Utrecht University

About: Utrecht University is a education organization based out in Utrecht, Utrecht, Netherlands. It is known for research contribution in the topics: Population & Poison control. The organization has 58176 authors who have published 139351 publications receiving 6214282 citations. The organization is also known as: UU & Universiteit Utrecht.

FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK.

Abstract: Forkhead transcription factors of the FOXO class are negatively regulated by PKB/c-Akt in response to insulin/IGF signalling, and are involved in regulating cell cycle progression and cell death. Here we show that, in contrast to insulin signalling, low levels of oxidative stress generated by treatment with H2O2 induce the activation of FOXO4. Upon treatment of cells with H2O2, the small GTPase Ral is activated and this results in a JNK-dependent phosphorylation of FOXO4 on threonine 447 and threonine 451. This Ral-mediated, JNK-dependent phosphorylation is involved in the nuclear translocation and transcriptional activation of FOXO4 after H2O2 treatment. In addition, we show that this signalling pathway is also employed by tumor necrosis factor α to activate FOXO4 transcriptional activity. FOXO members have been implicated in cellular protection against oxidative stress via the transcriptional regulation of manganese superoxide dismutase and catalase gene expression. The results reported here, therefore, outline a homeostasis mechanism for sustaining cellular reactive oxygen species that is controlled by signalling pathways that can convey both negative (PI-3K/PKB) and positive (Ras/Ral) inputs.

Soft matter with hard skin: From skin wrinkles to templating and material characterization

Abstract: The English-language dictionary defines wrinkles as “small furrows, ridges, or creases on a normally smooth surface, caused by crumpling, folding, or shrinking”. In this paper we review the scientific aspects of wrinkling and the related phenomenon of buckling. Specifically, we discuss how and why wrinkles/buckles form in various materials. We also describe several examples from everyday life, which demonstrate that wrinkling or buckling is indeed a commonplace phenomenon that spans a multitude of length scales. We will emphasize that wrinkling is not always a frustrating feature (e.g., wrinkles in human skin), as it can help to assemble new structures, understand important physical phenomena, and even assist in characterizing chief material properties.

A simple two-variable model of cardiac excitation

Abstract: We modified the FitzHugh-Nagumo model of an excitable medium so that it describes adequately the dymanics of pulse propagation in the canine myocardium. The modified model is simple enough to be used for intensive 3-dimensional (3D) computations of the whole heart. It simulates the pulse shape and the restitution property of the canine myocardium with good precision.

Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with L-lysine

Abstract: Defensins, antimicrobial peptides of the innate immune system, protect human mucosal epithelia and skin against microbial infections and are produced in large amounts by neutrophils. The bacterial pathogen Staphylococcus aureus is insensitive to defensins by virtue of an unknown resistance mechanism. We describe a novel staphylococcal gene, mprF, which determines resistance to several host defense peptides such as defensins and protegrins. An mprF mutant strain was killed considerably faster by human neutrophils and exhibited attenuated virulence in mice, indicating a key role for defensin resistance in the pathogenicity of S. aureus. Analysis of membrane lipids demonstrated that the mprF mutant no longer modifies phosphatidylglycerol with l-lysine. As this unusual modification leads to a reduced negative charge of the membrane surface, MprF-mediated peptide resistance is most likely based on repulsion of the cationic peptides. Accordingly, inactivation of mprF led to increased binding of antimicrobial peptides by the bacteria. MprF has no similarity with genes of known function, but related genes were identified in the genomes of several pathogens including Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Enterococcus faecalis. MprF thus constitutes a novel virulence factor, which may be of general relevance for bacterial pathogens and represents a new target for attacking multidrug resistant bacteria.