Characterisation of the main drivers of intra- and inter- breed variability in the plasma metabolome of dogs

INTRODUCTION: Dog breeds are a consequence of artificial selection for specific attributes. These closed genetic populations have metabolic and physiological characteristics that may be revealed by metabolomic analysis. OBJECTIVES: To identify and characterise the drivers of metabolic differences in the fasted plasma metabolome and then determine metabolites differentiating breeds. METHODS: Fasted plasma samples were collected from dogs maintained under two environmental conditions (controlled and client-owned at home). The former (n = 33) consisted of three breeds (Labrador Retriever, Cocker Spaniel and Miniature Schnauzer) fed a single diet batch, the latter (n = 96), client-owned dogs consisted of 9 breeds (Beagle, Chihuahua, Cocker Spaniel, Dachshund, Golden Retriever, Greyhound, German Shepherd, Labrador Retriever and Maltese) consuming various diets under differing feeding regimens. Triplicate samples were taken from Beagle (n = 10) and Labrador Retriever (n = 9) over 3 months. Non-targeted metabolite fingerprinting was performed using flow infusion electrospray-ionization mass spectrometry which was coupled with multivariate data analysis. Metadata factors including age, gender, sexual status, weight, diet and breed were investigated. RESULTS: Breed differences were identified in the plasma metabolome of dogs housed in a controlled environment. Triplicate samples from two breeds identified intra-individual variability, yet breed separation was still observed. The main drivers of variance in dogs maintained in the home environment were associated with breed and gender. Furthermore, metabolite signals were identified that discriminated between Labrador Retriever and Cocker Spaniels in both environments. CONCLUSION: Metabolite fingerprinting of plasma samples can be used to investigate breed differences in client-owned dogs, despite added variance of diet, sexual status and environment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-016-0997-6) contains supplementary material, which is available to authorized users

A Primitive Trait in Two Breeds of Equus Caballus Revealed by Comparative Anatomy of the Distal Limb

The 55-million-year history of equine phylogeny has been well-documented from the skeletal record; however, this is less true for the soft tissue structures that are now vestigial in modern horse. A recent study reported that two ligamentous structures resembling functional interosseous muscle II and IV were evident in Dutch Konik horses. The current study investigates this finding and compares it to members of the genus Equus to identify either a breed anomaly or functional primitive trait. Distal limbs (n = 574) were dissected from four species of Equus; E. caballus, E. asinus, E. przewalskii and E. quagga boehmi. E. caballus is represented by 18 breeds of horse, including the primitive Dutch Konik'. The interosseous muscle II and IV were evident in all four species, but only two breeds of E. caballus expressed this trait-the Dutch Konik and Bosnian Mountain Horse. These two breeds were the only close descendants of the extinct Equus ferus ferus (Tarpan) represented in this study. In conclusion, the interosseous muscle II and IV originated from the distal nodule of metacarpal II and IV, respectively, and inserted into the corresponding branches of interosseous muscle III proximal to the sesamoids. This suggests a functional role in medial and lateral joint stability and a primitive trait in modern equids

The political import of deconstruction—Derrida’s limits?: a forum on Jacques Derrida’s specters of Marx after 25 Years, part I

Jacques Derrida delivered the basis of The Specters of Marx: The State of the Debt, the Work of Mourning, & the New International as a plenary address at the conference ‘Whither Marxism?’ hosted by the University of California, Riverside, in 1993. The longer book version was published in French the same year and appeared in English and Portuguese the following year. In the decade after the publication of Specters, Derrida’s analyses provoked a large critical literature and invited both consternation and celebration by figures such as Antonio Negri, Wendy Brown and Frederic Jameson. This forum seeks to stimulate new reflections on Derrida, deconstruction and Specters of Marx by considering how the futures past announced by the book have fared after an eventful quarter century. Maja Zehfuss, Antonio Vázquez-Arroyo and Dan Bulley and Bal Sokhi-Bulley offer sharp, occasionally exasperated, meditations on the political import of deconstruction and the limits of Derrida’s diagnoses in Specters of Marx but also identify possible paths forward for a global politics taking inspiration in Derrida’s work of the 1990s

Reckoning up: sexual harassment and violence in the neoliberal university

This paper situates sexual harassment and violence in the neoliberal university. Using data from a ‘composite ethnography’ representing twelve years of research, I argue that institutional inaction on these issues reflects how they are ‘reckoned up’ in the context of gender and other structures. The impact of disclosure is projected in market terms: this produces institutional airbrushing which protects both the institution and those (usually privileged men) whose welfare is bound up with its success. Staff and students are differentiated by power/value relations, which interact with gender and intersecting categories. Survivors are often left with few alternatives to speaking out in the ‘outrage economy’ of the corporate media: however, this can support institutional airbrushing and bolster punitive technologies. I propose the method of Grounded Action Inquiry, implemented with attention to Lorde’s work on anger, as a parrhesiastic practice of ‘speaking in’ to the neoliberal institution

Cinnamomum cassia Bark in Two Herbal Formulas Increases Life Span in Caenorhabditis elegans via Insulin Signaling and Stress Response Pathways

Background: Proving the efficacy and corresponding mode of action of herbal supplements is a difficult challenge for evidence-based herbal therapy. A major hurdle is the complexity of herbal preparations, many of which combine multiple herbs, particularly when the combination is assumed to be vitally important to the effectiveness of the herbal therapy. This issue may be addressed through the use of contemporary methodology and validated animal models. Methods and Principal Findings: In this study, two commonly used traditional herbal formulas, Shi Quan Da Bu Tang (SQDB) and Huo Luo Xiao Ling Dan (HLXL) were evaluated using a survival assay and oxidative stress biomarkers in a well-established C. elegans model of aging. HLXL is an eleven herb formula modified from a top-selling traditional herbal formula for the treatment of arthritic joint pain. SQDB consists of ten herbs often used for fatigue and energy, particularly in the aged. We demonstrate here that SQDB significantly extend life span in a C. elegans model of aging. Among all individual herbs tested, two herbs Cinnamomum cassia bark (Chinese pharmaceutical name: Cinnamomi Cortex, CIN) and Panax ginseng root (Chinese pharmaceutical name: Ginseng Radix, GS) significantly extended life span in C. elegans. CIN in both SQDB and HLXL formula extended life span via modulation of multiple longevity assurance genes, including genes involved in insulin signaling and stress response pathways. All the life-span-extending herbs (SQDB, CIN and GS) also attenuated levels of H2O2 and enhanced small heat shock protein expression. Furthermore, the life spanextending herbs significantly delayed human amyloid beta (Aβ)-induced toxicity in transgenic C. elegans expressing human Aβ. Conclusion/Significance:These results validate an invertebrate model for rapid, systematic evaluation of commonly used Chinese herbal formulations and may provide insight for designing future evidence-based herbal therapy(s). Copyright: © 2010 Yu et al.published_or_final_versio

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

SN 2012fr: Ultraviolet, Optical, and Near-infrared Light Curves of a Type Ia Supernova Observed within a Day of Explosion

We present detailed ultraviolet, optical, and near-infrared light curves of the Type Ia supernova (SN) 2012fr, which exploded in the Fornax cluster member NGC 1365. These precise high-cadence light curves provide a dense coverage of the flux evolution from −12 to +140 days with respect to the epoch of B-band maximum (tBmax). Supplementary imaging at the earliest epochs reveals an initial slow and nearly linear rise in luminosity with a duration of ∼2.5 days, followed by a faster rising phase that is well reproduced by an explosion model with a moderate amount of 56Ni mixing in the ejecta. From our analysis of the light curves, we conclude that: (i) the explosion occurred 1800 Å) luminosity was 16.5 ± 0.6 days, (iii) the supernova suffered little or no host-galaxy dust reddening, (iv) the peak luminosity in both the optical and near-infrared was consistent with the bright end of normal Type Ia diversity, and (v) 0.60 ± 0.15 M⊙ of 56Ni was synthesized in the explosion. Despite its normal luminosity, SN 2012fr displayed unusually prevalent high-velocity Ca II and Si II absorption features, and a nearly constant photospheric velocity of the Si II λ6355 line at ∼12,000 km s-1 that began ∼5 days before tBmax. We also highlight some of the other peculiarities in the early phase photometry and the spectral evolution. SN 2012fr also adds to a growing number of Type Ia supernovae that are hosted by galaxies with direct Cepheid distance measurements.Facultad de Ciencias Astronómicas y GeofísicasInstituto de Astrofísica de La Plat

Study Protocol - Accurate assessment of kidney function in Indigenous Australians: aims and methods of the eGFR Study

Background: There is an overwhelming burden of cardiovascular disease, type 2 diabetes and chronic kidney disease among Indigenous Australians. In this high risk population, it is vital that we are able to measure accurately kidney function. Glomerular filtration rate is the best overall marker of kidney function. However, differences in body build and body composition between Indigenous and non-Indigenous Australians suggest that creatinine-based estimates of glomerular filtration rate derived for European populations may not be appropriate for Indigenous Australians. The burden of kidney disease is borne disproportionately by Indigenous Australians in central and northern Australia, and there is significant heterogeneity in body build and composition within and amongst these groups. This heterogeneity might differentially affect the accuracy of estimation of glomerular filtration rate between different Indigenous groups. By assessing kidney function in Indigenous Australians from Northern Queensland, Northern Territory and Western Australia, we aim to determine a validated and practical measure of glomerular filtration rate suitable for use in all Indigenous Australians

Carnegie Supernova Project-I and -II: Measurements of H0H_0 using Cepheid, TRGB, and SBF Distance Calibration to Type Ia Supernovae

We present an analysis of Type Ia Supernovae (SNe~Ia) from both the Carnegie Supernova Project~I (CSP-I) and II (CSP-II), and extend the Hubble diagram from the optical to the near-infrared wavelengths ($uBgVriYJH$). We calculate the Hubble constant, $H_0$, using various distance calibrators: Cepheids, Tip of the Red Giant Branch (TRGB), and Surface Brightness Fluctuations (SBF). Combining all methods of calibrations, we derive $\rm H_0=71.76 \pm 0.58 \ (stat) \pm 1.19 \ (sys) \ km \ s^{-1} \ Mpc^{-1}$from$B$-band, and$\rm H_0=73.22 \pm 0.68 \ (stat) \pm 1.28 \ (sys) \ km \ s^{-1} \ Mpc^{-1}$from$H$-band. By assigning equal weight to the Cepheid, TRGB, and SBF calibrators, we derive the systematic errors required for consistency in the first rung of the distance ladder, resulting in a systematic error of$1.2\sim 1.3 \rm \ km \ s^{-1} \ Mpc^{-1}$in$H_0$. As a result, relative to the statistics-only uncertainty, the tension between the late-time$H_0$we derive by combining the various distance calibrators and the early-time$H_0$from the Cosmic Microwave Background is reduced. The highest precision in SN~Ia luminosity is found in the$Y$band ($0.12\pm0.01$mag), as defined by the intrinsic scatter ($\sigma_{int}$). We revisit SN~Ia Hubble residual-host mass correlations and recover previous results that these correlations do not change significantly between the optical and the near-infrared wavelengths. Finally, SNe~Ia that explode beyond 10 kpc from their host centers exhibit smaller dispersion in their luminosity, confirming our earlier findings. Reduced effect of dust in the outskirt of hosts may be responsible for this effect.Comment: Revised calculations are made. Will be resubmitted to Ap