Leiden, Netherlands
Leiden, Netherlands

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Spijker A.T.,PsyQ The Hague | Giltay E.J.,Leiden University | van Rossum E.F.C.,Erasmus Medical Center | Manenschijn L.,Erasmus Medical Center | And 4 more authors.
Psychoneuroendocrinology | Year: 2011

Introduction: The hypothalamus-pituitary-adrenal (HPA)-axis is often found to be dysregulated in bipolar disorder (BD) while stress and changes in day-night rhythms can trigger a new mood episode. Genetic variants of the glucocorticoid receptor (GR)- and mineralocorticoid receptor (MR)-gene influence both the reactivity of the stress-response and associate with changes in mood. In this study we tested the hypothesis that these polymorphisms associate with different clinical characteristics of BD. Methods: We studied 326 outpatients with BD and performed GR genotyping of the TthIIII, ER22/23EK, N363S, BclI, and 9β polymorphisms, as well as MR genotyping of the 2G/C and I180V variants. All patients were interviewed for clinical characteristics. Results: Seasonal patterns of hypomania are related to the BclI haplotype and the T. thIIII. +. 9β haplotype of the GR gene (respectively, crude p= .007 and crude p= .005). Carriers of the ER22/23EK polymorphism had an almost 8 years earlier onset of their first (hypo)manic episode than non-carriers (crude p= .004, after adjustment p= .016). No evidence for a role of the MR in modifying clinical manifestations was found. Conclusion: Polymorphisms of the GR-gene are factors which influence some clinical manifestations of BD, with respect to seasonal pattern of (hypo)mania and age of onset. © 2011 Elsevier Ltd.


Van Der Linden W.A.,Gorlaeus Laboratories | Willems L.I.,Gorlaeus Laboratories | Shabaneh T.B.,Norris Cotton Cancer Center | Li N.,Gorlaeus Laboratories | And 6 more authors.
Organic and Biomolecular Chemistry | Year: 2012

Syringolins, a class of natural products, potently and selectively inhibit the proteasome and show promising antitumour activity. To gain insight in the mode of action of syringolins, the ureido structural element present in syringolins is incorporated in oligopeptide vinyl sulfones and peptide epoxyketones yielding a focused library of potent new proteasome inhibitors. The distance of the ureido linkage with respect to the electrophilic trap strongly influences subunit selectivity within the proteasome. Compounds 13 and 15 are β5 selective and their potency exceeds that of syringolin A. In contrast, 5 may well be the most potent β1 selective compound active in living cells reported to date.


PubMed | Gorlaeus Laboratories
Type: Journal Article | Journal: Organic & biomolecular chemistry | Year: 2011

Syringolins, a class of natural products, potently and selectively inhibit the proteasome and show promising antitumour activity. To gain insight in the mode of action of syringolins, the ureido structural element present in syringolins is incorporated in oligopeptide vinyl sulfones and peptide epoxyketones yielding a focused library of potent new proteasome inhibitors. The distance of the ureido linkage with respect to the electrophilic trap strongly influences subunit selectivity within the proteasome. Compounds 13 and 15 are 5 selective and their potency exceeds that of syringolin A. In contrast, 5 may well be the most potent 1 selective compound active in living cells reported to date.


Mom R.V.,Huygens Kamerlingh Onnes Laboratory | Rost M.J.,Huygens Kamerlingh Onnes Laboratory | Frenken J.W.M.,Huygens Kamerlingh Onnes Laboratory | Frenken J.W.M.,Advanced Research Center for Nanolithography | And 2 more authors.
Journal of Physical Chemistry C | Year: 2016

To investigate how the properties of model mixed metal oxide catalysts can be influenced by the choice of evaporating species during physical vapor deposition, we have compared MoOx on Al2O3/NiAl(110) prepared via an oxidic and a metallic precursor. In the former case, MoOx was prepared via direct deposition of MoOx, while in the latter case, metallic Mo was deposited in an O2 background. The structure of the resulting catalysts was compared to that of metallic Mo deposited on Al2O3/NiAl(110) in the absence of O2. For directly deposited MoOx, we observe predominantly point defect nucleation and high particle densities. In contrast, when MoOx is prepared by deposition of metallic Mo in 5 × 10-7 mbar O2, we find lower particle densities and preferential nucleation at step edges and domain boundaries, thus reflecting the particle dispersion of metallic Mo. This suggests that the Mo atoms are oxidized typically only after having attached to a stable Mo or MoOx nucleus. We interpret our findings in terms of the interaction between the deposited material and the support, which is stronger for MoOx than for Mo. These results demonstrate that the choice of evaporating material crucially influences the catalyst structure and is therefore a useful parameter in tuning the properties of model mixed oxide catalysts. © 2016 American Chemical Society.


PubMed | Gorlaeus Laboratories
Type: Journal Article | Journal: Arteriosclerosis, thrombosis, and vascular biology | Year: 2010

The consequences of macrophage triglyceride (TG) accumulation on atherosclerosis have not been studied in detail so far. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for the initial step in TG hydrolysis. Because ATGL knockout (KO) mice exhibit massive TG accumulation in macrophages, we used ATGL KO mice to study the effects of macrophage TG accumulation on atherogenesis.Low-density lipoprotein receptor (LDLr) KO mice were transplanted with bone marrow from ATGL KO (ATGL KOLDLr KO) or wild-type (WTLDLr KO) mice and challenged with a Western-type diet for 9 weeks. Despite TG accumulation in ATGL KO macrophages, atherosclerosis in ATGL KOLDLr KO mice was 43% reduced associated with decreased plasma monocyte chemoattractant protein-1 (MCP-1) and macrophage interleukin-6 concentrations. This coincided with a reduced amount of macrophages, possibly because of a 39% increase in intraplaque apoptosis and a decreased migratory capacity of ATGL KO macrophages. The reduced number of white blood cells might be due to a 36% decreased Lin(-)Sca-1(+)cKit(+) hematopoietic stem cell population.We conclude that the attenuation of atherogenesis in ATGL KOLDLr KO mice is due to decreased infiltration of less inflammatory macrophages into the arterial wall and increased macrophage apoptosis.

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