Phosphatidylserine-positive erythrocytes bind to immobilized and soluble thrombospondin-1 via its heparin-binding domain

Phosphatidylserine (PS)-dependent erythrocyte adhesion to endothelium and sub-endothelial matrix components is mediated in part via thrombospondin (TSP). While TSP exhibits multiple cell-binding domains, the PS-binding site on TSP is unknown. Since a cell-binding domain for anionic heparin is located at the amino-terminus, we hypothesized that PS-positive red cells (PS+ve-RBCs) bind to this domain. We demonstrate that both heparin and its low-molecular-weight derivative enoxaparin (0.5-50u/ml) inhibited PS+ve-RBC adhesion to immobilized TSP in a concentration-dependent manner (21-77% inhibition, P\u3c0.05). Pre-incubation of immobilized TSP with an antibody against the heparin-binding domain blocked PS+ve-RBC adhesion to TSP. Antibodies that recognize the collagen- and the carboxy-terminal CD47-binding domain on TSP had no effect on this process. While pre-incubation of PS+ve-RBCs with TSP-peptides from the heparin-binding domain containing the specific heparin-binding motif KKTRG inhibited PS+ve-erythrocyte adhesion to matrix TSP (P\u3c0.001), these peptides in the immobilized form supported PS-mediated erythrocyte adhesion. A TSP-peptide lacking the binding-motif neither inhibited nor supported PS+ve-RBC adhesion. Additional experiments show that soluble-TSP also interacted with PS+ve-RBCs via its heparin-binding domain. Our results demonstrate that PS-positive erythrocytes bind to both immobilized and soluble TSP via its heparin-binding domain and that both heparin and enoxaparin, at clinically relevant concentrations, block this interaction. Other studies have shown that heparin inhibited P-selectin- and soluble-TSP-mediated sickle erythrocyte adhesion to endothelial cells. Our results taken together with the previously documented findings provide a rational basis for clinical use of heparin or its low-molecular-weight derivatives as therapeutic agents in treating vaso-occlusive pain in patients with sickle cell disease

The Radiation Transfer at a Layer of Magnetized Plasma With Random Irregularities

The problem of radio wave reflection from an optically thick plane monotonous layer of magnetized plasma is considered at present work. The plasma electron density irregularities are described by spatial spectrum of an arbitrary form. The small-angle scattering approximation in the invariant ray coordinates is suggested for analytical investigation of the radiation transfer equation. The approximated solution describing spatial-and-angular distribution of radiation reflected from a plasma layer has been obtained. The obtained solution has been investigated numerically for the case of the ionospheric radio wave propagation. Two effects are the consequence of multiple scattering: change of the reflected signal intensity and anomalous refraction.Comment: 22 pages, 4 figure

Heme induces endothelial tissue factor expression: Potential role in hemostatic activation in patients with hemolytic anemia

Objectives: We explored the possibility that heme, an inflammatory mediator and a product of intravascular hemolysis in patients with hemolytic anemia including sickle cell disease, could modulate hemostasis by an effect on endothelial tissue factor (TF) expression. Methods: Levels of TF mRNA, protein and procoagulant activity were measured in heme-treated endothelial cells. Results: Heme induces TF expression on the surface of both macrovascular and microvascular endothelial cells in a concentration-dependent manner, with 12-fold to 50-fold induction being noted (enzyme-linked immunosorbent assay) between 1 and 100 μm heme (P \u3c 0.05). Complementary flow cytometry studies showed that the heme-mediated endothelial TF expression was quantitatively similar to that of tumor necrosis factor-alpha (TNF-α). Heme also upregulated the expression of TF mRNA (8-fold to 26-fold), protein (20-fold to 39-fold) and procoagulant activity (5-fold to 13-fold) in endothelial cells in a time-dependent manner. The time-course of heme-mediated TF antigen expression paralleled the induction of procoagulant activity, with antibody blocking studies demonstrating specificity for TF protein. Interleukin (IL)-1α, and TNF-α are not involved in mediating the heme effect, as antibodies against these cytokines and IL-1-receptor antagonist failed to block heme-induced TF expression. Inhibition of heme-induced TF mRNA expression by sulfasalazine and curcumin suggested that the transcription factor nuclear factor kappaB is involved in mediating heme-induced TF expression in endothelial cells. Conclusions: Our results demonstrate that heme induces TF expression by directly activating endothelial cells, and that heme-induced endothelial TF expression may provide a pathophysiologic link between the intravascular hemolytic milieu and the hemostatic perturbations previously noted in patients with hemolytic anemia including sickle cell disease

Shrinking harvest: Genetic consequences and challenges for sustainable harvesting of non-timber forest products

Non-timber forest products (NTFP) have been an important source of subsistence as well as livelihoods for many forest-dwelling and forest- fringe communities across the developing world. NTFP collection has been promoted as a win-win strategy to not only conserve biodiversity but also provide livelihood options to scores of forest-dwelling communities. There has been evidence both for, and against, the impacts of harvesting and the ecological sustainability of harvested species. Harvesting can act as a selective force and reduce the population genetic diversity, especially for species in which the reproductive parts are harvested. A debate has been raging among scientists, resource managers, as well as policy makers for decades, over which methods, and what levels of harvest, can be considered ecologically sustainabl

Comparison of Radiovisiography and Digital volume tomography to direct surgical measurements in the detection of infrabony defects

Objectives: To compare the linear measurements of Radiovisiography (RVG) and Digital volume tomography (DVT) to direct surgical measurements in the detection of periodontal infrabony defects. Study design: RVG and DVT images were taken prior to periodontal surgery for 28 infrabony periodontal defects. After defect debridement, direct bony defect measurements were made from the cemento enamel junction (CEJ) to the base of the defect (CEJ-BD) and to the alveolar crest (CEJ-AC) with a periodontal probe. These same measurements were made on the RVG and DVT images and then compared to the direct surgical values. Results: DVT correlated strongly with surgical measurements, whereas RVG correlated less favorably (P=0.0109, P=0.0193 respectively).No significant difference for CEJ-AC (P=0.0599) was seen between DVT and surgical measurements; however, there was a significant difference for the distance CEJ-BD (P=0.0105). Conclusion: DVT technique is significantly more accurate than RVG in the detection of infrabony periodontal defects

Adapting Translational Research Methods to Water, Sanitation, and Hygiene

Translational research applies scientific techniques to achieve practical outcomes, connecting pure research and pure practice. Many translational research types have arisen since the mid-1900s, reflecting the need to better integrate scientific advancement with policy and practice. Water, sanitation, and hygiene (WaSH) development efforts have aimed to reduce morbidity and mortality and improve service delivery; thus, associated research has a strong orientation toward applied studies that use diverse methods to support decision-making. Drawing from knowledge that emerged to support other professional fields, such as manufacturing and clinical healthcare, we characterize different types of translational research and clarify nomenclature and principles. We describe study approaches relevant to translational research questions, and offer overarching recommendations, specific examples, and resources for further study as practical advice to professionals who seek to apply translational methods to WaSH problems. To enhance collective outcomes, professionals should mindfully align projects within the translational spectrum. We further recommend overarching good practices such as documenting intervention adaptations, overtly considering contextual factors, and better distinguishing efficacy from effectiveness research by replicating studies in different contexts. By consciously improving the compatibility and linkages between WaSH science and practice, this guide can accelerate urgently needed progress toward global development goals

Grd19/Snx3p functions as a cargo-specific adapter for retromer-dependent endocytic recycling

Amajor function of the endocytic system is the sorting of cargo to various organelles. Endocytic sorting of the yeast reductive iron transporter, which is composed of the Fet3 and Ftr1 proteins, is regulated by available iron. When iron is provided to iron-starved cells, Fet3p–Ftr1p is targeted to the lysosome-like vacuole and degraded. In contrast, when iron is not available, Fet3p–Ftr1p is maintained on the plasma membrane via an endocytic recycling pathway requiring the sorting nexin Grd19/Snx3p, the pentameric retromer complex, and the Ypt6p Golgi Rab GTPase module. A recycling signal in Ftr1p was identified and found to bind directly to Grd19/Snx3p. Retromer and Grd19/Snx3p partially colocalize to tubular endosomes, where they are physically associated. After export from the endosome, Fet3p–Ftr1p transits through the Golgi apparatus for resecretion. Thus, Grd19/Snx3p, functions as a cargo-specific adapter for the retromer complex, establishing a precedent for a mechanism by which sorting nexins expand the repertoire of retromer-dependent cargos

Electronic properties, correlated topology and Green's function zeros

There is extensive current interest about electronic topology in correlated settings. In strongly correlated systems, contours of Green's function zeros may develop in frequency-momentum space, and their role in correlated topology has increasingly been recognized. However, whether and how the zeros contribute to electronic properties is a matter of uncertainty. Here we address the issue in an exactly solvable model for Mott insulator. We show that the Green's function zeros contribute to several physically measurable correlation functions, in a way that does not run into inconsistencies. In particular, the physical properties remain robust to chemical potential variations up to the Mott gap as it should be based on general considerations. Our work sets the stage for further understandings on the rich interplay among topology, symmetry and strong correlations.Comment: 15 pages, 3 figure

AN IN VITRO STUDY OF CINNAMOMUM ZEYLANICUM AS NATURAL INHIBITOR OF ANGIOTENSIN-CONVERTING ENZYME (ACE) ON SHEEP (OVIS ARIES) TISSUES

Objective: The present study was aimed to find the angiotensin-converting enzyme (ACE) inhibitory activity using the methanolic extract ofCinnamomum zeylanicum (as a natural inhibitor) on sheep tissues as the enzyme source.Methods: Hippuryl-histidyl-leucine (HHL) as a substrate, tissue ACE activity was measured spectrophotometrically at 228 nm. For an incubationperiod of 30 minutes at 37°C, the linearity of ACE activity of kidney, lung, and testis enzyme was established. A known medicinal plant C. zeylanicumwas used as natural inhibitor of ACE. In this enzyme assay, inhibitory effect of methanolic extract of C. zeylanicum on kidney, lung and testicular ACEwas determined. ACE activity was confirmed by captopril, a standard inhibitor of ACE.Results: In the presence of a methanolic extract of C. zeylanicum (10:1), ACE activity was determined and this has inhibited ACE activity verysignificantly. C. zeylanicum leaves extract has reduced sheep kidney, lung, and testis ACE activity by 70.06%, 12.63%, and 20.23%, respectively.Conclusion: Significant inhibition was observed in the kidney ACE than in lung and testis ACE activity. This can propose that there may be a possiblerole in controlling blood pressure or reduction in cardiovascular diseases. Some plants with the great medicinal property may be considered aspromising sources of natural inhibitors of ACE for medicine and commercial uses. This comprehensive study may show numerous beneficial effects asa potential therapeutic agent for lowering blood pressure.Keywords: Angiotensin-converting enzyme, Natural angiotensin-converting enzyme inhibitor, Kinetic assay, Hippuryl-histidyl-leucine, Cinnamomumzeylanicum, Cardiovascular diseases