SHANK3 (also called PROSAP2) genetic haploinsufficiency is thought to be the major cause of neuropsychiatric symptoms in Phelan-McDermid syndrome (PMS). PMS is a rare genetic disorder that causes a ...severe form of intellectual disability (ID), expressive language delays and other autistic features. Furthermore, a significant number of SHANK3 mutations have been identified in patients with autism spectrum disorders (ASD), and SHANK3 truncating mutations are associated with moderate to profound ID. The Shank3 protein is a scaffold protein that is located in the postsynaptic density (PSD) of excitatory synapses and is crucial for synapse development and plasticity. In this study, we investigated the molecular mechanisms associated with the ASD-like behaviors observed in Shank3Δ11
mice, in which exon 11 has been deleted. Our results indicate that Shank3 is essential to mediating metabotropic glutamate receptor 5 (mGlu5)-receptor signaling by recruiting Homer1b/c to the PSD, specifically in the striatum and cortex. Moreover, augmenting mGlu5-receptor activity by administering 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide ameliorated the functional and behavioral defects that were observed in Shank3Δ11
mice, suggesting that pharmaceutical treatments that increase mGlu5 activity may represent a new approach for treating patients that are affected by PMS and SHANK3 mutations.
ABSTRACT
The observable population of double neutron star (DNS) systems in the Milky Way allow us to understand the nature of supernovae and binary stellar evolution. Until now, all DNS systems in ...wide orbits (Porb > 1 d) have been found to have orbital eccentricities, e > 0.1. In this paper, we report the discovery of pulsar PSR J1325−6253: a DNS system in a 1.81-d orbit with a surprisingly low eccentricity of just e = 0.064. Through, 1.4 yr of dedicated timing with the Parkes radio telescope we have been able to measure its rate of advance of periastron, $\dot{\omega }=0{_{.}^{\circ}}138\pm 0{_{.}^{\circ}}002\, \mathrm{yr}^{-1}$. If this induced $\dot{\omega }$ is solely due to general relativity then the total mass of the system is, Msys = 2.57 ± 0.06 M⊙. Assuming an edge-on orbit the minimum companion mass is constrained to be Mc, min > 0.98 M⊙ which implies the pulsar mass is Mp, max < 1.59 M⊙. Its location in the P–$\dot{P}$ diagram suggests that, like other DNS systems, PSR J1325−6253 is a recycled pulsar and if its mass is similar to the known examples (>1.3 M⊙), then the companion neutron star is probably less than ∼1.25 M⊙ and the system is inclined at about 50°–60°. The low eccentricity along with the wide orbit of the system strongly favours a formation scenario involving an ultra-stripped supernova explosion.
Abstract
A new analysis of the data set from the Pierre Auger Observatory provides evidence for anisotropy in the arrival directions of ultra-high-energy cosmic rays on an intermediate angular scale, ...which is indicative of excess arrivals from strong, nearby sources. The data consist of 5514 events above
with zenith angles up to 80° recorded before 2017 April 30. Sky models have been created for two distinct populations of extragalactic gamma-ray emitters: active galactic nuclei from the second catalog of hard
Fermi
-LAT sources (2FHL) and starburst galaxies from a sample that was examined with
Fermi
-LAT. Flux-limited samples, which include all types of galaxies from the
Swift
-BAT and 2MASS surveys, have been investigated for comparison. The sky model of cosmic-ray density constructed using each catalog has two free parameters, the fraction of events correlating with astrophysical objects, and an angular scale characterizing the clustering of cosmic rays around extragalactic sources. A maximum-likelihood ratio test is used to evaluate the best values of these parameters and to quantify the strength of each model by contrast with isotropy. It is found that the starburst model fits the data better than the hypothesis of isotropy with a statistical significance of 4.0
σ
, the highest value of the test statistic being for energies above
. The three alternative models are favored against isotropy with 2.7
σ
–3.2
σ
significance. The origin of the indicated deviation from isotropy is examined and prospects for more sensitive future studies are discussed.
We present a detailed study of the large-scale anisotropies of cosmic rays with energies above 4 EeV measured using the Pierre Auger Observatory. For the energy bins 4, 8 EeV and E ≥ 8 EeV, the most ...significant signal is a dipolar modulation in R.A. at energies above 8 EeV, as previously reported. In this paper we further scrutinize the highest-energy bin by splitting it into three energy ranges. We find that the amplitude of the dipole increases with energy above 4 EeV. The growth can be fitted with a power law with index β = 0.79 0.19. The directions of the dipoles are consistent with an extragalactic origin of these anisotropies at all the energies considered. Additionally, we have estimated the quadrupolar components of the anisotropy: they are not statistically significant. We discuss the results in the context of the predictions from different models for the distribution of ultrahigh-energy sources and cosmic magnetic fields.
We report the discovery, mass, and radius determination of TOI-1801 b, a temperate mini-Neptune around a young M dwarf. TOI-1801 b was observed in TESS sectors 22 and 49, and the alert that this was ...a TESS planet candidate with a period of 21.3 days went out in April 2020. However, ground-based follow-up observations, including seeing-limited photometry in and outside transit together with precise radial velocity (RV) measurements with CARMENES and HIRES revealed that the true period of the planet is 10.6 days. These observations also allowed us to retrieve a mass of 5.74 ± 1.46
M
⊕
, which together with a radius of 2.08 ± 0.12
R
⊕
, means that TOI-1801 b is most probably composed of water and rock, with an upper limit of 2% by mass of H
2
in its atmosphere. The stellar rotation period of 16 days is readily detectable in our RV time series and in the ground-based photometry. We derived a likely age of 600–800 Myr for the parent star TOI-1801, which means that TOI-1801 b is the least massive young mini-Neptune with precise mass and radius determinations. Our results suggest that if TOI-1801 b had a larger atmosphere in the past, it must have been removed by some evolutionary mechanism on timescales shorter than 1 Gyr.
ABSTRACT We analyze the distribution of arrival directions of ultra-high-energy cosmic rays recorded at the Pierre Auger Observatory in 10 years of operation. The data set, about three times larger ...than that used in earlier studies, includes arrival directions with zenith angles up to 80°, thus covering from to in declination. After updating the fraction of events correlating with the active galactic nuclei (AGNs) in the Véron-Cetty and Véron catalog, we subject the arrival directions of the data with energies in excess of 40 EeV to different tests for anisotropy. We search for localized excess fluxes, self-clustering of event directions at angular scales up to 30°, and different threshold energies between 40 and 80 EeV. We then look for correlations of cosmic rays with celestial structures both in the Galaxy (the Galactic Center and Galactic Plane) and in the local universe (the Super-Galactic Plane). We also examine their correlation with different populations of nearby extragalactic objects: galaxies in the 2MRS catalog, AGNs detected by Swift-BAT, radio galaxies with jets, and the Centaurus A (Cen A) galaxy. None of the tests show statistically significant evidence of anisotropy. The strongest departures from isotropy (post-trial probability %) are obtained for cosmic rays with EeV in rather large windows around Swift AGNs closer than 130 Mpc and brighter than 1044 erg s−1 (18° radius), and around the direction of Cen A (15° radius).
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