Tandem <i>N</i>‑Alkylation/Vinylogous Aldol Reaction of β,γ-Alkenyl α‑Iminoester

This report describes a highly regioselective tandem <i>N</i>-alkylation/vinylogous aldol reaction of β,γ-alkenyl α-iminoesters. The sulfur group improves the regioselectivity of the directed vinylogous aldol reaction, providing a new synthetic method of 3-amino-2-pyrones

Quercetin inhibits the C/EBPβ-mediated activation of the human apoB promoter.

<p>(<b>A</b>) A map of the reporter plasmids was used. Gray circles, C/EBP-response element; closed box, SV40 promoter. (<b>B,C</b>) Caco-2 cells were transfected with the indicated reporters and expression plasmids for β-galactosidase and C/EBPβ. Luciferase activities were normalized to β-galactosidase activities; a value of 1 was set in the absence of C/EBPβ. Data are presented as mean ± SD (n = 3). **p < 0.01. (<b>D,E</b>) Caco-2 cells were transfected with the indicated reporters and expression plasmids for β-galactosidase and C/EBPβ. After transfection, cells were treated with vehicle or 100 μM quercetin for 24 h. Luciferase activities were normalized to β-galactosidase activities; a value of 1 was set in the absence of C/EBPβ. Data are presented as mean ± SD (n = 3). **p < 0.01, N.S., not significant.</p

Proposed model for quercetin-mediated repression of apoB expression.

<p>Quercetin represses expression of <i>apoB</i> through an inhibition of the transcriptional activity of C/EBPβ. Quercetin may interfere in the recruitment of coactivators by binding to C/EBPβ. The present results revealed novel quercetin-mediated regulation of apoB expression.</p

Quercetin inhibits the C/EBPβ-mediated activation of the human apoB promoter.

<p>(<b>A</b>) A map of the reporter plasmids was used. Gray circles, C/EBP-response element; closed box, SV40 promoter. (<b>B,C</b>) Caco-2 cells were transfected with the indicated reporters and expression plasmids for β-galactosidase and C/EBPβ. Luciferase activities were normalized to β-galactosidase activities; a value of 1 was set in the absence of C/EBPβ. Data are presented as mean ± SD (n = 3). **p < 0.01. (<b>D,E</b>) Caco-2 cells were transfected with the indicated reporters and expression plasmids for β-galactosidase and C/EBPβ. After transfection, cells were treated with vehicle or 100 μM quercetin for 24 h. Luciferase activities were normalized to β-galactosidase activities; a value of 1 was set in the absence of C/EBPβ. Data are presented as mean ± SD (n = 3). **p < 0.01, N.S., not significant.</p

Quercetin repressed the expression of genes related to lipoprotein metabolism in Caco-2 cells.

<p>(<b>A</b>) Differentiated Caco-2 cells were treated with vehicle or 100 μM quercetin for 24 h, after which total RNA was isolated. mRNA levels, which were determined by quantitative real-time PCR, are presented as relative expression after normalization to 36B4 mRNA. Relative mRNA levels in vehicle-treated cells were set to 1. Data are presented as mean ± SD (n = 3). *p < 0.05, **p < 0.01. (<b>B</b>) Differentiated Caco-2 cells were treated with vehicle (Veh) or 100 μM quercetin (Q) for 12 h. Proteins were extracted and immunoblots (IB) were performed. (<b>C</b>) Differentiated Caco-2 cells were exposed to vehicle or the indicated doses of quercetin for 24 h, after which total RNA was isolated. Data are presented as mean ± SD (n = 3). **p < 0.01.</p

Identification of the quercetin-response element of the human apoB promoter.

<p>(<b>A, B, D</b>) Caco-2 cells were transfected with the reporter gene, which contains the indicated upstream region of human <i>apoB</i> and an expression plasmid for β-galactosidase. After transfection, cells were exposed to vehicle or 100 μM quercetin for 24 h. Luciferase activities were normalized to β-galactosidase activities; a value of 1 was set in the absence of quercetin. Data are presented as mean ± SD (n = 3). *p < 0.05, **p < 0.01, N.S., not significant. (<b>C</b>) DNA sequences of the human apoB (NT_022184), mouse apoB (NC_000078), and rat apoB (NW_047758) promoters around the quercetin-response element. Conserved DNA sequences are marked by asterisks.</p

Intracellular quercetin binds to C/EBPβ.

<p>(<b>A</b>) Chemical structures of quercetin and quercetin 3-<i>O</i>-glucuronide. (<b>B</b>) Differentiated Caco-2 cells were treated with vehicle (Veh) or 100 μM quercetin (Q) or 100 μM quercetin 3-<i>O</i>-glucuronide (Q3G) for 24 h, after which total RNA was isolated. mRNA levels, which were determined by quantitative real-time PCR, are presented as relative expression after normalization to 36B4 mRNA. Relative mRNA levels in vehicle-treated cells were set to 1. Data are presented as mean ± SD (n = 3). *p < 0.05. (<b>C</b>) Caco-2 cells were exposed to vehicle (Veh) or 100 μM quercetin (Q) for 12 h, and cell lysates were prepared. Pre-cleared lysates with control beads were incubated with control (Ctrl) beads or quercetin (Q)-conjugated beads. The reacted beads were washed, and the coprecipitated proteins were detected by immunoblot (IB) analysis.</p

La diversité des formes d'habitat organisé dans la Grande Couronne francilienne : essai de typologie des ensembles d'habitat groupé

Document de travail provisoire, à paraître dans Les cahiers de l'IAU-IdFLes périphéries des grandes métropoles offrent aux visiteurs des paysages rapidement reconnaissables... Nombre de ces opérations sont produites dans le cadre d'opérations " groupées " par des promoteurs qui en ont intégré les différentes étapes. Elles apparaissent comme une "image-type" de l'étalement urbain et sont souvent "accusées" d'uniformiser les paysages et les types d'espaces périurbains. Deux éléments semblent favoriser la standardisation des formes produites : la concentration de l'offre au sein de quelques très grands groupes de promotion immobilière, et la production d'ensembles pavillonnaires de types standardisés, propres aux différents types de promoteurs. Cette logique de " marque " est appréhendée ici par la réalisation d'une typologie des ensembles pavillonnaires produits dans la Grande Couronne francilienne

Piperine stimulates SREBP activity.

<p>(<b>A</b>) HepG2 cells were cultured with piperine (100 μM) for 24 h, and total RNA was isolated. Real-time PCR analyses were performed, and mRNA expression of target genes was normalized to that of GAPDH mRNA and was expressed relative to mRNA levels in vehicle (DMSO)-treated controls. All data are expressed as mean ± SEM, n = 3; **<i>P</i> < 0.01. (<b>B</b>) HepG2 cells were cultured with piperine (100 μM) for 3 h and whole-cell extracts were isolated for SDS/PAGE and IB with anti-SREBP–1 (2A4), anti-SREBP–2 (Rs004), anti-SREBP–2 (1C6), or anti-β-actin antibodies (upper panel). Similar results were obtained in three separate experiments. The signals (n = 3) were quantified, and the signals of the control group are represented as 1 (lower panel). (<b>C</b>) HepG2 cells were cultured with indicated concentrations of piperine for 24 h, and whole-cell extracts were isolated for SDS/PAGE and IB with anti-SREBP–2 (1C6) or anti-β-actin antibodies (upper panel). Similar results were obtained in three separate experiments. The signals (n = 3) were quantified, and the signals of the control group are represented as 1 (lower panel).</p

Piperine increases the expression and activity of LDLR.

<p>(<b>A</b> and <b>B</b>) HepG2 cells were cultured with the indicated concentration of piperine for 24 h, and total RNA and whole cell extracts were isolated. (<b>A</b>) Real-time PCR analysis was performed and mRNA levels were normalized to those of GAPDH mRNA and expressed relative to those in vehicle (DMSO)-treated controls. All data are expressed as mean ± SEM, <i>n</i> = 3. Differing letters indicate significant differences, *<i>P</i> < 0.05. (<b>B</b>) Whole-cell extracts were subjected to SDS/PAGE and immunoblotting (IB) with anti-LDLR or anti-β-actin antibodies (upper panel). Similar results were obtained in three separate experiments. The signals (n = 3) were quantified, and the signals of the control group are represented as 1 (lower panel). (<b>C</b>) HepG2 cells were cultured with piperine (100 μM) for 24 h and were then cultured in medium supplemented with 10 μg/ml DiI-labeled LDL for the last 5 h. The cells were then examined using fluorescence microscopy (upper panel), and relative fluorescence levels were normalized to total cellular protein contents (lower panel). All data are expressed as mean ± SEM, <i>n</i> = 3; *<i>P</i> < 0.01.</p