Inhibition of methyltransferase activity of enhancer of zeste 2 leads to enhanced lipid accumulation and altered chromatin status in zebrafish

BACKGROUND: Recent studies indicate that exposure to environmental chemicals may increase susceptibility to developing metabolic diseases. This susceptibility may in part be caused by changes to the epigenetic landscape which consequently affect gene expression and lead to changes in lipid metabolism. The epigenetic modifier enhancer of zeste 2 (Ezh2) is a histone H3K27 methyltransferase implicated to play a role in lipid metabolism and adipogenesis. In this study, we used the zebrafish (Danio rerio) to investigate the role of Ezh2 on lipid metabolism and chromatin status following developmental exposure to the Ezh1/2 inhibitor PF-06726304 acetate. We used the environmental chemical tributyltin (TBT) as a positive control, as this chemical is known to act on lipid metabolism via EZH-mediated pathways in mammals. RESULTS: Zebrafish embryos (0-5 days post-fertilization, dpf) exposed to non-toxic concentrations of PF-06726304 acetate (5 μM) and TBT (1 nM) exhibited increased lipid accumulation. Changes in chromatin were analyzed by the assay for transposase-accessible chromatin sequencing (ATAC-seq) at 50% epiboly (5.5 hpf). We observed 349 altered chromatin regions, predominantly located at H3K27me3 loci and mostly more open chromatin in the exposed samples. Genes associated to these loci were linked to metabolic pathways. In addition, a selection of genes involved in lipid homeostasis, adipogenesis and genes specifically targeted by PF-06726304 acetate via altered chromatin accessibility were differentially expressed after TBT and PF-06726304 acetate exposure at 5 dpf, but not at 50% epiboly stage. One gene, cebpa, did not show a change in chromatin, but did show a change in gene expression at 5 dpf. Interestingly, underlying H3K27me3 marks were significantly decreased at this locus at 50% epiboly. CONCLUSIONS: Here, we show for the first time the applicability of ATAC-seq as a tool to investigate toxicological responses in zebrafish. Our analysis indicates that Ezh2 inhibition leads to a partial primed state of chromatin linked to metabolic pathways which results in gene expression changes later in development, leading to enhanced lipid accumulation. Although ATAC-seq seems promising, our in-depth assessment of the cebpa locus indicates that we need to consider underlying epigenetic marks as well.</p

Micropatterned 2D Hybrid Perovskite Thin Films with Enhanced Photoluminescence Lifetimes

The application of luminescent materials in display screens and devices requires micropatterned structures. In this work, we have successfully printed microstructures of a two-dimensional (2D), orange-colored organic/inorganic hybrid perovskite ((C6H5CH2NH3)2PbI4) using two different soft lithography techniques. Notably, both techniques yield microstructures with very high aspect ratios in the range of 1.5-1.8. X-ray diffraction reveals a strong preferential orientation of the crystallites along the c-axis in both patterned structures, when compared to nonpatterned, drop-casted thin films. Furthermore, (time-resolved) photoluminescence (PL) measurements reveal that the optical properties of (C6H5CH2NH3)2PbI4 are conserved upon patterning. We find that the larger grain sizes of the patterned films with respect to the nonpatterned film give rise to an enhanced PL lifetime. Thus, our results demonstrate easy and cost-effective ways to manufacture patterns of 2D organic/inorganic hybrid perovskites, while even improving their optical properties. This demonstrates the potential use of color-tunable 2D hybrids in optoelectronic devices

Photochromism in Ruddlesden-Popper copper-based perovskites:A light-induced change of coordination number at the surface

Ruddlesden-Popper organic-inorganic hybrid copper-based perovskites have been studied for decades owing to a variety of interesting properties, such as thermochromism and piezochromism, and the mechanisms behind these phenomena have been explained. Another possible property of these materials that has seldomly been investigated is photochromism. In this work, the photochromic properties of bis(phenethylammonium) tetrachlorocuprate (also known as phenethylammonium copper chloride) are reported for the first time. This material has attracted scientific interest owing to the fact that it shows both ferroelectric and ferromagnetic behavior. This work highlights the difference in stability between two Ruddlesden-Popper copper-based perovskites - with phenethylammonium (PEA) or methylammonium (MA) as the cations - during external stimuli. Various techniques, such as Raman and X-ray photoelectron spectroscopy, and grazing-incidence wide-angle X-ray scattering, combined with optical studies, were used to investigate the underlying photochemical processes at a molecular level. It is found that for the PEA compound, ultraviolet illumination causes a color change from yellow to brown. This is the result of two independent events, namely a Cu2+ reduction reaction and a transition from an octahedral copper-chloride structure to square-planar CuCl42-. After illumination, the material (brown color) is unstable in air, which is evident from a color change back to yellow. Interestingly, the similar compound bis(methylammonium) tetrachlorocuprate does not display photochromic behavior, which is attributed to the different nature of the two organic cations

NGO Legitimacy: Four Models

The aim of this paper is to examine NGOs’ legitimacy in the context of global politics. In order to yield a better understanding of NGOs’ legitimacy at the international level it is important to examine how their legitimacy claims are evaluated. This paper proposes dividing the literature into four models based on the theoretical and analytical approaches to their legitimacy claims: the market model, social change model, new institutionalism model and the critical model. The legitimacy criteria generated by the models are significantly different in their analytical scope of how one is to assess the role of NGOs operating as political actors contributing to democracy. The paper argues that the models present incomplete, and sometimes conflicting, views of NGOs’ legitimacy and that this poses a legitimacy dilemma for those assessing the political agency of NGOs in world politics. The paper concludes that only by approaching their legitimacy holistically can the democratic role of NGOs be explored and analysed in the context of world politics

Caregiver education in Parkinson’s disease: formative evaluation of a standardized program in seven European countries

The formative evaluation of a standardized psychosocial education program for patients with Parkinson's disease (PD) and their caregivers. The results of the participation of the caregivers are presented next to the data of the patients. Caregivers (n = 137) and patients with PD (n = 151) participated in the 8-week program in separate groups. Measurements were performed on psychosocial problems (BELA-P/A-k), health state (EQ-5D VAS), quality of life (PDQ-39) and depression (SDS) 1 week before and 1 week after the program. Participants rated their mood on a visual analogue scale before and after each session, and they filled in an evaluation questionnaire after the last session. Scores on the BELA-P/A-k improved significantly on the 'bothered by scale' as well as the 'need for help scale'. No improvements were found on EQ-5D VAS, PDQ-39 and SDS. Mood ratings improved significantly after each session. Most participants evaluated the program as positive. Feedback led to improvements in the program, which are incorporated in a final manual. The program was feasible to run in the different countries. This exploratory study led to improvements in the program and recommendations for further research. A study on the effectiveness of the program is the next step.Pathophysiology of paroxysmal and chronic degenerative progressive disorder of the central and periferal nervous syste

Should the teaching of biological evolution include the origin of life?

The development of mainstream research on the origin of life as an outcome of Darwinian evolution is discussed. It is argued that prebiotic evolution and the origin of life should not be excluded from the syllabus and should be part of classes on biological evolution, and that the transition from non-living to living matter is best understood when seen as part of evolutionary biology. The wide acceptance of evolutionary approaches to the study of the emergence of life in European and Latin American countries is discussed