bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibodies to SARS-CoV-2 are associated with protection against reinfection
Authors: Lumley Sheila F , O’Donnell Denise , Stoesser Nicole E , Matthews Philippa C , Howarth Alison , Hatch Stephanie B , Marsden Brian D , Cox Stuart , James Tim , Warren Fiona , Peck Liam J , Ritter Thomas G , de Toledo Zoe , Warren Laura , Axten David , Cornall Richard J , Jones E Yvonne , Stuart David I , Screaton Gavin , Ebner Daniel , Hoosdally Sarah , Chand Meera ,   Oxford University Hospitals Staff Testing Group, Crook Derrick W , O’Donnell Anne-Marie , Conlon Christopher P , Pouwels Koen B , Walker A Sarah , Peto Tim EA , Hopkins Susan , Walker Timothy M , Jeffery Katie , Eyre David W 
Published: November 2020

AbstractBackgroundIt is critical to understand whether infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) protects from subsequent reinfection.MethodsWe investigated the incidence of SARS-CoV-2 PCR-positive results in seropositive and seronegative healthcare workers (HCWs) attending asymptomatic and symptomatic staff testing at Oxford University Hospitals, UK. Baseline antibody status was determined using anti-spike and/or anti-nucleocapsid IgG assays and staff followed for up to 30 weeks. We used Poisson regression to estimate the relative incidence of PCR-positive results and new symptomatic infection by antibody status, accounting for age, gender and changes in incidence over time.ResultsA total of 12219 HCWs participated and had anti-spike IgG measured, 11052 were followed up after negative and 1246 after positive antibody results including 79 who seroconverted during follow up. 89 PCR-confirmed symptomatic infections occurred in seronegative individuals (0.46 cases per 10,000 days at risk) and no symptomatic infections in those with anti-spike antibodies. Additionally, 76 (0.40/10,000 days at risk) anti-spike IgG seronegative individuals had PCR-positive tests in asymptomatic screening, compared to 3 (0.21/10,000 days at risk) seropositive individuals. Overall, positive baseline anti-spike antibodies were associated with lower rates of PCR-positivity (with or without symptoms) (adjusted rate ratio 0.24 [95%CI 0.08-0.76, p=0.015]). Rate ratios were similar using anti-nucleocapsid IgG alone or combined with anti-spike IgG to determine baseline status.ConclusionsPrior SARS-CoV-2 infection that generated antibody responses offered protection from reinfection for most people in the six months following infection. Further work is required to determine the long-term duration and correlates of post-infection immunity.
Extracellular vesicles from human adipose stem cells are neuroprotective after stroke in rats
Authors: Rohden Francieli , Teixeira Luciele Varaschini , Bernardi Luis Pedro , Ferreira Marques Nicolly Paz , Colombo Mariana , Teixeira Geciele Rodrigues , dos Santos de Oliveira Fernanda , Cirne Lima Elizabeth Obino , Rodrigues Guma Fátima Costa , Souza Diogo Onofre 
Published: November 2020

ABSTRACTIschemic stroke is a prominent cause of death and disability, demanding innovative therapeutic strategies. Accordingly, extracellular vesicles (EVs) released from mesenchymal stem cells are promising tools for stroke treatment. In this study, we evaluated the potential neuroprotective properties of EVs released from human adipose tissue stem cells (hAT-MSC), which were obtained from a healthy individual submitted to liposuction. A single intranasal EVs administration was performed 24 h after the ischemic stroke in rats. The EVs brain penetration and the tropism to brain zone of ischemia was observed 18 h after administration. Thus, we measured EVs neuroprotection against the ischemic stroke-induced impairment on long-term motor and behavioral performance. Indeed, one single intranasal EVs administration reversed the stroke damages on: i) front paws symmetry; ii) working memory, short- and long-term memory; iii) anxiety-like behavior. These findings highlight hAT-MSC-derived EVs as a promising therapeutic strategy in stroke.
Bat influenza vectored NS1-truncated live vaccine protects pigs against heterologous virus challenge
Authors: Lee Jinhwa , Li Yonghai , Li Yuhao , Cino-Ozuna A. Giselle , Duff Michael , Lang Yuekun , Ma Jingjiao , Sunwoo Sunyoung , Richt Juergen A. , Ma Wenjun 
Published: November 2020

AbstractSwine influenza is an important disease for the swine industry. Currently used whole inactivated virus (WIV) vaccines can induce vaccine-associated enhanced respiratory disease (VAERD) in pigs when the vaccine strains mismatch with the infected viruses. Live attenuated influenza virus vaccine (LAIV) is effective to protect pigs against homologous and heterologous swine influenza virus infections without inducing VAERD, but has safety concerns due to potential reassortment with circulating viruses. Herein, we used a chimeric bat influenza Bat09:mH3mN2 virus, which contains both surface HA and NA gene open reading frames of the A/swine/Texas/4199-2/1998 (H3N2) and six internal genes from the novel bat H17N10 virus, to develop modified live-attenuated viruses (MLVs) as vaccine candidates which cannot reassort with canonical influenza A viruses by co-infection. Two attenuated MLV vaccine candidates including the virus that expresses a truncated NS1 (Bat09:mH3mN2-NS1-128, MLV1) or expresses both a truncated NS1 and the swine IL-18 (Bat09:mH3mN2-NS1-128-IL-18, MLV2) were generated and evaluated in pigs against a heterologous H3N2 virus using the WIV vaccineb as a control. Compared to the WIV vaccine, both MLV vaccines were able to reduce lesions and virus replication in lungs and limit nasal virus shedding without VAERD, also induced significantly higher levels of mucosal IgA response in lungs and significantly increased numbers of antigen-specific IFN-γ secreting cells against the challenge virus. However, no significant difference was observed in efficacy between the MLV1 and MLV2. These results indicate that bat influenza vectored MLV vaccines can be used as a safe live vaccine to prevent swine influenza.
Transgenerational Regulation of Sexual Attractiveness inC. elegansNematodes
Authors: Toker Itai Antoine , Lev Itamar , Mor Yael , Gurevich Yael , Fisher Doron , Houri-Zeevi Leah , Antonova Olga , Hadany Lilach , Shaham Shai , Rechavi Oded 
Published: November 2020

AbstractIt is unknown whether transient transgenerational epigenetic responses to environmental challenges affect the process of evolution, which typically unfolds over many generations. Here we show that inC. elegans, inherited small RNAs shape the hard-wired genome and control genetic variation by regulating the decision of whether to self-fertilize or outcross. We found that under stressful temperatures younger hermaphrodites secrete a male-attracting pheromone. Attractiveness transmits transgenerationally to unstressed progeny via heritable small RNAs and the Argonaute Heritable-RNAi-Deficient-1. We identified an endogenous small interfering RNA pathway, enriched in endo-siRNAs which target sperm genes, that transgenerationally regulates sexual attraction, male prevalence, and outcrossing rates. Multigenerational mating competitions and mathematical simulations revealed that over generations, animals that inherit attractiveness mate more, and their alleles spread in the population. We propose that sperm serves as a “stress sensor” which, via small RNA inheritance, can promote outcrossing in challenging environments, when increasing genetic variation is advantageous.
Forecasting the spread of COVID19 in Hungary
Authors: Khanday Owais Mujtaba , Dadvandipour Samad , Lone Mohd. Aaqib 
Published: November 2020

AbstractTime series analysis of the COVID19/ SARS-CoV-2 spread in Hungary is presented. Different methods effective for short-term forecasting are applied to the dataset, and predictions are made for the next 20 days. Autoregression and other exponential smoothing methods are applied to the dataset. SIR model is used and predicted 64% of the population could be infected by the virus considering the whole population is susceptible to be infectious Autoregression, and exponential smoothing methods indicated there would be more than a 60% increase in the cases in the coming 20 days. The doubling of the number of total cases is found to around 16 days using an effective reproduction number.
Common allotypes of ER aminopeptidase 1 have substrate-dependent and highly variable enzymatic properties
Authors: Hutchinson Jonathan P. , Temponeras Ioannis , Kuiper Jonas , Cortes Adrian , Korczynska Justyna , Kitchen Semra , Stratikos Efstratios 
Published: November 2020

AbstractObjectivePolymorphic variation of immune system proteins can drive variability of individual immune responses. ER aminopeptidase 1 (ERAP1) generates antigenic peptides for presentation by MHC class I molecules. Coding single nucleotide polymorphisms (SNPs) inERAP1have been associated with predisposition to inflammatory rheumatic disease and shown to affect functional properties of the enzyme, but the interplay between combinations of these SNPs as they exist in allotypes, has not been thoroughly explored.MethodsWe used phased genotype data to estimate ERAP1 allotype frequency in 2,504 individuals across five major human populations, generated highly pure recombinant enzymes corresponding to the 10 most common ERAP1 allotypes and systematically characterized theirin vitroenzymatic properties.ResultsWe find that ERAP1 allotypes possess a wide range of enzymatic activities, up to 60-fold, whose ranking is substrate-dependent. Strikingly, allotype 10, previously associated with Behçet’s disease, is consistently a low-activity outlier, suggesting that a significant percentage of individuals carry a sub-active ERAP1 gene. Enzymatic analysis revealed that ERAP1 allotypes can differ in both catalytic efficiency and substrate affinity, differences that can change intermediate accumulation in multi-step trimming reactions. Alterations in efficacy of an allosteric inhibitor that targets the regulatory site suggest that allotypic variation influences the communication between the regulatory and the active site.ConclusionOur work defines the wide landscape of ERAP1 activity in human populations and demonstrates how common allotypes can induce substrate-dependent variability in antigen processing, thus contributing, in synergy with MHC haplotypes, to immune response variability and to predisposition to chronic inflammatory conditions.
Genetic and pharmacological manipulations of glyoxalase 1 mediate ethanol withdrawal seizure susceptibility in mice
Authors: Barkley-Levenson Amanda M. , Lee Amy , Palmer Abraham A. 
Published: November 2020

AbstractCentral nervous system (CNS) hyperexcitability is a clinically significant feature of acute ethanol withdrawal. There is evidence for a genetic contribution to withdrawal severity, but specific genetic risk factors have not be identified. The gene glyoxalase 1(Glo1)has been previously implicated in ethanol consumption in mice, and GLO1 inhibition can attenuate drinking in mice and rats. Here, we investigated whether genetic and pharmacological manipulations of GLO1 activity can also mediate ethanol withdrawal seizure severity in mice. Mice from two transgenic lines overexpressingGlo1on different genetic backgrounds (C57BL/6J [B6] and FVB/NJ [FVB]) were tested for handling induced convulsions (HICs) as a measure of acute ethanol withdrawal. Following an injection of 4 g/kg alcohol, both B6 and FVB mice overexpressingGlo1showed increased HICs compared to wild type littermates, though only the FVB line showed a statistically significant difference. We also administered daily ethanol injections (2 g/kg + 9 mg/kg 4-methylpyrazole) to wild type B6 mice for 10 days and tested them for HICs on the 10thday, following treatment with either vehicle or a GLO1 inhibitor (S-bromobenzylglutathione cyclopentyl diester [pBBG]). Treatment with pBBG reduced HICs, although this effect was only statistically significant following two 10-day cycles of ethanol exposure and withdrawal. These results provide converging genetic and pharmacological evidence that GLO1 can mediate ethanol withdrawal seizure susceptibility. We discuss the possible role of GLO1’s substrate, methylglyoxal, acting as an agonist at GABAAreceptors.
Cisregulation within a cluster of viral microRNAs
Authors: Vilimova Monika , Contrant Maud , Randrianjafy Ramy , Dumas Philippe , Elbasani Endrit , Ojala Päivi , Pfeffer Sébastien , Fender Aurélie 
Published: November 2020

ABSTRACTMicroRNAs (miRNAs) are small regulatory RNAs involved in virtually all biological processes. Although many of them are co-expressed from clusters, little is known regarding the impact of this organization on the regulation of their accumulation. In this study, we set to decipher a regulatory mechanism controlling the expression of the ten clustered pre-miRNAs from Kaposi’s sarcoma associated herpesvirus (KSHV). We measuredin vitrothe efficiency of cleavage of each individual pre-miRNA by the Microprocessor and found that pre-miR-K1 and -K3 were the most efficiently cleaved pre-miRNAs. A mutational analysis showed that, in addition to producing mature miRNAs, they are also important for the optimal expression of the whole set of miRNAs. We showed that this feature depends on the presence of a canonical pre-miRNA at this location since we could functionally replace pre-miR-K1 by a heterologous pre-miRNA. Furtherin vitroprocessing analysis suggests that the two stem-loops act incisand that the cluster is cleaved in a sequential manner. Finally, we exploited this characteristic of the cluster to inhibit the expression of the whole set of miRNAs by targeting the pre-miR-K1 with LNA-based antisense oligonucleotides in cells either expressing a synthetic construct or latently infected with KSHV.
Effect of the BMPR-II-SMAD3/MRTF complex on proliferation and migration of ASMCs and the mechanism in asthma
Authors: Gu Wenbo , Lei Jiahui , Xie Jing , Xiao Yali , Zhang Zhenping , Zhao Limin 
Published: November 2020

AbstractPhenotype transformation of airway smooth muscle (ASM) is the key feature of airway remodelling in asthma. A variety of smooth muscle-specific genes and proteins, including SMAD3, BMPR-II, and MRTF, are involved in airway remodelling in asthma. Bone morphogenetic protein (BMP) signalling plays an important role in the physiological and pathological processes of asthma. As a receptor of BMP signalling, BMPR-II has important roles in variety of cellular processes. However, the understanding of the roles and underlying mechanism of BMPR-II in airway smooth muscle cells (ASMCs) in asthma remains incomplete. First, we observed significant increases in BMPR-II, SMAD3 and MRTF in asthmatic ASMCs at both the mRNA and protein levels. Second, we observed that silencing of siBMPR-II and siMRTF inhibits proliferation, migratory capacity and intracellular Ca2+concentration in ASMCs. Furthermore, our results revealed these three factors, BMPR-II, SMAD3 and MRTF, form a complex that affects the bioactivities of ASMCs. Taken together, this study indicates that the BMPR-II-SMAD3/MRTF signalling pathway is involved in the process of ASM remodelling, providing novel avenues for the identification of new therapeutic modalities.
Mixing the Message: Do Dung Beetles (Coleoptera: Scarabaeidae) Affect Dung-Generated Greenhouse Gas Emissions?
Authors: Fowler Fallon , Gillespie Christopher J. , Denning Steve , Hu Shuijin , Watson Wes 
Published: November 2020

AbstractBy mixing and potentially aerating dung, dung beetles may affect the microbes producing the greenhouse gases (GHGs): carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O). Here, their sum-total global warming effect is described as the carbon dioxide equivalent (CO2e). Our literature analysis of reported GHG emissions and statistics suggests that most dung beetles do not, however, reduce CO2e even if they do affect individual GHGs. Here, we compare the GHG signature of homogenized (“premixed”) and unhomogenized (“unmixed”) dung with and without dung beetles to test whether mixing and burial influence GHGs. Mixing by hand or by dung beetles did not reduce any GHG – in fact, tunneling dung beetles increased N2O medians by ≥1.8x compared with dung-only. This suggests that either: 1) dung beetles do not meaningfully mitigate GHGs as a whole; 2) dung beetle burial activity affects GHGs more than mixing alone; or 3) greater dung beetle abundance and activity is required to produce an effect.
Statistical calibration of microbial suspensions in carrier controls during a textile disinfection ring trial
Authors: Monleon-Getino Antonio ,   AC Marca Home Care
Published: November 2020

AbstractIntroductionThe high number of uncontrollable variables in microbiological systems increases experimental complexity and reduces accuracy, potentially leading to data misinterpretation or uncorrectable errors. During an interlaboratory calibration analysis it was observed that the microbial logarithmic reduction (LR) caused by disinfectants depends not only on the type of disinfectant but also on the initial microbial load in the fabric carriers, which can produce a misinterpretation of the results. Fabric carriers are commonly used in standard tests such as EN16616 and ASTM2274.ObjectiveA method based on statistical calibration is proposed using a regression line between N0(initial microbial load in the carrier) and LR to eliminate the influence of one on the other.ResultsAn example withCandida albicansis presented. Once the method was applied, the influence of N0on LR was eliminated and the new LR values can be used for factorial experiments, for example, to check the efficacy of disinfectants or detergents without depending on the microbial load placed in the carrier.
Oscillatory responses to generated and perceived rhythms
Authors: Ostarek Markus , Alday Phillip M. , Gawel Olivia , Wolfgruber Johannes , Knudsen Birgit , Mantegna Francesco , Huettig Falk 
Published: November 2020

AbstractNeural oscillations have been proposed as a mechanism for structure building in language and music. In music, this idea is appealing because of the intuitive mapping between perceptual and neural rhythms. The strongest evidence has come from studies in which participants listened to isochronous sequences of identical tones and were asked to imagine hearing them in binary (march) or ternary meter (waltz). The critical finding was that in addition to increased signal at the frequency corresponding to the tone rate there was increased signal at the imagined meter frequencies. While it is striking that meter tracking was observed without any acoustic cues in the input, rhythm perception was confounded with rhythm imagery involving active generation of rhythmic structure. We conducted two electroencephalography experiments with musicians and non-musicians, teasing apart the effects of rhythm perception and rhythm generation. Evidence for meter-related neural oscillations was only observed in situations where rhythmic structure was actively generated, either via rhythm imagery or in the form of overt behavior (tapping). Thus, our data suggest that mere rhythm perception is not sufficient to elicit oscillations at the meter frequency and that they are instead driven by the active generation of rhythm. This undermines the proposal that neural oscillations constitute a basic structure building mechanism in rhythm perception and raises questions about the role of oscillations in language processing.
Binding of dsRNA byD. melanogasterDicer-2 is substrate-dependent and regulated by Loquacious-PD
Authors: Jonely M. , Singh R. K. , Bass B. L. , Noriega R. 
Published: November 2020

ABSTRACTDrosophila melanogasterDicer-2 is a large, multidomain protein that cleaves double-stranded RNA (dsRNA) into small interfering RNAs in a terminus-dependent manner as part of the RNA interference pathway. We characterize the local binding environment involved in this substrate-selective molecular recognition event by monitoring the time-resolved photophysics of a cyanine dye linked to the dsRNA terminus. We observe substantial changes in the molecular rigidity and local freedom of motion of the probe as a function of distinct conformations of the biomolecular complex between Dicer-2 and dsRNA as a function of dsRNA termini, the presence of regulatory proteins, and the addition of a biochemical energy source (ATP) or a non-hydrolysable equivalent (ATP-γS). With a clustering analysis based solely on these molecular-scale measures of the local binding environment at the dsRNA terminus, we identify sub-populations of similar conformations that define distinct modes of molecular recognition which are correlated with biochemical activity. These observations reveal the important role of substrate-selective molecular recognition properties for proteins with multiple domains that can bind RNA, regulatory proteins, and cofactors.STATEMENT OF SIGNIFICANCEThe molecular-scale determinants of protein-RNA binding remain elusive, particularly when different subunits of a single protein confer specificity toward small structural differences of their RNA partners. An important case is that ofDrosophila melanogasterDicer-2, a critical component of the antiviral RNA interference response. Dicer-2 discriminates between double stranded RNA with blunt or 3’ overhang termini, a feature suggested to mediate recognition of “self” vs. “non-self” substrates. We study these interactions at the binding site with a fluorescent label at the RNA terminus, monitoring intramolecular and collective measures of flexibility to report on the local environment. Dicer-2 has distinct modes of molecular recognition which are regulated by accessory proteins and ATP, leading to different conformations and tuning biochemical activity.
Asymmetric outcome of community coalescence of seed and soil microbiota during early seedling growth
Authors: Rochefort Aude , Simonin Marie , Marais Coralie , Guillerm-Erckelboudt Anne-Yvonne , Barret Matthieu , Sarniguet Alain 
Published: November 2020

AbstractSeed microbial community constitutes a primary inoculum for plant microbiota assembly. Still, the persistence of seed microbiota when seeds encounter soil during plant emergence and early growth is barely documented. Here, we characterized the interchange event or coalescence of seed and soil microbiota and how it structured seedling bacterial and fungal communities. We performed eight contrasted coalescence events to identify drivers influencing seedling microbiota assembly: four seed lots of twoBrassica napusgenotypes were sown in two soils of contrasted diversity. We found that seedling root and stem microbiota were influenced by soil diversity but not by initial seed microbiota composition. A strong selection on the two-source communities occurred during microbiota assembly, with only 8-32% of soil taxa and 0.8-1.4% of seed-borne taxa colonizing seedlings. The recruitment of seedling microbiota came mainly from soil (35-72% of diversity) and not from seeds (0.3-15%). The outcome of seed and soil microbiota coalescence is therefore strongly asymmetrical with a dominance of soil taxa. Interestingly, seedling microbiota was primarily composed of initially rare taxa (from seed, soil or unknown origin) and sub-dominant soil taxa. Our results suggest that plant microbiome engineering success based on native seed or soil microbiota will rely on rare and sub-dominant taxa in source communities.