Current antipsychotic drugs primarily target dopamine D2 receptors (D2Rs), in conjunction with other receptors such as those for serotonin. However, these drugs have serious side effects such as ...extrapyramidal symptoms (EPS) and diabetes. Identifying a specific D2R signaling pathway that could be targeted for antipsychotic effects, without inducing EPS, would be a significant improvement in the treatment of schizophrenia. We report here that the D2R forms a protein complex with Disrupted in Schizophrenia 1 (DISC1) that facilitates D2R-mediated glycogen synthase kinase (GSK)-3 signaling and inhibits agonist-induced D2R internalization. D2R-DISC1 complex levels are increased in conjunction with decreased GSK-3α/β (Ser21/9) phosphorylation in both postmortem brain tissue from schizophrenia patients and in Disc1-L100P mutant mice, an animal model with behavioral abnormalities related to schizophrenia. Administration of an interfering peptide that disrupts the D2R-DISC1 complex successfully reverses behaviors relevant to schizophrenia but does not induce catalepsy, a strong predictor of EPS in humans.
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•D2R-DISC1 complex is increased in postmortem brain from schizophrenia patients•GSK-3α/β phosphorylation is also decreased in postmortem brain of these patients•Activation of D2R enhances D2R-DISC1 coupling and reduces GSK-3α/β phosphorylation•Disrupting the D2R-DISC1 complex has antipsychotic-like effects without EPS in vivo
DISC1 is a prominent schizophrenia susceptibility gene, and the main target of antipsychotic medications is the dopamine D2 receptor. Su et al. show that DISC1 and D2 form a complex. Disruption of this complex has antipsychotic-like effects without neurological side effects.
We present a multi-wavelength photometric catalog in the COSMOS field as part of the observations by the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey. The catalog is based on Hubble ...Space Telescope Wide Field Camera 3 (HST/WFC3) and Advanced Camera for Surveys observations of the COSMOS field (centered at R.A.: , Decl.: ). The final catalog has 38671 sources with photometric data in 42 bands from UV to the infrared ( ). This includes broadband photometry from HST, CFHT, Subaru, the Visible and Infrared Survey Telescope for Astronomy, and Spitzer Space Telescope in the visible, near-infrared, and infrared bands along with intermediate- and narrowband photometry from Subaru and medium-band data from Mayall NEWFIRM. Source detection was conducted in the WFC3 F160W band (at 1.6 m) and photometry is generated using the Template FITting algorithm. We further present a catalog of the physical properties of sources as identified in the HST F160W band and measured from the multi-band photometry by fitting the observed spectral energy distributions of sources against templates.
We measure new estimates for the galaxy stellar mass function and star formation rates for samples of galaxies at z ∼ 4, 5, 6 and 7 using data in the CANDELS GOODS South field. The deep near-infrared ...observations allow us to construct the stellar mass function at z ≥ 6 directly for the first time. We estimate stellar masses for our sample by fitting the observed spectral energy distributions with synthetic stellar populations, including nebular line and continuum emission. The observed UV luminosity functions for the samples are consistent with previous observations; however, we find that the observed M
UV-M
* relation has a shallow slope more consistent with a constant mass-to-light ratio and a normalization which evolves with redshift. Our stellar mass functions have steep low-mass slopes (α ≈ −1.9), steeper than previously observed at these redshifts and closer to that of the UV luminosity function. Integrating our new mass functions, we find the observed stellar mass density evolves from
$\log _{10} \rho _{*} = 6.64^{+0.58}_{-0.89}$
at z ∼ 7 to 7.36 ± 0.06 M⊙ Mpc− 3 at z ∼ 4. Finally, combining the measured UV continuum slopes (β) with their rest-frame UV luminosities, we calculate dust-corrected star formation rates (SFR) for our sample. We find the specific SFR for a fixed stellar mass increases with redshift whilst the global SFR density falls rapidly over this period. Our new SFR density estimates are higher than previously observed at this redshift.
Submillimeter/millimeter observations of dusty star-forming galaxies with the Atacama Large Millimeter/submillimeter Array (ALMA) have shown that dust continuum emission generally occurs in compact ...regions smaller than the stellar distribution. However, it remains to be understood how systematic these findings are. Studies often lack homogeneity in the sample selection, target discontinuous areas with inhomogeneous sensitivities, and suffer from modest
u
v
coverage coming from single array configurations. GOODS-ALMA is a 1.1 mm galaxy survey over a continuous area of 72.42 arcmin
2
at a homogeneous sensitivity. In this version 2.0, we present a new low resolution dataset and its combination with the previous high resolution dataset from the survey, improving the
u
v
coverage and sensitivity reaching an average of
σ
= 68.4 μJy beam
−1
. A total of 88 galaxies are detected in a blind search (compared to 35 in the high resolution dataset alone), 50% at
S
/
N
peak
≥ 5 and 50% at 3.5 ≤
S
/
N
peak
≤ 5 aided by priors. Among them, 13 out of the 88 are optically dark or faint sources (
H
- or
K
-band dropouts). The sample dust continuum sizes at 1.1 mm are generally compact, with a median effective radius of
R
e
= 0
.
″
10 ± 0
.
″
05 (a physical size of
R
e
= 0.73 ± 0.29 kpc at the redshift of each source). Dust continuum sizes evolve with redshift and stellar mass resembling the trends of the stellar sizes measured at optical wavelengths, albeit a lower normalization compared to those of late-type galaxies. We conclude that for sources with flux densities
S
1.1 mm
> 1 mJy, compact dust continuum emission at 1.1 mm prevails, and sizes as extended as typical star-forming stellar disks are rare. The
S
1.1 mm
< 1 mJy sources appear slightly more extended at 1.1 mm, although they are still generally compact below the sizes of typical star-forming stellar disks.
We present the public release of the stellar mass catalogs for the GOODS-S and UDS fields obtained using some of the deepest near-IR images available, achieved as part of the Cosmic Assembly ...Near-infrared Deep Extragalactic Legacy Survey project. We combine the effort from 10 different teams, who computed the stellar masses using the same photometry and the same redshifts. Each team adopted their preferred fitting code, assumptions, priors, and parameter grid. The combination of results using the same underlying stellar isochrones reduces the systematics associated with the fitting code and other choices. Thanks to the availability of different estimates, we can test the effect of some specific parameters and assumptions on the stellar mass estimate. The choice of the stellar isochrone library turns out to have the largest effect on the galaxy stellar mass estimates, resulting in the largest distributions around the median value (with a semi interquartile range larger than 0.1 dex). On the other hand, for most galaxies, the stellar mass estimates are relatively insensitive to the different parameterizations of the star formation history. The inclusion of nebular emission in the model spectra does not have a significant impact for the majority of galaxies (less than a factor of 2 for ~80% of the sample). Nevertheless, the stellar mass for the subsample of young galaxies (age <100 Myr), especially in particular redshift ranges (e.g., 2.2 < z < 2.4, 3.2 < z < 3.6, and 5.5 < z < 6.5), can be seriously overestimated (by up to a factor of 10 for <20 Myr sources) if nebular contribution is ignored.
Many of the results in modern astrophysics rest on the notion that the initial mass function (IMF) is universal. Our observations of a sample of H I selected galaxies in the light of Ha and the ...far-ultraviolet (FUV) challenge this result. The extinction-corrected flux ratio F Ha/f FUV from these two tracers of star formation shows strong correlations with the surface brightness in Ha and the R band: low surface brightness (LSB) galaxies have lower F Ha/f FUV ratios compared to high surface brightness galaxies as well as compared to expectations from equilibrium models of constant star formation rate (SFR) using commonly favored IMF parameters. Weaker but significant correlations of F Ha/f FUV with luminosity, rotational velocity, and dynamical mass as well as a systematic trend with morphology, are found. The correlated variations of F Ha/f FUV with other global parameters are thus part of the larger family of galaxy scaling relations. The F Ha/f FUV correlations cannot be due to residual extinction correction errors, while systematic variations in the star formation history (SFH) cannot explain the trends with both Ha and R surface brightness nor with other global properties. The possibility that LSB galaxies have a higher escape fraction of ionizing photons seems inconsistent with their high gas fraction, and observations of color-magnitude diagrams (CMDs) of a few systems which indicate a real deficit of O stars. The most plausible explanation for the correlations is the systematic variations of the upper mass limit and/or the slope g which define the upper end of the IMF. We outline a scenario of pressure driving the correlations by setting the efficiency of the formation of the dense star clusters where the highest mass stars preferentially form. Our results imply that the SFR measured in a galaxy is highly sensitive to the tracer used in the measurement. A nonuniversal IMF would also call into question the interpretation of metal abundance patterns in dwarf galaxies as well as SFHs derived from CMDs.
Of several dozen galaxies observed spectroscopically that are candidates for having a redshift (z) in excess of seven, only five have had their redshifts confirmed via Lyman α emission, at z = 7.008, ...7.045, 7.109, 7.213 and 7.215 (refs 1-4). The small fraction of confirmed galaxies may indicate that the neutral fraction in the intergalactic medium rises quickly at z > 6.5, given that Lyman α is resonantly scattered by neutral gas. The small samples and limited depth of previous observations, however, makes these conclusions tentative. Here we report a deep near-infrared spectroscopic survey of 43 photometrically-selected galaxies with z > 6.5. We detect a near-infrared emission line from only a single galaxy, confirming that some process is making Lyman α difficult to detect. The detected emission line at a wavelength of 1.0343 micrometres is likely to be Lyman α emission, placing this galaxy at a redshift z = 7.51, an epoch 700 million years after the Big Bang. This galaxy's colours are consistent with significant metal content, implying that galaxies become enriched rapidly. We calculate a surprisingly high star-formation rate of about 330 solar masses per year, which is more than a factor of 100 greater than that seen in the Milky Way. Such a galaxy is unexpected in a survey of our size, suggesting that the early Universe may harbour a larger number of intense sites of star formation than expected.
Context. The form and evolution of the galaxy stellar mass function (GSMF) at high redshifts provide crucial information on star formation history and mass assembly in the young Universe, close or ...even prior to the epoch of reionization. Aims. We used the unique combination of deep optical/near-infrared/mid-infrared imaging provided by HST, Spitzer, and the VLT in the CANDELS-UDS, GOODS-South, and HUDF fields to determine the GSMF over the redshift range 3.5 ≤ z ≤ 7.5. Methods. We used the HST WFC3/IR near-infrared imaging from CANDELS and HUDF09, reaching H ≃ 27 − 28.5 over a total area of 369 arcmin2, in combination with associated deep HST ACS optical data, deep Spitzer IRAC imaging from the SEDS programme, and deep Y and K-band VLT Hawk-I images from the HUGS programme, to select a galaxy sample with high-quality photometric redshifts. These have been calibrated with more than 150 spectroscopic redshifts in the range 3.5 ≤ z ≤ 7.5, resulting in an overall precision of σz/ (1 + z) ~ 0.037. With this database we have determined the low-mass end of the high-redshift GSMF with unprecedented precision, reaching down to masses as low as M∗ ~ 109 M⊙ at z = 4 and ~6 × 109 M⊙ at z = 7. Results. We find that the GSMF at 3.5 ≤ z ≤ 7.5 depends only slightly on the recipes adopted to measure the stellar masses, namely the photometric redshifts, the star formation histories, the nebular contribution, or the presence of AGN in the parent sample. The low-mass end of the GSMF is steeper than has been found at lower redshifts, but appears to be unchanged over the redshift range probed here. Meanwhile the high-mass end of the GSMF appears to evolve primarily in density, although there is also some evidence of evolution in characteristic mass. Our results are very different from previous mass function estimates based on converting UV galaxy luminosity functions into mass functions via tight mass-to-light relations. Integrating our evolving GSMF over mass, we find that the growth of stellar mass density is barely consistent with the time-integral of the star formation rate density over cosmic time at z> 4. Conclusions. These results confirm the unique synergy of the CANDELS+HUDF, HUGS, and SEDS surveys for the discovery and study of moderate/low-mass galaxies at high redshifts, and reaffirm the importance of space-based infrared selection for the unbiased measurement of the evolving GSMF in the young Universe.
Purpose NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and health-related quality of life during treatment with standard pelvic radiation or intensity-modulated ...radiation therapy (IMRT) in women with cervical and endometrial cancer. Methods Patients were randomly assigned to standard four-field radiation therapy (RT) or IMRT radiation treatment. The primary end point was change in patient-reported acute GI toxicity from baseline to the end of RT, measured with the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC). Secondary end points included change in patient-reported urinary toxicity, change in GI toxicity measured with the Patient-Reported Outcome Common Terminology Criteria for Adverse Events, and quality of life measured with the Trial Outcome Index. Results From 2012 to 2015, 289 patients were enrolled, of whom 278 were eligible. Between baseline and end of RT, the mean EPIC bowel score declined 23.6 points in the standard RT group and 18.6 points in the IMRT group ( P = .048), the mean EPIC urinary score declined 10.4 points in the standard RT group and 5.6 points in the IMRT group ( P = .03), and the mean Trial Outcome Index score declined 12.8 points in the standard RT group and 8.8 points in the IMRT group ( P = .06). At the end of RT, 51.9% of women who received standard RT and 33.7% who received IMRT reported frequent or almost constant diarrhea ( P = .01), and more patients who received standard RT were taking antidiarrheal medications four or more times daily (20.4% v 7.8%; P = .04). Conclusion Pelvic IMRT was associated with significantly less GI and urinary toxicity than standard RT from the patient's perspective.