Combined SIRT3 and SIRT5 deletion is associated with inner retinal dysfunction in a mouse model of type 1 diabetes

Abstract Diabetic retinopathy (DR) is a major cause of blindness in working adults in the industrialized world. In addition to vision loss caused by macular edema and pathological angiogenesis, DR patients often exhibit neuronal dysfunction on electrophysiological testing, suggesting that there may be an independent neuronal phase of disease that precedes vascular disease. Given the tremendous metabolic requirements of the retina and photoreceptors in particular, we hypothesized that derangements in metabolic regulation may accelerate retinal dysfunction in diabetes. As such, we induced hyperglycemia with streptozotocin in mice with monoallelic Nampt deletion from rod photoreceptors, mice lacking SIRT3, and mice lacking SIRT5 and tested multiple components of retinal function with electroretinography. None of these mice exhibited accelerated retinal dysfunction after induction of hyperglycemia, consistent with normal-appearing retinal morphology in hyperglycemic Sirt3 −/− or Sirt5 −/− mice. However, mice lacking both SIRT3 and SIRT5 (Sirt3 −/− Sirt5 −/− mice) exhibited significant evidence of inner retinal dysfunction after induction of hyperglycemia compared to hyperglycemic littermate controls, although this dysfunction was not accompanied by gross morphological changes in the retina. These results suggest that SIRT3 and SIRT5 may be involved in regulating neuronal dysfunction in DR and provide a foundation for future studies investigating sirtuin-based therapies

Perturbation theorems for Hele-Shaw flows and their applications

In this work, we give a perturbation theorem for strong polynomial solutions to the zero surface tension Hele-Shaw equation driven by injection or suction, so called the Polubarinova-Galin equation. This theorem enables us to explore properties of solutions with initial functions close to but are not polynomial. Applications of this theorem are given in the suction or injection case. In the former case, we show that if the initial domain is close to a disk, most of fluid will be sucked before the strong solution blows up. In the later case, we obtain precise large-time rescaling behaviors for large data to Hele-Shaw flows in terms of invariant Richardson complex moments. This rescaling behavior result generalizes a recent result regarding large-time rescaling behavior for small data in terms of moments. As a byproduct of a theorem in this paper, a short proof of existence and uniqueness of strong solutions to the Polubarinova-Galin equation is given.Comment: 25 page

Twisted and Nontwisted Bifurcations Induced by Diffusion

We discuss a diffusively perturbed predator-prey system. Freedman and Wolkowicz showed that the corresponding ODE can have a periodic solution that bifurcates from a homoclinic loop. When the diffusion coefficients are large, this solution represents a stable, spatially homogeneous time-periodic solution of the PDE. We show that when the diffusion coefficients become small, the spatially homogeneous periodic solution becomes unstable and bifurcates into spatially nonhomogeneous periodic solutions. The nature of the bifurcation is determined by the twistedness of an equilibrium/homoclinic bifurcation that occurs as the diffusion coefficients decrease. In the nontwisted case two spatially nonhomogeneous simple periodic solutions of equal period are generated, while in the twisted case a unique spatially nonhomogeneous double periodic solution is generated through period-doubling. Key Words: Reaction-diffusion equations; predator-prey systems; homoclinic bifurcations; periodic solutions.Comment: 42 pages in a tar.gz file. Use ``latex2e twisted.tex'' on the tex files. Hard copy of figures available on request from [email protected]

Stereospecific synthesis of the aglycone of pseudopterosin E

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Production and Decay of the Ge73-m Metastable State in a Low-Background Germanium Detector

The $\ge73m$ metastable states decay with a very characteristic signature which allow them to be tagged event-by-event. Studies were performed using data taken with a high-purity germanium detector in a low-background laboratory near a nuclear power reactor core where \nuebar-flux was $\rm{6.4 \times 10^{12} ~ cm^{-2} s^{-1}}$. The measured average and equilibrium production rates of $\ge73m$ were $\rm{(8.7 \pm 0.4)}$ and $\rm{(6.7 \pm 0.3) ~ kg^{-1} day^{-1}}$, respectively. The production channels were studied and identified. By studying the difference in the production of $\ge73m$ between the reactor ON and OFF spectra, the limiting sensitivities at the range of $\rm{\sim 10^{-42} - 10^{-43} ~ cm^2}$ for the cross-sections of neutrino-induced nuclear transitions were derived. The dominant background are due to $\beta$-decays of cosmic-ray induced $^{73}$Ga. The prospects of enhancing the sensitivities at underground locations are discussed.Comment: 16 pages, 10 figure