Crosstalk between HIF-1 and ROCK pathways in neuronal differentiation of mesenchymal stem cells, neurospheres and in PC12 neurite outgrowth.

This study demonstrates that the Rho-kinase (ROCK) inhibitor, Y-27632, potentiates not only the effect of cobalt chloride (CoCl(2)) but also that of deferoxamine, another HIF-1 inducer, on mesenchymal stem cell (MSC) neuronal differentiation. HIF-1 is essential for CoCl(2)+/-Y-27632-induced MSC neuronal differentiation, since agents inhibiting HIF-1 abolish the changes of morphology and cell cycle arrest-related gene or protein expressions (p21, cyclin D1) and the increase of neuronal marker expressions (Tuj1, NSE). Y-27632 potentiates the CoCl(2)-induced decrease of cyclin D1 and nestin expressions, the increase of HIF-1 activation and EPO expression, and decreases pVHL expression. Interestingly, CoCl(2) decreases RhoA expression, an effect potentiated by Y-27632, revealing crosstalk between HIF-1 and RhoA/ROCK pathways. Moreover, we demonstrate a synergistic effect of CoCl(2) and Y-27632 on neurosphere differentiation into neurons and PC12 neurite outgrowth underlining that a co-treatment targeting both HIF-1 and ROCK pathways might be relevant to differentiate stem cells into neurons

Azgp1 knockout changes mammary gland, adipose tissue and liver gene expression in lactating mice

Session 4: Nutrition to improve milk and meat qualityNational audienc

Azgp1 knockout changes mammary gland, adipose tissue and liver gene expression in lactating mice

Session 4: Nutrition to improve milk and meat qualityNational audienc

Milk fat composition modifies the texture and appearance of Cantal-type cheeses but not their flavor

In Press, Corrected ProofAlthough the effects of cow diet on cheese sensory properties have been well documented, the putative interactions between the biochemical and microbial milk components and their respective roles in the development of the sensory properties of cheeses have yet to be explored in depth. The aim of this study was to evaluate the specific contribution of milk fat composition to the formation of cheese sensory properties. Two creams with different fat compositions were obtained from cows fed either pasture or maize silage. Cheeses were manufactured from the same skim milk (identical chemical and microbial composition) with either the pasture- or maize silage-origin pasteurized cream added. The gross composition and microbial composition of milks did not vary with cream origin. In milks and cheeses, the fatty acid (FA) profiles were modified by the origin of the cream. The concentrations of C18:0 and unsaturated FA such as cis-9 C18:1, trans-11 C18:1, C18:3n-3, total conjugated linoleic acids, and mono- and polyunsaturated FA were higher in milks and cheeses with the pasture-origin cream than in those with the maize-origin cream. In contrast, the maize milks and cheeses had higher concentrations of short- and medium-chain saturated FA, C16:0, and C18:2n-6. The level of lipolysis was 11% in the cheese rind and only 0.30% in the cheese core. The rind of pasture cheeses had a higher concentration of free C18:0 and C18:3n-3 and a lower concentration of free C14:0 and free C16:0 than the rind of maize cheeses. The levels of major microbial groups were similar in pasture and maize cheeses at different stages of ripening. The pasture cheeses had a more elastic and creamier texture, a yellower color, and a thinner rind than the maize cheeses, but the odor and aroma of cheeses were not affected by the origin of the cream, despite a few modifications in the balance of volatile compounds from FA catabolism. Based on these results, we conclude that milk fat composition modulated by cow diet had a direct role in the texture of the cheese but no effect on flavor. The high degree of lipolysis in cheese rind, along with the higher concentration of long-chain unsaturated free FA in pasture cheeses may be responsible for antimicrobial activity, which could explain differences in the appearance of cheese rind

Bioassay-based profiling of steroid- and dioxin-like activities in French river waters using grab and integrative sampling

Effect-based methods (EBM) are relevant tools to monitor chemical quality of aquatic systems as they provide integrative assessment of contamination components and inform on hazard associated with complex mixtures. In the frame of a French national program aiming at demonstrating the operational performance of passive sampling to monitor priority chemicals in surface waters, we applied a panel of in vitro bioassays to investigate 1) the occurrence of steroid- and dioxin- /PAH-like activities, 2) their distribution in the water column using grab sampling and integrative passive sampling. In addition, we looked into the relevance of in vitro estrogenicity in the water as compared to established trigger values and in vivo assessment in zebrafish. Twenty surface water sites of different anthropogenic pressures were studied. For each of them, both grab (dissolved phase and particulate matter) and integrative sampling (POCIS and Silicone Rubber membranes) were performed over a 15 days period and organic extract of each sample was analyzed with the bioassays. In vitro toxicity profiles in grab water organic extracts showed contrasted contamination patterns depending on the time of sampling (T0 and T15) and the studied sites. Estrogenic and PAH-like activities were the most occurent activities, while glucocorticoidic and anti-androgenic ones were detected at specific sites. No androgenic activity was detected. PAH-like activity was associated with both the dissolved and particulate matter phases while endocrine activities were only found in the dissolved phase. At some sites, in vitro estradiol-equivalents were found above the generic trigger value considering environmental risk (0.4 ng E2Eq/L). For 7 sites out of the 10 tested in vivo, activities were coherent with those predicted by in vitro bioassays. The present study highlights the relevance of combining a set of effect-based tools and smart sampling to monitor site-specific contamination of surface water chemical quality and the partitioning of measured activities in the water column. Our approach further includes in vivo mechanism-based assays, which enhances the toxicological relevance of the assessment. Comparison of our data with established trigger values for some activities will be discussed. Finally, ongoing chemical analyses of more than 100 priority substances, including estrogenic hormones, will allow the determination of their contribution to the biological activities detected

Bioassay-based profiling of steroid- and dioxin-like activities in French river waters using grab and integrative sampling

Effect-based methods (EBM) are relevant tools to monitor chemical quality of aquatic systems as they provide integrative assessment of contamination components and inform on hazard associated with complex mixtures. In the frame of a French national program aiming at demonstrating the operational performance of passive sampling to monitor priority chemicals in surface waters, we applied a panel of in vitro bioassays to investigate 1) the occurrence of steroid- and dioxin- /PAH-like activities, 2) their distribution in the water column using grab sampling and integrative passive sampling. In addition, we looked into the relevance of in vitro estrogenicity in the water as compared to established trigger values and in vivo assessment in zebrafish. Twenty surface water sites of different anthropogenic pressures were studied. For each of them, both grab (dissolved phase and particulate matter) and integrative sampling (POCIS and Silicone Rubber membranes) were performed over a 15 days period and organic extract of each sample was analyzed with the bioassays. In vitro toxicity profiles in grab water organic extracts showed contrasted contamination patterns depending on the time of sampling (T0 and T15) and the studied sites. Estrogenic and PAH-like activities were the most occurent activities, while glucocorticoidic and anti-androgenic ones were detected at specific sites. No androgenic activity was detected. PAH-like activity was associated with both the dissolved and particulate matter phases while endocrine activities were only found in the dissolved phase. At some sites, in vitro estradiol-equivalents were found above the generic trigger value considering environmental risk (0.4 ng E2Eq/L). For 7 sites out of the 10 tested in vivo, activities were coherent with those predicted by in vitro bioassays. The present study highlights the relevance of combining a set of effect-based tools and smart sampling to monitor site-specific contamination of surface water chemical quality and the partitioning of measured activities in the water column. Our approach further includes in vivo mechanism-based assays, which enhances the toxicological relevance of the assessment. Comparison of our data with established trigger values for some activities will be discussed. Finally, ongoing chemical analyses of more than 100 priority substances, including estrogenic hormones, will allow the determination of their contribution to the biological activities detected

Combined therapeutic strategy using erythropoietin and mesenchymal stem cells potentiates neurogenesis after transient focal cerebral ischemia in rats.

International audienceMany studies showed beneficial effects of either erythropoietin (EPO) or mesenchymal stem cells (MSCs) treatment in cerebral ischemia. In addition to a neuroprotective role, not only EPO but also MSC favors neurogenesis and functional recovery. In an attempt to further improve postischemic tissue repair, we investigated the effect of a systemic administration of MSC, in the presence or not of EPO, on neurogenesis and functional recovery in a transient focal cerebral ischemia model in the adult rat. Twenty-four hours after ischemia, the rats were divided into four groups, namely vehicle, MSC, EPO, and MSC+EPO, and received a single intravenous injection of MSC (2 x 10(6) cells) and/or a repeated intraperitoneal administration of EPO (1,000 UI/kg) for 3 days. The lesion volume, the MSC outcome, neurogenesis, and functional recovery were assessed 51 days after ischemia. The results showed that cellular proliferation and neurogenesis were increased along the lateral ventricle wall in the MSC+EPO group, whereas no significant effect was observed in groups receiving MSC or EPO alone. This effect was accompanied by an improvement of mnesic performances. Mesenchymal stem cells expressing neuronal or glial markers were detected in the ischemic hemisphere. These results suggest that EPO could act in a synergistic way with MSC to potentiate the postischemic neurogenesis