bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-Tocky system to visualize proviral expression dynamics
Authors: Reda Omnia , Monde Kazuaki , Sugata Kenji , Rahman Akhinur , Sakhor Wajihah , Rajib Samiul Alam , Sithi Sharmin Nahar , Tan Benjy Jek Yang , Niimura Koki , Motozono Chihiro , Maeda Kenji , Ono Masahiro , Takeuchi Hiroaki , Satou Yorifumi 
Published: August 2023

AbstractThe stably integrated pool of HIV-1 proviruses in the host genome stands against curative strategies. This reservoir is extremely heterogeneous with respect to host cell type, anatomical location, integration site, and replication fitness. During the initial phase of infection, only a few infected cells can resist host immune clearance or cytopathic effect and establish this resistant pool. The mechanisms underlying HIV latency initiation are not fully resolved yet. In the current study, we propose and validate a new reporter model for monitoring HIV-1 provirus silencing and reactivation using Timer of cell kinetics and activity (Tocky). HIV-Tocky system uses a fluorescent Timer protein whose emission spectrum spontaneously shifts from blue to red to reveal HIV-1 provirus dynamics. We dissected provirus transcriptional phases into early, persistent, recently silenced, and latent. To our knowledge, this is the first report to distinguish two latent subsets: a directly non-expressing population and a recently silenced after brief expression. In-depth integration site analysis suggested that the distribution of proviruses in directly latent cells was similar to that in actively transcribing cell population, whereas recently silenced cells tended to harbor proviruses integrated into heterochromatin. Furthermore, we established a library of various single integration clones at which we utilized to demonstrate the efficiency of the block-and-lock strategy by capturing the fast dynamics of silencing that were overlooked in previous models. In summary, we propose HIV-Tocky system to serve as a time-sensitive model that can capture the dynamics of provirus expression, making it a useful tool for HIV latency research.Significance StatementDeterminants of HIV-1 latency establishment are yet to be elucidated. This reservoir comprises a rare fraction of infected cells that can survive host and virus-mediated killing.In vitroreporter models so far offered a feasible means to inspect this population, but with limited capabilities to dissect provirus silencing dynamics. Here, we describe a new HIV reporter model (HIV-Tocky) with dual fluorescence spontaneous shifting to reveal provirus silencing and reactivation dynamics. This unique feature allowed; for the first time, identifying two latent populations: a directly latent, and a recently silenced subset, with the latter having integration features suggestive of stable latency. Our proposed model can help address the heterogeneous nature of HIV reservoirs and offers new possibilities for evaluating eradication strategies.ClassificationBiological Sciences, Microbiology.
Plasmodium, theApicomplexaoutlier when it comes to protein synthesis
Authors: Jaramillo Ponce José R. , Frugier Magali 
Published: August 2023

ABSTRACTPlasmodiumis an obligate intracellular parasite that makes numerous interactions with different hosts during its elaborate life cycle. This is also the case for other parasites that belong to the same phylumApicomplexa. In this study, we identified bioinformatically the components of the multi-synthetase complexes (MSC) of severalApicomplexaparasites. By using AlphaFold2 modeling to compare their assembly, it appears that none of these MSCs resemble those identified inPlasmodium. In particular, the discrepancies between the core components ofPlasmodiumcomplexes, tRip and its homologs indicate that tRip-dependent exogenous tRNA import is not conserved in the otherApicomplexaparasites. Based on this observation, we looked for obvious differences that could explain this singularity inPlasmodium. The content of tRNA genes and amino acid usage in the different genomes highlighted the originality ofPlasmodiatranslation. This is evident with respect to asparagine amino acid, which is highly used in thePlasmodiumproteomes, and the scarcity of tRNAAsnrequired for protein synthesis, regardless of long homorepeats or AT content of the genomes.
Cell division machinery drives cell-specific gene activation during bacterial differentiation
Authors: Chareyre Sylvia , Li Xuesong , Anjuwon-Foster Brandon R. , Clifford Sarah , Brogan Anna , Su Yijun , Shroff Hari , Ramamurthi Kumaran S. 
Published: August 2023

ABSTRACTWhen faced with starvation, the bacteriumBacillus subtilistransforms itself into a dormant cell type called a "spore". Sporulation initiates with an asymmetric division event, which requires the relocation of the core divisome components FtsA and FtsZ, after which the sigma factor σFis exclusively activated in the smaller daughter cell. Compartment specific activation of σFrequires the SpoIIE phosphatase, which displays a biased localization on one side of the asymmetric division septum and associates with the structural protein DivIVA, but the mechanism by which this preferential localization is achieved is unclear. Here, we isolated a variant of DivIVA that indiscriminately activates σFin both daughter cells due to promiscuous localization of SpoIIE, which was corrected by overproduction of FtsA and FtsZ. We propose that a unique feature of the sporulation septum, defined by the cell division machinery, drives the asymmetric localization of DivIVA and SpoIIE to trigger the initiation of the sporulation program.
Spatial transcriptomics map of the embryonic mouse brain: a tool to explore neurogenesis
Authors: Marco Barbara Di , Vázquez-Marín Javier , Monyer Hannah , Centanin Lázaro , Alfonso Julieta 
Published: August 2023

ABSTRACTThe developing brain has a well-organized anatomical structure comprising different types of neural and non-neural cells. Stem cells, progenitors, and newborn neurons tightly interact with their neighbouring cells and tissue microenvironment, and this intricate interplay ultimately shapes the output of neurogenesis. Given the relevance of spatial cues during brain development, we acknowledge the necessity for a spatial transcriptomics map accessible to the neurodevelopmental community. To fulfil this need, we generated spatially-resolved RNAseq data from E13.5 mouse brain sections immunostained for mitotic active neural and vascular cells. Unsupervised clustering defined specific cell type populations of diverse lineages and differentiation states. Differential expression analysis revealed unique transcriptional signatures across specific brain areas, uncovering novel features inherent to particular anatomical domains. Finally, we integrated existing single-cell RNAseq datasets into our Spatial Transcriptomics map, adding tissue context to single-cell RNAseq data. In summary, we provide a valuable tool that enables the exploration and discovery of unforeseen molecular players involved in neurogenesis, particularly in the crosstalk between different cell types.Summary StatementDi Marco, Vázquez-Marín et al. provide an open-access spatial transcriptomics atlas of the embryonic mouse brain. This spatial map enables the exploration and discovery of gene functions within tissue context.
Utilization of 5’-deoxy-nucleosides as Growth Substrates by Extraintestinal PathogenicE. colivia the Dihydroxyacetone Phosphate Shunt
Authors: Huening Katherine A. , Groves Joshua T. , Wildenthal John A. , Tabita F. Robert , North Justin A. 
Published: August 2023

AbstractAll organisms utilizeS-adenosyl-L-methionine (SAM) as a key co-substrate for methylation of biological molecules, synthesis of polyamines, and radical SAM reactions. When these processes occur, 5’-deoxy-nucleosides are formed as byproducts such asS-adenosyl-L-homocysteine (SAH), 5’-methylthioadenosine (MTA), and 5’-deoxyadenosine (5dAdo). One of the most prevalent pathways found in bacteria for the metabolism of MTA and 5dAdo is the DHAP shunt, which converts these compounds into dihydroxyacetone phosphate (DHAP) and 2-methylthioacetaldehyde or acetaldehyde, respectively. Previous work has shown that the DHAP shunt can enable methionine synthesis from MTA or serve as an MTA and 5dAdo detoxification pathway. Here we show that in Extraintestinal PathogenicE. coil(ExPEC), the DHAP shunt serves none of these roles in any significant capacity, but rather physiologically functions as an assimilation pathway for use of MTA and 5dAdo as growth substrates. This is further supported by the observation that when MTA is the substrate for the ExPEC DHAP shunt, the sulfur components is not significantly recycled back to methionine, but rather accumulates as 2-methylthioethanol, which is slowly oxidized non-enzymatically under aerobic conditions. While the pathway is active both aerobically and anaerobically, it only supports aerobic ExPEC growth, suggesting that it primarily functions in oxygenic extraintestinal environments like blood and urine versus the predominantly anoxic gut. This reveals a heretofore overlooked role of the DHAP shunt in carbon assimilation and energy metabolism from ubiquitous SAM utilization byproducts and suggests a similar role may occur in other pathogenic and non-pathogenic bacteria with the DHAP shunt.ImportanceAcquisition and utilization of organic compounds that can serve as growth substrates is essential for pathogenicE. colito survive and multiply. Ubiquitous enzymatic reactions involvingS-adenosyl-L-methionine as a co-substrate result in the formation of the 5’-deoxy-nucleoside byproducts, 5’-methylthioadenosine and 5’-deoxyadenosine. AllE. colipossess a conserved nucleosidase that cleaves these 5’-deoxy-nucleosides into 5-deoxy-pentose sugars for adenine salvage. The DHAP shunt pathway, which is found in ExPEC strains but neither in intestinal pathogenic nor commensalE. coli,enables utilization of 5’-deoxy-nucleosides and 5-deoxy-pentose sugars as growth substrates by ExPEC strains. This provides insight into the diversity of sugar compounds accessible by ExPEC strains in recalcitrant and nutrient-poor environments such as the urinary tract during infection. Furthermore, given the dihydroxyacetone phosphate shunt pathway appears to only support aerobicE. coligrowth, this suggests an explanation as to why intestinal strains that primarily exist in anoxic environments lack this pathway.
Subinhibitory antibiotic concentrations promote the excision of a genomic island carried by the globally spread carbapenem-resistantKlebsiella pneumoniaeST258
Authors: Piña-Iturbe Alejandro , Hoppe-Elsholz Guillermo , Suazo Isidora D. , Kalergis Alexis M. , Bueno Susan M. 
Published: August 2023

AbstractThe ICEKp258.2 genomic island (GI) has been proposed as an important factor for the emergence and success of the globally spread carbapenem-resistantKlebsiella pneumoniaesequence type (ST) 258. However, a characterization of this horizontally acquired element is lacking. Using bioinformatic and experimental approaches, we found that ICEKp258.2 is not confined to ST258 and ST512 but also carried by ST3795 strains and emergent invasive multidrug-resistant pathogens from ST1519. We also identified several ICEKp258.2-like GIs spread among differentK. pneumoniaeSTs, otherKlebsiellaspecies, and even other pathogen genera, uncovering horizontal gene transfer events between different STs and bacterial genera. Also, in agreement with the origin of ST258 from ST11, the comparative and phylogenetic analyses of the ICEKp258.2-like GIs suggested that ICEKp258.2 was acquired from an ST11 strain. Importantly, we found that subinhibitory concentrations of antibiotics used in treatingK. pneumoniaeinfections can induce the excision of this GI and modulate its gene expression. Our findings provide the basis for the study of ICEKp258.2 and its role in the success ofK. pneumoniaeST258. They also highlight the potential role of antibiotics in the spread of ICEKp258.2-like GIs among bacterial pathogens.
A Genomic View of Environmental and Life History Controls on Microbial Nitrogen Acquisition Strategies
Authors: Reji Linta , Darnajoux Romain , Zhang Xinning 
Published: August 2023

ABSTRACTMicroorganisms have evolved diverse strategies to acquire the vital element nitrogen (N) from the environment. Ecological and physiological controls on the distribution of these strategies among microbes remain unclear. Here we examine the distribution of 10 major N-acquisition strategies in taxonomically and metabolically diverse microbial genomes, including those from the Genomic Catalog of Earth’s Microbiomes dataset. We utilize a marker gene-based approach to assess relationships between N acquisition strategy prevalence and microbial life history strategies. Our results underscore energetic costs of assimilation as a broad control on strategy distribution. The most prevalent strategies are the uptake of ammonium and simple amino acids, while biological nitrogen fixation is the least common. Deviations from this energy-based framework include the higher-than-expected prevalence of the assimilatory pathway for chitin, a large organic polymer. Notably, oxygen-respiring chemoorganotrophic and phototrophic microbes possess ∼2-fold higher numbers of total strategies compared to anaerobic microbes. Environmental controls on N acquisition are evidenced by the enrichment of inorganic N assimilation strategies among free-living taxa compared to host-associated taxa. Physiological constrains such as pathway incompatibility add further complexity to N-acquisition strategy distributions. Finally, we discuss the necessity for microbially-relevant environmental metadata for improving mechanistic and prediction-oriented analyses of genomic data.
Meta-analysis of the human upper respiratory tract microbiome reveals robust taxonomic associations with health and disease
Authors: Quinn-Bohmann Nick , Freixas-Coutin Jose A. , Seo Jin , Simmons Ruth , Diener Christian , Gibbons Sean M. 
Published: August 2023

AbstractThe human upper respiratory tract (URT) microbiome, like the gut microbiome, varies across individuals and between health and disease states. However, study-to-study heterogeneity in reported case-control results has made the identification of consistent and generalizable URT-disease associations difficult. In order to address this issue, we assembled 26 independent 16S amplicon sequencing data sets from case-control URT studies, with approximately 2-3 studies per respiratory condition and ten distinct conditions covering common chronic and acute respiratory diseases. We leveraged the healthy control data across studies to investigate URT associations with age, sex and geographic location, in order to isolate these associations from health and disease states. We found several robust genus-level associations, across multiple independent studies, with either health or disease status. We identified disease associations specific to a particular respiratory condition and associations general to all conditions. Ultimately, we reveal robust associations between the URT microbiome, health, and disease, which hold across multiple studies and can help guide follow-up work on potential URT microbiome diagnostics and therapeutics.
Mycobacterial formation of intracellular lipid inclusions is a dynamic process associated with rapid replication
Authors: Fines DM , Schichnes D , Knight M , Anaya-Sanchez A , Thuong NTT , Cox J , Stanley SA 
Published: August 2023

AbstractIntracellular lipid inclusions (ILI) are triacylglyceride rich organelles produced by mycobacteria thought to serve as energy reservoirs. It is believed that ILI are formed as a result of adosRmediated transition from replicative growth to non-replicating persistence (NRP). ILI richMycobacterium tuberculosis(Mtb) bacilli have been reported during infection and in sputum, establishing their importance in Mtb pathogenesis. Studies conducted in mycobacteria such asMycobacterium smegmatis, Mycobacterium abscessus,or lab Mtb strains have demonstrated ILI formation in the presence of hypoxic, nitric oxide, nutrient limitation, or low nitrogen stress, conditions believed to emulate the host environment within which Mtb resides. Here, we show thatM. marinumand clinical Mtb isolates make ILI during active replication in axenic culture independent of environmental stressors. By tracking ILI formation dynamics we demonstrate that ILI are quickly formed in the presence of fresh media or exogenous fatty acids but are rapidly depleted while bacteria are still actively replicating. We also show that the cell envelope is an alternate site for neutral lipid accumulation observed during stationary phase. In addition, we screen a panel of 60 clinical isolates and observe variation in ILI production during early log phase growth between and among Mtb lineages. Finally, we show thatdosRexpression level does not strictly correlate with ILI accumulation in fresh clinical isolates. Taken together, our data provide evidence of an active ILI formation pathway in replicating mycobacteria cultured in the absence of stressors, suggesting a decoupling of ILI formation from NRP.
Metabolic changes to host cells withToxoplasma gondiiinfection
Authors: Gallego-López Gina M. , Guzman Emmanuel Contreras , Knoll Laura J. , Skala Melissa 
Published: August 2023

ABSTRACTToxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular parasite that infects warm-blooded vertebrates across the world. In humans, seropositivity rates ofT. gondiirange from 10% to 90%. Despite its prevalence, few studies address howT. gondiiinfection changes the metabolism of host cells. Here, we investigate howT. gondiimanipulates the host cell metabolic environment by monitoring metabolic response over time using non-invasive autofluorescence lifetime imaging of single cells, seahorse metabolic flux analysis, reactive oxygen species (ROS) production, and metabolomics. Autofluorescence lifetime imaging indicates that infected host cells become more oxidized and have an increased proportion of bound NAD(P)H with infection. These findings are consistent with changes in mitochondrial and glycolytic function, decrease of intracellular glucose, fluctuations in lactate and ROS production in infected cells over time. We also examined changes associated with the pre-invasion “kiss and spit” process using autofluorescence lifetime imaging, which similarly showed a more oxidized host cell with an increased proportion of bound NAD(P)H over 48 hours. Glucose metabolic flux analysis indicated that these changes are driven by NADH and NADP+ inT. gondiiinfection. In sum, metabolic changes in host cells withT. gondiiinfection were similar during full infection, and kiss and spit. Autofluorescence lifetime imaging can non-invasively monitor metabolic changes in host cells over a microbial infection time-course.
A systematic analysis of the qualitative and quantitative evidence on the purpose of animal-assisted therapy in improving patients wellbeing
Authors: Himanshu K. , Gunjan K. , Mukherjee Riya , Pandey Ramendra Pati , Chang Chung-Ming 
Published: August 2023

AbstractBackgroundAnimal-assisted therapy, also known as pet therapy, is a therapeutic intervention that involves animals to enhance the well-being of individuals across various populations and settings. This systematic study aims to assess the outcomes of animal-assisted therapy interventions and explore the associated policies.MethodsA total of 16 papers published between 2015 and 2023 were selected for analysis. These papers were chosen based on their relevance to the research topic of animal-assisted therapy and their availability in scholarly databases. Thematic synthesis and meta-analysis were employed to synthesize the qualitative and quantitative data extracted from the selected papers.ResultsThe analysis included sixteen studies that met the inclusion criteria and were deemed to be of moderate or higher quality. Among these studies, four demonstrated positive results for therapeutic mediation and one for supportive mediation in psychiatric disorders. Additionally, all studies showed positive outcomes for depression and neurological disorders. Regarding stress and anxiety, three studies indicated supportive mediation while two studies showed activating mediation.ConclusionThe overall assessment of animal-assisted therapy shows promise as an effective intervention in promoting well-being among diverse populations. Further research and the establishment of standardized outcome assessment measures and comprehensive policies are essential for advancing the field and maximizing the benefits of animal-assisted therapy.
Inter-species gene flow drives ongoing evolution ofStreptococcus pyogenesandStreptococcus dysgalactiaesubsp.equisimilis
Authors: Xie Ouli , Morris Jacqueline M. , Hayes Andrew J. , Towers Rebecca J. , Jespersen Magnus G. , Lees John A. , Ben Zakour Nouri L. , Berking Olga , Baines Sarah L. , Carter Glen P. , Tonkin-Hill Gerry , Schrieber Layla , McIntyre Liam , Lacey Jake A. , James Taylah B. , Sriprakash Kadaba S. , Beatson Scott A. , Hasegawa Tadao , Giffard Phil , Steer Andrew C. , Batzloff Michael R. , Beall Bernie W. , Pinho Marcos D. , Ramirez Mario , Bessen Debra E. , Dougan Gordon , Bentley Stephen D. , Walker Mark J. , Currie Bart J. , Tong Steven Y. C. , McMillan David J. , Davies Mark R. 
Published: August 2023

AbstractStreptococcus dysgalactiaesubsp.equisimilis(SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species,Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE andS. pyogenes.More than 75% of core genes are shared between the two species with one third demonstrating evidence of cross-species recombination. Twenty-five percent of mobile genetic element (MGE) clusters and 16 of 55 SDSE MGE insertion regions were found across species. Assessing potential cross-protection from leadingS. pyogenesvaccine candidates on SDSE, 12/34 preclinical vaccine antigen genes were shown to be present in >99% of isolates of both species. Relevant to possible vaccine evasion, six vaccine candidate genes demonstrated evidence of inter-species recombination. These findings demonstrate previously unappreciated levels of genomic overlap between these closely related pathogens with implications for streptococcal pathobiology, disease surveillance and prevention.