bluuebunny/crossref_metadata_2025_split huggingface dataset:
TheEx VivoInfection of the Peripheral Bovine Mononuclear Cells (PBMCs) and the Bovine Spleen Cells with the Bovine Coronavirus (BCoV) Induced a Differential Expression of the Host Cytokine Genes Profiles and Modulates the Virus Replication
Authors: Shah Abid Ullah , Hemida Maged H 
Published: July 2024

AbstractThe adaptive immune response during BCoV infection of peripheral blood mononuclear cells (PBMCs), the bovine spleen cells, and their isolated T lymphocytes was not studied well. Our study confirmed successful BCoV infection in PBMCs and spleen T cells. This was evidenced by measuring genome copy numbers using real-time PCR, expression levels of BCoV spike and nucleocapsid proteins via western blot and immunofluorescence assays, and virus infectivity titration by plaque assay. In infected PBMCs, CD4 T-cell levels were 1.45-fold higher, and CD8 T-cell levels were 1.6-fold lower compared to sham-infected cells. Conversely, infected splenocytes showed a 0.88-fold decrease in CD4 T-cells and a 1.88-fold increase in CD8 T-cells. The cytokine gene expression analysis revealed that BCoV infection activated type 1 interferon and upregulated IL-6 expression in PBMCs and splenocytes. These findings demonstrate that BCoV successfully infects immune cells from PBMCs and spleen, inducing differential host cytokine gene expression favors virus replication.
tRNA modification profiling reveals epitranscriptome regulatory networks inPseudomonas aeruginosa
Authors: Sun Jingjing , Wu Junzhou , Yuan Yifeng , Fan Leon , Chua Wei Lin Patrina , Ling Yan Han Sharon , Balamkundu Seetharamsing , Dwijapriya  , Suen Suen Hazel Chay , de Crécy-Lagard Valérie , Dziergowska Agnieszka , Dedon Peter C. 
Published: July 2024

AbstractTransfer RNA (tRNA) modifications have emerged as critical posttranscriptional regulators of gene expression affecting diverse biological and disease processes. While there is extensive knowledge about the enzymes installing the dozens of post-transcriptional tRNA modifications – the tRNA epitranscriptome – very little is known about how metabolic, signaling, and other networks integrate to regulate tRNA modification levels. Here we took a comprehensive first step at understanding epitranscriptome regulatory networks by developing a high-throughput tRNA isolation and mass spectrometry-based modification profiling platform and applying it to aPseudomonas aeruginosatransposon insertion mutant library comprising 5,746 strains. Analysis of >200,000 tRNA modification data points validated the annotations of predicted tRNA modification genes, uncovered novel tRNA-modifying enzymes, and revealed tRNA modification regulatory networks inP. aeruginosa. Platform adaptation for RNA-seq library preparation would complement epitranscriptome studies, while application to human cell and mouse tissue demonstrates its utility for biomarker and drug discovery and development.
Antagonistic effects of actin-specific toxins onSalmonellaTyphimurium invasion into mammalian cells
Authors: Heisler David B. , Kudryashova Elena , Hitt Regan , Williams Blake , Dziejman Michelle , Gunn John , Kudryashov Dmitri S. 
Published: July 2024

AbstractCompetition between bacterial species is a major factor shaping microbial communities. In this work, we explored the hypothesis that competition between bacterial pathogens can be mediated through antagonistic effects of bacterial effector proteins on host systems, particularly the actin cytoskeleton. UsingSalmonellaTyphimurium invasion into cells as a model, we demonstrate that invasion is inhibited if the host actin cytoskeleton is disturbed by any of the four tested actin-specific toxins:Vibrio choleraeMARTX actin crosslinking and Rho GTPase inactivation domains (ACD and RID, respectively), TccC3 fromPhotorhabdus luminescens, andSalmonella’sown SpvB. We noticed that ACD, being an effective inhibitor of tandem G-actin binding assembly factors, is likely to inhibit the activity of anotherVibrioeffector, VopF. In reconstituted actin polymerization assays confirmed by live-cell microscopy, we confirmed that ACD potently halted the actin nucleation and pointed-end elongation activities of VopF, revealing competition between these twoV. choleraeeffectors. Together, the results suggest bacterial effectors from different species that target the same host machinery or proteins may represent an effective but largely overlooked mechanism of indirect bacterial competition in host-associated microbial communities. Whether the proposed inhibition mechanism involves the actin cytoskeleton or other host cell compartments, such inhibition deserves investigation and may contribute to a documented scarcity of human enteric co-infections by different pathogenic bacteria.
Prenylation controls proliferation in human pluripotent stem cell-derived cardiomyocytes
Authors: Batho Christopher A.P. , Reid Janice D. , Robinson Harley R. , Szappanos Henrietta Cserne , Devilée Lynn A.C. , Hoyte Sharon M. , Johnston Rebecca L. , Ziegman Rebekah , Hassan Sarah , Soday Lior , Fitzsimmons Rebecca L. , Foster Simon R. , Ng Dominic C. H. , Tate Edward , Porrello Enzo R. , Parker Benjamin L. , Mills Richard J. , Hudson James E. 
Published: July 2024

AbstractInduction of cardiomyocyte proliferation to replace damaged heart tissue is a promising therapeutic approach. A recent drug screen revealed that cardiomyocytes require the mevalonate pathway for proliferation, although the specific mechanisms are unknown. In this study, we use human pluripotent stem cell-derived cardiomyocytes and cardiac organoids to further interrogate the role of the mevalonate pathway in cardiomyocyte proliferation. Chemical and genetic perturbations of the mevalonate pathway indicated that the post-translational modification, prenylation, regulates cardiomyocyte proliferation. We use prenyl probes and mass spectrometry to identify a catalogue of 40 prenylated proteins in human cardiac cells, including proteins where prenylated function had not yet been investigated. We show that multiple prenylated proteins control cardiomyocyte proliferation including RRAS2 and NAP1L4. We demonstrate that prenylation has differential effects on distinct proteins, with RRAS2 prenylation controlling membrane localization and NAP1L4 prenylation regulating cardiomyocyte mitosis and centrosome homeostasis. Together, these data show that protein prenylation is required for cardiomyocyte proliferation through multiple targets and these processes may need to be re-activated for cardiac regeneration.
Single-cell proteomics of Arabidopsis leaf mesophyll identifies drought stress-related proteins
Authors: Fulcher James M. , Dawar Pranav , Balasubramanian Vimal Kumar , Williams Sarah M. , Nadeau Kyle D. , Winkler Tanya E. , Markillie Lye Meng , Mitchell Hugh D. , Ahkami Amir H. , Paša-Tolić Ljiljana , Zhu Ying 
Published: July 2024

AbstractThe application of single-cell omics tools to biological systems can provide unique insights into diverse cellular populations and their heterogeneous responses to internal and external perturbations. Thus far, most single-cell studies in plant systems have been limited to RNA-sequencing approaches, which only provide indirect readouts of cellular functions. Here, we present a single-cell proteomics workflow for plant cells that integrates tape-sandwich protoplasting, piezoelectric cell sorting, nanoPOTS sample preparation, and FAIMS-based MS data acquisition method for label-free single-cell proteomics analysis of Arabidopsis leaf mesophyll cells. From a single leaf protoplast, over 3,000 proteins were quantified with high precision. The workflow is demonstrated to identify stress associated changes in protein abundance by analyzing >80 protoplasts from well-watered and water-deficit stressed plants. Additionally, we describe a new approach for constructing covarying protein networks at the single-cell level and demonstrate how single-cell protein covariation analysis can reveal previously unrecognized protein functions while also capturing stress-induced changes in protein-protein dynamics.HighlightsThis study describes the first application of scProteomics to study abiotic stress-induced proteome regulation in leaf mesophyll cellsFrom a single Arabidopsis mesophyll protoplast, ∼2800 proteins on average were quantified with high precision using label free scProteomicsscProteomics of water-deficit Arabidopsis leaves revealed known and novel proteins involved in drought responseSingle-protoplast proteomics revealed water deficit-induced changes in protein covariation networks independent of changes in abundance
The microcephaly protein WDR62 regulates cellular purine metabolism through the HSP70/HSP90 chaperone machinery
Authors: Morris Matthew J. , Yeap Yvonne Y. , Chen Chi , Millard S. Sean , Pagan Julia K. , Ng Dominic C. H. 
Published: July 2024

AbstractInherited mutations in WD repeat-containing protein 62 (WDR62) are associated with microcephaly (MCPH2). While WDR62 plays important roles in mitosis and centriole biogenesis, additional WDR62 functions may cause abnormal brain growth. Here, we reveal a novel WDR62 role in the molecular chaperone network regulating purine metabolism. In response to hyperosmotic stress, WDR62 redistributes to purinosomes—phase-separated membraneless assemblies of purine metabolic enzymes and their chaperones. While WDR62 is not needed for purinosome formation, its loss disrupts purine homeostasis, resulting in the accumulation of purine nucleotide intermediates and a reduction in the levels of hypoxanthine-guanine phosphoribosyl transferase (HPRT), a key purine salvage enzyme. We link this to WDR62’s interaction with Bcl2-associated athanogene 2 (BAG2), a co-chaperone that modulates the function of HSP70/90. In cells lacking WDR62, BAG2 levels are elevated and HPRT stability is reduced. Knocking down BAG2 in these cells restores HPRT levels, underscoring the crucial role of WDR62-BAG2 interactions in chaperone-mediated stability and turnover of metabolic pathway enzymes. Notably, common microcephaly-associated mutations in WDR62 alter its interaction with BAG2, suggesting that purine metabolic defects resulting from WDR62 mutations may underlie microcephaly in humans.
De novocancer mutations frequently associate with recurrent chromosomal abnormalities during long-term human pluripotent stem cell culture
Authors: Al Delbany Diana , Ghosh Manjusha S , Krivec Nusa , Huygebaert Anfien , Regin Marius , Duong Chi Mai , Lei Yingnan , Sermon Karen , Olsen Catharina , Spits Claudia 
Published: July 2024

ABSTRACTHuman pluripotent stem cells (hPSC) are pivotal in regenerative medicine, yet theirin vitroexpansion often leads to genetic abnormalities, raising concerns about their safety in clinical applications. This study analyzed ten human embryonic stem cell lines across multiple passages to elucidate the dynamics of chromosomal abnormalities and single nucleotide variants (SNVs) in 380 cancer-related genes. Prolongedin vitroculture resulted in 80% of the lines acquiring gains of chromosomes 20q or 1q, both known for conferringin vitrogrowth advantage. 70% of lines also acquired other copy number variants (CNVs) outside the recurrent set. Additionally, we detected 122 SNVs in 88 genes, with all lines acquiring at least onede novoSNV during culture. Our findings show higher loads of both CNVs and SNVs at later passages which are due to the cumulative acquisition of mutations over a longer time in culture and not to an increased rate of mutagenesis over time. Importantly, we observed that SNVs and rare CNVs follow the acquisition of chromosomal gains in 1q and 20q, while most of the low-passage and genetically balanced samples were devoid cancer-associated mutations. This suggests that the recurrent chromosomal abnormalities are the potential drivers for the acquisition of other mutations.
Increased BMI associated with decreased breastfeeding initiation in Million Veteran Program participants
Authors: Lankester Joanna , Guarischi-Sousa Rodrigo , Hilliard Austin T ,   VA Million Veteran Program, Shere Labiba , Husary Marya , Crowe Susan , Tsao Philip S , Rehkopf David H , Assimes Themistocles L 
Published: July 2024

AbstractBackgroundBreastfeeding has been associated with maternal and infant health benefits but has been inversely associated with body mass index (BMI) prepartum. Breastfeeding and BMI are both linked to socioeconomic factors.MethodsData from parous female participants with available breastfeeding information from the Million Veteran Program cohort was included. BMI at enrollment and earliest BMI available were extracted, and polygenic scores (PGS) for BMI were calculated. We modeled breastfeeding for one month or more as a function of BMI at enrollment; earliest BMI where available pre-pregnancy; and PGS for BMI. We conducted Mendelian randomization for breastfeeding initiation using PGS as an instrumental variable.ResultsA higher BMI predicted a lower likelihood of breastfeeding for one month or more in all analyses. A +5 kg/m2BMI pre-pregnancy was associated with a 24% reduced odds of breastfeeding, and a +5 kg/m2genetically predicted BMI was associated with a 17% reduced odds of breastfeeding.ConclusionsBMI predicts a lower likelihood of breastfeeding for one month or longer. Given the high success of breastfeeding initiation regardless of BMI in supportive environments as well as potential health benefits, patients with elevated BMI may benefit from additional postpartum breastfeeding support.
Large-scale analysis of the medical discourse on rheumatoid arthritis: complementing a socio-anthropologic analysis
Authors: Santoro Mario , Nardini Christine 
Published: July 2024

ABSTRACTThe medical discourse, entails the analysis of the modalities, far from unbiased, by which hypotheses and results are laid out in the dissemination of findings in scientific publications, giving different emphases on the background, relevance, robustness, and assumptions that the audience should take for granted. While this concept is extensively studied in socio-anthropology, it remains generally overlooked within the scientific community conducting the research. Yet, analyzing the discourse is crucial for several reasons: to frame policies that take into account an appropriately large screen of medical opportunities, to avoid overseeing promising but less walked paths, to grasp different types of representations of diseases, therapies, patients, and other stakeholders, understanding and being aware of how these very terms are conditioned by time, culture and so on. While socio-anthropologists traditionally use manual curation methods, automated approaches like topic modeling offer a complementary way to explore the vast and ever-growing body of medical literature. In this work, we propose a complementary analysis of the medical discourse regarding the therapies offered for rheumatoid arthritis using topic modeling and large language model-based emotion and sentiment analysis.
Duodenal organoids from metabolic dysfunction-associated steatohepatitis patients exhibit altered digestive homeostasis
Authors: Hadefi Alia , Leprovots Morgane , Dinsart Gilles , Marefati Maryam , Vermeersch Marjorie , Monteyne Daniel , Pérez-Morga David , Lefort Anne , Libert Frédérick , Verset Laurine , Liefferinckx Claire , Moreno Christophe , Devière Jacques , Trépo Eric , Garcia Marie-Isabelle 
Published: July 2024

ABSTRACTBackground and AimsMetabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Though MASH is closely tied to metabolic risk factors, the underlying pathogenic mechanisms remain scarcely understood. Recent research underscores the importance of the gut-liver axis in its pathogenesis, an aspect less explored in human studies. Here, we investigated whether the duodenal epithelium of MASH patients, could exhibit intrinsic dysfunctions.MethodsDuodenal epithelial organoids were generated from 16 MASH patients and 14 healthy controls. Biopsies and patient-derived organoid transcriptomes were then analyzed to evaluate if specific intestinal pathways were differentially modulated in MASH subjects. Functional assays were performed to assess the duodenal epithelial digestive potential and barrier functionality.ResultsOrganoid formation efficiency was similar between control-derived epithelial organoids (CDEOs) and MASH-derived epithelial organoids (MDEOs) (71% and 69%, respectively). Despite global heterogeneity in growth patterns, MDEOs frequently exhibited cystic spheroid morphology. MDEOs displayed altered digestive homeostasis associated with reduced mature absorptive cell fate, but they retained their lipid metabolic capacity, possibly mediated by lipid oxidation in stem/progenitor cells. Additionally, MDEOs misexpressed components of tight and adherens junctions and desmosomes compared to controls. However, MDEOs maintained pore and leak pathway integrity, indicating that the duodenal epithelial barrier remained functionally preserved under tested conditions.ConclusionsThis study provides evidence that the duodenal epithelium of MASH patients exhibits significant alterations in its digestive and barrier functions. This study sheds light on the intricate dynamics of duodenal epithelial alterations in MASH, highlighting potential therapeutic avenues for restoring intestinal homeostasis.
Nitrogen Availability and Utilisation of Oligopeptides by Yeast in Industrial Scotch Grain Whisky Fermentation
Authors: Berg Hidde Yaël , Arju Georg , Nisamedtinov Ildar 
Published: July 2024

AbstractScotch grain whisky is produced with a substantial proportion of unmalted grains, which can result in nitrogen deficiency for yeast in the fermentable grain mash. This study examined nitrogen source availability and utilisation by three commercial whisky strains (Saccharomyces cerevisiae) during Scotch grain whisky fermentation, focusing on oligopeptides. Peptide uptake kinetics in synthetic whisky mash with defined peptides showed that oligopeptides of up to nine amino acids were taken up by the strains, albeit with some variability between the strains. The study found that peptides with appropriate molecular weights could replace free amino acids without negatively affecting fermentation kinetics. Moreover, fermentation performance improved when additional nitrogen was provided via peptides rather than diammonium phosphate. Analysis of industrial grain mash indicated that despite low initial yeast assimilable nitrogen, residual proteolytic activity from malt increased nitrogen availability during fermentation. Approximately 30% of the nitrogen consumed by yeast during grain mash fermentation was derived from peptides. LC-HRMS peptide analysis revealed complex dynamics of peptide formation, degradation, and utilisation. This study highlights the importance of oligopeptides in ensuring optimal fermentation efficiency in Scotch grain mash and similar substrates.
Identifying Genetic Variations inemm89Streptococcus pyogenesLinked to Severe Invasive Infections
Authors: Ono Masayuki , Yamaguchi Masaya , Motooka Daisuke , Hirose Yujiro , Higashi Kotaro , Sumitomo Tomoko , Miyoshi-Akiyama Tohru , Okuno Rumi , Yamaguchi Takahiro , Kawahara Ryuji , Otsuka Hitoshi , Nakanishi Noriko , Kazawa Yu , Nakagawa Chikara , Yamaguchi Ryo , Sakai Hiroo , Matsumoto Yuko , Ikebe Tadayoshi , Kawabata Shigetada 
Published: July 2024

SummaryStreptococcus pyogenescauses mild human infections as well as life-threatening invasive diseases. Since the mutations known to enhance virulence to date account for only half of the severe invasive infections, additional mechanisms/mutations need to be identified. Here, we conducted a genome-wide association study ofemm89S. pyogenesstrains to comprehensively identify pathology-related bacterial genetic factors (SNPs, indels, genes, or k-mers). Japanese (n=311) and global (n=666) cohort studies of strains isolated from invasive or non-invasive infections revealed 17 and 1,075 SNPs/indels and 2 and 169 genes, respectively, that displayed associations with invasiveness. We validated one of them, a non-invasiveness-related point mutation,fhuBT218C, by structure predictions and introducing it into a severe invasive strain and confirmed that the mutant showed slower growth in human blood. Thus, we report novel mechanisms that convertemm89S. pyogenesto an invasive phenotype and a platform for establishing novel treatments and prevention strategies.
A 3.5-minute-long reading-based fMRI localizer for the language network
Authors: Tuckute Greta , Lee Elizabeth Jiachen , Sathe Aalok , Fedorenko Evelina 
Published: July 2024

AbstractThe field of human cognitive neuroscience is increasingly acknowledging inter-individual differences in the precise locations of functional areas and the corresponding need for individual-level analyses in fMRI studies. One approach to identifying functional areas and networks within individual brains is based on robust and extensively validated ‘localizer’ paradigms—contrasts of conditions that aim to isolate some mental process of interest. Here, we present a new version of a localizer for the fronto-temporal language-selective network. This localizer is similar to a commonly-used localizer based on the reading of sentences and nonword sequences (Fedorenko et al., 2010) but uses speeded presentation (200ms per word/nonword). Based on a direct comparison between the standard version (450ms per word/nonword) and the speeded versions of the language localizer in 24 participants, we show that a single run of the speeded localizer (3.5 min) is highly effective at identifying the language-selective areas: indeed, it is more effective than the standard localizer given that it leads to an increased response to the critical (sentence) condition and a decreased response to the control (nonwords) condition. This localizer may therefore become the version of choice for identifying the language network in neurotypical adults or special populations (as long as they are proficient readers), especially when time is of essence.
Plasmids modulate microindel mutations inAcinetobacter baylyiADP1
Authors: Liljegren Mikkel M. , Gama João A. , Johnsen Pål J. , Harms Klaus 
Published: July 2024

AbstractPlasmids can impact the evolution of their hosts, e.g. due to carriage of mutagenic genes, through cross-talk with host genes or as result of SOS induction during transfer. Here we demonstrate that plasmids can cause microindel mutations in the host genome. These mutations are driven by the production of single-stranded DNA molecules that invade replication forks at microhomologies and subsequently get integrated into the genome. Using the gammaproteobacterial model organismAcinetobacter baylyi, we show that carriage of broad host range plasmids from different incompatibility groups can cause microindel mutations directly or indirectly. The plasmid pQLICE belonging to the incompatibility group Q (IncQ) and replicating by a characteristic strand displacement mechanism can generate chromosomal microindel mutations directly with short stretches of DNA originating from pQLICE. In addition, the presence of plasmids can increase microindel mutation frequencies indirectly (i.e., with chromosomal ectopic DNA) as shown with the IncP plasmid vector pRK415 (theta replication mechanism), presumably through plasmid-chromosome interactions that lead to DNA damages. These results provide new mechanistic insights into the microindel mutation mechanism, suggesting that single-stranded DNA repair intermediates are the causing agents. By contrast, the IncN plasmid RN3 appears to suppress host microindel mutations. The suppression mechanism remains unknown. Other plasmids in this study confer ambiguous or no quantifiable mutagenic effects.