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See detailImportance of steroid receptor coactivators in the modulation of steroid action on brain and behavior
Charlier, Thierry ULg

in Psychoneuroendocrinology (2009), 34

Steroid receptors such as estrogen and androgen receptors are nuclear receptors involved in the transcriptional regulation of a large number of target genes. Steroid-dependent protein expression in the ... [more ▼]

Steroid receptors such as estrogen and androgen receptors are nuclear receptors involved in the transcriptional regulation of a large number of target genes. Steroid-dependent protein expression in the brain controls a large array of biological processes including spatial cognition, copulatory behavior and neuroprotection. The discovery of a competition, or squelch- ing, between two different nuclear receptors introduced the notion that common cofactors may be involved in the modulation of transcriptional activity of nuclear receptors. These cofactors or coregulatory proteins are functionally divided into coactivators and corepressors and are involved in chromatin remodeling and stabilization of the general transcription machinery. Although a large amount of information has been collected about the in vitro function of these coregulatory proteins, relatively little is known regarding their physiological role in vivo, particularly in the brain. Our laboratory and others have demonstrated the importance of SRC-1 in the differentia- tion and activation of steroid-dependent sexual behaviors and the related neural genes. For example, we report that the inhibition of SRC-1 expression blocks the activating effects of exogenous testosterone on male sexual behaviors and increases the volume of the median preoptic area. Other coactivators are likely to be involved in the modulation in vivo of steroid receptor activity and it seems that the presence of a precise subset of coactivators could help define the phenotype of the cell by modulating a specific downstream pathway after steroid receptor activation. The very large number of coactivators and their association into preformed complexes potentially allows the determination of hundreds of different phenotypes. The study of the expression of the coactivator and their function in vivo is required to fully understand steroid action and specificity in the brain. [less ▲]

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See detailImportance of steroid receptor coregulators for neuronal phenotype determination: Modulation of steroid action
Charlier, Thierry ULg

in Trabajos del Instituto Cajal (2009), LXXXII

Steroid receptors such as estrogen receptors alpha and beta and androgen receptors are transcription factors involved in the transcriptional regulation of a large number of target genes. Steroid-dependent ... [more ▼]

Steroid receptors such as estrogen receptors alpha and beta and androgen receptors are transcription factors involved in the transcriptional regulation of a large number of target genes. Steroid-dependent expression in the brain controls a large array of biological processes including spatial cognition, copulatory behavior and neuroprotection. The discovery of a competition, or squelching, between two different nuclear receptors introduced the notion that common cofactors might be involved in the modulation of transcriptional activity of nuclear receptors. These cofactors, which are now known as coactivators, are involved in chromatin remodeling and stabilization of the general transcription machinery. Since the characterization of the steroid receptor coactivator 1 or SRC-1, more than 100 different cofactors have been identified. Although an increasingly large amount of information has been collected about the in vitro function of these coregulatory proteins, relatively little is known regarding their physiological role in vivo, particularly in the brain. Our laboratory and others have demonstrated the importance of SRC-1 in the differentiation and activation of steroid-dependent sexual behaviors and the related neural genes. In Japanese quail, the inhibition of SRC-1 expression by intracerebroventricular antisense injections blocked the activating effects of exogenous testosterone on male sexual behaviors and the steroid-dependent vasotocine expression and increase of the median preoptic area volume defined by Nissl staining as well as by aromatase immunoreactivity. These data therefore strongly suggested that SRC-1 is required to modulate estrogen receptor dependent gene-expression. It is however interesting to note that steroid receptors and SRC-1 are not always colocalized. For example, both glial cells and neurons in the hippocampus express estrogen receptor alpha but SRC-1 is rarely observed in glia. It is therefore possible that estrogen receptor alpha in glial cell require another coactivator or set of coactivators to induce estrogen-dependent gene transcription. It has been suggested very recently that SRC-1 is associated with neuronal differentiation of neural stem cell derived from the ganglionic eminence of mouse embryos. These stem cells differentiating into glial cell (GFAP-positive) did not express SRC-1. The presence of a specific coactivator could therefore determine a specific cell phenotype (neuronal vs glial). Another coactivator, the coactivator-associated arginine methyl transferase 1 or CARM-1 seems to be important to keep progenitor cells in a dividing state. The inhibition of CARM-1 expression leads to neuronal differentiation. Neurogenesis can therefore offers an excellent model to define the spatio-temporal role of different coactivators. It is indeed possible to study a subset of coactivators associated to various stages phenotype determination (proliferation vs. differentiation). The study of neurogenesis in the dentate gyrus of the hippocampus in female adult rats shows that around 40 % of proliferative cells express SRC-1 or CARM-1. Interestingly, 70% of proliferative cells express SRC-1 but only a very few cells (<5%) express CARM-1. We are currently investigating the temporal pattern of expression of these two coactivators during the neurogenesis in the hilus and dentate gyrus. The expression of the coactivators CARM-1 and SRC-1 is analyzed in proliferating and differentiating cells. We expect that proliferating and differentiating cells will differentially express the two coactivators. It seems that the presence of a precise subset of coactivators could help defining the phenotype of the cell by modulating a specific downstream pathway after steroid receptor activation. The very large number of coactivators and their association into preformed complexes potentially allows the determination of hundreds of different phenotypes. The study of the expression of the coactivator and their function in vivo is required to fully understand steroid action and specificity in the brain. [less ▲]

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See detailImportance of surfactin for plant resistance induction by Bacillus isolates
Cawoy, Hélène ULg; Mariutto, Martin; Jourdan, Emmanuel et al

Conference (2012, June 27)

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See detailImportance of synovitis in osteoarthritis: Evidence for the use of glycosaminoglycans against synovial inflammation.
Henrotin, Yves ULg; Lambert, Cécile ULg; Richette, Pascal

in Seminars in Arthritis & Rheumatism (2014), 43(5), 579-87

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See detailImportance of the alternative pathway of respiration for avoidance of ROS production and for optimisation of photosynthesis in Chlamydomonas
Franck, Fabrice ULg; Dinant, M.; Cardol, Pierre ULg et al

Conference (2008, June)

The physiological function of the alternative pathway of respiration has been investigated by analysing two RNAi C.reinhardtii lines deprived of alternative oxidase protein (AOX1). Compared to wild-type ... [more ▼]

The physiological function of the alternative pathway of respiration has been investigated by analysing two RNAi C.reinhardtii lines deprived of alternative oxidase protein (AOX1). Compared to wild-type, AOX1- lines exhibited modified growth curves and reduced maximal cell density. These differences were more pronounced at high irradiance and in nitrate-containing medium (TAP NO3) rather than in ammonium-containing medium (TAP NH4). Although the alternative pathway was inactive, respiration was not significantly altered in transgenics. Light-saturation curves of O2-evolution were only slightly modified. However, non-photochemical quenching of fluorescence (NPQ) was strongly reduced. Further analysis showed that AOX1- transgenics present a reduced ability to promote the change in energy distribution between photosystems, known as state transition. This effect, which explains low NPQ in the light, was most pronounced in high-light cells cultivated in TAP NO3 medium. Moreover, AOX1- transgenics exhibited higher levels of intracellular peroxides, which suggests that inhibition of state transition might result from higher ROS production. In support of this hypothesis, addition of millimolar-range concentrations of H2O2 to wild-type inhibited the state transition promoted by the reduction of the plastoquinone pool in darkness. [less ▲]

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See detailImportance of the apoprotein in the catalysis of hydroperoxide lyase
Delcarte, J.; Jacques, P.; Fauconnier, Marie-Laure ULg et al

Poster (1999, July 15)

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See detailImportance of the conserved residues in the peptidoglycan glycosyltransferase module of the class A penicillin-binding protein 1b of Escherichia coli.
Terrak, Mohammed ULg; Sauvage, Eric ULg; Derouaux, Adeline ULg et al

in Journal of Biological Chemistry (2008), 283(42), 28464-70

The peptidoglycan glycosyltransferase (GT) module of class A penicillin-binding proteins (PBPs) and monofunctional GTs catalyze glycan chain elongation of the bacterial cell wall. These enzymes belong to ... [more ▼]

The peptidoglycan glycosyltransferase (GT) module of class A penicillin-binding proteins (PBPs) and monofunctional GTs catalyze glycan chain elongation of the bacterial cell wall. These enzymes belong to the GT51 family, are characterized by five conserved motifs, and have some fold similarity with the phage lambda lysozyme. In this work, we have systematically modified all the conserved amino acid residues of the GT module of Escherichia coli class A PBP1b by site-directed mutagenesis and determined their importance for the in vivo and in vitro activity and the thermostability of the protein. To get an insight into the GT active site of this paradigm enzyme, a model of PBP1b GT domain was constructed based on the available crystal structures (PDB codes 2OLV and 2OLU). The data show that in addition to the essential glutamate residues Glu233 of motif 1 and Glu290 of motif 3, the residues Phe237 and His240 of motif 1 and Gly264, Thr267, Gln271, and Lys274 of motif 2, all located in the catalytic cavity of the GT domain, are essential for the in vitro enzymatic activity of the PBP1b and for its in vivo functioning. Thus, the first three conserved motifs contain most of the residues that are required for the GT activity of the PBP1b. The residues Asp234, Phe237, His240, Thr267, and Gln271 are proposed to maintain the structure of the active site and the positioning of the catalytic Glu233. [less ▲]

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See detailImportance of the creatinine calibration in the estimation of GFR by MDRD equation
Delanaye, Pierre ULg; Cavalier, Etienne ULg; Chapelle, Jean-Paul ULg et al

in Nephrology Dialysis Transplantation (2006), 21(4), 1130-1130

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See detailImportance of the E-46-D-160 Polypeptide Segment of the Non-Penicillin-Binding Module for the Folding of the Low-Affinity, Multimodular Class B Penicillin-Binding Protein 5 of Enterococcus Hirae
Mollerach, Marta E.; Partoune, Pierre; Coyette, Jacques ULg et al

in Journal of Bacteriology (1996), 178(6), 1774-1775

Compared with the other class B multimodular penicillin- binding proteins (PBPs), the low-affinity PBP5 responsible for penicillin resistance in Enterococcus hirae R40, has an extended non-penicillin ... [more ▼]

Compared with the other class B multimodular penicillin- binding proteins (PBPs), the low-affinity PBP5 responsible for penicillin resistance in Enterococcus hirae R40, has an extended non-penicillin-binding module because of the presence of an approximately 110-amino-acid E-46(-)D-160 insert downstream from the membrane anchor. Expression of pbp5 genes lacking various parts of the insert-encoding region gives rise to proteins that are inert in terms of penicillin binding, showing that during folding of the PBP, the insert plays a role in the acquisition of a correct penicillin-binding configuration by the G-364(-)Q-678 carboxy-terminal module. [less ▲]

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See detailThe importance of the effects of mora debitoris
Cavalleri, Vanessa ULg

Conference (2014, June 19)

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See detailImportance of the enveloppe glycoprotein gp51 in the diagnosis of BLV infection and in the development of an anti-BLV subunit vaccine.
Portetelle, Daniel ULg; Dandoy, Corinne; Gras, Hélène et al

in Journal of Cellular Biochemistry. Supplement (1986), (suppl 10 A), 209

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See detailImportance of the His-298 Residue in the Catalytic Mechanism of the Streptomyces R61 Extracellular Dd-Peptidase
Hadonou, Ayaovi M.; Jamin, Marc; Adam, Maggy et al

in Biochemical Journal (1992), 282(Pt 2), 495-500

Among the active-site-serine penicillin-recognizing proteins, the Streptomyces R61 extracellular DD-peptidase is the only one to have a His-Thr-Gly sequence [instead of Lys-Thr(Ser)-Gly] in 'box' VII. The ... [more ▼]

Among the active-site-serine penicillin-recognizing proteins, the Streptomyces R61 extracellular DD-peptidase is the only one to have a His-Thr-Gly sequence [instead of Lys-Thr(Ser)-Gly] in 'box' VII. The His residue was replaced by Gln or Lys. Both mutations induced a marked decrease in the rates of both tripeptide substrate hydrolysis and acylation by benzylpenicillin and cephalosporin C. The rate of hydrolysis of the thioester hippuryl thioglycollate was less affected. The most striking result was the disproportionate loss of transpeptidation properties by both mutants, indicating an important role of His-298 in this reaction. We believe that this result represents the first modification of a DD-peptidase leading to a specific decrease of the transpeptidation-to-hydrolysis ratio. [less ▲]

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See detailImportance Of The Hydrophobic Energy: Structural Determination Of A Hypoglycemic Drug Of The Meglitinide Family By Nuclear Magnetic Resonance And Molecular Modeling
Lins, Laurence ULg; Brasseur, Robert ULg; Malaisse, Wj. et al

in Biochemical Pharmacology (1996), 52(8), 1155-68

The molecular structure of (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionic acid (KAD-1229), a hypoglycemic drug of the meglitinide family, was studied by nuclear magnetic resonance (NMR ... [more ▼]

The molecular structure of (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionic acid (KAD-1229), a hypoglycemic drug of the meglitinide family, was studied by nuclear magnetic resonance (NMR) and molecular modeling. The results of the NMR experiments indicated that KAD-1229 existed in solution in the form of two stable conformers of equal population, called KADI and KADII in this paper. Three different molecular modelings were then applied: the classical molecular dynamics using the commercial Biosym and Hyperchem softwares and the Prot+ program, which is not based on a dynamical study but on a systematic conformational analysis of the molecule, which includes a term that allows the estimation of the hydrophobic interaction. The modeling results showed the following points. First, in contrast with classical molecular dynamics, which uses restraints from two-dimensional nuclear Overhauser effect (NOE) data, the Prot+ KAD structure provides conformations that support experimental NMR data without any external intervention. In the structures in agreement with NMR data, an important hydrophobic interaction between the phenyl cycle and the perhydroisoindole ring of KAD is observed. This interaction, which seems to play a role in the biological activity of the drug, is lost when no restraints are considered in classical molecular dynamics. Second, the difference between KADI and KADII arises mainly from slight distance geometric differences at the level of the perhydroisoindole and the phenyl rings. [less ▲]

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See detailImportance of the microbenthic loop of Posidonia oceanica meadows to detect anthropogenic perturbations early: first results
Pete, Dorothée ULg; Velimirov, Branko; Bouquegneau, Jean-Marie ULg et al

Conference (2008, August)

It was demonstrated that Posidonia oceanica, the marine magnoliophyte endemic to the Mediterranean Sea, is a valuable tool to assess environmental qualities of the coastal zones. However, only few studies ... [more ▼]

It was demonstrated that Posidonia oceanica, the marine magnoliophyte endemic to the Mediterranean Sea, is a valuable tool to assess environmental qualities of the coastal zones. However, only few studies have attempted to use characteristics of its sediment compartment as an indicator of the environment state of health. Yet, organisms living in this compartment have a turnover which is faster than for canopy-organisms which makes them useful as valid early descriptors of pollution. The study described here takes place in a project which aims to find an early holistic indicator of anthropogenic perturbations in the Mediterranean coastal zones. The investigation is based on the microbenthic loop (organic matter, bacteria, microphytobenthos and meiofauna) and was led in two different sites of Calvi Bay (Corsica, France), at 10 m depth, in March and June 2007. Only results about bacteria (abundance, biomass, morphotypes), microphytobenthos (biomass) and organic matter (biomass) will be presented. For both seasons, significant differences between sites are found, irrespective on whether variables are treated separately or together, thus indicating that the microbenthic loop has potential to be a good early indicator of pollution. [less ▲]

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See detailThe Importance of the Negative Charge of Beta-Lactam Compounds in the Interactions with Active-Site Serine Dd-Peptidases and Beta-Lactamases
Varetto, Louis ULg; De Meester, Fabien; Monnaie, Didier et al

in Biochemical Journal (1991), 278(Pt 3), 801-807

The interaction between various penicillins and cephalosporins the carboxylate group of which at C-3 or C-4 had been esterified or amidated and different penicillin-recognizing enzymes was studied. In ... [more ▼]

The interaction between various penicillins and cephalosporins the carboxylate group of which at C-3 or C-4 had been esterified or amidated and different penicillin-recognizing enzymes was studied. In general, our findings reinforced the common assumption that an anionic group at that position is necessary for the effective acylation of these enzymes. However, the relative activities of the modified beta-lactams as inactivators of the Streptomyces R61 DD-peptidase or as substrates of the Bacillus licheniformis, Streptomyces albus G and Enterobacter cloacae beta-lactamases did not fit a general scheme in which the intrinsic electronic and geometric properties of the beta-lactam compounds would be sufficient to explain their substrate or inactivator properties towards the various types of enzymes investigated. [less ▲]

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See detailThe importance of the negative charge of β-lactam compounds for the inactivation of the active-site serine DD-peptidase of Streptomyces R61
Varetto, Louis ULg; Frère, Jean-Marie ULg; Ghuysen, Jean-Marie ULg

in FEBS Letters (1987), 225(1-2), 218-222

The interaction between the Streptomyces R61 penicillin-sensitive DD-peptidase and deacetyl-cephalosporin C or its lactone derivative has been studied at different pH values. The results show the ... [more ▼]

The interaction between the Streptomyces R61 penicillin-sensitive DD-peptidase and deacetyl-cephalosporin C or its lactone derivative has been studied at different pH values. The results show the importance of an enzyme group of pK approximately equal to 9 which might form an ion pair with the free carboxylate of the former compound. This electrostatic interaction is shown to contribute to the formation of the first, non-covalent enzyme-inactivator complex by a factor of at least 50. [less ▲]

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See detailImportance of the PIKKs in NF-kappaB activation by genotoxic stress
Sabatel, Hélène ULg; Pirlot, Céline ULg; Piette, Jacques ULg et al

in Biochemical Pharmacology (2011), 82(10), 1371-83

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See detailImportance of the Two Tryptophan Residues in the Streptomyces R61 Exocellular Dd-Peptidase
Bourguignon-Bellefroid, Catherine; Wilkin, Jean-Marc; Joris, Bernard ULg et al

in Biochemical Journal (1992), 282(Pt 2), 361-367

Modification of the Streptomyces R61 DD-peptidase by N-bromosuccinimide resulted in a rapid loss of enzyme activity. In consequence, the role of the enzyme's two tryptophan residues was investigated by ... [more ▼]

Modification of the Streptomyces R61 DD-peptidase by N-bromosuccinimide resulted in a rapid loss of enzyme activity. In consequence, the role of the enzyme's two tryptophan residues was investigated by site-directed mutagenesis. Trp271 was replaced by Leu. The modification yielded a stable enzyme whose structural and catalytic properties were similar to those of the wild-type protein. Thus the Trp271 residue, though almost invariant among the beta-lactamases of classes A and C and the low-Mr penicillin-binding proteins, did not appear to be essential for enzyme activity. Mutations of the Trp233 into Leu and Ser strongly decreased the enzymic activity, the affinity for beta-lactams and the protein stability. Surprisingly, the benzylpenicilloyl-(W233L)enzyme deacylated at least 300-fold more quickly than the corresponding acyl-enzyme formed with the wild-type protein and gave rise to benzylpenicilloate instead of phenylacetylglycine. This mutant DD-peptidase thus behaved as a weak beta-lactamase. [less ▲]

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