Control of repair activities at DNA double strand breaks and telomeres

The DNA in our cells, storing the information that every cell needs to perform its specific function, needs to be carefully protected. Various sources, both externally and from inside the cell, constantly threaten the integrity of the DNA, causing DNA damage. DNA double strand breaks (DSBs) are the most detrimental to the cell, and lack of repair, or incorrect repair of such breaks can lead to cell death. Moreover, incorrect repair can introduce errors in the DNA such as mutations or chromosomal rearrangements, resulting in genomic instability which can eventually contribute to the development of cancer. Cells have therefore developed mechanisms that detect the damage and ensure rapid and correct DNA repair, and this is collectively referred to as the ‘DNA damage response’. Importantly, the ends of natural chromosomes resemble DSBs, but repair activities at chromosome-ends would have severe consequences for genome integrity. The ends of chromosomes are therefore protected by specialized structures known as telomeres. The aim of this thesis is to increase our understanding of how repair activities at DSBs and telomeres are controlled. For this we used various methods aiming at identifying novel proteins that act in the DNA damage response and mechanistically understand their function

Adrenocortical neoplasia: evolving concepts in tumorigenesis with an emphasis on adrenal cortical carcinoma variants

Adrenocortical carcinoma (ACC) is a rare, heterogeneous malignancy with a poor prognosis. According to WHO classification 2004, ACC variants include oncocytic ACCs, myxoid ACCs and ACCs with sarcomatous areas. Herein, we provide a comprehensive review of these rare subtypes of adrenocortical malignancy and emphasize their clinicopathological features with the aim of elucidating aspects of diagnostic categorization, differential diagnostics and biological behavior. The issue of current terminology, applied to biphasic tumors with pleomorphic, sarcomatous or sarcomatoid elements arising in adrenal cortex, is also discussed. We additionally present emerging evidence concerning the adrenal cortical tumorigenesis and the putative adenoma–carcinoma sequence as well

Compact polymer components for an integrated add-drop multiplexer

A phasar and a digital thermo optic switch have been designed and processed in a high index contrast polymer technology. Both devices are small enough to fabricate two integrated add-drop multiplexers on one 4 inch wafe

Anthranoid self-medication causing rapid development of melanosis coli

It is widely known that long-term use of anthranoid-containing laxatives is the cause of melanosis coli. We describe a case of melanosis coli, which occurred in a 39-year-old liver transplant patient who took an over-the-counter product containing aloe, rheum and frangula. The typical brownish pigmentation of the colonic mucosa developed in a period of ten months. The anthranoid medication was stopped and follow-up colonoscopy one year later showed normal looking mucosa once more. However, in contrast to previous examinations, a sessile polypoid lesion was found in the transverse colon. Histology showed tubulovillous adenoma with extensive low-grade dysplasia. Since there have been preliminary reports suggesting a possible role of anthranoid-containing laxatives in the development of colorectal adenomas and cancer, their use should be discouraged

De relatie tussen stikstofopname en gewasreflectie bij vijf buitenbloemen

Bij buitenbloemen is er een grote variatie aan gewassen. Het is daarom niet mogelijk om voor ieder gewas afzonderlijk bemestingsonderzoek uit te voeren. Een N -opnamecurve is een belangrijk hulpmiddel bij het ontwikkelen van bijmestsystemen. Onderzoek is gedaan naar de mogelijkheid om met non-destructieve middelen, o.a. refelectiemetingen, iets te zeggen over de vorm van de N-opnamecurve bij een vijftal gewassen, die representatief zijn voor een groot deel van het sortimen