CoA protects against the deleterious effects of caloric overload in Drosophila

We developed a Drosophila model of T2D in which high sugar (HS) feeding leads to insulin resistance. In this model, adipose TG storage is protective against fatty acid toxicity and diabetes. Initial biochemical and gene expression studies suggested that deficiency in CoA might underlie reduced TG synthesis in animals during chronic HS feeding. Focusing on the Drosophila fat body (FB), which is specialized for TG storage and lipolysis, we undertook a series of experiments to test the hypothesis that CoA could protect against the deleterious effects of caloric overload. Quantitative metabolomics revealed a reduction in substrate availability for CoA synthesis in the face of an HS diet. Further reducing CoA synthetic capacity by expressing FB-specific RNAi targeting pantothenate kinase (PK orfumble) or phosphopantothenoylcysteine synthase (PPCS) exacerbated HS-diet-induced accumulation of FFAs. Dietary supplementation with pantothenic acid (vitamin B5, a precursor of CoA) was able to ameliorate HS-diet-induced FFA accumulation and hyperglycemia while increasing TG synthesis. Taken together, our data support a model where free CoA is required to support fatty acid esterification and to protect against the toxicity of HS diets

Natural Areas Analysis and Evaluation: Oak Ridge Reservation

EXECUTIVE SUMMARY The Oak Ridge Reservation, encompassing 33,639 acres in the Valley and Ridge Physiographic Province of East Tennessee, has long been known for its unfragmented forests and high biodiversity. Many areas on the Reservation have been recognized as important natural areas, but no comprehensive treatment has been performed to evaluate the relative significance and importance of these areas compared to each other. The present study was conducted to develop a set of guidelines for evaluating the natural value of specific areas, to evaluate all the terrestrial areas that are currently delineated, and to rank all areas according to their relative biodiversity importance. All available data, reports and site-specific information relevant to Reservation lands, including Tennessee Division of Natural Areas database information, were evaluated and field work was conducted. Methodologies and criteria for assessment and evaluation of areas were developed; categories of criteria were devised; and a ranking system for evaluation of natural areas was produced. There were 70 areas evaluated during the study. The system is flexible, dynamic and easily revised to reflect updated and new information and interpretations. Eight categories of evaluation factors were established and used to characterize each site. These were the following: size of area, number or status taxa present, number of Endangered and Threatened taxa present, rarity of the Endangered and Threatened taxa on the Reservation, community diversity, site integrity and quality, disturbance and threat levels, and other significant features and factors. Each category generally consisted of a 5-point ranking scale from 0-4, allowing for a possible composite score of 32, with higher ranked, more important, sites attaining higher scores. Highly ranked sites are representative of regional natural diversity; contain outstanding natural features, communities or geology and/or very rare taxa or other elements; are relatively large in size with mature or old-growth community composition; lack current disturbance factors or potential threats and disturbances; are in excellent condition with good buffers; are places where ecological and evolutionary processes can occur relatively unaffected by humans; and can be reasonably defended and maintained as natural areas in an undeveloped condition. Highly ranked sites are the most significant and should receive the greatest protections. Composite scores of the ranked areas ranged from 1-25.5, with a mean score of 12. The ranked areas were divided into three Priority Groups. Group I, the most highly ranked group, included 20 sites and covered 5189 acres or 15.4% of Reservation lands; Group II included 31 sites and covered 4108 acres; Group III included 19 sites covering 400 acres of Reservation lands. All sites together comprise 9697 acres or 28.8% of Reservation lands. Six sites emerged as clearly the most significant natural areas on the Reservation. The study developed a number of recommendations that should be implemented in order to enhance and refine the natural areas data for the Reservation. There is a clear need for better and standardized ecological community classification and identification. Several areas are proposed for merger into larger units, and some new areas are proposed for inclusion and recognition in a natural areas system. Various gaps and discrepancies in the existing data are described and should be corrected. Other recommendations are made, including the development of a corollary system that can accommodate aquatic natural areas. The study relied primarily on the synthesis of information from many sources and from limited reconnaissance and direct observation during field work to produce a methodology for assessing natural area importance and assigning priorities for protection. Many instances of incomplete, missing or conflicting information made it difficult to complete thorough analysis. Further review and discussion among natural resources personnel will likely reveal possibilities for refinement and some additional factors that should be included in the evaluation. Despite the limitations, this study, as conducted, illustrates the importance of the Oak Ridge Reservation for protecting the nation s increasingly threatened and declining biodiversity

E2F8 is a nonreceptor activator of heterotrimeric G proteins

BACKGROUND: Heterotrimeric G proteins are important for numerous signaling events in eukaryotes, serving primarily to transduce signals that are initiated by G protein-coupled receptors. It has recently become clear that nonreceptor activators can regulate the level of heterotrimeric G protein signaling and, in some cases, drive cycles of receptor-independent G protein activation. In this study, we used a yeast expression cloning strategy to identify novel nonreceptor activators of heterotrimeric G proteins in a human adipocyte cDNA library. RESULTS: The human transcription factor E2F8 was found to activate heterotrimeric G proteins, suggesting a specific biological role for this recently described member of the E2F family. Epistasis studies showed that E2F8 acted at the level of G proteins and was specific for Gα(i )over Gpa1. E2F8 augmented receptor-driven signaling, but also activated G proteins in the absence of a receptor. The GTPase-activating protein RGS4 antagonized the effect of E2F8, showing that E2F8's effect on Gα involved nucleotide turnover. The entire E2F8 protein was required for full activity, but the majority of the signaling activity appeared to reside in the first 200 residues. CONCLUSION: In yeast, E2F8 is a guanine nucleotide exchange factor (GEF) for the α subunit of heterotrimeric G proteins. The molecular mechanism and biological significance of this effect remain to be determined

Determination of oxygen tension in the subcutaneous tissue of cosmonauts during the Salyut-6 mission

A polarographic technique was used to measure the oxygen tension in subcutaneous tissue of the forearm of a cosmonaut prior to, after, and on the fourth day of a space mission performed by Salut-6. A drop in the oxygen exchange rate in the peripheral tissues during weightlessness was observed. The mechanisms of this change are studied, taking into consideration the blood distribution in the organism and microcirculation disorders reflected by a decreased blood flow rate in arterial-venous junctions