We report on multifrequency observations performed during 2012 December-2013 August of the first narrow-line Seyfert 1 galaxy detected in gamma rays, PMN J0948+0022 (z equal to 0.5846). A gamma-ray ...flare was observed by the Large Area Telescope on board Fermi during 2012 December-2013 January, reaching a daily peak flux in the 0.1-100 GeV energy range of (155 plus or minus 31)×10(exp −8) ph cm (exp −2) s (exp −1) on 2013 January 1, corresponding to an apparent isotropic luminosity of approximately 1.5×10)exp 48) erg s(exp −1). The gamma-ray flaring period triggered Swift and VERITAS observations in addition to radio and optical monitoring by OVRO, MOJAVE, and CRTS. A strong flare was observed in optical, UV, and X- rays on 2012 December 30, quasi-simultaneously to the gamma-ray flare, reaching a record flux for this source from optical to gamma rays. VERITAS observations at very high energy (E greater than 100 GeV) during 2013 January 6-17 resulted in an upper limit of F(sub greater than 0.2 TeV) less than 4.0 × 10(exp −12) ph cm(exp −2) s(exp −1). We compared the spectral energy distribution (SED) of the flaring state in 2013 January with that of an intermediate state observed in 2011. The two SEDs, modelled as synchrotron emission and an external Compton scattering of seed photons from a dust torus, can be modelled by changing both the electron distribution parameters and the magnetic field.
ABSTRACT The F-type star KIC 8462852 has recently been identified as an exceptional target for search for extraterrestrial intelligence (SETI) observations. We describe an analysis methodology for ...optical SETI, which we have used to analyze nine hours of serendipitous archival observations of KIC 8462852 made with the VERITAS gamma-ray observatory between 2009 and 2015. No evidence of pulsed optical beacons, above a pulse intensity at the Earth of approximately , is found. We also discuss the potential use of imaging atmospheric Cherenkov telescope arrays in searching for extremely short duration optical transients in general.
Augmenting hippocampal neurogenesis represents a potential new strategy for treating depression. Here we test this possibility by comparing hippocampal neurogenesis in depression-prone ghrelin ...receptor (Ghsr)-null mice to that in wild-type littermates and by determining the antidepressant efficacy of the P7C3 class of neuroprotective compounds. Exposure of Ghsr-null mice to chronic social defeat stress (CSDS) elicits more severe depressive-like behavior than in CSDS-exposed wild-type littermates, and exposure of Ghsr-null mice to 60% caloric restriction fails to elicit antidepressant-like behavior. CSDS resulted in more severely reduced cell proliferation and survival in the ventral dentate gyrus (DG) subgranular zone of Ghsr-null mice than in that of wild-type littermates. Also, caloric restriction increased apoptosis of DG subgranular zone cells in Ghsr-null mice, although it had the opposite effect in wild-type littermates. Systemic treatment with P7C3 during CSDS increased survival of proliferating DG cells, which ultimately developed into mature (NeuN+) neurons. Notably, P7C3 exerted a potent antidepressant-like effect in Ghsr-null mice exposed to either CSDS or caloric restriction, while the more highly active analog P7C3-A20 also exerted an antidepressant-like effect in wild-type littermates. Focal ablation of hippocampal stem cells with radiation eliminated this antidepressant effect, further attributing the P7C3 class antidepressant effect to its neuroprotective properties and resultant augmentation of hippocampal neurogenesis. Finally, P7C3-A20 demonstrated greater proneurogenic efficacy than a wide spectrum of currently marketed antidepressant drugs. Taken together, our data confirm the role of aberrant hippocampal neurogenesis in the etiology of depression and suggest that the neuroprotective P7C3-compounds represent a novel strategy for treating patients with this disease.
Abstract Neurogenesis studies on the adult mouse hippocampal subgranular zone (SGZ) typically report increases or decreases in proliferation. However, key information is lacking about these ...proliferating SGZ precursors, from the fundamental—what dose of bromodeoxyuridine (BrdU) is appropriate for labeling all S phase cells?—to the detailed—what are the kinetics of BrdU-labeled cells and their progeny? To address these questions, adult C57BL/6J mice were injected with BrdU and BrdU-immunoreactive (IR) cells were quantified. Initial experiments with a range of BrdU doses (25–500 mg/kg) suggested that 150 mg/kg labels all actively dividing precursors in the mouse SGZ. Experiments using a saturating dose of BrdU suggested BrdU bioavailability is less than 15 min, notably shorter than in the developing mouse brain. We next explored precursor division and maturation by tracking the number of BrdU-IR cells and colabeling of BrdU with other cell cycle proteins from 15 min to 30 days after BrdU. We found that BrdU and the Gap2 and mitosis (G2 /M) phase protein pHisH3 maximally colocalized 8 h after BrdU, indicating that the mouse SGZ precursor cell cycle length is 14 h. In addition, triple labeling with BrdU and proliferating cell nuclear antigen (PCNA) and Ki-67 showed that BrdU-IR precursors and/or their progeny express these endogenous cell cycle proteins up to 4 days after BrdU injection. However, the proportion of BrdU/Ki-67-IR cells declined at a greater rate than the proportion of BrdU/PCNA-IR cells. This suggests that PCNA protein is detectable long after cell cycle exit, and that reliance on PCNA may overestimate the length of time a cell remains in the cell cycle. These findings will be critical for future studies examining the regulation of SGZ precursor kinetics in adult mice, and hopefully will encourage the field to move beyond counting BrdU-IR cells to a more mechanistic analysis of adult neurogenesis.
ABSTRACT The Galactic Center ridge has been observed extensively in the past by both GeV and TeV gamma-ray instruments revealing a wealth of structure, including a diffuse component and the point ...sources G0.9+0.1 (a composite supernova remnant) and Sgr A* (believed to be associated with the supermassive black hole located at the center of our Galaxy). Previous very high energy (VHE) gamma-ray observations with the H.E.S.S. experiment have also detected an extended TeV gamma-ray component along the Galactic plane in the >300 GeV gamma-ray regime. Here we report on observations of the Galactic Center ridge from 2010 to 2014 by the VERITAS telescope array in the >2 TeV energy range. From these observations we (1) provide improved measurements of the differential energy spectrum for Sgr A* in the >2 TeV gamma-ray regime, (2) provide a detection in the >2 TeV gamma-ray emission from the composite SNR G0.9+0.1 and an improved determination of its multi-TeV gamma-ray energy spectrum, and (3) report on the detection of VER J1746-289, a localized enhancement of >2 TeV gamma-ray emission along the Galactic plane.
ABSTRACT During moonlit nights, observations with ground-based Cherenkov telescopes at very high energies (VHEs, GeV) are constrained since the photomultiplier tubes (PMTs) in the telescope camera ...are extremely sensitive to the background moonlight. Observations with the VERITAS telescopes in the standard configuration are performed only with a moon illumination less than 35% of full moon. Since 2012, the VERITAS collaboration has implemented a new observing mode under bright moonlight, by either reducing the voltage applied to the PMTs (reduced-high-voltage; RHV configuration), or by utilizing UV-transparent filters. While these operating modes result in lower sensitivity and increased energy thresholds, the extension of the available observing time is useful for monitoring variable sources such as blazars and sources requiring spectral measurements at the highest energies. In this paper we report the detection of γ-ray flaring activity from the BL Lac object 1ES 1727+502 during RHV observations. This detection represents the first evidence of VHE variability from this blazar. The integral flux is above 250 GeV, which is about five times higher than the low-flux state. The detection triggered additional VERITAS observations during standard dark-time. Multiwavelength observations with the FLWO 48″ telescope, and the Swift and Fermi satellites are presented and used to produce the first spectral energy distribution (SED) of this object during γ-ray flaring activity. The SED is then fitted with a standard synchrotron-self-Compton model, placing constraints on the properties of the emitting region and of the acceleration mechanism at the origin of the relativistic particle population in the jet.
ABSTRACT Between the beginning of its full-scale scientific operations in 2007 and 2012, the VERITAS Cherenkov telescope array observed more than 130 blazars; of these, 26 were detected as ...very-high-energy (VHE; E > 100 GeV) γ-ray sources. In this work, we present the analysis results of a sample of 114 undetected objects. The observations constitute a total live-time of ∼570 hr. The sample includes several unidentified Fermi-Large Area Telescope (LAT) sources (located at high Galactic latitude) as well as all the sources from the second Fermi-LAT catalog that are contained within the field of view of the VERITAS observations. We have also performed optical spectroscopy measurements in order to estimate the redshift of some of these blazars that do not have spectroscopic distance estimates. We present new optical spectra from the Kast instrument on the Shane telescope at the Lick observatory for 18 blazars included in this work, which allowed for the successful measurement or constraint on the redshift of four of them. For each of the blazars included in our sample, we provide the flux upper limit in the VERITAS energy band. We also study the properties of the significance distributions and we present the result of a stacked analysis of the data set, which shows a 4 excess.
A variant in
ADGRE2,
encoding an adhesion G-protein–coupled receptor, is associated with vibratory urticaria. The variant probably causes disease; if so, it is likely to do so by weakening an ...autoinhibitory mechanism of the receptor.
Physical urticarias are disorders in which localized hives develop in response to any of various stimuli.
1
The histamine release that is associated with urticarias has implicated aberrant degranulation of mast cells in their pathogenesis.
2
Isolated or syndromic cold urticaria can be caused by variants in
NLRP3,
3
which encodes a component of the inflammasome signaling complex, or in
PLCG2,
4
which encodes a regulatory phospholipase. Otherwise, no pathogenic variants underlying physical urticarias have been identified.
ADGRE2
encodes a member of the epidermal growth factor (EGF)–seven transmembrane (TM7) subclass of adhesion G-protein–coupled receptors (GPCRs); the ADGRE2 protein has an N-terminal extracellular . . .
While stressful life events are an important cause of psychopathology, most individuals exposed to adversity maintain normal psychological functioning. The molecular mechanisms underlying such ...resilience are poorly understood. Here, we demonstrate that an inbred population of mice subjected to social defeat can be separated into susceptible and unsusceptible subpopulations that differ along several behavioral and physiological domains. By a combination of molecular and electrophysiological techniques, we identify signature adaptations within the mesolimbic dopamine circuit that are uniquely associated with vulnerability or insusceptibility. We show that molecular recapitulations of three prototypical adaptations associated with the unsusceptible phenotype are each sufficient to promote resistant behavior. Our results validate a multidisciplinary approach to examine the neurobiological mechanisms of variations in stress resistance, and illustrate the importance of plasticity within the brain's reward circuits in actively maintaining an emotional homeostasis.
The very high energy (VHE; E> 100 GeV) blazar Markarian 501 was observed between April 17 and May 5 (MJD 54 938–54 956), 2009, as part of an extensive multi-wavelength campaign from radio to VHE. ...Strong VHE γ-ray activity was detected on May 1st with Whipple and VERITAS, when the flux (E> 400 GeV) increased to 10 times the pre-flare baseline flux (3.9 × 10-11 ph cm-2 s-1), reaching five times the flux of the Crab Nebula. This coincided with a decrease in the optical polarization and a rotation of the polarization angle by 15°. This VHE flare showed a fast flux variation with an increase of a factor ~4 in 25 min, and a falling time of ~50 min. We present the observations of the quiescent state previous to the flare and of the high state after the flare, focusing on the flux and spectral variability from Whipple, VERITAS, Fermi-LAT, RXTE, and Swift combined with optical and radio data.