Belgian federalism after the sixth state reform

This paper highlights the most important institutional evolutions of Belgian federalism stemming from the implementation of the sixth state reform (2012-2014). This reform inter alia included a transfer of powers worth 20 billion euros from the federal level to the level of the federated states, a profound reform of the Senate, and a substantial increase in fiscal autonomy for the regions. This contribution critically analyses the current state of Belgian federalism. Although the sixth state reform realized important and long-awaited changes, further evolutions are to be expected. Since the Belgian state model has reached its limits with regard to complexity and creativity, politicians and academics should begin to reflect on the seventh state reform with the aim of increasing the transparency of the current Belgian institutional labyrint

Overcoming steroid resistance in T cell acute lymphoblastic leukemia

In a Perspective, Pieter Van Vlierberghe and Steven Goossens discuss Meijerink and colleagues' findings on steroid resistance in pediatric T cell acute lymphoblastic leukemia

Idiopathische haemochromatose : een onderzoek bij drie families

Haemochromatose kan op verschillende wijzen worden gedefinieerd. Zo verstaat de klinicus onder haemochromatose en haemosiderose vaak iets anders dan de patholoog-anatoom. In dit proefschrift wordt onder haemochromatose verstaan een syndroom, waarbij cirrhose of fibrose van de lever gepaard gaat met een vergrote ijzervoorraad. Onder idiopathische haemochromatose (LH.) verstaat men die ijzerstapelingsziekte die overblijft, nadat bekende oorzaken van ijzerstapeling zijn uitgesloten (zie hoofdstuk I, 4). Onder haemosiderose wordt vergrote ijzervoorraad zonder weefselbeschadiging verstaan. Uit de overzichtsartikelen van Sheldon (412), Finch and Finch (140), Darnis (107), Barry (28), Walker en Williams (468), Grace en Powell (175), Sourel en Sirnon (60) en Powell (373) blijkt, dat het klinisch beeld op zichzelf onvoldoende zekerheid biedt bij het stellen van de diagnose. Diabetes, pigmentatie van de huid en testisatrophie komen vaak voor bij de alcoholische levercirrhose en verschillende graden van ijzerstapeling kunnen voorkomen bij refractaire anaemieën, porphyria cutanea tarda of na porto-cavale anastomosen. Voor de diagnostiek is men dus aangewezen op de leverbiopsie en op methoden om een vergrote ijzervoorraad aan te tonen (zie hoofdstuk I, 6)

Developments in Belgian constitutional law : the year 2016 in review

This contribution presents an overview of the Belgian Constitutional Court and its activities during 2016. Two constitutional controversies that were at the forefront of political discussions and attracted much media attention are discussed, namely the separation of powers and the refugee "crisis" as well as the Comprehensive Economic and Trade Agreement (CETA) between the European Union and Canada. Moreover, the article gives an overview of the main cases of the Belgian Constitutional Court of the past year that may be of interest to an international audience. These cases are divided into the following categories: the Belgian Constitution in Europe and the world, separation of powers, justice and order, ethical issues and hot topics

Gene expression analysis in specific cell populations of bovine blastocysts using laser capture microdissection

Laser capture microdissection (LCM) has become a powerful technique for the isolation of specific cell populations from heterogeneous tissues for gene expression analysis. For standard laser capture microdissection procedures, snap freezing and cryosectioning is the optimal fixation and processing procedure. This sufficiently preserves RNA integrity for downstream molecular analysis. However, in the case of small sized samples, such as early stage embryos, snap freezing and cryosectioning is highly complex and frequently leads to the loss of valuable samples. In the present study, a protocol was optimized to specifically isolate the inner cell mass cells from bovine blastocysts with LCM on chemically fixated paraffin embedded embryos. Bovine blastocysts were fixed for 24h in a methacarn fixative (8 parts methanol, 1 part acetic acid), upon which they were embedded in 2% agarose. After paraffin embedding of the agarose blocks, serial sections of 10 µm were cut and adhered to glass slides. The slides were deparaffinized in xylene, stained with 0.1% cresyl violet in 85% ethanol, and dehydrated in xylene. Subsequently the trophectoderm cells and the inner cell mass cells were separately isolated using LCM. The RNA of the samples was isolated, and subjected to different tests to evaluate the purity of the samples and the quality of the RNA. Expression of Cytokeratin 18 which is only expressed in trophectoderm revealed that the isolated cells were highly pure. An amplicon length assay and a 3’-5’ assay revealed that the RNA quality was sufficient for gene expression analysis with RT-qPCR. In conclusion, LCM on blastocysts is well suited for gene expression analysis of specific cell populations, providing a novel strategy to investigate molecular pathways for pluripotency and cell fate development. This procedure is also compatible with micro-RNA profiling strategies, and the application for downstream transcriptome sequencing is currently being evaluated

Convergence of virulence and antimicrobial resistance in increasingly prevalent Escherichia coli ST131 papGII+ sublineages

Escherichia coli lineage ST131 is an important cause of urinary tract and bloodstream infections worldwide and is highly resistant to antimicrobials. Specific ST131 lineages carrying invasiveness-associated papGII pathogenicity islands (PAIs) were previously described, but it is unknown how invasiveness relates to the acquisition of antimicrobial resistance (AMR). In this study, we analysed 1638 ST131 genomes and found that papGII+ isolates carry significantly more AMR genes than papGII-negative isolates, suggesting a convergence of virulence and AMR. The prevalence of papGII+ isolates among human clinical ST131 isolates increased dramatically since 2005, accounting for half of the recent E. coli bloodstream isolates. Emerging papGII+ lineages within clade C2 were characterized by a chromosomally integrated blaCTX-M-15 and the loss and replacement of F2:A1:B- plasmids. Convergence of virulence and AMR is worrying, and further dissemination of papGII+ ST131 lineages may lead to a rise in severe and difficult-to-treat extraintestinal infections

Teaching an old dog new tricks : activity-on-target interferon to treat T-cell acute lymphoblastic leukemia

Background Type 1 interferon (IFN) has a long history in the treatment of cancer, including hematological malignancies. The anti-cancer effects induced by IFN result from a combination of 1) direct cancer cell growth inhibition by cell cycle arrest, apoptosis, or differentiation and 2) the activation of the immune system involving antigen presentation by Clec9A+ dendritic cells and priming of cytotoxic CD8+ T-cells. However, IFN therapy experienced variable and unpredictable success in the clinic. Its clinical application is severely impeded by a complex pattern of adverse side-effects, due to the multifaceted activity pattern of IFN. Therefore, safe exploitation of the anti-cancer potential of IFN requires strategies to direct their activity to selected target cells, avoiding systemic toxicity. Aims Safe exploitation of the anti-cancer potential of IFN requires strategies to direct their activity to selected target cells, avoiding systemic toxicity. Methods To improve the therapeutic index of IFN, we have developed AcTaferons (Activity-on-Target Interferon), optimized (mutant) immunocytokines. Mutated IFNa2Q124R, with a strongly reduced affinity for its receptor complex, was fused to single domain antibodies targeting cell-specific domains, which selectively restores the AcTaferon (AFN) activity in a cell-type specific manner. As such, CD8-AFN and Clec9A-AFN were generated which selectively target either CD8+ T(-ALL) cells or Clec9A+ dendritic cells. Results Using CD8- and CD8+ mouse T-ALL cell lines, we evaluated the direct and indirect anti-leukemic effects of our novel AFNs, in vitro and in vivo upon transplantation in immunocompromised and immunocompetent syngeneic hosts. A significant reduction in the leukemic burden was observed. These anti-cancer effects of AFN were similar as observed for the wildtype IFN, but in a cell-type specific manner and with drastically reduced adverse side-effects. Monotherapy was even sufficient to completely cure a proportion of leukemic mice, which highlights the strong anti-leukemic power of these optimized immunocytokines. Strinkingly only the direct effect CD8-AFN on in vivo CD8+ T-ALL was synergistic with asparaginase treatment. No synergism was observed between asparaginase and the indirect immune-mediated Clec9A-AFN anti-leukemic effect. Conclusion In conclusion, we have developed novel optimized immunocytokines as an off-the-shelve targeted immunotherapy for T-ALL