bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell analysis of bovine muscle-derived cell types for cultured meat production
Authors: Messmer Tobias , Dohmen Richard GJ , Schaeken Lieke , Melzener Lea , Hueber Rui , Godec Mary , Post Mark J , Flack Joshua E 
Published: September 2022

Abstract‘Cultured’ meat technologies leverage the proliferation and differentiation of animal-derived stem cells ex vivo to produce edible tissues for human consumption in a sustainable fashion. However, skeletal muscle is a dynamic and highly complex tissue, involving the interplay of numerous mono- and multinucleated cells, including muscle fibres, satellite cells (SCs) and fibro-adipogenic progenitors (FAPs), and recreation of the tissue in vitro thus requires the characterisation and manipulation of a broad range of cell types. Here, we use a single-cell RNA sequencing approach to characterise cellular heterogeneity within bovine muscle and muscle-derived cell cultures over time. Using this data, we identify numerous distinct cell type, and develop robust protocols for the easy purification and proliferation of several of these populations. We note overgrowth of undesirable cell types within heterogeneous proliferative cultures as a barrier to efficient cultured meat production, and use transcriptomics to identify conditions that favour the growth of SCs in the context of serum-free medium. Combining RNA velocities computed in silico with time-resolved flow cytometric analysis, we characterise dynamic subpopulations and transitions between active, quiescent, and committed states of SCs, and demonstrate methods for modulation of these states during long-term proliferative cultures. This work provides an important reference for advancing our knowledge of bovine skeletal muscle biology, and its application in the development of cultured meat technologies.
Arc ubiquitination regulates endoplasmic reticulum-mediated Ca2+release and CaMKII signaling
Authors: Ghane Mohammad A. , Allen Zachary D. , Miller Cassandra L. , Dong Bin , Yang Jenny J. , Fang Ning , Mabb Angela M. 
Published: September 2022

AbstractSynaptic plasticity relies on rapid, yet spatially precise signaling to alter synaptic strength. Arc is a brain enriched protein that is rapidly expressed during learning-related behaviors and is essential for regulating metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD). We previously showed that disrupting the ubiquitination capacity of Arc enhances mGluR-LTD; however, the mechanism by which this occurs and its consequences on other mGluR-mediated signaling events is unknown. Here we show that disrupting Arc ubiquitination on key amino acid residues leads to derangements in Ca2+release from the endoplasmic reticulum (ER) during pharmacological activation of Group I mGluRs. These alterations were observed in all neuronal subregions except secondary branchpoints. Deficits in Arc ubiquitination increased Arc self-association and enhanced its interaction with calcium/calmodulin-dependent protein kinase IIb (CaMKIIb) and constitutively active forms of CaMKII. Notably, these interactions were also excluded at secondary branchpoints. Finally, disruptions in Arc ubiquitination were found to increase Arc interaction with the integral ER protein Calnexin. These results suggest a previously unknown role for Arc ubiquitination in the fine tuning of ER-mediated Ca2+signaling that is needed for mGluR-LTD, which in turn, may regulate CaMKII and its interactions with Arc.
Divergent microbial traits influence the transformation of living versus dead root inputs to soil carbon
Authors: Sokol Noah W. , Foley Megan M. , Blazewicz Steven J. , Battacharyya Amrita , Estera-Molina Katerina , Firestone Mary , Greenlon Alex , Hungate Bruce A. , Kimbrel Jeffrey , Liquet Jose , Lafler Marissa , Marple Maxwell , Nico Peter , Slessarev Eric , Pett-Ridge Jennifer 
Published: September 2022

ABSTRACTSoil microorganisms influence the global carbon cycle by transforming plant inputs into soil organic carbon (SOC), but the microbial traits that facilitate this process are unresolved. While current theory and biogeochemical models suggest microbial carbon-use efficiency and growth rate are positive predictors of SOC, recent observations demonstrate these relationships can be positive, negative, or neutral. To parse these contradictory effects, we used a13C-labeling experiment to test whether different microbial traits influenced the transformation of plant C into SOC within the microbial habitats surrounding living root inputs (rhizosphere) versus decaying root litter (detritusphere), under both normal soil moisture and droughted conditions. In the rhizosphere, bacterial-dominated communities with fast growth, high carbon-use efficiency, and high production of extracellular polymeric substances formed microbial-derived SOC under normal moisture conditions. However, in the detritusphere – and the rhizosphere under drought – more fungal-dominated communities with slower growth but higher exoenzyme activity formed plant-derived SOC. These findings emphasize that microbial traits linked with SOC accrual are not universal, but contingent on how microorganisms allocate carbon under different resource conditions and environmental stressors.
An Arg/Ala-Rich Helix in the N-Terminal Region ofM. tuberculosisFtsQ Anchors FtsZ to Membranes
Authors: Smrt Sean T. , Escobar Cristian A. , Dey Souvik , Cross Timothy A. , Zhou Huan-Xiang 
Published: September 2022

AbstractMycobacteria tuberculosis (Mtb)inflicts a quarter of the worldwide population. Most drugs for treating tuberculosis target cell growth and division. With rising drug resistance, it becomes ever more urgent to better understandMtbcell division. This process begins with the formation of the Z-ring via polymerization of FtsZ and anchoring of the Z-ring to the inner membrane. Here, by combining solution and solid-state NMR spectroscopy with molecular dynamics simulations and other techniques, we show that the transmembrane protein FtsQ is a membrane anchor of theMtbZ-ring. In the otherwise disordered N-terminal cytoplasmic region of FtsQ (residues 1-99), a 29-residue, Arg/Ala-rich α-helix is formed that interacts with upstream acidic residues in solution and with acidic lipids at the membrane surface. The same helix also binds to the GTPase domain of FtsZ, with enormous implications for drug binding and Z-ring formation including its curvature.
Neighbourhood effect of weeds on wheat root endospheric mycobiota
Authors: Hu Jie , Ricono Claire , Fournier Paola , Mondy Samuel , Vandenkoornhuyse Philippe , Mony Cendrine 
Published: September 2022

AbstractMicroorganisms associated with plants provide essential functions to their hosts, and therefore affect ecosystem productivity. Agricultural intensification has modified microbial diversity in the soil reservoir and may affect plant microbial recruitment. Weeds develop spontaneously in crop fields, and could influence microorganisms associated with crop plants through a neighbourhood effect. We explore the effect of weed species on crop plant microbiota as potentially auxiliary plants that affect agricultural productivity.We combined field and controlled laboratory studies to analyse the neighbourhood effect of weeds on wheat root endospheric mycobiota and growth. First, we analysed the effect of weed species diversity and identity recorded in the neighbourhood of individual wheat plants on soil and wheat root mycobiota in the field. Second, we used a plant-matrix design in laboratory conditions to test the effect of weed identity (9 weed treatments) and their ability to transmit root mycobiota to wheat roots, and the resulting impact on wheat growth.In contrast to soil mycobiota, we demonstrated that wheat root endospheric mycobiota was influenced by the diversity and identity of weeds developing in their 1 m2 neighbourhood. Wheat root endospheric microbiota strongly differs in terms of richness and composition depending on the neighbouring weed plant species. Weed species transmitted from 13% to 74% of their root microbiota to wheat roots depending on weed identity in controlled conditions.Synthesis. Weed neighbours modified wheat plant performance, possibly as a result of competitive interactions and changes in microbiota. Our findings suggest that crop root mycobiota was variable and was modulated by their weed neighbourhood. Synergistic effects between mycobiota of crops and weeds could therefore contribute to soil biodiversity and sustainable agriculture.
Transcriptome and chromatin accessibility landscapes across 25 distinct human brain regions expand the susceptibility gene set for neuropsychiatric disorders
Authors: Dong Pengfei , Bendl Jaroslav , Misir Ruth , Shao Zhiping , Edelstien Jonathan , Davis David A , Haroutunian Vahram , Scott William K. , Acker Susanne , Lawless Nathan , Hoffman Gabriel E. , Fullard John F. , Roussos Panos 
Published: September 2022

AbstractBrain region- and cell-specific transcriptomic and epigenomic molecular features are associated with heritability for neuropsychiatric traits, but a systematic view, considering cortical and subcortical regions, is lacking. Here, we provide an atlas of chromatin accessibility and gene expression in neuronal and non-neuronal nuclei across 25 distinct human cortical and subcortical brain regions from 6 neurotypical controls. We identified extensive gene expression and chromatin accessibility differences across brain regions, including variation in alternative promoter-isoform usage and enhancer-promoter interactions. Genes with distinct promoter-isoform usage across brain regions are strongly enriched for neuropsychiatric disease risk variants. Using an integrative approach, we characterized the function of the brain region-specific chromatin co-accessibility and gene-coexpression modules that are robustly associated with genetic risk for neuropsychiatric disorders. In addition, we identified a novel set of genes that is enriched for disease risk variants but is independent of cell-type specific gene expression and known susceptibility pathways. Our results provide a valuable resource for studying molecular regulation across multiple regions of the human brain and suggest a unique contribution of epigenetic modifications from subcortical areas to neuropsychiatric disorders.
Characterization of b-value dependent T2 relaxation rates for probing neurite microstructure
Authors: Ning Lipeng , Westin Carl-Fredrik , Rathi Yogesh 
Published: September 2022

AbstractBrain tissue microstructure is characterized by heterogeneous diffusivity and transversal relaxation rates. Standard diffusion MRI (dMRI) is acquired using a single echo time (TE) and only provides information about heterogeneous diffusivity in the underlying tissue. Combined relaxation diffusion MRI (rdMR) integrates dMRI with multiple TEs to probe the coupling between relaxation rate and diffusivity. This work introduces a method to model rdMRI data signals by characterizing the apparent relaxation rate related to dMRI with different b-values. The proposed approach can extrapolate dMRI signals to ultra-long or ultra-short TEs to increase or reduce signals from intra-neurite water to improve the characterization of neurite microstructure without solving multi-compartment models. The performance of the proposed method was examined using an in vivo dataset acquired from a clinical scanner to estimate neurite sizes.
Temperature affects the host range of Rhabdochlamydia porcellionis and the infectivity of Waddlia chondrophila and Chlamydia trachomatis elementary bodies
Authors: Marquis Bastian , Ardissone Silvia , Greub Gilbert 
Published: September 2022

AbstractThe Rhabdochlamydiaceae family is a recent addition to the Chlamydiales order. Its members were discovered in cockroaches and woodlice but recent metagenomics surveys demonstrated the widespread distribution of this family in the environment. It was moreover estimated to be the largest family of the Chlamydiales order based on 16S rRNA encoding gene diversity. Unlike most chlamydia-like organisms, no Rhabdochlamydiaceae could be co-cultivated in amoebae and its host range remains largely unknown. Here, we tested the permissivity of various mammalian and arthropod cell lines to determine the host range of Rhabdochlamydia porcellionis, the only cultured representative of this family. While a growth could initially only be obtained in the Sf9 cell line, lowering the incubation temperature of the mammalian cells from 37 °C to 28 °C allowed R. porcellionis to grow in those cells. Furthermore, a 6 h exposure to 37 °C was sufficient to irreversibly block the replication of R. porcellionis, suggesting that this bacterium either lost or never acquired the ability to grow at 37 °C. We next sought to determine if temperature would also affect the infectivity of elementary bodies. Although we could not purify enough bacteria to reach a conclusive result for R. porcellionis, our experiment showed that the elementary bodies of Chlamydia trachomatis and Waddlia chondrophila lose their infectivity faster at 37 °C than at room temperature. Our results demonstrate that members of the Chlamydiales adapt to the temperature of their host organism and that this adaptation can in turn restrict their host range.ImportanceThe Rhabdochlamydiaceae family is part of the Chlamydiales, a bacterial order that includes obligate intracellular bacteria sharing the same biphasic developmental cycle. This family have been shown to be highly prevalent in the environment, particularly in freshwater and soil and despite being estimated to be the largest family in the Chlamydiales order, is only poorly studied. Members of the Rhabdochlamydiaceae have been detected in various arthropods like ticks, spiders, cockroaches and woodlice, but the full host range of this family is currently unknown. In this study, we showed that R. porcellionis, the only cultured representative of the Rhabdochlamydiaceae family cannot grow at 37 °C and is quickly inactivated at this temperature. A similar temperature sensitivity was also observed for elementary bodies of chlamydial species adapted to mammals. Our work demonstrates that some chlamydiae adapt to the temperature of their reservoir, making a jump between species with different body temperatures unlikely.
Extensive cellular multitasking within Bacillus subtilis biofilms
Authors: Yannarell Sarah M. , Beaudoin Eric S. , Talley Hunter S. , Schoenborn Alexi A. , Orr Galya , Anderton Christopher R. , Chrisler William B. , Shank Elizabeth A 
Published: September 2022

ABSTRACTBacillus subtilis is a soil-dwelling bacterium that can form biofilms, or communities of cells surrounded by a self-produced extracellular matrix. In biofilms, genetically identical cells often exhibit heterogeneous transcriptional phenotypes so that only subpopulations of cells carry out essential yet costly cellular processes that allow the entire community to thrive. Surprisingly, the extent of phenotypic heterogeneity and the relationships between subpopulations of cells within biofilms of even in well-studied bacterial systems like B. subtilis remains largely unknown. To determine relationships between these subpopulations of cells, we created 182 strains containing pairwise combinations of fluorescent transcriptional reporters for the expression state of 14 different genes associated with potential cellular subpopulations. We determined the spatial organization of the expression of these genes within biofilms using confocal microscopy, which revealed that many reporters localized to distinct areas of the biofilm, some of which were co-localized. We used flow cytometry to quantify reporter co-expression, which revealed that many cells ‘multi-task’, simultaneously expressing two reporters. These data indicate that prior models describing B. subtilis cells as differentiating into specific cell-types, each with a specific task or function, were oversimplified. Only a few subpopulations of cells, including surfactin and plipastatin producers, as well as sporulating and competent cells, appear to have distinct roles based on the set of genes examined here. These data will provide us with a framework with which to further study and make predictions about the roles of diverse cell phenotypes in B. subtilis biofilms.IMPORTANCEMany microbes differentiate, expressing diverse phenotypes to ensure their survival in various environments. However, studies on phenotypic differentiation have typically examined only a few phenotypes at one time, thus limiting our knowledge about the extent of differentiation and phenotypic overlap in the population. We investigated the spatial organization and gene expression relationships for genes important in B. subtilis biofilms. In doing so, we mapped spatial gene expression patterns and expanded the number of cell populations described in the B. subtilis literature. It is likely that other bacteria also display complex differentiation patterns within their biofilms. Studying the extent of cellular differentiation in other microbes may be important when designing therapies for disease-causing bacteria, where studying only a single phenotype may be masking underlying phenotypic differentiation relevant to infection outcomes.
Analysis of State-level Variation in Distribution of Oxycodone and its Adverse Effect Profile in the US from 2000-2021
Authors: Solgama Jay P. , Liu Edward Y. , Davis Mellar P. , Graham Jove , McCall Kenneth L. , Piper Brian J. 
Published: September 2022

ObjectivesCharacterize oxycodone’s distribution in the US by state and its adverse effect profile from 2000-2021.DesignObservationalSettingMore than 80,000 Americans died of an opioid overdose in 2021 as the United States (US) continues to struggle with an opioid crisis. Prescription opioids play a substantial role, introducing patients to opioids and providing a supply of drugs that can be redirected to those seeking to misuse them.MethodsThe Drug Enforcement Administration annual summary reports from the Automation of Reports and Consolidated Orders System (ARCOS) provided weights of oxycodone distributed per state by business type (pharmacies, hospitals, and practitioners). Weights were converted to Morphine Milligram Equivalents (MME) per capita and normalized for population.ResultsThere was a sharp 280.13% increase in total MME/person of oxycodone from 2000-2010, followed by a slower 54.34% decrease from 2010-2021. Florida (2007-11), Delaware (2003-20), and Tennessee (2012-21) displayed consistent and substantial elevations in combined MME/person compared to other states. In the peak year (2010), there was a 15-fold difference between the highest and lowest states. MME/person from only pharmacies, which constituted >94% of the total, showed similar results. Hospitals in Alaska (2000-01, 2008, 2010-21), Colorado (2008-21), and DC (2000-11) distributed substantially more MME/person over many years compared to other states. Florida stood out in practitioner-distributed oxycodone, with an elevation of almost 15-fold the average state from 2006-2010. The percentage of consumer reports in the FDA Adverse Drugs Events Reporting System (FAERS) increased from 6.3% (2001) to 95% (2021). Adverse effects distribution remained constant by age and sex, with higher average proportions in males (55%) and the 18-65 age group (79%).ConclusionsOxycodone distribution across the US showed marked differences between states and business types over time. Investigation of opioid policies in states of interest may provide insight for future actions to mitigate opioid misuse.Strengths and limitations of this studyARCOS is publicly accessible, comprehensive, and includes institutions that are unavailable in other commonly used databases (i.e. IQVIA).Diversion of oxycodone or whether the prescribed amounts were utilized cannot be determined from ARCOS data.FAERS data includes duplicates, incomplete results, and non-verifiable data which cannot be used to suggest causation between oxycodone and adverse events.These complementary results from two databases may not generalize to other countries with more restrictive oxycodone policies.
Aggregate expression of genes lacking CpG islands increases with age and is positively associated with human mortality
Authors: Kerber Richard A. , O’Brien Elizabeth , Cawthon Richard M. 
Published: September 2022

ABSTRACTIn both mice and humans the misexpression of many genes lacking CpG islands (CGI- genes) increases with age, promoting inflammation and degenerative changes (Lee et al. 2021, ref. 1). In light of this recent discovery, we have revisited and expanded upon our previous work on gene expressions vs. aging and mortality in the three-generation CEPH (Centre d’Etudes du Polymorphisme Humain) Utah (CEU) families (Kerber et al. 2009, ref. 2). That study examined gene expressions in lymphoblastoid cell lines (LCLs) established in the early 1980s from all three CEU generations, in relation to age at blood draw, and in relation to the long-term survival of the grandparent generation. The 2009 study did not, however, consider the CGI status of genes, and it excluded from analysis genes not expressed in all of the subjects; therefore, the contribution to variation in age-at-death of inter-individual variation in the misexpression of genes with increasing age was not investigated. For the current study, after categorizing genes by their CGI status (- or +), we now find that most CGI- gene expressions in the LCLs increased with donor age, and after adjustment for donor age and sex, were positively associated with mortality risks. In contrast, most CGI+ gene expressions decreased with donor age, with higher expressions associated with decreased mortality risks. Of 7025 genes with known CGI status with expression detected in sufficient numbers of subjects from the grandparent generation to allow testing of association with mortality, 1834 genes were expressed in all subjects’ LCLs across all three generations, and 5191 were expressed in some, but not all subjects. We found the set of “not always expressed” genes to be highly enriched for CGI- genes. Furthermore, 49.4% of the CGI- genes were never expressed from ages 0-14, but expressed sometimes or always at older ages; in contrast, only 22.3% of the CGI+ genes were never expressed from ages 0-14, but expressed at older ages. These data support the model proposed by Lee et al. 2021, whereby tissue-restricted CGI- gene expressions become increasingly misexpressed during aging, contributing to loss of cellular identity, multiple aging-related pathologies, and ultimately death.
Heterogeneous aging across multiple organ systems and prediction of chronic disease and mortality
Authors: Tian Ye Ella , Cropley Vanessa , Maier Andrea B. , Lautenschlager Nicola T. , Breakspear Michael , Zalesky Andrew 
Published: September 2022

AbstractBiological aging of human organ systems reflects the interplay of age, chronic disease, lifestyle and genetic risk. Using longitudinal brain imaging and physiological phenotypes from the UK Biobank, we establish normative models of biological age for 3 brain and 7 body systems. We find that an organ’s biological age selectively influences the aging of other organ systems, revealing a multiorgan aging network. We report organ age profiles for 16 chronic diseases, where advanced biological aging extends from the organ of primary disease to multiple systems. Advanced body age associates with several lifestyle and environmental factors, leucocyte telomere lengths and mortality risk, and predicts survival time (AUC=0.77) and premature death (AUC=0.86). Our work reveals the multisystem nature of human aging in health and chronic disease. It may enable early identification of individuals at increased risk of aging-related morbidity and inform new strategies to potentially limit organ-specific aging in such individuals.