The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle-associated immune complexes

Immunoglobulins, antigens and complement can assemble to form immune complexes (IC). ICs can be detrimental as they propagate inflammation in autoimmune diseases. Like ICs, submicron extracellular vesicles termed microparticles (MP) are present in the synovial fluid from patients affected with autoimmune arthritis. We examined MPs in rheumatoid arthritis (RA) using high sensitivity flow cytometry and electron microscopy. We find that the MPs in RA synovial fluid are highly heterogeneous in size. The observed larger MPs were in fact MP-containing ICs (mpICs) and account for the majority of the detectable ICs. These mpICs frequently express the integrin CD41, consistent with platelet origin. Despite expression of the Fc receptor FcγRIIa by platelet-derived MPs, we find that the mpICs form independently of this receptor. Rather, mpICs display autoantigens vimentin and fibrinogen, and recognition of these targets by anti-citrullinated peptide antibodies contributes to the production of mpICs. Functionally, platelet mpICs are highly pro-inflammatory, eliciting leukotriene production by neutrophils. Taken together, our data suggest a unique role for platelet MPs as autoantigen-expressing elements capable of perpetuating formation of inflammatory ICs

Estimating process capability index Cpm using a bootstrap sequential sampling procedure

Construction of a confidence interval for process capability index CPM is often based on a normal approximation with fixed sample size. In this article, we describe a different approach in constructing a fixed-width confidence interval for process capability index CPM with a preassigned accuracy by using a combination of bootstrap and sequential sampling schemes. The optimal sample size required to achieve a preassigned confidence level is obtained using both two-stage and modified two-stage sequential procedures. The procedure developed is also validated using an extensive simulation study.<br /

Fluorine-induced improvement of structural and optical properties of CdTe thin films for solar cell efficiency enhancement

CdTe thin films of different thicknesses were electrodeposited and annealed in air after different chemical treatments to study the effects of thickness and the different chemical treatments on these films for photovoltaic applications. The thicknesses of the samples range from 1.1 μm to 2.1 μm and the annealing process was carried out after prior CdCl2 treatment and CdCl2+CdF2 treatment as well as without any chemical treatment. Detailed optical and structural characterisation of the as-deposited and annealed CdTe thin films using UV-Vis spectrophotometry and x-ray diffraction reveal that incorporating fluorine in the well-known CdCl2 treatment of CdTe produces remarkable improvement in the optical and structural properties of the materials. This CdCl2+CdF2 treatment produced solar cell with efficiency of 8.3% compared to CdCl2 treatment, with efficiency of 3.3%. The results reveal an alternative method of post-deposition chemical treatment of CdTe which can lead to the production of CdTe-based solar cells with enhanced photovoltaic conversion efficiencies compared to the use of only CdCl2. Keywords: CdTe; CdCl2

INTERNATIONAL JOURNAL OF PHARMACY &amp; LIFE SCIENCES Screening of potential efficacy of dietary ginger on ethanol induced oxidative stress in rat cardiac tissue: A study on changes in basic metabolic profiles

Abstract The present study was premeditated to examine the possible mechanisms where by ginger (Zingiber officinale) could protect cardiac tissue from alcohol toxicity in rats. The carbohydrate metabolic profiles like total carbohydrates, pyruvate, total proteins, free amino acids and lactate levels were measured in heart tissue. The total carbohydrates, pyruvate, and total proteins were significant declined while free amino acids, lactate levels were significant increased in alcohol intoxicated rats. Whereas with ginger (200 mg/kg body weight) treatment shown significant increase in the total carbohydrates, total proteins and pyruvate levels, whereas free amino acids, lactate levels were significant drop in the cardiac tissues. From the present study, we conclude that ginger protects the heart tissue from alcohol toxicity in rats, this may be due to the presence of many bioactive compounds in ginger

Differential regulation of alanine aminotransferase homologues by abiotic stresses in wheat (Triticum aestivum L.) seedlings

Wheat (Triticum aestivum L.) seedlings contain four alanine aminotransferase (AlaAT) homologues. Two of them encode AlaAT enzymes, whereas two homologues act as glumate:glyoxylate aminotransferase (GGAT). To address the function of the distinct AlaAT homologues a comparative examination of the changes in transcript level together with the enzyme activity and alanine and glutamate content in wheat seedlings subjected to low oxygen availability, nitrogen and light deficiency has been studied. Shoots of wheat seedlings were more tolerant to hypoxia than the roots as judging on the basis of enzyme activity and transcript level. Hypoxia induced AlaAT1 earlier in roots than in shoots, while AlaAT2 and GGAT were unaffected. The increase in AlaAT activity lagged behind the increase in alanine content. Nitrogen deficiency has little effect on the activity of GGAT. In contrast, lower activity of AlaAT and the level of mRNA for AlaAT1 and AlaAT2 in wheat seedlings growing on a nitrogen-free medium seems to indicate that AlaAT is regulated by the availability of nitrogen. Both AlaAT and GGAT activities were present in etiolated wheat seedlings but their activity was half of that observed in light-grown seedlings. Exposure of etiolated seedlings to light caused an increase in enzyme activities and up-regulated GGAT1. It is proposed that hypoxia-induced AlaAT1 and light-induced peroxisomal GGAT1 appears to be crucial for the regulation of energy availability in plants grown under unfavourable environmental conditions

Structural and thermal studies of silver nanoparticles and electrical transport study of their thin films

This work reports the preparation and characterization of silver nanoparticles synthesized through wet chemical solution method and of silver films deposited by dip-coating method. X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), field emission transmission electron microscopy (FETEM), high-resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED), and energy dispersive spectroscopy (EDX) have been used to characterize the prepared silver nanoparticles and thin film. The morphology and crystal structure of silver nanoparticles have been determined by FESEM, HRTEM, and FETEM. The average grain size of silver nanoparticles is found to be 17.5 nm. The peaks in XRD pattern are in good agreement with that of face-centered-cubic form of metallic silver. TGA/DTA results confirmed the weight loss and the exothermic reaction due to desorption of chemisorbed water. The temperature dependence of resistivity of silver thin film, determined in the temperature range of 100-300 K, exhibit semiconducting behavior of the sample. The sample shows the activated variable range hopping in the localized states near the Fermi level

Metabolic Impact of Adult-Onset, Isolated, Growth Hormone Deficiency (AOiGHD) Due to Destruction of Pituitary Somatotropes

Growth hormone (GH) inhibits fat accumulation and promotes protein accretion, therefore the fall in GH observed with weight gain and normal aging may contribute to metabolic dysfunction. To directly test this hypothesis a novel mouse model of adult onset-isolated GH deficiency (AOiGHD) was generated by cross breeding rat GH promoter-driven Cre recombinase mice (Cre) with inducible diphtheria toxin receptor mice (iDTR) and treating adult Cre+/−,iDTR+/− offspring with DT to selectively destroy the somatotrope population of the anterior pituitary gland, leading to a reduction in circulating GH and IGF-I levels. DT-treated Cre−/−,iDTR+/− mice were used as GH-intact controls. AOiGHD improved whole body insulin sensitivity in both low-fat and high-fat fed mice. Consistent with improved insulin sensitivity, indirect calorimetry revealed AOiGHD mice preferentially utilized carbohydrates for energy metabolism, as compared to GH-intact controls. In high-fat, but not low-fat fed AOiGHD mice, fat mass increased, hepatic lipids decreased and glucose clearance and insulin output were impaired. These results suggest the age-related decline in GH helps to preserve systemic insulin sensitivity, and in the context of moderate caloric intake, prevents the deterioration in metabolic function. However, in the context of excess caloric intake, low GH leads to impaired insulin output, and thereby could contribute to the development of diabetes

A Phospholipidomic Analysis of All Defined Human Plasma Lipoproteins

Since plasma lipoproteins contain both protein and phospholipid components, either may be involved in processes such as atherosclerosis. In this study the identification of plasma lipoprotein-associated phospholipids, which is essential for understanding these processes at the molecular level, are performed. LC-ESI/MS, LC-ESI-MS/MS and High Performance Thin Layer Chromatography (HPTLC) analysis of different lipoprotein fractions collected from pooled plasma revealed the presence of phosphatidylethanolamine (PE), phosphatidylinositol (PI), and sphingomyeline (SM) only on lipoproteins and phosphatidylcholine (PC), Lyso-PC on both lipoproteins and plasma lipoprotein free fraction (PLFF). Cardiolipin, phosphatidylglycerol (PG) and Phosphatidylserine (PS) were observed neither in the lipoprotein fractions nor in PLFF. All three approaches led to the same results regarding phospholipids occurrence in plasma lipoproteins and PLFF. A high abundancy of PE and SM was observed in VLDL and LDL fractions respectively. This study provides for the first time the knowledge about the phospholipid composition of all defined plasma lipoproteins

Sphingomyelin Functions as a Novel Receptor for Helicobacter pylori VacA

The vacuolating cytotoxin (VacA) of the gastric pathogen Helicobacter pylori binds and enters epithelial cells, ultimately resulting in cellular vacuolation. Several host factors have been reported to be important for VacA function, but none of these have been demonstrated to be essential for toxin binding to the plasma membrane. Thus, the identity of cell surface receptors critical for both toxin binding and function has remained elusive. Here, we identify VacA as the first bacterial virulence factor that exploits the important plasma membrane sphingolipid, sphingomyelin (SM), as a cellular receptor. Depletion of plasma membrane SM with sphingomyelinase inhibited VacA-mediated vacuolation and significantly reduced the sensitivity of HeLa cells, as well as several other cell lines, to VacA. Further analysis revealed that SM is critical for VacA interactions with the plasma membrane. Restoring plasma membrane SM in cells previously depleted of SM was sufficient to rescue both toxin vacuolation activity and plasma membrane binding. VacA association with detergent-resistant membranes was inhibited in cells pretreated with SMase C, indicating the importance of SM for VacA association with lipid raft microdomains. Finally, VacA bound to SM in an in vitro ELISA assay in a manner competitively inhibited by lysenin, a known SM-binding protein. Our results suggest a model where VacA may exploit the capacity of SM to preferentially partition into lipid rafts in order to access the raft-associated cellular machinery previously shown to be required for toxin entry into host cells

Potential of Pandanus odoratissimus as a CNS depressant in Swiss albino mice

In this study, several neuropharmacological effects of methanolic leaf extract of Pandanus odoratissimus (PO) (family; Pandanaceae) were studied in albino mice using various experimental models. The effect of PO on the CNS was studied by using different neuropharmacological paradigms including spontaneous motor activity, rota-rod performance and potentiation of Pentobarbital sodium sleeping time in albino mice. Preliminary phytochemical evaluation and acute toxicity studies were also carried out where LD50 >2000 mg/kg was considered non-toxic through acute exposure in rats by the oral route. The methanolic leaf extract (50,100 and 200 mg/kg i. p.) produced a reduction in spontaneous motor activity, motor coordination and prolonged Pentobarbital sodium sleeping time. Preliminary qualitative chemical studies indicated the presence of steroids, saponins, terpinoids, glycosides, tannins, flavonoids and phenolics in the extract. These observations suggest that the leaf of Pandanus odoratissimus contains some active principles which possess potential CNS-depressant actionEstudaram-se alguns efeitos neurofarmacológicos do extrato metanólico de Pandanus odoratissimus (PO) (família Pandanaceae) em camundongos albinos, usando vários modelos experimentais. O efeito do PO no SNC foi estudado por meio de diferentes paradigmas neurofarmacológicos, como atividade motora espontânea, desempenho na haste rotatória e a potenciação do tempo de sono em camundongos albinos pelo pentobarbital sódico. A avaliação fitoquímica preliminar e os estudos de toxicidade aguda foram realizados e a DL50 >2000 mg/kg é considerada não tóxica, por meio da exposição aguda, por via oral, em ratos. O extrato metanólico de folha (50,100 e 200 mg/kg i. p.) produziu redução da atividade motora espontânea, da coordenação motora e tempo prolongado de sono pelo pentobarbital sódico. Estudos químicos qualitativos preliminares indicaram a presença de esteróide, saponinas, terpenóides, glicosídios, taninos, flavonóides e fenólicos no extrato. As observações sugerem que a folha de Pandanus odoratissimus contém alguns princípios ativos com atividade potencial como depressores do SNC