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See detailScience policy narratives in Flanders and Wallonia: The interplay of characters and ideas
Charlier, Nathan ULg

Scientific conference (2015, January 27)

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See detailGigantism and acromegaly due to Xq26 microduplications and GPR101 mutation
Beckers, Albert ULg

Scientific conference (2015, January 27)

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See detailEffects of α-synuclein levels on cerebral synaptic function: Validation of a novel PET radioligand for the early diagnosis of Parkinson’s disease
Tarragon Cros, Ernesto ULg; Ferrara, André ULg; Tirelli, Ezio ULg et al

Poster (2015, January 27)

Background In Parkinson’s disease, converging evidence supports a pathogenic role for excessive α–synuclein accumulation in synaptic terminals that may propagate back to the soma of vulnerable nerve cells ... [more ▼]

Background In Parkinson’s disease, converging evidence supports a pathogenic role for excessive α–synuclein accumulation in synaptic terminals that may propagate back to the soma of vulnerable nerve cells such as neurons in the substantia nigra pars compacta. The resulting loss of dopaminergic terminals in the striatum can be demonstrated in vivo using 18F-Dopa-PET (positron emission tomography). However, there’s currently no validated biomarker of the progressive synaptic dysfunction in other vulnerable areas such as the cerebral cortex. Goal In this longitudinal study, we will test the hypothesis that the loss of synaptic terminals in a mouse model of excessive α–synuclein accumulation can be demonstrated in vivo before the occurrence of behavioural disturbances using 18F-UCB-H, a new PET biomarker developed at CRC. We will also test if this new imaging modality is sensitive enough to study the effect of a disease modifying therapy such as chronic physical exercise. Methods We will use microPET for the in vivo quantification of 18F-UCB-H brain uptake in 16 wild type animals and 16 transgenic (Tg) mice overexpressing human α–syn under the mThy1 promotor every 2 months. Data will be validated against post-mortem analyses after the last PET study. Predictions We predict decreased tracer uptake over time in the basal ganglia and cerebral cortex in Tg mice as compared with WT animals. Also, we predict a relationship between 18F-UCB-H uptake levels in basal ganglia and cerebral cortex and progressive alterations in both motor and cognitive functions, respectively. Further, we also expect that chronic exercise will slow down both motor and cognitive disturbances, as well as the rate of 18F-UCB-H brain uptake decreases. Conclusion If 18F-UCB-H PET proves to be a valid biomarker for the early detection of α–synuclein accumulation in the pre-clinical model of PD, the methods will tested on human clinical populations. [less ▲]

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See detailShould I Stay or Should I Go ?
Ozer, Pierre ULg

Speech/Talk (2015)

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See detailDéveloppement de nouveaux marqueurs neuroradiologiques de la maladie de Parkinson par reconnaissance de motifs
Himri, Khadidja ULg; Depierreux, Frédérique ULg; GARRAUX, Gaëtan ULg

Poster (2015, January 27)

Background and objectives: Automatic classification of Parkinson’s disease (PD) versus healthy controls (HC) based on structural MRI has so far focused on unimodal approaches. However, this method is ... [more ▼]

Background and objectives: Automatic classification of Parkinson’s disease (PD) versus healthy controls (HC) based on structural MRI has so far focused on unimodal approaches. However, this method is subject to a poor temporal and spatial resolution leading to low classification accuracy. To overcome this limitation we propose to integrate different modalities by generating a single decision function based on a multi-kernel method, exploiting the complementary information it offers. We predict that the integration of multiple modalities produces greater classification enhancement. Materials and methods: 3Tesla MRI was acquired in 42 patients with PD and 42 age and gender matched healthy controls. We relied on Unified Parkinson’s Disease Rating Scale (UPDRS) for evaluating the clinical status. We used structural and quantitative maps of T1, T2*, proton density (PD), magnetization transfer (MT), Multi-parameter (MT magnetization transfer, proton density (A), Iron Deposit (R2 *), mixing water content, iron, and the fraction of macromolecules tissues (R1) at 1 × 1 × 1 mm3 resolution. We identified cortical and subcortical brain regions (cortex, putamen, globus pallidus, substantia nigra), and cortical grey matter. We applied existing classification algorithms in the field of neuroscience using a classification algorithm based on Support Vector Machines (SVMs) [1], executed using the Pattern Recognition for Neuroimaging Toolbox (PRoNTo) [2]. The processes of classification was the following, data were mean centered and leave one subject out cross-validation was performed, making the test set independent from the training set. Analyses were restricted to voxels where all subjects had non-zero values. Statistical significance of the classifications was tested using permutation testing (1000 permutations) with random assignment of group class to the input image. Subsequently, we combined different modalities (MT, A, R1, R2) and identified the combination giving the highest sensitivity and sensibility in PD classification. As classifier we used support vector machines that are inspired by statistical learning theory Vladimir Vapnik and Multiple Kernel Learning approach, introduced by Lanckriet [3],[4]. Our approach can be seen as an analogue of MKL with SVMs. Conclusion & Future work: Identification of brain areas with affected intensity in the Parkinson’s group compared to Healthy Controls in single modalities using pronto is helpful. However, the subsequent multi-kernel approach utilizes unimodal information in a combined fashion so that emergent information is obtained, transcending effectiveness unimodal approaches. In conclusion, our findings suggest that combining different imaging modalities and different regions of interest increase classification accuracy significantly. These results are promising for objective diagnosis in medical practice. [less ▲]

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See detail[18F]UCB-H as a new PET radiotracer for Synaptic vesicle protein 2A: A first clinical trial
Bahri, Mohamed Ali ULg; Stifkens, Mathieu; Bastin, Christine ULg et al

Poster (2015, January 27)

SV2A is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is shown, e.g., by the fact that it is ... [more ▼]

SV2A is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is shown, e.g., by the fact that it is a binding site and the primary mechanism of levetiracetam. Levetiracetam is an antiepileptic drug which has recently been suggested to reduce synaptic deficits in a mouse model for Alzheimer’s disease. We here aimed to investigate the cerebral distribution of [18F]UCB-H, which has a high affinity with the SV2A. Dynamic PET data of the head of 4 healthy volunteers were acquired over 100 minutes after injection of 170.4 ± 24.9 MBq of GMP produced [18F]UCB-H. The arterial input function (IF) was obtained by blood sampling. The IF was also derived from the dynamic data using the correlation coefficient method. Blood data revealed a consistent amount of [18F]UCB-H in whole blood and plasma indicating a very low degree of binding of the tracer to the red blood cells. The image-derived arterial IFs were showed to be very similar to the measured ones with a peak-ratio around 0.91 and an area-under-curve ratio about 0.98. The [18F]UCB-H PET data showed a high and rapid uptake in the grey matter structures, matching the known ubiquitous distribution of the SV2A in the brain. The kinetics of the tracer in the brain was characterized by an initial high uptake phase followed by rapid washout allowing the standard compartmental modeling (1-tissue, 2-tissue, and Logan Plot). The three models gave similar results with both the measured and image-derived IFs. The total distribution volume of the tracer in the brain was greater than 7 mL/cm3. Our results suggest that [18F]UCB-H is a good candidate as radiotracer for brain SV2A proteins and could be used for human studies. Image-derived IF showed to be useful for quantitative studies without the need to the arterial blood sampling. SV2A modifications may consequently be assessed in neurological pathologies such as Alzheimer’s disease. [less ▲]

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See detailHuman cortical excitability depends on time awake and circadian phase
Gaggioni, Giulia ULg; Ly, Julien; Chellappa, Sarah Laxhmi ULg et al

Poster (2015, January 27)

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See detailComparison of brain functional connectivity methods for the diagnosis of Parkinson’s disease using resting state fMRI
Baquero Duarte, Katherine Andrea ULg; Rouillard, Maud; Depierreux, Frédérique ULg et al

Scientific conference (2015, January 27)

Background In the absence of validated biomarkers, the early diagnosis of Parkinson’s disease (PD), the second most common neurodegenerative disorder worldwide [1], is challenging and is prone to low ... [more ▼]

Background In the absence of validated biomarkers, the early diagnosis of Parkinson’s disease (PD), the second most common neurodegenerative disorder worldwide [1], is challenging and is prone to low accuracy [2]. Recent evidence suggests that the average pattern of functional connectivity (FC) between the basal ganglia and cerebral cortex assessed in the resting state using functional magnetic resonance imaging (rs-fMRI) might discriminate between mild PD and healthy controls with 85% overall accuracy [3]. Goal We will test if this finding can be replicated in our population. We will also compare the diagnosis accuracy of this approach, which depicts an average pattern of connectivity during the whole scanning period, with that of dynamic FC that investigates the spontaneous fluctuations of the pattern of connectivity over the scanning period [4]. Methods We are currently processing and analyzing rs-fMRI data prospectively acquired on a 3T MRI in 39 patients with PD (mean disease duration 5.4 years; mean Hoehn and Yahr stage 1.5) and 39 healthy controls matched for age, gender and levels of education. For dynamic FC we will compare two different methods [4], one that use slice-time windows to capture brain dynamics with another that captures spatial co-activation patters (CAPs) at specific time points. Conclusion The selected methods will be further validated in a new cohort of de novo drug-naïve PD patients. [1] Tessitore, A., et al. Sensorimotor connectivity in Parkinson’s disease: the role of functional neuroimaging. Frontiers in neurology 5 (2014). [2] Adler et al. Low clinical diagnostic accuracy of early vs advanced Parkinson disease. Clinicopathologic study. Neurology 2014;83:406–412 [3] Szewczyk-Krolikowski, K., et al. Functional connectivity in the basal ganglia network differentiates PD patients from controls. Neurology 83.3 (2014): 208-214. [4] Hutchison, M., et al. Dynamic functional connectivity: promise, issues, and interpretations. Neuroimage 80 (2013): 360-378. [less ▲]

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See detailProtocol Optimization for Alpha–Synuclein Immuno-Labeling in the Autonomous Nervous System in Parkinson’s Disease
Pasquet, Coralie ULg; Garraux, Gaëtan ULg; Borgs, Laurence ULg et al

Scientific conference (2015, January 27)

Reviewing and testing of published protocols for the immuno-labelling of α–synuclein in the autonomous nervous system in Parkinson’s disease.

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See detailLocalization of rDNA transcription sites within reptilian nucleoli
Bartholomé, Odile ULg; Franck, Claire; Thiry, Marc ULg

Poster (2015, January 27)

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See detailHDAC5 Depletion in Cancer Cells Induces an Oxidative Stress and Leads to a Metabolic Reprogramming toward Glucose and Glutamine Metabolism
Hendrick, Elodie ULg; Peixoto, Paul ULg; Polese, Catherine ULg et al

Poster (2015, January 27)

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum ... [more ▼]

Histone deacetylases (HDAC) is a family of eighteen enzymes, which modulates the acetylation level of histones and non-histone proteins to regulate gene expression and chromatin structure. Broad-spectrum inhibitors of these enzymes such as SAHA can inhibit tumor growth both in vitro and in vivo and are currently used as anti-cancer agents in clinic. For many years, we are investigating the specific role of individual HDAC members in cancer biology and we have recently demonstrated that specific depletion of HDAC5 using siRNA technology reduced cancer cells proliferation and survival1 The goal of this study is to further understand the molecular mechanisms of action of HDAC5 in cancer cells. Screening transcriptomic study demonstrated that HDAC5 depletion induces a down-regulation of subunits of the complex I of the mitochondrial respiratory chain (NDUFB5-NDUFA3) as well as anti-oxydant proteins (Ferritin, Metalothionein,¿) through modulation of mRNA stability. Therefore, HDAC5 depletion causes a significant increase of ROS production inducing both apoptosis and mechanisms of mitochondria quality control (mitophagy and mitobiogenesis). This HDAC5 depletion-induced mitochondrial dysfunction provokes metabolic adaptation associated with increased importance of glucose and glutamine. Indeed, interference with both glucose and glutamine supply in HDAC5-depleted cancer cells significantly increases apoptotic cell death suggesting that glucose or glutamine deprivation might be combined to HDAC5 inhibition as a therapeutic strategy to kill cancer cells. Our study demonstrated for the first time that specific HDAC5 inhibition induces metabolic reprogramming and provides insight into a valuable experimental strategy for manipulation of specific HDAC5 inhibition and glucose metabolism in therapy against cancer. 1.Peixoto, P. et al. HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. Cell death and differentiation, 2012; 1-14. Presenting author e-mail: elodie.hendrick@student.ulg.ac.be [less ▲]

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See detailTransfer of communication skills to the workplace: Impact of a 38-hour communication skills training program designed for radiotherapy teams
Merckaert, Isabelle; Delevallez, France; Gibon, Anne-Sophie et al

in Journal of Clinical Oncology (2015)

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See detailLe jeu vidéo comme objet de recherche
Barnabé, Fanny ULg

Scientific conference (2015, January 26)

Présentation du jeu vidéo en tant qu'objet de recherche et de l'histoire des game studies, avec un accent mis sur la question de la narration et sur le rôle qu'elle a joué dans la structuration du champ.

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See detailOncologie et revalidation physique
Leclerc, Anne-France ULg; Foidart-Dessalle, Marguerite ULg; COUCKE, Philippe ULg et al

in Abstract Book du Colloque "Femmes et Santé" (Université d'Hiver) (2015, January 26)

Le cancer constitue une maladie fréquente en Belgique puisqu'un homme sur trois et une femme sur quatre sont confrontés à la maladie avant l'âge de septante-cinq ans (Fondation Registre du Cancer, 2008 ... [more ▼]

Le cancer constitue une maladie fréquente en Belgique puisqu'un homme sur trois et une femme sur quatre sont confrontés à la maladie avant l'âge de septante-cinq ans (Fondation Registre du Cancer, 2008). La détection précoce et l'amélioration des traitements du cancer, généralement une combinaison de chirurgie, radiothérapie, chimiothérapie, hormonothérapie et thérapie ciblée, ont permis une augmentation du taux de survie. Cependant, ces traitements peuvent être à l'origine de nombreux effets secondaires, non seulement précoces, mais également tardifs, réduisant la qualité de vie. De nombreux programmes de réhabilitation après cancer sont basés sur la psychothérapie et le support social uniquement, or ceux-ci n'agissent généralement pas sur les problèmes physiques encourus par les patients tels que la fatigue, la prise de poids et la diminution des capacités fonctionnelles. C'est pourquoi nous émettons l'hypothèse qu'une revalidation physique, associée à des séances psycho-éducatives et constituant ainsi une prise en charge multidisciplinaire, permettrait d'améliorer d'autant plus la qualité de vie et le bien-être tant physique que psychologique des patients ayant été traités pour un cancer. [less ▲]

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See detailL'observation des interactions précoces mère-bébé ultérieurement diagnostiqué autsite
Boulard, Aurore ULg

Conference given outside the academic context (2015)

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See detailTargeting osteopontin suppresses glioblastoma stem-like cell character and tumorigenicity in vivo
Lamour, Virginie; Henry, Aurélie ULg; Kroonen, Jerome et al

in International Journal of Cancer = Journal International du Cancer (2015)

Osteopontin (OPN) is a secreted protein involved in most aspects of tumor progression and metastasis development. Elevated OPN expression has been reported in multiple types of cancer including ... [more ▼]

Osteopontin (OPN) is a secreted protein involved in most aspects of tumor progression and metastasis development. Elevated OPN expression has been reported in multiple types of cancer including glioblastoma (GBM), the highest grade and most aggressive brain tumor. GBMs contain a subpopulation of glioma-initiating cells (GICs) implicated in progression, therapeutic resistance and recurrence. We have previously demonstrated that OPN silencing inhibited GBM cell growth in vitro and in vivo. Moreover, activation of CD44 signaling upon OPN ligation has been recently implicated in the acquisition of a stem cell phenotype by GBM cells. The present study is aimed to explore OPN autocrine function using shRNA silencing strategy in GICs enriched from GBM cell lines and a human primary GBM grown in EGF and bFGF defined medium. The removal of these growth factors and addition of serum induced a significant loss of OPN expression in GICs. We showed that OPN-silenced GICs were unable to grow as spheres and this capacity was restored by exogenous OPN. Importantly, the expression of Sox2, Oct3/4 and Nanog, key stemness transcription factors, was significantly decreased in GICs upon OPN targeting. We identified Akt/mTOR/p70S6K as the main signaling pathway triggered following OPN-mediated EGFR activation in GICs. Finally, in an orthotopic xenograft mouse model, the tumorigenic potential of U87-MG sphere cells was completely abrogated upon OPN silencing. Our demonstration of endogenous OPN major regulatory effects on GICs stemness phenotype and tumorigenicity implies a greater role than anticipated for OPN in GBM pathogenesis from initiation and progression to probable recurrence. [less ▲]

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See detailComprendre la voix et Comment optimaliser sa voix
Morsomme, Dominique ULg; Remacle, Angélique ULg

Conference given outside the academic context (2015)

Detailed reference viewed: 27 (5 ULg)