bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial behaviors and seasonal habitat use of the increasingly endangered thick-billed parrot (Rhynchopsitta pachyrhyncha)
Authors: Sheppard James K , Cruz Javier , Torres González Luz Francelia , Cruz Nieto Miguel Ángel , Swaisgood Ronald R. , Lamberski Nadine 
Published: September 2023

AbstractThe thick-billed parrot (Rhynchopsitta pachyrhyncha) inhabits highland pine forests in the Sierra Madre Occidental ranges of northwestern Mexico. Their populations have declined significantly to <2000 individuals due to habitat loss, illegal hunting and increasing predation. Despite their ecological and cultural importance and increasingly endangered status, the species is data deficient. Our study aimed to inform and enhance conservation management strategies for thick-billed parrots with information on their spatial ecology, habitat use, migratory behaviors and social associations. We deployed biotelemetry devices to conduct the first tracking study of wild thick-billed parrots. Our study revealed that thick-billed parrots are seasonal migrators, departing their breeding habitats around October and returning from southern habitats around April. Our research also identified previously unknown overwintering sites and migratory stopover locations, as well as a new nesting site. The parrots exhibited high spatial variability in range shifting behavior, but all tracked parrots exhibited range shifts during migration, with durations of 3 to 181 days and distances of 173 to 765 km. They traveled in close social groups and migratory routes primarily followed high-elevation forests along the Sierra Madre Occidental ranges. Home range analysis indicated smaller breeding site ranges and larger overwintering ranges, possibly reflecting nesting constraints and winter food resource dispersion. Parrot spatial associations favored high-elevation forest landscapes with tall and wide-trunked trees, underscoring the importance of preserving old-growth forests for nesting and foraging. Less than 20 % of parrot habitats have formal regulatory protections. Conservation management efforts must focus on increasing protections for nesting areas, overwintering habitats, and key migratory stopover sites. As climate change exacerbates regional threats, integrated management plans involving local stakeholders and communities are essential for the parrots’ long-term survival and the preservation of their old-growth forest habitats.
Exploring “dark matter” protein folds using deep learning
Authors: Harteveld Zander , Van Hall-Beauvais Alexandra , Morozova Irina , Southern Joshua , Goverde Casper , Georgeon Sandrine , Rosset Stéphane , Defferrard Michëal , Loukas Andreas , Vandergheynst Pierre , Bronstein Michael M. , Correia Bruno E. 
Published: September 2023

AbstractDe novoprotein design aims to explore uncharted sequence-and structure areas to generate novel proteins that have not been sampled by evolution. One of the main challenges inde novodesign involves crafting “designable” structural templates that can guide the sequence search towards adopting the target structures. Here, we present an approach to learn patterns of protein structure based on a convolutional variational autoencoder, dubbed Genesis. We coupled Genesis with trRosetta to design sequences for a set of protein folds and found that Genesis is capable of reconstructing native-like distance-and angle distributions for five native folds and three novel, so-called “dark-matter” folds as a demonstration of generalizability. We used a high-throughput assay to characterize protease resistance of the designs, obtaining encouraging success rates for folded proteins and further biochemically characterized folded designs. The Genesis framework enables the exploration of the protein sequence and fold space within minutes and is not bound to specific protein topologies. Our approach addresses the backbone designability problem, showing that structural patterns in proteins can be efficiently learned by small neural networks and could ultimately contribute to thede novodesign of proteins with new functions.
Human Ageing Genomic Resources: updates on key databases in ageing research
Authors: de Magalhães João Pedro , Abidi Zoya , Arantes dos Santos Gabriel , Avelar Roberto A. , Barardo Diogo , Chatsirisupachai Kasit , Clark Peter , De-Souza Evandro A. , Johnson Emily J. , Lopes Inês , Novoa Guy , Senez Ludovic , Talay Angelo , Thornton Daniel , To Paul Ka Po 
Published: September 2023

AbstractAgeing is a complex and multifactorial process. For two decades, the Human Ageing Genomic Resources (HAGR) have aided researchers in the study of various aspects of ageing and its manipulation. Here we present the key features and recent enhancements of these resources, focusing on its six main databases. One database, GenAge, focuses on genes related to ageing, featuring 307 genes linked to human ageing and 2205 genes associated with longevity and ageing in model organisms. AnAge focuses on ageing, longevity, and life-history across animal species, containing data on 4645 species. DrugAge includes information about 1097 longevity drugs and compounds in model organisms such as mice, rats, flies, worms, and yeast. GenDR provides a list of 214 genes associated with the life-extending benefits of dietary restriction in model organisms. CellAge contains a catalogue of 866 genes associated with cellular senescence. The LongevityMap serves as a repository for genetic variants associated with human longevity, encompassing 3144 variants pertaining to 884 genes. Additionally, HAGR provides various tools as well as gene expression signatures of ageing, dietary restriction, and replicative senescence based on meta-analyses. Our databases are integrated, regularly updated, and manually curated by experts. HAGR is freely available online (https://genomics.senescence.info/).
Gene count normalization in single-cell imaging-based spatially resolved transcriptomics
Authors: Atta Lyla , Clifton Kalen , Anant Manjari , Aihara Gohta , Fan Jean 
Published: September 2023

AbstractRecent advances in imaging-based spatially resolved transcriptomics (im-SRT) technologies now enable high-throughput profiling of targeted genes and their locations in fixed tissues. Normalization of gene expression data is often needed to account for technical factors that may confound underlying biological signals. Here, we investigate the potential impact of different gene count normalization methods with different targeted gene panels in the analysis and interpretation of im-SRT data. Using different simulated gene panels that overrepresent genes expressed in specific tissue regions or cell types, we demonstrate how normalization methods based on detected gene counts per cell differentially impact normalized gene expression magnitudes in a region- or cell type-specific manner. We show that these normalization-induced effects may reduce the reliability of downstream analyses including differential gene expression, gene fold change, and spatially variable gene analysis, introducing false positive and false negative results when compared to results obtained from gene panels that are more representative of the gene expression of the tissue’s component cell types. These effects are not observed with normalization approaches that do not use detected gene counts for gene expression magnitude adjustment, such as with cell volume or cell area normalization. We recommend using non-gene count-based normalization approaches when feasible and evaluating gene panel representativeness before using gene count-based normalization methods if necessary. Overall, we caution that the choice of normalization method and gene panel may impact the biological interpretation of the im-SRT data.
Translocation of gut commensal bacteria to the brain
Authors: Thapa Manoj , Kumari Anuradha , Chin Chui-Yoke , Choby Jacob E. , Jin Fengzhi , Bogati Bikash , Chopyk Daniel M. , Koduri Nitya , Pahnke Andrew , Elrod Elizabeth J. , Burd Eileen M. , Weiss David S. , Grakoui Arash 
Published: September 2023

AbstractThe gut-brain axis, a bidirectional signaling network between the intestine and the central nervous system, is crucial to the regulation of host physiology and inflammation. Recent advances suggest a strong correlation between gut dysbiosis and neurological diseases, however, relatively little is known about how gut bacteria impact the brain. Here, we reveal that gut commensal bacteria can translocate directly to the brain when mice are fed an altered diet that causes dysbiosis and intestinal permeability, and that this also occurs without diet alteration in distinct murine models of neurological disease. The bacteria were not found in other systemic sites or the blood, but were detected in the vagus nerve. Unilateral cervical vagotomy significantly reduced the number of bacteria in the brain, implicating the vagus nerve as a conduit for translocation. The presence of bacteria in the brain correlated with microglial activation, a marker of neuroinflammation, and with neural protein aggregation, a hallmark of several neurodegenerative diseases. In at least one model, the presence of bacteria in the brain was reversible as a switch from high-fat to standard diet resulted in amelioration of intestinal permeability, led to a gradual loss of detectable bacteria in the brain, and reduced the number of neural protein aggregates. Further, in murine models of Alzheimer’s disease, Parkinson’s disease, and autism spectrum disorder, we observed gut dysbiosis, gut leakiness, bacterial translocation to the brain, and microglial activation. These data reveal a commensal bacterial translocation axis to the brain in models of diverse neurological diseases.
Vγ9Vδ2 T cells recognize butyrophilin 2A1 and 3A1 heteromers
Authors: Fulford Thomas S. , Soliman Caroline , Castle Rebecca G. , Rigau Marc , Ruan Zheng , Dolezal Olan , Seneviratna Rebecca , Brown Hamish G. , Hanssen Eric , Hammet Andrew , Li Shihan , Redmond Samuel J. , Chung Amy , Gorman Michael A. , Parker Michael W. , Patel Onisha , Peat Thomas S. , Newman Janet , Behren Andreas , Gherardin Nicholas A. , Godfrey Dale I. , Uldrich Adam P. 
Published: September 2023

AbstractButyrophilin (BTN) molecules are emerging as key regulators of T cell immunity, however, how they trigger cell-mediated responses is poorly understood. Here, the crystal structure of a gamma-delta T cell receptor (γδTCR) in complex with BTN member 2A1 (BTN2A1) revealed that BTN2A1 engages the side of the γδTCR, leaving the apical TCR surface bioavailable. We reveal that BTN3A1 is a second γδTCR ligand, that co-engages γδTCR via binding to this accessible apical surface. BTN2A1 and BTN3A1 also directly interact with each other in cis, and structural analysis revealed formation of W-shaped heteromeric multimers. This BTN2A1–BTN3A1 interaction involved the same epitopes that BTN2A1 and BTN3A1 each use to engage γδTCR; indeed, either forced separation or locking together of BTN2A1 and BTN3A1 resulted in enhanced or abrogated γδTCR interaction, respectively. Our findings reveal a new paradigm in immune activation, whereby γδTCRs recognize dual epitopes on BTN2A1 and BTN3A1 complexes.
Enhancement of Protein Stability by Quenching Millisecond Conformational Dynamics
Authors: Hou Xue-Ni , Zhao Chang , Song Bin , Ruan Mei-Xia , Dong Xu , Gong Zhou , Weng Yu-Xiang , Zheng Jie , Tang Chun 
Published: September 2023

AbstractProtein folding may involve folding intermediates. Ubiquitin (Ub) is a 76-residue small protein essential in post-translational modification and cell signaling. Ub is also a model system of protein folding. Previous studies have indicated the involvement of a folding intermediate, as Ub C-terminal residues, including strand β5, only dock correctly at a later stage. The natively folded Ub undergoes conformational dynamics over a vast range of timescales. At the millisecond timescale, Ub transiently digresses to a C-terminally retracted state, which is extremely rare and has only been recently identified at an elevated temperature. Herein through a conjoint use of NMR, MS, and MD simulations, we have established a link between Ub millisecond dynamics and protein stability. Among the alanine mutations that have been systematically introduced to the hydrophobic residues in β5, L67A and L69A elevate the population of the retracted state and enhance conformational interconversion, which facilitates the undocking of β5 and the exposure of protein hydrophobic core. Conversely, L71A and L73A mutations decrease the population of the retracted state and quench millisecond dynamics, which causes a significant enhancement of protein stability. As such, the transition state of Ub millisecond dynamics is the much sought-after folding intermediate, whereas C-terminal mutations alleviate the dependence on this intermediate and reduce the unfolding to an all-or-none process. Though having a negative impact on protein stability, Ub millisecond dynamics likely facilitate proper protein turnover and allow the fulfillment of its biological function.
Effects of pharmacological interventions on short- and long-term mortality in patients with takotsubo syndrome: a report from the SWEDEHEART registry
Authors: Petursson P , Oštarijaš E , Redfors B , Råmunddal T , Angerås O , Völz S , Rawshani A , Hambraeus K , Koul S , Alfredsson J , Hagström H , Loghman H , Hofmann R , Fröbert O , Jernberg T , James S , Erlinge D , Omerovic E 
Published: September 2023

AbstractAimTakotsubo cardiomyopathy (TS) is a heart condition mimicking acute myocardial infarction. TS is characterized by a sudden weakening of the heart muscle, usually triggered by physical or emotional stress. In this study, we aimed to investigate the effect of pharmacological interventions on short– and long-term mortality in patients with TS.MethodsWe analyzed data from the SWEDEHEART (The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry, which included 1,724 patients with TS among 228,263 unique individuals who underwent coronary angiography between 2009 and 2016. The majority of patients were female (77.0%), and the average age was 66 ± 14 years.ResultsNearly half of the TS patients (49.4%) presented with non-ST-elevation acute coronary syndrome and a quarter (25.9%) presented as ST-elevation myocardial infarction. Most patients had non-obstructive coronary artery disease on angiography, while 11.7% had a single-vessel disease and 9.2% had multivessel disease. All patients received at least one pharmacological intervention, most used being beta-blockers or antiplatelet agents. All-cause mortality rates were 3.9% after 30-days and and 16.7% at long-term follow-up (median 877 days). Intravenous use of inotropes, diuretics, and orally administered digoxin were associated with increased mortality in TS, while ACE-I and statins were associated with decreased long-term mortality. Unfractionated and low-molecular-weight heparin (UH/LMWH) were associated with reduced 30-day mortality. However, medications such as ARBs, oral anticoagulants, P2Y12 antagonists, aspirin, and beta-blockers did not statistically correlate with mortality.ConclusionOur findings suggest that some medications commonly used to treat TS are associated with higher mortality while others with lower mortality. These results could inform clinical decision-making and improve patient outcomes in TS. Further research is warranted to validate these findings and to identify optimal pharmacological interventions for patients with TS.
Comparative evaluation of bioinformatic tools for virus-host prediction and their application to a highly diverse community in the Cuatro Ciénegas Basin, Mexico
Authors: Cisneros-Martínez Alejandro Miguel , Rodriguez-Cruz Ulises E. , Alcaraz Luis D. , Becerra Arturo , Eguiarte Luis E. , Souza Valeria 
Published: September 2023

AbstractThe sheer diversity of unculturable viruses has prompted the need to describe new viruses through culture-independent techniques. The associated host is one important phenotypic feature that can be inferred from metagenomic viral contigs -- thanks to the development of various bioinformatic tools. Here we compare the performance of recently developed tools for virus-host prediction on a dataset of 1,046 virus-host pairs and then apply the best-performing tools on a metagenomic dataset derived from a highly diverse transiently hypersaline site known as Archaean Domes within the Cuatro Ciénegas Basin, Coahuila, Mexico. We also introduce a virus-host prediction tool called CrisprCustomDB, which uses specific criteria to solve controversial host assignments with custom spacers databases. Host-dependent alignment-based methods showed an average precision of 83% and a sensitivity from 13.7% to 17.7%, whereas host-dependent alignment-free methods achieved an average precision of 75.7% and a sensitivity of 57.5%. RaFAH, a virus-dependent alignment-based tool, had the best performance overall (F1_score = 95.7%). However, when applied to the highly diverse metagenomic dataset, the host-dependent alignment-based (e.g., CrisprCustomDB) and alignment-free (e.g., PHP) methods showed the greatest agreement with each other, even though they are fundamentally different methods. This is because instead of depending on known hosts or viruses-with-known-host databases, they can directly relate metagenomic viral contigs and metagenome-assembled genomes from the same dataset. Such methods also showed the greatest consistency between the source environment and the predicted host taxonomy, habitat, lifestyle, or metabolism, revealing that Archaean Domes viruses likely infect halophilic Archaea as well as a variety of Bacteria which may be halophilic, halotolerant, alkaliphilic, thermophilic, oligotrophic, sulfate-reducing or marine-related. Consequently, using a combination of methods and qualitative validations relating to the source environment and the predicted host biology will increase the number of correct predictions, mainly when dealing with novel viruses.
PTMNavigator: Interactive Visualization of Differentially Regulated Post-Translational Modifications in Cellular Signaling Pathways
Authors: Müller Julian , Bayer Florian P. , Wilhelm Mathias , Schuh Maximilian G. , Kuster Bernhard , The Matthew 
Published: September 2023

AbstractPost-translational modifications (PTMs) play pivotal roles in regulating cellular signaling, fine-tuning protein function, and orchestrating complex biological processes. Despite their importance, the lack of comprehensive tools for studying PTMs from a pathway-centric perspective has limited our ability to understand how PTMs modulate cellular pathways on a molecular level. Here, we present PTMNavigator, a tool integrated into the ProteomicsDB platform, which offers an interactive interface for researchers to overlay experimental PTM data with pathway diagrams. PTMNavigator provides ∼3000 canonical pathways from manually curated databases and further enables users to modify and create custom diagrams, tailored to their data. Additionally, PTMNavigator automatically runs multiple kinase and pathway enrichment algorithms whose results are directly integrated into the visualization. This offers a comprehensive view of the intricate relationship between PTMs and signaling pathways. To demonstrate the utility of PTMNavigator, we applied it to two phosphoproteomics perturbation datasets. First, PTMNavigator enhanced pathway enrichment analysis by showing how the regulated peptides and proteins are distributed in the pathways with high enrichment scores. Second, it visualized how drug treatments result in a discernable flow of PTM-driven signaling within pathways. Third, PTMNavigator aided in proposing extensions to an existing pathway by suggesting putative new links between both PTMs and pathway components. By enhancing our understanding of cellular signaling dynamics and facilitating the discovery of novel PTM-pathway interactions, PTMNavigator advances our knowledge of PTM biology and its implications in health and disease.
Gut microbes contribute to variation in foraging intensity in the honey bee,Apis mellifera
Authors: Vernier Cassondra L. , Nguyen Thi Lan Anh , Gernat Tim , Ahmed Amy Cash , Chen Zhenqing , Robinson Gene E. 
Published: September 2023

AbstractGut microbiomes are increasingly recognized for mediating diverse biological aspects of their hosts, including complex behavioral phenotypes. While many studies have reported that experimental disruptions to the gut microbiome result in atypical host behavior, studies that address how gut microbes contribute to adaptive behavioral trait variation are rare. Eusocial insects represent a powerful model to test this, due to their simple microbiomes and complex division of labor characterized by colony-level variation in behavioral phenotypes. While previous studies report correlational differences in gut microbiome associated with division of labor, here, we provide evidence that gut microbes play a causal role in defining differences in foraging behavior between honey bees. Gut microbial community structure consistently differed between hive-based nurse bees and bees that leave the hive to forage for floral resources. These differences were associated with variation in the abundance of individual microbes, includingBifidobacterium asteroides, Bombilactobacillus mellis,andLactobacillus melliventris. Manipulations of colony demography and individual foraging experience suggested that differences in microbiome composition were associated with task experience. Moreover, single microbe inoculations withB. asteroides,B. mellis,andL. melliventriscaused changes in foraging intensity. These results demonstrate that gut microbes contribute to division of labor in a social insect, and support a role of gut microbes in modulating host behavioral phenotypic variation.
Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53
Authors: Lee Jonathan D. , Menasche Bridget L. , Mavrikaki Maria , Uyemura Madison M. , Hong Su Min , Kozlova Nina , Wei Jin , Alfajaro Mia M. , Filler Renata B. , Müller Arne , Saxena Tanvi , Posey Ryan R. , Cheung Priscilla , Muranen Taru , Heng Yujing J. , Paulo Joao A. , Wilen Craig B. , Slack Frank J. 
Published: September 2023

AbstractCOVID-19 remains a significant public health threat due to the ability of SARS-CoV-2 variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and MERS-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here we used our recently developed integrative DNA And Protein Tagging (iDAPT) methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses. SARS-CoV-2 infection induces TP53 stabilization on chromatin, which contributes to its host cytopathic effect. We mapped this TP53 stabilization to the SARS-CoV-2 spike and its propensity to form syncytia, a consequence of cell-cell fusion. Differences in SARS-CoV-2 spike variant-induced syncytia formation modify chromatin accessibility, cellular senescence, and inflammatory cytokine release via TP53. Our findings suggest that differences in syncytia formation alter senescence-associated inflammation, which varies among SARS-CoV-2 variants.