bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bulk and single-cell transcriptomics identify tobacco-use disparity in lung gene expression of ACE2, the receptor of 2019-nCov
Authors: Cai Guoshuai 
Published: February 2020

AbstractIn current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed five large-scale bulk transcriptomic datasets of normal lung tissue and two single-cell transcriptomic datasets to investigate the disparities related to race, age, gender and smoking status in ACE2 gene expression and its distribution among cell types. We didn’t find significant disparities in ACE2 gene expression between racial groups (Asian vs Caucasian), age groups (>60 vs <60) or gender groups (male vs female). However, we observed significantly higher ACE2 gene expression in former smoker’s lung compared to non-smoker’s lung. Also, we found higher ACE2 gene expression in Asian current smokers compared to non-smokers but not in Caucasian current smokers, which may indicate an existence of gene-smoking interaction. In addition, we found that ACE2 gene is expressed in specific cell types related to smoking history and location. In bronchial epithelium, ACE2 is actively expressed in goblet cells of current smokers and club cells of non-smokers. In alveoli, ACE2 is actively expressed in remodelled AT2 cells of former smokers. Together, this study indicates that smokers especially former smokers may be more susceptible to 2019-nCov and have infection paths different with non-smokers. Thus, smoking history may provide valuable information in identifying susceptible population and standardizing treatment regimen.
Reported autism diagnosis strongly predicts psychotic-like experiences in the Adolescent Brain Cognitive Development cohort
Authors: Jutla Amandeep , Donohue Meghan Rose , Veenstra-VanderWeele Jeremy , Foss-Feig Jennifer H. 
Published: February 2020

AbstractAlthough the schizophrenia rate is increased in autism spectrum disorder (ASD), it is difficult to identify which youth with ASD will go on to develop psychosis. We explored the relationship between ASD and emerging psychotic-like experiences in the Adolescent Brain Cognitive Development (ABCD) cohort of school-aged children. We predicted that ASD would robustly predict psychotic-like experience severity, even relative to other established predictors, and that ASD youth with psychotic-like experiences would have a characteristic neurocognitive profile. In a sample of 9,130 youth aged 9–11, we fit regression models that included parent-reported ASD, family history of psychosis, lifetime trauma, executive function, processing speed, working memory, age, sex, race, ethnicity, and income-to-needs ratio as predictors of Prodromal Questionnaire – Brief Child (PQ-BC) score. We assessed cognitive profiles using analysis of variance on NIH Toolbox measures. ASD increased PQ-BC distress scores by 2.46 points (95% CI 1.32 – 3.60), an effect at least as large as those of family history of psychosis (1.05 points, 95% CI 0.56 – 1.53), Latinx ethnicity (0.99 points, 95% CI 0.52 – 1.45) and black race (0.89 points, 95% CI 0.30 – 1.48). We did not identify a unique cognitive profile for ASD youth with psychotic-like experiences. Our finding that ASD predicts psychotic-like symptoms in youth is consistent with previous literature, and adds new information in suggesting that ASD is a strong predictor of psychotic-like experiences even when compared to other established SCZ risk factors.
Transmission Dynamics of COVID-19 in Malaysia Prior to the Movement Control Order
Authors: Labadin J , Hong B.H 
Published: February 2020

AbstractThis paper focuses on the formulation of a deterministic COVID-19 transmission model by considering the exposed and recovered populations with immunity. The scenario of the simulation is depicted based on the patient zero in Malaysia. The transmission model is found to be able to predict the next confirmed case given a single case is introduced in a fully susceptible population. The mathematical model is developed based on the SEIR model which has susceptible, exposed, infectious and recovered populations. The system of equations which were obtained were solved numerically and the simulation results were analyzed. The analysis includes the impact of the disease if no control is taken.
Circular RNA and its mechanisms in diabetic retinopathy: a systematic review
Authors: He Miao , Zhou Rouxi , Liu Sen , Cheng Weijing , Wang Wei 
Published: February 2020

ABSTRACTCircular RNAs (CircRNAs) are endogenous long non-coding RNAs. Unlike linear RNAs, they are structurally continuous and covalently closed, without 5 ’caps or 3’ polyadenylation tails. High-throughput RNA sequencing has enabled people to find several endogenous circRNAs in different species and tissues. circRNA mainly acts as a sponge for microRNAs in cytoplasm to regulates protein translation, or interacts with RNA-binding proteins to generate RNA protein complexes that control transcription. circRNAs are closely associated with diseases such as diabetes, neurological disorders, cardiovascular diseases and cancer, which indicates that circRNAs are closely related to and also play an important functional role in the occurrence and development of human diseases. Recent studies have shown that they are differentially expressed in healthy and diseased eye tissues. There lacks of biomarkers for early detection of diabetic retinopathy, and the newly discovered circRNAs seem to be an ideal candidate of novel molecular markers and therapeutic targets. However, the molecular mechanism of circRNAs activity in the occurrence and development of diabetic retinopathy are not clear yet. This systematic review aims to summarize the research status on function and mechanism of circRNAs in regulating the occurrence of diabetic retinopathy.
CAR T cells for solid tumors: genome-wide dysfunction signature confirms value of c-Jun overexpression, but signals heterogeneity
Authors: Benhenda Mostapha 
Published: February 2020

AbstractChimeric antigen receptor (CAR) T cells still have limited effects in cancer, and especially in solid tumors, due to T cell dysfunction and exhaustion. CAR T cells overexpressing c-Jun (JUN CAR T cells) have been introduced to solve this problem. In this paper, we analyze JUN CAR T cells scRNA-seq data in solid tumors, by applying a genome-wide signature of T cell dysfunction, TID. This signature comes from the bulk RNA-seq signature TIDE, introduced to predict immune checkpoint inhibitor response. Our analysis confirms that on average, JUN CAR T cells are less dysfunctional than non-JUN CAR T cells. However, it also shows heterogeneity within JUN CAR T cells, which brings uncertainty about possible tumor resistance. We conclude that genome-wide dysfunction signature TID helps de-risking CAR T cell therapy for solid tumors.
Estimation of the Time-Varying Reproduction Number of COVID-19 Outbreak in China
Authors: You Chong , Deng Yuhao , Hu Wenjie , Sun Jiarui , Lin Qiushi , Zhou Feng , Pang Cheng Heng , Zhang Yuan , Chen Zhengchao , Zhou Xiao-Hua 
Published: February 2020

BackgroundThe 2019-nCoV outbreak in Wuhan, China has attracted world-wide attention. As of February 11, 2020, a total of 44730 cases of novel coronavirus-infected pneumonia associated with COVID-19 were confirmed by the National Health Commission of China.MethodsThree approaches, namely Poisson likelihood-based method (ML), exponential growth rate-based method (EGR) and stochastic Susceptible-Infected-Removed dynamic model-based method (SIR), were implemented to estimate the basic and controlled reproduction numbers.ResultsA total of 71 chains of transmission together with dates of symptoms onset and 67 dates of infections were identified among 5405 confirmed cases outside Hubei as reported by February 2, 2020. Based on this information, we find the serial interval having an average of 4.41 days with a standard deviation of 3.17 days and the infectious period having an average of 10.91 days with a standard deviation of 3.95 days.ConclusionsThe controlled reproduction number is declining. It is lower than one in most regions of China, but is still larger than one in Hubei Province. Sustained efforts are needed to further reduce the Rc to below one in order to end the current epidemic.
Assessing the plausibility of supercritical transmission for an emerging or re-emerging pathogen
Authors: Blumberg Seth , Lu Phoebe , Lietman Thomas M , Porco Travis C 
Published: February 2020

AbstractRapid assessment of the transmission potential of an emerging or reemerging pathogen is a cornerstone of public health response. A simple approach is shown for using the number of disease introductions and secondary cases to determine whether the upper bound of the reproduction number exceeds the critical value of one.
RATTLE: Reference-free reconstruction and quantification of transcriptomes from Nanopore sequencing
Authors: de la Rubia Ivan , Srivastava Akanksha , Xue Wenjing , Indi Joel A , Carbonell-Sala Silvia , Lagarde Julien , Albà M Mar , Eyras Eduardo 
Published: February 2020

AbstractNanopore sequencing enables the efficient and unbiased measurement of transcriptomes from any sample. However, current methods for transcript identification and quantification rely of mapping reads to a reference genome, which precludes the study of species with a partial or missing reference or the identification of disease-specific transcripts not readily identifiable from a reference. Here we present RATTLE, a tool to perform reference-free reconstruction and quantification of transcripts using only Nanopore reads. Using simulated data and experimental data from isoform spike-ins, human tissues, and cell lines, we show that RATTLE accurately determines transcript sequences and their abundances, and shows good scalability with the number of transcripts. RATTLE provides unprecedented access to transcriptomes from any sample and species without relying on a reference or additional technologies.
The effect of travel restrictions on the spread of the 2019 novel coronavirus (2019-nCoV) outbreak
Authors: Chinazzi Matteo , Davis Jessica T. , Ajelli Marco , Gioannini Corrado , Litvinova Maria , Merler Stefano , y Piontti Ana Pastore , Rossi Luca , Sun Kaiyuan , Viboud Cécile , Xiong Xinyue , Yu Hongjie , Halloran M. Elizabeth , Longini Ira M. , Vespignani Alessandro 
Published: February 2020

AbstractMotivated by the rapid spread of a novel coronavirus (2019-nCoV) in Mainland China, we use a global metapopulation disease transmission model to project the impact of both domestic and international travel limitations on the national and international spread of the epidemic. The model is calibrated on the evidence of internationally imported cases before the implementation of the travel quarantine of Wuhan. By assuming a generation time of 7.5 days, the reproduction number is estimated to be 2.4 [90% CI 2.2-2.6]. The median estimate for number of cases before the travel ban implementation on January 23, 2020 is 58,956 [90% CI 40,759 - 87,471] in Wuhan and 3,491 [90% CI 1,924 - 7,360] in other locations in Mainland China. The model shows that as of January 23, most Chinese cities had already received a considerable number of infected cases, and the travel quarantine delays the overall epidemic progression by only 3 to 5 days. The travel quarantine has a more marked effect at the international scale, where we estimate the number of case importations to be reduced by 80% until the end of February. Modeling results also indicate that sustained 90% travel restrictions to and from Mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.
Assessing the Tendency of 2019-nCoV (COVID-19) Outbreak in China
Authors: Liu Qinghe , Liu Zhicheng , Li Deqiang , Gao Zefei , Zhu Junkai , Yang Junyan , Wang Qiao 
Published: February 2020

ABSTRACTSince December 1, 2019, the spread of COVID-19 is increasing every day. It is particularly important to predict the trend of the epidemic for the timely adjustment of the economy and industries. We proposed a Flow-SEHIR model in this paper to perform the trends of 2019-nCoV (COVID-19) in China.The results show that the number of daily confirmed new cases reaches the inflection point on Feb. 6 – 10 outside Hubei. For the maximum of temporal infected cases number, the predicted peak value in China except Hubei was estimated to be 21721 (95% CI: 18764 - 24929). The peak arrival time is on March 3 - 9. The temporal number of patients in most areas of China outside Hubei will peak from March 12 to March 15. The peak values of more than 73.5% provinces or regions in China will be controlled within 1000. According to Flow-SEHIR model and estimations from the data of evacuation of nationals from Wuhan, the real peak cumulative number of patients in Hubei is estimated to be 403481 (95% CI: 143284 – 1166936).
Both DNA binding domains of p53 are required for its ultra-rapid recruitment to sites of UV damage
Authors: Wang YH. , Ho T. , Hariharan A. , Goh HC. , Sheetz MP. , Lane DP. 
Published: February 2020

Abstractp53 concentrates at DNA damage sites within two seconds upon UV laser micro-irradiation. Structural analysis shows that this very rapid response requires both the DNA binding and C-terminal domains of p53. This early recruitment response is also PARP-dependent. As mutations within the DNA binding domain of p53, that are commonly associated with cancer also inhibit this rapid binding, we suggest that this is an important initial step for p53 function as a tumor suppressor.One Sentence Summaryp53 is an early responder to DNA damage
Plasmin improves oedematous blood-gas barrier by cleaving epithelial sodium channels
Authors: Zhao Runzhen , Ali Gibran , Nie Hong-Guang , Chang Yongchang , Bhattarai Deepa , Su Xuefeng , Zhao Xiaoli , Matthay Michael A. , Ji Hong-Long 
Published: February 2020

ABSTRACTBackground and PurposeLung oedema in association with suppressed fibrinolysis is a hallmark of lung injury. We aimed to test whether plasmin cleaves epithelial sodium channels (ENaC) to resolve lung oedema fluid.Experimental ApproachesHuman lungs and airway acid-instilled mice were used for analysing fluid resolution.In silicoprediction, mutagenesis,Xenopusoocytes, immunoblotting, voltage clamp, mass spectrometry, protein docking, and alveolar fluid clearance were combined for identifying plasmin specific cleavage sites and benefits.Key ResultsPlasmin led to a marked increment in lung fluid resolution in both human lungs ex vivo and injured mice. Plasmin specifically activated αβγENaC channels in oocytes in a time-dependent manner. Deletion of four consensus proteolysis tracts (αΔ432-444, γΔ131-138, γΔ178-193, and γΔ410-422) eliminated plasmin-induced activation significantly. Further, immunoblotting assays identified 7 cleavage sites (K126, R135, K136, R153, K168, R178, K179) for plasmin to trim both furin-cleaved C-terminal fragments and full-length human γENaC proteins. In addition to confirming the 7 cleavage sites, 9 new sites (R122, R137, R138, K150, K170, R172, R180, K181, K189) in synthesized peptides were found to be cleaved by plasmin with mass spectrometry. These cleavage sites were located in the finger and the thumb, particularly the GRIP domain of human ENaC 3D model composed of two proteolytic centres for plasmin. Novel uncleaved sites beyond the GRIP domain in both α and γ subunits were identified to interrupt the plasmin cleavage-induced conformational change in ENaC channel complexes. Additionally, plasmin could regulate ENaC activity via the G protein signal.Conclusion and ImplicationsWe demonstrate that plasmin could cleave ENaC to benefit the blood-gas exchange by resolving oedema fluid as a potent fibrinolytic therapy for oedematous pulmonary diseases.Bullet point summaryWhat is already knowSerine proteases proteolytically cleave epithelial sodium channels, including plasmin and uPA acutely.Activity of epithelial sodium channels is increased post proteolysis.What this study addsPlasmin cleaves up to 16 sites composed of two proteolytic centres in both full-length and furin-cleaved human γ subunit of epithelial sodium channels in hours.Non-proteolytic sites in both α and γ subunits interrupt the plasmin cleavage-induced channel gating.Intratracheally instilled plasmin facilitates alveolar fluid clearance in normal human and injured mouse lungs.Clinical significanceActivation of human lung epithelial sodium channels by plasmin may benefit lung oedema resolution as a novel therapy for ARDS.
Bursty Expression Enhances Reliability of Messaging in Gene Networks
Authors: Gama Leonardo R. , Giovanini Guilherme , Balázsi Gábor , Ramos Alexandre F. 
Published: February 2020

AbstractThe promoter state of a gene and its expression levels are modulated by the amounts of transcription factors interacting with its regulatory regions. Hence, one may interpret a gene network as a communicating system in which the state of the promoter of a gene (thesource) is communicated by the amounts of transcription factors that it expresses (themessage) to modulate the state of the promoter and expression levels of another gene (thereceptor). The reliability of the gene network dynamics can be quantified by the Shannon’s entropy of the message and the mutual information between the message and the promoter state. Here we consider a stochastic model for a binary gene and use its exact steady state solutions to calculate the entropy and mutual information. We show that a slow switching promoter having long and equally standing ON and OFF states maximizes the mutual information and reduces entropy. That is a bursty regime generating a high variance message governed by a bimodal probability distribution with peaks of the same height. Our results indicate that Shannon’s theory can be a powerful framework for understanding how bursty gene expression conciliates with the striking spatio-temporal precision exhibited in pattern formation of developing organisms.
BET Bromodomain Proteins Regulate Transcriptional Reprogramming in Genetic Dilated Cardiomyopathy
Authors: Antolic Andrew , Wakimoto Hiroko , Jiao Zhe , Gorham Joshua M. , DePalma Steven R. , Conner David A. , Lee Da Young , Qi Jun , Seidman Jonathan G. , Bradner James E. , Brown Jonathan D. , Haldar Saptarsi M. , Seidman Christine E. , Burke Michael A. 
Published: February 2020

ABSTRACTThe bromodomain and extraterminal (BET) family of epigenetic reader proteins are key regulators of pathologic gene expression in the heart. Using mice carrying a human mutation in phospholamban (PLNR9C) that develop progressive dilated cardiomyopathy (DCM), we previously identified the activation of inflammatory gene networks as a key early driver of DCM. We reasoned that BETs control this inflammatory process, representing a key node in the progression of genetic DCM. Using a chemical genetic strategy, PLNR9Cor age-matched wild type mice were treated longitudinally with the BET inhibitor JQ1 or vehicle. JQ1 abrogated DCM, reduced cardiac fibrosis, and prolonged survival in PLNR9Cmice by inhibiting inflammatory gene network expression at all disease stages. Cardiac fibroblast proliferation was also substantially reduced by JQ1. Interestingly, JQ1 had profound effects on pathologic gene network expression in cardiac fibroblasts, while having little effect on transcription in cardiomyocytes. Using co-immunoprecipitation, we identified BRD4 as a direct and essential regulator of NFκB-mediated inflammatory gene transcription in cardiac fibroblasts. In this this model of chronic, heritable DCM, BETs activate inflammatory gene networks in cardiac fibroblasts via an NFκB-dependent mechanism, marking them as critical effectors of pathologic gene expression.
ScaleQC: A Scalable Lossy to Lossless Solution for NGS Sequencing Data Compression
Authors: Yu Rogshan , Yang Wenxian 
Published: February 2020

AbstractMotivationPer-base quality values in NGS sequencing data take a significant portion of storage even after compression. Lossy compression technologies could further reduce the space used by quality values. However, in many applications lossless compression is still desired. Hence, sequencing data in multiple file formats have to be prepared for different applications.ResultsWe developed a scalable lossy to lossless compression solution for quality values named ScaleQC. ScaleQC is able to provide bit-stream level scalability. More specifically, the losslessly compressed bit-stream by ScaleQC can be further truncated to lower data rates without re-encoding. Despite its scalability, ScaleQC still achieves same or better compression performance at both lossless and lossy data rates compared to the state-of-the-art lossless or lossy compressors.AvailabilityScaleQC has been integrated with SAMtools as a special quality value encoding mode for CRAM. Its source codes can be obtained from our integrated SAMtools (https://github.com/xmuyulab/samtools) with dependency on integrated HTSlib (https://github.com/xmuyulab/htslib).
Genome-wide molecular effects of the neuropsychiatric 16p11 CNVs in an iPSC-to-iN neuronal model
Authors: Ward Thomas R. , Zhang Xianglong , Leung Louis C. , Zhou Bo , Muench Kristin , Roth Julien G. , Khechaduri Arineh , Plastini Melanie J. , Charlton Carol , Pattni Reenal , Ho Steve , Ho Marcus , Huang Yiling , Hallmayer Joachim F. , Mourrain Phillippe , Palmer Theo D. , Urban Alexander E. 
Published: February 2020

AbstractCopy number variants (CNVs), either deletions or duplications, at the 16p11.2 locus in the human genome are known to increase the risk for autism spectrum disorders (ASD), schizophrenia, and for several other developmental conditions. Here, we investigate the global effects on gene expression and DNA methylation using a 16p11.2 CNV patient-derived induced pluripotent stem cell (iPSC) to induced neuron (iN) cell model system. This approach revealed genome-wide and cell-type specific alterations to both gene expression and DNA methylation patterns and also yielded specific leads on genes potentially contributing to some of the known 16p11.2 patient phenotypes. PCSK9 is identified as a possible contributing factor to the symptoms seen in carriers of the 16p11.2 CNVs. The protocadherin (PCDH) gene family is found to have altered DNA methylation patterns in the CNV patient samples. The iPSC lines used for this study are available through a repository as a resource for research into the molecular etiology of the clinical phenotypes of 16p11.2 CNVs and into that of neuropsychiatric and neurodevelopmental disorders in general.
Gut microbiome modulates behaviour and life history in two wild rodents
Authors: Jameson Joël W. , Réale Denis , Kembel Steven W. 
Published: February 2020

ABSTRACTLaboratory studies demonstrate that the gut microbiome can regulate host anxiety and exploratory behaviour. While this has implications for human health, it could have ecological and evolutionary implications for wild populations, a hitherto untested hypothesis. We tested whether the microbiome can directly modulate host behaviour and thereby affect life history in wild mice (Peromyscus maniculatus) and voles (Myodes gapperi). We compared the microbiome composition, exploration and anxiety behaviours, and home range of mice and voles before and after chronic antibiotic treatment and measured survival during treatment. Treated animals had lower diversity and relative abundance of most bacterial phyla save for Proteobacteria which increased in relative abundance. In mice, antibiotic treatment increased exploration and decreased home range without impacting survival. In voles, it lowered survival such that we could not test its effect on behaviour. Therefore, the microbiome can directly impact behaviour and host life history in the wild.