33 research outputs found

    Breed differences in development of anti-insulin antibodies in diabetic dogs and investigation of the role of dog leukocyte antigen (DLA) genes

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    Administration of insulin for treatment of diabetes mellitus in dogs can stimulate an immune response, with a proportion of animals developing anti-insulin antibodies (AIA). For an IgG antibody response to occur, this would require B cell presentation of insulin peptides by major histocompatibility complex (MHC) class II molecules, encoded by dog leukocyte antigen (DLA) genes, in order to receive T-cell help for class switching. DLA genes are highly polymorphic in the dog population and vary from breed to breed. The aim of the present study was to evaluate AIA reactivity in diabetic dogs of different breeds and to investigate whether DLA genes influence AIA status. Indirect ELISA was used to determine serological reactivity to insulin in diabetic dogs, treated with either a porcine or bovine insulin preparation. DLA haplotypes for diabetic dogs were determined by sequence-based typing of DLA-DRB1, -DQA1 and -DQB1 loci. Significantly greater insulin reactivity was seen in treated diabetic dogs (n = 942) compared with non-diabetic dogs (n = 100). Relatively few newly diagnosed diabetic dogs (3/109) were found to be AIA positive, although this provides evidence that insulin autoantibodies might be involved in the pathogenesis of the disease in some cases. Of the diabetic dogs treated with a bovine insulin preparation, 52.3% (182/348) were AIA positive, compared with 12.6% (75/594) of dogs treated with a porcine insulin preparation, suggesting that bovine insulin is more immunogenic. Breeds such as dachshund, Cairn terrier, miniature schnauzer and Tibetan terrier were more likely to develop AIA, whereas cocker spaniels were less likely to develop AIA, compared with crossbreed dogs. In diabetic dogs, DLA haplotype DRB1*0015--DQA1*006--DQB1*023 was associated with being AIA positive, whereas the haplotype DLA-DRB1*006--DQA1*005--DQB1*007 showed an association with being AIA negative. These research findings suggest that DLA genes influence AIA responses in treated diabetic dogs

    High-Precision Branching Ratio Measurement for the Superallowed + Emitter 74Rb

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    A high-precision branching-ratio measurement for the superallowed β + decay of 74Rb was performed at the TRIUMF Isotope Separator and Accelerator (ISAC) radioactive ion-beam facility. The scintillating electronpositron tagging array (SCEPTAR), composed of 10 thin plastic scintillators, was used to detect the emitted β particles; the 8π spectrometer, an array of 20 Compton-suppressed HPGe detectors, was used for detecting γ rays that were emitted following Gamow-Teller and nonanalog Fermi β + decays of 74Rb; and the Pentagonal Array of Conversion Electron Spectrometers (PACES), an array of 5 Si(Li) detectors, was employed for measuring β-delayed conversion electrons. Twenty-three excited states were identified in 74Kr following 8.241(4) × 108 detected 74Rb β decays. A total of 58 γ -ray and electron transitions were placed in the decay scheme, allowing the superallowed branching ratio to be determined as B0 = 99.545(31)%. Combined with previous half-life and Q-value measurements, the superallowed branching ratio measured in this work leads to a superallowed f t value of 3082.8(65) s. Comparisons between this superallowed f t value and the world-average-corrected Ft value, as well as the nonanalog Fermi branching ratios determined in this work, provide guidance for theoretical models of the isospin-symmetry-breaking corrections in this mass region.IS

    Reorientation-effect measurement of the first 2+ state in 12C : Confirmation of oblate deformation

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    A Coulomb-excitation reorientation-effect measurement using the TIGRESS γ−ray spectrometer at the TRIUMF/ISAC II facility has permitted the determination of the 〈21 +‖E2ˆ‖21 +〉 diagonal matrix element in 12C from particle−γ coincidence data and state-of-the-art no-core shell model calculations of the nuclear polarizability. The nuclear polarizability for the ground and first-excited (21 +) states in 12C have been calculated using chiral NN N4LO500 and NN+3NF350 interactions, which show convergence and agreement with photo-absorption cross-section data. Predictions show a change in the nuclear polarizability with a substantial increase between the ground state and first excited 21 + state at 4.439 MeV. The polarizability of the 21 + state is introduced into the current and previous Coulomb-excitation reorientation-effect analyses of 12C. Spectroscopic quadrupole moments of QS(21 +)=+0.053(44) eb and QS(21 +)=+0.08(3) eb are determined, respectively, yielding a weighted average of QS(21 +)=+0.071(25) eb, in agreement with recent ab initio calculations. The present measurement confirms that the 21 + state of 12C is oblate and emphasizes the important role played by the nuclear polarizability in Coulomb-excitation studies of light nuclei

    The dynamic architecture of the metabolic switch in Streptomyces coelicolor

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    Background: During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples. Results: Surprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly coherent clusters of genes show drastic changes in gene expression already many hours before the classically defined transition phase where the switch from primary to secondary metabolism was expected. The main switch in gene expression takes only 2 hours, and changes in antibiotic biosynthesis genes are delayed relative to the metabolic rearrangements. Furthermore, global variation in morphogenesis genes indicates an involvement of cell differentiation pathways in the decision phase leading up to the commitment to antibiotic biosynthesis. Conclusions: Our study provides the first detailed insights into the complex sequence of early regulatory events during and preceding the major metabolic switch in S. coelicolor, which will form the starting point for future attempts at engineering antibiotic production in a biotechnological setting
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