Genetic Association Analysis of ITGB3 Polymorphisms with Age at Onset of Schizophrenia

Schizophrenia (SCZ) is a debilitating disorder with a prevalence of approximately 1 % worldwide. SCZ is known to have a high degree of genetic and clinical heterogeneity and is a major health problem worldwide. The integrin-β 3 subunit gene (ITGB3) gene at 17q21.32 has been implicated in psychiatric disorders. We therefore hypothesized that ITGB3 gene polymorphisms might also play a role in SCZ and age at onset (AAO) of SCZ. We investigated the genetic associations of 23 single-nucleotide polymorphisms (SNPs) of the ITGB3 gene with AAO in SCZ in two Caucasian samples (2,166 cases and 2,525 controls) using linear regression analysis and meta-analysis. We observed four ITGB3-SNPs associated with AAO in SCZ in a non-Genetic Association Information Network (GAIN) sample (p?<?10^?3). Three of these four SNPs were replicated in the GAIN sample. The SNP rs16941771 was most significantly associated with AAO (p?=?7.47?×?10^?5). Meta-analysis showed that 6 of 23 SNPs were associated with AAO. The haplotype analysis also supports the association of ITGB3 with AAO. Three disease-associated SNPs were located at species-conserved regions, indicating functional importance. This is the first report which shows that ITGB3 variants are associated with AAO in SCZ, providing direct evidence of the use of AAO as an intermediate phenotype to dissect the complex genetics of SCZ.     

Predatory behavior of Synthesiomyia nudiseta larvae (Diptera: Muscidae) on several necrophagous blowfly species (Diptera: Calliphoridae)

Intraguild interactions play a prominent role in sarcosaprophagous communities, so intraspecific and interspecific competition phenomena between fly larvae take place. Synthesiomyia nudiseta is a species that has recently been recorded on human corpses in Europe, and it has been cited in forensic cases in Spain and Italy. The mature larvae are known to be facultative predators on necrophagous fly larvae, but their role as predators is unknown. The aim of this paper is to investigate the predatory behavior of S. nudiseta on the most abundant blowfly larvae in sarcosaprophagous communities in southwestern Europe (i.e., Chrysomya albiceps, Lucilia sericata, and Calliphora vicina). Intraspecific and interspecific competition experiments were carried out to study the effect of this species in the necrophagous diptera community. First-instar larvae were placed in plastic cups with the same amount of pig liver (15 g) at different densities (50, 100, 150, and 300 individuals/cup). Mortality in blowflies increased when S. nudiseta larvae were present: up to 98.40% in Ch. albiceps, 89.60% in L. sericata, and 84.93% in C. vicina. Pre-imaginal developmental time and adult wing size were analyzed and compared under each of the intraspecific and interspecific conditions; both variables were affected by competition in all cases. The implications of the presence of S. nudiseta for sarcosaprophagous community dynamics and its effect on the estimation of postmortem interval (PMI) are discussed.

     

Morphometric analysis of facial landmark data to characterize the facial phenotype associated with fetal alcohol syndrome

Procrustes analysis and principal component analysis were applied to stereo-photogrammetrically obtained landmarks to compare the facial features associated with fetal alcohol syndrome (FAS) in subjects with FAS and normal controls. Two studies were performed; both compared facial landmark data of FAS and normal subjects, but they differed in the number of landmarks chosen. The first study compared landmarks representing palpebral fissure length, upper lip thinness and philtrum smoothness and revealed no significant difference in shape. The second study added to the landmarks used in the first those affected by mid-face hypoplasia, and revealed significant differences in shape between the two groups, broadly confirming the FAS gestalt reported in the literature. Some disagreement in the characteristic FAS facial shape between our results and those reported in the literature may be due to ethnic variation.     

Morphological effects of two protocols of passive stretch over the immobilized rat soleus muscle

This study evaluated two different stretching protocols employed during a period of hind-limb immobilization in terms of their effects on muscle morphology. Quantitative data regarding the soleus muscle were obtained based on the clinical hypothesis that a high frequency of this exercise would improve the recovery of muscle structure. Twenty-four male Wistar rats were divided into four groups (n = 6 each): the control group (C); the immobilized group, in which the left hind limb was immobilized in order to maintain the soleus muscle in a fully shortened position for 3 weeks (I); the 'immobilized and stretched every 3 days' group, in which the left hind limb was immobilized as in the immobilized group, but with the soleus muscle stretched every 3 days for 40 min (Ist3); and the 'immobilized (as in the immobilized group) and stretched every 7 days' group (ISt7). All soleus muscles were excised 21 days after the beginning of the experiment, and were processed for (1) haematoxylin and eosin and myosin ATPase to evaluate muscle morphology and cross-sectional area and the proportions of the different fibre types, and (2) ultrastructural analysis. The cross-sectional area was found to have decreased in all fibre types (I, II and C), mainly in ISt7, when compared with the C group and ISt3 group. The proportion of the different fibre types did not show statistical difference between groups. Light and electron microscopy examination revealed signs of cell degeneration that was more intense in the group immobilized and stretched three times a week. In conclusion, sessions of passive stretching applied to the soleus during immobilization induce muscle fibre injury, suggesting that this therapeutic tool should be applied carefully to disused muscles.     

Human pancreatic secretory trypsin inhibitor stabilizes intestinal mucosa against noxious agents

Pancreatic secretory trypsin inhibitor (PSTI) is a serine protease inhibitor, expressed in gut mucosa, whose function is unclear. We, therefore, examined the effects of PSTI on gut stability and repair. Transgenic mice overexpressing human PSTI within the jejunum (FABPi(-1178 to +28) hPSTI construct) showed no change in baseline morphology or morphometry but reduced indomethacin-induced injury in overexpressing hPSTI region by 42% (P < 0.01). Systemic recombinant hPSTI did not affect baseline morphology or morphometry but truncated injurious effects in prevention and recovery rat models of dextran-sodium-sulfate-induced colitis. In vitro studies showed PSTI stimulated cell migration but not proliferation of human colonic carcinoma HT29 or immortalized mouse colonic YAMC cells. PSTI also induced changes in vectorial ion transport (short-circuit current) when added to basolateral but not apical surfaces of polarized monolayers of Colony-29 cells. Restitution and vectorial ion transport effects of PSTI were dependent on the presence of a functioning epidermal growth factor (EGF) receptor because cells with a disrupted (EGFR(-/-) immortalized cells) or neutralized (EGFR blocking antibodies or tyrosine kinase inhibitor) receptor prevented these effects. PSTI also reduced the cytokine release of lipopolysaccharide-stimulated dendritic cells. We conclude that administration of PSTI may provide a novel method of stabilizing intestinal mucosa against noxious agents and stimulating repair after injury.     

Valproatverordnungen bei Mädchen und Frauen im gebärfähigen Alter in Deutschland

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Aufgrund des teratogenen Potenzials von Valproat wurden die Empfehlungen zur Risikoaufklärung und Verordnung bei...