InnateDB: systems biology of innate immunity and beyond—recent updates and continuing curation

peer-reviewedInnateDB (http://www.innatedb.com) is an integrated analysis platform that has been specifically designed to facilitate systems-level analyses of mammalian innate immunity networks, pathways and genes. In this article, we provide details of recent updates and improvements to the database. InnateDB now contains >196 000 human, mouse and bovine experimentally validated molecular interactions and 3000 pathway annotations of relevance to all mammalian cellular systems (i.e. not just immune relevant pathways and interactions). In addition, the InnateDB team has, to date, manually curated in excess of 18 000 molecular interactions of relevance to innate immunity, providing unprecedented insight into innate immunity networks, pathways and their component molecules. More recently, InnateDB has also initiated the curation of allergy- and asthma-related interactions. Furthermore, we report a range of improvements to our integrated bioinformatics solutions including web service access to InnateDB interaction data using Proteomics Standards Initiative Common Query Interface, enhanced Gene Ontology analysis for innate immunity, and the availability of new network visualizations tools. Finally, the recent integration of bovine data makes InnateDB the first integrated network analysis platform for this agriculturally important model organism.This work was supported by Genome BC through the Pathogenomics of Innate Immunity (PI2) project and by the Foundation for the National Institutes of Health and the Canadian Institutes of Health Research under the Grand Challenges in Global Health Research Initiative [Grand Challenges ID: 419]. Further funding was also provided by AllerGen grants 12ASI1 and 12B&B2. D.J.L. was funded in part during this project by a postdoctoral trainee award from the Michael Smith Foundation for Health Research (MSFHR). F.S.L.B. is a MSFHR Senior Scholar and R.E.W.H. holds a Canada Research Chair (CRC). Funding to enable bovine systems biology in InnateDB is provided by Teagasc [RMIS6018] and the Teagasc Walsh Fellowship scheme. IMEx is funded by the European Commission under the PSIMEx project [contract number FP7-HEALTH-2007-223411]. Funding for open access charge: Teagasc [RMIS6018]

Gut microbes shape microglia and cognitive function during malnutrition

Fecal-oral contamination promotes malnutrition pathology. Lasting consequences of early life malnutrition include cognitive impairment, but the underlying pathology and influence of gut microbes remain largely unknown. Here, we utilize an established murine model combining malnutrition and iterative exposure to fecal commensals (MAL-BG). The MAL-BG model was analyzed in comparison to malnourished (MAL mice) and healthy (CON mice) controls. Malnourished mice display poor spatial memory and learning plasticity, as well as altered microglia, non-neuronal CNS cells that regulate neuroimmune responses and brain plasticity. Chronic fecal-oral exposures shaped microglial morphology and transcriptional profile, promoting phagocytic features in MAL-BG mice. Unexpectedly, these changes occurred independently from significant cytokine-induced inflammation or blood-brain barrier (BBB) disruption, key gut-brain pathways. Metabolomic profiling of the MAL-BG cortex revealed altered polyunsaturated fatty acid (PUFA) profiles and systemic lipoxidative stress. In contrast, supplementation with an ω3 PUFA/antioxidant-associated diet (PAO) mitigated cognitive deficits within the MAL-BG model. These findings provide valued insight into the malnourished gut microbiota-brain axis, highlighting PUFA metabolism as a potential therapeutic target

A Phenomenological Analysis of Gluon Mass Effects in Inclusive Radiative Decays of the J/ψ\rm{J/\psi} and $\Upsilon

The shapes of the inclusive photon spectra in the processes \Jp \to \gamma X and \Up \to \gamma X have been analysed using all available experimental data. Relativistic, higher order QCD and gluon mass corrections were taken into account in the fitted functions. Only on including the gluon mass corrections, were consistent and acceptable fits obtained. Values of $0.721^{+0.016}_{-0.068}$ GeV and $1.18^{+0.09}_{-0.29}$ GeV were found for the effective gluon masses (corresponding to Born level diagrams) for the \Jp and \Up respectively. The width ratios \Gamma(V \to {\rm hadrons})/\Gamma(V \to \gamma+ {\rm hadrons}) V=\Jp, \Up were used to determine $\alpha_s(1.5 {\rm GeV})$ and $\alpha_s(4.9 {\rm GeV})$. Values consistent with the current world average $\alpha_s$ were obtained only when gluon mass correction factors, calculated using the fitted values of the effective gluon mass, were applied. A gluon mass $\simeq 1$ GeV, as suggested with these results, is consistent with previous analytical theoretical calculations and independent phenomenological estimates, as well as with a recent, more accurate, lattice calculation of the gluon propagator in the infra-red region.Comment: 50 pages, 11 figures, 15 table

Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort

Background: Vaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts. Methods: We applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres. Results: Using both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response. Conclusion: This study provides further evidence that baseline cellular and molecular characteristics of an individual’s immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets

Non-minimal coupling of the scalar field and inflation

We study the prescriptions for the coupling constant of a scalar field to the Ricci curvature of spacetime in specific gravity and scalar field theories. The results are applied to the most popular inflationary scenarios of the universe; their theoretical consistency and certain observational constraints are discussed.Comment: 23 pages, LaTex, no figures, to appear in Physical Review

Burden and risk factors for Pseudomonas aeruginosa community-acquired pneumonia:a Multinational Point Prevalence Study of Hospitalised Patients

Pseudornonas aeruginosa is a challenging bacterium to treat due to its intrinsic resistance to the antibiotics used most frequently in patients with community-acquired pneumonia (CAP). Data about the global burden and risk factors associated with P. aeruginosa-CAP are limited. We assessed the multinational burden and specific risk factors associated with P. aeruginosa-CAP. We enrolled 3193 patients in 54 countries with confirmed diagnosis of CAP who underwent microbiological testing at admission. Prevalence was calculated according to the identification of P. aeruginosa. Logistic regression analysis was used to identify risk factors for antibiotic-susceptible and antibiotic-resistant P. aeruginosa-CAP. The prevalence of P. aeruginosa and antibiotic-resistant P. aeruginosa-CAP was 4.2% and 2.0%, respectively. The rate of P. aeruginosa CAP in patients with prior infection/colonisation due to P. aeruginosa and at least one of the three independently associated chronic lung diseases (i.e. tracheostomy, bronchiectasis and/or very severe chronic obstructive pulmonary disease) was 67%. In contrast, the rate of P. aeruginosa-CAP was 2% in patients without prior P. aeruginosa infection/colonisation and none of the selected chronic lung diseases. The multinational prevalence of P. aeruginosa-CAP is low. The risk factors identified in this study may guide healthcare professionals in deciding empirical antibiotic coverage for CAP patients