Molecular Implication of PP2A and Pin1 in the Alzheimer's Disease Specific Hyperphosphorylation of Tau

Tau phosphorylation and dephosphorylation regulate in a poorly understood manner its physiological role of microtubule stabilization, and equally its integration in Alzheimer disease (AD) related fibrils. A specific phospho-pattern will result from the balance between kinases and phosphatases. The heterotrimeric Protein Phosphatase type 2A encompassing regulatory subunit PR55/Bα (PP2A(T55α)) is a major Tau phosphatase in vivo, which contributes to its final phosphorylation state. We use NMR spectroscopy to determine the dephosphorylation rates of phospho-Tau by this major brain phosphatase, and present site-specific and kinetic data for the individual sites including the pS202/pT205 AT8 and pT231 AT180 phospho-epitopes.We demonstrate the importance of the PR55/Bα regulatory subunit of PP2A within this enzymatic process, and show that, unexpectedly, phosphorylation at the pT231 AT180 site negatively interferes with the dephosphorylation of the pS202/pT205 AT8 site. This inhibitory effect can be released by the phosphorylation dependent prolyl cis/trans isomerase Pin1. Because the stimulatory effect is lost with the dimeric PP2A core enzyme (PP2A(D)) or with a phospho-Tau T231A mutant, we propose that Pin1 regulates the interaction between the PR55/Bα subunit and the AT180 phospho-epitope on Tau.Our results show that phosphorylation of T231 (AT180) can negatively influence the dephosphorylation of the pS202/pT205 AT8 epitope, even without an altered PP2A pool. Thus, a priming dephosphorylation of pT231 AT180 is required for efficient PP2A(T55α)-mediated dephosphorylation of pS202/pT205 AT8. The sophisticated interplay between priming mechanisms reported for certain Tau kinases and the one described here for Tau phosphatase PP2A(T55α) may contribute to the hyperphosphorylation of Tau observed in AD neurons

Appendicite aiguë d'expression clinique gauche: apport diagnostique de la tomodensitométrie.

BACKGROUND: Some cases of left-sided appendicitis related to malrotation or situs inversus have been reported. Another type of left-sided appendicitis is reported. CASE REPORT: A 9 year-old boy was admitted suffering from a 2-day history of severe left-sided abdominal pain of the lower quadrant with fever at 38 degrees C. He presented abdominal tenderness and guarding, maximal in the left lower quadrant. His leukocyte count was 22,000/mm3. Ultrasonography showed a digestive tubular structure with thick walls in the left lower quadrant. CT scan revealed a dilated right-sided appendix with localized perforation, whose extremity was located in the left lower quadrant along the lateral wall. The diagnosis was confirmed by median laparotomy. CONCLUSION: Left-sided appendicitis can also be related to a dilated right appendix with its extremity in the left lower-quadrant near the lateral wall. CT scan can then be helpful for diagnosis when ultrasonography remains unconclusive

Influence de l'activité physique sur le contenu minéral osseux des femmes ménopausées

peer reviewe

Interactive delineation of brain sulci and their merging into functional PET images.

A set of software tools has been developed to assist the neuro(physio)logist in the analysis of a series of cerebral images from single subjects by fusing sulci manually delineated on MRI brain surface into PET functional data. The procedure requires coregistered datasets and involves 4 steps: (i) segmentation of anatomical MRI data in order to extract the brain surface, (ii) generate the brain surface views by parallel ray casting, (iii) manual delineation of the relevant sulci from the surface views and (iv) fusion of the landmarks into any coregistered dataset from the same subject. The brain surface is segmented automatically from 3D MRI data using a new “Directional Watershed Transform” algorithm. From the segmented brain surface, 8 orthogonal surface views are calculated as visual support for interactive stereo definition of the major brain sulci. Each sulcus is built as a 3D trace line using a few vertices which are manually defined on one or several surface views. This technique allows one to follow the brain surface curvature rather independently of the number and the position of the vertices. The sulci are saved in an individual file for further use. The brain surface viewer is linked (via the 3D cursor position) to an independent volume viewer containing a coregistered (anatomical or functional) volume. Sulcal landmarks are finally projected onto this volume allowing further volume of interest definition. The use of the tool set is illustrated by a single subject brain activation study after 15O water injection

Implementation of a distributed compressed sensing algorithm on USRP2 platforms

info:eu-repo/semantics/nonPublishe