Impact of RNA Editing on Functions of the Serotonin 2C Receptor in vivo

Transcripts encoding 5-HT2C receptors are modified posttranscriptionally by RNA editing, generating up to 24 protein isoforms. In recombinant cells, the fully edited isoform, 5-HT2C-VGV, exhibits blunted G-protein coupling and reduced constitutive activity. The present studies examine the signal transduction properties of 5-HT2C-VGV receptors in brain to determine the in vivo consequences of altered editing. Using mice solely expressing the 5-HT2C-VGV receptor (VGV/Y), we demonstrate reduced G-protein coupling efficiency and high-affinity agonist binding of brain 5-HT2C-VGV receptors. However, enhanced behavioral sensitivity to a 5-HT2C receptor agonist was also seen in mice expressing 5-HT2C-VGV receptors, an unexpected finding given the blunted G-protein coupling. In addition, mice expressing 5-HT2C-VGV receptors had greater sensitivity to a 5-HT2C inverse agonist/antagonist enhancement of dopamine turnover relative to wild-type mice. These behavioral and biochemical results are most likely explained by increases in 5-HT2C receptor binding sites in the brains of mice solely expressing 5-HT2C-VGV receptors. We conclude that 5-HT2C-VGV receptor signaling in brain is blunted, but this deficiency is masked by a marked increase in 5-HT2C receptor binding site density in mice solely expressing the VGV isoform. These findings suggest that RNA editing may regulate the density of 5-HT2C receptor binding sites in brain. We further caution that the pattern of 5-HT2C receptor RNA isoforms may not reflect the pattern of protein isoforms, and hence the inferred overall function of the receptor

The Role of Training Variables in Effective Dissemination of Evidence-Based Parenting Interventions

From a public health perspective, mental health in parents and children can be promoted through population-based dissemination of parenting and family support interventions. However, it is critical that service providers who are acquiring evidence-based parenting interventions complete the training regimen to optimize dissemination and impact. This article examines training completion and its relationship to individual service provider characteristics, barriers to program use and subsequent implementation of an evidence-based program, the Triple P - Positive Parenting Program. In this study, 83.7% of the service providers completed the two-part training. Individual-level variables did not predict training completion. Service providers from diverse backgrounds were equally likely to complete training, were highly satisfied with the training provided and reported relatively few barriers to implementation. The majority of those who completed training (67.6%) went on to deliver the program with families in the community, whereas only 37.8% of those who did not complete training used the program subsequently. Implications are discussed for fidelity in delivery, cost-effectiveness in dissemination efforts, and population-wide health promotion

Relative effects of disturbance on red imported fire ants and native ant species in a longleaf pine ecosystem

Abstract: The degree to which changes in community composition mediate the probability of colonization and spread of non-native species is not well understood, especially in animal communities. High species richness may hinder the establishment of non-native species. Distinguishing between this scenario and cases in which no

Is the Alma Ata vision of comprehensive primary health care viable? Findings from an international project

BACKGROUND: The 4-year (2007 2011) Revitalizing Health for All international research program (http://www. globalhealthequity.ca/projects/proj_revitalizing/index.shtml) supported 20 research teams located in 15 lowand middle-income countries to explore the strengths and weaknesses of comprehensive primary health care (CPHC) initiatives at their local or national levels. Teams were organized in a triad comprised of a senior researcher, a new researcher, and a 'research user' from government, health services, or other organizations with the authority or capacity to apply the research findings. Multiple regional and global team capacityenhancement meetings were organized to refine methods and to discuss and assess cross-case findings. OBJECTIVE: Most research projects used mixed methods, incorporating analyses of qualitative data (interviews and focus groups), secondary data, and key policy and program documents. Some incorporated historical case study analyses, and a few undertook new surveys. The synthesis of findings in this report was derived through qualitative analysis of final project reports undertaken by three different reviewers. RESULTS: Evidence of comprehensiveness (defined in this research program as efforts to improve equity in access, community empowerment and participation, social and environmental health determinants, and intersectoral action) was found in many of the cases. CONCLUSION: Despite the important contextual differences amongst the different country studies, the similarity of many of their findings, often generated using mixed methods, attests to certain transferable health systems characteristics to create and sustain CPHC practices. These include: 1. Well-trained and supported community health workers (CHWs) able to work effectively with marginalized communities 2. Effective mechanisms for community participation, both informal (through participation in projects and programs, and meaningful consultation) and formal (though program management structures) 3. Co-partnership models in program and policy development (in which financial and knowledge supports from governments or institutions are provided to communities, which retain decision-making powers in program design and implementation) 4. Support for community advocacy and engagement in health and social systems decision making These characteristics, in turn, require a political context that supports state responsibilities for redistributive health and social protection measures.IS

The Empirical Foundations of Telemedicine Interventions for Chronic Disease Management

The telemedicine intervention in chronic disease management promises to involve patients in their own care, provides continuous monitoring by their healthcare providers, identifies early symptoms, and responds promptly to exacerbations in their illnesses. This review set out to establish the evidence from the available literature on the impact of telemedicine for the management of three chronic diseases: congestive heart failure, stroke, and chronic obstructive pulmonary disease. By design, the review focuses on a limited set of representative chronic diseases because of their current and increasing importance relative to their prevalence, associated morbidity, mortality, and cost. Furthermore, these three diseases are amenable to timely interventions and secondary prevention through telemonitoring. The preponderance of evidence from studies using rigorous research methods points to beneficial results from telemonitoring in its various manifestations, albeit with a few exceptions. Generally, the benefits include reductions in use of service: hospital admissions/re-admissions, length of hospital stay, and emergency department visits typically declined. It is important that there often were reductions in mortality. Few studies reported neutral or mixed findings.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140284/1/tmj.2014.9981.pd

The Farthest Known Supernova: Support for an Accelerating Universe and a Glimpse of the Epoch of Deceleration

We present photometric observations of an apparent Type Ia supernova (SN Ia) at a redshift of ~1.7, the farthest SN observed to date. SN 1997ff, was discovered in a repeat observation by the HST of the HDF-), and serendipitously monitored with NICMOS on HST throughout the GTO campaign. The SN type can be determined from the host galaxy type:an evolved, red elliptical lacking enough recent star formation to provide a significant population of core-collapse SNe. The class- ification is further supported by diagnostics available from the observed colors and temporal behavior of the SN, both of which match a typical SN Ia. The photo- metric record of the SN includes a dozen flux measurements in the I, J, and H bands spanning 35 days in the observed frame. The redshift derived from the SN photometry, z=1.7+/-0.1, is in excellent agreement with the redshift estimate of z=1.65+/-0.15 derived from the U_300,B_450,V_606,I_814,J_110,J_125,H_160, H_165,K_s photometry of the galaxy. Optical and near-infrared spectra of the host provide a very tentative spectroscopic redshift of 1.755. Fits to observations of the SN provide constraints for the redshift-distance relation of SNe~Ia and a powerful test of the current accelerating Universe hypothesis. The apparent SN brightness is consistent with that expected in the decelerating phase of the preferred cosmological model, Omega_M~1/3, Omega_Lambda~2/3. It is inconsistent with grey dust or simple luminosity evolution, candidate astro- physical effects which could mimic past evidence for an accelerating Universe from SNe Ia at z~0.5.We consider several sources of possible systematic error including lensing, SN misclassification, selection bias, and calibration errors. Currently, none of these effects appears likely to challenge our conclusions.Comment: Accepted to the Astrophysical Journal 38 pages, 15 figures, Pretty version available at http://icarus.stsci.edu/~stefano/ariess.tar.g

National Telemedicine Initiatives: Essential to Healthcare Reform

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78116/1/tmj.2009.9960.pd

The SEGUE Stellar Parameter Pipeline. II. Validation with Galactic Globular and Open Clusters

We validate the performance and accuracy of the current SEGUE (Sloan Extension for Galactic Understanding and Exploration) Stellar Parameter Pipeline (SSPP), which determines stellar atmospheric parameters (effective temperature, surface gravity, and metallicity) by comparing derived overall metallicities and radial velocities from selected likely members of three globular clusters (M 13, M 15, and M 2) and two open clusters (NGC 2420 and M 67) to the literature values. Spectroscopic and photometric data obtained during the course of the original Sloan Digital Sky Survey (SDSS-I) and its first extension (SDSS-II/SEGUE) are used to determine stellar radial velocities and atmospheric parameter estimates for stars in these clusters. Based on the scatter in the metallicities derived for the members of each cluster, we quantify the typical uncertainty of the SSPP values, sigma([Fe/H]) = 0.13 dex for stars in the range of 4500 K < Teff < 7500 K and 2.0 < log g < 5.0, at least over the metallicity interval spanned by the clusters studied (-2.3 < [Fe/H] < 0). The surface gravities and effective temperatures derived by the SSPP are also compared with those estimated from the comparison of the color-magnitude diagrams with stellar evolution models; we find satisfactory agreement. At present, the SSPP underestimates [Fe/H] for near-solar-metallicity stars, represented by members of M 67 in this study, by about 0.3 dex.Comment: 56 pages, 8 Tables, 15 figures, submitted to the Astronomical Journa

Characterisation of the muon beams for the Muon Ionisation Cooling Experiment

A novel single-particle technique to measure emittance has been developed and used to characterise seventeen different muon beams for the Muon Ionisation Cooling Experiment (MICE). The muon beams, whose mean momenta vary from 171 to 281 MeV/c, have emittances of approximately 1.2–2.3 π mm-rad horizontally and 0.6–1.0 π mm-rad vertically, a horizontal dispersion of 90–190 mm and momentum spreads of about 25 MeV/c. There is reasonable agreement between the measured parameters of the beams and the results of simulations. The beams are found to meet the requirements of MICE