Investigation of potential new targets for the diagnosis and/or the treatment of osteoarthritis

in Osteoarthritis and Cartilage (2013, April), 21(Supplement April 2013),

Purpose: Synovial inflammation plays a key role in the pathophysiology process of osteoarthritis (OA). We have previously compared the gene expression pattern of synovial cells isolated from inflammatory ... [more ▼]

Purpose: Synovial inflammation plays a key role in the pathophysiology process of osteoarthritis (OA). We have previously compared the gene expression pattern of synovial cells isolated from inflammatory (I) or normal/reactive (N/R) areas of a synovial membrane harvested from the same OA patient. We identified a large number of mediators belonging to key pathways involved in OA pathogenesis. The aim of this study was to validate different potential new targets for the diagnosis and/or the treatment OA. Methods: Synovial cells (SC) were isolated from synovial specimens obtained from OA patients undergoing knee replacement. The inflammatory status of the synovial membrane was characterized according to macroscopic criteria. The biopsies from N/R and I areas were cultured separately for a period of 7 days. Microarray gene expression profiling between N/R and I areas was performed. The biological relevance of up- and down-regulated genes was analyzed with Ingenuity Pathways Analysis. Western blot and immunohistochemistry confirmed the identified genes most differentially expressed in the key pathways. The production of the triggering receptor expressed on myeloid cells-1 (TREM1), the alarmin S100 calcium binding protein A9 (S100A9), the wingless-type MMTV integration site family, member 5A (Wnt-5A) and the stanniocalcin 1 (STC1) were evaluated by Western blot. S100A9, hyaluronan synthase-1 (HAS1) and STC1 expression and localization were investigated by immunohistochemistry. Results: 896 genes differentially expressed in N/R and I areas were identified. The key pathways were related to inflammation, cartilage metabolism, Wnt signaling and angiogenesis. In the inflammatory gene pattern, TREM1 and S100A9 were strongly upregulated. We validated the production of these proteins in OA synovial biopsies by Western blot. TREM1 and S100A9 were increased in I compared to N/R synovial cells culture. S100A9 was observed in the perivascular area and in sublining cells in I synovial biopsies, but not in N/R biopsies. An increased staining was also observed in the intima lining layer of I when compared to N/R biopsies. The most upregulated anabolism enzyme in I synovial biopsies was HAS1. Using immunohistochemistry, we observed in I areas an increase of the HAS1-positive cells mainly in the intima lining. We also studied the protein production of Wnt-5A, the most upregulated intermediate of Wnt signaling pathway. The protein level was increased in I compared to N/R areas. Finally, in the angiogenesis pathway, one the most u-regulated gene was STC1. A significant increase of STC1 production was observed in I areas compared to N/R areas by Western blot. This result was also supported by the immunohistochemical analysis. In I area, the staining for STC1 was more intense in perivascular and sublining cells. Conclusions: Synovial membrane inflammation is a key target for OA treatments. In this work, we have identified proteins involved in the synovitis pathways like angiogenesis, cells infiltration and matrix remodeling. These proteins could be targeted by drugs and used as companion biomarkers for evaluating their efficacy. Although qualitative, our results could also yield to the identification of markers of the disease. This investigation has to be further pursued. [less ▲]

Substrate Marking by an Invasive Ladybeetle: Seasonal Changes in Hydrocarbon Composition and Behavioral Responses

in PLoS ONE (2013), 8(4),

The multicolored Asian ladybeetle, Harmonia axyridis (Pallas), aggregates inside dwellings during the winter to survive the cold. Recent published reports have highlighted that overwintering individuals ... [more ▼]

The multicolored Asian ladybeetle, Harmonia axyridis (Pallas), aggregates inside dwellings during the winter to survive the cold. Recent published reports have highlighted that overwintering individuals use hydrocarbon markings deposited on surfaces by conspecifics to orient toward aggregation sites. In the current study, monthly GC-MS analyses revealed seasonal modifications in the chemical profile of substrate markings deposited by moving individuals. The markings of overwintering ladybeetles contained larger proportions of heptacosadiene, nonacosadiene, hentriacontadienes, and methyl-nonacosanes, along with a lower proportion of heptacosene and nonacosene. This finding suggests the importance of the unsaturated and/or branched hydrocarbons in the H. axyridis aggregation process. Subsequently, we conducted behavioral assays to test whether (1) there is seasonal variation in the behavioral response of H. axyridis individuals toward substrate markings deposited by conspecifics in the same physiological state and (2) the observed behavioral modification is due to a change in ladybeetle sensitivity and/or a change in the chemical composition of the substrate marking. The results indicate that overwintering individuals exhibit a stronger ‘‘following’’ response toward conspecific substrate markings. This behavior is linked to both the physiological state of ladybeetles and the specific chemical profile of the marking biomolecules deposited under overwintering conditions. [less ▲]

Trente ans de lutte contre le racisme en Belgique : bilan et perspectives

in Revue Nouvelle (2013), année 68(numéro 4),

Historia de la Acromegalia y del Gigantismo

Scientific conference (2013, April)

Numerical simulations of asperity crushing using boundary conditions encountered in cold-rolling

in Key Engineering Materials [=KEM] (2013), 554-557

Asperity flattening has a huge influence on friction and wear in metal forming processes. Nevertheless, phenomena that occur at the microscopic scale are still not well understood. Since no experiment can ... [more ▼]

Asperity flattening has a huge influence on friction and wear in metal forming processes. Nevertheless, phenomena that occur at the microscopic scale are still not well understood. Since no experiment can be easily performed in real forming conditions, numerical models are essential to achieve a better knowledge of what happens in these contact regions. In this paper, two finite elements models are presented. The first one represents the flattening of a serrated asperity field in plane-strain conditions. The results are compared to the experiments published by Sutcliffe [1]. The second one is a tri-dimensional asperity model flattened by a rigid plane. The boundary conditions applied to this model correspond to the ones encountered in a real cold-rolling case. The results are compared to the relative contact area computed by a strip rolling model using the analytical laws proposed by Wilson & Sheu [2] and Marsault [3]. [less ▲]

Amenability for processing of oolitic iron ore concentrate for phosphorus removal

in Minerals Engineering (2013), 46-47

Beneficiation routes aimed at dephosphorisation of oolitic gravity magnetic concentrate and involving a combination of roasting, re-grinding, magnetic separation and water and acid leaching are ... [more ▼]

Beneficiation routes aimed at dephosphorisation of oolitic gravity magnetic concentrate and involving a combination of roasting, re-grinding, magnetic separation and water and acid leaching are investigated. Roasting was carried out at 900ºC for one hour without or with lime or sodium hydroxide as roasting additives. When additives were used, cement phases of Si-Al-Na-Ca-O type were detected as well as the mineral giuseppettite. During the thermal process sodium silicate is liquefied and the newly formed phases coat the oolites and penetrate inside the cracks. Energy Dispersive Spectroscopy analysis has indicated that the zone surrounding the oolites consists of Na, Al and Si phases with part of phosphorus being captured there. As a result of the alkaline roasting, goethite is partly transformed to magnetite and this reduction is reinforced with an increase in sodium hydroxide dosage. Investigation of redistribution of phosphorous shows that it could be only partly separated if leaching is not accompanied by re-grinding and physical separation. The recommended dosage of the reductive agent for the final flowsheet is 8 % mass ratio to concentrate. Grinding to a mean size of 0.040 mm, with water and acid leaching and double magnetic separation creates conditions to obtain a high-quality iron concentrate with 65.97 % Fe and recovery of 92.43 %, with simultaneous decrease in the phosphorus content from 0.71 % to 0.05 %. [less ▲]

Chitosan-based biomaterials for tissue engineering

in European Polymer Journal (2013), 49(4), 780-792

Derived from chitin, chitosan is a unique biopolymer that exhibits outstanding properties, beside biocompatibility and biodegradability. Most of these peculiar properties arise from the presence of ... [more ▼]

Derived from chitin, chitosan is a unique biopolymer that exhibits outstanding properties, beside biocompatibility and biodegradability. Most of these peculiar properties arise from the presence of primary amines along the chitosan backbone. As a consequence, this polysaccharide is a relevant candidate in the field of biomaterials, especially for tissue engineering. The current article highlights the preparation and properties of innovative chitosan-based biomaterials, with respect to their future applications. The use of chitosan in 3D-scaffolds – as gels and sponges – and in 2D-scaffolds – as films and fibers – is discussed, with a special focus on wound healing application. [less ▲]

Modélisation régionale et locale sur base des données de la carte géologique

in Renard, José (Ed.) La carte hydrogéologique de Wallonie : un outil au service de tous - Synthèse des exposés (2013, April)

Identification et caractérisation des sous-unités ELP5 et ELP6 du complexe Elongator humain

Doctoral thesis (2013)

Familial Dysautonomia is a neurodegenerative disorder that affects the autonomic and sensory nervous systems. This disease results from loss-of-function mutations of the ELP1-encoding gene. ELP1 is ... [more ▼]

Familial Dysautonomia is a neurodegenerative disorder that affects the autonomic and sensory nervous systems. This disease results from loss-of-function mutations of the ELP1-encoding gene. ELP1 is required for the integrity of the so-called Elongator complex, which is composed of two sub-proteins complexes, namely the core-Elongator (ELP1 to ELP3) and HAP (ELP4 to ELP6). While ELP3 is acting as an acetyltransferase that target multiple substrates such as nuclear histones and cytoplasmic α-tubulin, the ELP4-6 has been recently described as an ATPase. This complex has been initially identified as a component of a hyperphosphorylated RNA polymerase II holoenzyme. As a result, Elongator is involved in transcriptional elongation. Since, other roles have been assigned. Elongator is indeed also required for some tRNA modifications in the cytoplasm and consequently controls translation fidelity. Those molecular functions underlie the capacity of Elongator to regulate cell division, DNA-damage response and cell motility. It is likely that a better understanding of the molecular functions of Elongator will clarify its role in these cellular processes and probably highlight new features. The identity of human ELP1 through ELP4 has been reported but human ELP5 and ELP6 have remained uncharacterized. We therefore initiated a study dedicated to the identification and characterization of both proteins. A biochemical purification of ELP4 was conducted to isolate all associated proteins. Such experimental approach led to the identification of DERP6 and C3ORF75 as human ELP5 and ELP6 subunits of the Elongator complex, respectively. We further investigated the cellular functions of both subunits by combining biochemical analysis and cellular assays. Our results show that DERP6/Elp5 is required for the integrity and the fucntion of Elongator and directly connects ELP3 to ELP4. Our laboratory has previously demonstrated the key role of Elongator in cell migration. As cell motility is required for cell invasion and metastasis, we therefore investigated to which extent Elongator is involved in those processes. The migration and tumorigenicity of melanoma-derived cells are significantly decreased upon Elongator invalidation through Elp1 or Elp3 depletion. Strikingly, DERP6/Elp5 and C3ORF75/Elp6-depleted melanoma cells have similar defects, further supporting the idea that DERP6/Elp5 and C3ORF75/Elp6 are essential for Elongator function. Together, our data identify DERP6/ELP5 and C3ORF75/ELP6 as key players for migration, invasion and tumorigenicity of melanoma cells, as integral subunits of Elongator. [less ▲]

Analytical evaluation of virgin olive oils produced from three varieties Koroneiki , Arbequina and Arbosana grown in east of Morocco

Poster (2013, April)