Toll-like receptor 4 mediates intrauterine growth restriction after systemic Campylobacter rectus infection in mice: TLR4 mediates IUGR after C. rectus infection

Campylobacter rectus is associated with fetal exposure and low-birth weight in humans. C. rectus also invades placental tissues and induces fetal intrauterine growth-restriction (IUGR) in mice, along with Toll-like receptors (TLR4) overexpression, suggesting that TLR4 may mediate placental immunity and IUGR in mice. To test this hypothesis we examined the effect of in vitroTLR4 neutralization in trophoblastic proinflammatory activity and studied the IUGR phenotype in a congenic TLR4-mutant mouse strain after in vivo C. rectus infection. Human trophoblasts were pretreated with TLR4 neutralizing antibodies and infected with C. rectus; pro-inflammatory cytokine production was assessed by cytokine multiplexing assays. Neutralizing TLR4 antibodies significantly impaired the production of pro-inflammatory cytokines in trophoblastic cells after infection in a dose-dependent manner. We used a subcutaneous chamber model to provide a C. rectus challenge in BALB/cAnPt (TLR4Lps-d) and wild-type(WT) females. Females were mated with WT or TLR4Lps-dmales once/week; pregnant mice were infected at (E)7.5 and sacrificed at (E)16.5 to establish IUGR phenotypes. Maternal C. rectus infection significantly decreased fetal weight/length in infected WT when compared to sham WT controls(PLps-d−/− mice did not show statistically significant differences in fetal weight and length when compared to WT controls(P>0.05). Furthermore, heterozygous TLR4Lps-d −/+fetuses showed IUGR phenotype rescue. We concluded that TLR4 is an important mediator of trophoblastic proinflammatory responses and TLR4-deficient fetuses do not develop IUGR phenotypes after C. rectus infection, suggesting that placental cytokine activation is likely to be mediated by TLR4 during low birth weight/preterm delivery pathogenesis

Age and synchronicity of planktonic foraminiferal bioevents across the Cenomanian–Turonian boundary interval (Late Cretaceous)

The upper Cenomanian \u2013 lower Turonian is a key-stratigraphic interval, as it encompasses the Late Cretaceous supergreenhouse and a major perturbation of the global carbon cycle (i. e., Oceanic Anoxic Event 2) as evidenced by a global positive carbon isotope excursion and by the nearly world-wide deposition of organic-rich marine facies. A turnover in planktonic foraminiferal assemblages and in other marine organisms is documented across this stratigraphic interval, but reconstruction of the timing and identification of the cause and effect relationships between environmental perturbations and organism response require a highly- resolved stratigraphic framework. The appearance and extinction levels of planktonic foraminiferal species generally allow accurate intra- and supra-basinal correlations. However, bioevents cannot be assumed to be globally synchronous, because the stratigraphic and geographic distribution of species is modulated by ecological preferences exhibited by each taxon and controlled by oceanic circulation, often resulting in earlier or delayed events in certain geographic areas (i. e., diachronous datums). The aim of this study is to test the synchronicity of the planktonic foraminiferal bioevents recognized across the C/T boundary and to provide the most reliable sequence of events for correlation of low to mid-latitude localities. For this purpose, we have compiled a highly-resolved biostratigraphic analysis of the European reference section for the C/T boundary at Eastbourne, Gun Gardens (UK), and core S57 (Tarfaya, Morocco), and correlated the sequence of bioevents identified with those recorded in other coeval sections available in the literature, including the GSSP section for the base of the Turonian Stage at Rock Canyon, Pueblo (Colorado), where we calculated reliable estimates of planktonic foraminiferal events that are well-constrained by radioisotopically and astrochronologically dated bentonite layers. Results indicate that the extinctions of Thalmanninella deeckei, Thalmanninella greenhornensis, Rotalipora cushmani and \u201cGlobigerinelloides\u201d bentonensis in the latest Cenomanian are reliable bioevents for correlation. In addition, our analysis highlights other promising lowest occurrences (LOs) that need to be better constrained by bio- and chemostratigraphy, including the LO of Marginotruncana schneegansi falling close to the C/T boundary. By contrast, the appearance of Helvetoglobotruncana helvetica and of some Dicarinella species, the extinction of anaticinellids and the onset of the \u201cHeterohelix\u201d shift are likely diachronous across low to mid-latitude localities. Finally, our study suggests that different species concepts among authors, different sample size and sampling resolution, as well as species paleoecology are important factors that control the stratigraphic position at which bioevents are identified

Allelic loss of chromosome 1p as a predictor of unfavorable outcome in patients with neuroblastoma

Background. Neuroblastoma is a childhood tumor derived from cells of the neural crest, with a widely variable outcome. Differences in the behavior and prognosis of the tumor suggest that neuroblastoma can be divided into several biologic subgroups. We evaluated the most frequent genetic abnormalities in neuroblastoma to determine their prognostic value. Methods. We used Southern blot analysis to study the allelic loss of chromosomes 1p, 4p, 11q, and 14q, the duplication of chromosome 17q, and the amplification of the N-myc oncogene in 89 neuroblastomas. We also determined the nuclear DNA content of the tumor cells. Results. Allelic loss of chromosome 1p, N-myc amplification, and extra copies of chromosome 17q were significantly associated with unfavorable outcomes. In a multivariate analysis, loss of chromosome 1p was the most powerful prognostic factor. It provided strong prognostic information when it was included in multivariate models containing the prognostic factors of age and stage or serum ferritin level and stage. Among the patients with stage I, II, or IVS disease, the mean (±SD) three-year event-free survival was 100 percent in those without allelic loss of chromosome 1p and 34±15 percent in those with such loss; the rates of three- year event-free survival among the patients with stage III and stage IV disease were 53±10 percent and 0 percent, respectively. Conclusions. The loss of chromosome 1p is a strong prognostic factor in patients with neuroblastoma, independently of age and stage. It reliably identifies patients at high risk in stages I, II, and IVS, which are otherwise clinically favorable. More intensive therapy may be considered in these patients. Patients in stages III and IV with allelic loss of chromosome 1p have a very poor outlook, whereas those without such loss are at moderate risk

Chondroprotective actions of selective COX-2 inhibitors in vivo: A systematic review

Knee osteoarthritis (OA) is a condition mainly characterized by cartilage degradation. Currently, no effective treatment exists to slow down the progression of OA-related cartilage damage. Selective COX-2 inhibitors may, next to their pain killing properties, act chondroprotective in vivo. To determine whether the route of administration is important for the efficacy of the chondroprotective properties of selective COX-2 inhibitors, a systematic review was performed according to the PRISMA guidelines. Studies investigating OA-related cartilage damage of selective COX-2 inhibitors in vivo were included. Nine of the fourteen preclinical studies demonstrated chondroprotective effects of selective COX-2 inhibitors using systemic administration. Five clinical studies were included and, although in general non-randomized, failed to demonstrate chondroprotective actions of oral selective COX-2 inhibitors. All of the four preclinical studies using bolus intra-articular injections demonstrated chondroprotective actions, while one of the three preclinical studies using a slow release system demonstrated chondroprotective actions. Despite the limited evidence in clinical studies that have used the oral administration route, there seems to be a preclinical basis for considering selective COX-2 inhibitors as disease modifying osteoarthritis drugs when used intra-articularly. Intra-articularly injected selective COX-2 inhibitors may hold the potential to provide chondroprotective effects in vivo in clinical studies

NOD2 regulates hematopoietic cell function during graft-versus-host disease

Nucleotide-binding oligomerization domain 2 (NOD2) polymorphisms are independent risk factors for Crohn's disease and graft-versus-host disease (GVHD). In Crohn's disease, the proinflammatory state resulting from NOD2 mutations have been associated with a loss of antibacterial function of enterocytes such as paneth cells. NOD2 has not been studied in experimental allogeneic bone marrow transplantation (allo-BMT). Using chimeric recipients with NOD2−/− hematopoietic cells, we demonstrate that NOD2 deficiency in host hematopoietic cells exacerbates GVHD. We found that proliferation and activation of donor T cells was enhanced in NOD-deficient allo-BMT recipients, suggesting that NOD2 plays a role in the regulation of host antigen-presenting cells (APCs). Next, we used bone marrow chimeras in an experimental colitis model and observed again that NOD2 deficiency in the hematopoietic cells results in increased intestinal inflammation. We conclude that NOD2 regulates the development of GVHD through its inhibitory effect on host APC function

Genuine Correlations of Like-Sign Particles in Hadronic Z0 Decays

Correlations among hadrons with the same electric charge produced in Z0 decays are studied using the high statistics data collected from 1991 through 1995 with the OPAL detector at LEP. Normalized factorial cumulants up to fourth order are used to measure genuine particle correlations as a function of the size of phase space domains in rapidity, azimuthal angle and transverse momentum. Both all-charge and like-sign particle combinations show strong positive genuine correlations. One-dimensional cumulants initially increase rapidly with decreasing size of the phase space cells but saturate quickly. In contrast, cumulants in two- and three-dimensional domains continue to increase. The strong rise of the cumulants for all-charge multiplets is increasingly driven by that of like-sign multiplets. This points to the likely influence of Bose-Einstein correlations. Some of the recently proposed algorithms to simulate Bose-Einstein effects, implemented in the Monte Carlo model PYTHIA, are found to reproduce reasonably well the measured second- and higher-order correlations between particles with the same charge as well as those in all-charge particle multiplets.Comment: 26 pages, 6 figures, Submitted to Phys. Lett.

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio