bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Bacille Calmette-Guérin Vaccination on the Composition of the Intestinal Microbiome in Neonates From the MIS BAIR Trial
Authors: Zimmermann Petra , Pittet Laure F. , Jakob William , Messina Nicole L. , Falquet Laurent , Curtis Nigel 
Published: December 2023

Introduction:
The early-life intestinal microbiome plays an important role in the development and regulation of the immune system. It is unknown whether the administration of vaccines influences the composition of the intestinal microbiome.

Objective:
To investigate whether Bacille Calmette-Guérin (BCG) vaccine given in the first few days of life influences the abundance of bacterial taxa and metabolic pathways in the intestinal microbiome at 1 week of age.

Methods:
Healthy, term-born neonates were randomized at birth to receive BCG or no vaccine within the first few days of life. Stool samples were collected at 1 week of age from 335 neonates and analyzed using shotgun metagenomic sequencing and functional analyses.

Results:
The composition of the intestinal microbiome was different between neonates born by cesarean section (CS) and those born vaginally. Differences in the composition between BCG-vaccinated and BCG-naïve neonates were only minimal. CS-born BCG-vaccinated neonates had a higher abundance of Staphylococcus lugdunensis compared with CS-born BCG-naïve neonates. The latter had a higher abundance of Streptococcus infantis and Trabulsiella guamensis. Vaginally-born BCG-vaccinated neonates had a higher abundance of Clostridiaceae and Streptococcus parasanguinis compared with vaginally-born BCG-naïve neonates, and a lower abundance of Veillonella atypica and Butyricimonas faecalis. Metabolic pathways that were differently abundant between BCG-vaccinated and BCG-naïve neonates were mainly those involved in sugar degradation and nucleotide/nucleoside biosynthesis.

Conclusion:
BCG given in the first few days of life has little effect on the composition of the intestinal microbiome at 1 week of age but does influence the abundance of certain metabolic pathways.
Tracking SARS-CoV-2 variants of concern in wastewater: an assessment of nine computational tools using simulated genomic data
Authors: Sutcliffe Steven G. , Kraemer Susanne A. , Ellmen Isaac , Knapp Jennifer J. , Overton Alyssa K. , Nash Delaney , Nissimov Jozef I. , Charles Trevor C. , Dreifuss David , Topolsky Ivan , Baykal Pelin I. , Fuhrmann Lara , Jablonski Kim P. , Beerenwinkel Niko , Levy Joshua I. , Olabode Abayomi S. , Becker Devan G. , Gugan Gopi , Britnell Erin , Poon Art F.Y. , Valieris Renan , Drummond Rodrigo D. , Defelicibus Alexandre , Dias-Neto Emmanuel , Rosales Rafael A. , da Silva Israel Tojal , Orfanou Aspasia , Psomopoulos Fotis , Pechlivanis Nikolaos , Pipes Lenore , Chen Zihao , Baaijens Jasmijn A. , Baym Michael , Shapiro B. Jesse 
Published: December 2023

AbstractWastewater-based surveillance (WBS) is an important epidemiological and public health tool for tracking pathogens across the scale of a building, neighbourhood, city, or region. WBS gained widespread adoption globally during the SARS-CoV-2 pandemic for estimating community infection levels by qPCR. Sequencing pathogen genes or genomes from wastewater adds information about pathogen genetic diversity which can be used to identify viral lineages (including variants of concern) that are circulating in a local population. Capturing the genetic diversity by WBS sequencing is not trivial, as wastewater samples often contain a diverse mixture of viral lineages with real mutations and sequencing errors, which must be deconvoluted computationally from short sequencing reads. In this study we assess nine different computational tools that have recently been developed to address this challenge. We simulated 100 wastewater sequence samples consisting of SARS-CoV-2 BA.1, BA.2, and Delta lineages, in various mixtures, as well as a Delta-Omicron recombinant and a synthetic “novel” lineage. Most tools performed well in identifying the true lineages present and estimating their relative abundances, and were generally robust to variation in sequencing depth and read length. While many tools identified lineages present down to 1% frequency, results were more reliable above a 5% threshold. The presence of an unknown synthetic lineage, which represents an unclassified SARS-CoV-2 lineage, increases the error in relative abundance estimates of other lineages, but the magnitude of this effect was small for most tools. The tools also varied in how they labelled novel synthetic lineages and recombinants. While our simulated dataset represents just one of many possible use cases for these methods, we hope it helps users understand potential sources of noise or bias in wastewater sequencing data and to appreciate the commonalities and differences across methods.
Translationally active soil microorganisms during substrate-induced respiration
Authors: Camillone Nina Rose , Bruns Mary Ann Victoria , Román Raúl , Wasner Daniel , Couradeau Estelle 
Published: December 2023

ABSTRACTSoil microorganisms carry out many processes that are fundamental to soil functions. Among the millions of microbial cells present in a gram of soil, however, less than 2% are commonly estimated to be active at any point in time. Because the respiratory response of a bulk soil to carbon substrate addition would be expected to reflect the number of active cells, we hypothesized a positive correlation between active cells and soil respiration rates during substrate-induced respiration (SIR) assays. To test this, we monitored respiration and active cell counts during 24-h incubations of agricultural soil subsamples after treating with two carbon substrates or a water-only control. We enumerated active cells with the Bioorthogonal Non-canonical Amino Acid Tagging (BONCAT) method. BONCAT provides a labeled amino acid for active cells to incorporate into newly synthesized proteins, which can then be tagged with a fluorescent dye to enable enumeration by flow cytometry. Both respiration rates and active cell counts increased over time and were positively correlated with each other after 6 h of incubation. After 24 h, increases in active cells were proportionally greater than increases in respiration. Additionally, carbon-amended soils had higher respiration rates than water-only soils with similar active cell counts, suggesting differences in carbon use efficiency. Our study documents for the first time the respiratory response fromin-situmicrobial activation induced by substrate amendment of soil within 6 h, a short enough timescale to exclude most cell replication. This study also demonstrates that the correlation between active cell numbers and respiration is substrate-dependent.IMPORTANCEWhile many critical ecosystem services provided by soil are known to rely on microbial activity, the soil microbial community largely remains a black box. While respiration is a common indicator of bulk soil microbial activity, this study demonstrates that the relationship between respiration and the number of active cells differs based on available carbon substrates. Advancing knowledge in this area will both enable better interpretation of biological soil tests by land managers and inform researchers modeling contributions of soil microbial respiration to global carbon dynamics.
PARP inhibitors enhance reovirus-mediated cell killing through the death-inducing signaling complex (DISC) with an associated NF-κB-regulated immune response
Authors: Kyula-Currie Joan , Roulstone Victoria , Wright James , Butera Francesca , Legrand Arnaud , Elliott Richard , McLaughlin Martin , Bozhanova Galabina , Krastev Dragomir , Pettitt Stephen , Tenev Tencho , Dillon Magnus , Foo Shane , Patin Emmanuel , Jennings Victoria , Chan Charleen , Appleton Elizabeth , Pedersen Malin , Rullan Antonio , Choudhary Jyoti , Bakal Chris , Meier Pascal , Lord Christopher J , Melcher Alan , Harrington Kevin 
Published: December 2023

AbstractOncolytic Reovirus type 3 Dearing (RT3D), is a naturally occurring double-stranded (ds) RNA virus that is under development as an oncolytic immunotherapy We used an unbiased high-throughput cytotoxicity screen of different targeted therapeutic agents with the aim of identifying potential drug-viral sensitizers to enhance RT3D tumour killing. Talazoparib, a clinical poly(ADP)-ribose polymerase 1 (PARP-1) inhibitor, was identified as a top hit and found to cause profound sensitisation to RT3D. This effect was not seen with other classes of oncolytic virus and was not mediated by enhanced viral replication or PARP inhibitor-related effects on the DNA damage response.RT3D interacts with retinoic acid-induced gene-1 (RIG-I) and activates PARP-1, with consequent PARylation of components of the extrinsic apoptosis pathway. Pharmacological and genetic inhibition of PARP-1 abrogates this PARylation and increases levels of extrinsic apoptosis, NF-kB signalling and pro-inflammatory cell death. Direct interaction between PARP-1 and RIG-I following RT3D/talazoparib treatment is a key factor in activating downstream signaling pathways that lead to IFN-β and TNF-α/TRAIL production which, in turn, amplify the therapeutic effect through positive feedback. Critically, it was possible to phenocopy the effect of RT3D through the use of non-viral ds-RNA therapy and RIG-I agonism. Inin vivostudies, we demonstrated profound combinatorial efficacy of RT3D and talazoparib in human A375 melanoma in immunodeficient mice. More impressively, in immunocompetent mouse models of 4434 murine melanoma, we achieved 100% tumour control and protection from subsequent tumour rechallenge with the combination regimen. Correlative immunophenotyping confirmed significant innate and adaptive immune activation with the combination of RT3D and PARP inhibition. Taken together, these data provide a clear line of sight to clinical translation of combined regimens of PARP inhibition or ds-RNA agonism, with either viral or non-viral agents, in tumour types beyond the relatively narrow confines of current licensed indications for PARP inhibition.
Lateralization of feeding behaviour in white-fronted lemur (Eulemur albifrons) and ring-tailed lemur (Lemur catta) in captivity
Authors: Calvo Heredia Laura , de Miguel Águeda Francisco Javier 
Published: December 2023

AbstractFunctional cerebral asymmetry is reflected in the lateralization of some behavioural patterns in many vertebrate species. In primates, behavioural lateralization has been related to both life style and age and sex, and it affects behaviours such as feeding and other tasks that require precision movements.We have studied feeding lateralization concerning the use of right and left hand to take the food in two species of lemurs, the mainly arboreal white-fronted lemur and the more terrestrial ring-tailed lemur, taking also account the age and the sex of the individuals. Half of the white-fronted lemurs (7 of 14) showed lateralization in feeding, while only a few ring-tailed lemurs (3 of 19) showed it. In the first species, a light bias seems to emerge (5 individuals used mostly the right hand for taking the food, while only 2 used mainly the left hand), while in the second species no bias could really be appreciated. No clear effect of age and sex on the presence and direction of lateralization could be evidenced.The results somehow contrast with what the postural theory of lateralization postulates about the preferential use of the right hand in terrestrial species.
IRAK4 autophosphorylation controls inflammatory signaling by activating IRAK oligomerization
Authors: Srikanth Niranjan , Deliz-Aguirre Rafael , Gola Deepika Kumari , Bilay Margaux , Ziska Elke , Taylor Marcus J. 
Published: December 2023

AbstractThe controlled oligomerization of signaling proteins is an essential feature of many inflammatory signaling pathways. An example is IL-1 receptor signaling, which relies on the oligomerization of the Death Domain (DD)-containing proteins MyD88 and IRAK family kinases. This process leads to the assembly of the Myddosome signaling complex, and disrupting assembly holds potential for anti-inflammatory treatments. However, IRAKs’ signaling activity is also regulated by auto-/trans-phosphorylation, and it is unclear if these processes operate at or downstream of Myddosome assembly. Here, we find that the initial stage of Myddosome assembly is solely controlled by MyD88:IRAK4 DD interactions. In later stages, IRAK4 auto-phosphorylation serves as a switch, regulating IRAK1/2/3 incorporation and DD oligomerization. Small molecule inhibitors of IRAK4 kinase activity block this later stage of assembly, explaining how they dampen inflammatory signaling. Our data reveals IRAK4 auto-phosphorylation as an energy-dependent switch activating the heterotypic assembly of IRAKs’ DDs and downstream inflammatory IL-1 signaling. This highlights how a signaling cascade integrates phosphorylation and protein oligomerization steps.
Characterization and hierarchy of the spermatogonial stem cell compartment in human spermatogenesis by spectral cytometry using a 16-colors panel
Authors: Lapoujade C. , Blanco M. , Givelet M. , Gille A.S , Allemand I. , Lenez L. , Thiounn N. , Roux S. , Wolf J.P. , Patrat C. , Riou L. , Barraud-Lange V. , Fouchet P. 
Published: December 2023

ABSTRACTAbout one in six couples experience fertility problems, and male infertility accounts for about half of these cases. Spermatogenesis originates from a small pool of spermatogonial stem cells (SSCs), which are of interest for the treatment of infertility but remain poorly characterized in humans. Using multiparametric spectral flow cytometric analysis with a 16-colours (16-C) panel of cell markers, we identify novel markers of SSCs and provide insights into unravelling and resolving the heterogeneity of the human spermatogonial cells. This 16-C panel of markers allowed the identification of a primitive SSCs state with the β-2M−CD51/61−ITGA6+SSEA4+TSPAN33+THY1+CD9+EPCAMmedCD155+CD148+CD47highCD7highphenotype, with a profile close to the most primitive SSCs states 0 and SSC1-B previously defined by sc-RNAseq approach. The hierarchy of events in the spermatogonial stem cell and progenitor compartment of human spermatogenesis has been delineated. This highlights the importance of a multi-parametric and spectral cytometry approach. The in-depth characterization of testicular cells should help to overcome the lack of stem cell knowledge, that hinders the understanding of the regenerative potential of SSCs, and is a critical parameter for the successful development of new SSCs-based cell therapies.
A new guest to the blood feast: a novel symbiotic lineage associated with a haematophagous leech from the genusHaementeria
Authors: Sosa-Jiménez Víctor Manuel , Kvist Sebastian , Manzano-Marín Alejandro , Oceguera-Figueroa Alejandro 
Published: December 2023

ABSTRACTSimilarly to other strict blood-feeders, leeches from theHaementeriagenus (Hirudinida: Glossiphoniidae) have established a symbiotic association with bacteria harboured intracellularly in oesophageal bacteriomes. Previous genome sequence analyses of these endosymbionts revealed co-divergence with their hosts, a strong genome reduction, and a simplified metabolism largely dedicated to the production of B vitamins, which are nutrients lacking from a blood diet.CandidatusProvidencia siddallii has been identified as the obligate nutritional endosymbiont of a monophyletic clade of Mexican and South AmericanHaementeriaspp. Nonetheless, given a lack of molecular investigations, the identity of the symbiont housed in the bacteriomes of its sister clade of Central and South American congeners remained unknown. In this work, we report on a novel bacterial endosymbiont found in a representative from thisHaementeriaclade. We found that this symbiont lineage has evolved from within thePluralibactergenus, known mainly from clinical, but also environmental strains. Similarly toCa. Providencia siddallii, theHaementeria-associatedPluralibactersymbiont displays clear signs of genome reduction, accompanied by an A+T-biased sequence composition. Genomic analysis of its metabolic potential revealed a retention of pathways related to B vitamin biosynthesis, supporting its role as a nutritional endosymbiont. Finally, comparative genomics of bothHaementeriasymbiont lineages suggests that the ancientProvidenciasymbiont was likely replaced by the novelPluralibacterone, thus constituting the first reported case of nutritional symbiont replacement in a leech without morphological changes in the bacteriome.
Multi-omics investigations uncover unique pathogenic markers in clinicalKlebsiella pneumoniaethat could be leveraged as novel antimicrobial targets
Authors: Swiatek Lena-Sophie , Surmann Kristin , Eger Elias , Müller Justus Ursus , Salazar Manuela Gesell , Guenther Sebastian , Werner Guido , Hübner Nils-Olaf , Bohnert Jürgen A. , Becker Karsten , Heiden Stefan E. , Völker Uwe , Schwabe Michael , Schaufler Katharina 
Published: December 2023

AbstractBackgroundKlebsiella pneumoniae(KP), often multidrug-resistant (MDR), is a significant public health concern and frequently associated with various diseases including urinary-tract infection. In addition, in recent years, an increasing number of studies reports on the emergence of convergent KP that combine MDR with hypervirulence leading to severely limited treatment options and thus calling for alternative approaches.MethodsIn this study, we compared high-risk clonal KP lineages with less pathogenicKlebsiella variicola(KV) andKlebsiella quasipneumoniae(KQ) strains on multiple-omics levels and performed integrative data analysis to identify unique markers that could be subsequently leveraged as novel targets in alternative treatment strategies.ResultsOur initial genomic analysis revealed 107 genes as part of the patho-core genome in eight clinical KP that were associated with different metabolic pathways. Subsequent transcriptome and proteome analyses in infection-mimicking media demonstrated similar regulatory patterns among KP vs. otherKlebsiellastrains, again with metabolic responses playing a pivotal role. In total, we identified 193 KP-specific, differentially expressed genes on transcriptomic and/or proteomic levels. When then comparing these regulated genes to over 6,000 publicly availableKlebsiellagenomes, we identified unique markers either in KP genomes or adaptively regulated on transcriptomics and/or proteomics levels. An example for the latter was a gene cluster for the cellobiose phosphotransferase system that has been previously described in the context of bacterial virulence and biofilm formation.ConclusionIn conclusion, our study not only highlights that KP strains demonstrate metabolic flexibility in response to particular environmental conditions, which is potentially important for their success as opportunistic pathogens, but identified unique KP-markers. Subsequent studies are needed to explore whether these markers might be prospectively used as novel anti-virulence targets, providing alternatives to traditional antibiotics.
Histone H2A variant H2A.B is enriched in transcriptionally active HSV-1 lytic chromatin
Authors: Flores Esteban , Saddoris Sarah M. , Owens Arryn K , Gibeault Rebecca , Depledge Daniel P. , Schang Luis M. 
Published: December 2023

AbstractHerpes simplex virus 1 (HSV-1) transcription is restricted in latently infected neurons and the genomes are in mostly silenced chromatin, whereas all viral genes are transcribed in lytically infected cells, in which the genomes are dynamically chromatinized. Epigenetic regulation modulates HSV-1 transcription during lytic, latent, and reactivating infections, but the precise mechanisms are not fully defined. Nucleosomes are dynamic; they slide, breathe, assemble and disassemble. We and others have proposed that the most dynamic HSV-1 chromatin is transcriptionally competent whereas the least dynamic is silenced. However, the mechanisms yielding the unusually dynamic viral chromatin remain unknown. Histone variants affect nucleosome dynamics. The dynamics of H2A, H2A.X and macroH2A were enhanced in infected cells, whereas those of H2A.B uniquely decreased. We constructed stably transduced cells expressing tagged histone H2A, H2A.B, macroH2A, or H2B, which assembles the H2A/H2B nucleosome dimers with all H2A variants. All H2A variants, ectopic, and endogenous H2B, were assembled into HSV-1 chromatin evenly throughout the genome, but canonical H2A was relatively depleted from the viral chromatin whereas H2A.B was enriched in the most dynamic viral chromatin. When viral transcription was restricted, H2A.B became as depleted from the viral chromatin through the entire genome as H2A. We propose that lytic HSV-1 nucleosomes are enriched in the dynamic variant H2A.B/H2B dimers to promote HSV-1 chromatin dynamics and transcriptional competency, and conclude that the dynamics of HSV-1 chromatin are determined in part by the H2A variants.ImportanceHSV-1 transcription is epigenetically regulated during latent and lytic infections, and epigenetic inhibitors have been proposed as potential antiviral drugs to modulate latency and reactivation. However, the detailed mechanisms of regulation of HSV-1 transcription by epigenetics have not been fully characterized and may differ from those regulating cellular transcription. In particular, the lytic HSV-1 chromatin is unusually dynamic, whereas the latent silenced one is not, but the mechanisms resulting in the unique dynamics of the lytic chromatin remain unknown. Here we identify the enrichment on the highly dynamic histone 2A variant H2A in the most dynamic viral chromatin, which provides a mechanistic understanding for its unique dynamics. Future work to identify the mechanisms of enrichment in H2A.B on the viral chromatin may identify novel druggable epigenetic regulators that modulate HSV-1 latency and reactivation.
The ICF2 gene Zbtb24 specifically regulates the differentiation of B1 cellsviapromoting heme synthesis
Authors: Wang Jun , Gao He , Zhao Sai , Dai Xiao-Qiu , Qin Xiao-Yuan , Zheng Wei-Long , Zhu Can , Wang Hong-Min , Zhu Xue-Mei , Gong Fang-Yuan , Gao Xiao-Ming , Zhao Ying 
Published: December 2023

ABSTRACTLoss-of-function mutations ofZBTB24cause the Immunodeficiency, Centromeric Instability and Facial Anomalies syndrome 2 (ICF2). ICF2 is a rare autosomal recessive disorder with immunological defects in serum antibodies and circulating memory B cells, indicating an essential role of ZBTB24 in the terminal differentiation of B cells. Here we generated B-cell specific Zbtb24-deficient mice and systemically investigated its role in B cell development and function bothin vivoandin vitro. Zbtb24 is dispensable for B cell development & maintenance in naive mice. Surprisingly, B-cell specific deletion of Zbtb24 does not evidently compromise germinal center reactions and the resulting primary & secondary antibody responses induced by T-cell dependent antigens, but significantly inhibits T-cell independent antigen-elicited antibody productionsin vivo. At the cellular level, Zbtb24-deficiency specifically impedes the plasma cell differentiation of B1 cells without impairing their survival, activation and proliferationin vitro. Mechanistically, Zbtb24-ablation attenuates heme biosynthesis partially through mTORC1 in B1 cells, and addition of exogenous hemin abrogates the differentiation defects of Zbtb24-null B1 cells. Our study suggests that the defected B1 functions may contribute to recurrent infections in ICF2 patients, and discloses a B1-specific role of Zbtb24 in regulating plasma cell differentiation and antibody production, which is relevant for barrier defenses against invading pathogens.