Tissue-selective estrogen complexes with bazedoxifene prevent metabolic dysfunction in female mice

Pairing the selective estrogen receptor modulator bazedoxifene (BZA) with estrogen as a tissue-selective estrogen complex (TSEC) is a novel menopausal therapy. We investigated estrogen, BZA and TSEC effects in preventing diabetisity in ovariectomized mice during high-fat feeding. Estrogen, BZA or TSEC prevented fat accumulation in adipose tissue, liver and skeletal muscle, and improved insulin resistance and glucose intolerance without stimulating uterine growth. Estrogen, BZA and TSEC improved energy homeostasis by increasing lipid oxidation and energy expenditure, and promoted insulin action by enhancing insulin-stimulated glucose disposal and suppressing hepatic glucose production. While estrogen improved metabolic homeostasis, at least partially, by increasing hepatic production of FGF21, BZA increased hepatic expression of Sirtuin1, PPARα and AMPK activity. The metabolic benefits of BZA were lost in estrogen receptor-α deficient mice. Thus, BZA alone or in TSEC produces metabolic signals of fasting and caloric restriction and improves energy and glucose homeostasis in female mice

An open-access long oligonucleotide microarray resource for analysis of the human and mouse transcriptomes

Two collections of oligonucleotides have been designed for preparing pangenomic human and mouse microarrays. A total of 148 993 and 121 703 oligonucleotides were designed against human and mouse transcripts. Quality scores were created in order to select 25 342 human and 24 109 mouse oligonucleotides. They correspond to: (i) a BLAST-specificity score; (ii) the number of expressed sequence tags matching each probe; (iii) the distance to the 3′ end of the target mRNA. Scores were also used to compare in silico the two microarrays with commercial microarrays. The sets described here, called RNG/MRC collections, appear at least as specific and sensitive as those from the commercial platforms. The RNG/MRC collections have now been used by an Anglo-French consortium to distribute more than 3500 microarrays to the academic community. Ad hoc identification of tissue-specific transcripts and a ∼80% correlation with hybridizations performed on Affymetrix GeneChip™ suggest that the RNG/MRC microarrays perform well. This work provides a comprehensive open resource for investigators working on human and mouse transcriptomes, as well as a generic method to generate new microarray collections in other organisms. All information related to these probes, as well as additional information about commercial microarrays have been stored in a freely-accessible database called MEDIANTE

Group membership, group change, and intergroup attitudes: a recategorization model based on cognitive consistency principles

The present article introduces a model based on cognitive consistency principles to predict how new identities become integrated into the self-concept, with consequences for intergroup attitudes. The model specifies four concepts (self-concept, stereotypes, identification, and group compatibility) as associative connections. The model builds on two cognitive principles, balance–congruity and imbalance–dissonance, to predict identification with social groups that people currently belong to, belonged to in the past, or newly belong to. More precisely, the model suggests that the relative strength of self-group associations (i.e., identification) depends in part on the (in)compatibility of the different social groups. Combining insights into cognitive representation of knowledge, intergroup bias, and explicit/implicit attitude change, we further derive predictions for intergroup attitudes. We suggest that intergroup attitudes alter depending on the relative associative strength between the social groups and the self, which in turn is determined by the (in)compatibility between social groups. This model unifies existing models on the integration of social identities into the self-concept by suggesting that basic cognitive mechanisms play an important role in facilitating or hindering identity integration and thus contribute to reducing or increasing intergroup bias

Evolution of Endoscopic Lesions in Steroid-Refractory Acute Severe Ulcerative Colitis Responding to Infliximab or Cyclosporine

BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS >= 6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p CONCLUSION: In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.Peer reviewe

Enantioselective addition of organolithium reagents on isoquinoline

1-Methyl-1,2-dihydroisoquinoline and 1-butyl-1,2-dihydroisoquinoline were obtained by enantioselective addition of organolithium reagents on the isoquinoline. (-)-Sparteine was used as an external catalytic chiral ligand and an enantiomeric excess of 57% could be obtained

VERS UNE ARCHITECTURE PARALLELE RECONFIGURABLE DEDIEE AU TRAITEMENT D'IMAGE ET A LA VISION

ROUEN-BU Sciences (764512102) / SudocROUEN-BU Sciences Madrillet (765752101) / SudocSudocFranceF

Stabilité, transport et métabolisme de microconstituants phénoliques dans le tube digestif

Les polyphénols constituent la famille de microconstituants la plus représentée dans les aliments d origine végétale. Des études chez l animal et quelques études épidémiologiques associent la forte consommation de certaines classes de polyphénols avec une moindre incidence de maladies évolutives telles que l athérosclérose ou le cancer. Les effets biologiques d une molécule dépendent de sa biodisponibilité, et celle des polyphénols est mal connue. Deux aspects déterminants de la biodisponibilité ont été abordés : 1) La stabilité au cours du processus de digestion gastro-intestinal. Des études, menées à l aide d un modèle in vitro, ont montré que la stabilité des polyphénols dépend de leur structure. Il a également été observé que les polyphénols sont capables de protéger d autres classes d antioxydants alimentaires (vitamine E et caroténoïdes) contre l oxydation dans la partie haute du tube digestif. Ces résultats pourraient expliquer l échec de certaines études de supplémentation. 2) L absorption et le métabolisme entérocytaire. Deux molécules fréquemment rencontrées dans l alimentation, la vanilline et la naringine ont fait l objet d études d absorption au travers d une monocouche de cellules Caco-2/TC7 différenciée en entérocytes. Ces travaux ont mis en évidence que les mécanismes de transport et de métabolisme dépendent de la structure étudiée, et des métabolites ont été mis en évidence. Une absorption entérocytaire limitée de la naringine et une forte métabolisation entérocytaire dans le cas de la vanilline sont responsables de la faible absorption intestinale de ces molécules. Ces données pourraient contribuer à la compréhension des mécanismes d action des polyphénols in vivo.Polyphenols are the most widely occuring microconstituent family of our diet. Animal studies as well as some epidemiological data show an inverse association between the high intake of some popyphenol classes and the incidence of evolutive diseases such as atherosclerosis and cancer. Biological effects of a molecule depend on its bioavailability, and polyphenol bioavailability remains obscure. In the present work, two determinant aspects of bioavailabilty have been investigated: 1) Stability during gastro-intestinal digestion. In vitro acellular studies have shown that polyphenol stability depends on their molecular structure. Moreover, it has been observed that polyphenols are able to protect other classes of dietary antioxidants (vitamin E and carotenoids) from oxidation in the upper digestive tract. These results could explain the of some supplementation studies. 2) Absorption and metabolism by enterocytes. Absorption studies across differentiated Caco-2/TC7 cells have been performed with two frequently dietary occurring molecules, vanillin and naringin. Data displayed that transport and metabolism mechanisms depend on the structure, and several metabolites have been identified. Weak absorption of naringin and extensive metabolism of vanillin by enterocytes are responsible of the poor intestinal absorption of these compounds. Taken together, these data could contribute to the elucidation of the in vivo biological effects of polyphenols.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Enantioselective nucleophilic addition of organometallic reagents to quinoline: regio-, stereo- and enantioselectivity

Some 2-alkyl-1,2-dihydroquinoline and some 2-aryl-1,2-dihydroquinoline were obtained by enantioselective addition of methyl-, butyl-, phenyl- and 1-naphthyllithium on quinoline. Bisoxazolines were used as external chiral ligands, giving enantiomeric excess up to 79%. The ligand could be used in catalytic amounts without significant loss of enantioselectivity