Allagnat F.,Free University of Colombia |
Cunha D.,Free University of Colombia |
Moore F.,Free University of Colombia |
Vanderwinden J.M.,Universitelibre Of Bruxelles Ulb |
And 2 more authors.
Cell Death and Differentiation | Year: 2011
Pancreatic Β-cell apoptosis is a key feature of diabetes mellitus and the mitochondrial pathway of apoptosis is a major mediator of Β-cell death. We presently evaluated the role of the myeloid cell leukemia sequence 1 (Mcl-1), an antiapoptotic protein of the Bcl-2 family, in Β-cells following exposure to well-defined Β-cell death effectors, for example, pro-inflammatory cytokines, palmitate and chemical endoplasmic reticulum (ER) stressors. All cytotoxic stresses rapidly and preferentially decreased Mcl-1 protein expression as compared with the late effect observed on the other antiapoptotic proteins, Bcl-2 and Bcl-xL. This was due to ER stress-mediated inhibition of translation through eIF2α phosphorylation for palmitate and ER stressors and through the combined action of translation inhibition and JNK activation for cytokines. Knocking down Mcl-1 using small interference RNAs increased apoptosis and caspase-3 cleavage induced by cytokines, palmitate or thapsigargin, whereas Mcl-1 overexpression partly prevented Bax translocation to the mitochondria, cytochrome c release, caspase-3 cleavage and apoptosis induced by the Β-cell death effectors. Altogether, our data suggest that Mcl-1 downregulation is a crucial event leading to Β-cell apoptosis and provide new insights into the mechanisms linking ER stress and the mitochondrial intrinsic pathway of apoptosis. Mcl-1 is therefore an attractive target for the design of new strategies in the treatment of diabetes. © 2011 Macmillan Publishers Limited All rights reserved.
Antoine C.,Universitelibre Of Bruxelles Ulb |
Ameye L.,Institute Jules Bordet |
Paesmans M.,Institute Jules Bordet |
De Azambuja E.,Institute Jules Bordet |
Rozenberg S.,Universitelibre Of Bruxelles Ulb
Maturitas | Year: 2016
Introduction The use of menopausal hormone therapy (MHT) has decreased in many countries in the past 10 years. This is a consequence of the initial publication of the results of the Women's Health Initiative (WHI) randomized trial of estrogen plus progestin. In various countries, further studies then analyzed the incidence of breast cancer (BC) in relation to changes in MHT use. Some reported a decreased BC incidence following cessation of MHT, but others did not. This may reflect differences in BC incidence, in MHT use or in confounding factors, but also in study methodology. Aim To analyze the changes in BC incidence and MHT use, using the same methodology, in 11 European countries. Materials & method We limited the study to women between the ages of 45 and 69. BC incidence data were provided from cancer registries. MHT sales data were extracted from health sales databases for the years 2003-2013. The association between BC incidence and the rate of MHT use during the past year in Europe was assessed using linear mixed models. Results A drop in MHT sales was consistent in all countries for the whole period of follow-up. This was not the case for BC incidence. We found no evidence of a relation between BC incidence and MHT sales in the past year, except for sales of tibolone. Conclusions The longer observation period did not confirm the results of studies that had a shorter follow-up, except in relation to tibolone. The role of confounding factors needs to be clarified. © 2015 Elsevier Ireland Ltd. All rights reserved.
Brenguier R.,Universitelibre Of Bruxelles Ulb |
Raskin J.-F.,Universitelibre Of Bruxelles Ulb
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2015
In this paper, we study the set of thresholds that the protagonist can force in a zero-sum two-player multidimensional mean-payoff game. The set of maximal elements of such a set is called the Pareto curve, a classical tool to analyze trade-offs. As thresholds are vectors of real numbers in multiple dimensions, there exist usually an infinite number of such maximal elements. Our main results are as follow. First, we study the geometry of this set and show that it is definable as a finite union of convex sets given by linear inequations. Second, we provide a Σ2P algorithm to decide if this set intersects a convex set defined by linear inequations, and we prove the optimality of our algorithm by providing a matching complexity lower bound for the problem. Furthermore, we show that, under natural assumptions, i.e. fixed number of dimensions and polynomially bounded weights in the game, the problem can be solved in deterministic polynomial time. Finally, we show that the Pareto curve can be effectively constructed, and under the former natural assumptions, this construction can be done in deterministic polynomial time. © Springer International Publishing Switzerland 2015.
Desir J.,Universitelibre Of Bruxelles Ulb |
Sznajer Y.,Hopital Erasme ULB |
Sznajer Y.,Clinical Genetics Unit |
Depasse F.,Hopital Erasme ULB |
And 5 more authors.
European Journal of Human Genetics | Year: 2010
The latent TGFΒ-binding proteins (LTBPs) and fibrillins are a superfamily of large, multidomain proteins with structural and TGFΒ-signalling roles in the extracellular matrix. Their importance is underscored by fibrillin-1 mutations responsible for Marfan syndrome, but their respective roles are still incompletely understood. We report here on two families where children from healthy, consanguineous parents, presented with megalocornea and impaired vision associated with small, round, dislocated lenses (microspherophakia and ectopia lentis) and myopia, as well as a high-arched palate, and, in older children, tall stature with an abnormally large arm span over body height ratio, that is, associated features of Marfan syndrome. Glaucoma was not present at birth, but was diagnosed in older children. Whole genome homozygosity mapping followed by candidate gene analysis identified homozygous truncating mutations of LTBP2 gene in patients from both families. Fibroblast mRNA analysis was consistent with nonsense-mediated mRNA decay, with no evidence of mutated exon skipping. We conclude that biallelic null LTBP2 mutations cause the ocular phenotype in both families and could lead to Marfan-like features in older children. We suggest that intraocular pressures should be followed-up in young children with an ocular phenotype consisting of megalocornea, spherophakia and/or lens dislocation, and recommend LTBP2 gene analysis in these patients. © 2010 Macmillan Publishers Limited All rights reserved.
Pironio S.,Universitelibre Of Bruxelles Ulb
Journal of Physics A: Mathematical and Theoretical | Year: 2014
The correlations that admit a local hidden-variable model are described by a family of polytopes, whose facets are the Bell inequalities. The Clauser-Home-Shimony-Holt (CHSH) inequality is the simplest such Bell inequality and is a facet of every Bell polytope. We investigate for which Bell polytopes the CHSH inequality is also the unique (non-trivial) facet. We prove that the CHSH inequality is the unique facet for all bipartite polytopes where at least one party has a binary choice of dichotomic measurements, irrespective of the number of measurement settings and outcomes for the other party. Based on numerical results, we conjecture that it is also the unique facet for all bipartite polytopes involving two measurements per party where at least one measurement is dichotomic. Finally, we remark that these two situations can be the only ones for which the CHSH inequality is the unique facet, i.e., any polytope that does not correspond to one of these two cases necessarily has facets that are not of the CHSH form. As a byproduct of our approach, we derive a new family of facet inequalities. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to '50 years of Bell's theorem'. © 2014 IOP Publishing Ltd.