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See detailGene knock down via antisense oligonucleotides to the steroid receptor coactivator SRC-1 modulates testosterone-dependent male sexual behavior and neural gene expression
Charlier, Thierry ULg; Ball, Gregory F; Balthazart, Jacques ULg

in Hormones & Behavior (2004), 46

Studies of eukaryotic genome expression demonstrate the importance of steroid receptor coactivators in mediating efficient gene transcription. Little is know about the physiological role of these ... [more ▼]

Studies of eukaryotic genome expression demonstrate the importance of steroid receptor coactivators in mediating efficient gene transcription. Little is know about the physiological role of these coactivators in vivo. We recently showed that the Steroid Receptor Coactivator SRC-1 is densely expressed in steroid-sensitive brain areas in birds and its expression is steroid-dependent and sexually differentiated. We tested the role of SRC-1 in the activation by testosterone of male sexual behavior in quail. Daily injections of LNA antisense oligonucleotides in the third ventricle (AS group) significantly reduced the expression of male copulatory behavior in response to exogenous testosterone compared to control animals (Ctrl group) receiving the vehicle alone or scrambled LNA. Sexual behavior was restored and even enhanced within 48 hours after interruption of LNA injection (ASSC group). Western blot analysis confirmed the decrease of SRC-1 expression in AS animals and suggested an over-expression of the coactivator in ASSC animals. The effect of SRC-1 knock down on behavior was correlated with a reduced volume of the medial preoptic nucleus (POM) defined by Nissl-staining and aromatase immunohistochemistry. In addition, the amount of aromatase-immunoreactive material in POM, defined as the relative optical density of the aromatase immunoreactivity multiplied by the percentage of surface covered within the nucleus and by the total POM volume of the POM, was decreased in the AS compared to the Ctrl group, suggesting a blockade of aromatase transcription. Together, these data indicate that SRC-1 functions as a critical regulatory molecule in the brain that modulates steroid-dependent gene transcription and behavior. [less ▲]

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See detailGene regulation in Arabidopsis halleri, a model system to understand zinc homeostasis in plants.
Hanikenne, Marc ULg; Talke, Ina N.; Lanz, Christa et al

Conference (2006, December 18)

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See detailGene regulatory network inference from systems genetics data using tree-based methods
Huynh-Thu, Vân Anh ULg; Wehenkel, Louis ULg; Geurts, Pierre ULg

in de la Fuente, Alberto (Ed.) Gene Network Inference - Verification of Methods for Systems Genetics Data (2013)

One of the pressing open problems of computational systems biology is the elucidation of the topology of gene regulatory networks (GRNs). In an attempt to solve this problem, the idea of systems genetics ... [more ▼]

One of the pressing open problems of computational systems biology is the elucidation of the topology of gene regulatory networks (GRNs). In an attempt to solve this problem, the idea of systems genetics is to exploit the natural variations that exist between the DNA sequences of related individuals and that can represent the randomized and multifactorial perturbations necessary to recover GRNs. In this chapter, we present new methods, called GENIE3-SG-joint and GENIE3- SG-sep, for the inference of GRNs from systems genetics data. Experiments on the artificial data of the StatSeq benchmark and of the DREAM5 Systems Genetics challenge show that exploiting jointly expression and genetic data is very helpful for recovering GRNs, and one of our methods outperforms by a large extent the official best performing method of the DREAM5 challenge. [less ▲]

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See detailGene Regulatory Network Inference via Conditional Inference Trees and Forests
Bessonov, Kyrylo ULg

Poster (2014, August 28)

Trees are classical data structures allowing effectively classifying and predicting responses. Due to versatility and high performance in classification and prediction, there exist plenty of tree-based ... [more ▼]

Trees are classical data structures allowing effectively classifying and predicting responses. Due to versatility and high performance in classification and prediction, there exist plenty of tree-based methods including popular Conditional Inference Tree (CIT) and Forests (CIF), Random Forests (RF), Randomized Trees (RT), randomized C4.5, etc. In this work we assessed the performance of CIT and CIF methods in correct gene regulatory network (GRN) prediction from expression data by using reference golden standard built from real transcriptional regulatory network of E. coli. The synthetic microarray expression data was obtained from DREAM4 challenge. The performance of each network inference method was assessed via Area Under Receiver Operating Characteristic (AUROC) and Area Under Precision Recall (AUPR) metrics. Our preliminary results show that CIT and CIF successfully predict directed GRNs at acceptable performance rates although not optimal (the best AUROC at 0.68 and AUPR at 0.13 for CIF and the best AUROC at 0.58 and AUPR at 0.18 for CIT). Surprisingly by using the current aggregation scheme of feature importance that prefers features with the highest number of observations, a single CIT was a better performer compared to CIFs in all 5 networks. Nevertheless, the CIFs showed an overall 10% improvement in AUROC. A single CIT has 24% and CIFs have 27% lower overall performance compared to the best performer of DREAM4 Challenge based on cumulative areas of PR and ROC curves. We plan to test other feature importance aggregation techniques in a single tree and in tree ensembles in order to outperform the top DREAM4 algorithms. In addition the effects of expression data standardization to unit variance will be presented. In future, the developed CIF framework will be used to perform data integration analysis of multi-omics datasets. [less ▲]

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See detailA gene regulatory network model evaluating the impact of individual factors in the hypertrophic switch
Kerkhofs, Johan ULg; Van Oosterwyck, Hans; Geris, Liesbet ULg

Conference (2013, September 11)

Chondrocytes undergoing hypertrophy show a major switch in phenotype underlied by a change in expression from the chondrocyte master gene, Sox9, to the osteoblastic one, Runx2. Strategies to stimulate or ... [more ▼]

Chondrocytes undergoing hypertrophy show a major switch in phenotype underlied by a change in expression from the chondrocyte master gene, Sox9, to the osteoblastic one, Runx2. Strategies to stimulate or inhibit this switch are of use in bone and cartilage tissue engineering respectively, as well as in the prevention of ectopic hypertrophy in osteoarthritis. We have constructed a literature based network comprised of 46 nodes and 161 interactions shown to play a part in chondrocyte hypertrophy. Network dynamics are simulated in discrete time through random updating by the use of additive functions to determine each node’s value. Furthermore, each species is represented by a fast variable (activity level, as determined by post translation modifications) which is assumed to be in equilibrium with a slow variable (mRNA) at all times. Through a Monte Carlo approach the importance of each node in the stability of chondrocytic phenotypes (proliferating, hypertrophic) is assessed in random initial conditions. A perturbation analysis of the stable states is used to determine the transition likelihood between states and the influence of individual nodes in this transition as a second measure of stability. Our results show that the hypertrophic state, marked by Runx2 expression, has a larger attractor basin and is more stable to perturbation than the proliferative state characterized by Sox9. The added time resolution seems to favour the Runx2 phenotype. The results for single nodes in overexpression or knockout simulations show a certain asymmetry, indicating that factors that are necessary for maintaining a certain phenotype are not necessarily useful in inducing it. [less ▲]

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See detailA Gene Regulatory Network Model to Assess the Stability of the Cartilage Phenotype
Kerkhofs, Johan ULg; Van Oosterwyck, Hans; Geris, Liesbet ULg

Poster (2013, August 29)

Introduction Chondrocyte hypertrophy entails the switching of a genetic program driven by Sox9 to one under control of the osteoblast master regulator Runx2. The switch is a prerequisite step in the bone ... [more ▼]

Introduction Chondrocyte hypertrophy entails the switching of a genetic program driven by Sox9 to one under control of the osteoblast master regulator Runx2. The switch is a prerequisite step in the bone forming process (endochondral ossification) during development and in postnatal fracture repair of larger bone defects. However, this switch can also be detrimental in tissue engineered cartilage constructs and in osteoarthritis development [Saito, 2010]. Therefore, a detailed model of the pathways that can facilitate, or inhibit, this phenotypic switch will lead to a more profound understanding of these processes and provide hints as to how to manipulate them. Methods The model formalism accommodates the qualitative information that is typically available in developmental studies. The literature based network comprises 46 nodes and 161 interactions, shown to be important in endochondral ossification. To simulate network dynamics in discrete time the normalized value of each gene is determined by additive functions where all interactions are assumed to be equally powerful. Furthermore, each species is represented by a fast variable (activity level, as determined by post translation modifications) which is assumed to be in equilibrium with a slow variable (mRNA) at all times. Through a Monte Carlo approach the importance of each node in the stability of chondrocytic phenotypes (proliferating, hypertrophic) is assessed in random initial conditions. A perturbation analysis of the stable states is used to determine the transition likelihood between them as a second measure of stability. Results Both measures of stability indicate that the hypertrophic (Runx2 driven) state is more stable than the proliferating one driven by Sox9. The results for the second measure are given in Fig.1. This higher stability seems to be partly conferred by faster reactions that favour the hypertrophic phenotype. In addition, the results point out that some transcription factors are necessary for the induction of a certain phenotype, whereas other transcription factors are required to maintain the phenotype, but are not necessary capable of inducing it. Discussion These results may relate to the difficulty experienced by researchers in maintaining a stable cartilage phenotype in culture and the occurrence of ectopic hypertrophy in osteoarthritis. By analysing the effect of changes to individual nodes, strategies to stabilise the proliferating phenotype can be developed. Overall, the model allows the importance of several important factors in the fate decision of mesenchymal cells to be quantitatively assessed based mainly on topological information. [less ▲]

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See detailGene structure and promoter function of a teleost ribosomal protein: a tilapia (Oreochromis mossambicus) L18 gene
Molina, Alfredo; Iyengar, Arati; Marins, Luis F. et al

in Biochimica et Biophysica Acta (2001), 1520(3), 195-202

We have cloned and characterized a tilapia (Oreochromis mossambicus) L18 ribosomal protein gene, including the complete transcribed region and 488 bp of upstream regulatory sequences. We have also ... [more ▼]

We have cloned and characterized a tilapia (Oreochromis mossambicus) L18 ribosomal protein gene, including the complete transcribed region and 488 bp of upstream regulatory sequences. We have also isolated two L18 cDNAs from another tilapia (Oreochromis niloticus) with a few conservative nucleotide differences. Our results suggest the presence of two genes in both species. Reporter constructs were tested for transient expression in CV1 cells and in microinjected zebrafish and tilapia embryos. The tilapia L18 promoter was able to drive expression of the reporter gene in all three experiments, with no apparent preference for a particular tissue. The tilapia L18 promoter is therefore likely to be a powerful tool to drive tissue-independent gene expression in fish. [less ▲]

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See detailGene transcript quantitation by real-time RT-PCR in cells selected by immunohistochemistry-laser capture microdissection.
Lindeman, Neal; Waltregny, David ULg; Signoretti, Sabina et al

in Diagnostic Molecular Pathology : The American Journal of Surgical Pathology, Part B (2002), 11(4), 187-92

Studying tissue-based gene expression in different cell populations often requires immunohistochemistry-guided microdissection. However, mRNA degradation occurs during long staining procedures. We ... [more ▼]

Studying tissue-based gene expression in different cell populations often requires immunohistochemistry-guided microdissection. However, mRNA degradation occurs during long staining procedures. We combined a novel rapid immunoperoxidase technique with laser capture microdissection (LCM) and real-time quantitative RT-PCR to compare p27 mRNA expression in prostatic basal/secretory cells. Eight frozen prostate sections were immunostained with antibody 34betaE12 (high-molecular-weight keratin). Secretory and basal cells were separately collected by LCM. p27 transcripts from each cell group were quantitated by real-time RT-PCR, with GAPDH as standard. Immunostaining took 22 minutes, with RNA extraction from approximately 40 dissected cells from each compartment initiated within 40 minutes. Qualitative RT-PCR gave a product of the expected size from each sample. Quantitative RT-PCR gave basal/secretory p27/GAPDH ratios of 0.99-16.24 (mean 5.53 +/- 0.643). Immunostaining for keratin 34betaE12 can be done on frozen sections in approximately 20 minutes, and mRNA from pure cell populations can be quantitated by RT-PCR. We used this technique to show that p27 transcript levels are greater in basal than in secretory prostate cells, suggesting, when combined with prior studies, that regulation of p27 occurs at the protein level in normal cells. This technique may have wide applicability to studies of gene expression in distinct cell populations in heterogeneous tissues. [less ▲]

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See detailGene transfer in inner ear cells: a challenging race
Sacheli, Rosalie ULg; Delacroix, Laurence ULg; Van Den Ackerveken, Priscilla ULg et al

in Gene Therapy (2013), 20

Recent advances in human genomics led to the identification of numerous defective genes causing deafness, which represent novel putative therapeutic targets. Future gene-based treatment of deafness ... [more ▼]

Recent advances in human genomics led to the identification of numerous defective genes causing deafness, which represent novel putative therapeutic targets. Future gene-based treatment of deafness resulting from genetic or acquired sensorineural hearing loss may include strategies ranging from gene therapy to antisense delivery. For successful development of gene therapies, a minimal requirement involves the engineering of appropriate gene carrier systems. Transfer of exogenous genetic material into the mammalian inner ear using viral or non-viral vectors has been characterized over the last decade. The nature of inner ear cells targeted, as well as the transgene expression level and duration, are highly dependent on the vector type, the route of administration and the strength of the promoter driving expression. This review summarizes and discusses recent advances in inner ear gene-transfer technologies aimed at examining gene function or identifying new treatment for inner ear disorders. [less ▲]

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See detailGene-based replication strategy and meta-analysis in the context of epistasis: application for Alzheimer’s disease.
Gusareva, Elena ULg; van der Lee, Sven; Katsumata, Yuriko et al

Speech/Talk (2015)

Although the discovery of biological epistasis via statistical methods remains a big challenge, large-scale epistasis studies have become more and more popular nowadays. Considering the power of genome ... [more ▼]

Although the discovery of biological epistasis via statistical methods remains a big challenge, large-scale epistasis studies have become more and more popular nowadays. Considering the power of genome-wide association interaction analysis (GWAI) is conceptually lower when comparing to GWA using the same data, the genome-wide screenings for epistasis often ends with no statistically significant findings. Therefore, sound meta-analytic methodologies for combining evidence across independent gene-gene interaction studies, taking into account characteristics of individual studies, as well as protocols for good standard practice of meta-GWAI analysis are missing so far. The existing methodologies, whereas is suboptimal, may still be the first choice in meta-GWAI. In our study, the genome-wide significant interaction between two var¬¬iants of WWC1 and TLN2 genes were first discovered in males of EADI1 of Alzheimer’s disease (AD) case/control cohort. Adopting the gene-based replication approach recently advocated by Gusareva and Van Steen (Hum Genet 2014), we assessed association between all available variants from the pair of genes to test for pair-wise interactions in three independent AD replication cohorts (GERAD1, AD cohort from Rotterdam study - RS, and ADGC). Particularly, we used regression modeling with co-dominant coding of genetic markers (the one that was found to be the most powerful to identify epistasis and gives the least false positive results) and taking into account possible confounding factors (age and the first four PCs). We further meta-analyzed p-values for the interaction effects across all pairs of markers in males and females using Fisher summary test statistic. For the most interesting epistasis signal that occur in males of EADI1 cohort and two replication cohorts (RS and ADGC), we also conducted multi-locus genotype (MLG) association analysis (quantifies effects sizes of each of eight multilocus genotypes derived from the SNPs-pair versus the reference category - homozygous for the major alleles) and then met-analyzed results using the random effect or fixed effect models depending on presence of heterogeneity between studies. Adopting this approach we statistically replicated the interaction between WWC1 and TLN2 genes. Although, the biological validation of this finding is still ahead, we can already demonstrate effectiveness of the adopted meta-analysis pipeline to identify novel genetic factors potentially predisposing to AD. [less ▲]

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See detailGene-based replication strategy and meta-analysis in the context of epistasis: application for Alzheimer’s disease.
Gusareva, Elena ULg; van der Lee, Sven; Katsumata, Yuriko et al

Poster (2015, May 22)

Although the discovery of biological epistasis via statistical methods remains a big challenge, large-scale epistasis studies have become more and more popular nowadays. Considering the power of genome ... [more ▼]

Although the discovery of biological epistasis via statistical methods remains a big challenge, large-scale epistasis studies have become more and more popular nowadays. Considering the power of genome-wide association interaction analysis (GWAI) is conceptually lower when comparing to GWA using the same data, the genome-wide screenings for epistasis often ends with no statistically significant findings. Therefore, sound meta-analytic methodologies for combining evidence across independent gene-gene interaction studies, taking into account characteristics of individual studies, as well as protocols for good standard practice of meta-GWAI analysis are missing so far. The existing methodologies, whereas is suboptimal, may still be the first choice in meta-GWAI. In our study, the genome-wide significant interaction between two var¬¬iants of WWC1 and TLN2 genes were first discovered in males of EADI1 of Alzheimer’s disease (AD) case/control cohort. Adopting the gene-based replication approach recently advocated by Gusareva and Van Steen (Hum Genet 2014), we assessed association between all available variants from the pair of genes to test for pair-wise interactions in three independent AD replication cohorts (GERAD1, AD cohort from Rotterdam study - RS, and ADGC). Particularly, we used regression modeling with co-dominant coding of genetic markers (the one that was found to be the most powerful to identify epistasis and gives the least false positive results) and taking into account possible confounding factors (age and the first four PCs). We further meta-analyzed p-values for the interaction effects across all pairs of markers in males and females using Fisher summary test statistic. For the most interesting epistasis signal that occur in males of EADI1 cohort and two replication cohorts (RS and ADGC), we also conducted multi-locus genotype (MLG) association analysis (quantifies effects sizes of each of eight multilocus genotypes derived from the SNPs-pair versus the reference category - homozygous for the major alleles) and then met-analyzed results using the random effect or fixed effect models depending on presence of heterogeneity between studies. Adopting this approach we statistically replicated the interaction between WWC1 and TLN2 genes. Although, the biological validation of this finding is still ahead, we can already demonstrate effectiveness of the adopted meta-analysis pipeline to identify novel genetic factors potentially predisposing to AD. [less ▲]

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See detailGénéalogie de la figure : Médiation esthétique et destination
Servais, Christine ULg

Doctoral thesis (2000)

Detailed reference viewed: 38 (7 ULg)
See detailGénéalogie de la figure : Médiation esthétique et destination
Servais, Christine ULg

Book published by Presses universitaires du Septentrion (2001)

Detailed reference viewed: 37 (11 ULg)
See detailGénéalogie de la peinture de paysage au XVIe siècle
Allart, Dominique ULg

in Toussaint, Jacques (Ed.) Autour de Henri Bles (2002)

Detailed reference viewed: 57 (10 ULg)
See detailLa généalogie de Tydée et de Diomède
Renaud, Jean-Michel ULg

in Auger, Danièle; Saïd, Suzanne (Eds.) Généalogies mythiques. Actes du VIIIe Colloque international du Centre de Recherches Mythologiques de l'Université de Paris-X (Chantilly, 14-16 septembre 1995) (1998, April)

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See detailGénéalogie éditoriale et génétique textuelle. Les premières éditions du Déserteur de Sébastien Mercier (1770-1772)
Droixhe, Daniel ULg

in Le livre et l'Estampe (2012), 58(178), 7-64

We establish the "stammbaum" organization of textual variations in editions whose printers are identified by their typographical material: Jay and Veuve Duchesne in Paris, Castaud in Lyon, Chambon in ... [more ▼]

We establish the "stammbaum" organization of textual variations in editions whose printers are identified by their typographical material: Jay and Veuve Duchesne in Paris, Castaud in Lyon, Chambon in Paris, Fantet in Besançon. We propose that some variations are due to the author, S. Mercier, himself and that Jay's edition of 1772, as well as an un-dated Brunet edition, announces the definitive 1786 edition. [less ▲]

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See detailDe genegeerde kunst
Meesters, Gert ULg

Article for general public (2007)

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See detailA general and effective approach for the optimal design of fibers reinforced composite structures
Bruyneel, Michaël ULg

in Composites Science & Technology (2006), 66

Detailed reference viewed: 18 (0 ULg)