Type I hyperprolinemia: genotype/phenotype correlations.

Type I hyperprolinemia (HPI) is an autosomal recessive disorder associated with cognitive and psychiatric troubles, caused by alterations of the Proline Dehydrogenase gene (PRODH) at 22q11. HPI results from PRODH deletion and/or missense mutations reducing proline oxidase (POX) activity. The goals of this study were first to measure in controls the frequency of PRODH variations described in HPI patients, second to assess the functional effect of PRODH mutations on POX activity, and finally to establish genotype/enzymatic activity correlations in a new series of HPI patients. Eight of 14 variants occurred at polymorphic frequency in 114 controls. POX activity was determined for six novel mutations and two haplotypes. The c.1331G>A, p.G444D allele has a drastic effect, whereas the c.23C>T, p.P8L allele and the c.[56C>A; 172G>A], p.[Q19P; A58T] haplotype result in a moderate decrease in activity. Among the 19 HPI patients, 10 had a predicted residual activity <50%. Eight out of nine subjects with a predicted residual activity > or = 50% bore at least one c.824C>A, p.T275N allele, which has no detrimental effect on activity but whose frequency in controls is only 3%. Our results suggest that PRODH mutations lead to a decreased POX activity or affect other biological parameters causing hyperprolinemia.

Haut potentiel intellectuel et TDA/H: ressemblances, différences, co-existence ?

Si les particularités du haut potentiel intellectuel (HPI) et du trouble déficit d'attention avec/sans hyperactivité (TDA/H) sont largement décrites dans la littérature, les liens entre ces deux profils sont moins connus. Il est pourtant établi que HPI et TDA/H partagent des manifestations communes comme l'agitation, les difficultés scolaires ou les troubles du comportement. Cette similitude sémiologique est responsable de confusions, d'errance diagnostique, voire de choix thérapeutiques discutables. Et la mission du médecin devient même particulièrement délicate lorsqu'il s'agit d'envisager une éventuelle « co-morbidité ». La clinique nous apprend en effet que le HPI et le TDA/H peuvent cohabiter chez le même enfant. Ainsi, les identifier et les prendre en charge devient un exercice complexe mais indispensable, car l'approche et le soutien de ces enfants aux besoins particuliers est très différente selon les cas de figure.

Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C.

Based on the partial efficacy of the HIV/AIDS Thai trial (RV144) with a canarypox vector prime and protein boost, attenuated poxvirus recombinants expressing HIV-1 antigens are increasingly sought as vaccine candidates against HIV/AIDS. Here we describe using systems analysis the biological and immunological characteristics of the attenuated vaccinia virus Ankara strain expressing the HIV-1 antigens Env/Gag-Pol-Nef of HIV-1 of clade C (referred as MVA-C). MVA-C infection of human monocyte derived dendritic cells (moDCs) induced the expression of HIV-1 antigens at high levels from 2 to 8 hpi and triggered moDCs maturation as revealed by enhanced expression of HLA-DR, CD86, CD40, HLA-A2, and CD80 molecules. Infection ex vivo of purified mDC and pDC with MVA-C induced the expression of immunoregulatory pathways associated with antiviral responses, antigen presentation, T cell and B cell responses. Similarly, human whole blood or primary macrophages infected with MVA-C express high levels of proinflammatory cytokines and chemokines involved with T cell activation. The vector MVA-C has the ability to cross-present antigens to HIV-specific CD8 T cells in vitro and to increase CD8 T cell proliferation in a dose-dependent manner. The immunogenic profiling in mice after DNA-C prime/MVA-C boost combination revealed activation of HIV-1-specific CD4 and CD8 T cell memory responses that are polyfunctional and with effector memory phenotype. Env-specific IgG binding antibodies were also produced in animals receiving DNA-C prime/MVA-C boost. Our systems analysis of profiling immune response to MVA-C infection highlights the potential benefit of MVA-C as vaccine candidate against HIV/AIDS for clade C, the prevalent subtype virus in the most affected areas of the world.

Spatial pattern of landslides in Swiss Rhone valley

The present study analyses the spatial pattern of quaternary gravitational slope deformations (GSD) and historical/present-day instabilities (HPI) inventoried in the Swiss Rhone Valley. The main objective is to test if these events are clustered (spatial attraction) or randomly distributed (spatial independency). Moreover, analogies with the cluster behaviour of earthquakes inventoried in the same area were examined. The Ripley's K-function was applied to measure and test for randomness. This indicator allows describing the spatial pattern of a point process at increasing distance values. To account for the non-constant intensity of the geological phenomena, a modification of the K-function for inhomogeneous point processes was adopted. The specific goal is to explore the spatial attraction (i.e. cluster behaviour) among landslide events and between gravitational slope deformations and earthquakes. To discover if the two classes of instabilities (GSD and HPI) are spatially independently distributed, the cross K-function was computed. The results show that all the geological events under study are spatially clustered at a well-defined distance range. GSD and HPI show a similar pattern distribution with clusters in the range 0.75?9 km. The cross K-function reveals an attraction between the two classes of instabilities in the range 0?4 km confirming that HPI are more prone to occur within large-scale slope deformations. The K-function computed for GSD and earthquakes indicates that both present a cluster tendency in the range 0?10 km, suggesting that earthquakes could represent a potential predisposing factor which could influence the GSD distribution.