Identification of novel post-transcriptional features in olfactory receptor family mRNAs.

Olfactory receptor (Olfr) genes comprise the largest gene family in mice. Despite their importance in olfaction, how most Olfr mRNAs are regulated remains unexplored. Using RNA-seq analysis coupled with analysis of pre-existing databases, we found that Olfr mRNAs have several atypical features suggesting that post-transcriptional regulation impacts their expression. First, Olfr mRNAs, as a group, have dramatically higher average AU-content and lower predicted secondary structure than do control mRNAs. Second, Olfr mRNAs have a higher density of AU-rich elements (AREs) in their 3'UTR and upstream open reading frames (uORFs) in their 5 UTR than do control mRNAs. Third, Olfr mRNAs have shorter 3' UTR regions and with fewer predicted miRNA-binding sites. All of these novel properties correlated with higher Olfr expression. We also identified striking differences in the post-transcriptional features of the mRNAs from the two major classes of Olfr genes, a finding consistent with their independent evolutionary origin. Together, our results suggest that the Olfr gene family has encountered unusual selective forces in neural cells that have driven them to acquire unique post-transcriptional regulatory features. In support of this possibility, we found that while Olfr mRNAs are degraded by a deadenylation-dependent mechanism, they are largely protected from this decay in neural lineage cells

Plasma deposition of constrained layer damping coatings

Plasma techniques are used to generate constrained layer damping (CLD) coatings on metallic substrates. The process involves the deposition of relatively thick, hard ceramic layers on to soft polymeric damping materials while maintaining the integrity of both layers. Reactive plasma sputter-deposition from an aluminium alloy target is used to deposit alumina layers, with Young's modulus in the range 77-220GPa and thickness up to 335 μ, on top of a silicone film. This methodology is also used to deposit a 40 μ alumina layer on a conventional viscoelastic damping film to produce an integral damping coating. Plasma CLD systems are shown to give at least 50 per cent more damping than equivalent metal-foil-based treatments. Numerical methods for rapid prediction of the performance of such coatings are discussed and validated by comparison with experimental results

Effects of Art Intervention on Pediatric Anxiety and Pain in the Medical Setting

Introduction: Hospitalization and illness can be a painful and stressful time for a child. There may be anxiety over procedures and inpatient stays disrupt normal routines. Previous research found that for pre-school aged children, having parents around, having the help of the hospital staff, and playing an active role in alleviating their fears were the most helpful in reducing anxiety. Another study found that visual creative expressions can be meaningful experiences for young adult cancer survivors. Additionally, there is abundant literature on formal art therapy and its favorable effects on children in the hospital, however, there are fewer studies investigating less standardized “art intervention” in the same population. The purpose of our project was to assess whether art intervention reduces anxiety and pain in inpatient and outpatient pediatric patients.https://scholarworks.uvm.edu/comphp_gallery/1224/thumbnail.jp

Damping and decoherence of a nanomechanical resonator due to a few two level systems

We consider a quantum model of a nanomechanical flexing beam resonator interacting with a bath comprising a few damped tunneling two level systems (TLS's). In contrast with a resonator interacting bilinearly with an ohmic free oscillator bath (modeling clamping loss, for example), the mechanical resonator damping is amplitude dependent, while the decoherence of quantum superpositions of mechanical position states depends only weakly on their spatial separation

Time-Course Analysis of Brain Regional Expression Network Responses to Chronic Intermittent Ethanol and Withdrawal: Implications for Mechanisms Underlying Excessive Ethanol Consumption

Long lasting abusive consumption, dependence, and withdrawal are characteristic features of alcohol use disorders (AUD). Mechanistically, persistent changes in gene expression are hypothesized to contribute to brain adaptations leading to ethanol toxicity and AUD. We employed repeated chronic intermittent ethanol (CIE) exposure by vapor chamber as a mouse model to simulate the cycles of ethanol exposure and withdrawal commonly seen with AUD. This model has been shown to induce progressive ethanol consumption in rodents. Brain CIE-responsive expression networks were identified by microarray analysis across five regions of the mesolimbic dopamine system and extended amygdala with tissue harvested from 0-hours to 7-days following CIE. Weighted Gene Correlated Network Analysis (WGCNA) was used to identify gene networks over-represented for CIE-induced temporal expression changes across brain regions. Differential gene expression analysis showed that long-lasting gene regulation occurred 7-days after the final cycle of ethanol exposure only in prefrontal cortex (PFC) and hippocampus. Across all brain regions, however, ethanol-responsive expression changes occurred mainly within the first 8-hours after removal from ethanol. Bioinformatics analysis showed that neuroinflammatory responses were seen across multiple brain regions at early time-points, whereas co-expression modules related to neuroplasticity, chromatin remodeling, and neurodevelopment were seen at later time-points and in specific brain regions (PFC or HPC). In PFC a module containing Bdnf was identified as highly CIE responsive in a biphasic manner, with peak changes at 0 hours and 5 days following CIE, suggesting a possible role in mechanisms underlying long-term molecular and behavioral response to CIE. Bioinformatics analysis of this network and several other modules identified Let-7 family microRNAs as potential regulators of gene expression changes induced by CIE. Our results suggest a complex temporal and regional pattern of widespread gene network responses involving neuroinflammatory and neuroplasticity related genes as contributing to physiological and behavioral responses to chronic ethanol

Serine Phosphorylation of SR Proteins Is Required for Their Recruitment to Sites of Transcription In Vivo

Expression of most RNA polymerase II transcripts requires the coordinated execution of transcription, splicing, and 3′ processing. We have previously shown that upon transcriptional activation of a gene in vivo, pre-mRNA splicing factors are recruited from nuclear speckles, in which they are concentrated, to sites of transcription (Misteli, T., J.F. Cáceres, and D.L. Spector. 1997. Nature. 387:523–527). This recruitment process appears to spatially coordinate transcription and pre-mRNA splicing within the cell nucleus. Here we have investigated the molecular basis for recruitment by analyzing the recruitment properties of mutant splicing factors. We show that multiple protein domains are required for efficient recruitment of SR proteins from nuclear speckles to nascent RNA. The two types of modular domains found in the splicing factor SF2/ ASF exert distinct functions in this process. In living cells, the RS domain functions in the dissociation of the protein from speckles, and phosphorylation of serine residues in the RS domain is a prerequisite for this event. The RNA binding domains play a role in the association of splicing factors with the target RNA. These observations identify a novel in vivo role for the RS domain of SR proteins and suggest a model in which protein phosphorylation is instrumental for the recruitment of these proteins to active sites of transcription in vivo

The neural correlates of emotion regulation by implementation intentions

Several studies have investigated the neural basis of effortful emotion regulation (ER) but the neural basis of automatic ER has been less comprehensively explored. The present study investigated the neural basis of automatic ER supported by ‘implementation intentions’. 40 healthy participants underwent fMRI while viewing emotion-eliciting images and used either a previously-taught effortful ER strategy, in the form of a goal intention (e.g., try to take a detached perspective), or a more automatic ER strategy, in the form of an implementation intention (e.g., “If I see something disgusting, then I will think these are just pixels on the screen!”), to regulate their emotional response. Whereas goal intention ER strategies were associated with activation of brain areas previously reported to be involved in effortful ER (including dorsolateral prefrontal cortex), ER strategies based on an implementation intention strategy were associated with activation of right inferior frontal gyrus and ventro-parietal cortex, which may reflect the attentional control processes automatically captured by the cue for action contained within the implementation intention. Goal intentions were also associated with less effective modulation of left amygdala, supporting the increased efficacy of ER under implementation intention instructions, which showed coupling of orbitofrontal cortex and amygdala. The findings support previous behavioural studies in suggesting that forming an implementation intention enables people to enact goal-directed responses with less effort and more efficiency

Debris-covered glacier systems and associated glacial lake outburst flood hazards:Challenges and prospects

Glaciers respond sensitively to climate variability and change, with associated impacts on meltwater production, sea-level rise and geomorphological hazards. There is a strong societal interest in understanding the current response of all types of glacier systems to climate change and how they will continue to evolve in the context of the whole glacierized landscape. In particular, understanding the current and future behaviour of debris-covered glaciers is a 'hot topic' in glaciological research because of concerns for water resources and glacier-related hazards. The state of these glaciers is closely related to various hazardous geomorphological processes which are relatively poorly understood. Understanding the implications of debris-covered glacier evolution requires a systems approach. This includes the interplay of various factors such as local geomorphology, ice ablation patterns, debris characteristics and glacier lake growth and development. Such a broader, contextualized understanding is prerequisite to identifying and monitoring the geohazards and hydrologic implications associated with changes in the debris-covered glacier system under future climate scenarios. This paper presents a comprehensive review of current knowledge of the debris-covered glacier landsystem. Specifically, we review state-of-the-art field-based and the remote sensing-based methods for monitoring debris-covered glacier characteristics and lakes and their evolution under future climate change. We advocate a holistic process-based framework for assessing hazards associated with moraine-dammed glacio-terminal lakes that are a projected end-member state for many debris-covered glaciers under a warming climat

Effects of the Selective GSK3B Inhibitor, Tideglusib, on Ethanol Consumption, Anxiety-like Behavior, Taste Preference, and Downstream Proteins

Background: We have shown modulations in glycogen synthase kinase 3 beta (GSK3B) abundance or activity regulate ethanol consumption, suggesting potential as a therapeutic target for alcohol use disorder (AUD). Here we report the GSK3B inhibitor tideglusib’s actions on ethanol consumption, basal behaviors, and modulation of GSK3B targets. Methods: C57BL/6J males and females received i.g. 200mg/kg tideglusib, except drinking-in-the-dark (males;100mg/kg i.p.). Drinking-in-the-dark (DID): Mice given 20% ethanol 4-hours, 4-days/week x 3 weeks and then i.p. tideglusib or vehicle x 4 days in a Latin Square design with ethanol consumption measured daily. Light/Dark Box: Mice gavaged with tideglusib or vehicle and i.p. injected with 1.8g/kg ethanol or saline then tested for 10-min. Taste Preference: Mice received tideglusib x 6 days and then tested daily for saccharin or quinine taste preference. Western Blots: Mice received tideglusib or vehicle i.g. 3x/week for 2-weeks and mPFC assayed for phosphorylated and total GSK3B, Dynamin1, and PSD-95. Results: Tideglusib decreased ethanol DID consumption, transiently increased locomotion, and had no effect on anxiety-like behaviors or taste preference. Only total Dynamin1 showed tideglusib-induced modulation where females had increased Dynamin1 and decreased pDynamin1/total Dynamin1. Conclusion: Tideglusib is a promising AUD therapeutic, rapidly decreasing ethanol consumption in a binge-drinking model. Tideglusib is likely not reducing consumption by altering taste or anxiety-like behaviors. Dynamin1 is integral in activity-dependent bulk endocytosis and requires GSK3B-induced rephosphorylation. Tideglusib increased Dynamin1 levels likely represent a compensatory response to decreased GSK3B activity, providing insight to tideglusib’s mechanism in ethanol behaviors. Funded by NIAAA grant R01AA027581.https://scholarscompass.vcu.edu/gradposters/1177/thumbnail.jp