Identification of pannexin 1-regulated genes, interactome, and pathways in rhabdomyosarcoma and its tumor inhibitory interaction with AHNAK

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, is an aggressive cancer with a poor prognosis. Despite current management, the 5-year survival rate for patients with metastatic RMS is ∼30%; underscoring the need to develop better treatment strategies. We have recently reported that pannexin 1 (PANX1) levels are downregulated in RMS and that restoring its expression inhibits RMS progression. Here, we have surveyed and characterized the molecular changes induced by PANX1 re-expression in RMS. We cataloged transcriptomic changes in this context by RNA sequencing. At the protein level, we unveiled PANX1 interactors using BioID, complemented by co-immunoprecipitation coupled to high-performance liquid chromatography/electrospray ionization tandem mass spectrometry performed in PANX1-enriched fractions. Using these data, we generated searchable public databases for the PANX1 interactome and changes to the RMS transcriptome occurring when PANX1 expression is restored. STRING network analyses revealed a PANX1 interactome involving plasma membrane and cytoskeleton-associated proteins including the previously undescribed interactor AHNAK. Indeed, AHNAK knockdown abrogated the PANX1-mediated reduction in RMS cell viability and migration. Using these unbiased approaches, we bring insight to the mechanisms by which PANX1 inhibits RMS progression, identifying the cell migration protein AHNAK as a key modifier of PANX1-mediated changes in RMS malignant properties

Lamin A/C truncation in dilated cardiomyopathy with conduction disease

BACKGROUND: Mutations in the gene encoding the nuclear membrane protein lamin A/C have been associated with at least 7 distinct diseases including autosomal dominant dilated cardiomyopathy with conduction system disease, autosomal dominant and recessive Emery Dreifuss Muscular Dystrophy, limb girdle muscular dystrophy type 1B, autosomal recessive type 2 Charcot Marie Tooth, mandibuloacral dysplasia, familial partial lipodystrophy and Hutchinson-Gilford progeria. METHODS: We used mutation detection to evaluate the lamin A/C gene in a 45 year-old woman with familial dilated cardiomyopathy and conduction system disease whose family has been well characterized for this phenotype [1]. RESULTS: DNA from the proband was analyzed, and a novel 2 base-pair deletion c.908_909delCT in LMNA was identified. CONCLUSIONS: Mutations in the gene encoding lamin A/C can lead to significant cardiac conduction system disease that can be successfully treated with pacemakers and/or defibrillators. Genetic screening can help assess risk for arrhythmia and need for device implantation

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Estimating the Diets of Animals Using Stable Isotopes and a Comprehensive Bayesian Mixing Model

Using stable isotope mixing models (SIMMs) as a tool to investigate the foraging ecology of animals is gaining popularity among researchers. As a result, statistical methods are rapidly evolving and numerous models have been produced to estimate the diets of animals—each with their benefits and their limitations. Deciding which SIMM to use is contingent on factors such as the consumer of interest, its food sources, sample size, the familiarity a user has with a particular framework for statistical analysis, or the level of inference the researcher desires to make (e.g., population- or individual-level). In this paper, we provide a review of commonly used SIMM models and describe a comprehensive SIMM that includes all features commonly used in SIMM analysis and two new features. We used data collected in Yosemite National Park to demonstrate IsotopeR's ability to estimate dietary parameters. We then examined the importance of each feature in the model and compared our results to inferences from commonly used SIMMs. IsotopeR's user interface (in R) will provide researchers a user-friendly tool for SIMM analysis. The model is also applicable for use in paleontology, archaeology, and forensic studies as well as estimating pollution inputs

Factors contributing to attrition behavior in diabetes self-management programs: A mixed method approach

<p>Abstract</p> <p>Background</p> <p>Diabetes self-management education is a critical component in diabetes care. Despite worldwide efforts to develop efficacious DSME programs, high attrition rates are often reported in clinical practice. The objective of this study was to examine factors that may contribute to attrition behavior in diabetes self-management programs.</p> <p>Methods</p> <p>We conducted telephone interviews with individuals who had Type 2 diabetes (n = 267) and attended a diabetes education centre. Multivariable logistic regression was performed to identify factors associated with attrition behavior. Forty-four percent of participants (n = 118) withdrew prematurely from the program and were asked an open-ended question regarding their discontinuation of services. We used content analysis to code and generate themes, which were then organized under the Behavioral Model of Health Service Utilization.</p> <p>Results</p> <p>Working full and part-time, being over 65 years of age, having a regular primary care physician or fewer diabetes symptoms were contributing factors to attrition behaviour in our multivariable logistic regression. The most common reasons given by participants for attrition from the program were conflict between their work schedules and the centre's hours of operation, patients' confidence in their own knowledge and ability when managing their diabetes, apathy towards diabetes education, distance to the centre, forgetfulness, regular physician consultation, low perceived seriousness of diabetes, and lack of familiarity with the centre and its services. There was considerable overlap between our quantitative and qualitative results.</p> <p>Conclusion</p> <p>Reducing attrition behaviour requires a range of strategies targeted towards delivering convenient and accessible services, familiarizing individuals with these services, increasing communication between centres and their patients, and creating better partnerships between centres and primary care physicians.</p

Plasma and neutrophil fatty acid composition in advanced cancer patients and response to fish oil supplementation

Metabolic demand and altered supply of essential nutrients is poorly characterised in patients with advanced cancer. A possible imbalance or deficiency of essential fatty acids is suggested by reported beneficial effects of fish oil supplementation. To assess fatty acid status (composition of plasma and neutrophil phospholipids) in advanced cancer patients before and after 14 days of supplementation (12±1 g day−1) with fish (eicosapentaenoic acid, and docosahexaenoic acid) or placebo (olive) oil. Blood was drawn from cancer patients experiencing weight loss of >5% body weight (n=23). Fatty acid composition of plasma phospholipids and the major phospholipid classes of isolated neutrophils were determined using gas liquid chromatography. At baseline, patients with advanced cancer exhibited low levels (<30% of normal values) of plasma phospholipids and constituent fatty acids and elevated 20 : 4 n-6 content in neutrophil phospholipids. High n-6/n-3 fatty acid ratios in neutrophil and plasma phospholipids were inversely related to body mass index. Fish oil supplementation raised eicosapentaenoic acid and docosahexaenoic acid content in plasma but not neutrophil phospholipids. 20 : 4 n-6 content was reduced in neutrophil PI following supplementation with fish oil. Change in body weight during the supplementation period related directly to increases in eicosapentaenoic acid in plasma. Advanced cancer patients have alterations in lipid metabolism potentially due to nutritional status and/or chemotherapy. Potential obstacles in fatty acid utilisation must be addressed in future trials aiming to improve outcomes using nutritional intervention with fish oils

Measurements of integrated and differential cross sections for isolated photon pair production in pp collisions at √s=8 TeV with the ATLAS detector

A measurement of the production cross section for two isolated photons in proton-proton collisions at a center-of-mass energy of √s=8 TeV is presented. The results are based on an integrated luminosity of 20.2 fb−1 recorded by the ATLAS detector at the Large Hadron Collider. The measurement considers photons with pseudorapidities satisfying |ηγ|40GeV and EγT,2>30 GeV for the two leading photons ordered in transverse energy produced in the interaction. The background due to hadronic jets and electrons is subtracted using data-driven techniques. The fiducial cross sections are corrected for detector effects and measured differentially as a function of six kinematic observables. The measured cross section integrated within the fiducial volume is 16.8 ± 0.8  pb . The data are compared to fixed-order QCD calculations at next-to-leading-order and next-to-next-to-leading-order accuracy as well as next-to-leading-order computations including resummation of initial-state gluon radiation at next-to-next-to-leading logarithm or matched to a parton shower, with relative uncertainties varying from 5% to 20%

Search for the direct production of charginos and neutralinos in final states with tau leptons in √s=13 TeV collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with at least two hadronically decaying tau leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of 36.1 fb−1, recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 13TeV.Nosignificant deviation from the expected Standard Model background is observed. Limits are derived in scenarios of ˜χ+1 ˜χ−1 pair production and of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 production in simplified models where the neutralinos and charginos decay solely via intermediate left-handed staus and tau sneutrinos, and the mass of the ˜ τL state is set to be halfway between the masses of the ˜χ±1 and the ˜χ01. Chargino masses up to 630 GeV are excluded at 95% confidence level in the scenario of direct production of ˜χ+1 ˜χ−1 for a massless ˜χ01. Common ˜χ±1 and ˜χ02 masses up to 760 GeV are excluded in the case of production of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 assuming a massless ˜χ01. Exclusion limits for additional benchmark scenarios with large and small mass-splitting between the ˜χ±1 and the ˜χ01 are also studied by varying the ˜ τL mass between the masses of the ˜χ±1 and the ˜χ01

Search for dark matter at √s=13 TeV in final states containing an energetic photon and large missing transverse momentum with the ATLAS detector

Results of a search for physics beyond the Standard Model in events containing an energetic photon and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. As the number of events observed in data, corresponding to an integrated luminosity of 36.1 fb−1 of proton–proton collisions at a centre-of-mass energy of 13 TeV, is in agreement with the Standard Model expectations, model-independent limits are set on the fiducial cross section for the production of events in this final state. Exclusion limits are also placed in models where dark-matter candidates are pair-produced. For dark-matter production via an axial-vector or a vector mediator in the s-channel, this search excludes mediator masses below 750–1200 GeV for dark-matter candidate masses below 230–480 GeV at 95% confidence level, depending on the couplings. In an effective theory of dark-matter production, the limits restrict the value of the suppression scale M∗ to be above 790 GeV at 95% confidence level. A limit is also reported on the production of a high-mass scalar resonance by processes beyond the Standard Model, in which the resonance decays to Zγ and the Z boson subsequently decays into neutrinos