Opposing effects of monomeric and pentameric C-reactive protein on endothelial progenitor cells

C-reactive protein (CRP) has been linked to the pathogenesis of atherosclerosis. The dissociation of native, pentameric (p)CRP to monomeric (m)CRP on the cell membrane of activated platelets has recently been demonstrated. The dissociation of pCRP to mCRP may explain local pro-inflammatory reactions at the site of developing atherosclerotic plaques. As a biomarker, pCRP predicts cardiovascular adverse events and so do reduced levels and function of circulating endothelial progenitor cells (EPCs). We hypothesised that mCRP and pCRP exert a differential effect on EPC function and differentiation. EPCs were treated with mCRP or pCRP for 72 h, respectively. Phenotypical characterisation was done by flow cytometry and immunofluorescence microscopy, while the effect of mCRP and pCRP on gene expression was examined by whole-genome gene expression analysis. The functional capacity of EPCs was determined by colony forming unit (CFU) assay and endothelial tube formation assay. Double staining for acetylated LDL and ulex lectin significantly decreased in cells treated with pCRP. The length of tubuli in a matrigel assay with HUVECs decreased significantly in response to pCRP, but not to mCRP. The number of CFUs increased after pCRP treatment. RNA expression profiling demonstrated that mCRP and pCRP cause highly contradictory gene regulation. Interferon-responsive genes (IFI44L, IFI44, IFI27, IFI 6, MX1, OAS2) were among the highly up-regulated genes after mCRP, but not after pCRP treatment. In conclusion, EPC phenotype, genotype and function were differentially affected by mCRP and pCRP, strongly arguing for differential roles of these two CRP conformations. The up-regulation of interferon-inducible genes in response to mCRP may constitute a mechanism for the local regulation of EPC function

Systems Biology approach to metabolomics in cancer studies

The astonishing development of high-throughput techniques in the last decades has fostered a renewed, dynamical comprehension of cell and tissue metabolism, giving unexpected insights into the ‘systemic aspects’ of cancer, namely pointing out that metabolism should be considered a truly “systems property. Both internal and microenvironmental cues tightly cooperate in shaping tissue metabolomic fingerprint. tumour metabolome hardly could be mechanistically linked to the linear dynamics of few gene regulatory networks; otherwise it is likely to be the complex end point of several interacting non-linear pathways, involving both cells and their microenvironment. As such, tumour metabolism might be considered an emerging, “systems property”, arising at the integrated scale of the whole system and behaving like an “attractor” in a specific space phase defined by thermodynamic constraints . Therefore, metabolomics ‘strategies’ are settled in order to understand complex biological systems from an integrated (‘holistic’) point of view. Metabolomics measurements are hence correlated with the time-dependent changes in concentrations of other components (proteins, gene-expression data), in order to obtain an integrated model of the gene-protein-metabolite interactions. Such framework represents a meaningful discontinuity with respect to the reductionist and qualitative molecular biology, and discloses new perspective to scientific researc

EXTRACTION OF THE GLUON DENSITY OF THE PROTON AT X RID B-9165-2008 RID C-5889-2009 RID A-4818-2008 RID C-1693-2008

The gluon momentum density xg(x, Q(2)) of the proton was extracted at Q(2) = 20 GeV2 for small values of x between 4 x 10(-4) and 10(-2) from the scaling violations of the proton structure function F-2 measured recently by ZEUS in deep inelastic neutral current ep scattering at HERA. The extraction was performed in two ways. Firstly, using a global NLO fit to the ZEUS data on F-2 at low x constrained by measurements from NMC at larger x; and secondly using published approximate methods for the solution of the GLAP QCD evolution equations. Consistent results are obtained. A substantial increase of the gluon density is found at small x in comparison with the NMC result obtained at larger values of x

NEUTRAL STRANGE PARTICLE-PRODUCTION IN DEEP-INELASTIC SCATTERING AT HERA RID B-9165-2008 RID C-5889-2009 RID A-4818-2008 RID C-1693-2008

This paper presents measurements of K-0 and Lambda production in neutral current, deep inelastic scattering of 26.7 GeV electrons and 820 GeV protons in the kinematic range 10 0.04. Average multiplicities for K-0 and Lambda production are determined for transverse momenta p(T) > 0.5 GeV and pseudorapidities \eta\ < 1.3. The multiplicities favour a stronger strange to light quark suppression in the fragmentation chain than found in e(+)e(-) experiments. The production properties of K-0's in events with and without a large rapidity gap with respect to the proton direction are compared. The ratio of neutral K-0's to charged particles per event in the measured kinematic range is, within the present statistics, the same in both samples

MEASUREMENT OF TOTAL AND PARTIAL PHOTON PROTON CROSS-SECTIONS AT 180 GEV CENTER-OF-MASS ENERGY RID C-1693-2008 RID B-9165-2008 RID C-5889-2009 RID A-4818-2008

Photon proton cross sections for elastic light vector meson production, sigma(el)gammap, inelastic diffractive production, sigma(d)gammap, non-diffractive production, sigma(nd)gammap, as well as the total cross section, sigma(tot)gammap, have been measured at an average gammap center of mass energy of 180 GeV with the ZEUS detector at HERA. The resulting values are sigma(el)gammap = 18 +/- 7 mub, sigma(d)gammap = 33 +/- 8 mub, sigma(nd)gammap = 91 +/- 11 mub, and sigma(tot)gammap = 143 +/- 17 mub, where the errors include statistical and systematic errors added in quadrature

MEASUREMENT OF THE DIFFRACTIVE STRUCTURE-FUNCTION IN DEEP-INELASTIC SCATTERING AT HERA RID B-9165-2008 RID C-5889-2009 RID A-4818-2008 RID C-1693-2008

This paper presents an analysis of the inclusive properties of diffractive deep inelastic scattering events produced in ep interactions at HERA. The events are characterised by a rapidity gap between the outgoing proton system and the remaining hadronic system. Inclusive distributions are presented and compared with Monte Carlo models for diffractive processes. The data are consistent with models where the pomeron structure function has a hard and a soft contribution. The diffractive structure function is measured as a function of x(p), the momentum fraction lost by the proton, of beta, the momentum fraction of the struck quark with respect to x(p), and of Q(2) in the range 6.3 10(-4) < x(p) < 10(-2), 0.1 < .beta < 0.8 and 8 < Q(2) < 100 GeV2. The x(p) dependence is consistent with the form (1/x(p))(alpha) where alpha = 1.30 +/- 0.08 (stat)(-0.14)(+0.08) (sys) in all bins of beta and Q(2). In the measured Q(2) range, the diffractive structure function approximately scales with Q(2) at fixed beta. In an Ingelman-Schlein type model where commonly used pomeron flux factor normalisations are assumed, it is found that the quarks within the pomeron do not saturate the momentum sum rule