The effect of the epigenome on the Vitamin D Receptor target genes

Background. Humans produce vitamin D3 by exposure to sunlight that includes ultraviolet B (UVB) radiation, but also via the intake of nutrients. In the body, the Vitamin D3 is converted to its active form, which is called 1, 25(OH)2D3. This can bind to the Vitamin D Receptor (VDR), which is located on several genes which are called the VDR target genes. Objective. The present study investigated which genes are regulated by the 1, 25(OH)2D3 and checked whether the epigenetic modifications are measured in two cell lines within the ENCODE project. The data of the epigenetic modifications will be linked to the promoter regions of the VDR target genes. In this way the epigenetic control of the VDR target genes could be investigated in more detail. Methods. The human VDR target genes were identified with an extensive literature search. The promoter regions of the VDR target genes were found with Genomatix. Two types of epigenetic modifications, DNA methylation and histone modification, which were determined in two cell lines, IMR90 and H1ESC, in the ENCODE project were linked to the promoter regions of the VDR target genes. In the network analysis program Cytoscape the VDR target genes and the measured epigenetic modifications were integrated and visualized in an epigenetics-VDR target genes network. Results. In total 185 VDR target genes were found in 25 literature papers. There were 528 promoter regions in the 185 VDR target genes identified. In the H1ESC were 445 histone modifications linked to the VDR target gene promoters and in the IMR90 were 259 histone modifications linked to the VDR target gene promoters. In the IMR90 were 158 promoter regions with a DNA methylation region and in the H1ESC were this 177 promoter regions with a DNA methylation region. In the combined network of DNA methylation and histone modifications were in the IMR90 99 genes and in the H1ESC 111 genes selected. Conclusion. The epigenetics-VDR target genes network can be used in further research to understand the role of the epigenetic control of the VDR target genes

The role of non-specific interactions in nuclear organization

The most important organelle in eukaryotic cells is the nucleus. Many processes occurring within the nucleus depend on spatial organization of the nucleus. The spatial organization of the eukaryotic nucleus derives from interactions between its constituents. Both specific interactions, for instance the interactions between a DNA binding protein and its target DNA sequence, and non-specific interactions occur. Non-specific interactions stem from physical encounters between molecules or particles, which can favour particular organizations, i.e. the ones that have the lowest entropy. The role of non-specific interactions in nuclear organization is so far not extensively studied. Here, we investigate the effects of non-specific interactions on nuclear organization, using molecular dynamics simulation techniques. Chromatin folding models can be implemented in these simulations as chains of monomers, which can form loops, branches or networks. Through a comparison of simulation results with experimental data, these models can be verified or falsified. We used MD simulations of models for Arabidopsis chromatin organisation to show that non-specific interactions can explain the in vivo localisation of nucleoli and chromocenters. Also, we quantitatively demonstrate that chromatin looping contributes to the formation of chromosome territories. Focussing on the forces driving nuclear organization in the rosette model, we derive effective interaction potentials for rosette-loop interactions. These potentials are weak, but nevertheless drive chromocenters and nucleoli to the nuclear periphery and away from each other. We also study the folding of a single human chromosome within its territory. The results of our simulations are analysed using a virtual confocal microscope algorithm which has the same limitations as a real confocal microscope. Thus we show that chromatin looping increases the volume occupied by a 10Mbp chromosomal sub-domain, but decreases the overlap between two neighbouring sub-domains. Our results furthermore show that the measured amount of overlap is highly dependent on both spatial resolution and signal detection threshold of the confocal microscope, and that in typical fluorescence in situ hybridisation experiments these two factors contribute to a gross underestimation of the real overlap. Zooming out to whole nucleus organization, we show that an interplay between interactions between heterochromatin and nuclear lamina generates a wide variety of nuclear organizations, with those occurring in nature requiring a fine balance between both interactions. The differences between chromosome folding in human and Arabidopsis can be explained through differences in genomic structure and chromosome loop formation, but the underlying mechanisms and forces that organize the nucleus are very similar. The insight how specific and non-specific forces cooperate to shape nuclear organization, is therefore the most important contribution of this thesis to scientific progress. <br/

The Emergence of Predators in Early Life: There was No Garden of Eden

BACKGROUND: Eukaryote cells are suggested to arise somewhere between 0.85~2.7 billion years ago. However, in the present world of unicellular organisms, cells that derive their food and metabolic energy from larger cells engulfing smaller cells (phagocytosis) are almost exclusively eukaryotic. Combining these propositions, that eukaryotes were the first phagocytotic predators and that they arose only 0.85~2.7 billion years ago, leads to an unexpected prediction of a long period (approximately 1-3 billion years) with no phagocytotes -- a veritable Garden of Eden. METHODOLOGY: We test whether such a long period is reasonable by simulating a population of very simple unicellular organisms -- given only basic physical, biological and ecological principles. Under a wide range of initial conditions, cellular specialization occurs early in evolution; we find a range of cell types from small specialized primary producers to larger opportunistic or specialized predators. CONCLUSIONS: Both strategies, specialized smaller cells and phagocytotic larger cells are apparently fundamental biological strategies that are expected to arise early in cellular evolution. Such early predators could have been 'prokaryotes', but if the earliest cells on the eukaryote lineage were predators then this explains most of their characteristic features

Adolescents Who Intend to Change Multiple Health Behaviours Choose Greater Exposure to an Internet-delivered Intervention

Despite a growth of Internet-delivered interventions, exposure rates to such interventions are still low. In total, 35,104 adolescents participated in the E-MOVO project: an Internet-delivered lifestyle intervention aimed at multiple health behaviours. By means of multilevel analyses, we demonstrated the relationship between intention to change behaviour and adolescents' exposure to E-MOVO's functionalities. There was a clustering of intention to change risk taking behaviours in an unhealthy way and energy balance-related behaviours in a healthy way. This should be taken into account with the design of Internet-delivered interventions. AD - Maastricht University, The Netherlands. [email protected]. FAU - Crutzen, Rik AU - Crutzen R FAU - de Nooijer, Jascha AU - de Nooijer J FAU - Candel, Math J J M AU - Candel MJ FAU - de Vries, Nanne K AU - de Vries NK LA - eng PT - Journal Article PL - England TA - J Health Psychol JT - Journal of health psychology JID - 9703616 SB - I

Modulation of the Extracellular Matrix in Advanced Atherosclerosis

UBL - phd migration 201

Professionalization of Public Health – an exploratory case study

Introduction: Public health is continuously challenged by a shortage of workforce. There are various reasons for this: 1) public health is less visible than traditional health professions and people may be unfamiliar with the nature and opportunities involved in entering this career field; 2) lack of official recognition of public health as a professional category; and 3) no umbrella organization that supports its members and governs professional standards as is the case of other more established professions. To adequately address the challenges of public health for the 21st century, a key policy element will need to focus on adequately cultivating, training and growing the future workforce of professionals in the field. The aim of this study was to examine why professionalization of public health in Europe is not as robust as it deserves to be and what steps can be taken to assure an adequate supply of professionals with the proper education and training background, and career guidance to tackle the public health needs of the future. Method: A case study approach was used collecting data via a scoping literature review, a focus group with public health students and interviews with public health experts for convergence. Data was analysed using directed content analysis and pattern matching logic. Results: Public health fulfilled five out of seven attributes of a profession, such as skills, training and education, certification and an altruistic service. Recognition of Public Health as multidisciplinary and multi-professional field, derived from the interviews as an additional characteristic. A code of ethics and professional conduct and a formal organization were missing. Conclusion: Public health professionals and organisations that govern best practices in this field should consider introducing a shared code of ethics and professional conduct as well as establishing a coordinated body to help advance the public status as a the profession to increase interest in studying and specializing in this area. &nbsp; &nbsp; Conflicts of interest: None declared. &nbsp