Effects of Ursolic Acid and its Analogues on Soybean 15-Lipoxygenase Activity and the Proliferation Rate of A human Gastric Tumour Cell Line

The authors have previously isolated and purified ursolic acid from heather flowers (Calluna vulgarts). This terpene was found to inhibit HL-60 leukaemic cell proliferation and arachidonic acid oxidative metabolism in various cell species. The effects of ursolic acid and its analogues on soybean 15-lipoxygenase activity and on the proliferation of a human gastric tumour cell line (HGT), have been assessed. These triterpenes inhibited soybean 15-lipoxygenase at its optimal activity (pH 9). The proliferation ofHGT was decreased in a dose-dependent manner. At 20 μM the rank order is: ursolic acid > uvaol > oleanolic acid > methyl ursolate. The carboxylic group at the C28 position of ursolic acid appears to be implicated in the inhibition of both lipoxygenase activity and cell proliferation. Thus methylation of this group decreases these two inhibitory properties. Oleanolic acid, which differs by the position of one methyl group (C20 instead of C19) is less inhibitory than ursolic acid. The lipophilicity of the terpene is also implicated since uvaol appears to be more inhibitory than methyl ursolate

Le site gaulois et antique de « La Carie », entre oppidum et ville romaine à Entrammes (Mayenne)

À mi-chemin entre oppidum gaulois et thermes antiques, le site de « La Carie » à Entrammes, installé près d’un gué sur un affluent de la Mayenne, a livré une succession stratigraphique débutant vers le milieu de La Tène moyenne, prenant son ampleur au Haut-Empire et finissant par une petite nécropole mérovingienne. Ces éléments s’organisent au sud, puis des deux côtés d’une large voie gauloise puis antique. L’habitat gaulois, peu dense, va en se complexifiant avant un abandon vers la fin de La Tène D1. Sur les mêmes bases, le site est réoccupé à partir de Tibère, des fours de potiers marquant la création d’une zone artisanale périphérique au nouveau chef-lieu du pagus gallo-romain d’Entrammes. À la période flavienne, de nouvelles structures sont élevées et agrandies jusqu’au début de la période sévérienne. Au Bas-Empire, si l’habitat est abandonné, la voie continue d’être utilisée ; une petite nécropole mérovingienne atteste de la permanence de cette dernière au moins jusqu’au viiie siècle. Enfin, mentionnons qu’un abondant mobilier, peu diversifié, illustre l’occupation, essentiellement de la période gauloise à la fin du Haut-Empire.Midway between the Gallic oppidum and the ancient spa, just before a ford on a Mayenne tributary, the site of “La Carie” at Entrammes has yielded a stratigraphic succession dating from the mid Celtic (La Tène) period, reaching its zenith during the time of the early Roman Empire with its end denoted by a small Merovingian necropolis. These elements are all arranged firstly to the south and then on either side of a large ancient Gallic well. Gallic habitation, firstly insignificant, became more complex before being abandoned towards the end of La Tène D1. Using the same base, the site was reoccupied from the time of Tiberius; potter’s kilns indicating the installation of a craft area were found on the periphery of the new administrative town of Entrammes, the former pagus. During the Flavian period, further structures were erected and enlarged through to the beginning of the Severan period. During the Late Empire, although the habitation was abandoned, the road continued to be used; a small Merovingian necropolis ensuring its permanence up to at least the fifteenth century. Finally, we should mention that abundant furniture, not particularly varied, illustrates occupation primarily from the Gallic period to the end of the Early Empire

A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients

[[abstract]]Background:Human hepatocellular carcinoma (HCC) cells are largely deficient of argininosuccinate synthetase and thus auxotrophic for arginine. This study aims to investigate the efficacy and pharmacodynamics of pegylated arginine deiminase (ADI-PEG 20), a systemic arginine deprivation agent, in Asian HCC patients. Methods:Patients with advanced HCC who were not candidates for local therapy were eligible and randomly assigned to receive weekly intramuscular injections of ADI-PEG 20 at doses of 160 or 320 IU m-2. The primary end point was disease-control rate (DCR). Results:Of the 71 accruals, 43.6% had failed previous systemic treatment. There were no objective responders. The DCR and the median overall survival (OS) of the intent-to-treat population were 31.0% (95% confidence interval (CI): 20.5-43.1) and 7.3 (95% CI: 4.7-9.9) months respectively. Both efficacy parameters were comparable between the two study arms. The median OS of patients with undetectable circulating arginine for more than or equal to and <4 weeks was 10.0 (95% CI: 2.1-17.9) and 5.8 (95% CI: 1.4-10.1) months respectively (P=0.251, log-rank test). The major treatment-related adverse events were grades 1-2 local and/or allergic reactions. Conclusions:ADI-PEG 20 is safe and efficacious in stabilising the progression of heavily pretreated advanced HCC in an Asian population, and deserves further exploration.British Journal of Cancer advance online publication, 31 August 2010; doi:10.1038/sj.bjc.6605856 www.bjcancer.com

Genome-wide methylation and gene expression changes in newborn rats following maternal protein restriction and reversal by folic acid

A large body of evidence from human and animal studies demonstrates that the maternal diet during pregnancy can programme physiological and metabolic functions in the developing fetus, effectively determining susceptibility to later disease. The mechanistic basis of such programming is unclear but may involve resetting of epigenetic marks and fetal gene expression. The aim of this study was to evaluate genome-wide DNA methylation and gene expression in the livers of newborn rats exposed to maternal protein restriction. On day one postnatally, there were 618 differentially expressed genes and 1183 differentially methylated regions (FDR 5%). The functional analysis of differentially expressed genes indicated a significant effect on DNA repair/cycle/maintenance functions and of lipid, amino acid metabolism and circadian functions. Enrichment for known biological functions was found to be associated with differentially methylated regions. Moreover, these epigenetically altered regions overlapped genetic loci associated with metabolic and cardiovascular diseases. Both expression changes and DNA methylation changes were largely reversed by supplementing the protein restricted diet with folic acid. Although the epigenetic and gene expression signatures appeared to underpin largely different biological processes, the gene expression profile of DNA methyl transferases was altered, providing a potential link between the two molecular signatures. The data showed that maternal protein restriction is associated with widespread differential gene expression and DNA methylation across the genome, and that folic acid is able to reset both molecular signatures

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

La préparation endodontique par instrument unique (étude comparative in vitro de la mise en forme canalaire du Protaper®-Wave One®)

LYON1-BU Santé Odontologie (693882213) / SudocSudocFranceF

A propos d’un contexte de la fin de l’Antiquité à Vannes (Morbihan) et de la découverte de quelques amphores orientales et africaines tardives en Bretagne

International audienc

L’Industrie musicale québécoise

L’industrie musicale s’est emparée du phénomène des chaînes de blocs dans de nombreux champs d’applications allant de la relation au public à la gestion des droits en passant par les nouvelles possibilités de création. L’intérêt suscité pour cette nouvelle technologie est propulsé par un discours médiatique qui met en avant une plus-value monétaire pour les artistes et une facilitation de la gestion des données. En regardant le cas spécifique de l’industrie musicale québécoise, nous présentons comment les acteurs du milieu entrevoient l’adoption des technologies des chaînes de blocs, notamment au regard des enjeux de protection de l’exception culturelle musicale québécoise. Nous proposons avec cet article de participer à ces discussions en mobilisant l’aspect théorique des communs de la connaissance d’Oström à travers un scénario de création d’un registre distribué des métadonnées autogouvernées par les acteurs de l’industrie.The music industry has taken hold of the blockchain phenomenon in many fields of application ranging from audience relations to rights management to new creative possibilities. The interest generated by this new technology is propelled by a media discourse that puts forward a monetary added value for artists and an easier data management. By looking at the specific case of the Quebec music industry, we present how the actors in the field see the adoption of blockchain technologies, particularly regarding the protection of Quebec’s musical cultural exception. We propose in this paper to participate in these discussions by mobilizing Oström’s theoretical lens of the knowledge commons through a scenario of creating a metadata distributed ledger self-governed by industry’s actors

Horizon céramique de la fin du IIe s.-première moitié du IIIe s. à Vannes (<i>Darioritum</i>, Morbihan)

International audienc

Horizon céramique de la fin du IIe s.-première moitié du IIIe s. à Vannes (<i>Darioritum</i>, Morbihan)

International audienc