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Analysis of the hemodynamic impact of coronary plaque morphology in mild coronary artery stenosis.
Comput Methods Programs Biomed
January 2025
Department of Mechanics & Engineering, College of Architecture & Environment, Sichuan University, Chengdu 610065, China; Sichuan University Yibin Park / Yibin Istitute of Industrial Technology, Yibin 644000, China. Electronic address:
Objectives: As is well known, plaque morphology plays an important role in the hemodynamics of stenotic coronary arteries, thus their clinic outcomes. However, so far, there has been no research on how the cross-sectional shape of a stenotic lumen affects its hemodynamics. Therefore, this study aims to explore the impact of plaque cross-sectional shape on coronary hemodynamics under mild or moderate stenosis conditions (diameter stenosis degree ≤50 %).
View Article and Find Full Text PDFDe novo design of peptide binders to conformationally diverse targets with contrastive language modeling.
Sci Adv
January 2025
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Designing binders to target undruggable proteins presents a formidable challenge in drug discovery. In this work, we provide an algorithmic framework to design short, target-binding linear peptides, requiring only the amino acid sequence of the target protein. To do this, we propose a process to generate naturalistic peptide candidates through Gaussian perturbation of the peptidic latent space of the ESM-2 protein language model and subsequently screen these novel sequences for target-selective interaction activity via a contrastive language-image pretraining (CLIP)-based contrastive learning architecture.
View Article and Find Full Text PDFWWC proteins-mediated compensatory mechanism restricts schwannomatosis driven by loss of function.
Sci Adv
January 2025
Institute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
NF2-related schwannomatosis, previously known as neurofibromatosis type 2, is a genetic disorder characterized by nerve tumors due to gene mutations. Mice with deletion develop schwannomas slowly with low penetrance, hence inconvenient for preclinical studies. Here, we show that NF2, by recruiting E3 ubiquitin ligases β-TrCP1/2, promotes WWC1-3 ubiquitination and degradation.
View Article and Find Full Text PDFDistributed representations of temporally accumulated reward prediction errors in the mouse cortex.
Sci Adv
January 2025
Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232, Singapore.
Reward prediction errors (RPEs) quantify the difference between expected and actual rewards, serving to refine future actions. Although reinforcement learning (RL) provides ample theoretical evidence suggesting that the long-term accumulation of these error signals improves learning efficiency, it remains unclear whether the brain uses similar mechanisms. To explore this, we constructed RL-based theoretical models and used multiregional two-photon calcium imaging in the mouse dorsal cortex.
View Article and Find Full Text PDFThe deubiquitinase USP5 prevents accumulation of protein aggregates in cardiomyocytes.
Sci Adv
January 2025
Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Protein homeostasis is crucial for maintaining cardiomyocyte (CM) function. Disruption of proteostasis results in accumulation of protein aggregates causing cardiac pathologies such as hypertrophy, dilated cardiomyopathy (DCM), and heart failure. Here, we identify ubiquitin-specific peptidase 5 (USP5) as a critical determinant of protein quality control (PQC) in CM.
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