Acute Ethanol Administration Rapidly Increases Phosphorylation of Conventional Protein Kinase C in Specific Mammalian Brain Regions in Vivo

Background Protein kinase C (PKC) is a family of isoenzymes that regulate a variety of functions in the central nervous system including neurotransmitter release, ion channel activity, and cell differentiation. Growing evidence suggests that specific isoforms of PKC influence a variety of behavioral, biochemical, and physiological effects of ethanol in mammals. The purpose of this study was to determine whether acute ethanol exposure alters phosphorylation of conventional PKC isoforms at a threonine 674 (p-cPKC) site in the hydrophobic domain of the kinase, which is required for its catalytic activity. Methods Male rats were administered a dose range of ethanol (0, 0.5, 1, or 2 g/kg, intragastric) and brain tissue was removed 10 minutes later for evaluation of changes in p-cPKC expression using immunohistochemistry and Western blot methods. Results Immunohistochemical data show that the highest dose of ethanol (2 g/kg) rapidly increases p-cPKC immunoreactivity specifically in the nucleus accumbens (core and shell), lateral septum, and hippocampus (CA3 and dentate gyrus). Western blot analysis further showed that ethanol (2 g/kg) increased p-cPKC expression in the P2 membrane fraction of tissue from the nucleus accumbens and hippocampus. Although p-cPKC was expressed in numerous other brain regions, including the caudate nucleus, amygdala, and cortex, no changes were observed in response to acute ethanol. Total PKC? immunoreactivity was surveyed throughout the brain and showed no change following acute ethanol injection

Antagonism of neurosteroid modulation of native γ-aminobutyric acid receptors by (3α,5α)-17-phenylandrost-16-en-3-ol

Endogenous pregnane neurosteroids are allosteric modulators at γ-aminobutyric acid type-A (GABAA) receptors at nanomolar concentrations. There is direct evidence for multiple distinct neurosteroid binding sites on GABAA receptors, dependent upon subunit composition and stoichiometry. This view is supported by the biphasic kinetics of various neuroactive steroids, enantioselectivity of some neurosteroids, selective mutation studies of recombinantly expressed receptors and the selectivity of the neurosteroid antagonist (3α,5α)-17-phenylandrost-16-en-3-ol (17PA) on 5α-pregnane steroid effects on recombinant GABAA receptors expressed in Xenopus oocytes and native receptors in dissociated neurons. However, it is unclear whether this antagonist action is present in a mature mammalian system. The present study evaluated the antagonist activity of 17PA on neurosteroid agonists both in vivo and in vitro by examining the effects of 17PA on 5α-pregnane-induced sedation in rats, native mature GABAA receptor ion channels utilizing the chloride flux assay and further studies in recombinant α1β2γ2 receptors. The data show that 17PA preferentially inhibits 3α,5α-THP vs. alphaxalone in vivo, preferentially inhibits 3α,5α-THDOC vs. alphaxalone potentiation of GABA-mediated Cl- uptake in adult cerebral cortical synaptoneurosomes, but shows no specificity for 3α,5α-THDOC vs. alphaxalone in recombinant α1β2γ2 receptors. These data provide further evidence of the specificity of 17PA and the heterogeneity of neurosteroid recognition sites on GABAA receptors in the CNS

National Register Testing At Sites 41BP585, 41BP594, And 41BP595 Three Oaks Mine, Bastrop County, Texas

Between October 2012 and July 2013, Atkins conducted National Register of Historic Places (NRHP) eligibility testing at historic sites 41BP585 and 41BP594 and prehistoric site 41BP595, located within the Three Oaks Mine in Bastrop County, Texas, which is owned and operated by Luminant. Impacts to all three sites are anticipated as a result of planned mine development. This work was conducted under the direction of Principal Investigator David L. Sherman. This report of investigations was written at Atkins and is being finalized by Blanton & Associates, with David L. Sherman remaining as the Principal Investigator. This work demonstrated that significant archeological deposits that may contribute to the overall NRHP eligibility statuses of the two historic sites are absent at both sites. Standing architecture at 41BP594, however, has previously been determined to be eligible for listing on the NRHP (Martin 2001). Archival research conducted as part of the current investigation into the histories of the historic sites remains inconclusive with respect to the identity of their 1870s and earlier occupants. Testing at prehistoric site 41BP595 indicated it resulted from multiple occupational episodes during the period from the late Paleoindian to the Late Prehistoric. Shovel testing and mechanical trenching revealed the presence of an expansive buried anthrogenic A soil horizon, or midden, replete with preserved subsistence remains. Mechanical trenching also exposed a variety of burned rock cooking facilities partially surrounding the midden area. Radiocarbon assays of burned nut shells recovered from feature contexts, along with the assemblage of diagnostic lithic artifacts, suggest the site was most intensively occupied from the Late Archaic to the early Late Prehistoric. A suite of special studies was conducted on burned rock samples recovered from four of the better-preserved burned rock features. These studies, which include residue, starch, and phytolith analysis, suggest that the burned rock features were used in part to process tubers/roots and grass seeds for subsistence. Macrobotanical analysis of flotation samples recovered from feature contexts identified spent fuel remains including oak and hickory wood and subsistence remains including oak, hickory, black walnut, and acorn burned nut shells. A small amount of burned bulb, possibly representing wild onion, was also recovered through flotation. These findings suggest that significant archeological deposits important to understanding the Late Archaic to early Late Prehistoric period have been preserved at 41BP595

The Grizzly, September 24, 1982

Crime Comes to Collegeville: Attempted Assault on Main Street • New Advising System for Freshmen Students • Union Program Board Projects VCR Movies • McNamara to Speak at Ursinus Gym • What? More New Faculty? • Speech Exemption Exam Set • Writing Center Opens • Time for Action • Name That Tune! • In the Limelight • USGA Notes • Forum Review • Kohler Exhibits at Myrin • Brown Sets X-country Record • Volleyball Team Keeps Their Winning Ways • Field Hockey Tops Gettysburg in O.T. • U.C. Soccer Wins Their First • Grizzlies Look Tough in 6-6 Tiehttps://digitalcommons.ursinus.edu/grizzlynews/1082/thumbnail.jp

Antagonism of neurosteroid modulation of native gamma-aminobutyric acid receptors by (3alpha,5alpha)-17-phenylandrost-16-en-3-ol.

Endogenous pregnane neurosteroids are allosteric modulators at ?-aminobutyric acid type-A (GABAA) receptors at nanomolar concentrations. There is direct evidence for multiple distinct neurosteroid binding sites on GABAA receptors, dependent upon subunit composition and stoichiometry. This view is supported by the biphasic kinetics of various neuroactive steroids, enantioselectivity of some neurosteroids, selective mutation studies of recombinantly expressed receptors and the selectivity of the neurosteroid antagonist (3?,5?)-17-phenylandrost-16-en-3-ol (17PA) on 5?-pregnane steroid effects on recombinant GABAA receptors expressed in Xenopus oocytes and native receptors in dissociated neurons. However, it is unclear whether this antagonist action is present in a mature mammalian system. The present study evaluated the antagonist activity of 17PA on neurosteroid agonists both in vivo and in vitro by examining the effects of 17PA on 5?-pregnane-induced sedation in rats, native mature GABAA receptor ion channels utilizing the chloride flux assay and further studies in recombinant ?1?2?2 receptors. The data show that 17PA preferentially inhibits 3?,5?-THP vs. alphaxalone in vivo, preferentially inhibits 3?,5?-THDOC vs. alphaxalone potentiation of GABA-mediated Cl? uptake in adult cerebral cortical synaptoneurosomes, but shows no specificity for 3?,5?-THDOC vs. alphaxalone in recombinant ?1?2?2 receptors. These data provide further evidence of the specificity of 17PA and the heterogeneity of neurosteroid recognition sites on GABAA receptors in the CNS

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO