Transkingdom Networks: A Systems Biology Approach to Identify Causal Members of Host-Microbiota Interactions

Improvements in sequencing technologies and reduced experimental costs have resulted in a vast number of studies generating high-throughput data. Although the number of methods to analyze these "omics" data has also increased, computational complexity and lack of documentation hinder researchers from analyzing their high-throughput data to its true potential. In this chapter we detail our data-driven, transkingdom network (TransNet) analysis protocol to integrate and interrogate multi-omics data. This systems biology approach has allowed us to successfully identify important causal relationships between different taxonomic kingdoms (e.g. mammals and microbes) using diverse types of data

APOGEE chemical abundances of globular cluster giants in the inner Galaxy

We report chemical abundances obtained by Sloan Digital Sky Survey (SDSS)-III/Apache Point Observatory Galactic Evolution Experiment for giant stars in five globular clusters located within 2.2 kpc of the Galactic Centre. We detect the presence of multiple stellar populations in four of those clusters (NGC 6553, NGC 6528, Terzan 5 and Palomar 6) and find strong evidence for their presence in NGC 6522. All clusters with a large enough sample present a significant spread in the abundances of N, C, Na and Al, with the usual correlations and anticorrelations between various abundances seen in other globular clusters. Our results provide important quantitative constraints on theoretical models for self-enrichment of globular clusters, by testing their predictions for the dependence of yields of elements such as Na, N, C and Al on metallicity. They also confirm that, under the assumption that field N-rich stars originate from globular cluster destruction, they can be used as tracers of their parental systems in the high-metallicity regime

Comparison of the intracellular trafficking itinerary of ctla-4 orthologues.

CTLA-4 is an essential inhibitor of T cell immune responses. At steady state, most CTLA-4 resides in intracellular compartments due to constitutive internalisation mediated via a tyrosine based endocytic motif (YVKM) within the cytoplasmic domain. This domain is highly conserved in mammals suggesting strong selective pressure. In contrast, the C-terminal domain varies considerably in non-mammals such as fish, xenopus and birds. We compared the ability of the C-terminus of these species to direct the trafficking of CTLA-4 with human CTLA-4. Using a chimeric approach, endocytosis was found to be conserved between human, xenopus and chicken CTLA-4 but was reduced substantially in trout CTLA-4, which lacks the conserved YXXM motif. Nevertheless, we identified an alternative YXXF motif in trout CTLA-4 that permitted limited endocytosis. Post-internalisation, CTLA-4 was either recycled or targeted for degradation. Human and chicken CTLA-4, which contain a YVKM motif, showed efficient recycling compared to xenopus CTLA-4 which contains a less efficient YEKM motif. Specific mutation of this motif in human CTLA-4 reduced receptor recycling. These findings suggest evolutionary development in the endocytic and recycling potential of CTLA-4, which may facilitate more refined functions of CTLA-4 within the mammalian immune system

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

DNA methylation dynamics of the human preimplantation embryo

In mammals, cytosine methylation is predominantly restricted to CpG dinucleotides and stably distributed across the genome, with local, cell type-specific regulation directed by DNA binding factors1-3. This comparatively static landscape dramatically contrasts the events of fertilization, where the paternal genome is globally reprogrammed. Paternal genome demethylation includes the majority of CpGs, though methylation is maintained at several notable features4-7. While these dynamics have been extensively characterized in the mouse, only limited observations are available in other mammals, and direct measurements are required to understand the extent to which early embryonic landscapes are conserved8-10. We present genome-scale DNA methylation maps of human preimplantation development and embryonic stem cell (ESC) derivation, confirming a transient state of global hypomethylation that includes most CpGs, while sites of persistent maintenance are primarily restricted to gene bodies. While most features share similar dynamics to mouse, maternally contributed methylation is divergently targeted to species-specific sets of CpG island (CGI) promoters that extend beyond known Imprint Control Regions (ICRs). Retrotransposon regulation is also highly diverse and transitions from maternally to embryonically expressed, species-specific elements. Together, our data confirm that paternal genome demethylation is a general attribute of early mammalian development that is characterized by distinct modes of epigenetic regulation

UK adults' implicit and explicit attitudes towards obesity: a cross-sectional study.

Background: Anti-fat attitudes may lead to stigmatisation of and lowered self-esteem in obese people. Examining anti-fat attitudes is warranted given that there is an association with anti-fat behaviours. Previous studies, mainly outside the UK, have demonstrated that anti-fat attitudes are increasing over time. Methods: The study was cross-sectional with a sample of 2380 participants (74.2 % female; aged 18–65 years). In an online survey participants reported demographic characteristics and completed a range of implicit and explicit measures of obesity related attitudes. Results: Perceptions of obesity were more negative than reported in previously. Main effects indicated more negative perceptions in males, younger respondents and more frequent exercisers. Attitudes about obesity differed in relation to weight category, and in general were more positive in obese than non-obese respondents. Conclusions: This is the first study to demonstrate anti-fat attitudes across different sections of the UK population. As such, this study provides the first indication of the prevalence of anti-fat attitudes in UK adults. Interventions to modify these attitudes could target specific groups of individuals with more negative perceptions as identified here. Future work would be useful that increases understanding of both implicit and explicit attitudes towards obesity

A fast and reliable approach to simulating the output from an x-ray tube used for developing security backscatter imaging

Copyright 2017 Society of Photo-Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited.The PENELOPE Monte Carlo simulation code was used alongside the SpekCalc code to simulate X-ray energy spectra from a VJ Technologies’ X-ray generator at a range of anode voltages. The PENELOPE code is often utilised in medicine but is here applied to develop coded aperture and pinhole imaging systems for security purposes. The greater computational burden of PENELOPE over SpekCalc is warranted by its greater flexibility and output information. The model was designed using the PENGEOM sub-tool and consists of a tungsten anode and five layers of window materials. The photons generated by a mono-energetic electron beam are collected by a virtual detector placed after the last window layer, and this records the spatial, angular and energy distributions which are then used as the X-ray source for subsequent simulations. The process of storing X-ray outputs and using them as a virtual photon source can then be used efficiently for exploring a range of imaging conditions as the computationally expensive electron interactions in the anode need not be repeated. The modelled spectra were validated with experimentally determined spectra collected with an Amptek X-123 Cadmium Telluride detector placed in front of the source

From research to practice: Lay adherence counsellors' fidelity to an evidence-based intervention for promoting adherence to antiretroviral treatment in the Western Cape, South Africa

In the Western Cape, lay counsellors are tasked with supporting antiretroviral (ARV) adherence in public healthcare clinics. Thirty-nine counsellors in 21 Cape Town clinics were trained in Options for Health (Options), an evidence-based intervention based on motivational interviewing (MI). We evaluated counsellors’ ability to deliver Options for addressing poor adherence following 5 days training. Audio-recordings of counselling sessions collected following training were transcribed and translated into English. Thirty-five transcripts of sessions conducted by 35 counsellors were analysed for fidelity to the Options protocol, and using the Motivational Interviewing Treatment and Integrity (MITI) code. Counsellors struggled with some of the strategies associated with MI, such as assessing readiness-to-change and facilitating change talk. Overall, counsellors failed to achieve proficiency in the approach of MI according to the MITI. Counsellors were able to negotiate realistic plans for addressing patients’ barriers to adherence. Further efforts aimed at strengthening the ARV adherence counselling programme are needed.Department of HE and Training approved lis

Atypical Mg-poor Milky Way Field Stars with Globular Cluster Second-generation-like Chemical Patterns

We report the peculiar chemical abundance patterns of 11 atypical Milky Way (MW) field red giant stars observed by the Apache Point Observatory Galactic Evolution Experiment (APOGEE). These atypical giants exhibit strong Al and N enhancements accompanied by C and Mg depletions, strikingly similar to those observed in the so-called second-generation (SG) stars of globular clusters (GCs). Remarkably, we find low Mg abundances ([Mg/Fe] < 0.0) together with strong Al and N overabundances in the majority (5/7) of the metal-rich ([Fe/H] gsim −1.0) sample stars, which is at odds with actual observations of SG stars in Galactic GCs of similar metallicities. This chemical pattern is unique and unprecedented among MW stars, posing urgent questions about its origin. These atypical stars could be former SG stars of dissolved GCs formed with intrinsically lower abundances of Mg and enriched Al (subsequently self-polluted by massive AGB stars) or the result of exotic binary systems. We speculate that the stars Mg-deficiency as well as the orbital properties suggest that they could have an extragalactic origin. This discovery should guide future dedicated spectroscopic searches of atypical stellar chemical patterns in our Galaxy, a fundamental step forward to understanding the Galactic formation and evolution

Modulation of the endocannabinoids N-Arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) on Executive Functions in Humans

Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = −.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = −.17) or AEA (r = −.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches