bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosome-scale genome assembly and gene annotation of the hydrothermal vent annelidAlvinella pompejanayield insight into animal evolution in extreme environments
Authors: El Hilali Sami , Dru Philippe , Le Moan Alan , Li Yang I , Huynen Martijn A. , Hoelz André , Robinson Robert C. , Martín-Durán José M. , Jollivet Didier , Claridge-Chang Adam , Copley Richard R. 
Published: June 2024

AbstractThe types of genomic change needed for environmental adaptation are of great interest. Annelid worms are a large phylum found in a rich diversity of habitats, giving opportunities to explore this issue. We report the chromosome level genome sequence of the Pompeii worm, the annelidAlvinella pompejana, an inhabitant of an extreme deep-sea hydrothermal vent environment. We find strong but heterogeneously distributed genetic divergence between populations taken from either side of the equator. Using transcript data, we produced a set of gene models and analysed the predicted protein set in the light of past hypotheses about the thermotolerance ofAlvinella, and compared it to other recently sequenced annelid vent worms. We do not find evidence of a more extreme genome wide amino acid composition than other species, neither do we find evidence for rapid genome evolution in the form of disrupted synteny. We discount the hypothesis of loss of amino acid biosynthesis genes associated with obligate symbioses reported in siboglinid annelids. We do find evidence of a parallel increase in the number of globin encoding genes and loss of light sensitive opsins and cryptochromes.Alvinellaencodes several respiratory enzymes unusual for bilaterian animals, suggesting an ability to better tolerate hypoxic environments.
A functional network model for body column neural connectivity inHydra
Authors: Braun Wilhelm , Jenderny Sebastian , Giez Christoph , Pavleska Dijana , Klimovich Alexander , Bosch Thomas C. G. , Ochs Karlheinz , Hövel Philipp , Hilgetag Claus C. 
Published: June 2024

AbstractHydrais a non-senescent animal with a relatively small number of cell types and overall low structural complexity, but a surprisingly rich behavioral repertoire. The main drivers ofHydra’s behavior are neurons that are arranged in two nerve nets comprising several distinct neuronal populations. Among these populations is the ectodermal nerve net N3 which is located throughout the animal. It has been shown that N3 is necessary and sufficient for the complex behavior of somersaulting and is also involved inHydrafeeding behavior. Despite being a behavioral jack-of-all-trades, there is insufficient knowledge on the coupling structure of neurons in N3, its connectome, and its role in activity propagation and function. We construct a model connectome for the part of N3 located on the body column. Using experimental data on the placement of neuronal somata and the spatial dimensions of the body column, we show that a generative network model combining non-random placement of neuronal somata and the preferred orientation of primary neurites yields good agreement with experimentally observed distributions of connection distances, connection angles, and the number of primary neurites per neuron. Having validated the N3 connectome model in this fashion, we place a simple excitable dynamical model on each node of the body column network and show that it generates directed, short-lived, fast propagating patterns of activity. In addition, by slightly changing the parameters of the dynamical model, the same structural network can also generate persistent activity. Finally, we use a neuromorphic circuit based on the Morris-Lecar model to show that the same structural connectome can, in addition to through-conductance with biologically plausible time scales, also host a dynamical pattern related to the complex behavioral pattern of somersaulting. We speculate that such different dynamical regimes act as dynamical substrates for the different functional roles of N3, allowingHydrato exhibit behavioral complexity with a relatively simple nervous system that does not possess modules or hubs.
Oldest attested languages in the Near East reveal deep transformations in the distribution of linguistic features
Authors: Efrat-Kowalsky Nour , Ranacher Peter , Neureiter Nico , Widmer Paul , Bickel Balthasar 
Published: June 2024

AbstractIt is an unresolved question to what extent the current frequency distributions of linguistic features inform us about what is representative of the language faculty and does not instead result from historical contingencies. We probe this question by leveraging unique data from the oldest attested languages, those preserved through writing from up to 5,000 years ago in the Ancient Near East. We examine 70 grammatical features for which there is sufficient evidence in the available records. After controlling for relatedness we find robust deviations of two of the oldest languages, Hurrian and Sumerian from both the ancient languages and the modern distribution. The spatial and temporal placement of these two languages reveal a divergent distribution of features in the region in prehistory, suggesting massive transformations of the linguistic distributions in the past few millennia. This challenges inferences about general characteristics of language based on modern distributions.
Meta-Analysis of Urinary Metabolite GWAS Studies Identifies Three Novel Genome-Wide Significant Loci
Authors: Zaki Jihan K. , Tomasik Jakub , McCune Jade , Scherman Oren , Bahn Sabine 
Published: June 2024

AbstractGenome-wide association studies (GWAS) have substantially enhanced the understanding of genetic influences on phenotypic outcomes; however, realizing their full potential requires an aggregate analysis of numerous studies. Here we represent the first comprehensive meta-analysis of urinary metabolite GWAS studies, aiming to consolidate existing data on metabolite-SNP associations, evaluate consistency across studies, and unravel novel genetic links. Following an extensive literature review and data collection through the EMBL-EBI GWAS Catalog, PubMed, and metabolomix.com, we employed a sample size-based meta-analytic approach to evaluate the significance of previously reported GWAS associations. Our results showed that 1226 SNPs are significantly associated with urinary metabolite levels, including 48 lead SNPs correlated with 14 analytes: alanine, 3-aminoisobutyrate, betaine, creatine, creatinine, formate, glycine, glycolate, histidine, 2-hydroxybutyrate, lysine, threonine, trimethylamine, and tyrosine. Notably, the results revealed three previously unknown associations: rs4594899 with tyrosine (P = 6.6 × 10-9, N = 5447), rs1755609 with glycine (P = 3.3 × 10-10, N = 5447), and rs79053399 with 3-aminoisobutyrate (P = 6.9 × 10-10, N = 4656). These findings underscore the potential of urinary metabolite GWAS meta-analyses in revealing novel genetic factors that may aid in the understanding of disease processes, and highlight the necessity for larger and more comprehensive future studies.Author summaryIn this extensive study, we’ve meta-analysed data from various genome-wide association studies to better understand the genetic determinants of urinary metabolite levels. These metabolites are small molecules found in urine that reflect our body’s biochemical activities and can indicate states of health or disease. By combining results from previous research, we’ve identified 48 significant independent associations between single nucleotide polymorphisms (SNPs) and the levels of 14 metabolites in urine. Among these, we highlight three novel SNP-metabolite associations that offer new insights into the genetic architecture underlying metabolite regulation.Our findings contribute to the growing body of evidence that demonstrates the value of large-scale genetic meta-analyses. The significant SNP-metabolite links uncovered may serve as biomarkers for complex biological processes and disease mechanisms. This work takes us a step closer to a more nuanced understanding of the genetic factors that influence metabolic pathways and holds promise for improving diagnostic and therapeutic strategies through precision medicine. However, the complexity of genetic contributions to metabolite variations calls for continued research, underscoring the need for larger and more comprehensive studies in the future.
Zebrafish do not have calprotectin
Authors: Orlandi Kona N. , Harms Michael J. 
Published: June 2024

ABSTRACTThe protein heterodimer calprotectin and its component proteins, S100A8 and S100A9, play important antibacterial and proinflammatory roles in the mammalian innate immune response. Gaining mechanistic insights into the regulation and biological function of calprotectin will help facilitate patient diagnostics and therapy and further our understanding of the host-microbe interface. Recent literature has identified zebrafish s100a10b as zebrafish calprotectin based on sequence similarity, genomic context, and transcriptional upregulation during the immune response to bacterial infections. The field would benefit from expanding the breadth of calprotectin studies into a zebrafish innate immunity model. Here, we carefully evaluated the possibility that zebrafish possess a calprotectin. We found that zebrafish do not possess an ortholog of mammalian S100A8 or S100A9. We then identified four zebrafish s100 proteins— including s100a10b—that are expressed in immune cells and upregulated during the immune response. We recombinantly expressed and purified these proteins and measured the antimicrobial and proinflammatory characteristics. We found that none of the zebrafish proteins exhibited activity comparable to mammalian calprotectin. Our work demonstrates conclusively that zebrafish have no ortholog of calprotectin, and the most plausible candidate proteins have not convergently evolved similar functions.
Complement 3a Receptor 1 on Macrophages and Kupffer cells is not required for the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease
Authors: Homan Edwin A. , Gilani Ankit , Rubio-Navarro Alfonso , Johnson Maya A. , Schaepkens Odin M. , Cortada Eric , Pereira de Lima Renan , Stoll Lisa , Lo James C. 
Published: June 2024

AbstractTogether with obesity and type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global epidemic. Activation of the complement system and infiltration of macrophages has been linked to progression of metabolic liver disease. The role of complement receptors in macrophage activation and recruitment in MASLD remains poorly understood. In human and mouse,C3AR1in the liver is expressed primarily in Kupffer cells, but is downregulated in humans with MASLD compared to obese controls. To test the role of complement 3a receptor (C3aR1) on macrophages and liver resident macrophages in MASLD, we generated mice deficient in C3aR1 on all macrophages (C3aR1-MjKO) or specifically in liver Kupffer cells (C3aR1-KpKO) and subjected them to a model of metabolic steatotic liver disease. We show that macrophages account for the vast majority ofC3ar1expression in the liver. Overall, C3aR1-MjKO and C3aR1-KpKO mice have similar body weight gain without significant alterations in glucose homeostasis, hepatic steatosis and fibrosis, compared to controls on a MASLD-inducing diet. This study demonstrates that C3aR1 deletion in macrophages or Kupffer cells, the predominant liver cell type expressingC3aR1, has no significant effect on liver steatosis, inflammation or fibrosis in a dietary MASLD model.
Targeted sequencing ofEnterobacteralesbacteria using CRISPR-Cas9 enrichment and Oxford Nanopore Technologies
Authors: Cottingham Hugh , Judd Louise M. , Wisniewski Jessica A. , Wick Ryan R. , Stanton Thomas D. , Vezina Ben , Macesic Nenad , Peleg Anton Y. , Okeke Iruka N. , Holt Kathryn E. , Hawkey Jane 
Published: June 2024

AbstractSequencing DNA directly from patient samples enables faster pathogen characterisation compared to traditional culture-based approaches, but often yields insufficient sequence data for effective downstream analysis. CRISPR-Cas9 enrichment is designed to improve yield of low abundance sequences but has not been thoroughly explored with Oxford Nanopore Technologies (ONT) for use in clinical bacterial epidemiology. We designed CRISPR-Cas9 guide RNAs to enrich for the human pathogenKlebsiella pneumoniae, by targeting multi-locus sequence type (MLST) and transfer RNA (tRNA) genes, as well as common antimicrobial resistance (AMR) genes and the resistance-associated integron geneintI1. We validated enrichment performance in bacterial isolates before comparing enriched and unenriched sequencing of three human faecal samples spiked withK. pneumoniaeat varying abundance. Enriched sequencing generated 56x and 11.3x the number of AMR and MLST reads respectively compared to unenriched sequencing and required approximately one third of the computational storage space. Targeting theintI1gene often led to detection of 10-20 proximal resistance genes due to the long reads produced by ONT sequencing. We demonstrated that CRISPR-Cas9 enrichment combined with ONT sequencing enabled improved genomic characterisation outcomes over unenriched sequencing of patient samples. This method could be used to inform infection control strategies by identifying patients colonised with high-risk strains.
Integrated forward and reverse degradomics uncovers the proteolytic landscape of aortic aneurysms and the roles of MMP9 and mast cell chymase
Authors: Bhutada Sumit , Martin Daniel R. , Cikach Frank , da Silva Emidio Germano , Willard Belinda B. , Ramkhelawon Bhama , Chung Mina K. , Dahal Satakshi , Ramamurthi Anand , Joshi Jayadev P. , Blankenburg Daniel , Barnard John , Blackstone Eugene H. , Roselli Eric E. , Apte Suneel S. 
Published: June 2024

AbstractBackgroundDysregulated proteolysis is implicated in thoracic (TAA) and abdominal aortic aneurysm (AAA) pathogenesis, but the proteolytic landscapes (degradomes) of aneurysmal and normal aorta, and contributions of individual proteases remain undefined. Here, a proteome-wide approach was used to uncover TAA and AAA degradomes, compare them quantitatively and define the specific role in aortic remodeling of two proteases consistently identified in the aneurysms, mast cell chymase (CMA1) and matrix metalloprotease 9 (MMP9).MethodsThe mass spectrometry-based N-terminomics strategyTerminalAmine IsotopicLabeling ofSubstrates (TAILS) was applied to Marfan syndrome TAAs (n=5), AAAs (n=16) and corresponding non-diseased aorta (TAs, n=4, and AAs, n=8) as a forward degradomics application, i.e., to define substrate and protease degradomes, and 8-plex iTRAQ-TAILS was used for quantitative comparison. Cleavage sites of CMA1 and MMP9 were sought by reverse degradomics, i.e., digestion of aortic proteins with these proteases, followed by 6-plex iTRAQ-TAILS. CMA1 and MMP9 proteolysis of biglycan was investigated usingAmino-TerminalOrientedMass spectrometry ofSubstrates (ATOMS).ResultsWe experimentally annotated 16,923 proteolytically derived peptides (substrate degradome) and 90 proteases (protease degradome) in the aorta. Quantitative substrate degradome comparisons identified specific differentially modulated pathways and networks in TAA and AAA. Reverse degradomics elucidated > 300 CMA1 and MMP9 substrate cleavage sites, of which, many, including orthogonally validated biglycan cleavage, occurred in the disease degradomes.ConclusionsUnbiased, proteome-wide forward degradomics of the aortic wall from TAA, AAA and non-diseased tissue generated the first systems biology view of vascular wall breakdown and public resource for the hitherto occult proteolytic landscape, demonstrating widespread extracellular matrix remodeling. The findings provide insights on aortic aneurysm pathways and potential disease biomarkers. Mapping of specific contributions of CMA1 and MMP9 on the aortic forward substrate degradome using reverse degradomics provides a strategy for defining the activities of all proteases involved in aortic disease.
Vitamin a deficiency causes apoptosis in the mammary gland of rats
Authors: Vasquez-Gomez M. , Filippa V. , Acosta M. , Mohamed F. , Campo Verde F. , Ferrari C. , Jahn G.A. , Giménez M.S. , Ramirez D.C. , Gomez Mejiba S.E. 
Published: June 2024

ABSTRACTSubchronic dietary vitamin A deficiency (VAD) causes severe abnormalities, including dysfunction of the epithelia of the mammary gland. However, the underlying mechanism of this process is partially known. Therefore, herein, we used a nulliparous-rat experimental model of dietary VAD for a total dieting regime of 3 and 6 months and intervened (refeed) with a vitamin A sufficient (VAS) diet for 0.5 or 1 month before the end of the diet regime and investigated the underlying molecular mechanism of mammary tissue dysfunction. Dietary vitamin A deficiency for 3 and 6 months caused increased inflammatory cell infiltration in the mammary gland parenchyma and glandular cells, with increased inflammation and apoptosis and reduced cell proliferation. These changes can be reversed with a VAS diet. Mammary gland dysfunction after a subchronic VAD is caused by an imbalance between NFκB and retinoic acid-triggered signaling. Inflammation, apoptosis, and impaired proliferation lead to dysfunction of the epithelia of the mammary gland of nulliparous rats fed a VAD diet.
Unveil the mechanism of Jinzhen Oral Liquid combined with Azithromycin in the treatment of Mycoplasma pneumoniae pneumonia based on Network pharmacology and clinical trials
Authors: Zhong Chengliang , Guo Shengxuan , Liu Qingyuan , Sun Deyang , Wang Boyang , Hu Siyuan , Li Xinmin , Ding Ying , Yuan Bin , Liu Jing , Xiang Long , Li Nan , Xue Zheng , Li Yan , Teng Yiqun , Yi Rongsong , Li Shao , Ma Rong 
Published: June 2024

AbstractMycoplasma pneumoniae pneumonia (MPP) is a common type of pneumonia among school-aged children and adolescents. Jinzhen Oral Liquid (JZOL) and Azithromycin (AZ) are commonly used treatment options in traditional Chinese medicine (TCM) and Western medicine, respectively. There are several clinical and basic research reports on their solo effect against MPP, enabling their combined treatment to become possible. However, the mechanisms and specific pharmacodynamics of their combined therapy remain unclear. In this study, we conducted a mechanistic analysis of the combination of JZOL and AZ based on network target, elucidating their modular network regulatory mechanisms. The modular mechanisms involve four modules, including hormone response, cell differentiation and migration, signal transduction, oxygen and hypoxia response, centered by TNF signaling pathway-mediated regulation. Under the instruction of computational analysis, we conducted a randomized, double-blind, three-armed, parallel-controlled, multicenter clinical study of different doses of JZOL combined with AZ for the treatment of MPP in children. At the study endpoint, the median time to clinical recovery showed statistically significant differences, which were also observed between groups for time to complete fever remission, time to relief of cough/phlegm, effective rate of chest X-ray improvement, and rate of healing of TCM symptoms. During the treatment period, there were no statistically significant differences in the rates of adverse events, serious adverse events, or adverse reactions between the groups. Different doses of JZOL combined with AZ in the treatment of MPP in children have shown the effects of shortening the course of the disease, relieving the symptoms, and improving the prognosis. The research program composed of computational prediction and clinical trials can significantly accelerate the research and development process and identify more effective treatment with good safety, which is worthy of clinical promotion.
Herpes zoster vaccination and new diagnoses of dementia: A quasi-randomized study in Australia
Authors: Pomirchy Michael , Bommer Christian , Pradella Fabienne , Michalik Felix , Peters Ruth , Geldsetzer Pascal 
Published: June 2024

AbstractIncreasing evidence suggests that neurotropic herpesviruses could play a role in the development of dementia, possibly through a neuroinflammatory process. Herpes zoster (HZ) vaccination has been reported to lead to a reduced probability of being diagnosed with dementia in several correlational studies and in a prior analysis by our team in Wales. This present study constitutes the first investigation to use a quasi-randomized study design in an electronic health record dataset from a large and diverse nation (Australia) to aim to determine the effect of HZ vaccination on dementia. In Australia, starting on November 1 2016, live-attenuated HZ vaccination was provided for free to individuals aged 70 to 79 years of age through primary care providers. Thus, those whose 80thbirthday was just a few days prior to November 1 2016 never became eligible, whereas those whose 80thbirthday was just a few days later were eligible. The key advantage of our approach is that one would not expect that these population groups who differ in their age by only a minute degree would, on average, differ in any of their health characteristics and behaviors. We used detailed primary healthcare records with week-of-birth information from 65 general practices across Australia. We analyzed our data using a regression discontinuity approach. Our sample consisted of 101,219 patients. As expected, patients born just before versus shortly after the date-of-birth eligibility threshold (November 2 1936) for HZ vaccination were well-balanced in their past preventive health services uptake and chronic disease diagnoses. There was an abrupt increase of 15.7 (95% CI: [12.2 – 19.3], p < 0.001) percentage points in the probability of ever receiving HZ vaccination between patients born shortly before versus shortly after the eligibility threshold. The eligibility rules of the HZ vaccination program, thus, created comparison groups just on either side of the date-of-birth eligibility threshold who were similar to each other, except for a large difference in their probability of receiving the intervention (HZ vaccination) of interest. Eligibility for HZ vaccination (i.e., being born shortly before versus shortly after November 2 1936) decreased the probability of receiving a new dementia diagnosis over 7.4 years by 2.0 percentage points (95% CI: [0.3 – 3.7], p = 0.021). Being eligible for HZ vaccination did not affect the probability of taking up other preventive health services (including other vaccinations), nor the probability of being diagnosed with other common chronic conditions than dementia. This study provides important evidence on the potential benefits of HZ vaccination for dementia because its quasi-randomized design allows for conclusions that are more likely to be causal than those of the existing associational evidence.