A proinflammatory role for Fas in joints of mice with collagen-induced arthritis

Collagen-induced arthritis (CIA) is a chronic inflammatory disease bearing all the hallmarks of rheumatoid arthritis, e.g. polyarthritis, synovitis, and subsequent cartilage/bone erosions. One feature of the disease contributing to joint damage is synovial hyperplasia. The factors responsible for the hyperplasia are unknown; however, an imbalance between rates of cell proliferation and cell death (apoptosis) has been suggested. To evaluate the role of a major pathway of cell death – Fas (CD95)/FasL – in the pathogenesis of CIA, DBA/1J mice with a mutation of the Fas gene (lpr) were generated. The susceptibility of the mutant DBA-lpr/lpr mice to arthritis induced by collagen type II was evaluated. Contrary to expectations, the DBA-lpr/lpr mice developed significantly milder disease than the control littermates. The incidence of disease was also significantly lower in the lpr/lpr mice than in the controls (40% versus 81%; P < 0.05). However DBA-lpr/lpr mice mounted a robust immune response to collagen, and the expression of local proinflammatory cytokines such as, e.g., tumor necrosis factor α (TNF-α) and IL-6 were increased at the onset of disease. Since the contribution of synovial fibroblasts to inflammation and joint destruction is crucial, the potential activating effect of Fas on mouse fibroblast cell line NIH3T3 was investigated. On treatment with anti-Fas in vitro, the cell death of NIH3T3 fibroblasts was reduced and the expression of proinflammatory cytokines TNF-α and IL-6 was increased. These findings suggest that impairment of immune tolerance by increased T-cell reactivity does not lead to enhanced susceptibility to CIA and point to a role of Fas in joint destruction

Search for Doubly-Charged Higgs Boson Production at HERA

A search for the single production of doubly-charged Higgs bosons H^{\pm \pm} in ep collisions is presented. The signal is searched for via the Higgs decays into a high mass pair of same charge leptons, one of them being an electron. The analysis uses up to 118 pb^{-1} of ep data collected by the H1 experiment at HERA. No evidence for doubly-charged Higgs production is observed and mass dependent upper limits are derived on the Yukawa couplings h_{el} of the Higgs boson to an electron-lepton pair. Assuming that the doubly-charged Higgs only decays into an electron and a muon via a coupling of electromagnetic strength h_{e \mu} = \sqrt{4 \pi \alpha_{em}} = 0.3, a lower limit of 141 GeV on the H^{\pm\pm} mass is obtained at the 95% confidence level. For a doubly-charged Higgs decaying only into an electron and a tau and a coupling h_{e\tau} = 0.3, masses below 112 GeV are ruled out.Comment: 15 pages, 3 figures, 1 tabl

Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA

An investigation of the hadronic final state in diffractive and non--diffractive deep--inelastic electron--proton scattering at HERA is presented, where diffractive data are selected experimentally by demanding a large gap in pseudo --rapidity around the proton remnant direction. The transverse energy flow in the hadronic final state is evaluated using a set of estimators which quantify topological properties. Using available Monte Carlo QCD calculations, it is demonstrated that the final state in diffractive DIS exhibits the features expected if the interaction is interpreted as the scattering of an electron off a current quark with associated effects of perturbative QCD. A model in which deep--inelastic diffraction is taken to be the exchange of a pomeron with partonic structure is found to reproduce the measurements well. Models for deep--inelastic $ep$ scattering, in which a sizeable diffractive contribution is present because of non--perturbative effects in the production of the hadronic final state, reproduce the general tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil

Single and repeated moderate consumption of native or dealcoholized red wine show different effects on antioxidant parameters in blood and DNA strand breaks in peripheral leukocytes in healthy volunteers: a randomized controlled trial [ISRCTN68505294]

BACKGROUND: Red wine (RW) is rich in antioxidant polyphenols that might protect from oxidative stress related diseases, such as cardiovascular disease and cancer. Antioxidant effects after single ingestion of RW or dealcoholized RW (DRW) have been observed in several studies, but results after regular consumption are contradictory. Thus, we examined if single or repeated consumption of moderate amounts of RW or DRW exert antioxidant activity in vivo. METHODS: Total phenolic content and concentration of other antioxidants in plasma/serum, total antioxidant capacity (TEAC) in plasma as well as DNA strand breaks in peripheral leukocytes were measured in healthy non-smokers A) before, 90 and 360 min after ingestion of one glass of RW, DRW or water; B) before and after consumption of one glass of RW or DRW daily for 6 weeks. DNA strand breaks (SB) were determined by single cell gel electrophoresis (Comet Assay) in untreated cells and after induction of oxidative stress ex vivo with H(2)O(2 )(300 μM, 20 min). RESULTS: Both RW and DRW transiently increased total phenolic content in plasma after single consumption, but only RW lead to a sustained increase if consumed regularly. Plasma antioxidant capacity was not affected by single or regular consumption of RW or DRW. Effects of RW and DRW on DNA SB were conflicting. DNA strand breaks in untreated cells increased after a single dose of RW and DRW, whereas H(2)O(2 )induced SB were reduced after DRW. In contrast, regular RW consumption reduced SB in untreated cells but did not affect H(2)O(2 )induced SB. CONCLUSION: The results suggest that consumption of both RW and DRW leads to an accumulation of phenolic compounds in plasma without increasing plasma antioxidant capacity. Red wine and DRW seem to affect the occurrence of DNA strand breaks, but this cannot be referred to antioxidant effects

Measurement of the charm and beauty structure functions using the H1 vertex detector at HERA

Inclusive charm and beauty cross sections are measured in e − p and e + p neutral current collisions at HERA in the kinematic region of photon virtuality 5≤Q 2≤2000 GeV2 and Bjorken scaling variable 0.0002≤x≤0.05. The data were collected with the H1 detector in the years 2006 and 2007 corresponding to an integrated luminosity of 189 pb−1. The numbers of charm and beauty events are determined using variables reconstructed by the H1 vertex detector including the impact parameter of tracks to the primary vertex and the position of the secondary vertex. The measurements are combined with previous data and compared to QCD predictions

Study of Charm Fragmentation into D^{*\pm} Mesons in Deep-Inelastic Scattering at HERA

The process of charm quark fragmentation is studied using $D^{*\pm}$ meson production in deep-inelastic scattering as measured by the H1 detector at HERA. Two different regions of phase space are investigated defined by the presence or absence of a jet containing the $D^{*\pm}$ meson in the event. The parameters of fragmentation functions are extracted for QCD models based on leading order matrix elements and DGLAP or CCFM evolution of partons together with string fragmentation and particle decays. Additionally, they are determined for a next-to-leading order QCD calculation in the fixed flavour number scheme using the independent fragmentation of charm quarks to $D^{*\pm}$ mesons.Comment: 33 pages, submitted to EPJ

Measurement of charged particle spectra in deep-inelastic ep scattering at HERA

Charged particle production in deep-inelastic ep scattering is measured with the H1 detector at HERA. The kinematic range of the analysis covers low photon virtualities, 5 LT Q(2) LT 100 GeV2, and small values of Bjorken-x, 10(-4) LT x LT 10(-2). The analysis is performed in the hadronic centre-of-mass system. The charged particle densities are measured as a function of pseudorapidity (n(*)) and transverse momentum (p(T)(*)) in the range 0 LT n(*) LT 5 and 0 LT p(T)(*) LT 10 GeV in bins of x and Q(2). The data are compared to predictions from different Monte Carlo generators implementing various options for hadronisation and parton evolutions

Jet production in ep collisions at high Q(2) and determination of alpha(s)

The production of jets is studied in deep-inelastic e(+/-) p scattering at large negative four momentum transfer squared 150 LT Q(2) LT 15000 GeV2 using HERA data taken in 1999-2007, corresponding to an integrated luminosity of 395 pb(-1). Inclusive jet, 2-jet and 3-jet cross sections, normalised to the neutral current deep-inelastic scattering cross sections, are measured as functions of Q(2), jet transverse momentum and proton momentum fraction. The measurements are well described by perturbative QCD calculations at next-to-leading order corrected for hadronisation effects. The strong coupling as determined from these measurement

Simulated microgravity upregulates gene expression of the skeletal regulator core binding factor α1/Runx2 in Medaka fish larvae in vivo

Long-term space flight results in significant bone loss in humans. However, it remains to be shown how microgravity affects the expression of genes involved in modeling and remodeling of bone material in vivo. For these analyses, animal models are instrumental to study alterations at the molecular and cellular level. Although it is not known at present, whether fish lose bone in microgravity, they show many experimental advantages to approach these questions in vivo. Here, we report for the first time that living Medaka larvae can be used in hypergravitation and clinorotation experiments to study the effect of altered gravity on gene expression in a whole-animal situation. Living Medaka larvae at 1 day post-hatching were exposed to hypergravity and simulated microgravity for 24 hours (h) and the level of mRNA expression of skeletal regulators was determined by real-time RT-PCR. No effect of altered gravity was observed on the expression of osteoprotegerin (opg) genes that regulate osteoclast formation in humans. However, clinorotation resulted in a significant increase of expression of core binding factor α1(cbfa1/runx2), a crucial regulator of osteoblast formation. Exposure to hypergravitation for 24 h on the other hand had no effect on cbfa1/runx2 expression. This shows that cbfa1/runx2 responds to reduced gravity by expression level changes in vivo. Furthermore, it demonstrates that Medaka provides a valuable experiental model to study molecular mechanisms for compensating microgravity induced bone loss