bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying high-risk groups for change in weight and body mass index: population cohort of 11 million measurements in 2.3 million adults
Authors: Katsoulis Michail , Lai Alvina G , Diaz-Ordaz Karla , Gomes Manuel , Pasea Laura , Banerjee Amitava , Denaxas Spiros , Tsilidis Kostas , Lagiou Pagona , Misirli Gesthimani , Bhaskaran Krishnan , Wannamethee Goya , Dobson Richard , Batterham Rachel L , Kipourou DK , Lumbers R Thomas , Wareham Nick , Langenberg Claudia , Hemingway Harry 
Published: January 2021

ABSTRACTBackgroundAdult obesity prevention policies, which are largely untargeted, have met with limited success globally. Population groups with the highest risk of weight gain, if they could be reliably identified using readily available information, might benefit from targeted policy. The relative importance of age, sex, ethnicity, geographical region and social deprivation for weight gain is unknown.MethodsWe calculated longitudinal changes in BMI over one, five and ten years and investigated transition between BMI categories using 11,187,383 clinically recorded, repeated measures of BMI from population-based electronic health records of 2,328,477 adults in England (1998-2016). The influence of risk factors was tested using logistic regression.FindingsThe youngest adult age group (18-24 years) was more strongly associated with risk of weight gain than older age, male sex, socioeconomic deprivation, ethnicity or geographic region. Among the youngest adults, the top quartile gained 15.9kg in men and 12kg in women at 10 years. The odds of transitioning to a higher BMI category over 10 years were 4-6 times higher in the youngest (18-24 years) compared to oldest (65-74 years) individuals; odds ratio (95% confidence interval) 4.22 (3.85-4.62)) from normal weight to overweight or obesity, 4.60 (4.06-5.22) for overweight to obesity, and 5.87 (5.23-6.59) from obesity to severe obesity in multiple adjusted analyses. Among the youngest adults, socially deprived men were at greater risk of transitioning from normal weight to overweight (72%) and from overweight to obesity (68%) over 10 years. We provide an open access online risk calculator (https://pasea.shinyapps.io/bmi_shiny_app/) and present high resolution obesity risk charts over a 1-, 5- and 10-year follow-up.InterpretationA radical shift in policy is required to focus on those at highest risk of weight gain-young adults-for individual and population level prevention of obesity and its long-term consequences for health and health care.FundingBHF, HDR-UK, MRC
A comprehensive antigen production and characterization study for easy-to-implement, highly specific and quantitative SARS-CoV-2 antibody assays
Authors: Klausberger Miriam , Dürkop Mark , Haslacher Helmuth , Wozniak-Knopp Gordana , Cserjan-Puschmann Monika , Perkmann Thomas , Lingg Nico , Aguilar Patricia Pereira , Laurent Elisabeth , De Vos Jelle , Hofer Manuela , Holzer Barbara , Stadler Maria , Manhart Gabriele , Vierlinger Klemens , Egger Margot , Milchram Lisa , Gludovacz Elisabeth , Marx Nicolas , Köppl Christoph , Tauer Christopher , Beck Jürgen , Maresch Daniel , Grünwald-Gruber Clemens , Strobl Florian , Satzer Peter , Stadlmayr Gerhard , Vavra Ulrike , Huber Jasmin , Wahrmann Markus , Eskandary Farsad , Breyer Marie-Kathrin , Sieghart Daniela , Quehenberger Peter , Leitner Gerda , Strassl Robert , Egger Alexander E. , Irsara Christian , Griesmacher Andrea , Hoermann Gregor , Weiss Günter , Bellmann-Weiler Rosa , Loeffler-Ragg Judith , Borth Nicole , Strasser Richard , Jungbauer Alois , Hahn Rainer , Mairhofer Jürgen , Hartmann Boris , Binder Nikolaus B. , Striedner Gerald , Mach Lukas , Weinhäusl Andreas , Dieplinger Benjamin , Grebien Florian , Gerner Wilhelm , Binder Christoph J. , Grabherr Reingard 
Published: January 2021

AbstractAntibody tests are essential tools to investigate humoral immunity following SARS-CoV-2 infection. While first-generation antibody tests have primarily provided qualitative results with low specificity, accurate seroprevalence studies and tracking of antibody levels over time require highly specific, sensitive and quantitative test setups. Here, we describe two quantitative ELISA antibody tests based on the SARS-CoV-2 spike receptor-binding domain and the nucleocapsid protein. Comparative expression in bacterial, insect, mammalian and plant-based platforms enabled the identification of new antigen designs with superior quality and high suitability as diagnostic reagents. Both tests scored excellently in clinical validations with multi-centric specificity and sensitivity cohorts and showed unprecedented correlation with SARS-CoV-2 neutralization titers. Orthogonal testing increased assay specificity to 99.8%, thereby enabling robust serodiagnosis in low-prevalence settings. The inclusion of a calibrator permits accurate quantitative monitoring of antibody concentrations in samples collected at different time points during the acute and convalescent phase of COVID-19.
City Reduced Probability of Infection (CityRPI) for Indoor Airborne Transmission of SARS-CoV-2 and Urban Building Energy Impacts
Authors: Katal Ali , Albettar Maher , Wang Liangzhu (Leon) 
Published: January 2021

ABSTRACTAirborne transmission of aerosols produced by asymptomatic individuals is a large portion of the SARS-CoV-2 spread indoors. Outdoor air ventilation rate, air filtration, room occupancy, exposure time, and mask-wearing are among the key parameters that affect its airborne transmission in indoor spaces. In this work, we developed a new web-based platform, City Reduced Probability of Infection - CityRPI, to calculate the indoor airborne transmission of COVID-19 in various buildings of a city scale. An archetype library of twenty-nine building types is developed based on several standards and references. Among the mitigation strategies recommended to reduce infection risk, some could result in significant energy impacts on buildings. To study the combined effects of energy consumption and reduced infection probability, we integrated CityRPI with City Building Energy Model. We applied the integrated model to Montreal City and studied the impact of six mitigation measures on the infection risk and peak energy demand in winter. It shows that the same strategy could perform quite differently, depending on building types and properties. In the winter season, increasing the outdoor air ventilation rate may cause massive building energy consumption. All strategies are shown to reduce the infection risk but wearing a mask and reducing exposure time are the most effective strategies in many buildings, with around 60% reduction. Doubling the outdoor air ventilation rate is not as effective as other strategies to reduce the risk with less than 35% reduction. It also significantly increases building peak heating demand with 10-60%.
Enhancing the Human Health Status Prediction: the ATHLOS Project
Authors: Anagnostou Panagiotis , Tasoulis Sotiris , Vrahatis Aristidis G. , Georgakopoulos Spiros , Prina Matthew , Ayuso-Mateos José Luis , Bickenbach Jerome , Bayes Ivet , Caballero Francisco Félix , Egea-Cortés Laia , García-Esquinas Esther , Leonardi Matilde , Scherbov Sergei , Tamosiunas Abdonas , Galas Aleksander , Haro Josep Maria , Sanchez-Niubo Albert , Plagianakos Vassilis , Panagiotakos Demosthenes 
Published: January 2021

AbstractPreventive healthcare is a crucial pillar of health as it contributes to staying healthy and having immediate treatment when needed. Mining knowledge from longitudinal studies has the potential to significantly contribute to the improvement of preventive healthcare. Unfortunately, data originated from such studies are characterized by high complexity, huge volume and a plethora of missing values. Machine Learning, Data Mining and Data Imputation models are utilized as part of solving the aforementioned challenges, respectively. Towards this direction, we focus on the development of a complete methodology for the ATHLOS (Ageing Trajectories of Health: Longitudinal Opportunities and Synergies) Project - funded by the European Union’s Horizon 2020 Research and Innovation Program, which aims to achieve a better interpretation of the impact of aging on health. The inherent complexity of the provided dataset lie in the fact that the project includes 15 independent European and international longitudinal studies of aging. In this work, we particularly focus on the HealthStatus (HS) score, an index that estimates the human status of health, aiming to examine the effect of various data imputation models to the prediction power of classification and regression models. Our results are promising, indicating the critical importance of data imputation in enhancing preventive medicine’s crucial role.
Transspecies beak color polymorphism in the Darwin’s finch radiation
Authors: Enbody Erik D. , Sprehn C. Grace , Abzhanov Arhat , Bi Huijuan , Dobreva Mariya P. , Osborne Owen G. , Rubin Carl-Johan , Grant Peter R. , Grant B. Rosemary , Andersson Leif 
Published: January 2021

AbstractCarotenoid-based polymorphisms are widespread in populations of birds, fish, and reptiles1, but little is known of how they affect fitness and are maintained as species multiply2. We report a combined field and molecular-genetic investigation of a nestling beak color polymorphism in Darwin’s finches. Beaks are pink or yellow, and yellow is recessive3. Here we show that the polymorphism arose in the Galápagos approximately half a million years ago through a regulatory mutation in theBCO2gene, and is shared by 14 descendant species. The frequency of the yellow genotype is associated with cactus flower abundance in cactus finches, and is altered by introgressive hybridization. The polymorphism is most likely a balanced polymorphism, maintained by ecological selection pressures associated with diet, and augmented by occasional interspecific introgression. Polymorphisms that are hidden as adults, as here, may contribute to evolutionary diversification in underappreciated ways in other systems.
Rapid protection from COVID-19 in nonhuman primates vaccinated intramuscularly but not intranasally with a single dose of a recombinant vaccine
Authors: Furuyama Wakako , Shifflett Kyle , Pinski Amanda N. , Griffin Amanda J. , Feldmann Friederike , Okumura Atsushi , Gourdine Tylisha , Jankeel Allen , Lovaglio Jamie , Hanley Patrick W. , Thomas Tina , Clancy Chad S. , Messaoudi Ilhem , O’Donnell Kyle L. , Marzi Andrea 
Published: January 2021

AbstractThe ongoing pandemic of Coronavirus disease 2019 (COVID-19) continues to exert a significant burden on health care systems worldwide. With limited treatments available, vaccination remains an effective strategy to counter transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent discussions concerning vaccination strategies have focused on identifying vaccine platforms, number of doses, route of administration, and time to reach peak immunity against SARS-CoV-2. Here, we generated a single dose, fast-acting vesicular stomatitis virus-based vaccine derived from the licensed Ebola virus (EBOV) vaccine rVSV-ZEBOV, expressing the SARS-CoV-2 spike protein and the EBOV glycoprotein (VSV-SARS2-EBOV). Rhesus macaques vaccinated intramuscularly (IM) with a single dose of VSV-SARS2-EBOV were protected within 10 days and did not show signs of COVID-19 pneumonia. In contrast, intranasal (IN) vaccination resulted in limited immunogenicity and enhanced COVID-19 pneumonia compared to control animals. While IM and IN vaccination both induced neutralizing antibody titers, only IM vaccination resulted in a significant cellular immune response. RNA sequencing data bolstered these results by revealing robust activation of the innate and adaptive immune transcriptional signatures in the lungs of IM-vaccinated animals only. Overall, the data demonstrates that VSV-SARS2-EBOV is a potent single-dose COVID-19 vaccine candidate that offers rapid protection based on the protective efficacy observed in our study.One sentence summaryVSV vaccine protects NHPs from COVID-19 in 10 days
Coordinated action of RTBV and RTSV proteins suppress host RNA silencing machinery
Authors: Anand Abhishek , Pinninti Malathi , Tripathi Anita , Mangrauthia Satendra Kumar , Sanan-Mishra Neeti 
Published: January 2021

AbstractRNA silencing is as an adaptive immune response in plants that limits accumulation or spread of invading viruses. Successful virus infection entails countering the RNA silencing for efficient replication and systemic spread in the host. The viruses encode proteins having the ability to suppress or block the host silencing mechanism, resulting in severe pathogenic symptoms and diseases. Tungro virus disease caused by a complex of two viruses provides an excellent system to understand these host and virus interactions during infection. It is known thatRice tungro bacilliform virus(RTBV) is the major determinant of the disease whileRice tungro spherical virus(RTSV) accentuates the symptoms. This study brings to focus the important role of RTBV ORF-IV in Tungro disease manifestation, by acting as both the victim and silencer of the RNA silencing pathway. The ORF-IV is a weak suppressor of the S-PTGS or pre-established stable silencing but its suppression activity is augmented in the presence of RTSV proteins. The RTBV and RTSV proteins interact to suppress localized silencing as well as spread of silencing, in the host plants.
(p)ppGpp inhibits 70S ribosome formation inStaphylococcus aureusby impeding GTPase-ribosome interactions
Authors: Bennison Daniel J. , Nakamoto Jose A. , Craggs Timothy D. , Milón Pohl , Rafferty John B. , Corrigan Rebecca M. 
Published: January 2021

ABSTRACTDuring nutrient limitation, bacteria produce the alarmones (p)ppGpp as effectors of the stress signalling network termed the stringent response. Screening for (p)ppGpp-binding targets withinStaphylococcus aureusidentified four ribosome-associated GTPases (RA-GTPases), RsgA, RbgA, Era and HflX, each of which are cofactors in ribosome assembly, where they cycle between the ON (GTP-bound) and OFF (GDP-bound) states. Entry into the OFF-state from the ON-state occurs upon hydrolysis of GTP, with GTPase activity increasing substantially upon ribosome association. When bound to (p)ppGpp, GTPase activity is inhibited, reducing 70S ribosome assembly. Here, we sought to determine how (p)ppGpp impacts RA-GTPase-ribosome interactions by examining the affinity and kinetics of binding between RA-GTPases and ribosomes in various nucleotide-bound states. We show that RA-GTPases preferentially bind to 5′-diphosphate-containing nucleotides GDP and ppGpp over GTP, which is likely exploited as a regulatory mechanism within the cell. Binding to (p)ppGpp reduces stable association of RA-GTPases to ribosomal subunits compared to the GTP-bound state bothin vitroand within bacterial cells by inducing the OFF-state conformation. We propose that in this conformation, the G2/switch I loop adopts a conformation incompatible with ribosome association. Altogether, we highlight (p)ppGpp-mediated inhibition of RA-GTPases as a major mechanism of stringent response-mediated growth control.
Intron-mediated induction of phenotypic heterogeneity
Authors: Lukačišin Martin , Espinosa-Cantú Adriana , Bollenbach Tobias 
Published: January 2021

AbstractIntrons are universally present in the nuclear genomes of eukaryotes1. The budding yeast, an otherwise intron-poor species, preserves two sets of ribosomal protein (RP) genes differing primarily in their introns2–4. Despite recent findings on the role of RP introns under stress and starvation5–7, understanding the contribution of introns to ribosome regulation remains challenging. Here, combining isogrowth profiling8with single-cell protein measurements9, we found that introns can mediate inducible phenotypic heterogeneity conferring a clear fitness advantage. Osmotic stress leads to bimodal expression of the small ribosomal subunit protein Rps22B, mediated by an intron in the 5’ untranslated region of its transcript. The two resulting yeast subpopulations differ in their ability to cope with starvation. Low Rps22B protein levels resulted in prolonged survival under sustained starvation, while high Rps22B levels enabled cells to grow faster after transient starvation. Further, yeast growing at high sugar concentrations – similar to those in ripe grapes – exhibit bimodal Rps22B expression when approaching stationary phase. Differential intron-mediated regulation of RP genes thus provides a way to diversify the population when starvation looms in natural environments. Our findings reveal a new role for introns in inducing phenotypic heterogeneity in changing environments and suggest that duplicated RP genes in yeast contribute to resolving the evolutionary conflict between precise expression control and environmental responsiveness10.
BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2
Authors: Samelson Avi J. , Tran Quang Dinh , Robinot Rémy , Carrau Lucia , Rezelj Veronica V. , Kain Alice Mac , Chen Merissa , Ramadoss Gokul N. , Guo Xiaoyan , Lim Shion A. , Lui Irene , Nunez James , Rockwood Sarah J. , Wang Jianhui , Liu Na , Carlson-Stevermer Jared , Oki Jennifer , Maures Travis , Holden Kevin , Weissman Jonathan S. , Wells James A. , Conklin Bruce R. , TenOever Benjamin R. , Chakrabarti Lisa A. , Vignuzzi Marco , Tian Ruilin , Kampmann Martin 
Published: January 2021

AbstractSARS-CoV-2 infection of human cells is initiated by the binding of the viral Spike protein to its cell-surface receptor ACE2. We conducted a targeted CRISPRi screen to uncover druggable pathways controlling Spike protein binding to human cells. We found that the protein BRD2 is required forACE2transcription in human lung epithelial cells and cardiomyocytes, and BRD2 inhibitors currently evaluated in clinical trials potently block endogenousACE2expression and SARS-CoV-2 infection of human cells, including those of human nasal epithelia. Moreover, pharmacological BRD2 inhibition with the drug ABBV-744 inhibited SARS-CoV-2 replication in Syrian hamsters. We also found that BRD2 controls transcription of several other genes induced upon SARS-CoV-2 infection, including the interferon response, which in turn regulates the antiviral response. Together, our results pinpoint BRD2 as a potent and essential regulator of the host response to SARS-CoV-2 infection and highlight the potential of BRD2 as a novel therapeutic target for COVID-19.
UniverSC: a flexible cross-platform single-cell data processing pipeline
Authors: Kelly S. Thomas , Battenberg Kai , Hetherington Nicola A. , Hayashi Makoto , Minoda Aki 
Published: January 2021

AbstractSingle-cell RNA-sequencing analysis to quantify RNA molecules in individual cells has become popular owing to the large amount of information one can obtain from each experiment. We have developed UniverSC (https://github.com/minoda-lab/universc), a universal single-cell processing tool that supports any UMI-based platform. Our command-line tool enables consistent and comprehensive integration, comparison, and evaluation across data generated from a wide range of platforms.
Bazooka/Par3 cooperates with Sanpodo for the assembly of Notch signaling clusters following asymmetric division ofDrosophilasensory organ precursor cells
Authors: Houssin Elise , Pinot Mathieu , Bellec Karen , Le Borgne Roland 
Published: January 2021

SummaryIn multiple cell lineages, Delta-Notch signaling regulates cell fate decisions owing to unidirectional signaling between daughter cells. InDrosophilapupal sensory organ lineage, Notch regulates pIIa/pIIb fate decision at cytokinesis. Notch and Delta that localize apically and basally at the pIIa-pIIb interface, are expressed at low levels and their residence time at the plasma membrane is in the order of the minute. How Delta can effectively interact with Notch to trigger signaling from a large plasma membrane remains poorly understood. Here, we report that the signaling interface possesses a unique apicobasal polarity with Par3/Bazooka localizing in the form of nano-clusters at the apical and basal level. Notch is preferentially targeted to the pIIa-pIIb interface where it co-clusters with Bazooka and the Notch cofactor Sanpodo. Clusters whose assembly relies on Bazooka and Sanpodo activities, are also positive for Neuralized, the E3 ligase required for Delta-activity. We propose that the nano-clusters act as snap buttons at the new pIIa-pIIb interface to allow efficient intra-lineage signaling.
freqpcr: estimation of population allele frequency using qPCR ΔΔCq measures from bulk samples
Authors: Sudo Masaaki , Osakabe Masahiro 
Published: January 2021

AbstractPCR techniques, both quantitative (qPCR) and non-quantitative, have been used to estimate allele frequency in a population. However, the labor required to sample numerous individuals, and subsequently handle each sample, makes quantification of rare mutations, including pesticide resistance genes at the early stages of resistance development, challenging. Meanwhile, pooling DNA from multiple individuals as a “bulk sample” may reduce handling costs. The qPCR output for a bulk sample, however, contains uncertainty owing to variations in DNA yields from each individual, in addition to measurement errors. In this study, we developed a statistical model for the interval estimation of allele frequency using ΔΔCq-based qPCR analyses of multiple bulk samples collected from a population. We assumed a gamma distribution as the individual DNA yield and developed an R package for parameter estimation, which was verified with real DNA samples from acaricide-resistant spider mites, as well as a numerical simulation. Our model resulted in unbiased point estimates of the allele frequency compared with simple averaging of the ΔΔCq values, while their confidence intervals suggest that collecting and pooling additional samples from individuals may produce higher precision than individual PCR tests with moderate sample sizes.
Xanthomonastranscriptome inside cauliflower hydathodes reveals bacterial virulence strategies and physiological adaptation at early infection stages
Authors: Luneau Julien S. , Cerutti Aude , Roux Brice , Carrère Sébastien , Jardinaud Marie-Françoise , Gaillac Antoine , Gris Carine , Lauber Emmanuelle , Berthomé Richard , Arlat Matthieu , Boulanger Alice , Noël Laurent D. 
Published: January 2021

AbstractXanthomonas campestrispv.campestris(Xcc) bacterium is a seed-transmitted vascular pathogen causing black rot disease on cultivated and wildBrassicaceae. Xccenters the plant tissues preferentially via hydathodes which are organs localized at leaf margins. In order to decipher both physiological and virulence strategies deployed byXccduring early stages of infection, the transcriptomic profile ofXccwas analyzed three days after entry into cauliflower hydathodes. Despite the absence of visible plant tissue alterations and a bacterial biotrophic lifestyle, 18% ofXccgenes undergo a transcriptional reprogramming, including a striking repression of chemotaxis and motility functions.Xccfull repertoire of virulence factors was not yet activated but the expression of the 95-gene HrpG regulon, including genes coding for the type three secretion machinery important for suppression of plant immunity, was induced. The expression of genes involved in metabolic adaptations such as catabolism of plant compounds, transport functions, sulfur and phosphate metabolism was upregulated while limited stress responses were observed three days post infection. These transcriptomic observations give information about the nutritional and stress status of bacteria during the early biotrophic infection stages and help to decipher the adaptive strategy ofXccto the hydathode environment.