GPCRs: The most promiscuous druggable receptor of the mankind.

All physiological events in living organisms originated as specific chemical/biochemical signals on the cell surface and transmitted into the cytoplasm. This signal is translated within milliseconds-hours to a specific and unique order required to maintain optimum performance and homeostasis of living organisms. Examples of daily biological functions include neuronal communication and neurotransmission in the process of learning and memory, secretion (hormones, sweat, and saliva), muscle contraction, cellular growth, differentiation and migration during wound healing, and immunity to fight infections.

PARK2 polymorphisms predict disease progression in patients infected with hepatitis C virus.

Unlabelled:  Background. The protein encoded by PARK2 gene is a component of the ubiquitin-proteasome system that mediates targeting of proteins for the degradation pathway. Genetic variations at PARK2 gene were linked to various diseases including leprosy, typhoid and cancer.

Human Cytokinome Analysis for Interferon Response.

Unlabelled: Cytokines are a group of small secreted proteins that mediate a diverse range of immune and nonimmune responses to inflammatory and microbial stimuli. Only a few of these cytokines mount an antiviral response, including type I, II, and III interferons (IFNs). During viral infections and under inflammatory conditions, a number of cytokines and chemokines are coproduced with IFN; however, no systematic study exists on the interactions of the cytokine repertoire with the IFN response.

The association of toll-like receptor 4 polymorphism with hepatitis C virus infection in Saudi Arabian patients.

Hepatitis C virus (HCV) is a single stranded RNA virus. It affects millions of people worldwide and is considered as a leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. A recent study reported that TLR4 gene polymorphisms are good prognostic predictors and are associated with protection from liver fibrosis among Caucasians.

Bioinformatics and experimental derivation of an efficient hybrid 3' untranslated region and use in expression active linear DNA with minimum poly(A) region.

Untranslated regions at the 3' end of the messenger RNA (3' UTR) contain regulatory elements that affect mRNA stability and translation and subsequently the protein levels. In this report, we performed bioinformatics analysis on housekeeping genes with putative stable mRNAs in comparison with Class II AU-rich elements (ARE)-containing mRNAs, a group of mRNAs known to represent many labile transcripts. We have found that ARE-mRNAs are less abundant and had longer 3' UTR than stable housekeeping mRNAs.

Expressed gene clusters associated with cellular sensitivity and resistance towards anti-viral and anti-proliferative actions of interferon.

Interferons (IFN) are multi-functional proteins that induce a large number of genes which mediate many biological processes including host defense, cell growth control, signaling, and metabolism. Bioinformatics analysis of the 3'-untranslated regions of IFN-stimulated genes (ISGs) showed that the AU-rich elements (ARE) exist in approximately 10% of the mRNA induced by IFN. The human epithelial cell lines, WISH and 293, and the human B cell lines, Daudi and RPMI 1788, were assessed for their response to type-I IFN.

RNase L mediates transient control of the interferon response through modulation of the double-stranded RNA-dependent protein kinase PKR.

The transient control of diverse biological responses that occurs in response to varied forms of stress is often a highly regulated process. During the interferon (IFN) response, translational repression due to phosphorylation of eukaryotic initiation factor 2alpha, eIF2alpha, by the double-stranded RNA-dependent protein kinase, PKR, constitutes a means of inhibiting viral replication. Here we show that the transient nature of the IFN response against acute viral infections is regulated, at least in part, by RNase L.

Suppression of ovarian carcinoma cell growth in vivo by the interferon-inducible plasma membrane protein, phospholipid scramblase 1.

Phospholipid scramblase 1 (PLSCR1) is an IFN-inducible, endofacial plasma membrane protein that has been proposed to mediate accelerated transbilayer movement of plasma membrane phospholipids in cells exposed to elevated cytoplasmic [Ca (2+)]. The marked transcriptional up-regulation of this gene by IFN in a wide variety of cell types suggested that PLSCR1 might also contribute to biological effects associated with IFN. To study the potential contribution of cellular PLSCR1 to the antiproliferative and tumor-suppressive activities of IFN, PLSCR1 cDNA was stably expressed in the human ovarian cancer cell line HEY1B, and the growth of these cells was compared with matched vector transfected controls both in vitro and in vivo.

Transcriptional control of the human plasma membrane phospholipid scramblase 1 gene is mediated by interferon-alpha.

Interferons (IFNs) mediate their diverse biologic activities through induction of the expression of multiple genes. Whereas the mode of action of certain of these IFN-regulated genes has been well characterized, most of the molecular and cellular events underlying the constellation of biologic responses to the IFNs remain unresolved. This study showed that the newly identified PLSCR1 gene for phospholipid scramblase, previously implicated in remodeling of plasma membrane phospholipids, is regulated at the transcriptional level by IFN-alpha.

The alpha chemokine, interleukin 8, inhibits the antiviral action of interferon alpha.

Interferon (IFN) exhibits a potent antiviral activity in vitro and plays a major role in the early defense against viruses. Like IFN, the proinflammatory chemokine, interleukin (IL)-8, is induced by viruses and appears in circulation during viral infections. In an in vitro cytopathic effect assay for IFN, we found that IL-8 can inhibit IFN-alpha activity in a dose-dependent manner.

Interleukin-8 selectively enhances cytopathic effect (CPE) induced by positive-strand RNA viruses in the human WISH cell line.

Interleukin-8 (IL-8), a proinflammatory chemokine, is induced by viruses and appears in circulation during viral infections. We found that IL-8 enhanced cytopathic effect induced by the positive strand RNA virus, encephalomyocarditis virus (EMCV), in the human WISH cell line. The enhancement was dependent on IL-8 dose and virus dose and was reversible by specific monoclonal antibodies to IL-8.

MTS interferon assay: a simplified cellular dehydrogenase assay for interferon activity using a water-soluble tetrazolium salt.

MTS, a tetrazolium dye, is reduced by hydrogenases in living cells to a water-soluble formazan. When it is added to the medium at the end of a cytopathic effects (CPE) inhibition interferon assay, the formazan formed diffuses into the medium; the resultant optical density directly and quantitatively measures how much cellular damage has been produced by the challenge virus in the presence of different amounts of interferon. The use of MTS has considerable advantages in that after it is added, no further steps, such as washing of the cells, extraction of dye, or other manipulations, are needed.