Technologie en innovatie in Vlaanderen: Prioriteiten.

Vlaanderen;

The human homologue of Caenorhabditis elegans CED-6 specifically promotes phagocytosis of apoptotic cells

AbstractA key feature of the process of programmed cell death (apoptosis) is the efficiency with which the dying cells are recognized and engulfed by phagocytes [1]. Apoptotic cells are rapidly cleared either by neighbouring cells acting as semi-professional phagocytes or by experts of the macrophage line, so that an inflammatory response is avoided [2]. The Caenorhabditis elegans gene ced-6 is required for efficient engulfment of apoptotic cells [3] and is one of a group of genes that define two partially redundant parallel pathways for the engulfment process [4,5]. These pathways may be conserved across evolution, as two other engulfment genes have human homologues. A CED-5 homologue is part of a human CrkII–DOCK180–Rac signaling pathway proposed to mediate cytoskeletal reorganization [6–8] and a CED-7 homologue is similar to the ABC transporters [9,10]. Here, we report the cloning and characterization of human CED-6, a human homologue of C. elegans CED-6. The 34 kDa hCED-6 protein is expressed in most tissues, some human cancer cells, and in primary human macrophages. We developed an assay that quantitates the phagocytic activity of mammalian macrophages: the number of apoptotic cells that have been internalized is measured by the uptake of lacZ-positive apoptotic cells by adherent transgenic macrophages. The results of this assay demonstrate that overexpression of hCED-6 promotes phagocytosis only of apoptotic cells and suggest that hCED-6 is the mammalian orthologue of C. elegans CED-6 and is a part of a highly conserved pathway that specifically mediates the phagocytosis of apoptotic cells

EPTRI Belgian Joint Research Unit : harmonisation and concertation of paediatric research in Belgium to ensure better and safer healthcare for children

We want to put the excellent translational paediatric research in Belgium on the ESFRI national roadmap in order to participate in the European Paediatric Translational Research Infrastructure (EPTRI) project. Therefore, we are in the preparatory phase to form a Belgian national EPTRI Joint Research Unit (JRU). Academic research organisations and hospitals from both regions, Flanders and Wallonia are currently involved. The Belgian JRU partners will gather complementary scientific and technological competencies in the different EPTRI thematic research platforms: 1. Paediatric medicines discovery: with different types of “in vitro” paediatric models, placental and umbilical cord and 3D organoid cell cultures from paediatric samples and juvenile animal models such as the rabbit BPD model, juvenile Göttingen minipig, juvenile conventional pig model and developmental zebrafish model; 2. Paediatric biomarkers and biosamples: identification, characterisation and validation of the biomarkers used as prognostic tools, safety markers and diagnostic tools in paediatric diseases; 3. Developmental pharmacology: including PK (bioavaibility/bioequivalence) studies, Population PKPD analysis and PK/PD modelling; 4. Paediatric medicines formulations and medical devices: including regulatory knowledge of paediatric medical devices. The partners will ensure a strong liaison with other RI’s such as the BBMRI-ERIC for paediatric biobanking and the IMI conect4children network paediatric clinical trials. We propose an integrated paediatric research system that links together EPTRI Belgium with landmark RIs, conect4children and the many paediatric clinical research networks and institutions that provide services to paediatric research. This integrated system can provide: expertise, experienced facilities and practical support for pre-clinical and clinical paediatric research in Belgium and Europe. Sharing understanding of patients’ needs and concerted efforts in paediatric research will further enhance the health of children

Bilaterale osteochondritis dissecans van de laterale taluskam bij een jonge rottweiler

In this case report, a young Rottweiler is described that suffered from bilateral osteochondritis dissecans of the talus. The signalment, history and clinical signs were typical for this condition, but atypically, the lateral trochlear ridges were affected. Due to the large size of the fragments, the prognosis was reserved. However, one year after surgery, the clinical outcome was surprisingly good. The left and right trochlear ridges seemed to be filled up with osseous material

Tumorbank@uza: A Collection of Tissue, Fluid Samples and Associated Data of Oncology Patients for the Use in Translational Research

Tumorbank@UZA is an academic hospital integrated biobank that collects tissue, blood and urine samples from oncology patients. We work according to a quality management system and have established SOPs for all work procedures in the biobank. Tumorbank@UZA is funded by the National Cancer Plan, an initiative from the Belgian government since 2009. Samples from our biobank are available for both academic as well as commercial researchers, through a well-established access procedure. Currently the collection consists of more than 85.000 samples of more than 8000 patients. Funding statement: Tumorbank@UZA is funded by the National Cancer Plan (initiative 27) from the Ministry of Health of the Belgian Federal Government.</p

Differential Effects of Awake Glioma Surgery in "Critical" Language Areas on Cognition:4 Case Studies

Awake surgery with electrocorticosubcortical stimulation is the golden standard treatment for gliomas in eloquent areas. Preoperatively, mostly mild cognitive disturbances are observed with postoperative deterioration. We describe pre- and postoperative profiles of 4 patients (P1–P4) with gliomas in “critical” language areas (“Broca,” “Wernicke,” and the arcuate fasciculus) undergoing awake surgery to get insight into the underlying mechanism of neuroplasticity. Neuropsychological examination was carried out preoperatively (at T1) and postoperatively (at T2, T3). At T1, cognition of P1 was intact and remained stable. P2 had impairments in all cognitive domains at T1 with further deterioration at T2 and T3. At T1, P3 had impairments in memory and executive functions followed by stable recovery. P4 was intact at T1, followed by a decline in a language test at T2 and recovery at T3. Intraoperatively, in all patients language positive sites were identified. Patients with gliomas in “critical” language areas do not necessarily present cognitive disturbances. Surgery can either improve or deteriorate (existing) cognitive impairments. Several factors may underlie the plastic potential of the brain, for example, corticosubcortical networks and tumor histopathology. Our findings illustrate the complexity of the underlying mechanism of neural plasticity and provide further support for a “hodotopical” viewpoint

Biobanking for Viral Hepatitis Research

Introduction: Viral hepatitis is a worldwide, important health issue. The optimal management of viral hepatitis infections faces numerous challenges. In this paper, we describe how biobanking of biological samples derived from viral hepatitis patients collected both in-hospital and during community outreach screenings provides a unique collection of samples. Materials and Methods: All samples and materials were provided with a study code within the SLIMS system Study protocols and an informed consent form were approved by the Antwerp University Hospital/University of Antwerp Ethical Committee. Systematic biobanking was initiated in October 2014. Collected sample types include: (1) serum and plasma of all newly diagnosed HBV, HCV, HDV, and HEV positive patients; (2) left-over serum and plasma samples from all PCR analyses for HBV and HCV performed in the context of routine clinical care; (3) left-over liver tissue not needed for routine histological diagnosis after liver biopsy; and (4) additional virus-specific, appropriate sample types using a scientific rationale-based approach. A community outreach screening program was performed in three major Belgian cities. Serum, EDTA, Tempus Blood RNA and BD Vacutainer CPT were collected. CPT tubes were centrifuged on-site and mononuclear cells collected within 24 h. Results: Concerning community screening: 298 individuals supplied all 4 sample types. Samples were stored at −150°C and were logged in the biobank SLIMS database. Samples were used for HBV-related immunological and biomarker studies. DNA isolated from plasma samples derived from chronic HBV patients was used to investigate Single Nucleotide Polymorphism rs 1790008. Serum samples collected from chronic hepatitis C patients were used to assess the efficacy of HCV treatment. Peripheral Blood Mononuclear Cells (PBMC) isolated from chronic HBV patients and healthy controls were used for different immunological study purposes. Virus isolated from biobanked stool of a chronic hepatitis E patient was used to establish a mouse model for Hepatitis E infections, allowing further HEV virology studies. Conclusion: The establishment of a biobank with samples collected both in-hospital and during community-outreach screening resulted in a unique, continuously expanding collection of biological samples which provides an excellent platform for prompt answers to clinically and translational relevant research questions

What is influencing the phenotype of the common homozygous polymerase-γ mutation p.Ala467Thr?

Polymerase-γ (POLG) is a major human disease gene and may account for up to 25% of all mitochondrial diseases in the UK and in Italy. To date, >150 different pathogenic mutations have been described in POLG. Some mutations behave as both dominant and recessive alleles, but an autosomal recessive inheritance pattern is much more common. The most frequently detected pathogenic POLG mutation in the Caucasian population is c.1399G>A leading to a p.Ala467Thr missense mutation in the linker domain of the protein. Although many patients are homozygous for this mutation, clinical presentation is highly variable, ranging from childhood-onset Alpers-Huttenlocher syndrome to adult-onset sensory ataxic neuropathy dysarthria and ophthalmoparesis. The reasons for this are not clear, but familial clustering of phenotypes suggests that modifying factors may influence the clinical manifestation. In this study, we collected clinical, histological and biochemical data from 68 patients carrying the homozygous p.Ala467Thr mutation from eight diagnostic centres in Europe and the USA. We performed DNA analysis in 44 of these patients to search for a genetic modifier within POLG and flanking regions potentially involved in the regulation of gene expression, and extended our analysis to other genes affecting mitochondrial DNA maintenance (POLG2, PEO1 and ANT1). The clinical presentation included almost the entire phenotypic spectrum of all known POLG mutations. Interestingly, the clinical presentation was similar in siblings, implying a genetic basis for the phenotypic variability amongst homozygotes. However, the p.Ala467Thr allele was present on a shared haplotype in each affected individual, and there was no correlation between the clinical presentation and genetic variants in any of the analysed nuclear genes. Patients with mitochondrial DNA haplogroup U developed epilepsy significantly less frequently than patients with any other mitochondrial DNA haplotype. Epilepsy was reported significantly more frequently in females than in males, and also showed an association with one of the chromosomal markers defining the POLG haplotype. In conclusion, our clinical results show that the homozygous p.Ala467Thr POLG mutation does not cause discrete phenotypes, as previously suggested, but rather there is a continuum of clinical symptoms. Our results suggest that the mitochondrial DNA background plays an important role in modifying the disease phenotype but nuclear modifiers, epigenetic and environmental factors may also influence the severity of disease