The role of DT-diaphorase in the maintenance of the reduced antioxidant form of coenzyme Q in membrane systems.

The experiments reported here were designed to test the hypothesis that the two-electron quinone reductase DT-diaphorase [NAD(P)H:(quinone-acceptor) oxidoreductase, EC 1.6.99.2] functions to maintain membrane-bound coenzyme Q (CoQ) in its reduced antioxidant state, thereby providing protection from free radical damage. DT-diaphorase was isolated and purified from rat liver cytosol, and its ability to reduce several CoQ homologs incorporated into large unilamellar vesicles was demonstrated. Addition of NADH and DT-diaphorase to either large unilamellar or multilamellar vesicles containing homologs of CoQ, including CoQ9 and CoQ10, resulted in the essentially complete reduction of the CoQ. The ability of DT-diaphorase to maintain the reduced state of CoQ and protect membrane components from free radical damage as lipid peroxidation was tested by incorporating either reduced CoQ9 or CoQ10 and the lipophylic azoinitiator 2,2'-azobis(2,4-dimethylvaleronitrile) into multilamellar vesicles in the presence of NADH and DT-diaphorase. The presence of DT-diaphorase prevented the oxidation of reduced CoQ and inhibited lipid peroxidation. The interaction between DT-diaphorase and CoQ was also demonstrated in an isolated rat liver hepatocyte system. Incubation with adriamycin resulted in mitochondrial membrane damage as measured by membrane potential and the release of hydrogen peroxide. Incorporation of CoQ10 provided protection from adriamycin-induced mitochondrial membrane damage. The incorporation of dicoumarol, a potent inhibitor of DT-diaphorase, interfered with the protection provided by CoQ. The results of these experiments provide support for the hypothesis that DT-diaphorase functions as an antioxidant in both artificial membrane and natural membrane systems by acting as a two-electron CoQ reductase that forms and maintains the antioxidant form of CoQ. The suggestion is offered that DT-diaphorase was selected during evolution to perform this role and that its conversion of xenobiotics and other synthetic molecules is secondary and coincidental.

Retrograde axonal transport of glial cell line-derived neurotrophic factor in the adult nigrostriatal system suggests a trophic role in the adult.

The recently cloned, distant member of the transforming growth factor beta (TGF-beta) family, glial cell line-derived neurotrophic factor (GDNF), has potent trophic actions on fetal mesencephalic dopamine neurons. GDNF also has protective and restorative activity on adult mesencephalic dopaminergic neurons and potently protects motoneurons from axotomy-induced cell death. However, evidence for a role for endogenous GDNF as a target-derived trophic factor in adult midbrain dopaminergic circuits requires documentation of specific transport from the sites of synthesis in the target areas to the nerve cell bodies themselves. Here, we demonstrate that GDNF is retrogradely transported by mesencephalic dopamine neurons of the nigrostriatal pathway. The pattern of retrograde transport following intrastriatal injections indicates that there may be subpopulations of neurons that are GDNF responsive. Retrograde axonal transport of biologically active 125I-labeled GDNF was inhibited by an excess of unlabeled GDNF but not by an excess of cytochrome c. Specificity was further documented by demonstrating that another TGF-beta family member, TGF-beta 1, did not appear to affect retrograde transport. Retrograde transport was also demonstrated by immunohistochemistry by using intrastriatal injections of unlabeled GDNF. GDNF immunoreactivity was found specifically in dopamine nerve cell bodies of the substantia nigra pars compacta distributed in granules in the soma and proximal dendrites. Our data implicate a specific receptor-mediated uptake mechanism operating in the adult. Taken together, the present findings suggest that GDNF acts endogenously as a target-derived physiological survival/maintenance factor for dopaminergic neurons.

The ubiquitin-proteasome system in retinal health and disease

The ubiquitin–proteasome system (UPS) is the main intracellular pathway for modulated protein turnover, playing an important role in the maintenance of cellular homeostasis. It also exerts a protein quality control through degradation of oxidized, mutant, denatured, or misfolded proteins and is involved in many biological processes where protein level regulation is necessary. This system allows the cell to modulate its protein expression pattern in response to changing physiological conditions and provides a critical protective role in health and disease. Impairments of UPS function in the central nervous system (CNS) underlie an increasing number of genetic and idiopathic diseases, many of which affect the retina. Current knowledge on the UPS composition and function in this tissue, however, is scarce and dispersed. This review focuses on UPS elements reported in the retina, including ubiquitinating and deubiquitinating enzymes (DUBs), and alternative proteasome assemblies. Known and inferred roles of protein ubiquitination, and of the related, SUMO conjugation (SUMOylation) process, in normal retinal development and adult homeostasis are addressed, including modulation of the visual cycle and response to retinal stress and injury. Additionally, the relationship between UPS dysfunction and human neurodegenerative disorders affecting the retina, including Alzheimer's, Parkinson's, and Huntington's diseases, are dealt with, together with numerous instances of retina-specific illnesses with UPS involvement, such as retinitis pigmentosa, macular degenerations, glaucoma, diabetic retinopathy (DR), and aging-related impairments. This information, though still basic and limited, constitutes a suitable framework to be expanded in incoming years and should prove orientative toward future therapy design targeting sight-affecting diseases with a UPS underlying basis.

Fish diversity and traditional fishing methods in semiarid irrigated system in the Bajo Vinalopó region, Southeastern Spain

The aim of this paper is to obtain a comprehensive picture of the importance of the fish fauna in the wetlands and coastal lagoons of the Bajo Vinalopó region (Alicante, South eastern Spain) and the ecological, historical and cultural value of the traditional knowledge on fishing maintained by local people. We have compiled data from different information sources: (1) the revision of historical archives, (2) personal interviews and collaborative research, and (3) ecological and water quality data. The results show that the area sustains important fish fauna diversity (17 species) and that local people have inherited a considerable traditional knowledge on fishing methods (11 modalities), on the maintenance and sound management of the water system and on the ecology and behaviour of fish. We conclude that a comprehensive consideration of all these ecological, historical and socio-cultural aspects related to fish and fishing shows clearly the value of this ecological and cultural heritage and provides a necessary base for a sustainable management of the area.

Optimization of test and maintenance of ageing components consisting of multiple items and addressing effectiveness

There are many models in the literature that have been proposed in the last decades aimed at assessing the reliability, availability and maintainability (RAM) of safety equipment, many of them with a focus on their use to assess the risk level of a technological system or to search for appropriate design and/or surveillance and maintenance policies in order to assure that an optimum level of RAM of safety systems is kept during all the plant operational life. This paper proposes a new approach for RAM modelling that accounts for equipment ageing and maintenance and testing effectiveness of equipment consisting of multiple items in an integrated manner. This model is then used to perform the simultaneous optimization of testing and maintenance for ageing equipment consisting of multiple items. An example of application is provided, which considers a simplified High Pressure Injection System (HPIS) of a typical Power Water Reactor (PWR). Basically, this system consists of motor driven pumps (MDP) and motor operated valves (MOV), where both types of components consists of two items each. These components present different failure and cause modes and behaviours, and they also undertake complex test and maintenance activities depending on the item involved. The results of the example of application demonstrate that the optimization algorithm provide the best solutions when the optimization problem is formulated and solved considering full flexibility in the implementation of testing and maintenance activities taking part of such an integrated RAM model.

Experimental evaluation of a portable energy absorbing system for highway service vehicles. Final report for phase II.

Connecticut Department of Transportation, Bureau of Planning and Research, Wethersfield

Experimental evaluation of a portable energy absorbing system for highway service vehicles. Final report for phase I.

Connecticut Department of Transportation, Bureau of Planning and Research, Wethersfield

Development of a low cost anti-lock brake system for small motorcycles. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Thesaurus for SOYA : computerized bibliographic database on soybean utilization, processing, marketing nutrition, production, and history, 1100 B.C. to the 1980s /

Mode of access: Internet.

Organizational, direct support, and general support maintenance repair parts and special tools list for combat vehicle, anti-tank, improved TOW vehicle, M901A1, NSN 2350-01-103-5641 (EIC: AEV).

"October 1992."

Organizational maintenance manual : engagement control station, guided missile, truck mounted, AN/MSQ-104.

Includes index.

Direct support and general support maintenance repair parts and special tools list (including depot maintenance repair parts and special tools) for TOW subsystem consisting of TOW launcher assembly, NSN 1440-01-085-5517, command guidance electronics, NSN 1430-01-085-5521.

Includes index.

Organizational maintenance repair parts and special tools list for guided missile main assemblage M5 1420-01-133-0537 (in container), control surface, guided missile M29 1420-01-013-8036 (in container), M30 1420-01-013-8035 (in container), shipping and storage container guided missile M599 8140-00-152-0068 ...

Includes index.

Direct support and general support maintenance repair parts and special tools list including depot maintenance repair parts and special tools for azimuth laying set, guided missile AN/TSQ-110(X0-1) 1430-00-399-5318, encoder, shaft angle, digital (in container) 1430-01-034-2268, gyro reference unit (in container) 1430-01-033-4044 ...

Includes index.

Organizational maintenance manual for combat vehicle, anti-tank, improved tow vehicle, M901, SN 2350-01-045-1123.

"June 1979."