bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spike mutation D614G alters SARS-CoV-2 fitness and neutralization susceptibility
Authors: Plante Jessica A. , Liu Yang , Liu Jianying , Xia Hongjie , Johnson Bryan A. , Lokugamage Kumari G. , Zhang Xianwen , Muruato Antonio E. , Zou Jing , Fontes-Garfias Camila R. , Mirchandani Divya , Scharton Dionna , Bilello John P. , Ku Zhiqiang , An Zhiqiang , Kalveram Birte , Freiberg Alexander N. , Menachery Vineet D. , Xie Xuping , Plante Kenneth S. , Weaver Scott C. , Shi Pei-Yong 
Published: September 2020

AbstractA spike protein mutation D614G became dominant in SARS-CoV-2 during the COVID-19 pandemic. However, the mutational impact on viral spread and vaccine efficacy remains to be defined. Here we engineer the D614G mutation in the SARS-CoV-2 USA-WA1/2020 strain and characterize its effect on viral replication, pathogenesis, and antibody neutralization. The D614G mutation significantly enhances SARS-CoV-2 replication on human lung epithelial cells and primary human airway tissues, through an improved infectivity of virions with the spike receptor-binding domain in an “up” conformation for binding to ACE2 receptor. Hamsters infected with D614 or G614 variants developed similar levels of weight loss. However, the G614 virus produced higher infectious titers in the nasal washes and trachea, but not lungs, than the D614 virus. The hamster results confirm clinical evidence that the D614G mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increases transmission. For antibody neutralization, sera from D614 virus-infected hamsters consistently exhibit higher neutralization titers against G614 virus than those against D614 virus, indicating that (i) the mutation may not reduce the ability of vaccines in clinical trials to protect against COVID-19 and (ii) therapeutic antibodies should be tested against the circulating G614 virus before clinical development.ImportanceUnderstanding the evolution of SARS-CoV-2 during the COVID-19 pandemic is essential for disease control and prevention. A spike protein mutation D614G emerged and became dominant soon after the pandemic started. By engineering the D614G mutation into an authentic wild-type SARS-CoV-2 strain, we demonstrate the importance of this mutation to (i) enhanced viral replication on human lung epithelial cells and primary human airway tissues, (ii) improved viral fitness in the upper airway of infected hamsters, and (iii) increased susceptibility to neutralization. Together with clinical findings, our work underscores the importance of this mutation in viral spread, vaccine efficacy, and antibody therapy.
Potential universal PCR method to detect decapod hepanhamaparvovirus (DHPV) in crustaceans
Authors: Srisala Jiraporn , Thaiue Dararat , Sanguanrut Piyachat , Aldama-Cano Diva January , Flegel Timothy W. , Sritunyalucksana Kallaya 
Published: September 2020

ABSTRACTParvoviruses that infect the hepatopancreas (HP) of the penaeid shrimpPenaeus chinensis,P. monodon, andP. merquiensiswere previously called hepatopancreatic parvoviruses (HPV). They are now classified in the familyParvoviridae, sub-familyHamaparvovirinaeas members of the same genus calledHepanhamaparvovirusand referred to as decapod hepanhamaparvovirus, designated here as DHPV. However, a virus that causes similar lesions in the HP of the giant river prawnMacrobrachium rosenbergiiresembles hepanhamaparvoviruses by microscopy and histochemistry. Unfortunately, no genome information is yet available and PCR detection methods that work for DHPV inP. monodondo not work withM. rosenbergii. For hatchery samples ofM. rosenbergiiin Thailand with DHPV-like lesions, we hypothesized it might be possible to design primer pairs from 8 full DHPV genome sequences at GenBank for use in PCR detection of DHPV inM. rosenbergii. Using this strategy, we successfully designed a new set of primers and a PCR protocol called the DHPV-U method that gave an amplicon with DNA extracts from larvae of M. rosenberigii samples that showed DHPV-like lesions, while extracts from normal larvae gave none. DNA extracts fromP. monodoninfected with DHPV also gave amplicons. At the same time, the normal PCR method for DHPV inP. monodongave no amplicon with theM. rosenbergiiDNA extracts. The DHPV-U amplicons fromP. monodonandM. rosenbergiishared 99% sequence identity, andin situhybridization (ISH) assays using the DIG-labeled amplicon gave positive histochemical results in the HP tissue of bothP. monodonandM. rosenbergii. The DHPV-U method is now being used in Thailand for detection of DHPV in bothP. monodonandM. rosenbergii. Overall, the results support the proposal that the HP virus inM. rosenbergiiis also ahepanhamaparvovirus. Based on 100% sequence identity of the target region in the currently published DHPV sequences at GenBank, the DHPV-U method may also work for detection of other DHPV isolates.
“SARS-CoV-2 antibody seroprevalence and stability in a tertiary care hospital-setting”
Authors: Siddiqui Samreen , Naushin Salwa , Pradhan Shalini , Misra Archa , Tyagi Akansha , Loomba Menka , Waghdhare Swati , Pandey Rajesh , Sengupta Shantanu , Jha Sujeet 
Published: September 2020

AbstractBackgroundSARS-CoV-2 infection has caused 64,469 deaths in India, with 7, 81, 975 active cases till 30th August 2020, lifting it to 3rd rank globally. To estimate the burden of the disease with time it is important to undertake a longitudinal seroprevalence study which will also help to understand the stability of anti SARS-CoV-2 antibodies. Various studies have been conducted worldwide to assess the antibody stability. However, there is very limited data available from India. Healthcare workers (HCW) are the frontline workforce and more exposed to the COVID-19 infection (SARS-CoV-2) compared to the community. This study was conceptualized with an aim to estimate the seroprevalence in hospital and general population and determine the stability of anti SARS-CoV-2 antibodies in HCW.MethodsStaff of a tertiary care hospital in Delhi and individuals visiting that hospital were recruited between April to August 2020. Venous blood sample, demographic, clinical, COVID-19 symptoms, and RT-PCR data was collected from all participants. Serological testing was performed using the electro-chemiluminescence based assay developed by Roche Diagnostics, in Cobas Elecsys 411. Seropositive participants were followed- upto 83 days to check for the presence of antibodies.ResultsA total of 780 participants were included in this study, which comprised 448 HCW and 332 individuals from the general population. Among the HCW, seroprevalence rates increased from 2.3% in April to 50.6% in July. The cumulative prevalence was 16.5% in HCW and 23.5% (78/332) in the general population with a large number of asymptomatic individuals. Out of 74 seropositive HCWs, 51 were followed-up for the duration of this study. We observed that in all seropositive cases the antibodies were sustained even up to 83 days.ConclusionThe cumulative prevalence of seropositivity was lower in HCWs than the general population. There were a large number of asymptomatic cases and the antibodies developed persisted through the duration of the study. More such longitudinal serology studies are needed to better understand the antibody response kinetics.
An epidemic model for economical impact predicting and spatiotemporal spreading of COVID-19
Authors: Cámara Mateo , Miravete Mario , Navarro Eduardo 
Published: September 2020

AbstractSince the emergence of a new strain of coronavirus known as SARS-CoV-2, many countries around the world have reported cases of COVID-19 disease caused by this virus. Numerous people’s lives have been affected both from a health and an economic point of view. The long tradition of using mathematical models to generate insights about the transmission of a disease, as well as new computer techniques such as Artificial Intelligence, have opened the door to diverse investigations providing relevant information about the evolution of COVID-19. In this research, we seek to advance the existing epidemiological models based on microscopic Markov chains to predict the impact of the pandemic at medical and economic levels. For this purpose, we have made use of the Spanish population movements based on mobile-phone geographically-located information to determine its economic activity using Artificial Intelligence techniques and have developed a novel advanced epidemiological model that combines this information with medical data. With this tool, scenarios can be released with which to determine which restriction policies are optimal and when they have to be applied both to limit the destruction of the economy and to avoid the feared possible upsurge of the disease.
COMPARISON OF ARTIFICIAL INTELLIGENCE ENABLED METHODS IN THE COMPUTED TOMOGRAPHIC ASSESSMENT OF COVID-19 DISEASE
Authors: Kapoor Atul , Mahajan Goldaa , Kapoor Aprajita 
Published: September 2020

AbstractObjectivesComparison of three different Artificial intelligence (AI) methods of assessment for patients undergoing Computed tomography (CT) for suspected Covid-19 disease. Parameters studied were probability of diagnosis, quantification of disease severity and the time to reach the diagnosis.Methods107 consecutive patients of suspected Covid-19 patients were evaluated using the three AI methods labeled as Al-I,II, III alongwith visual analysis labeled as VT for predicting probability of Covid-19, determining CT severity score (CTSS) and index (CTSI), percentage opacification (PO) and high opacification (POHO). Sensitivity, specificity along with area under curves were estimated for each method and the CTSS and CTSI correlated using Friedman test.ResultsOut of 107 patients 71 patients were Covid-19 positive and 20 negative by RT-PCR while 16 did not get RT-PCR done. Al-III method showed higher sensitivity and specificity of 93% and 88% respectively to predict probability of Covid 19. It had 2 false positive patients of interstitial lung disease. Al-II method had sensitivity and specificity of 66% and 83% respectively while visual (VT) analysis showed sensitivity and specificity of 59.7% and 62% respectively. Statistically significant differences were also seen in CTSI and PO estimation between Al-I and III methods (p< 0.0001) with Al-III showing fastest time to calculate results.ConclusionsAl-III method gave better results to make an accurate and quick diagnosis of the Covid-19 with AUC of 0.85 to predict probability of Covid-19 alongwith quantification of Covid-19 lesions in the form of PO, POHO as compared to other AI methods and also by visual analysis.KEY POINTSCT examinations of the chest can be more accurate and informative in detecting Covid-19 if combined with AI methods which are being designed to achieve this objective. In this study we compared three AI methods with Visual analysis and the results show.
Al-III method had a higher sensitivity and specificity of 93% and 88% compared to other methods in predicting probability of Covid-19.Significant inter method variations were seen in quantifying Covid-19 opacities as CTSS,CTSI, PO and POHO variables (p< 0.0001). Al-III method showed no statistical difference with VT method for PO variable (p = 0.24) and was the only method which depicted all the variables..Time to processing results was the shortest with Al-III method.
Could seasonal influenza vaccination influence COVID-19 risk?
Authors: Wals P. De , Divangahi M. 
Published: September 2020

AbstractBackgroundWith possible resurgence of the SARS-CoV-2 and low seasonal influenza virus circulation next winter, reviewing evidence on a possible interaction between influenza vaccination and COVID-19 risk is important.ObjectiveTo review studies on the effect of influenza vaccines on non-influenza respiratory disease (NIRD).MethodsUsing different search strategies, 18 relevant studies were identified and their strength, limitations and significance were assessed.ResultsAnalysis of 4 RCT datasets did not suggest increased NIRD risk in recipients of live-attenuated vaccines (LAIV) and results of a cohort study suggested short-term protection consistent with the hypothesis of ‘trained immunity’. One RCT, four cohort studies and one test-negative case-control suggested increased NIRD risk in recipients of inactivated influenza vaccines (IIV), whereas five test-negative case-control studies did not show an increased risk associated with a specific viral pathogen. Cross-protection against COVID-19 was suggested in one cross-sectional study on IIV but major biases could not be excluded. Results of four recent ecological studies on COVID-19 were challenging to interpret.ConclusionsAvailable data on LAIV are reassuring but not all those on IIV. A drastic reorientation of 2020–2021 influenza campaigns is probably not warranted but studies aiming to test COVID-19 risk modification among recipients of seasonal influenza vaccines should be planned and funded.
Inflammation mediates lung cancer-induced increase in the epidermal green autofluorescence of mice
Authors: Zhang Mingchao , Tang Wanzhi , Ying Weihai 
Published: September 2020

AbstractSkin’s autofluorescence (AF) holds great promise for non-invasive diagnosis of diseases. Our previous study has indicated that keratin-based skin’s AF holds great promise to become a novel biomarker for diagnosis of multiple major diseases, including lung cancer, acute ischemic stroke, Parkinson’s diseases, stable coronary artery disease and myocardial infarction. It is critical to investigate the mechanisms underlying the increased skin’s AF of the patients. Our previous study has shown that development of lung cancer can induce increased skin’s green AF of mice, while the mechanisms underlying the increased AF have remained unclear. We hypothesized that the inflammation in the mice with lung cancer is causative to the increased AF. Our study found that the anti-inflammation drug indomethacin virtually abolished the lung cancer-induced increase in the skin’s green AF. We further found that the AF was originated from the epidermis of the mice. Our findings have provided critical information for understanding the mechanisms underlying the lung cancer-induced increase in the epidermal green AF, indicating that at least for lung cancer, the disease-induced increase in the skin’s AF mainly results from increased inflammation in the body.
Distinct clonal evolution of B-cells in HIV controllers with neutralizing antibody breadth
Authors: Cizmeci Deniz , Lofano Giuseppe , Dugast Anne-Sophie , Kim Dongkyoon , Cavet Guy , Nguyen Ngan , Tan Yann Chong , Seaman Michael S. , Alter Galit , Julg Boris 
Published: September 2020

AbstractA minor subset of individuals infected with HIV-1 develop antibody neutralization breadth during the natural course of the infection, often linked to chronic, high level viremia. Despite significant efforts, vaccination strategies have been unable to induce similar neutralization breadth and the mechanisms underlying neutralizing antibody induction remain largely elusive. Broadly neutralizing antibody responses can also be found in individuals who control HIV to low and even undetectable plasma levels in the absence of antiretroviral therapy, suggesting that high antigen exposure is not a strict requirement for neutralization breadth. We therefore performed an analysis of paired heavy and light chain B-cell receptor repertoires in 12,591 HIV-1 Envelope-specific single memory B-cells to determine alterations in the BCR immunoglobulin gene repertoire and B-cell clonal expansions that associate with neutralizing antibody breadth in 22 HIV controllers. We found that the frequency of genomic mutations in IGHV and IGLV was directly correlated with serum neutralization breadth. The repertoire of the most mutated antibodies was dominated by a small number of large clones with evolutionary signatures suggesting that these clones had reached peak affinity maturation. These data demonstrate that even in the setting of low plasma HIV antigenemia, similar to what a vaccine can potentially achieve, BCR selection for extended somatic hypermutation and clonal evolution can occur in some individuals suggesting that host-specific factors might be involved that could be targeted with future vaccine strategies.
Synthetic mammalian signaling circuits for robust cell population control
Authors: Ma Yitong , Budde Mark W. , Mayalu Michaëlle N. , Zhu Junqin , Lu Andrew C. , Murray Richard M. , Elowitz Michael B. 
Published: September 2020

SummaryIn multicellular organisms, cells actively sense and control their own population density. Synthetic mammalian quorum sensing circuits could provide insight into principles of population control and extend cell therapies. However, a key challenge is reducing their inherent sensitivity to “cheater” mutations that evade control. Here, we repurposed the plant hormone auxin to enable orthogonal mammalian cell-cell communication and quorum sensing. We designed a paradoxical population control circuit, termedParadaux,in which auxin stimulates and inhibits net cell growth at different concentrations. This circuit limited population size over extended timescales, of up to 42 days of continuous culture. By contrast, when operating in a non-paradoxical regime, the same cells limited population growth, but were more susceptible to mutational escape. These results establish auxin as a versatile “private” communication system, and demonstrate that paradoxical circuit architectures can provide robust population control.
Fine-scale population structure and demographic history of British Pakistanis
Authors: Arciero Elena , Dogra Sufyan A. , Mezzavilla Massimo , Tsismentzoglou Theofanis , Huang Qin Qin , Hunt Karen A. , Mason Dan , van Heel David A. , Sheridan Eamonn , Wright John , Small Neil , Carmi Shai , Iles Mark M. , Martin Hilary C. 
Published: September 2020

AbstractPrevious genetic and public health research in the Pakistani population has focused on the role of consanguinity in increasing recessive disease risk, but little is known about its recent population history or the effects of endogamy. Here, we investigate fine-scale population structure, history and consanguinity patterns using genetic and questionnaire data from >4,000 British Pakistani individuals, mostly with roots in Azad Kashmir and Punjab. We reveal strong recent population structure driven by thebiraderisocial stratification system. We find that all subgroups have had low effective population sizes (Ne) over the last 50 generations, with some showing a decrease in Ne15-20 generations ago that has resulted in extensive identity-by-descent sharing and increased homozygosity. Using new theory, we show that the footprint of regions of homozygosity in the two largest subgroups is about twice that expected naively based on the self-reported consanguinity rates and the inferred historical Netrajectory. These results demonstrate the impact of the cultural practices of endogamy and consanguinity on population structure and genomic diversity in British Pakistanis, and have important implications for medical genetic studies.
Iodoacetic acid disrupts mouse oocyte maturation by inducing oxidative stress and spindle abnormalities
Authors: Jiao Xiaofei , Gonsioroski Andressa , Flaws Jodi A , Qiao Huanyu 
Published: September 2020

AbstractDisinfection by-products (DBPs) are compounds produced during the water disinfection process. Iodoacetic acid (IAA) is one of the unregulated DBPs in drinking water, with potent cytotoxicity and genotoxicity in animals. However, whether IAA has toxic effects on oocyte maturation remains unclear. Here, we show that IAA exposure resulted in metaphase I (MI) arrest and polar-body-extrusion failure in mouse oocytes, indicating that IAA had adverse effects on mouse oocyte maturationin vitro. Particularly, IAA treatment caused abnormal spindle assembly and chromosome misalignment. Previous studies reported that IAA is a known inducer of oxidative stress in non-germline cells. Correspondingly, we found that IAA exposure increased the reactive oxygen species (ROS) levels in oocytes in a dose-dependent manner, indicating IAA exposure could induce oxidative stress in oocytes. Simultaneously, DNA damage was also elevated in the nuclei of these IAA-exposed mouse oocytes, evidenced by increased γ-H2AX focus number. In addition, the un-arrested oocytes entered metaphase II (MII) with severe defects in spindle morphologies and chromosome alignment after 14-hour IAA treatment. An antioxidant, N-acetyl-L-cysteine (NAC), reduced the elevated ROS level and restored the meiotic maturation in the IAA. exposed oocytes, which indicates that IAA-induced maturation failure in oocytes was mainly mediated by oxidative stress. Collectively, our results indicate that IAA exposure interfered with mouse oocyte maturation by elevating ROS levels, disrupting spindle assembly, inducing DNA damage, and causing MI arrest.
A high-throughput CRISPR interference screen for dissecting functional regulators of GPCR/cAMP signaling
Authors: Semesta Khairunnisa Mentari , Tian Ruilin , Kampmann Martin , von Zastrow Mark , Tsvetanova Nikoleta G. 
Published: September 2020

AbstractG protein-coupled receptors (GPCRs) allow cells to respond to chemical and sensory stimuli through generation of second messengers, such as cyclic AMP (cAMP), which in turn mediate a myriad of processes, including cell survival, proliferation, and differentiation. In order to gain deeper insights into the complex biology and physiology of these key cellular pathways, it is critical to be able to globally map the molecular factors that shape cascade function. Yet, to this date, efforts to systematically identify regulators of GPCR/cAMP signaling have been lacking. Here, we combined genome-wide screening based on CRISPR interference with a novel sortable transcriptional reporter that provides robust readout for cAMP signaling, and carried out a functional screen for regulators of the pathway. Due to the sortable nature of the platform, we were able to assay regulators with strong and weaker phenotypes by analyzing sgRNA distribution among three fractions with distinct reporter expression. We identified 45 regulators with strong and 50 regulators with weaker phenotypes not previously known to be involved in cAMP signaling. In follow-up experiments, we validated the functional effects of seven newly discovered mediators (NUP93, PRIM1, RUVBL1, PKMYT1, TP53, SF3A2, andHRAS), and showed that they control distinct steps of the pathway. Thus, our study provides proof of principle that the screening platform can be applied successfully to identify bona fide regulators of GPCR/second messenger cascades in an unbiased and high-throughput manner, and illuminates the remarkable functional diversity among GPCR regulators.Author summaryCells sense and respond to changes in their surrounding environment through G protein-coupled receptors (GPCRs) and their associated cascades. The proper function of these pathways is essential to human physiology, and GPCRs have become a prime target for drug development for a range of human diseases. Therefore, it is of utmost importance to be able to map how these pathways operate to enable cells to fine-tune their responsiveness. Here, we describe a screening approach that we have devised to systematically identify regulators of GPCR function. We have developed a sortable reporter system and coupled that with silencing of genes across the entire human genome in order to uncover a range of novel mediators of GPCR activity. We characterize a few of these new regulators and show that they function at different steps of the cascade. Therefore, this study serves as proof of principle for the new screening platform. We envision that the approach can be used to dissect additional dimensions of GPCR function, including regulators of drug-specific responses, functional characterization of receptor features, and identification of novel drugs, and thus advance a genome-scale understanding of these critical pathways.