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See detailLes "maladies rares" en Belgique : Processus de co-construction d'un objet-frontière
Duysens, Fanny ULiege

Conference (2017, November 20)

La présentation a retracé l'évolution de la catégorie "maladies rares" à l'échelle internationale puis nationale, telle qu'elle se donne à observer aujourd'hui sur le terrain de la Belgique, tout en ... [more ▼]

La présentation a retracé l'évolution de la catégorie "maladies rares" à l'échelle internationale puis nationale, telle qu'elle se donne à observer aujourd'hui sur le terrain de la Belgique, tout en soulevant certains enjeux et défis relatifs aux processus de co-construction dont elle fait l'objet dans les rapports entre les multiples acteurs impliqués. En outre, dans le cadre de cette journée d’étude interdisciplinaire, la présentation visait à croiser les observations empiriques avec des réflexions épistémologiques et méthodologiques relatives aux pratiques de recherche en sciences sociales. Il s'agissait d'expliciter l'approche mise en œuvre pour étudier l'objet "maladies rares" : comment le suivre, le construire, puis le restituer dans l’analyse ? [less ▲]

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See detail“A Genome Mining Toolbox for CRISPR-associated Cas9 orthologues”
Golestan Hashemi, Farahnaz Sadat ULiege

Scientific conference (2017, November 19)

CRISPR-associated protein system can facilitate accurate and targeted editing of genomes. RNA-guided Cas9 can be employed as an efficient genome editing tool in human, plants, and animals. The Cas9 ... [more ▼]

CRISPR-associated protein system can facilitate accurate and targeted editing of genomes. RNA-guided Cas9 can be employed as an efficient genome editing tool in human, plants, and animals. The Cas9 nuclease can be programmed by guide RNA (gRNA) in order to cut DNA at targeted regions. Therefore, concise mutations are introduced by homologous recombination or non-homologous end-joining repairing. Although the CRISPR/Cas9 is a powerful system, alternative strategies have been developed to decrease the risk of off-target activities such as using Cas9 orthologs. Additionally, only one activity can be mediated by the Cas9 protein from Streptococcus pyogenes (Sp) at different target regions. In other words, it is unable to simultaneously mediate a different activity at other targets. Besides SpCas9, some orthologous CRISPR–Cas9 systems from different species have been discovered and utilized for genome editing. Therefore, in order for wider application of CRISPR-Cas, new and applicable Cas proteins, with different requirements for PAM sequence, gRNA length, and tracrRNA and crRNA sequences, have emerged from several species as a new tool for effective genome editing. Consequently, discovery of various potential Cas9 proteins becomes a major concern for CRISPR/Cas-mediated genome editing technology to develop straightforward bioinformatics tools with high efficiency and versatility to facilitate the artificial design of possible gRNAs. Hence, we aimed to create an application tool to perform high-throughput detection of target sites based on the specific sequence and length of PAM followed by a constant length of target site for not only common Streptococcus pyogenes (SpCas9) but also for other CRISPR-Cas systems. To this end, different search modes for gRNA detection were applied including i) coding strand searching, ii) anti-coding strand searching, iii) both strand searching. Also, a complete list of all possible gRNAs along with their useful information can be provided for various potential Cas9 orthologs. Such progress expands the toolbox of genome editing and the possibilities for the site-specific genome engineering. [less ▲]

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See detailBig Data and Geomatics - Towards a new paradigm in spatial information management
Kasprzyk, Jean-Paul ULiege; Hallot, Pierre ULiege

Conference (2017, November 17)

Big Data and Geomatics : towards a new paradigm in spatial information management During the last decade, the technological advances allowed a massive acquisition of digital data whose volume grows ... [more ▼]

Big Data and Geomatics : towards a new paradigm in spatial information management During the last decade, the technological advances allowed a massive acquisition of digital data whose volume grows exponentially. Going from location-based social networks to smartphones, users produce huge amounts of data that are located in space and time. The various exploitations of these large and heterogeneous datasets have created a new field called “Big Data”. As most of these data are characterized by spatial and temporal components, it has become the next challenge to handle for geomatics researchers within the next incoming year. In this presentation, we provide an overview of the main domains in geomatics that are impacted by big data. Related fields are among other things: terrestrial spatial data acquisition where the rise of powerful laser scanners, that can acquire millions of points per second in order to precisely represent built heritage in 3D, revolutionized topography; Global Navigation Satellite Systems (GNSS), powered by the European constellation Galileo, imply original researches able to increase the position accuracy of a simple smartphone user; remote sensing is now enriched by a wide open access capability thanks to Copernicus satellites which provide timely information for the management of the environment. In order to effectively manage and analyse information related to each of these revolutions, Geographical Information System (GIS) research uses innovative data storage strategies based on CityGML for 3D data, semantic web linked-data and non-structured databases (NoSQL) for the integration of heterogeneous information, data warehouses and OnLine Analytical Processing (OLAP) for decision support. The presentation is based on concrete applications about smart cities, remote sensing, firefighting… [less ▲]

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See detailFirm Performance and Multi-Scale Territorial Resources in Wallonia: Towards a Model using Business Accounting?
Wilmotte, Pierre-François ULiege; Halleux, Jean-Marie ULiege

Poster (2017, November 17)

In Europe (and in Wallonia), most public policies related to regional development and economic development aim to stimulate/reinforce the ‘’territorial resources’’ in order to improve the competitiveness ... [more ▼]

In Europe (and in Wallonia), most public policies related to regional development and economic development aim to stimulate/reinforce the ‘’territorial resources’’ in order to improve the competitiveness of the (Walloon, Belgian or European) firms. For instance, in Wallonia, one of the key action of the Marshall Plan (i.e. the main regional strategy in the domain of economic development) aims to “mobilize the territory” (in French, « mobilisation du territoire à destination du développement économique »). In this perspective, our objective is to quantify and analyse the territorial resources that impact the performance of Walloon or Belgian firms, with the final aim to advice the policy makers and to improve the related public policies. This topic is related to questions such as: Does a better accessibility of economic estates improve the performance of firms? Are cultural amenities (in order to attract talents) and land prices (in order to reduce their costs) strategic competitive advantages for firms? The poster describes some methodological issues of (in general) the PhD research and (particularly) one part of the research, concerning a multivariate statistics analysis of business accounting. [less ▲]

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See detailCoupling an atmospheric model to an ocean model to study air-ice-ocean interactions in Antarctica: challenges and applications
Kittel, Christoph ULiege

Conference (2017, November 17)

Interactions between atmosphere, ice sheet and ocean play a crucial role in the Antarctic climate. For example, sea-air exchanges in leads and polynyas can strengthen cyclonic activities by warming and ... [more ▼]

Interactions between atmosphere, ice sheet and ocean play a crucial role in the Antarctic climate. For example, sea-air exchanges in leads and polynyas can strengthen cyclonic activities by warming and water vapour loading of air masses while associated sea heat loss and brine rejection modify water density and contribute to the dense water formation. Due to the harsh weather conditions in Antarctica, climate and ocean models appear as suitable tools to complement the scarcity of observations and to study the Antarctic climate. Nonetheless, only few models are able to represent typical processes found at high latitudes such as katabatic winds, drifting snow for the atmosphere or sea ice formation, accretion and deformation for oceans. Furthermore, due to their high non-linearity, those processes are difficult to model as they occur at different spatial and temporal scales. Current models are often forced by outputs: atmospheric conditions are provided to ocean models and ocean models outputs are used as surface conditions in atmospheric models meaning air feedbacks on ocean (or inversely) are muted. One can think models should be coupled at each time steps to take into account instantaneous interactions. Nonetheless, this method involves (too) high computational costs. The main challenge of this coupling is to take into account air-ice-ocean interactions and the temporal scale of associated processes in order to define an appropriate coupling time step. We will present both ocean and ice-atmosphere processes relative to polar climates and the specificities of the two models as well as technical coupling aspects. [less ▲]

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See detailGames to understand urban planning
Dethier, Perrine ULiege; Halleux, Jean-Marie ULiege

Conference (2017, November 17)

Planning is not anymore seeing as a neutral concept. During a long period planning has been conducted as a technical activity only. Nevertheless, space “is no longer a neutral category as it was between ... [more ▼]

Planning is not anymore seeing as a neutral concept. During a long period planning has been conducted as a technical activity only. Nevertheless, space “is no longer a neutral category as it was between the 1960s and the 1980s that is viewed as a container for economic and social processes, but is rather the result of social relations among people living in a certain area or region where culture and cultural influences play a crucial role”(Knieling & Othengrafen, 2009, p. xxiii)1. Planning is indeed deeply depending on cultural context of a country and a region. Since the 1990s, the term planning culture covers comparative spatial planning research. This concept can be define as “the collective ethos and dominant attitudes of planners regarding the appropriate role of the state, market forces, and civil society in influencing social outcomes” (Sanyal, 2005, p. xxi)2. To date, planning culture literature concentrates on listing the observations and expert analyses. Our goal is to operationalise this concept as a set of values and attitudes shared by a particular group of people. For this purpose, we use experimental economics to gain empirical evidences on planning practices. Our presentation will be structured in three parts. At first, we will develop the concept of planning culture and illustrate it by the comparison of planning in Belgium and in the Netherlands. Despite many common characteristics, planning in those two countries strongly differs. On the one hand, both countries are densely populated and their territories are relatively similar. Although, on the other hand, their urban form are highly contrasted. Indeed, Belgium is characterized by an extreme sprawl whereas Netherlands has controlled the sub-urbanization processes. The second part of our presentation will be dedicated to the explanation of experimental economics. Experimental economics are experiments motivated by economics questions. “Experiments are a controlled data generation process. ‘Control’ means that most factors which influence behaviour are held constant and only one factor of interest (the “treatment”) is varied at a time”(Croson and Gächter, 2010, p. 124)3. To illustrate the field, we will realise an experiment in real time with the audience.Finally, we will finish our presentation by presenting some results of our current research that intends to objectify the role of planning culture in urban development. Based on experimental economics, our research aims to study the risk aversion as well as the importance of trust and cooperation in the development of partnership. To do so, we have organized four experiments with urban planning stakeholders in three different countries: Belgium, the Netherlands and Norway. [less ▲]

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See detailCarte interactomique entre l'oncoprotéine Tax du virus HTLV-1 et les protéines à domaines PDZ.
Blibek, Karim ULiege

Doctoral thesis (2017)

HTLV-1 (Human T-cell Leukemia Virus) is the etiologic agent of human adult T-cell leukemia (ATL) and tropical spastic paraparesis (TSP). More than 20 million people worldwide are infected with the HTLV-1 ... [more ▼]

HTLV-1 (Human T-cell Leukemia Virus) is the etiologic agent of human adult T-cell leukemia (ATL) and tropical spastic paraparesis (TSP). More than 20 million people worldwide are infected with the HTLV-1 virus, but only about 5 % develop the associated pathologies. At present, efforts are invested in the search for treatments that may improve the survival expectancy of patients infected by the HTLV-1 virus. The diagnosis of HTLV-1 infection is hampered by the viral genome latency (up to 40 years) and treatment options are limited. To propose novel therapeutic opportunities, it thus is necessary to better understand the host molecular mechanisms perturbed by the HTLV-1 infection. The HTLV-1 genome encodes for the Tax-1 protein, which confers the transforming ability of the virus. The Tax-1 protein is known as the transactivator factor of the HTLV-1 virus genome expression (TransActivator of pX region). It is also involved in the destabilization of several molecular mechanisms within the host, leading to cellular transformation. Tax-1 protein displays several functional domains and interacts with a wide range of cellular proteins. In particular, the Tax-1 protein sequence contains, at its carboxy-terminal end, a motif of four amino acids able to interact with PDZ domain (PSD95-DLG1-ZO1) containing proteins. It has been demonstrated that deletion of the PDZ binding motif (PBM) of the Tax-1 protein leads to a decrease of its oncogenic capacity in vitro. Cellular proteins containing PDZ domains are involved in the formation of cellular junctions, synapses and in cellular receptors assembly. Some of PDZ proteins are capable of relaying extracellular signals and participate in the control of proliferation. The human genome codes for at least 150 proteins with PDZ domains. However, the specificity of the oncoprotein Tax-1 to target these proteins remains unknown. In this study, we have mapped The Tax-1 - PDZ interactome using a combination of several methods. We reveal that Tax-1 selectively target a number of PDZ domains-containing proteins potentially involved in HTLV-1 pathogenesis. We validated our approach by focusing on the role of SDCBP and LNX2 proteins in HTLV-1 biology. Our work also demonstrated that the Tax-1-PDZ interactome might represent an attractive therapeutic target for HTLV-1-induced diseases. [less ▲]

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See detailPratiques d’évaluation des acquis, ancienneté et attitudes face à l’évaluation
Romainville, Marc; Detroz, Pascal ULiege; Auquière, Amélie ULiege et al

Conference (2017, November 16)

La présente communication est issue d’une recherche plus globale visant à identifier et à mieux comprendre les pratiques d’évaluation des acquis des étudiants auxquelles recourent les enseignants de ... [more ▼]

La présente communication est issue d’une recherche plus globale visant à identifier et à mieux comprendre les pratiques d’évaluation des acquis des étudiants auxquelles recourent les enseignants de l’enseignement supérieur et en particulier les facteurs personnels (ancienneté, attitudes vis-à-vis de l’évaluation…) et contextuels (année d’étude, taille du groupe, disciplines…) qui influencent ces pratiques. Les données ont été recueillies en 2016, d’une part, via une enquête en ligne (élaborée à l’aide du logiciel d’enquêtes Qualtrics) auprès d’enseignants de l’enseignement supérieur belge francophone que ce soit à l’Université ou en Hautes écoles (2292 réponses) et, d’autre part, via 37 entretiens semi-structurés individuels réalisés auprès d’un échantillon de ces mêmes enseignants dans des filières d’études contrastées. Les résultats présentés dans le cadre de cette communication ont trait à l’impact de deux variables personnelles : l’ancienneté des enseignants et leurs attitudes vis-à-vis de l’évaluation. Autrement dit, on cherchera à savoir si l’ancienneté et le développement professionnel qui l’accompagne traditionnellement ont des incidences sur le type de pratiques d’évaluation des acquis des enseignants. En particulier, recourent-ils à des outils de plus en plus diversifiés ou ont-ils tendance à se spécialiser dans l’un ou l’autre ? Et si oui, pourquoi ? Accentuent-ils par ailleurs le recours à l’évaluation continue par rapport au poids du contrôle terminal ? On cherchera ensuite à comprendre comment les pratiques se reconfigurent en fonction des attitudes des enseignants vis-à-vis de l’évaluation et en particulier vis-à-vis de sa fonction et de son rapport à l’apprentissage : dans quel sens une conception davantage intégrative de l’évaluation colore-t-elle les pratiques déclarées d’évaluation ? [less ▲]

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See detailCarte interactomique entre l'oncoprotéine Tax du virus HTLV-1 et les protéines à domaines PDZ.
Blibek, Karim ULiege

Scientific conference (2017, November 16)

ABSTRACT HTLV-1 (Human T-cell Leukemia Virus) is the etiologic agent of human adult T-cell leukemia (ATL) and tropical spastic paraparesis (TSP). More than 20 million people worldwide are infected with ... [more ▼]

ABSTRACT HTLV-1 (Human T-cell Leukemia Virus) is the etiologic agent of human adult T-cell leukemia (ATL) and tropical spastic paraparesis (TSP). More than 20 million people worldwide are infected with the HTLV-1 virus, but only about 5 % develop the associated pathologies. At present, efforts are invested in the search for treatments that may improve the survival expectancy of patients infected by the HTLV-1 virus. The diagnosis of HTLV-1 infection is hampered by the viral genome latency (up to 40 years) and treatment options are limited. To propose novel therapeutic opportunities, it thus is necessary to better understand the host molecular mechanisms perturbed by the HTLV-1 infection. The HTLV-1 genome encodes for the Tax-1 protein, which confers the transforming ability of the virus. The Tax-1 protein is known as the transactivator factor of the HTLV-1 virus genome expression (TransActivator of pX region). It is also involved in the destabilization of several molecular mechanisms within the host, leading to cellular transformation. Tax-1 protein displays several functional domains and interacts with a wide range of cellular proteins. In particular, the Tax-1 protein sequence contains, at its carboxy-terminal end, a motif of four amino acids able to interact with PDZ domain (PSD95-DLG1-ZO1) containing proteins. It has been demonstrated that deletion of the PDZ binding motif (PBM) of the Tax-1 protein leads to a decrease of its oncogenic capacity in vitro. Cellular proteins containing PDZ domains are involved in the formation of cellular junctions, synapses and in cellular receptors assembly. Some of PDZ proteins are capable of relaying extracellular signals and participate in the control of proliferation. The human genome codes for at least 150 proteins with PDZ domains. However, the specificity of the oncoprotein Tax-1 to target these proteins remains unknown. In this study, we have mapped The Tax-1 - PDZ interactome using a combination of several methods. We reveal that Tax-1 selectively target a number of PDZ domains-containing proteins potentially involved in HTLV-1 pathogenesis. We validated our approach by focusing on the role of SDCBP and LNX2 proteins in HTLV-1 biology. Our work also demonstrated that the Tax-1-PDZ interactome might represent an attractive therapeutic target for HTLV-1-induced diseases. KEYWORDS: HTLV-1, Leukemia, Tax-1, interactions, PDZ. [less ▲]

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See detailL'Europe est-elle plus verte ?
Habran, Maxime ULiege

Conference given outside the academic context (2017)

Bilan de la politique environnementale et de la lutte contre le changement climatique au sein des politiques européennes

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See detailOverview and future challenges of nearly Zero Energy Buildings (nZEB) design in Southern Europe
Attia, Shady ULiege; Polyvios, Eleftheriou; Xeni, Flouris et al

in Energy and Buildings (2017), 155

In times of great transition of the European construction sector to energy efficient and nearly zero energy buildings (nZEB), a market observation containing qualitative and quantitative indications ... [more ▼]

In times of great transition of the European construction sector to energy efficient and nearly zero energy buildings (nZEB), a market observation containing qualitative and quantitative indications should help to fill out some of the current gaps concerning the EU 2020 carbon targets. Next to the economic challenges, there are equally important factors that hinder renovating the existing residential building stock and adding newly constructed high performance buildings. Under these circumstances this paper summarises the findings of a cross-comparative study of the societal and technical barriers of nZEB implementation in 7 Southern European countries. The study analyses the present situation and provides an overview on future prospects for nZEB in Southern Europe. The result presents an overview of challenges and provides recommendations based on available empirical evidence to further lower those barriers in the European construction sector. The paper finds that the most Southern European countries are poorly prepared for nZEB implementation and especially to the challenge/opportunity of retrofitting existing buildings. Creating a common approach to further develop nZEB targets, concepts and definitions in synergy with the climatic, societal and technical state of progress in Southern Europe is essential. The paper provides recommendations for actions to shift the identified gaps into opportunities for future development of climate adaptive high performance buildings. [less ▲]

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See detailTowards a Typology of Business Models in the Biotechnology Industry
Segers, Jean Pierre ULiege

E-print/Working paper (2017)

The purpose of this paper is to identify a selection of key business models - “typology” - applied in the biotechnology industry. The focus is on the differences between traditional/closed or stand-alone ... [more ▼]

The purpose of this paper is to identify a selection of key business models - “typology” - applied in the biotechnology industry. The focus is on the differences between traditional/closed or stand-alone business models opposed to open or networked business models. A number of illustrative case studies and good practices are presented to show that new biotechnology firms are gradually adopting a “best of both worlds” strategy, with both closed business models and open, networked models as a way for gaining access to the market, in close collaboration with large global pharmaceutical companies. The case firms and good practices are taken from a recent country study for Belgium. [less ▲]

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See detailOut of hospital neonatal resuscitation: a control randomised study
Servotte, Jean-Christophe ULiege; Ghuysen, Alexandre ULiege; Simonet et al

Conference (2017, November 14)

Introduction : En 2014, 64 accouchements inopinés sont survenus en Wallonie. 5,3% des naissances ont nécessité une réanimation néonatale. Or, de nombreux professionnels de l’urgence terminent leur ... [more ▼]

Introduction : En 2014, 64 accouchements inopinés sont survenus en Wallonie. 5,3% des naissances ont nécessité une réanimation néonatale. Or, de nombreux professionnels de l’urgence terminent leur formation avec une expertise insuffisante dans ce domaine (Nadel et al. 2000). En effet, la réanimation néonatale nécessite des compétences cognitives, techniques et comportementales spécifiques (Halamek et al. 2016). Objectifs : Notre étude randomisée contrôlée a évalué l’impact d’une formation utilisant la simulation clinique sur l’évolution des connaissances et des compétences techniques en réanimation néonatale, avec l’hypothèse que cette méthode a un impact supérieur à l’enseignement clinique traditionnel. Matériel & Méthodes : Des infirmiers se spécialisant en soins intensifs et aide médicale urgente (SIAMU) ont été assignés, après randomisation, à un groupe expérimental (GE) ou à un groupe contrôle (GC). Le GE a reçu un cours théorique suivi d’une formation par simulation (2h) et de 4 semaines de stage. Le GC a reçu un cours théorique suivi de 4 semaines de stage. La population a été évaluée à 2 reprises au moyen d’une simulation de réanimation néonatale et de questionnaires: avant et après la formation, à 4 semaines d’intervalle. Deux experts ont évalué à l’aveugle sur base d’une grille critériée les compétences techniques lors de la simulation. Résultats : 36 participants ont été inclus dans l’étude. Les 2 groupes ont amélioré leurs connaissances. Comparativement, le GE a davantage amélioré ses connaissances globales (p = 0,0001) et spécifiques (p = 0,0007). La formation a permis une amélioration des compétences techniques de 83,3% pour le GC et de 175% pour le GE. Cette différence est significative (p = 0,003). Conclusions : Les deux méthodes pédagogiques ont amélioré les connaissances et les compétences techniques des infirmiers SIAMU. Toutefois, l’impact est significativement supérieur en faveur de la formation utilisant la simulation par rapport à l’enseignement clinique traditionnel. [less ▲]

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See detailAnomalies des gonadorophines LH et FSH: tableaux cliniques
VALDES SOCIN, Hernan Gonzalo ULiege

Scientific conference (2017, November 14)

L’hormone lutéinisante (LH) et l’hormone folliculostimulante (FSH) – hormones glycoprotéiques hypophysaires – régulent de concert la production de stéroïdes sexuels et la reproduction. Les stéroïdes ... [more ▼]

L’hormone lutéinisante (LH) et l’hormone folliculostimulante (FSH) – hormones glycoprotéiques hypophysaires – régulent de concert la production de stéroïdes sexuels et la reproduction. Les stéroïdes sexuels sont indispensables à la virilisation et à la féminisation, et participent également à la gamétogenèse (spermatogenèse chez l’homme et folliculogenèse chez la femme). Cette présentation fait le point sur la physiologie et la pathologie de LH et de FSH en reproduction humaine. [less ▲]

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See detailCaractérisation ontogénique, phénotypique et fonctionnelle des macrophages interstitiels pulmonaires après exposition à des composés bactériens
Sabatel, Catherine ULiege

Doctoral thesis (2017)

Respiratory mucosal surfaces are continuously exposed to harmless antigens and immunostimulatory molecules of microbial origin. According to the « self/non self » and « danger » theories, this should ... [more ▼]

Respiratory mucosal surfaces are continuously exposed to harmless antigens and immunostimulatory molecules of microbial origin. According to the « self/non self » and « danger » theories, this should normally result in the developpment of unwanted immune responses towards these inhaled antigens such as Th2-mediated allergic responses. This is however not the case in most people. The hygiene hypothesis postulates that living in an environment rich in microbial components paradoxically protects from airway allergy, implying the existence in the lung of suppressive mechanisms triggered by these immunogenic signals. In this study, we showed that synthetic bacterial DNA rich in unmethylated CpG motifs (CpG) has the unique ability to significantly increase the population of lung interstitial regulatory macrophages (IM) from CCR2-independent monocytes residing in the lung or mobilized from the spleen. Moreover these CpG-induced IM demonstrated a hypersuppressive profile as they produced more IL-10 than their steady state counterparts. Using mice models of airway allergy we showed that the transfert of IM isolated from CpG-treated mice recapitulated the protective effects of CpG when administered before allergen sensitization or challenge. This IM-mediated protection was dependant from IL-10 as CpG-induced Il10-/- IM had no protective effect. The expansion of pulmonary regulatory IM from CCR2-independent pulmonary and splenic monocytes upon CpG exposure could be a possible mechanism by which exposure to an environment rich in microbial products protects against asthma. [less ▲]

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See detailThe Physiology of The Thymus
Geenen, Vincent ULiege

Scientific conference (2017, November 13)

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See detailL'économie collaborative
Gautier, Axel ULiege

Conference given outside the academic context (2017)

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See detailElastic scattering, total cross sections and 𝝆 parameters at the LHC
Cudell, Jean-René ULiege

Speech/Talk (2017)

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See detailEtude de la transmission du gammaherpèsvirus murin 4: importance de la glycoprotéine gp150 et développement de stratégies antivirales basées sur l'utilisation du cidofovir
Zeippen, Caroline ULiege

Doctoral thesis (2017)

Gammaherpèsviruses are important pathogens in human medicine. Indeed, Epstein Barr virus and Kaposi Sarcoma associated herpesvirus are responsible for numerous lymphoproliferative diseases and cancers ... [more ▼]

Gammaherpèsviruses are important pathogens in human medicine. Indeed, Epstein Barr virus and Kaposi Sarcoma associated herpesvirus are responsible for numerous lymphoproliferative diseases and cancers. Murid Herpesvirus-4 (MuHV-4) is usually used as a model for human gammaherpèsviruses. Until now, the major limitation of this model was the absence of transmission in laboratory animals. Recently, a sexual transmission of MuHV-4 has been described in laboratory mice. This observation allows, on the one hand, to study mechanisms underlying natural transmission, such as cellular trospism, importance of viral proteins, or immunity response during this part of the cycle. On the other hand, this transmission model allows to test efficiency of measures to reduce transmission. Indeed, herpesvirus are archetype of persistant viruses as infection persists lifelong once established. Studying mechanisms underlying transmission and how to use these mechanisms to reduce it efficiently is therefore of primordial importance. In a first study, we focussed on the biological relevance of mechanisms described previously in vitro. Indeed, a MuHV-4 glycoprotein, gp150, has been shown to participate to the release of infectious particles from cells and to evasion of humoral immunity, two functions that could be important for the virus during transmission. Our results showed that gp150 is essential for an efficient sexual transmission of the MuHV-4. Indeed, gp150 promotes the release of infectious particles from infected vaginal epithelial cells. These results has been published in Journal of Virology in July 2017. In a second study, the same model was used to test efficiency of an antiviral molecule to reduce sexual transmission of the MuHV-4. A nucleotide analogue, the cidofovir, was administrated to mice according to different protocols. A daily administration of cidofovir reduced drastically genital shedding, but also prevent completely infection of naive mice after sexual contact. Finally, a single injection of cidofovir, administered 24 hours after sexual contact, reduced significantly transmission. Altogether, in this work, we used a transmission model of a gammaherpèsvirus in two differents studies: the first foccused on glycoprotein implicated during the transmission and established the importance of a single viral glycoprotein for an efficient transmission. The second study highlighted the efficiency of antiviral drugs to prevent infection by gammaherpesviruses. [less ▲]

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