Comportement des provenances australiennes d'Eucalyptus camaldulensis dans la forêt de la Mâamora (Maroc) Cas des dispositifs de Machrâa El Kettane et Bouirat Cherrat

Ce travail porte sur l'étude de la variabilité intra-spécifique pour l'adaptation et la production chez 30 provenances australiennes d'Eucalyptus camaldulensis. Ces provenances proviennent de peuplements géographiquement disjoints, répartis entre 15 et 750 m d'altitude. L'étude a été menée dans des dispositifs expérimentaux implantés en 1992 en Mâamora occidentale et orientale, dans le but de sélectionner la, ou les meilleures provenance(s) pour les reboisements dans la région. Les caractères étudiés sont des caractères d'adaptation, de vigueur et de production. L'analyse de la variance met en évidence une variabilité intraspécifique importante. L'étude de l'effet station montre d'une part, l'existence de provenances stables lors du passage d'un dispositif à l'autre et d'autre part, l'importance de la station sur l'adaptation, la vigueur et la production des provenances. Les résultats obtenus mettent en relief la supériorité des provenances originaires de Victoria qui présentent une bonne adaptation aux conditions écologiques. Les corrélations entre les caractères d'adaptation sont non significatives, ce qui impose une vigilance lors de la sélection. Autrement dit, il est nécessaire de laisser à la plantation le temps nécessaire pour qu'elle puisse exprimer son comportement vis-à-vis des conditions du milieu

Photo-affinity labelling and biochemical analyses identify the target of trypanocidal simplified natural product analogues

This work was supported by the Leverhulme Trust (Grant number RL2012-025). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Current drugs to treat African sleeping sickness are inadequate and new therapies are urgently required. As part of a medicinal chemistry programme based upon the simplification of acetogenin-type ether scaffolds, we previously reported the promising trypanocidal activity of compound 1 , a bis-tetrahydropyran 1,4-triazole (B-THP-T) inhibitor. This study aims to identify the protein target(s) of this class of compound in Trypanosoma brucei to understand its mode of action and aid further structural optimisation. We used compound 3 , a diazirine- and alkyne-containing bi-functional photo-affinity probe analogue of our lead B-THP-T, compound 1 , to identify potential targets of our lead compound in the procyclic form T. brucei. Bi-functional compound 3 was UV cross-linked to its target(s) in vivo and biotin affinity or Cy5.5 reporter tags were subsequently appended by Cu(II)-catalysed azide-alkyne cycloaddition. The biotinylated protein adducts were isolated with streptavidin affinity beads and subsequent LC-MSMS identified the FoF1-ATP synthase (mitochondrial complex V) as a potential target. This target identification was confirmed using various different approaches. We show that (i) compound 1 decreases cellular ATP levels (ii) by inhibiting oxidative phosphorylation (iii) at the FoF1-ATP synthase. Furthermore, the use of GFP-PTP-tagged subunits of the FoF1-ATP synthase, shows that our compounds bind specifically to both the α- and β-subunits of the ATP synthase. The FoF1-ATP synthase is a target of our simplified acetogenin-type analogues. This mitochondrial complex is essential in both procyclic and bloodstream forms of T. brucei and its identification as our target will enable further inhibitor optimisation towards future drug discovery. Furthermore, the photo-affinity labeling technique described here can be readily applied to other drugs of unknown targets to identify their modes of action and facilitate more broadly therapeutic drug design in any pathogen or disease model.Publisher PDFPeer reviewe

Age-dependent cell death and the role of ATP in hydrogen peroxide-induced apoptosis and necrosis

Cell death plays a pivotal role in the body to maintain homeostasis during aging. Studies have shown that damaged cells, which must be removed from the body, accumulate during aging. Decay of the capacity and/or control of cell death during aging is widely considered to be involved in some age-dependent diseases. We investigated the accumulation of protein carbonyls and the role of cell death induced by hydrogen peroxide in human fibroblasts from individuals of various ages (17–80 years). The results showed that levels of oxidatively modified proteins increased with age, not only in whole-cell lysates but also in mitochondrial fractions, and this change correlates with a decline in the intracellular ATP level. Exposure of fibroblasts to hydrogen peroxide led to cell death by apoptosis and necrosis. Younger (<60 years old) cells were more resistant to necrosis induced by hydrogen peroxide than were older cells (>60 years old), which contained lower levels of free ATP than did younger cells. Treatment of cells of all ages with inhibitors of ATP synthesis (oligomycin, 2,4-dinitrophenol, or 2-deoxyglucose) made them more susceptible to cell death but also led to a switch in the death mode from apoptosis to necrosis. Furthermore, hydrogen peroxide treatment led to a greater accumulation of several inflammatory cytokines (IL-6, IL-7, IL-16, and IL-17) and increased necrosis in older cells. These results suggest that age-related decline in the ATP level reduces the capacity to induce apoptosis and promotes necrotic inflammation. This switch may trigger a number of age-dependent disorders