The Impact of Pig Health on Public Health: Quantitative Data for Risk Assessments

Management practices can play an important role in affecting animal health. Sub-clinically ill animals entering harvest can have pleural adhesions known as peel-outs. The focus of this study was to examine how these pleural adhesions can be associated with Salmonella and respiratory pathogens, as well as to get a national estimate of peel-outs. The results suggest pleural adhesions are not significantly associated with Salmonella or respiratory bacterial contamination

A20 protects cells from TNF-induced apoptosis through linear ubiquitin-dependent and -independent mechanisms

The cytokine TNF promotes inflammation either directly by activating the MAPK and NF-kappa B signaling pathways, or indirectly by triggering cell death. A20 is a potent anti-inflammatory molecule, and mutations in the gene encoding A20 are associated with a wide panel of inflammatory pathologies, both in human and in the mouse. Binding of TNF to TNFR1 triggers the NF-kappa B-dependent expression of A20 as part of a negative feedback mechanism preventing sustained NF-kappa B activation. Apart from acting as an NF-kappa B inhibitor, A20 is also well-known for its ability to counteract the cytotoxic potential of TNF. However, the mechanism by which A20 mediates this function and the exact cell death modality that it represses have remained incompletely understood. In the present study, we provide in vitro and in vivo evidences that deletion of A20 induces RIPK1 kinase-dependent and -independent apoptosis upon single TNF stimulation. We show that constitutively expressed A20 is recruited to TNFR1 signaling complex (Complex I) via its seventh zinc finger (ZF7) domain, in a cIAP1/2-dependent manner, within minutes after TNF sensing. We demonstrate that Complex I-recruited A20 protects cells from apoptosis by stabilizing the linear (M1) ubiquitin network associated to Complex I, a process independent of its E3 ubiquitin ligase and deubiquitylase (DUB) activities and which is counteracted by the DUB CYLD, both in vitro and in vivo. In absence of linear ubiquitylation, A20 is still recruited to Complex I via its ZF4 and ZF7 domains, but this time protects the cells from death by deploying its DUB activity. Together, our results therefore demonstrate two distinct molecular mechanisms by which constitutively expressed A20 protect cells from TNF-induced apoptosis

Cross-sectional associations between air pollution and chronic bronchitis: an ESCAPE meta-analysis across five cohorts

BACKGROUND: This study aimed to assess associations of outdoor air pollution on prevalence of chronic bronchitis symptoms in adults in five cohort studies (Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project. METHODS: Annual average particulate matter (PM10, PM2.5, PMabsorbance, PMcoarse), NO2, nitrogen oxides (NOx) and road traffic measures modelled from ESCAPE measurement campaigns 2008-2011 were assigned to home address at most recent assessments (1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for ≥3 months of the year for ≥2 years), chronic cough (with/without phlegm) and chronic phlegm (with/without cough). Cohort-specific cross-sectional multivariable logistic regression analyses were conducted using common confounder sets (age, sex, smoking, interview season, education), followed by meta-analysis. RESULTS: 15 279 and 10 537 participants respectively were included in the main NO2 and PM analyses at assessments in 1998-2011. Overall, there were no statistically significant associations with any air pollutant or traffic exposure. Sensitivity analyses including in asthmatics only, females only or using back-extrapolated NO2 and PM10 for assessments in 1985-2002 (ECRHS, NSHD, SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations were positive, but reached statistical significance only for chronic phlegm with PMcoarse OR 1.31 (1.05 to 1.64) per 5 µg/m(3) increase and PM10 with similar effect size. Sensitivity analyses of older cohorts showed increased risk of chronic cough with PM2.5abs (black carbon) exposures. CONCLUSIONS: Results do not show consistent associations between chronic bronchitis symptoms and current traffic-related air pollution in adult European populations

IceCube Science

We discuss the status of the kilometer-scale neutrino detector IceCube and its low energy upgrade Deep Core and review its scientific potential for particle physics. We subsequently appraise IceCube's potential for revealing the enigmatic sources of cosmic rays. After all, this aspiration set the scale of the instrument. While only a smoking gun is missing for the case that the Galactic component of the cosmic ray spectrum originates in supernova remnants, the origin of the extragalactic component remains as inscrutable as ever. We speculate on the role of the nearby active galaxies Centaurus A and M87.Comment: 19 pages, 8 figures; Talk at Discrete 08, Valencia, Spai

Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses

Soil Settlement and Uplift Damage to Architectural Heritage Structures in Belgium: Country-Scale Results from an InSAR-Based Analysis

Soil movement may be induced by a wide variety of natural and anthropogenic causes, which are detectable in the local scale, but may influence the movement of the soil over vast geographical expanses. Space borne interferometric synthetic aperture radar (InSAR) measurements of ground movement provide a method for the remote sensing of soil settlement and uplift over wide geographic areas. Based on this settlement and uplift evaluation, the assessment of the potential damage to architectural heritage structures is possible. In this paper an interdisciplinary monitoring and analysis method is presented that processes satellite, cadastral, patrimonial and building geometry data, used for the calculation of settlement and uplift damage to architectural heritage structures in Belgium. It uses processed InSAR data for the determination of the soil movement profile around each case study, of which the typology is determined from patrimonial information databases and the geometry is calculated from digital elevation models. The impact on the historic structures is calculated from the determined soil movement profile based on various soilstructure interaction models for buildings. The resulting damage is presented in terms of a numerical index illustrating its severity according to different criteria. In this way the potential soil movement damage is quantified in a large number of buildings in an easily interpretable and user-friendly fashion. The processing of InSAR data collected over the previous 3 decades allows the determination of the progress of settlement- and uplift-induced damage in this time period. With the integration of newly acquired and more accurate data, the methodology will continue to produce results in the coming years, both for the evaluation of soil settlement and uplift in Belgium as for introducing related damage risk data for existing architectural heritage buildings. Results of the analysis chain are presented in terms of potential current damage for selected areas and buildings

Understanding interpersonal relationships and psychopathy

Although psychopathy is widely recognised for its importance in forensic and criminal justice settings, the range of interpersonal relationships that are experienced and engaged in by individuals with psychopathy is understudied. A Rapid Evidence Assessment (Study 1) examined what is known empirically about the nature and quality of relationships for individuals with psychopathy. Affective, Cognitive and Lifestyle Assessment (ACL) interviews and genograms were then analysed in conjunction with Psychopathy Checklist: Screening Version (PCL:SV) scores to explore the extent, nature, and quality of interpersonal relationships in student and forensic psychiatric samples (Study 2). Quantitative data indicated that total psychopathy score predicted a smaller number of positive interpersonal relationships. Findings regarding Factors 1 and 2 and numbers of positive and negative interpersonal relationships varied between samples. Qualitative analyses demonstrated that psychopathic participants used less positive descriptors than non-psychopathic participants when discussing their interpersonal relationships. Findings are examined with regards to implications for future research