Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition

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

Metabolic profile and psychological variables after bariatric surgery: association with weight outcomes

Purpose This study aims to examine associations between metabolic profile and psychological variables in post-bariatric patients and to investigate if metabolic and psychological variables, namely high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glycated hemoglobin (HbA 1c), impulsivity, psychological distress, depressive and eating disorder symptoms are independently associated with percentage of excess weight loss (%EWL) after bariatric surgery.Methods One hundred and fifty bariatric patients (BMI = 33.04 +/- 5.8 kg/m(2)) who underwent to bariatric surgery for more than 28.63 +/- 4.9 months were assessed through a clinical interview, a set of self-report measures and venous blood samples. Pearson's correlations were used to assess correlations between %EWL, metabolic and psychological variables. Multiple linear regression was conducted to investigate which metabolic and psychological variables were independently associated with %EWL, while controlling for type of surgery.Results Higher TG blood levels were associated with higher disordered eating, psychological distress and depression scores. HDL-C was associated with higher depression scores. Both metabolic and psychological variables were associated with %EWL. Regression analyses showed that, controlling for type of surgery, higher % EWL is significantly and independently associated with less disordered eating symptoms and lower TG and HbA_1c blood concentrations (R-2 aj = 0.383, F (4, 82) = 14.34, p < 0.000).Conclusion An association between metabolic and psychological variables, particularly concerning TG blood levels, disordered eating and psychological distress/depression was found. Only higher levels of disordered eating, TG and HbA_1c showed and independent correlation with less weight loss. Targeting maladaptive eating behaviors may be a reasonable strategy to avoid weight regain and optimize health status post-operatively.This research was partially supported by Fundacao para a Ciencia e a Tecnologia/Foundation for Science and Technology through European Union COMPETE program Grant to Eva Conceicao (IF/01219/2014) and (PTDC/MHC-PCL/4974/2012), doctoral scholarship (SFRH/BD/104159/2014) to Ana Pinto-Bastos and doctoral scholarship (SFRH/BD/104182/2014) to Sofia Ramalho

Barriers to identifying eating disorders in pregnancy and in the postnatal period: a qualitative approach.

BACKGROUND: Eating Disorders (ED) are mental health disorders that typically effect women of childbearing age and are associated with adverse maternal and infant outcomes. UK healthcare guidance recommends routine enquiry for current and past mental illness in antenatal and postnatal care for all women, and that pregnant women with a known ED are offered enhanced monitoring and support. Midwives and health visitors are ideally placed to identify and support women with ED as they are often the primary point of contact during the antenatal and postnatal periods. However, research on the barriers to identifying ED in the perinatal period is limited. This study aimed to understand the barriers to disclosure and identification of ED in pregnancy and postnatally as perceived by women with past or current ED, and midwives and health visitors working in the UK National Health Service. METHODS: Two studies were undertaken: mixed-measures survey of pregnant and postnatal women with current or past ED; focus groups with student and qualified midwives and health visitors. RESULTS: Five themes emerged on the barriers to disclosure in pregnancy as perceived by women: stigma, lack of opportunity, preference for self-management, current ED symptomatology and illness awareness. Four themes were identified on the barriers to identification of ED in pregnancy and in the postnatal period as perceived by health professionals: system constraints, recognition of role, personal attitudes, and stigma and taboo. CONCLUSIONS: Several barriers to the identification of ED during and after pregnancy were described, the main factors were stigma and poor professional training. Perinatal mental health is becoming increasingly prioritised within national policy initiatives; however, ED continue to be neglected and increased awareness is needed. Similarly, clinical guidance aimed at responding to the rising prevalence of obesity focus on changing nutrition but not on assessing for the presence of ED behaviours that might be affecting nutrition. Improving education and training for health professionals may contribute to reducing stigma and increase confidence in identifying ED. The barriers identified in this research need to be addressed if recognition and response to women with ED during the perinatal period is to improve

Synergistic Interactions between the NS3hel and E Proteins Contribute to the Virulence of Dengue Virus Type 1

Dengue virus constitutes a significant public health problem in tropical regions of the world. Despite the high morbidity and mortality of this infection, no effective antiviral drugs or vaccines are available for the treatment or prevention of dengue infections. The profile of clinical signs associated with dengue infection has changed in recent years with an increase in the number of episodes displaying unusual signs. We use reverse genetics technology to engineer DENV-1 viruses with subsets of mutations previously identified in highly neurovirulent strains to provide insights into the molecular mechanisms underlying dengue neuropathogenesis. We found that single mutations affecting the E and NS3hel proteins, introduced in a different genetic context, had a synergistic effect increasing DENV replication capacity in human and mosquito derived cells in vitro. We also demonstrated correlations between the presence of these mutations and viral replication efficiency, viral loads, the induction of innate immune response genes and pathogenesis in a mouse model. These results should improve our understanding of the DENV-host cell interaction and contribute to the development of effective antiviral strategies

Curation of viral genomes: challenges, applications and the way forward

BACKGROUND: Whole genome sequence data is a step towards generating the 'parts list' of life to understand the underlying principles of Biocomplexity. Genome sequencing initiatives of human and model organisms are targeted efforts towards understanding principles of evolution with an application envisaged to improve human health. These efforts culminated in the development of dedicated resources. Whereas a large number of viral genomes have been sequenced by groups or individuals with an interest to study antigenic variation amongst strains and species. These independent efforts enabled viruses to attain the status of 'best-represented taxa' with the highest number of genomes. However, due to lack of concerted efforts, viral genomic sequences merely remained as entries in the public repositories until recently. RESULTS: VirGen is a curated resource of viral genomes and their analyses. Since its first release, it has grown both in terms of coverage of viral families and development of new modules for annotation and analysis. The current release (2.0) includes data for twenty-five families with broad host range as against eight in the first release. The taxonomic description of viruses in VirGen is in accordance with the ICTV nomenclature. A well-characterised strain is identified as a 'representative entry' for every viral species. This non-redundant dataset is used for subsequent annotation and analyses using sequenced-based Bioinformatics approaches. VirGen archives precomputed data on genome and proteome comparisons. A new data module that provides structures of viral proteins available in PDB has been incorporated recently. One of the unique features of VirGen is predicted conformational and sequential epitopes of known antigenic proteins using in-house developed algorithms, a step towards reverse vaccinology. CONCLUSION: Structured organization of genomic data facilitates use of data mining tools, which provides opportunities for knowledge discovery. One of the approaches to achieve this goal is to carry out functional annotations using comparative genomics. VirGen, a comprehensive viral genome resource that serves as an annotation and analysis pipeline has been developed for the curation of public domain viral genome data . Various steps in the curation and annotation of the genomic data and applications of the value-added derived data are substantiated with case studies

Search for High-Mass Resonances Decaying to τν in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for high-mass resonances decaying to τν using proton-proton collisions at √s=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W′ bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2–3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level

Performance of missing transverse momentum reconstruction with the ATLAS detector using proton–proton collisions at √s = 13 TeV

The performance of the missing transverse momentum (EmissT) reconstruction with the ATLAS detector is evaluated using data collected in proton–proton collisions at the LHC at a centre-of-mass energy of 13 TeV in 2015. To reconstruct EmissT, fully calibrated electrons, muons, photons, hadronically decaying τ -leptons, and jets reconstructed from calorimeter energy deposits and charged-particle tracks are used. These are combined with the soft hadronic activity measured by reconstructed charged-particle tracks not associated with the hard objects. Possible double counting of contributions from reconstructed charged-particle tracks from the inner detector, energy deposits in the calorimeter, and reconstructed muons from the muon spectrometer is avoided by applying a signal ambiguity resolution procedure which rejects already used signals when combining the various EmissT contributions. The individual terms as well as the overall reconstructed EmissT are evaluated with various performance metrics for scale (linearity), resolution, and sensitivity to the data-taking conditions. The method developed to determine the systematic uncertainties of the EmissT scale and resolution is discussed. Results are shown based on the full 2015 data sample corresponding to an integrated luminosity of 3.2 fb−1

Measurement of VH, H → b b ¯ production as a function of the vector-boson transverse momentum in 13 TeV pp collisions with the ATLAS detector

Cross-sections of associated production of a Higgs boson decaying into bottom-quark pairs and an electroweak gauge boson, W or Z, decaying into leptons are measured as a function of the gauge boson transverse momentum. The measurements are performed in kinematic fiducial volumes defined in the `simplified template cross-section' framework. The results are obtained using 79.8 fb-1 of proton-proton collisions recorded by the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 13 TeV. All measurements are found to be in agreement with the Standard Model predictions, and limits are set on the parameters of an effective Lagrangian sensitive to modifications of the Higgs boson couplings to the electroweak gauge bosons