Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through alpha2beta1 integrin.

Endorepellin, the COOH-terminal domain of the heparan sulfate proteoglycan perlecan, inhibits several aspects of angiogenesis. We provide evidence for a novel biological axis that links a soluble fragment of perlecan protein core to the major cell surface receptor for collagen I, alpha2beta1 integrin, and provide an initial investigation of the intracellular signaling events that lead to endorepellin antiangiogenic activity. The interaction between endorepellin and alpha2beta1 integrin triggers a unique signaling pathway that causes an increase in the second messenger cAMP; activation of two proximal kinases, protein kinase A and focal adhesion kinase; transient activation of p38 mitogen-activated protein kinase and heat shock protein 27, followed by a rapid down-regulation of the latter two proteins; and ultimately disassembly of actin stress fibers and focal adhesions. The end result is a profound block of endothelial cell migration and angiogenesis. Because perlecan is present in both endothelial and smooth muscle cell basement membranes, proteolytic activity during the initial stages of angiogenesis could liberate antiangiogenic fragments from blood vessels' walls, including endorepellin.

A Recently Discovered Pathogenic Paramyxovirus, Sosuga Virus, is Present in Rousettus aegyptiacus Fruit Bats at Multiple Locations in Uganda.

In August 2012, a wildlife biologist became ill immediately following a 6-wk field trip to collect bats and rodents in South Sudan and Uganda. After returning to the US, the biologist was admitted to the hospital with multiple symptoms including fever, malaise, headache, generalized myalgia and arthralgia, stiffness in the neck, and sore throat. Soon after admission, the patient developed a maculopapular rash and oropharynx ulcerations. The patient remained hospitalized for 14 d. Several suspect pathogens, including viral hemorrhagic fever viruses such as Ebola viruses and Marburg viruses, were ruled out through standard diagnostic testing. However, deep sequencing and metagenomic analyses identified a novel paramyxovirus, later named Sosuga virus, in the patient's blood. To determine the potential source, bat tissues collected during the 3-wk period just prior to the onset of symptoms were tested for Sosuga virus, and several Egyptian rousette bats (Rousettus aegyptiacus) were found to be positive. Further analysis of archived Egyptian rousette tissues collected at other localities in Uganda found additional Sosuga virus-positive bats, suggesting this species could be a potential natural reservoir for this novel paramyxovirus.

Safety of oscillating-rotating powered brushes compared to manual toothbrushes: a systematic review.

BACKGROUND: Oscillating-rotating power toothbrushes have been proven clinically efficacious. To our knowledge, a comprehensive review of all clinical and laboratory investigations solely comparing the safety of these toothbrushes to the standard of care (i.e., manual toothbrushes) has not been published. The aim of this systematic review is to examine the literature concerning the relative soft and/or hard tissue safety outcomes with the use of oscillating-rotating toothbrushes compared to manual toothbrushes. METHODS: With the use of electronic databases of the National Library of Medicine (PubMed-MEDLINE), the Cochrane Central Register of Controlled Trials (Cochrane-CENTRAL), and the Excerpta Medical Database (EMBASE), a search of in vivo and in vitro trials through May 2010 was conducted to identify appropriate studies that evaluated the effects of an oscillating-rotating power toothbrush compared to a manual toothbrush with respect to soft and/or hard tissue safety. Eligible trials incorporated a safety evaluation as a primary or secondary outcome parameter (i.e., gingival recession, observed/reported adverse events, and hard tissue effects) or used a surrogate parameter (i.e., stained gingival abrasion and brushing force) to assess safety. Data extraction for the primary- and surrogate-measure safety studies, which included mean values and SDs when available, and a meta-analysis of the gingival recession data were performed. RESULTS: Independent screening of the titles and abstracts of 697 PubMed-MEDLINE, 436 Cochrane-CENTRAL, and 664 EMBASE papers resulted in 35 publications that met the eligibility criteria. The mean change in gingival recession was not significantly different among toothbrush groups in the two selected trials with safety as a primary outcome (weighted mean difference: 0.03). A meta-analysis of the five trials that evaluated safety with a surrogate parameter was not possible; however, there were no significant between-group differences at the study end in any trial. A descriptive analysis of the 24 selected studies assessing safety as a secondary outcome revealed few brushing-related adverse events. The heterogeneity in objectives and methodology of the four in vitro trials that met the eligibility criteria precluded generalization of the results. CONCLUSION: A large body of published research in the preceding 2 decades has consistently shown oscillating-rotating toothbrushes to be safe compared to manual toothbrushes, demonstrating that these power toothbrushes do not pose a clinically relevant concern to hard or soft tissues.

Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the alpha2beta1-integrin receptor.

Endorepellin, a C-terminal fragment of the vascular basement membrane proteoglycan perlecan, inhibits angiogenesis via the alpha2beta1-integrin receptor. Because this integrin is also implicated in platelet-collagen responses and because endorepellin or its fragments are generated in response to injury and inflammation, we hypothesized that endorepellin could also affect platelet biology. We discovered that endorepellin supported alpha2beta1-dependent platelet adhesion, without appreciably activating or aggregating platelets. Notably, endorepellin enhanced collagen-evoked responses in platelets, in a src kinase-dependent fashion, and enhanced the collagen-inhibitory effect of an alpha2beta1-integrin function-blocking antibody. Collectively, these results suggest that endorepellin/alpha2beta1-integrin interaction and effects are specific and dependent on cell type, differ from those emanated by exposure to collagen, and may be due to cellular differences in alpha2beta1-integrin activation/ligand affinity state. These studies also suggest a heretofore unrecognized role for angiostatic basement membrane fragments in platelet biology.

Biologically active decorin is a monomer in solution.

It has been reported that decorin and its protein core can have molecular masses nearly double the size of those previously published, suggesting a dimeric structure. In this study we tested whether biologically active decorin and its glycoprotein core would form dimers in solution. We used homo- and hetero-bifunctional chemical cross-linking reagents, BS3 and sulfo-SMPB, respectively, as well as glutaraldehyde and found no preferential dimer formation, whether chemical cross-linking was performed in the presence or absence of live cells. Under the same experimental conditions, we easily detected dimers of epidermal growth factor receptor and basic fibroblast growth factor, two glycoproteins known to dimerize. Only at very high cross-linker to decorin molar ratios (2000:1) were trimers and multimers observed, but performing the chemical cross-linking in the presence of a reducing agent abolished these. The elution of decorin protein core in Superose 6 gel chromatography gave masses compatible with monomeric proteins, both before and after denaturation with 2.5 M guanidine HCl. Matrix-assisted laser desorption ionization gave a mass of 44,077 Da for decorin protein core, without any evidence of dimers or oligomers. Extensive oligomerization of the decorin protein core was observed only after dialysis against water and freeze-drying. These oligomers were considered artifacts because they were independent of chemical cross-linking and were resistant to heat denaturation and disulfide-bond reduction. Oligomeric preparations showed markedly reduced biological activity in both phosphorylation and collagen fibrillogenesis assays. Thus, biologically active decorin is a monomer in solution and, as such, is a monovalent ligand for various extracellular matrix proteins, growth factors, and cell surface receptors.