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

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

There are no author-identified significant results in this report

Genome-wide association studies for feedlot and growth traits in cattle

A genome wide-association study for production traits in cattle was carried out using genotype data from the 10K Affymetrix (Santa Clara, CA) and the 50K Illumina (San Diego, CA) SNP chips. The results for residual feed intake (RFI), BW, and hip height in 3 beef breed types (Bos indicus, Bos taurus, and B. indicus × B. taurus), and for stature in dairy cattle, are presented. The aims were to discover SNP associated with all traits studied, but especially RFI, and further to test the consistency of SNP effects across different cattle populations and breed types. The data were analyzed within data sets and within breed types by using a mixed model and fitting 1 SNP at a time. In each case, the number of significant SNP was more than expected by chance alone. A total of 75 SNP from the reference population with 50K chip data were significant (P < 0.001) for RFI, with a false discovery rate of 68%. These 75 SNP were mapped on 24 different BTA. Of the 75 SNP, the 9 most significant SNP were detected on BTA 3, 5, 7, and 8, with P ≤ 6.0 × 10 . In a population of Angus cattle divergently selected for high and low RFI and 10K chip data, 111 SNP were significantly (P < 0.001) associated with RFI, with a false discovery rate of 7%. Approximately 103 of these SNP were therefore likely to represent true positives. Because of the small number of SNP common to both the 10K and 50K SNP chips, only 27 SNP were significantly (P < 0.05) associated with RFI in the 2 populations. However, other chromosome regions were found that contained SNP significantly associated with RFI in both data sets, although no SNP within the region showed a consistent effect on RFI. The SNP effects were consistent between data sets only when estimated within the same breed type

Thermomechanical Characterization of Carbon Black Reinforced Rubbers During Rapid Adiabatic Straining

The thermo-mechanical properties of carbon black reinforced natural and styrene butadiene rubbers are investigated under rapid adiabatic conditions. Eleven carbon black grades with varying surface area and structure properties at 40 parts per hundred (phr) loading are studied and the unreinforced equivalents are included for reference. The results show a strong correlation of the modulus, mechanical hysteresis, temperature rise and calculated crystallinity of the rubbers measured in tensile extension with strain amplification factors. This highlights the influence of matrix overstraining on microstructural deformations of the rubber upon extension. The strain amplification factors are calculated via the Guth-Gold equation directly from carbon black type and loading, allowing a correlation of the fundamental morphological properties of carbon black with thermal and mechanical properties of rubbers upon extension. Analysis of the thermal measurements of the rubber compounds upon extension and retraction and contrasting between crystallizing and non-crystallizing rubbers reveals that a substantial irreversible heat generation is present upon extension of the rubber compounds. These irreversible effects most likely originate from microstructural damage mechanisms which have been proposed to account for the Mullins Effect in particle reinforced rubbers

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

Written education materials for stroke patients and their carers: perspectives and practices of health professionals

Inadequacies in the provision of written education materials to stroke patients and their carers have been reported. In this study, 20 stroke team health professionals were surveyed regarding their use of and perspectives on written education materials. Seventy percent of participants provided materials to 25% or fewer stroke patients and 90% believed that patients and carers are only occasionally or rarely provided with sufficient written information. Health professionals were uncertain which team members provided written information and identified the need to improve the quality of materials used. Stroke teams should implement a system that facilitates the routine provision of quality written materials to patients and carers, communication among team members, and documentation and verbal reinforcement of the information provided

Strategies for Investigating Early Mars Using Returned Samples

The 2011 Visions & Voyages Planeary Science Decadal Survey identified making significant progress toward the return of samples from Mars as the highest priority goal for flagship missions in next decade. Numerous scientific objectives have been identified that could be advanced through the potential return and analysis of martian rock, regolith, and atmospheric samples. The analysis of returned martian samples would be particularly valuable in in-creasing our understanding of Early Mars. There are many outstanding gaps in our knowledge about Early Mars in areas such as potential astrobiology, geochronology, planetary evolution (including the age, context, and processes of accretion, differentiation, magmatic, and magnetic history), the history of water at the martian surface, and the origin and evolution of the martian atmosphere. Here we will discuss scientific objectives that could be significantly advanced by Mars sample return

Effects of Increasing Standardized Ileal Digestible Lysine During Gestation on Growth and Reproductive Performance of Gilts and Sows Under Commercial Conditions

A study was conducted on a commercial sow farm to evaluate the effects of increasing dietary standardized ileal digestible (SID) lysine (Lys) intake in gestation on sow performance and piglet birth weight. A total of 936 females (498 gilts, 438 sows; Camborough, PIC, Hendersonville, TN) were group-housed (approximately 275 females per pen) and individually fed with electronic sow feeders (ESF). Scales were located in the alleyway after the feeding stations returning into the pen. Females were moved from the breeding stall to pens on d 4 of gestation and were allotted to 1 of 4 dietary treatments on d 5. Dietary treatments included increasing SID Lys intake (11, 13.5, 16, and 18.5 g/d). Gilts and sows received 4.6 and 5.1 lb/d, respectively, (5.3 and 5.7 Mcal NE/d) of feed throughout the entire study. Dietary treatments were achieved by different blends of low (0.48% SID Lys) and high (0.88% SID Lys) Lys diets via ESF based on the females’ set feed allowance. Initial and final BW and backfat were obtained on d 4 and 112 of gestation. Individual piglet BW was obtained within 12 h of birth on litters from 895 females. Data were analyzed using the GLIMMIX procedure of SAS. Body weight at d 112 of gestation increased within each parity group (linear, P \u3c 0.001) as SID Lys increased with gilts and sows consuming 18.5 g/d SID Lys weighing 16 and 11 lb more, respectively, than gilts and sows consuming 11 g/d SID Lys. There was no evidence for differences in d 112 backfat depth. Average total born for gilts and sows was 15.3 and 16.0, respectively with no evidence for differences among treatments. However, the percentage of pigs born alive increased (P = 0.006) with increasing SID Lys intake for sows but not in gilts. This is explained by the treatment × parity group interaction (P = 0.043) for percentage of stillborn pigs. In gilts, there was no evidence for differences among treatments in the percentage of stillborn pigs; however, in sows, as dietary SID Lys intake increased, the percentage of stillborn pigs decreased (linear, P = 0.002). Increasing SID Lys intake during gestation did not affect the percentage of mummified fetuses, total born, or born alive piglet birth weight in this study. In addition, increasing SID Lys intake during gestation did not affect subsequent reproductive performance. In conclusion, increasing dietary SID Lys intake in gestation increased female BW, without changing backfat or total born litter weight, indicating these females are depositing more lean tissue. The impact on female reproductive performance suggests that increasing SID Lys intake may increase the percentage of piglets born alive by reducing the number of stillborns in sows, but not in gilts

First assessment of the comparative toxicity of ivermectin and moxidectin in adult dung beetles: Sub-lethal symptoms and pre-lethal consequences

Among macrocyclic lactones (ML), ivermectin (IVM) and moxidectin (MOX) potentially affect all Ecdysozoan species, with dung beetles being particularly sensitive. The comparative effects of IVM and MOX on adult dung beetles were assessed for the first time to determine both the physiological sub-lethal symptoms and pre-lethal consequences. Inhibition of antennal response and ataxia were tested as two intuitive and ecologically relevant parameters by obtaining the lowest observed effect concentration (LOEC) values and interpolating other relevant toxicity thresholds derived from concentration-response curves (IC50, as the concentration of each ML where the antennal response is inhibited by half; and pLC50, as the quantity of ingested ML where partial paralysis was observed by half of treated individuals) from concentration-response curves. Both sub-lethal and pre-lethal symptoms obtained in this study coincided in that IVM was six times more toxic than MOX for adult dung beetles. Values of LOEC, IC50 and pLC50 obtained for IVM and MOX evaluated in an environmental context indicate that MOX, despite needing more time for its elimination in the faeces, would be half as harmful to dung beetles as IVM. This approach will be valuable to clarify the real impact of MLs on dung beetle health and to avoid the subsequent environmental consequences