bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity
Authors: Riou Catherine , Keeton Roanne , Moyo-Gwete Thandeka , Hermanus Tandile , Kgagudi Prudence , Baguma Richard , Tegally Houriiyah , Doolabh Deelan , Iranzadeh Arash , Tyers Lynn , Mutavhatsindi Hygon , Tincho Marius B. , Benede Ntombi , Marais Gert , Chinhoyi Lionel R. , Mennen Mathilda , Skelem Sango , du Bruyn Elsa , Stek Cari ,   SA-CIN, de Oliveira Tulio , Williamson Carolyn , Moore Penny L. , Wilkinson Robert J. , Ntusi Ntobeko A. B. , Burgers Wendy A. 
Published: June 2021

AbstractSARS-CoV-2 variants have emerged that escape neutralization and potentially impact vaccine efficacy. T cell responses play a role in protection from reinfection and severe disease, but the potential for spike mutations to affect T cell immunity is poorly studied. We assessed both neutralizing antibody and T cell responses in 44 South African COVID-19 patients infected either with B.1.351, now dominant in South Africa, or infected prior to its emergence (‘first wave’), to provide an overall measure of immune evasion. We show for the first time that robust spike-specific CD4 and CD8 T cell responses were detectable in B.1.351-infected patients, similar to first wave patients. Using peptides spanning only the B.1.351 mutated regions, we identified CD4 T cell responses targeting the wild type peptides in 12/22 (54.5%) first wave patients, all of whom failed to recognize corresponding B.1.351-mutated peptides (p=0.0005). However, responses to the mutated regions formed only a small proportion (15.7%) of the overall CD4 response, and few patients (3/44) mounted CD8 responses that targeted the mutated regions. First wave patients showed a 12.7 fold reduction in plasma neutralization of B.1.351. This study shows that despite loss of recognition of immunodominant CD4 epitope(s), overall CD4 and CD8 T cell responses to B.1.351 are preserved. These observations may explain why, despite substantial loss of neutralizing antibody activity against B.1.351, several vaccines have retained the ability to protect against severe COVID-19 disease.One Sentence SummaryT cell immunity to SARS-CoV-2 B.1.351 is preserved despite some loss of variant epitope recognition by CD4 T cells.
The zinc transporter ZnuABC is critical for the virulence of Chromobacterium violaceum and contributes to diverse zinc-dependent physiological processes
Authors: Santos Renato E. R. S. , da Silva Júnior Waldir P. , Harrison Simone , Skaar Eric P. , Chazin Walter J. , da Silva Neto José F. 
Published: June 2021

ABSTRACTChromobacterium violaceum is a ubiquitous environmental bacterium that causes sporadic life-threatening infections in humans. How C. violaceum acquires zinc to colonize environmental and host niches is unknown. In this work, we demonstrated that C. violaceum employs the zinc uptake system ZnuABC to overcome zinc limitation in the host, ensuring the zinc supply for several physiological demands. Our data indicated that the C. violaceum ZnuABC transporter is encoded in a zur-CV_RS15045-CV_RS15040-znuCBA operon. This operon was repressed by the zinc uptake regulator Zur and derepressed in the presence of the host protein calprotectin (CP) and the synthetic metal chelator EDTA. A ΔznuCBA mutant strain showed impaired growth under these zinc-chelated conditions. Moreover, the deletion of znuCBA provoked a reduction in violacein production, swimming motility, biofilm formation, and bacterial competition. Remarkably, the ΔznuCBA mutant strain was highly attenuated for virulence in an in vivo mouse infection model and showed a low capacity to colonize the liver, grow in the presence of CP, and resist neutrophil killing. Overall, our findings demonstrate that ZnuABC is essential for C. violaceum virulence, contributing to subvert the zinc-based host nutritional immunity.
Prevalence of laboratory-related musculoskeletal disorders among biomedical scientists
Authors: Alwahaibi Nasar , Al Sadairi Mallak , Al Abri Ibrahim , Al Rawahi Samira 
Published: June 2021

AbstractBackgroundLaboratory–related musculoskeletal disorders (LMSDs) are injuries resulted from working in the laboratory. Biomedical scientists (BMSs) play an important role in any health care system. However, they are at high risk of exposure to LMSDs. This study aimed to estimate the prevalence and the associated risk factors of LMSDs among this group of healthcare professionals.MethodsA cross-sectional survey (Nordic musculoskeletal) was used to estimate the prevalence of LMSDs among BMSs. Data were analyzed using Statistical Package for Social Science software version 25. Chi-square was performed to find the significant association between LMSDs and different risk factors.ResultsThe study included 83 BMSs. Females represented 63.9% and 36.1% were in the age group of 35–44. The overall prevalence of LMSDs was 77.1%. The most prevalent LMSDs were neck, shoulders, and lower back with 50.6%, 49.4%, and 43.4%, respectively. Neck complaints and upper back complaints were found statistically significant with the female gender. Shoulders complaints were associated with pipetting and microscopy. Lower back complaints were associated with pipetting and heavy work at home. A total of 65.57% of BMSs had irregular symptoms of LMSDs, 54.10% experienced moderate pain due to these symptoms, and 44.26% had symptoms that persisted from hours to days.ConclusionThe study found that the prevalence of LMSDs among BMSs was high. Good knowledge, attitude, practice, and training of ergonomics may minimize the prevalence of LMSDs among BMSs.
Limits and potential of combined folding and docking using PconsDock
Authors: Pozzati Gabriele , Zhu Wensi , Bassot Claudio , Lamb John , Kundrotas Petras , Elofsson Arne 
Published: June 2021

AbstractIn the last decade, de novo protein structure prediction accuracy for individual proteins has improved significantly by utilising deep learning (DL) methods for harvesting the co-evolution information from large multiple sequence alignments (MSA). In CASP14, the best groups predicted the structure of most proteins with impressive accuracy. The same approach can, in principle, also be used to extract information about evolutionary-based contacts across protein-protein interfaces. However, most of the earlier studies have not used the latest DL methods for inter-chain contact distance prediction. This paper introduces a fold-and-dock method, PconsDock, based on predicted residue-residue distances with trRosetta. PconsDock can simultaneously predict the tertiary and quaternary structure of a protein pair, even when the structures of the monomers are not known. The straightforward application of this method to a standard dataset for protein-protein docking yielded limited success. However, using alternative methods for MSA generating allowed us to dock accurately significantly more proteins. We also introduced a novel scoring function, PconsDock, that accurately separates 98% of correctly and incorrectly folded and docked proteins. The average performance of the method is comparable to the use of traditional, template-based or ab initio shape-complementarity-only docking methods. However, no a priori structural information for the individual proteins is needed. Moreover, the results of conventional and fold-and-dock approaches are complementary, and thus a combined docking pipeline could increase overall docking success significantly. PconsDocck contributed to the best model for one of the CASP14 oligomeric targets, H1065.
Automated Generation of Cerebral Blood Flow Maps Using Deep Learning and Multiple Delay Arterial Spin-Labelled MRI
Authors: Luciw Nicholas J. , Shirzadi Zahra , Black Sandra E. , Goubran Maged , MacIntosh Bradley J. 
Published: June 2021

AbstractThe purpose of this work was to develop and evaluate a deep learning approach for estimation of cerebral blood flow (CBF) and arterial transit time (ATT) from multiple post-label delay (PLD) arterial spin-labelled (ASL) MRI. Six-PLD ASL MRI was acquired on a 1.5T or 3T system among 99 older males and females with and without cognitive impairment. We trained and compared two network architectures: standard feed-forward convolutional neural network (CNN) and U-Net. Mean absolute error (MAE) was evaluated between model estimates and ground truth obtained through conventional processing. The best-performing model was re-trained on inputs with missing PLDs to investigate generalizability to different PLD schedules. Relative to the CNN, the U-Net yielded lower MAE on training data. On test data, the U-Net MAE was 8.4±1.4 ml/100g/min for CBF and 0.22±0.09 s for ATT. Model uncertainty, estimated with Monte Carlo dropout, was associated with model error. Network estimates remained stable when tested on inputs with up to three missing PLD images. Mean processing times were: U-Net pipeline = 10.77s; ground truth pipeline = 10min 41s. These results suggest hemodynamic parameter estimation from 1.5T and 3T multi-PLD ASL MRI is feasible and fast with a deep learning image-generation approach.
OrtSuite – from genomes to prediction of microbial interactions within targeted ecosystem processes
Authors: Saraiva João Pedro , Bartholomäus Alexandre , Kallies René , Gomes Marta , Bicalho Marcos , Vogt Carsten , Chatzinotas Antonis , Stadler Peter , Dias Oscar , da Rocha Ulisses Nunes 
Published: June 2021

AbstractThe high complexity found in microbial communities makes the identification of microbial interactions challenging. To address this challenge, we present OrtSuite, a flexible workflow to predict putative microbial interactions based on genomic content of microbial communities and targeted to specific ecosystem processes. The pipeline is composed of three user-friendly bash commands. OrtSuite combines ortholog clustering with genome annotation strategies limited to user-defined sets of functions allowing for hypothesis-driven data analysis such as assessing microbial interactions in specific ecosystems. OrtSuite matched, on average, 96 % of experimentally verified KEGG orthologs involved in benzoate degradation in a known group of benzoate degraders. Identification of putative synergistic species interactions was evaluated using the sequenced genomes of an independent study which had previously proposed potential species interactions in benzoate degradation. OrtSuite is an easy to use workflow that allows for rapid functional annotation based on a user curated database and can easily be extended to ecosystem processes where connections between genes and reactions are known. OrtSuite is an open-source software available at https://github.com/mdsufz/OrtSuite.
The biaxial mechanics of thermally denaturing skin - Part I: Experiments
Authors: Meador William D. , Sugerman Gabriella P. , Tepole Adrian Buganza , Rausch Manuel K. 
Published: June 2021

AbstractThe mechanics of collageneous soft tissues, such as skin, are sensitive to heat. Thus, quantifying and modeling thermo-mechanical coupling of skin is critical to our understanding of skin’s physiology, pathophysiology, as well as its treatment. However, key gaps persist in our knowledge about skin’s coupled thermo-mechanics. Among them, we haven’t quantified the role of skin’s microstructural organization in its response to superphysiological loading. To fill this gap, we conducted a comprehensive set of experiments in which we combined biaxial mechanical testing with histology and two-photon imaging under liquid heat treatment. Among other observations, we found that unconstrained skin, when exposed to high temperatures, shrinks anisotropically with the principle direction of shrinkage being aligned with collagen’s principle orientation. Additionally, we found that when skin is isometrically constrained, it produces significant forces during denaturing that are also anisotropic. Finally, we found that denaturation significantly alters the mechanical behavior of skin. For short exposure times, this alteration is reflected in a reduction of stiffness at high strains. At long exposure times, the tissue softened to a point where it became untestable. We supplemented our findings with confirmation of collagen denaturation in skin via loss of birefringence and second harmonic generation. Finally, we captured all time-, temperature-, and direction-dependent experimental findings in a hypothetical model. Thus, this work fills a fundamental gap in our current understanding of skin thermo-mechanics and will support future developments in thermal injury prevention, thermal injury management, and thermal therapeutics of skin.
A Xeno-free Media for the In Vitro Expansion of Human Spermatogonial Stem Cells
Authors: Robinson Meghan , Witherspoon Luke , Willerth Stephanie , Flannigan Ryan 
Published: June 2021

ABSTRACTIn vitro expansion of spermatogonial stem cells (SSCs) has been established using animal-derived fetal bovine serum (FBS) and bovine serum albumin (BSA). However, the use of animal components during cell culture introduces the risk of contaminating cells with pathogens, and leads to animal epitope expression, rendering them unsuitable for medical use. Therefore, this study set out to develop a xeno-free, fully defined media for the expansion of human SSCs. We show that the molecules Prostaglandin D2 (PGD-2) and Insulin-Like Growth Factor 1 (IGF-1) can replace FBS and BSA in cell culture media without loss of viability or expansion capability, and that Rho-Associated, Coiled-Coil Containing Protein Kinase (ROCK) inhibitor Y-27632 supplementation improves viability after cryopreservation. Long-term SSC cultures expanded in xeno-free, defined culture conditions shared identical protein expression profiles for well-known SSC markers, while gene expression analyses revealed a significant improvement in quiescent SSC and pan-germ markers. This xeno-free, defined formulation allows for standardized SSC culture free of animal pathogens.
Common Permutation Methods in Animal Social Network Analysis Do Not Control for Non-independence
Authors: Hart Jordan D. A. , Weiss Michael N. , Brent Lauren J. N. , Franks Daniel W. 
Published: June 2021

AbstractThe non-independence of social network data is a cause for concern among behavioural ecologists conducting social network analysis. This has led to the adoption of several permutation-based methods for testing common hypotheses. One of the most common types of analysis is nodal regression, where the relationships between node-level network metrics and nodal covariates are analysed using a permutation technique known as node-label permutations. We show that, contrary to accepted wisdom, node-label permutations do not automatically account for the non-independences assumed to exist in network data, because regression-based permutation tests still assume exchangeability of residuals. The same assumption also applies to the quadratic assignment procedure (QAP), a permutation-based method often used for conducting dyadic regression. We highlight that node-label permutations produce the same p-values as equivalent parametric regression models, but that in the presence of non-independence, parametric regression models can also produce accurate effect size estimates. We also note that QAP only controls for a specific type of non-independence between edges that are connected to the same nodes, and that appropriate parametric regression models are also able to account for this type of non-independence. Based on this, we suggest that standard parametric models could be used in the place of permutation-based methods. Moving away from permutation-based methods could have several benefits, including reducing over-reliance on p-values, generating more reliable effect size estimates, and facilitating the adoption of alternative types of statistical analysis.
Influence of the metallized coils on human leg blood circulation
Authors: Dehtjars Jurijs , Jašina Ksenija , Larins Viesturs , Okss Aleksandrs , Pudovskis Konstantins , Tolmača Nelli , Vadhiraj Vijay Vyas 
Published: June 2021

AbstractThe aim of the study was to find out if magnetic field generated by the human body affects a human blood flow. The idea is based on Lenz’s law where the blood flow induces an opposing alternating magnetic field (OAMF). In the experiment the OAMF will be modulated by repeating heart contractions (pulses). In an experiment with metallized coils it was found that wearing metal coils affects blood flow and it differs from when coils were not worn.
Combustible and electronic cigarette exposures increase ACE2 activity and SARS-CoV-2 Spike binding
Authors: Ghosh Arunava , Girish Vishruth , Yuan Monet Lou , Coakley Raymond D. , Alexis Neil E. , Sausville Erin L. , Vasudevan Anand , Chait Alexander R. , Sheltzer Jason M. , Tarran Robert 
Published: June 2021

ABSTRACTThe outbreak of coronavirus disease 2019 (COVID-19) has extensively impacted global health. The causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), binds to the angiotensin-converting enzyme 2 (ACE2) receptor, a transmembrane metallo-carboxypeptidase that is expressed in both membrane-anchored (mACE2) and soluble (sACE2) forms in the lung. Tobacco use has been speculated as a vulnerability factor for contracting SARS-CoV-2 infection and subsequent disease severity, whilst electronic cigarettes (e-cigarettes) have been shown to induce harmful proteomic and immune changes in the lungs of vapers. We therefore tested the hypothesis that combustible tobacco (e.g. cigarettes) and non-combustible e-cigarettes could affect ACE2 activity and subsequent SARS-CoV-2 infection. We observed that sACE2 activity was significantly higher in bronchoalveolar lavage fluid from both smokers and vapers compared to age-matched non-smokers. Exposure to cigarette smoke increased ACE2 levels, mACE2 activity, and sACE2 in primary bronchial epithelial cultures. Finally, treatment with either cigarette smoke condensate or JUUL e-liquid increased infections with a spike-coated SARS-CoV-2 pseudovirus. Overall, these observations suggest that tobacco product use elevates ACE2 activity and increases the potential for SARS-CoV-2 infection through enhanced spike protein binding.
Revealing the full biosphere structure and versatile metabolic functions in the deepest ocean sediment of the Challenger Deep
Authors: Chen Ping , Zhou Hui , Huang Yanyan , Xie Zhe , Zhang Mengjie , Wei Yuli , Li Jia , Ma Yuewei , Luo Min , Ding Wenmian , Cao Junwei , Jiang Tao , Nan Peng , Fang Jiasong , Li Xuan 
Published: June 2021

AbstractBackgroundThe full biosphere structure and functional exploration of the microbial communities of the Challenger Deep of the Mariana Trench, the deepest known hadal zone on Earth, lag far behind that of other marine realms.ResultsWe adopt a deep metagenomics approach to investigate the microbiome in the sediment of Challenger Deep, Mariana Trench. We construct 178 metagenome-assembled genomes (MAGs) representing 26 phyla, 16 of which are reported from hadal sediment for the first time. Based on the MAGs, we find the microbial community functions are marked by enrichment and prevalence of mixotrophy and facultative anaerobic metabolism. The microeukaryotic community is found to be dominated by six fungal groups that are characterized for the first time in hadal sediment to possess the assimilatory and dissimilatory nitrate/sulfate reduction, and hydrogen sulfide oxidation pathways. By metaviromic analysis, we reveal novel hadal Caudovirales clades, distinctive virus-host interactions, and specialized auxiliary metabolic genes for modulating hosts’ nitrogen/sulfur metabolism. The hadal microbiome is further investigated by large-scale cultivation that cataloged 1070 bacterial and 19 fungal isolates from the Challenger Deep sediment, many of which are found to be new species specialized in the hadal habitat.ConclusionOur hadal MAGs and isolates increase the diversity of the Challenger Deep sediment microbial genomes and isolates present in the public. The deep metagenomics approach fills the knowledge gaps in structure and diversity of the hadal microbiome, and provides novel insight into the ecology and metabolism of eukaryotic and viral components in the deepest biosphere on earth.
Repurposing diphenylbutylpiperidine-class antipsychotic drugs for host-directed therapy ofMycobacterium tuberculosisandSalmonella entericainfections
Authors: Heemskerk MT , Korbee CJ , Esselink J , Carvalho dos Santos C , van Veen S , Gordijn IF , Vrieling F , Walburg KV , Engele CG , Dijkman K , Wilson L , Verreck FAW , Ottenhoff THM , Haks MC 
Published: June 2021

AbstractThe persistent increase of multidrug-resistant (MDR)Mycobacterium tuberculosis(Mtb) infections negatively impacts Tuberculosis (TB) treatment outcomes. Host-directed therapies (HDT) pose an complementing strategy, particularly sinceMtbis highly successful in evading host-defense by manipulating host-signaling pathways. Here, we screened a library containing autophagy-modulating compounds for their ability to inhibit intracellularMtb-bacteria. Several active compounds were identified, including two drugs of the diphenylbutylpiperidine-class, Fluspirilene and Pimozide, commonly used as antipsychotics. Both molecules inhibited intracellularMtbin pro- as well as anti-inflammatory primary human macrophages in a host-directed manner and synergized with conventional anti-bacterials. Importantly, these inhibitory effects extended to MDR-Mtbstrains and the unrelated intracellular pathogen,Salmonella entericaserovar Typhimurium (Stm). Mechanistically Fluspirilene and Pimozide were shown to regulate autophagy and alter the lysosomal response, partly correlating with increased bacterial localization to autophago(lyso)somes. Pimozide’s and Fluspirilene’s efficacy was inhibited by antioxidants, suggesting involvement of the oxidative-stress response inMtbgrowth control. Furthermore, Fluspirilene and especially Pimozide counteractedMtb-induced STAT5 phosphorylation, thereby reducingMtbphagosome-localized CISH that promotes phagosomal acidification.In conclusion, two approved antipsychotic drugs, Pimozide and Fluspirilene, constitute highly promising and rapidly translatable candidates for HDT againstMtbandStmand act by modulating the autophagic/lysosomal response by multiple mechanisms.
Revealing A-T and G-C Hoogsteen base pairs in stressed protein-bound duplex DNA
Authors: Shi Honglue , Kimsey Issac J. , Liu Hsuan-Fu , Pham Uyen , Schumacher Maria A. , Al-Hashimi Hashim M. 
Published: June 2021

AbstractWatson-Crick base pairs (bps) are the fundamental unit of genetic information and the building blocks of the DNA double helix. However, A-T and G-C can also form alternative ‘Hoogsteen’ bps, expanding the functional complexity of DNA. We developed ‘Hoog-finder’, which uses structural fingerprints to rapidly screen Hoogsteen bps, which may have been mismodeled as Watson-Crick in crystal structures of protein-DNA complexes. We uncovered seventeen Hoogsteen bps, seven of which were in complex with six proteins never before shown to bind Hoogsteen bps. The Hoogsteen bps occur near mismatches, nicks, and lesions and some appear to participate in recognition and damage repair. Our results suggest a potentially broad role for Hoogsteen bps in stressed regions of the genome and call for a community-wide effort to identify these bps in current and future crystal structures of DNA and its complexes.