A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes

SummaryObjectiveRecent studies revealed a close connection between adipose tissue, adipokines and articular degenerative inflammatory diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). The goal of this work was to investigate the activity of adiponectin in human and murine chondrocytes and to study its functional role in the modulation of nitric oxide synthase type II (NOS2). For completeness, interleukin (IL)-6, IL-1β, matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, prostaglandin E2 (PGE2), leukotriene B4 (LTB4), tumor necrosis factor alpha (TNF)-α and monocyte chemoattractant protein-1 (MCP-1) accumulation have been evaluated in adiponectin-stimulated chondrocytes cell culture supernatants.MethodsMurine ATDC5 cell line, C28/I2, C20A4, TC28a2 human immortalized chondrocytes, and human cultured chondrocytes were used. Nitrite accumulation was determined by Griess reaction. Adiponectin receptors (AdipoRs) expression was evaluated by immunofluorescence microscopy and confirmed by reverse transcriptase-polymerase chain reaction. NOS2 expression was evaluated by Western blot analysis whereas cytokines, prostanoids and metalloproteinases production was evaluated by specific enzyme-linked immunosorbent assays.ResultsHuman and murine chondrocytes express functional AdipoRs. Adiponectin induces NOS2. This effect is inhibited by aminoguanidine, dexamethasone and by a selective inhibitor of phosphatidylinositol 3-kinase. In addition, adiponectin is able to increase IL-6, MMP-3, MMP-9 and MCP-1 by murine cultured chondrocytes whereas it was unable to modulate TNF-α, IL-1β, MMP-2, TIMP-1, PGE2 and LTB4 release.ConclusionsThese results bind more closely the interactions between fat-derived adipokines and articular inflammatory diseases, and suggest that adiponectin is a novel key element in the maintenance of cartilage homeostasis which might be considered as a potential therapeutical target in joint degenerative diseases

Effects of heavy modes on vacuum stability in supersymmetric theories

We study the effects induced by heavy fields on the masses of light fields in supersymmetric theories, under the assumption that the heavy mass scale is much higher than the supersymmetry breaking scale. We show that the square-masses of light scalar fields can get two different types of significant corrections when a heavy multiplet is integrated out. The first is an indirect level-repulsion effect, which may arise from heavy chiral multiplets and is always negative. The second is a direct coupling contribution, which may arise from heavy vector multiplets and can have any sign. We then apply these results to the sGoldstino mass and study the implications for the vacuum metastability condition. We find that the correction from heavy chiral multiplets is always negative and tends to compromise vacuum metastability, whereas the contribution from heavy vector multiplets is always positive and tends on the contrary to reinforce it. These two effects are controlled respectively by Yukawa couplings and gauge charges, which mix one heavy and two light fields respectively in the superpotential and the Kahler potential. Finally we also comment on similar effects induced in soft scalar masses when the heavy multiplets couple both to the visible and the hidden sector.Comment: LaTex, 24 pages, no figures; v2 some comments and references adde

On the Effective Description of Large Volume Compactifications

We study the reliability of the Two-Step moduli stabilization in the type-IIB Large Volume Scenarios with matter and gauge interactions. The general analysis is based on a family of N=1 Supergravity models with a factorizable Kaehler invariant function, where the decoupling between two sets of fields without a mass hierarchy is easily understood. For the Large Volume Scenario particular analyses are performed for explicit models, one of such developed for the first time here, finding that the simplified version, where the Dilaton and Complex structure moduli are regarded as frozen by a previous stabilization, is a reliable supersymmetric description whenever the neglected fields stand at their leading F-flatness conditions and be neutral. The terms missed by the simplified approach are either suppressed by powers of the Calabi-Yau volume, or are higher order operators in the matter fields, and then irrelevant for the moduli stabilization rocedure. Although the power of the volume suppressing such corrections depends on the particular model, up to the mass level it is independent of the modular weight for the matter fields. This at least for the models studied here but we give arguments to expect the same in general. These claims are checked through numerical examples. We discuss how the factorizable models present a context where despite the lack of a hierarchy with the supersymmetry breaking scale, the effective theory still has a supersymmetric description. This can be understood from the fact that it is possible to find vanishing solution for the auxiliary components of the fields being integrated out, independently of the remaining dynamics. Our results settle down the question on the reliability of the way the Dilaton and Complex structure are treated in type-IIB compactifications with large compact manifold volumina.Comment: 23 pages + 2 appendices (38 pages total). v2: minor improvements, typos fixed. Version published in JHE

ECLIM-SEHOP, a new platform to set up and develop international academic clinical trials for childhood cancer and blood disorders in Spain

Introduction: Cancer and blood disorders in children are rare. The progressive improvement in survival over the last decades largely relies on the development of international academic clinical trials that gather the sufcient number of patients globally to elaborate solid conclusions and drive changes in clinical practice. The participation of Spain into large international academic trials has traditionally lagged behind of other European countries, mainly due to the burden of administrative tasks to open new studies, lack of fnancial support and limited research infrastructure in our hospitals. Methods: The objective of ECLIM-SEHOP platform (Ensayos Clínicos Internacionales Multicéntricos-SEHOP) is to overcome these difculties and position Spain among the European countries leading the advances in cancer and blood disorders, facilitate the access of our patients to novel diagnostic and therapeutic approaches and, most importantly, continue to improve survival and reducing long-term sequelae. ECLIM-SEHOP provides to the Spanish clinical investigators with the necessary infrastructural support to open and implement academic clinical trials and registries. Results: In less than 3 years from its inception, the platform has provided support to 20 clinical trials and 8 observational studies, including 8 trials and 4 observational studies where the platform performs all trial-related tasks (integral support: trial setup, monitoring, etc.) with more than 150 patients recruited since 2017 to these studies. In this manuscript, we provide baseline metrics for academic clinical trial performance that permit future comparisons. Conclusions: ECLIM-SEHOP facilitates Spanish children and adolescents diagnosed with cancer and blood disorders to access state-of-the-art diagnostic and therapeutic strategies

A first worldwide multispecies survey of invasive Mediterranean pine bark beetles (Coleoptera: Curculionidae, Scolytinae)

Several European and Mediterranean species of pine bark beetles (Coleoptera: Curculionidae: Scolytinae) have become established in North America and the southern hemisphere, posing a novel threat to planted and naturally-occurring pine forests. Our objectives were to investigate (1) the occurrence and relative abundance of pine bark beetles in these regions, and (2) the trapping performance of different blends of multispecies lures. In 2016–2017 a network of interception traps was installed in six non-European countries (Argentina, Australia, New Zealand, South Africa, the United States, and Uruguay), and in six European countries (France, Greece, Hungary, Italy, Portugal, and Spain) for comparison. Half of the traps were baited with alpha-pinene and ethanol, and the other half with alpha-pinene, ethanol, and a combination of bark beetle pheromones (ipsdienol, ipsenol, and Z-verbenol). Five Mediterranean scolytine species (Hylurgus ligniperda, Hylastes ater, H. angustatus, Orthotomicus erosus, and O. laricis) were found in non-European countries. Hylurgus ligniperda and Hylastes ater were the most widespread species found in several of the invaded regions, while O. laricis and H. angustatus occurred only in Argentina and South Africa, respectively. Despite large variation among species and countries, most species were trapped with the blend containing bark beetle pheromones, except O. erosus, which was more attracted to alpha-pinene and ethanol alone. This study represents the first step towards the development of an international monitoring protocol based on multi-lure traps for the survey and early-interception of invasive alien bark beetle species.MBIE (New Zealand, contract C04X1104), from PICT 2016-0705 (Argentina), from FCT UID/AGR/00239/2013 (Portugal) and from DOR-UNIPD (Italy).http://link.springer.com/journal/10530hj2021Forestry and Agricultural Biotechnology Institute (FABI)Zoology and Entomolog

Safety and immunomodulatory effects of three probiotic strains isolated from the feces of breast-fed infants in healthy adults: SETOPROB study

We previously described the isolation and characterization of three probiotic strains from the feces of exclusively breast-fed newborn infants: Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036. These strains were shown to adhere to intestinal mucus in vitro, to be sensitive to antibiotics and to resist biliary salts and low pH. In the present study, a multicenter, randomized, double-blind, placebo-controlled trial with 100 healthy volunteers in three Spanish cities was carried out to evaluate the tolerance, safety, gut colonization and immunomodulatory effects of these three probiotics. Volunteers underwent a 15-day washout period, after which they were randomly divided into 5 groups that received daily a placebo, a capsule containing one of the 3 strains or a capsule containing a mixture of two strains for 30 days. The intervention was followed by another 15-day washout period. Patients did not consume fermented milk for the entire duration of the study. Gastrointestinal symptoms, defecation frequency and stool consistency were not altered by probiotic intake. No relevant changes in blood and serum, as well as no adverse events occurred during or after treatment. Probiotic administration slightly modified bacterial populations in the volunteers’ feces. Intestinal persistence occurred in volunteers who received L. rhamnosus CNCM I-4036. Administration of B. breve CNCM I-4035 resulted in a significant increase in fecal secretory IgA content. IL-4 and IL-10 increased, whereas IL-12 decreased in the serum of volunteers treated with any of the three strains. These results demonstrate that the consumption of these three bacterial strains was safe and exerted varying degrees of immunomodulatory effects.Part of the research currently in progress in the authors' laboratory is funded by the company Hero Spain, S. A. through the grant #3582 managed by the Fundacion General Empresa-Universidad de Granada

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction