Coopération entre processus guidés par les données et par les modèles pour la segmentation

Parmi les méthodes de segmentation existantes on peut distinguer deux grands types d'approches : les approches guidées par les données, utilisant l'information sur les niveaux de gris, et les approches à base de modèles, exploitant de la connaissance a priori. Cependant, les résultats obtenus par l'une ou l'autre de ces approches ne sont pas suffisamment satisfaisants (cas de mauvais contrastes pour les approches bas-niveau,trop grande variabilité morphologique pour les approches à base de modèles...) . Nous nous intéressons donc à l'étude et à la mise en oeuvre de techniques de coopération dans le but d'améliorer les résultats de la segmentation. Le travail est appliqué à l'IRM du cerveau

Wnt Signaling Is Regulated by Endoplasmic Reticulum Retention

Precise regulation of Wnt signaling is important in many contexts, as in development of the vertebrate forebrain, where excessive or ectopic Wnt signaling leads to severe brain defects. Mutation of the widely expressed oto gene causes loss of the anterior forebrain during mouse embryogenesis. Here we report that oto is the mouse ortholog of the gpi deacylase gene pgap1, and that the endoplasmic reticulum (ER)-resident Oto protein has a novel and deacylase-independent function during Wnt maturation. Oto increases the hydrophobicities of Wnt3a and Wnt1 by promoting the addition of glycophosphatidylinositol (gpi)-like anchors to these Wnts, which results in their retention in the ER. We also report that oto-deficient embryos exhibit prematurely robust Wnt activity in the Wnt1 domain of the early neural plate. We examine the effect of low oto expression on Wnt1 in vitro by knocking down endogenous oto expression in 293 and M14 melanoma cells using shRNA. Knockdown of oto results in increased Wnt1 secretion which is correlated with greatly enhanced canonical Wnt activity. These data indicate that oto deficiency increases Wnt signaling in vivo and in vitro. Finally, we address the mechanism of Oto-mediated Wnt retention under oto-abundant conditions, by cotransfecting Wnt1 with gpi-specific phospholipase D (GPI-PLD). The presence of GPI-PLD in the secretory pathway results in increased secretion of soluble Wnt1, suggesting that the gpi-like anchor lipids on Wnt1 mediate its retention in the ER. These data now provide a mechanistic framework for understanding the forebrain defects in oto mice, and support a role for Oto-mediated Wnt regulation during early brain development. Our work highlights a critical role for ER retention in regulating Wnt signaling in the mouse embryo, and gives insight into the notoriously inefficient secretion of Wnts

Global defects in collagen secretion in a Mia3/TANGO1 knockout mouse

Mia3’s contribution to protein secretion is broader than previously realized—its absence impairs collagen deposition and normal development of cartilage and bone

Directions for Future Patient-Centered and Comparative Effectiveness Research for People With Serious Mental Illness in a Learning Mental Health Care System

This supplement, while ambitious in scope, presents its major concepts with elegance and clarity. In this critical appraisal of mental health services treatment and outcomes, the authors have extended the utility of research findings by systematically gathering data on the experiences and preferences of numerous stakeholders. Key among the report’s conclusions is the need for patient-centered, patient-developed measures that can be used at all levels of a learning system to assess service provision approaches, compare treatment interventions, and improve outcomes

Where do the elderly die? The impact of nursing home utilisation on the place of death. Observations from a mortality cohort study in Flanders

BACKGROUND: Most of the research concerning place of death focuses on terminally ill patients (cancer patients) while the determinants of place of death of the elderly of the general population are not intensively studied. Studies showed the influence of gender, age, social-economical status and living arrangements on the place of death, but a facet not taken into account so far is the influence of the availability of nursing homes. METHODS: We conducted a survey of deaths, between January 1999 and December 2000 in a small densely populated area in Belgium, with a high availability of nursing homes (within 5 to 10 km of the place of residence of every elderly). We determined the incidence of total mortality (of subjects >60 years) from local official death registers that we consulted via the priest or the mortician of the local parish, to ask where the decedent had died and whether the deceased had lived in a nursing home. We compared the distribution of the places of death between parishes with a nursing home and with parishes without nursing home. RESULTS: 240 women and 217 men died during the two years study period. Only 22% died at home, while the majority (78%) died in an institutional setting, either a hospital (50%) or a nursing home (28%). Place of death was influenced by individual factors (age and gender) and the availability of a nursing home in the 'own' parish. The chance of in-hospital death was 65% higher for men (95% Confidence Interval [CI]: 14 to 138%; p = 0.008) and decreased by 4% (CI: -5.1% to -2.5%; p < 0.0001) for each year increase in age. Independent of gender and age, the chance of in-hospital death was 41% (CI: -60% to -13%; p = 0.008) lower in locations with a nursing home. CONCLUSION: Demographic, but especially social-contextual factors determine where elderly will end their life. The majority of elderly in Flanders die in an institution. Age, gender and living situation are predictors of the place of death but the embedment of a nursing home in the local community seems to be a key predictor

The Experience of Quality in Higher Education in the United Arab Emirates: In Times of Rapid Change and Complexities

In less than five decades, from offering formal education only in a few schools to a small tribal community to providing a selection of three public and approximately 100 private higher education institutions to the citizens of seven emirates creates a unique context in the United Arab Emirates (UAE). It is an evolution that corresponds with its remarkable economic growth. Quality assurance of diverse higher educational institutions requires complex schemes to ensure their fitness for purpose, while perhaps development and enhancement aspects need time to mature. The quality of the education is especially important because the UAE yearns for the diversified and knowledge-based economy; one that is led by its own citizens whose contribution to the workforce is currently less than 10%. This chapter highlights contextual complexities in the UAE that might have direct and/or indirect impacts on the quality experiences in the higher education sector, with proposed recommendations

High glucose environment inhibits cranial neural crest survival by activating excessive autophagy in the chick embryo

High glucose levels induced by maternal diabetes could lead to defects in neural crest development during embryogenesis, but the cellular mechanism is still not understood. In this study, we observed a defect in chick cranial skeleton, especially parietal bone development in the presence of high glucose levels, which is derived from cranial neural crest cells (CNCC). In early chick embryo, we found that inducing high glucose levels could inhibit the development of CNCC, however, cell proliferation was not significantly involved. Nevertheless, apoptotic CNCC increased in the presence of high levels of glucose. In addition, the expression of apoptosis and autophagy relevant genes were elevated by high glucose treatment. Next, the application of beads soaked in either an autophagy stimulator (Tunicamycin) or inhibitor (Hydroxychloroquine) functionally proved that autophagy was involved in regulating the production of CNCC in the presence of high glucose levels. Our observations suggest that the ERK pathway, rather than the mTOR pathway, most likely participates in mediating the autophagy induced by high glucose. Taken together, our observations indicated that exposure to high levels of glucose could inhibit the survival of CNCC by affecting cell apoptosis, which might result from the dysregulation of the autophagic process

Msx1 and Msx2 are required for endothelial-mesenchymal transformation of the atrioventricular cushions and patterning of the atrioventricular myocardium

<p>Abstract</p> <p>Background</p> <p><it>Msx1 </it>and <it>Msx2</it>, which belong to the highly conserved <it>Nk </it>family of homeobox genes, display overlapping expression patterns and redundant functions in multiple tissues and organs during vertebrate development. <it>Msx1 </it>and <it>Msx2 </it>have well-documented roles in mediating epithelial-mesenchymal interactions during organogenesis. Given that both <it>Msx1 </it>and <it>Msx2 </it>are crucial downstream effectors of Bmp signaling, we investigated whether <it>Msx1 </it>and <it>Msx2 </it>are required for the Bmp-induced endothelial-mesenchymal transformation (EMT) during atrioventricular (AV) valve formation.</p> <p>Results</p> <p>While both <it>Msx1-/- </it>and <it>Msx2-/- </it>single homozygous mutant mice exhibited normal valve formation, we observed hypoplastic AV cushions and malformed AV valves in <it>Msx1-/-; Msx2-/- </it>mutants, indicating redundant functions of <it>Msx1 </it>and <it>Msx2 </it>during AV valve morphogenesis. In <it>Msx1/2 </it>null mutant AV cushions, we found decreased Bmp2/4 and <it>Notch1 </it>signaling as well as reduced expression of <it>Has2</it>, <it>NFATc1 </it>and <it>Notch1</it>, demonstrating impaired endocardial activation and EMT. Moreover, perturbed expression of chamber-specific genes <it>Anf</it>, <it>Tbx2</it>, <it>Hand1 </it>and <it>Hand2 </it>reveals mispatterning of the <it>Msx1/2 </it>double mutant myocardium and suggests functions of <it>Msx1 </it>and <it>Msx2 </it>in regulating myocardial signals required for remodelling AV valves and maintaining an undifferentiated state of the AV myocardium.</p> <p>Conclusion</p> <p>Our findings demonstrate redundant roles of <it>Msx1 </it>and <it>Msx2 </it>in regulating signals required for development of the AV myocardium and formation of the AV valves.</p

Bmp7 Regulates the Survival, Proliferation, and Neurogenic Properties of Neural Progenitor Cells during Corticogenesis in the Mouse

Bone morphogenetic proteins (BMPs) are considered important regulators of neural development. However, results mainly from a wide set of in vitro gain-of-function experiments are conflicting since these show that BMPs can act either as inhibitors or promoters of neurogenesis. Here, we report a specific and non-redundant role for BMP7 in cortical neurogenesis in vivo using knockout mice. Bmp7 is produced in regions adjacent to the developing cortex; the hem, meninges, and choroid plexus, and can be detected in the cerebrospinal fluid. Bmp7 deletion results in reduced cortical thickening, impaired neurogenesis, and loss of radial glia attachment to the meninges. Subsequent in vitro analyses of E14.5 cortical cells revealed that lack of Bmp7 affects neural progenitor cells, evidenced by their reduced proliferation, survival and self-renewal capacity. Addition of BMP7 was able to rescue these proliferation and survival defects. In addition, at the developmental stage E14.5 Bmp7 was also required to maintain Ngn2 expression in the subventricular zone. These data demonstrate a novel role for Bmp7 in the embryonic mouse cortex: Bmp7 nurtures radial glia cells and regulates fundamental properties of neural progenitor cells that subsequently affect Ngn2-dependent neurogenesis