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On the calculation of carbon and nutrient transport to the oceans
mPEG-PCL modified Caffeic acid eye drops for endotoxin-induced uveitis treatment
Axonal RNA localization is essential for long-term memory
Abstract Localization of mRNAs to neuronal terminals, coupled to local translation, has emerged as a prevalent mechanism controlling the synaptic proteome. However, the physiological regulation and function of this process in the context of mature in vivo memory circuits has remained unclear. Here, we combined synaptosome RNA profiling with whole brain high-resolution imaging to uncover mRNAs with different localization patterns in the axons of Drosophila Mushroom Body memory neurons, some exhibiting regionalized, input-dependent, recruitment along axons. By integrating transcriptome-wide binding approaches and functional assays, we show that the conserved Imp RNA binding protein controls the transport of mRNAs to Mushroom Body axons and characterize a mutant in which this transport is selectively impaired. Using this unique mutant, we demonstrate that axonal mRNA localization is required for long-term, but not short-term, behavioral memory. This work uncovers circuit-dependent mRNA targeting in vivo and demonstrates the importance of local RNA regulation in memory consolidation.
Multilingual hope speech detection from tweets using transfer learning models
Abstract Social media has become a powerful tool for public discourse, shaping opinions and the emotional landscape of communities. The extensive use of social media has led to a massive influx of online content. This content includes instances where negativity is amplified through hateful speech but also a significant number of posts that provide support and encouragement, commonly known as hope speech. In recent years, researchers have focused on the automatic detection of hope speech in languages such as Russian, English, Hindi, Spanish, and Bengali. However, to the best of our knowledge, detection of hope speech in Urdu and English, particularly using translation-based techniques, remains unexplored. To contribute to this area we have created a multilingual dataset in English and Urdu and applied a translation-based approach to handle multilingual challenges and utilized several state-of-the-art machine learning, deep learning, and transfer learning based methods to benchmark our dataset. Our observations indicate that a rigorous process for annotator selection, along with detailed annotation guidelines, significantly improved the quality of the dataset. Through extensive experimentation, our proposed methodology, based on the Bert transformer model, achieved benchmark performance, surpassing traditional machine learning models with accuracies of 87% for English and 79% for Urdu. These results show improvements of 8.75% in English and 1.87% in Urdu over baseline models (SVM 80% English and 78% in Urdu).
Neurotransmitters’ white matter mapping unveils the neurochemical fingerprints of stroke
Cardiopulmonary exercise capacity markers and their link to symptom burden in patients at risk for heart failure with non-reduced ejection fraction
Abstract The American Heart Association (AHA) guidelines assess heart failure (HF) via comorbidities, laboratory markers, and echocardiography, while the New York Heart Association (NYHA) classification evaluates functional capacity. The primary objective of this study was to investigate the correlation between objectified HF-related symptoms and cardiac and muscular exercise capacity in Stage B HF patients with non-reduced ejection fraction. As secondary endpoints, we stratified this analysis for subgroups of NYHA classes to evaluate the primary endpoint for different levels of impairment and for sex to address for differences between men and women. Sixty-two Stage B HF patients with non-reduced EF were screened from an HF-risk cohort. Assessments included medical history, HF-related symptoms (Kansas City Cardiomyopathy Questionnaire, KCCQ), physical examination, laboratory tests, echocardiography, and cardiopulmonary exercise testing (CPET) with cardiac output monitoring. Correlations were analyzed between KCCQ score and exercise capacity markers: maximal oxygen uptake (VO2max), arterio-venous oxygen difference (avDO2), cardiac power output (CPO), mean arterial pressure (MAP), and respiratory efficiency (Ve/VO2). Subgroup analyses were performed by sex and NYHA class determined by VO2max or KCCQ functional scores. Our HF patient cohort showed reduced KCCQ scores (78.3) and VO₂max (22.9 ml/kg/min), and a progressed reduction in avDO₂. In the total cohort, KCCQ scores showed moderate correlations with Ve/VO₂ (r = -0.39) and MAP (r = 0.27). NYHA stratification by VO₂max revealed differences in avDO₂ and cardiac output but not KCCQ scores, while KCCQ-functional stratification only showed differences in Ve/VO₂. Sex-specific analysis showed KCCQ scores correlated with CPO in men (r = 0.65) and Ve/VO2 in women (r = -0.68). Our identified Stage B HFpEF cohort showed already alterations in total, cardiac and muscular exercise limitation. The HF symptom severity was weakly associated to the higher blood pressure and ventilatory inefficiency and, but moderately to strongly correlated CPO in men and Ve/VO2 in women in sex-specific analyses.
Regulation of acetyl-CoA biosynthesis via an intertwined acetyl-CoA synthetase/acetyltransferase complex
Abstract Acetyl-CoA synthetase (Acs) generates acetyl-coenzyme A (Ac-CoA) but its excessive activity can deplete ATP and lead to a growth arrest. To prevent this, Acs is regulated through Ac-CoA-dependent feedback inhibition executed by Ac-CoA-dependent acetyltransferases such as AcuA in Bacillus subtilis. AcuA acetylates the catalytic lysine of AcsA turning the synthetase inactive. Here, we report that AcuA and AcsA form a tightly intertwined complex – the C-terminal domain binds to acetyltransferase domain of AcuA, while the C-terminus of AcuA occupies the CoA-binding site in the N-terminal domain of AcsA. Formation of the complex reduces AcsA activity in addition to the well-established acetylation of the catalytic lysine 549 in AcsA which we show can disrupt the complex. Thus, different modes of regulation accomplished through AcuA adjust AcsA activity to the concentrations of the different substrates of the reaction. In summary, our study provides detailed mechanistic insights into the regulatory framework underlying acetyl-CoA biosynthesis from acetate.
Chronic administration of ivabradine improves cardiac Ca handling and function in a rat model of Duchenne muscular dystrophy
Abstract Duchenne muscular dystrophy (DMD), a severe muscle disease caused by mutations in the gene encoding for the intracellular protein dystrophin, is associated with impaired cardiac function and arrhythmias. A causative factor for complications in the dystrophic heart is abnormal calcium (Ca) handling in ventricular cardiomyocytes, and restoration of normal Ca homeostasis has emerged as therapeutic strategy. Here, we used a rodent model of DMD, the dystrophin-deficient DMDmdx rat, to test the following hypothesis: chronic administration of ivabradine (IVA), a drug clinically approved for the treatment of heart failure, improves Ca handling in dystrophic ventricular cardiomyocytes and thereby enhances contractile performance in the dystrophic heart. Intracellular Ca measurements revealed that 4-months administration of IVA to DMDmdx rats significantly improves Ca handling properties in dystrophic ventricular cardiomyocytes. In particular, IVA treatment increased electrically-evoked Ca transients and speeded their decay. This suggested enhanced sarcoplasmic reticulum Ca release and faster removal of Ca from the cytosol. Chronic IVA administration also enhanced the sarcoplasmic reticulum Ca load. Transthoracic echocardiography revealed a significant improvement of cardiac systolic function in IVA-treated DMDmdx rats. Thus, left ventricular ejection fraction and fractional shortening were enhanced, and end-systolic as well as end-diastolic diameters were diminished by the drug. Finally, chronic IVA administration neither significantly attenuated cardiac fibrosis and apoptosis, nor was vascular function improved by the drug. Collectively our findings suggest that long-term IVA administration enhances contractile function in the dystrophic heart by improvement of Ca handling in ventricular cardiomyocytes. Chronic IVA administration may be beneficial for DMD patients.
Midbrain ghrelin receptor signalling regulates binge drinking in a sex specific manner
Abstract Risky drinking rates are rising, particularly in women, yet sex as a biological variable has only recently gained traction. The centrally projecting Edinger-Westphal (EWcp) nucleus has emerged as a key regulator of alcohol consumption. Here we found that EWcppeptidergic cells reduce binge drinking specifically in female mice. We show this effect is mediated by the ghrelin receptor (GHSR), with EWcppeptidergic inhibition blocking ghrelin-induced drinking and Ghsr knockdown in EWcppeptidergic, but not EWcpglutamatergic or ventral tegmental area cells, reducing binge drinking in females, independent of circulating sex hormones. Female mice showed higher EWcp Ghsr expression, and EWcppeptidergic neurons were more sensitive to ghrelin. Moreover, intra-EWcp delivery of GHSR inverse agonist and antagonist reduced binge drinking, suggesting direct actions of ghrelin. These findings highlight the EWcp as a critical mediator of excessive alcohol consumption via GHSR in female mice, offering insights into the ghrelin system’s role in alcohol consumption.
Multimodal machine learning for deception detection using behavioral and physiological data
Uncovering local integrability in quantum many-body dynamics
Relationship between serum uric acid levels and metabolism associated fatty liver disease in postmenopausal women based on NHANES 2017–2020
Abstract Studies have shown that postmenopausal women have more metabolic abnormalities than premenopausal women. No consensus exists on how serum uric acid (sUA) affects metabolism-associated fatty liver disease (MAFLD) in postmenopausal women.This prospective observational study examined this link using National Health and Nutrition Examination Survey (NHANES) 2017 to 2020 data. We divided women’s sUA levels into four quartiles and used logistic regression, subgroup analyses, and restricted triple spline methods to compare the prevalence of MAFLD in postmenopausal and non-menopausal women. We also used histograms to analyze the effect of BMI-based indices. This population-based study involved 4477 women, including 1139 postmenopausal women aged 55–73 years. Multivariate logistic regression showed that, in the fully adjusted model, we found that participants in the highest quartile of sUA had a statistically significant 254% increased risk of MAFLD compared with participants in the lowest quartile (OR: 3.54; 95% CI 3.54 1.47–8.55; P < 0.001). Subgroup analyses showed no significant interaction between sUA levels and specific subgroups P( > 0.05 for all interactions). Additionally, RCS and threshold analysis showed a linear correlation (P = 0.186) and an ideal inflection point of 4.6 (P = 0.818) to the left. Right of the inflection point, the effect size was 1.524 (95% CI 1.291–1.814; P < 0.01). Histograms demonstrated that postmenopausal BMI increased sUA’s influence on MAFLD and higher sUA levels and BMI may enhance the prevalence of MAFLA in US postmenopausal women. The results of this study suggest that monitoring sUA levels in the postmenopausal period is critical in determining the occurrence of and interventions for MAFLD.
A TaSnRK1α-TaCAT2 model mediates resistance to Fusarium crown rot by scavenging ROS in common wheat
Genome-wide association studies of dairy cattle resistance to digital dermatitis recorded at four distinct lactation stages
Abstract Digital dermatitis (DD) is an endemic infectious hoof disease causing lameness in dairy cattle. The aim of the present study was to investigate the genetic profile of DD development using phenotypic and genotypic data on 2192 Holstein cows. The feet of each cow were clinically examined four times: pre-calving, shortly after calving, near peak of milk production, and in late lactation. Presence or absence of disease and proportion of healthy feet per cow constituted two DD phenotypes of study. For each phenotype and timepoint of clinical examination, we conducted single-step genome-wide association analyses to identify individual markers and genomic regions linked to DD. We focused on the ten 1-Mb windows that explained the largest proportion of the total genetic variance as well as windows that enclosed significant markers. Functional enrichment analysis was also applied to determine functional candidate genes for DD. Significant (P < 0.05) genomic heritability estimates were derived ranging from 0.21 to 0.25. Results revealed two markers on chromosomes 7 and 15 that were related to both disease phenotypes. Furthermore, we identified three genomic windows on chromosome 14 and one window on chromosome 7 each explaining more than 1% of the trait additive genetic variance. Functional enrichment analysis revealed multiple promising candidate genes implicated in hoof health, wound healing, and inflammatory skin diseases. Collectively, our results provide novel insights into the biological mechanism of host resistance to DD development in dairy cattle and support genomic selection towards improving foot health.
Spatiotemporally resolved mapping of extracellular proteomes via in vivo-compatible TyroID
DSS-YOLO: an improved lightweight real-time fire detection model based on YOLOv8
Caspase 9-induced apoptosis enables efficient fetal cell ablation and disease modeling
Abstract Fetal cell ablation models are crucial for studying congenital diseases, organ regeneration, and xenotransplantation. However, conventional knockout models offer limited control over disease severity, while conditional ablation models often require fetus-harming inducers. In the present study, we demonstrate that the inducible caspase 9 system enables precise targeting of fetal nephron progenitor cells in mice through the intrinsic apoptotic pathway. Using a safe, placenta-permeable inducer, this system facilitates specific, rapid, and efficient cell ablation. The system’s temporal control allows precise adjustment of disease severity, generating reproducible models ranging from congenital kidney deficiency to severe chronic kidney disease. Cells with low expression levels of inducible caspase 9 and those in solid organs are less susceptible to apoptosis. However, this limitation can be overcome by inhibiting the X-linked inhibitor of apoptosis protein, thereby expanding the system’s applicability. Additionally, this model provides a developmental environment suitable for chimeric kidney regeneration. This system advances understanding of induced cell death mechanisms, enhances pathological research tools, and supports therapeutic development in kidney disease and xenotransplantation applications.