Decreased infarct size after focal cerebral ischemia in mice chronically infected with Toxoplasma gondii

To determine whether Toxoplasma gondii infection could modify biological phenomena associated with brain ischemia, we investigated the effect of permanent middle cerebral artery occlusion (MCAO) on neuronal survival, inflammation and redox state in chronically infected mice. Infected animals showed a 40% to 50% decrease of infarct size compared with non-infected littermates 1, 4 and 14 days after MCAO. The resistance of infected mice may be associated with increased basal levels of anti-inflammatory cytokines and/or a marked reduction of the MCAO-related brain induction of two pro-inflammatory cytokines, tumor necrosis factor-alpha and interferon-gamma (IFNγ). In addition, potential anti-inflammatory/neuroprotective factors such as nerve growth factor, suppressor of cytokine signaling-3, superoxide dismutase activity, uncoupling protein-2 and glutathione (GSH) were upregulated in the brain of infected mice. Consistent with a role of GSH in central cytokine regulation, GSH depletion by diethyl maleate inhibited Toxoplasma gondii lesion resistance by increasing the proinflammatory cytokine IFNγ brain levels. Overall, these findings indicate that chronic toxoplasmosis decisively influences both the inflammatory molecular events and outcome of cerebral ischemia

Osteosarcoma: correlation between radiological and histological changes after intra-arterial chemotherapy

The statistical correlation between three different radiological methods (conventional radiography, computed tomography and angiography) and tumor necrosis (TN) of the resected specimen have been studied in a series of 31 patients diagnosed with osteosarcoma (OS). They were treated with a multidisciplinary approach including intraarterial and intravenous chemotherapy followed by limb salvage procedures, plus intraoperative radiotherapy and adjuvant chemotherapy. A clear statistical correlation has been obtained between TN and angiography (p = 0.02) and between TN and two specific radiological signs: 'tumoral stain and neovascularity' (p = 0.02) and 'peritumoral fat planes' (p = 0.05). Conventional radiography, computed tomography and other radiological signs studied (nutrient vessel, soft tissue mass and central peripheral calcifications) did not show any significant correlation with TN. These results seem to suggest that angiography is a method to evaluate TN preoperatively and also to define the efficacy of neoadjuvant chemotherapy in OS

Role of the satiety factor oleoylethanolamide in alcoholism

Oleoylethanolamide (OEA) is a satiety factor that controls motivational responses to dietary fat. Here we show that alcohol administration causes the release of OEA in rodents, which in turn reduces alcohol consumption by engaging peroxisome proliferator-activated receptor-alpha (PPAR-α). This effect appears to rely on peripheral signaling mechanisms as alcohol self-administration is unaltered by intracerebral PPAR-α agonist administration, and the lesion of sensory afferent fibers (by capsaicin) abrogates the effect of systemically administered OEA on alcohol intake. Additionally, OEA is shown to block cue-induced reinstatement of alcohol-seeking behavior (an animal model of relapse) and reduce the severity of somatic withdrawal symptoms in alcohol-dependent animals. Collectively, these findings demonstrate a homeostatic role for OEA signaling in the behavioral effects of alcohol exposure and highlight OEA as a novel therapeutic target for alcohol use disorders and alcoholism

Gluten-induced RNA methylation changes regulate intestinal inflammation via allele-specific XPO1 translation in epithelial cells

[EN] Objectives Coeliac disease (CD) is a complex autoimmune disorder that develops in genetically susceptible individuals. Dietary gluten triggers an immune response for which the only available treatment so far is a strict, lifelong gluten free diet. Human leucocyte antigen (HLA) genes and several non-HLA regions have been associated with the genetic susceptibility to CD, but their role in the pathogenesis of the disease is still essentially unknown, making it complicated to develop much needed non-dietary treatments. Here, we describe the functional involvement of a CD-associated single-nudeotide polymorphism (SNP) located in the 5'UTR of XPO1 in the inflammatory environment characteristic of the coeliac intestinal epithelium. Design The function of the CD-associated SNP was investigated using an intestinal cell line heterozygous for the SNP, N6-methyladenosine (m(6)A)-related knock-out and HLA-DQ2 mice, and human samples from patients with CD. Results Individuals harbouring the risk allele had higher m(6)A methylation in the 5'UTR of XPO1 RNA, rendering greater XPO1 protein amounts that led to downstream nuclear factor kappa B (NFkB) activity and subsequent inflammation. Furthermore, gluten exposure increased overall m(6)A methylation in humans as well as in in vitro and in vivo models. Conclusion We identify a novel m(6)A-XPO1-NFkB pathway that is activated in CD patients. The findings will prompt the development of new therapeutic approaches directed at m(6)A proteins and XPO1, a target under evaluation for the treatment of intestinal disorders.This study was supported by a grant from the Spanish Ministry of Science, Universities and Innovation (PGC2018-097573-A-I00) to AC-R. JRB was funded by ISCIII Research project PI16/00258, cofinanced by the Spanish Ministry of Economy and Competitiveness and by the European Union ERDF/ESF 'A way to make Europe'. AO-G and MS-D were funded by predoctoral fellowships from the Basque Government and the University of the Basque Country respectively. DS and LH were funded by the Spanish Ministry (MINECO) (SAF2017-83813-C3-1-R) and cofunded by the ERDF, the Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y la Nutricion (CIBEROBN) (Grant CB06/03/0001 to DS), the Government of Catalonia (2017SGR278 to DS), and the Fundacio La Marato de TV3 (201627-30 to DS). CH is a Howard Hughes Medical Institute Investigator and has been funded by the National Institute of Health HG008935. We would like to thank Xuechen Yu and Justin Vargas for processing the adult CD biopsy samples obtained from Columbia University. EFV is supported by a CIHR grant 168840 and holds a Canada Research Chair

A digital waveguide-based approach for Clavinet modeling and synthesis

The Clavinet is an electromechanical musical instrument produced in the mid-twentieth century. As is the case for other vintage instruments, it is subject to aging and requires great effort to be maintained or restored. This paper reports analyses conducted on a Hohner Clavinet D6 and proposes a computational model to faithfully reproduce the Clavinet sound in real time, from tone generation to the emulation of the electronic components. The string excitation signal model is physically inspired and represents a cheap solution in terms of both computational resources and especially memory requirements (compared, e.g., to sample playback systems). Pickups and amplifier models have been implemented which enhance the natural character of the sound with respect to previous work. A model has been implemented on a real-time software platform, Pure Data, capable of a 10-voice polyphony with low latency on an embedded device. Finally, subjective listening tests conducted using the current model are compared to previous tests showing slightly improved results

[Real Madrid I] [Material gráfico]

Contiene fotografías pertenecientes al archivo fotográfico del diario "Región", publicadas entre 1974 y 1983Algunas fotos no indican autoría; el resto firmadas por Foto Sierra (Oviedo), Foto E. Gar (Oviedo), Foto Arsenio (Trubia, Oviedo), Foto Piñera (Oviedo), Gil del Espinar (Bilbao), Europa Press, Efe, Cifra Gráfic

The role of retinal fluid location in atrophy and fibrosis evolution of patients with neovascular age-related macular degeneration long-term treated in real world

Purpose: To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world. Methods: An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed. Results: After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81). Conclusion: Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model