bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure ofBifidobacterium bifidumglycoside hydrolase family 110 α-galactosidase specific for blood group B antigen
Authors: Kashima Toma , Akama Megumi , Wakinaka Takura , Arakawa Takatoshi , Ashida Hisashi , Fushinobu Shinya 
Published: March 2024

AbstractTo overcome incompatibility issues and increase the possibility of blood transfusion, technologies that enable efficient conversion of A- and B-type red blood cells to the universal donor O-type is desirable. Although several blood type-converting enzymes have been identified, detailed understanding about their molecular functions is limited. α-Galactosidase fromBifidobacterium bifidumJCM 1254 (AgaBb), belonging to glycoside hydrolase (GH) 110 subfamily A, specifically acts on blood group B antigen. Here we present the crystal structure of AgaBb, including the catalytic GH110 domain and part of the C-terminal uncharacterized regions. Based on this structure, we deduced a possible binding mechanism of blood group B antigen to the active site. Site-directed mutagenesis confirmed that R270 and E380 recognize the fucose moiety in the B antigen. Thermal shift assay revealed that the C-terminal uncharacterized region significantly contributes to protein stability. This region is shared only among GH110 enzymes fromB. bifidumand someRuminococcusspecies. The elucidation of the molecular basis for the specific recognition of blood group B antigen is expected to lead to the practical application of blood group conversion enzymes in the future.
Activation of the imprinted Prader-Willi Syndrome locus by CRISPR-based epigenome editing
Authors: Rohm Dahlia , Black Joshua B. , McCutcheon Sean R. , Barrera Alejandro , Morone Daniel J. , Nuttle Xander , de Esch Celine E. , Tai Derek J.C. , Talkowski Michael E. , Iglesias Nahid , Gersbach Charles A. 
Published: March 2024

SummaryEpigenome editing with DNA-targeting technologies such as CRISPR-dCas9 can be used to dissect gene regulatory mechanisms and potentially treat associated disorders. For example, Prader-Willi Syndrome (PWS) is caused by loss of paternally expressed imprinted genes on chromosome 15q11.2-q13.3, although the maternal allele is intact but epigenetically silenced. Using CRISPR repression and activation screens in human induced pluripotent stem cells (iPSCs), we identified genomic elements that control expression of the PWS geneSNRPNfrom the paternal and maternal chromosomes. We showed that either targeted transcriptional activation or DNA demethylation can activate the silenced maternalSNRPNand downstream PWS transcripts. However, these two approaches function at unique regions, preferentially activating different transcript variants and involving distinct epigenetic reprogramming mechanisms. Remarkably, transient expression of the targeted demethylase leads to stable, long-term maternalSNRPNexpression in PWS iPSCs. This work uncovers targeted epigenetic manipulations to reprogram a disease-associated imprinted locus and suggests possible therapeutic interventions.
Identification of Interaction Partners of Outer Inflammatory Protein A: Computational and Experimental Insights into How Helicobacter pylori Infects Host Cells
Authors: Akcelik-Deveci Sümeyye , Kılıç Elif , Mansur Ozen Nesteren , Timucin Emel , Buyukcolak Yaren , Oktem-Okullu Sinem 
Published: March 2024

AbstractAdherence to the gastric epithelium is an essential feature ofHelicobacter pylorifor its colonization. Outer membrane proteins (OMPs) play a pivotal role in adherence potentiating the survival of the microbe in the gastric tissue. Among these proteins, Outer inflammatory protein A (OipA) is a critical protein that is known to help bacteria to colonize on the host gastric epithelial cell surface. Although the role of OipA in theH. pyloriattachment and the association between OipA-positiveH. pyloristrains and clinical outcomes have been demonstrated, there is limited information on the structural mechanism of the OipA action in the adherence ofH. pylorito the gastric epithelial cell surface. Our study utilizes experimental and computational methodologies to investigate the interaction partners of OipA on the gastric epithelial cell surface. Initially, we performed a proteomic analysis to decipher the OipA interactome in the human gastric epithelial cells using a pull-down assay of the recombinant OipA and the membrane proteins of the gastric epithelial cells. Proteomic analysis has revealed 704 unique proteins that interacted with OipA. We have further analyzed 16 partners of OipA using molecular modeling tools. Structural findings obtained from the prediction of the protein-protein complexes of OipA and candidate partners unraveled 3 human proteins whose OipA interactions could base an explanation about howH. pylorirecruits OipA for adherence. Altogether, the findings presented here provide insights into novel mechanisms ofH. pyloriand host interactions through OipA, reflecting the potential of these mechanisms and interactions as therapeutic targets to combatH. pyloriinfection.Key pointsOuter membrane proteins (OMPs) are an emerging topic in bacterial infection.OipA is a candidate for an adherence-receptor network on the gastric epithelial cell surface withH. pylori.OipA interactome partners on gastric epithelial cell surfaces are valuable therapeutic targets for theH. pyloriinfection.
Epigenetic Mechanisms Regulating the Association betweenOR2L13and Major Psychiatric Disorders
Authors: Du Xiujuan , Zhang Lingli , Ren Tai , He Hua , Zhao Jian , Li Fei 
Published: March 2024

AbstractBackgroundPreviously, population-based cohort studies have identified the association between epigenetic modifications ofOR2L13related to mental disorders and Gestational diabetes mellitus (GDM). However, the causal nature of these associations remains difficult to establish owing to confounding.AimsThe purpose of the study was to investigate the causal effect of methylation ofOR2L13and offspring mental health outcomes.MethodWe performed two-sample mendelian randomisation to assess the effect of methylation ofOR2L13on mental disorders. Methylation of 7 CpG sites withinOR2L13related to GDM from two previous studies were used as exposure. Genome wide significant single nucleotide polymorphisms for methylation ofOR2L13retrieved from published data were used as instrumental variables. Their causal impact on major psychiatric disorders was assessed using summary-level data mostly from the Psychiatric Genomics Consortium.ResultsLowerOR2L13methylation was casually associated with a higher risk of PD in offspring [cg03748376: odds ratio (OR)=0.81, 95% confidence interval (CI) =0.68–0.97, P =0.02]. However, little evidence was found for a causal relationship between the methylation levels ofOR2L13and autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), schizophrenia (SCZ), major depressive disorder (MDD), bipolar disorder (BD) and obsessive-compulsive disorder (OCD).ConclusionsEvidence from our study supported a causal effect of lowerOR2L13methylation on PD risk.
Challenges in identifying and quantifying country-level participation in multi-country randomised controlled trials involving Ireland as a collaborating partner
Authors: Larkin James , Alanza Uchechukwu , Raj Nagarajan Vikneswaran , Collins Maurice , Termanini Sami , Farrington Emmet , Clyne Barbara , Fahey Tom , Moriarty Frank 
Published: March 2024

AbstractBackground and ObjectiveRandomised controlled trials (RCTs) provide vital information about healthcare interventions. Accurate reporting is vital for effective RCT dissemination. This study aimed to assess the reporting quality of multi-country RCTs, using Ireland as a case study, examining trial characteristics, adherence to reporting standards and the reporting of participation from Ireland.Study Design and SettingThis is a secondary analysis of RCTs identified in a previous observational study of RCTs where ≥80% of participants were recruited in Ireland. This current study focuses on multi-country RCTs with Ireland as a participating country. The current study involved an additional screening process according to these inclusion criteria: RCTs conducted on humans in a healthcare setting with centres based in Ireland, and <80% of participants recruited in Ireland. The primary outcome variables were trial characteristics and reporting rates for: trial registration, use of standardised reporting guidelines, number of Irish centres and number of participants recruited in Ireland. Descriptive statistics were used for analysis.ResultsOverall, 239 RCTs were included. The most common intervention was a drug (74.9% of RCTs). The most common setting was an ambulatory setting (74.1% of RCTs). The most common clinical domain was the cardiovascular system (18.0% of RCTs). Among RCTs published after the CONSORT reporting guideline was published (1996), 8.3% referred to a standardised reporting guideline. Among RCTs published after the International Committee of Medical Journal Editors mandated clinical trial registration (2005), 81.8% provided registration numbers. Number of Irish centres was reported in 75.3% (N=180) of RCTs. Number of participants recruited in Ireland was reported in 27.2% (N=65) of RCTs.ConclusionOur findings show deficits in reporting quality for multi-country RCTs, particularly in referring to reporting guidelines and reporting number of participants for the examined country. Institutions should create policies to ensure transparent RCT dissemination.
Determining the feasibility of linked claims and vaccination data for a Covid-vaccine pharmaco-epidemiological study in Germany – RiCO feasibility study protocol
Authors: Timmesfeld Nina , Ihle Peter , Denz Robin , Meiszl Katharina , Scholz Katrin , Oberle Doris , Drechsel-Bäuerle Ursula , Keller-Stanislawski Brigitte , Diebner Hans H. , Meyer Ingo 
Published: March 2024

AbstractIn Germany, there has been no population-level pharmaco-epidemiological study on the safety of the Covid-19 vaccines. One factor preventing such a study so far relates to challenges combining the different relevant data bodies on vaccination with suitable outcome data, specifically statutory health insurance claims data. Individual identifiers used across these data bodies are of unknown quality and reliability for data linkage. As part of a larger pharmaco-vigilance study on the COVID-19 vaccines, called RiCO (German "Risikoevaluation der COVID-19-Impfstoffe”, Englisch "Risk assessment of COVID-19 vaccines”), a feasibility study is being conducted to determine the overall confidence level with which existing data can be analysed in relation to the safety of the COVID-19 vaccine. This RiCO feasibility study will establish a dataflow combining claims data and vaccination data for a sub-sample of the total German population, describe data quality for each data set from the various sources, estimate the proportion of the different linkage errors and will develop various approaches for linking the data in addition to the simple form of linkage using a common identifier in order to reduce possible linkage errors. These last three points are the core objective of the feasibility study. A secondary objective is to test the viability of the required dataflow involving multiple stakeholders from different parts of the healthcare system. Results will be published and used to plan the actual pharmaco-vigilance study on the COVID-19 vaccines for Germany, as well as future research on the role of COVID vaccines as risk or protective factors for long-term COVID-19 effects.Strength and limitationsPotential for a population-level pharmaco-epidemiological study on the safety of the Covid-19 vaccines for Germany, based on vaccination data combined with statutory health insurance claims data.Introduction and estimation of quality metrics pertaining to the linkability of the various data bodies existing in Germany.Direct measurement of linkage error based on the available identifiers is not possible, proxy metrics and descriptive analytics need to be used.An attempt at linkage with the vaccination data could only be made using data from one smaller statutory health insurance, which may limit the extent to which the data can be analysed.
Systematic Review of Large Language Models for Patient Care: Current Applications and Challenges
Authors: Busch Felix , Hoffmann Lena , Rueger Christopher , van Dijk Elon HC , Kader Rawen , Ortiz-Prado Esteban , Makowski Marcus R , Saba Luca , Hadamitzky Martin , Kather Jakob Nikolas , Truhn Daniel , Cuocolo Renato , Adams Lisa C , Bressem Keno K 
Published: March 2024

AbstractThe introduction of large language models (LLMs) into clinical practice promises to improve patient education and empowerment, thereby personalizing medical care and broadening access to medical knowledge. Despite the popularity of LLMs, there is a significant gap in systematized information on their use in patient care. Therefore, this systematic review aims to synthesize current applications and limitations of LLMs in patient care using a data-driven convergent synthesis approach. We searched 5 databases for qualitative, quantitative, and mixed methods articles on LLMs in patient care published between 2022 and 2023. From 4,349 initial records, 89 studies across 29 medical specialties were included, primarily examining models based on the GPT-3.5 (53.2%, n=66 of 124 different LLMs examined per study) and GPT-4 (26.6%, n=33/124) architectures in medical question answering, followed by patient information generation, including medical text summarization or translation, and clinical documentation. Our analysis delineates two primary domains of LLM limitations: design and output. Design limitations included 6 second-order and 12 third-order codes, such as lack of medical domain optimization, data transparency, and accessibility issues, while output limitations included 9 second-order and 32 third-order codes, for example, non-reproducibility, non-comprehensiveness, incorrectness, unsafety, and bias. In conclusion, this study is the first review to systematically map LLM applications and limitations in patient care, providing a foundational framework and taxonomy for their implementation and evaluation in healthcare settings.
Evaluation of efficacy of formic acid and thermal remediation for management ofTropilaelapsandVarroamites in central Thailand
Authors: Sankovitz Madison , Steinhauer Nathalie , Yemor Tanawat , Cook Steven C. , Evans Jay D. , Ramsey Samuel D. 
Published: March 2024

AbstractThe western honey bee,Apis mellifera, faces a new threat from the spread of parasiticTropilaelaps(Tropi) mites, specificallyT. mercedesae, which adds additional complexity to an apicultural landscape heavily impacted byVarroa destructor. In this study conducted in central Thailand, we investigated the efficacy of two methods of applying formic acid and a thermal remediation technique in controlling Tropi mites andVarroa, focusing our attention on the reproductive stage of the mites which is restricted to capped brood cells. Results revealed that both formic acid treatments (Formic Pro and liquid formic acid) demonstrated an immediate and substantial reduction in live Tropi andVarroapopulations, maintaining near-zero levels for the 3- week duration of the study. In contrast, thermal remediation, employing heating pads, exhibited a more gradual decline, achieving an 85.42% reduction in Tropi mites and a 92.33% reduction inVarroamites by week three. Notably, heat-treated colonies experienced an unexpected resurgence in mite populations during week two. The findings contribute valuable insights into potential strategies for mitigating the threat of Tropi mites and highlight the urgency of further research to safeguard global honey bee populations.
Bsp22 protein polymerization drives dynamic adaptation of theBordetellatype III secretion system injectisome
Authors: Malcova Ivana , Kamanova Jana 
Published: March 2024

AbstractMany gram-negative bacteria are equipped with a type III secretion system (T3SS) injectisome, enabling the direct translocation of effector proteins from the bacterial cytoplasm into host cells. In the case ofBordetella bronchiseptica, a respiratory pathogen of diverse mammals, the T3SS injectisome exhibits a unique needle tip filament formed by the Bsp22 protein, essential for bacterial persistence in mice. Here, we usedB. bronchisepticaandB. pertussiswith in-frame insertions of short peptide tags into the Bsp22 to elucidate its formation and characteristics via super-resolution imaging with fluorophore-labeled nanobodies and biarsenic probes. We report that on abiotic surfaces, Bsp22 forms flexible filaments that protrude up to several µm from bacterial cells. In these conditions, Bsp22 filaments grow continuously without any apparent growth control, with Bsp22 subunits being added at the distal end. Remarkably, during host cell infection, the growth of Bsp22 filaments is constrained, accompanied by downregulated Bsp22 protein production. When infecting HeLa cells, some Bsp22 filaments form a short physical bridge between the bacterium and the host cell surface. In nasal epithelium, whereB. bronchisepticacolonization is specifically restricted to ciliated cells, Bsp22 filaments align parallel to the cilia, pointing towards the cell apical surface. These results highlight the context-specific and environment-influenced dynamic modulation of the length and orientation ofBordetellaneedle tip filament, uncovering the adaptability of theBordetellaT3SS injectisome in response to conditions encountered during host cell infection.
Lords of the flies: Dipteran migrants are diverse, abundant and ecologically important
Authors: Hawkes Will L. , Menz Myles H.M. , Wotton Karl R. 
Published: March 2024

AbstractInsect migrants are hugely abundant and recent studies have identified Diptera as the major component of many migratory assemblages, often totalling up to 90% of all individuals. Despite this, studies into their migratory behaviour have been widely eschewed in favour of the more ‘charismatic’ migrant insects such as butterflies, dragonflies, and moths. Here we review the available literature on Dipteran migration and identify 13 lines of evidence that we use to determine migratory behaviour. Using this approach, we find species from 60 out of 130 Dipteran families that show evidence of migration, with Syrphidae fulfilling 12 of these criteria, followed by the Tephritidae with 10. In contrast to these groups, 22 families fulfilled just two lines of evidence or fewer, underlining the need for more research into the migratory characteristics of these groups. In total, 622 species of Diptera were found to have migratory behaviour (0.5% of the total Dipteran species count), a figure rising to 3% for the Syrphidae, a percentage mirrored by other animal taxa such as butterflies, noctuid moths, and bats. Research was biased to locations in Europe (49% of publications) and while vast regions remain understudied, our review identified major flyways used by Dipteran migrants across all biogeographic realms. Finally, we detail the ecological and economic roles of these migrants and review how these services are being affected by anthropogenic change through population declines and phenological shifts. Overall, this review highlights how little is known about Dipteran migration and how vital their migratory behaviour may be to the health of global ecosystems.
Integrativein vivoanalysis of the ethanolamine utilization bacterial microcompartment inEscherichia coli.
Authors: Jallet Denis , Soldan Vanessa , Shayan Ramteen , Stella Alexandre , Ismail Nour , Zenati Rania , Cahoreau Edern , Burlet-Schiltz Odile , Balor Stéphanie , Millard Pierre , Heux Stéphanie 
Published: March 2024

AbstractBacterial microcompartments (BMCs) are self-assembling protein megacomplexes that encapsulate metabolic pathways. Although approximately 20% of sequenced bacterial genomes contain operons encoding putative BMCs, few have been thoroughly characterized, nor any in the most studiedEscherichia colistrains. We used an interdisciplinary approach to gain deep molecular and functional insights into the ethanolamine utilization (Eut) BMC system encoded by theeutoperon inE. coliK-12. Theeutgenotype was linked with the ethanolamine utilization phenotype using deletion and overexpression mutants. The subcellular dynamics and morphology of theE. coliEut BMC were characterizedin cellulaby fluorescence microscopy and electron (cryo)microscopy. The minimal proteome reorganization required for ethanolamine utilization and thein vivostochiometric composition of the Eut BMC were determined by quantitative proteomics. Finally, the first flux map connecting the Eut BMC with central metabolismin cellulawas obtained by genome scale modelling and13C-fluxomics. Our results reveal that, contrary to previous suggestions, ethanolamine serves both as a nitrogen and a carbon source inE. coliK-12, while also contributing significant metabolic overflow. Overall, this study provides a quantitative molecular and functional understanding of the BMCs involved in ethanolamine assimilation byE. coli.ImportanceThe properties of BMCs make them an ideal tool to build orthogonal network structures with minimal interactions with native metabolic and regulatory networks. However, this requires an understanding of how BMCs work natively. In this study, we combined genetic manipulation, multi-omics, modelling and microscopy to address this issue for Eut BMCs. We show that the Eut BMC inE. coliturns ethanolamine into usable carbon and nitrogen substrates to sustain growth. These results improve our understanding of compartmentalization in a widely used bacterial chassis.
Systematic classification of phage receptor-binding proteins predicts surface glycopolymer structure inStaphylococcuspathogens
Authors: Krusche Janes , Beck Christian , Lehmann Esther , Gerlach David , Wolz Christiane , Peschel Andreas 
Published: March 2024

SummaryWall teichoic acids (WTAs) are major surface polymers of staphylococcal pathogens and commensals, whose variable structure governs interaction with host receptors, immunoglobulins, and bacteriophages. The ribitol phosphate (RboP) WTA type contributes to virulence, for instance inStaphylococcus aureus, but we lack comprehensive knowledge of WTA types and cognate phages.We developed a computational pipeline to identify the receptor-binding proteins (RBPs) in 335 Staphylococcus phage genomes, yielding multiple distinct RBP clusters. Notably, many phages had two separate RBPs with in part different WTA preferences. RBP representatives differed in specificity for RboP WTA glycosylation types, recapitulating the specificity of the corresponding phage. Based on these results, we created a publicly available bioinformatic tool to predict phage host specificity based on RBP similarity.The RboP WTA specific Φ13-RBP also revealed that the presence of RboP WTA on non-aureus staphylococci is more common than previously thought. Our approach facilitates the characterization of opportunistic Staphylococcus pathogens according to WTA types, which has major implications for phage-mediated interspecies horizontal gene transfer and future phage therapies.