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See detailGene expression of the lipoxygenase pathway in a tomato species tolerant to salt stress
Ghars, Mohamed Ali ULg; Muhovski, Y.; Ghanem, M. et al

Poster (2010)

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See detailGene expression pattern of synovial cells from inflammatory and normal areas of osteoarthritis synovial membrane.
Lambert, Cécile ULg; Dubuc, Jean-Emile; Montell, Eulalia et al

in Arthritis and Rheumatism (2014), sous presse

Objective: The aim of this study was to compare the gene expression pattern of synovial cells from inflammatory (I) or normal/reactive (N/R) areas of a synovial membrane harvested from the same ... [more ▼]

Objective: The aim of this study was to compare the gene expression pattern of synovial cells from inflammatory (I) or normal/reactive (N/R) areas of a synovial membrane harvested from the same osteoarthritis (OA) patient. Methods: Synovial tissues were obtained from 12 knee OA patients at the time of total knee replacement. The inflammatory status of the synovial membrane was characterized according to macroscopic criteria and sorted as N/R and I. Biopsies were cultured separately for 7 days. Microarray gene expression profiling between N/R and I areas was performed. Western blot and immunohistochemistry confirmed the identified genes that were differentially expressed. Results: 896 differentially expressed genes between N/R and I zones were identified. The key pathways were related to inflammation, cartilage metabolism, Wnt signaling and angiogenesis. In the inflammatory network, TREM1 and S100A9 were strongly up-regulated. MMP-3 and -9, cathepsin H and S were significantly up-regulated in the cartilage catabolism pathway, whereas the most up-regulated anabolism enzyme was HAS1. Wnt-5A and LRP5 were up-regulated whereas FZD2 and DKK3 were down-regulated in the Wnt signaling. Finally, STC1, a protein involved in angiogenesis was identified as the most up-regulated gene in I zones compared to N/R zones. Conclusion: This study is the first to identify different expression pattern between two areas of the synovial membrane in the same patient. These differences concern several key pathways involved in OA pathogenesis. This analysis also provides information regarding new genes and proteins as potential targets for the future therapeutic. (c) 2013 American College of Rheumatology. [less ▲]

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See detailGene expression profile of human lymphocytes exposed to (211)At alpha particles
Turtoi, Andrei ULg; Brown, Ian; Schläger, Martin et al

in Radiation Research (2010), 174

In this study, the Whole Human Genome 44K DNA microarray assay was used for the first time to obtain gene expression profiles in human peripheral blood lymphocytes 2 h after exposure (in suspension) to 6 ... [more ▼]

In this study, the Whole Human Genome 44K DNA microarray assay was used for the first time to obtain gene expression profiles in human peripheral blood lymphocytes 2 h after exposure (in suspension) to 6.78 MeV mean energy alpha particles from extracellular (211)At. Lymphocytes were exposed to fluences of 0.3-9.6 x 10(6) alpha particles/cm(2) [corresponding to mean absorbed alpha-particle doses (D(alpha)) of 0.05-1.60 Gy] over 30 min. Significantly modulated expression was identified in 338 early-response genes. Up-regulated expression was evident in 183 early-response genes, while the remaining 155 were down-regulated. Over half of the up-regulated genes and 40% of the down-regulated genes had a known biological process related primarily to cell growth and maintenance and cell communication. Genes associated with cell death were found only in the up-regulated genes and those with development only in the down-regulated genes. Eight selected early-response genes that displayed a sustained up- or down-regulation (CD36, HSPA2, MS4A6A, NFIL3, IL1F9, IRX5, RASL11B and SULT1B1) were further validated in alpha-particle-irradiated lymphocytes of two human individuals using the TaqMan(R) RT-qPCR technique. The results confirmed the observed microarray gene expression patterns. The expression modulation profiles of IL1F9, IRX5, RASL11B and SULT1B1 genes demonstrated similar trends in the two individuals studied. However, no significant linear correlation between increasing relative gene expression and the alpha-particle dose was evident. The results suggest the possibility that a panel of genes that react to alpha-particle radiation does exist and that they merit further study in a greater number of individuals to determine their possible value regarding alpha-particle biodosimetry. [less ▲]

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See detailThe gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (T-FH) cells
de Leval, Laurence ULg; Rickman, David; Thielen, Caroline ULg et al

in Blood (2007), 109(11), 4952-4963

The molecular alterations underlying the pathogenesis of angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unspecified (PTCL-u) are largely unknown. In order to characterize the ... [more ▼]

The molecular alterations underlying the pathogenesis of angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unspecified (PTCL-u) are largely unknown. In order to characterize the ontogeny and molecular differences between both entities, a series of AITLs (n = 18) and PTCLs-u (n = 16) was analyzed using gene expression profiling. Unsupervised clustering correlated with the pathological classification and with CD30 expression in PTCL-u. The molecular profile of AITLs was characterized by a strong microenvironment imprint (overexpression of B-cell- and follicular dendritic cell-related genes, chemokines, and genes related to extracellular matrix and vascular biology), and overexpression of several genes characteristic of normal follicular helper T (T-FH) cells (CXCL13, BCL6, PDCD1, CD40L, NFATC1). By gene set enrichment analysis, the AITL molecular signature was significantly enriched in published T-FH-specific genes. The enrichment was higher for sorted AITL cells than for tissue samples. Overexpression of several T-FH genes was validated by immunohistochemistry in AITLs. A few cases with molecular T-FH-like features were identified among CD30(-) PTCLs-u. Our findings strongly support that TFH cells represent the normal counterpart of AITL, and suggest that the AITL spectrum may be wider than suspected, as a subset of CD30(-) PTCLs-u may derive from or be related to AITL. [less ▲]

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See detailGene expression profiles in canine idiopathic pulmonary fibrosis
Krafft, Emilie ULg; Heikkilä, H.P.; Peters, I. et al

in Proceedings of 17th International consortium on lung and airways fibrosis (2012, October 01)

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See detailGene expression profiles in canine idiopathic pulmonary fibrosis
Krafft, Emilie ULg; Heikkilä, HP; Vanherberghen, Morgane ULg et al

in Proceedings of the 29th ACVIM Forum (2011, June)

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See detailGene expression profiling from leukocytes of horses affected by osteochondrosis.
Serteyn, Didier ULg; Piquemal, D.; Vander Heyden, Laurent ULg et al

in Journal of Orthopaedic Research (2010)

Osteochondrosis (OC) is a developmental disease that affects growing horses and that severely affects their ability to perform. The genetic basis of its pathogenesis is poorly understood. The aim of the ... [more ▼]

Osteochondrosis (OC) is a developmental disease that affects growing horses and that severely affects their ability to perform. The genetic basis of its pathogenesis is poorly understood. The aim of the study was to analyze the transcript profile of leukocytes from horses affected with OC. Two transcriptome libraries were constructed from leukocytes of OC-affected and non-OC-affected horses using digital gene expression analysis (DGE) and real-time PCR. Statistical analysis allowed selection of 1,008 tags upregulated in the non-OC-affected group and 1,545 tags upregulated in the OC-affected group. Among these genes, 16 regulated genes and 5 housekeeping genes were selected. Metabolic pathways analysis showed an obvious dysregulation of several signaling pathways related to cartilage formation or cartilage repair, including Wnt, Indian hedgehog, and TGF-beta signaling. Other genes, including ISG, ApoB, MGAT4, and TBC1D9, showed a significantly different expression between groups. These genes may play a role in high carbohydrate diet, abnormal insulin metabolism, or inflammation, mechanisms suspected to be involved in OC. This DGE analysis of the transcript profile of leukocytes from OC-affected horses demonstrated significant differences in comparison to the control library. These results open new perspectives for the understanding of equine OC. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. [less ▲]

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See detailGene expression profiling of hypothalamic hamartomas: a search for genes associated with central precocious puberty
Parent, Anne-Simone ULg; Matagne, Valérie; Westphal, Manfred et al

in Hormone Research (2008), 69

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See detailGene expression profiling to predict the response of infliximab in patients with UC
Arijs, Ingrid; Van lommel, Leertje; Van Steen, Kristel ULg et al

in Gastroenterology (2007), 132(4), 174-174

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See detailGene expression profiling to predict the response of infliximab in patients with UC
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Journal of Crohn’s and Colitis [=JCC] (2007), 1(1), 34

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See detailGene flow among wild Phaseolus lunatus L. populations in the Central Valley of Costa Rica
Ouedraogo, M.; Maquet, A.; Baudoin, Jean-Pierre ULg

in Annual Report Bean Improvement Cooperative (2003), 46

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See detailThe gene INPPL1, encoding the lipid phosphatase SHIP2, is a candidate for type 2 diabetes in rat and man
Marion, Evelyne; Kaisaki, Pamela Jane; Pouillon, Valérie et al

in Diabetes (2002), 51

Genetic susceptibility to type 2 diabetes involves many genes, most of which are still unknown. The lipid phosphatase SHIP2 is a potent negative regulator of insulin signaling and sensitivity in vivo and ... [more ▼]

Genetic susceptibility to type 2 diabetes involves many genes, most of which are still unknown. The lipid phosphatase SHIP2 is a potent negative regulator of insulin signaling and sensitivity in vivo and is thus a good candidate gene. Here we report the presence of SHIP2 gene mutations associated with type 2 diabetes in rats and humans. The R1142C mutation specifically identified in Goto-Kakizaki (GK) and spontaneously hypertensive rat strains disrupts a potential class II ligand for Src homology (SH)-3 domain and slightly impairs insulin signaling in cell culture. In humans, a deletion identified in the SHIP2 3' untranslated region (UTR) of type 2 diabetic subjects includes a motif implicated in the control of protein synthesis. In cell culture, the deletion results in reporter messenger RNA and protein overexpression. Finally, genotyping of a cohort of type 2 diabetic and control subjects showed a significant association between the deletion and type 2 diabetes. Altogether, our results show that mutations in the SHIP2 gene contribute to the genetic susceptibility to type 2 diabetes in rats and humans [less ▲]

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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 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

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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