The b iosynthesis of histidine: imidazoleglycerol phosphate, imidazoleacteol phosphate, and histidinol phosphate

This is a report on the isolation and characterization of D-erythro-imidazoleglycerol phosphate (IGP), imidazoleacetol phosphate (IAP), and L-histidinol phosphate, which are accumulated in the mycelia of several of these mutants

Prevention of Mutation, Cancer, and Other Age-Associated Diseases by Optimizing Micronutrient Intake

I review three of our research efforts which suggest that optimizing micronutrient intake will in turn optimize metabolism, resulting in decreased DNA damage and less cancer as well as other degenerative diseases of aging. (1) Research on delay of the mitochondrial decay of aging, including release of mutagenic oxidants, by supplementing rats with lipoic acid and acetyl carnitine. (2) The triage theory, which posits that modest micronutrient deficiencies (common in much of the population) accelerate molecular aging, including DNA damage, mitochondrial decay, and supportive evidence for the theory, including an in-depth analysis of vitamin K that suggests the importance of achieving optimal micronutrient intake for longevity. (3) The finding that decreased enzyme binding constants (increased Km) for coenzymes (or substrates) can result from protein deformation and loss of function due to an age-related decline in membrane fluidity, or to polymorphisms or mutation. The loss of enzyme function can be compensated by a high dietary intake of any of the B vitamins, which increases the level of the vitamin-derived coenzyme. This dietary remediation illustrates the importance of understanding the effects of age and polymorphisms on optimal micronutrient requirements. Optimizing micronutrient intake could have a major effect on the prevention of cancer and other degenerative diseases of aging

Controlling Costs: The 6-3-5 Method

Naval Postgraduate School Acquisition Research Progra

Mitochondrial decay in aging

AbstractSeveral mitochondrial functions decline with age. The contributing factors include, the intrinsic rate of proton leakage across the inner mitochondrial membrane (a correlate of oxidant formation), decreased membrane fluidity, and decreased levels and function of cardiolipin, which supports the function of many of the proteins of the inner mitochondrial membrane. Oxidants generated by mitochondria appear to be the major source of the oxidative lesions that accumulate with age. Evidence supports the suggestion that age-associated accumulation of mitochondrial deficits due to oxidative damage is likely to be a major contributor to cellular, tissue, and organismal aging

Lifestyle and late life cognitive health: Sufficient evidence to act now?

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Enhancement of Mutual Discovery, Search, and Access of Data for Users of NASA and GEOSS-Cataloged Data Systems

An ongoing NASA-funded Data Rods (time series) project has demonstrated the removal of a longstanding barrier to accessing NASA data (i.e., accessing archived time-step array data as point-time series) for selected variables of the North American and Global Land Data Assimilation Systems (NLDAS and GLDAS, respectively) and other NASA data sets. Data rods are pre-generated or generated on-the-fly (OTF), leveraging the NASA Simple Subset Wizard (SSW), a gateway to NASA data centers. Data rods Web services are accessible through the CUAHSI Hydrologic Information System (HIS) and the Goddard Earth Sciences Data and Information Services Center (GES DISC) but are not easily discoverable by users of other non-NASA data systems. An ongoing GEOSS Water Services project aims to develop a distributed, global registry of water data, map, and modeling services cataloged using the standards and procedures of the Open Geospatial Consortium and the World Meteorological Organization. Preliminary work has shown GEOSS can be leveraged to help provide access to data rods. A new NASA-funded project is extending this early work

(R)-␣-Lipoic Acid Protects Retinal Pigment Epithelial Cells from Oxidative Damage

PURPOSE. To determine whether (R)-␣-lipoic acid (LA) protects cultured human fetal retinal pigment epithelial (hfRPE) cells against oxidative injury and identify the pathways that may mediate protection. METHODS. Cultured hfRPE cells were pretreated with various concentrations of LA for 14 to 16 hours followed by treatment with a chemical oxidant, tert-butylhydroperoxide (t-BuOOH; 0.8 mM, 3 hours). Reactive oxygen species (ROS) production and cell viability were measured using H 2 DCF and MTT assays, respectively. RPE cells were evaluated with fluorescent dyes (SYTOX Orange and SYTO Green; Molecular Probes, Eugene, OR), which differentiate between live and dead cells. Apoptosis was visualized by using the TUNEL assay. Changes in mitochondrial membrane potential were detected by JC-1 dye. Intracellular levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were measured by HPLC. Regulation of ␥-glutamylcysteine ligase (GCL), the rate-controlling enzyme of GSH production, was assayed by RT-PCR. RESULTS. Pretreatment of hfRPE cells with LA, 0.2 mM and 0.5 mM, significantly reduced the levels of t-BuOOH-induced intracellular ROS, by 23% and 49%, respectively. LA (0.5 mM) prevented oxidant-induced cell death and apoptosis and also increased the viability of oxidant-treated hfRPE cells from 38% to 90% of control. LA upregulated the mRNA expression of GCL, and was protective against t-BuOOH-induced decreases in both mitochondrial membrane potential and intracellular levels of GSH and GSH/GSSG. CONCLUSIONS. The present study suggests that the protective effect of LA involves multiple pathways and that LA could be effective against age-associated increase in oxidative stress and mitochondrial dysfunction in RPE cells. (Invest Ophthalmol Vis Sci. 2005;46:4302-4310) DOI:10.1167/iovs.04-1098 A ge-related macular degeneration (AMD) is the major cause of severe visual impairment for elderly individuals in developed countries. 1-3 Although the underlying pathogenic mechanisms and risk factors are not well understood, 1-9 epidemiologic studies suggest that environmental factors associated with oxidative stress-for example, cigarette smoking, sunlight exposure, and low dietary intake of antioxidants-are contributing factors in the development of AMD. 4 -7 Recent results have shown that antioxidants and zinc protect against the progression of the disease. 8 There is good evidence to suggest that the retinal pigment epithelium (RPE), choriocapillaris, and distal retina are all involved in this process, but the pathology associated with each can be difficult to distinguish, given their close anatomic, physiologic, and metabolic relationships. 7,15 A significant oxidative load is associated with the RPE phagocytosis of photoreceptor outer segments, 16 Cellular membranes with high polyunsaturated fatty acids are particularly susceptible to radical-induced chain reactions of lipid peroxidation. 17 Age-associated decreases in antioxidant defense mechanisms throughout the body can further increase the levels of RPE exposure to oxidants. For example, the levels of plasma glutathione (GSH), one of the major water-soluble antioxidants, decrease with age. 19 -21 Oxidantinduced mitochondrial dysfunction and death of RPE cells may contribute to the onset of AMD. 27-29 ␣-Lipoic acid is a potent intracellular antioxidant that can induce all three cellular protective mechanisms. 36 t-BuOOH is a relatively stable alkyl peroxide that readily penetrates cell membranes From th

Push-pull farming systems

Farming systems for pest control, based on the stimulo-deterrent diversionary strategy or push–pull system, have become an important target for sustainable intensification of food production. A prominent example is push–pull developed in sub-Saharan Africa using a combination of companion plants delivering semiochemicals, as plant secondary metabolites, for smallholder farming cereal production, initially against lepidopterous stem borers. Opportunities are being developed for other regions and farming ecosystems. New semiochemical tools and delivery systems, including GM, are being incorporated to exploit further opportunities for mainstream arable farming systems. By delivering the push and pull effects as secondary metabolites, for example, (E)-4,8-dimethyl-1,3,7-nonatriene repelling pests and attracting beneficial insects, problems of high volatility and instability are overcome and compounds are produced when and where required