bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversion to metabolic autonomy underpins evolutionary rescue of a bacterial obligate mutualism
Authors: Melero-Jiménez Ignacio J. , Sorokin Yael , Merlin Ami , Couce Alejandro , Friedman Jonathan 
Published: July 2024

AbstractPopulations facing lethal environmental change can avoid extinction by undergoing rapid genetic adaptation, a phenomenon termed evolutionary rescue. While this phenomenon has been the focus of much theoretical and empirical research, our understanding of evolutionary rescue in communities consisting of interacting species is still limited, especially in mutualistic communities, where evolutionary rescue is expected to be constrained by the less adaptable partner. Here, we explored empirically the likelihood, population dynamics, and genetic mechanisms underpinning evolutionary rescue in an obligate mutualism in which auxotrophicEscherichia colistrains exchanged essential amino acids reciprocally. We observed that >80% of the communities avoided extinction when exposed to two different types of lethal and abrupt stresses. Of note, only one of the strains survived in all cases. Genetic and phenotypic analyses show that this strain reverted to autonomy by metabolically bypassing the auxotrophy, but we found little evidence of specific adaptation to the stressors. Crucially, we found that the mutualistic partners were substantially more sensitive to both stresses than prototrophs, so that reversion to autonomy was sufficient to alleviate stress below lethal levels. We observed that increased sensitivity was common across several other stresses, suggesting that this may be a general property of obligate mutualisms mediated by amino acid exchange. Our results reveal that evolutionary rescue may depend critically on the specific genetic and physiological details of the interacting partners, adding rich layers of complexity to the endeavor of predicting the fate of microbial communities facing intense environmental deterioration.
In vitro genotoxic and mutagenic potentials of combustion particles from marine fuels with different sulfur contents
Authors: Jeong Seongho , Pantzke Jana , Offer Svenja , Käfer Uwe , Bendl Jan , Saraji-Bozorgzad Mohammad , Huber Anja , Michalke Bernhard , Etzien Uwe , Jakobi Gert , Orasche Jürgen , Czech Hendryk , Rüger Christopher P. , Schnelle-Kreis Jürgen , Streibel Thorsten , Buchholz Bert , Adam Thomas , Sklorz Martin , Bucchianico Sebastiano Di , Zimmermann Ralf 
Published: July 2024

AbstractShip emissions cause serious environmental impacts and adverse effects toward human health. Therefore, the International Maritime Organization (IMO) restricted the fuel sulfur content (FSC) of marine fuels: FSC must be <0.5% m/m or <0.1% m/m in sulfur emission control areas, covering a range of fuels from distillate diesel-like fuels to low-sulfur heavy fuel oils (HFOs). As a result, ship emissions, e.g., sulfur oxides and particulate matter (PM) have been reduced. However, how FSC correlates with the toxicological potential of ship emissions is still uncertain. The objective of this study was to understand how the physical and chemical properties of particulate emissions from a marine engine operating on five marine fuels with different FSCs influence their toxicological outcome. For this scope, cytotoxic, genotoxic, mutagenic, and pro-inflammatory potentials of collected particles were evaluated in lung cell model systems. The involvement of intracellular reactive oxygen species and xenobiotic metabolism was also explored. While PM from different fuels’ combustion resulted in up to approximately 20% of reduction of cytotoxicity at the highest concentration, other toxicological outcomes, including clonogenic and genotoxic potentials, showed a stronger trend with the polycyclic aromatic hydrocarbon contents in PM compared with FSC. This trend was supported by evidence of a significant increase in gene mutation frequency and alterations in cellular mechanisms induced by an aromatic-rich HFO with an intermediate FSC. In conclusion, apart from reducing FSC in marine fuels, additional particle abatement systems should be considered to reduce the adverse effects of particulate emissions from shipping operations on human health.
Ultrafast and accurate sequence alignment and clustering of viral genomes
Authors: Zielezinski Andrzej , Gudyś Adam , Barylski Jakub , Siminski Krzysztof , Rozwalak Piotr , Dutilh Bas E. , Deorowicz Sebastian 
Published: July 2024

AbstractViromics produces millions of viral genomes and fragments annually, overwhelming traditional sequence comparison methods. We introduce Vclust, a novel approach that determines average nucleotide identity by Lempel-Ziv parsing and clusters viral genomes with thresholds endorsed by authoritative viral genomics and taxonomy consortia. Vclust demonstrates superior accuracy and efficiency compared to existing tools, clustering millions of virus genomes in a few hours on a mid-range workstation.
SCEMENT: Scalable and Memory Efficient Integration of Large-scale Single Cell RNA-sequencing Data
Authors: Chockalingam Sriram P , Aluru Maneesha , Aluru Srinivas 
Published: July 2024

AbstractMotivationIntegrative analysis of large-scale single cell data collected from diverse cell populations promises an improved understanding of complex biological systems. While several algorithms have been developed for single cell RNA-sequencing data integration, many lack scalability to handle large numbers of datasets and/or millions of cells due to their memory and run time requirements. The few tools which can handle large data do so by reducing the computational burden through strategies such as subsampling of the data or selecting a reference dataset, to improve computational efficiency and scalability. Such shortcuts however hamper accuracy of downstream analyses, especially those requiring quantitative gene expression information.ResultsWe present SCEMENT, a SCalablE and Memory-Efficient iNTegration method to overcome these limitations. Our new parallel algorithm builds upon and extends the linear regression model previously applied in ComBat, to an unsupervised sparse matrix setting to enable accurate integration of diverse and large collections of single cell RNA-sequencing data. Using tens to hundreds of real single cell RNA-seq datasets, we show that SCEMENT outperforms ComBat as well as FastIntegration and Scanorama in runtime (upto 214X faster) and memory usage (upto 17.5X less). It not only performs batch correction and integration of millions of cells in under 25 minutes, but also facilitates discovery of new rare cell-types and more robust reconstruction of gene regulatory networks with full quantitative gene expression information.Availability and implementationSource code freely available for download athttps://github.com/AluruLab/scement, implemented in C++ and supported on Linux.Contactaluru@cc.gatech.eduSupplementary informationSupplementary data are available atBioinformaticsonline.
Sulfur Amino Acid Restriction Enhances Exercise Capacity in Mice by Boosting Fat Oxidation in Muscle
Authors: Mann Charlotte G , MacArthur Michael R , Zhang Jing , Gong Songlin , AbuSalim Jenna E , Hunter Craig J. , Lu Wenyun , Agius Thomas , Longchamp Alban , Allagnat Florent , Rabinowitz Joshua , Mitchell James R , De Bock Katrien , Mitchell Sarah J 
Published: July 2024

SummaryDietary restriction of the sulfur-containing amino acids methionine and cysteine (SAAR) improves body composition, enhances insulin sensitivity, and extends lifespan; benefits seen also with endurance exercise. Yet, the impact of SAAR on skeletal muscle remains largely unexplored. Here we demonstrate that one week of SAAR in sedentary, young, male mice increases endurance exercise capacity. Indirect calorimetry showed that SAAR increased lipid oxidation at rest and delayed the onset of carbohydrate utilization during exercise. Transcriptomic analysis revealed increased expression of genes involved in fatty acid catabolism especially in glycolytic muscle following SAAR. These findings were functionally supported by increased fatty acid circulatory turnover flux and muscle β-oxidation. Reducing lipid uptake from circulation through endothelial cell (EC)-specific CD36 deletion attenuated the running phenotype. Mechanistically, VEGF-signaling inhibition prevented exercise increases following SAAR, without affecting angiogenesis, implicating noncanonical VEGF signaling and EC CD36-dependent fatty acid transport in regulating exercise capacity by influencing muscle substrate availability.
Human erythroid progenitors express antigen presentation machinery
Authors: Clements Rebecca L. , Kennedy Elizabeth A. , Song David , Campbell Ariana , An Hyun Hyung , Amses Kevin R. , Miller-Ensminger Taylor , Addison Mary M. , Eisenlohr Laurence C. , Chou Stella T. , Jurado Kellie Ann 
Published: July 2024

AbstractEarly-life immune exposures can profoundly impact lifelong health. However, functional mechanisms underlying fetal immune development remain incomplete. Erythrocytes are not typically considered active immune mediators, primarily because erythroid precursors discard their organelles as they mature, thus losing the ability to alter gene expression in response to stimuli. Erythroid progenitors and precursors circulate in human fetuses and neonates. Although there is limited evidence that erythroid precursors are immunomodulatory, our understanding of the underlying mechanisms remains inadequate. To define the immunobiological role of fetal and perinatal erythroid progenitors and precursors, we analyzed single cell RNA-sequencing data and found that transcriptomics support erythroid progenitors as putative immune mediators. Unexpectedly, we discovered that human erythroid progenitors constitutively express Major Histocompatibility Complex (MHC) class II antigen processing and presentation machinery, which are hallmarks of specialized antigen presenting immune cells. Furthermore, we demonstrate that erythroid progenitors internalize and cleave foreign proteins into peptide antigens. Unlike conventional antigen presenting cells, erythroid progenitors express atypical costimulatory molecules and immunoregulatory cytokines that direct the development of regulatory T cells, which are critical for establishing maternal-fetal tolerance. Expression of MHC II in definitive erythroid progenitors begins during the second trimester, coinciding with the appearance of mature T cells in the fetus, and is absent in primitive progenitors. Lastly, we demonstrate physical and molecular interaction potential of erythroid progenitors and T cells in the fetal liver. Our findings shed light on a unique orchestrator of fetal immunity and provide insight into the mechanisms by which erythroid cells contribute to host defense.
Interspecies interactions alter the antibiotic sensitivity ofPseudomonas aeruginosa
Authors: Koumans C.I.M. , Tandar S.T. , Liakopoulos A. , van Hasselt J.G.C. 
Published: July 2024

AbstractPolymicrobial infections are infections that are caused by multiple pathogens, and are common in patients with cystic fibrosis (CF). Although polymicrobial infections are associated with poor treatment responses in CF, the effects of the ecological interactions between co-infecting pathogens on antibiotic sensitivity and treatment outcome are poorly characterized. To this end, we systematically quantified the impact of these effects on the antibiotic sensitivity ofPseudomonas aeruginosafor nine antibiotics in the presence of thirteen secondary cystic fibrosis-associated bacterial and fungal pathogens through time-kill assays. We fitted pharmacodynamic models to these kill curves for each antibiotic-species combination and found that interspecies interactions changing the antibiotic sensitivity ofP. aeruginosaare abundant. Interactions that lower antibiotic sensitivity are more common than those that increase it, with generally more substantial reductions than increases in sensitivity. For a selection of co-infecting species, we performed pharmacokinetic-pharmacodynamic modelling ofP. aeruginosatreatment. We predicted that interspecies interactions can either improve or reduce treatment response to the extent that treatment is rendered ineffective from a previously effective antibiotic dosing schedule and vice versa. In summary, we show that quantifying the ecological interaction effects as pharmacodynamic parameters is necessary to determine the abundance and the extent to which these interactions affect antibiotic sensitivity in polymicrobial infections.ImportanceIn cystic fibrosis (CF) patients, chronic respiratory tract infections are often polymicrobial, involving multiple pathogens simultaneously. Polymicrobial infections are difficult to treat as they often respond unexpectedly to antibiotic treatment, which might possibly be explained because co-infecting pathogens can influence each other’s antibiotic sensitivity, but it is unknown to what extent such effects occur. To investigate this, we systematically quantified the impact of co-infecting species on antibiotic sensitivity, focusing onP. aeruginosa, a common CF pathogen. We studied for a large set co-infecting species and antibiotics whether changes in antibiotic response occur. Based on these experiments, we used mathematical modeling to simulateP. aeruginosa’s response to colistin and tobramycin treatment in the presence of multiple pathogens. This study offers comprehensive data on altered antibiotic sensitivity of P. aeruginosa in polymicrobial infections, serves as a foundation for optimizing treatment of such infections, and consolidates the importance of considering co-infecting pathogens.
FKBP12-BOUND CALCINEURIN CONTROL TMEM16A ACTIVITY
Authors: Guzmán-Hernández María Luisa , Huerta Miriam , López-Romero Ana E. , Morán-Zendejas Rita , Betanzos Abigail , Pérez-Cornejo Patricia , Arreola Jorge 
Published: July 2024

ABSTRACTThe Ca2+-dependent Cl-channel TMEM16A activity is vital for mammals. Critical functions such as blood pressure, pain, fluid and electrolyte secretion, peristalsis, and electrical activity depend on TMEM16A Cl-fluxes. Ciclosporin A (CsA) and FK506, two immunosuppressants that inhibit calcineurin (CaN), down-regulate TMEM16A function. However, the underlying mechanism remains undetermined. CsA binds to cyclophilin 1, whereas FK506 binds to FKBP12, and both complexes subsequently inhibit CaN, a phosphatase that maintains TMEM16A function. Here, we show that TMEM16A-EGFP and mRFP-FKBP12 colocalize in HEK-AD293 cells stimulated with the Ca2+ionophore ionomycin, FKBP12 co-immunoprecipitated with TMEM16A expressed in CaN-depleted HEK-AD293 cells, ionomycin favoured TMEM16A and FKBP12 interaction in a bimolecular fluorescence complementation assay in live cells, and TMEM16A currents recorded from CaN-depleted HEK-AD293 cells were insensitive to CsA and FK506. These data support the idea that FKBP12 works as an auxiliary protein of TMEM16A, thus enabling the interaction of CaN under physiological conditions. This heteromerization is essential to sustain TMEM16A activity. On the contrary, disrupting the Ca2+-stimulated CaN-FKBP12-TMEM16A heterotrimer or inhibiting CaN with CsA or FK506 does not preclude TMEM16A activation but decreases activity.
Comprehensive evaluation of phosphoproteomic-based kinase activity inference
Authors: Müller-Dott Sophia , Jaehnig Eric J. , Munchic Khoi Pham , Jiang Wen , Yaron-Barir Tomer M. , Savage Sara R. , Garrido-Rodriguez Martin , Johnson Jared L. , Lussana Alessandro , Petsalaki Evangelia , Lei Jonathan T. , Dugourd Aurelien , Krug Karsten , Cantley Lewis C. , Mani D.R. , Zhang Bing , Saez-Rodriguez Julio 
Published: July 2024

AbstractKinases play a central role in regulating cellular processes, making their study essential for understanding cellular function and disease mechanisms. To investigate the regulatory state of a kinase, numerous methods have been, and continue to be, developed to infer kinase activities from phosphoproteomics data. These methods usually rely on a set of kinase targets collected from various kinase-substrate libraries. However, only a small percentage of measured phosphorylation sites can usually be attributed to an upstream kinase in these libraries, limiting the scope of kinase activity inference. In addition, the inferred activities from different methods can vary making it crucial to evaluate them for accurate interpretation. Here, we present a comprehensive evaluation of kinase activity inference methods using multiple kinase-substrate libraries combined with different inference algorithms. Additionally, we try to overcome the coverage limitations for measured targets in kinase substrate libraries by adding predicted kinase-substrate interactions for activity inference. For the evaluation, in addition to classical cell-based perturbation experiments, we introduce a tumor-based benchmarking approach that utilizes multi-omics data to identify highly active or inactive kinases per tumor type. We show that while most computational algorithms perform comparably regardless of their complexity, the choice of kinase-substrate library can highly impact the inferred kinase activities. Hereby, manually curated libraries, particularly PhosphoSitePlus, demonstrate superior performance in recapitulating kinase activities from phosphoproteomics data. Additionally, in the tumor-based evaluation, adding predicted targets from NetworKIN further boosts the performance, while normalizing sites to host protein levels reduces kinase activity inference performance. We then showcase how kinase activity inference can help in characterizing the response to kinase inhibitors in different cell lines. Overall, the selection of reliable kinase activity inference methods is important in identifying deregulated kinases and novel drug targets. Finally, to facilitate the evaluation of novel methods in the future, we provide both benchmarking approaches in the R package benchmarKIN.Graphical Abstract
Vaginal Microbiota Transplantation (VMT) for treatment of vaginal dysbiosis without the use of antibiotics – A Double-Blinded Randomized Controlled Trial in healthy women with vaginal dysbiosis
Authors: Wrønding Tine , Vomstein Kilian , DeLong Kevin , Lundgaard Agnete Troen , Mollerup Sarah , Mortensen Brynjulf , Bosma Elleke F. , Hellerung Ann Marie , Engel Emilie Vester , Wiil Klara Dortea , Heintz Julie Elm , Halkjær Sofie Ingdam , Hugerth Luisa W , Hartwig Tanja Schlaikjær , Petersen Andreas Munk , Thomsen Anne Bloch , Westergaard David , Freiesleben Nina La Cour , Westh Henrik , van Hylckama Vlieg Johan E.T. , Ensign Laura M. , Nielsen Henriette Svarre 
Published: July 2024

AbstractHere we describe the first double-blinded, randomized, placebo-controlled trial (RCT) on vaginal microbiota transplantation (VMT) without antibiotics in women withbothsymptomatic and asymptomatic vaginal dysbiosis. Forty-nine women were randomly assigned to VMT or placebo. The trial did not show a significant conversion to our predefinedLactobacillus-dominated microbiome. However, in participants not initially converting, antiseptic pretreatment before a subsequent VMT led to a 50% conversion rate, associated with an anti-inflammatory shift in gene expression. Metagenomic sequencing and strain-level genetic analysis confirmed donor engraftment in five of 10 women who showed microbiome conversion. Extensive exploration of the microbiome, immune response and metadata revealed differences in baseline energy metabolism in participants who later experienced donor engraftment. Treatments for vaginal dysbiosis are urgently needed and given that VMT can lead to donor engraftment and change the vaginal immune profile, future studies should focus on optimizing this treatment for various women’s health diseases.
Changes in vaginalUreaplasmaandLactobacillusdue to antibiotic regimen for premature rupture of membranes
Authors: Kawaguchi Haruna , Nakura Yukiko , Yamamoto Ryo , Hayashi Shusaku , Takeuchi Makoto , Ishii Keisuke , Yanagihara Itaru 
Published: July 2024

AbstractPreterm premature rupture of membranes (PPROM) is associated with preterm delivery and neonatal complications. PPROM is often complicated by intra-amniotic inflammation and/or microbial invasion of the amniotic cavity withUreaplasmaorMycoplasma. Various prophylactic antibiotic therapies have been proposed to prolong latency between PPROM and delivery, reduce the risk of clinical chorioamnionitis, and improve neonatal complications. However, information on the potential of azithromycin administration to reduce the microbial load of vaginalUreaplasmaandMycoplasmaremains lacking. This prospective cohort study included singleton pregnancies managed with prophylactic antibiotics for PPROM at less than 36 weeks of gestation. All patients received the standard antibiotic regimen for PPROM, which consisted of a single oral azithromycin and intravenous ampicillin every for 2 days followed by 5 days of oral amoxicillin. Vaginal swabs samples were collected when PPROM was confirmed and after the antibiotic regimen administration. The main outcome measures were to investigate the changes in vaginalUreaplasma, Mycoplasma,andLactobacillus spp.due to the antibiotic regimen. In addition, the association between the presence and changes in vaginalUreaplasmaandMycoplasma, pregnancy outcomes, and neonatal complications were examined. Out of 82 eligible PPROM, 51 had positive vaginalUreaplasma. Thirty-six patients (52.2%) completed the antibiotic regimen. Among those with positive vaginalUreaplasmawho completed the antibiotic regimen, 75% experienced an increase in vaginalUreaplasmalevels. For those who delivered before completing all antibiotic doses, 40% had increased vaginalUreaplasmalevels. Furthermore, the antibiotic regimen resulted in decreasedLactobacillus spp.in almost all cases. However, vaginalUreaplasmachanges were not found to be associated with neonatal sepsis or bronchopulmonary dysplasia. This suggests thatUreaplasmabecame resistant to azithromycin. Future studies are needed to revalidate current antibiotic therapy for PPROM.
Neural Stem Cell Relay from B1 to B2 cells in the adult mouse Ventricular-Subventricular Zone
Authors: Cebrian-Silla Arantxa , Assis Nascimento Marcos , Mancia Walter , Gonzalez-Granero Susana , Romero-Rodriguez Ricardo , Obernier Kirsten , Steffen David M , Lim Daniel. A. , Garcia-Verdugo Jose Manuel , Alvarez-Buylla Arturo 
Published: July 2024

SummaryNeurogenesis and gliogenesis continue in the Ventricular-Subventricular Zone (V-SVZ) of the adult rodent brain. B1 cells are astroglial cells derived from radial glia that function as primary progenitors or neural stem cells (NSCs) in the V-SVZ. B1 cells, which have a small apical contact with the ventricle, decline in numbers during early postnatal life, yet neurogenesis continues into adulthood. Here we found that a second population of V-SVZ astroglial cells (B2 cells), that do not contact the ventricle, function as NSCs in the adult brain. B2 cell numbers increase postnatally, remain constant in 12-month-old mice and decrease by 18 months. Transcriptomic analysis of ventricular-contacting and non-contacting B cells revealed key molecular differences to distinguish B1 from B2 cells. Transplantation and lineage tracing of B2 cells demonstrate their function as primary progenitors for adult neurogenesis. This study reveals how NSC function is relayed from B1 to B2 progenitors to maintain adult neurogenesis.