The integrity of the myelin sheath of the spinal cord (SC) is essential for motor coordination. Seipin is an endoplasmic reticulum transmembrane protein highly expressed in adipose tissue and motor neurons in the SC. It was reported Seipin deficiency induced lipid dysregulation and neurobehavioral deficits, but the underlying mechanism, especially in SC, remains to be elucidated.
View Article and Find Full Text PDFComputer-aided drug discovery (CADD) utilizes computational methods to accelerate the identification and optimization of potential drug candidates. Free energy perturbation (FEP) and thermodynamic integration (TI) play a critical role in predicting differences in protein binding affinities between drug molecules. Here, we implement SPONGE-FEP, which incorporates selective integrated tempering sampling (SITS) to enhance sampling efficiency and contains an automated workflow for relative binding free energy (RBFE) calculations.
View Article and Find Full Text PDFBackground: Penile metastasis originating from prostate cancer is an extremely rare condition, typically associated with a poor prognosis. Therapeutic approaches are not well established and may require individualized adaptation based on clinical assessment. Radiotherapy is commonly utilized to alleviate symptoms.
View Article and Find Full Text PDFNucleosome repositioning is essential for establishing nucleosome-depleted regions (NDRs) to initiate transcription. This process has been extensively studied using structural, biochemical, and single-molecule approaches, which require homogenously positioned nucleosomes. This is often achieved using the Widom 601 sequence, a highly efficient nucleosome positioning element (NPE) selected for its unusually strong binding to the H3-H4 histone tetramer.
View Article and Find Full Text PDFBackground: Brain stimulation therapy (BST) has significant potential in treating psychiatric, movement, and cognitive disorders. Given the high prevalence of comorbidities among these disorders, we conducted an umbrella review to comprehensively assess the efficacy of BSTs in treating the core symptoms across these three categories of disorders.
Methods: We systematically searched for meta-analyses and network meta-analyses of randomized controlled trials with sham controls up to September 25, 2024, from databases including PubMed, PsycINFO, Embase, and the Cochrane Library.