The Herschel–ATLAS data release 2, Paper I. Submillimeter and far-infrared images of the South and North Galactic Poles: the largest Herschel survey of the extragalactic sky

We present the largest submillimeter images that have been made of the extragalactic sky. The Herschel Astrophysical Terahertz Large Area Survey (H-ATLAS) is a survey of 660 deg2 with the PACS and SPIRE cameras in five photometric bands: 100, 160, 250, 350, and 500 μm. In this paper we present the images from our two largest fields, which account for ~75% of the survey. The first field is 180.1 deg2 in size, centered on the north Galactic pole (NGP), and the second is 317.6 deg2 in size, centered on the south Galactic pole. The NGP field serendipitously contains the Coma cluster. Over most (~80%) of the images, the pixel noise, including both instrumental noise and confusion noise, is approximately 3.6, and 3.5 mJy pix−1 at 100 and 160 μm, and 11.0, 11.1 and 12.3 mJy beam−1 at 250, 350 and 500 μm, respectively, but reaches lower values in some parts of the images. If a matched filter is applied to optimize point-source detection, our total 1σ map sensitivity is 5.7, 6.0, and 7.3 mJy at 250, 350, and 500 μm, respectively. We describe the results of an investigation of the noise properties of the images. We make the most precise estimate of confusion in SPIRE maps to date, finding values of 3.12 ± 0.07, 4.13 ± 0.02, and 4.45 ± 0.04 mJy beam−1 at 250, 350, and 500 μm in our un-convolved maps. For PACS we find an estimate of the confusion noise in our fast-parallel observations of 4.23 and 4.62 mJy beam−1 at 100 and 160 μm. Finally, we give recipes for using these images to carry out photometry, both for unresolved and extended sources

Multi-wavelength lens construction of a Planck and Herschel-detected star-bursting galaxy

We present a source-plane reconstruction of a Herschel and Planck-detected gravitationally lensed dusty star-forming galaxy (DSFG) at z = 1.68 using Hubble, Submillimeter Array (SMA), and Keck observations. The background submillimeter galaxy (SMG) is strongly lensed by a foreground galaxy cluster at z = 0.997 and appears as an arc with a length of ∼15″ in the optical images. The continuum dust emission, as seen by SMA, is limited to a single knot within this arc. We present a lens model with source-plane reconstructions at several wavelengths to show the difference in magnification between the stars and dust, and highlight the importance of multi-wavelength lens models for studies involving lensed DSFGs. We estimate the physical properties of the galaxy by fitting the flux densities to model spectral energy distributions leading to a magnification-corrected starformation rate (SFR) of 390 ± 60 M yr−1 and a stellar mass of 1.1 ± 0.4 10 x 11 M. These values are consistent with high-redshift massive galaxies that have formed most of their stars already. The estimated gas-to-baryon fraction, molecular gas surface density, and SFR surface density have values of 0.43 ± 0.13, 350 ± 200 M pc−2, and ~ 12 7 M yr−1 kpc−2, respectively. The ratio of SFR surface density to molecular gas surface density puts this among the most star-forming systems, similar to other measured SMGs and local ULIRGs

Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies

Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype

Involvement of the endocannabinoid system in the physiological response to transient common carotid artery occlusion and reperfusion

Background: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) may trigger a physiological response in an attempt to preserve tissue and function integrity. There are several candidate molecules among which the endocannabinoid system (ECS) and/or peroxisome-proliferator activated receptor-alpha (PPAR-alpha) may play a role in modulating oxidative stress and inflammation. The aims of the present study are to evaluate whether the ECS, the enzyme cyclooxygenase-2 (COX-2) and PPAR-alpha are involved during BCCAO/R in rat brain, and to identify possible markers of the ongoing BCCAO/R-induced challenge in plasma. Methods: Adult Wistar rats underwent BCCAO/R with 30 min hypoperfusion followed by 60 min reperfusion. The frontal and temporal-occipital cortices and plasma were analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS) to determine concentrations of endocannabinoids (eCBs) and related molecules behaving as ligands of PPAR-alpha, and of oxidative-stress markers such as lipoperoxides, while Western Blot and immunohistochemistry were used to study protein expression of cannabinoid receptors, COX-2 and PPAR-alpha. Unpaired Student's t-test was used to evaluate statistical differences between groups. Results: The acute BCCAO/R procedure is followed by increased brain tissue levels of the eCBs 2-arachidonoylglycerol and anandamide, palmitoylethanolamide, an avid ligand of PPAR-alpha, lipoperoxides, type 1 (CB1) and type 2 (CB2) cannabinoid receptors, and COX-2, and decreased brain tissue concentrations of docosahexaenoic acid (DHA), one of the major targets of lipid peroxidation. In plasma, increased levels of anandamide and lipoperoxides were observed. Conclusions: The BCCAO/R stimulated early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The observed variations suggest that the positive modulation of the ECS and the increase of proinflammatory substances are directly correlated events. Increase of plasmatic levels of anandamide and lipoperoxides further suggests that dysregulation of these molecules may be taken as an indicator of an ongoing hypoperfusion/reperfusion challenge

Molecular Mechanisms Generating and Stabilizing Terminal 22q13 Deletions in 44 Subjects with Phelan/McDermid Syndrome

In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17–74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS

PRISM (Polarized Radiation Imaging and Spectroscopy Mission): an extended white paper

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