Association between the C957T polymorphism of the dopamine D2 receptor gene and schizophrenia

The aim of this study was to investigate the relationship between the functional C957T single-nucleotide polymorphism of the dopamine D2 receptor (DRD2) gene and the risk for schizophrenia. We therefore conducted a case-control association study of 188 Finnish schizophrenia patients meeting the DSM-IV criteria and 384 healthy controls. The 5' nuclease assay (TaqMan) was used to determine genotypes. A greater proportion of patients with schizophrenia than healthy controls were C-allele carriers (odds ratio 1.5, 95% confidence interval (CI) 1.0-2.3, P=0.05). Our results are in agreement with an earlier association study suggesting that the C957T C-allele plays a role in the genetic vulnerability for schizophrenia and support the involvement of the DRD2 gene in schizophrenia pathogenesis.     

Repression of cap-dependent translation attenuates the transformed phenotype in non-small cell lung cancer both in vitro and in vivo

Aberrant hyperactivation of the cap-dependent protein synthesis apparatus has been documented in a wide range of solid tumors, including epithelial carcinomas, but causal linkage has only been established in breast carcinoma. In this report, we sought to determine if targeted disruption of deregulated cap-dependent translation abrogates tumorigenicity and enhances cell death in non-small cell lung cancer (NSCLC). NSCLC cell lines were stably transfected with either wild-type 4E-BP1 (HA-4E-BP1) or the dominant-active mutant 4E-BP1(A37/A46) (HA-TTAA). Transfected NSCLC cells with enhanced translational repression showed pronounced cell death following treatment with gemcitabine. In addition, transfected HA-TTAA and HA-4E-BP1wt proteins suppressed growth in a cloning efficiency assay. NSCLC cells transduced with HA-TTAA also show decreased tumorigenicity in xenograft models. Xenograft tumors expressing HA-TTAA were significantly smaller than control tumors. This work shows that hyperactivation of the translational machinery is necessary for maintenance of the malignant phenotype in NSCLC, identifies the molecular strategy used to activate translation, and supports the development of lung cancer therapies that directly target the cap-dependent translation initiation complex.     

Processing of audiovisual speech in Broca's area

We investigated cerebral processing of audiovisual speech stimuli in humans using functional magnetic resonance imaging (fMRI). Ten healthy volunteers were scanned with a 'clustered volume acquisition' paradigm at 3 T during observation of phonetically matching (e.g., visual and acoustic /y/) and conflicting (e.g., visual /a/ and acoustic /y/) audiovisual vowels. Both stimuli activated the sensory-specific auditory and visual cortices, along with the superior temporal, inferior frontal (Broca's area), premotor, and visual-parietal regions bilaterally. Phonetically conflicting vowels, contrasted with matching ones, specifically increased activity in Broca's area. Activity during phonetically matching stimuli, contrasted with conflicting ones, was not enhanced in any brain region. We suggest that the increased activity in Broca's area reflects processing of conflicting visual and acoustic phonetic inputs in partly disparate neuron populations. On the other hand, matching acoustic and visual inputs would converge on the same neurons.     

Apolipoprotein E genotype is related to plasma levels of C-reactive protein and lipids and to longevity in nonagenarians

OBJECTIVE: Apolipoprotein E (APOE) genotype is a regulator of hepatic lipoprotein metabolisms and has been linked with longevity. The relationship between APOE genotype and plasma C-reactive protein (CRP), which is produced by the liver during inflammation, has not been studied in nonagenarians. The aim of the present study was to establish whether APOE genotype is related to plasma concentrations of CRP and lipids, or longevity among nonagenarians. DESIGN AND PATIENTS: This cross-sectional study consisted of 291 Finnish nonagenarians and three previously described and genotyped control populations from the same area (i.e. newborns, 40-year-olds, and 70-year-olds). RESULTS: In all nonagenarians and especially in women (P= 0.038), CRP level decreased linearly in the genotype order of epsilon2/2, epsilon2/3, epsilon3/3, epsilon2/4, epsilon3/4 and epsilon4/4. Total (P= 0.009) and low-density lipoprotein (LDL) cholesterol (P = 0.076) levels, in turn, were increased in the epsilon4 allele carriers. In newborns, the epsilon4 frequency was 0.192, in 40-year-olds 0.181, in 70-year-olds 0.179 and in nonagenarians 0.095 (P < 0.0001). The decrease in the epsilon4 allele frequency in the elderly was more clearly seen in women than in men. CONCLUSIONS: APOEepsilon4 allele seems to be associated with decreased inflammatory response as measured by CRP among nonagenarians. This finding may partly explain why some epsilon4 allele carriers can reach very old age despite increased risk of hypercholesterolaemia.     

The Pro12Ala polymorphism of the PPARγ2 gene is associated with hepatic glucose uptake during hyperinsulinemia in subjects with type 2 diabetes mellitus

The Ala12 allele of the peroxisome proliferator-activated receptor γ gene (PPARG2) has been associated with reduced risk of type 2 diabetes mellitus (T2DM) and increased whole-body and skeletal muscle insulin sensitivity in nondiabetic subjects. The effect of the Pro12Ala polymorphism on tissue specific insulin sensitivity in subjects with T2DM has not been previously investigated. We studied the effect of the Pro12Ala polymorphism on the rates of whole-body, skeletal muscle, and subcutaneous adipose tissue glucose uptake (GU) in T2DM subjects, and the rates of hepatic GU in nondiabetic and T2DM subjects during hyperinsulinemia. Our study included 105 T2DM subjects whose whole-body, skeletal muscle, subcutaneous adipose tissue, and hepatic GUs were measured using ¹⁸F-fluorodeoxyglucose and positron emission tomography during the hyperinsulinemic euglycemic clamp. Hepatic GU was also measured in 68 nondiabetic subjects. In obese (body mass index ≥27 kg/m²) subjects with T2DM, the rate of hepatic GU was 28% lower in subjects with the Pro12Pro genotype than in carriers of the Ala12 allele (P = .001); and a similar trend was observed in nondiabetic obese subjects (P = .137). No effect of the Pro12Ala polymorphism on the rates of whole-body, skeletal muscle, or subcutaneous adipose tissue GU was observed in T2DM subjects. We conclude that the Ala12 allele of PPARG2 is associated with higher hepatic GU in obese subjects with T2DM.     

Probiotics modulate the Bifidobacterium microbiota of elderly nursing home residents

Gut Bifidobacterium microbiota of the elderly has been suggested to differ from that of adults, possibly promoting the risk of infections and gut barrier dysfunction. Specific probiotics may improve the gut barrier. In this randomized, placebo-controlled intervention study, 66 elders consumed a fermented oat drink containing probiotic Bifidobacterium longum 46 and B. longum 2C or a non-fermented placebo oat drink for 6 months. Faecal samples were collected before, during and after the intervention. Levels of faecal bifidobacteria were determined using species-specific quantitative PCR and plate counting. The Bifidobacterium levels in the elderly were high and the species composition diverse. Probiotic intervention increased the levels bifidobacteria significantly. Specifically, the levels of B. catenulatum, B. bifidum and B. breve were enhanced. Consumption of the fermented oat drink itself was also associated with certain changes in microbiota. In conclusion, Bifidobacterium microbiota of elderly subjects may be modulated by probiotic administration. In some healthy elderly populations, Bifidobacterium microbiota may be more abundant and diverse than previously suggested.