753 research outputs found

    VX penetration following percutaneous poisoning: a dermal microdialysis study in the guinea pig

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    VX, a potent organophosphorus compound, acts primarily by irreversibly inhibiting acetylcholinesterase resulting in an accumulation of acetylcholine, which produces the characteristic signs of nerve agent poisoning. VX is a low-volatility agent, and therefore the most likely route of absorption into the body is via the skin. This study demonstrates for the first time that it is possible to follow the time course of percutaneous VX penetration using the technique of dermal microdialysis and that VX is absorbed through the skin of the anesthetized guinea pig in a concentration-dependent manner. A linear microdialysis probe (5-kDa cut-off) was implanted in the dermis of the back of the guinea pig and perfused (5 mu L/min) with physiological Ringer's solution. VX (296 or 592 mu g/kg) was applied (33 mu L/kg) over the site of the microdialysis probe and dialysate samples collected for up to 6 h. The VX dialysate concentration was measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Quantitation was performed over the range 0.1 to 100 ng/mL and the calibration was linear. VX was detected within 15 min, reaching a peak at 30 min following both VX doses. After this time the VX concentration decreased. There was a clear dose-dependent recovery of VX in the dialysate and the total amount recovered was statistically significant between the two doses. This study has clearly shown that microdialysis can be used to follow the time course of the percutaneous absorption of VX in the anesthetized guinea pig and will be used in future studies to develop improved medical countermeasures

    Early presynaptic and late postsynaptic components contribute independently to Brain-Derived Neurotrophic Factor-induced synaptic plasticity

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    Trophin-induced synaptic plasticity consists of both presynaptic and postsynaptic processes. The potential interdependence of these mechanisms and their temporal relationships are undefined. The synaptic vesicle protein Rab3A is required for the early, initial 10 min phase, but not for the later phase of BDNF-enhanced transmission. We now examine the temporal distinction and mechanistic relationships between these phases of BDNF action. Rab3A mutant cells did not exhibit increased mEPSC frequency in response to BDNF in cell culture, indicating absence of the presynaptic component. In contrast, BDNF enhanced post-synaptic glutamate-induced current in the mutant neurons as in the wildtype, indicating that the postsynaptic component of the response was intact. Finally, the postsynaptic NMDA receptor subunit NR2B was phosphorylated at Tyr1472 by BDNF in Rab3A knockouts, as previously shown in wildtype. Our results are the first to demonstrate that presynaptic and postsynaptic components of BDNF-enhanced synaptic activity are independent and temporally distinct.Peer reviewe

    Leduc, Janet L. Kaminski. Zebra mussels

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    1 online resource (2 pages)"February 23, 2021."Summarizes laws and regulations in New England that restrict the movement or possession of zebra mussels. Updates OLR research report 2011-R-001

    [Review of] Reading Joss Whedon. Rhonda V. Wilcox, Tanya R. Cochran, Cynthea Masson, and David Lavery, eds. Syracuse: Syracuse University Press, 2014

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    Review of volume of essays on Joss Whedon's television, film, and comic book output

    Leduc, Janet L. Kaminski. Carrying handguns in state parks or forests

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    1 online resource (3 pages)"October 29, 2020."Discusses a person's ability to legally carry a handgun (i.e., a pistol or revolver) in a Connecticut state park or forest. Updates OLR research report 2010-R-047

    Rab3A is required for brain-derived neurotrophic factor-induced synaptic plasticity: transcriptional analysis at the population and single-cell levels

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    Brain-derived neurotrophic factor (BDNF) modulates synaptic strength in hippocampal neurons, in addition to promoting survival and differentiation. To identify genes involved in trophic regulation of synaptic plasticity, we have used a multidisciplinary approach of differential display and family-specific slot blots in combination with whole-cell patch-clamp recordings of dissociated hippocampal neurons. Three hour exposure to BDNF elicited a 2.6-fold increase in synaptic charge and a concomitant induction of 11 genes as revealed by differential display, including the small GTP-binding vesicular trafficking protein Rab3A and the enzymeguanylate cyclase (GC). Slot blot analysis on a population of neurons confirmed an average of 3.1-fold induction of these clones. In contrast, individual pyramidal-like neurons that were first characterized electrophysiologically in the presence of BDNF and subjected to transcriptional analysis displayed more robust increases (4.8-fold), emphasizing the neuronal heterogeneity. Transcriptional changes of Rab3A and GC were accompanied by translational regulation, shown by Western blot analysis. Furthermore, a number of GC-associated and Rab3A effector molecules were induced by BDNF at either the gene or protein levels. The functional role of Rab3A in BDNF-induced synaptic plasticity was assessed using cells derived from Rab3A knock-out mice. These neurons failed to show an increase in synaptic charge in response to BDNF at 10 min; however a late response to BDNF was detected at 20 min. This late response was similar in time course to that induced by postsynaptic activation of glutamate receptors. Our results demonstrate a requirement for Rab3A and may reveal a temporal distinction between presynaptic and postsynaptic mechanisms of BDNF-induced synaptic plasticity associated with learning and memory.Peer reviewe

    Brain-Derived Neurotrophic Factor-Induced Gene Expression Reveals Novel Actions of VGF in Hippocampal Synaptic Plasticity

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    Synaptic strengthening induced by brain-derived neurotrophic factor (BDNF) is associated with learning and is coupled to transcriptional activation. However, identification of the spectrum of genes associated with BDNF-induced synaptic plasticity and the correlation of expression with learning paradigms in vivo has not yet been studied. Transcriptional analysis of BDNF-induced synaptic strengthening in cultured hippocampal neurons revealed increased expression of the immediate early genes (IEGs), c-fos, early growth response gene 1 (EGR1), activity-regulated cytoskeletal-associated protein (Arc) at 20 min, and the secreted peptide VGF (non-acronymic) protein precursor at 3 hr. The induced genes served as prototypes to decipher mechanisms of both BDNF-induced transcription and plasticity. BDNF-mediated gene expression was tyrosine kinase B and mitogen-activated protein kinase-dependent, as demonstrated by pharmacological studies. Single-cell transcriptional analysis of Arc after whole-cell patch-clamp recordings indicated that increased gene expression correlated with enhancement of synaptic transmission by BDNF. Increased expression in vitro predicted elevations in vivo: VGF and the IEGs increased after trace eyeblink conditioning, a hippocampal-dependent learning paradigm. VGF protein was also upregulated by BDNF treatment and was expressed in a punctate manner in dissociated hippocampal neurons. Collectively, these findings suggested that the VGF neuropeptides may regulate synaptic function. We found a novel function for VGF by applying VGF peptides to neurons. C-terminal VGF peptides acutely increased synaptic charge in a dose-dependent manner, whereas N-terminal peptide had no effect. These observations indicate that gene profiling in vitro can reveal new mechanisms of synaptic strengthening associated with learning and memory.Peer reviewe

    State park and forest funding / analyst: Janet Kaminski Leduc

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    1 online resource (2 unnumbered pages)"December 22, 2020."; Includes bibliographical references (2nd unnumbered page)Discusses funding of Connecticut state parks and forest

    Hemp production in Connecticut / analyst: Janet Kaminski Leduc

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    1 online resource (2 unnumbered pages)November 4, 2020."; Includes bibliographical references (2nd unnumbered page)Discusses state law concerning hemp and hemp product
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