In this work, we investigate the investment of entomopathogenic

Newborn piglets were submitted to normobaric hypoxia (5% O 2 , 95% N 2 ) for either 1 or 4 h. The effects of hypoxia on the neonatal brain were characterized through a time-course analysis of levels of various proteins such as heat shock proteins (HSP27, 70, and 90), hypoxia inducible factor-1␣ (HIF-1␣), neuronal nitric oxide synthase (nNOS), hemeoxygenase-2 (HO-2), and caspase-3. The expression of these proteins was determined at different stages of recovery up to 72 h in cerebellum, cortex, and hippocampus by Western blot analysis in hypoxic maintained animals that were made hypoxic at either 20 or 37°C. In all regions of the brain, HIF-1␣ and HSP27 expression were strongly increased until 22 h of recovery. No significant changes were observed for HSP70, HSP90, and HO-2. A small elevation of expression of nNOS was observed at early stages in the cerebellum and the cortex with no change in the hippocampus.Expression of caspase 3 was strongly increased in the cortex 24 and 48 h after hypoxia but unchanged in the hippocampus. These results are presented in terms of the porcine model of nonischemic hypoxia and its delayed neuronal effects on the cerebral outcome. Because of their recently established biochemical and functional interactions, the expression of the main HSPs, HIF-1␣, nNOS, and caspase-3 after hypoxia are delineated. Perinatal asphyxia and hypoxia are common causes of neonatal morbidity. Among survivors, several disabilities are observed, including pulmonary, renal, cardiac, and encephalopathic dysfunction (1,2). Asphyxia at birth can result in severe auditory problems for the infant (3,4) as well as increased risks of amnesia (5) and schizophrenia presenting at different stages (6). Outcomes of asphyxia and/or hypoxia-ischemia can also result in cognitive impairment and developmental delay for the infants (7). Such severe sequelae of birth hypoxia are apparent early at the molecular level in the brain. Impairment as a result of hypoxia includes the transient reduction of GABA receptor numbers (8), altered expression of glutamate transporters (9), and/or a disruption of myelin gene expression (10). Because of the severe consequences of hypoxia at birth time on cerebral functions, a better characterization of molecular changes within the hypoxic neonatal brain is of crucial importance.The study of the expression and induction of stress proteins in the hypoxic brain is of particular interest because heat shock proteins (HSPs) have cytoprotective properties and are induced after a variety of stressors, such as elevated temperature (11-13) or hypoxia (14). HSPs are classified in three large families according to their molecular weights (11-13). However, very few studies have described the developmental changes of HSPs at the time of birth (15-17). The protective role of HSPs against hypoxia at birth has not been investigated, although in the brain, these proteins are known to be cytoprotective after hypoxia-ischemia (18,19). Other proteins induced by neonatal hypoxic stress are also of interest. Hypoxia i...

Maturity Onset Diabetes of the Young type 3 (MODY3), linked to mutations in the transcription factor HNF1A, is the most prevalent form of monogenic diabetes mellitus. HNF1alpha-deficiency leads to defective insulin secretion via a molecular mechanism that is still not completely understood. Moreover, in MODY3 patients the severity of insulin secretion can be extremely variable even in the same kindred, indicating that modifier genes may control the onset of the disease. With the use of a mouse model for HNF1alpha-deficiency, we show here that specific genetic backgrounds (C3H and CBA) carry a powerful genetic suppressor of diabetes. A genome scan analysis led to the identification of a major suppressor locus on chromosome 3 (Moda1). Moda1 locus contains 11 genes with non-synonymous SNPs that significantly interacts with other loci on chromosomes 4, 11 and 18. Mechanistically, the absence of HNF1alpha in diabetic-prone (sensitive) strains leads to postnatal defective islets growth that is remarkably restored in resistant strains. Our findings are relevant to human genetics since Moda1 is syntenic with a human locus identified by genome wide association studies of fasting glycemia in patients. Most importantly, our results show that a single genetic locus can completely suppress diabetes in Hnf1a-deficiency.