Physiological Effects of Superoxide Dismutase on Altered Visual Function of Retinal Ganglion Cells in db/db Mice

Background: The C57BLKS/J db/db (db/db) mouse is a widely used type 2 diabetic animal model, and this model develops early inner retinal neuronal dysfunction beginning at 24 weeks. The neural mechanisms that mediate early stage retinal dysfunction in this model are unknown. We evaluated visual response properties of retinal ganglion cells (RGCs) during the early stage of diabetic insult (8, 12, and 20 wk) in db/db mice and determined if increased oxidative stress plays a role in impaired visual functions of RGCs in 20 wk old db/db mice. Methodology/Principal Findings: In vitro extracellular single-unit recordings from RGCs in wholemount retinas were performed. The receptive field size, luminance threshold, and contrast gain of the RGCs were investigated. Although ONand OFF-RGCs showed a different time course of RF size reduction, by 20 wk, the RF of ON- and OFF-RGCs were similarly affected. The LT of ON-RGCs was significantly elevated in 12 and 20 wk db/db mice compared to the LT of OFF-RGCs. The diabetic injury also affected contrast gains of ON- and OFF-RGCs differently. The generation of reactive oxidative species (ROS) in fresh retina was estimated by dihydroethidium. Superoxide dismutase (SOD) (300 unit/ml) was applied in Ames medium to the retina, and visual responses of RGCs were recorded for five hours. ROS generation in the retinas of db/db mice increased at 8wk and continued to progress at 20 wk of ages. In vitro application of SOD improved visual functions in 20 wk db/db mice but the SOD treatment affected ON- and OFF-RGCs differently in db/m retina

The Epistatic Relationship between BRCA2 and the Other RAD51 Mediators in Homologous Recombination

RAD51 recombinase polymerizes at the site of double-strand breaks (DSBs) where it performs DSB repair. The loss of RAD51 causes extensive chromosomal breaks, leading to apoptosis. The polymerization of RAD51 is regulated by a number of RAD51 mediators, such as BRCA1, BRCA2, RAD52, SFR1, SWS1, and the five RAD51 paralogs, including XRCC3. We here show that brca2-null mutant cells were able to proliferate, indicating that RAD51 can perform DSB repair in the absence of BRCA2. We disrupted the BRCA1, RAD52, SFR1, SWS1, and XRCC3 genes in the brca2-null cells. All the resulting double-mutant cells displayed a phenotype that was very similar to that of the brca2-null cells. We suggest that BRCA2 might thus serve as a platform to recruit various RAD51 mediators at the appropriate position at the DNA–damage site

Competition between Replicative and Translesion Polymerases during Homologous Recombination Repair in Drosophila

In metazoans, the mechanism by which DNA is synthesized during homologous recombination repair of double-strand breaks is poorly understood. Specifically, the identities of the polymerase(s) that carry out repair synthesis and how they are recruited to repair sites are unclear. Here, we have investigated the roles of several different polymerases during homologous recombination repair in Drosophila melanogaster. Using a gap repair assay, we found that homologous recombination is impaired in Drosophila lacking DNA polymerase zeta and, to a lesser extent, polymerase eta. In addition, the Pol32 protein, part of the polymerase delta complex, is needed for repair requiring extensive synthesis. Loss of Rev1, which interacts with multiple translesion polymerases, results in increased synthesis during gap repair. Together, our findings support a model in which translesion polymerases and the polymerase delta complex compete during homologous recombination repair. In addition, they establish Rev1 as a crucial factor that regulates the extent of repair synthesis

"D-3He Fueled FRC Reactor ""Artemis-L"""

"A neutron-lean D- ^3He fueled FRC fusion reactor is studied on the bases of former high-efficiency ARTEMIS design. Certain improvements such as effective axial contracting plasma heating and cusp-type direct energy converters as well as an empirical scale of the energy confinement are introduced. The resultant total neutron load onto the first wall of the plasma chamber is as low as 0.1 MW/m^2, which enable the life of the first wall or the structural materials to be longer than the whole life of the reactor. The attractive characteristics of the neutron-lean reactor follow in the ARTEMIS design: it is socially acceptable in views of radioactivity and fuel resources, and the cost of electricity appears to be cheap compared with that from a light vater reactor. Critical physics and engineering issues for performing the ARTEMIS-L reactor are clarified.

"Conceptual Design of D-^3He FRC Reactor ""ARTEMIS"""

"A comprehensive design study of the D-^3He fueled FRC reactor ""ARTEMIS"" is carried out for the purpose of proving its attractive characteristics and clarifying the critical issues for a commercial fusion reactor. The FRC burning plasma is stabilized and sustained in a steady equilibrium by means of a preferential trapping of D-^3He fusion-produced energetic protons. A novel direct energy converter for 15MeV protons is also presented. On the bases of a consistent scenario of the fusion plasma production and simple engineering, a compact and simple reactor concept is presented The design of the D-^3He FRC power plant definitely offers the most attractive prospect for energy development. It is environmentally acceptable in view of radio-activity and fuel resources; and the estimated cost of electricity is low compared to a light water reactor. Critical issues concerning physics or engineering for the development of the D-^3He FRC reactor are clarified.