Glial Cell Activity within the Ventrolateral Periaqueductal Gray of Male and Female Rats

Morphine is one of the most commonly prescribed medications for the relief of prolonged pain. Both basic science and clinical studies indicate that females require 2-3 times more morphine than males to achieve the same analgesic effect. To date, the mechanisms underlying sex differences in opiate responsiveness are unknown. Recent studies suggest that glial cells are potent modulators of morphine-based analgesia, and in particular, decrease the analgesic effect of opiates. Therefore, we tested the hypothesis that the sexually dimorphic effects of morphine were due to sex differences in glial cell activity. Our studies focused on the midbrain periaqueductal gray (PAG) as this region of the brain is critical for the analgesic effects of morphine. Adult male and female Sprague Dawley rats (250g- 400g) were procured from Charles River Laboratories, and were allowed 7 days to acclimate to the new facility. On the day of the experiment, animals received a subcutaneous injection of morphine (5mg/kg) or were handled in a similar manner. Thirty or 60 minutes after injections or handling, animals were perfused with a 4% paraformaldehyde and 2.5% acrolein tissue fixative solution. Brains were removed and stored in 20% sucrose until ready for sectioning. Brains were sectioned at 25mm using a freezing microtome, and immunohistochemical localization of markers for astrocyte glial cell activity was performed. Antibodies to glial fibrillary acidic protein (GFAP) were used to label activated astrocytes. If our hypothesis is correct, then females will have significantly greater density of the astrocyte cell activity marker GFAP as compared with males. Sex differences in PAG glial cell activity may provide the biological bases for the sexually dimorphic effect of morphine. This research may lead to better treatment for females experiencing prolonged chronic or neuropathic pain

The small FNR regulon of Neisseria gonorrhoeae: comparison with the larger Escherichia coli FNR regulon and interaction with the NarQ-NarP regulon

BACKGROUND: Neisseria gonorrhoeae can survive during oxygen starvation by reducing nitrite to nitrous oxide catalysed by the nitrite and nitric oxide reductases, AniA and NorB. The oxygen-sensing transcription factor, FNR, is essential for transcription activation at the aniA promoter, and full activation also requires the two-component regulatory system, NarQ-NarP, and the presence of nitrite. The only other gene known to be activated by the gonococcal FNR is ccp encoding a cytochrome c peroxidase, and no FNR-repressed genes have been reported in the gonococcus. In contrast, FNR acts as both an activator and repressor involved in the control of more than 100 operons in E. coli regulating major changes in the adaptation from aerobic to anaerobic conditions. In this study we have performed a microarray-led investigation of the FNR-mediated responses in N. gonorrhoeae to determine the physiological similarities and differences in the role of FNR in cellular regulation in this species. RESULTS: Microarray experiments show that N. gonorrhoeae FNR controls a much smaller regulon than its E. coli counterpart; it activates transcription of aniA and thirteen other genes, and represses transcription of six genes that include dnrN and norB. Having previously shown that a single amino acid substitution is sufficient to enable the gonococcal FNR to complement an E. coli fnr mutation, we investigated whether the gonococcal NarQ-NarP can substitute for E. coli NarX-NarL or NarQ-NarP. A plasmid expressing gonococcal narQ-narP was unable to complement E. coli narQP or narXL mutants, and was insensitive to nitrate or nitrite. Mutations that progressively changed the periplasmic nitrate sensing region, the P box, of E. coli NarQ to the sequence of the corresponding region of gonococcal NarQ resulted in loss of transcription activation in response to the availability of either nitrate or nitrite. However, the previously reported ligand-insensitive ability of gonococcal NarQ, the "locked on" phenotype, to activate either E. coli NarL or NarP was confirmed. CONCLUSION: Despite the sequence similarities between transcription activators of E. coli and N. gonorrhoeae, these results emphasise the fundamental differences in transcription regulation between these two types of pathogenic bacteria

The Broadband Infrared Emission Spectrum of the Exoplanet HD 189733b

We present Spitzer Space Telescope time series photometry of the exoplanet system HD 189733 spanning two times of secondary eclipse, when the planet passes out of view behind the parent star. We estimate the relative eclipse depth in 5 distinct bands and find the planet-to-star flux ratio to be 0.256 +/- 0.014% (3.6 microns), 0.214 +/- 0.020% (4.5 microns), 0.310 +/- 0.034% (5.8 microns), 0.391 +/- 0.022% (8.0 microns), and 0.598 +/- 0.038% (24 microns). For consistency, we re-analyze a previously published time series to deduce a contrast ratio in an additional band, 0.519 +/- 0.020% (16 microns). Our data are strongly inconsistent with a Planck spectrum, and we clearly detect emission near 4 microns as predicted by published theoretical models in which this feature arises from a corresponding opacity window. Unlike recent results for the exoplanet HD 209458b, we find that the emergent spectrum from HD 189733b is best matched by models that do not include an atmospheric temperature inversion. Taken together, these two studies provide initial observational support for the idea that hot Jupiter atmospheres diverge into two classes, in which a thermal inversion layer is present for the more strongly irradiated objects.Comment: 20 pages, 3 figures, accepted to the Astrophysical Journal, minor revision

Next generation software environments : principles, problems, and research directions

The past decade has seen a burgeoning of research and development in software environments. Conferences have been devoted to the topic of practical environments, journal papers produced, and commercial systems sold. Given all the activity, one might expect a great deal of consensus on issues, approaches, and techniques. This is not the case, however. Indeed, the term "environment" is still used in a variety of conflicting ways. Nevertheless substantial progress has been made and we are at least nearing consensus on many critical issues.The purpose of this paper is to characterize environments, describe several important principles that have emerged in the last decade or so, note current open problems, and describe some approaches to these problems, with particular emphasis on the activities of one large-scale research program, the Arcadia project. Consideration is also given to two related topics: empirical evaluation and technology transition. That is, how can environments and their constituents be evaluated, and how can new developments be moved effectively into the production sector

Transcriptomic profiling of 39 commonly-used neuroblastoma cell lines

Neuroblastoma cell lines are an important and cost-effective model used to study oncogenic drivers of the disease. While many of these cell lines have been previously characterized with SNP, methylation, and/or mRNA expression microarrays, there has not been an effort to comprehensively sequence these cell lines. Here, we present raw whole transcriptome data generated by RNA sequencing of 39 commonly-used neuroblastoma cell lines. These data can be used to perform differential expression analysis based on a genetic aberration or phenotype in neuroblastoma (e.g., MYCN amplification status, ALK mutation status, chromosome arm 1p, 11q and/or 17q status, sensitivity to pharmacologic perturbation). Additionally, we designed this experiment to enable structural variant and/or long-noncoding RNA analysis across these cell lines. Finally, as more DNase/ATAC and histone/transcription factor ChIP sequencing is performed in these cell lines, our RNA-Seq data will be an important complement to inform transcriptional targets as well as regulatory (enhancer or repressor) elements in neuroblastoma

Physical therapy and exercise interventions in Huntington's disease: a mixed methods systematic review protocol

Review question/objective: : The review seeks to evaluate the effectiveness of physical therapy and exercise interventions in Huntington's disease (HD). The review question is: What is the effectiveness of physiotherapy and therapeutic exercise interventions in people with HD, and what are patients’, families’ and caregivers’ perceptions of these interventions? Review question/objective: The specific objectives are: Review question/objective: This mixed methods review seeks to develop an aggregated synthesis of quantitative, qualitative and narrative systematic reviews on physiotherapy and exercise interventions in HD, in an attempt to derive conclusions and recommendations useful for clinical practice and policy decision-making

The Age of the Oldest Stars in the Local Galactic Disk From Hipparcos Parallaxes of G and K Subgiants

We review the history of the discovery of field subgiant stars and their importance in the age dating of the Galactic disk. We use the cataloged data from the Hipparcos satellite in this latter capacity. Based on Hipparcos parallaxes accurate to 10% or better, the absolute magnitude of the lower envelope of the nearly horizontal subgiant sequence for field stars in the H-R diagram for B-V colors between 0.85 and 1.05 is measured to be M_V = 4.03 +/- 0.06. The age of the field stars in the solar neighborhood is found to be 7.9 +/- 0.7 Gyr by fitting the theoretical isochrones for [Fe/H] = +0.37 to the lower envelope of the Hipparcos subgiants. The same grid of isochrones yields ages, in turn, of 4.0 +/- 0.2 Gyr, 6.2 +/- 0.5 Gyr, and 7.5 to 10 Gyr for the old Galactic clusters M67, NGC188, and NGC6791. The ages of both the Galactic disk in the solar neighborhood and of NGC6791 are, nevertheless, likely between 3 and 5 Gyr younger than the oldest halo globular clusters, which have ages of 13.5 Gyr. The most significant results are (1) the supermetallicity of the oldest local disk stars, and (2) the large age difference between the most metal-poor component of the halo and the thick and thin disk in the solar neighborhood. These facts are undoubtedly related and pose again the problem of the proper scenario for the timing of events in the formation of the halo and the Galactic disk in the solar neighborhood. [Abstract Abridged]Comment: 44 pages, 12 Figures; accepted for publication in PASP; high resolution versions of Figures 1, 2, 6 and 9 available at http://bubba.ucdavis.edu/~lubin/Sandage

Comparing the degree of land–atmosphere interaction in four atmospheric general circulation models

Permission to place copies of these works on this server has been provided by the American Meteorological Society (AMS). The AMS does not guarantee that the copies provided here are accurate copies of the published work. © Copyright 2002 American Meteorological Society (AMS). Permission to use figures, tables, and brief excerpts from this work in scientific and educational works is hereby granted provided that the source is acknowledged. Any use of material in this work that is determined to be “fair use” under Section 107 of the U.S. Copyright Act or that satisfies the conditions specified in Section 108 of the U.S. Copyright Act (17 USC §108, as revised by P.L. 94-553) does not require the AMS’s permission. Republication, systematic reproduction, posting in electronic form on servers, or other uses of this material, except as exempted by the above statement, requires written permission or a license from the AMS. Additional details are provided in the AMS Copyright Policy, available on the AMS Web site located at (http://www.ametsoc.org/AMS) or from the AMS at 617-227-2425 or [email protected] strength of the coupling between the land and the atmosphere, which controls, for example, the degree to which precipitation-induced soil moisture anomalies affect the overlying atmosphere and thereby the subsequent generation of precipitation, has been examined and quantified with many atmospheric general circulation models (AGCMs). Generally missing from such studies, however, is an indication of the extent to which the simulated coupling strength is model dependent. Four modeling groups have recently performed a highly controlled numerical experiment that allows an objective intermodel comparison of land–atmosphere coupling strength, focusing on short (weekly down to subhourly) timescales. The experiment essentially consists of an ensemble of 1-month simulations in which each member simulation artificially maintains the same (model specific) time series of surface prognostic variables. Differences in atmospheric behavior between the ensemble members then indicate the degree to which the state of the land surface controls atmospheric processes in that model. A comparison of the four sets of experimental results shows that coupling strength does indeed vary significantly among the AGCMs

Positive Parenting Approaches and Their Association with Child Eating and Weight: A Narrative Review from Infancy to Adolescence

Parents play a critical role in the development of children\u27s eating behaviours and weight status, serving as providers, models and regulators of the food environment. Many research reviews have focused on the robust body of evidence on coercive control in feeding: how parenting practices such as restriction and pressure to eat increase children\u27s risk for developing undesirable eating behaviours and unhealthy weight outcomes. Fewer reviews adopt a strengths-based perspective focusing on the ways that parents can actively support the development of healthy eating behaviours and weight trajectories. Emerging research on such positive parenting styles and practices offers solutions beyond the avoidance of coercive control, as well as opportunities to highlight parallels between research on food parenting and the broader, well-established developmental literature on positive parenting. The focus of this review is to summarize what is known regarding benefits of positive parenting styles and practices for child eating and weight outcomes and discuss recommendations for future research. Current evidence supports starting with responsive feeding and parenting during infancy and incorporating structure and limit setting in early childhood, with monitoring and mealtime structure remaining important during middle childhood and adolescence. Areas for future research include: (1) further examination of the implications of identified food parenting practices and styles among diverse groups and caregivers; (2) increased consideration of child factors (eg, temperament) as moderators or mediators; and (3) further clarification of the relationship between general parenting and food parenting