Regulation of Dopamine Release by CASK-β Modulates Locomotor Initiation in Drosophila melanogaster

CASK is an evolutionarily conserved scaffolding protein that has roles in many cell types. In Drosophila, loss of the entire CASK gene or just the CASK- transcript causes a complex set of adult locomotor defects. In this study, we show that the motor initiation component of this phenotype is due to loss of CASK- in dopaminergic neurons and can be specifically rescued by expression of CASK- within this subset of neurons. Functional imaging demonstrates that mutation of CASK- disrupts coupling of neuronal activity to vesicle fusion. Consistent with this, locomotor initiation can be rescued by artificially driving activity in dopaminergic neurons. The molecular mechanism underlying this role of CASK- in dopaminergic neurons involves interaction with Hsc70-4, a molecular chaperone previously shown to regulate calcium-dependent vesicle fusion. These data suggest that there is a novel CASK- -dependent regulatory complex in dopaminergic neurons that serves to link activity and neurotransmitter release.Fil: Slawson, Justin B. Brandeis University; Estados UnidosFil: Kuklin, Elena A. Brandeis University; Estados UnidosFil: Mukherjee, Konark. Brandeis University; Estados UnidosFil: Pírez, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. Brandeis University; Estados UnidosFil: Donelson, Nathan C. Brandeis University; Estados UnidosFil: Griffith, Leslie C. Brandeis University; Estados Unido

Central Regulation of Locomotor Behavior of Drosophila melanogaster Depends on a CASK Isoform Containing CaMK-Like and L27 Domains

Genetic causes for disturbances of locomotor behavior can be due to muscle, peripheral neuron, or central nervous system pathologies. The Drosophila melanogaster homolog of human CASK (also known as caki or camguk) is a molecular scaffold that has been postulated to have roles in both locomotion and plasticity. These conclusions are based on studies using overlapping deficiencies that largely eliminate the entire CASK locus, but contain additional chromosomal aberrations as well. More importantly, analysis of the sequenced Drosophila genome suggests the existence of multiple protein variants from the CASK locus, further complicating the interpretation of experiments using deficiency strains. In this study, we generated small deletions within the CASK gene that eliminate gene products containing the CaMK-like and L27 domains (CASK-β), but do not affect transcripts encoding the smaller forms (CASK-α), which are structurally homologous to vertebrate MPP1. These mutants have normal olfactory habituation, but exhibit a striking array of locomotor problems that includes both initiation and motor maintenance defects. Previous studies had suggested that presynaptic release defects at the neuromuscular junction in the multigene deficiency strain were the likely basis of its locomotor phenotype. The locomotor phenotype of the CASK-β mutant, however, cannot be rescued by expression of a CASK-β transgene in motor neurons. Expression in a subset of central neurons that does not include the ellipsoid body, a well-known pre-motor neuropil, provides complete rescue. Full-length CASK-β, while widely expressed in the nervous system, appears to have a unique role within central circuits that control motor output

Ga-In Alloy Segregation within a Porous Glass as Studied by SANS

Nanolattices can play the role of templates for metals and metallic alloys to produce functional nanocomposites with particular properties affected by nanoconfinement. To imitate the impact of nanoconfinement on the structure of solid eutectic alloys, we filled porous silica glasses with the Ga-In alloy, which is widely used in applications. Small-angle neutron scattering was observed for two nanocomposites, which comprised alloys of close compositions. The results obtained were treated using different approaches: the common Guinier and extended Guinier models, the recently suggested computer simulation method based on the initial formulae for neutron scattering, and ordinary estimates of the scattering hump positions. All of the approaches predicted a similar structure of the confined eutectic alloy. The formation of ellipsoid-like indium-rich segregates was demonstrated

SANS Studies of the Gallium–Indium Alloy Structure within Regular Nanopores

Potential applications of nanolattices often require filling their empty space with eutectic metallic alloys. Due to confinement to nanolattices, the structure of phase segregates in eutectic alloys can differ from that in bulk. These problems are poorly understood now. We have used small angle neutron scattering (SANS) to study the segregation in the Ga-In alloy confined to an opal template with the regular pore network, created by a strict regularity of opal constituents in close similarity with nanolattices. We showed that SANS is a powerful tool to reveal the configuration of segregated phases within nanotemplates. The In-rich segregates were found to have specific structural features as small sizes and ordered arrangement

Electrochemical Properties and Structure of Membranes from Perfluorinated Copolymers Modified with Nanodiamonds

In this study, we aimed to design and research proton-conducting membranes based on Aquivion®-type material that had been modified with detonation nanodiamonds (particle size 4–5 nm, 0.25–5.0 wt. %). These nanodiamonds carried different functional groups (H, OH, COOH, F) that provided the hydrophilicity of the diamond surface with positive or negative potential, or that strengthened the hydrophobicity of the diamonds. These variations in diamond properties allowed us to find ways to improve the composite structure so as to achieve better ion conductivity. For this purpose, we prepared three series of membrane films by first casting solutions of perfluorinated Aquivion®-type copolymers with short side chains mixed with diamonds dispersed on solid substrates. Then, we removed the solvent and the membranes were structurally stabilized during thermal treatment and transformed into their final form with –SO3H ionic groups. We found that the diamonds with a hydrogen-saturated surface, with a positive charge in aqueous media, contributed to the increase in proton conductivity of membranes to a greater rate. Meanwhile, a more developed conducting diamond-copolymer interface was formed due to electrostatic attraction to the sulfonic acid groups of the copolymer than in the case of diamonds grafted with negatively charged carboxyls, similar to sulfonic groups of the copolymer. The modification of membranes with fluorinated diamonds led to a 5-fold decrease in the conductivity of the composite, even when only a fraction of diamonds of 1 wt. % were used, which was explained by the disruption in the connectivity of ion channels during the interaction of such diamonds mainly with fluorocarbon chains of the copolymer. We discussed the specifics of the mechanism of conductivity in composites with various diamonds in connection with structural data obtained in neutron scattering experiments on dry membranes, as well as ideas about the formation of cylindrical micelles with central ion channels and shells composed of hydrophobic copolymer chains. Finally, the characteristics of the network of ion channels in the composites were found depending on the type and amount of introduced diamonds, and correlations between the structure and conductivity of the membranes were established

Quality Of Life As The Main Factor In Increasing The Economic Safety Of The Region

Статья посвящена оценке качества жизни в рамках экономической безопасности регионов России. В статье представлен методический подход к интегральной оценке качества жизни населения регионов. Комплексная методика диагностики качества жизни состоит из восьми индикативных модулей, отражающих различные характеристики категории «качество жизни»: качество населения, занятость населения, уровень жизни населения, условия жизни населения, приемлемость окружающей природной среды для проживания населения, безопасность личности, детерминанты внутренней и внешней миграции населения, социальная защищенность населения. Диагностика качества жизни проводится в рамках экономической безопасности с использованием индикативного метода анализа. Рассмотрены состояние и динамика изменения качества жизни населения и его отдельных составляющих для субъектов РФ, входящих в состав Уральского федерального округа, в период 2000-2011 . Article is devoted to an assessment of quality of life within economic security of regions of Russia. In article the methodical approach to an integrated assessment of quality of life of the population of regions is presented. The complex technique of diagnosis of quality of life consists of eight indicative modules reflecting various characteristics of category «quality of life»: quality of a population, population employment, a population standard of living, population living conditions, an acceptability of environment for population accommodation, security of the personality, determinants of internal and external migration of a population, social security of a population. Diagnosis of quality of life is carried out within economic security with use of an indicative method of the analysis. The condition and dynamics of change of quality of life of a population and its separate components for the subjects of the Russian Federation (Ural federal district) in 2000-2011 are considered

Improving PFSA Membranes Using Sulfonated Nanodiamonds

Aquivion®-type perfluorosulfonic acid membranes with a polytetrafluoroethylene backbone and short side chains with sulfonic acid groups at the ends have great prospects for operating in hydrogen fuel cells. To improve the conducting properties of membranes, various types of nanofillers can be used. We prepared compositional Aquivion®-type membranes with embedded detonation nanodiamond particles. Nanodiamonds were chemically modified with sulfonic acid groups to increase the entire amount of ionogenic groups involved in the proton conductivity mechanism in compositional membranes. We demonstrated the rise of proton conductivity at 0.5–2 wt.% of sulfonated nanodiamonds in membranes, which was accompanied by good mechanical properties. The basic structural elements, conducting channels in membranes, were not destroyed in the presence of nanodiamonds, as follows from small-angle neutron scattering data. The prepared compositional membranes can be used in hydrogen fuel cells to achieve improved performance

PDF cells are a GABA-responsive wake-promoting component of the Drosophila sleep circuit

SummaryDaily sleep cycles in humans are driven by a complex circuit within which GABAergic sleep-promoting neurons oppose arousal. Drosophila sleep has recently been shown to be controlled by GABA, which acts on unknown cells expressing the Rdl GABAA receptor. We identify here the relevant Rdl-containing cells as PDF-expressing small and large ventral lateral neurons (LNvs) of the circadian clock. LNv activity regulates total sleep as well as the rate of sleep onset; both large and small LNvs are part of the sleep circuit. Flies mutant for pdf or its receptor are hypersomnolent, and PDF acts on the LNvs themselves to control sleep. These features of the Drosophila sleep circuit, GABAergic control of onset and maintenance as well as peptidergic control of arousal, support the idea that features of sleep-circuit architecture as well as the mechanisms governing the behavioral transitions between sleep and wake are conserved between mammals and insects