Pour une approche normative de l’aménagement. Simulation de scénarios de développement résidentiel au Luxembourg

National audienceL’objectif de cette communication est de présenter les résultats obtenus dans le cadre d’un travail de thèse (projet COSMELUX, financé par le Fond National de la Recherche du Luxembourg, 2010-2014) dont l’objectif est de proposer et d’évaluer différents scénarios de croissance résidentielle sur le Grand-Duché du Luxembourg à l’horizon 2030. Les simulations de développement résidentiel ont été réalisées avec l’application MUP-City (Tannier et al., 2012). Les scénarios simulés ont d’abord été évalués au moyen de mesures d’accessibilité spatiale (distance minimale pour atteindre l’aménité la plus proche, nombre d’aménités à une distance donnée, indicateurs de diversité de l’offre en aménités) calculées avec MUP-City

Dominant-Negative Tumor Necrosis Factor Protects from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) and Endotoxin-Induced Liver Injury without Compromising Host Immunity to BCG and Mycobacterium tuberculosis

BackgroundTumor necrosis factor (TNF) is associated with the development of inflammatory pathologies. Antibodies and soluble TNF (solTNF) receptors that neutralize excessive TNF are effective therapies for inflammatory and autoimmune diseases. However, clinical use of TNF inhibitors is associated with an increased risk of infections MethodsA novel dominant-negative (DN) strategy of selective TNF neutralization, consisting of blocking solTNF while sparing transmembrane TNF (tmTNF), was tested in mouse models of mycobacterial infection and acute liver inflammation. XENP1595, a DN-TNF biologic, was compared with etanercept, a TNF receptor 2 (TNFR2)-IgG1 Fc fusion protein that inhibits murine solTNF and tmTNF ResultsXENP1595 protected mice from acute liver inflammation induced by endotoxin challenge in Mycobacterium bovis bacillus Calmette-Guérin (BCG)-infected mice, but, in contrast to etanercept, it did not compromise host immunity to acute M. bovis BCG and Mycobacterium tuberculosis infections in terms of bacterial burden, granuloma formation, and innate immune responses ConclusionsA selective inhibitor of solTNF efficiently protected mice from acute liver inflammation yet maintained immunity to mycobacterial infections. In contrast, nonselective inhibition of solTNF and tmTNF suppressed immunity to M. bovis BCG and M. tuberculosis. Therefore, selective inhibition of solTNF by DN-TNF biologics may represent a new therapeutic strategy for the treatment of inflammatory diseases without compromising host immunit

Interface Gain-of-Function Mutations in TLR7 Cause Systemic and Neuro-inflammatory Disease

TLR7 recognizes pathogen-derived single-stranded RNA (ssRNA), a function integral to the innate immune response to viral infection. Notably, TLR7 can also recognize self-derived ssRNA, with gain-of-function mutations in human TLR7 recently identified to cause both early-onset systemic lupus erythematosus (SLE) and neuromyelitis optica. Here, we describe two novel mutations in TLR7, F507S and L528I. While the L528I substitution arose de novo, the F507S mutation was present in three individuals from the same family, including a severely affected male, notably given that the TLR7 gene is situated on the X chromosome and that all other cases so far described have been female. The observation of mutations at residues 507 and 528 of TLR7 indicates the importance of the TLR7 dimerization interface in maintaining immune homeostasis, where we predict that altered homo-dimerization enhances TLR7 signaling. Finally, while mutations in TLR7 can result in SLE-like disease, our data suggest a broader phenotypic spectrum associated with TLR7 gain-of-function, including significant neurological involvement

Juvenile neuropsychiatric systemic lupus erythematosus: identification of novel central neuroinflammation biomarkers

International audienceIntroduction Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic autoimmune disease affecting multiple organs. Ranging from minor features, such as headache or mild cognitive impairment, to serious and life-threatening presentations, j-neuropsychiatric SLE (j-NPSLE) is a therapeutic challenge. Thus, the diagnosis of NPSLE remains difficult, especially in pediatrics, with no specific biomarker of the disease yet validated. Objectives To identify central nervous system (CNS) disease biomarkers of j-NPSLE. Methods A 5-year retrospective tertiary reference monocentric j-SLE study. A combination of standardized diagnostic criteria and multidisciplinary pediatric clinical expertise was combined to attribute NP involvement in the context of j-SLE. Neopterin and interferon-alpha (IFN-α) protein levels in cerebrospinal fluid (CSF) were assessed, together with routine biological and radiological investigations. Results Among 51 patients with j-SLE included, 39% presented with j-NPSLE. J-NPSLE was diagnosed at onset of j-SLE in 65% of patients. No specific routine biological or radiological marker of j-NPSLE was identified. However, CSF neopterin levels were significantly higher in active j-NPSLE with CNS involvement than in j-SLE alone ( p = 0.0008). Neopterin and IFN-α protein levels in CSF were significantly higher at diagnosis of j-NPSLE with CNS involvement than after resolution of NP features (respectively p = 0.0015 and p = 0.0010) upon immunosuppressive treatment in all patients tested ( n = 10). Both biomarkers correlated strongly with each other ( R s = 0.832, p < 0.0001, n = 23 paired samples). Conclusion CSF IFN-α and neopterin constitute promising biomarkers useful in the diagnosis and monitoring of activity in j-NPSLE

Simulation de scénarios fractals d’urbanisation et des mobilités quotidiennes résultantes

International audienc

Comparaison de scénarios de croissance urbaine au Luxembourg : mesurer l'accessibilité aux aménités

National audienc

Dominant-negative tumor necrosis factor protects from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) and endotoxin-induced liver injury without compromising host immunity to BCG and Mycobacterium tuberculosis

Tumor necrosis factor (TNF) is associated with the development of inflammatory pathologies. Antibodies and soluble TNF (solTNF) receptors that neutralize excessive TNF are effective therapies for inflammatory and autoimmune diseases. However, clinical use of TNF inhibitors is associated with an increased risk of infections