Interferometric Follow-Up of WISE Hyper-Luminous Hot, Dust-Obscured Galaxies

WISE has discovered an extraordinary population of hyper-luminous dusty galaxies which are faint in the two bluer passbands ($3.4\, \mu$m and $4.6\, \mu$m) but are bright in the two redder passbands of WISE ($12\, \mu$m and $22\, \mu$m). We report on initial follow-up observations of three of these hot, dust-obscured galaxies, or Hot DOGs, using the CARMA and SMA interferometer arrays at submm/mm wavelengths. We report continuum detections at $\sim$ 1.3 mm of two sources (WISE J014946.17+235014.5 and WISE J223810.20+265319.7, hereafter W0149+2350 and W2238+2653, respectively), and upper limits to CO line emission at 3 mm in the observed frame for two sources (W0149+2350 and WISE J181417.29+341224.8, hereafter W1814+3412). The 1.3 mm continuum images have a resolution of 1-2 arcsec and are consistent with single point sources. We estimate the masses of cold dust are 2.0$\times 10^{8} M_{\odot}$ for W0149+2350 and 3.9$\times 10^{8} M_{\odot}$ for W2238+2653, comparable to cold dust masses of luminous quasars. We obtain 2$\sigma$ upper limits to the molecular gas masses traced by CO, which are 3.3$\times 10^{10} M_{\odot}$ and 2.3$\times 10^{10} M_{\odot}$ for W0149+2350 and W1814+3412, respectively. We also present high-resolution, near-IR imaging with WFC3 on the Hubble Space Telescope for W0149+2653 and with NIRC2 on Keck for W2238+2653. The near-IR images show morphological structure dominated by a single, centrally condensed source with effective radius less than 4 kpc. No signs of gravitational lensing are evident.Comment: 13 pages, 3 figures. ApJ in pres

A New Population of High-z, Dusty Lyα Emitters and Blobs Discovered by WISE: Feedback Caught in the Act?

By combining data from the NASA Wide-field Infrared Survey Explorer (WISE) mission with optical spectroscopy from the W. M. Keck telescope, we discover a mid-IR color criterion that yields a 78% success rate in identifying rare, typically radio-quiet, 1.6 ≾ z ≾ 4.6 dusty Lyα emitters (LAEs). Of these, at least 37% have emission extended on scales of 30-100 kpc and are considered Lyα "blobs" (LABs). The objects have a surface density of only ~0.1 deg^(–2), making them rare enough that they have been largely missed in deep, small area surveys. We measured spectroscopic redshifts for 92 of these galaxies, and find that the LAEs (LABs) have a median redshift of 2.3 (2.5). The WISE photometry coupled with data from Herschel (Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA) reveals that these galaxies are in the Hyper Luminous IR galaxy regime (L IR ≳ 10^(13)-10^(14) L_☉) and have warm colors. They are typically more luminous and warmer than other dusty, z ~ 2 populations such as submillimeter-selected galaxies and dust-obscured galaxies. These traits are commonly associated with the dust being illuminated by intense active galactic nucleus activity. We hypothesize that the combination of spatially extended Lyα, large amounts of warm IR-luminous dust, and rarity (implying a short-lived phase) can be explained if the galaxies are undergoing brief, intense "feedback" transforming them from an extreme dusty starburst/QSO into a mature galaxy

A Multi-Site Survey Study of Patient Satisfaction with Teledermatology

Introduction. Telemedicine has been of heightened focus due to spikes in usage during the COVID-19 pandemic. Disparities in health care may affect patient satisfaction with this resource depending on factors such as patient race, age, or socioeconomic background. The purpose of this study was to analyze patient satisfaction with teledermatology to identify any differences in satisfaction based on race, age, and income during the COVID-19 pandemic period. Methods. A 21-question, IRB-approved survey was administered to patients at two academic dermatology clinics in Kansas City. Patient satisfaction was measured using a five-point Likert scale. Results. A total of 64 completed surveys were analyzed (17.8% response rate). Most of the participants were female (n = 48, 75%), age 45 to 60 (n = 17, 26.6%), and reported White for race (n = 55, 85.9%). Overall, 73.4% (n = 47) of patients reported being satisfied with their visit. However, only 38.7% (n = 24) of participants were likely to choose a video over an in-person visit. Reasons for low patient satisfaction included concerns regarding ability to perform an accurate physical exam with a video visit (n = 9, 14.1%), receiving inadequate care (n = 4, 6.3%), protected privacy (n = 3, 4.7%), and provider understanding the patient (n = 2, 3.1%). Conclusions. Our findings were similar to prior studies stating no difference in patient satisfaction with regards to age, income, or race and patients reporting high satisfaction with teledermatology appointments despite a preference for in-person dermatology visits. Future studies with a larger diverse cohort of participants are needed to elucidate and address possible disparities associated with teledermatology use

Enhanced Proteolysis of β-Amyloid in APP Transgenic Mice Prevents Plaque Formation, Secondary Pathology, and Premature Death

AbstractConverging evidence suggests that the accumulation of cerebral amyloid β-protein (Aβ) in Alzheimer's disease (AD) reflects an imbalance between the production and degradation of this self-aggregating peptide. Upregulation of proteases that degrade Aβ thus represents a novel therapeutic approach to lowering steady-state Aβ levels, but the consequences of sustained upregulation in vivo have not been studied. Here we show that transgenic overexpression of insulin-degrading enzyme (IDE) or neprilysin (NEP) in neurons significantly reduces brain Aβ levels, retards or completely prevents amyloid plaque formation and its associated cytopathology, and rescues the premature lethality present in amyloid precursor protein (APP) transgenic mice. Our findings demonstrate that chronic upregulation of Aβ-degrading proteases represents an efficacious therapeutic approach to combating Alzheimer-type pathology in vivo

Restriction landmark genomic scanning (RLGS) spot identification by second generation virtual RLGS in multiple genomes with multiple enzyme combinations.

BackgroundRestriction landmark genomic scanning (RLGS) is one of the most successfully applied methods for the identification of aberrant CpG island hypermethylation in cancer, as well as the identification of tissue specific methylation of CpG islands. However, a limitation to the utility of this method has been the ability to assign specific genomic sequences to RLGS spots, a process commonly referred to as "RLGS spot cloning."ResultsWe report the development of a virtual RLGS method (vRLGS) that allows for RLGS spot identification in any sequenced genome and with any enzyme combination. We report significant improvements in predicting DNA fragment migration patterns by incorporating sequence information into the migration models, and demonstrate a median Euclidian distance between actual and predicted spot migration of 0.18 centimeters for the most complex human RLGS pattern. We report the confirmed identification of 795 human and 530 mouse RLGS spots for the most commonly used enzyme combinations. We also developed a method to filter the virtual spots to reduce the number of extra spots seen on a virtual profile for both the mouse and human genomes. We demonstrate use of this filter to simplify spot cloning and to assist in the identification of spots exhibiting tissue-specific methylation.ConclusionThe new vRLGS system reported here is highly robust for the identification of novel RLGS spots. The migration models developed are not specific to the genome being studied or the enzyme combination being used, making this tool broadly applicable. The identification of hundreds of mouse and human RLGS spot loci confirms the strong bias of RLGS studies to focus on CpG islands and provides a valuable resource to rapidly study their methylation

Characterisation of the pathogenic effects of the in vivo expression of an ALS-linked mutation in D-amino acid oxidase: Phenotype and loss of spinal cord motor neurons

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular disorder characterised by selective loss of motor neurons leading to fatal paralysis. Current therapeutic approaches are limited in their effectiveness. Substantial advances in understanding ALS disease mechanisms has come from the identification of pathogenic mutations in dominantly inherited familial ALS (FALS). We previously reported a coding mutation in D-amino acid oxidase (DAOR199W) associated with FALS. DAO metabolises D-serine, an essential co-agonist at the N-Methyl-D-aspartic acid glutamate receptor subtype (NMDAR). Using primary motor neuron cultures or motor neuron cell lines we demonstrated that expression of DAOR199W, promoted the formation of ubiquitinated protein aggregates, activated autophagy and increased apoptosis. The aim of this study was to characterise the effects of DAOR199W in vivo, using transgenic mice overexpressing DAOR199W. Marked abnormal motor features, e.g. kyphosis, were evident in mice expressing DAOR199W, which were associated with a significant loss (19%) of lumbar spinal cord motor neurons, analysed at 14 months. When separated by gender, this effect was greater in females (26%; p< 0.0132). In addition, we crossed the DAOR199W transgenic mouse line with the SOD1G93A mouse model of ALS to determine whether the effects of SOD1G93A were potentiated in the double transgenic line (DAOR199W/SOD1G93A). Although overall survival was not affected, onset of neurological signs was significantly earlier in female double transgenic animals than their female SOD1G93A littermates (125 days vs 131 days, P = 0.0239). In summary, some significant in vivo effects of DAOR199W on motor neuron function (i.e. kyphosis and loss of motor neurons) were detected which were most marked in females and could contribute to the earlier onset of neurological signs in double transgenic females compared to SOD1G93A littermates, highlighting the importance of recognizing gender effects present in animal models of ALS

A New Population of High Redshift, Dusty Lyman-Alpha Emitters and Blobs Discovered by WISE

We report a new technique to select 1.6<z<4.6 dusty Lyman-alpha emitters (LAEs), over a third of which are `blobs' (LABs) with emission extended on scales of 30-100kpc. Combining data from the NASA Wide-field Infrared Survey Explorer (WISE) mission with optical spectroscopy from the W.M. Keck telescope, we present a color criteria that yields a 78% success rate in identifying rare, dusty LAEs of which at least 37% are LABs. The objects have a surface density of only ~0.1 per square degree, making them rare enough that they have been largely missed in narrow surveys. We measured spectroscopic redshifts for 92 of these WISE-selected, typically radio-quiet galaxies and find that the LAEs (LABs) have a median redshift of 2.3 (2.5). The WISE photometry coupled with data from Herschel reveals that these galaxies have extreme far-infrared luminosities (L_IR>10^{13-14}L_sun) and warm colors, typically larger than submillimeter-selected galaxies (SMGs) and dust-obscured galaxies (DOGs). These traits are commonly associated with the dust being energized by intense AGN activity. We hypothesize that the combination of spatially extended Lyman-alpha, large amounts of warm IR-luminous dust, and rarity (implying a short-lived phase) can be explained if the galaxies are undergoing strong `feedback' transforming them from an extreme dusty starburst to a QSO.Comment: Submitted to ApJ Letters, 6 pages, 4 figures. Comments welcom

Spitzer Photometry of WISE-Selected Brown Dwarf and Hyper-Luminous Infrared Galaxy Candidates

We present Spitzer 3.6 and 4.5 $\mu$m photometry and positions for a sample of 1510 brown dwarf candidates identified by the WISE all-sky survey. Of these, 166 have been spectroscopically classified as objects with spectral types M(1), L(7), T(146), and Y(12); Sixteen other objects are non-(sub)stellar in nature. The remainder are most likely distant L and T dwarfs lacking spectroscopic verification, other Y dwarf candidates still awaiting follow-up, and assorted other objects whose Spitzer photometry reveals them to be background sources. We present a catalog of Spitzer photometry for all astrophysical sources identified in these fields and use this catalog to identify 7 fainter (4.5 $\mu$m $\sim$ 17.0 mag) brown dwarf candidates, which are possibly wide-field companions to the original WISE sources. To test this hypothesis, we use a sample of 919 Spitzer observations around WISE-selected high-redshift hyper-luminous infrared galaxy (HyLIRG) candidates. For this control sample we find another 6 brown dwarf candidates, suggesting that the 7 companion candidates are not physically associated. In fact, only one of these 7 Spitzer brown dwarf candidates has a photometric distance estimate consistent with being a companion to the WISE brown dwarf candidate. Other than this there is no evidence for any widely separated ($>$ 20 AU) ultra-cool binaries. As an adjunct to this paper, we make available a source catalog of $\sim$ 7.33 $\times 10^5$ objects detected in all of these Spitzer follow-up fields for use by the astronomical community. The complete catalog includes the Spitzer 3.6 and 4.5 $\mu$m photometry, along with positionally matched $B$ and $R$ photometry from USNO-B; $J$, $H$, and $K_s$ photometry from 2MASS; and $W1$, $W2$, $W3$, and $W4$ photometry from the WISE all-sky catalog

Visualizing the Interface of Biotin and Fatty Acid Biosynthesis through SuFEx Probes

Site-specific covalent conjugation offers a powerful tool to identify and understand protein-protein interactions. In this study, we discover that sulfur fluoride exchange (SuFEx) warheads effectively crosslink the Escherichia coli acyl carrier protein (AcpP) with its partner BioF, a key pyridoxal 5′-phosphate (PLP)-dependent enzyme in the early steps of biotin biosynthesis by targeting a tyrosine residue proximal to the active site. We identify the site of crosslink by MS/MS analysis of the peptide originating from both partners. We further evaluate the BioF-AcpP interface through protein crystallography and mutational studies. Among the AcpP-interacting BioF surface residues, three critical arginine residues appear to be involved in AcpP recognition so that pimeloyl-AcpP can serve as the acyl donor for PLP-mediated catalysis. These findings validate an evolutionary gain-of-function for BioF, allowing the organism to build biotin directly from fatty acid biosynthesis through surface modifications selective for salt bridge formation with acidic AcpP residues.</p