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Theoretical monitoring of aromaticity induction from noble gases to Borole structure
Prebiotic formation of thioesters via cyclic anhydrides as a key step in the emergence of metabolism
Abstract Thioesters are high-energy derivatives of carboxylic acids that are essential in the functioning of today’s living cells. Their central role argues in favor of their early introduction in the abiotic reaction network which led to the emergence of life on Earth. We propose that the first thioesters appeared during the establishment of the reverse tricarboxylic acid (rTCA) cycle, an effective metabolic cycle for the synthesis of organic molecules from CO2. Most of the acids in this cycle are 1,4-diacids. We show that the formation of a cyclic anhydride from aqueous solutions of succinic or citric acid is possible using drying conditions over silica, as it could happen in an evaporating pond. When these 1,4-diacids are dried in the presence of thiols, thioesters are obtained. Our experimental and theoretical results demonstrate that analogs of succinyl-CoA and citryl-CoA, thioesters from the rTCA cycle, can be produced. Such a process highlights the importance of 1,4-diacids, which would have been introduced in the metabolism then under construction because of their ability to form anhydrides and to be activated in the absence of triphosphates or of any other activating agent. At its beginning, the rTCA cycle should therefore be interpreted mainly as a “1,4-diacid cycle”.
Children consider others’ need and reputation in costly sharing decisions
Abstract Children’s sharing decisions are shaped by recipient characteristics such as need and reputation, yet studies often focus on one characteristic at a time. This research examines how combinations of recipient characteristics impact costly sharing decisions among 3- to 9-year-old children (N = 186). Children were informed about the material need (needy or not needy) and reputation (sharing or not sharing) of potential recipients before having the opportunity to share stickers with them. Results indicated that sharing was higher when the recipient was needy and increased more when the recipient had a reputation for sharing. Children shared over half of their stickers with a needy, sharing recipient, and less than half with a not needy, not sharing recipient. Children shared equally with recipients who were needy and not sharing or not needy and sharing, suggesting no preference for either characteristic. To explore the emotional benefits of sharing, children rated their own and the recipient’s mood before and after sharing, showing a greater increase in ratings of the recipient’s mood when more resources were shared. These findings suggest that children consider multiple recipient characteristics in their sharing decisions, demonstrating altruism toward those in need and indirectly reciprocating past sharing based on reputation.
First report of Sarcocystis halieti in Asia: the genetic confirmation in muscles of the Eurasian sparrowhawk (Accipiter nisus) from Iran
A survey on the frequency of polycystic ovary morphology (PCOM) in infertile patients with septate and arcuate uterine anomalies: a cross-sectional study
Improving ALS detection and cognitive impairment stratification with attention-enhanced deep learning models
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease marked by motor deterioration and cognitive decline. Early diagnosis is challenging due to the complexity of sporadic ALS and the lack of a defined risk population. In this study, we developed Miniset-DenseSENet, a convolutional neural network combining DenseNet121 with a Squeeze-and-Excitation attention mechanism, using 190 autopsy brain images from the Gregory Laboratory at the University of Aberdeen. The model distinguishes controls, ALS patients with no cognitive impairment, and ALS patients with cognitive impairment (ALS-frontotemporal dementia) with 97.37% accuracy, addressing a significant challenge in overlapping neurodegenerative disorders involving TDP-43 proteinopathy. Miniset-DenseSENet outperformed other transfer learning models, achieving a sensitivity of 1 and specificity of 0.95. These findings suggest that integrating transfer learning and attention mechanisms into neuroimaging can enhance diagnostic accuracy, enabling earlier ALS detection and improving patient stratification. This model has the potential to guide clinical decisions and support personalied therapeutic strategies.
Effects of 12-week whole-body vibration training versus resistance training in older people with sarcopenia
PTPRO represses breast cancer lung metastasis by inhibiting the JAK2-YAP axis
Abstract Lung metastasis is the primary cause of breast cancer-related mortality. Protein tyrosine phosphatases such as PTPRO are important in cancer progression. However, the role and underlying mechanisms of PTPRO in breast cancer lung metastasis are largely unknown. The function of PTPRO in breast cancer metastasis was examined in mice with ptpro deficiency driven by the PyMT promoter. The regulatory role of PTPRO in JAK2–YAP activation was tested in cell-based knockdown, overexpression and catalytic-dead mutation assays. Bioinformatics analyses and assays of human cancer specimens and mouse tumour samples were performed to investigate PTPRO-regulated pathways and functions. Ptpro deletion in MMTV-PyMT transgenic mice led to increased lung metastasis. Bioinformatics analyses and subsequent assays of human breast cancer specimens revealed a reverse correlation between PTPRO expression and JAK2–YAP pathway activity. Both in vitro and in vivo data demonstrated that PTPRO inactivates the JAK2–YAP pathway and diminishes the metastatic ability of breast cancer. Analysis of catalytic-dead PTPRO mutant breast cancer cells confirmed that functional PTPRO is a determinant of the activation of the JAK2–YAP pathway and the suppression of breast cancer metastasis. Data from patient, animal and cell-based models collectively demonstrated that PTPRO suppresses breast cancer lung metastasis by inhibiting JAK2–YAP dephosphorylation. Therefore, strengthening PTPRO or targeting PTPRO-mediated pathways could be potential strategies for inhibiting breast cancer lung metastasis.
Does a cell’s gene expression always reflect its function?
Fenugreek seeds as a natural source of L-arginine-encapsulated lipid nanoparticles against diabetes
Association between climate related hazards and depression among coastal communities in Indonesia
Abstract Climate change has a profound impact on the mental health and well-being of people all over the world. However, studies on the impacts of climate-driven rising sea levels on mental health remain few. This study aims to examine the risk of depression among people who live in coastal areas susceptible to the natural hazards associated with climate change. We used the Indonesia Basic Health Survey 2018, which included 642,419 adults in Indonesia. Multivariable logistic regression analysis was conducted to examine the relationship between living in a coastal hazard area and depression. We included socio-demographics, health status, and health access information in the analysis to identify the most vulnerable groups. Our findings show that people who live in coastline hazard areas have 1.13 times higher odds to have depression than people who live outside those areas. Individuals living in the coastal hazards areas who were less likely to have autonomous mobility or resources, including young adults, females, those with low socio-economic conditions, and those with pre-existing health conditions, had a higher risk of depression than other groups. Culturally acceptable and effective mental health interventions should thus target these vulnerable populations and settings to effectively reduce climate-related health risks.
The efficacy of DASH combined with time-restricted feeding (16/8) on metabolic associated fatty liver disease management: a randomized controlled trial
Mapping cells through time and space with moscot
Abstract Single-cell genomic technologies enable the multimodal profiling of millions of cells across temporal and spatial dimensions. However, experimental limitations hinder the comprehensive measurement of cells under native temporal dynamics and in their native spatial tissue niche. Optimal transport has emerged as a powerful tool to address these constraints and has facilitated the recovery of the original cellular context 1–4 . Yet, most optimal transport applications are unable to incorporate multimodal information or scale to single-cell atlases. Here we introduce multi-omics single-cell optimal transport (moscot), a scalable framework for optimal transport in single-cell genomics that supports multimodality across all applications. We demonstrate the capability of moscot to efficiently reconstruct developmental trajectories of 1.7 million cells from mouse embryos across 20 time points. To illustrate the capability of moscot in space, we enrich spatial transcriptomic datasets by mapping multimodal information from single-cell profiles in a mouse liver sample and align multiple coronal sections of the mouse brain. We present moscot.spatiotemporal, an approach that leverages gene-expression data across both spatial and temporal dimensions to uncover the spatiotemporal dynamics of mouse embryogenesis. We also resolve endocrine-lineage relationships of delta and epsilon cells in a previously unpublished mouse, time-resolved pancreas development dataset using paired measurements of gene expression and chromatin accessibility. Our findings are confirmed through experimental validation of NEUROD2 as a regulator of epsilon progenitor cells in a model of human induced pluripotent stem cell islet cell differentiation. Moscot is available as open-source software, accompanied by extensive documentation.
Evaluation of magnetic resonance spectroscopy total sodium concentration measures, and associations with microstructure and physical impairment in cervical myelopathy
Abstract Spinal cord injury causes a cascade of physiological responses, which may trigger a subsequent neurotoxic increase in intracellular sodium. This can lead to neurodegeneration, both at and beyond the site of injury, causing clinical symptoms and loss of function. However, in vivo measurements of tissue sodium remain challenging. Here we utilise sodium magnetic resonance spectroscopy (23Na-MRS) at 3T to measure tissue sodium concentration (TSC) and its association with microstructural measures and macromolecular MRI metrics in the cervical spinal cord, distal to the site of injury. Twenty people with cervical myelopathy and twenty healthy controls, were studied. Associations with motor and sensory impairments were explored using ASIA and jOAMEQ scores. No significant difference in TSC in the cervical myelopathy group (39 ± 10 mM) relative to healthy controls (35 ± 13 mM) was found. However, patients had a significantly lower cord-cross-sectional area than controls (70 ± 9 mm2 vs. 82 ± 9 mm2, p < 0.001). Lower-extremity function positively correlated with intracellular volume fraction (p = 0.031). In conclusion, using 23Na-MRS, TSC in cervical myelopathy patients was successfully measured. Differences in TSC relative to healthy controls did not reach significance, despite a significant reduction in cord-cross-sectional area. However, lower intracellular volume fraction, indicating reduced neurite density distal to the site of injury, was associated with physical impairment.