Astrocytic glutamate transport regulates a Drosophila CNS synapse that lacks astrocyte ensheathment.

Anatomical, molecular, and physiological interactions between astrocytes and neuronal synapses regulate information processing in the brain. The fruit fly Drosophila melanogaster has become a valuable experimental system for genetic manipulation of the nervous system and has enormous potential for elucidating mechanisms that mediate neuron-glia interactions. Here, we show the first electrophysiological recordings from Drosophila astrocytes and characterize their spatial and physiological relationship with particular synapses. Astrocyte intrinsic properties were found to be strongly analogous to those of vertebrate astrocytes, including a passive current-voltage relationship, low membrane resistance, high capacitance, and dye-coupling to local astrocytes. Responses to optogenetic stimulation of glutamatergic premotor neurons were correlated directly with anatomy using serial electron microscopy reconstructions of homologous identified neurons and surrounding astrocytic processes. Robust bidirectional communication was present: neuronal activation triggered astrocytic glutamate transport via excitatory amino acid transporter 1 (Eaat1), and blocking Eaat1 extended glutamatergic interneuron-evoked inhibitory postsynaptic currents in motor neurons. The neuronal synapses were always located within 1 μm of an astrocytic process, but none were ensheathed by those processes. Thus, fly astrocytes can modulate fast synaptic transmission via neurotransmitter transport within these anatomical parameters. J. Comp. Neurol. 524:1979-1998, 2016. © 2016 Wiley Periodicals, Inc.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/cne.2401

The synergistic action of imidacloprid and flumethrin and their release kinetics from collars applied for ectoparasite control in dogs and cats

<p>Abstract</p> <p>Background</p> <p>The control of tick and flea burdens in dogs and cats has become essential to the control of important and emerging vector borne diseases, some of which are zoonoses. Flea worry and flea bite hypersensitivity are additionally a significant disease entity in dogs and cats. Owner compliance in maintaining the pressure of control measures has been shown to be poor. For these reasons efforts are continuously being made to develop ectoparasiticides and application methods that are safe, effective and easy to apply for pet owners. A new polymer matrix collar has recently been developed which is registered for 8 months use in cats and dogs. The basic properties of this collar have been investigated in several <it>in vitro </it>and <it>in vivo </it>studies.</p> <p>Methods</p> <p>The effects of imidacloprid, flumethrin and the combination were evaluated in vitro by means of whole cell voltage clamp measurement experiments conducted on isolated neuron cells from <it>Spodoptera frugiperda</it>. The in vitro efficacy of the two compounds and the combination against three species of ticks and their life stages and fleas were evaluated in a dry surface glass vial assay. The kinetics of the compounds over time in the collar were evaluated by the change in mass of the collar and measurement of the surface concentrations and concentrations of the actives in the collar matrix by HPLC. Hair clipped from collar treated dogs and cats, collected at various time points, was used to assess the acaricidal efficacy of the actives ex vivo.</p> <p>Results</p> <p>An <it>in vitro </it>isolated insect nerve model demonstrated the synergistic neurotoxic effects of the pyrethroid flumethrin and the neonicotinoid imidacloprid. An <it>in vitro </it>glass vial efficacy and mortality study against various life stages of the ticks <it>Ixodes ricinus, Rhipicephalus sanguineus </it>and <it>Dermacentor reticulatus </it>and against the flea (<it>Ctenocephalides felis</it>) demonstrated that the combination of these products was highly effective against these parasites. The release kinetics of these actives from a neck collar (compounded with 10% imidacloprid and 4.5% flumethrin) was extensively studied in dogs and cats under laboratory and field conditions. Acaricidal concentrations of the actives were found to be consistently released from the collar matrix for 8 months. None of the collar studies in dogs or cats were associated with any significant collar related adverse event.</p> <p>Conclusion</p> <p>Here we demonstrated the synergism between the pyrethroid flumethrin and the neonicotinoid imidacloprid, both provided in therapeutically relevant doses by a slow release collar matrix system over 8 months. This collar is therefore a convenient and safe tool for a long-term protection against ectoparasites.</p

Neuroglial ATP release through innexin channels controls microglial cell movement to a nerve injury

Microglia, the immune cells of the central nervous system, are attracted to sites of injury. The injury releases adenosine triphosphate (ATP) into the extracellular space, activating the microglia, but the full mechanism of release is not known. In glial cells, a family of physiologically regulated unpaired gap junction channels called innexons (invertebrates) or pannexons (vertebrates) located in the cell membrane is permeable to ATP. Innexons, but not pannexons, also pair to make gap junctions. Glial calcium waves, triggered by injury or mechanical stimulation, open pannexon/innexon channels and cause the release of ATP. It has been hypothesized that a glial calcium wave that triggers the release of ATP causes rapid microglial migration to distant lesions. In the present study in the leech, in which a single giant glial cell ensheathes each connective, hydrolysis of ATP with 10 U/ml apyrase or block of innexons with 10 µM carbenoxolone (CBX), which decreased injury-induced ATP release, reduced both movement of microglia and their accumulation at lesions. Directed movement and accumulation were restored in CBX by adding ATP, consistent with separate actions of ATP and nitric oxide, which is required for directed movement but does not activate glia. Injection of glia with innexin2 (Hminx2) RNAi inhibited release of carboxyfluorescein dye and microglial migration, whereas injection of innexin1 (Hminx1) RNAi did not when measured 2 days after injection, indicating that glial cells’ ATP release through innexons was required for microglial migration after nerve injury. Focal stimulation either mechanically or with ATP generated a calcium wave in the glial cell; injury caused a large, persistent intracellular calcium response. Neither the calcium wave nor the persistent response required ATP or its release. Thus, in the leech, innexin membrane channels releasing ATP from glia are required for migration and accumulation of microglia after nerve injury

The anatomy of a malaria disaster: drug policy choice and mortality in African children

Drug-resistant malaria is a substantial problem throughout Africa and most countries must regularly adapt their antimalarial drug policies to ensure a continued coverage of effective antimalarial treatment. The timing of drug policy change can be guided by several sources of data: molecular markers of resistance, in-vitro parasite sensitivity, parasitological and clinical failure rates, and community morbidity and mortality rates. Through mathematical simulations of the spread of parasite mutations through a population exposed to high-endemic malaria, we explore the causal and chronological relations between these indicators and show which of them are obscured or confounded by other factors. Taking into account the logistical and practical advantages and disadvantages of each type of data collection, we critically appraise the value of each indicator. A major problem is shown to be that drug efficacy as perceived by people at risk will remain high even after drugs have become almost completely ineffective, resulting in a lack of community pressure for drug policy change. We show that parasitological failure is the most sensitive and timely indicator, which allows around 2-3 years for drug policy change to be implemented, so as to prevent the most rapid rise in malaria-related mortality

Autonomous Airborne Wind Energy Systems: Accomplishments and Challenges

Airborne wind energy (AWE) is a fascinating technology to convert wind power into electricity with an autonomous tethered aircraft. Deemed a potentially game-changing solution, AWE is attracting the attention of policy makers and stakeholders with the promise of producing large amounts of cost-competitive electricity with wide applicability worldwide. Since the pioneering experimental endeavors in the years 2000-2010, there has been a clear technology convergence trend and steady progress in the field. Today, AWE systems can operate automatically with minimal supervision in all operational phases. A first product is also being commercialized. However, all-around fully autonomous operation still presents important fundamental challenges that are conceptually similar to those of other systems that promise to change our lives, such as fully autonomous passenger cars or service drones. At the same time, autonomous operation is necessary to enable large-scale AWE, thus combining challenging fundamental problems with high potential impact on society and the economy. This article describes the state of the art of this technology from a system perspective and with a critical view on some fundamental aspects, presents the latest automatic control results by prominent industrial players, and finally points out the most important challenges on the road to fully autonomous AWE systems

Aging of steel containments and liners in nuclear power plants

Aging of the containment pressure boundary in light water reactor plants is being addressed to understand the significant factors relating occurrence of corrosion efficacy of inspection and structural capacity reduction of steel containments and liners of concrete containments. and to make recommendations on use of risk models in regulatory decisions. Current regulatory in-service inspection requirements are reviewed and a summary of containment related degradation experience is presented. Current and emerging nondestructive examination techniques and a degradation assessment methodology for characterizing and quantifying the amount of damage present are described. Quantitative tools for condition assessment of aging structures using time dependent structural reliability analysis methods are summarized. Such methods provide a framework for addressing the uncertainties attendant to aging in the decision process. Results of this research provide a means for establishing current and estimating future structural capacity margins of containments, and to address the significance of incidences of reported containment degradation

Structural response testing of thermal barrier load bearing ceramic pads. [HTGR]

A load-bearing insulating structure for use in a high-temperature gas-cooled reactor (HTGR) was investigated. The structure was composed of dense ceramic materials in the form of circular pads arranged in a stack. Specifically, the test program was structured to investigate the isolation effectiveness of interface materials placed between the ceramic pads to reduce the effectiveness of mechanically induced loads. The tests were conducted at room temperature using tapered loading platens on single ceramic pads. Seventeen alumina specimens, representing two types of material and two thicknesses, were tested. Three interface material thicknesses were introduced using silica cloth and graphite foil. Pre- and post-test nondestructive examinations were conducted in an effort to identify potential damage-inducing anomalies in the ceramic pads. A total of 62 tests was conducted with all specimens eventually loaded to failure