ALTERATION IN SERUM ZINC AND COPPER CONCENTRATIONS AND EFFECT OF ORAL THERAPEUTIC SUPPLEMENTATION OF ZINC ON TRANSFUSION DEPENDANT BETA THALASSEMIA MAJOR PATIENTS

Zinc is one of the essential micronutrients in human and act as a cofactor for more than 300 enzymes and plays an essential role in human growth and development. It has been observed that there was low serum zinc and elevated  copper level in β-thalassemia major compared with normal. Zinc deficiency is considered one of the main factors contributing to growth, cardiovascular diseases, and puberty disorders in β-thalassemic patients. Aim: The goal of the study was to scrutinize the impact of serum zinc and copper concentration in patients with beta-thalassemia major and also to observe the effect of zinc supplementation on transfusion dependent beta-thalassemia patients for six months. Method: 52 beta-thalassemia major patients were studied before and after supplementation of zinc for six months, and status was compared with 52 age and sex-matched healthy normal.  Serum zinc and copper concentration were measured by atomic absorption spectrophotometry (AAS) method. Result: There was a significant depleted activity of  serum zinc level (p<0.001), and the copper level was increased significantly (p<0.001) in patients when compared with normal. After six months of supplementation of zinc, there was a significantly enhanced zinc concentration (p<0.001),and copper was marginally increased (p>0.05) when compared with normal and baselines. Conclusion: Beta Thalassemia  major children are on numerous blood transfusions all the way through their life. Due  to this  thalassemic children are at risk of secondary iron burden. This further leads to the  enhanced  oxidative stress. One of the way to may overcome this situation to supply regular zinc supplementation along with treatment, which may be helpful to manage the situation. &nbsp

Arabidopsis Sec1/Munc18 protein SEC11 is a competitive and dynamic modulator of SNARE binding and SYP121-dependent vesicle traffic

The Arabidopsis thaliana Qa-SNARE SYP121 (=SYR1/PEN1) drives vesicle traffic at the plasma membrane of cells throughout the vegetative plant. It facilitates responses to drought, to the water stress hormone abscisic acid, and to pathogen attack, and it is essential for recovery from so-called programmed stomatal closure. How SYP121-mediated traffic is regulated is largely unknown, although it is thought to depend on formation of a fusion-competent SNARE core complex with the cognate partners VAMP721 and SNAP33. Like SYP121, the Arabidopsis Sec1/Munc18 protein SEC11 (=KEULE) is expressed throughout the vegetative plant. We find that SEC11 binds directly with SYP121 both in vitro and in vivo to affect secretory traffic. Binding occurs through two distinct modes, one requiring only SEC11 and SYP121 and the second dependent on assembly of a complex with VAMP721 and SNAP33. SEC11 competes dynamically for SYP121 binding with SNAP33 and VAMP721, and this competition is predicated by SEC11 association with the N terminus of SYP121. These and additional data are consistent with a model in which SYP121-mediated vesicle fusion is regulated by an unusual “handshaking” mechanism of concerted SEC11 debinding and rebinding. They also implicate one or more factors that alter or disrupt SEC11 association with the SYP121 N terminus as an early step initiating SNARE complex formation

A new scheme of radiation transfer in H II regions including transient heating of grains

A new scheme of radiation transfer for understanding infrared spectra of H II regions, has been developed. This scheme considers non-equilibrium processes (e. g. transient heating of the very small grains, VSG; and the polycyclic aromatic hydrocarbon, PAH) also, in addition to the equilibrium thermal emission from normal dust grains (BG). The spherically symmetric interstellar dust cloud is segmented into a large number of "onion skin" shells in order to implement the non-equilibrium processes. The scheme attempts to fit the observed SED originating from the dust component, by exploring the following parameters : (i) geometrical details of the dust cloud, (ii) PAH size and abundance, (iii) composition of normal grains (BG), (iv) radial distribution of all dust (BG, VSG & PAH). The scheme has been applied to a set of five compact H II regions (IRAS 18116- 1646, 18162-2048, 19442+2427, 22308+5812 & 18434-0242) whose spectra are available with adequate spectral resolution. The best fit models and inferences about the parameters for these sources are presented.Comment: 16 pages total including 3 tables and 2 figure

PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis

The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al

Mental health issues in unaccompanied refugee minors

Previous studies about unaccompanied refugee minors (URMs) showed that they are a highly vulnerable group who have greater psychiatric morbidity than the general population. This review focuses on mental health issues among URMs. Articles in databases PsycINFO, Medline and PubMed from 1998 to 2008 addressing this topic were reviewed. The literature had a considerable emphasis on the assessment of PTSD symptoms. Results revealed higher levels of PTSD symptoms in comparison to the norm populations and accompanied refugee minors. In several studies, age and female gender predicted or influenced PTSD symptoms. The existing literature only permits limited conclusions on this very hard to reach population. Future research should include the analysis of long-term outcomes, stress management and a more thorough analysis of the whole range of psychopathology. Additionally, the development of culturally sensitive norms and standardized measures for diverse ethnic groups is of great importance

The influence of semantic and phonological factors on syntactic decisions: An event-related brain potential study

During language production and comprehension, information about a word's syntactic properties is sometimes needed. While the decision about the grammatical gender of a word requires access to syntactic knowledge, it has also been hypothesized that semantic (i.e., biological gender) or phonological information (i.e., sound regularities) may influence this decision. Event-related potentials (ERPs) were measured while native speakers of German processed written words that were or were not semantically and/or phonologically marked for gender. Behavioral and ERP results showed that participants were faster in making a gender decision when words were semantically and/or phonologically gender marked than when this was not the case, although the phonological effects were less clear. In conclusion, our data provide evidence that even though participants performed a grammatical gender decision, this task can be influenced by semantic and phonological factors

High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor

The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structurefunction relationship of GPCRs. © 2014 Bill et al

Stabilization of Ion Concentration Polarization Using a Heterogeneous Nanoporous Junction

We demonstrate a recycled ion-flux through heterogeneous nanoporous junctions, which induce stable ion concentration polarization with an electric field. The nanoporous junctions are based on integration of ionic hydrogels whose surfaces are negatively or positively charged for cationic or anionic selectivity, respectively. Such heterogeneous junctions can be matched up in a way to achieve continuous ion-flux operation for stable concentration gradient or ionic conductance. Furthermore, the combined junctions can be used to accumulate ions on a specific region of the device.Korea Research Foundation (Grant MOEHRD: KRF-2007-331-D00040)Korean Science and Engineering Foundation (Grant MOST: R01-2007-000-20675-0)Korea Research Foundation (Grant MOEHRD: KRF-J03000)National Research Foundation of Korea (Grant NRF-2009- 352-D00034)National Institutes of Health (U.S.) (EB005743)National Science Foundation (U.S.). (CBET-0347348