Genome-wide association study identifies a common variant associated with risk of endometrial cancer

Endometrial cancer is the most common malignancy of the female genital tract in developed countries. To identify genetic variants associated with endometrial cancer risk, we performed a genome-wide association study involving 1,265 individuals with endometrial cancer (cases) from Australia and the UK and 5,190 controls from the Wellcome Trust Case Control Consortium. We compared genotype frequencies in cases and controls for 519,655 SNPs. Forty seven SNPs that showed evidence of association with endometrial cancer in stage 1 were genotyped in 3,957 additional cases and 6,886 controls. We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 × 10(-10)) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes.     

A bivalent Huntingtin binding peptide suppresses polyglutamine aggregation and pathogenesis in Drosophila

Huntington disease is caused by the expansion of a polyglutamine repeat in the Huntingtin protein (Htt) that leads to degeneration of neurons in the central nervous system and the appearance of visible aggregates within neurons. We have developed and tested suppressor polypeptides that bind mutant Htt and interfere with the process of aggregation in cell culture. In a Drosophila model, the most potent suppressor inhibits both adult lethality and photoreceptor neuron degeneration. The appearance of aggregates in photoreceptor neurons correlates strongly with the occurrence of pathology, and expression of suppressor polypeptides delays and limits the appearance of aggregates and protects photoreceptor neurons. These results suggest that targeting the protein interactions leading to aggregate formation may be beneficial for the design and development of therapeutic agents for Huntington disease.     

BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice

Faithful segregation of replicated chromosomes is essential for maintenance of genetic stability and seems to be monitored by several mitotic checkpoints. Various components of these checkpoints have been identified in mammals, but their physiological relevance is largely unknown. Here we show that mutant mice with low levels of the spindle assembly checkpoint protein BubR1 develop progressive aneuploidy along with a variety of progeroid features, including short lifespan, cachectic dwarfism, lordokyphosis, cataracts, loss of subcutaneous fat and impaired wound healing. Graded reduction of BubR1 expression in mouse embryonic fibroblasts causes increased aneuploidy and senescence. Male and female mutant mice have defects in meiotic chromosome segregation and are infertile. Natural aging of wild-type mice is marked by decreased expression of BubR1 in multiple tissues, including testis and ovary. These results suggest a role for BubR1 in regulating aging and infertility.     

Chronic effects of nicotine on gastric secretion in vagotomized rats

Résumé La sécrétion gastrique a été mesurée dans des rats mâles avec ligature pylorique de deux heures, après 14 jours d'injections sous-cutanées de nicotine ou de NaCl. Les résultats de l'administration de nicotine furent une augmentation du volume du suc gastrique, de la production d'acide et de la production de pepsine. La vagotomie abdominale bilatérale a prévenu la stimulation gastrique secreteuse, provoquée par la nicotine.     

The chronic effects of nicotine monomethidide on gastric secretion in pylorus-ligated rats

Résumé L'action de la nicotine monométhyliodine (NMI) sur la sécrétion gastrique basique et sur les concentrations de choline de cervelles, d'acétylcholine et de nicotine et sur l'activité de la transacétylcholinestérase a été étudiée chez des rats. Le NMI, sel quaternaire de nicotine, qui ne traverse pas la barrière hématoencéphalique, a été administré dans de la gélatine à 6% en dosage sous-cutané de 1000 g/ml/kg/jour pendant 14 jours. Le NMI n'a pas changé de paramètres et aucune trace de nicotine n'a été découverte dans les homogénates de cervelles complètes.     

Degradation of encephalitogenic protein in aerobic ascorbic acid solutions.

Aerobic ascorbic acid solutions are capable of extensively cleaving the peptide chain of the myelin basic protein. Cleavage occurred most readily with C-terminal to aspartic acid, serine, threonine, glutamic acid and leucine residues.