Sports d'hiver et Politiques climatiques : les cas de la vallée de la Tarentaise

International audienceLa France est l'une des premières nations pour les sports d'hiver avec les Etats Unis et l'Autriche. Le département de la Savoie rassemble 39,2 % de part de marché, 37% de la fréquentation touristique hivernale se regroupent dans 13 très grandes stations dont 8 se trouvent en Savoie . Au sein de ce même département la fréquentation est concentrée sur la Tarentaise . La Tarentaise a donc un poids important dans l'industrie des sports d'hiver, engendrant une quasi mono-économie sur le territoire. Il semble donc intéressant de questionner ces " très grandes stations " au regard des changements climatiques et de leur liens avec le territoire dans un contexte de construction territoriale. Certain élus locaux cherchent à renforcer leur légitimé à travers une politique climatique et la mise en place de politiques territoriales volontaire : Schéma de Cohérence Territoriale, Plan Climat Energie. Deux grandes questions souhaitent être traitées dans cet article : comment la spécialisation dans le tourisme hivernal, modèle performant économiquement, a entraîné une forte vulnérabilité du territoire face aux changements climatiques ? Et de fait, comment le système touristique est pris en charge dans les politiques climatiques territoriales ? Et comment celle-ci sont comprises dans des politiques territoriales plus large

Specifics of cardiac magnetic resonance imaging in children

SummaryThis review points out three specific features of cardiac magnetic resonance imaging (MRI) in children: the small size of the heart modifies the usual balance between signal-to-noise ratio and spatial resolution; the higher and more variable heart rate limits tissue characterization and temporal resolution; and motion artefacts (notably respiratory motions) must be dealt with. In the second part of this review, we present the current and future practices of cardiac magnetic resonance (CMR) in children, based on the experience of all French paediatric cardiac MRI centres

Quality check of cardiac MRI exams for Fallot patients: Interest of a simple formula to detect invalid exams

PurposeCardiac MRI (CMR) is the key exam for Fallot patients but remains tricky. The CMR report should at least mention left and right ventricle end-diastole volumes (Vl and Vr), ejection fraction (EFl and EFr) and pulmonary regurgitation (PR). Obviously, these variables are linked together by basic physiology rules and indeed Vl×EFl=Vr×EFr×(1-PR). We investigated the interest of using such formula as quality check during Fallot CMR exams in our center.Methods98 consecutive CMR examinations for Fallot (or Fallot-like) cardiopathy between 2010 and 2014 were retrospectively included. The exams failing to pass the formula (with a 10% tolerance) constituted the Invalid-group and a control group of the same size was also constituted. CMR of both groups were randomly submitted to a blinded senior observer. The inter-observer limits of agreements were compared for the different variables within both groups.Results(Fig. 1) 12 CMR (12%) failed to pass the validation formula. From the 24 reanalyzed CMR, only 4 failed to pass the formula (all from the Invalid-group). Two had persistent defect (VSD or ASD) which were not mentioned to the radiologist and not detected during the CMR. Two had significant artefacts in the aorta or pulmonary trunk due to sterna wires. The inter-observer disagreements for the 8 other CMR of the Invalid-group concerned the Right ventricle end-diastole volume (P<0.05).ConclusionThe use of a simple formula as quality check of CMR examinations for Fallot patients was useful to detect a total of 12% of CMR with issues. 8% of the CMR corresponded to uncertain right ventricle contours, 2% to persistent septal defects that should have been noticed during the examination and 2% to unreliable aortic or pulmonary flow due to artifacts. The formula could have permitted either to detect the anomalies or at least to conclude that the quality of the exams was impaired

Aggregation dynamics and identification of aggregation-prone mutants of the von Hippel-Lindau tumor suppressor protein

International audienceQuality control mechanisms promote aggregation and degradation of misfolded proteins. In budding yeast, the human von Hippel-Lindau protein (pVHL, officially known as VHL) is misfolded and forms aggregates. Here, we investigated the aggregation of three pVHL isoforms (pVHL213, pVHL160, pVHL172) in fission yeast. The full-length pVHL213 isoform aggregates in highly dynamic small puncta and in large spherical inclusions, either close to the nucleus or to the cell ends. The large inclusions contain the yeast Hsp104 chaperone. Aggregate clearance is regulated by proteasomal degradation. The pVHL160 isoform forms dense foci and large irregularly shaped aggregates. In silico, prediction of pVHL aggregation propensity identified a key aggregation-promoting region within exon 2. Consistently, the pVHL172 isoform, which lacks exon 2, formed rare reduced inclusions. We studied the aggregation propensity of pVHL variants harbouring missense mutations found in kidney carcinomas. We show that the P86L mutation stimulated small aggregate formation, the P146A mutation increased large inclusion formation, whereas the I151S mutant destabilized pVHL. The prefoldin subunit Pac10 (the human homolog VBP-1 binds to pVHL) is required for pVHL stability. Reduction of soluble functional pVHL might be crucial in VHL-related diseases

Système rénine-angiotensine et cancers urologiques / Renin-angiotensin system and urological cancers.

International audienceIntroduction: A controversy animates the literature on the potential role of the rennin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the involvement of this pathway in cancer, and more specifically in urological cancers. Material and Method: We made a systematic review of articles referenced in Pubmed, using the following keywords alone or combined: cancer, renin, angiotensin, VEGF, AT1R, antagonists of angiotensin-2 receptors, inhibitors of angiotensinogen converting. Results: Many types of cancers overexpress AT1-R in their tumoral tissues (breast, stomach, bladder, astrocytoma, glioblastoma, ovary, uterus, pancreas, kidney, prostate, adrenal gland). Ang-II can induce VEGF-A expression and promote neoangiogenesis, but also can trigger different molecular pathways involved in cell proliferation or inhibit apoptosis. Several xenograft murin models demonstrated anti-tumoral efficacy of RAS blockers, alone or using combined therapies, targeting angiogenesis and slowing down tumor growth. Retrospective studies in patients have also revealed a better progression-free survival and a better response to therapies in those treated with RAS blockers. Conclusion: Many data seem to demonstrate the involvement of the RAS in carcinogenesis, as well as anti-tumoral effect of RAS blockers in addition to anti-cancer treatments. Clinical data are now expected to confirm these experimental findings

Spatio-temporal expression patterns of aurora kinases a, B, and C and cytoplasmic polyadenylation-element-binding protein in bovine oocytes during meiotic maturation.

International audienceMaturation of immature bovine oocytes requires cytoplasmic polyadenylation and synthesis of a number of proteins involved in meiotic progression and metaphase-II arrest. Aurora serine-threonine kinases--localized in centrosomes, chromosomes, and midbody--regulate chromosome segregation and cytokinesis in somatic cells. In frog and mouse oocytes, Aurora A regulates polyadenylation-dependent translation of several mRNAs such as MOS and CCNB1, presumably by phosphorylating CPEB, and Aurora B phosphorylates histone H3 during meiosis. We analyzed the expression of three Aurora kinase genes--AURKA, AURKB, and AURKC--in bovine oocytes during meiosis by reverse transcription followed by quantitative real-time PCR and immunodetection. Aurora A was the most abundant form in oocytes, both at mRNA and protein levels. AURKA protein progressively accumulated in the oocyte cytoplasm during antral follicle growth and in vitro maturation. AURKB associated with metaphase chromosomes. AURKB, AURKC, and Thr-phosphorylated AURKA were detected at a contractile ring/midbody during the first polar body extrusion. CPEB, localized in oocyte cytoplasm, was hyperphosphorylated during prophase/metaphase-I transition. Most CPEB degraded in metaphase-II oocytes and remnants remained localized in a contractile ring. Roscovitine, U0126, and metformin inhibited meiotic divisions; they all induced a decrease of CCNB1 and phospho-MAPK3/1 levels and prevented CPEB degradation. However, only metformin depleted AURKA. The Aurora kinase inhibitor VX680 at 100 nmol/L did not inhibit meiosis but led to multinuclear oocytes due to the failure of the polar body extrusion. Thus, in bovine oocyte meiosis, massive destruction of CPEB accompanies metaphase-I/II transition, and Aurora kinases participate in regulating segregation of the chromosomes, maintenance of metaphase-II, and formation of the first polar body

Cytogénétique des carcinomes rénaux [Cytogenetics profiles of renal carcinoma]

National audienc

Transforming acidic coiled-coil 3 and Aurora-A interact in human thyrocytes and their expression is deregulated in thyroid cancer tissues

Aurora-A kinase has recently been shown to be deregulated in thyroid cancer cells and tissues. Among the Aurora-A substrates identified, transforming acidic coiled-coil (TACC3), a member of the TACC family, plays an important role in cell cycle progression and alterations of its expression occur in different cancer tissues. In this study, we demonstrated the expression of the TACC3 gene in normal human thyroid cells (HTU5), and its modulation at both mRNA and protein levels during cell cycle. Its expression was found, with respect to HTU5 cells, unchanged in cells derived from a benign thyroid follicular tumor (HTU42), and significantly reduced in cell lines derived from follicular (FTC-133), papillary (B-CPAP), and anaplastic thyroid carcinomas (CAL-62 and 8305C). Moreover, in 16 differentiated thyroid cancer tissues, TACC3 mRNA levels were found, with respect to normal matched tissues, reduced by twofold in 56% of cases and increased by twofold in 44% of cases. In the same tissues, a correlation between the expression of the TACC3 and Aurora-A mRNAs was observed. TACC3 and Aurora-A interact in vivo in thyroid cells and both proteins localized onto the mitotic structure of thyroid cells. Finally, TACC3 localization on spindle microtubule was no more observed following the inhibition of Aurora kinase activity by VX-680. We propose that Aurora-A and TACC3 interaction is important to control the mitotic spindle organization required for proper chromosome segregation

A constant and similar assembly defect of mitochondrial respiratory chain complex I allows rapid identification of NDUFS4 mutations in patients with Leigh syndrome

AbstractIsolated complex I deficiency is a frequent cause of respiratory chain defects in childhood. In this study, we report our systematic approach with blue native PAGE (BN-PAGE) to study mitochondrial respiratory chain assembly in skin fibroblasts from patients with Leigh syndrome and CI deficiency. We describe five new NDUFS4 patients with a similar and constant abnormal BN-PAGE profile and present a meta-analysis of the literature. All NDUFS4 mutations that have been tested with BN-PAGE result in a constant and similar abnormal assembly profile with a complete loss of the fully assembled complex I usually due to a truncated protein and the loss of its canonical cAMP dependent protein kinase phosphorylation consensus site. We also report the association of abnormal brain MRI images with this characteristic BN-PAGE profile as the hallmarks of NDUFS4 mutations and the first founder NDUFS4 mutations in the North-African population

Cytoplasmic PAR-3 protein expression is associated with adverse prognostic factors in clear cell renal cell carcinoma and independently impacts survival.

International audienceClear cell renal cell carcinomas (ccRCCs) represent 70% of renal cancers, and several clinical and histolopathological factors are implicated in their prognosis. We recently demonstrated that the overexpression of PAR-3 protein encoded by the PARD3 gene could be implicated in renal oncogenesis. The object of this work was to study the association of intratumoral PAR-3 expression with known prognostic parameters and clinical outcome. In this aim, PAR-3 expression was assessed by immunohistochemistry in ccRCC tumors of 101 patients from 2003 to 2005. The immunostaining of PAR-3 was scored either as membranous (mPAR-3) or as both membranous and cytoplasmic (cPAR-3). Cytoplasmic PAR-3 was significantly associated with worse histopathological and clinical prognostic factors: Fuhrman grades 3 and 4, tumor necrosis, sarcomatoid component, adrenal invasion, renal and hilar fat invasion, eosinophilic component, a noninactivated VHL gene, higher tumor grade, lymph node involvement, metastasis, and worse clinical Eastern Cooperative Oncology Group and S classification scores. After multivariate analysis, 2 parameters were independently associated with cPAR-3: necrosis and eosinophilic components. In addition, cPAR-3 patients had shorter overall and progression-free survivals independently from strong prognostic validated factors like metastases. A cytoplasmic expression of PAR-3 is therefore implicated in worse clinical and pathological cancer features in ccRCC and could be useful to identify patients with high-risk tumors