bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cortactin interacts with αDystrobrevin-1 and regulates neuromuscular junction morphology
Authors: De Cicco Teresa , Pęziński Marcin , Wójcicka Olga , Rottner Klemens , Prószyński Tomasz J. 
Published: October 2023

AbstractBackgroundNeuromuscular junctions allow for transmitting signals from the nervous system to skeletal muscles, triggering their contraction, and their proper organization is essential for breathing and voluntary movements. αDystrobrevin-1 is a cytoplasmic component of the dystrophin-glycoprotein complex and has pivotal functions in regulating the integrity of muscle fibres and neuromuscular junctions. Previous studies identified that αDystrobrevin-1 functions in the organization of the neuromuscular junction and that its phosphorylation in the C-terminus is required in this process.MethodsWe used synthetic peptides corresponding to the phosphorylated tyrosine Y730 at the C-terminal part of αDystrobrevin-1 to precipitate interacting proteins from homogenate of differentiated muscle cells. Isolated proteins were identified by mass spectrometry, and co-immunoprecipitation and bimolecular fluorescence complementation experiments in skeletal muscles were used to validate interactions. We used immunohistochemical analysis and muscle electroporation to study cortactin localization in skeletal muscles. To study the function of cortactin in the neuromuscular system, we used cortactin KO mice. Synaptic morphology was studied using unbiased automatic image analysis, and muscle strength was assessed in grip-strength experiments and an animal’s ability to run on voluntary wheels and a treadmill.ResultsOur proteomic screen identified a number of putative αDystrobrevin-1 interactors recruited to the Y730 site in both its phosphorylated and unphosphorylated state. Amongst various actin regulators, we identified the Arp2/3 complex regulator cortactin. We showed that similarly to αDystrobrevin-1, cortactin is strongly enriched at the neuromuscular postsynaptic machinery and obtained results suggesting that these two proteins interact in cell homogenates and at the neuromuscular junctions. Analysis of synaptic morphology cortactin knockout mice showed abnormalities in the slow-twitching soleus muscle and not in the fast-twitching tibialis. However, muscle strength examination did not reveal apparent deficits in knockout animals.ConclusionsOur studies identified cortactin as a novel interactor of the dystrophin-glycoprotein complex, pivotal in maintaining muscle and neuromuscular junction integrity. We have shown that cortactin is a novel postsynaptic machinery component that can be essential in organizing the neuromuscular junctions.
Cross-sector collaboration is more effective than single sector actions at mitigating SARS-CoV-2 in white-tailed deer
Authors: Cook Jonathan D. , Rosenblatt Elias , Direnzo Graziella , Campbell Grant Evan H. , Mosher Brittany A. , Arce Fernando , Christensen Sonja , Ghai Ria R. , Runge Michael C. 
Published: October 2023

AbstractOne Health helps achieve optimal health outcomes for people, animals, plants, and their shared environments. We describe a multidisciplinary effort to better understand and mitigate SARS-CoV-2 spread in white-tailed deer across One Health sectors. We first framed the risk problem with three governance sectors that manage captive and wild deer and human public health. The framing included the objectives for each sector, interactions that facilitate human-to-deer and deer-to-deer transmission, and alternatives intended to reduce risk. We then developed a dynamic compartmental model that linked wild and captive deer herds and humans and simulated SARS-CoV-2 dynamics. For baseline conditions, we estimated that median SARS-CoV-2 prevalence in wild and captive herds varied between 0.03 – 0.07, incidence between 0.68 – 1.46, and probability of persistence between 0.64 – 0.97 across 120-day simulations. We then tested single-sector alternatives alone and in combination with other sector actions. We found that single sector alternatives varied in their ability to reduce transmission and that the best performing alternative required collaborative actions among wildlife management, agricultural management, and public health agencies.
Identifying summary statistics for approximate Bayesian computation in a phylogenetic island biogeography model
Authors: Xie Shu , Valente Luis , Etienne Rampal S. 
Published: October 2023

AbstractEstimation of parameters of evolutionary island biogeography models, such as colonization and diversification rates, is important for a better understanding of island systems. A popular statistical inference framework is likelihood-based estimation of parameters using island species richness and phylogenetic data. Likelihood approaches require that the likelihood can be computed analytically or numerically, but with the increasing complexity of island biogeography models, this is often unfeasible. Simulation-based estimation methods may then be a promising alternative. One such method is approximate Bayesian computation (ABC), which compares summary statistics of the empirical data with the output of model simulations. However, ABC demands the definition of summary statistics that sufficiently describe the data, which is yet to be explored in island biogeography. Here, we propose a set of summary statistics and use it in an ABC framework for the estimation of parameters of an island biogeography model, DAISIE (Dynamic Assembly of Island biota through Speciation, Immigration and Extinction). For this model, likelihood-based inference is possible, which gives us the opportunity to assess the performance of the summary statistics. DAISIE currently only allows maximum likelihood estimation (MLE), so we additionally develop a likelihood-based Bayesian inference framework using Markov Chain Monte Carlo (MCMC) to enable comparison with the ABC results (i.e., making the same assumptions on prior distributions). We simulated phylogenies of island communities subject to colonization, speciation, and extinction using the DAISIE simulation model and compared the estimated parameters using the three inference approaches (MLE, MCMC and ABC). Our results show that the ABC algorithm performs well in estimating colonization and diversification rates, except when the species richness or amount of phylogenetic information from an island are low. We find that compared to island species diversity statistics, summary statistics that make use of phylogenetic and temporal patterns (e.g., the number of species through time) significantly improve ABC inference accuracy, especially in estimating colonization and anagenesis rates, as well as making inference converge considerably faster and perform better under the same number of iterations. Island biogeography is rapidly developing new simulation models that can explain the complexity of island biodiversity, and our study provides a set of informative summary statistics that can be used in island biogeography studies for which likelihood-based inference methods are not an option.
Genome-wide meta-analysis conducted in three large biobanks expands the genetic landscape of lumbar disc herniations
Authors: Salo Ville , Määttä Juhani , Sliz Eeva ,   FinnGen, Reimann Ene , Mägi Reedik ,   Estonian Biobank Research Team, Reis Kadri , Elhanas Abdelrahman G. , Reigo Anu , Palta Priit , Esko Tõnu , Karppinen Jaro , Kettunen Johannes 
Published: October 2023

Introductory paragraphGiven that lumbar disc herniation (LDH) is a prevalent spinal condition that causes significant individual suffering and societal costs1, the genetic basis of LDH has received relatively little research. Our aim was to increase understanding of the genetic factors influencing LDH. We performed a genome-wide association analysis (GWAS) of LDH in the FinnGen project and in Estonian and UK biobanks, followed by a genome-wide meta-analysis to combine the results. In the meta-analysis, we identified 41 loci that have not been associated with LDH in prior studies on top of the 23 known risk loci. We detected LDH-associated loci in the vicinity of genes related to inflammation, disc-related structures, and synaptic transmission. Overall, our research contributes to a deeper understanding of the genetic factors behind LDH, potentially paving the way for the development of new therapeutics, prevention methods, and treatments for symptomatic LDH in the future.
Comprehensive Identification of Pathogenic Microbes and Antimicrobial Resistance Genes in Food Products Using Nanopore Sequencing-Based Metagenomics
Authors: Lee Annie Wing-Tung , Ng Iain Chi-Fung , Wong Evelyn Yin-Kwan , Wong Ivan Tak-Fai , Sze Rebecca Po-Po , Chan Kit-Yu , So Tsz-Yan , Zhang Zhipeng , Fung Sharon Ka-Yee , Wong Sally Choi-Ying , Tam Wing-Yin , Lao Hiu-Yin , Lee Lam-Kwong , Leung Jake Siu-Lun , Chan Chloe Toi-Mei , Ng Timothy Ting-Leung , Chow Franklin Wang-Ngai , Leung Polly Hang-Mei , Siu Gilman Kit-Hang 
Published: October 2023

AbstractFoodborne pathogens, particularly antimicrobial-resistant (AMR) bacteria, remain a significant threat to global health. Conventional culture-based approaches for detecting infectious agents are limited in scope and time-consuming. Metagenomic sequencing of food products offers a rapid and comprehensive approach to detect pathogenic microbes, including AMR bacteria. In this study, we used nanopore-based metagenomic sequencing to detect pathogenic microbes and antimicrobial resistance genes (ARGs) in 260 food products, including raw meat, sashimi, and ready-to-eat (RTE) vegetables. We identifiedClostridium botulinumandStaphylococcus aureusas the predominant foodborne pathogens in the food samples, particularly prevalent in fresh, peeled, and minced foods. Importantly, RTE-vegetables, which harboredAcinetobacter baumanniiandToxoplasma gondiias the dominant foodborne pathogens, displayed the highest abundance of carbapenem resistance genes among the different food types. ExclusiveblaCTX-Mgene-carrying plasmids were found in both RTE-vegetables and sashimi. Additionally, we assessed the impact of host DNA and sequencing depth on microbial profiling and ARG detection, highlighting the preference for nanopore sequencing over Illumina for ARG detection. A lower sequencing depth of around 25,000 is adequate for effectively profiling bacteria in food samples, whereas a higher sequencing depth of approximately 700,000 is required to detect ARGs. Our workflow provides insights into the development of food safety monitoring tools and can assess the potential risk to human health from foodborne pathogens and ARGs. This approach has the potential to revolutionize the screening of food products and enable more efficient and accurate detection of foodborne pathogens and ARGs, thereby reducing the risks of foodborne illness and improving public health.
ZHX2 alleviates vascular remodeling and smooth muscle cell proliferation by transcriptional regulation of GADD45G
Authors: Fan Siyuan , Yang Liuye , Wu Xuelian , Wu Yichen , Wang Pengchao , Qiao Baoru , Li Yue , Huang Kai , Zheng Zhe 
Published: October 2023

AbstractObjectiveThis study explores the role of ZHX2 in vascular remodeling, specifically focusing on its effects on VSMC proliferation, migration, and neointima formation following vascular injury. Methods and Results: Data from both human atherosclerotic samples and a mouse carotid injury model indicated a decrease in ZHX2 levels.In vivo, ZHX2 overexpression reduced neointima formation in mice subjected to carotid artery ligation.In vitro, ZHX2 inhibited the proliferation and migration of primary VSMCs. Conversely, specific knockout of ZHX2 in SMCsin vivoor knockdown of ZHX2 in primary VSMCs had opposite effects. RNA- seq analysis revealed that ZHX2 overexpression significantly affected the expression of cell cycle-related genes. Using Chromatin Immunoprecipitation Sequencing (ChIP-seq) and luciferase reporter assays, we demonstrated that ZHX2 plays a crucial role in the transcriptional regulation of GADD45G, identifying GADD45G as the downstream target responsible for ZHX2-mediated effects. Conclusions: ZHX2 emerges as a key player in pathological vascular remodeling, suppressing VSMC proliferation and migration through its regulatory impact on GADD45G transcription and cell cycle-related gene expression.
The guide RNA sequence dictates the slicing kinetics and conformational dynamics of the Argonaute silencing complex
Authors: Wang Peter Y. , Bartel David P. 
Published: October 2023

SUMMARYThe RNA-induced silencing complex (RISC), which powers RNA interference (RNAi), consists of a guide RNA and an Argonaute protein that slices target RNAs complementary to the guide. We find that for different guide-RNA sequences, slicing rates of perfectly complementary, bound targets can be surprisingly different (>250-fold range), and that faster slicing confers better knockdown in cells. Nucleotide sequence identities at guide-RNA positions 7, 10, and 17 underlie much of this variation in slicing rates. Analysis of one of these determinants implicates a structural distortion at guide nucleotides 6–7 in promoting slicing. Moreover, slicing directed by different guide sequences has an unanticipated, 600-fold range in 3′-mismatch tolerance, attributable to guides with weak (AU-rich) central pairing requiring extensive 3′ complementarity (pairing beyond position 16) to more fully populate the slicing-competent conformation. Together, our analyses identify sequence determinants of RISC activity and provide biochemical and conformational rationale for their action.HIGHLIGHTSSequence of guide RNA can alter slicing rate of fully paired substrate by 250-foldSequences that cause more rapid slicing direct more efficient RNAi in cellsStrong central pairing imparts tolerance for mismatches to the guide 3′ regionThis tolerance is attributable to more fully populating the slicing conformation
Bacillus subtilismaintains antibiofilm activity againstStaphylococcus aureusfollowing adaptive laboratory evolution
Authors: Leistikow Kyle R. , Solis Elisabeth , Khaled Jehan , Marshall Christopher W. , Hristova Krassimira R. 
Published: October 2023

AbstractQuorum sensing interference has been touted as an ideal mechanism for the development of new anti-virulence therapies. Recent work has establishedBacillus subtilis6D1, a Gram-positive spore forming bacterium with probiotic qualities, produces metabolites that inhibitStaphylococcus aureusvirulence and biofilm formation via quorum sensing interference. However, it remains unknown how long-term exposure to these molecules driveS. aureusadaptation and evolution.S. aureusplanktonic cells and biofilms were propagated in the presence ofB. subtilis6D1 cell free extracts (CFE) for ∼73 generations. Fitness, virulence, and antibiotic resistance assays of the ancestor and all evolved lineages revealed the emergence of treatment and lifestyle associated ecological traits. Compared to the ancestor and media-evolved lineages,S. aureuslineages evolved in the presence ofB. subtilis6D1 CFE were less competitive in a biofilm and exhibited increased phenotypic sensitivity to multiple antibiotics. Notably,B. subtilis6D1 CFE maintained its ability to inhibitS. aureusbiofilm growth and disassemble mature biofilm in all evolved lineages.S. aureuspopulations propagated in the presence of CFE acquired missense mutations in genes associated with plasmid-borne efflux systems and RNA polymerase. Furthermore, CFE-evolved lineages did not develop mutations in both competence and drug resistance pathways found in similarly evolved control lineages. Our data suggest long-term exposure to biofilm inhibitory molecules, like those produced byB. subtilis6D1, can reduceS. aureus’fitness in a biofilm and increase sensitivity to multiple antibiotics.ImportanceQuorum sensing interference (QSI) has been touted as an ideal mechanism to diminish bacterial virulence and improve antibiotic killing, however few studies investigate the genetic and phenotypic adaptations that occur after long-term exposure to QSI therapies. Recent studies revealedBacillus subtilisreduces biofilm formation and virulence via signaling interference with theS. aureusAgr QS system; however, it remains unclear how long-term exposure to these compounds drivesS. aureusadaptation and evolution. This study helps to address these gaps by investigating whether QSI strategies deployed by probiotic bacteria are viable approaches to increase antibiotic efficacy without increasing antibiotic resistance evolution.
DiGAS: Differential gene allele spectrum as descriptor in genetic studies
Authors: Aparo Antonino , Bonnici Vincenzo , Avesani Simone , Cascione Luciano , Giugno Rosalba 
Published: October 2023

AbstractDiagnosing subjects in complex genetic diseases is a very challenging task. Computational methodologies exploit information at genotype level by taking into account single nucleotide polymorphisms (SNP). They leverage the result of genome-wide association studies analysis to assign a statistical significance to each SNP. Recent methodologies extend such an approach by aggregating SNP significance at genetic level in order to identify genes that are related to the condition under study. However, such methodologies still suffer from the initial single-SNP analysis. Here, we present DiGAS, a tool for diagnosing genetic conditions by computing significance, by means of SNP information, but directly at the gene level. Such an approach is based on a generalized notion of allele spectrum, which evaluates the complete genetic alterations of the SNP set composing a gene at population level. Statistical significance of a gene is then evaluated by means of a differential analysis between the healthy and ill portions of the population. Tests, performed on well-established data sets regarding Alzheimer’s disease, show that DiGAS outperforms the state-of-the-art in distinguishing between ill and healthy subjects.HighlightsWe introduce a new generalized version of allele frequency spectrum.We propose a methodology, called DiGAS, based on the new defined genomic information and independent from GWAS analysis that out-performs existing methods in distinguish healthy/ill subjects with a speed up of 5x.On a reference Alzheimer’s disease genomic datasets, ADNI, DiGAS reaches F1 score up to 0.92.DiGAS methodology manages any type of genomic features, such as genes, exons, upstream/downstream regions.
Mapping total microbial communities and waterborne pathogens in household drinking water in China by citizen science and metabarcoding
Authors: Wen Xinyi , Fang Chutong , Huang Lihan , Miao Jiazheng , Lin Yajuan 
Published: October 2023

AbstractEnsuring safe drinking water is one of the top priorities in public health as waterborne diseases remain a global challenge. In China, microbial contamination in drinking water is of particular concern and comprehensive survey/monitoring of the drinking water microbiome is necessary. However, traditional culture-based microbial monitoring methods have significant limitations, and nationwide tap water survey/monitoring in China would require significant resources. Here, a cost-effective and culture-independent citizen science approach was developed to sample the microbiome in household drinking water (n = 50) from 19 provinces in China from December 2020 to August 2021, including a few opportunistic samples collected in situ right after extreme weather events such as the 2021 Henan Floods and Typhoon In-Fa Landfall. Using a protocol optimized for low-biomass samples, 22 out of 50 tap water samples were tested positive for microbial DNA. 16S rRNA gene metabarcoding were conducted on pooled samples, yielding 7,635 Amplicon Sequence Variants (ASVs), which revealed a diverse microbiome in household tap water. Alarmingly, pathogenic bacteria includingMycobacteriumspp.,Acinetobacterspp., andLegionellaspp. were detected in all PCR positive samples. Despite the limited number of samples, a significant number of pathogenic species (e.g.,Salmonella enterica) and/or toxin-producing cyanobacteria (e.g.,Microcystisspp.) were detected in local tap water samples from Zhengzhou and Changzhou following the 2021 Henan Floods and Typhoon In-Fa Landfall, respectively. Overall, this study underscores the utility of citizen science in enhancing microbial monitoring and informs future public health strategies for water safety.
Rapid propagation of Ca2+waves and electrical signals in a liverwortMarchantia polymorpha
Authors: Watanabe Kenshiro , Hashimoto Kenji , Hasegawa Kota , Shindo Hiroki , Tsuruda Yushin , Kupisz Kamila , Koselski Mateusz , Wasko Piotr , Trebacz Kazimierz , Kuchitsu Kazuyuki 
Published: October 2023

AbstractIn response to both biotic and abiotic stresses, vascular plants transmit long-distance Ca2+and electrical signals from localized stress sites to distant tissues through their vasculature. Various models have been proposed for the mechanisms underlying the long-distance signaling, primarily centered around the presence of vascular bundles. We here demonstrate that the non-vascular liverwort Marchantia polymorpha possesses a mechanism for propagating Ca2+waves and electrical signals in response to wounding. The propagation velocity of these signals was approximately 1-2 mm/s, equivalent to that observed in vascular plants. Both Ca2+waves and electrical signals were inhibited by La3+as well as tetraethylammonium chloride, suggesting crucial importance of both Ca2+channel(s) and K+channel(s) in wound-induced membrane depolarization as well as the subsequent long-distance signal propagation. Simultaneous recordings of Ca2+and electrical signals indicated a tight coupling between the dynamics of these two signaling modalities. Furthermore, molecular genetic studies revealed that a GLUTAMATE RECEPTOR-LIKE (GLR) channel plays a central role in the propagation of both Ca2+waves and electrical signals. Conversely, none of the three two-pore channels (TPCs) were implicated in either signal propagation. These findings shed light on the evolutionary conservation of rapid long-distance Ca2+wave and electrical signal propagation involving GLRs in land plants, even in the absence of vascular tissue.