9 research outputs found
Impacts des changements climatiques sur la gestion des barrages-réservoirs du bassin de la Seine - Premiers résultats du projet Climaware
International audienceLes projections climatiques Ă©tablies par le GIECC indiquent que des changements significatifs dans les prĂ©cipitations et les tempĂ©ratures sont Ă attendre en Europe dans les prochaines dĂ©cennies, ce qui devrait impacter la disponibilitĂ© en eau. Le projet europĂ©en Climaware (2010-2013, financĂ© par IWRM-Net) a Ă©tĂ© montĂ© pour dĂ©velopper des mesures d'adaptation telles que des instruments de gestion intĂ©grĂ©e pour une gestion durable des ressources en eau tenant compte des changements climatiques. Au sein du projet, le cas d'Ă©tude sur la riviĂšre Seine se concentre sur l'adaptation de la gestion de barrages (et Ă©ventuellement de la capacitĂ© de stockage) pour deux objectifs principaux : le soutien d'Ă©tiage et l'Ă©crĂȘtement de crues, avec des enjeux socio-Ă©conomiques importants, en particulier dans la rĂ©gion parisienne. Les quatre grands barrages gĂ©rĂ©s par l'EPTB Seine Grands Lacs sont situĂ©s sur la partie amont du bassin sur quatre sous-bassins diffĂ©rents. Un modĂšle hydrologique semi-distribuĂ© a Ă©tĂ© dĂ©veloppĂ© pour simuler la transformation pluie-dĂ©bit sur le bassin. Le modĂšle a Ă©tĂ© calĂ© en utilisant les donnĂ©es de dĂ©bits naturalisĂ©s sur 25 stations hydromĂ©triques sur le bassin. Le modĂšle a ensuite Ă©tĂ© alimentĂ© par des projections climatiques dĂ©sagrĂ©gĂ©es issues de sept modĂšles climatiques diffĂ©rents. Les rĂ©sultats indiquent que les dĂ©bits d'Ă©tiage pourraient ĂȘtre significativement diminuĂ©s sur le bassin d'ici Ă 2050. Ceci appelle Ă dĂ©finir des stratĂ©gies de gestion adaptĂ©es. Plusieurs options seront testĂ©es pour tenir compte de ces modifications sur le bassin. / Climate projections established by the IPCC indicate that significant changes in precipitation and temperature are to be expected in Europe in the next decades, which should impact regional water availability. The Climaware European project (2010-2013, funded by IMWR-Net) was set up to develop adaptation measures such as integrated planning instruments for sustainable water resources management accounting for the impacts of climate change. Within the project, the Seine River case study focuses on the adaptation of dam management (and possibly dam storage capacity) for two main objectives: low-flow augmentation and flood alleviation, with important socio-economic stakes especially in the great Paris area. The four large reservoirs managed by the Seine Grands Lacs public basin authority, are situated on the upstream part of the basin on four different sub-basins. A semi-distributed hydrological model was developed to simulate the rainfall-runoff transformation on the basin. The model was calibrated using the naturalized flow data available on 25 gauging station across the basin. Then it was fed with climate projections downscaled from seven different climate models. Results indicate that low flows may be significantly reduced on the basin by 2050. This calls for defining adapted management strategies. Various options will be tested to account for these modifications on the basin
Mechanical properties of 3D bioprinted dermis: characterization and improvement
International audienceBioprinting is a promising way to create native-equivalent tissues for skin replacement in several pathologies and trauma. These last few years, various constructs have been reported, composed of fibroblasts and keratinocytes used to recapitulate the dermo-epidermal structure. However, the ability to control and characterize the mechanical properties of such constructs is a critical point to insure the transfer of these engineered products to clinic in a near future. In the present study, we had investigated the modulation of the biomechanics of a bioprinted dermis model through physical constrain during tissue maturation. Two passive tension devices were then designed and tested to mature the tissue after printing. Decrease in tissue retraction and increase of collagen I densities, associated to modulations of Young's modulus were obtained after 20 days of tissue maturation. Taken together, these results attest for the first time in literature of promising methods to modulate the mechanical properties of bioprinted skin models
The Lysyl Oxidase LOX Is Absent in Basal and Squamous Cell Carcinomas and Its Knockdown Induces an Invading Phenotype in a Skin Equivalent Model
A Nuclear Export Signal and Phosphorylation Regulate Dok1 Subcellular Localization and Functions
Dok1 is believed to be a mainly cytoplasmic adaptor protein which down-regulates mitogen-activated protein kinase activation, inhibits cell proliferation and transformation, and promotes cell spreading and cell migration. Here we show that Dok1 shuttles between the nucleus and cytoplasm. Treatment of cells with leptomycin B (LMB), a specific inhibitor of the nuclear export signal (NES)-dependent receptor CRM1, causes nuclear accumulation of Dok1. We have identified a functional NES ((348)LLKAKLTDPKED(359)) that plays a major role in the cytoplasmic localization of Dok1. Src-induced tyrosine phosphorylation prevented the LMB-mediated nuclear accumulation of Dok1. Dok1 cytoplasmic localization is also dependent on IKKÎČ. Serum starvation or maintaining cells in suspension favor Dok1 nuclear localization, while serum stimulation, exposure to growth factor, or cell adhesion to a substrate induce cytoplasmic localization. Functionally, nuclear NES-mutant Dok1 had impaired ability to inhibit cell proliferation and to promote cell spreading and cell motility. Taken together, our results provide the first evidence that Dok1 transits through the nucleus and is actively exported into the cytoplasm by the CRM1 nuclear export system. Nuclear export modulated by external stimuli and phosphorylation may be a mechanism by which Dok1 is maintained in the cytoplasm and membrane, thus regulating its signaling functions
A preliminary study for an intraoperative 3D bioprinting treatment of severe burn injuries.
Abstract Background : Intraoperative three-dimensional (3D) fabrication of living tissues could be the next biomedical revolution in patient treatment. Approach : We developed a surgery-ready robotic 3D bioprinter and demonstrated that a bioprinting procedure using medical grade hydrogel could be performed using a 6-axis robotic arm in vivo for treating burn injuries. Results : We conducted a pilot swine animal study on a deep third-degree severe burn model. We observed that the use of cell-laden bioink as treatment substantially affects skin regeneration, producing in situ fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF), necessary for tissue regeneration and re-epidermalization of the wound. Innovation and Conclusion: We described an animal study of intraoperative 3D bioprinting living tissue. This emerging technology brings the first proof of in vivo skin printing feasibility using a surgery-ready robotic arm-based bioprinter. Our positive outcome in skin regeneration, joined with this procedure's feasibility, allow us to envision the possibility of using this innovative approach in a human clinical trial in the near future
Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis
A growing body of evidence suggests that the multifunctional protein E4F1 is involved in signaling pathways that play essential roles during normal development and tumorigenesis. We generated E4F1 conditional knockout mice to address E4F1 functions in vivo in newborn and adult skin. E4F1 inactivation in the entire skin or in the basal compartment of the epidermis induces skin homeostasis defects, as evidenced by transient hyperplasia in the interfollicular epithelium and alteration of keratinocyte differentiation, followed by loss of cellularity in the epidermis and severe skin ulcerations. E4F1 depletion alters clonogenic activity of epidermal stem cells (ESCs) ex vivo and ends in exhaustion of the ESC pool in vivo, indicating that the lesions observed in the E4F1 mutant skin result, at least in part, from cell-autonomous alterations in ESC maintenance. The clonogenic potential of E4F1 KO ESCs is rescued by Bmi1 overexpression or by Ink4a/Arf or p53 depletion. Skin phenotype of E4F1 KO mice is also delayed in animals with Ink4a/Arf and E4F1 compound gene deficiencies. Our data identify a regulatory axis essential for ESC-dependent skin homeostasis implicating E4F1 and the Bmi1âArfâp53 pathway