Differential apoptotic pathways activated in response to Cu-induced or HOCl-induced LDL oxidation in U937 monocytic cell line

We compared the apoptotic mechanism involved in U937 human monocytic cell line in presence of oxidized low-density lipoproteins (oxLDL) obtained after treatment with hypochlorous acid (HOCl) or copper (Cu).Both types of oxLDL induced U937 apoptotic cell death via the mitochondrial pathway. In contrast to HOCl-oxLDL, Cu-oxLDL induced apoptosis via a caspase-independent mechanism, with no activation of pro-caspase-3, but via the release of apoptosis inducing factor (AIF) from mitochondria.The apoptotic program of the monocyte differs depending on the mode of LDL oxidation, based on differences in the oxidatively modified components of the two oxLDL types.     

Passive drag is still a good evaluator of swimming aptitude

The passive drag (Dp) of 218 competitive swimmers was studied and related to their performance level. To study this relationship, specific attention was given to anthropometric and joint laxity (JL) variations. The Dp was measured at 1.40 m.s-1, using a mechanical winch and a strain gauge with a load cell connected to a strain bridge. Swimmers were towed in a prone position holding their breath after a maximal inspiration. Buoyancy was evaluated by the hydrostatic lift (HL), i.e., the maximal weight just necessary to maintain the swimmer in a balanced position under the water after a maximal inspiration. The JL was assessed by a standard scoring system. The Dp was related mainly to the surface area (SA) (r = 0.73 and 0.53; P less than 0.01, for males and females, respectively). For a given SA, Dp was inversely related to the performance level. The JL explained 7% of the variability of Dp. On average, Dp measured after a maximal expiration, increases of about 22% SD 3% (P less than 0.01). This increase was related to individual vital capacities (r = 0.86, P less than 0.01). As Dp was mainly related to SA and HL, it is suggested that the body exerts a large pressure effect on the water. The contribution to performance might be related to the gliding phase of swimming.     

Modeling of adaptations to physical training by using a recursive least squares algorithm

Busso, Thierry, Christian Denis, Régis Bonnefoy,André Geyssant, and Jean-René Lacour. Modeling ofadaptations to physical training by using a recursive least squaresalgorithm. J. Appl. Physiol. 82(5):1685-1693, 1997.The present study assesses the usefulnessof a systems model with time-varying parameters for describing theresponses of physical performance to training. Data for two subjectswho undertook a 14-wk training on a cycle ergometer were used to testthe proposed model, and the results were compared with a model withtime-invariant parameters. Two 4-wk periods of intensive training wereseparated by a 2-wk period of reduced training and followed by a 4-wkperiod of reduced training. The systems input ascribed to the trainingdoses was made up of interval exercises and computed in arbitraryunits. The systems output was evaluated one to five times per week byusing the endurance time at a constant workload. The time-invariantparameters were fitted from actual performances by using the leastsquares method. The time-varying parameters were fitted by using arecursive least squares algorithm. The coefficients of determinationr² were 0.875 and0.879 for the two subjects using the time-varying model, higher thanthe values of 0.682 and 0.666, respectively, obtained with thetime-invariant model. The variations over time in the model parametersresulting from the expected reduction in the residuals appearedgenerally to account for changes in responses to training. Such a modelwould be useful for investigating the underlying mechanisms ofadaptation and fatigue.

     

Adjuvant treatment with polyadenylic-polyuridylic acid in operable breast cancer: updated results of a randomised trial.

The results of a randomised trial of polyadenylic-polyuridylic acid given as adjuvant treatment for operable breast cancer were reviewed after a mean follow up period of 87 months. Of the 300 patients included in the original trial, 145 had been allocated to conventional treatment alone and served as controls. At the time of review the overall survival of the group given polyadenylic-polyuridylic acid was significantly improved (p less than 0.05) as compared with that of the controls given conventional treatment alone. Significant benefit (p less than 0.02) was also observed among patients with evidence of disease in lymph nodes, the best results occurring in those with up to three invaded nodes, who showed a significant increase in both overall and relapse free survival. No evidence of toxicity was recorded. These findings confirm the value of polyadenylic-polyuridylic acid as adjuvant treatment for operable breast cancer. Results in an experimental model and in patients receiving the adjuvant suggested a possible role of interferon and natural killer (NK) cells in the mechanism of action.     

Rat enterocyte Na+ transport in vitro. Action of parathyroid hormone and calcitonin

Parathyroid hormone (PTH) and calcitonin exert well known effects on the renal tubule which are thought to involve specific hormone receptors and adenyl cyclase. In the intestine, it is not clear whether the action of PTH and calcitonin is only indirect or also direct, and their mechanisms of action are much less well established. In the present study, possible direct effects of PTH and calcitonin on Na+ transport in isolated intestinal epithelial cells of rats were investigated. In the presence of bovine PTH (1.2 I.U/ml) in the incubation medium, the Na+ efflux rate constant (oKNa) of isolated enterocytes was significantly reduced when compared to that in control experiments with the hormone vehicle only. The mean depression of oKNa induced by bovine PTH was 26% as compared to the control (100%) and to that induced by ouabain (4.0 mM) which was 44%. No depressant effect of bovine PTH on oKNa was observed when the isolated enterocytes were incubated with ouabain (4.0 mM). Thus, bovine PTH appeared to inhibit the ouabain-sensitive Na+ pump. When incubating the isolated epithelial cells in an EGTA-containing CA2+-free medium, bovine PTH lost its capacity to inhibit oKNa. Thus, the presence of extracellular Ca2+ appeared necessary for the inhibitory effect of bovine PTH. In contrast to its effect on oKNa, bovine PTH induced no change in net Na+ uptake by isolated enterocytes. Moreover, no significant effect on enterocyte Na+ transport could be demonstrated for salmon or porcine calcitonin at two different concentrations in the incubation medium, Neither bovine PTH nor salmon calcitonin induced significant changes in enterocyte cyclic AMP or cycle GMP concentrations. It was concluded that bovine PTH, but not calcitonin, exerted a directed inhibitory effect on the ouabain-sensitive oKNa of isolated rat enterocytes. The effect of bovine PTH occurred without measurable activation of the cyclic nucleotide system but needed the presence of Ca2+ in the incubation medium to be operative.     

The Spread of Aedes albopictus in Metropolitan France: Contribution of Environmental Drivers and Human Activities and Predictions for a Near Future

Invasion of new territories by insect vector species that can transmit pathogens is one of the most important threats for human health. The spread of the mosquito Aedes albopictus in Europe is emblematic, because of its major role in the emergence and transmission of arboviruses such as dengue or chikungunya. Here, we modeled the spread of this mosquito species in France through a statistical framework taking advantage of a long-term surveillance dataset going back to the first observation of Ae. albopictus in the Metropolitan area. After validating the model, we show that human activities are especially important for mosquito dispersion while land use is a major factor for mosquito establishment. More importantly, we show that Ae. albopictus invasion is accelerating through time in this area, resulting in a geographic range extending further and further year after year. We also show that sporadic “jump” of Ae. albopictus in a new location far from the colonized area did not succeed in starting a new invasion front so far. Finally, we discuss on a potential adaptation to cooler climate and the risk of invasion into Northern latitudes.     

Influence of tyrosine-kinase Wzc activity on colanic acid production in Escherichia coli K12 cells

Bacterial tyrosine-kinases have been demonstrated to participate in the regulation of capsule polysaccharides (CPS) and exopolysaccharides (EPS) production and export. However, discrepant data have been reported on the molecular mechanism responsible for this regulation depending on the bacterial species analyzed. Special attention was previously paid to the tyrosine-kinase Wzc_ca of Escherichia coli K-12, which is involved in the production of the exopolysaccharide, colanic acid, and autophosphorylates by using a cooperative two-step process. In this work, we took advantage of these observations to investigate in further detail the effect of Wzc_ca phosphorylation on the colanic acid production. First, it is shown that expression of the phosphorylated form of Wzc prevents production of colanic acid whereas expression of the non-phosphorylated form allows biosynthesis of this exopolysaccharide. However, we provide evidence that, in the latter case, the size distribution of the colanic acid polymer is less scattered than in the case of the wild-type strain expressing both phosphorylated and non-phosphorylated forms of Wzc. It is then demonstrated that colanic acid production is not merely regulated by an on/off mechanism and that, instead, both phosphorylated and non-phosphorylated forms of Wzc are required to promote colanic acid synthesis. Moreover, a series of data suggests that besides the involvement of phosphorylated and non-phosphorylated forms of Wzc in the production of colanic acid, two particular regions of this kinase play as such an important role in the synthesis of this exopolysaccharide: a proline-rich domain located in the N-terminal part of Wzc_ca, and a tyrosine cluster present in the C-terminal portion of the enzyme. Furthermore, considering that polysaccharides are known to facilitate bacterial resistance to certain environmental stresses, it is shown that the resistance of E. coli to desiccation is directly connected with the phosphorylation state of Wzc_ca.     

The effect of n-3 PUFA on eNOS activity and expression in Ea hy 926 cells

The aim of this study was to evaluate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on NO synthase (eNOS) activation in Ea hy 926 endothelial cells. EPA or DHA (0-80 microM), added to the culture medium during 24h, were dose-dependently incorporated into the cells. In control medium, eNOS activity (evaluated by the citrulline assay) and eNOS phosphorylation on Ser 1177 were correlated. They were increased by 10 microM histamine and prevented by 20 microM lysophosphatidylcholine (LPC). By contrast, EPA or DHA increased basal phosphorylation without affecting eNOS activity in non-stimulated cells, but dose-dependently decreased this activity in histamine-stimulated cells without modifying the phosphorylation level. Furthermore, EPA and DHA did not prevent the deleterious effects of LPC on histamine stimulation. In conclusion, incorporation of EPA and DHA could be deleterious for endothelial cells by deregulating the activation of eNOS and preventing NO liberation.     

APC is required for muscle stem cell proliferation and skeletal muscle tissue repair

The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues.