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Dive into the research topics where Georges Alves is active.

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Featured researches published by Georges Alves.


Plant Physiology | 2003

Plasma Membrane Aquaporins Are Involved in Winter Embolism Recovery in Walnut Tree

Soulaiman Sakr; Georges Alves; Raphaël Morillon; Karine Maurel; Mélanie Decourteix; Agnès Guilliot; Pierrette Fleurat-Lessard; Jean-Louis Julien; Maarten J. Chrispeels

In perennial plants, freeze-thaw cycles during the winter months can induce the formation of air bubbles in xylem vessels, leading to changes in their hydraulic conductivity. Refilling of embolized xylem vessels requires an osmotic force that is created by the accumulation of soluble sugars in the vessels. Low water potential leads to water movement from the parenchyma cells into the xylem vessels. The water flux gives rise to a positive pressure essential for the recovery of xylem hydraulic conductivity. We investigated the possible role of plasma membrane aquaporins in winter embolism recovery in walnut (Juglans regia). First, we established that xylem parenchyma starch is converted to sucrose in the winter months. Then, from a xylem-derived cDNA library, we isolated two PIP2 aquaporin genes (JrPIP2,1 and JrPIP2,2) that encode nearly identical proteins. The water channel activity of the JrPIP2,1 protein was demonstrated by its expression in Xenopus laevis oocytes. The expression of the two PIP2 isoforms was investigated throughout the autumn-winter period. In the winter period, high levels of PIP2 mRNA and corresponding protein occurred simultaneously with the rise in sucrose. Furthermore, immunolocalization studies in the winter period show that PIP2 aquaporins were mainly localized in vessel-associated cells, which play a major role in controlling solute flux between parenchyma cells and xylem vessels. Taken together, our data suggest that PIP2 aquaporins could play a role in water transport between xylem parenchyma cells and embolized vessels.


Journal of Medicinal Chemistry | 2011

Synthesis, Protein Kinase Inhibitory Potencies, and in Vitro Antiproliferative Activities of Meridianin Derivatives

Francis Giraud; Georges Alves; Eric Debiton; Lionel Nauton; Vincent Théry; Emilie Durieu; Yoan Ferandin; Olivier Lozach; Laurent Meijer; Fabrice Anizon; Elisabeth Pereira; Pascale Moreau

The synthesis of new meridianin derivatives is described. The indolic ring system was substituted at the C-4 to C-7 positions either by a bromine atom or by nitro or amino groups. Additionally, an iodine atom or various aryl groups were introduced at the C-5 position of the 2-aminopyrimidine ring. These compounds as well as some of their synthetic intermediates were tested for their kinase inhibitory potencies and for their in vitro antiproliferative activities. We found that this series of compounds is particularly interesting in the development of new inhibitors of DYRK1A and CLK1 kinases. The most effective compounds toward these two kinase families are the 6- and 7-bromo derivatives 30, 33, and 34 that showed more than 45-fold selectivity toward DYRK1A/CLK1 kinases over the other kinases tested. Meridianin derivatives could thus be developed toward potent and selective inhibitors of key RNA splicing regulators and potential therapeutic agents.


Circulation Research | 2009

Induction of Transglutaminase 2 by a Liver X Receptor/Retinoic Acid Receptor α Pathway Increases the Clearance of Apoptotic Cells by Human Macrophages

Cédric Rébé; Magalie Raveneau; Angélique Chevriaux; Daniela Lakomy; Anne-Laure Sberna; Annie Costa; Ginette Bessède; Anne Athias; Eric Steinmetz; Jean Marc A. Lobaccaro; Georges Alves; Alexandre Menicacci; Sébastien Vachenc; Eric Solary; Philippe Gambert; David Masson

Rationale: Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that are involved in the control of cholesterol homeostasis and inflammatory response. Human monocytes and macrophages express high levels of these receptors and are appropriate cells to study the response to LXR agonists. Objective: The purpose of this study was to identify new LXR targets in human primary monocytes and macrophages and the consequences of their activation. Methods and Results: We show that LXR agonists significantly increase the mRNA and protein levels of the retinoic acid receptor (RAR)&agr; in primary monocytes and macrophages. LXR agonists promote RAR&agr; gene transcription through binding to a specific LXR response element on RAR&agr; gene promoter. Preincubation of monocytes or macrophages with LXR agonists before RAR&agr; agonist treatment enhances synergistically the expression of several RAR&agr; target genes. One of these genes encodes transglutaminase (TGM)2, a key factor required for macrophage phagocytosis. Accordingly, the combination of LXR and RAR&agr; agonists at concentrations found in human atherosclerotic plaques markedly enhances the capabilities of macrophages to engulf apoptotic cells in a TGM2-dependent manner. Conclusions: These results indicate an important role for LXRs in the control of phagocytosis through an RAR&agr;-TGM2–dependent mechanism. A combination of LXR/RAR&agr; agonists that may operate in atherosclerosis could also constitute a promising strategy to improve the clearance of apoptotic cells by macrophages in other pathological situations.


Journal of Plant Physiology | 2001

Plasma membrane H+-ATPase, succinate and isocitrate dehydrogenases activities of vessel-associated cells in walnut trees

Georges Alves; Jörg J. Sauter; Jean-Louis Julien; Pierrette Fleurat-Lessard; Thierry Ameglio; Agnes Guillot; Gilles Pétel; André Lacointe

Summary In winter and spring, walnut trees exhibit variations of sugar content in the vascular sap. According to their location, the vessel-associated cells (VACs, also called contact cells) could control nutrient exchanges between the storage parenchyma and the xylem vessels. According to the literature, the recovery of sap (influx) occurs at the VAC/vessel interface via an H+/sugar symport that depends on the transmembrane pH gradient generated by the plasma membrane H+-ATPase. The aim of this study was to investigate the ATPase activity, using a perfusion technique that allows the use of several effectors: carbonyl cyanide m-chlorophenylhydrazone (CCCP) and fusicoccin (FC). During winter, the uncoupler CCCP revealed a low pH gradient between the xylem vessels and the vessel-associated cells. Under these conditions, FC, an activator of the H+-ATPase, had no effect on the pH of the perfusion solution, suggesting that the enzyme could be lightly active. In contrast, close to bud break, a high pH gradient was revealed by the use of CCCP, and an acidification of the perfusion solution was observed in the presence of FC. Moreover, cytochemical investigation showed high activity of two respiratory enzymes located in mitochondria: NAD-dependent isocitrate dehydrogenase and succinate dehydrogenase. The hypothesis is that in spring this high respiratory activity of VACs provides a consequent increase in available ATP that can be utilized by the plasma membrane H+-ATPase.


Endocrinology | 2009

Absence of Nuclear Receptors for Oxysterols Liver X Receptor Induces Ovarian Hyperstimulation Syndrome in Mice

Kevin Mouzat; Fanny Volat; Silvère Baron; Georges Alves; Aurélien Pommier; David H. Volle; Geoffroy Marceau; Angélique DeHaze; Pierre Déchelotte; Raj Duggavathi; Françoise Caira; Jean-Marc A. Lobaccaro

Ovarian hyperstimulation syndrome is a frequent complication occurring during in vitro fertilization cycles. It is characterized by a massive ovarian enlargement associated with an accumulation of extra vascular fluid. Here we show that liver X receptor (LXR)-alpha and LXR-beta deficient mice present many clinical and biological signs of ovarian hyperstimulation syndrome: ovarian enlargement, hemorrhagic corpora lutea, increased ovarian vascular permeability, and elevated estradiol. Ovulation stimulation resulted in excessive ovarian response to exogenous gonadotropins because follicle number and estradiol production were higher in transgenic mice. LXR deficiency also leads to perturbations in general inflammatory status, associated with ovarian il-6 deregulation. Upon treatment with the synthetic LXR agonist T09101317, serum estradiol and expression of star and cyp11a1 genes were markedly increased in wild-type mice, showing that LXRs are key regulators of ovarian steroidogenesis. These results suggest that LXRs control the ovulation by regulating endocrine and vascular processes.


PLOS Genetics | 2013

Liver X Receptors Protect from Development of Prostatic Intra-Epithelial Neoplasia in Mice

Aurélien Pommier; Julie Dufour; Georges Alves; Emilie Viennois; Hugues De Boussac; Amalia Trousson; David H. Volle; Françoise Caira; Pierre Val; Philippe Arnaud; Jean-Marc A. Lobaccaro; Silvère Baron

LXR (Liver X Receptors) act as “sensor” proteins that regulate cholesterol uptake, storage, and efflux. LXR signaling is known to influence proliferation of different cell types including human prostatic carcinoma (PCa) cell lines. This study shows that deletion of LXR in mouse fed a high-cholesterol diet recapitulates initial steps of PCa development. Elevation of circulating cholesterol in Lxrαβ-/- double knockout mice results in aberrant cholesterol ester accumulation and prostatic intra-epithelial neoplasia. This phenotype is linked to increased expression of the histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2), which results in the down-regulation of the tumor suppressors Msmb and Nkx3.1 through increased methylation of lysine 27 of histone H3 (H3K27) on their promoter regions. Altogether, our data provide a novel link between LXR, cholesterol homeostasis, and epigenetic control of tumor suppressor gene expression.


Chemical Communications | 2011

A platinum Chugaev carbene complex as a potent anticancer agent

Georges Alves; Laurent Morel; Malika El-Ghozzi; Daniel Avignant; Bertrand Legeret; Lionel Nauton; Federico Cisnetti; Arnaud Gautier

A platinum Chugaev complex was synthesised and fully characterized by multinuclear NMR spectroscopy and X-ray crystallography. This cis bis acyclic diamino carbene complex acts as a cytotoxic compound and behaves as a cisplatin equivalent by interacting with supercoiled DNA and thiols. Stability of the ligand is also discussed.


PLOS ONE | 2013

Lack of liver X receptors leads to cell proliferation in a model of mouse dorsal prostate epithelial cell.

Julie Dufour; Aurélien Pommier; Georges Alves; Hugues De Boussac; Corinne Lours-Calet; David H. Volle; Jean-Marc A. Lobaccaro; Silvère Baron

Recent studies underline the implication of Liver X Receptors (LXRs) in several prostate diseases such as benign prostatic hyperplasia (BPH) and prostate cancer. In order to understand the molecular mechanisms involved, we derived epithelial cells from dorsal prostate (MPECs) of wild type (WT) or Lxrαβ−/− mice. In the WT MPECs, our results show that LXR activation reduces proliferation and correlates with the modification of the AKT-survival pathway. Moreover, LXRs regulate lipid homeostasis with the regulation of Abca1, Abcg1 and Idol, and, in a lesser extent, Srebp1, Fas and Acc. Conversely cells derived from Lxrαβ−/− mice show a higher basal phosphorylation and consequently activation of the survival/proliferation transduction pathways AKT and MAPK. Altogether, our data point out that the cell model we developed allows deciphering the molecular mechanisms inducing the cell cycle arrest. Besides, we show that activated LXRs regulate AKT and MAPK transduction pathways and demonstrate that LXRs could be good pharmacological targets in prostate disease such as cancer.


PLOS ONE | 2011

Dietary Cholesterol-Induced Post-Testicular Infertility

Aurélia Ouvrier; Georges Alves; Christelle Damon-Soubeyrand; Geoffroy Marceau; Rémi Cadet; Laurent Janny; Florence Brugnon; Ayhan Kocer; Aurélien Pommier; Jean-Marc A. Lobaccaro; Joël R. Drevet; Fabrice Saez

This work shows that an overload of dietary cholesterol causes complete infertility in dyslipidemic male mice (the Liver X Receptor-deficient mouse model). Infertility resulted from post-testicular defects affecting the fertilizing potential of spermatozoa. Spermatozoa of cholesterol-fed lxr−/− animals were found to be dramatically less viable and motile, and highly susceptible to undergo a premature acrosome reaction. We also provide evidence, that this lipid-induced infertility is associated with the accelerated appearance of a highly regionalized epididymal phenotype in segments 1 and 2 of the caput epididymidis that was otherwise only observed in aged LXR-deficient males. The epididymal epithelial phenotype is characterized by peritubular accumulation of cholesteryl ester lipid droplets in smooth muscle cells lining the epididymal duct, leading to their transdifferentiation into foam cells that eventually migrate through the duct wall, a situation that resembles the inflammatory atherosclerotic process. These findings establish the high level of susceptibility of epididymal sperm maturation to dietary cholesterol overload and could partly explain reproductive failures encountered by young dyslipidemic men as well as ageing males wishing to reproduce.


Tree Physiology | 2004

Temperature effects on xylem sap osmolarity in walnut trees: evidence for a vitalistic model of winter embolism repair

Thierry Ameglio; Méanie Decourteix; Georges Alves; Vincent Valentin; Soulaiman Sakr; Jean-Louis Julien; Gilles Pétel; Agnès Guilliot; André Lacointe

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Thierry Ameglio

Institut national de la recherche agronomique

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Gilles Pétel

Blaise Pascal University

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Laurent Morel

Blaise Pascal University

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Marc Bonhomme

Institut national de la recherche agronomique

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Lionel Nauton

Centre national de la recherche scientifique

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