Hepatitis C virus in vitro replication is efficiently inhibited by acridone Fac4

Hepatitis C Virus (HCV) affects about 170 million people worldwide. The current treatment has a high cost and variable response rates according to the virus genotype. Acridones, a group of compounds extracted from natural sources, showed potential antiviral actions against HCV. Thus, this study aimed to evaluate the effect of a panel of 14 synthetic acridones on the HCV life cycle. The compounds were screened using an Huh7.5 cell line stably harboring the HCV genotype 2a subgenomic replicon SGR-JFH1-FEO. Cells were incubated in the presence or absence of compounds for 72 hours and cell viability and replication levels were assessed by MTT and luciferase assays, respectively. The acridone Fac4 at 5 μM inhibited approximately 90% of HCV replication with 100 % of cell viability. The effects of Fac4 on virus replication, entry and release steps were evaluated in Huh7.5 cells infected with the JFH-1 isolate of HCV (HCVcc). Fac4 inhibited approximately 70 % of JFH-1 replication, while no effect was observed on virus entry. The antiviral activity of Fac4 was also observed on the viral release, with almost 80% of inhibition. No inhibitory effect was observed against genotype 3 replication. Fac4 demonstrated 40% of intercalation into dsRNA, however did not inhibit T7 polymerase activity, as well as translation by IRES interaction. Although its mode of action is partly understood, the Fac4 presents significant inhibition of Hepatitis C virus replication and can therefore be considered as a candidate for the development of a future anti-HCV treatment

Vitamins A, C and E and the risk of breast cancer: results from a case-control study in Greece

Although several dietary compounds are hypothesized to have anticarcinogenic properties, the role ofpecific micronutrients in the development of breast cancer remains unclear. To address this issue, we assessed intake of retinol, β-carotene, vitamin C and vitamin E in relation to breast cancer risk in a case–control study in Greece. Eight hundrednd twenty women with histologically confirmed breast cancer were compared with 1548 control women. Dietary data were collectedhrough a 115-item semiquantitative food frequency questionnaire. Data were modelled by logistic regression, with adjustment forotal energy intake and established breast cancer risk factors, as well as mutual adjustment among the micronutrients. Amongost-menopausal women, there was no association between any of the micronutrients evaluated and risk of breast cancer. Amongremenopausal women, β-carotene, vitamin C and vitamin E were each inversely associated with breast cancer risk, but afterutual adjustment among the three nutrients only β-carotene remained significant; the odds ratio (OR) for a one-quintilencrease in β-carotene intake was 0.84 (95% confidence interval 0.73–0.97). The inverse association observed with β-carotene intake, however, is slightly weaker than the association previously observed with vegetable intake in these data,aising the possibility that the observed β-carotene effect is accounted for by another component of vegetables. ©1999 Cancer Research Campaig

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement.

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways

Search for neutral MSSM Higgs bosons decaying to a pair of tau leptons in pp collisions

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Measurement of top quark–antiquark pair production in association with a W or Z boson in pp collisions at √s=8 TeV

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Searches for electroweak production of charginos, neutralinos, and sleptons decaying to leptons and W, Z, and Higgs bosons in pp collisions at 8 TeV

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Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

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Measurement of prompt J/ψ pair production in pp collisions at √s = 7 Tev

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