Transcriptional Responses of Cultured Rat Sympathetic Neurons during BMP-7-Induced Dendritic Growth

Dendrites are the primary site of synapse formation in the vertebrate nervous system; however, relatively little is known about the molecular mechanisms that regulate the initial formation of primary dendrites. Embryonic rat sympathetic neurons cultured under defined conditions extend a single functional axon, but fail to form dendrites. Addition of bone morphogenetic proteins (BMPs) triggers these neurons to extend multiple dendrites without altering axonal growth or cell survival. We used this culture system to examine differential gene expression patterns in naïve vs. BMP-treated sympathetic neurons in order to identify candidate genes involved in regulation of primary dendritogenesis.To determine the critical transcriptional window during BMP-induced dendritic growth, morphometric analysis of microtubule-associated protein (MAP-2)-immunopositive processes was used to quantify dendritic growth in cultures exposed to the transcription inhibitor actinomycin-D added at varying times after addition of BMP-7. BMP-7-induced dendritic growth was blocked when transcription was inhibited within the first 24 hr after adding exogenous BMP-7. Thus, total RNA was isolated from sympathetic neurons exposed to three different experimental conditions: (1) no BMP-7 treatment; (2) treatment with BMP-7 for 6 hr; and (3) treatment with BMP-7 for 24 hr. Affymetrix oligonucleotide microarrays were used to identify differential gene expression under these three culture conditions. BMP-7 significantly regulated 56 unique genes at 6 hr and 185 unique genes at 24 hr. Bioinformatic analyses implicate both established and novel genes and signaling pathways in primary dendritogenesis.This study provides a unique dataset that will be useful in generating testable hypotheses regarding transcriptional control of the initial stages of dendritic growth. Since BMPs selectively promote dendritic growth in central neurons as well, these findings may be generally applicable to dendritic growth in other neuronal cell types

Condensed Phase Adsorption and Reactivity: Extraterrestrial Ices, Isotopic Enrichment, Olefin Oxidation, and Nerve Agent Simulants

This thesis probes interfacial dynamics of complex molecular thin films. This work is focused on sticking and hydrogen bonding of small molecules on and in astrophysical ices, differential condensation of isotopologues, oxidation of an important industrial alkene, and thermal destruction of a chemical warfare agent. While these systems vary greatly, they all focus on elucidating how film structure and morphology impact adsorption and reactivity. When examining different astrophysical ices (crystalline, non-porous amorphous solid water, and porous amorphous-solid water), we find that ice morphology vastly changed the interaction with small hydrocarbons. Not only do the pores allow more multiple collisions yielding a higher sticking probability for methane, the undercoordinated water molecules in the porous films form more hydrogen bonds with acetone. When switching away from ices to methane isotopologues, we determine that film composition vastly impacts adsorption behavior. By making a small mass adjustment from methane to heavy methane, we find that there is preferential condensation for heavy methane (CD4). This finding, confirmed from both experimental as well as novel theoretical gas-surface chemical trajectory simulations indicates a better energy transfer for the heavier isotopologue. We next focus on a larger hydrocarbon (propene) to facilitate increased chemical complexity upon exposure to oxygen. We conclude that oxygen is only able to diffuse through and react with the ordered film indicating the important role that film structure and morphology play in limiting reactivity even for reactions with low barriers. Lastly, we determined the mechanism for the destruction of the nerve agent simulant, diisopropyl methylphosphonate (DIMP), under atmospheric and oxygen depleted conditions which can directly inform chemical warfare mitigation strategies

Isotopic Enrichment Resulting from Differential Condensation of Methane Isotopologues Involving Non-equilibrium Gas–Surface Collisions Modeled with Molecular Dynamics Simulations

We employ molecular dynamics simulations to understand the energy transfer processes involved during the collisions of CH4 and CD4 with CH4 layered surfaces at 20 K in order to explain our experimental finding of preferential adsorption of CD4 compared to CH4. There is good agreement between our MD simulations and our experimental results. We find that gas–surface collisional energy accommodation is dominated by exchange involving the translational degrees of freedom of the incident molecule and intermolecular vibrations of the interface. This observation allows us to understand that the cause of CD4 preferential sticking arises from its propensity to lose more energy during its first impact with the surface, inducing longer residence times and leading to increased probability of becoming trapped and condensed onto the surface. Systematic trends are seen for sticking probabilities and energy transfer when we explore the behavior of the other H/D-substituted isotopologues of methane. These molecular insights provide context into the adsorption behavior occurring on icy dust grains in our solar system. Because adsorption is often the first step, trapping efficiency differences between isotopologues have notable implications for condensed phase reaction probabilities involving isotopically substituted species and subsequent events leading to increased molecular complexity. Aside from astrophysical significance, our findings have direct implications for novel isotope enrichment mechanisms under non-equilibrium conditions involving the preferential condensation of heavier isotopes and isotopologues during gas–surface collisions under specifically selected substrate, gas mixture, and incident kinematic conditions

Laboratory astrochemistry of and on dust and ices: general discussion

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Behavioral management leads to reduction in aggression in a child and adolescent psychiatric inpatient unit

Objective: Aggression is common in children and adolescents admitted to psychiatric inpatient units. Few interventions for reducing aggressive behaviors have been identified. This study aimed to evaluate the impact of a milieu-based behavioral management program on the frequency of aggressive behaviors in a child and adolescent mental health inpatient unit. Method: The behavioral management program incorporated individualized patient management plans, early detection and prevention, staff training, reinforcement of appropriate behaviors, and intervention using the least restrictive option. Outcomes were assessed for 6 months before and after program introduction, and included episodes of aggressive behavior, injuries, use of physical restraint, seclusion, p.r.n. sedation, use of security services, and staffing factors. Results: Implementation of behavioral management led to a significant reduction in the episodes of aggressive behavior (p < .05) and other unwanted outcomes including injuries (p < .05), use of physical restraint (p < .001), and duration of seclusion (p < .001). These outcomes were achieved without reducing the number of admissions, changing the types of patients admitted, increasing staff costs, or increasing the use of p.r.n. medications. Conclusions: Aggressive behaviors in child and adolescent psychiatric inpatient units can be reduced by implementing a broad-based behavioral management program. These findings highlight the importance of organizational approaches to behavior and risk management