Biochemical profile of heifers with spontaneous humeral fractures suggest that protein-energy malnutrition could be an important factor in the pathology of this disease.

CAUL Read and Publish Agreement.CASE HISTORY: Serum and liver samples from 35, 2-year-old dairy heifers that had fractured one or both humeri post-calving between July and December 2019 were submitted to a diagnostic laboratory for analysis. Serum samples were analysed for albumin, β-hydroxybutyrate (BHB), creatinine, Ca, Mg, phosphate, non-esterified fatty acids (NEFA), and serum Cu concentration. Liver samples were analysed for liver Cu concentration. Data were compared to published reference intervals. Data values for heifers that prior to fracture had grazed fodder beet were also compared to values for those that had grazed pasture. CLINICAL FINDINGS: Sixty-nine percent of heifers with humeral fracture had serum creatinine concentrations below the lower value of the reference range (55-130 µmol/L). In 3/32 (9%) heifers, serum NEFA concentrations were increased above the reference value indicating body fat mobilisation (≥1.2 mmol/L for peri-partum cows) and in 20/35 (57%) heifers BHB serum concentrations were above the reference value indicating subclinical ketosis (≥1.1 mmol/L for peri-partum cows). In 24/35 (69%) heifers, liver Cu concentration was low (≤ 44 µmol/kg) or marginal (45-94 µmol/kg). The concentration of Cu in serum was low (≤ 4.5 µmol/L) in 2/33 (6%) heifers and marginal (4.6-7.9 µmol/L) in 5/33 (15%) heifers. There was moderate positive correlation between the logged concentrations of Cu in paired liver and serum samples, r(31) = 0.43; (95% CI = 0.1-0.79; p = 0.014). One heifer had a serum phosphate concentration below the lower limit of the reference range (< 1.10 mmol/L). For all heifers, the concentrations of albumin, Ca, and Mg in serum were within the reference intervals (23-38 g/L, 2.00-2.60 mmol/L, and 0.49-1.15 mmol/L respectively). Over winter, 15/35 (43%) heifers grazed predominantly pasture, 14/35 (40%) grazed fodder beet and 6/35 (17%) had a mixed diet. CLINICAL RELEVANCE: In some of these heifers with humeral fractures, there was evidence for protein and/or energy malnutrition in the form of elevated NEFA and BHB concentrations and low creatinine concentrations in serum. Liver Cu concentrations were also reduced in most affected heifers. However, the absence of a control group means it is not possible to determine if these are risk factors for fracture or features common to all periparturient heifers. Clinical trials and molecular studies are needed to determine the true contribution of Cu and protein-energy metabolism to the pathogenesis of spontaneous humeral fractures in dairy heifers. ABBREVIATIONS: BHB: ß-hydroxybutyrate; NEFA: Non-esterified fatty acids.Publishe

Bone quality changes as measured by Raman and FTIR spectroscopy in primiparous cows with humeral fracture from New Zealand.

The occurrence of spontaneous humeral fractures in primiparous dairy cows from New Zealand prompted the study of bone material from affected cows to further characterize this condition and to outline a likely pathogenesis. Previous studies indicate that these cows developed osteoporosis due to periods of suboptimal bone formation followed by increased bone resorption during the period of lactation complicated by copper deficiency. We hypothesized that there are significant differences in the chemical composition/bone quality in bones from cows with spontaneous humeral fracture compared to cows without humeral fractures. In this study, Raman and Fourier transform infrared spectroscopy band ratios were, for the first time, measured, calculated, and compared in bone samples from 67 primiparous dairy cows that suffered a spontaneous fracture of the humerus and 14 age-matched post-calving cows without humeral fractures. Affected bone showed a significantly reduced mineral/matrix ratio, increased bone remodeling, newer bone tissue with lower mineralization and, lower carbonate substitution, and reduced crystallinity. As such, is likely that these have detrimentally impacted bone quality and strength in affected cows.Published onlin

VizieR Online Data Catalog: 1Jy northern AGN sample (Planck+, 2016)

The complete sample presented in this paper consists of 104 northern and equatorial radio-loud AGN. It includes all AGN with declination >=-10° that have a measured average radio flux density at 37GHz exceeding 1Jy. Most of the sample sources have been monitored at Metsahovi Radio Observatory for many years, and the brightest sources have been observed for up to 30yr. (1 data file)

Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer.

Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution.Wellcome Trust Investigator Award, 102942/Z/13/A Elizabeth P Murchison Leverhulme Trust Philip Leverhulme Prize Elizabeth P Murchison Royal Society Research Grant, RG130615 Elizabeth P Murchiso

Somatic evolution and global expansion of an ancient transmissible cancer lineage

Made available in DSpace on 2019-10-06T15:53:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-08-02GPD Charitable TrustLeverhulme TrustThe canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and survives by “metastasizing” between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage's worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer's evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution.Transmissible Cancer Group Department of Veterinary Medicine University of CambridgeAnimal Management in Rural and Remote Indigenous Communities (AMRRIC)World VetsAnimal Shelter Stichting Dierenbescherming SurinameSikkim Anti-Rabies and Animal Health Programme Department of Animal Husbandry Livestock Fisheries and Veterinary Services Government of SikkimRoyal (Dick) School of Veterinary Studies Roslin Institute University of Edinburgh Easter Bush CampusConserLab Animal Preventive Medicine Department Faculty of Animal and Veterinary Sciences University of ChileCorozal Veterinary Hospital University of PanamáSt. George's UniversityNakuru District Veterinary Scheme LtdAnimal Medical CentreInternational Animal Welfare Training Institute UC Davis School of Veterinary MedicineCentro Universitário de Rio Preto (UNIRP)Department of Clinical and Veterinary Surgery São Paulo State University (UNESP)Ladybrand Animal ClinicVeterinary Clinic Sr. Dog'sWorld Vets Latin America Veterinary Training CenterNational Veterinary Research InstituteAnimal ClinicIntermunicipal Stray Animals Care Centre (DIKEPAZ)Animal Protection Society of SamoaFaculty of Veterinary Science University of ZuliaVeterinary Clinic BIOCONTROLFaculty of Veterinary Medicine School of Health Sciences University of ThessalyVeterinary Clinic El Roble Animal Healthcare Network Faculty of Animal and Veterinary Sciences University of ChileOnevetGroup Hospital Veterinário BernaUniversidade Vila VelhaVeterinary Clinic ZoovetservisÉcole Inter-états des Sciences et Médecine Vétérinaires de DakarDepartment of Small Animal Medicine Faculty of Veterinary Medicine Utrecht UniversityVetexpert Veterinary GroupVeterinary Clinic Lopez QuintanaClinique Veterinaire de Grand Fond Saint Gilles les BainsDepartment of Veterinary Sciences University of MessinaFacultad de Medicina Veterinaria y Zootecnia Universidad Autónoma del Estado de MéxicoSchool of Veterinary Medicine Universidad de las AméricasCancer Development and Innate Immune Evasion Lab Champalimaud Center for the UnknownTouray and Meyer Vet ClinicHillside Animal HospitalKampala Veterinary SurgeryAsavet Veterinary CharitiesVets Beyond BordersFaculty of Veterinary Medicine Autonomous University of YucatanLaboratorio de Patología Veterinaria Universidad de CaldasInterdisciplinary Centre of Research in Animal Health (CIISA) Faculty of Veterinary Medicine University of LisbonFour Paws InternationalHelp in SufferingVeterinary Clinic Dr José RojasDepartment of Biotechnology Balochistan University of Information Technology Engineering and Management SciencesCorozal Veterinary ClinicVeterinary Clinic VetmasterState Hospital of Veterinary MedicineJomo Kenyatta University of Agriculture and TechnologyLaboratory of Biomedicine and Regenerative Medicine Department of Clinical Sciences Faculty of Animal and Veterinary Sciences University of ChileFaculty of Veterinary and Agricultural Sciences University of MelbourneAnimal Anti Cruelty LeagueClinical Sciences Department Faculty of Veterinary Medicine BucharestDepartment of Pathology Faculty of Veterinary Medicine Ankara UniversityFaculty of Veterinary Sciences National University of AsuncionLilongwe Society for Protection and Care of Animals (LSPCA)Wellcome Sanger InstituteDepartment of Cellular and Molecular Medicine University of California San DiegoDepartment of Clinical and Veterinary Surgery São Paulo State University (UNESP)Leverhulme Trust: 102942/Z/13/

Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer

Abstract: Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for ‘selfish’ traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby ‘selfish’ positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells

Multiband variability studies and novel broadband SED modeling of Mrk 501 in 2009

Aims. We present an extensive study of the BL Lac object Mrk 501 based on a data set collected during the multi-instrument campaign spanning from 2009 March 15 to 2009 August 1, which includes, among other instruments, MAGIC, VERITAS, Whipple 10 m, and Fermi-LAT to cover the gamma-ray range from 0.1 GeV to 20 TeV; RXTE and Swift to cover wavelengths from UV to hard X-rays; and GASP-WEBT, which provides coverage of radio and optical wavelengths. Optical polarization measurements were provided for a fraction of the campaign by the Steward and St. Petersburg observatories. We evaluate the variability of the source and interband correlations, the gamma-ray flaring activity occurring in May 2009, and interpret the results within two synchrotron self-Compton (SSC) scenarios.Methods. The multiband variability observed during the full campaign is addressed in terms of the fractional variability, and the possible correlations are studied by calculating the discrete correlation function for each pair of energy bands where the significance was evaluated with dedicated Monte Carlo simulations. The space of SSC model parameters is probed following a dedicated grid-scan strategy, allowing for a wide range of models to be tested and offering a study of the degeneracy of model-to-data agreement in the individual model parameters, hence providing a less biased interpretation than the "single-curve SSC model adjustment" typically reported in the literature.Results. We find an increase in the fractional variability with energy, while no significant interband correlations of flux changes are found on the basis of the acquired data set. The SSC model grid-scan shows that the flaring activity around May 22 cannot be modeled adequately with a one-zone SSC scenario (using an electron energy distribution with two breaks), while it can be suitably described within a two (independent) zone SSC scenario. Here, one zone is responsible for the quiescent emission from the averaged 4.5-month observing period, while the other one, which is spatially separated from the first, dominates the flaring emission occurring at X-rays and very-high-energy (> 100 GeV, VHE) gamma-rays. The flaring activity from May 1, which coincides with a rotation of the electric vector polarization angle (EVPA), cannot be satisfactorily reproduced by either a one-zone or a two-independent-zone SSC model, yet this is partially affected by the lack of strictly simultaneous observations and the presence of large flux changes on sub-hour timescales (detected at VHE gamma rays).Conclusions. The higher variability in the VHE emission and lack of correlation with the X-ray emission indicate that, at least during the 4.5-month observing campaign in 2009, the highest energy (and most variable) electrons that are responsible for the VHE gamma rays do not make a dominant contribution to the similar to 1 keV emission. Alternatively, there could be a very variable component contributing to the VHE gamma-ray emission in addition to that coming from the SSC scenario. The studies with our dedicated SSC grid-scan show that there is some degeneracy in both the one-zone and the two-zone SSC scenarios probed, with several combinations of model parameters yielding a similar model-to-data agreement, and some parameters better constrained than others. The observed gamma-ray flaring activity, with the EVPA rotation coincident with the first gamma-ray flare, resembles those reported previously for low frequency peaked blazars, hence suggesting that there are many similarities in the flaring mechanisms of blazars with different jet properties

Novel Assessment of Collagen and Its Crosslink Content in the Humerus from Primiparous Dairy Cows with Spontaneous Humeral Fractures Due to Osteoporosis from New Zealand.

Numerous cases of spontaneous humeral fracture in primiparous dairy cows from New Zealand have prompted the study of the condition to establish probable causes or risk factors associated with the condition. Previous studies identified inadequate protein-calorie malnutrition as an important contributory factor. Earlier case studies also reported that ~50% of cows have low liver and/or serum copper concentration at the time of humeral fracture. Because copper is so closely associated with the formation of collagen cross-links, the aim of this study was to compare collagen and collagen crosslink content in the humerus from primiparous cows with and without humeral fractures and to determine the role of copper in the occurrence of these fractures. Humeri were collected from cows with and without humeral fractures, ground, and the collagen and collagen cross-link content measured using high-performance liquid chromatography. Collagen content was significantly higher in the humeri of cows without humeral fractures, while total collagen crosslink content was significantly higher in the humerus of cows with humeral fractures. These results indicate other factor/s (e.g., protein-calorie undernutrition) might be more important than the copper status in the occurrence of humeral fractures in dairy cows in New Zealand.Published onlin