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Data-Driven Equation-Free Dynamics Applied to Many-Protein Complexes: The Microtubule Tip Relaxation.
Biophys J
January 2025
Department of Chemistry, Chicago Center for Theoretical Chemistry, The James Franck Institute, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois 60637, United States. Electronic address:
Microtubules (MTs) constitute the largest components of the eukaryotic cytoskeleton and play crucial roles in various cellular processes, including mitosis and intracellular transport. The property allowing MTs to cater to such diverse roles is attributed to dynamic instability, which is coupled to the hydrolysis of GTP (guanosine-5'-triphosphate) to GDP (guanosine-5'-diphosphate) within the β-tubulin monomers. Understanding the equilibrium dynamics and the structural features of both GDP- and GTP-complexed MT tips, especially at an all-atom level, remains challenging for both experimental and computational methods because of their dynamic nature and the prohibitive computational demands of simulating large, many-protein systems.
View Article and Find Full Text PDFIntegrating malaria vaccine and CRISPR/Cas9 gene drive: a comprehensive strategy for accelerated malaria eradication.
Malar J
January 2025
Department of Medicine, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
Malaria remains a significant public health challenge, particularly in low- and middle-income countries, despite ongoing efforts to eradicate the disease. Recent advancements, including the rollout of malaria vaccines, such as RTS,S/AS01 and R21/Matrix-M™, offer new avenues for prevention. However, the rise of resistance to anti-malarial medications necessitates innovative strategies.
View Article and Find Full Text PDFCardiovascular safety of osteoanabolic agents.
J Bone Miner Metab
January 2025
Toranomon Hospital Endocrine Center, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Purpose: Several osteoanabolic agents have been developed to build new bone more efficiently than anti-resorptive drugs. Among them, romosozumab, an anti-sclerostin antibody, is a potent pharmacological tool to prevent fractures in osteoporosis patients. The efficacy of romosozumab in preventing osteoporotic fractures is robust.
View Article and Find Full Text PDFSafety, efficacy, and immunogenicity of a novel IgG degrading enzyme (KJ103): results from two randomised, blinded, phase 1 clinical trials.
Gene Ther
January 2025
Shanghai Bao Pharmaceuticals Co., Ltd., No. 28 Luoxin Road, Baoshan, Shanghai, China.
The approved intravenous adeno-associated virus (AAV) therapies are limited by the widespread prevalence of pre-existing anti-AAV antibodies in the general population, which are known to restrict patients' ability to receive gene therapy and limit transfection efficacy in vivo. To address this challenge, we have developed a novel recombinant human immunoglobulin G degrading enzyme KJ103, characterized by low immunogenicity and clinical value for the elimination of anti-AAV antibodies in gene transfer. Herein, we conducted two randomized, blinded, placebo-controlled, single ascending dose Phase I studies in China and New Zealand, to evaluate the pharmacokinetics, pharmacodynamics, safety and immunogenicity of KJ103 in healthy volunteers.
View Article and Find Full Text PDFAdherence to multi-target stool DNA testing for colorectal cancer screening in the United States.
Int J Colorectal Dis
January 2025
Exact Sciences Corporation, Madison, WI, USA.
Purpose: Colorectal cancer (CRC) is the second leading cause of cancer mortality in the USA and is highly preventable, with early screening vital for improving outcomes. This study aimed to evaluate adherence rates of multi-target stool DNA (mt-sDNA) testing, following updated guidelines recommending screening starting at age 45.
Methods: This retrospective cohort study used aggregated data from Exact Sciences Laboratories LLC, examining new users (first-time testers) aged 45-85 with commercial, Medicare, or Medicaid insurance who received mt-sDNA test kits (point-of-care) between January 1, 2023, and June 1, 2023.
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