APSIC: Training and fitting amputees during situations of daily living

Today, the prevalence of major amputation in France can be estimated between 90,000 and 100,000 and the incidence is about 8300 new amputations per year (according to French National Authority for Health estimation). This prevalence is expected to increase in the next decade due to the ageing of the population. Even if prosthetic fitting allows amputee people recovering the walking ability, their autonomy remains limited when crossing obstacles such as slopes, stairs or cross-slopes frequently encountered during outdoors displacements. The aim of the project APSIC was to complete scientific knowledge about adaptation strategies to situations of daily living compared to level walking through an extensive motion analysis study of transtibial and transfemoral amputee compared to non-amputee people. APSIC succeeded in identifying physiologic joint functions and current prosthetic joint limitations in the studied situations, which notably resulted in the design of a prototype of ankle-knee prosthesis adapted to multimodal locomotion of transfemoral amputee. Perspectives of the clinical use of motion analysis within the rehabilitation process were explored and proved to be relevant for personalized approach of motor learning

Control of Gene Expression by the Retinoic Acid-Related Orphan Receptor Alpha in HepG2 Human Hepatoma Cells

Retinoic acid-related Orphan Receptor alpha (RORα; NR1F1) is a widely distributed nuclear receptor involved in several (patho)physiological functions including lipid metabolism, inflammation, angiogenesis, and circadian rhythm. To better understand the role of this nuclear receptor in liver, we aimed at displaying genes controlled by RORα in liver cells by generating HepG2 human hepatoma cells stably over-expressing RORα. Genes whose expression was altered in these cells versus control cells were displayed using micro-arrays followed by qRT-PCR analysis. Expression of these genes was also altered in cells in which RORα was transiently over-expressed after adenoviral infection. A number of the genes found were involved in known pathways controlled by RORα, for instance LPA, NR1D2 and ADIPOQ in lipid metabolism, ADIPOQ and PLG in inflammation, PLG in fibrinolysis and NR1D2 and NR1D1 in circadian rhythm. This study also revealed that genes such as G6PC, involved in glucose homeostasis, and AGRP, involved in the control of body weight, are also controlled by RORα. Lastly, SPARC, involved in cell growth and adhesion, and associated with liver carcinogenesis, was up-regulated by RORα. SPARC was found to be a new putative RORα target gene since it possesses, in its promoter, a functional RORE as evidenced by EMSAs and transfection experiments. Most of the other genes that we found regulated by RORα also contained putative ROREs in their regulatory regions. Chromatin immunoprecipitation (ChIP) confirmed that the ROREs present in the SPARC, PLG, G6PC, NR1D2 and AGRP genes were occupied by RORα in HepG2 cells. Therefore these genes must now be considered as direct RORα targets. Our results open new routes on the roles of RORα in glucose metabolism and carcinogenesis within cells of hepatic origin

Transglutaminase and diseases of the central nervous system.

Alzheimer's disease, Parkinson's disease and diseases of expanded polyglutamine are associated with insoluble protein aggregates and neuronal death. A role for transglutaminase in the stabilization of these aggregates has been proposed. Diseases of polyglutamine expansion have been the most thoroughly investigated and a large body of studies supports the causative role of transglutaminase in aggregation of expanded polyglutamine. However none of the evidence is conclusive. Indisputable evidence of cross-linking by transglutaminase will be required in order to provide firm support for therapeutic measures based on the role of transglutaminase

Systematic Repeat Addition at a Precise Location in the Coding Region of the Involucrin Gene of Wild Mice Reveals Their Phylogeny

The involucrin gene encodes a protein of terminally differentiated keratinocytes. Its segment of repeats, which represents up to 80% of the coding region, is highly polymorphic in mouse strains derived from wild progenitors. Polymorphism includes nucleotide substitutions, but is most strikingly due to the recent addition of a variable number of repeats at a precise location within the segment of repeats. Each mouse taxon examined showed consistent and distinctive patterns of evolution of its variable region: very rapid changes in most M. m. domesticus alleles, slow changes in M. m. musculus, and complete arrest in M. spretus. We conclude that changes in the variable region are controlled by the genetic background. One of the M. m. domesticus alleles (DIK-L), which is of M. m. musculus origin, has undergone a recent repeat duplication typical of M. m. domesticus. This suggests that the genetic background controls repeat duplications through trans-acting factors. Because the repeat pattern differs in closely related murine taxa, involucrin reveals with greater sensitivity than random nucleotide substitutions the evolutionary relations of the mouse and probably of all murids