Project description:Next-generation proteomics of Caballeronia mineralivorans PML1(12) to decipher the potential molecular mechanisms explaining its mineral weathering effectiveness.
Project description:Decreased mineral density is a risk factor for skeletal pathologies including bone metastasis, the leading cause of mortality in patients with advanced breast cancer, but the underlying mechanisms are poorly understood. While reduced mineral density can drive pathological bone remodeling via direct effects on select cell types, indirect effects due to broad changes of the microenvironment may be similarly important. However, how bone mineral content affects microenvironmental heterogeneity remains to be elucidated. Here, we leverage decellularized bone matrices with varied mineral content in combination with single-cell RNA-sequencing to study how reduced bone mineral content affects microenvironmental complexity and tumor growth. We performed single-cell RNA sequencing on implanted decellularized bovine bone scaffolds in which the mineral was either maintained at physiological levels or removed to simulate scenarios of impaired bone mineralization as, for example, present during aging. Using this approach, we explored the heterogeneous stromal response to varied bone mineral content in both an immunocompromised and immunocompetent, syngeneic mouse model in the presence and absence of cancer cells.
Project description:The weathering of volcanic minerals makes a significant contribution to the global silicate weathering budget, influencing carbon dioxide drawdown and climate control. Basalt rocks may account for over 30% of the global carbon dioxide drawdown in silicate weathering. Yet the genetics of biological rock weathering are unknown. For the first time, we apply a DNA microarray to investigate the genes involved in weathering by the heavy metal resistant organism, Cupriavidus metallidurans CH34; in particular we investigate the sequestering of iron. The results show that the bacterium sequesters iron in the ferrous state (FeII); therefore, not requiring siderophores. Instead an energy efficient process involving upregulation of large porins is employed concomitantly with genes associated with biofilm formation. We hypothesise that rock weathering is induced by changes in chemical equilibrium at the microbe-mineral interface, reducing the saturation state of iron. We also demonstrate that low concentrations of metals in the basalt induce heavy metal resistant genes. Volcanic environments are analogous to some of the earliest environments on Earth. These results not only elucidate the mechanisms by which microorganisms might have sequestered nutrients on the early Earth but they also provide an explanation for the evolution of multiple heavy metal resistance genes long before the creation of contaminated industrial biotopes by human activity.
Project description:The weathering of volcanic minerals makes a significant contribution to the global silicate weathering budget, influencing carbon dioxide drawdown and climate control. Basalt rocks may account for over 30% of the global carbon dioxide drawdown in silicate weathering. Yet the genetics of biological rock weathering are unknown. For the first time, we apply a DNA microarray to investigate the genes involved in weathering by the heavy metal resistant organism, Cupriavidus metallidurans CH34; in particular we investigate the sequestering of iron. The results show that the bacterium sequesters iron in the ferrous state (FeII); therefore, not requiring siderophores. Instead an energy efficient process involving upregulation of large porins is employed concomitantly with genes associated with biofilm formation. We hypothesise that rock weathering is induced by changes in chemical equilibrium at the microbe-mineral interface, reducing the saturation state of iron. We also demonstrate that low concentrations of metals in the basalt induce heavy metal resistant genes. Volcanic environments are analogous to some of the earliest environments on Earth. These results not only elucidate the mechanisms by which microorganisms might have sequestered nutrients on the early Earth but they also provide an explanation for the evolution of multiple heavy metal resistance genes long before the creation of contaminated industrial biotopes by human activity. Cultures of Cupriavidus metallidurans CH34 were grown in Tris buffered medium MM284 media (with iron), MM284 without iron and MM284 without iron with sterilized basalt at 25 rpm, 30°C until mid-log phase. RNA was extracted from the cells. Three biological replicates of both samples were differentially labeled (resp. Cy3 and Cy5) and hybridized to three CH34 60-mer oligonucleotide glass-spotted microarray carrying three technical repeats.
Project description:Anti-EGFR (Epidermal Growth Factor Receptor) therapies, namely cetuximab and panitumumab, have become standards in the management of metastatic colorectal and head and neck cancers. These therapies are used in daily practice, that requiring to manage their skin and digestive toxicities. However, anti-EGFR are also frequently responsible for hypomagnesemia often neglected and under-treated.
Hypomagnesemia may manifest as asthenia, cramps, muscle weakness, mood disorders. She is often underestimated because they are difficult to identify and accountable by clinicians in the context of cancer under chemotherapy.
There is currently no national or international recommendation on the management of hypomagnesaemia in oncology and medicine in general. There are, however, on the market many nutritional supplements rich in magnesium in the form of tablets or oral solution, in multiple dosages.
These food supplements rich in magnesium are sold without proof of effectiveness. Moreover, the prescription of oral magnesium supplementation adds to the oncology patient an over-medicalization, which can be poorly tolerated at the digestive level, and responsible for diarrhea and a lack of compliance.
The European Food Safety Authority (EFSA) recommends in its opinion on "Dietary reference values for water" to consume 2 liters for women and 2.5 liters for men every day, all sources combined (food and beverages). The drink represent 80% of the water intake, that is about 1.5 Liter per day excluding food. However, there are multiple water marketed or distributed freely, with different compositions. Thus the quantity and quality of the mineral water consumed can influence the metabolism. Rozana mineral water, has the double advantage of being the French water the most concentrated in magnesium (160 mg / L) and of being lowly concentrated in sulphate, responsible of the laxative power of certain waters.
Instead of adding magnesium supplements with a poor digestive tolerance, to patients with metastatic cancer and often with a heavy treatment , the aim of this study is to evaluate whether a change in oral hydration in quantitative and qualitative terms can decrease the rate of hypomagnesemia in patients treated with anti-EGFR.
Project description:The human protozoan parasiteEntamoeba histolyticais responsible for amebiasis, a disease endemic to developing countries.E. histolyticatrophozoites colonize the large intestine, primarily feeding on bacteria. However, in the GI, as well as in aquatic and soil microenvironments, bacterial cells form aggregates or structured communities, called biofilm, too large for phagocytosis. However, trophozoites are still able to invade and degrade bacteria under biofilm form by a mechanism mimicking digestive exophagy. E.histolytica cysteine proteinase degrade TasA, one of the main component of the biofilm matrix. Biofilm also play an important role protecting trophozoites against oxidative stress. The specific mechanism suggests that amoeba is adapted to biofilm predation and may serve as a new unexplored reservoir of novel therapeutic approaches to treat biofilms. Consistently, amoeba’s products restored antibiotic sensitivity to biofilm cells. Furthermore, our findings here show that probiotic biofilms may serve as a protective shield for mammalian cells, hindering the progression of the parasite towards them.
Project description:Concerning the roles of LCN2 in chronic inflammation and fibrosis, we investigated chronic liver inflammation and fibrosis using repeated carbon tetrachloride (CCl4) in mineral oil injection. We found that mice treated with the mineral oil vehicle alone also showed liver inflammation and more severe in wild-type mice compared to lipocalin 2 null mice.