Academic clinical trials run by the transplant committee of the Belgian Hematological Society

The Transplantation Committee of the Belgian Hematological Society (BHS) is supported by all university centers and nonuniversity centers with significant transplant activity. The committee is involved in the development of transplant guidelines and recommendations, the transplant peer review process, contacts with regulatory authorities, the introduction of expanded access and medical need programs and the initiation of academic studies addressing important questions in the transplant field. Since 2008, 8 clinical trials have been initiated after approval by the Ethics Committees and the National Competent Authority (AFMPS/FAGG). So far, one of them has been completed and is being prepared for publication. In this paper, we briefly describe the rationale, objectives, treatment arms, major inclusion criteria and current status of these different trials. In addition and for each trial a link is provided to the BHS website to obtain more details regarding inclusion criteria, participating centers and administrative/contact informatio

HIV viraemic patients downregulate CD94/NKG2A inhibitory receptors on NK as well as CD8 T cells in comparison with aviraemic counterparts

Background: The CD94/NKG2 heterodimer is a C-type lectin receptor formed by the association of CD94 and one of the NKG2 molecules (namely NKG2A, -B, -C or –E). The interaction of CD94/NKG2A with non classical HLA-E molecules delivers inhibitory signals. CD94/NKG2A is normally expressed on most NK cells whereas less than 5% of peripheral resting CD8+ T cells are positive. Although several reports have clearly shown an upregulation of CD94 on CD8 T cells in HIV infection, the simultaneous expression of both subunits of the inhibitory receptor on NK and T cells and its relation with viral load is largely unknown. Methods: PBLs from 30 HIV-infected patients (16 viraemic and 14 aviraemic under HAART) and 18 healthy volunteers were analysed by flow cytometry after staining with the following monoclonal antibodies (Percp-conjugated anti-CD8, FITC-conjugated anti-CD3, APC-conjugated anti-CD94, PE-conjugated anti-NKG2A). Results: The proportion of CD8 T cells expressing the CD94/NKG2A inhibitory receptor was not significantly increased in HIV-infected patients (5.68 ± 3.72%) in comparison with non-infected controls (4.90±2.84%). Interestingly, patients with viral load < 50 copies/ml had a higher proportion of CD8 T cells expressing the inhibitory receptor (7.15 ± 3.63%) than patients with HIV viraemia (4.40 ± 3.40%), p= 0.041. The same pattern was observed for NK cells and was even more pronounced. In aviraemic individuals, 61.75 ± 20.39% of NK cells expressed the inhibitory receptor vs 42.88 ± 26.38% in viraemic patients. The proportion of CD94/NKG2A positive cells was correlated between NK and CD8 T cell subsets (p=0.0351) but there was no correlation with absolute or relative CD4 counts. Conclusions: Our results suggest that chronic stimulation with HIV antigens in viraemic patients could lead to decreased rather than increased expression of inhibitory receptors on NK and CD8 T cells. This could contribute to the abnormal activation of the immune system associated with advanced HIV disease

Downregulation of CD94/NKG2A inhibitory receptors on CD8+ T cells in HIV infection is more pronounced in subjects with detected viral load than in their aviraemic counterparts

The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small fraction of activated CD8+ T lymphocytes. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection. In this study, CD94/NKG2A receptor expression on CD8+ T lymphocytes and NK cells was assessed in 46 HIV-1-infected patients (24 viraemic, 22 aviraemic) and 10 healthy volunteers. The percentage of CD8+ T lymphocytes expressing the CD94/NKG2A inhibitory heterodimer was very significantly decreased in HIV-1-infected patients in comparison with non-infected controls. Within the HIV infected patients, the proportion of CD8+ T lymphocytes and NK cells expressing CD94/NKG2A was higher in subjects with undetectable viral loads in comparison with their viraemic counterparts. No significant difference was detected in the proportion of CD8+ T lymphocytes expressing the activatory CD94/NKG2C heterodimer between the HIV-1 infected patients and the healthy donors, nor between the vireamic and avireamic HIV-1 infected patients. In conclusion, chronic stimulation with HIV antigens in viraemic patients leads to a decreased rather than increased CD94/NKG2A expression on CD8+ T lymphocytes and NK cells

Improving Vaccine-Induced Immunity: Can Baseline Predict Outcome?

Immune signatures measured at baseline and immediately prior to vaccination may predict the immune response to vaccination. Such pre-vaccine assessment might allow not only population-based, but also more personalized vaccination strategies ('precision vaccination'). If baseline immune signatures are predictive, the underlying mechanism they reflect may also determine vaccination outcome. Thus, baseline signatures might contribute to identifying interventional targets to be modulated prior to vaccination in order to improve vaccination responses. This concept has the potential to transform vaccination strategies and usher in a new approach to improve global health

1T Pixel Using Floating-Body MOSFET for CMOS Image Sensors

We present a single-transistor pixel for CMOS image sensors (CIS). It is a floating-body MOSFET structure, which is used as photo-sensing device and source-follower transistor, and can be controlled to store and evacuate charges. Our investigation into this 1T pixel structure includes modeling to obtain analytical description of conversion gain. Model validation has been done by comparing theoretical predictions and experimental results. On the other hand, the 1T pixel structure has been implemented in different configurations, including rectangular-gate and ring-gate designs, and variations of oxidation parameters for the fabrication process. The pixel characteristics are presented and discussed

Methylation of the Vitamin D Receptor (VDR) Gene, Together with Genetic Variation, Race, and Environment Influence the Signaling Efficacy of the Toll-Like Receptor 2/1-VDR Pathway

BackgroundThe disparity in prevalence of infectious diseases across the globe is common knowledge. Vitamin D receptor (VDR)-mediated toll-like receptor (TLR) 2/1 signaling produces antimicrobial peptides, which is critical as a first line of defense in innate immunity. Numerous studies disclosed the independent role of genetic polymorphisms in this pathway, vitamin D status or season and more recently epigenetics, as factors contributing to infectious disease predisposition. Few studies address the interaction between environment, genetics, and epigenetics. Here, we hypothesized that VDR-mediated TLR2/1 signaling is influenced by a combination of environment, epigenetics and genetics, collectively influencing differential innate immunity.MethodsHealthy Black and White South Africans (n = 100) donated blood, while ultraviolet index (UVI) was recorded for the duration of the study. LC-MS/MS supported 25(OH)D3 quantification. Monocyte/macrophage cultures, supplemented with/without 1,25(OH)2D3, were activated with the TLR2/1 elicitor, Pam3CSK4. VDR, cathelicidin antimicrobial peptide, hCAP-18, and 25-hydroxyvitamin D3-24-hydroxylase expression were quantified by RT-qPCR or flow cytometry. Pyrosequencing facilitated VDR methylation analysis and single-nucleotide polymorphism (SNP) genotyping in regions pinpointed through a bioinformatics workflow.ResultsSeason interacted with race showing 25(OH)D3 deficiency in Blacks. UVI correlated with 25(OH)D3 and VDR methylation, likely influencing race differences in the latter. Regarding the TLR2/1 pathway, race differences in SNP genotype distribution were confirmed and functional analysis of VDR-mediated signaling showed interaction between race, season, and 25(OH)D3 status. Multivariate OPLS-DA mirrored several interactions between UVI, 25(OH)D3 status, DNA sequence, and methylation variants. Methylation of the third cytosine-phosphate-guanine dinucleotide (CpG) in the promoter CpG island (CGI) 1062, CGI 1062 CpG 3, significantly discriminated a 5.7-fold above average mean in VDR protein level upon TLR2/1 elicitation, the variation of which was further influenced by 25(OH)D3 status and the VDR SNP TaqI.ConclusionRegulation of VDR-mediated TLR2/1 signaling is multifactorial, involving interaction between environment [UVI and consequent 25(OH)D3 status], epigenetics (VDR methylation at key regulatory sites), and genetics (TLR1, TIRAP, and VDR SNPs)

Identification of metabolic pathways influenced by the G-protein coupled receptors GprB and GprD in Aspergillus nidulans

Heterotrimeric G-protein-mediated signaling pathways play a pivotal role in transmembrane signaling in eukaryotes. Our main aim was to identify signaling pathways regulated by A. nidulans GprB and GprD G-protein coupled receptors (GPCRs). When these two null mutant strains were compared to the wild-type strain, the DeltagprB mutant showed an increased protein kinase A (PKA) activity while growing in glucose 1% and during starvation. In contrast, the DeltagprD has a much lower PKA activity upon starvation. Transcriptomics and (1)H NMR-based metabolomics were performed on two single null mutants grown on glucose. We noted modulation in the expression of 11 secondary metabolism gene clusters when the DeltagprB and DeltagprD mutant strains were grown in 1% glucose. Several members of the sterigmatocystin-aflatoxin gene cluster presented down-regulation in both mutant strains. The genes of the NR-PKS monodictyphenone biosynthesis cluster had overall increased mRNA accumulation in DeltagprB, while in the DeltagprD mutant strain the genes had decreased mRNA accumulation. Principal component analysis of the metabolomic data demonstrated that there was a significant metabolite shift in the DeltagprD strain. The (1)H NMR analysis revealed significant expression of essential amino acids with elevated levels in the DeltagprD strain, compared to the wild-type and DeltagprB strains. With the results, we demonstrated the differential expression of a variety of genes related mainly to secondary metabolism, sexual development, stress signaling, and amino acid metabolism. We propose that the absence of GPCRs triggered stress responses at the genetic level. The data suggested an intimate relationship among different G-protein coupled receptors, fine-tune regulation of secondary and amino acid metabolisms, and fungal development

Brief reports: are voluntary switches corrected repetitions?

While recent years have witnessed a growing interest in Voluntary Task Switching (VTS), the control mechanisms that are required in order to switch tasks on a voluntary basis remain to be identified. Starting from the finding that in VTS the proportion of task repetitions is usually higher than the proportion of task switches (task-repetition bias), the present electrophysiological study tests and confirms the hypothesis that, during VTS, one initially re-selects the previously executed task, before correcting this bias and selecting the alternative task. On the one hand, these findings allow us to describe how people switch cognitive tasks voluntarily. On the other hand, our approach underlines the usefulness of electrophysiological measures in understanding the processes by which voluntary behavior occurs

Rottlerin inhibits human T cell responses.

Rottlerin is a pharmacological inhibitor of protein kinase C (PKC) theta, a novel PKC selectively expressed in T lymphocytes. PKC theta is known to regulate T cell receptor (TCR)/CD28 signalling pathways in T lymphocytes, but the impact of PKC theta inhibition on human T cell responses remains undefined. In this work, we describe the effects of rottlerin on the responses of CD4+ and CD8+ human T lymphocytes upon polyclonal activation. We observed a dose-dependent inhibition of CD4+ and CD8+ T cell proliferation in response to anti-CD3/anti-CD28 antibodies stimulation in the presence of rottlerin. This inhibition was associated with impaired CD25 expression and decreased interleukin (IL)-2 production in activated T cells. In contrast, rottlerin did not alter IL-2-induced T cell proliferation. Furthermore, we demonstrated that rottlerin blocked interferon (IFN) gamma, IL-10 and IL-13 mRNA expression in TCR/CD28 activated CD4+ T cells. These findings place rottlerin as a potent immunosuppressive agent for the development of novel therapies in T cell mediated immune disorders.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Observation au MEB environnemental des gonflements de films fin d'argile induits par des variations d'humidité relative

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