Annotation of the Nuclear Receptors in an Estuarine Fish species, \u3ci\u3eFundulus heteroclitus\u3c/i\u3e

The nuclear receptors (NRs) are ligand-dependent transcription factors that respond to various internal as well as external cues such as nutrients, pheromones, and steroid hormones that play crucial roles in regulation and maintenance of homeostasis and orchestrating the physiological and stress responses of an organism. We annotated the Fundulus heteroclitus (mummichog; Atlantic killifish) nuclear receptors. Mummichog are a non-migratory, estuarine fish with a limited home range often used in environmental research as a field model for studying ecological and evolutionary responses to variable environmental conditions such as salinity, oxygen, temperature, pH, and toxic compounds because of their hardiness. F. heteroclitus have at least 74 NRs spanning all seven gene subfamilies. F. heteroclitus is unique in that no RXRα member was found within the genome. Interestingly, some of the NRs are highly conserved between species, while others show a higher degree of divergence such as PXR, SF1, and ARα. Fundulus like other fish species show expansion of the RAR (NR1B), Rev-erb (NR1D), ROR (NR1F), COUPTF (NR2F), ERR (NR3B), RXR (NR2B), and to a lesser extent the NGF (NR4A), and NR3C steroid receptors (GR/AR). Of particular interest is the co-expansion of opposing NRs, Reverb-ROR, and RAR/RXR-COUPTF

Methods of inhibiting multiple cytochrome P450 genes with siRNA

The present invention relates to siRNAs that are targeted to RNAs encoding two or more enzymes of a subfamily of cytochrome P450 (CYP) enzymes, along with vectors, cells, and kits comprising the siRNAs. The invention further relates to methods of decreasing expression of two or more CYP subfamily genes in a non-human animal, animals in which expression of two or more CYP subfamily genes has been decreased, and methods of using such animals to study the function of cytochrome P450 enzymes

A Synopsis of Interfacial Phenomena in Lithium-Based Polymer Electrolyte Electrochemical Cells

The interfacial regions between electrode materials, electrolytes and other cell components play key roles in the overall performance of lithium-based batteries. For cell chemistries employing lithium metal, lithium alloy or carbonaceous materials (i.e., lithium-ion cells) as anode materials, a "solid electrolyte interphase" (SEI) layer forms at the anode/electrolyte interface, and the properties of this "passivating" layer significantly affect the practical cell/battery quality and performance. A thin, ionically-conducting SEI on the electrode surface can beneficially reduce or eliminate undesirable side reactions between the electrode and the electrolyte, which can result in a degradation in cell performance. The properties and phenomena attributable to the interfacial regions existing at both anode and cathode surfaces can be characterized to a large extent by electrochemical impedance spectroscopy (EIS) and related techniques. The intention of the review herewith is to support the future development of lithium-based polymer electrolytes by providing a synopsis of interfacial phenomena that is associated with cell chemistries employing either lithium metal or carbonaceous "composite" electrode structures which are interfaced with polymer electrolytes (i.e., "solvent-free" as well as "plasticized" polymer-binary salt complexes and single ion-conducting polyelectrolytes). Potential approaches to overcoming poor cell performance attributable to interfacial effects are discussed

Experimental Lithium-Ion Battery Developed for Demonstration at the 2007 NASA Desert Research and Technology Studies (D-RATS) Program

The NASA Glenn Research Center (GRC) Electrochemistry Branch designed and built five lithium-ion battery packs for demonstration in spacesuit simulators as a part of the 2007 Desert Research and Technology Studies (D-RATS) activity at Cinder Lake, Arizona. The experimental batteries incorporated advanced, NASA-developed electrolytes and included internal protection against over-current, overdischarge and over-temperature. The 500-g experimental batteries were designed to deliver a constant power of 22 W for 2.5 hr with a minimum voltage of 13 V. When discharged at the maximum expected power output of 38.5 W, the batteries operated for 103 min of discharge time, achieving a specific energy of 130 Wh/kg. This report summarizes design details and safety considerations. Results for field trials and laboratory testing are summarized

Assessment of Lithium-based Battery Electrolytes Developed under the NASA PERS Program

Recently, NASA formally completed the Polymer Energy Rechargeable System (PERS) Program, which was established in 2000 in collaboration with the Air Force Research Laboratory (AFRL) to support the development of polymer-based, lithium-based cell chemistries and battery technologies to address the next generation of aerospace applications and mission needs. The goal of this program was to ultimately develop an advanced, space-qualified battery technology, which embodied a solid polymer electrolyte (SPE) and complementary components, with improved performance characteristics that would address future aerospace battery requirements. Programmatically, the PERS initiative exploited both interagency collaborations to address common technology and engineering issues and the active participation of academia and private industry. The initial program phases focused on R&D activities to address the critical technical issues and challenges at the cell level. A variety of cell and polymeric electrolyte concepts were pursued as part of the development efforts undertaken at numerous governmental, industrial and academic laboratories. Numerous candidate electrolyte materials were developed, synthesized and optimized for evaluation. Utilizing the component screening facility and the "standardized" test procedures developed at the NASA Glenn Research Center, electrochemical screening and performance evaluations of promising candidate materials were completed. This overview summarizes test results for a variety of candidate electrolyte materials that were developed under the PERS Program. Electrolyte properties are contrasted and compared to the original project goals, and the strengths and weaknesses of the electrolyte chemistries are discussed. Limited cycling data for full-cells using lithium metal and vanadium oxide electrodes are also presented. Based on measured electrolyte properties, the projected performance characteristics and temperature limitations of batteries utilizing the advanced electrolytes and components have been estimated. Limitations for the achievement of practical performance levels are also discussed, as well as needs for future research and development

Gender differences in diet-induced steatotic disease in Cyp2b-null mice

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease; however, progression to nonalcoholic steatohepatitis (NASH) is associated with most adverse outcomes. CYP2B metabolizes multiple xeno- and endobiotics, and male Cyp2b-null mice are diet-induced obese (DIO) with increased NAFLD. However, the DIO study was not performed long enough to assess progression to NASH. Therefore, to assess the role of Cyp2b in fatty liver disease progression from NAFLD to NASH, we treated wildtype (WT) and Cyp2b-null mice with a normal diet (ND) or choline-deficient, L-amino acid-defined high fat diet (CDAHFD) for 8 weeks and determined metabolic and molecular changes. CDAHFD-fed WT female mice gained more weight and had greater liver and white adipose tissue mass than their Cyp2b-null counterparts; males experienced diet-induced weight loss regardless of genotype. Serum biomarkers of liver injury increased in both CDAHFD-fed female and male mice; however CDAHFD-fed Cyp2b-null females exhibited significantly lower serum ALT, AST, and ASP concentrations compared to WT mice, indicating Cyp2b-null females were protected from liver injury. In both genders, hierarchical clustering of RNA-seq data demonstrates several gene ontologies responded differently in CDAHFD-fed Cyp2b-null mice compared to WT mice (lipid metabolism \u3e fibrosis \u3e inflammation). Oil Red O staining and direct triglycerides measurements confirmed that CDAHFD-fed Cyp2b-null females were protected from NAFLD. CDAHFD-fed Cyp2b-null mice showed equivocal changes in fibrosis with transcriptomic and serum markers suggesting less inflammation due to glucocorticoid-mediated repression of immune responses. In contrast to females, CDAHFD-fed Cyp2b-null males had higher triglyceride levels. Results indicate that female Cyp2b-null mice are protected from NAFLD while male Cyp2b-null mice are more susceptible to NAFLD, with few significant changes in NASH development. This study confirms that increased NAFLD development does not necessarily lead to progressive NASH. Furthermore, it indicates a role for Cyp2b in fatty liver disease that differs based on gender

Exchange of polar lipids from adults to neonates in \u3ci\u3eDaphnia magna\u3c/i\u3e: Perturbations in sphingomyelin allocation by dietary lipids and environmental toxicants

Because xenosensing nuclear receptors are also lipid sensors that regulate lipid allocation, we hypothesized that toxicant-induced modulation of HR96 activity would alter lipid profiles and the balance between adult survival and neonate production following exposure in Daphnia magna. Adult daphnids were exposed to unsaturated fatty acid- and toxicant- activators or inhibitors of HR96 and later starved to test whether chemical exposure altered allocation toward survival or reproduction. The HR96 activators, linoleic acid and atrazine, decreased reproduction as expected with concomitant changes in the expression of HR96 regulated genes such as magro. The HR96 inhibitors, docosahexaenoic acid (DHA) and triclosan, increased reproduction or neonate starvation survival, respectively. However, pre-exposure to triclosan increased in neonate survival at the expense of reproductive maturation. Lipidomic analysis revealed that sphingomyelins (SM) are predominantly found in neonates and therefore we propose are important in development. DHA and triclosan increased neonatal SM, consistent with HR96’s regulation of Niemann-Pick genes. While DHA altered expression of magro, Niemann-Pick 1b, mannosidase, and other HR96-regulated genes as expected, triclosan primarily perturbed sphingomyelinase and mannosidase expression indicating different but potentially overlapping mechanisms for perturbing SM. Overall, SM appears to be a key lipid in Daphnia maturation and further support was provided by carmofur, which inhibits sphingomyelin/ceramide metabolism and in turn severely represses Daphnia maturation and initial brood production. In conclusion, toxicants can perturb lipid allocation and in turn impair development and reproduction

Battery Separator Characterization and Evaluation Procedures for NASA's Advanced Lithium-Ion Batteries

To address the future performance and safety requirements for the electrical energy storage technologies that will enhance and enable future NASA manned aerospace missions, advanced rechargeable, lithium-ion battery technology development is being pursued within the scope of the NASA Exploration Technology Development Program s (ETDP's) Energy Storage Project. A critical cell-level component of a lithium-ion battery which significantly impacts both overall electrochemical performance and safety is the porous separator that is sandwiched between the two active cell electrodes. To support the selection of the optimal cell separator material(s) for the advanced battery technology and chemistries under development, laboratory characterization and screening procedures were established to assess and compare separator material-level attributes and associated separator performance characteristics