Speech Communication

Contains research objectives and reports on three research projects.U. S. Air Force (Electronic Systems Division) under Contract AF19(628)-5661National Institutes of Health (Grant 5 RO1 NB-04332-04

A role of mitochondrial complex II defects in genetic models of Huntington's disease expressing N-terminal fragments of mutant huntingtin.

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal expansion of a CAG repeat encoding a polyglutamine tract in the huntingtin (Htt) protein. The mutation leads to neuronal death through mechanisms which are still unknown. One hypothesis is that mitochondrial defects may play a key role. In support of this, the activity of mitochondrial complex II (C-II) is preferentially reduced in the striatum of HD patients. Here, we studied C-II expression in different genetic models of HD expressing N-terminal fragments of mutant Htt (mHtt). Western blot analysis showed that the expression of the 30 kDa Iron-Sulfur (Ip) subunit of C-II was significantly reduced in the striatum of the R6/1 transgenic mice, while the levels of the FAD containing catalytic 70 kDa subunit (Fp) were not significantly changed. Blue native gel analysis showed that the assembly of C-II in mitochondria was altered early in N171-82Q transgenic mice. Early loco-regional reduction in C-II activity and Ip protein expression was also demonstrated in a rat model of HD using intrastriatal injection of lentiviral vectors encoding mHtt. Infection of the rat striatum with a lentiviral vector coding the C-II Ip or Fp subunits induced a significant overexpression of these proteins that led to significant neuroprotection of striatal neurons against mHtt neurotoxicity. These results obtained in vivo support the hypothesis that structural and functional alterations of C-II induced by mHtt may play a critical role in the degeneration of striatal neurons in HD and that mitochondrial-targeted therapies may be useful in its treatment

Stage and treatment variation with age in postmenopausal women with breast cancer: compliance with guidelines

Breast cancer-specific mortality is static in older women despite having fallen in younger age groups, possibly due to lack of screening and differences in treatment. This study compared stage and treatment between two cohorts of postmenopausal women (55–69 vs 470 years) in a single cancer network over 6 months. A total of 378 patients were studied (470: N ¼ 167, 55–69 years: N ¼ 210). Older women presented with more advanced disease (470: metastatic/locally advanced 12%, 55–69 years: 3%, Po0.01). Those with operable cancer had a worse prognosis (Nottingham Prognostic Index (NPI) 470: median NPI 4.4, 55–69 years: 4.25, Po0.03). These stage differences were partially explained by higher screening rates in the younger cohort. Primary endocrine therapy was used in 42% of older patients compared with 3% in the younger group (Po0.001). Older women with cancers suitable for breast conservation were more likely to choose mastectomy (470: 57.5% mastectomy rate vs 55–69 years: 20.6%, Po0.01). Nodal surgery was less frequent in older patients (470: 6.7% no nodal surgery, 55–69 years: 0.5%, Po0.01) and was more likely to be inadequate (470: 10.7% o4 nodes excised, 55–69 years: 3.4%, Po0.02). In summary, older women presented with more advanced breast cancer, than younger postmenopausal women and were treated less comprehensively

L'apoptose des cellules folliculaires: son implication dans les protocoles de stimulation ovarienne

National audienc

L'apoptose des cellules folliculaires: son implication dans les protocoles de stimulation ovarienne

National audienc

Involvement of theca cells and steroids in the regulation of granulosa cell apoptosis in rabbit preovulatory follicles

International audienc

Subtle temperature increase can interact with individual size and social context in shaping phenotypic traits of a coldwater fish

Temperature and individual egg size have been long studied in the development of fishes because of their direct effects on individual fitness. Here we studied the combined effects of three important factors for fish development, i.e. egg size, social environment and water temperature. Arctic charr (Salvelinus alpinus), a coldwater fish known to be phenotypically plastic, was used to investigate how these factors may affect growth and foraging behaviour of juvenile fish in a benign environment. We accounted for the social environment during early development by comparing fish raised in groups and in isolation. We examined the effect of egg size and a 2 degrees C difference on foraging behaviour, activity and growth a few weeks after first feeding. Growth trajectories of fish originating from large and small eggs were similar within each temperature: larger fish coming large eggs were at all time larger than smaller fish. There was no indication that small fish raised at a higher temperature grew faster than larger fish raised at a lower temperature. A 2 degrees C difference in temperature affected the behaviour of fish differently according to body size and/or social context. The foraging probability difference between fish raised in groups and fish briefly isolated was higher at 4.5 degrees C than at 6.5 degrees C for both size fish. Finally, there was no repeatability in foraging behaviour and mobility for isolated individuals. These results highlight the importance of small changes in temperature when evaluating growth and behaviour of fishes, and reveal the importance of considering the interaction of temperature with other factors, e.g. individual size and social environment, especially at early stages of development in fishes. We discuss these findings in the context of rapid changes in temperature and how temperature and its interaction with other factors may affect the phenotypes, ecology and evolution of coldwater fishes