The gravitationally lensed, luminous infrared galaxy IRAS F10214+4724 observed with XMM-Newton

We report on a short XMM-Newton observation of the gravitationally-lensed, luminous infrared galaxy IRAS F10214+4724 at z=2.3. A faint X-ray source is detected at 4 sigma. The observed 0.5-2 keV (1.7-6.6 keV in the rest-frame) flux is 1.3e-15 erg/s/cm2 and the spectral slope in the rest-frame 1-10 keV band is Gamma~2. These results agree with those obtained from the Chandra X-ray Observatory, given the large uncertainties in both measurements. While possible evidence for excess emission above 5 keV is seen, we suspect this excess might be either spurious or not related to the infrared galaxy.Comment: 4 pages, 2 figures, New Astronomy in pres

Neuroinflammation in Multiple System Atrophy: Response to and Cause of α-Synuclein Aggregation

Multiple system atrophy (MSA) is a progressive neurodegenerative disease presenting with combinations of autonomic dysfunction, parkinsonism, cerebellar ataxia and/or pyramidal signs. Oligodendroglial cytoplasmic inclusions (GCIs) rich in α-synuclein (α-syn) constitute the disease hallmark, accompanied by neuronal loss and activation of glial cells which indicate neuroinflammation. Recent studies demonstrate that α-syn may be released from degenerating neurons to mediate formation of abnormal inclusion bodies and to induce neuroinflammation which, interestingly, might also favor the formation of intracellular α-syn aggregates as a consequence of cytokine release and the shift to a pro-inflammatory environment. Here, we critically review the relationships between α-syn and astrocytic and microglial activation in MSA to explore the potential of therapeutics which target neuroinflammation.9 page(s

Deep Submillimeter Surveys: Luminous Infrared Galaxies at High Redshift

Deep surveys at 850microns from Mauna Kea using the SCUBA camera on the JCMT appear to have discovered a substantial population of ultraluminous infrared galaxies (ULIGs: L_ir > 10^{12} L_sun). The cumulative space density of these sources (~10,000 per sq.deg with S_850 > 1mJy) is sufficient to account for nearly all of the extragalactic background light at submillimeter wavelengths. Current estimates of the redshift distribution suggest a peak in the comoving space density of SCUBA sources at z = 1-3, similar to what is observed for QSOs and radio galaxies. The luminosity density in the far-infrared/submillimeter exceeds that in the UV by factors of 3-10 over this redshift range, implying that as much as 80-90% of the "activity" in galaxies at z < 4 is hidden by dust. The SCUBA sources plausibly represent the primary epoch in the formation of spheroids and massive black holes triggered by major mergers of large gas-rich disks.Comment: LaTex, 14 pages with 9 embedded .eps figures. To appear in ``Space Infrared Telescopes and Related Science", 32nd COSPAR workshop, Nagoya, Japan 1998, ed. T. Matsumoto, T. de Graau

The CO line SED and atomic carbon in IRAS F10214+4724

Using the IRAM 30m telescope and the Plateau de Bure interferometer we have detected the \ctwo and the CO 3$-$2, 4$-$3, 6$-$5, 7$-$6 transitions as well as the dust continuum at 3 and 1.2 mm towards the distant luminous infrared galaxy IRAS F10214+4724 at $z=2.286$. The \ctwo line is detected for the first time towards this source and IRAS F10214+4724 now belongs to a sample of only 3 extragalactic sources at any redshift where both of the carbon fine structure lines have been detected. The source is spatially resolved by our \ctwo\ observation and we detect a velocity gradient along the east-west direction. The CI line ratio allows us to derive a carbon excitation temperature of 42$^{+12}_{-9}$ K. The carbon excitation in conjunction with the CO ladder and the dust continuum constrain the gas density to n(\hh) = $10^{3.6-4.0}$ cm$^{-3}$ and the kinetic temperature to $T\rm_{kin}$ = 45--80 K, similar to the excitation conditions found in nearby starburst galaxies. The rest-frame 360 $\mu$m dust continuum morphology is more compact than the line emitting region, which supports previous findings that the far infrared luminosity arises from regions closer to the active galactic nucleus at the center of this system.Comment: 11 pages, 9 figures, accepted by A&

Highly-excited CO emission in APM08279+5255 at z=3.9

We report the detection of the CO 4-3, 6-5, 9-8, 10-9, and 11-10 lines in the Broad Absorption Line quasar APM08279+5255 at z=3.9 using the IRAM 30m telescope. We also present IRAM PdBI high spatial resolution observations of the CO 4-3 and 9-8 lines, and of the 1.4mm dust radiation as well as an improved spectrum of the HCN(5-4) line. Unlike CO in other QSO host galaxies, the CO line SED of APM08279+5255 rises up to the CO(10-9) transition. The line fluxes in the CO ladder and the dust continuum fluxes are best fit by a two component model, a "cold" component at ~65K with a high density of n(H2)= 1x10^5 cm^-3, and a "warm", ~220K component with a density of 1x10^4 cm^-3. We show that IR pumping via the 14 micron bending mode of HCN is the most likely channel for the HCN excitation. From our models we find, that the CO(1-0) emission is dominated by the {\it dense} gas component which implies that the CO conversion factor is higher than usually assumed for high-z galaxies with alpha~5 SM/(K km/s pc^2). Using brightness temperature arguments, the results from our high-resolution mapping, and lens models from the literature, we argue that the molecular lines and the dust continuum emission arise from a very compact (r~100-300 pc), highly gravitationally magnified (m= 60-110) region surrounding the central AGN. Part of the difference relative to other high-$z$ QSOs may therefore be due to the configuration of the gravitational lens, which gives us a high-magnification zoom right into the central 200-pc radius of APM08279+5255 where IR pumping plays a significant role for the excitation of the molecular lines.Comment: 18 pages, 14 figures, accepted for publication in A&

Gravitational Lensing at Millimeter Wavelengths

With today's millimeter and submillimeter instruments observers use gravitational lensing mostly as a tool to boost the sensitivity when observing distant objects. This is evident through the dominance of gravitationally lensed objects among those detected in CO rotational lines at z>1. It is also evident in the use of lensing magnification by galaxy clusters in order to reach faint submm/mm continuum sources. There are, however, a few cases where millimeter lines have been directly involved in understanding lensing configurations. Future mm/submm instruments, such as the ALMA interferometer, will have both the sensitivity and the angular resolution to allow detailed observations of gravitational lenses. The almost constant sensitivity to dust emission over the redshift range z=1-10 means that the likelihood for strong lensing of dust continuum sources is much higher than for optically selected sources. A large number of new strong lenses are therefore likely to be discovered with ALMA, allowing a direct assessment of cosmological parameters through lens statistics. Combined with an angular resolution <0.1", ALMA will also be efficient for probing the gravitational potential of galaxy clusters, where we will be able to study both the sources and the lenses themselves, free of obscuration and extinction corrections, derive rotation curves for the lenses, their orientation and, thus, greatly constrain lens models.Comment: 69 pages, Review on quasar lensing. Part of a LNP Topical Volume on "Dark matter and gravitational lensing", eds. F. Courbin, D. Minniti. To be published by Springer-Verlag 2002. Paper with full resolution figures can be found at ftp://oden.oso.chalmers.se/pub/tommy/mmviews.ps.g

Environmental Factors Controlling the Distribution of Symbiodinium Harboured by the Coral Acropora millepora on the Great Barrier Reef

Background: The Symbiodinium community associated with scleractinian corals is widely considered to be shaped by seawater temperature, as the coral's upper temperature tolerance is largely contingent on the Symbiodinium types harboured. Few studies have challenged this paradigm as knowledge of other environmental drivers on the distribution of Symbiodinium is limited. Here, we examine the influence of a range of environmental variables on the distribution of Symbiodinium associated with Acropora millepora collected from 47 coral reefs spanning 1,400 km on the Great Barrier Reef (GBR), Australia

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease