Stress induces aggregation of RNA-binding proteins to form inclusions, termed stress granules (SGs). Recent evidence suggests that SG proteins also colocalize with neuropathological structures, but ...whether this occurs in Alzheimer's disease is unknown. We examined the relationship between SG proteins and neuropathology in brain tissue from P301L Tau transgenic mice, as well as in cases of Alzheimer's disease and FTDP-17. The pattern of SG pathology differs dramatically based on the RNA-binding protein examined. SGs positive for T-cell intracellular antigen-1 (TIA-1) or tristetraprolin (TTP) initially do not colocalize with tau pathology, but then merge with tau inclusions as disease severity increases. In contrast, G3BP (ras GAP-binding protein) identifies a novel type of molecular pathology that shows increasing accumulation in neurons with increasing disease severity, but often is not associated with classic markers of tau pathology. TIA-1 and TTP both bind phospho-tau, and TIA-1 overexpression induces formation of inclusions containing phospho-tau. These data suggest that SG formation might stimulate tau pathophysiology. Thus, study of RNA-binding proteins and SG biology highlights novel pathways interacting with the pathophysiology of AD, providing potentially new avenues for identifying diseased neurons and potentially novel mechanisms regulating tau biology.
We report the discovery of a galaxy overdensity around a Compton-thick Fanaroff–Riley type II (FRII) radio galaxy at z = 1.7 in the deep multiband survey around the z = 6.3 quasi-stellar object (QSO) ...SDSS J1030+0524. Based on a 6 h VLT/MUSE and on a 4 h LBT/LUCI observation, we identify at least eight galaxy members in this structure with spectroscopic redshift z = 1.687 − 1.699, including the FRII galaxy at z = 1.699. Most members are distributed within 400 kpc from the FRII core. Nonetheless, the whole structure is likely much more extended, as one of the members was serendipitously found at ∼800 kpc projected separation. The classic radio structure of the FRII itself extends for ∼600 kpc across the sky. Most of the identified overdensity members are blue, compact galaxies that are actively forming stars at rates of ∼8–60 M⊙ yr−1. For the brightest of them, a half-light radius of 2.2 ± 0.8 kpc at 8000 Å rest-frame was determined based on adaptive optics-assisted observations with LBT/SOUL in the Ks band. We do not observe any strong galaxy morphological segregation or concentration around the FRII core. This suggests that the structure is far from being virialized and likely constitutes the progenitor of a local massive galaxy group or cluster caught in its main assembly phase. Based on a 500 ks Chandra ACIS-I observation, we found that the FRII nucleus hosts a luminous QSO (L2 − 10 keV = 1.3 × 1044 erg s−1, intrinsic and rest-frame) that is obscured by Compton-thick absorption (NH = 1.5 ± 0.6 × 1024 cm−2). Under standard bolometric corrections, the total measured radiative power (Lrad ∼ 4 × 1045 erg s−1) is similar to the jet kinetic power that we estimated from radio observations at 150 MHz (Pkin = 6.3 × 1045 erg s−1), in agreement with what is observed in powerful jetted AGN. Our Chandra observation is the deepest so far for a distant FRII within a galaxy overdensity. It revealed significant diffuse X-ray emission within the region that is covered by the overdensity. In particular, X-ray emission extending for ∼240 kpc is found around the eastern lobe of the FRII. Four out of the six MUSE star-forming galaxies in the overdensity are distributed in an arc-like shape at the edge of this diffuse X-ray emission. These objects are concentrated within 200 kpc in the plane of the sky and within 450 kpc in radial separation. Three of them are even more concentrated and fall within 60 kpc in both transverse and radial distance. The probability of observing four out of the six z = 1.7 sources by chance at the edge of the diffuse emission is negligible. In addition, these four galaxies have the highest specific star formation rates of the MUSE galaxies in the overdensity and lie above the main sequence of field galaxies of equal stellar mass at z = 1.7. We propose that the diffuse X-rays originate from an expanding bubble of gas that is shock heated by the FRII jet, and that star formation is promoted by the compression of the cold interstellar medium of the galaxies around the bubble, which may be remarkable evidence of positive AGN feedback on cosmological scales. We emphasize that our conclusions about the feedback are robust because even assuming that the diffuse X-ray emission arises from inverse Compton scattering of photons of the cosmic microwave background by the relativistic electrons in the radio lobe, star formation may be promoted by the nonthermal pressure of the expanding lobe.
We present the first estimate of age, stellar metallicity and chemical abundance ratios, for an individual early-type galaxy at high-redshift (z = 1.426) in the COSMOS (Cosmological Evolution Survey) ...field. Our analysis is based on observations obtained with the X-Shooter instrument at the Very Large Telescope (VLT), which cover the visual and near-infrared spectrum at high (R > 5000) spectral resolution. We measure the values of several spectral absorptions tracing chemical species, in particular magnesium and iron, besides determining the age-sensitive D4000 break. We compare the measured indices to stellar population models, finding good agreement. We find that our target is an old (t > 3 Gyr), high-metallicity (Z/H > 0.5) galaxy which formed its stars at z
form >5 within a short time-scale ∼0.1 Gyr, as testified by the strong α/Fe ratio (>0.4), and has passively evolved in the first >3–4 Gyr of its life. We have verified that this result is robust against the choice and number of fitted spectral features, and stellar population model. The result of an old age and high-metallicity has important implications for galaxy formation and evolution confirming an early and rapid formation of the most massive galaxies in the Universe.
Iatrogenic pancreatic cancer metastasis after islet infusion is a potential risk of islet autotransplantation performed after pancreatectomy. To model this risk, islets and/or pancreatic exocrine ...clusters obtained from a genetically engineered mouse model for pancreatic ductal adenocarcinoma (the LSL‐KrasG12D/+;LSL‐Trp53R172H/+;Pdx‐1‐Cre, termed KPC mouse) were transplanted via the portal vein in syngeneic wild type (WT) severely diabetic recipients in the following treatment groups: group A (n = 11) received KPC exocrine clusters in volume equal to 250 islet equivalents (IEQs); group B (n = 12) received 250 WT IEQs mixed with KPC exocrine clusters (1:1 volume ratio); group C (n = 5) received 250 KPC IEQs, and group D (n = 7) received 250 WT IEQs. The incidence of hepatic metastasis was assessed by magnetic resonance imaging and histology over the 13 months of follow‐up. Overall survival was not different in the four groups. No mice developed liver metastases during the follow‐up. Two mice developed spontaneous tumors: a liver hepatocellular tumor in group A and a malignant lymphoma in group D. Islets and/or exocrine clusters obtained by KPC mouse, a model that develops pancreatic cancer with 100% penetrance, do not retain the same risk of tumor development when transplanted via the portal vein in a syngeneic diabetic recipient.
Premalignant pancreatic exocrine tissue is not able to develop tumoral lesions after intrahepatic islet transplantation in a syngeneic severely diabetic wild type recipient.
Pulmonary hypertension (PH) that occurs after left-heart failure (LHF), classified as Group 2 PH, involves progressive pulmonary vascular remodeling induced by smooth muscle cell (SMC) proliferation. ...However, mechanisms involved in the activation of SMCs remain unknown. The objective of this study was to determine the involvement of peroxynitrite and phosphatase-and-tensin homolog on chromosome 10 (PTEN) in vascular SMC proliferation and remodeling in the LHF-induced PH (LHF-PH). LHF was induced by permanent ligation of left anterior descending coronary artery in rats for 4 weeks. MRI, ultrasound, and hemodynamic measurements were performed to confirm LHF and PH. Histopathology, Western blot, and real-time polymerase chain reaction analyses were used to identify key molecular signatures. Therapeutic intervention was demonstrated using an antiproliferative compound, HO-3867. LHF-PH was confirmed by significant elevation of pulmonary artery pressure (mean pulmonary artery pressure/mm Hg35.9±1.8 versus 14.8±2.0, control; P<0.001) and vascular remodeling. HO-3867 treatment decreased mean pulmonary artery pressure to 22.6±0.8 mm Hg (P<0.001). Substantially higher levels of peroxynitrite and significant loss of PTEN expression were observed in the lungs of LHF rats when compared with control. In vitro studies using human pulmonary artery SMCs implicated peroxynitrite-mediated downregulation of PTEN expression as a key mechanism of SMC proliferation. The results further established that HO-3867 attenuated LHF-PH by decreasing oxidative stress and increasing PTEN expression in the lung. In conclusion, peroxynitrite and peroxynitrite-mediated PTEN inactivation seem to be key mediators of lung microvascular remodeling associated with PH secondary to LHF.
This paper describes the observations and the first data release (DR1) of the ESO public spectroscopic survey “VANDELS, a deep VIMOS survey of the CANDELS CDFS and UDS fields”. The main targets of ...VANDELS are star-forming galaxies at redshift 2.4 < z < 5.5, an epoch when the Universe had not yet reached 20% of its current age, and massive passive galaxies in the range 1 < z < 2.5. By adopting a strategy of ultra-long exposure times, ranging from a minimum of 20 h to a maximum of 80 h per source, VANDELS is specifically designed to be the deepest-ever spectroscopic survey of the high-redshift Universe. Exploiting the red sensitivity of the refurbished VIMOS spectrograph, the survey is obtaining ultra-deep optical spectroscopy covering the wavelength range 4800–10 000 Å with a sufficiently high signal-to-noise ratio to investigate the astrophysics of high-redshift galaxy evolution via detailed absorption line studies of well-defined samples of high-redshift galaxies. VANDELS-DR1 is the release of all medium-resolution spectroscopic data obtained during the first season of observations, on a 0.2 square degree area centered around the CANDELS-CDFS (Chandra deep-field south) and CANDELS-UDS (ultra-deep survey) areas. It includes data for all galaxies for which the total (or half of the total) scheduled integration time was completed. The DR1 contains 879 individual objects, approximately half in each of the two fields, that have a measured redshift, with the highest reliable redshifts reaching zspec ~ 6. In DR1 we include fully wavelength-calibrated and flux-calibrated 1D spectra, the associated error spectrum and sky spectrum, and the associated wavelength-calibrated 2D spectra. We also provide a catalog with the essential galaxy parameters, including spectroscopic redshifts and redshift quality flags measured by the collaboration. We present the survey layout and observations, the data reduction and redshift measurement procedure, and the general properties of the VANDELS-DR1 sample. In particular, we discuss the spectroscopic redshift distribution and the accuracy of the photometricredshifts for each individual target category, and we provide some examples of data products for the various target typesand the different quality flags. All VANDELS-DR1 data are publicly available and can be retrieved from the ESO archive. Two further data releases are foreseen in the next two years, and a final data release is currently scheduled for June 2020, which will include an improved rereduction of the entire spectroscopic data set.
VANDELS is an ESO Public Spectroscopic Survey designed to build a sample of high-signal-to-noise ratio, medium-resolution spectra of galaxies at redshifts between 1 and 6.5. Here we present the final ...Public Data Release of the VANDELS Survey, comprising 2087 redshift measurements. We provide a detailed description of sample selection, observations, and data reduction procedures. The final catalogue reaches a target selection completeness of 40% at
i
AB
= 25. The high signal-to-noise ratio of the spectra (above 7 in 80% of the spectra) and the dispersion of 2.5 Å allowed us to measure redshifts with high precision, the redshift measurement success rate reaching almost 100%. Together with the redshift catalogue and the reduced spectra, we also provide optical mid-infrared photometry and physical parameters derived through fitting the spectral energy distribution. The observed galaxy sample comprises both passive and star forming galaxies covering a stellar mass range of 8.3 < Log(
M
*
/
M
⊙
) < 11.7.
PDF
