5). CONCLUSIONS 3DE based pre-operative modeling of surgical implantation of stent-based valves in the mitral position may improve quantification of mitral valve dimensions and inform risk stratification for potential LVOTO. BACKGROUND Poly-ADP-ribose polymerases (PARPs) are key mediators of cellular stress response. They are intimately linked to cellular metabolism through the consumption of NAD+. PARP1/ARTD1 in the nucleus is the major NAD+ consuming activity and plays a key role in maintaining genomic integrity. SCOPE OF REVIEW In this review, we discuss how different organelles are linked through NAD+ metabolism and how PARP1 activation in the nucleus can impact the function of distant organelles. We discuss how differentiated cells tame PARP1 function by upregulating an endogenous inhibitor, the histone variant macroH2A1.1. MAJOR CONCLUSIONS The presence of macroH2A1.1, particularly in differentiated cells, raises the threshold for the activation of PARP1 with consequences for DNA repair, gene transcription, and NAD+ homeostasis. BACKGROUND Metabolic diseases such as obesity are known to be driven by both environmental and genetic factors. Although genome-wide association studies of common variants and their impact on complex traits have provided some biological insight into disease etiology, identified genetic variants have been found to contribute only a small proportion to disease heritability, and to map mainly to non-coding regions of the genome. To link variants to function, association studies of cellular traits, such as epigenetic marks, in disease-relevant tissues are commonly applied. SCOPE OF THE REVIEW We review large-scale efforts to generate genome-wide maps of coordinated epigenetic marks and their utility in complex disease dissection with a focus on DNA methylation. We contrast DNA methylation profiling methods and discuss the advantages of using targeted methods for single-base resolution assessments of methylation levels across tissue-specific regulatory regions to deepen our understanding of contributing factors leading to complex diseases. MAJOR CONCLUSIONS Large-scale assessments of DNA methylation patterns in metabolic disease-linked study cohorts have provided insight into the impact of variable epigenetic variants in disease etiology. In-depth profiling of epigenetic marks at regulatory regions, particularly at tissue-specific elements, will be key to dissect the genetic and environmental components contributing to metabolic disease onset and progression. BACKGROUND One of the fascinating aspects of epigenetic regulation is that it provides means to rapidly adapt to environmental change. This is particularly relevant in the plant kingdom, where most species are sessile and exposed to increasing habitat fluctuations due to global warming. D-1553 Although the inheritance of epigenetically controlled traits acquired through environmental impact is a matter of debate, it is well documented that environmental cues lead to epigenetic changes, including chromatin modifications, that affect cell differentiation or are associated with plant acclimation and defense priming. Still, in most cases, the mechanisms involved are poorly understood. An emerging topic that promises to reveal new insights is the interaction between epigenetics and metabolism. SCOPE OF REVIEW This study reviews the links between metabolism and chromatin modification, in particular histone acetylation, histone methylation, and DNA methylation, in plants and compares them to examples from the mammalian field, where the relationship to human diseases has already generated a larger body of literature. This study particularly focuses on the role of reactive oxygen species (ROS) and nitric oxide (NO) in modulating metabolic pathways and gene activities that are involved in these chromatin modifications. As ROS and NO are hallmarks of stress responses, we predict that they are also pivotal in mediating chromatin dynamics during environmental responses. MAJOR CONCLUSIONS Due to conservation of chromatin-modifying mechanisms, mammals and plants share a common dependence on metabolic intermediates that serve as cofactors for chromatin modifications. In addition, plant-specific non-CG methylation pathways are particularly sensitive to changes in folate-mediated one-carbon metabolism. Finally, reactive oxygen and nitrogen species may fine-tune epigenetic processes and include similar signaling mechanisms involved in environmental stress responses in plants as well as animals. BACKGROUND Many metabolites serve as important signalling molecules to adjust cellular activities and functions based on nutrient availability. Links between acetyl-CoA metabolism, histone lysine acetylation, and gene expression have been documented and studied over the past decade. In recent years, several additional acyl modifications to histone lysine residues have been identified, which depend on acyl-coenzyme A thioesters (acyl-CoAs) as acyl donors. Acyl-CoAs are intermediates of multiple distinct metabolic pathways, and substantial evidence has emerged that histone acylation is metabolically sensitive. Nevertheless, the metabolic sources of acyl-CoAs used for chromatin modification in most cases remain poorly understood. Elucidating how these diverse chemical modifications are coupled to and regulated by cellular metabolism is important in deciphering their functional significance. SCOPE OF REVIEW In this article, we review the metabolic pathways that produce acyl-CoAs, as well as emerging evidence for acyl-CoA species on these enzymes make determining the relative abundance of acyl-CoA species in specific contexts important to understand the regulation of chromatin acylation. An improved and more nuanced understanding of metabolic regulation of chromatin and its roles in physiological and disease-related processes will emerge as these questions are answered. BACKGROUND Approved drugs for Alzheimer's disease (AD) only have a symptomatic effects and do not intervene causally in the course of the disease. Olesoxime (TRO19622) has been tested in AD disease models characterized by improved amyloid precursor protein processing (AβPP) and mitochondrial dysfunction. METHODS Three months old Thy-1-AβPPSL (tg) and wild type mice (wt) received TRO19622 (100 mg/kg b.w.) in supplemented food pellets for 15 weeks (tg TRO19622). Mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) levels were determined in dissociated brain cells (DBC). Respiration was analyzed in mitochondria isolated from brain tissue. Citrate synthase (CS) activity and beta-amyloid peptide (Aβ1-40) levels were determined in brain tissue. Malondialdehyde (MDA) levels were determined as an indicator for lipid peroxidation. DBC and brain homogenates were additionally stressed with Rotenone and FeCl2, respectively. Mitochondrial respiration and Aβ1-40 levels were also determined in HEK-AβPPsw-cells.