Major pathologic changes in the proximal aorta underlie the life-threatening aortic aneurysms and dissections in Marfan Syndrome; current treatments delay aneurysm development without addressing the primary pathology. Because excess oxidative stress and nitric oxide/protein kinase G signaling likely contribute to the aortopathy, we hypothesized that cobinamide, a strong antioxidant that can attenuate nitric oxide signaling, could be uniquely suited to prevent aortic disease. In a well-characterized mouse model of Marfan Syndrome, cobinamide dramatically reduced elastin breaks, prevented excess collagen deposition and smooth muscle cell apoptosis, and blocked DNA, lipid, and protein oxidation and excess nitric oxide/protein kinase G signaling in the ascending aorta.
View Article and Find Full Text PDFAndrogen binding to the androgen receptor (AR) in the cytoplasm induces the AR to translocate to the nucleus, where it regulates the expression of target genes. Here, we found that androgens rapidly activated a plasma membrane-associated signaling node that enhanced nuclear AR functions. In murine primary osteoblasts, dihydrotestosterone (DHT) binding to a membrane-associated form of AR stimulated plasma membrane-associated protein kinase G type 2 (PKG2), leading to the activation of multiple kinases, including ERK.
View Article and Find Full Text PDFBackground: Veterans with post-traumatic stress disorder (PTSD) are more likely to report chronic pain than veterans without PTSD. Yoga has been shown to reduce both chronic pain and PTSD symptoms in clinical trials. The goal of our study was to assess the feasibility and acceptability of conducting a randomized controlled trial (RCT) that combined yoga and mantram repetition (Yoga + MR) into one program for military veterans with both chronic pain and PTSD.
View Article and Find Full Text PDFBackground: Trust is essential for healthy, reciprocal relationships; creating safe environments; engaging in transparent interactions; successfully negotiating power differentials; supporting equity and putting trauma informed approaches into practice. Less is known, however, about the ways that trust-building may be at the forefront of consideration during community capacity building efforts, what trust-building elements are perceived as essential for optimally engaging communities, and what practices might support these efforts.
Methods: The present study examines an evolving understanding of trust-building over the course of 3 years, from qualitative data derived during interviews with nine agency leads from a large and diverse urban community, who are spearheading community-based partnerships to create more trauma-informed communities and foster resiliency.
Cardiac contraction is modulated by the phosphorylation state of myosin regulatory light chain 2 (MLC-2v). The level of MLC-2v phosphorylation is dependent on the opposing activities of MLC kinases and phosphatases. The predominant MLC phosphatase found in cardiac myocytes contains Myosin Phosphatase Targeting Subunit 2 (MYPT2).
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