Université catholique de Louvain

About: Université catholique de Louvain is a education organization based out in Louvain-la-Neuve, Belgium. It is known for research contribution in the topics: Population & Catalysis. The organization has 25319 authors who have published 57360 publications receiving 2172080 citations. The organization is also known as: University of Louvain & UCLouvain.

Antiparallel beta-sheet: a signature structure of the oligomeric amyloid beta-peptide.

Abstract: AD (Alzheimer's disease) is linked to Abeta (amyloid beta-peptide) misfolding. Studies demonstrate that the level of soluble Abeta oligomeric forms correlates better with the progression of the disease than the level of fibrillar forms. Conformation-dependent antibodies have been developed to detect either Abeta oligomers or fibrils, suggesting that structural differences between these forms of Abeta exist. Using conditions which yield well-defined Abeta-(1-42) oligomers or fibrils, we studied the secondary structure of these species by ATR (attenuated total reflection)-FTIR (Fourier-transform infrared) spectroscopy. Whereas fibrillar Abeta was organized in a parallel beta-sheet conformation, oligomeric Abeta displayed distinct spectral features, which were attributed to an antiparallel beta-sheet structure. We also noted striking similarities between Abeta oligomers spectra and those of bacterial outer membrane porins. We discuss our results in terms of a possible organization of the antiparallel beta-sheets in Abeta oligomers, which may be related to reported effects of these highly toxic species in the amyloid pathogenesis associated with AD.

JAK/STAT signaling in hematological malignancies

Abstract: The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is central to signaling by cytokine receptors, a superfamily of more than 30 transmembrane proteins that recognize specific cytokines, and is critical in blood formation and immune response. Many of those receptors transmit anti-apoptotic, proliferative and differentiation signals, and their expression and functions are critical for the formation of blood lineages. Several cancers, including blood malignancies, have been associated with constitutive activation of members of the STAT family, which normally require JAK-mediated tyrosine phosphorylation for transcriptional activation. More recently, human myeloproliferative neoplasms were discovered to be associated with a unique acquired somatic mutation in JAK2 (JAK2 V617F), rare exon 12 JAK2 mutations, or thrombopoietin receptor mutations that constitutively activate wild-type JAK2. Prompted by these observations, many studies have explored the possibility that JAKs, cytokine receptors, or other components of the JAK/STAT pathway are mutated or upregulated in several hematological malignancies. This has been observed in certain pediatric acute lymphoblastic leukemias and adult T-cell lymphoblastic leukemias, and overexpression of JAK2 seems to be important in Hodgkin lymphoma. Here we discuss the nature and respective contribution of mutations dysregulating the JAK/STAT pathway in hematological malignancies and present examples in which such mutations drive the disease, contribute to the phenotype, or provide a survival and proliferative advantage. JAK inhibitors are making their way into the therapeutic arsenal (for example, in myelofibrosis), and we discuss the possibility that other hematological diseases might benefit from treatment with these inhibitors in combination with other agents.

Polycyanoacrylate nanocapsules as potential lysosomotropic carriers: preparation, morphological and sorptive properties

Abstract: p. COUVREUR*§, B. KANTE*, M. ROLAND', P. C h O T I ' , P. BAUDUIN'f, P. SPEISER~, Laboratoire de Pharmacie Galinique, Universite' Catholique de Louvain, B-1200 Bruxelles Belgium. t Laboratoire de Chimie Physiologique, UniversitP Catholique de Louvain and International Institute of Cellular and Molecular Pathology, B-1200 Bruxelles, Belgium. '$ Phartnareutische Institut, Eidgenossische Technische Hochschule, CH-Zurich, Switzerland.