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Charge Reversal of the Uppermost Arginine in Sliding Helix S4-I Affects Gating of Cardiac Sodium Channel.
Int J Mol Sci
January 2025
Almazov National Medical Research Centre, 197341 St. Petersburg, Russia.
Several mutations of the uppermost arginine, R219, in the voltage-sensing sliding helix S4 of cardiac sodium channel Nav1.5 are reported in the ClinVar databases, but the clinical significance of the respective variants is unknown (VUSs). AlphaFold 3 models predicted a significant downshift of S4 in the R219C VUS.
View Article and Find Full Text PDFDiverse Interactions of Sterols with Amyloid Precursor Protein Transmembrane Domain Can Shift Distribution Between Alternative Amyloid-β Production Cascades in Manner Dependent on Local Lipid Environment.
Int J Mol Sci
January 2025
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997 Moscow, Russia.
Alzheimer's disease (AD) pathogenesis is correlated with the membrane content of various lipid species, including cholesterol, whose interactions with amyloid precursor protein (APP) have been extensively explored. Amyloid-β peptides triggering AD are products of APP cleavage by secretases, which differ depending on the APP and secretase location relative to ordered or disordered membrane microdomains. We used high-resolution NMR to probe the interactions of the cholesterol analog with APP transmembrane domain in two membrane-mimicking systems resembling ordered or perturbed lipid environments (bicelles/micelles).
View Article and Find Full Text PDFDynamic emotion intensity estimation from physiological signals facilitating interpretation via appraisal theory.
PLoS One
January 2025
Faculty of Engineering, Free University of Bozen-Bolzano, Bolzano, South Tyrol, Italy.
Appraisal models, such as the Scherer's Component Process Model (CPM), represent an elegant framework for the interpretation of emotion processes, advocating for computational models that capture emotion dynamics. Today's emotion recognition research, however, typically classifies discrete qualities or categorised dimensions, neglecting the dynamic nature of emotional processes and thus limiting interpretability based on appraisal theory. In our research, we estimate emotion intensity from multiple physiological features associated to the CPM's neurophysiological component using dynamical models with the aim of bringing insights into the relationship between physiological dynamics and perceived emotion intensity.
View Article and Find Full Text PDFIDH-mutant glioma risk stratification via whole slide images: Identifying pathological feature associations.
iScience
January 2025
Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
This article aims to develop and validate a pathological prognostic model for predicting prognosis in patients with isocitrate dehydrogenase (IDH)-mutant gliomas and reveal the biological underpinning of the prognostic pathological features. The pathomic model was constructed based on whole slide images (WSIs) from a training set ( = 486) and evaluated on internal validation set ( = 209), HPPH validation set ( = 54), and TCGA validation set ( = 352). Biological implications of PathScore and individual pathomic features were identified by pathogenomics set ( = 100).
View Article and Find Full Text PDFA randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study).
J Psychopharmacol
January 2025
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Background: Options for 'treatment-resistant bipolar depression' (TRBD) are limited. Two small, short-term, trials of pramipexole suggest it might be an option.
Aims: To evaluate the clinical effectiveness and safety of pramipexole in the management of TRBD.
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