University of Antwerp

About: University of Antwerp is a education organization based out in Antwerp, Belgium. It is known for research contribution in the topics: Population & Context (language use). The organization has 16682 authors who have published 48837 publications receiving 1689748 citations. The organization is also known as: Universiteit Antwerpen & UAntwerp.

Phagocytosis of Apoptotic Cells by Macrophages Is Impaired in Atherosclerosis

Abstract: Objective— Apoptotic cell death has been demonstrated in advanced human atherosclerotic plaques. Apoptotic cells (ACs) should be rapidly removed by macrophages, otherwise secondary necrosis occurs, which in turn elicits inflammatory responses and plaque progression. Therefore, we investigated the efficiency of phagocytosis of ACs by macrophages in atherosclerosis. Methods and Results— Human endarterectomy specimens and human tonsils were costained for CD68 (macrophages) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) (apoptosis). Free and phagocytized ACs were counted in both tissues. The ratio of free versus phagocytized AC was 19-times higher in human atherosclerotic plaques as compared with human tonsils, indicating a severe defect in clearance of AC. Impaired phagocytosis of AC was also detected in plaques from cholesterol-fed rabbits and did not further change with plaque progression. In vitro experiments with J774 or peritoneal mouse macrophages showed that several factors caused impaired phagocytosis of AC including cytoplasmic overload of macrophages with indigestible material (beads), free radical attack, and competitive inhibition among oxidized red blood cells, oxidized low-density lipoprotein and ACs for the same receptor(s) on the macrophage. Conclusion— Our data demonstrate that phagocytosis of ACs is impaired in atherosclerotic plaques, which is at least partly attributed to oxidative stress and cytoplasmic saturation with indigestible material.

Proline motifs in peptides and their biological processing.

Abstract: Many biologically important peptide sequences contain proline. It confers unique conformational constraints on the peptide chain in that the side-chain is cyclized back onto the backbone amide position. Inside an alpha-helix the possibility of making hydrogen bonds to the preceding turn is lost and a kink will be introduced. The conformational restrictions imposed by proline motifs in a peptide chain appear to imply important structural or biological functions as can be deduced from their often remarkably high degree of conservation as found in many proteins and peptides, especially cytokines, growth factors, G-protein-coupled receptors, V3 loops of the HIV envelope glycoprotein gp 120, and neuro- and vasoactive peptides. Only a limited number of peptidases are known to be able to hydrolyze proline adjacent bonds. Their activity is influenced by the isomeric state (cis-trans) as well as the position of proline in the peptide chain. The three proline specific metallo-peptidases (aminopeptidase P, carboxype...

Locus-Specific Mutation Databases for Neurodegenerative Brain Diseases

Abstract: The Alzheimer disease and frontotemporal dementia (AD&FTLD) and Parkinson disease (PD) Mutation Databases make available curated information of sequence variations in genes causing Mendelian forms of the most common neurodegenerative brain disease AD, frontotemporal lobar degeneration (FTLD), and PD. They are established resources for clinical geneticists, neurologists, and researchers in need of comprehensive, referenced genetic, epidemiologic, clinical, neuropathological, and/or cell biological information of specific gene mutations in these diseases. In addition, the aggregate analysis of all information available in the databases provides unique opportunities to extract mutation characteristics and genotype–phenotype correlations, which would be otherwise unnoticed and unexplored. Such analyses revealed that 61.4% of mutations are private to one single family, while only 5.7% of mutations occur in 10 or more families. The five mutations with most frequent independent observations occur in 21% of AD, 43% of FTLD, and 48% of PD families recorded in the Mutation Databases, respectively. Although these figures are inevitably biased by a publishing policy favoring novel mutations, they probably also reflect the occurrence of multiple rare and few relatively common mutations in the inherited forms of these diseases. Finally, with the exception of the PD genes PARK2 and PINK1, all other genes are associated with more than one clinical diagnosis or characteristics thereof. Hum Mutat 33:1340–1344, 2012. © 2012 Wiley Periodicals, Inc.

The properties of warm dark matter haloes

Abstract: Well-motivated elementary particle candidates for the dark matter, such as the sterile neutrino, behave as warm dark matter (WDM). For particle masses of order a keV, free streaming produces a cutoff in the linear fluctuation power spectrum at a scale corresponding to dwarf galaxies. We investigate the abundance and structure of WDM haloes and subhaloes on these scales using high resolution cosmological N-body simulations of galactic haloes of mass similar to the Milky Way’s. On scales larger than the free-streaming cutoff, the initial conditions have the same power spectrum and phases as one of the cold dark matter (CDM) haloes previously simulated by Springel et al as part of the Virgo consortium Aquarius project. We have simulated four haloes with WDM particle masses in the range 1.4 − 2.3 keV and, for one case, we have carried out further simulations at varying resolution. N-body simulations in which the power spectrum cutoff is resolved are known to undergo artificial fragmentation in filaments producing spurious clumps which, for small masses (< 10 7 M ⊙ in our case) outnumber genuine haloes. We have developed a robust algorithm to identify these spurious objects and remove them from our halo catalogues. We find that the WDM subhalo mass function is suppressed by well over an order magnitude relative to the CDM case for masses < 10 9 M ⊙ . Requiring that there should be at least as many subhaloes as there are observed satellites in the Milky Way leads to a conservative lower limit to the (thermal equivalent) WDM particle mass of ∼ 1.5keV. WDM haloes and subhaloes have cuspy density distributions that are well described by NFW or Einasto profiles. Their central densities are lower for lower WDM particle masses and none of the models we have considered suffer from the “too big to fail” problem recently highlighted by Boylan-Kolchin et al.