Differential Transcriptome Responses to Aflatoxin B1 in the Cecal Tonsil of Susceptible and Resistant Turkeys

The nearly-ubiquitous food and feed-borne mycotoxin aflatoxin B1 (AFB1) is carcinogenic and mutagenic, posing a food safety threat to humans and animals. One of the most susceptible animal species known and thus a good model for characterizing toxicological pathways, is the domesticated turkey (DT), a condition likely due, at least in part, to deficient hepatic AFB1-detoxifying alpha-class glutathione S-transferases (GSTAs). Conversely, wild turkeys (Eastern wild, EW) are relatively resistant to the hepatotoxic, hepatocarcinogenic and immunosuppressive effects of AFB1 owing to functional gene expression and presence of functional hepatic GSTAs. This study was designed to compare the responses in gene expression in the gastrointestinal tract between DT (susceptible phenotype) and EW (resistant phenotype) following dietary AFB1 challenge (320 ppb for 14 days); specifically in cecal tonsil which functions in both nutrient absorption and gut immunity. RNAseq and gene expression analysis revealed significant differential gene expression in AFB1-treated animals compared to control-fed domestic and wild birds and in within-treatment comparisons between bird types. Significantly upregulated expression of the primary hepatic AFB1-activating P450 (CYP1A5) as well as transcriptional changes in tight junction proteins were observed in AFB1-treated birds. Numerous pro-inflammatory cytokines, TGF-β and EGF were significantly down regulated by AFB1 treatment in DT birds and pathway analysis suggested suppression of enteroendocrine cells. Conversely, AFB1 treatment modified significantly fewer unique genes in EW birds; among these were genes involved in lipid synthesis and metabolism and immune response. This is the first investigation of the effects of AFB1 on the turkey gastro-intestinal tract. Results suggest that in addition to the hepatic transcriptome, animal resistance to this mycotoxin occurs in organ systems outside the liver, specifically as a refractory gastrointestinal tract

Altered Gene Response to Aflatoxin B\u3csub\u3e1\u3c/sub\u3e in the Spleens of Susceptible and Resistant Turkeys

Susceptibility and/or resistance to aflatoxin B1 (AFB1) is a threshold trait governed principally by glutathione S transferase (GST)-mediated detoxification. In poultry, domesticated turkeys are highly sensitive to AFB1, most likely due to dysfunction in hepatic GSTs. In contrast, wild turkeys are comparatively resistant to aflatoxicosis due to the presence of functional hepatic GSTAs and other possible physiological and immunological interactions. The underlying genetic basis for the disparate GST function in turkeys is unknown as are the broader molecular interactions that control the systemic response. This study quantifies the effects of dietary AFB1 on gene expression in the turkey spleen, specifically contrasting genetically distinct domesticated (DT, susceptible) and Eastern wild (EW, resistant) birds. Male turkey poults were subjected to a short-term AFB1 treatment protocol with feed supplemented with 320 ppb AFB1 beginning on day 15 of age and continuing for 14 days. Spleen tissues were harvested and subjected to deep RNA sequencing and transcriptome analysis. Analysis of differential gene expression found the effects of AFB1 treatment on the spleen transcriptomes considerably more prominent in the DT birds compared to EW. However, expression of the differentially expressed genes (DEGs) was directionally biased, with the majority showing higher expression in EW (i.e., down-regulation in DT). Significantly altered pathways included FXR/RXR and LXR/RXR activation, coagulation system, prothrombin activation, acute phase response, and atherosclerosis signaling. Differential extra-hepatic expression of acute phase protein genes was confirmed by quantitative real time PCR (qRT-PCR) in the original experiment and additional turkey lines. Results demonstrate that wild turkeys possess a capacity to more effectively respond to AFB1exposure

Functional Approach to Quantum Decoherence and the Classical Final Limit

For a wide set of quantum systems it is demonstrated that the quantum regime can be considered as the transient phase while the final classical statistical regime is a permanent state. A basis where exact matrix decoherence appears for these final states is found. The relation with the decoherence of histories formalism is studied. A set of final intrinsically consistent histories is found.Comment: 20 pages. Phys. Rev A in press 200

Expression of miRNAs in turkey muscle satellite cells and differential response to thermal challenge

Thermal stress alters the transcriptome and subsequent tissue physiology of poultry; thus, it can negatively impact poultry production through reduced meat quality, egg production, and health and wellbeing. The modulation of gene expression is critical to embryonic development and cell proliferation, and growing evidence suggests the role of non-coding RNAs (RNA:RNA interaction) in response to thermal stress in animals. MicroRNAs (miRNAs) comprise a class of small regulatory RNAs that modulate gene expression through posttranscriptional interactions and regulate mRNAs, potentially altering numerous cellular processes. This study was designed to identify and characterize the differential expression of miRNAs in satellite cells (SCs) from the turkey pectoralis major muscle and predict important miRNA:mRNA interactions in these developing SCs under a thermal challenge. Small RNA sequencing was performed on RNA libraries prepared from SCs cultured from 1-week-old male Nicholas commercial turkeys (NCTs) and non-selected Randombred Control Line 2 turkeys during proliferation and differentiation at the control temperature (38°C) or under a thermal challenge (33°C or 43°C). A total of 353 miRNAs (161 known and 192 novel) were detected across the sequenced libraries. Expression analysis found fewer differentially expressed miRNAs in the SCs of NCT birds, suggesting that the miRNA response to heat stress has been altered in birds selected for their modern commercial growth traits. Differentially expressed miRNAs, including those with described roles in muscle development, were detected both among temperature treatments and between genetic lines. A prominent differential expression of miR-206 was found in proliferating turkey SCs with a significant response to thermal challenges in both lines. In differentiating SCs, isoforms of miR-1 had significant differential responses, with the expression of miR-206 being mainly affected only by cold treatment. Target gene predictions and Gene Ontology analysis suggest that the differential expression of miRNAs during thermal stress could significantly affect cellular proliferation and differentiation

COINSTAC: A Privacy Enabled Model and Prototype for Leveraging and Processing Decentralized Brain Imaging Data

The field of neuroimaging has embraced the need for sharing and collaboration. Data sharing mandates from public funding agencies and major journal publishers have spurred the development of data repositories and neuroinformatics consortia. However, efficient and effective data sharing still faces several hurdles. For example, open data sharing is on the rise but is not suitable for sensitive data that are not easily shared, such as genetics. Current approaches can be cumbersome (such as negotiating multiple data sharing agreements). There are also significant data transfer, organization and computational challenges. Centralized repositories only partially address the issues. We propose a dynamic, decentralized platform for large scale analyses called the Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation (COINSTAC). The COINSTAC solution can include data missing from central repositories, allows pooling of both open and ``closed'' repositories by developing privacy-preserving versions of widely-used algorithms, and incorporates the tools within an easy-to-use platform enabling distributed computation. We present an initial prototype system which we demonstrate on two multi-site data sets, without aggregating the data. In addition, by iterating across sites, the COINSTAC model enables meta-analytic solutions to converge to ``pooled-data'' solutions (i.e. as if the entire data were in hand). More advanced approaches such as feature generation, matrix factorization models, and preprocessing can be incorporated into such a model. In sum, COINSTAC enables access to the many currently unavailable data sets, a user friendly privacy enabled interface for decentralized analysis, and a powerful solution that complements existing data sharing solutions

The Reed-Stanton press rig for the generation of reproducible fingermarks : towards a standardised methodology for fingermark research

In the search for better or new methods/techniques to visualise fingermarks or to analyse them exploiting their chemical content, fingermarks inter-variability may hinder the assessment of the method effectiveness. Variability is due to changes in the chemical composition of the fingermarks between different donors and within the same donor, as well as to differential contact time, pressure and angle. When validating a method or comparing it with existing ones, it is not always possible to account for this type of variability. One way to compensate for these issues is to employ, in the early stages of the method development, a device generating reproducible fingermarks. Here the authors present their take on such device, as well as quantitatively describing its performance and benefits against the manual production of marks. Finally a short application is illustrated for the use of this device, at the method developmental stages, in an emerging area of fingerprinting research concerning the retrieval of chemical intelligence from fingermarks

A Nonsynonymous Change in Adhesion G Protein–Coupled Receptor L3 Associated With Risk for Equine Degenerative Myeloencephalopathy in the Caspian Horse

Equine degenerative myeloencephalopathy (EDM), a neurological disease of young horses, causes progressive development of symmetric ataxia predominantly in the pelvic limbs. Equine degenerative myeloencephalopathy is likely inherited and with no known treatment affected horses frequently need euthanasia. Alpha-tocopherol deficiency during early life appears to contribute to the phenotype. This study sought to identify any genetic variants correlated with EDM in Caspian foals. Two half-sibling EDM-diagnosed cases were genotyped at 52,063 loci and evaluated by the Autozygosity by Difference statistic. Additional horses not affected by EDM were used for genetic comparison to identify regions unique to the case phenotype. The associated region on chromosome 3 contains only one gene encoding adhesion G protein–coupled receptor L3 (ADGRL3). Adhesion G protein–coupled receptor L3 is a member of the latrophilin subfamily of G protein–coupled receptors and may contribute to attention deficit/hyperactivity disorder in humans and hyperactive motor function in mice and zebrafish. Analysis of the predicted coding regions for Equine ADGRL3 in affected horses revealed a nonsynonymous single nucleotide polymorphism at Chr3:71,917,591 bp. Caspian and Caspian cross-relatives (n = 81) of the two initial cases and unrelated horses from similar breeds (n = 130, including Arabians, American Miniatures, and Shetlands) possessed this allele at 5% frequency, with no homozygotes observed within the non-Caspian breeds. This study suggests that a polymorphism in ADGRL3 could contribute to a genetic predisposition to Caspian horse EDM

A novel design process for selection of attributes for inclusion in discrete choice experiments:Case study exploring variation in clinical decision-making about thrombolysis in the treatment of acute ischaemic stroke

On-line structured prioritisation exercise (SPE). Full survey used to collect data. (DOCX 42 kb

DCMIP2016: a review of non-hydrostatic dynamical core design and intercomparison of participating models

Atmospheric dynamical cores are a fundamental component of global atmospheric modeling systems and are responsible for capturing the dynamical behavior of the Earth's atmosphere via numerical integration of the Navier-Stokes equations. These systems have existed in one form or another for over half of a century, with the earliest discretizations having now evolved into a complex ecosystem of algorithms and computational strategies. In essence, no two dynamical cores are alike, and their individual successes suggest that no perfect model exists. To better understand modern dynamical cores, this paper aims to provide a comprehensive review of 11 non-hydrostatic dynamical cores, drawn from modeling centers and groups that participated in the 2016 Dynamical Core Model Intercomparison Project (DCMIP) workshop and summer school. This review includes a choice of model grid, variable placement, vertical coordinate, prognostic equations, temporal discretization, and the diffusion, stabilization, filters, and fixers employed by each syste

The Atacama Cosmology Telescope: Cosmological parameters from three seasons of data

We present constraints on cosmological and astrophysical parameters from high-resolution microwave background maps at 148 GHz and 218 GHz made by the Atacama Cosmology Telescope (ACT) in three seasons of observations from 2008 to 2010. A model of primary cosmological and secondary foreground parameters is fit to the map power spectra and lensing deflection power spectrum, including contributions from both the thermal Sunyaev-Zeldovich (tSZ) effect and the kinematic Sunyaev-Zeldovich (kSZ) effect, Poisson and correlated anisotropy from unresolved infrared sources, radio sources, and the correlation between the tSZ effect and infrared sources. The power ell^2 C_ell/2pi of the thermal SZ power spectrum at 148 GHz is measured to be 3.4 +\- 1.4 muK^2 at ell=3000, while the corresponding amplitude of the kinematic SZ power spectrum has a 95% confidence level upper limit of 8.6 muK^2. Combining ACT power spectra with the WMAP 7-year temperature and polarization power spectra, we find excellent consistency with the LCDM model. We constrain the number of effective relativistic degrees of freedom in the early universe to be Neff=2.79 +\- 0.56, in agreement with the canonical value of Neff=3.046 for three massless neutrinos. We constrain the sum of the neutrino masses to be Sigma m_nu < 0.39 eV at 95% confidence when combining ACT and WMAP 7-year data with BAO and Hubble constant measurements. We constrain the amount of primordial helium to be Yp = 0.225 +\- 0.034, and measure no variation in the fine structure constant alpha since recombination, with alpha/alpha0 = 1.004 +/- 0.005. We also find no evidence for any running of the scalar spectral index, dns/dlnk = -0.004 +\- 0.012.Comment: 26 pages, 22 figures. This paper is a companion to Das et al. (2013) and Dunkley et al. (2013). Matches published JCAP versio