdrawn by the authors as it was submitted and made public without the full consent of all the authors. The authors would like to redesign and perform additional experimental work. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Gabra2is a genetic modifier of Dravet syndrome in mice
Authors: Hawkins Nicole A. , Nomura Toshihiro , Duarte Samantha , Williams Robert W. , Homanics Gregg E. , Mulligan Megan K. , Contractor Anis , Kearney Jennifer A. 
Published: April 2020

AbstractPathogenic variants in epilepsy genes result in a spectrum of clinical presentation, ranging from benign phenotypes to intractable epilepsies with significant co-morbidities and increased risk of sudden unexpected death in epilepsy (SUDEP). One source of this phenotypic heterogeneity is modifier genes that affect penetrance, dominance or expressivity of a primary pathogenic variant. Mouse models of epilepsy also display varying degrees of clinical severity on different genetic backgrounds. Mice with heterozygous deletion ofScn1a(Scn1a+/−) model Dravet syndrome, a severe epilepsy most often caused bySCN1Ahaploinsufficiency.Scn1a+/−heterozygous mice recapitulate key features of Dravet syndrome, including febrile and afebrile spontaneous seizures, SUDEP, and cognitive and behavioral deficits. TheScn1a+/−mouse model also exhibits strain-dependent phenotype severity.Scn1a+/−mice maintained on the 129S6/SvEvTac (129) strain have normal lifespan and no overt seizures. In contrast, admixture with C57BL/6J (B6) results in severe epilepsy and premature lethality in [B6×129]F1.Scn1a+/−mice. In previous work, we identified Dravet Survival Modifier loci (Dsm1-Dsm5) responsible for strain-dependent differences in survival.Gabra2, encoding the GABAAα2 subunit, was nominated as the top candidate modifier at theDsm1locus on chromosome 5. Direct measurement of GABAAreceptors found lower abundance of α2-containing receptors in hippocampal synapses of B6 mice relative to 129. We also identified a B6-specific single nucleotide intronic deletion withinGabra2that lowers mRNA and protein by nearly 50%. Repair of thisde novodeletion reestablished normal levels ofGabra2transcript and protein expression. In the current study, we used B6 mice with the repairedGabra2allele to validate it as a modifier of phenotype severity inScn1a+/−mice. Repair ofGabra2restored transcript and protein expression, increased abundance of α2-containing GABAAreceptors in hippocampal synapses, and improved seizure and survival phenotypes ofScn1a+/−mice. These findings validateGabra2as a genetic modifier of Dravet syndrome.