The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) formulated with 2-phenoxyethanol in multidose vials given with routine vaccination in healthy infants: An open-label randomized controlled trial.

BACKGROUND: This open-label randomized controlled trial in infants compared safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated with the preservative 2-phenoxyethanol (2-PE) in a multidose vial (MDV) to the current PCV13 without 2-PE in a single-dose syringe (SDS). METHODS: Gambian infants were randomized 1:1 to receive PCV13 as either MDV or SDS at ages 2, 3, and 4months. Serotype-specific antipneumococcal antibody responses and opsonophagocytic activity ([OPA]; subset) were measured at age 5months. Noninferiority was declared if the lower bound of the 97.5% CI for the difference (MDV-SDS) in proportions of subjects achieving IgG concentrations ≥0.35μg/mL (primary endpoint) was greater than -10%. IgG geometric mean concentrations (GMCs) were noninferior if the lower limit of the two-sided 97.5% CI of the geometric mean ratio (MDV vs SDS) was greater than 0.5. Reactogenicity and other adverse events were collected. RESULTS: 500 participants were randomized and vaccinated; 489 (MDV: n=245; SDS: n=244) completed the trial. Noninferiority of MDV was demonstrated for all serotypes as measured by percentage of subjects achieving antibody responses above ≥0.35μg/mL. IgG GMCs (coprimary endpoint) also demonstrated noninferiority of MDV; OPA results supported these findings. Safety and tolerability were comparable between groups. CONCLUSIONS: PCV13 in MDV was safe and immunogenic when administered according to the routine schedule to infants. MDV was noninferior to SDS for all 13 pneumococcal serotypes. Comparable immunogenicity and safety profiles of PCV13 MDV and SDS suggest PCV13 MDV can help optimize vaccination in resource-limited settings. ClinicalTrials.gov NCT01964716 https://clinicaltrials.gov/ct2/show/NCT01964716

Psychotropic drug influences on brain acetylcholine utilization

The cholinergic antisynthesis agent HC-3 was given intraventricularly to young male rats 20–30 days old to deplete brain acetylcholine (ACh). The rate of HC-3 induced depletion of ACh was used as an index of ACh utilization. Total brain ACh was determined following various doses of chlordiazepoxide, pentobarbital, chlorpromazine, methotrimeprazine, imipramine, morphine, d -amphetamine, scopolamine, LSD-25, and phencyclidine given i.p. alone and after intraventricular administration of HC-3. It was found that psychotropic drugs have marked differential effects on the rate of HC-3 induced ACh depletion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46382/1/213_2004_Article_BF00421968.pd

NEUROPSYCHOPHARMACOLOGIC STUDIES OF MARIJUANA: SOME SYNTHETIC AND NATURAL THC DERIVATIVES IN ANIMALS AND MAN *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74859/1/j.1749-6632.1971.tb13996.x.pd

Effects of stress and REM sleep deprivation on the patterns of avoidance learning and brain acetylcholine in the mouse

Pure bred DBA/2J mice were subjected to varying degrees of stress and “water tank” REM sleep deprivation using one-animal cages, large platforms and/or poles. Subsequently, the animals were studied for acquisition, short-term and long-term retention using a conditioned avoidance procedure in a Warner type automated shuttle box. In addition, various groups of animals subjected to the same stressful procedures were sacrificed and brain acetylcholine (ACh) was measured by the frog rectus abdominus muscle bioassay. It was found that stress and REM sleep deprivation had no significant effect on acquisition and short-term retention but did impair long term retention of conditioned behavior. Moderate environmental stress also produced significant behavioral changes. Total brain ACh, under these environmental conditions, showed no significant changes from normal.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46385/1/213_2004_Article_BF00429278.pd

Measurement of the inclusive cross-section for the production of jets in association with a Z boson in proton-proton collisions at 8 TeV using the ATLAS detector

The inclusive cross-section for jet production in association with a Z boson decaying into an electron–positron pair is measured as a function of the transverse momentum and the absolute rapidity of jets using 19.9 fb −1 of s√=8 TeV proton–proton collision data collected with the ATLAS detector at the Large Hadron Collider. The measured Z + jets cross-section is unfolded to the particle level. The cross-section is compared with state-of-the-art Standard Model calculations, including the next-to-leading-order and next-to-next-to-leading-order perturbative QCD calculations, corrected for non-perturbative and QED radiation effects. The results of the measurements cover final-state jets with transverse momenta up to 1 TeV, and show good agreement with fixed-order calculations

Identification of boosted Higgs bosons decaying into b-quark pairs with the ATLAS detector at 13 TeV

This paper describes a study of techniques for identifying Higgs bosons at high transverse momenta decaying into bottom-quark pairs, H→bb¯ , for proton–proton collision data collected by the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy s√=13 TeV . These decays are reconstructed from calorimeter jets found with the anti- kt R=1.0 jet algorithm. To tag Higgs bosons, a combination of requirements is used: b-tagging of R=0.2 track-jets matched to the large-R calorimeter jet, and requirements on the jet mass and other jet substructure variables. The Higgs boson tagging efficiency and corresponding multijet and hadronic top-quark background rejections are evaluated using Monte Carlo simulation. Several benchmark tagging selections are defined for different signal efficiency targets. The modelling of the relevant input distributions used to tag Higgs bosons is studied in 36 fb −1 of data collected in 2015 and 2016 using g→bb¯ and Z(→bb¯)γ event selections in data. Both processes are found to be well modelled within the statistical and systematic uncertainties

Observation of Electroweak Production of a Same-Sign W Boson Pair in Association with Two Jets in pp Collisions root s=13 TeV with the ATLAS Detector

This Letter presents the observation and measurement of electroweak production of a same-sign W boson pair in association with two jets using 36.1     fb − 1 of proton-proton collision data recorded at a center-of-mass energy of √ s = 13     TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed in the detector fiducial phase-space region, defined by the presence of two same-sign leptons, electron or muon, and at least two jets with a large invariant mass and rapidity difference. A total of 122 candidate events are observed for a background expectation of 69 ± 7 events, corresponding to an observed signal significance of 6.5 standard deviations. The measured fiducial signal cross section is σ fid = 2.89 + 0.51 − 0.48 ( stat ) + 0.29 − 0.28 ( syst )     fb

Effects of physostigmine on rat brain acetylcholine, acetylcholinesterase and conditioned pole jumping,

The present study was designed to provide evidence that the behavioral effects of physostigmine are related to inhibition of brain acetylcholinesterase (AChE). Adult male Holtzman rats were trained to pole jump to a buzzer as the conditioned stimulus and to electric shock to the grid floor as the unconditioned stimulus. All drugs were given s.c. as base. Physostigmine (0.125-0.25 mg/kg) depressed pole jump behavior in methyl atropine (2.1 mg/kg) or saline-treated rats. (-) Hyoscyamine (1 mg/kg) blocked the actions of physostigmine, suggesting a central site of action.Total brain acetylcholine (ACh) and AChE were determined in various groups of animals. The increase in brain ACh and the decrease in AChE activity were negatively correlated in physostigmine-treated rats. These changes were highly correlated during the onset and peak of physostigmine behavioral effects but not during the recovery period. Although (-) hyoscyamine antagonized the behavioral effects of physostigmine, it did not alter the increase in brain ACh or decrease in brain AChE. It is concluded that most of the behavioral effects of physostigmine are related to central AChE inhibition.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33200/1/0000588.pd