Linkage disequilibrium mapping of schizophrenia susceptibility to the CAPON region of chromosome 1q22

Previously, we have reported linkage of markers from chromosome 1q22 to schizophrenia, a finding supported by several independent studies. We have now examined the region of strongest linkage for evidence of linkage disequilibrium (LD) in a sample of 24 Canadian familial-schizophrenia pedigrees. Analysis of 14 microsatellites and 15 single-nucleotide polymorphisms (SNPs) from the 5.4-Mb region between D1S1653 and D1S1677 produced significant evidence (nominal P<.05) of LD between schizophrenia and 2 microsatellites and 6 SNPs. All of the markers exhibiting significant LD to schizophrenia fall within the genomic extent of the gene for carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON), making it a prime positional candidate for the schizophrenia-susceptibility locus on 1q22, although initial mutation analysis of this gene has not identified any schizophrenia-associated changes within exons. Consistent with several recently identified candidate genes for schizophrenia, CAPON is involved in signal transduction in the NMDA receptor system, highlighting the potential importance of this pathway in the etiology of schizophrenia.     

IL-10 inhibits Fc epsilon RI expression in mouse mast cells

FcepsilonRI expression and function is a central aspect of allergic disease. Using bone marrow-derived mouse mast cell populations, we have previously shown that the Th2 cytokine IL-4 inhibits FcepsilonRI expression and function. In the current study we show that the Th2 cytokine IL-10 has similar regulatory properties, and that it augments the inhibitory effects of IL-4. FcepsilonRI down-regulation was functionally significant, as it diminished inflammatory cytokine production and IgE-mediated FcepsilonRI up-regulation. IL-10 and IL-4 reduced FcepsilonRI beta protein expression without altering the alpha or gamma subunits. The ability of IL-4 and IL-10 to alter FcepsilonRI expression by targeting the beta-chain, a critical receptor subunit known to modulate receptor expression and signaling, suggests the presence of a Th2 cytokine-mediated homeostatic network that could serve to both initiate and limit mast cell effector function.     

Tumor necrosis factor-alpha-induced TRPC1 expression amplifies store-operated Ca2+ influx and endothelial permeability

We determined the effects of TNF-alpha on the expression of transient receptor potential channel (TRPC) homologues in human vascular endothelial cells and the consequences of TRPC expression on the endothelial permeability response. We observed that TNF-alpha exposure increased TRPC1 expression without significantly altering expression of other TRPC isoforms in human pulmonary artery endothelial cells (HPAEC). Because TRPC1 belongs to the store-operated cation channel family, we measured the Ca(2+) store depletion-mediated Ca(2+) influx in response to thrombin exposure. We observed that thrombin-induced Ca(2+) influx in TNF-alpha-stimulated HPAEC was twofold greater than in control cells. To address the relationship between store-operated Ca(2+) influx and TRPC1 expression, we overexpressed TRPC1 by three- to fourfold in the human dermal microvascular endothelial cell line (HMEC) using the TRPC1 cDNA. Thrombin-induced store Ca(2+) depletion in these cells caused approximately twofold greater increase in Ca(2+) influx than in control cells. Furthermore, the inositol 1,4,5-trisphosphate-sensitive store-operated cationic current was increased greater than twofold in TRPC1-transfected cells compared with control. To address the role of Ca(2+) influx via TRPC1 in signaling endothelial permeability, we measured actin-stress fiber formation and transendothelial monolayer electrical resistance (TER) in the TRPC1 cDNA-transfected HMEC and TNF-alpha-challenged HPAEC. Both thrombin-induced actin-stress fiber formation and a decrease in TER were augmented in TRPC1-overexpressing HMEC compared with control cells. TNF-alpha-induced increased TRPC1 expression in HPAEC also resulted in marked endothelial barrier dysfunction in response to thrombin. These findings indicate the expression level of TRPC1 in endothelial cells is a critical determinant of Ca(2+) influx and signaling of the increase in endothelial permeability.     

Microbiological and Histological Examinations of Endangered Neurergus kaiseri Tissues Displaying Red-leg Syndrome

Presence of the red leg syndrome （RLS） was documented through bacterial and histological examinations in the endangered Kaiser＇s mountain newt Neurergus kaiseri obtained from a pet shop. The individuals which were severely infected showed lethargy, appetite loss, weight loss, abdominal skin redness and skin ulcers on hind legs. This study reveals the presence of two bacteria causing RLS on the skin of captive AT. kaiseri including Proteus vulgaris and Bacillus cereus. Sections of skin in affected areas and internal organs were examined through standard histological procedures. Histologically, epidermal necrosis and ulcers, epidermal gland depletion, myositis and subcutaneous edema, gastric submucosal edema and hepatomegaly were seen. There were also correlations between the microbial infection and structural changes in tissues of Kaiser＇s mountain newt. The severity of the structural changes are related to the level of microbial infection in the target organs and could be sustained by the isolation of P. vulgaris and other pathogens. The presence of the infective bacterial population and their interaction on the skin of the newt may have changed the normal skin flora and facilitate the prevalence of other disease.     

Dysregulated cannabinoid signaling disrupts uterine receptivity for embryo implantation

The mechanisms by which synchronized embryonic development to the blastocyst stage, preparation of the uterus for the receptive state, and reciprocal embryo-uterine interactions for implantation are coordinated are still unclear. We show in this study that preimplantation embryo development became asynchronous in mice that are deficient in brain-type (CB1) and/or spleen-type (CB2) cannabinoid receptor genes. Furthermore, whereas the levels of uterine anandamide (endocannabinoid) and blastocyst CB1 are coordinately down-regulated with the onset of uterine receptivity and blastocyst activation prior to implantation, these levels remained high in the nonreceptive uterus and in dormant blastocysts during delayed implantation and in pregnant, leukemia inhibitory factor (LIF)-deficient mice with implantation failure. These results suggest that a tight regulation of endocannabinoid signaling is important for synchronizing embryo development with uterine receptivity for implantation. Indeed this is consistent with our finding that while an experimentally induced, sustained level of an exogenously administered, natural cannabinoid inhibited implantation in wild-type mice, it failed to do so in CB1(-/-)/CB2(-/-) double mutant mice. The present study is clinically important because of the widely debated medicinal use of cannabinoids and their reported adverse effects on pregnancy.     

Effect of four different nutrition regimes on the alpha-amylase gene expression in the Indian moth,Plodia interpunctella

Plodia interpunctella (Hübner 1813) (Lepidoptera: Pyralidae) is a cosmopolitan species known to infest a wide range of dried plant materials, including legumes and cereals. In this study, enzyme activity and expression of alpha-amylase gene in larval P. interpunctella grown on four different nutrition regimes was studied. The different nutrition regimes caused differential change in expression of alpha-amylase gene. Compared with the control (artificial diet), the walnut regime caused a 10.8% increase in expression of the alpha-amylase gene, whereas 79.3, 52.5, and 7.5% decreases were observed in the larvae grown on dates, raisins and oleaster respectively. The results also showed that glucose repression varied among larvae feeding on different food diets. The results revealed that expression of the alpha-amylase coding gene was significantly reduced in the larvae grown on date and raisin containing high amounts of glucose. A biochemical assay indicated overlapping of alpha-amylase activity and expression. Complexity in expression of amylase genes suggests the existence of a negative feedback mechanism in the insect larvae. Different parameters can affect gene expression and activation, which may explain the results presented here.