Publications by authors named "Richard C Stahl"

Introduction: Hidradenitis suppurativa (HS) is a prevalent and persistent inflammatory skin disorder, lacking a known cure or effective biomarkers for early diagnosis at present. The genetic determinants of HS have not been fully documented, but it is believed to result from a combination of genetic and environmental factors.

Methods: To identify relevant HS gene variants in sporadic HS patients, this study utilized longitudinal electronic health records (EHRs) and whole-exome sequencing.

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Article Synopsis
  • Truncating variants in the Titin gene (TTNtvs) are linked to idiopathic dilated cardiomyopathy (DCM) but their effects across different ancestries and clinical contexts have not been fully explored.
  • The study analyzed genetic data from over 71,000 individuals, identifying those with TTNtvs, particularly in heart-expressed regions, and assessed their health records for DCM-related outcomes.
  • The findings revealed that TTNtvs significantly increased the risk of DCM in individuals of European ancestry, but had a negligible association in those of African ancestry, pointing to the influence of genetic background on disease risk profiles.
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Many studies have shown that tetraspanins play important role in cell-cell and cell-extracellular matrix (ECM) interactions. The repertoire and functions of tetraspanins in Schwann cells, glial cells of the peripheral nervous system have remained largely uncharacterized. This study was undertaken to identify Schwann cell tetraspanins and to elucidate their possible functions.

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The extracellular matrix of peripheral nerve is formed from a diverse set of macromolecules, including glycoproteins, collagens and proteoglycans. Recent studies using knockout animal models have demonstrated that individual components of the extracellular matrix play a vital role in peripheral nerve development and regeneration. In this study we identified fibrillin-1 and fibrillin-2, large modular structural glycoproteins, as components of the extracellular matrix of peripheral nerve.

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The Schwann cell basal lamina acts as an organizer of peripheral nerve tissue and influences many aspects of cell behavior during development and regeneration. A principal component of the Schwann cell basal lamina is laminin-2. This study was undertaken to identify Schwann cell receptors for laminin-2.

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Phospholemman (PLM), a member of the FXYD family of small ion transport regulators, inhibits cardiac Na+/Ca2+ exchanger (NCX1). NCX1 is made up of N-terminal domain consisting of the first five transmembrane segments (residues 1-217), a large intracellular loop (residues 218-764), and a C-terminal domain comprising the last four transmembrane segments (residues 765-938). Using glutathione S-transferase (GST) pull-down assay, we demonstrated that the intracellular loop, but not the N- or C-terminal transmembrane domains of NCX1, was associated with PLM.

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Embryonic sensory neurons express membrane-anchored growth factors that stimulate proliferation and differentiation of Schwann cells. The most important of these are members of the neuregulin-1 (Nrg-1) family that activate the erbB2/erbB3 receptor kinase on Schwann cells. Nrg-1 growth factors display a complex pattern of alternative mRNA splicing.

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Schwann cell myelination requires interactions with the extracellular matrix (ECM) mediated by cell surface receptors. Previously, we identified a type V collagen family member, alpha4(V) collagen, which is expressed by Schwann cells during peripheral nerve differentiation. This collagen binds with high affinity to heparan sulfate through a unique binding motif in the noncollagenous N-terminal domain (NTD).

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Messenger RNA levels of phospholemman (PLM), a member of the FXYD family of small single-span membrane proteins with putative ion-transport regulatory properties, were increased in postmyocardial infarction (MI) rat myocytes. We tested the hypothesis that the previously observed reduction in Na+-K+-ATPase activity in MI rat myocytes was due to PLM overexpression. In rat hearts harvested 3 and 7 days post-MI, PLM protein expression was increased by two- and fourfold, respectively.

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Overexpression of phospholemman (PLM) in normal adult rat cardiac myocytes altered contractile function and cytosolic Ca2+ concentration ([Ca2+]i) homeostasis and inhibited Na+/Ca2+ exchanger (NCX1). In addition, PLM coimmunoprecipitated and colocalized with NCX1 in cardiac myocyte lysates. In this study, we evaluated whether the cytoplasmic domain of PLM is crucial in mediating its effects on contractility, [Ca2+]i transients, and NCX1 activity.

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During peripheral nerve development, Schwann cells synthesize collagen type V molecules that contain alpha4(V) chains. This collagen subunit possesses an N-terminal domain (NTD) that contains a unique high affinity heparin binding site. The alpha4(V)-NTD is adhesive for Schwann cells and sensory neurons and is an excellent substrate for Schwann cell and axonal migration.

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Mutations in sarcoglycans (SG) have been reported to cause autosomal-recessive limb-girdle muscular dystrophy (LGMD) and dilated cardiomyopathy. In skeletal and cardiac muscle, sarcoglycans exist as a complex of four transmembrane proteins (alpha-, beta-, gamma-, and delta-SG). In this study, the assembly of the sarcoglycan complex was examined in a heterologous expression system.

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Schwann cells transiently express the transmembrane heparan sulfate proteoglycan syndecan-3 during the late embryonic and early postnatal periods of peripheral nerve development. Neonatal rat Schwann cells released soluble syndecan-3 into the culture medium by a process that was blocked by inhibition of endogenous matrix metalloproteinase activity. When Schwann cells were plated on a substratum that binds syndecan-3, the released proteoglycan bound to the substratum adjacent to the cell border.

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Previous studies have shown that overexpression of phospholemman (PLM) affected contractile function and Ca(2+) homeostasis in adult rat myocytes. We tested the hypothesis that PLM modulated Na(+)/Ca(2+) exchanger (NCX1) activity. PLM was overexpressed in adult rat myocytes by adenovirus-mediated gene transfer.

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Oligodendrocyte progenitors originate in the subventricular zone, proliferate, migrate to their final destinations, differentiate, and interact with axons to produce multilamellar myelin sheaths. These processes are regulated by a variety of environmental signals, including growth factors, the extracellular matrix, and adhesion molecules. Heparan sulfate proteoglycans are premier candidates as participants in this regulation by virtue of their structural diversity and their capacity to function as coreceptors for both growth factors and extracellular matrix molecules.

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Previously we reported that type V collagen synthesized by Schwann cells inhibits the outgrowth of axons from rat embryo dorsal root ganglion neurons but promotes Schwann cell migration (Chernousov, M. A., Stahl, R.

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