La stratégie du SMTC en faveur de l'accessibilité des transports en commun aux personnes à mobilité réduite au regard de la loi du 11 février 2005

La loi du 11 février 2005 pour l'égalité des droits et des chances, la participation et la citoyenneté des personnes handicapées a instauré de nouvelles obligations aux autorités organisatrices de transports. Ces obligations sont, pour la première fois, assorties de mesures coercitives. Le Syndicat Mixte des Transports en Commun de l'agglomération grenobloise mène depuis le milieu des années 1980 une politique ambitieuse en faveur de l'accessibilité des transports en commun aux personnes à mobilité réduite : innovation mondiale du premier tramway à plancher bas en 1987, une première ligne de bus déclarée accessible en 1996. La concertation est la clé de voûte de cette dynamique. L'année 2006 marque un nouvel essor pour l'accessibilité des transports en commun de l'agglomération grenobloise par la formalisation d'un certain nombre d'outils et d'instances de concertation ou encore l'élaboration du PDU 2006-2012 de l'agglomération grenobloise qui contient désormais une annexe dédiée.transports en commun, accessibilité, PMR (Personnes à mobilité réduite), personnes handicapées, PDU (Plan de Déplacements Urbains), Grenoble (France)

Searching for material symmetries in the burr wood of thuja by a direct contact ultrasonic method on spherical samples

International audienceThis work is part of a program that aims at studying the burr wood of thuja (Tetraclinis articulata). The goal of this work is to identify material symmetries of burr wood to improve its machining. To have a sufficient number of data and to limit the variability between samples, an ultrasonic experimental device, in direct contact on spherical samples, has been developed and improved. Until now, the geometry used in direct contact ultrasonic methods was either cubic or polyhedral allowing to obtain, on the same sample, 3 (cube) to 13 (polyhedron) measurements or usable data. By choosing a reasonable angular gap, the spherical geometry allows the ultrasonic velocity to be measured in 133 different directions on the same specimen. We present here the adaptation and development of the ultrasonic experimental device and results obtained on (i) aluminum chosen as a reference material, (ii) beech wood and (iii) burr wood of thuja

AMPK protects proximal tubular epithelial cells from lysosomal dysfunction and dedifferentiation induced by lipotoxicity

Renal proximal tubules are a primary site of injury in metabolic diseases. In obese patients and animal models, proximal tubular epithelial cells (PTECs) display dysregulated lipid metabolism, organelle dysfunctions, and oxidative stress that contribute to interstitial inflammation, fibrosis and ultimately end-stage renal failure. Our research group previously pointed out AMP-activated protein kinase (AMPK) decline as a driver of obesity-induced renal disease. Because PTECs display high macroautophagic/autophagic activity and rely heavily on their endo-lysosomal system, we investigated the effect of lipid stress on autophagic flux and lysosomes in these cells. Using a model of highly differentiated primary PTECs challenged with palmitate, our data placed lysosomes at the cornerstone of the lipotoxic phenotype. As soon as 6 h after palmitate exposure, cells displayed impaired lysosomal acidification subsequently leading to autophagosome accumulation and activation of lysosomal biogenesis. We also showed the inability of lysosomal quality control to restore acidic pH which finally drove PTECs dedifferentiation. When palmitate-induced AMPK activity decline was prevented by AMPK activators, lysosomal acidification and the differentiation profile of PTECs were preserved. Our work provided key insights on the importance of lysosomes in PTECs homeostasis and lipotoxicity and demonstrated the potential of AMPK in protecting the organelle from lipid stress

AMPK protects proximal tubular epithelial cells from lysosomal dysfunction and dedifferentiation induced by lipotoxicity

Renal proximal tubules are a primary site of injury in metabolic diseases. In obese patients and animal models, proximal tubular epithelial cells (PTECs) display dysregulated lipid metabolism, organelle dysfunctions, and oxidative stress that contribute to interstitial inflammation, fibrosis and ultimately end-stage renal failure. Our research group previously pointed out AMP-activated protein kinase (AMPK) decline as a driver of obesity-induced renal disease. Because PTECs display high macroautophagic/autophagic activity and rely heavily on their endo-lysosomal system, we investigated the effect of lipid stress on autophagic flux and lysosomes in these cells. Using a model of highly differentiated primary PTECs challenged with palmitate, our data placed lysosomes at the cornerstone of the lipotoxic phenotype. As soon as 6 h after palmitate exposure, cells displayed impaired lysosomal acidification subsequently leading to autophagosome accumulation and activation of lysosomal biogenesis. We also showed the inability of lysosomal quality control to restore acidic pH which finally drove PTECs dedifferentiation. When palmitate-induced AMPK activity decline was prevented by AMPK activators, lysosomal acidification and the differentiation profile of PTECs were preserved. Our work provided key insights on the importance of lysosomes in PTECs homeostasis and lipotoxicity and demonstrated the potential of AMPK in protecting the organelle from lipid stress

Searching for material symmetries in the burr wood of thuja by a direct contact ultrasonic method on spherical samples

This work is part of a program that aims at studying the burr wood of thuja (Tetraclinis articulata). The goal of this work is to identify material symmetries of burr wood to improve its machining. To have a sufficient number of data and to limit the variability between samples, an ultrasonic experimental device, in direct contact on spherical samples, has been developed and improved. Until now, the geometry used in direct contact ultrasonic methods was either cubic or polyhedral allowing to obtain, on the same sample, 3 (cube) to 13 (polyhedron) measurements or usable data. By choosing a reasonable angular gap, the spherical geometry allows the ultrasonic velocity to be measured in 133 different directions on the same specimen. We present here the adaptation and development of the ultrasonic experimental device and results obtained on (i) aluminum chosen as a reference material, (ii) beech wood and (iii) burr wood of thuja

The Transcription Factor E4F1 Coordinates CHK1-Dependent Checkpoint and Mitochondrial Functions

Recent data support the notion that a group of key transcriptional regulators involved in tumorigenesis, including MYC, p53, E2F1, and BMI1, share an intriguing capacity to simultaneously regulate metabolism and cell cycle. Here, we show that another factor, the multifunctional protein E4F1, directly controls genes involved in mitochondria functions and cell-cycle checkpoints, including Chek1, a major component of the DNA damage response. Coordination of these cellular functions by E4F1 appears essential for the survival of p53-deficient transformed cells. Acute inactivation of E4F1 in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS production, energy stress, and inhibition of de novo pyrimidine synthesis. This deadly cocktail leads to the accumulation of uncompensated oxidative damage to proteins and extensive DNA damage, ending in cell death. This supports the rationale of therapeutic strategies simultaneously targeting mitochondria and CHK1 for selective killing of p53-deficient cancer cells

Different aspects of emotional processes in apathy: Application of the French translated dimensional apathy scale

Apathy is a behavioural symptom that occurs in neuropsychiatric, neurological and neurodegenerative disease. It is defined as a lack of motivation and/or a quantitative reduction of goal-directed behaviour. Levy and Dubois Cerebral Cortex, 16(7), 916–928 (2006) proposed a triadic substructure of apathy and similar subtypes can be assessed using the Dimensional Apathy Scale (DAS), via the Executive, Emotional and Initiation subscales. The aim of this study was to translate the DAS in to French (f-DAS), examine its psychometric properties and the substructure of apathy using Confirmatory Factor Analysis (CFA). The results showed an acceptable internal consistency reliability of the f-DAS and a similar relationship to depression as in the original DAS development study. The CFA supported a triadic dimensional substructure of the f-DAS, similar to the original DAS but suggested a more complex substructure, specifically, two further processes of the Emotional apathy dimension relating to “Social Emotional” and “Individual Emotional” aspects of demotivation. To conclude, the f-DAS is a robust and reliable tool for assessing multidimensional apathy. Further research should explore the utility of the f-DAS in patients with neuropsychiatric diseases in view of social emotional aspects in apathy

Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review

Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients’ characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05–1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6–13/20 vs. 10–18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use