bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two DOT1 enzymes cooperatively mediate efficient ubiquitin-independent histone H3 lysine 76 tri-methylation in kinetoplastids
Authors: Frisbie Victoria S. , Hashimoto Hideharu , Xie Yixuan , De Luna Vitorino Francisca N. , Baeza Josue , Nguyen Tam , Yuan Zhangerjiao , Kiselar Janna , Garcia Benjamin A. , Debler Erik W. 
Published: March 2024

AbstractIn higher eukaryotes, a single DOT1 histone H3 lysine 79 (H3K79) methyltransferase processively produces H3K79me2/me3 through histone H2B mono-ubiquitin interaction, while the kinetoplastid Trypanosoma brucei di-methyltransferase DOT1A and tri-methyltransferase DOT1B efficiently methylate the homologous H3K76 without H2B mono-ubiquitination. Based on structural and biochemical analyses of DOT1A, we identify key residues in the methyltransferase motifs VI and X for efficient ubiquitin-independent H3K76 methylation in kinetoplastids. Substitution of a basic to an acidic residue within motif VI (Gx6K) is essential to stabilize the DOT1A enzyme-substrate complex, while substitution of the motif X sequence VYGE by CAKS renders a rigid active-site loop flexible, implying a distinct mechanism of substrate recognition. We further reveal distinct methylation kinetics and substrate preferences of DOT1A (H3K76me0) and DOT1B (DOT1A products H3K76me1/me2) in vitro, determined by a Ser and Ala residue within motif IV, respectively, enabling DOT1A and DOT1B to mediate efficient H3K76 tri-methylation non-processively but cooperatively, and suggesting why kinetoplastids have evolved two DOT1 enzymes.
Legionella metaeffector MavL reverses ubiquitin ADP-ribosylation via a conserved arginine-specific macrodomain
Authors: Zhang Zhengrui , Fu Jiaqi , Rack Johannes Gregor Matthias , Li Chuang , Voorneveld Jim , Filippov Dmitri V. , Ahel Ivan , Luo Zhao-Qing , Das Chittaranjan 
Published: March 2024

AbstractADP-ribosylation is a reversible post-translational modification involved in various cellular activities. Removal of ADP-ribosylation requires (ADP-ribosyl)hydrolases, with macrodomain enzymes being a major family in this category. The pathogen Legionella pneumophila mediates atypical ubiquitination of host targets using the SidE effector family in a process that involves ubiquitin ADP-ribosylation on arginine 42 as an obligatory step. Here, we show that the Legionella macrodomain effector MavL regulates this pathway by reversing the arginine ADP-ribosylation, likely to minimize potential detrimental effects caused by the modified ubiquitin. We determine the crystal structure of ADP-ribose-bound MavL, providing structural insights into recognition of the ADP-ribosyl group and catalytic mechanism of its removal. Further analyses reveal DUF4804 as a class of MavL-like macrodomain enzymes whose representative members show unique selectivity for mono-ADP-ribosylated arginine residue in synthetic substrates. We find such enzymes are also present in eukaryotes, as exemplified by two previously uncharacterized (ADP-ribosyl)hydrolases in Drosophila melanogaster. Crystal structures of several proteins in this class provide insights into arginine specificity and a shared mode of ADP-ribose interaction distinct from previously characterized macrodomains. Collectively, our study reveals a new regulatory layer of SidE-catalyzed ubiquitination and expands the current understanding of macrodomain enzymes.
Elevated blood remnant cholesterol and triglycerides are causally related to the risks of cardiometabolic multimorbidity
Authors: Zhao Yimin , Zhuang Zhenhuang , Li Yueying , Xiao Wendi , Song Zimin , Huang Ninghao , Wang Wenxiu , Dong Xue , Jia Jinzhu , Clarke Robert , Huang Tao 
Published: March 2024

AbstractThe connection between triglyceride-rich lipoproteins and cardiometabolic multimorbidity, characterized by the concurrence of at least two of type 2 diabetes, ischemic heart disease, and stroke, has not been definitively established. We aim to examine the prospective associations between serum remnant cholesterol, triglycerides, and the risks of progression from first cardiometabolic disease to multimorbidity via multistate modeling in the UK Biobank. We also evaluate the causality of these associations via Mendelian randomization using 13 biologically relevant SNPs as the genetic instruments. Here we show that elevated remnant cholesterol and triglycerides are significantly associated with gradually higher risks of cardiometabolic multimorbidity, particularly the progression of ischemic heart disease to the multimorbidity of ischemic heart disease and type 2 diabetes. These results advocate for effective management of remnant cholesterol and triglycerides as a potential strategy in mitigating the risks of cardiometabolic multimorbidity.
Long-term effects of Omicron BA.2 breakthrough infection on immunity-metabolism balance: a 6-month prospective study
Authors: Li Yanhua , Qin Shijie , Dong Lei , Qiao Shitong , Wang Xiao , Yu Dongshan , Gao Pengyue , Hou Yali , Quan Shouzhen , Li Ying , Fan Fengyan , Zhao Xin , Ma Yueyun , Gao George Fu 
Published: March 2024

AbstractThere have been reports of long coronavirus disease (long COVID) and breakthrough infections (BTIs); however, the mechanisms and pathological features of long COVID after Omicron BTIs remain unclear. Assessing long-term effects of COVID-19 and immune recovery after Omicron BTIs is crucial for understanding the disease and managing new-generation vaccines. Here, we followed up mild BA.2 BTI convalescents for six-month with routine blood tests, proteomic analysis and single-cell RNA sequencing (scRNA-seq). We found that major organs exhibited ephemeral dysfunction and recovered to normal in approximately six-month after BA.2 BTI. We also observed durable and potent levels of neutralizing antibodies against major circulating sub-variants, indicating that hybrid humoral immunity stays active. However, platelets may take longer to recover based on proteomic analyses, which also shows coagulation disorder and an imbalance between anti-pathogen immunity and metabolism six-month after BA.2 BTI. The immunity-metabolism imbalance was then confirmed with retrospective analysis of abnormal levels of hormones, low blood glucose level and coagulation profile. The long-term malfunctional coagulation and imbalance in the material metabolism and immunity may contribute to the development of long COVID and act as useful indicator for assessing recovery and the long-term impacts after Omicron sub-variant BTIs.
Competition quenching strategies reduce antibiotic tolerance in polymicrobial biofilms
Authors: Lories Bram , Belpaire Tom E. R. , Smeets Bart , Steenackers Hans P. 
Published: March 2024

AbstractBacteria typically live in dense communities where they are surrounded by other species and compete for a limited amount of resources. These competitive interactions can induce defensive responses that also protect against antimicrobials, potentially complicating the antimicrobial treatment of pathogens residing in polymicrobial consortia. Therefore, we evaluate the potential of alternative antivirulence strategies that quench this response to competition. We test three competition quenching approaches: (i) interference with the attack mechanism of surrounding competitors, (ii) inhibition of the stress response systems that detect competition, and (iii) reduction of the overall level of competition in the community by lowering the population density. We show that either strategy can prevent the induction of antimicrobial tolerance of Salmonella Typhimurium in response to competitors. Competition quenching strategies can thus reduce tolerance of pathogens residing in polymicrobial communities and could contribute to the improved eradication of these pathogens via traditional methods.
AccessPD as a next generation registry to accelerate Parkinson’s disease research
Authors: Chang Yun-Hsuan , Periñan Maria Teresa , Wilson Matt , Noyce Alastair J. 
Published: March 2024

AbstractRecruitment is a major rate-limiting factor in Parkinson’s disease (PD) research. AccessPD is a unique platform that aims to create a registry of more than 2000 PD patients and a rich database of PD-relevant information. Potential participants are identified using electronic health records (EHRs) in primary care. They are contacted via text message with an individualized link to the study portal. Electronic patient-reported outcomes (ePRO) are collected via online questionnaires and integrated with existing EHR. 200 participants were recruited within the first 6 months, of which 191 answered the follow-up questionnaire. Here, to showcase the potential of AccessPD, we described the most common diagnoses before and after PD diagnosis, the most commonly prescribed drugs, and identified participants who could benefit from device-aided therapies using consensus criteria. AccessPD shows its unique ability to link different data sources for patient stratification in longitudinal studies and recruitment into clinical trials.
Global trend of methane abatement inventions and widening mismatch with methane emissions
Authors: Jiang Jingjing , Yin Deyun , Sun Zhuoluo , Ye Bin , Zhou Nan 
Published: March 2024

AbstractSubstantially reducing methane emissions is the fastest way to repress near-term warming and is an essential prerequisite for reaching the 1.5 °C target. However, knowledge about the global invention trend, sectoral and national distribution and international diffusion of methane-targeted abatement technologies (MTATs) remains limited. On the basis of patent data, we identify more than 175,000 MTAT inventions applied between 1990 and 2019 by 133 countries or dependent territories. Our results revealed that after sustained growth of more than fourfold, the number of global high-quality MTAT inventions declined by 3.5% annually from 2010 to 2019. The sectoral and national-level distributions of MTAT inventions and methane emissions are strongly mismatched. Additionally, the international diffusion of MTATs is 11.1% lower than that of overall climate change mitigation technologies and most transfers occur between developed countries or flow to China, South Korea and Brazil; however, other developing countries and the least developed countries are rarely involved.
Assessing microbiome population dynamics using wild-type isogenic standardized hybrid (WISH)-tags
Authors: Daniel Benjamin B. J. , Steiger Yves , Sintsova Anna , Field Christopher M. , Nguyen Bidong D. , Schubert Christopher , Cherrak Yassine , Sunagawa Shinichi , Hardt Wolf-Dietrich , Vorholt Julia A. 
Published: March 2024

AbstractMicrobiomes feature recurrent compositional structures under given environmental conditions. However, these patterns may conceal diverse underlying population dynamics that require intrastrain resolution. Here we developed a genomic tagging system, termed wild-type isogenic standardized hybrid (WISH)-tags, that can be combined with quantitative polymerase chain reaction and next-generation sequencing for microbial strain enumeration. We experimentally validated the performance of 62 tags and showed that they can be differentiated with high precision. WISH-tags were introduced into model and non-model bacterial members of the mouse and plant microbiota. Intrastrain priority effects were tested using one species of isogenic barcoded bacteria in the murine gut and the Arabidopsis phyllosphere, both with and without microbiota context. We observed colonization resistance against late-arriving strains of Salmonella Typhimurium in the mouse gut, whereas the phyllosphere accommodated Sphingomonas latecomers in a manner proportional to their presence at the late inoculation timepoint. This demonstrates that WISH-tags are a resource for deciphering population dynamics underlying microbiome assembly across biological systems.
Heterogeneity and predictors of the effects of AI assistance on radiologists
Authors: Yu Feiyang , Moehring Alex , Banerjee Oishi , Salz Tobias , Agarwal Nikhil , Rajpurkar Pranav 
Published: March 2024

AbstractThe integration of artificial intelligence (AI) in medical image interpretation requires effective collaboration between clinicians and AI algorithms. Although previous studies demonstrated the potential of AI assistance in improving overall clinician performance, the individual impact on clinicians remains unclear. This large-scale study examined the heterogeneous effects of AI assistance on 140 radiologists across 15 chest X-ray diagnostic tasks and identified predictors of these effects. Surprisingly, conventional experience-based factors, such as years of experience, subspecialty and familiarity with AI tools, fail to reliably predict the impact of AI assistance. Additionally, lower-performing radiologists do not consistently benefit more from AI assistance, challenging prevailing assumptions. Instead, we found that the occurrence of AI errors strongly influences treatment outcomes, with inaccurate AI predictions adversely affecting radiologist performance on the aggregate of all pathologies and on half of the individual pathologies investigated. Our findings highlight the importance of personalized approaches to clinician–AI collaboration and the importance of accurate AI models. By understanding the factors that shape the effectiveness of AI assistance, this study provides valuable insights for targeted implementation of AI, enabling maximum benefits for individual clinicians in clinical practice.
Identification of key genes for atherosclerosis in different arterial beds
Authors: Wu Xize , Pan Xue , Zhou Yi , Pan Jiaxiang , Kang Jian , Yu J. J. Jiajia , Cao Yingyue , Quan Chao , Gong Lihong , Li Yue 
Published: March 2024

AbstractAtherosclerosis (AS) is the pathologic basis of various cardiovascular and cerebrovascular events, with a high degree of heterogeneity among different arterial beds. However, mechanistic differences between arterial beds remain unexplored. The aim of this study was to explore key genes and potential mechanistic differences between AS in different arterial beds through bioinformatics analysis. Carotid atherosclerosis (CAS), femoral atherosclerosis (FAS), infrapopliteal atherosclerosis (IPAS), abdominal aortic atherosclerosis (AAS), and AS-specific differentially expressed genes (DEGs) were screened from the GSE100927 and GSE57691 datasets. Immune infiltration analysis was used to identify AS immune cell infiltration differences. Unsupervised cluster analysis of AS samples from different regions based on macrophage polarization gene expression profiles. Weighted gene co-expression network analysis (WGCNA) was performed to identify the most relevant module genes with AS. Hub genes were then screened by LASSO regression, SVM-REF, and single-gene differential analysis, and a nomogram was constructed to predict the risk of AS development. The results showed that differential expression analysis identified 5, 4, 121, and 62 CAS, FAS, IPAS, AAS-specific DEGs, and 42 AS-common DEGs, respectively. Immune infiltration analysis demonstrated that the degree of macrophage and mast cell enrichment differed significantly in different regions of AS. The CAS, FAS, IPAS, and AAS could be distinguished into two different biologically functional and stable molecular clusters based on macrophage polarization gene expression profiles, especially for cardiomyopathy and glycolipid metabolic processes. Hub genes for 6 AS (ADAP2, CSF3R, FABP5, ITGAX, MYOC, and SPP1), 4 IPAS (CLECL1, DIO2, F2RL2, and GUCY1A2), and 3 AAS (RPL21, RPL26, and RPL10A) were obtained based on module gene, gender stratification, machine learning algorithms, and single-gene difference analysis, respectively, and these genes were effective in differentiating between different regions of AS. This study demonstrates that there are similarities and heterogeneities in the pathogenesis of AS between different arterial beds.
Investigating the interplay between gaming disorder and functional impairments in professional esports gaming
Authors: Pontes Halley M. , Rumpf Hans-Jürgen , Selak Špela , Montag Christian 
Published: March 2024

AbstractThe relationship between Gaming Disorder (GD) and the experience of functional impairments has received considerable theoretical attention in the recent past and current diagnostic approaches underscore the centrality of functional impairments as a requirement for GD diagnosis. However, there is limited empirical evidence illuminating the interplay between GD and functional impairments, particularly among specific vulnerable groups. The present study seeks to bridge this gap by investigating an English-speaking sample (N = 5198) comprising an age- and gender-matched group of Professional Gamers (PG, n = 2599) and Non-Professional Gamers (NPG, n = 2599) sub-sampled from a larger sample of 192,260 individuals. The results revealed that PG were at a greater risk for GD compared to NPG as the prevalence rate of GD among PG (3.31%) was significantly higher and almost doubled that of NPG (1.73%), with PG further exhibiting higher overall GD symptom-load and weekly time spent gaming compared to NPG. Furthermore, PG reported experiencing significantly higher frequency of gaming-related functional impairments compared to NPG, with the in particular affected areas for both PG and NPG being ‘school and/or work’, ‘physical health’, and ‘family’, with other key differences emerging in relation to other outcomes. Overall, the present findings show that not only GD symptom-load but also some functional impairment is higher in PG compared to NPG which highlights the need to develop and support prevention and intervention strategies for this at-risk population.
Social cognition, socioeconomic status and subjective well-being of Chinese migrant workers
Authors: Huang Weichao , Su Shipeng , Sun Xiaoyu 
Published: March 2024

AbstractSubjective well-being is based on the unity of internal and external needs, as well as material and non-material needs. However, existing research lacks consideration of the impact of both objective material conditions and subjective psychological cognition on the subjective well-being of migrant workers. Thus, based on data from the 2017 China General Social Survey, this paper applies ordered logit models and OLS models to investigate the impact of social cognition and socioeconomic status on the subjective well-being of migrant workers and their intergenerational differences. The results indicate that: (1) Social cognition has a significant impact, and the impact of fairness perception is more pronounced than depression perception and class change perception; (2) among socioeconomic status, personal income did not have a significant effect as education level, car ownership and house property ownership; (3) there are intergenerational differences. The emotional state of the older generation is the most critical factor influencing their subjective well-being. In contrast, the new generation is more concerned with their feelings about future expectations. The older generation is more concerned with their house property ownership, while the increase in income, education and car ownership can significantly increase the subjective well-being of the new generation. For this reason, we believe that the Chinese government should gradually change the existing urban and rural management system to create a fair and just social environment; make migrant workers receive the same protection as urban residents and improve the income distribution mechanism; pay attention to the social security of the older generation of migrant workers and the development opportunities of the new generation of migrant workers and their ability to integrate into the city to improve their subjective well-being.
GPS/BDS triple-frequency cycle slip detection and repair based on moving window global search method
Authors: Wang Jianying , Huang Dewu 
Published: March 2024

AbstractCycle slip detection and repair are crucial steps in achieving high accuracy in Global Navigation Satellite System (GNSS) data processing. The use of Global Positioning System (GPS) and BeiDou Navigation Satellite System (BDS) triple frequency observations allows for more accurate detection and repair of cycle slips compared to single or dual frequency. This study presents a moving window global search method by selecting three sets of combined coefficients to construct geometry-free (GF) models to minimize the influence of the ionosphere, using a moving window to update the standard deviation of cycle slip estimation, applying the "3$$\upsigma$$σ" criterion to constrain the range, and utilizing a global search method to detect and repair triple-frequency cycle slips. Through five sets of 1 Hz GNSS data experiments, the results demonstrate the effectiveness of this method in determining the position and size of triple-frequency cycle slips while avoiding multi-value problems. The detection success rate for GPS ranges from 98.0 to 100.0%, while BDS ranges from 92.0 to 100.0%. On average, GPS achieves a detection rate of 99.2%, and BDS reaches 96.7%, which is 0.8% and 1.8% higher than the direct rounding method, respectively. Compared to existing methods, it is also effective for the vast majority of small cycle slips within 2 cycles.
MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study
Authors: Dakroub Fatima , Kobeissy Firas , Mondello Stefania , Yang Zhihui , Xu Haiyan , Sura Livia , Rossignol Candace , Albayram Mehmet , Rajderkar Dhanashree , Wang Kevin , Weiss Michael D. 
Published: March 2024

Abstract
Neonatal Encephalopathy (NE) is a major cause of lifelong disability and neurological complications in affected infants. Identifying novel diagnostic biomarkers in this population may assist in predicting MRI injury and differentiate neonates with NE from those with low-cord pH or healthy neonates and may help clinicians make real-time decisions. To compare the microRNA (miRNA) profiles between neonates with NE, healthy controls, and neonates with low cord pH. Moreover, miRNA concentrations were compared to brain injury severity in neonates with NE. This is a retrospective analysis of miRNA profiles from select samples in the biorepository and data registry at the University of Florida Health Gainesville. The Firefly miRNA assay was used to screen a total of 65 neurological miRNA targets in neonates with NE (n = 36), low cord pH (n = 18) and healthy controls (n = 37). Multivariate statistical techniques, including principal component analysis and orthogonal partial least squares discriminant analysis, and miRNA Enrichment Analysis and Annotation were used to identify miRNA markers and their pathobiological relevance. A set of 10 highly influential miRNAs were identified, which were significantly upregulated in the NE group compared to healthy controls. Of these, miR-323a-3p and mir-30e-5p displayed the highest fold change in expression levels. Moreover, miR-34c-5p, miR-491-5p, and miR-346 were significantly higher in the NE group compared to the low cord pH group. Furthermore, several miRNAs were identified that can differentiate between no/mild and moderate/severe injury in the NE group as measured by MRI. MiRNAs represent promising diagnostic and prognostic tools for improving the management of NE.