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Common inflammatome gene signatures as well as disease-specific signatures were identified by analyzing 12 expression profiling data sets derived from 9 different tissues isolated from 11 rodent inflammatory disease models. The inflammatome signature significantly overlaps with known drug targets and co-expressed gene modules linked to metabolic disorders and cancer. A large proportion of genes in this signature are tightly connected in tissue-specific Bayesian networks (BNs) built from multiple independent mouse and human cohorts. Both the inflammatome signature and the corresponding consensus BNs are highly enriched for immune response-related genes supported as causal for adiposity, adipokine, diabetes, aortic lesion, bone, muscle, and cholesterol traits, suggesting the causal nature of the inflammatome for a variety of diseases. Integration of this inflammatome signature with the BNs uncovered 151 key drivers that appeared to be more biologically important than the non-drivers in terms of their impact on disease phenotypes. The identification of this inflammatome signature, its network architecture, and key drivers not only highlights the shared etiology but also pinpoints potential targets for intervention of various common diseases.

It has been possible to characterize the human orphan G-protein-coupled receptor HG55 as the CysLT1 receptor. Two different Xenopus laevis functional systems were used to characterize GH55 (CysLT1)-receptor activation. It was found that all three marketed cysteinyl leukotriene antagonists, zafirlukast (Accolate), montelukast (Singulair) and pranlukast (Onon) are potent competitors for the binding of radiolabelled leukotriene D4 to the CysLT1 receptor.

This paper reports a sub-set of results from a mixed-method ethnographic study of literacy among female graduates and undergraduates of a United Arab Emirates public university. With reference to survey data and two in-depth interviews, the paper focuses in particular on the predispositions and preferences of these women with regard to reading and writing in English and Modern Standard Arabic. Employing a New Literacy Studies theoretical framework along with a number of concepts developed by Bourdieu, the paper finds that literacy practices in this context are developing rapidly, influenced by the diverse transnational linguistic marketplaces in which these women grow up. Suggestions are made with regard to possible directions for curricular development in higher education in this region based on the opinions expressed by these young women. [ABSTRACT FROM AUTHOR]

Nicotinic acid (NA) is commonly used to treat dyslipidemia, but it elicits an adverse effect, termed flushing, which consists of cutaneous vasodilation with associated discomfort. An animal model of NA-induced flushing has been established in mice. As in humans, NA stimulated vasodilation in a dose-dependent manner, was associated with an increase of the vasodilatory prostaglandin (PG) D2 in plasma and could be blocked by pretreatment with aspirin. Two PGD2 receptors have been identified: PGD2 receptor 1 (DP1, also called DP) and PGD2 receptor 2 (DP2, sometimes termed CRTH2). DP2 does not mediate NA-induced vasodilation; the DP2-specific agonist DK-PGD2 (13,14-dihydro-15-keto-PGD2) did not induce cutaneous vasodilation, and DP2-/- mice had a normal vasodilatory response to NA. By contrast, BW245C, a DP1-selective agonist, induced vasodilation in mice, and MK-0524, a DP1-selective antagonist, blocked both PGD2- and NA-induced vasodilation. NA-induced vasodilation was also studied in DP1+/+, DP1+/-, and DP1-/- mice; although NA-induced vasodilation depended almost completely on DP1 in female mice, it depended only partially on DP1 in male mice. The residual NA-induced vasodilation in male DP-/- mice was aspirin-sensitive. Thus, in the mouse, DP1 appears to be an important component involved in NA-induced vasodilation, but other cyclooxygenase-dependent mechanisms also may be involved. A clinical study in healthy men and women demonstrated that treatment with MK-0524 reduced the symptoms of flushing and the increase in skin perfusion after the administration of NA. These studies suggest that DP1 receptor antagonism may be an effective means to suppress NA-induced flushing in humans. [ABSTRACT FROM AUTHOR]

1 The recombinant human prostaglandin D[SUB2] (PGD[SUB2]) receptor, hCRTH2, has been expressed in HEK293(EBNA) and characterized with respect to radioligand binding and signal transduction properties High and low affinity binding sites for PGD[SUB2] were identified in the CRTH2 receptor population by saturation analysis with respective equilibrium dissociation constants (K[SUBD]) of 2.5 and 109 nM. This reveated that the affinity of PGD[SUB2] for CRTH2 is eight times less than its affinity for the DP receptor. 2 Equilibrium competition blinding assays revealed that of the compounds tested, only PGD[SUB2] and several related metabotites bound with high affinity to CRTH2 (K[SUBi] values ranging from 2.4 to 34.0 nM) with the following rank order of potency PGD[SUB2] > 13,14-dihydro-15-keto PGD[SUB2] > 15-deoxy-Δ[SUP12, 14]-PGJ[SUB2] > PGJ[SUB2] > Δ[SUP12]-PGJ[SUB2] > 15(S)-15 methyl-PGD[SUB2]. This is in sharp Contrast with the rank order of potency obtained at DP : PGD[SUB2] > PGJ[SUB2] > Δ[SUP12]-PGJ[SUB2] > 15-deoxy Δ[SUP12, 14]-PGJ[SUB2] > > > 13, 14-dihydro-15-keto-PGD[SUB2]. 3 Functional studies demonstrated that PGD[SUB2] activation of recombinant CRTH2 results in decrease of intracellular cAMP in a pertussis toxin-sensitive manner. Therefore, we showed that CRTH2 can functionally couple to the G-protein G[SUBxi/o] PGD[SUB2] and related metabolites were tested and their rank order of potency followed the results of the membrane binding assay. 4 By Northern blot analysis, we showed that, besides haemopoietic cells, CRTH2 is expressed in many other tissues such as brain, heart, thymus, spleen and various tissues of the digestive system. In addition, in situ hybridization studies revealed that CRTH2 mRNA is expressed in human eosinophils. Finally, radioligand binding studies demonstrated that two eosinophilic cell lines. butyric acid-differentiated HL-60 and AML 14.3D10, also endogenously express CRTH2. [ABSTRACT FROM AUTHOR]