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Luxembourg, Luxembourg

Szpakowska M.,CRP Sante | Fievez V.,CRP Sante | Arumugan K.,CRP Sante | Van Nuland N.,Vrije Universiteit Brussel | And 3 more authors.
Biochemical Pharmacology

Chemokines and their receptors play fundamental roles in many physiological and pathological processes such as leukocyte trafficking, inflammation, cancer and HIV-1 infection. Chemokine-receptor interactions are particularly intricate and therefore require precise orchestration. The flexible N-terminal domain of human chemokine receptors has regularly been demonstrated to hold a crucial role in the initial recognition and selective binding of the receptor ligands. The length and the amino acid sequences of the N-termini vary considerably among different receptors but they all show a high content of negatively charged residues and are subject to post-translational modifications such as O-sulfation and N- or O-glycosylation. In addition, a conserved cysteine that is most likely engaged in a receptor-stabilizing disulfide bond delimits two functionally distinct parts in the N-terminus, characterized by specific molecular signatures. Structural analyses have shown that the N-terminus of chemokine receptors recognizes a groove on the chemokine surface and that this interaction is stabilized by high-affinity binding to a conserved sulfotyrosine-binding pocket. Altogether, these data provide new insights on the chemokine-receptor molecular interplay and identify the receptor N-terminus-binding site as a new target for the development of therapeutic molecules. This review presents and discusses the diversity and function of human chemokine receptor N-terminal domains and provides a comprehensive annotated inventory of their sequences, laying special emphasis on the presence of post-translational modifications and functional features. Finally, it identifies new molecular signatures and proposes a computational model for the positioning and the conformation of the CXCR4 N-terminus grafted on the first chemokine receptor X-ray structure. © 2012 Elsevier Inc. Source

Arendt J.,Center Hospitalier Luxembourg
Bulletin de la Société des sciences médicales du Grand-Duché de Luxembourg

In the case of early ovary extinction, the only way to have a child is either adoption or egg/embryo reception by donation. To day, egg donation is prohibited in Luxembourg by ministerial decision in 2003. Germ cell donation is part of artificial reproductive therapy. Oocyte donation, in particular, needs to be done by IVF treatment, which makes it more complicated then sperm donation What makes it more difficult is the fact that there are no oocyte bank yet. Today, prohibition encourages procreative tourism what only wealthy people can afford. Although donation programs are well established many questions arise about egg donation such as refunds, divulging information, women's age limit, health insurance participation. Source

Lesur A.,CRP Sante | Ancheva L.,CRP Sante | Kim Y.J.,CRP Sante | Berchem G.,CRP Sante | And 3 more authors.
Proteomics - Clinical Applications

Purpose: We report an immunocapture strategy to extract proteins known to harbor driver mutations for a defined cancer type before the simultaneous assessment of their mutational status by MS. Such a method bypasses the sensitivity and selectivity issues encountered during the analysis of unfractionated complex biological samples. Experimental design: Fast LC separations using short nanobore columns hyphenated with a high-resolution quadrupole-orbitrap mass spectrometer have been devised to take advantage of fast MS cycle times in conjunction with sharp chromatographic peak widths to accelerate the sample analysis throughput. Such an analytical platform is well suited to analyze simple protein mixtures obtained after immunoaffinity enrichment. Results: After establishing the technical performance of the platform, the method was applied to the quantitative profiling of cellular Ras and EGFR protein isoforms, as well as serum amyloid A isoforms in plasma. Conclusions and clinical relevance: Immunoaffinity purification combined with fast LC-MS detection for the detection of driver mutations in tissue and tumor biomarkers in plasma samples can assist clinicians to select an optimal therapeutic intervention for patients. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Delhalle S.,CRP Sante | Schmit J.-C.,CRP Sante | Schmit J.-C.,Center Hospitalier Luxembourg | Chevigne A.,CRP Sante
International Journal of Molecular Sciences

The complex hide-and-seek game between HIV-1 and the host immune system has impaired the development of an efficient vaccine. In addition, the high variability of the virus impedes the long-term control of viral replication by small antiviral drugs. For more than 20 years, phage display technology has been intensively used in the field of HIV-1 to explore the epitope landscape recognized by monoclonal and polyclonal HIV-1-specific antibodies, thereby providing precious data about immunodominant and neutralizing epitopes. In parallel, biopanning experiments with various combinatorial or antibody fragment libraries were conducted on viral targets as well as host receptors to identify HIV-1 inhibitors. Besides these applications, phage display technology has been applied to characterize the enzymatic specificity of the HIV-1 protease. Phage particles also represent valuable alternative carriers displaying various HIV-1 antigens to the immune system and eliciting antiviral responses. This review presents and summarizes the different studies conducted with regard to the nature of phage libraries, target display mode and biopanning procedures. © 2012 by the authors. Source

Corsten M.F.,Universiteitssingel 50 | Dennert R.,Universiteitssingel 50 | Jochems S.,Universiteitssingel 50 | Kuznetsova T.,Catholic University of Leuven | And 7 more authors.
Circulation: Cardiovascular Genetics

Background - Small RNA molecules, called microRNAs, freely circulate in human plasma and correlate with varying pathologies. In this study, we explored their diagnostic potential in a selection of prevalent cardiovascular disorders. Methods and Results - MicroRNAs were isolated from plasmas from well-characterized patients with varying degrees of cardiac damage: (1) acute myocardial infarction, (2) viral myocarditis, (3) diastolic dysfunction, and (4) acute heart failure. Plasma levels of selected microRNAs, including heart-associated (miR-1, -133a, -208b, and -499), fibrosisassociated (miR-21 and miR-29b), and leukocyte-associated (miR-146, -155, and -223) candidates, were subsequently assessed using real-time polymerase chain reaction. Strikingly, in plasma from acute myocardial infarction patients, cardiac myocyte-associated miR-208b and -499 were highly elevated, 1600-fold (P<0.005) and 100-fold (P<0.0005), respectively, as compared with control subjects. Receiver operating characteristic curve analysis revealed an area under the curve of 0.94 (P<10-10) for miR-208b and 0.92 (P<10-9) for miR-499. Both microRNAs correlated with plasma troponin T, indicating release of microRNAs from injured cardiomyocytes. In viral myocarditis, we observed a milder but significant elevation of these microRNAs, 30-fold and 6-fold, respectively. Plasma levels of leukocyte-expressed microRNAs were not significantly increased in acute myocardial infarction or viral myocarditis patients, despite elevated white blood cell counts. In patients with acute heart failure, only miR-499 was significantly elevated (2-fold), whereas no significant changes in microRNAs studied could be observed in diastolic dysfunction. Remarkably, plasma microRNA levels were not affected by a wide range of clinical confounders, including age, sex, body mass index, kidney function, systolic blood pressure, and white blood cell count. Conclusions - Cardiac damage initiates the detectable release of cardiomyocyte-specific microRNAs-208b and -499 into the circulation. © 2010 American Heart Association, Inc. Source

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