bluuebunny/crossref_metadata_2025_split huggingface dataset:
An optimized high-yield protocol for expression and purification of monomeric full-length BAX protein
Authors: Chen Yiyang , Gelles Jesse D. , Mohammed Jarvier N. , Chipuk Jerry Edward 
Published: October 2023

AbstractDiverse developmental signals and pro-death stresses converge on regulation of the mitochondrial pathway of apoptosis. BAX, a pro-apoptotic BCL-2 effector, directly forms proteolipid pores in the outer mitochondrial member to activate the mitochondrial pathway of apoptosis. BAX is a viable pharmacological target for various human diseases, and increasing efforts have been made to study the molecular regulation of BAX and identify small molecules selectively targeting BAX. However, generating large quantities of monomeric and functionally-competent BAX has been challenging due to its aggregation-prone nature. Additionally, there is a lack of detailed and instructional protocols available for investigators who are not already familiar with recombinant BAX production. Here, we present a comprehensive high-yield protocol for expressing, purifying, and storing functional recombinant BAX protein. We utilize an intein-tagged BAX construct and employ a two-step chromatography strategy to capture and purify BAX, and provide example standard assays to observe BAX activation. We also highlight best practices for handling and storing BAX to effectively preserve its quality, shelf-life, and function.
Functional Tissue Units in the Human Reference Atlas
Authors: Bidanta Supriya , Börner Katy , Herr Bruce W. , Nagy Marcell , Gustilo Katherine S. , Bajema Rachel , Maier Libby , Molontay Roland , Weber Griffin 
Published: October 2023

AbstractFunctional tissue units (FTUs) form the basic building blocks of organs and are important for understanding and modeling the healthy physiological function of the organ and changes during disease states. In this first comprehensive catalog of FTUs, we document the definition, physical dimensions, vasculature, and cellular composition of 22 anatomically correct, nested functional tissue units (FTUs) in 10 healthy human organs. The catalog includes datasets, illustrations, an interactive online FTU explorer, and a large printable poster. All data and code are freely available. This is part of a larger ongoing international effort to construct a Human Reference Atlas (HRA) of all cells in the human body.
Fecal microbial transfer and complex carbohydrates mediate protection against COPD
Authors: Budden Kurtis F. , Shukla Shakti D. , Bowerman Kate L. , Gellatly Shaan , Wood David L.A. , Lachner Nancy , Idrees Sobia , Patel Vyoma K. , Faiz Alen , Rehman Saima Firdous , Donovan Chantal , Alemao Charlotte A. , Shen SJ , Vanka Kanth S. , Mason Jazz , Haw Tatt Jhong , Fricker Michael , Keely Simon , Hansbro Nicole G. , Belz Gabrielle T. , Horvat Jay C. , Ashhurst Thomas M. , van Vreden Caryn , McGuire Helen M. , de St Groth Barbara Fazekas , King Nicholas J.C. , Crossett Ben , Cordwel Stuart J. , Bonaguro Lorenzo , Schultze Joachim L. , Forster Samuel C , Cooper Matthew A. , Segal Leopoldo N. , Vaughan Annalicia , Collins Peter F. , Bowman Rayleen V. , Fong Kwun M. , Yang Ian A. , Wark Peter A. , Dennis Paul G. , Hugenholtz Philip , Hansbro Philip M. 
Published: October 2023

ABSTRACTObjectiveChronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseasesviathe gut-lung axis, but its role is unclear.DesignUsing anin vivomouse model of cigarette smoke-induced COPD and fecal microbial transfer (FMT), we characterized the fecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology, and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in sixteen COPD patients using a randomized, double-blind, placebo-controlled pilot study of inulin supplementation.ResultsFMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation. Disease features correlated with the relative abundance ofMuribaculaceae, DesulfovibrionaceaeandLachnospiraceaefamily members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in cigarette smoke-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes.ConclusionThe gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.What is already known on this topicChanges in gut microbiota are associated with COPD but the underlying host and microbial mechanisms are unclear, limiting the therapeutic applications.What this study addsMicrobiome composition and metabolism is reproducibly correlated with lung and gastrointestinal pathology in experimental COPD.Microbiome modifying interventions effectively alleviate disease, including protective effects supplementing smoking cessation.Nutritional interventions targeting the microbiome in COPD patients demonstrate efficacy in a small pilot study.How this study might affect research, practice or policyMicrobiome-targeting therapeutics and nutritional interventions may be developed for COPD, including as supplements to smoking cessation.
Quantifying and mitigating recorder-induced variability in ecological acoustic indices
Authors: Luna-Naranjo David , Martínez Juan D. , Sánchez-Giraldo Camilo , Daza Juan M. , López José D. 
Published: October 2023

AbstractDue to the complexity of soundscapes, Ecological Acoustic indices (EAI) are frequently used as metrics to summarize ecologically meaningful information from audio recordings. Recent technological advances have allowed the rapid development of many audio recording devices with significant hardware/firmware variations among brands, whose effects in calculating EAI have not yet be determined. In this work, we show how recordings of the same landscape with different devices effectively hinder reproducibility and produce contradictory results. To address these issues, we propose a preprocessing pipeline to reduce EAI variability resulting from different hardware without altering the target information in the audio. To this end, we tested eight EAI commonly used in soundscape analyses. We targeted three common cases of variability caused by recorder characteristics: sampling frequency, microphone gain variation, and frequency response. We quantified the difference in the probability density functions of each index among recorders according to the Kullback-Leibler divergence. As a result, our approach reduced up to 75% variations among recorders from different brands (AudioMoth and SongMeter) and identified the conditions in which these devices are comparable. In conclusion, we demonstrated that different devices effectively affect EAI and show how these variations can be mitigated.Graphical AbstractHighlightsAddressing recorder-induced biases in acoustic indices for improved reproducibility.Proposing an effective method to mitigate recorder-related biases.Evaluating pipeline proposed performance via acoustic index distribution analysis.
A comprehensive neuroanatomical survey of theDrosophilaLobula Plate Tangential Neurons with predictions for their optic flow sensitivity
Authors: Zhao Arthur , Nern Aljoscha , Koskela Sanna , Dreher Marisa , Erginkaya Mert , Laughland Connor W. , Ludwigh Henrique , Thomson Alex , Hoeller Judith , Parekh Ruchi , Romani Sandro , Bock Davi D. , Chiappe Eugenia , Reiser Michael B. 
Published: October 2023

AbstractFlying insects exhibit remarkable navigational abilities controlled by their compact nervous systems.Optic flow, the pattern of changes in the visual scene induced by locomotion, is a crucial sensory cue for robust self-motion estimation, especially during rapid flight. Neurons that respond to specific, large-field optic flow patterns have been studied for decades, primarily in large flies, such as houseflies, blowflies, and hover flies. The best-known optic-flow sensitive neurons are the large tangential cells of the dipteran lobula plate, whose visual-motion responses, and to a lesser extent, their morphology, have been explored using single-neuron neurophysiology. Most of these studies have focused on the large, Horizontal and Vertical System neurons, yet the lobula plate houses a much larger set of ‘optic-flow’ sensitive neurons, many of which have been challenging to unambiguously identify or to reliably target for functional studies. Here we report the comprehensive reconstruction and identification of the Lobula Plate Tangential Neurons in an Electron Microscopy (EM) volume of a wholeDrosophilabrain. This catalog of 58 LPT neurons (per brain hemisphere) contains many neurons that are described here for the first time and provides a basis for systematic investigation of the circuitry linking self-motion to locomotion control. Leveraging computational anatomy methods, we estimated the visual motion receptive fields of these neurons and compared their tuning to the visual consequence of body rotations and translational movements. We also matched these neurons, in most cases on a one-for-one basis, to stochastically labeled cells in genetic driver lines, to the mirror-symmetric neurons in the same EM brain volume, and to neurons in an additional EM data set. Using cell matches across data sets, we analyzed the integration of optic flow patterns by neurons downstream of the LPTs and find that most central brain neurons establish sharper selectivity for global optic flow patterns than their input neurons. Furthermore, we found that self-motion information extracted from optic flow is processed in distinct regions of the central brain, pointing to diverse foci for the generation of visual behaviors.
Improved science communication and student gains from an undergraduate biomedical research experience
Authors: Ward Donna , Han Yueh-Ying , Qoyawayma Christopher , Dukes April , McClendon T. Brooke , Manni Michelle L. 
Published: October 2023

ABSTRACTSummer research experiences expose undergraduate students to biomedical research in a laboratory or clinical setting, but often do not incorporate formal learning on scientific communication. Proper written and oral communication of science is essential to succeed in biomedical fields. This study examined whether participation in a science communication series (SCS) would increase gains in research and written communication abilities among students participated in the University of Pittsburgh School of Medicine Department of Pediatrics Summer Research Internship Program. Surveys were administered at the beginning and end of the program to evaluate their summer undergraduate research experience (SURE). Positive personal and professional gains in research and communication skills were identified through participation in both SURE and SCS. Participation in the SCS also significantly improved the quality and presentation of research abstracts. Focused learning in science communication during SUREs would improve undergraduate students’ personal and professional abilities in biomedical research and medicine.
Ribosomal S6 kinase 1 regulates ‘inflammaging’ via the senescence secretome
Authors: Gallage Suchira , Irvine Elaine E. , Pedroni Silvia M.A. , Barragan Avila Jose Efren , Khadayate Sanjay , Pombo Joaquim , Brookes Sharon , Heide Danijela , Dharmalingham Gopuraja , Choudhury Agharul I. , Herranz Nicolás , Vernia Santiago , Heikenwalder Mathias , Gil Jesús , Withers Dominic J. 
Published: October 2023

ABSTRACTInhibition of the nutrient-responsive mTOR (mammalian target of rapamycin) signalling pathway including the key downstream effector S6 kinase 1 (S6K1) extends lifespan and improves healthspan in mice. However, the underlying mechanisms contributing to the broad range of age-related benefits observed with loss of S6K1 signalling are unclear. Cellular senescence is a stable growth arrest accompanied by an inflammatory phenotype (termed the senescence-associated secretory phenotype, or SASP). While both cellular senescence and SASP-mediated chronic inflammation contribute to age-related pathology, the specific role of S6K1 signalling in these processes has not been determined. Here, focussing on mouse liver, a key target tissue for the beneficial metabolic effects of loss of S6K1 signalling, we show that S6K1 deletion does not reduce senescence but ameliorates inflammation and immune cell infiltration in aged livers. Using human and mouse models of senescence, we demonstrated that reduced inflammation is a liver-intrinsic effect associated with S6K deletion. Furthermore, gene expression analysis suggested that downregulated cGAS/STING and IRF3 activation might mediate the impaired SASP observed upon S6K deletion. Using a hepatic oncogene induced senescence model, we showedin vivo thatS6K1deletion results in reduced IRF3 activation, impaired production of cytokines such as IL1ý and reduced immune infiltration. Overall, deletion of S6K reduces inflammation in the liver suggesting that suppression of the inflammatory SASP by loss of S6K could contribute to explain the beneficial effects of inhibiting this pathway on healthspan and lifespan.
OPUS-Rota5: A Highly Accurate Protein Side-chain Modeling Method with 3D-Unet and RotaFormer
Authors: Xu Gang , Luo Zhenwei , Yan Yaming , Wang Qinghua , Ma Jianpeng 
Published: October 2023

AbstractAccurate protein side-chain modeling is crucial for protein folding and design. This is particularly true for molecular docking as ligands primarily interact with side chains. A protein structure with large errors in side chains has limited usage such as in drug design. Previous research on AlphaFold2 (AF2) predictions of GPCR targets indicates that the docking of natural ligands back on AF2-predicted structures has limited successful rate presumably due to large errors in side chains. Here, we introduce a two-stage side-chain modeling approach called OPUS-Rota5. It leverages a modified 3D-Unet to capture the local environmental features including ligand information of each residue, and then employs RotaFormer module to aggregate various types of feature. Evaluation on three test sets, including recently released targets from CAMEO and CASP15, reveals that side chains modeled by OPUS-Rota5 are significantly more accurate than those predicted by other methods. We also employ OPUS-Rota5 to refine the side chains of 25 GPCR targets predicted by AF2 and then performed docking of their natural ligands back with a significantly improved successful rate. Such results suggest that OPUS-Rota5 could be a valuable tool for molecular docking, particularly for targets with relatively accurate predicted backbones, but not side chains.
The human cytomegalovirus-encoded pUS28 antagonizes CD4+ T-cell recognition by targeting CIITA
Authors: Maaßen Fabienne , Le-Trilling Vu Thuy Khanh , Betke Luisa , Bracht Thilo , Schuler Corinna , Bayer Malte , Belter Antonia , Becker Tanja , Katschinski Benjamin , Frappier Lori , Sitek Barbara , Fleischhauer Katharina , Trilling Mirko 
Published: October 2023

SummaryHuman cytomegalovirus (HCMV) is a relevant pathogen especially for individuals with impaired immunity. Harnessing potent immune antagonists, HCMV circumvents sterile immunity. Given that HCMV prevents the upregulation ofhuman leukocyte antigen(HLA)-DP and HLA-DR, we screened a library of HCMV genes by co-expression with the HLA class II (HLA-II)-inducing transcription coordinatorclass II transactivator(CIITA). We identified the latency regulator pUS28 as interaction factor and potent viral antagonist of CIITA-driven expression of CD74, HLA-DR, HLA-DM, HLA-DQ, and HLA-DP. Both wt-pUS28 and a mutant incapable to induce G-protein-coupled signaling (R129A), but not a mutant lacking the C-terminus, drastically reduced the CIITA protein abundance post-transcriptionally. While control CD4+ T cells from HCMV-seropositive individuals vigorously responded to CIITA-expressing cells decorated with HCMV antigens, pUS28 expression was sufficient to inhibit HLA-II induction and immune recognition by HCMV-specific CD4+ T cells. Our data uncover a mechanism employed by HCMV to evade HLA-II-mediated recognition by CD4+ T cells.
MOAL: Multi-Omic Analysis at Lab. A simplified methodology workflow to make reproducible omic bioanalysis
Authors: Dumont Florent , Ponsardin Emy , Bernadat Guillaume , Cohen-Kaminsky Sylvia 
Published: October 2023

AbstractOmic data research projects are still developing today, but analysis suffers from not having a standardized workflow for biostatistics and functional integration steps that we gather here as bioanalysis. To make bioanalysis more reproducible and accessible, we created MOAL (Multi-Omic Analysis at Lab), an R package including a omic() function that automates most classical tasks. We reproduced in one go the results of a published dataset starting from unfiltered available data confirming the capabilities to automate the production of omic bioanalysis using MOAL.
The genetic architecture of protein interaction affinity and specificity
Authors: Bendel Alexandra M. , Faure André J. , Klein Dominique , Shimada Kenji , Kempf Georg , Cavadini Simone , Lehner Ben , Diss Guillaume 
Published: October 2023

AbstractProteins function in crowded cellular environments in which they must bind to specific target proteins but also avoid binding to many other off-target proteins. In large protein families this task is particularly challenging because many off-target proteins have very similar structures. How this specificity of physical protein-protein interactions in cellular networks is encoded and evolves is not very well understood. Here we address the question of specificity-encoding by comprehensively quantifying the effects of all mutations in one protein, JUN, on its binding to all other members of a protein family, the 54 human basic leucine zipper transcription factors. Fitting a global thermodynamic model to the data reveals that most affinity changing mutations equally affect JUN’s propensity to bind to all its interaction partners. Mutations that alter the specificity of binding are much rarer. These specificity-altering mutations are, however, distributed throughout the JUN interaction interface. JUN’s interaction specificity is encoded by both positive determinants that promote on-target interactions and negative determinants that prevent off-target interactions. Indeed, about half of the specificity-defining residues in JUN have dual functions and both promote on-target binding and prevent off-target binding. Whereas nearly all mutations that alter specificity are pleiotropic and also alter the affinity of binding to all interaction partners, the converse is not true with mutations outside of the interface able to tune affinity without affecting specificity. Our results provide the first global view of how mutations in a protein affect binding to all its potential interaction partners and reveal the distributed encoding of specificity and affinity in an interaction interface. They also show how the modular architecture of coiled-coils provides an elegant solution to the challenge of optimising specificity and affinity in a large protein family.
A novel approach to identify cross-identity peptides between Epstein-Barr virus and central nervous system proteins in Guillain-Barré syndrome and multiple sclerosis
Authors: do Patrocínio Helmut Kennedy Azevedo , Fiúza Tayná da Silva , Oliveira Jonas Ivan Nobre , Rodrigues-Neto João Firmino , Jerônimo Selma Maria Bezerra , de Souza Gustavo Antônio , Lima João Paulo Matos Santos 
Published: October 2023

AbstractBackgroundGuillain-Barré Syndrome (GBS) and multiple sclerosis are autoimmune diseases associated with an immune system attack response against peripheral and central nervous system autoantigens, respectively. Given the potential of Epstein-Barr virus (EBV) as a risk factor for both multiple sclerosis and GBS, the present study aimed to identify crucial residues among potential EBV CD4+ T lymphocyte epitopes and nervous system proteins.MethodsPublic databases (Allele Frequency Net Database, Immune Epitope Database, Genevestigator and Protein Atlas) were used to select proteins abundant in the nervous system, EBV immunogenic proteins, and HLA haplotypes. Computational tools were employed for predicting HLA-binding peptides and immunogenicity. For this, we developed immuno-cross, a Python tool (https://github.com/evoMOL-Lab/immuno-cross) to compare residue identity among nonamers.ResultsWe found ten proteins from the nervous system and 28 from EBV, which were used for predicting the binding peptides of 21 common HLAs in the world population. A total of 1411 haplotypes were distributed among 51 pairs of HLAs. Simulations were performed to determine whether nonamers from the EBV and nervous system proteins targeted TCR-contact residues. Then, three selection criteria were used, based on the relevance of each contact in the TCR-peptide-MHC interaction. The primary contact has to be located at position P5, and the positions P2, P3, and P8 were weighed as secondary, and P4, P6, and P7 were considered tertiary. Nonamers of EBV proteins and myelin proteins were combined in pairs and compared based on predefined selection criteria. The Periaxin protein had the highest number of nonamers pairs among PNS proteins, with 35 pairs. Four nonamers pairs from APLP1, two from CNP, and two from MBP bind to alleles of the haplotype DR-15.ConclusionsThe new approach proposed herein revealed that peptides derived from nervous system and EBV proteins share identical residues at critical contact points, which supports molecular mimicry. These findings suggest cross-reactivity between them and that the nonamer pairs identified with this approach have the potential to be an autoantigen. Experimental studies are needed to validate these findings.
Acute toxicity effects of pesticides on predatory snout mites (family Bdellidae)
Authors: Knapp Rosemary A. , Mata Luis , McDougall Robert , Yang Qiong , Hoffmann Ary A. , Umina Paul A. 
Published: October 2023

AbstractPredatory mites biologically control a range of arthropod crop pests and are often central to agricultural IPM strategies globally. Conflict between chemical and biological pest control has prompted increasing interest in selective pesticides with fewer off-target impacts on beneficial invertebrates, including predatory mites. However, the range of predatory mite species included in standardised pesticide toxicity assessments does not match the diversity of naturally-occurring species contributing to biocontrol, with most testing carried out on species from the family Phytoseiidae. Here, we aim to bridge this knowledge gap by investigating the impacts of 22 agricultural pesticides on the predatory snout miteOdontoscirus lapidaria(Kramer) (family Bdellidae). Using internationally standardised testing methodologies, we identified several active ingredients with minimal impact onO. lapidariamortality, includingBacillus thuringiensis, nuclear polyhedrosis virus, flonicamid, afidopyropen, chlorantraniliprole and cyantraniliprole, which may therefore be good candidates for IPM strategies utilising both chemical and biological control. Importantly, we reveal differences between Bdellidae and Phytoseiidae in responses to a number of chemicals, including the miticides diafenthiuron and abamectin, highlighting the risk of making generalisations around acute toxicity based on tests with one beneficial mite family. We also explored the impacts of several pesticides on a second Bdellidae species and found differences in the response to chlorpyrifos compared withO. lapidaria, further highlighting the taxon-specific nature of non-target toxicity effects.