Tonic inhibition of accumbal spiny neurons by extrasynaptic 4 GABAA receptors modulates the actions of psychostimulants

Within the nucleus accumbens (NAc), synaptic GABAA receptors (GABAARs) mediate phasic inhibition of medium spiny neurons (MSNs) and influence behavioral responses to cocaine. We demonstrate that both dopamine D1- and D2-receptor-expressing MSNs (D-MSNs) additionally harbor extrasynaptic GABAARs incorporating α4, β, and δ subunits that mediate tonic inhibition, thereby influencing neuronal excitability. Both the selective δ-GABAAR agonist THIP and DS2, a selective positive allosteric modulator, greatly increased the tonic current of all MSNs from wild-type (WT), but not from δ−/− or α4−/− mice. Coupling dopamine and tonic inhibition, the acute activation of D1 receptors (by a selective agonist or indirectly by amphetamine) greatly enhanced tonic inhibition in D1-MSNs but not D2-MSNs. In contrast, prolonged D2 receptor activation modestly reduced the tonic conductance of D2-MSNs. Behaviorally, WT and constitutive α4−/− mice did not differ in their expression of cocaine-conditioned place preference (CPP). Importantly, however, mice with the α4 deletion specific to D1-expressing neurons (α4D1−/−) showed increased CPP. Furthermore, THIP administered systemically or directly into the NAc of WT, but not α4−/− or α4D1−/− mice, blocked cocaine enhancement of CPP. In comparison, α4D2−/− mice exhibited normal CPP, but no cocaine enhancement. In conclusion, dopamine modulation of GABAergic tonic inhibition of D1- and D2-MSNs provides an intrinsic mechanism to differentially affect their excitability in response to psychostimulants and thereby influence their ability to potentiate conditioned reward. Therefore, α4βδ GABAARs may represent a viable target for the development of novel therapeutics to better understand and influence addictive behaviors

Parent Body Influences on Amino Acids in the Tagish Lake Meteorite

The Tagish Lake meteorite is a primitive C2 carbonaceous chondrite with a mineralogy, oxygen isotope, and bulk chemical. However, in contrast to many CI and CM carbonaceous chondrites, the Tagish Lake meteorite was reported to have only trace levels of indigenous amino acids, with evidence for terrestrial L-amino acid contamination from the Tagish Lake meltwater. The lack of indigenous amino acids in Tagish Lake suggested that they were either destroyed during parent body alteration processes and/or the Tagish Lake meteorite originated on a chemically distinct parent body from CI and CM meteorites where formation of amino acids was less favorable. We recently measured the amino acid composition of three different lithologies (11h, 5b, and 11i) of pristine Tagish Lake meteorite fragments that represent a range of progressive aqueous alteration in order 11h < 5b < 11i as inferred from the mineralogy, petrology, bulk isotopes, and insoluble organic matter structure. The distribution and enantiomeric abundances of the one- to six-carbon aliphatic amino acids found in hot-water extracts of the Tagish Lake fragments were determined by ultra performance liquid chromatography fluorescence detection and time of flight mass spectrometry coupled with OPA/NAC derivatization. Stable carbon isotope analyses of the most abundant amino acids in 11h were measured with gas chromatography coupled with quadrupole mass spectrometry and isotope ratio mass spectrometry

The relevance of ERTS-1 data to the state of Ohio

There are no author-identified significant results in this report

Compound-specific Carbon Isotope Compositions of Aldehydes and Ketones in the Murchison Meteorite

Compoundspecific carbon isotope analysis (13C) of meteoritic organic compounds can be used to elucidate the abiotic chemical reactions involved in their synthesis. The soluble organic content of the Murchison carbonaceous chondrite has been extensively investigated over the years, with a focus on the origins of amino acids and the potential role of Streckercyanohydrin synthesis in the early solar system. Previous 13C investigations have targeted amino acid and hydroxy acid Strecker products and reactant HCN; however, 13C values for meteoritic aldehydes and ketones (Strecker precursors) have not yet been reported. As such, the distribution of aldehydes and ketones in the cosmos and their role in prebiotic reactions have not been fully investigated. Here, we have applied an optimized O(2,3,4,5,6pentafluorobenzyl)hydroxylamine (PFBHA) derivatization procedure to the extraction, identification, and 13C analysis of carbonyl compounds in the Murchison meteorite. A suite of aldehydes and ketones, dominated by acetaldehyde, propionaldehyde, and acetone, were detected in the sample. 13C values, ranging from 10.0 to +66.4, were more 13Cdepleted than would be expected for aldehydes and ketones derived from the interstellar medium, based on interstellar 12C/13C ratios. These relatively 13Cdepleted values suggest that chemical processes taking place in asteroid parent bodies (e.g., oxidation of the IOM) may provide a secondary source of aldehydes and ketones in the solar system. Comparisons between 13C compositions of meteoritic aldehydes and ketones and other organic compound classes were used to evaluate potential structural relationships and associated reactions, including Strecker synthesis and alterationdriven chemical pathways

A More Reduced Mantle Source for Enriched Shergottites; Insights from the Olivine-Phyric Shergottite Lar 06319

A detailed petrographic study of melt inclusions and Cr-Fe-Ti oxides of LAR 06319 leads to two main conclusions: 1) this enriched oxidized olivine- phyric shergottite represents nearly continuous crystallization of a basaltic shergottite melt, 2) the melt became more oxidized during differentiation. The first crystallized mineral assemblages record the oxygen fugacity which is closest to that of the melt s mantle source, and which is lower than generally attributed to the enriched shergottite group

Economic evidence for the prevention and treatment of atopic eczema: a protocol for a systematic review

Background: Eczema, synonymous with atopic eczema or atopic dermatitis, is a chronic skin disease that has a similar impact on health-related quality of life as other chronic diseases. The proposed research aims to provide a comprehensive systematic assessment of the economic evidence base available to inform economic modelling and decision making on interventions to prevent and treat eczema at any stage of the life course. Whilst the Global Resource of Eczema Trials (GREAT) database collects together the effectiveness evidence for eczema there is currently no such systematic resource on the economics of eczema. It is important to gain an overview of the current state of the art of economic methods in the field of eczema in order to strengthen the economic evidence base further. Methods/design: The proposed study is a systematic review of the economic evidence surrounding interventions for the prevention and treatment of eczema. Relevant search terms will be used to search MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment, Cumulative Index to Nursing and Allied Health Literature, Econ Lit, Scopus, Cost-Effectiveness Analysis Registry and Web of Science in order to identify relevant evidence. To be eligible for inclusion studies will be primary empirical studies evaluating the cost, utility or full economic evaluation of interventions for preventing or treating eczema. Two reviewers will independently assess studies for eligibility and perform data abstraction. Evidence tables will be produced presenting details of study characteristics, costing methods, outcome methods and quality assessment. The methodological quality of studies will be assessed using accepted checklists. Discussion: The systematic review is being undertaken to identify the type of economic evidence available, summarise the results of the available economic evidence and critically appraise the quality of economic evidence currently available to inform future economic modelling and resource allocation decisions about interventions to prevent or treat eczema. We aim to use the review to offer guidance about how to gather economic evidence in studies of eczema and/or what further research is necessary in order to inform this

The changing of the guard: groupwork with people who have intellectual disabilities

This paper considers the impact of service systems on group activities. It describes an inter-professional groupwork project facilitated by a social worker and a community nurse. The project provided an emancipatory experience for a group of adults who had intellectual disabilities. The group was charged with the task of reviewing and updating the recruitment and interview processes used by a 'Learning Disability Partnership Board', when employing new support workers. The paper begins with a brief history of intellectual disability and provides a context to the underpinning philosophical belief that people should be encouraged and supported to inhabit valued social roles no matter what disability they may have. It then identifies the ways in which the sponsoring health, education and social care services impacted on the creation and development of a groupwork project. It might have been expected that the nature of the intellectual disability would have been the major influence on group process. However the paper reveals that organisational constraints had a significant impact on group functioning. Issues including, staffing budgets and transport contracts impacted on group process and function. The results of the project show how, with adequate support, people with intellectual disability can make important decisions that have long-reaching impacts on the services

Thermal structure of a gas-permeable lava dome and timescale separation in its response to perturbation

The thermal boundary layer at the surface of a volcanic lava dome is investigated through a continuum model of the thermodynamic advection diffusion processes resulting from magmatic gas flow through the dome matrix. The magmatic gas mass flux, porosity and permeability of the rock are identified as key parameters. New, theoretical, nonlinear steady-state thermal profiles are reported which give a realistic surface temperature of 210 degC for a region of lava dome surface through which a gas flux of 3.5 x 10-3 kg s-1 m-2 passes. This contrasts favourably with earlier purely diffusive thermal models, which cool too quickly. Results are presented for time-dependent perturbations of the steady states as a response to: changes in surface pressure, a sudden rockfall from the lava dome surface, and a change in the magmatic gas mass flux at depth. Together with a generalized analysis using the method of multiple scales, this identifies two characteristic time scales associated with the thermal evolution of a dome carapace: a short time scale of several minutes, over which the magmatic gas mass flux, density, and pressure change to a new quasi-steady-state, and a longer time scale of several days, over which the thermal profile changes to a new equilibrium distribution. Over the longer time scale the dynamic properties of the dome continue to evolve, but only in slavish response to the ongoing temperature evolution. In the light of this time scale separation, the use of surface temperature measurements to infer changes in the magmatic gas flux for use in volcanic hazard prediction is discussed

New Insights into the Heterogeneity of the Tagish Lake Meteorite: Soluble Organic Compositions of Variously Altered Specimens

The Tagish Lake carbonaceous chondrite exhibits a unique compositional heterogeneity that may be attributed to varying degrees of aqueous alteration within the parent body asteroid. Previous analyses of soluble organic compounds from four Tagish Lake meteorite specimens (TL5b, TL11h, TL11i, TL11v) identified distinct distributions and isotopic compositions that appeared to be linked to their degree of parent body processing (Herd et al. 2011; Glavin et al. 2012; Hilts et al. 2014). In the present study, we build upon these initial observations and evaluate the molecular distribution of amino acids, aldehydes and ketones, monocarboxylic acids, and aliphatic and aromatic hydrocarbons, including compoundspecific 13C compositions, for three additional Tagish Lake specimens: TL1, TL4, and TL10a. TL1 contains relatively high abundances of soluble organics and appears to be a moderately altered specimen, similar to the previously analyzed TL5b and TL11h lithologies. In contrast, specimens TL4 and TL10a both contain relatively low abundances of all of the soluble organic compound classes measured, similar to TL11i and TL11v. The organicdepleted composition of TL4 appears to have resulted from a relatively low degree of parent body aqueous alteration. In the case of TL10a, some unusual properties (e.g., the lack of detection of intrinsic monocarboxylic acids and aliphatic and aromatic hydrocarbons) suggest that it has experienced extensive alteration and/or a distinct organicdepleted alteration history. Collectively, these varying compositions provide valuable new insights into the relationships between asteroidal aqueous alteration and the synthesis and preservation of soluble organic compounds

Psychopathy and Attachment: The Effect of Security Priming on Psychopathy in a College Student Sample

Psychopathy has been defined as a pattern of negative behaviors, social interactions, and affective features, including impoverishment of emotion, unethical and manipulative actions, and impulsivity (Neumann & Hare, 2008). It is estimated that between 15 to 30 percent of incarcerated adults meet the criteria for psychopathy (Hare, 1991, 1996; Salekin, Rogers, Ustad, & Sewell, 1998). Because psychopathy is linked with deviant behaviors and a significant portion of incarcerated adults are high in psychopathy, methods of reducing psychopathy are needed. The current longitudinal study sought to reduce state psychopathy levels through secure attachment priming. It was first hypothesized that the mean of state levels of psychopathy would correlate with trait measures of psychopathy. Secondly, it was hypothesized that participants primed with secure attachment would report higher levels of state secure attachment and lower levels of state avoidant and anxious attachment. Finally, it was hypothesized that participants primed with secure attachment would report lower levels of state psychopathy than participants primed with a neutral concept. Forty undergraduate students (33 women and 7 men) participated in the experiment. Results indicated that the mean of state levels of psychopathy were positively associated with trait measures of psychopathy. Contrary to hypotheses, however, the secure attachment prime did not significantly affect levels of state security, anxiety, or avoidance, and the security prime did not reduce state levels of psychopathy over time. These findings provide initial support for a measure of state psychopathy, and call for further research to better understand the relationship between attachment and psychopathy