Phospholipid Scramblase 4 (PLSCR4) Regulates Adipocyte Differentiation via PIP3-Mediated AKT Activation

Phospholipid scramblase 4 (PLSCR4) is a member of a conserved enzyme family with high relevance for the remodeling of phospholipid distribution in the plasma membrane and the regulation of cellular signaling. While PLSCR1 and -3 are involved in the regulation of adipose-tissue expansion, the role of PLSCR4 is so far unknown. PLSCR4 is significantly downregulated in an adipose-progenitor-cell model of deficiency for phosphatase and tensin homolog (PTEN). PTEN acts as a tumor suppressor and antagonist of the growth and survival signaling phosphoinositide 3-kinase (PI3K)/AKT cascade by dephosphorylating phosphatidylinositol-3,4,5-trisphosphate (PIP3). Patients with PTEN germline deletion frequently develop lipomas. The underlying mechanism for this aberrant adipose-tissue growth is incompletely understood. PLSCR4 is most highly expressed in human adipose tissue, compared with other phospholipid scramblases, suggesting a specific role of PLSCR4 in adipose-tissue biology. In cell and mouse models of lipid accumulation, we found PLSCR4 to be downregulated. We observed increased adipogenesis in PLSCR4-knockdown adipose progenitor cells, while PLSCR4 overexpression attenuated lipid accumulation. PLSCR4 knockdown was associated with increased PIP3 levels and the activation of AKT. Our results indicated that PLSCR4 is a regulator of PI3K/AKT signaling and adipogenesis and may play a role in PTEN-associated adipose-tissue overgrowth and lipoma formation

Erprobung des Wasserabrasivsuspensionsstrahlverfahrens (WASS) bei der Zerlegung aktivierter metallischer Reaktorkomponenten (RDB u.a.) unter realen Bedingungen Endbericht

Das Wasserabrasivsuspensionsstrahlschneiden war in vorangegangenen Forschungsvorhaben auf seine generelle Einsatzbarkeit untersucht worden. Die Aufgabenziele waren, die Zerlegung des Kernmantelunterteiles sowie die Zerlegung des Reaktordruckbehaelters. Zu diesem Zweck wurden mit der Laboranlage der Universitaet Hannover Untersuchungen verschiedener Abrasivmittel bezueglich Schneidfaehigkeit und Truebung, Versuche zur Optimierung der Werkzeugueberwachung und -handhabung, Ermittlung der Kraefte am Handhabungssystem, Anpassung der Schneidparameter an die Schneidaufgabe und Untersuchungen zur Sichterhaltung im RDB durchgefuehrt. Aufbauend auf diese Ergebnisse wurden am Versuchsstand in VAK die ermittelten Parameter mit der ALBA-WASS-Anlage verifiziert. Diese Arbeiten dienten gleichzeitig der Schulung des Personals und fuehrten zur Qualifizierung des Verfahrens durch den zustaendigen Gutachter. Waehrend dieser Vorversuche wurde eine Absaug- und Reinigungsanlage entwickelt, die den Einsatz des Verfahrens unter Wasser ermoeglichte. Der Kernmantelunterteil wurde dann mit einer 1400 bar-WASS-Anlage in endlagerbehaeltergerechte Segmente zerlegt. Fuer das Durchtrennen der Reaktordruckbehaelterwandung wurde eine 2000 bar-WASS-Anlage erprobt und fuer die Durchfuehrung eingesetzt. Nach Abschluss der Arbeiten kann man jetzt feststellen, dass fuer den Rueckbau von Kernkraftwerken ein weiteres wirkungsvolles Trennverfahren zur Verfuegung steht. (orig.)The water abrasive suspension jetstream cutting (WASJ) was tested during the past research program for its general practicability. The programs goal was to investigate the dismantling of the lower part of the core baffel as well as of the reactor-pressure-vessel itself. For this purpose the University of Hanover established a lab-scale testing program to optimize the following parameters: different abrasives, cutting performance, remote tools monitoring and handling, verification of the forces to the manipulators, adaptation of cutting parameters to the different cutting tasks and the analyses for water-processing to maintain sub-aquatic visibility. Based on the results obtained in minor-scale testing the process parameters were adapted to the pilot manifold (ALBA-WASS) in VAK. This program served also for the training of personnel and the certification of the procedure by experts and the authorities. During the pre-operational phase a solids extraction and water-purification device was developed to enable the use of the technique under sub-aquatic conditions. The core-baffel was dismantled with the 1400 bar WASS into parts ready for final storage. For the cutting of the reactor-pressure-vessel itself, the WASS was modified to a jetstream-pressure of 2000 bar. At the end of the operation we were able to determine that for the dismantling of nuclear-power-plants an additional efficient cutting technique is now available. (orig.)Available from TIB Hannover: F00B950+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Osteuropäische 24-Stunden-Betreuerinnen - Gestalterinnen ihrer eigenen Lebenslage

Pflegearrangements wie die 24-Stunden-Betreuung in der Häuslichkeit einer pflegebedürftigen Person im Ausland verändern maßgeblich die Lebenssituation derjenigen, die diese Leistung anbieten, da sie in der Regel weite geografische Entfernung zwischen dem Wohnort im Heimatland und Einsatzort bewältigen müssen. Die Abwesenheit von zu Hause verlangt von ihnen besondere Kompetenzen sowie Handlungsfähigkeit für die Gestaltung der ihnen zur Verfügung stehenden Handlungsspielräume, vor allem auf der Beziehungsebene, aber auch in den anderen Lebensbereichen wie z. B. Freizeit, Bildung, Wohnen, Beschäftigung etc. Wie groß oder begrenzt die Handlungsspielräume der Pendlerinnen sind, wie sich das Pendeln und der Beschäftigungsstatus »irregulär«/»regulär« auf deren Handlungsmöglichkeiten auswirken und wie die Pendlerinnen ihre Handlungsspielräume nutzen sind Inhalte des folgenden Beitrags

Pressure-induced and store-operated cation influx in vascular smooth muscle cells is independent of TRPC1

Among the classical transient receptor potential (TRPC) subfamily, TRPC1 is described as a mechanosensitive and store-operated channel proposed to be activated by hypoosmotic cell swelling and positive pipette pressure as well as regulated by the filling status of intracellular Ca(2+) stores. However, evidence for a physiological role of TRPC1 may most compellingly be obtained by the analysis of a TRPC1-deficient mouse model. Therefore, we have developed and analyzed TRPC1(-/-) mice. Pressure-induced constriction of cerebral arteries was not impaired in TRPC1(-/-) mice. Smooth muscle cells from cerebral arteries activated by hypoosmotic swelling and positive pipette pressure showed no significant differences in cation currents compared to wild-type cells. Moreover, smooth muscle cells of TRPC1(-/-) mice isolated from thoracic aortas and cerebral arteries showed no change in store-operated cation influx induced by thapsigargin, inositol-1,4,5 trisphosphate, and cyclopiazonic acid compared to cells from wild-type mice. In contrast to these results, small interference RNAs decreasing the expression of stromal interaction molecule 1 (STIM1) inhibited thapsigargin-induced store-operated cation influx, demonstrating that STIM1 and TRPC1 are mutually independent. These findings also imply that, as opposed to current concepts, TRPC1 is not an obligatory component of store-operated and stretch-activated ion channel complexes in vascular smooth muscle cells

Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis

Nitric oxide (NO) and hydrogen peroxide (H(subscript 2)O(subscript 2)) are synthesized within cardiac myocytes and play key roles in modulating cardiovascular signaling. Cardiac myocytes contain both the endothelial (eNOS) and neuronal (nNOS) NO synthases, but the differential roles of these NOS isoforms and the interplay of reactive oxygen species and reactive nitrogen species in cardiac signaling pathways are poorly understood. Using a recently developed NO chemical sensor [Cu(subscript 2)(FL2E)] to study adult cardiac myocytes from wild-type, eNOSnull, and nNOSnull mice, we discovered that physiological concentrations of H(subscript 2)O(subscript 2) activate eNOS but not nNOS. H(subscript 2)O(subscript 2)-stimulated eNOS activation depends on phosphorylation of both the AMP-activated protein kinase and kinase Akt, and leads to the robust phosphorylation of eNOS. Cardiac myocytes isolated from mice infected with lentivirus expressing the recently developed H(subscript 2)O(subscript 2) biosensor HyPer2 show marked H2O2 synthesis when stimulated by angiotensin II, but not following β-adrenergic receptor activation. We discovered that the angiotensin-II-promoted increase in cardiac myocyte contractility is dependent on H2O2, whereas β-adrenergic contractile responses occur independently of H(subscript 2)O(subscript 2) signaling. These studies establish differential roles for H(subscript 2)O(subscript 2) in control of cardiac contractility and receptor-dependent NOS activation in the heart, and they identify new points for modulation of NO signaling responses by oxidant stress.National Institutes of Health (U.S.) (grant GM36259)National Institutes of Health (U.S.) (grant HL46457)National Institutes of Health (U.S.) (grant HL48743)National Institutes of Health (U.S.) (grant K99GM092970)National Science Foundation (U.S.) (grant CHE-0907905