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Oligodendrocyte precursor cells facilitate neuronal lysosome release
Abstract Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes. A reduction in the number or branching of OPCs reduces these contacts, which is associated with lysosome accumulation and altered metabolism in neurons and more senescent neurons with age. A similar reduction in OPC branching and neuronal lysosome accumulation is seen in an early-stage mouse model of Alzheimer’s disease. Our findings have implications for the prevention of age-related pathologies and the treatment of neurodegenerative diseases.
Pediatric Diabetic Ketoacidosis (PDKA) among newly diagnosed diabetic patients at Dilla University Hospital, Dilla, Ethiopia: Prevalence and predictors
Background Diabetic ketoacidosis (DKA) is a morbid complication of Type 1 diabetes mellitus(T1DM), and its occurrence at diagnosis has rarely been studied in Ethiopia, despite the many cases seen in the pediatric population. Objective The aim of this study was to know the prevalence of DKA among patients with newly diagnosed diabetes mellitus and identify avoidable risk factors. Method This institution-based retrospective cross-sectional study was conducted from December 1, 2018 to December1, 2022. Newly diagnosed T1DM under 15 years were included in the study. DKA and the new diagnosis of type 1 DM were defined based on the 2022 ISPAD and other international guidelines. A data collection form was used to collect sociodemographic and clinical data. Descriptive, bivariate, and multivariate logistic regression analyses were conducted to identify the risk factors. Result Among the 61 newly diagnosed T1DM pediatric patients admitted, DKA was the initial presentation in 37 patients, accounting for 60.7% of the cases. The mean age at diagnosis was 8 (±3.85) years, with females being more affected. Clinical presentation revealed vomiting accompanied by signs of dehydration (32.4%), with polyuria, polydipsia and weight loss (26.2%) being the most common symptoms. The presence of adequate knowledge of signs and symptoms of DM (AOR = 0.07, 95%CI 0.019–0.0897, P value 0.017) and a family history of DM (AOR = 0.129 95%CI 0.019–0.897, P value 0.039) were protective factors against DKA as the initial diagnosis of DM. Moreover, new-onset type 1 DM without DKA was 1.5 times higher in children from families with a high monthly income (AOR = 1.473, 95% CI 0.679–3.195 p value 0.000) compared to those from families with low income. The presence of an infection prior to DKA (AOR = 11.69,95%CI 1.34–10.1,P value 0.026) was associated with the diagnosis of DKA at the initial presentation of DM. Conclusion A high number of children present with diabetic ketoacidosis (DKA) at the initial diagnosis of diabetes mellitus (DM), which is associated with inadequate knowledge of the signs and symptoms of DM as well as the masking effect of concomitant infections in these children. Healthcare professionals should endeavor to suspect and screen children. Continuous awareness creation of DM is encouraged to diagnose diabetes mellitus earlier and to decrease the prevalence of DKA as an initial presentation.
Scrutinizing the evidence of anthracene toxicity on adrenergic receptor beta-2 and its bioremediation by fungal manganese peroxidase via in silico approaches
Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction
ISLRWR: A network diffusion algorithm for drug–target interactions prediction
Machine learning techniques and computer-aided methods are now widely used in the pre-discovery tasks of drug discovery, effectively improving the efficiency of drug development and reducing the workload and cost. In this study, we used multi-source heterogeneous network information to build a network model, learn the network topology through multiple network diffusion algorithms, and obtain compressed low-dimensional feature vectors for predicting drug–target interactions (DTIs). We applied the metropolis–hasting random walk (MHRW) algorithm to improve the performance of the random walk with restart (RWR) algorithm, forming the basis by which the self-loop probability of the current node is removed. Additionally, the propagation efficiency of the MHRW was improved using the improved metropolis–hasting random walk (IMRWR) algorithm, facilitating network deep sampling. Finally, we proposed a correction of the transfer probability of the entire network after increasing the self-loop rate of isolated nodes to form the ISLRWR algorithm. Notably, the ISLRWR algorithm improved the area under the receiver operating characteristic curve (AUROC) by 7.53 and 5.72%, and the area under the precision-recall curve (AUPRC) by 5.95 and 4.19% compared to the RWR and MHRW algorithms, respectively, in predicting DTIs performance. Moreover, after excluding the interference of homologous proteins (popular drugs or targets may lead to inflated prediction results), the ISLRWR algorithm still showed a significant performance improvement.
Application of mean maximum Young’s modulus value as a new parameter for differential diagnosis of prostate diseases
SEC-MX: an approach to systematically study the interplay between protein assembly states and phosphorylation
Abstract A protein’s molecular interactions and post-translational modifications (PTMs), such as phosphorylation, can be co-dependent and reciprocally co-regulate each other. Although this interplay is central for many biological processes, a systematic method to simultaneously study assembly states and PTMs from the same sample is critically missing. Here, we introduce SEC-MX (Size Exclusion Chromatography fractions MultipleXed), a global quantitative method combining Size Exclusion Chromatography and PTM-enrichment for simultaneous characterization of PTMs and assembly states. SEC-MX enhances throughput, allows phosphopeptide enrichment, and facilitates quantitative differential comparisons between biological conditions. Conducting SEC-MX on HEK293 and HCT116 cells, we generate a proof-of-concept dataset, mapping thousands of phosphopeptides and their assembly states. Our analysis reveals intricate relationships between phosphorylation events and assembly states and generates testable hypotheses for follow-up studies. Overall, we establish SEC-MX as a valuable tool for exploring protein functions and regulation beyond abundance changes.
Effect of the intrinsic and extrinsic factors on the growth and development of young foals under subtropical conditions of Pakistan
This study was designed to explore the impact of intrinsic (breed of foal, age of dam, and age of foal at weaning) and extrinsic (season of birth and housing type) factors on the growth and survival of foals in the subtropical conditions of Pakistan. For the growth study, retrospective data analysis of foals (n = 150) born from purebred brood mares of Thoroughbred, Arabs, and Percheron breeds (n1, n2, and n3 = 50 each) was made. Six hundred and twenty-four (n = 624) foals born between 2020 to 2022 were observed for the study of foal survival rate. The survival of these foals till the age of one year was considered. To study the growth and development of foals, height, bone, and girth measurements were taken at multiple developmental stages (3, 6, 9, 12, 15, and 18 months of age). Statistical analysis revealed that late-weaned foals demonstrated superior growth metrics compared to early-weaned foals (P = 0.001) and sheltered housing conditions markedly enhanced growth parameters across all breeds and measurement intervals (P = 0.002). However, no significant effect of season (P > 0.05) on the growth measurements across breeds was found. Arab and Thoroughbred breeds demonstrated significant early growth advantages in foals from middle-aged dams, with marked differences in height, bone width, and girth; however, by 15 months, these differences were not statistically significant (P > 0.05). In contrast, Percheron foals showed consistent growth regardless of the dam’s age, suggesting breed-specific developmental influences (P = 0.885). Regarding the effects of extrinsic and intrinsic factors on foal survival, environmental conditions, and maternal age significantly impacted survival rates. Extreme winter conditions were associated with a notably lower survival probability (P = 0.002), and middle-aged dams exhibited significantly enhanced survival odds (P = 0.03). However, the influences of housing conditions and weaning age on survival were not statistically significant (P > 0.05), indicating these factors do not substantially affect foal survival within the first year. These results underscore the critical roles of weaning age, housing conditions, and age of dams in influencing foal growth and survival, highlighting the importance of tailored management practices in optimizing outcomes for the growth and development of young equines under subtropics.
Proteomic insights into dual-species biofilm formation of E. coli and E. faecalis on urinary catheters
Abstract Infections associated with urinary catheters are often caused by biofilms composed of various bacterial species that form on the catheters’ surfaces. In this study, we investigated the intricate interplay between Escherichia coli and Enterococcus faecalis during biofilm formation on urinary catheter segments using a dual-species culture model. We analyzed biofilm formation and global proteomic profiles to understand how these bacteria interact and adapt within a shared environment. Our findings demonstrated dynamic population shifts within the biofilms, with E. coli initially thriving in the presence of E. faecalis, then declining during biofilm development. E. faecalis exhibited a rapid decrease in cell numbers after 48 h in both single- and dual-species biofilms. Interestingly, the composition of the dual-species biofilms was remarkably diverse, with some predominantly composed of E. coli or of E. faecalis; others showed a balanced ratio of both species. Notably, elongated E. faecalis cells were observed in dual-species biofilms, a novel finding in mixed-species biofilm cultures. Proteomic analysis revealed distinct adaptive strategies E. coli and E. faecalis employed within biofilms. E. coli exhibited a more proactive response, emphasizing motility, transcription, and protein synthesis for biofilm establishment; whereas E. faecalis displayed a more reserved strategy, potentially downregulating metabolic activity, transcription, and translation in response to cohabitation with E. coli. Both E. coli and E. faecalis displayed significant downregulation of virulence-associated proteins when coexisting in dual-species biofilms. By delving deeper into these dynamics, we can gain a more comprehensive understanding of challenging biofilm-associated infections, paving the way for novel strategies to combat them.
Methylammonium-free, high-efficiency, and stable all-perovskite tandem solar cells enabled by multifunctional rubidium acetate
Retraction: Long Noncoding RNA-EBIC Promotes Tumor Cell Invasion by Binding to EZH2 and Repressing E-Cadherin in Cervical Cancer
Optimized deep learning model with integrated spectrum focus transformer for pavement distress recognition and classification
Coalescence of multiple topological orders in quasi-one-dimensional bismuth halide chains
The changes in health-related quality of life after attending cardiac rehabilitation: A qualitative systematic review of the perspective of patients living with heart disease
Background Although the benefits of engaging in cardiac rehabilitation are well established, patient perceptions of the changes in their health-related quality of life are poorly documented. This systematic review synthesized qualitative studies on patients’ perspectives of change in their health-related quality of life after attending cardiac rehabilitation. Objective To identify and synthesize the best available evidence on the perspective of patients living with heart disease about the changes in their health-related quality of life after attending cardiac rehabilitation. Methods Eight databases were used to identify relevant papers published in English and peer-reviewed, and no date restrictions were considered for the search. This systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to appraise the quality of each paper, and two independent reviewers conducted it. A meta-aggregation approach was used to synthesize the findings of the included studies. Results The search identified 10813 titles. Thirty-five full-text papers were reviewed after duplicates were removed, and the titles and abstracts were reviewed. Thirteen papers were retained for data synthesis. The synthesized findings were divided into three categories: building healthier habits, peer interaction, and improving mental health. Conclusion This review demonstrates the positive changes in health-related quality of life for those patients engaged in cardiac rehabilitation. Peer interaction with other patients improved both mental and physical health. This review indicated that adopting healthier habits, including healthy eating and regular physical activity, had substantial benefits in formulating healthy behavior. The role of peers in supporting the development of a healthy lifestyle appears to be an understudied avenue and has potential for development.
Orally administered live BCG and heat-inactivated Mycobacterium bovis protect bison against experimental bovine tuberculosis
Abstract Bovine tuberculosis (BTB) is an infectious disease of livestock and wildlife species that is caused by pathogenic members of the Mycobacterium tuberculosis complex such as Mycobacterium bovis. Due to the introduction of M. bovis-infected bison in the 1920s, BTB is now endemic in wood bison (Bison bison athabascae) population within the Wood Buffalo National Park (WBNP) in northern Canada. This disease poses a grave threat to the long-term survival of this ecologically and culturally important species and has the potential to cause zoonotic TB and spill over to BTB-free livestock and other bison herds that live in the surrounding areas. Thus, effective BTB control strategies in WBNP bison are urgently needed. To this end, we aerosol challenged young bison with different doses of virulent M. bovis and observed disease-associated delayed-type hypersensitivity, gross lung and lymph node pathology and histopathology, as well as M. bovis burden in target organs, thus confirming the establishment of BTB in challenged animals. We then assessed the safety and efficacy of oral live BCG versus oral heat-inactivated M. bovis (HIMB) given in a homologous prime-boost regimen in bison. While both BCG and HIMB offered protection against BTB, BCG-treated bison thrived more, presented with fewer lung lesions at necropsy and lower burden of virulent M. bovis than HIMB-treated animals. Strikingly, oral HIMB induced almost no delayed-type hypersensitivity to intradermal tuberculin while oral live BCG induced very low sensitivity to tuberculin in bison, indicating their potential as DIVA (differentiating infected from vaccinated animals) vaccines for use in this important wildlife species.
‘Dark proteins’ hiding in our cells could hold clues to cancer and other diseases
Biocatalytic enantioselective formation and ring-opening of oxetanes
Correction: LGBTQ+ identities in the Indian audiovisual advertisements: A content analysis
Patterns of physical activity in hunter-gatherer children compared with US and UK children
Abstract Contemporary hunter-gatherers are highly active, but little is known about physical activity levels in hunter-gatherer children. We analysed 150 days of accelerometer data from 51 BaYaka hunter-gatherer children (aged 3–18) in the Republic of Congo, comparing it with British and American children using samples from Millennium Cohort Study (MCS) and National Health and Nutrition Examination Survey (NHANES). BaYaka children were highly active, engaging in over 3 h of moderate-to-vigorous physical activity (MVPA) daily, surpassing British adolescents by over 70 min. Unlike US children, whose activity diminished with age, BaYaka children’s activity levels increased, irrespective of gender. This trend suggests that formal education may suppress activity among American children, a pattern not seen in the BaYaka community. Reflecting their foraging lifestyle, activity patterns varied within and between days in BaYaka children, a contrast to the more uniform daily activity observed in American children. Furthermore, our data challenges the concept of ‘teenage chronotypes’ prevalent in post-industrial societies, with adolescent BaYaka maintaining shorter sleep phases and later bedtimes, synchronized with sunrise. These findings highlight the impact of a foraging upbringing on children’s activity levels, providing a benchmark for understanding childhood physical activity and wellbeing.