bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-spike antibody response to natural infection with SARS-CoV-2 and its activity against emerging variants
Authors: Chen Cheng-Pin , Huang Kuan-Ying A. , Shih Shin-Ru , Lin Yi-Chun , Cheng Chien-Yu , Huang Yhu-Chering , Lin Tzou-Yien , Cheng Shu-Hsing 
Published: March 2022

AbstractThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has substantially impacted human health globally. Spike-specific antibody response plays a major role in protection against SARS-CoV-2. Here, we demonstrated that acute SARS-CoV-2 infection elicits rapid and robust spike-binding and ACE2-blocking antibody responses, which wane approximately 11 months after infection. Serological responses were found to be correlated with the frequency of spike-specific memory B cell responses to natural infections. Further, significantly higher spike-binding, ACE2-blocking, and memory B cell responses were detected in patients with fever and pneumonia. Spike-specific antibody responses were found to be greatly affected by spike mutations in emerging variants, especially the Beta and Omicron variants. These results warrant continued surveillance of spike-specific antibody responses to natural infections and highlight the importance of maintaining functional anti-spike antibodies through immunization.ImportanceAs spike protein-specific antibody responses play a major role in protection against SARS-CoV-2, we examined the spike-binding and ACE2-blocking antibody responses in SARS-CoV-2 infection at different time points. We found robust responses following acute infection, which waned approximately 11 months after infection. Further, the serological responses were correlated with the frequency of spike-specific memory B cell responses to natural infections. Patients with fever and pneumonia showed significantly stronger spike-binding, ACE2-blocking antibody, and memory B cell responses. Moreover, the spike-specific antibody responses were substantially affected by the emerging variants, especially the Beta and Omicron variants. These results warrant continued surveillance of spike-specific antibody responses to natural infections and highlight the importance of maintaining functional anti-spike antibodies through immunization.
Skeletal Muscle TFEB Signaling Promotes Central Nervous System Function and Reduces Neuroinflammation during Aging and Neurodegenerative Disease
Authors: Matthews Ian , Birnbaum Allison , Gromova Anastasia , Huang Amy W. , Liu Kailin , Liu Eleanor A. , Coutinho Kristen , McGraw Megan , Patterson Dalton C. , Banks Macy T. , Nobles Amber C. , Nguyen Nhat , Merrihew Gennifer E. , Wang Lu , Baeuerle Eric , Fernandez Elizabeth , Musi Nicolas , MacCoss Michael J. , Miranda Helen C. , La Spada Albert R. , Cortes Constanza J. 
Published: March 2022

SummarySkeletal muscle has recently arisen as a novel regulator of Central Nervous System (CNS) function and aging, secreting bioactive molecules known as myokines with metabolism-modifying functions in targeted tissues, including the CNS. Here we report the generation of a novel transgenic mouse with enhanced skeletal muscle lysosomal and mitochondrial function via targeted overexpression of Transcription Factor E-B (TFEB). We have discovered that the resulting geroprotective effects in skeletal muscle reduce neuroinflammation and the accumulation of tau-associated pathological hallmarks in a mouse model of tau pathology. Muscle-specific TFEB overexpression also significantly ameliorates proteotoxicity, reduces neuroinflammation and promotes transcriptional remodeling of the aged CNS, preserving cognition and memory in aged mice. Our results implicate the maintenance of skeletal muscle function throughout aging to direct regulation of CNS health and disease, and suggest that skeletal-muscle originating factors may act as novel therapeutic targets against age-associated neurodegenerative disorders.
The genomic landscapes of desert birds form over multiple time scales
Authors: Provost Kaiya , Shue Stephanie Yun , Forcellati Meghan , Smith Brian Tilston 
Published: March 2022

AbstractSpatial models show that genetic differentiation between populations can be explained by factors ranging from geographic distance to environmental resistance across the landscape. However, genomes exhibit a landscape of differentiation, which could indicate that multiple spatial models better explain divergence in different portions of the genome. We test whether alternative geographic predictors of intraspecific differentiation vary across the genome in ten bird species that co-occur in Sonoran and Chihuahuan Deserts of North America. Using population-level genomic data, we characterized the genomic landscapes across species and modeled five predictors that represented historical and contemporary mechanisms. The characteristics of genomic landscapes differed across the ten species, influenced by varying levels of population structuring and admixture between deserts. General dissimilarity matrix modeling indicated that the best-fit models differed from the whole genome and partitions along the genome. Almost all of the historical and contemporary mechanisms were important in explaining genetic distance, but particularly historical and contemporary environment, while contemporary abundance, position of the barrier to gene flow, and distance explained relatively less. Individual species have significantly different patterns of genomic variation. These results illustrate that the genomic landscape of differentiation was influenced by alternative geographic factors operating on different portions of the genome.
Gender-based disparities and biases in science: an observational study of a virtual conference
Authors: Zhang Junhanlu , Torchet Rachel , Julienne Hanna 
Published: March 2022

AbstractSuccess in STEM (Science, Technology, Engineering, and Math) remains influenced by race, gender, and socioeconomic status. Here, we focus on the impact of gender on question-asking behavior during the 2021 JOBIM virtual conference (Journées Ouvertes en Biologie et Mathématiques). We gathered quantitative and qualitative data including : demographic information, question asking motivations, live observations and interviews of participants. Quantitative analyses include unprecedented figures such as the fraction of the audience identifying as LGBTQIA+ and an increased attendance of women in virtual conferences. Although parity was reached in the audience, women asked half as many questions as men. This under-representation persisted after accounting for seniority of the asker. Interviews of participants highlighted several barriers to oral expression encountered by women and gender minorities : negative reactions to their speech, discouragement to pursue a career in research, and gender discrimination/sexual harassment. Informed by the study,guidelinesfor conference organizers have been written.
Alnustone inhibits Streptococcus pneumoniae virulence by targeting pneumolysin and sortase A
Authors: Zhang Can , Wang Xinyu , Shi Linlin , Zhan Baihe , Hou NaNa , Liu Suohong , Bao Manjie , Chi Gefu , Fang Tianqi 
Published: March 2022

AbstractStreptococcus pneumoniae (S. pneumoniae) is a significant Gram-positive opportunistic pathogen responsible for a variety of lethal infections. This bacterium accounts for more deaths from diseases than any other single pathogen worldwide. Distinctively, these symptoms arise despite effective antibiotic therapy. This study unveiled a novel mechanism of resistance to S. pneumoniae infection by targeting pneumolysin (PLY) and sortase A (Srt A), the key virulence factors of S. pneumoniae. Through protein phenotype assays, we found alnustone to be a potent drug that inhibits both PLY and Srt A. Using a PLY-mediated hemolysis assay, we found that albumin can effectively reduce Srt A peptidase activity by blocking PLY oligomerization, thereby directly inhibiting PLY-expressing cytolysis. Co-incubation of S. pneumoniae D39 Srt A with small-molecule inhibitors reduces cell wall-bound Nan A (pneumococcal-anchored surface protein Srt A), inhibits biofilm formation, and significantly reduces biomass. But more interestingly, the protective effect of invasive pneumococcal disease (IPD) on murine streptococcus pneumoniae was further demonstrated. Our study proposes a detailed bacteriostatic mechanism of pneumococcal and highlights the major translational potential of targeting circulating PLY and Srt A to protect against pneumococcal infections. Our results suggest that the antiviral strategy of directly targeting PLY and Srt A with alnustone is a promising treatment option for Streptococcus pneumoniae and that alnustone can be used as an effective inhibitor of PLY and Srt A.
Aerosolized Ad5-nCoV booster vaccination elicited potent immune response against the SARS-CoV-2 Omicron variant after inactivated COVID-19 vaccine priming
Authors: Zhang Zhe , Wu Shipo , Liu Yawei , Li Kailiang , Fan Pengfei , Song Xiaohong , Wang Yudong , Zhao Zhenghao , Zhang Xianwei , Shang Jin , Zhang Jinlong , Xu Jinghan , Li Yao , Li Yaohui , Zhang Jipeng , Fu Kefan , Wang Busen , Hao Meng , Zhang Guanying , Long Pengwei , Qiu Ziyu , Zhu Tao , Liu Shuling , Zhang Yue , Shao Fangze , Lv Peng , Yang Yilong , Zhao Xiaofan , Sun Yufa , Hou Lihua , Chen Wei 
Published: March 2022

AbstractThe SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant around the world and exhibits immune escape to current COVID-19 vaccines to some extent due to its numerous spike mutations. Here, we evaluated the immune responses to booster vaccination with intramuscular adenovirus-vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines 6 months prior. We found that the Ad5-nCoV booster induced potent neutralizing activity against the wild-type virus and Omicron variant, while aerosolized Ad5-nCoV generated the greatest neutralizing antibody responses against the Omicron variant at day 28 after booster vaccination, at 14.1-fold that of CoronaVac, 5.6-fold that of ZF2001 and 2.0-fold that of intramuscular Ad5-nCoV. Similarly, the aerosolized Ad5-nCoV booster produced the greatest IFNγ T-cell response at day 14 after booster vaccination. The IFNγ T-cell response to aerosolized Ad5-nCoV was 12.8-fold for CoronaVac, 16.5-fold for ZF2001, and 5.0-fold for intramuscular Ad5-nCoV. Aerosolized Ad5-nCoV booster also produced the greatest spike-specific B cell response. Our findings suggest that inactivated vaccine recipients should consider adenovirus-vectored vaccine boosters in China and that aerosolized Ad5-nCoV may provide a more efficient alternative in response to the spread of the Omicron variant.
Trends and factors associated with initiation of HIV treatment and uptake of viral load testing among PLHIV in Jamaica
Authors: Cushnie Anya , Reintjes Ralf , Artama Miia , Figueroa J. Peter 
Published: March 2022

AbstractIntroductionJamaica did not achieve the UNAIDS 90-90-90 targets in 2020. This study aims to examine trends and factors associated with uptake of HIV treatment and viral load testing among people living with HIV (PLHIV) in Jamaica, to make recommendations for improving patient management and outcomes.MethodsThis secondary analysis uses patient-level data from the National Treatment Service Information System. The baseline sample is PLHIV initiating anti-retroviral treatment (ART) between January 2015-December 2019. Descriptive statistics are used to summarize demographic and clinical variables. Multivariable logistic regression is used to assess factors associated with ART initiation (31+ days vs. same day) and viral load testing uptake (viral load test vs. no test), using categorical variables for age group, gender and regional health authority. Adjusted odds ratios and 95% confidence intervals are reported.ResultsSame day ART initiation increased by 72% over 5 years. The coverage of 1st viral load test was 90% but declined to 79% for the 2nd test. Testing occurred mostly after 0-6 months on ART (n=3047, 55%) and uptake was highest in the South-East Region (n=2885, 53%). Those virally suppressed were significantly more likely to have same day ART initiation compared to those non-suppressed (aOR=1.58, CI=1.43-1.75). Males were significantly more likely to have same day ART initiation (aOR=1.46, CI=1.32-1.62) but no first viral load test (aOR=1.55, CI=1.27-1.90) compared to females.ConclusionThe goal of immediate ART initiation is increasingly being met and is significantly associated with viral suppression at the first viral load test. Males were less likely to have a viral load test after ART initiation. A qualitative assessment should be conducted to understand important challenges faced to access routine viral load testing, followed by implementation of differentiated service care models, targeting males.
Self-injury, suicidal ideation and -attempt and eating disorders in young people following the initial and second COVID-19 lockdown
Authors: Danielsen Stine , Joensen Andrea , Andersen Per Kragh , Madsen Trine , Strandberg-Larsen Katrine 
Published: March 2022

SummaryBackgroundThe initial COVID-19 lockdowns have had negative effect on different mental health measures, especially in young women. However, the impact on self-injury, suicidality and eating disorder (ED) are less elucidated and remains inconsistent. We compare self-reported self-injury, suicide ideation and -attempt and symptoms of EDs from before through different pandemic periods until spring 2021.MethodsYoung participants in the Danish National Birth Cohort reported these measures in an 18-year follow-up in 2015-2021 and in a COVID-19 survey in spring 2021 when participants were aged 19-24 years. Changes in measures from pre to post lockdown were estimated with longitudinal data (N=7,597) and with repeated cross-sectional data (N=24,625) by linear regression.FindingsIn the longitudinal comparisons 14% of women and 7% of men reported self-injury pre lockdown, which decreased 6%-points (95% CI:-7%;-5%) for women and 3%-points (95% CI:-4%;-2%) for men during lockdown. For suicide ideation, the pre lockdown proportions were 25% and 18% for women and men respectively, and decreased 7%-points (95% CI:-8%;-6%) for women and 3%-points (95% CI:-5%;-1%) for men. For suicide attempt no change was observed. Pre lockdown 15% and 3% of women and men, respectively, had symptoms of EDs, which decreased 2%-points (95% CI:-3%;-1%) for women. We observed no changes in proportions of self-injury, suicide ideation or EDs in the repeated cross-sectional data.InterpretationOur findings provide no support for increase in self-injury, suicidality and EDs following the lockdowns, and if anything, indicate a reduction in self-injury and suicide ideation as well as EDs in women.
Donor whole blood DNA methylation is not a strong predictor of acute graft versus host disease in unrelated donor allogeneic haematopoietic cell transplantation
Authors: Webster Amy P. , Ecker Simone , Moghul Ismail , Dhami Pawan , Marzi Sarah , Paul Dirk S. , Kuxhausen Michelle , Lee Stephanie J. , Spellman Stephen R. , Wang Tao , Feber Andrew , Rakyan Vardhman , Peggs Karl S. , Beck Stephan 
Published: March 2022

AbstractAllogeneic hematopoietic cell transplantation (HCT) is used to treat many blood-based disorders and malignancies. While this is an effective treatment, it can result in serious adverse events, such as the development of acute graft-versus-host disease (aGVHD). This study aimed to develop a donor-specific epigenetic classifier that could be used in donor selection in HCT to reduce the incidence of aGVHD.The discovery cohort of the study consisted of 288 donors from a population receiving HLA-A, -B, -C and -DRB1 matched unrelated donor HCT with T cell replete peripheral blood stem cell grafts for treatment of acute leukaemia or myelodysplastic syndromes after myeloablative conditioning. Donors were selected based on recipient aGVHD outcome; this cohort consisted of 144 cases with aGVHD grades III-IV and 144 controls with no aGVHD that survived at least 100 days post-HCT matched for sex, age, disease and GVHD prophylaxis.Genome-wide DNA methylation was assessed using the Infinium Methylation EPIC BeadChip (Illumina), measuring CpG methylation at >850,000 sites across the genome. Following quality control, pre-processing and exploratory analyses, we applied a machine learning algorithm (Random Forest) to identify CpG sites predictive of aGVHD. Receiver operating characteristic (ROC) curve analysis of these sites resulted in a classifier with an encouraging area under the ROC curve (AUC) of 0.91.To test this classifier, we used an independent validation cohort (n=288) selected using the same criteria as the discovery cohort. Different attempts to validate the classifier using the independent validation cohort failed with the AUC falling to 0.51. These results indicate that donor DNA methylation may not be a suitable predictor of aGVHD in an HCT setting involving unrelated donors, despite the initial promising results in the discovery cohort.Our work highlights the importance of independent validation of machine learning classifiers, particularly when developing classifiers intended for clinical use.
The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK
Authors: Hill Verity , Du Plessis Louis , Peacock Thomas P. , Aggarwal Dinesh , Colquhoun Rachel , Carabelli Alesandro M. , Ellaby Nicholas , Gallagher Eileen , Groves Natalie , Jackson Ben , McCrone JT , O’Toole Áine , Price Anna , Sanderson Theo , Scher Emily , Southgate Joel , Volz Erik ,   The COVID-19 genomics UK (COG-UK) consortium, Barclay Wendy S. , Barrett Jeffrey C. , Chand Meera , Connor Thomas , Goodfellow Ian , Gupta Ravindra K. , Harrison Ewan M. , Loman Nicholas , Myers Richard , Robertson David L , Pybus Oliver G , Rambaut Andrew 
Published: March 2022

AbstractThe first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organisation (WHO) as Alpha. Originating in early Autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is more typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK, and the imposition of new restrictions, in particular the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages which preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically-infected individual. We conclude that the last hypothesis provides the best explanation of the observed behaviour and dynamics of the variant, although we find that the individual need not be immunocompromised, as persistently-infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs to each other, and identify that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations, and its lack of rapid evolutionary rate on the ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms) it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence.
Geneticin shows selective antiviral activity against SARS-CoV-2 by interfering with programmed -1 ribosomal frameshifting
Authors: Varricchio Carmine , Mathez Gregory , Pillonel Trestan , Bertelli Claire , Kaiser Laurent , Tapparel Caroline , Brancale Andrea , Cagno Valeria 
Published: March 2022

SummarySARS-CoV-2 is currently causing an unprecedented pandemic. While vaccines are massively deployed, we still lack effective large-scale antiviral therapies. In the quest for antivirals targeting conserved structures, we focused on molecules able to bind viral RNA secondary structures. Aminoglycosides are a class of antibiotics known to interact with the ribosomal RNA of both prokaryotes and eukaryotes and have previously been shown to exert antiviral activities by interacting with viral RNA. Here we show that the aminoglycoside geneticin is endowed with antiviral activity against all tested variants of SARS-CoV-2, in different cell lines and in a respiratory tissue model at non-toxic concentrations. The mechanism of action is an early inhibition of RNA replication and protein expression related to a decrease in the efficiency of the -1 programmed ribosomal frameshift (PRF) signal of SARS-CoV-2. Using in silico modelling, we have identified a potential binding site of geneticin in the pseudoknot of frameshift RNA motif. Moreover, we have selected, through virtual screening, additional RNA binding compounds, interacting with the same site with increased potency.
Flexible estimation of biodiversity with short-range multispectral imaging in a temperate grassland
Authors: Jackson J. , Lawson C. S. , Adelmant C. , Huhtala E. , Fernandes P. , Hodgson R. , King H. , Williamson L. , Maseyk K. , Hawes N. , Hector A. , Salguero-Gómez R 
Published: March 2022

AbstractImage sensing technologies are rapidly increasing the cost-effectiveness of biodiversity monitoring efforts. Species differences in the reflectance of electromagnetic radiation have recently been highlighted as a promising target to estimate plant biodiversity using multispectral image data.However, these efforts are currently hampered by logistical difficulties in broad-scale implementation and their use in characterizing biodiversity at different spatial scales.Here, we investigate the utility of multispectral imaging technology from commercially available unmanned aerial vehicles (UAVs, or drones) in estimating biodiversity metrics at short-range (<10 m image recording height) in a temperate calcareous grassland ecosystem in Oxfordshire, UK. We calculate a suite of moments (coefficient of variation, standard deviation, skew, kurtosis) for the distribution of radiance from multispectral images at five wavelength bands (Blue 450±16 nm; Green 560±16 nm; Red 650±16 nm; Red Edge 730±16 nm; Near Infrared 840±16 nm) and test their effectiveness at estimating ground-truthed biodiversity metrics fromin-situbotanical surveys for 37 - 1 m × 1 m quadrats.We find positive associations between the average coefficient of variation in spectral radiance and both the Shannon-Weiner and Simpsons biodiversity indices. Furthermore, we find that the average coefficient of variation in spectral radiance is consistent and highly repeatable, across sampling days and recording heights. Positive associations with biodiversity indices hold irrespective of the image recording height (2-8 m), but we report reductions in estimates of spectral diversity with increases to UAV recording height. UAV imaging reduced sampling time by 16-fold relative toin-situbotanical surveys.Synthesis- We demonstrate the utility of multispectral radiance moments as an indicator of grassland biodiversity metrics at high spatial resolution using a widely available UAV monitoring system at a coarse spectral resolution. The use of UAV technology with multispectral sensors has far-reaching potential to provide cost-effective and high-resolution monitoring of biodiversity in complex environments.