bluuebunny/crossref_metadata_2025_split huggingface dataset:
KLHDC7B, a novel gene associated with age-related hearing loss in humans, is required for the maintenance of hearing in mice
Authors: Kaufman Alexandra M. , Silver Benjamin , Donnianni Roberto A , Aguilar Carlos , Niu Lingzi , Johnson Daniel , Bullen Anwen , Corona Alma , van Soldt Benjamin J. , Vora Nilay , Batista Gervasio , Cortes-Burgos Luz , Copeland Jacqueline , Fallah Elika , Zhang Norman , Lehmkuhl Marina , Cancelarich Sarah , Campos Kara , Di Battista Miani Daniela , Mumphrey Jaylen , Croll Susan D , Walls Johnathon R. , Germino Mary , Bowl Michael R , Drummond Meghan C , Dawson Sally J. 
Published: October 2024

AbstractBackgroundAge-related hearing loss (ARHL) is the most common sensory loss in older adults, but the underlying pathological mechanisms remain unclear. Recent genome wide association studies (GWAS) have linked variation in a large number of genes with increased risk of ARHL for the first time. Amongst the strongest of these associations is variation inKLHDC7B,a gene of unknown function and one not previously linked to hearing.MethodsTo confirm whether KLHDC7B plays a role in hearing we investigated auditory function in two independent knockout mutant mouse models ofKlhdc7b: Klhdc7bIMPC−/−andKlhdc7bRegnΔ/Δon the C57BL/6N background and the B6.CAST-Cdh23753A>Gbackground respectively. The B6.CAST-Cdh23753A>Gbackground was backcrossed to correct a known age-related hearing loss (ahl) mutation incadherin 23present in both the C57BL/6N and C57BL/6J strains.ResultsWe showed thatKlhdc7bis expressed exclusively in inner and outer sensory hair cells within the cochlea of mice at the RNA and protein level. Homozygous mutants for both knockout mouse models display a similar early-onset, progressive and severe hearing loss. Histological characterization of the two mouse models suggests that hair cells develop normally and are present in neonates. However, after the onset of hearing there is a progressive loss of outer hair cells in a gradient from base to apex of the cochlea consistent with the hearing deficit in the mice and the pattern of hearing loss in ARHL. Inner hair cells remain intact up to the latest age examined (~8 weeks).ConclusionsOur data suggests KLHDC7B is required for maintenance of auditory function rather than in its development, supporting the novel association with ARHL in humans detected in recent GWAS. To our knowledge, this is the first validation in mouse of an ARHL association in humans detected in a GWAS. Our work also provides two distinct mouse models to further investigate the role of KLHDC7B in auditory function and for use in the development of therapeutic tools to prevent or treat ARHL.
Disentangling the effects of Anxious, Autistic and Psychotic Traits on Perceptual Inference
Authors: Bévalot Caroline , Meyniel Florent 
Published: October 2024

ABSTRACTThe brain combines sensory information and prior information, taking into account uncertainty, to perceive the world. This inference process approaches optimality in humans but with inter-individual differences associated with psychological traits. Previous results on these differences are in fact highly heterogeneous and even contradictory. We highlight experimental, modeling, and analysis choices that may contribute to this heterogeneity. We propose a set of tasks utilizing explicit and implicit priors, combined with computational modeling, to isolate the decision and learning stages of perceptual inference. Using a multidimensional approach, we characterized differences in perceptual inference associated with anxious, autistic and psychotic traits in two large samples from the general population. Our findings reveal that anxious, autistic, and psychotic traits form three distinct, yet correlated, dimensions. More anxious traits were associated with enhanced performance and greater reliance on sensory information at the decision stage. Autistic traits were not associated with any difference in perceptual inference; results for psychotic traits were inconsistent across the two samples. Results are partly different when using unidimensional analyses. Together, these results stress the importance of a multidimensional approach that takes anxious traits into account to characterize inter-individual differences in perceptual inference.
ISWI chromatin remodeler SMARCA5 is essential for meiotic gene expression and male fertility in mammals
Authors: Kataruka Shubhangini , Malla Aushaq B , Rainsford Shannon R , Lesch Bluma J 
Published: October 2024

AbstractRegulation of the transcriptome to promote meiosis is important for sperm development and fertility. However, how chromatin remodeling directs the transcriptome during meiosis in male germ cells is largely unknown. Here, we demonstrate that the ISWI family ATP-dependent chromatin remodeling factor SMARCA5 (SNF2H) plays a critical role in regulating meiotic prophase progression during spermatogenesis. Males with germ cell-specific depletion of SMARCA5 are infertile and unable to form sperm. Loss ofSmarca5results in failure of meiotic progression with abnormal spermatocytes beginning at the pachytene stage and an aberrant global increase in chromatin accessibility, especially at genes important for meiotic prophase.
Telomere length and cognitive function among middle-aged and older participants from communities underrepresented in aging research: A preliminary study
Authors: McLester-Davis Lauren W. Y. , Norton Derek , Papale Ligia A. , James Taryn T. , Salazar Hector , Asthana Sanjay , Johnson Sterling C. , Gooding Diane C. , Roy Trevor R. , Alisch Reid S. , Drury Stacy S. , Gleason Carey E. , Zuelsdorff Megan 
Published: October 2024

AbstractObjectiveAccelerated biological aging is a plausible and modifiable determinant of dementia burden facing minoritized communities, but is not well-studied in these historically underrepresented populations. Our objective was to preliminarily characterize relationships between telomere length and cognitive health among American Indian/Alaska Native (AI/AN) and Black/African American (B/AA) middle-aged and older adults.MethodsThis study included data on telomere length and cognitive test performance from 187 participants, enrolled in one of two community-based cognitive aging cohorts and who identified their primary race as AI/AN or B/AA.ResultsNested multivariable regression models revealed preliminary evidence for associations between telomere length and cognitive performance, and these associations were partially independent of chronological age.DiscussionSmall sample size limited estimate precision, however, findings suggest future work on telomere length and cognitive health in underrepresented populations at high risk for dementia is feasible and valuable as a foundation for social and behavioral intervention research.
Epigenetic and 3D genome reprogramming during the aging of human hippocampus
Authors: Zemke Nathan R. , Lee Seoyeon , Mamde Sainath , Yang Bing , Berchtold Nicole , Garduño B. Maximiliano , Indralingam Hannah S. , Bartosik Weronika M. , Lau Pik Ki , Dong Keyi , Yang Amanda , Tani Yasmine , Chen Chumo , Zeng Qiurui , Ajith Varun , Tong Liqi , Seng Chanrung , Li Daofeng , Wang Ting , Xu Xiangmin , Ren Bing 
Published: October 2024

AbstractAge-related cognitive decline is associated with altered physiology of the hippocampus. While changes in gene expression have been observed in aging brain, the regulatory mechanisms underlying these changes remain underexplored. We generated single-nucleus gene expression, chromatin accessibility, DNA methylation, and 3D genome data from 40 human hippocampal tissues spanning adult lifespan. We observed a striking loss of astrocytes, OPC, and endothelial cells during aging, including astrocytes that play a role in regulating synapses. Microglia undergo a dramatic switch from a homeostatic state to a primed inflammatory state through DNA methylome and 3D genome reprogramming. Aged cells experience erosion of their 3D genome architecture. Our study identifies age-associated changes in cell types/states and gene regulatory features that provide insight into cognitive decline during human aging.
An increase in reactive oxygen species underlies neonatal cerebellum repair
Authors: Pakula Anna , El Nagar Salsabiel , Bayin N. Sumru , Christensen Jens Bager , Stephen Daniel N. , Reid Adam James , Koche Richard , Joyner Alexandra L. 
Published: October 2024

AbstractThe neonatal mouse cerebellum shows remarkable regenerative potential upon injury at birth, wherein a subset of Nestin-expressing progenitors (NEPs) undergoes adaptive reprogramming to replenish granule cell progenitors that die. Here, we investigate how the microenvironment of the injured cerebellum changes upon injury and contributes to the regenerative potential of normally gliogenic-NEPs and their adaptive reprogramming. Single cell transcriptomic and bulk chromatin accessibility analyses of the NEPs from injured neonatal cerebella compared to controls show a temporary increase in cellular processes involved in responding to reactive oxygen species (ROS), a known damage-associated molecular pattern. Analysis of ROS levels in cerebellar tissue confirm a transient increased one day after injury at postanal day 1, overlapping with the peak cell death in the cerebellum. In a transgenic mouse line that ubiquitously overexpresses human mitochondrial catalase (mCAT), ROS is reduced 1 day after injury to the granule cell progenitors, and we demonstrate that several steps in the regenerative process of NEPs are curtailed leading to reduced cerebellar growth. We also provide preliminary evidence that microglia are involved in one step of adaptive reprogramming by regulating NEP replenishment of the granule cell precursors. Collectively, our results highlight that changes in the tissue microenvironment regulate multiple steps in adaptative reprogramming of NEPs upon death of cerebellar granule cell progenitors at birth, highlighting the instructive roles of microenvironmental signals during regeneration of the neonatal brain.
Multimodal predictions of end stage chronic kidney disease from asymptomatic individuals for discovery of genomic biomarkers
Authors: Rabinovici-Cohen Simona , Platt Daniel E , Iwamori Toshiya , Guez Itai , Dey Sanjoy , Bose Aritra , Kudo Michiharu , Cosmai Laura , Porta Camillo , Koseki Akira , Meyer Pablo 
Published: October 2024

AbstractChronic kidney disease (CKD) is a complex condition where the kidneys are damaged and progressively lose their ability to filter blood, 10% of the world population have the disease that often goes undetected until it is too late for intervention. Using the UK Biobank (UKBB) we constructed a CKD cohort of patients (n=46,986) with genomic, clinical and demographic data available, a subset (n=2,151) having also whole body Magnetic Resonance Imaging (MRI) scans. We used this multimodal cohort to successfully predict, from initially healthy patients, their 5-year outcomes for End-Stage Renal Disease (ESRD, n=210, AUC=0.804 ± 0.03 with 5 fold cross-validation) and the larger cohort for validation to predict time-to ESRD and perform Genome-wide association studies (GWAS). Extracting important clinical, phenotypic and genetic features from the models, we were able to stratify the cohorts based on a novel set of significant previously unreported SNPs related to mitochondria/cell death, kidney development and function. In particular, we show that the risk allele of SNP rs1383063 present in 30% of the population irrespective of ancestry and putatively regulatingMAGI-1, a gene expressed in the podocyte slit diaphragm, is a strong predictor of ESRD and stratifies male populations of older age.
Understanding Pain in Polycystic Ovary Syndrome: Health Risks and Treatment Effectiveness
Authors: Cherlin Tess , Mohammed Stephanie , Ottey Sasha , Sherif Katherine , Verma Shefali S. 
Published: October 2024

AbstractPolycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women, often accompanied by various symptoms including significant pain, such as dysmenorrhea, abdominal, and pelvic pain, which remains underexplored. This retrospective study examines electronic health records (EHR) data to assess the prevalence of pain in women with PCOS. Conducted on May 29, 2024, using data from 120 Health Care Organizations within the TriNetX Global Network, the study involved 76,859,666 women from diverse racial backgrounds. The analysis focused on the prevalence of pain among women with PCOS, both overall and in those prescribed PCOS-related medications. Relative risk ratios (RR) were calculated for future health outcomes and stratified by self-reported race. The study found that 19.21% of women with PCOS experienced pain, with the highest prevalence among Black or African American (32.11%) and White (30.75%) populations. Both the PCOS and PCOS and Pain cohorts exhibited increased RR for various health conditions, with significant differences noted across racial groups for infertility, ovarian cysts, obesity, and respiratory diseases. Additionally, women with PCOS who were treated with PCOS-related medications showed a decrease in pain diagnoses following treatment. In conclusion, this study highlights the critical need to address pain in the diagnosis and management of PCOS due to its significant impact on patient health outcomes.Impact StatementInsufficient data exist on the prevalence of pain in women with a PCOS diagnosis, and its associations with future health outcomes. Among, 444,348 women with PCOS in the TriNextX Global Network, 19.21% have dysmenorrhea, abdominal, and pelvic pain. Women with PCOS and Pain are at increased risk for developing ovarian cysts, infertility, T2D, and fatty liver disease and are at further risk when stratified by self-reported race groups.
Mortality and lost to follow-up among Tuberculosis patients on treatment in Meru County, Kenya: a retrospective cohort study
Authors: Ngari Moses M. , Mberia Jane K. , Kanana Eunice , Sanga Deche , Ngari Martin K. , Nyagah David N. , Abdullahi Osman A. 
Published: October 2024

AbstractTuberculosis (TB) remains a leading cause of death globally. Patients who get lost-to-follow-up (LTFU) during TB treatment have high risk of relapse, mortality, treatment failure and developing Multidrug resistant TB. Empirical data to monitor long-term TB treatment outcomes in low-and-middle income countries (LMICs) are sparse. We determined proportion of TB patients who die or are LTFU during six months of treatment and identified factors independently associated with mortality or LTFU. A retrospective cohort using data from routine Meru County TB surveillance system. We included 38020 records of TB patients aged ≥15 years on treatment 2012 to 2022. TB treatment outcomes of interest were LTFU or death within six months of treatment. Survival analyses accounting for competing events were performed. Among the 38020 patients included, 27608 (73%) were male and the median (IQR) age was 32 [25‒42] years. 26599 (70%) had bacteriologically confirmed TB while 11421 (30%) were clinically diagnosed. During 16531 person-years of follow-up, 2385 (6.3%, 95%CI 6.0‒6.5) and 1942 (5.1%, 95%CI 4.9‒5.3) patients were LTFU and died respectively. In the multivariable model, patients on re-treatment after LTFU or after failure and those previously treated compared to new TB patients were positively associated with LTFU. Patients coinfected with HIV and those with unknown HIV status were positively associated with LTFU. In contrast, females, clinically diagnosed, extra-pulmonary TB and older patients were negatively associated with LTFU. Patients HIV infected on ARVs, not on ARVs and unknown HIV status versus not infected were positively associated with mortality. Other comorbidities (not HIV), clinically diagnosed, undernourished and older patients were positively associated with mortality. More than 10% of TB patients either die or are LTFU before completing treatment. TB patients on re-treatment, HIV infected, clinically diagnosed, undernourished and the elderly needs more targeted interventions to improve survival and successfully treatment.
Prevalence and Risk Factors for Non-Communicable Chronic Diseases in Low and Middle-Income Countries: A Systematic Review and Meta-Analysis
Authors: Xavier Sancho Pedro , Gotine Ana Raquel Manuel , Vasco Melsequisete Daniel , Victor Audêncio 
Published: October 2024

AbstractBackgroundNon-communicable chronic diseases (NCDs) have become increasingly prominent in low- and middle-income countries (LMIC), driven by a rapid rise in their incidence. Current estimates suggest that these conditions account for approximately 80% of deaths in these regions. This study aimed to analyze the prevalence of NCDs and their associated risk factors in LMIC.MethodsElectronic searches were conducted in the PubMed, Embase, Scopus, Cochrane, and Virtual Health Library (VHL) databases between June and July 2023. Studies on the prevalence of NCDs, with or without associated risk factor analysis, were included. The quality of these studies was assessed using NIH tools, and a meta-analysis was conducted using the random-effects model.ResultsA total of 34 studies on hypertension and 22 studies on diabetes were included in the systematic review and meta-analysis. The estimated prevalence of hypertension was 24% (95% CI: 21.0; 28.0) and diabetes mellitus (DM) was 11% (95% CI: 10.0; 13.0), with future predictions for similar populations ranging from 11.0-46.0% for hypertension and 6.0-21.0% for DM. Geographic analysis revealed a lower prevalence of hypertension in Latin America and the Caribbean (7.0%) with no statistically significant differences compared to other regions (p-value = 0.101). The prevalence of DM was lower in Sub-Saharan Africa (5.0%; p-value < 0.001). The identified risk factors for hypertension included increased age, male sex, elevated BMI, alcohol consumption, excessive salt intake, and stress. For diabetes, the risk factors were increased age, lack of religious affiliation, elevated BMI, family history of DM, hypertension, high hemoglobin concentration (HbA1c), waist-to-hip ratio, smoking, and infection with Taenia spp.ConclusionNCDs such as hypertension and DM pose a growing public health challenge in low- and middle-income countries. Our findings may assist policymakers in identifying high-risk groups and recommending appropriate prevention strategies.Systematic Review RegistrationThe protocol was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) (registration number: CRD42024520601).
Spontaneous formation of different forms of alpha-synuclein fibrils from a recombinant protein
Authors: Egorov V.V. , Grudinina N.A. , Polyakov D.S. , Zabrodskaya Y.A. , Gavrilova N.V. , Shavlovsky M.M. 
Published: October 2024

AbstractAlpha-synuclein is a protein, the conformational changes of which lead to the development of such socially significant diseases as Parkinson’s disease and amyotrophic lateral sclerosis. The methods for differential diagnostics of these diseases based on the use of alpha-synuclein in a non-native conformation obtained from patients as a seed for inducing fibrillogenesis and studying the morphology of the resulting amyloid-like fibrils were described in a number of studies. The authors associate such properties of the seed with the presence of post-translational modifications in the protein obtained from patients. At the same time, the production of fibrils differing in morphology from recombinant alpha-synuclein under various conditions of fibrillogenesis is also described. In this work, we show that the formation of morphologically distinct fibril types from recombinant alpha-synuclein lacking post-translational modifications is possible under the same conditions, and that spontaneously arising different fibril types, when used as a seed for fibrillogenesis, lead to the formation of recombinant protein fibrils morphological similar to the parental seed. The results of the work can be used both in studying the fundamental mechanisms of conformation transfer and in developing test systems for synucleinopathies.
Microbial iCLIP2: Enhanced mapping of RNA-Protein interaction by promoting protein and RNA stability
Authors: Stoffel Nina Kim , Sankaranarayanan Srimeenakshi , Müntjes Kira , Körtel Nadine , Busch Anke , Zarnack Kathi , König Julian , Feldbrügge Michael 
Published: October 2024

AbstractThe entire RNA lifecycle, spanning from transcription to decay, is intricately regulated by RNA-binding proteins (RBPs). To understand their precise functions, it is crucial to identify direct targets, pinpoint their exact binding sites, and unravel the underlying specificityin vivo. Individual-nucleotide resolution UV crosslinking and immunoprecipitation 2 (iCLIP2) is a state-of-the-art technique that enables the identification of RBP binding sites at single-nucleotide resolution. However, in the field of microbiology, optimized iCLIP protocols compared to mammalian systems are lacking. Here, we present the first microbial iCLIP2 approach using the multi-RRM domain protein Rrm4 from the fungusUstilago maydisas an example. Key challenges such as inherently high RNase and protease activity in fungi were addressed by improving mechanical cell disruption and lysis buffer composition. Our modifications increased the yield of crosslink events and improved the identification of Rrm4 binding sites. Thus, we were able to pinpoint that Rrm4 binds the stop codons of nuclear-encoded mRNAs of mitochondrial respiratory complex I, III and V – revealing an intimate link between endosomal mRNA transport and mitochondrial physiology. Thus, our study serves as a paradigm for optimizing iCLIP2 procedures in challenging organisms or tissues under high RNase/ protease conditions.
Strong segregation promotes self-destructive cooperation
Authors: Wen Lingling , Bai Yang , Lan Yunquan , Shen Yaxin , She Xiaoyi , Dong Peng , Wang Teng , Fu Xiongfei , Huang Shuqiang 
Published: October 2024

AbstractSelf-destructive cooperator (SDC), where individuals sacrifice themselves for others, poses significant personal costs yet is widespread in nature. Traditional group selection theory struggles to explain its persistence, as the extreme cost of self-destruction typically exceeds the benefit to these individuals. Here, we predict that this behavior can endure in structured environments with strong segregation, where populations are divided into homogenous groups originating from one or two founding members. In such contexts, the benefits derived from SDC are primarily confined within the homogenous SDC groups, thus preserving the value of this altruistic sacrifice and ensuring its maintenance. To validate our hypothesis, we employ a synthetic system with engineered bacteria to mimic both SDC and non-sacrificing cheaters. We then conduct automated experiments facilitated by biofoundry technology to monitor and operate the subgroups with diverse growth behaviors stemming from a restricted number of initial cells because of strong segregation. Eventually, we demonstrate that SDC indeed maintains under strong segregation, and high stress benefits SDC because it reduces the benefits received by cheaters in heterogenous subgroups. This study extends the group selection theory to encompass even the most extreme manifestations of altruism and highlights the potential of automation in evolutionary research.