| 1. |
- Huang-Doran, Isabel, et al.
(författare)
-
Insulin resistance uncoupled from dyslipidemia due to C-terminal PIK3R1 mutations.
- 2016
-
Ingår i: JCI insight. - 2379-3708. ; 1:17
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity-related insulin resistance is associated with fatty liver, dyslipidemia, and low plasma adiponectin. Insulin resistance due to insulin receptor (INSR) dysfunction is associated with none of these, but when due to dysfunction of the downstream kinase AKT2 phenocopies obesity-related insulin resistance. We report 5 patients with SHORT syndrome and C-terminal mutations in PIK3R1, encoding the p85α/p55α/p50α subunits of PI3K, which act between INSR and AKT in insulin signaling. Four of 5 patients had extreme insulin resistance without dyslipidemia or hepatic steatosis. In 3 of these 4, plasma adiponectin was preserved, as in insulin receptor dysfunction. The fourth patient and her healthy mother had low plasma adiponectin associated with a potentially novel mutation, p.Asp231Ala, in adiponectin itself. Cells studied from one patient with the p.Tyr657X PIK3R1 mutation expressed abundant truncated PIK3R1 products and showed severely reduced insulin-stimulated association of mutant but not WT p85α with IRS1, but normal downstream signaling. In 3T3-L1 preadipocytes, mutant p85α overexpression attenuated insulin-induced AKT phosphorylation and adipocyte differentiation. Thus, PIK3R1 C-terminal mutations impair insulin signaling only in some cellular contexts and produce a subphenotype of insulin resistance resembling INSR dysfunction but unlike AKT2 dysfunction, implicating PI3K in the pathogenesis of key components of the metabolic syndrome.
|
|
| 2. |
- Journeau, Christophe, et al.
(författare)
-
SAFEST ROADMAP FOR CORIUM EXPERIMENTAL RESEARCH IN EUROPE
- 2016
-
Ingår i: PROCEEDINGS OF THE 24TH INTERNATIONAL CONFERENCE ON NUCLEAR ENGINEERING, 2016, VOL 4. - : ASME Press. - 9780791850046
-
Konferensbidrag (refereegranskat)abstract
- SAFEST (Severe Accident Facilities for European Safety Targets) is a European project networking the European corium experimental laboratories with the objective to establish coordination activities, enabling the development of a common vision and research roadmaps for the next years, and of the management structure to achieve these goals. In this frame, a European roadmap on corium experimental research has been written to define research challenges to contribute to further reinforcement of Gen II and III NPP safety. It is based on the research priorities deteimined by SARNET SARP group as well as those from the recently formulated in the NUGENIA Roadmap for severe accidents and the recently published NUGENIA Global Vision report. It also takes into account issues identified in the analysis of the European stress tests and from the interpretation of the Fukushima accident. 19 relevant issues related to corium have been selected during these prioritization efforts. These issues have been compared to a survey of the European corium experimental facilities and corium analysis laboratories. Finally, the coherence between European infrastructures and R&D needs has been assessed and a table linking issues and infrastructures has been derived. It shows a few lacks in EU corium infrastructures, especially in the domains of core late reflooding impact on source term, Reactor Pressure Vessel failure and corium release, Spent Fuel Pool accidents, as well as the need for a large mass (100500 kg) prototypic corium facility.
|
|
