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Arrhythmogenic calmodulin variants D131E and Q135P disrupt interaction with the L-type voltage-gated Ca channel (Ca1.2) and reduce Ca-dependent inactivation.
Acta Physiol (Oxf)
February 2025
Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.
Aim: Long QT syndrome (LQTS) and catecholaminergic polymorphism ventricular tachycardia (CPVT) are inherited cardiac disorders often caused by mutations in ion channels. These arrhythmia syndromes have recently been associated with calmodulin (CaM) variants. Here, we investigate the impact of the arrhythmogenic variants D131E and Q135P on CaM's structure-function relationship.
View Article and Find Full Text PDFPancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines.
J Immunother Cancer
January 2025
Internal Medicine I, Ulm University Hospital, Ulm, Germany
Background: Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a "cold" tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.
View Article and Find Full Text PDFSquamocin Suppresses Tumor Growth through Triggering an Endoplasmic Reticulum Stress-Associated Degradation of EZH2/MYC Axis.
Adv Sci (Weinh)
January 2025
School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China.
Despite substantial advances in the antitumor effects of annonaceous acetogenins (ACGs), the absence of a defined biological action mechanism remains a major barrier to their clinical application. Here, it is found that squamocin effectively depletes both EZH2 and MYC in multiple cancer cell lines, including head and neck squamous cell carcinoma, and gastric and colorectal cancer, demonstrating potent efficacy in suppressing these in vivo tumor models. Through the combination of surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), and cellular thermal shift assay (CETSA), heat shock protein 90α (HSP90α) is identified as the direct binding target of squamocin.
View Article and Find Full Text PDFThe role of socioeconomic factors in sex differences in intrinsic capacity among older adults: A cross-sectional study in Taiwan.
Prev Med Rep
November 2024
National Center for Geriatrics and Welfare Research, National Health Research Institutes, Yunlin, Taiwan.
Objectives: The World Health Organization's Integrated Care for Older People (ICOPE) framework launched in 2019 is used to assess the intrinsic capacity of older individuals. Older women may face greater socioeconomic disadvantages, which can impact their physical and mental well-being. Therefore, we examined sex differences in intrinsic capacity and the influence of socioeconomic status.
View Article and Find Full Text PDFDifferential Relations Between Parenting and Emotion Regulation in Children with ASD Across Dyadic and Independent Contexts.
J Autism Dev Disord
January 2025
Department of Psychological Science and Claremont Autism Center, Claremont Mckenna College, Claremont, CA, USA.
Many children with ASD exhibit difficulties with emotion regulation that greatly impair functioning. Certain intrinsic correlates of dysregulation have been identified in this population, but the search for potential environmental influences has been less fruitful. The current study examined several aspects of parenting as correlates of observed regulation in Autistic children, as measured in both parent-child and independent regulatory contexts.
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