4,678 research outputs found

    Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior

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    Increased tonic activity of locus coeruleus noradrenergic (LC-NE) neurons induces anxiety-like and aversive behavior. While some information is known about the afferent circuitry that endogenously drives this neural activity and behavior, the downstream receptors and anatomical projections that mediate these acute risk aversive behavioral states via the LC-NE system remain unresolved. Here we use a combination of retrograde tracing, fast-scan cyclic voltammetry, electrophysiology, and in vivo optogenetics with localized pharmacology to identify neural substrates downstream of increased tonic LC-NE activity in mice. We demonstrate that photostimulation of LC-NE fibers in the BLA evokes norepinephrine release in the basolateral amygdala (BLA), alters BLA neuronal activity, conditions aversion, and increases anxiety-like behavior. Additionally, we report that β-adrenergic receptors mediate the anxiety-like phenotype of increased NE release in the BLA. These studies begin to illustrate how the complex efferent system of the LC-NE system selectively mediates behavior through distinct receptor and projection-selective mechanisms

    Phosphorylation of pRb: mechanism for RB pathway inactivation in MYCN-amplified retinoblastoma.

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    A small, but unique subgroup of retinoblastoma has been identified with no detectable mutation in the retinoblastoma gene (RB1) and with high levels of MYCN gene amplification. This manuscript investigated alternate pathways of inactivating pRb, the encoded protein in these tumors. We analyzed the mutation status of the RB1 gene and MYCN copy number in a series of 245 unilateral retinoblastomas, and the phosphorylation status of pRb in a subset of five tumors using immunohistochemistry. There were 203 tumors with two mutations in RB1 (RB1(-/-) , 83%), 29 with one (RB1(+/-) , 12%) and 13 with no detectable mutations (RB1(+/+) , 5%). Eighteen tumors carried MYCN amplification between 29 and 110 copies: 12 had two (RB1(-/-) ) or one RB1 (RB1(+/-) ) mutations, while six had no mutations (RB1(+/+) ). Immunohistochemical staining of tumor sections with antibodies against pRb and phosphorylated Rb (ppRb) displayed high levels of pRb and ppRb in both RB1(+/+) and RB1(+/-) tumors with MYCN amplification compared to no expression of these proteins in a classic RB1(-/-) , MYCN-low tumor. These results establish that high MYCN amplification can be present in retinoblastoma with or without coding sequence mutations in the RB1 gene. The functional state of pRb is inferred to be inactive due to phosphorylation of pRb in the MYCN-amplified retinoblastoma without coding sequence mutations. This makes inactivation of RB1 by gene mutation or its protein product, pRb, by protein phosphorylation, a necessary condition for initiating retinoblastoma tumorigenesis, independent of MYCN amplification

    Mini workshop - Real World Engineering Projects: Discovery-based curriculum modules for first-year students

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    This mini workshop is organized to provide an interactive forum for the introduction a set of six new curriculum modules developed under IEEE's Real World Engineering Projects (RWEP) program. The modules, which are representative of a larger collection of curriculum modules available to the public via an open-access RWEP web portal, are designed for use in the first-year engineering and computer science classroom, and are hands-on, team-based projects that emphasize the societal impact of the work that engineers do. After a brief introduction to the RWEP program and the six showcased curriculum modules, the authors of the modules will present their ideas and demonstrate the laboratory activities associated with their modules in interactive, informal simultaneous sessions. © 2010 IEEE.published_or_final_versionThe 40th ASEE/IEEE Frontiers in Education Conference (FIE) 2010, Arlington, VA., 27-30 October 2010. In Proceedings of 40th FIE, 2010, p. T2A1-T2A

    Mini workshop - Real World Engineering Projects: Discovery-based curriculum modules for first-year students

    Get PDF
    This mini workshop is organized to provide an interactive forum for the introduction a set of six new curriculum modules developed under IEEE's Real World Engineering Projects (RWEP) program. The modules, which are representative of a larger collection of curriculum modules available to the public via an open-access RWEP web portal, are designed for use in the first-year engineering and computer science classroom, and are hands-on, team-based projects that emphasize the societal impact of the work that engineers do. After a brief introduction to the RWEP program and the six showcased curriculum modules, the authors of the modules will present their ideas and demonstrate the laboratory activities associated with their modules in interactive, informal simultaneous sessions. © 2010 IEEE.published_or_final_versionThe 40th ASEE/IEEE Frontiers in Education Conference (FIE) 2010, Arlington, VA., 27-30 October 2010. In Proceedings of 40th FIE, 2010, p. T2A1-T2A

    HAT-P-56b: An inflated massive Hot Jupiter transiting a bright F star followed up with K2 Campaign 0 observations

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    We report the discovery of HAT-P-56b by the HATNet survey, an inflated hot Jupiter transiting a bright F type star in Field 0 of NASA's K2 mission. We combine ground-based discovery and follow-up light curves with high precision photometry from K2, as well as ground-based radial velocities from TRES on the FLWO 1.5m telescope to determine the physical properties of this system. HAT-P-56b has a mass of 2.18MJ2.18 M_J, radius of 1.47RJ1.47 R_J, and transits its host star on a near-grazing orbit with a period of 2.7908 d. The radius of HAT-P-56b is among the largest known for a planet with Mp>2MJM_p > 2 M_J. The host star has a V-band magnitude of 10.9, mass of 1.30 MM_\odot, and radius of 1.43 RR_\odot. The periodogram of the K2 light curve suggests the star is a γ\gamma Dor variable. HAT-P-56b is an example of a ground-based discovery of a transiting planet, where space-based observations greatly improve the confidence in the confirmation of its planetary nature, and also improve the accuracy of the planetary parameters.Comment: 13 pages, 11 figures, accepted by A

    Inter-observer agreement of canine and feline paroxysmal event semiology and classification by veterinary neurology specialists and non-specialists

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    Background: Advances in mobile technology mean vets are now commonly presented with videos of paroxysmal events by clients, but the consistency of the interpretation of these videos has not been investigated. The objective of this study was to investigate the level of agreement between vets (both neurology specialists and non-specialists) on the description and classification of videos depicting paroxysmal events, without knowing any results of diagnostic workup. An online questionnaire study was conducted, where participants watched 100 videos of dogs and cats exhibiting paroxysmal events and answered questions regarding: epileptic seizure presence (yes/ no), seizure type, consciousness status, and the presence of motor, autonomic and neurobehavioural signs. Agreement statistics (percentage agreement and kappa) calculated for each variable, with prevalence indices calculated to aid their interpretation. Results: Only a fair level of agreement (kappa = 0.40) was found for epileptic seizure presence. Overall agreement of seizure type was moderate (kappa = 0.44), with primary generalised seizures showing the highest level of agreement (kappa = 0.60), and focal the lowest (kappa = 0.31). Fair agreement was found for consciousness status and the presence of autonomic signs (kappa = 0.21-0.40), but poor agreement for neurobehavioral signs (kappa = 0.16). Agreement for motor signs ranged from poor (kappa = <= 0.20) to moderate (kappa = 0.41-0.60). Differences between specialists and non-specialists were identified. Conclusions: The relatively low levels of agreement described here highlight the need for further discussions between neurology experts regarding classifying and describing epileptic seizures, and additional training of non-specialists to facilitate accurate diagnosis. There is a need for diagnostic tools (e.g. electroencephalogram) able to differentiate between epileptic and non-epileptic paroxysms
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