Behavior in dogs with spontaneous hypothyroidism during treatment with levothyroxine

Background Thyroid hormone supplementation anecdotally has been described as a valid treatment option for dogs with aggression‐related problems. However, prospective, controlled, and blinded trials evaluating behavior and neurohormonal status in hypothyroid dogs during treatment with levothyroxine are lacking. Objective Levothyroxine supplementation will have a significant influence on the behavior and neurohormonal status of dogs with spontaneous hypothyroidism. Animals Twenty client‐owned dogs diagnosed with spontaneous hypothyroidism. Methods This prospective study was to evaluate the behavior of dogs, which was screened at initial presentation, and after 6 weeks, and 6 months of treatment with levothyroxine (starting dosage 10 μg/kg PO q12h) using the standardized Canine Behavioral Assessment and Research Questionnaire (C‐BARQ). At each time period, circulating serotonin and prolactin (PRL) concentrations were evaluated using a commercially validated ELISA kit and heterologous radioimmunoassay, respectively. Results After 6 weeks of thyroid hormone supplementation, C‐BARQ scores demonstrated a significant increase in activity of hypothyroid dogs (P  .99 and P = .46) and PRL (P = .99 and P = .37) were noted between the 6‐week and 6‐month periods compared with baseline. Conclusions and Clinical Importance The results of this study indicate increased activity of hypothyroid dogs after 6 weeks of thyroid hormone supplementation. None of the hypothyroid dogs in this cohort showed a significant change in any of the evaluated behavioral signs and neurohormonal status after 6 months of thyroid hormone supplementation

Neutrino Beams From Electron Capture at High Gamma

We investigate the potential of a flavor pure high gamma electron capture electron neutrino beam directed towards a large water cherenkov detector with 500 kt fiducial mass. The energy of the neutrinos is reconstructed by the position measurement within the detector and superb energy resolution capabilities could be achieved. We estimate the requirements for such a scenario to be competitive to a neutrino/anti-neutrino running at a neutrino factory with less accurate energy resolution. Although the requirements turn out to be extreme, in principle such a scenario could achieve as good abilities to resolve correlations and degeneracies in the search for sin^2(2 theta_13) and delta_CP as a standard neutrino factory experiment.Comment: 21 pages, 7 figures, revised version, to appear in JHEP, Fig.7 extended, minnor changes, results unchange

Structure of an archaeal PCNA1-PCNA2-FEN1 complex: elucidating PCNA subunit and client enzyme specificity.

The archaeal/eukaryotic proliferating cell nuclear antigen (PCNA) toroidal clamp interacts with a host of DNA modifying enzymes, providing a stable anchorage and enhancing their respective processivities. Given the broad range of enzymes with which PCNA has been shown to interact, relatively little is known about the mode of assembly of functionally meaningful combinations of enzymes on the PCNA clamp. We have determined the X-ray crystal structure of the Sulfolobus solfataricus PCNA1-PCNA2 heterodimer, bound to a single copy of the flap endonuclease FEN1 at 2.9 A resolution. We demonstrate the specificity of interaction of the PCNA subunits to form the PCNA1-PCNA2-PCNA3 heterotrimer, as well as providing a rationale for the specific interaction of the C-terminal PIP-box motif of FEN1 for the PCNA1 subunit. The structure explains the specificity of the individual archaeal PCNA subunits for selected repair enzyme 'clients', and provides insights into the co-ordinated assembly of sequential enzymatic steps in PCNA-scaffolded DNA repair cascades