bluuebunny/crossref_metadata_2025_split huggingface dataset:
Memory B cells dominate the early antibody-secreting cell response to SARS-CoV-2 mRNA vaccination in naïve individuals independently of their antibody affinity
Authors: Li Zhe , Obraztsova Anna , Shang Fuwei , Oludada Opeyemi Ernest , Malapit Joshua , Busch Katrin , van Straaten Monique , Stebbins Erec , Murugan Rajagopal , Wardemann Hedda 
Published: December 2023

AbstractMemory B cells (MBCs) formed over the individual’s lifetime constitute nearly half of the adult peripheral blood B cell repertoire in humans. To assess their response to novel antigens, we tracked the origin and followed the differentiation paths of MBCs in the early anti-S response to mRNA vaccination in SARS-CoV-2-naïve individuals on single-cell and monoclonal antibody level. Newly generated and pre-existing MBCs differed in their differentiation paths despite similar levels of SARS-CoV-2 and common corona virus S-reactivity. Pre-existing highly mutated MBCs showed no signs of germinal center re-entry and rapidly developed into mature antibody secreting cells (ASCs). In contrast, newly generated MBCs derived from naïve precursors showed strong signs of antibody affinity maturation before differentiating into ASCs. Thus, although pre-existing human MBCs have an intrinsic propensity to differentiate into ASCs, the quality of the anti-S antibody and MBC response improved through the clonal selection and affinity maturation of naïve precursors.HighlightsmRNA vaccination of SARS-CoV-2 naïve individuals recruits naïve and pre-existing MBCs with similar levels of S-reactivity into the responseS-reactive naïve but not pre-existing MBCs undergo affinity maturationS-reactive pre-existing MBCs dominate the early ASC response independent of their antigen affinityHigh-affinity S-reactive MBCs and ASCs develop over time and originate from affinity matured naïve precursors
Environmental and ecological signals predict periods of nutritional stress for Eastern Australian flying fox populations
Authors: Lagergren John , Ruiz-Aravena Manuel , Becker Daniel J. , Madden Wyatt , Ruytenberg Lib , Hoegh Andrew , Han Barbara , Peel Alison J. , Eby Peggy , Jacobson Daniel , Plowright Raina K. 
Published: December 2023

AbstractFood availability determines where animals use space across a landscape and therefore affects the risk of encounters that lead to zoonotic spillover. This relationship is evident in Australian flying foxes (Pteropusspp; fruit bats), where acute food shortages precede clusters of Hendra virus spillovers. Using explainable artificial intelligence, we predicted months of food shortages from climatological and ecological covariates (1996-2022) in eastern Australia. Overall accuracy in predicting months of low food availability on a test set from 2018 up to 2022 reached 93.33% and 92.59% based on climatological and bat-level features, respectively. Seasonality and Oceanic El Niño Index were the most important environmental features, while the number of bats in rescue centers and their body weights were the most important bat-level features. These models support predictive signals up to nine months in advance, facilitating action to mitigate spillover risk.
Examining the role of oxygen-binding proteins on the early evolution of multicellularity
Authors: Wong Whitney , Bravo Pablo , Yunker Peter J. , Ratcliff William C. , Burnetti Anthony J. 
Published: December 2023

AbstractOxygen availability is a key factor in the evolution of multicellularity, as larger and more sophisticated organisms often require mechanisms allowing efficient oxygen delivery to their tissues. One such mechanism is the presence of oxygen-binding proteins, such as globins and hemerythrins, which arose in the ancestor of bilaterian animals. Despite their importance, the precise mechanisms by which oxygen-binding proteins influenced the early stages of multicellular evolution under varying environmental oxygen levels are not yet clear. We addressed this knowledge gap by heterologously expressing the oxygen binding proteins myoglobin and myohemerythrin in snowflake yeast, a model system of simple, undifferentiated multicellularity. These proteins increased the depth and rate of oxygen diffusion, increasing the fitness of snowflake yeast growing aerobically. Experiments show that, paradoxically, oxygen-binding proteins confer a greater fitness benefit for larger organisms under high, not low, O2conditions. We show via biophysical modeling that this is because facilitated diffusion is more efficient when oxygen is abundant, transporting a greater quantity of O2which can be used for metabolism. By alleviating anatomical diffusion limitations to oxygen consumption, the evolution of O2-binding proteins in the oxygen-rich Neoproterozoic may have been a key breakthrough enabling the evolution of increasingly large, complex multicellular metazoan lineages.
Proteomic and Physiological Signatures of Altitude Adaptation in aMyrsine coriaceaPopulation under Common Garden Conditions
Authors: Paschoa Roberta Pena da , Pinto Vitor Batista , Pereira Jéssica Priscilla , Cavatte Paulo Cezar , Garbin Mário Luís , Godinho Tiago de Oliveira , Xavier Lucas Rodrigues , Carrijo Tatiana Tavares , Silveira Vanildo 
Published: December 2023

AbstractPlants exhibit phenotypic plasticity in response to environmental variations, which can lead to stable genetic and physiological adaptations if exposure to specific conditions is prolonged.Myrsine coriaceademonstrates this through its ability to thrive in diverse environments. The objective of the article is to investigate the adaptive responses ofM. coriaceaby cultivating plants from seeds collected at four different altitudes in a common garden experiment. Through integrated physiological and proteomic analyses, we identified 170 differentially accumulated proteins and observed significant physiological differences among the populations. The high-altitude population (POP1) exhibited a unique proteomic profile with significant down-regulation of proteins involved in carbon fixation and energy metabolism, suggesting a potential reduction in photosynthetic efficiency. Physiological analyses showed lower leaf nitrogen content, net CO2assimilation rate, specific leaf area, and relative growth rate in stem height for POP1, alongside higher leaf carbon isotopic composition (δ13C) and leaf carbon (C) content. These findings provide insight into the complex interplay between proteomic and physiological adaptations inM. coriacea and underscore the importance of local adaptations. This study enhances our understanding of how altitude-specific selection pressures can shape plant molecular biology and physiology, offering valuable perspectives for predicting plant responses to global environmental changes.HighlightThis study unveils proteomic and physiological adaptations in a high-altitudeM. coriaceapopulation with reduced carbon fixation and energy metabolism.
Design of SARS-CoV-2 papain-like protease inhibitor with antiviral efficacy in a mouse model
Authors: Tan Bin , Zhang Xiaoming , Ansari Ahmadullah , Jadhav Prakash , Tan Haozhou , Li Kan , Chopra Ashima , Ford Alexandra , Chi Xiang , Ruiz Francesc Xavier , Arnold Eddy , Deng Xufang , Wang Jun 
Published: December 2023

AbstractThe emergence of SARS-CoV-2 variants and drug-resistant mutants calls for additional oral antivirals. The SARS-CoV-2 papain-like protease (PLpro) is a promising but challenging drug target. In this study, we designed and synthesized 85 noncovalent PLproinhibitors that bind to the newly discovered Val70Ubsite and the known BL2 groove pocket. Potent compounds inhibited PLprowith inhibitory constant Kivalues from 13.2 to 88.2 nM. The co-crystal structures of PLprowith eight leads revealed their interaction modes. Thein vivoleadJun12682inhibited SARS-CoV-2 and its variants, including nirmatrelvir-resistant strains with EC50from 0.44 to 2.02 µM. Oral treatment withJun12682significantly improved survival and reduced lung viral loads and lesions in a SARS-CoV-2 infection mouse model, suggesting PLproinhibitors are promising oral SARS-CoV-2 antiviral candidates.One-Sentence SummaryStructure-guided design of SARS-CoV-2 PLproinhibitors within vivoantiviral efficacy in a mouse model.
Image-based force inference by biomechanical simulation
Authors: Vanslambrouck Michiel , Thiels Wim , Vangheel Jef , van Bavel Casper , Smeets Bart , Jelier Rob 
Published: December 2023

AbstractDuring morphogenesis, cells precisely generate forces that drive cell shape changes and cellular motion. These forces predominantly arise from contractility of the actomyosin cortex, allowing for cortical tension, protrusion formation, and cell division. Image-based force inference can derive such forces from microscopy images, without complicated and time-consuming experimental set-ups. However, current methods do not account for common effects, such as physical confinement and local force generation. Here we propose a force-inference method based on a biophysical model of cell shape, and assess relative cellular surface tension, adhesive tension between cells, as well as cytokinesis and protrusion formation. We applied our method on fluorescent microscopy images of the earlyC. elegansembryo. Predictions for cell surface tension at the 7-cell stage were validated by measurements using cortical laser ablation. Our non-invasive method facilitates the accurate tracking of force generation, and offers many new perspectives for studying morphogenesis.Author summaryAn important challenge in understanding morphogenesis is to determine where forces are generated. Force generation, such as differential cortical tension, plays a key role in cellular self-organization. However, measuring these forces experimentally is a big challenge that typically requires complicated experiments and direct access to the cells being investigated. A non-invasive method, such as force inference based on cell shapes, would have important advantages. Unfortunately, current methods can only be applied in certain cases. Here, we describe a more flexible 3D force inference method, FIDES, that can account for physical confinement, cell divisions and protrusions. We applied the method to infer forces throughout earlyC. elegansembryogenesis. By using cortical laser ablations, we confirmed that FIDES correctly inferred cell surface tensions in a dynamic stage of the nematode’s embryogenesis. Our approach offers a route to routinely infer force generation in complex movements during morphogenesis, with microscopy images of cell shapes as the sole experimental input.
SLCO1B1functional variants and statin-induced myopathy in people with recent genealogical ancestors from Africa: a population-based real-world study
Authors: Yee Sook Wah , Haldar Tanushree , Kvale Mark , Yang Jia , Douglas Michael P , Oni-Orisan Akinyemi 
Published: December 2023

AbstractBackgroundClinical pharmacogenetic implementation guidelines for statin therapy are derived from evidence of primarily Eurocentric study populations. FunctionalSLCO1B1variants that are rare in these study populations have not been investigated as a determinant of statin myotoxicity and are thus missing from guideline inclusion.ObjectiveDetermine the relationship between candidate functionalSLCO1B1variants and statin-induced myopathy in people with recent genealogical ancestors from Africa.DesignPopulation-based pharmacogenetic study using real-world evidence from electronic health record-linked biobanksSettingVarious health care settingsParticipantsSelf-identified white and Black statin users with genome-wide genotyping data available.MeasurementsPrimarily, the odds of statin-induced myopathy + rhabdomyolysis. Secondarily, total bilirubin levels. Thirdly, cell-based functional assay results.ResultsMeta-analyses results demonstrated an increased risk of statin-induced myopathy + rhabdomyolysis with c.481+1G>T (odds ratio [OR] = 3.27, 95% confidence interval [CI] 1.43-7.46,P=.005) and c.1463G>C (OR = 2.45, 95% CI 1.04-5.78,P=.04) for Black participants. For White participants, c.521T>C was also significantly associated with increased risk of statin-induced myopathy + rhabdomyolysis (OR = 1.41, 95% CI 1.20-1.67,P=5.4x10−5). This effect size for c.521T>C was similar in the Black participants, but did not meet the level of statistical significance (OR = 1.47, 95% CI 0.58-3.73,P=0.41). Supporting evidence using total bilirubin as an endogenous biomarker ofSLCO1B1function as well as from cell-based functional studies corroborated these findings.LimitationsData limited to severe statin myotoxicity events.ConclusionOur findings implicate AfrocentricSLCO1B1variants on preemptive pharmacogenetic testing panels, which could have an instant impact on reducing the risk of statin-associated myotoxicity in historically excluded groups.Primary Funding SourceNational Institutes of Health, Office of the Director - All of Us (OD-AoURP)
In field use of water samples for genomic surveillance of ISKNV infecting tilapia fish in Lake Volta, Ghana
Authors: Alathari Shayma , Joseph Andrew , Bolaños Luis M. , Studholme David , Jeffries Aaron , Appenteng Patrick , Duodu Kwaku , Sawyerr Eric , Paley Richard , Tyler Charles R. , Temperton Ben 
Published: December 2023

AbstractViral outbreaks are a constant threat to aquaculture, limiting production for better global food security. A lack of diagnostic testing and monitoring in resource-limited areas hinders the capacity to respond rapidly to disease outbreaks and to prevent viral pathogens becoming endemic in fisheries productive waters. Recent developments in diagnostic testing for emerging viruses, however, offers a solution for rapidin situmonitoring of viral outbreaks. Genomic epidemiology has furthermore proven highly effective in detecting viral mutations involved in pathogenesis and assisting in resolving chains of transmission.Here, we demonstrate the application of an in-field epidemiological tool kit to track viral outbreaks in aquaculture on farms with reduced access to diagnostic labs, and with non-destructive sampling. Inspired by the “lab in a suitcase” approach used for genomic surveillance of human viral pathogens and wastewater monitoring of COVID19, we evaluated the feasibility of real-time genome sequencing surveillance of the fish pathogen, Infectious spleen and kidney necrosis virus (ISKNV) in Lake Volta. Viral fractions from water samples collected from cages holding Nile tilapia (Oreochromis niloticus) with suspected ongoing ISKNV infections were concentrated and used as a template for whole genome sequencing, using a previously developed tiled PCR method for ISKNV. Mutations in ISKNV in samples collected from the water surrounding the cages matched those collected from infected caged fish, illustrating that water samples can be used for detecting predominant ISKNV variants in an ongoing outbreak. This approach allows for the detection of ISKNV and tracking of the dynamics of variant frequencies, and may thus assist in guiding control measures for the rapid isolation and quarantine of infected farms and facilities.
Xanthomonas euvesicatoriaeffectorXeAvrRxo1 triggers a Rxo1-mediated defense response inNicotiana benthamianaand its chaperone Xe4429 functions as an antitoxin, an expression repressor, and an enhancer ofXeAvrRxo1 secretion
Authors: Wang Zhibo , Zhou Changhe , Roach Tiffany G. , Li Qi , Wang Kunru , Miao Jiamin , Toro Carlos , Wu Shuchi , Tang Yu , Han Qian , Sun Furong , Capelluto Daniel G. S. , Li Jianyong , Zhao Bingyu 
Published: December 2023

SummaryXanthomonas euvesicatoria(X. euvesicatoria) is the causal agent of bacterial spot disease that threatens pepper and tomato production around the globe.X. euvesicatoriageneXe4428encodes a type III effector (T3E) that shares 89.67% amino acid identity withXanthomonas oryzaepv.oryzicola(Xoc) T3E AvrRxo1. Deletion ofXe4428in the genome ofX. euvesicatoria(strain Xcv85-10) compromised its virulence to infect pepper andNicotiana benthamianaplants. Transient co-expression of Xe4428 andRxo1on pepper andN. benthamianaplant leaves results in a robust hypersensitive reaction. Thus, Xe4428, renamed asXeAvrRxo1, is a bona fide orthologue ofXocAvrRxo1 that possesses both virulence and avirulence functions. Expression ofXeAvrRxo1 inE. coliandX. euvesicatoriais toxic to both bacterial cells. AnotherX. euvesicatoriageneXe4429, encodes a putative chaperone ofXeAvrRxo1, which can interact with XeAvrRxo1 to suppress its toxicity inX. euvesicatoriaandE. colibacterial cells. Xe4429 also binds to the promoter region ofXeavrRxo1and represses its transcription/translation inX. euvesicatoriabacterial cells. In addition, expression of Xe4429 can enhance the secretion and translocation ofXeAvrRxo1 into plant cells. Therefore, Xe4429 functions as an antitoxin, a transcription repressor, and a type III chaperone that is capable of enhancing the secretion and translocation ofXeAvrRxo1 during pathogenesis.
Cortical Network Disruption is Minimal in Early Stages of Psychosis
Authors: Van Dyken Peter C. , MacKinley Michael , Khan Ali R. , Palaniyappan Lena 
Published: December 2023

1AbstractBackground and HypothesisChronic schizophrenia is associated with white matter disruption and topological reorganization of cortical connectivity but the trajectory of these changes over the disease course are poorly understood. Current white matter studies in first-episode psychosis (FEP) patients using diffusion magnetic resonance imaging (dMRI) suggest such disruption may be detectable at the onset of psychosis, but specific results vary widely and few reports have contextualized their findings with direct comparison to chronic patients. Here, we test the hypothesis that structural changes are not a significant feature of early psychosis.Study DesignDiffusion and T1-weighted 7T MR scans were obtained from N=113 (61 FEP patients, 37 controls, 15 chronic patients) recruited from an established cohort in London, Ontario. Voxel- and network-based analyses were used to detect changes in diffusion microstructural parameters. Graph theory metrics were used to probe changes in the cortical network hierarchy and to assess the vulnerability of hub regions to disruption. Experiments were replicated with N=167 (111 patients, 56 controls) from the Human Connectome Project - Early Psychosis (HCP-EP) dataset.Study ResultsWidespread microstructural changes were found in chronic patients, but changes in FEP patients were minimal. Unlike chronic patients, no appreciable topological changes in the cortical network were observed in FEP patients. These results were replicated in the early psychosis patients of the HCP-EP datasets, which were indistinguishable from controls on nearly all metrics.ConclusionsThe white matter structural changes observed in chronic schizophrenia are not a prominent feature in the early stages of this illness.
Developing clinician-centred design principles for Genomic Test Reports in Pakistan
Authors: Agha Momal , Khan Faisal F 
Published: December 2023

AbstractDespite rapid technological progress being made in genomics, a growing disparity is emerging between healthcare in developed and developing countries. Thisgenomic dividecan be partly explained by the scarcity of available genomics workforce and in some parts by limited genomic literacy of healthcare professionals that reportedly deters them from proposing genomic testing in a clinical setting. This study aims to study this gap in a local context and learn how we can reduce thisgenomic divideby developing a user-centred design of genomic test reports in Pakistan. The user being the clinician in this study.We selected two commonly used genomic reports which varied in language, content, and layout. Report A was a one-page genomic report from the Laboratory for Molecular Medicine at Partner’s Healthcare. Report B was a report with multiple pages of information from FoundationOneCDx. We employed a qualitative descriptive study design, including a survey of trainees, non-specialists, and specialists. The parameters recorded were: subjective comprehension, overall visual impression, level of difficulty of the language, and communication efficacy depending on the reports’ graphical representation, along with actionability and degree of reliability.A total of 49 medical professionals across 11 institutes in Pakistan participated in the survey. Based on the answers and suggestions provided by the participants, we extracted 11 recommendations and broadly grouped them into four categories, i.e. language, content, layout and reliability.Our findings highlights key areas that need to be taken into consideration when designing impactful genomic reports for clinicians in Pakistan. This incudes accessible and appropriate language, adequate content and a non-overwhelming and friendly layout as well as an emphasis on establishing reliability and actionability of what the clinician finds in the report. This can be instrumental in helping us improve the adoption of genomic testing in clinics around Pakistan, and potentially in other similar contexts.
Effect of mRNA vaccination on pulmonary sequelae after mild COVID-19
Authors: Gagiannis D , Hackenbroch C , Zech F , Kirchhoff F , Bloch W , Junghans K , Steinestel K 
Published: December 2023

ABSTRACTBackgroundPrevious studies indicate a protective role for SARS-CoV-2 vaccination against development of pulmonary post-acute sequelae of COVID (PASC). We compared clinical, imaging, histopathology and ultrastructural features of pulmonary PASC with and without prior vaccination in a consecutive cohort of 54 unvaccinated, 17 partially vaccinated and 28 fully vaccinated patients who presented with dyspnea on exertion after mild COVID-19 (without hospitalization).MethodsPatients underwent full clinical evaluation including autoantibody (ANA/ENA) serology, high-resolution computed tomography (HRCT), bronchioloalveolar lavage fluid (BAL) analysis and transbronchial biopsy followed by histopathological and ultrastructural analysis and SARS-CoV-2 immunohistochemistry.ResultsWhile vaccinated patients were younger (p=0.0056), included more active smokers (p=0.0135) and a longer interval since infection (35 vs. 17 weeks, p=0.0002), dyspnea on exertion and impaired lung function were not different between vaccinated and unvaccinated patients. Ground glass opacities in HRCT and centrilobular fibrosis were more frequent in unvaccinated patients (p=0.0154 and p=0.0353), but presence of autoantibodies, BAL lymphocytosis and bronchiolitis were common findings in all groups. While vaccination against SARS-CoV-2 is associated with a longer time span between infection and consultation along with a reduced frequency of ground glass opacities and centrilobular fibrosis, impaired lung function, bronchiolitis and presence of autoantibodies are comparable between vaccinated and unvaccinated patients. Residual virus was not detected in lung tissue in all but 1 patient.ConclusionWhile differences between the investigated groups with regard to age, smoking status and SARS-CoV-2 variants have to be taken into account, a proposed protective role of SARS-CoV-2 vaccination against pulmonary PASC is so far not fully explained by clinical and histopathology findings.KEY MESSAGESThe role of SARS-CoV-2 vaccination in the protection against pulmonary post-acute sequelae of COVID-19 (PASC) is unclear. Using a multidimensional approach integrating clinical, serological, imaging and histopathology data as well as ultrastructural analyses, we show here that previous vaccination has no impact on lung function, bronchiolitis or the detection of autoantibodies or residual virus in a previously healthy cohort of 99 PASC patients after mild COVID-19. While a higher frequency of ground glass opacities in unvaccinated patients might be due to the longer interval between infection and consultation, the observed fibrotic remodeling should prompt further investigation of a possible pro-fibrotic role of SARS-CoV-2 infection in the lung.