Desmosomes first assemble in the E3.5 mouse trophectoderm, concomitant with establishment of epithelial polarity and appearance a blastocoel cavity. Throughout development, they increase size number are especially abundant epidermis heart muscle. mediate cell–cell adhesion through desmosomal cadherins, which differ from classical cadherins their attachments to intermediate filaments (IFs), rather than actin filaments. Of proteins implicated making this IF connection, only desmoplakin (DP) is...

In epidermal cells, keratin intermediate filaments connect with desmosomes to form extensive cadherin-mediated cytoskeletal architectures. Desmoplakin (DPI), a desmosomal component lacking transmembrane domain, has been implicated in this interaction, although most studies have conducted cells that contain few or no desmosomes, and efforts demonstrate direct interactions between desmoplakin not successful. report, we explore the biochemical nature of connections keratinocytes. We show...

The role of intracellular Ca 2+ mobilization in the mechanism increased endothelial permeability was studied. Human umbilical vein cells (HUVECs) were exposed to thapsigargin or thrombin at concentrations that resulted similar increases concentration ([Ca ] i ) . rise [Ca both cases due release from stores and influx extracellular Both agents decreased cell monolayer electrical resistance (a measure shape change) transendothelial 125 I‐albumin permeability. Thapsigargin induced activation...

The mechanisms involved in the restoration of endothelial cell junctions subsequent to barrier disruption remain unclear. It is known that formation adherens (AJs) affects cytoskeletal actin arrangement and Rho GTPases regulate state polymerization. In present study, we examined role GTPases, Rho, Rac, Cdc42 reannealing AJs. We studied response thrombin, which increases permeability through disassembly AJs, followed by recovery function junctional within 2 hours. was activated late, at...

We determined the role of vascular endothelial (VE)-cadherin complex in regulating permeability pulmonary microvessels. Studies were made mouse lungs perfused with albumin-Krebs containing EDTA, a Ca(2+) chelator, added to study VE-cadherin junctional disassembly. then repleted perfusate restore integrity. Confocal microscopy showed disappearance immunostaining time- and dose-dependent manner after chelation reassembly within 5 min repletion. (125)I-labeled albumin permeability-surface area...

The adherens junction is a multiprotein complex consisting of the transmembrane vascular endothelial cadherin (VEC) and cytoplasmic catenins (p120, β-catenin, plakoglobin, α-catenin) responsible for maintenance barrier function. Junctional disassembly modifications in cadherin/catenin lead to increased paracellular permeability barrier. However, mechanisms junctional remain unclear. In this study, we used proinflammatory mediator thrombin compromise function test hypothesis that...

The endothelial adherens junctions (AJs) consist of trans-oligomers membrane spanning vascular (VE)-cadherin proteins, which bind beta-catenin through their cytoplasmic domain. beta-Catenin in turn binds alpha-catenin and connects the AJ complex with actin cytoskeleton. We addressed vivo effects loss VE-cadherin interactions on lung permeability role specific Rho GTPase effectors regulating increase induced by destabilization. used cationic liposomes encapsulating mutant lacking...

Using mutagenesis, we investigated the importance of two vimentin domains: (a) a highly conserved segment near carboxy end alpha-helical rod, and (b) tail, with which rod is known to interact. As judged by in vitro filament assembly expression transiently transfected cells lacking an endogenous network, rod-tail interaction not essential for 10 nm structure or formation fibrous arrays culture. However, when mutated, amino acid residues within tail segments can cause perturbations IF network...

The cytoplasmic domain of cadherins and the associated catenins link cytoskeleton with signal transduction pathways. To study signaling function non-junctional VE-cadherin, which can form during loss VE-cadherin homotypic adhesion, wild type or (ΔEXD) was expressed in sub-confluent endothelial cells. We observed that Cdc42 activated transfected cells these also developed Cdc42-dependent >70-μm-long plasma membrane protrusions. formation structures required actin polymerization, they...

To identify sites of self-association in type III intermediate filament (IF) proteins, we have taken an "anti-idiotypic antibody" approach. A mAb (anti-Ct), recognizing a similar feature near the end rod domain vimentin, desmin, and peripherin (epsilon site or epsilon epitope), was characterized. Anti-idiotypic antibodies, generated by immunizing rabbits with purified anti-Ct, recognize (presumably "complementary" to epitope) common among (beta beta epitope). The epitope is represented...

Increased pulmonary vascular resistance in hypertension (PH) is caused by vasoconstriction and obstruction of small arteries proliferating cells. In analogy to cancer, subsets cells may be derived from endothelial transitioning into a mesenchymal phenotype. To understand phenotypic shifts transpiring within PH, we injected rats with alkaloid monocrotaline induce PH measured lung tissue levels endothelial-specific protein critical differentiation marker (VE)-cadherin. VE-cadherin expression...

The Covid-19 pandemic has required nonpharmaceutical interventions, primarily physical distancing, personal hygiene and face mask use, to limit community transmission, irrespective of seasons. In fact, the seasonality attributes this remain one its biggest unknowns. Early studies based on past experience from respiratory diseases focused temperature or humidity, with disappointing results. Our hypothesis that ultraviolet (UV) radiation levels might be a factor more appropriate parameter...

Activation of the Rho GTPase Cdc42 has been shown in endothelial cell monolayers to prevent disassembly interendothelial junctions and increase permeability. Here, we addressed vivo role activity mediating barrier protection lungs by generating mice expressing dominant active mutant V12Cdc42 protein vascular cells targeted via VE-cadherin promoter. These developed normally exhibited constitutively GTP-bound Cdc42. The lung permeability gain tissue water content response intraperitoneal...

Nearly all intermediate filament (IF) proteins share two sequence motifs located at the N- and C-terminal ends of their helical rod domain (‘coil 1a’ ‘coil 2b’, respectively). To examine structural role coil 2b motif, we have performed in vitro assembly studies vivo microinjection experiments employing site-specific reagents: (a) a 20-residue synthetic peptide (C-2) representing conserved motif itself (b) monoclonal antibody (anti-IFA) that recognises an epitope within sequence. We...

The intermediate filament (IF) proteins vimentin, desmin and peripherin share a 9-residue sequence motif (beta-site) located near the end of their COOH-terminal tail domain. Peptide inhibition experiments have previously suggested that beta-site is involved in interactions limit lateral growth IFs prevent inappropriate filament-filament associations. To investigate this question further, we constructed expressed, Escherichia coli, hamster vimentin bearing different mutations beta-site. We...

Previous studies have shown that nuclear lamin B binds specifically to the C-terminal domains of type I11 intermediate filament (IF) proteins under in vitro conditions.To further explore such site-specific interactions, we used a two-step anti-idiotypic antibody approach.First, monoclonal disrupting cytoplasmic IF network organization living cells (mAb7A3) (Matteoni, R., and Kreis, T. E. (1987) J. Cell Biol.105,[1253][1254][1255][1256][1257][1258][1259][1260][1261][1262][1263][1264][1265]...

Lung inflammatory disease is characterized by increased polymorphonuclear leukocyte (PMN) infiltration and vascular permeability. PMN into tissue involves signaling between endothelial cells migrating PMNs, which leads to alterations in the organization of adherens junctions (AJs). We addressed possible role protein constituents AJs, endothelium-specific vascular-endothelial (VE)-cadherin, migration PMNs. Studies were made using VE-cadherin mutant constructs lacking extracellular domain...

More attention should be paid to ultraviolet radiation for the seasonality of Covid-19, based on previous SARS and MERS epidemics, not ‘warmer days’ summer.

<ns4:p>The Covid-19 pandemic has spread across the world during early 2020, with unforeseen consequences. Beyond social measures and biomedical research, it is important to assess seasonality of epidemic inform strategies, limited available data in short period time between March equinox June solstice. While effect multiple factors being investigated, little attention been paid ultraviolet (UV) radiation, a key parameter seasonal forcing. We review effects UV proposing as potential element...

The generation of cell-penetrating peptides as cargo-delivery systems has produced an immense number studies owing to the importance these tools deliver molecules into cells, well due interest shed light a yet unclear mechanism entrance cells. However, many might present drawbacks causing cellular toxicity, or being entrapped in endosomes, result their degradation before they meet target. In this work, cargo transporting molecule, Cell Penetrating Sequential Oligopeptide Carrier (CPSOC),...

Embryonic Stem (ES) or induced Pluripotent (iPS) cells are important sources for cardiomyocyte generation, targeted regenerative therapies. Several in vitro protocols currently utilized their differentiation, but the value of cell-based approaches remains unclear. Here, we characterized a cardiovascular progenitor population derived during ES after selection based on VE-cadherin promoter (Pvec) activity. ESCs were genetically modified with an episomal vector, allowing expression puromycin...