Akt Activation Emulates Chk1 Inhibition and Bcl2 Overexpression and Abrogates G2 Cell Cycle Checkpoint by Inhibiting BRCA1 Foci

Akt is perhaps the most frequently activated oncoprotein in human cancers. Overriding cell cycle checkpoint in combination with the inhibition of apoptosis are two principal requirements for predisposition to cancer. Here we show that the activation of Akt is sufficient to promote these two principal processes, by inhibiting Chk1 activation with concomitant inhibition of apoptosis. These activities of Akt cannot be recapitulated by the knockdown of Chk1 alone or by overexpression of Bcl2. Rather the combination of Chk1 knockdown and Bcl2 overexpression is required to recapitulate Akt activities. Akt was shown to directly phosphorylate Chk1. However, we found that Chk1 mutants in the Akt phosphorylation sites behave like wild-type Chk1 in mediating G2 arrest, suggesting that the phosphorylation of Chk1 by Akt is either dispensable for Chk1 activity or insufficient by itself to exert an effect on Chk1 activity. Here we report a new mechanism by which Akt affects G2 cell cycle arrest. We show that Akt inhibits BRCA1 function that induces G2 cell cycle arrest. Akt prevents the translocation of BRCA1 to DNA damage foci and, thereby, inhibiting the activation of Chk1 following DNA damage.     

Biodiversity and ecosystem functioning: It is time for dispersal experiments

The experimental study of the relationship between biodiversity and ecosystem function has mainly addressed the effect of species and number of functional groups. In theory, this approach has mainly focused on how extinction affects function, whereas dispersal limitation of ecosystem function has been rarely discussed. A handful of seed introduction experiments, as well as numerous observations of the effects of long‐distance dispersal of alien species, indicate that ecosystem function may be strongly determined by dispersal limitation at the local, regional and/or global scales. We suggest that it is time to replace biodiversity manipulation experiments, based on random draw of species, with those addressing realistic scenarios of either extinction or dispersal. Experiments disentangling the dispersal limitation of ecosystem function should have to take into account the probability of arrival. The latter is defined as the probability that a propagule of a particular species will arrive at a particular community. Arrival probability depends on the dispersal ability and the number of propagules of a species, the distance a species needs to travel, and the permeability of the matrix landscape. Current databases, in particular those in northwestern and central Europe now enable robust estimation of arrival probability in plant communities. We suggest a general hypothesis claiming that dispersal limitation according to arrival probability will have ecosystem‐level effects different from those arising due to random arrival. This hypothesis may be rendered more region‐, landscape‐ or ecosystem‐specific by estimating arrival probabilities for different background conditions.     

Functional Effects of Adiponectin on Endothelial Progenitor Cells

Adiponectin is an adipokine whose plasma levels are inversely correlated to metabolic syndrome components. Adiponectin protects against atherosclerosis and decreases risks in myocardial infarction. Endothelial progenitor cells (EPCs) are a heterogeneous population of circulating cells involved in vascular repair and neovascularization. EPCs number is reduced in patients with cardiovascular disease. We hypothesize that the positive effects of adiponectin against atherosclerosis are explained in part by its interactions with EPCs. Cells were obtained from healthy volunteers' blood by mononuclear cell isolation and plating on collagen‐coated dishes. Three sub‐populations of EPCs were identified and characterized using flow cytometry. EPCs' expression of adiponectin receptors, AdipoR1, and AdipoR2 was evaluated by quantitative PCR. The effects of recombinant adiponectin on EPCs' susceptibility to apoptosis were assessed. Finally, expression of neutrophil elastase by EPCs and activity of this enzyme on adiponectin processing were assessed. Quantitative PCR analysis of EPCs mRNAs showed that AdipoR1 mRNA is expressed at higher levels than AdipoR2. Expression of AdipoR1 protein was confirmed by western blot. Adiponectin significantly increased survival of two sub‐populations of EPCs in conditions of serum deprivation. Such effect could not be demonstrated in the third EPCs sub‐population. We also demonstrated that EPCs, particularly one sub‐population, express neutrophil elastase. Neutrophil elastase activity was confirmed in EPCs' conditioned media. Adiponectin protects some EPCs sub‐populations against apoptosis and therefore could modulate EPCs ability to induce repair of vascular damage. Neutrophil elastase activity of EPCs could locally modulate adiponectin activity by its involvement in the generation of the globular form of adiponectin.     

Urine selenium level in healthy adult population

The level of urine selenium in healthy adult population, 230 persons, was examined. Persons were selected regarding sex, ages, and smoking habits. No differences versus these observations have been found. For a total, group values are 16.96 Se nmol/creatinine mmol, SD=5.44. It is possible from a single-void specimen to express daily excretion of selenium.     

LEFKOVITCH'S ERROR

Abstract — Lefkovitch's formula for the probability of incompatibility between two binary characters can give incorrect results because it redundantly counts some possible compatibilities. The inaccuracy occurs when the characters have the same number of terminals showing the apomorphic state.