bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microgroove substrates unveil topography-driven, dynamic 3D nuclear deformations
Authors: Leclech Claire , Roellinger Bettina , Frederick Joni , Mamchaoui Kamel , Coirault Catherine , Barakat Abdul I. 
Published: February 2024

AbstractNavigating complex extracellular environments requires extensive deformation of cells and their nuclei. Nuclear deformations are intricately linked to nuclear structure and mechanical properties, and abnormalities in nuclear mechanics contribute to various diseases including laminopathies and cancer. Mostin vitrosystems used to study nuclear deformations are typically designed to generate strong whole-cell confinement relevant for specific cell types such as immune or cancer cells. Here, we use microgroove substrates as a model of anisotropic basement membrane topography and we report that adherent cells including endothelial cells and myoblasts exhibit significant 3D (in-plane and out-of-plane) nuclear deformations, with partial to complete penetration into the microgrooves. These deformations are dynamic with nuclei cyclically entering and exiting the microgrooves. AFM measurements show that these deformation cycles are accompanied by transient changes in nuclear mechanical properties. We also show that nuclear penetration into the grooves is principally driven by cell-substrate adhesion, without the need for cytoskeleton-associated forces. Finally, we demonstrate that myoblasts from patients withLMNAmutations exhibit abnormal nuclear deformations which can be rapidly identified and quantified using automated image analysis. We therefore propose the use of microgrooves as a novel simple, tunable, and high throughput system to study nuclear deformations in adherent cells, with the potential to serve as a functional diagnostic platform for pathological alterations in nuclear mechanics.
BRD4-mediated epigenetic regulation of endoplasmic reticulum-mitochondria contact sites is governed by the mitochondrial complex III
Authors: Chen Brandon , Stark Drew C. , Jadhav Pankaj V. , Lynn-Nguyen Theophilus M. , Halligan Benjamin S. , Rossiter Nicholas J. , Sindoni Nicole , Shin Myunsun , Paulo Joao A. , Chang Matthew , Koo Imhoi , Koshkin Sergei , Eyunni Sanjana , Ronchi Paolo , Paulsen Michelle T. , Morlacchi Pietro , Hanna David A. , Lin Jason , Guerra Rachel M. , Pagliarini David J. , Banerjee Ruma , Parolia Abhijit , Ljungman Mats E. , Patterson Andrew D. , Mancias Joseph D. , Mosalaganti Shyamal , Sexton Jonathan Z. , Calì Tito , Lyssiotis Costas A. , Shah Yatrik M. 
Published: February 2024

AbstractInter-organellar communication is critical for cellular metabolic homeostasis. One of the most abundant inter-organellar interactions are those at the endoplasmic reticulum and mitochondria contact sites (ERMCS). However, a detailed understanding of the mechanisms governing ERMCS regulation and their roles in cellular metabolism are limited by a lack of tools that permit temporal induction and reversal. Through unbiased screening approaches, we identified fedratinib, an FDA-approved drug, that dramatically increases ERMCS abundance by inhibiting the epigenetic modifier BRD4. Fedratinib rapidly and reversibly modulates mitochondrial and ER morphology and alters metabolic homeostasis. Moreover, ERMCS modulation depends on mitochondria electron transport chain complex III function. Comparison of fedratinib activity to other reported inducers of ERMCS revealed common mechanisms of induction and function, providing clarity and union to a growing body of experimental observations. In total, our results uncovered a novel epigenetic signaling pathway and an endogenous metabolic regulator that connects ERMCS and cellular metabolism.
Single-cell and bulk transcriptional profiling of mouse ovaries reveals novel genes and pathways associated with DNA damage response in oocytes
Authors: Mills Monique , Emori Chihiro , Kumar Parveen , Boucher Zachary , George Joshy , Bolcun-Filas Ewelina 
Published: February 2024

AbstractImmature oocytes enclosed in primordial follicles stored in female ovaries are under constant threat of DNA damage induced by endogenous and exogenous factors. Checkpoint kinase 2 (CHEK2) is a key mediator of the DNA damage response in all cells. Genetic studies have shown that CHEK2 and its downstream targets, p53 and TAp63, regulate primordial follicle elimination in response to DNA damage, however the mechanism leading to their demise is still poorly characterized. Single-cell and bulk RNA sequencing were used to determine the DNA damage response in wildtype andChek2-deficient ovaries. A low but oocyte-lethal dose of ionizing radiation induces a DNA damage response in ovarian cells that is solely dependent on CHEK2. DNA damage activates multiple ovarian response pathways related to apoptosis, p53, interferon signaling, inflammation, cell adhesion, and intercellular communication. These pathways are differentially employed by different ovarian cell types, with oocytes disproportionately affected by radiation. Novel genes and pathways are induced by radiation specifically in oocytes, shedding light on their sensitivity to DNA damage, and implicating a coordinated response between oocytes and pre-granulosa cells within the follicle. These findings provide a foundation for future studies on the specific mechanisms regulating oocyte survival in the context of aging, as well as therapeutic and environmental genotoxic exposures.
A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and tankyrase
Authors: Vu Jonathan T. , Tavasoli Katherine U. , Mandjikian Lori , Sheedy Connor J. , Bacal Julien , Morrissey Meghan A. , Richardson Chris D. , Gardner Brooke M. 
Published: February 2024

AbstractPeroxisomes are membrane-bound organelles harboring metabolic enzymes. In humans, peroxisomes are required for normal development, yet the genes regulating peroxisome function remain unclear. We performed a genome-wide CRISPRi screen to identify novel factors involved in peroxisomal homeostasis. We found that inhibition of RNF146, an E3 ligase activated by poly(ADP-ribose), reduced the import of proteins into peroxisomes. RNF146-mediated loss of peroxisome import depended on the stabilization and activity of the poly(ADP-ribose) polymerase tankyrase, which binds the peroxisomal membrane protein PEX14. We propose that RNF146 and tankyrase regulate peroxisome import efficiency by PARsylation of proteins at the peroxisome membrane. Interestingly, we found that the loss of peroxisomes increased tankyrase and RNF146-dependent degradation of non-peroxisomal substrates, including the beta-catenin destruction complex component AXIN1, which was sufficient to alter the amplitude of beta-catenin transcription. Together, these observations not only suggest previously undescribed roles for RNF146 in peroxisomal regulation, but also a novel role in bridging peroxisome function with Wnt/beta-catenin signaling during development.
APCalign: an R package workflow and app for aligning and updating flora names to the Australian Plant Census
Authors: Wenk Elizabeth , Cornwell William , Fuchs Anne , Kar Fonti , Monro Anna , Sauquet Hervé , Stephens Ruby , Falster Daniel S 
Published: February 2024

AbstractHere we present “APCalign”, an R package and accompanying browser-sourced application to align and update scientific names for Australian vascular plants to the most likely currently accepted name using the Australian Plant Census (APC) or a name in the Australian Plant Names Index (APNI). Scientific names are the label assigned to unique taxon concepts by the scientific community, but this common terminology is most useful if a taxon concept is consistently referred to by the same name. These links can be broken due to either spelling mistakes or taxonomic changes. Automated tools are required to resolve taxon lists, aligning and updating long lists of possibly erroneous scientific names to the most likely currently accepted names. It is essential that tools specific to the APC/APNI be developed, as these lists specify an endorsed national-level nomenclature used in government legislation and include the uniquely Australian concept of phrase names, absent in global taxonomic datasets. To align input names to names within the APC or APNI, “APCalign” works progressively through a sequence of checks that combine different permutations of the input name, exact versus fuzzy matches, matches that consider the entire name input versus a subset of words, and character strings that indicate a name can only be resolved to a genus or family. The aligned names are then, when possible, updated to a currently accepted taxon concept within the APC. This package should facilitate all research outputs that require diverse scientific name lists to be merged or outdated lists to be updated.
Long-term gut colonization with ESBL-producingEscherichia coliin participants without known risk factors from the southeastern United States
Authors: Garcia Coralis Rodriguez , Norfolk William A. , Howard Amanda K. , Glatter Amanda L. , Beaudry Megan S. , Mallis Nicholas A. , Welton Michael , Glenn Travis C. , Lipp Erin K. , Ottesen Elizabeth A. 
Published: February 2024

AbstractWe evaluated gut carriage of extended spectrum beta lactamase producingEnterobacteriaceae(ESBL-E) in southeastern U.S. residents without recent in-patient healthcare exposure. Study enrollment was January 2021-February 2022 in Athens, Georgia, U.S. and included a diverse population of 505 adults plus 50 child participants (age 0-5). Based on culture-based screening of stool samples, 4.5% of 555 participants carried ESBL-Es. This is slightly higher than reported in studies conducted 2012-2015, which found carriage rates of 2.5-3.9% in healthy U.S. residents.All ESBL-E confirmed isolates (n=25) were identified asEscherichia coli. Isolates belonged to 11 sequence types, with 48% classified as ST131. Ninety six percent of ESBL-E isolates carried ablaCTX-Mgene. Isolated ESBL-Es frequently carried virulence genes as well as multiple classes of antibiotic resistance genes. Long-term colonization was common, with 64% of ESBL-E positive participants testing positive when rescreened three months later. One participant yielded isolates belonging to two differentE. colisequence types that carriedblaCTX-M-1genes on near-identical plasmids, suggesting intra-gut plasmid transfer.Isolation ofE. colion media without antibiotics revealed that ESBL-E. colitypically made up a minor fraction of the overall gutE. colipopulation, although in some cases they were the dominant strain. ESBL-E carriage was not associated with a significantly different stool microbiome composition. However, some microbial taxa were differentially abundant in ESBL-E carriers. Together, these results suggest that a small subpopulation of US residents are long-term, asymptomatic carriers of ESBL-Es, and may serve as an important reservoir for community spread of these ESBL genes.ImportanceAntibiotic resistant bacteria, especiallyEnterobacteriaceaecarrying ESBLs, have become an increasing public health threat. Increasing numbers of community-associated infections (47% of ESBL-E infections in the U.S.) in participants without healthcare exposure is particularly concerning. This study found that 4.5% of a southeastern United States study population, without in-patient healthcare exposure, were asymptomatically colonized with ESBL-E, and 64% of ESBL-E positive participants were still positive when rescreened 3 months later. This suggests that the gut microbiome of healthy participants may represent an understudied community reservoir of ESBL genes and ESBLEscherichia coliin the U.S.
Metatranscriptomic analysis of wastewater sites reveals a high abundance of antimicrobial resistance genes from hospital wastewater
Authors: Musundi Sebastian , Ng’ang’a Samuel , Wanjiru Esther Wangui , Sagoe Kate , Wandera Ernest , Kanoi Bernard , Gitaka Jesse 
Published: February 2024

AbstractObjectiveThis study analyzed the metatranscriptome of wastewater samples from different sites with a focus of identifying antibiotic resistance genes and the bacterial community.MethodsTwenty-four wastewater samples were collected from a hospital, university sewer, and the influent and effluent of a wastewater treatment plant (WWTP). The metatranscriptome was sequenced to identify antimicrobial resistance genes (ARGs), mobile genetic elements, and bacterial community composition.ResultsMetatranscriptome analysis revealed varying abundances of ARG transcripts across different sites, with 84, 27, 14, and 9 ARG transcripts identified in wastewater collected from the hospital, university, influent, and effluent of a WWTP, respectively. Notably, hospital wastewater contained clinically relevant beta-lactam ARGs, includingbla-NDM-1and severalblaOXAtranscripts. Four core ARGs, against sulfonamidessul1andsul2and aminoglycosidesaph(6)-ldandaph(’3’)-lbwere also identified. The predominant bacterial community comprised ofGammaproteobacteria,with priority pathogens likeNeisseria gonorrheaandHelicobacter pyloripresent in hospital wastewater and WWTP influent.ConclusionThese findings provide insights into the wastewater resistome and how meta-transcriptomic data can be utilized for the surveillance of antibiotic resistance. Overall, our study highlights the utility of wastewater surveillance in understanding and addressing the dissemination of antibiotic resistance and emphasizes the crucial role of proper wastewater management in protecting public and environmental health.
Improving rice drought tolerance through host-mediated microbiome selection
Authors: Styer Alex , Pettinga Dean , Caddell Daniel , Coleman-Derr Devin 
Published: February 2024

AbstractPlant microbiome engineering remains a significant challenge due to challenges associated with accurately predicting microbiome assembly and function in complex, heterogeneous soil environments. However, host-mediated selection can simplify the process by using plant host phenotype as a reporter of microbiome function; by iteratively selecting microbiomes from hosts with desired phenotypes and using them to inoculate subsequent cohorts of hosts, artificial selection can steer the microbiome towards a composition producing optimized plant phenotypes. In this study, we inoculated rice with wild microbial communities from fallow rice field, desert, and serpentine seep field soils. By challenging these plants with drought and iteratively selecting microbiomes from the least drought stressed plants across multiple generations, we derived simplified microbiomes that enhanced both the growth and drought tolerance of rice. Across selection cycles, microbiomes within and between soil treatments became increasingly similar, implicating both dispersal and selection as drivers of community composition. With amplicon sequencing data we identified specific bacterial taxa associated with improved rice drought phenotypes; while many of these taxa have been previously described as plant growth promoters, we also identified novel taxa exhibiting strong positive correlation with improved drought performance. Lastly, we resolved 272 metagenome-assembled genomes (MAGs) and used these MAGs to identify functions enriched in bacteria driving enhanced drought tolerance. The most significantly enriched functions—particularly glycerol-3-phosphate and iron transport—have been previously implicated as potential mediators of plant-microbe interactions during drought. Altogether, these data demonstrate that host-mediated selection provides an efficient framework for microbiome engineering through the identification of both individual taxa and simplified communities associated with enhanced plant phenotypes.
P. aeruginosatRNA-fMet halves secreted in outer membrane vesicles suppress lung inflammation in Cystic Fibrosis
Authors: Li Zhongyou , Barnaby Roxanna , Nymon Amanda , Roche Carolyn , Koeppen Katja , Ashare Alix , Hogan Deborah A. , Gerber Scott A. , Taatjes Douglas J. , Hampton Thomas H. , Stanton Bruce A. 
Published: February 2024

AbstractAlthough tobramycin increases lung function in people with cystic fibrosis (pwCF), the density ofPseudomonas aeruginosa (P. aeruginosa)in the lungs is only modestly reduced by tobramycin; hence, the mechanism whereby tobramycin improves lung function is not completely understood. Here, we demonstrate that tobramycin increases 5′ tRNA-fMet halves in outer membrane vesicles (OMVs) secreted by laboratory and CF clinical isolates ofP. aeruginosa. The 5′ tRNA-fMet halves are transferred from OMVs into primary CF human bronchial epithelial cells (CF-HBEC), decreasing OMV-induced IL-8 and IP-10 secretion. In mouse lung, increased expression of the 5′ tRNA-fMet halves in OMVs attenuated KC secretion and neutrophil recruitment. Furthermore, there was less IL-8 and neutrophils in bronchoalveolar lavage fluid isolated from pwCF during the period of exposure to tobramycin versus the period off tobramycin. In conclusion, we have shown in mice andin vitrostudies on CF-HBEC that tobramycin reduces inflammation by increasing 5′ tRNA-fMet halves in OMVs that are delivered to CF-HBEC and reduce IL-8 and neutrophilic airway inflammation. This effect is predicted to improve lung function in pwCF receiving tobramycin forP. aeruginosainfection.New and noteworthyThe experiments in this report identify a novel mechanim whereby tobramycin reduces inflammation in two models of CF. Tobramycin increased the secretion of tRNA-fMet haves in OMVs secreted byP. aeruginiosa, which reduced the OMV-LPS induced inflammatory response in primary cultures of CF-HBEC and in mouse lung, an effect predicted to reduce lung damage in pwCF.Graphical abstractThe anti-inflammatory effect of tobramycin mediated by 5′ tRNA-fMet halves secreted inP. aeruginosaOMVs.(A)P. aeruginosacolonizes the CF lungs and secrets OMVs. OMVs diffuse through the mucus layer overlying bronchial epithelial cells and induce IL-8 secretion, which recruits neutrophils that causes lung damage. (B) Tobramycin increases 5′ tRNA-fMet halves in OMVs secreted byP. aeruginosa. 5′ tRNA-fMet halves are delivered into host cells after OMVs fuse with lipid rafts in CF-HBEC and down-regulate protein expression of MAPK10, IKBKG, and EP300, which suppresses IL-8 secretion and neutrophils in the lungs. A reduction in neutrophils in CF BALF is predicted to improve lung function and decrease lung damage.
Genomic and environmental controls onCastellaniellabiogeography in an anthropogenically disturbed subsurface
Authors: Goff Jennifer L. , Szink Elizabeth G. , Durrence Konnor L. , Lui Lauren M. , Nielsen Torben N. , Kuehl Jennifer V. , Hunt Kristopher A. , Chandonia John-Marc , Huang Jiawen , Thorgersen Michael P. , Poole Farris L. , Stahl David A. , Chakraborty Romy , Deutschbauer Adam M. , Arkin Adam P. , Adams Michael W. W. 
Published: February 2024

ABSTRACTCastellaniellaspecies have been isolated from a variety of mixed-waste environments including the nitrate and multiple metal contaminated subsurface at the Oak Ridge Reservation (ORR). Previous studies examining microbial community composition and nitrate removal at ORR during biostimulation efforts reported increased abundances of members of theCastellaniellagenus concurrent to increased denitrification rates. Thus, we asked how genomic and abiotic factors control theCastellaniellabiogeography at the site to understand how these factors may influence nitrate transformation in an anthropogenically impacted setting. ORRCastellaniellastrains showed a higher degree of genetic diversification than those originating from non-ORR sites, which we attribute to the multitude of extreme stressors faced in the ORR subsurface. We report the isolation and characterization of severalCastellaniellastrains from the ORR subsurface. Five of these isolates match at 100% identity (at the 16S rRNA gene V4 region) to twoCastellaniellaamplicon sequence variants (ASVs), ASV1 and ASV2, that have persisted in the ORR subsurface for at least two decades. However, ASV2 has consistently higher relative abundance in samples taken from the site and was also the dominant blooming denitrifier population during a prior biostimulation effort. We found that the ASV2 representative strain has greater resistance to mixed metal stress than the ASV1 representative strains. We attribute this resistance, in part, to the large number of unique heavy metal resistance genes identified on a genomic island in the ASV2 representative genome. Additionally, we suggest that the relatively lower fitness of ASV1 may be connected to the loss of the nitrous oxide reductase (nos) operon (and associated nitrous oxide reductase activity) due to the insertion at this genomic locus of a mobile genetic element carrying copper resistance genes. This study demonstrates the value of integrating genomic, environmental, and phenotypic data to characterize the biogeography of key microorganisms in contaminated sites.
Time resolved multi-omics reveals diverse metabolic strategies ofSalmonelladuring diet-induced inflammation
Authors: Kokkinias Katherine , Sabag-Daigle Anice , Kim Yongseok , Leleiwi Ikaia , Shaffer Michael , Kevorkian Richard , Daly Rebecca A. , Wysocki Vicki H. , Borton Mikayla A. , Ahmer Brian M. M. , Wrighton Kelly C. 
Published: February 2024

AbstractWith a rise in antibiotic resistance and chronic infection, the metabolic response ofSalmonella entericaserovar Typhimurium to various dietary conditions over time remains an understudied avenue for novel, targeted therapeutics. Elucidating how enteric pathogens respond to dietary variation not only helps us decipher the metabolic strategies leveraged for expansion but also assists in proposing targets for therapeutic interventions. Here, we use a multi-omics approach to identify the metabolic response ofSalmonella entericaserovar Typhimurium in mice on both a fibrous diet and high-fat diet over time. When comparingSalmonellagene expression between diets, we found a preferential use of respiratory electron acceptors consistent with increased inflammation of the high-fat diet mice. Looking at the high-fat diet over the course of infection, we noticed heterogeneity of samples based onSalmonellaribosomal activity, which separated into three infection phases: early, peak, and late. We identified key respiratory, carbon, and pathogenesis gene expression descriptive of each phase. Surprisingly, we identified genes associated with host-cell entry expressed throughout infection, suggesting sub-populations ofSalmonellaor stress-induced dysregulation. Collectively, these results highlight not only the sensitivity ofSalmonellato its environment but also identify phase-specific genes that may be used as therapeutic targets to reduce infection.ImportanceIdentifying novel therapeutic strategies forSalmonellainfection that occur in relevant diets and over time is needed with the rise of antibiotic resistance and global shifts towards Western diets that are high in fat and low in fiber. Mice on a high-fat diet are more inflamed compared to those on a fibrous diet, creating an environment that results in more favorable energy generation forSalmonella. Over time on a high-fat diet, we observed differential gene expression across infection phases. Together, these findings reveal the metabolic tuning ofSalmonellato dietary and temporal perturbations. Research like this, exploring the dimensions of pathogen metabolic plasticity, can pave the way for rationally designed strategies to control disease.