Groei en begrazing van mosselzaad, primaire productie en picoplankton in de Waddenzee: Technisch Rapport project Meerjarig effect- en productiemetingen aan MZI's in de Westerlijke Waddenzee, Oosterschelde en Voordelta

In het kader van het project: “Meerjarige effectmetingen aan MZI’s in de Westelijke Waddenzee en de Oosterschelde”, uitgevoerd door IMARES in opdracht van het Ministerie van LNV (thans EZ), zijn er in 2010 tot en met 2013 veldmetingen verricht bij een MZI. Centrale vraag binnen deelproject 1 betreft de mogelijke invloed van MZI’s op de draagkracht van de Waddenzee en de Oosterschelde. In dit rapport worden de resultaten gepresenteerd van het onderzoek aan de MZI’s in de Waddenzee

Towards norms for accreditation of biobanks for human health and medical research:Compilation of existing guidelines into an ISO certification/accreditation norm-compatible format

In recent years, biobanks have evolved into professional infrastructures that acquire, validate, process, store, manage and distribute biological material of human origin to public or private end-users/researchers. This article (a) highlights the importance of quality assurance for both the biobank basic processes and sample annotation in order to ensure reliable results of research based on these samples, (b) suggests that certification according to international standards can contribute to the organization of the biobanking processes while accreditation can contribute to the organization of sample characterization/validation, and (c) provides a compilation of all existing guidelines against an International Organization for Standardization (ISO) format.</p

Length-and weight-dependent clearance rates of juvenile mussels (Mytilus edulis) on various planktonic prey items

Filtration capacity and feeding behaviour has been intensely studied for adult mussels (Mytilus edulis), but less information is available for juvenile mussels (1.5–25 mm

Factors that drive the increasing use of FFPE tissue in basic and translational cancer research

The decision to use 10% neutral buffered formalin fixed, paraffin embedded (FFPE) archival pathology material may be dictated by the cancer research question or analytical technique, or may be governed by national ethical, legal and social implications (ELSI), biobank, and sample availability and access policy. Biobanked samples of common tumors are likely to be available, but not all samples will be annotated with treatment and outcomes data and this may limit their application. Tumors that are rare or very small exist mostly in FFPE pathology archives. Pathology departments worldwide contain millions of FFPE archival samples, but there are challenges to availability. Pathology departments lack resources for retrieving materials for research or for having pathologists select precise areas in paraffin blocks, a critical quality control step. When samples must be sourced from several pathology departments, different fixation and tissue processing approaches create variability in quality. Researchers must de

The promoter and the enhancer region of the KLK 3 (prostate specific antigen) gene is frequently mutated in breast tumours and in breast carcinoma cell lines

KLK3 or prostate specific antigen (PSA) is a serine protease, which is an established tumour marker of prostatic adenocarcinoma. PSA is now used widely for the diagnosis and monitoring of patients with prostate cancer. Recent studies have demonstrated that about 70% of breast cancers produce PSA. In this study, we examined the molecular mechanism underlying the expression of the PSA gene in breast cancer and breast cancer cell lines. We analysed nine breast tumours categorized on the basis of high- or low-PSA expression in tumour cytosols and four breast cancer cell lines. To determine abnormalities associated with PSA expression in breast tumours, genomic DNA was extracted and all five exons of the PSA gene were polymerase chain reaction (PCR) amplified and sequenced on both strands. PCR amplification was also performed for the promoter and enhancer elements of the PSA gene. No mutations were observed in the coding portion of the gene. A polymorphism was observed in exon 2 from three breast tumours. However, sequencing of the promoter and the enhancer elements of the PSA gene reveals several point mutations. Within a 5.8-kb promoter/enhancer region of the PSA gene, we detected 16 different mutational hotspots (appearing more than once in the nine tumours). Among these hotspots, two appeared in seven out of nine tumours. Most importantly, the androgen response element (ARE I) in the proximal promoter was found mutated in four tumours and in the breast carcinoma cell line MCF-7. Mutations associated with the ARE I have been shown previously to result in an 80% decrease in PSA gene expression. The mutations in the core enhancer and promoter region probably contribute to the aberrant expression of the PSA gene in breast tumours, possibly by altering the regulation of the gene by steroid hormones. © 1999 Cancer Research Campaig

Distinct, dosage-sensitive requirements for the autism-associated factor CHD8 during cortical development

Background: CHD8 haploinsufficiency causes autism and macrocephaly with high penetrance in the human population. Chd8 heterozygous mice exhibit relatively subtle brain overgrowth and little gene expression changes in the embryonic neocortex. The purpose of this study was to generate new, sub-haploinsufficient Chd8 mouse models to allow us to identify and study the functions of CHD8 during embryonic cortical development. Methods: To examine the possibility that certain phenotypes may only appear at sub-heterozygous Chd8 levels in the mouse, we created an allelic series of Chd8-deficient mice to reduce CHD8 protein levels to approximately 35% (mild hypomorph), 10% (severe hypomorph) and 0% (neural-specific conditional knockout) of wildtype levels. We used RNA sequencing to compare transcriptional dysregulation, structural MRI and brain weight to investigate effects on brain size, and cell proliferation, differentiation and apoptosis markers in immunostaining assays to quantify changes in neural progenitor fate. Results: Mild Chd8 hypomorphs displayed significant postnatal lethality, with surviving animals exhibiting more pronounced brain hyperplasia than heterozygotes. Over 2000 genes were dysregulated in mild hypomorphs, including autism-associated neurodevelopmental and cell cycle genes. We identify increased proliferation of non-ventricular zone TBR2+ intermediate progenitors as one potential cause of brain hyperplasia in these mutants. Severe Chd8 hypomorphs displayed even greater transcriptional dysregulation, including evidence for p53 pathway&nbsp;upregulation. In contrast to mild hypomorphs, these mice displayed reduced brain size and increased apoptosis in the embryonic neocortex. Homozygous, conditional deletion of Chd8 in early neuronal progenitors resulted in pronounced brain hypoplasia, partly caused by p53 target gene derepression and apoptosis in the embryonic neocortex. Limitations Our findings identify an important role for the autism-associated factor CHD8 in controlling the proliferation of intermediate progenitors in the mouse neocortex. We propose that CHD8 has a similar function in human brain development, but studies on human cells are required to confirm this. Because many of our mouse mutants with reduced CHD8 function die shortly after birth, it is not possible to fully determine to what extent reduced CHD8 function results in autism-associated behaviours in mice. Conclusions: Together, these findings identify important, dosage-sensitive functions for CHD8 in p53 pathway repression, neurodevelopmental gene expression and neural progenitor fate in the embryonic neocortex. We conclude that brain development is acutely sensitive to reduced CHD8 expression and that the varying sensitivities of different progenitor populations and cellular processes to CHD8 dosage result in non-linear effects on gene transcription and brain growth. Shaun Hurley, Conor Mohan and Philipp Suetterlin have contributed equally to this work

Report from the OECI Oncology Days 2014

The 2014 OECI Oncology Days was held at the ‘Prof. Dr. Ion Chiricuta’ Oncology Institute in Cluj, Romania, from 12 to 13 June. The focus of this year’s gathering was on developments in personalised medicine and other treatment advances which have made the cost of cancer care too high for many regions throughout Europe

Effect of continuous nutrient enrichment on microalgae colonizing hard substrates

In order to understand the effect of changing nutrient conditions on benthic microalgae on hard substrates, in-situ experiments with artificial substrates were conducted in Kiel Fjord, Western Baltic Sea. As an extension of previous investigations, we used artificial substrates without silicate and thus were able to supply nutrient media with different Si:N ratios to porous substrates, from where they trickled out continuously. The biofilm developing on these substrates showed a significant increase in biovolume due to N + P enrichment, while Si alone had only minor effects. The stoichiometric composition of the biomass indicated nitrogen limitation during most of the year. The C:N ratios were lowered by the N + P addition. The algae were dominated by diatoms in most cases, but rhodophytes and chlorophytes also became important. The nutrient treatment affected the taxonomic composition mostly at the species level. The significance of the results with regard to coastal eutrophication is discussed

Bringing onco‐innovation to Europe’s healthcare systems. The potential of biomarker testing, real world evidence, tumour agnostic therapies to empower personalised medicine

Rapid and continuing advances in biomarker testing are not being matched by uptake in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. The potential that genomics has brought to biomarker testing in diagnosis, prediction and research is being realised, pre‐eminently in many cancers, but also in an ever‐wider range of conditions— notably BRCA1/2 testing in ovarian, breast, pancreatic and prostate cancers. Nevertheless, the implementation of genetic testing in clinical routine setting is still challenging. Development is impeded by country‐related heterogeneity, data deficiencies, and lack of policy alignment on standards, approval—and the role of real‐world evidence in the process—and reimbursement. The acute nature of the problem is compellingly illustrated by the particular challenges facing the development and use of tumour agnostic therapies, where the gaps in preparedness for taking advantage of this innovative approach to cancer therapy are sharply exposed. Europe should already have in place a guarantee of universal access to a minimum suite of biomarker tests and should be planning for an optimum testing scenario with a wider range of biomarker tests integrated into a more sophisticated health system articulated around personalised medicine. Improving healthcare and winning advantages for Europe’s industrial competitiveness and innovation require an appropriate policy framework—starting with an update to outdated recommendations. We show herein the main issues and proposals that emerged during the previous advisory boards organised by the European Alliance for Personalized Medicine which mainly focus on possible scenarios of harmonisation of both oncogenetic testing and management of cancer patients