Maastricht University

About: Maastricht University is a education organization based out in Maastricht, Limburg, Netherlands. It is known for research contribution in the topics: Population & Health care. The organization has 19263 authors who have published 53291 publications receiving 2266866 citations. The organization is also known as: Universiteit Maastricht & UM.

Disease variants alter transcription factor levels and methylation of their binding sites.

Abstract: Most disease-associated genetic variants are noncoding, making it challenging to design experiments to understand their functional consequences. Identification of expression quantitative trait loci (eQTLs) has been a powerful approach to infer the downstream effects of disease-associated variants, but most of these variants remain unexplained. The analysis of DNA methylation, a key component of the epigenome, offers highly complementary data on the regulatory potential of genomic regions. Here we show that disease-associated variants have widespread effects on DNA methylation in trans that likely reflect differential occupancy of trans binding sites by cis-regulated transcription factors. Using multiple omics data sets from 3,841 Dutch individuals, we identified 1,907 established trait-associated SNPs that affect the methylation levels of 10,141 different CpG sites in trans (false discovery rate (FDR) < 0.05). These included SNPs that affect both the expression of a nearby transcription factor (such as NFKB1, CTCF and NKX2-3) and methylation of its respective binding site across the genome. Trans methylation QTLs effectively expose the downstream effects of disease-associated variants.

Electrical remodeling due to atrial fibrillation in chronically instrumented conscious goats: roles of neurohumoral changes, ischemia, atrial stretch, and high rate of electrical activation.

Abstract: Background Recently, we developed a goat model of chronic atrial fibrillation (AF). Due to AF, the atrial effective refractory period (AERP) shortened and its physiological rate adaptation inversed, whereas the rate and stability of AF increased. The goal of the present study was to evaluate the role of (1) the autonomic nervous system, (2) ischemia, (3) stretch, (4) atrial natriuretic factor (ANF), and (5) rapid atrial pacing in this process of electrical remodeling. Methods and Results Twenty-five goats were chronically instrumented with multiple epicardial atrial electrodes. Infusion of atropine (1.0 mg/kg; n=6) or propranolol (0.6 mg/kg; n=6) did not abolish the AF-induced shortening of AERP or interval (AFI). Blockade of K+ATP channels by glibenclamide (10 μmol/kg; n=6) slightly increased the AFI from 95±4 to 101±5 ms, but AFI remained considerably shorter than during acute AF (145 ms). Glibenclamide had no significant effect on AERP after electrical cardioversion of AF (69±14 versus 75±15 ms). Volum...

Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease

Abstract: MR imaging was used to show global, diffusely distributed leakage of the blood-brain barrier in patients with early Alzheimer disease, which suggests that a compromised blood-brain barrier is part of the early pathology of Alzheimer disease and might be part of a cascade of pathologic events that eventually lead to cognitive decline.

Faces Are "Spatial"—Holistic Face Perception Is Supported by Low Spatial Frequencies

Abstract: Faces are perceived holistically, a phenomenon best illustrated when the processing of a face feature is affected by the other features. Here, the authors tested the hypothesis that the holistic perception of a face mainly relies on its low spatial frequencies. Holistic face perception was tested in two classical paradigms: the whole-part advantage (Experiment 1) and the composite face effect (Experiments 2-4). Holistic effects were equally large or larger for low-pass filtered faces as compared to full-spectrum faces and significantly larger than for high-pass filtered faces. The disproportionate composite effect found for low-pass filtered faces was not observed when holistic perception was disrupted by inversion (Experiment 3). Experiment 4 showed that the composite face effect was enhanced only for low spatial frequencies, but not for intermediate spatial frequencies known be critical for face recognition. These findings indicate that holistic face perception is largely supported by low spatial frequencies. They also suggest that holistic processing precedes the analysis of local features during face perception.