bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise intensity shapes acute and prolonged immune and extracellular vesicle responses in older adults
Authors: Garza Alejandra P. , Morton Lorena , Motsch Anna-Lena , Puta Christian , Stiebler Marvin , Lading Yves , Schreiber Stefanie , Braun-Dullaeus Rüdiger , Müller Patrick , Dunay Ildiko R. 
Published: November 2024

AbstractRegular physical activity is a cornerstone of healthy aging, offering a wide range of benefits, including the modulation of immune regulation and reduction of chronic inflammation. With aging closely linked to persistent, low-grade inflammation, i.e. inflammaging, the effects of exercise intensity on acute immune responses in older adults remain not fully understood. In this study, we explored how moderate and intense acute continuous exercise impact immune cell activation, cytokine production and large extracellular vesicle (lEV) release in healthy elderly individuals. Fourteen participants completed a moderate continuous exercise intervention (60% VO2maxfor 30 minutes), while nineteen engaged in an intense continuous exercise session until exhaustion. Blood samples were collected at baseline, and at 1- and 24-hours post-exercise. Immune cell characterization by flow cytometry revealed distinct changes in monocyte subsets and NK cells activation across both exercise intensities. Intense exercise was associated with elevated proinflammatory TNFα levels, accumulation of circulating plasma-derived lEV and changes in their surface marker expression after 24 hours. Additionally, we identified sex-specific differences, including distinct activation profiles in innate immunity, alterations in EV release from CD4+and HLA+ cells, and an exercise-induced increase in IL-6 observed exclusively in females. These findings suggest that moderate continuous acute exercise enhances immune cell activation without altering cell counts, while intense continuous exercise triggers acute proinflammatory immune response. Further research should clarify the long-term implications and fundamental mechanisms of exercise-induced immune modulation in aging populations.Key points summaryDiminished immune function upon aging is increasing disease risk. This study examines how tailored acute exercise interventions stimulate immune regulation in older adults addressing age-related inflammatory challenges.Acute continuous moderate and intense exercise elicit distinct immune responses in elderly individuals with marked differences between sexes. Interestingly, IL-6 levels increased 30 min moderate exercise exclusively in females.Exercise promotes the release of extracellular vesicles (EVs) and modulates peripheral immunity, suggesting a potent mechanism by which physical activity supports immune resilience in aging.Tailored acute exercise regimens for older adults may enhance immune health, mitigating age-related inflammatory risks and enhancing resilience.This study emphasizes the need for further research on exercise-driven modulation focusing on sex differences and their implications for targeted interventions upon aging.
An epigenetic basis for sustained inflammatory epithelial progenitor cell states in Crohn’s disease
Authors: Karakasheva Tatiana A. , Morral Martinez Clara , Zhou Yusen , Qui Jingya , Chen Xinyi E. , Soto Gloria E. , Nettleford Shaneice K. , Hix Olivia T. , Roach Daana M. , Laguerta Alyssa M. , Thadi Anusha , Edwards Rachael M. , Aleynick Daniel , Weinbrom Sarah , Borodyanskaya Elizaveta , Pickering Oliver H. , Fulton MaryKate , Chen Chia-Hui , Peterson Bella V. , Hagen Erik B. , Yannuzzi Ian P. , Haider Zainab , Cramer Zvi , Conrad Maire , Li Ning , Bewtra Meenakshi , Uzun Yasin , Tan Kai , Kelsen Judith R. , Minn Andy J. , Lengner Christopher J. , Hamilton Kathryn E. 
Published: November 2024

SUMMARYDefining consequential differences in intestinal epithelial stem cells in healthy humans versus those with inflammatory bowel disease (Crohn’s disease and ulcerative colitis) is essential for the development of much needed therapies to restore the epithelial barrier and maintain its fidelity. Employing single cell transcriptomic/epigenomic approaches and colonoid models from children and adults with Crohn’s disease led us to identify an inflammatory secretory progenitor (ISP) cell state present almost exclusively in patients with Crohn’s disease compared to control subjects. ISPs exhibit gene expression profiles consistent with normal secretory progenitor cells but concomitantly express a suite of distinguishing pro-inflammatory genes. Mechanistically, ISPs exhibit open chromatin and gene expression of ISP signature genes. While these ISP-specific genes are not expressed in intestinal stem cells, their chromatin is accessible in Crohn’s disease stem cells suggesting that ISP genes are epigenetically poised in stem cells and are transcriptionally activated in ISP cells in the presence of inflammatory stimuli. Consistently, Crohn’s disease colonoids exhibit sustained ISP gene expression that can be elicited further with pro-inflammatory cytokines or via co-culture with pro-inflammatory macrophages. In summary, we define differences in the epithelial stem and progenitor compartment of patients with Crohn’s disease suggesting aberrant stem cell differentiation and inflammatory gene expression arises during disease.HIGHLIGHTSWe identify an inflammatory secretory progenitor cell state in endoscopically non-inflamed tissue from pediatric and adult patients with Crohn’s disease.Crohn’s disease epithelial stem and progenitor cells display increased chromatin accessibility preceding the emergence of inflammatory secretory progenitor cell states.Crohn’s disease colonoids from non-inflamed regions contain inflammatory secretory progenitor cells in the absence of inflammatory stimuliInflammatory secretory progenitor cells expand in colonoid culture in response to cytokine stimulation or co-culture with pro-inflammatory macrophages
TMVisDB: Annotation and 3D-visualization of transmembrane proteins
Authors: Olenyi Tobias , Marquet Céline , Grekova Anastasia , Houri Leen , Heinzinger Michael , Dallago Christian , Rost Burkhard 
Published: November 2024

AbstractSince the rise of cellular life, transmembrane proteins (TMPs) have been crucial to various cellular processes through their central role as gates and gatekeepers. Despite their importance, experimental high-resolution structures for TMPs remain underrepresented due to experimental challenges. Given its performance leap, structure predictions have begun to close the gap. However, identifying the membrane regions and topology in three-dimensional structure files on a large scale still requires additionalin silicopredictions. Here, we introduceTMVisDBto sieve through millions of predicted structures for TMPs. This resource enables both browsing through 46 million predicted TMPs and visualizing them along with their topological annotations without having to tap into costly predictions of the AlphaFold3-style.TMVisDBjoinsAlphaFoldDBstructure predictions and transmembrane topology predictions from the protein language model (pLM) based methodTMbed. We showcase the utility of TMVisDB for the analysis of proteins through two use cases, namely the B-lymphocyte antigen CD20(Homo sapiens) and the cellulose synthase (Novosphingobium sp. P6W). We demonstrate the value ofTMVisDBfor large-scale analyses through findings pertaining to all TMPs predicted for the human proteome. TMVisDB is freely available athttps://tmvisdb.rostlab.org
Shroom3-Rock interaction and profibrotic function: Resolving mechanism of an intronic CKD risk allele
Authors: Reghuvaran Anand , Kumar Ashwani , Lin Qisheng , Rajeevan Nallakandi , Sun Zeguo , Shi Hongmei , Barsotti Gabriel , Tanvir EM , Pell John , Perincheri Sudhir , Wei Chengguo , Planoutene Marina , Eichmann Anne , Mas Valeria , Zhang Weijia , Das Bhaskar , Cantley Lloyd , Xu Leyuan , He Cijiang John , Menon Madhav C 
Published: November 2024

AbstractCommon intronic enhancer SNPs in Shroom3 associate with CKD in GWAS, although there is paucity of detailed mechanism. Previously, we reported a role for Shroom3 in mediating crosstalk between TGFβ1- & Wnt/Ctnnb1 pathways promoting renal fibrosis (TIF). However, beneficial roles for Shroom3 in proteinuria have also been reported suggesting pleiotropic effects. Here we focused on identifying the specific profibrotic Shroom3 motif. Given known therapeutic roles for Rho-kinase inhibitors in experimental CKD, and the established interaction between Shroom3 and Rock via its ASD2 domain, we hypothesized that Shroom3-mediated ROCK activation played a crucial role in its profibrotic function in high expressors. To test this hypothesis, we developed transgenic mice and cell lines that inducibly overexpressed wild-type- (WT-Sh3) or ASD2-domain deletion- Shroom3 (ASD2Δ-Sh3). Prior scRNAseq data showed that during TIF, Shroom3 and Rock co-expression occurred in injured tubular cells and fibroblasts, highlighting cell-types where this mechanism could be involved. Using HEK293T cells, we first confirmed absent ROCK binding and inhibited TGFβ1-signaling with ASD2Δ-Sh3-overexpression vs WT-Sh3. In mIMCD cells, ASD2Δ-Sh3 overexpression, reduced Rock activation (phospho-MYPT1), pro-fibrotic and pro-inflammatory transcripts vs WT-Sh3. Fibroblast proliferation (3T3) was also reduced with ASD2Δ-Sh3.In vivo, we studied ureteric obstruction (UUO) and Aristolochic nephropathy (AAN) as TIF models. In AAN, inducible global-, or Pan-tubular specific-, WTSh3-overexpression showed increased azotemia, and TIF vs ASD2Δ-Sh3 mice. WT-Sh3 mice consistently showed significant enrichment of Rho-GTPase, TGFβ1- and Wnt/CtnnB1- signaling in kidney transcriptome, paralleling Shroom3-coexpressed genes in tubulo-interstitial transcriptomes from human CKD. In UUO, again WT-Sh3 mice recapitulated increased fibrosis vs ASD2Δ-Sh3. Importantly, ASD2Δ-Sh3 did not develop albuminuria vs WT-Sh3, while mutating a disparate Fyn-binding Shroom3 motif induced albuminuria in mice, suggesting motif-specific roles for Shroom3 in the kidney. Hence, our data show a critical role for the Rock-binding, ASD2-domain in mediating TIF in milieu of Shroom3 excess, with relevance to human CKD.
Social isolation reduces metabolic rate and social preference in Wild-type Zebrafish(Danio rerio)
Authors: Ghosh Arpita , Rao Aakash Madhav , Middha Prarthna , Rai Shambhavi , Rajaraman Bittu Kaveri 
Published: November 2024

AbstractThe adaptive and maladaptive effects of social isolation in various animal models, especially under pathogen stress, have generated particular interest since the COVID-19 pandemic. We examined metabolic, social and movement outcomes induced by a month of visual and olfactory social isolation in adult wild-type zebrafish. Our primary interest was examining metabolic savings and changes in social preference, with movement reduction as a manipulation check for effective social isolation. We found that socially isolated fish demonstrated a significant decrease in metabolic rate, social preference and average speed of movement compared to the pre-intervention baseline. The reduction in metabolic rate could lead to contextually beneficial energy expenditure savings for the fish; however, the more mixed effects of reduced social preference and average speed of movement might only be helpful in environments with a high predatory threat and high food and mate abundance. This study opens up various possibilities to explore the adaptive significance of social isolation in various ecological frameworks.
Host specificity of gastrointestinal parasites in free-ranging sloths from Costa Rica
Authors: Vanderhoeven Ezequiel A. , Florida Madeleine G. , Cliffe Rebecca , Guzman José , Notarnicola Juliana , Kartzinel Tyler R. 
Published: November 2024

AbstractThe diversity and host specificity of gastrointestinal parasites infecting free-ranging sloths is poorly known. We characterized gastrointestinal parasites of two sloth species from Costa Rica— three-fingered sloth (Bradypus variegatus) and two-fingered sloth (Choloepus hoffmanni)—for the first time in both a primary forest and an urban habitat. We asked whether host-parasite interactions were predominantly structured by host identity, the habitats in which hosts occurred, or both. Protozoa and nematode eggs were present in both species, but cestode eggs were recorded only inC. hoffmanni. We found eight parasitic morphotypes, which matches the total number of parasite taxa described in sloths over the past 100 years, and these first reports of gastrointestinal parasites of sloths from primary forest radically expand our knowledge of the general diversity and host specificity of sloth parasites. We found no significant difference in overall parasite richness between sloth species or habitats, but the parasite richness ofC. hoffmanniwas 2-fold greater in the primary forest vs. urban habitat. As no parasite sharing was observed between sloth species, we found strong and significant differences in parasite composition between host species regardless of habitat. InB. variegatus, we observed eggs of four nematode taxa (Spirocercidae, Subuluroidea, Spirurida, Ascaridida) and cysts of Eimeriidae (Apicomplexa). By contrast, inC. hoffmanni, we observed cestodes (Anoplocephalidae), a different nematode from the family Spirocercidae and also cysts of Eimeriidae (Apicomplexa). Many rare taxa were recorded only in samples from the primary forest, and these did not match any sloth parasites that had been previously described in the literature, suggesting that at least some could be undescribed species. Together, these results highlight the need for further research in comparative wildlife parasitology, the characterization of host-parasite transmission networks, and the identification of any intermediate hosts that may be relevant to sloth health.
VIACOT: a web server for interactive visualization and comparison of cell lineage trees
Authors: Yang Junnan , Li Zizhang , Zhang Xiaoyu , Chen Feng , Wu Peng , Yang Wenjing , He Xingxing , Shan Yuyan , Yang Jian-Rong 
Published: November 2024

AbstractThe cell lineage tree (CLT) records some or all cell division events during the development of multicellular organisms, as well as the functional characteristics of terminal cells, and is therefore commonly considered one of the most fundamental types of biological data. The combining of single-cell RNA sequencing with DNA barcoding has recently led to the rapid accumulation of CLT datasets. Unlike biological sequence data, web-based analysis and visualization tools for CLT data are currently lacking. In order to facilitate studies surrounding CLT, we built a webserver named VIACOT (Visualize Interactively And COmpare Trees). VIACOT is not only a comprehensive repository of published CLT datasets, but also a web tool that enables three preliminary analyses of preprocessed CLT datasets, including. (i) interactive visualization of CLT allowing fine-grain or coarse-grain exploration. (ii) calculations of correlations among single-cell metrics, such as gene expression levels, either using the original metrics or their phylogenetic independent contrasts. (iii) comparison among different CLTs to identify differences in cell fate. We anticipate that VIACOT will be a useful tool for exploration and biological interpretation of CLTs.
Freeze-tolerant crickets fortify their actin cytoskeleton in fat body tissue
Authors: van Oirschot Maranda L. , Toxopeus Jantina 
Published: November 2024

AbstractAnimals that overwinter in temperate climates must prevent or repair damage to their cells to survive winter, but we know little about how they protect cellular structure at the cytoskeletal level. Both chilling (no ice formation) and freezing (ice formation) are hypothesized to cause substantial challenges to cell structure and the cytoskeleton. The spring field cricketGryllus veletisbecomes freeze-tolerant following a 6-week acclimation to fall-like conditions, during which they differentially express multiple cytoskeleton-related genes. We tested the hypothesis thatG. veletisalter their cytoskeleton during acclimation to support maintenance of cytoskeletal structure during freezing and thawing. We used immunocytochemistry and confocal microscopy to characterize changes in microfilaments (F-actin, a polymer of G-actin) and microtubules (a polymer of α- and β-tubulin) in three tissues. While we saw no effect of acclimation on microtubules, crickets increased the abundance of microfilaments in fat body and Malpighian tubules. When we chilled or froze these freeze-tolerant crickets, there was no apparent damage to the actin or tubulin cytoskeleton in fat body, but there was decreased cytoskeleton abundance in Malpighian tubules. When we froze freeze-intolerant (unacclimated) crickets, microfilament abundance decreased in fat body tissue, while microfilaments were unaffected by chilling to the same subzero temperature. Our study shows that freeze-tolerant crickets are able to prevent or rapidly repair ice-induced damage to the actin cytoskeleton in fat body, likely due to preparatory changes in advance of freezing – i.e., during acclimation. We suggest future directions examining the mechanisms that underlie these structural changes.Summary StatementFreeze-tolerant crickets (Gryllus veletis) modify their actin cytoskeleton in select tissues to prevent freeze-induced cellular damage, while freeze-intolerant crickets of the same species experience irreparable cytoskeleton damage during freezing.
Effects of primary-care led self-management and low carbohydrate diet on glycaemic control in individuals with type 2 diabetes mellitus: study protocol of a cluster randomised controlled trial
Authors: Chadwick Joshua , Ganeshkumar P , Kathiresan Jeyashree , Shewade Hemant Deepak , Madhanraj K , Devika S , Lokesh S 
Published: November 2024

AbstractIntroductionType 2 diabetes mellitus (T2D) poses a significant global health burden, contributing to mortality and morbidity primarily through its complications such as renal failure, cardiovascular events, and others. Dietary patterns, particularly low carbohydrate diet and diabetes self-management education (DSME) have shown promise in improving glycaemic control and other metabolic parameters. However, evidence on the safety and long-term efficacy of such diets including health education, especially in populations like India with a high carbohydrate dietary tradition, is limited. This paper outlines a randomised controlled trial to determine the effectiveness of adopting a low carbohydrate diet in addition to standard care for T2D patients compared to those following standard care alone.Methods and analysisThis is a cluster randomized controlled trial that adheres to the Recommendations for Interventional Trials as outlined by the Standard Protocol Items. The study will be conducted in 16 urban primary health centres (UPHCs). UPHCs randomized to either standard care or low carbohydrate diet intervention. Outcome: generating evidence on improving HbA1c levels without increasing anti-hyperglycaemic medication. This will be achieved through the use of CGM technology and personalized nutrition counselling, which will focus on dietary carbohydrate restriction for patients with T2DM.DiscussionResults of this study will be published in peer-reviewed journals. The trial will provide insights into the efficacy and feasibility of implementing low carbohydrate diets and DSME in T2D management within public health settings. This protocol is registered on Clinical Trials Registry-India. The registration number for this trial is CTRI/2024/02/062202.
Visual outcome and associated risk factors in patients following small incision cataract surgery at the National Referral Hospital, Bhutan
Authors: Tamang Sandip , Lepcha Nor Tshering , Dukpa Mendu , Tenzin Karma 
Published: November 2024

AbstractPurposeTo evaluate small incision cataract surgery visual outcomes and associated risk factors in a tertiary eye care center in Bhutan.MethodsThis was a hospital-based prospective longitudinal study. A total of 310 patients who met the eligibility criteria were included in the study.ResultsThe mean age of the patients was 68.36 (SD: 12.74 years), and 157 (50.6%) were male. 285 (91.94%) of the cataract-operated eyes had best-corrected vision greater than 6/60, while 25 (8.06%) of the eyes had vision less than 6/60. 47 individuals (15.16%) had pre-existing ocular co-morbidity. Intraoperative complications were seen in 19 eyes (6%). At the 6-week follow-up visit, based on best-corrected visual acuity (BCVA), 90.65% had a good visual outcome. Analysis of multiple logistic regression showed that patients with preoperative ocular comorbidities (OR 50.92; 95% CI 10.23, 253.37) and those with operative complications (OR 16.59; 95% CI 3.54, 77.70) were significantly associated with poor visual outcome.ConclusionsThis study shows that cataract surgery can restore good visual acuity. However, patients should be followed up on for a longer period, and greater emphasis should be given to monitoring outcomes after cataract surgery.
ALS driven by mutant NEK1 aggregation is accelerated byPmlloss, but clinically reversed through pharmacologic induction ofPml-mediated degradation
Authors: Georgiadou Panagiota , Erkaya Bahriye , Kawakita Michiko , Sahin Egemen , Öztürk Harun , Tiryaki Fatmanur , Yildiz Kutay , Özgenç Idil , Pekbilir Emre , Dogan Sukru Anil , Lallemand-Breitenbach Valérie , Vargas Stephanie , Prochiantz Alain , Firat-Karalar Elif Nur , de Thé Hugues , Sahin Umut 
Published: November 2024

ABSTRACTGerminal mono-allelic loss-of-function mutations ofNEK1drive Amyotrophic Lateral Sclerosis (ALS) at variable penetrance, potentially through haploinsufficiency. Modeling the ALS-associated Arg812Ter mutation in mice revealed that the resulting truncated NEK1 (NEK1t) is aggregation-prone, notably in alpha-motoneurons (αMNs), and drives multiple ALS-like symptoms when bi-allelically expressed. Promyelocytic leukemia (Pml) is a key genetic interactor, since its loss allows for ALS symptoms to occur even inNek1wt/tanimals, mimicking the human situation.Pmlprecludes disease onset by promoting SUMO-facilitated degradation of NEK1tproteins.Pmlupregulation by interferon alpha or poly(I:C) eliminates NEK1taggregates in αMNs ofNek1t/tanimals, dramatically improving ALS-associated symptoms and extending survival by 6 months. Our study highlights the role of NEK1 aggregates in ALS pathogenesis and identifies interferon or poly(I:C) as a promising candidate therapy acting throughPml-triggered degradation of toxic misfolded proteins.
Versatile Stain Transfer in Histopathology Using a Unified Diffusion Framework
Authors: Yan Xudong , Yuan Mingze , Lu Yao , Zhang Ying , Chen Zifan , Bao Peng , Li Zehua , Dong Bin , Yang Li , Zhang Li , Zhou Fangxu 
Published: November 2024

ABSTRACTHistological staining is vital in clinical pathology for visualizing tissue structures. However, these techniques are laborious and time-consuming. Digital virtual staining offers a promising solution, but existing methods typically rely on Generative Adversarial Networks (GANs), which may suffer from artifacts and mode collapse. Motivated by the success of diffusion models, we present DUST, a novelDiffusion-basedUnified framework for versatileStainTransfer in histopathology. To enhance domain awareness and task-specific performance, we propose a dual encoding strategy that integrates the stain types of both the source and target domains. Additionally, we introduce a dynamic dual-output head to address the unstable intensity issue encountered with conventional DDPM implementations. Validated on a curated fourstain kidney histopathological dataset (H&E, MT, PAS, and PASM), DUST demonstrates superior versatile stain transfer capabilities. Our research highlights the potential of diffusion models to advance virtual staining, paving the way for more efficient digital pathology analyses.