Engineered G-protein Coupled Receptors are Powerful Tools to Investigate Biological Processes and Behaviors

Understanding how discreet tissues and neuronal circuits function in relation to the whole organism to regulate physiological processes and behaviors is a fundamental goal of modern biological science. Powerful and important new tools in this discovery process are modified G-protein coupled receptors (GPCRs) known as ‘Receptors Activated Solely by Synthetic Ligands (RASSLs),’ and ‘Designer Receptors Exclusively Activated by a Designer Drug (DREADDs).’ Collectively, these are GPCRs modified either through rational design or directed molecular evolution, that do not respond to native ligand, but functionally respond only to synthetic ligands. Importantly, the utility of these receptors is not limited to examination of the role of GPCR-coupled effector signal transduction pathways. Due to the near ubiquitous expression of GPCRs throughout an organism, this technology, combined with whole animal transgenics to selectively target expression, has the ability to regulate activity of discreet tissues and neuronal circuits through effector pathway modulation to study function and behavior throughout the organism. Advantages over other systems currently used to modify in vivo function include the ability to rapidly, selectively and reversibly manipulate defined signal transduction pathways both in short term and long term studies, and no need for specialized equipment due to convenient systemic treatment with activating ligand

State of the U.S. Ocean and Coastal Economies 2014

The nation\u27s coasts and oceans contribute much to the United States economy. For the past 14 years, the National Ocean Economics Program (NOEP), now a program of the Center for the Blue Economy at the Monterey Institute of International Studies, has compiled time-series data that track economic activities, demographics, ports and cargo volume and value, natural resource production and value, non-market values, and federal expenditures in the U.S. coastal zone both on land and in the water. A report on the ocean and coastal economies of the United States was released by NOEP in 2009 covering data through 2005. The present report is an update of that study covering the period 2007-2012. State summaries from this report are available on the NOEP website (www.oceaneconomics.org) under Publications

Factors Influencing Depression and Anxiety among Black Sexual Minority Men

The primary aim of this study was to examine the relationships between depression and anxiety, and ethnic and sexual identity development, and discrimination and harassment (DH) among Black sexual minority men. Additional aims were to determine whether an interaction effect existed between ethnic and sexual identity and whether coping skills level moderated these relationships. Using an observational cross-sectional design, 54 participants recruited through snowball sampling completed self-administered online surveys. Stepwise multiple regression analysis was used. Sixty-four percent of the variance in depression scores and 53% of the variance in anxiety scores were explained by DH and internalized homonegativity together. Thirty percent of the sample had scale scores indicating likelihood of depression and anxiety. Experience of DH and internalized homonegativity explained a large portion of the variability in depression and anxiety among Black sexual minority men. The study showed high prevalence of mental distress among this sample

Pesticide Ground Water Monitoring Project Phase VIII

During Phase VIII monitoring (March 24, 2000 to June 30, 2001 ), 86 samples were collected from 77 new wells and 9 samples were collected from wells with previous detectable herbicide

Valuing Transgenic Cotton Technologies Using a Risk/Return Framework

Stochastic Efficiency with Respect to a Function (SERF) is used to rank transgenic cotton technology groups and place an upper and lower bound on their value. Yield and production data from replicated plot experiments are used to build cumulative distribution functions of returns for nontransgenic, Roundup Ready, Bollgard, and stacked gene cotton cultivars. Analysis of Arkansas data indicated that the stacked gene and Roundup Ready technologies would be preferred by a large number of risk neutral and risk averse producers as long as the costs of the technology and seed are below the lower bounds calculated in this manuscript.cotton, financial risk, market value, SERF, transgenic, Agribusiness, Crop Production/Industries, Risk and Uncertainty, Q12, Q16,

Sentinel Case of Candida auris in the Western United States Following Prolonged Occult Colonization in a Returned Traveler from India.

Candida auris is an emerging multidrug-resistant yeast with high mortality. We report the sentinel C. auris case on the United States West Coast in a patient who relocated from India. We identified close phylogenetic relatedness to the South Asia clade and ERG11 Y132F and FKS1 S639Y mutations potentially explaining antifungal resistance

Serotonin 5-HT\u3csub\u3e2\u3c/sub\u3e receptor activation prevents allergic asthma in a mouse model

© 2015 the American Physiological Society. Asthma is an inflammatory disease of the lung characterized by airways hyper-responsiveness (AHR), inflammation, and mucus hyperproduction. Current main-stream therapies include bronchodilators that relieve bronchoconstriction and inhaled glucocorticoids to reduce inflammation. The small molecule hormone and neurotransmitter serotonin has long been known to be involved in inflammatory processes; however, its precise role in asthma is unknown. We have previously established that activation of serotonin 5-hydroxytryptamine (5-HT)2A receptors has potent anti-inflammatory activity in primary cultures of vascular tissues and in the whole animal in vasculature and gut tissues. The 5-HT2A receptor agonist, (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] is especially potent. In this work, we have examined the effect of (R)-DOI in an established mouse model of allergic asthma. In the ovalbumin mouse model of allergic inflammation, we demonstrate that inhalation of (R)-DOI prevents the development of many key features of allergic asthma, including AHR, mucus hyperproduction, airways inflammation, and pulmonary eosinophil recruitment. Our results highlight a likely role of the 5-HT2 receptors in allergic airways disease and suggest that 5-HT2 receptor agonists may represent an effective and novel small molecule-based therapy for asthma

Lipid, sterols and fatty acid composition of abyssal holothurians and ophiuroids from the North-East Pacific Ocean: Food web implications

The lipid, fatty acid (FA), and sterol composition of two ophiuroids and four holothurians from the abyssal eastern North Pacific were analysed to assess their feeding habits and to ascertain their composition for use in a larger study to examine food web dynamics and trophic ecology. Holothurians were rich in phytosterols and algal derived FA such as docosahexaenoic acid and eicosapentaenoic suggesting tight trophic coupling to phytodetritus. Large proportions of stanols were found, probably a result of enteric bacteria but they may come from sterol metabolism in the holothurians themselves. Oneirophanta mutabilis was distinct with much higher levels of stanols and bacterially derived FA suggesting specific selection of bacteria rich detrital particles or the activity of enteric and integumental bacteria. The ophiuroids sterol and FA compositions differed greatly from the holothurians and reflected consumption of animal material in addition to phytodetritus. Large proportions of energy storage lipids suggested a sporadic food supply. Several unusual fatty acids were found in these abyssal echinoderms. Tetracosahexaenoic acid, 24:6ω3, in ophiuroids and 23:1 in holothurians may be good biomarkers for food web studies. We report the first occurrence of αOH 24:1 in holothurians with none detected in ophiuroids. Its function is presently unknown

DREADDs in Drosophila: A Pharmacogenetic Approach for Controlling Behavior, Neuronal Signaling, and Physiology in the Fly

SummaryWe have translated a powerful genetic tool, designer receptors exclusively activated by designer drugs (DREADDs), from mammalian systems to Drosophila melanogaster to selectively, rapidly, reversibly, and dose-dependently control behaviors and physiological processes in the fly. DREADDs are muscarinic acetylcholine G protein-coupled receptors evolved for loss of affinity to acetylcholine and for the ability to be fully activated by an otherwise biologically inert chemical, clozapine-N-oxide. We demonstrate its ability to control a variety of behaviors and processes in larvae and adults, including heart rate, sensory processing, diurnal behavior, learning and memory, and courtship. The advantages of this particular technology include the dose-responsive control of behaviors, the lack of a need for specialized equipment, and the capacity to remotely control signaling in essentially all neuronal and nonneuronal fly tissues