Intra-accumbens baclofen, but not muscimol, increases second order instrumental responding for food reward in rats

Stimulation of either GABA(A) or GABA(B) receptors within the nucleus accumbens shell strongly enhances food intake in rats. However the effects of subtype-selective stimulation of GABA receptors on instrumental responses for food reward are less well characterized. Here we contrast the effects of the GABA(A) receptor agonist muscimol and GABA(B) receptor agonist baclofen on instrumental responding for food using a second order reinforcement schedule. Bilateral intra-accumbens administration of baclofen (220-440 pmol) stimulated responding but a higher dose (660 pmol) induced stereotyped oral behaviour that interfered with responding. Baclofen (220-660 pmol) also stimulated intake of freely available chow. Muscimol (220-660 pmol) was without effect on responding for food on this schedule but did stimulate intake of freely available chow. Unilateral administration of either baclofen or muscimol (220 pmol) induced similar patterns of c-fos immunoreactivity in several hypothalamic sites but differed in its induction in the central nucleus of the amygdala. We conclude that stimulation of GABA(A) or GABA(B) receptors in the nucleus accumbens shell of rats produces clearly distinguishable effects on operant responding for food

Transciptome Analysis Illuminates the Nature of the Intracellular Interaction in a Vertebrate-Algal Symbiosis

During embryonic development, cells of the green alga Oophila amblystomatis enter cells of the salamander Ambystoma maculatum forming an endosymbiosis. Here, using de novo dual-RNA seq, we compared the host salamander cells that harbored intracellular algae to those without algae and the algae inside the animal cells to those in the egg capsule. This two-by-two-way analysis revealed that intracellular algae exhibit hallmarks of cellular stress and undergo a striking metabolic shift from oxidative metabolism to fermentation. Culturing experiments with the alga showed that host glutamine may be utilized by the algal endosymbiont as a primary nitrogen source. Transcriptional changes in salamander cells suggest an innate immune response to the alga, with potential attenuation of NF-κB, and metabolic alterations indicative of modulation of insulin sensitivity. In stark contrast to its algal endosymbiont, the salamander cells did not exhibit major stress responses, suggesting that the host cell experience is neutral or beneficial

Co-Cultures of Oophila Amblystomatis Between Ambystoma Maculatum and Ambystoma Gracile Hosts Show Host-Symbiont Fidelity

A unique symbiosis occurs between embryos of the spotted salamander (Ambystoma maculatum) and a green alga (Oophila amblystomatis). Unlike most vertebrate host-symbiont relationships, which are ectosymbiotic, A. maculatum exhibits both an ecto- and an endo-symbiosis, where some of the green algal cells living inside egg capsules enter embryonic tissues as well as individual salamander cells. Past research has consistently categorized this symbiosis as a mutualism, making this the first example of a “beneficial” microbe entering vertebrate cells. Another closely related species of salamander, Ambystoma gracile, also harbors beneficial Oophila algae in its egg capsules. However, our sampling within the A. gracile range consistently shows this to be a strict ectosymbiotic interaction—with no sign of tissue or presumably cellular entry. In this study we swapped cultured algae derived from intracapsular fluid of different salamander hosts to test the fidelity of tissue entry in these symbioses. Both A. maculatum and A. gracile embryos were raised in cultures with their own algae or algae cultured from the other host. Under these in vitro culture conditions A. maculatum algae will enter embryonic A. maculatum tissues. Additionally, although at a much lower frequency, A. gracile derived algae will also enter A. maculatum host tissues. However, neither Oophila strain enters A. gracile hosts in these co-culture conditions. These data reveal a potential host-symbiont fidelity that allows the unique endosymbiosis to occur in A. maculatum, but not in A. gracile. However, preliminary trials in our study found that persistent endogenous A. maculatum algae, as opposed to the cultured algae used in subsequent trials, enters host tissues at a higher frequency. An analysis of previously published Oophila transcriptomes revealed dramatic differences in gene expression between cultured and intracapsular Oophila. These include a suite of genes in protein and cell wall synthesis, photosynthesis, central carbon metabolism suggesting the intracapsular algae are assimilating ammonia for nitrogen metabolism and may be undergoing a life-cycle transition. Further refinements of these co-culture conditions could help determine physiological differences between cultured and endogenous algae, as well as rate-limiting cues provided for the alga by the salamander

Midazolam Efficacy Against Acute Hydrogen Sulfide-Induced Mortality and Neurotoxicity.

Hydrogen sulfide (H2S) is a colorless, highly neurotoxic gas. It is not only an occupational and environmental hazard but also of concern to the Department of Homeland Security for potential nefarious use. Acute high-dose H2S exposure causes death, while survivors may develop neurological sequelae. Currently, there is no suitable antidote for treatment of acute H2S-induced neurotoxicity. Midazolam (MDZ), an anti-convulsant drug recommended for treatment of nerve agent intoxications, could also be of value in treating acute H2S intoxication. In this study, we tested the hypothesis that MDZ is effective in preventing/treating acute H2S-induced neurotoxicity. This proof-of-concept study had two objectives: to determine whether MDZ prevents/reduces H2S-induced mortality and to test whether MDZ prevents H2S-induced neurological sequelae. MDZ (4 mg/kg) was administered IM in mice, 5 min pre-exposure to a high concentration of H2S at 1000 ppm or 12 min post-exposure to 1000 ppm H2S followed by 30 min of continuous exposure. A separate experiment tested whether MDZ pre-treatment prevented neurological sequelae. Endpoints monitored included assessment of clinical signs, mortality, behavioral changes, and brain histopathological changes. MDZ significantly reduced H2S-induced lethality, seizures, knockdown, and behavioral deficits (p < 0.01). MDZ also significantly prevented H2S-induced neurological sequelae, including weight loss, behavior deficits, neuroinflammation, and histopathologic lesions (p < 0.01). Overall, our findings show that MDZ is a promising drug for reducing H2S-induced acute mortality, neurotoxicity, and neurological sequelae

Analysis of Local Health Department Factors that Accelerate Population-based Intervention Strategies: Preliminary Findings

Introduction: This practice-based research study capitalized on the statewide implementation of a comprehensive, locally-driven initiative to implement evidence-based policy, system and environmental changes related to obesity and tobacco use. The study examined local health department (LHD) performance and factors such as organizational quality improvement (QI) maturity, structure and governance. Methods: State health department staff reviewed grant reports and documentation pertaining to all LHD grantees, which collectively represented all 87 counties and 4 cities in Minnesota (MN), in order to designate grantees as either: “Exceeds Expectations,” “Meets Expectations” or “Approaching Expectations.” A study team of state, local and academic partners then used select measures from the QI Maturity Tool to calculate a QI Maturity Score, and subsequently place grantees into three levels of QI maturity: low, medium and high. Multivariate regression was performed to examine the potential relationship between grantee performance and QI maturity, as well as other covariates. Results: Of the final sample of 91 counties/cities, 87 had complete data for multivariate analysis. The distribution of grantee performance was: exceeds expectations (29.7%), meets expectations (55.0%) and approaching expectations (15.3%). Organizational QI maturity was strongly, positively associated with grantee performance comparing the “exceeds expectations” to those who “met or approached expectations” (OR=4.29, 95 % CI: 1.90-9.73, p=0.0005). Implications: Organizational QI maturity was strongly associated with LHD performance. More research is needed to determine whether a more mature approach to quality improvement is merely a marker for overall LHD capacity or has its own unique contribution to performance. Findings have been used to inform the next funding cycle of this initiative and provide support to implementing annual assessment of QI maturity in MN

A Contextual Approach to Social Skills Assessment in the Peer Group: Who Is the Best Judge?

Using a contextual approach to social skills assessment in the peer group, this study examined the criterion- related validity of contextually relevant social skills and the incremental validity of peers and teachers as judges of children’s social skills. Study participants included 342 (180 male and 162 female) students and their classroom teachers (N = 22) from rural communities. As expected, contextually relevant social skills were significantly related to a variety of social status indicators (i.e., likability, peer- and teacher-assessed popularity, reciprocated friendships, clique centrality) and positive school functioning (i.e., school liking and academic competence). Peer-assessed social skills, not teacher-assessed social skills, demonstrated consistent incremental validity in predicting various indicators of social status outcomes; peer- and teacher-assessed social skills alike showed incremental validity in predicting positive school functioning. The relation between contextually relevant social skills and study outcomes did not vary by child gender. Findings are discussed in terms of the significance of peers in the assessment of children’s social skills in the peer group as well as the usefulness of a contextual approach to social skills assessment

Broad spectrum proteomics analysis of the inferior colliculus following acute hydrogen sulfide exposure.

Acute exposure to high concentrations of H2S causes severe brain injury and long-term neurological disorders, but the mechanisms involved are not known. To better understand the cellular and molecular mechanisms involved in acute H2S-induced neurodegeneration we used a broad-spectrum proteomic analysis approach to identify key molecules and molecular pathways involved in the pathogenesis of acute H2S-induced neurotoxicity and neurodegeneration. Mice were subjected to acute inhalation exposure of up to750 ppm of H2S. H2S induced behavioral deficits and severe lesions including hemorrhage in the inferior colliculus (IC). The IC was microdissected for proteomic analysis. Tandem mass tags (TMT) liquid chromatography mass spectrometry (LC-MS/MS)-based quantitative proteomics was applied for protein identification and quantitation. LC-MS/MS identified 598, 562, and 546 altered proteomic changes at 2 h, and on days 2 and 4 post-H2S exposure, respectively. Of these, 77 proteomic changes were statistically significant at any of the 3 time points. Mass spectrometry data were subjected to Perseus 1.5.5.3 statistical analysis, and gene ontology heat map clustering. Expressions of several key molecules were verified to confirm H2S-dependent proteomics changes. Webgestalt pathway overrepresentation enrichment analysis with Panther engine revealed H2S exposure disrupted several biological processes including metabotropic glutamate receptor group 1 and inflammation mediated by chemokine and cytokine signaling pathways among others. Further analysis showed that energy metabolism, integrity of blood-brain barrier, hypoxic, and oxidative stress signaling pathways were also implicated. Collectively, this broad-spectrum proteomics data has provided important clues to follow up in future studies to further elucidate mechanisms of H2S-induced neurotoxicity

A Contextual Approach to Social Skills Assessment in the Peer Group: Who Is the Best Judge?

Using a contextual approach to social skills assessment in the peer group, this study examined the criterion- related validity of contextually relevant social skills and the incremental validity of peers and teachers as judges of children’s social skills. Study participants included 342 (180 male and 162 female) students and their classroom teachers (N = 22) from rural communities. As expected, contextually relevant social skills were significantly related to a variety of social status indicators (i.e., likability, peer- and teacher-assessed popularity, reciprocated friendships, clique centrality) and positive school functioning (i.e., school liking and academic competence). Peer-assessed social skills, not teacher-assessed social skills, demonstrated consistent incremental validity in predicting various indicators of social status outcomes; peer- and teacher-assessed social skills alike showed incremental validity in predicting positive school functioning. The relation between contextually relevant social skills and study outcomes did not vary by child gender. Findings are discussed in terms of the significance of peers in the assessment of children’s social skills in the peer group as well as the usefulness of a contextual approach to social skills assessment