New insights on the mechanism of quinoline-based DNA methyltransferase inhibitors

Among the epigenetic marks, DNA methylation is one of the most studied. It is highly deregulated in numerous diseases, including cancer. Indeed, it has been shown that hypermethylation of tumor suppressor genes promoters is a common feature of cancer cells. Because DNA methylation is reversible, the DNA methyltransferases (DNMTs), responsible for this epigenetic mark, are considered promising therapeutic targets. Several molecules have been identified as DNMT inhibitors and, among the non-nucleoside inhibitors, 4-aminoquinoline-based inhibitors, such as SGI-1027 and its analogs, showed potent inhibitory activity. Here we characterized the in vitro mechanism of action of SGI-1027 and two analogs. Enzymatic competition studies with the DNA substrate and the methyl donor cofactor, S-adenosyl-L-methionine (AdoMet), displayed AdoMet non-competitive and DNA competitive behavior. In addition, deviations from the Michaelis-Menten model in DNA competition experiments suggested an interaction with DNA. Thus their ability to interact with DNA was established; although SGI-1027 was a weak DNA ligand, analog 5, the most potent inhibitor, strongly interacted with DNA. Finally, as 5 interacted with DNMT only when the DNA duplex was present, we hypothesize that this class of chemical compounds inhibit DNMTs by interacting with the DNA substrate

Viability of Bifidobacterium longum in cheddar cheese curd during manufacture and storage: effect of microencapsulation and point of inoculation

International audienceThe goal of this study was to assess the effect of methods of inoculation on the viability of probiotic bacteria during cheddar cheese manufacture as well as their stability during storage. Bifidobacterium longum ATCC 15708 was freeze-dried and microencapsulated by spray-coating. The effect of inoculation of free whole cell or microencapsulated cells at three points during manufacture (milk before renneting, at cheddaring or at salting) on the viable counts in cheese and whey was investigated. Microencapsulation had no effect on viable counts, chemical parameters (lactose, lactic acid, total nitrogen, nitrogen soluble in TCA, moisture) or sensory properties during manufacturing or storage of the fresh cheeses for 14 days. Inoculation of the bifidobacteria in milk before renneting resulted in higher viable counts in comparison to other points of inoculation. Bifidobacteria added at the salting step, which survived pressing, were subsequently more stable during storage than those inoculated in milk. The stability of B. longum 15708 during storage was greater in the pressed cheeses that in the free curds. The results of this study provides technological data for cheese makers on the optimum point of inoculation as well as the benefit of pressing the curds in order to ensure high levels of probiotics in fresh cheddar cheese

Interactions entre le droit des sûretés sous le Code civil du Québec et la loi sur les banques

The purpose of this study is to provide a precise and exhaustive study as well as an analysis of the place occupied by the banking security under Quebec Law in relation to the coming into force of the Civil Code of Quebec on January 1st 1994.The author shall emphasize her research on specific elements that have changed with the existence of new rules of civil law and that will contribute to the creation of new conflicts between financing banks of specific classes of debtors under the Bank Act mechanism and the other creditors of the latter.A first step will be to review constitutional principles underlying conflicts between provincial private law and federal exclusive jurisdiction matters, an analysis being considered necessary in order to study specific conflicts that might exist along the overlap situations between the Civil Code of Quebec and the Bank Act.This text core shall emphasize on the nature of the right conferred to the bank by the banking security under the light of the new Quebec law of real security, the effect of article 1801 C.c.Q. in relation to the banking conventions, and the multiple interactions between the banking security and certain types of hypotheses

Implication de l'ADN alpha satellite dans les processus de duplications segmentaires au sein des régions péricentromériques et sous télomériques des chromosomes humains

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Occurrence of a growth hormone-releasing hormone-like messenger ribonucleic acid and immunoreactive peptide in the sheep placenta

International audienc

Harnessing olfactory bulb oscillations to perform fully brain-based sleep-scoring and real-time monitoring of anaesthesia depth

International audienc