MIF Signal Transduction Initiated by Binding to CD74

Macrophage migration inhibitory factor (MIF) accounts for one of the first cytokine activities to have been described, and it has emerged recently to be an important regulator of innate and adaptive immunity. MIF is an upstream activator of monocytes/macrophages, and it is centrally involved in the pathogenesis of septic shock, arthritis, and other inflammatory conditions. The protein is encoded by a unique but highly conserved gene, and X-ray crystallography studies have shown MIF to define a new protein fold and structural superfamily. Although recent work has begun to illuminate the signal transduction pathways activated by MIF, the nature of its membrane receptor has not been known. Using expression cloning and functional analysis, we report herein that CD74, a Type II transmembrane protein, is a high-affinity binding protein for MIF. MIF binds to the extracellular domain of CD74, and CD74 is required for MIF-induced activation of the extracellular signal–regulated kinase–1/2 MAP kinase cascade, cell proliferation, and PGE2 production. A recombinant, soluble form of CD74 binds MIF with a dissociation constant of ∼9 × 10−9 Kd, as defined by surface plasmon resonance (BIAcore analysis), and soluble CD74 inhibits MIF-mediated extracellular signal–regulated kinase activation in defined cell systems. These data provide a molecular basis for MIF's interaction with target cells and identify it as a natural ligand for CD74, which has been implicated previously in signaling and accessory functions for immune cell activation

The mass assembly of galaxy groups and the evolution of the magnitude gap

We investigate the assembly of groups and clusters of galaxies using the Millennium dark matter simulation and the associated gas simulations and semi-analytic catalogues of galaxies. In particular, in order to find an observable quantity that could be used to identify early-formed groups, we study the development of the difference in magnitude between their brightest galaxies to assess the use of magnitude gaps as possible indicators. We select galaxy groups and clusters at redshift z=1 with dark matter halo mass M(R200) > 1E13/h Msun, and trace their properties until the present time (z=0). We consider only the systems with X-ray luminosity L_X> 0.25E42/h^2 erg/s at z=0. While it is true that a large magnitude gap between the two brightest galaxies of a particular group often indicates that a large fraction of its mass was assembled at an early epoch, it is not a necessary condition. More than 90% of fossil groups defined on the basis of their magnitude gaps (at any epoch between 0<z<1) cease to be fossils within 4 Gyr, mostly because other massive galaxies are assembled within their cores, even though most of the mass in their haloes might have been assembled at early times. We show that, compared to the conventional definition of fossil galaxy groups based on the magnitude gap Delta m(12)> 2 (in the R-band, within 0.5R200 of the centre of the group), an alternative criterion Delta m(14)>2.5 (within the same radius) finds 50% more early-formed systems, and those that on average retain their fossil phase longer. However, the conventional criterion performs marginally better at finding early-formed groups at the high-mass end of groups. Nevertheless, both criteria fail to identify a majority of the early-formed systems.Comment: 16 pages, 11 figures, 2 tables. Accepted for publication in MNRA

Continuum Halos in Nearby Galaxies -- an EVLA Survey (CHANG-ES) -- I: Introduction to the Survey

We introduce a new survey to map the radio continuum halos of a sample of 35 edge-on spiral galaxies at 1.5 GHz and 6 GHz in all polarization products. The survey is exploiting the new wide bandwidth capabilities of the Karl G. Jansky Very Large Array (i.e. the Expanded Very Large Array, or EVLA) in a variety of array configurations (B, C, and D) in order to compile the most comprehensive data set yet obtained for the study of radio halo properties. This is the first survey of radio halos to include all polarization products. In this first paper, we outline the scientific motivation of the survey, the specific science goals, and the expected improvements in noise levels and spatial coverage from the survey. Our goals include investigating the physical conditions and origin of halos, characterizing cosmic ray transport and wind speed, measuring Faraday rotation and mapping the magnetic field, probing the in-disk and extraplanar far-infrared - radio continuum relation, and reconciling non-thermal radio emission with high-energy gamma-ray models. The sample size allows us to search for correlations between radio halos and other properties, including environment, star formation rate, and the presence of AGNs. In a companion paper (Paper II) we outline the data reduction steps and present the first results of the survey for the galaxy, NGC 4631.Comment: 17 pages, 1 figure, accepted to the Astronomical Journal, Version 2 changes: added acknowledgement to NRA

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain–behavior relationships after stroke

The goal of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well‐powered meta‐ and mega‐analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large‐scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided

The Extraordinary Amount of Substructure in the Hubble Frontier Fields Cluster Abell 2744

We present a joint optical/X-ray analysis of the massive galaxy cluster Abell 2744 (z=0.308). Our strong- and weak-lensing analysis within the central region of the cluster, i.e., at R < 1 Mpc from the brightest cluster galaxy, reveals eight substructures, including the main core. All of these dark-matter halos are detected with a significance of at least 5σ and feature masses ranging from 0.5 to 1.4× 1014M⊙ within R < 150 kpc. Merten et al. (2011) and Medezinski et al. (2016) substructures are also detected by us. We measure a slightly higher mass for the main core component than reported previously and attribute the discrepancy to the inclusion of our tightly constrained strong-lensing mass model built on Hubble Frontier Fields data. X-ray data obtained by XMM-Newton reveal four remnant cores, one of them a new detection, and three shocks. Unlike Merten et al. (2011), we find all cores to have both dark and luminous counterparts. A comparison with clusters of similar mass in the MXXL simulations yields no objects with as many massive substructures as observed in Abell 2744, confirming that Abell 2744 is an extreme system. We stress that these properties still do not constitute a challenge to ΛCDM, as caveats apply to both the simulation and the observations: for instance, the projected mass measurements from gravitational lensing and the limited resolution of the sub-haloes finders. We discuss implications of Abell 2744 for the plausibility of different dark-matter candidates and, finally, measure a new upper limit on the self-interaction cross-section of dark matter of σDM < 1.28 cm2g−1(68% CL), in good agreement with previous results from Harvey et al. (2015)

Inflationary perturbations from a potential with a step

We use a numerical code to compute the density perturbations generated during an inflationary epoch which includes a spontaneous symmetry breaking phase transition. A sharp step in the inflaton potential generates $k$ dependent oscillations in the spectrum of primordial density perturbations. The amplitude and extent in wavenumber of these oscillations depends on both the magnitude and gradient of the step in the inflaton potential. We show that observations of the cosmic microwave background anisotropy place strong constraints on the step parameters.Comment: 6 pages, Revtex - v2. reference adde