Microduplication of Xp11.23p11.3 with effects on cognition, behavior, and craniofacial development.

We report an ~1.3 Mb tandem duplication at Xp11.23p11.3 in an 11-year-old boy with pleasant personality, hyperactivity, learning and visual-spatial difficulties, relative microcephaly, long face, stellate iris pattern, and periorbital fullness. This clinical presentation is milder and distinct from that of patients with partially overlapping Xp11.22p11.23 duplications which have been described in males and females with intellectual disability, language delay, autistic behaviors, and seizures. The duplicated region harbors three known X-linked mental retardation genes: FTSJ1, ZNF81, and SYN1. Quantitative polymerase chain reaction from whole blood total RNA showed increased expression of three genes located in the duplicated region: EBP, WDR13, and ZNF81. Thus, over-expression of genes in the interval may contribute to the observed phenotype. Many of the features seen in this patient are present in individuals with Williams-Beuren syndrome (WBS). Interestingly, the SYN1 gene within the duplicated interval, as well as the STX1A gene, within the WBS critical region, co-localize to presynaptic active zones, and play important roles in neurotransmitter release.

Regulation of the Y1 neuropeptide Y receptor gene expression in PC12 cells.

The Y1 receptor for neuropeptide Y (NPY-Y1) is constitutively expressed in PC12 cells. In this study, we examined the role of nerve growth factor (NGF), pituitary adenylyl cyclase activating polypeptide (PACAP) and dexamethasone on the expression of the gene encoding the rat NPY-Y1 receptor in PC12 cells. A fusion gene (pY1-Luc) was constructed where the reporter enzyme firefly luciferase was placed under the control of 700 bp of the promoter region of the rat NPY-Y1 receptor gene. This promoter region contains recognition consensus sequences for various transcription factors, including one activation protein-1 (AP-1) site, two cyclic AMP responsive element sites, one estrogen receptor element site and four glucocorticoid receptor element sites. NGF increased luciferase activity in a concentration dependent manner. This increase was inhibited by K-252a, a trk A receptor inhibitor, and calphostin C, a PKC inhibitor. PACAP-38 increased luciferase activity in a concentration dependent manner. This activation was inhibited by H-89. Dexamethasone increased transcription of NPY-Y1 gene in PC12 cells. These results indicate that differentiation of PC12 cells into endocrine-like phenotype by dexamethasone and into a neuronal-like phenotype by either NGF or PACAP-38 increases the transcriptional activity of the NPY-Y1 receptor gene in PC12 cells.

Wnt-1 dependent activation of the survival factor NF-kappaB in PC12 cells.

Expression of the Wnt-1 oncogene in PC12 cells induces morphological and biochemical changes, including up-regulation of cell adhesion and lack of differentiation in response to growth factors. The survival of PC12 cells is known to be mediated in part by phosphatidylinositol-3 kinase (PI-3 kinase)-dependent activation of the transcription factor nuclear factor-kappaB (NF-kappaB). We investigated the effect of Wnt-1 expression on cell survival and NF-kappaB activation using PC12 cells expressing Wnt-1 (PC12/Wnt1) and a reporter vector in which firefly luciferase expression is under the control of NF-kappaB consensus sequences. Serum deprivation caused apoptosis and decreased NF-kappaB activity in wild type PC12 cells. PC12/Wnt-1 cells showed less apoptosis in the absence of serum, and the levels of NF-kappaB activity were higher than in wild type PC12 cells. NF-kappaB activity was also increased by the transient expression of Wnt-1 in PC12 cells and it was completely inhibited in both PC12 and PC12/Wnt-1 cells by a dominant negative mutant IkappaB-alpha that has been shown to prevent NF-kappaB activation. Agents known to inhibit NF-kappaB-induced apoptosis in PC12 as well as in PC12/Wnt-1 cells, indicating a role of NF-kappaB activation in the anti-apoptotic effect of Wnt-1. Inhibition of PI-3 kinase with wortmannin, or with a dominant negative p85 regulatory subunit of the PI-3 kinase, blocked NF-kappaB activity in PC12 cells but caused only partial inhibition in PC12/Wnt-1 cells. The effect of Wnt-1 in activating NF-kappaB can be mimicked by inhibition of glycogen synthase kinase-3beta (GSK-3beta) with lithium or with a dominant negative GSK-3beta. Our results show that expression of Wnt-1 increases survival of PC12 cells in the absence of serum by activating the anti-apoptotic factor NF-kappaB. Wnt-1-induced activation of NF-kappaB is partially independent of PI-3 kinase and can be mimicked by inhibition of GSK-3beta.

[Calculation of optimized and individualized hip prosthesis. A study of feasibility]. / Calcul d'une prothèse de hanche optimisée et individualisée. Etude de faisabilité.

As logical consequence of a series of basic research studies on human femoral bones with unipodal support and under static stress, performed with physicomathematic modelling methods (finite-elements method) then confirmed by direct visualization of deformations resulting from such stress using holographic interferometry, the authors have worked on the definition of an optimized and individualized hip prosthesis. Thick CT sections digitized with a table and entered into a specially programmed computer allowed three-dimensional modelling of the femur as a volume, i.e. with its external contour and its medullary canal, and therefore of the implantable space. The prosthesis was then defined taking a number of hypotheses into account: necessity to regularize cortical bone spicules inside spongious bone, which are so often present opposite the rough line, partial machining at the level of the calcar, reduced tail length, presence or absence of collar. Thus an optimized and individualized prosthesis was defined. A prototype corresponding to a given femoral bone could then have been produced. However, the authors found it preferable to use simulation with computer synthetic images to check easy insertion and removal.

[Study of turbulence in the normal and stenotic vessel]. / Untersuchungen zur Turbulenz im normalen und stenotischen Gefäss.

Velocity measurements were performed at the test bench, in dogs and in patients with pulsed ultrasound. A new zero crossing counter was used to measure the different frequencies of the doppler spectrum in real time. The ratio of the standard deviation of the radial mean velocity to the radial mean velocity expressed as a percentage proved to be a useful turbulence index to describe stability of flow.