Two step activation of FOXO3 by AMPK generates a coherent feed-forward loop determining excitotoxic cell fate

Cerebral ischemia and excitotoxic injury induce transient or permanent bioenergetic failure, and may result in neuronal apoptosis or necrosis. We have previously shown that ATP depletion and activation of AMP-activated protein kinase (AMPK) during excitotoxic injury induces neuronal apoptosis by transcription of the proapoptotic BH3 only protein, Bim. AMPK, however, also exerts pro-survival functions in neurons. The molecular switches that determine these differential outcomes are not well understood. Using an approach combining biochemistry, single cell imaging and computational modeling, we here demonstrate that excitotoxic injury activated the bim promoter in a FOXO3-dependent manner. The activation of AMPK reduced AKT activation, and led to dephosphorylation and nuclear translocation of FOXO3. Subsequent mutation studies indicated that bim gene activation during excitotoxic injury required direct FOXO3 phosphorylation by AMPK in the nucleus as a second activation step. Inhibition of this phosphorylation prevented Bim expression and protected neurons against excitotoxic and oxygen/glucose deprivation-induced injury. Systems analysis and computational modeling revealed that these two activation steps defined a coherent feedforward loop; a network motif capable of filtering any effects of short-term AMPK activation on bim gene induction. This may prevent unwanted AMPK-mediated Bim expression and apoptosis during transient or physiological bioenergetic stress

Photographs of the Legendary Tempelhof Airport

Classified as a historical monument, it is the worldis third biggest building and was once the oldest airport in service. In accordance with the designs of Ernst Sagebiel, a student of Erich Mendelsohn, construction work started in 1936. The outbreak of the Second World War prevented the completion of the building project. After the war, the area became an American military base, gaining international fame in the postwar period, thanks to the Allied airlift Luftbru_cke

AICA-riboside induces apoptosis of pancreatic beta cells through stimulation of AMP-activated protein kinase.

AIMS/HYPOTHESIS: Prolonged exposure of beta cells to low glucose concentrations triggers their apoptosis and is known to activate AMP-activated protein kinase (AMPK) in beta cell lines. We examined whether prolonged activation of AMPK can trigger apoptosis in rodent beta cells. METHODS: Primary beta cells were FACS-purified from rats, and from wild-type and AMPK(alpha2)-deficient mice. AMPK activation in beta cells was induced by the adenosine analog AICA-riboside and detected by immunoblotting using a phosphospecific antibody. Apoptosis of rodent beta cells was monitored by FACS analysis of beta cell DNA content, by direct counting of apoptotic cells using fluorescence microscopy, or by measurement of their caspase-3 activity. RESULTS: Dose-dependent and time-dependent apoptosis of the cells, concommittant with an activation of caspase-3, were suppressed by the caspase inhibitors zVAD-fmk and zDEVD-fmk. Apoptosis induction by AICA-riboside was also prevented by adding the MAPK-inhibitor SB203580 which blocked the AICA-riboside-induced phosphorylation of AMPK. Beta cells isolated from AMPK-(alpha2)-deficient mice were resistant against AICA-riboside induced apoptosis. CONCLUSION/INTERPRETATION: Sustained activation of AMPK by AICA-riboside can trigger a caspase-dependent apoptosis of pancreatic beta cells

Évaluation des services écosystémiques du Banc d'Arguin, Mauritanie : rapport final

Cette étude est la première du genre portant sur cette vaste aire protégée, à la fois marine et terrestre. Elle a été réalisée par un consortium de consultants et financée par le FFEM, l’AFD et le BaCoMab pour le Parc national du Banc d’Arguin (PNBA).Selon cette étude, la valeur annuelle des principaux services de régulation et d’approvisionnement est estimée à 8,1 milliards MRU par an soit 198,8 millions €/an. Les deux services les plus importants sont ceux relatifs à la séquestration du carbone fournie par les herbiers (3,3 milliards MRU) et à la contribution du PNBA aux pêcheries de la ZEE de la Mauritanie (3 milliards MRU). Parmi les autres services de support et de régulation évalués, ceux de nurserie et de bioremédiation affichent des valeurs monétaires respectives de 92 et 49 millions MRU/an. Le service de prélèvement par la flotte de pêche artisanale atteint 52 millions MRU/an. La valeur de non usage du PNBA se situe a 1,6 milliard MRU d’après la perception de l’importance accordée aux différents services écosystèmiques par les Mauritaniens.Les services évalués concernent essentiellement la partie maritime du PNBA qui couvre 5400 km2.L’étude met aussi en avant le rôle fondamental du PNBA pour la pêche opérant dans la ZEE de la Mauritanie, pour la séquestration du carbone atmosphérique et dissous, pour les populations d’oiseaux et les services qu’ils apportent et pour l’identité Imraguen. Outre la valeur économique des principaux services rendus par les écosystèmes du Banc d’Arguin, la préservation des milieux naturels et de la faune associée au PNBA est favorable a l’atteinte des objectifs des différentes conventions et traites internationaux dont la Mauritanie est signataire. La part de CO2 séquestre annuellement par les écosystèmes marins du Parc national du Banc d’Arguin atteint 732 057 tCO2eq soit 11 % des émissions de GES du pays