Human T cell glycosylation and implications on immune therapy for cancer

Glycosylation is an important post-translational modification, giving rise to a diverse and abundant repertoire of glycans on the cell surface, collectively known as the glycome. When focusing on immunity, glycans are indispensable in virtually all signaling and cell-cell interactions. More specifically, glycans have been shown to regulate key pathophysiological steps within T cell biology such as T cell development, thymocyte selection, T cell activity and signaling as well as T cell differentiation and proliferation. They are of major importance in determining the interaction of human T cells with tumor cells. In this review, we will describe the role of glycosylation of human T cells in more depth, elaborate on the importance of glycosylation in the interaction of human T cells with tumor cells and discuss the potential of cancer immunotherapies that are based on manipulating the glycome functions at the tumor immune interface

A guide to Mycobacterium mutagenesis

The genus Mycobacterium includes several pathogens that cause severe disease in humans, like Mycobacterium tuberculosis (M. tb), the infectious agent causing tuberculosis. Genetic tools to engineer mycobacterial genomes, in a targeted or random fashion, have provided opportunities to investigate M. tb infection and pathogenesis. Furthermore, they have allowed the identification and validation of potential targets for the diagnosis, prevention, and treatment of tuberculosis. This review describes the various methods that are available for the generation of mutants in Mycobacterium species, focusing specifically on tools for altering slow-growing mycobacteria from the M. tb complex. Among others, it incorporates the recent new molecular biological technologies (e.g. ORBIT) to rapidly and/or genome-wide comprehensively obtain targeted mutants in mycobacteria. As such, this review can be used as a guide to select the appropriate genetic tools to generate mycobacterial mutants of interest, which can be used as tools to aid understanding of M. tb infection or to help developing TB intervention strategies

Working Paper 08-08 - Welvaartsbinding van de sociale zekerheidsuitkeringen : een overzicht van de recente ontwikkelingen

Welfare programs, Social Security benefits

Reference genome and comparative genome analysis for the WHO reference strain for Mycobacterium bovis BCG Danish, the present tuberculosis vaccine

Background: Mycobacterium bovis bacillus Calmette-Guerin (M. bovis BCG) is the only vaccine available against tuberculosis (TB). In an effort to standardize the vaccine production, three substrains, i.e. BCG Danish 1331, Tokyo 172-1 and Russia BCG-1 were established as the WHO reference strains. Both for BCG Tokyo 172-1 as Russia BCG-1, reference genomes exist, not for BCG Danish. In this study, we set out to determine the completely assembled genome sequence for BCG Danish and to establish a workflow for genome characterization of engineering-derived vaccine candidate strains.ResultsBy combining second (Illumina) and third (PacBio) generation sequencing in an integrated genome analysis workflow for BCG, we could construct the completely assembled genome sequence of BCG Danish 1331 (07/270) (and an engineered derivative that is studied as an improved vaccine candidate, a SapM KO), including the resolution of the analytically challenging long duplication regions. We report the presence of a DU1-like duplication in BCG Danish 1331, while this tandem duplication was previously thought to be exclusively restricted to BCG Pasteur. Furthermore, comparative genome analyses of publicly available data for BCG substrains showed the absence of a DU1 in certain BCG Pasteur substrains and the presence of a DU1-like duplication in some BCG China substrains. By integrating publicly available data, we provide an update to the genome features of the commonly used BCG strains. Conclusions: We demonstrate how this analysis workflow enables the resolution of genome duplications and of the genome of engineered derivatives of the BCG Danish vaccine strain. The BCG Danish WHO reference genome will serve as a reference for future engineered strains and the established workflow can be used to enhance BCG vaccine standardization

Working Paper 22-10 - Toereikendheid van het pensioen en budgettaire kosten van de vergrijzing: evaluatie van beleidsmaatregelen en van alternatieve scenario’s

Statutory pensions, Adequacy, Microsimulation, Social security

Working Paper 04-11 - Welvaartsbinding van sociale en bijstandsuitkeringen

One of the main sections in the current draft of the 2011-2012 Interprofessional Agreement concerns the welfare adjustment of social benefits. This draft results from a long process and fits in with the law concerning the Solidarity Pact between the Generations, which established a structural mechanism at the end of 2005, linking social benefits to welfare evolution. This working paper ‘Welfare adjustment of social benefits' describes the first stage of that process: estimating the disposable financial means for the welfare adjustment of social benefits for the period 2011-2012, to which the Federal Planning Bureau contributed. In the employees scheme these means amount to 233.8 million in 2011 and to 497.9 million in 2012, of which the draft of the Interprofessional Agreement proposes to utilize merely 60%. Furthermore, this paper offers an overview of Belgian social policy by portraying its main turning points on the one hand and analysing the evolution of the average amounts of the main social benefits since 1980 on the other. The outcome is marked with contrast: over the period 1980-2009 the relative standard of living globally improved for pensioners, as opposed to the unemployed and the disabled.Welfare programs, Social Security benefits

Characterization of genome-wide ordered sequence-tagged Mycobacterium mutant libraries by Cartesian Pooling-Coordinate Sequencing

Reverse genetics research approaches require the availability of methods to rapidly generate specific mutants. Alternatively, where these methods are lacking, the construction of pre-characterized libraries of mutants can be extremely valuable. However, this can be complex, expensive and time consuming. Here, we describe a robust, easy to implement parallel sequencing-based method (Cartesian Pooling-Coordinate Sequencing or CP-CSeq) that reports both on the identity as well as on the location of sequence-tagged biological entities in well-plate archived clone collections. We demonstrate this approach using a transposon insertion mutant library of the Mycobacterium bovis BCG vaccine strain, providing the largest resource of mutants in any strain of the M. tuberculosis complex. The method is applicable to any entity for which sequence-tagged identification is possible