bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal learning among prefrontal and striatal ensembles
Authors: Emmons Eric , Tunes-Chiuffa Gabriela , Choi Jeeyu , Bruce R. Austin , Weber Matthew A. , Kim Youngcho , Narayanan Nandakumar S. 
Published: March 2020

AbstractBehavioral flexibility requires the prefrontal cortex and striatum. Here, we investigate neuronal ensembles in the medial frontal cortex (MFC) and the dorsomedial striatum (DMS) during one form of behavioral flexibility: learning a new temporal interval. We studied corticostriatal neuronal activity as rodents trained to respond after a 12-second fixed interval (FI12) learned to respond at a shorter 3-second fixed interval (FI3). On FI12 trials, we discovered time-related ramping was reduced in the MFC but not in the DMS in two-interval vs. one-interval sessions. We also found that more DMS neurons than MFC neurons exhibited differential interval-related activity on the first day of two-interval performance. Finally, MFC and DMS ramping was similar with successive days of two-interval performance but DMS temporal decoding increased on FI3 trials. These data suggest that the MFC and DMS play distinct roles during temporal learning and provide insight into corticostriatal circuits.
Amygdala-cortical control of striatal plasticity drives the acquisition of goal-directed action
Authors: Fisher Simon D. , Ferguson Lachlan A. , Bertran-Gonzalez Jesus , Balleine Bernard W. 
Published: March 2020

SummaryThe acquisition of goal-directed action requires the encoding of specific action-outcome associations involving plasticity in the posterior dorsomedial striatum (pDMS). We first investigated the relative involvement of the major inputs to the pDMS argued to be involved in this learning-related plasticity, from prelimbic prefrontal cortex (PL) and from the basolateral amygdala (BLA). Using ex vivo optogenetic stimulation of PL or BLA terminals in pDMS, we found that goal-directed learning potentiated the PL input to direct pathway spiny projection neurons (dSPNs) bilaterally but not to indirect pathway neurons (iSPNs). In contrast, learning-related plasticity was not observed in the direct BLA-pDMS pathway. Using toxicogenetics, we ablated BLA projections to either pDMS or PL and found that only the latter was necessary for goal-directed learning. Importantly, transient inactivation of the BLA during goal-directed learning prevented the PL-pDMS potentiation of dSPNs, establishing that the BLA input to the PL is necessary for the corticostriatal plasticity underlying goal-directed learning.
A comprehensive survey on the nature of ring:ring nucleobase stacking interactions in RNA: occurrence, structural variability and classification of the associated contacts
Authors: Jhunjhunwala Ayush , Ali Zakir , Bhattacharya Sohini , Halder Antarip , Mitra Abhijit , Sharma Purshotam 
Published: March 2020

ABSTRACTThe astonishing diversity in folding patterns of RNA 3D structures is crafted by myriads of noncovalent contacts, of which base pairing and stacking are the most prominent. Although the classification scheme proposed by Leontis and Westhof (RNA(2001), 7, 499) has been widely accepted for the annotation of RNA base pairs, the absence of an unambiguous classification system for base stacks appears to be a roadblock for exploring the stacking diversity in RNA. Here we provide an unambiguous and structurally-intuitive scheme for a geometry cum topology based classification of base stacking, where a stack is essentially classified in terms of the topology of the interacting nucleobase faces and the geometry described by the relative orientation of the glycosidic bonds. For heterodimeric stacks, this generates eight basic stacking geometric families, whereas for homodimeric stacks, this generates six of those. Further annotation in terms of the identity of the bases and the region of involvement of purines (5-membered, 6-membered or both rings), leads to the enumeration of 384 distinct RNA base stacks. Based on our classification scheme, we also present an algorithm for automated identification of stacks in RNA crystal structures. Overall, the work described here is expected to greatly facilitate structure-based RNA research.
Estimating weight in patients of all-ages: a prospective study in Rwanda
Authors: Cattermole Giles N , Manirafasha Appolinaire 
Published: March 2020

ABSTRACTIntroductionWeight estimation of both adult and paediatric patients is often necessary in emergency or low-resource settings when it is not possible to weigh the patient. There are many methods for paediatric weight estimation, but no standard methods for adults. PAWPER and Mercy tapes are used in children, but have not been assessed in adults. The primary aim of this study was to assess weight estimation methods in patients of all ages.MethodsPatients were prospectively recruited from emergency and out-patient departments. Subjects (or guardians) were asked to estimate weight. Investigators collected weight, height, mid-arm circumference (MAC) and humeral-length data. In all subjects, estimates of weight were calculated from height and MAC (PAWPER tapes), MAC and humeral-length (Mercy tape). In children, Broselow tape and age-based formulae were also used. Primary outcome measures were proportions of estimates within 10%, 20% and 30% of actual weight (p10, p20, p30).Results947 subjects were recruited: 307 children, 309 adolescents and 331 adults. For p20, the best methods were: in children, guardian estimate (90.2%) and PAWPER XL-MAC (89.3%); in adolescents, PAWPER XL-MAC (91.3%) and guardian estimate (90.9%); in adults, subject estimate (98.5%) and PAWPER XL-MAC (83.7%).ConclusionThis is the first prospective study of weight estimation methods in Rwanda, and the first adult study of PAWPER and Mercy tapes. In children, age-based rules performed poorly. In patients of all ages, the PAWPER XL-MAC and guardian/subject estimates of weight were the most reliable and we would recommend their use in this setting.
An epidemiological forecast model and software assessing interventions on COVID-19 epidemic in China
Authors: Wang Lili , Zhou Yiwang , He Jie , Zhu Bin , Wang Fei , Tang Lu , Eisenberg Marisa , Song Peter X.K. 
Published: March 2020

AbstractWe develop a health informatics toolbox that enables public health workers to timely analyze and evaluate the time-course dynamics of the novel coronavirus (COVID-19) infection using the public available data from the China CDC. This toolbox is built upon a hierarchical epidemiological model in which two observed time series of daily proportions of infected and removed cases are emitted from the underlying infection dynamics governed by a Markov SIR infectious disease process. We extend the SIR model to incorporate various types of time-varying quarantine protocols, including government-level macro isolation policies and community-level micro inspection measures. We develop a calibration procedure for under-reported infected cases. This toolbox provides forecast, in both online and offline forms, of turning points of interest, including the time when daily infected proportion becomes smaller than the previous ones and the time when daily infected proportions becomes smaller than that of daily removed proportion, as well as the ending time of the epidemic. An R software is made available for the public, and examples on the use of this software are illustrated. Some possible extensions of our novel epidemiological models are discussed.
smiFISH and embryo segmentation for single-cell multi-gene RNA quantification in arthropods
Authors: Calvo Llilians , Ronshaugen Matthew , Pettini Tom 
Published: March 2020

ABSTRACTRecently, advances in fluorescent in-situ hybridization techniques and in imaging technology have enabled visualisation and counting of individual RNA molecules in single cells. This has greatly enhanced the resolution in our understanding of transcriptional processes. Here, we adapt a recently published smiFISH protocol (single-molecule inexpensive fluorescent in-situ hybridization) to whole embryos across a range of arthropod model species, and also to non-embryonic tissues. Using multiple fluorophores with distinct spectra and white light laser confocal imaging, we simultaneously detect and separate single RNAs from up to eight different genes in a whole embryo. We also combine smiFISH with cell membrane immunofluorescence, and present an imaging and analysis pipeline for 3D cell segmentation and single-cell RNA counting in whole blastoderm embryos. Finally, using whole embryo single-cell RNA count data, we propose two alternative single-cell variability measures to the commonly used Fano factor, and compare the capacity of these three measures to address different aspects of single-cell expression variability.
Identification of PCNA interacting protein motifs in human DNA polymerase delta
Authors: Khandagale Prashant , Thakur Shweta , Acharya Narottam 
Published: March 2020

AbstractDNA polymerase delta (Polδ) is a highly processive essential replicative DNA polymerase. In humans, Polδ holoenzyme consists of p125, p50, p68, and p12 subunits and recently, we have shown that p12 exists as a dimer. Extensive biochemical studies suggest that all the subunits of Polδ interact with the processivity factor proliferating cell nuclear antigen (PCNA) to carry out a pivotal role in genomic DNA replication. While PCNA interaction protein (PIP) motifs in p68, p50 and p12 have been mapped, the PIP in p125, the catalytic subunit of the holoenzyme, remains elusive. Therefore, in this study by using multiple approaches we have conclusively mapped a non-canonical PIP box from residues999VGGLLAFA1008in p125, which binds to inter domain-connecting loop of PCNA with high affinity. Collectively, including previous studies, we conclude that similar toS. cerevisiaePolδ, each of the human Polδ subunits possess motif to interact with PCNA and significantly contribute towards the processive nature of this replicative DNA polymerase.
E93-depleted adult insects preserve the prothoracic gland and molt again
Authors: Kamsoi Orathai , Belles Xavier 
Published: March 2020

ABSTRACTInsect metamorphosis originated around the middle Devonian, associated with the innovation of the final molt; this occurs after the histolysis of the prothoracic gland (PG; which produces the molting hormone) in the first days of adulthood. We previously hypothesized that transcription factor E93 was crucial in the emergence of metamorphosis, since it triggers metamorphosis in extant insects. This work on the cockroachBlattella germanicareveals that E93 also plays a crucial role in the histolysis of PG, which fits the above hypothesis. Previous studies have shown that the transcription factor FTZ-F1 is essential for PG histolysis. We have found that FTZ-F1 depletion, towards the end of the final nymphal instar, downregulates the expression ofE93, while E93-depleted nymphs molt to adults that retain a functional PG. Interestingly, these adults are able to molt again, which is exceptional in insects. The study of insects able to molt again in the adult stage may reveal clues as to how nymphal epidermal cells definitively become adult cells, and if it is possible to revert this process.Summary statementThe prothoracic gland disintegrates after insect metamorphosis. It was believed that the factor FTZ-F1 determines this disintegration. This work reveals that FTZ-F1 action is mediated by the factor E93.
Gene-environment interactions in Multiple Sclerosis: a UK Biobank study
Authors: Jacobs Benjamin Meir , Noyce Alastair , Bestwick Jonathan , Belete Daniel , Giovannoni Gavin , Dobson Ruth 
Published: March 2020

AbstractImportanceMultiple Sclerosis (MS) is a neuro-inflammatory disorder caused by a combination of environmental exposures and genetic risk factors. We sought to determine whether genetic risk modifies the effect of environmental MS risk factors.MethodsPeople with MS were identified within UK Biobank using ICD10-coded MS or self-report. Associations between environmental risk factors and MS risk were quantified with a case-control design using multivariable logistic regression. Polygenic risk scores (PRS) were derived using the clumping-and-thresholding approach with external weights from the largest genome-wide association study of MS. Separate scores were created including (PRSMHC) and excluding (PRSNon-MHC) the MHC locus. The best performing PRS were identified in 30% of the cohort and validated in the remaining 70%. Interaction between environmental and genetic risk factors was quantified using the Attributable Proportion due to interaction (AP) and multiplicative interaction.ResultsData were available for 2250 people with MS and 486,000 controls. Childhood obesity, earlier age at menarche, and smoking were associated with MS. The optimal PRS were strongly associated with MS in the validation cohort (PRSMHC: Nagelkerke’s Pseudo-R20.033, p=3.92×10−111; PRSNon-MHC: Nagelkerke’s Pseudo-R20.013, p=3.73×10−43). There was strong evidence of interaction between polygenic risk for MS and childhood obesity (PRSMHC: AP=0.17, 95% CI 0.06 - 0.25, p=0.004; PRSNon-MHC: AP=0.17, 95% CI 0.06 - 0.27, p=0.006).Conclusions and RelevanceThis study provides novel evidence for an interaction between childhood obesity and a high burden of autosomal genetic risk. These findings may have significant implications for our understanding of MS biology and inform targeted prevention strategies.
Somatic cell-derived BMPs induce male germ cell meiosis initiation during embryonic stage via regulatingDazlexpression
Authors: Zhang Lianjun , Li Yaqiong , Hu Yuqiong , Lin Limei , Zhou Jingjing , Chen Min , Qin Yan , Zhou Yang , Chen Min , Cui Xiuhong , Tang Fuchou , Gao Fei 
Published: March 2020

AbstractGerm cell fate is believed to be determined by the signaling from sexually differentiated somatic cell. However, the molecular mechanism remains elusive. In this study, ectopic initiation of meiosis in male germ cells was observed during embryonic stage by over-activating CTNNB1 in Sertoli cells. Somatic cell transcriptome and single germ cell RNA-seq analysis indicated that TGF-β signaling was activated after CTNNB1 over-activation.In vitroandin vivoexperiments confirmed somatic cell-derived BMPs played crucial roles in germ cell meiosis initiation. Further studies revealed thatDazlwas significantly increased in germ cells of CTNNB1 over-activated testes and induced by BMP signaling. DNMT3a and DNA methylation was also reduced in germ cells of CTNNB1 over-activated testes and increased by BMP signaling inhibitor treatment. Taken together, this study demonstrates that germ cell fate could be reprogrammed after sex determination. BMP signaling pathway is involved in germ cell meiosis initiation via up-regulatingDazlexpression.
Estimation of local novel coronavirus (COVID-19) cases in Wuhan, China from off-site reported cases and population flow data from different sources
Authors: Zhuang Zian , Cao Peihua , Zhao Shi , Lou Yijun , Yang Shu , Wang Weiming , Yang Lin , He Daihai 
Published: March 2020

AbstractBackgroundsIn December 2019, a novel coronavirus (COVID-19) pneumonia hit Wuhan, Hubei Province, China and spread to the rest of China and overseas. The emergence of this virus coincided with the Spring Festival Travel Rush in China. It is possible to estimate total number of cases of COVID-19 in Wuhan, by 23 January 2020, given the cases reported in other cities and population flow data between cities.MethodsWe built a model to estimate the total number of cases in Wuhan by 23 January 2020, based on the number of cases detected outside Wuhan city in China, with the assumption that if the same screening effort used in other cities applied in Wuhan. We employed population flow data from different sources between Wuhan and other cities/regions by 23 January 2020. The number of total cases was determined by the maximum log likelihood estimation.FindingsFrom overall cities/regions data, we predicted 1326 (95% CI: 1177, 1484), 1151 (95% CI: 1018, 1292) and 5277 (95% CI: 4732, 5859) as total cases in Wuhan by 23 January 2020, based on different source of data from Changjiang Daily newspaper, Tencent, and Baidu. From separate cities/regions data, we estimated 1059 (95% CI: 918, 1209), 5214 (95% CI: 4659, 5808) as total cases in Wuhan in Wuhan by 23 January 2020, based on different sources of population flow data from Tencent and Baidu.ConclusionSources of population follow data and methods impact the estimates of local cases in Wuhan before city lock down.
Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019
Authors: Zhao Juanjuan , Yuan Quan , Wang Haiyan , Liu Wei , Liao Xuejiao , Su Yingying , Wang Xin , Yuan Jing , Li Tingdong , Li Jinxiu , Qian Shen , Hong Congming , Wang Fuxiang , Liu Yingxia , Wang Zhaoqin , He Qing , Li Zhiyong , He Bin , Zhang Tianying , Ge Shengxiang , Liu Lei , Zhang Jun , Xia Ningshao , Zhang Zheng 
Published: March 2020

SummaryBackgroundThe novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated.MethodsA total of 173 patients with confirmed SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during the hospitalization period were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2 using immunoassays. The dynamics of antibodies with the progress and severity of disease was analyzed.ResultsAmong 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1% (161/173), 82.7% (143/173) and 64.7% (112/173), respectively. Twelve patients who had not seroconverted were those only blood samples at the early stage of illness were collected. The seroconversion sequentially appeared for Ab, IgM and then IgG, with a median time of 11, 12 and 14 days, respectively. The presence of antibodies was < 40% among patients in the first 7 days of illness, and then rapidly increased to 100.0%, 94.3% and 79.8% for Ab, IgM and IgG respectively since day 15 after onset. In contrast, the positive rate of RNA decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15 to 39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 patients (p < 0.001), even in early phase of 1-week since onset (p = 0.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (p = 0.006).ConclusionsThe antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.
Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2
Authors: Kim Youngchang , Jedrzejczak Robert , Maltseva Natalia I. , Endres Michael , Godzik Adam , Michalska Karolina , Joachimiak Andrzej 
Published: March 2020

ABSTRACTSevere Acute Respiratory Syndrome Coronavirus 2 is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS- and MERS-CoVs the detailed information about SARS-CoV-2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies and antivirals. We applied high-throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS-CoV-2 proteins and structures. Here we report the high-resolution crystal structure of endoribonuclease Nsp15/NendoU from SARS-CoV-2 – a virus causing current world-wide epidemics. We compare this structure with previously reported models of Nsp15 from SARS and MERS coronaviruses.
Investigation of Codon Alternation Patterns in Genetic Diseases through Numerical Representation and Codon Classification
Authors: Sengupta Antara , Chakraborty Subhadip , Choudhury Pabitra Pal , Roy Swarup , Das Jayanta Kumar , Mallick Ditipriya , Jana Siddhartha S 
Published: March 2020

AbstractAlteration of amino acids is possible due to mutation in codons that could have potential reasons to occur disease. Single nucleotide substitutions (SNS) in genetic codon thus have prime importance for their ability to occur mutations that may be deleterious indeed. Effective mutation analysis can help to predict the fate of the diseased individual which can be validated later by in-vitro experiments. Hence in this present study, we try to investigate the codon alteration patterns and their impact during mutation for the genes known to be responsible for a particular disease. We use a numerical representation of four nucleotides based on the number of hydrogen bonds in their chemical structures and make a classification of 64 codons as well as corresponding 20 amino acids into three different classes (Strong, Weak and Transitional). The entire analysis has been carried out based on these classifications. For our current study, we consider two neurodegenerative diseases, Parkinson’s disease, and Glaucoma. Several evidences claim similarities between both the diseases but proper pathogenetic factors are still unknown. The analysis reveals that the strong class of codons is highly mutated followed by the weak and transitional class. We observe that most of the mutations occur in the first or second positions in the codon rather than the third and mutations that occurred at the second place of codons are majorly deleterious. In most cases, the change in the determinative degree of codon due to mutation is directly proportional to the physical density property. Furthermore, we derive a determinative degree of five wild-type amino acid sequences, which can help biologists to understand the evolutionary relationship among them based on amino acid occurrence frequencies in proteins. In this regard we proposed an alignment-free methodSSADDA(SequenceSimilarityAnalysis usingDeterminativeDegree ofAmino acid). Thus, our scheme gives a more microscopic and alternative representation of the existing codon table that helps in deciphering interesting codon alteration patterns during mutations in disease pathogenesis.
Deficiency in Translesion DNA Polymerase ζ Induces an Innate Immune Response
Authors: Martin Sara K. , Tomida Junya , Wood Richard D. 
Published: March 2020

ABSTRACTDNA polymerase pol ζ is regarded as a specialized DNA polymerase for bypass of DNA lesions. In mammalian cells, pol ζ also contributes to genomic stability during normal DNA replication. Disruption ofRev3l(the catalytic subunit of pol ζ) is toxic to cells and mice, with increased constitutive chromosome damage, including micronuclei. As the cellular manifestations of this genomic stress have remained unexplored, we measured genome-wide transcriptional changes by RNA-seq in pol ζ-defective cells. Expression of 1117 transcripts was altered by 4-fold or more inRev3lknockout mouse embryonic fibroblasts (MEFs), with a pattern showing an induction of an innate immune response. We validated the increased expression of known interferon-stimulated genes (ISG) at the mRNA and protein levels. We found that the cGAS-STING axis, which senses cytosolic DNA, drives ISG expression inRev3lknockout MEFs. These results reveal a new genome protective function of pol ζ and indicate that inhibition of pol ζ may be therapeutically useful by simultaneously increasing sensitivity to genotoxins and inducing a cytotoxic innate immune response.