bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signatures in domesticated beet genomes pointing at genes under selection in a sucrose-storing root crop
Authors: Dhiman Amar Singh , Taliadoros Demetris , Stukenbrock Eva H. , McGrath J. Mitchell , Emrani Nazgol , Jung Christian 
Published: May 2024

AbstractThe genusBetaencompasses important crops such as sugar, table, fodder, and leaf beets. All cultivated beets are believed to have originated from the wild sea beet,B.vulgarissubsp.maritima. Sugar beet, a recent crop dating back nearly 200 years, was selectively bred for enhanced root yield in combination with high sucrose content. We assembled aBetadiversity panel comprising wild and cultivated beet accessions. Whole-genome sequencing identified 10.3 million SNP markers. Four distinct genetic clusters were identified: table beet, sugar beet, Mediterranean sea beet, and Atlantic sea beet. A phylogenetic analysis revealed that cultivated beet accessions were genetically closer to Mediterranean than to Atlantic sea beet and that cultivated beets producing storage roots share a common ancestor. Cultivated beets exhibited genome regions with reduced nucleotide diversity compared to Mediterranean sea beets, indicating selection signatures. These regions contained putative candidate genes with potential roles in root development, suppression of lateral root formation, flowering time, and sucrose metabolism. A yet unknown sucrose transporter on chromosome 6 showed reduced nucleotide diversity exclusively in sugar beet accessions compared to otherBetatypes with low sucrose content, suggesting its role in sucrose storage. Within a region of high nucleotide diversity between accessions with contrasting root phenotypes, we found two genes encoding auxin response factors, which play a crucial role in root development. We reason these genes to be significant root thickening regulators in root crops.
Periodic ER-plasma membrane junctions support long-range Ca2+signal integration in dendrites
Authors: Benedetti Lorena , Fan Ruolin , Weigel Aubrey V. , Moore Andrew S. , Houlihan Patrick R. , Kittisopikul Mark , Park Grace , Petruncio Alyson , Hubbard Philip M. , Pang Song , Xu C. Shan , Hess Harald F. , Saalfeld Stephan , Rangaraju Vidhya , Clapham David E. , De Camilli Pietro , Ryan Timothy A. , Lippincott-Schwartz Jennifer 
Published: May 2024

SummaryNeuronal dendrites must relay synaptic inputs over long distances, but the mechanisms by which activity-evoked intracellular signals propagate over macroscopic distances remain unclear. Here, we discovered a system of periodically arranged endoplasmic reticulum-plasma membrane (ER-PM) junctions tiling the plasma membrane of dendrites at ∼1 μm intervals, interlinked by a meshwork of ER tubules patterned in a ladder-like array. Populated with Junctophilin-linked plasma membrane voltage-gated Ca2+channels and ER Ca2+-release channels (ryanodine receptors), ER-PM junctions are hubs for ER-PM crosstalk, fine-tuning of Ca2+homeostasis, and local activation of the Ca2+/calmodulin-dependent protein kinase II. Local spine stimulation activates the Ca2+modulatory machinery facilitating voltage-independent signal transmission and ryanodine receptor-dependent Ca2+release at ER-PM junctions over 20 μm away. Thus, interconnected ER-PM junctions support signal propagation and Ca2+release from the spine-adjacent ER. The capacity of this subcellular architecture to modify both local and distant membrane-proximal biochemistry potentially contributes to dendritic computations.HighlightsPeriodic ER-PM junctions tile neuronal dendritic plasma membrane in rodent and fly.ER-PM junctions are populated by ER tethering and Ca2+release and influx machinery.ER-PM junctions act as sites for local activation of CaMKII.Local spine activation drives Ca2+release from RyRs at ER-PM junctions over 20 μm.
The External Microbiome Communicates with the Developing Zebrafish (Danio rerio) Embryo Through the Chorion and Influences Developmental Trajectory
Authors: Green Emily M. , Harishchandra Akila , Lickwar Colin R. , Rawls John F. , Di Giulio Richard T. , Jayasundara Nishad 
Published: May 2024

AbstractThe microbiome has a significant influence on host physiological processes including energy metabolism and neurobiology. However, current knowledge is largely limited to post-embryonic development, highlighting a notable gap in host-microbe communication during embryonic development, particularly in oviparous organisms. This is because the developing embryo is protected from the external environment by the chorion and typically considered to be sterile. We hypothesized the external microbiome influences embryonic development in oviparous organisms despite lack of physical contact with microbes, shaping host physiology beyond embryogenesis. To test this interaction, we utilized zebrafish (Danio rerio) reared germ-free or conventionalized with microbes at different times during embryonic development (6 and 24 hours post fertilization) to examine changes in transcriptomics, proteomics, and physiology at 32 hours post-fertilization. In contrast to the prevailing notion, we reveal a significant role of the external aquatic microbial community in regulating embryonic transcript and protein abundance associated with critical developmental processes including energy metabolism and neurodevelopment. Furthermore, we demonstrate the external microbial community drives differential expression of genes involved in cytochrome P450 directed xenobiotic metabolism and associated bioenergetic and behavioral responses following exposure to a CYP1A activator during embryogenesis. These findings reveal embryonic development is an integration of host genetic blueprints and external microbial cues, enhancing knowledge of fundamental developmental processes influenced by embryo-microbe interactions that shape developmental susceptibility to environmental stressors.Significance StatementHost-microbiome interactions play a crucial role in shaping vertebrate physiology. However, the impact of these interactions during embryonic development remains poorly understood which has limited our evaluation of environmental drivers of developmental disorders and disease. Here, we provide evidence that the external microbiome indirectly communicates with the developing zebrafish (Danio rerio) embryo through the chorion, influencing physiological processes including bioenergetics, neurodevelopment, and xenobiotic responses. These findings signify a critical role of the external microbiome during the early stages of embryonic development and may inform research addressing the effects of the maternal microbiome on human embryonic and fetal development, particularly in the context of developmental origins of disease and prenatal chemical exposures.
Genomic and functional analysis ofrmplocus variants inKlebsiella pneumoniae
Authors: Lam Margaret M.C. , Salisbury Stephen M. , Treat Logan P. , Wick Ryan R. , Judd Louise M. , Wyres Kelly L. , Brisse Sylvain , Walker Kimberly A. , Miller Virginia L. , Holt Kathryn E. 
Published: May 2024

AbstractBackgroundKlebsiella pneumoniaeis an opportunistic pathogen and a leading cause of healthcare-associated infections in hospitals, which are frequently antimicrobial resistant (AMR). Exacerbating the public health threat posed byK. pneumoniae, some strains also harbor additional hypervirulence determinants typically acquired via mobile genetic elements such as the well-characterised large virulence plasmid KpVP-1. ThermpADClocus is considered a key virulence feature ofK. pneumoniaeand is associated with upregulated capsule expression and the hypermucoid phenotype, which can enhance virulence by contributing to serum resistance. Typically such strains have been susceptible to all antimicrobials besides ampicillin, however the recent emergence of AMR hypermucoid strains is concerning.MethodsHere, we investigate the genetic diversity, evolution, mobilisation and prevalence ofrmpADC, in a dataset of 14000 genomes from isolates of theKlebsiella pneumoniaespecies complex, and describe the RmST virulence typing scheme for trackingrmpADCvariants for the purposes of genomic surveillance. Additionally, we examine the functionality of representatives for variants ofrmpADCintroduced into a mutant strain lacking its nativermpADClocus.ResultsThermpADClocus was detected in 7% of the dataset, mostly from genomes ofK. pneumoniaeand a very small number ofK. variicolaandK. quasipneumoniae. Sequence variants ofrmpADCgrouped into five distinct lineages (rmp1, rmp2, rmp2A, rmp3andrmp4) that corresponded to unique mobile elements, and were differentially distributed across different populations (i.e. clonal groups) ofK. pneumoniae. All variants were demonstrated to produce enhanced capsule production and hypermucoviscosity.ConclusionThese results provide an overview of the diversity and evolution of a prominentK. pneumoniaevirulence factor and support the idea that screening forrmpADCinK. pneumoniaeisolates and genomes is valuable to monitor the emergence and spread of hypermucoidK. pneumoniae, including AMR strains.
Exploring evolution to uncover insights into protein mutational stability
Authors: Hermans Pauline , Tsishyn Matsvei , Schwersensky Martin , Rooman Marianne , Pucci Fabrizio 
Published: May 2024

AbstractDetermining the impact of mutations on the thermodynamic stability of proteins is essential for a wide range of applications such as rational protein design and genetic variant interpretation. Since protein stability is a major driver of evolution, evolutionary data are often used to guide stability predictions. Many state-of-the-art stability predictors extract evolutionary information from multiple sequence alignments (MSA) of proteins homologous to a query protein, and leverage it to predict the effects of mutations on protein stability. To evaluate the power and the limitations of such methods, we used the massive amount of stability data recently obtained by deep mutational scanning to study how best to construct MSAs and optimally extract evolutionary information from them. We tested different evolutionary models and found that, unexpectedly, independent-site models achieve similar accuracy to more complex epistatic models. A detailed analysis of the latter models suggests that their inference often results in noisy couplings, which do not appear to add predictive power over the independent-site contribution, at least in the context of stability prediction. Interestingly, by combining any of the evolutionary features with a simple structural feature, the relative solvent accessibility of the mutated residue, we achieved similar prediction accuracy to supervised, machine learning-based, protein stability change predictors. Our results provide new insights into the relationship between protein evolution and stability, and show how evolutionary information can be exploited to improve the performance of mutational stability prediction.
Guidance for triangulating data and estimates of HIV prevalence among pregnant women and coverage of PMTCT using the Spectrum AIDS Impact Module
Authors: Walters Magdalene K. , Korenromp Eline L. , Yakusik Anna , Wanyeki Ian , Kaboré André , Poimouribou Arthur , Ki Célestine , Dao Coumbo , Bambara Paul , Derme Salam , Ouedraogo Théophile , Tang Kai Hon , Boily Marie-Claude , Mahy Mary , Imai-Eaton Jeffrey W. 
Published: May 2024

AbstractBackgroundMost countries use the Spectrum AIDS Impact Module (Spectrum-AIM), antenatal care routine HIV testing, and antiretroviral treatment data to estimate HIV prevalence among pregnant women. Non-representative programme data may lead to inaccurate estimates HIV prevalence and treatment coverage for pregnant women.Setting154 locations in 126 countries.MethodsUsing 2023 UNAIDS HIV estimates, we calculated three ratios: (1) HIV prevalence among pregnant women to all women 15-49y (prevalence), (2) ART coverage before pregnancy to women 15-49y ART coverage (ART pre-pregnancy), and (3) ART coverage at delivery to women 15-49y ART coverage (PMTCT coverage). We developed an algorithm to identify and adjust inconsistent results within regional ranges in Spectrum-AIM, illustrated using Burkina Faso’s estimates.ResultsIn 2022, the mean regional ratio of prevalence among pregnant women to all women ranged from 0.68 to 0.95. ART coverage pre-pregnancy ranged by region from 0.40 to 1.22 times ART coverage among all women. Mean regional PMTCT coverage ratios ranged from 0.85 to 1.51. The prevalence ratio in Burkina Faso was 1.59, above the typical range 0.62-1.04 in western and central Africa. Antenatal clinics reported more PMTCT recipients than estimated HIV-positive pregnant women from 2015 to 2019. We adjusted inputted PMTCT programme data to enable consistency of HIV prevalence among pregnant women from programmatic routine HIV testing at antenatal clinics with values typical for Western and central Africa.ConclusionThese ratios offer Spectrum-AIM users a tool to gauge the consistency of their HIV prevalence and treatment coverage estimates among pregnant women with other countries in the region.
Neuropsychological and social predictors of participation in a deep brain stimulation study of Parkinson’s disease and dystonia
Authors: Hahn Amelia , Lazar Ann A. , Cernera Stephanie , Little Simon , Wang Sarah S. , Starr Philip A. , Racine Caroline A. 
Published: May 2024

AbstractObjectivesParticipation is essential to DBS research, yet circumstances that affect diverse participation remain unclear. Here we evaluate factors impacting participation in an adaptive DBS study of Parkinson’s disease (PD) and dystonia.MethodsTwenty participants were implanted with a sensing-enabled DBS device (Medtronic Summit RC+S) that allows neural data streaming in naturalistic settings and encouraged to stream as much as possible for the first five months after surgery. Using standardized baseline data obtained through neuropsychological evaluation, we compared neuropsychological and social variables to streaming hours.ResultsMarital status and irritability significantly impacted streaming hours (estimate=136.7, bootstrapped (b)CIb=45.0 to 249.0,pb=0.016, and estimate=-95.1,CIb=-159.9 to -49.2,pb=0.027, respectively). These variables remained significant after multivariable analysis. Composite scores on verbal memory evaluations predicted the number of hours of data streamed (R2=0.284, estimate=67.7,CIb=20.1 to 119.9,pb=0.019).DiscussionVerbal memory impairment, irritability, and lack of a caregiver may be associated with decreased participation. Further study of factors that impact research participation is critical to the sustained inclusion of diverse participants.
The Influence of Parkinson’s Disease on Depression Through Structural Equation Modeling
Authors: Moon Jasmine , Winninghoff Jonah , Paracha Mariam 
Published: May 2024

ABSTRACTObjectiveTo analyze and compare the magnitudes of nonmotor symptoms in depressed individuals with and without Parkinson’s Disease.MethodsDownloaded in January 2023, symptoms and characteristics of depressed individuals with and without Parkinson’s Disease were extracted from the longitudinal study Fox Insight. The directed acyclic graph theory was used to represent causal relationships and to determine the associations between nonmotor symptoms, depression, and Parkinson’s Disease. The 2-PL and the Rasch models were used to better fit the data and identify the items consistent with the assumptions.ResultsDropped interests and activitieswas the item that was of greatest impact and most characteristic for depressed individuals both with and without PD.Double visionwas the item of least difficulty while an additional item of significant impact wasPreferred to stay at home. Education attainment had little to no impact on depression severity in individuals with and without PD.ConclusionsDropped interests and activitieswas most severe within both populations. Relatedly, an increased average number of leisure hours was associated with greater depression severity. Overall, as an individual’s depression worsens, there is an overall upward trend in the severity of their nonmotor symptoms. We recommend additional analyses on the strength of relationships between these neurologic disorders and nonmotor symptoms.
Antimalarial Drug Resistance inPlasmodium falciparumfrom Tak Province, Thailand (1998-2001): A TaqMan Array Card Study
Authors: Thaloengsok Sasikanya , Chaisatit Chaiyaporn , Saingam Piyaporn , Lertsethtakarn Paphavee , Spring Michele , Sabaithip Sriwichai , Pholwat Suporn , Guler Jennifer L , Houpt Eric , Vesely Brian 
Published: May 2024

AbstractDespite declining malaria cases in Thailand, surveillance in endemic areas is crucial. Retrospectively analyzing samples from Tak province, Thailand, we found prevalent drugresistantPlasmodium falciparum, particularly to mefloquine and sulfadoxine/pyrimethamine. Notably, mutations indicating resistance to artemisinin were detected at low frequencies, suggesting evolving resistance. These findings stress the need for continuous surveillance to guide control strategies and prevent outbreaks, even with decreasing cases, to sustain malaria elimination efforts.
Associations between mosaic loss of sex chromosomes and incident hospitalization for atrial fibrillation in the United Kingdom
Authors: Lim Jungeun , Hubbard Aubrey K. , Blechter Batel , Shi Jianxin , Zhou Weiyin , Loftfield Erikka , Machiela Mitchell J. , Wong Jason Y.Y. 
Published: May 2024

AbstractBackgroundMosaic loss of chromosome Y (mLOY) in leukocytes of men reflects genomic instability from aging, smoking, and environmental exposures. A similar mosaic loss of chromosome X (mLOX) occurs among women. However, the associations between mLOY, mLOX, and risk of incident heart diseases are unclear.MethodsWe estimated associations between mLOY, mLOX, and risk of incident heart diseases requiring hospitalization, including atrial fibrillation, myocardial infarction, ischemic heart disease, cardiomyopathy, and heart failure. We analyzed 190,613 men and 224,853 women with genotyping data from the UK Biobank. Among these participants, we analyzed 37,037 men with mLOY and 13,978 women with mLOX detected using Mosaic Chromosomal Alterations caller. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of each incident heart disease in relation to mLOY in men and mLOX in women. Additionally, Mendelian randomization (MR) was conducted to estimate causal associations.ResultsAmong men, detectable mLOY was associated with elevated risk of atrial fibrillation (HR=1.06, 95%CI:1.03-1.11). The associations were apparent in both never-smokers (HR=1.07, 95%:1.01-1.14) and ever-smokers (HR=1.05, 95%CI:1.01-1.11) as well as men > and ≤60 years of age. MR analyses supported causal associations between mLOY and atrial fibrillation (HRMR-PRESSO=1.15, 95%CI:1.13-1.18). Among post-menopausal women, we found a suggestive inverse association between detectable mLOX and atrial fibrillation risk (HR=0.90, 95%CI:0.83-0.98). However, associations with mLOY and mLOX were not found for other heart diseases.ConclusionsOur findings suggest that mLOY and mLOX reflect sex-specific biological processes or exposure profiles related to incident atrial fibrillation requiring hospitalization.WHAT IS KNOWN?A previous population study found links between death from atrial fibrillation and heart failure, and mosaic loss of chromosome Y (mLOY) in leukocytes, which is a marker of genomic instability, environmental exposures, and aging. Additionally, mLOY has been associated cross-sectionally with prevalent cardiovascular and metabolic diseases.A similar but less common mosaic loss of chromosome X (mLOX) occurs among women but is role in disease pathogenesis is less characterized.The contributions of mLOY and mLOX to risk of hospitalization for incident atrial fibrillation, heart failure syndrome, and other heart diseases are unclear.WHAT THE STUDY ADDS?Among men, mLOY was associated with elevated risk of incident atrial fibrillation. Further, we found suggestive evidence linking mLOX to atrial fibrillation risk among women. Taken together, mLOY and mLOX potentially reflects sex-specific factors related to the pathogenesis of atrial fibrillation.
Carotid Intima-media thickness, carotid distensibility and incident heart failure in older men: The British Regional Heart Study
Authors: Akinmolayan Atinuke , Papacosta A Olia , Lennon Lucy T , Ellins Elizabeth A , Halcox Julian PJ , Whincup Peter H , Wannamethee S Goya 
Published: May 2024

AbstractObjectivesCarotid intima-media thickness (CIMT) and carotid distensibility are markers of arterial change, however little is known of the prognostic value in incident HF. We aimed to assess this prospective association.DesignLongitudinal analysis of data from the British Regional Heart Study, a prospective cohort studyParticipants1069 men aged 71-92 years, without a diagnosis of heart failure or myocardial infarction (MI) at baseline.MethodsBetween 2010-2012, participants completed a questionnaire, underwent a physical examination, and provided a fasting blood sample. CIMT and carotid artery distension were measured and carotid distensibility was calculated. Cox proportional hazards modelling was used to assess the multivariate-adjusted hazard ratios of incident HF by quartiles of CIMT and distensibility.ResultsAdjusted for age, social class, smoking, physical activity, alcohol status, BMI, use of statins and antihypertensives, prevalent diabetes mellitus and stroke, pulse pressure, and presence of atrial arrhythmias, lower carotid distensibility was associated with increased risk of incident HF (HR 2.55, 95% CI 1.24 to 5.24, p=0.01). The association persisted after further adjustment for CIMT and incident MI (HR 2.53, 95% CI 1.23 to 5.22, p=0.01). Higher CIMT was associated with increased risk of incident HF (HR 2.20, 95% CI 1.14 to 4.23, p=0.02). However, this was attenuated after adjustment for both CIMT and incident MI (HR 1.64, 95% CI 0.84 to 3.21, p=0.1).ConclusionsLow carotid artery distensibility, but not high carotid intima-media thickness (CIMT), was associated with an increased risk of incident heart failure, independent of the development of myocardial infarction.
Long-term risk of Stroke after Acute Coronary Syndrome. The ABC-10* Study on Heart Disease
Authors: Mahmoud Heba T. , Cordiano Rocco , Merotto David , Dario Mattia Ludovico , Cavuto Fiorella , Berton Giuseppe 
Published: May 2024

AbstractBackgroundPrevious studies link myocardial infarction to increased stroke risk. This long-term prospective study examines stroke incidence and outcomes in acute coronary syndrome (ACS) patients, identifying risk factors and geographic disparities.MethodsWe enrolled 535 ACS patients admitted to hospitals across three provinces in the Veneto region of Italy. Patients’ residences were classified into three urban and three rural areas in each province. Patients were followed prospectively for 24 years or until death.ResultsAll patients, except for three, completed the follow-up, totaling 6151 person-years. During follow-up, 84 patients experienced a stroke, with 85% being ischemic and 15% hemorrhagic, proving fatal in 43 cases. The stroke incidence rate was 14/1000 person-years. Multivariable Cox regression analysis identified older age (HR 1.84; 95% CI 1.30-2.60), atrial fibrillation (AF) (HR 2.64; 95% CI 1.49-4.67), and a higher albumin-to-creatinine ratio (HR 1.38; 95% CI 1.04-1.83) as independent predictors of overall stroke risk, while higher eGFR (HR 0.71; 95% CI 0.53-0.95) was independently associated with a lower risk.A sub-analysis revealed older age (HR 2.67; 95% CI 1.60-4.45) and AF (HR 2.95; 95% CI 1.38-6.32) as independent predictors of fatal stroke. Unexpectedly, we observed a higher fatal stroke risk in urban areas (HR 1.89; 95% CI 1.03-3.48) and southern provinces (HR 1.71; 95% CI 1.15-2.53).ConclusionThe ABC study identified several baseline clinical predictors associated with higher stroke risk long after ACS. A geographical association with the risk of fatal stroke was also observed, underscoring the importance of considering both individual clinical predictors and broader geographic factors in stroke prevention policies.