bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitophagy protects beta cells from inflammatory damage in diabetes
Authors: Sidarala Vaibhav , Pearson Gemma L. , Parekh Vishal S. , Thompson Benjamin , Christen Lisa , Gingerich Morgan A. , Zhu Jie , Stromer Tracy , Ren Jianhua , Reck Emma , Chai Biaoxin , Corbett John A. , Mandrup-Poulsen Thomas , Satin Leslie S. , Soleimanpour Scott A. 
Published: June 2020

AbstractInflammatory damage contributes to β-cell failure in type 1 and 2 diabetes (T1D and T2D). Mitochondria are damaged by inflammatory signaling in β-cells, resulting in impaired bioenergetics and initiation of pro-apoptotic machinery. Hence, the identification of protective responses to inflammation could lead to new therapeutic targets. Here we report that mitophagy serves as a protective response to inflammatory stress in both human and rodent β-cells. Utilizingin vivomitophagy reporters, we observed that diabetogenic pro-inflammatory cytokines induced mitophagy in response to nitrosative/oxidative mitochondrial damage. Mitophagy-deficient β-cells were sensitized to inflammatory stress, leading to the accumulation of fragmented dysfunctional mitochondria, increased β-cell death, and hyperglycemia. Overexpression ofCLEC16A, a T1D gene and mitophagy regulator whose expression in islets is protective against T1D, ameliorated cytokine-induced human β-cell apoptosis. Thus, mitophagy promotes β-cell survival and prevents diabetes by countering inflammatory injury. Targeting this pathway has the potential to prevent β-cell failure in diabetes and may be beneficial in other inflammatory conditions.
Metabolic plasticity in cancer activates apocryphal pathways for lipid desaturation
Authors: Young Reuben S.E. , Bowman Andrew P. , Williams Elizabeth D. , Tousignant Kaylyn D. , Bidgood Charles L. , Narreddula Venkateswara R. , Gupta Rajesh , Marshall David L. , Poad Berwyck L.J. , Nelson Colleen C. , Ellis Shane R. , Heeren Ron M.A. , Sadowski Martin C. , Blanksby Stephen J. 
Published: June 2020

AbstractFatty acid (FA) modifications, such as enzymatic desaturation and elongation, have long been thought to involve sequential and highly specific enzyme-substrate interactions, which result in canonical products that are well-defined in their chain lengths, degree of unsaturation and double bond positions.1These products act as a supply of building blocks for the synthesis of complex lipids supporting a symphony of lipid signals and membrane macrostructure. Recently, it was brought to light that differences in substrate availability due to enzyme inhibition can activate alternative pathways in a range of cancers, potentially altering the total species repertoire of FA metabolism.2,3We have used isomer-resolved lipidomics to analyse human prostate tumours and cancer cell lines and reveal, for the first-time, the full extent of metabolic plasticity in cancer. Assigning the double bond position(s) in simple and complex lipids allows mapping of fatty acid desaturation and elongation via hitherto apocryphal metabolic pathways that generate FAs with unusual sites of unsaturation. Downstream utilisation of these FAs is demonstrated by their incorporation into complex structural lipids. The unsaturation profiles of different phospholipids reveal substantive structural variation between classes that will, necessarily, modulate lipid-centred biological processes in cancer cells including membrane fluidity3-5and signal transduction.6-8
Higher rates of processed pseudogene acquisition in humans and three great apes revealed by long read assemblies
Authors: Feng Xiaowen , Li Heng 
Published: June 2020

AbstractLINE-1 mediated retrotransposition of protein-coding mRNAs is an active process in modern humans for both germline and somatic genomes. Prior works that surveyed human data or human cohorts mostly relied on detecting discordant mappings of paired-end short reads, or assumed L1 hallmarks such as polyA tails and target site duplications. Moreover, there has been few genome-wide comparison between gene retrocopies in great apes and humans. In this study, we introduced a more sensitive and accurate approach to the discovery of processed pseudogene. Our method utilizes long read assemblies, and more importantly, is able to provide full retrocopy sequences as well as the neighboring sequences which are missed by short-read based methods reads. We provided an overview of novel gene retrocopies of 40 events (38 parent genes) in 20 human assemblies, a significantly higher discovery rate than previous reports (39 events of 36 parent genes out of 939 individuals). We also performed comprehensive analysis of lineage specific retrocopies in chimpanzee, gorilla and orangutan genomes.
Mortality Analysis of COVID-19 Confirmed Cases in Pakistan
Authors: Chaudhry Ambreen , Ikram Aamer , Baig Mirza Amir , Salman Muhammad , Ghafoor Tamkeen , Zakir Hussain , Khan Mumtaz Ali , Ansari Jamil Ahmed , Syed Asif , Javed Wasif , Larik Ehsan , Mohsan Muhammad , Masood Naveed , Iqbal Zeeshan , Akram Khurram 
Published: June 2020

AbstractIntroductionCOVID-19, a novel disease, appeared in December 2019 in China and rapidly spread across the world. Till second week of April 2020, high incidence (2.9/100,000) and cases fatality rates (1.7%)was observed in Pakistan.This study was conducted to determine temporal and spatial distribution of first 100 deaths attributed to COVID-19 in Pakistan and their associated demographic factors.MethodWe conducted a descriptive epidemiological analysis of first 100 deaths reported among RT-PCR confirmed COVID-19 cases. Demographic, epidemiological and risk factors information was obtained associated comorbidities and clinical signs and symptoms were recorded and frequencies were determined.ResultsA total of 100 mortalities with overall Case Fatality Rate 1.67% (CFR) were analysed. Median age of patients was 64.5 years (IQR: 54–70) with 75% (n = 75) Males. Among all deaths reported, 71 (71%) cases had one or more documented comorbidities at the time of diagnosis. Most frequently reported co-morbidities were; hypertension (67 %), followed by Diabetes Mellitus 945%) and Ischemic Heart Diseases (27%). First death was reported on 18 March 2020 and the most frequent presenting symptoms were shortness of breath (87%) and fever (79%). Median duration of illness was eight days (IQR: 4–11 days), median delay reaching hospital to seek health care was three days (IQR: 0–6 days) while median duration of hospital stay was also three days (IQR: 1–7 days). Among all reported deaths, 62% were attributed to local transmission as these cases had no history of international travel. The most affected age group was 60–69 years while no death reported in age group below 20 years.ConclusionHigh CFR among old age group and its association with co-morbidities (chronic disease) suggests targeted interventions such as social distancing and strict quarantine measure for elderly and morbid people. Comparative studies among deaths and recovered patients are recommended to explore further disease dynamics.
Dynamics of IgG seroconversion and pathophysiology of COVID-19 infections
Authors: Staines Henry M , Kirwan Daniela E , Clark David J , Adams Emily R , Augustin Yolanda , Byrne Rachel L , Cocozza Michael , Cubas-Atienzar Ana I , Cuevas Luis E. , Cusinato Martina , Davies Benedict M O , Davis Mark , Davis Paul , Duvoix Annelyse , Eckersley Nicholas M , Forton Daniel , Fraser Alice J , Garrod Gala , Hadcocks Linda , Hu Qinxue , Johnson Michael , Kay Grant A , Klekotko Kesja , Lewis Zawditu , Macallan Derek C , Mensah-Kane Josephine , Menzies Stefanie , Monahan Irene , Moore Catherine M , Nebe-von-Caron Gerhard , Owen Sophie I , Sainter Chris , Sall Amadou A , Schouten James , Williams Chris , Wilkins John , Woolston Kevin , Fitchett Joseph R A , Krishna Sanjeev , Planche Tim 
Published: June 2020

AbstractWe report dynamics of seroconversion to SARS-CoV-2 infections detected by IgG ELISA in 177 individuals diagnosed by RT-PCR. Longitudinal analysis identifies 2-8.5% of individuals who do not seroconvert even weeks after infection. They are younger than seroconverters who have increased co-morbidity and higher inflammatory markers such as C-Reactive Protein. Higher antibody responses are associated with non-white ethnicity. Antibody responses do not decline during follow up almost to 2 months. Serological assays increase understanding of disease severity. Their application in regular surveillance will clarify the duration and protective nature of humoral responses to SARS-CoV-2.
Impact of Timing of and Adherence to Social Distancing Measures on COVID-19 Burden in the US: A Simulation Modeling Approach
Authors: Alagoz Oguzhan , Sethi Ajay K. , Patterson Brian W. , Churpek Matthew , Safdar Nasia 
Published: June 2020

ABSTRACTBackgroundAcross the U.S., various social distancing measures were implemented to control COVID-19 pandemic. However, there is uncertainty in the effectiveness of such measures for specific regions with varying population demographics and different levels of adherence to social distancing. The objective of this paper is to determine the impact of social distancing measures in unique regions.MethodsWe developed COVid-19 Agent-based simulation Model (COVAM), an agent-based simulation model (ABM) that represents the social network and interactions among the people in a region considering population demographics, limited testing availability, imported infections from outside of the region, asymptomatic disease transmission, and adherence to social distancing measures. We adopted COVAM to represent COVID-19-associated events in Dane County, Wisconsin, Milwaukee metropolitan area, and New York City (NYC). We used COVAM to evaluate the impact of three different aspects of social distancing: 1) Adherence to social distancing measures; 2) timing of implementing social distancing; and 3) timing of easing social distancing.ResultsWe found that the timing of social distancing and adherence level had a major effect on COVID-19 occurrence. For example, in NYC, implementing social distancing measures on March 5, 2020 instead of March 12, 2020 would have reduced the total number of confirmed cases from 191,984 to 43,968 as of May 30, whereas a 1-week delay in implementing such measures could have increased the number of confirmed cases to 1,299,420. Easing social distancing measures on June 1, 2020 instead of June 15, 2020 in NYC would increase the total number of confirmed cases from 275,587 to 379,858 as of July 31.ConclusionThe timing of implementing social distancing measures, adherence to the measures, and timing of their easing have major effects on the number of COVID-19 cases.Primary Funding SourceNational Institute of Allergy and Infectious Diseases Institute
Cooperative interactions among females and even more extraordinary sex ratios
Authors: Iritani Ryosuke , West Stuart A , Abe Jun 
Published: June 2020

AbstractHamilton’s local mate competition theory provided an explanation for extraordinary female biased sex ratios in a range of organisms. When mating takes place locally, in structured populations, a female biased sex ratio is favoured to reduce competition between related males, and to provide more mates for males. However, there are a number of wasp species where the sex ratios appear to more female biased than predicted by Hamilton’s theory. We investigated theoretically the extent to which cooperative interactions between related females can interact with local mate competition to favour even more female biased sex ratios. We found that: (i) cooperative interactions between females can lead to sex ratios that are more female biased than predicted by local competition theory alone; (ii) sex ratios can be more female biased when the cooperative interactions are offspring helping parents before dispersal, rather than cooperation between siblings after dispersal. Our results can be applied to a range of organisms, and provide an explanation for the extreme sex ratio biases that have been observed inSclerodermusandMelittobiawasps.
Reconstructing Full-Field Flapping Wing Dynamics from Sparse Measurements
Authors: Johns William , Davis Lisa , Jankauski Mark 
Published: June 2020

AbstractFlapping insect wings deform during flight. This deformation benefits the insect’s aerodynamic force production as well as energetic efficiency. However, it is challenging to measure wing displacement field in flying insects. Many points must be tracked over the wing’s surface to resolve its instantaneous shape. To reduce the number of points one is required to track, we propose a physics-based reconstruction method called System Equivalent Reduction Expansion Processes (SEREP) to estimate wing deformation and strain from sparse measurements. Measurement locations are determined using a Weighted Normalized Modal Displacement (NMD) method. We experimentally validate the reconstruction technique by flapping a paper wing from 5-9 Hz with 45° and measuring strain at three locations. Two measurements are used for the reconstruction and the third for validation. Strain reconstructions had a maximal error of 30% in amplitude. We extend this methodology to a more realistic insect wing through numerical simulation. We show that wing displacement can be estimated from sparse displacement or strain measurements, and that additional sensors spatially average measurement noise to improve reconstruction accuracy. This research helps overcome some of the challenges of measuring full-field dynamics in flying insects and provides a framework for strain-based sensing in insect-inspired flapping robots.
ATAV: a comprehensive platform for population-scale genomic analyses
Authors: Ren Zhong , Povysil Gundula , Goldstein David B. 
Published: June 2020

AbstractBackgroundA common approach for sequencing studies is to do joint-calling and store variants of all samples in a single file. If new samples keep being added or controls are re-used for several studies, the cost and time required to perform joint-calling for each analysis can become prohibitive.ResultsWe present ATAV, an analysis platform for large-scale whole-exome and whole-genome sequencing projects. ATAV stores variant and per site coverage data for all samples in a centralized database, which is efficiently queried by ATAV to support diagnostic analyses for trios and singletons, as well as rare-variant collapsing analyses for finding disease associations in complex diseases. Runtime logs ensure full reproducibility and the modularized ATAV framework makes it extensible to continuous development. Besides helping with the identification of disease-causing variants for a range of diseases, ATAV has also enabled the discovery of disease-genes by rare-variant collapsing on datasets containing more than 20,000 samples. Analyses to date have been performed on data of more than 110,000 individuals demonstrating the scalability of the framework.The ATAV data browser (http://atavdb.org/) is a web-based interface that allows users to easily access variant-level data directly from the database. Summary-level data for more than 40,000 samples can be queried by the general public representing a mix of cases and controls of diverse ancestries. Users have access to phenotype categories of variant carriers, as well as predicted ancestry, gender, and quality metrics. In contrast to many other platforms, the data browser is able to show data of newly-added samples in real-time and is therefore evolving rapidly as more and more samples are sequenced.ConclusionsSince all code is freely available on GitHub, ATAV can easily be used by other groups to build up their own platform, database, and user interface. In addition to that users can query one of the largest variant databases for patients sequenced at a tertiary care center and look up their own genes or variants of interest.
Temporal expectation modulates the neural dynamics of delayed responses to working memory representations
Authors: Chen Fang-Wen , Li Chun-Hui , Kuo Bo-Cheng 
Published: June 2020

AbstractTemporal expectation can induce anticipatory attention to enhance perceptual processing and optimise behaviours. However, it remains unexplored whether temporal expectation benefits delayed responses to information maintained in working memory (WM) and the underlying neural dynamics that support the benefits. Here we addressed these issues in behavioural and electroencephalography (EEG) experiments. Participants performed a rotation discrimination WM task. Temporal expectation was manipulated by varying the predictability for when a test probe would occur after a delay interval. We first demonstrated that temporal predictability benefited WM performance. Our EEG results showed decreased alpha power over the left posterior brain regions during the delay interval for high than low predictability trials. Importantly, we found earlier enhancement of the lateralised alpha power and the lateralised readiness potential for high than low predictability trials when WM contents were accessed for responses during the probe period. Finally, we found concurrent selection and preparation for responses when the probe onset was predictable but motor preparation lagged behind response selection when the probe onset was more variable. Together, this study provides new insights into the proactive, dynamic nature of the anticipatory deployment of attention in guiding WM maintenance and delayed responses.
SARS-CoV-2-specific T cells exhibit phenotypic features reflecting robust helper function, lack of terminal differentiation, and high proliferative potential
Authors: Neidleman Jason , Luo Xiaoyu , Frouard Julie , Xie Guorui , Gill Gurjot , Stein Ellen S. , McGregor Matthew , Ma Tongcui , George Ashley F. , Kosters Astrid , Greene Warner C. , Vasquez Joshua , Ghosn Eliver , Lee Sulggi , Roan Nadia R. 
Published: June 2020

ABSTRACTConvalescing COVID-19 patients mount robust T cell responses against SARS-CoV-2, suggesting an important role for T cells in viral clearance. To date, the phenotypes of SARS-CoV-2-specific T cells remain poorly defined. Using 38-parameter CyTOF, we phenotyped longitudinal specimens of SARS-CoV-2-specific CD4+ and CD8+ T cells from nine individuals who recovered from mild COVID-19. SARS-CoV-2-specific CD4+ T cells were exclusively Th1 cells, and predominantly Tcm with phenotypic features of robust helper function. SARS-CoV-2-specific CD8+ T cells were predominantly Temra cells in a state of less terminal differentiation than most Temra cells. Subsets of SARS-CoV-2-specific T cells express CD127, can homeostatically proliferate, and can persist for over two months. Our results suggest that long-lived and robust T cell immunity is generated following natural SARS-CoV-2 infection, and support an important role for SARS-CoV-2-specific T cells in host control of COVID-19.
Rapid whole genome sequence typing reveals multiple waves of SARS-CoV-2 spread
Authors: Moustafa Ahmed M. , Planet Paul J. 
Published: June 2020

AbstractAs the pandemic SARS-CoV-2 virus has spread globally its genome has diversified to an extent that distinct clones can now be recognized, tracked, and traced. Identifying clonal groups allows for assessment of geographic spread, transmission events, and identification of new or emerging strains that may be more virulent or more transmissible. Here we present a rapid, whole genome, allele-based method (GNUVID) for assigning sequence types to sequenced isolates of SARS-CoV-2 sequences. This sequence typing scheme can be updated with new genomic information extremely rapidly, making our technique continually adaptable as databases grow. We show that our method is consistent with phylogeny and recovers waves of expansion and replacement of sequence types/clonal complexes in different geographical locations.GNUVID is available as a command line application (https://github.com/ahmedmagds/GNUVID).
An Inexpensive RT-PCR Endpoint Diagnostic Assay for SARS-CoV-2 Using Nested PCR: Direct Assessment of Detection Efficiency of RT-qPCR Tests and Suitability for Surveillance
Authors: Davda Jayeshkumar Narsibhai , Frank Keith , Prakash Sivakumar , Purohit Gunjan , Vijayashankar Devi Prasad , Vedagiri Dhiviya , Tallapaka Karthik Bharadwaj , Harshan Krishnan Harinivas , Siva Archana Bharadwaj , Mishra Rakesh Kumar , Dhawan Jyotsna , Siddiqi Imran 
Published: June 2020

AbstractWith a view to extending testing capabilities for the ongoing SARS-CoV-2 pandemic we have developed a test that lowers cost and does not require real time quantitative reverse transcription polymerase chain reaction (RT-qPCR). We developed a reverse transcription nested PCR endpoint assay (RT-nPCR) and showed that RT-nPCR has comparable performance to the standard RT-qPCR test. In the course of comparing the results of both tests, we found that the standard RT-qPCR test can have low detection efficiency (less than 50%) in a real testing scenario which may be only partly explained by low viral representation in many samples. This finding points to the importance of directly monitoring detection efficiency in test environments. We also suggest measures that would improve detection efficiency.
Enhanced production of taxadiene inSaccharomyces cerevisiae
Authors: Nowrouzi Behnaz , Li Rachel , Walls Laura E. , d’Espaux Leopold , Malci Koray , Lungang Liang , Borrego Nestor Jonguitud , Escalera Albert I. Lerma , Morones-Ramirez Jose R. , Keasling Jay D. , Solis Leonardo Rios 
Published: June 2020

AbstractCost-effective production of the highly effective anti-cancer drug, paclitaxel (Taxol®), remains limited despite growing global demands. Low yields of the critical taxadiene precursor remains a key bottleneck in microbial production. In this study, the key challenge of poor taxadiene synthase (TASY) solubility inS. cerevisiaewas revealed, and the strains were strategically engineered to relieve this bottleneck. Multi-copy chromosomal integration ofTASYharbouring a selection of fusion solubility tags improved taxadiene titres 22-fold, up to 57 ± 3 mg/L at 30 °C at shake flask scale. The scalability of the process was highlighted through achieving similar titres during scale up to 25 mL and 250 mL in shake flask and bioreactor cultivations, respectively. Maximum taxadiene titres of 129 ± 15 mg/L and 119 mg/L were achieved through shake flask and bioreactor cultivation, respectively, of the optimal strain at a reduced temperature of 20 °C. The results highlight the positive effect of coupling molecular biology tools with bioprocess variable optimisation on synthetic pathway development.HighlightsMaximum taxadiene titre of 129 ± 15 mg/L inSaccharomyces cerevisiaeat 20 °CIntegrating fusion protein tagged-taxadiene synthase improved taxadiene titre.Consistent taxadiene titres were achieved at the micro-and mini-bioreactor scales.
Satellite repeat transcripts modulate heterochromatin condensates and safeguard chromosome stability in mouse embryonic stem cells
Authors: Novo Clara Lopes , Wong Emily , Hockings Colin , Poudel Chetan , Sheekey Eleanor , Walker Simon , Schierle Gabriele S. Kaminski , Narlikar Geeta J. , Rugg-Gunn Peter J. 
Published: June 2020

SummaryHeterochromatin maintains genome integrity and function, and is organised into distinct nuclear domains. Some of these domains are proposed to form by phase separation through the accumulation of HP1α. Mammalian heterochromatin contains noncoding major satellite repeats (MSR), which are highly transcribed in mouse embryonic stem cells (ESCs). Here, we report that MSR transcripts can drive the formation of HP1α dropletsin vitro, and scaffold heterochromatin into dynamic condensates in ESCs, leading to the formation of large nuclear domains that are characteristic of pluripotent cells. Depleting MSR transcripts causes heterochromatin to transition into a more compact and static state. Unexpectedly, changing heterochromatin’s biophysical properties has severe consequences for ESCs, including chromosome instability and mitotic defects. These findings uncover an essential role for MSR transcripts in modulating the organisation and properties of heterochromatin to preserve genome stability. They also provide new insights into the processes that could regulate phase separation and the functional consequences of disrupting the properties of heterochromatin condensates.