HLA Class I or Class II and Disease Association: Catch the Difference if You Can

The association of autoimmune diseases with HLA has been known for many decades. To date, however, the underlying mechanisms have not been fully understood. The recently introduced genome-wide association studies (GWAS) have suggested that several genes converging in common pathways contribute to the genetic susceptibility in such disorders. Nevertheless, for most autoimmune/autoinflammatory diseases, the HLA genes are by far the strongest risk factors. The basis of some associations has now been elucidated, particularly in those cases in which exogenous factors are involved

Surveying the Agents of Galaxy Evolution in the Tidally Stripped, Low Metallicity Small Magellanic Cloud (SAGE-SMC). I. Overview

The Small Magellanic Cloud (SMC) provides a unique laboratory for the study of the lifecycle of dust given its low metallicity (~1/5 solar) and relative proximity (~60 kpc). This motivated the SAGE-SMC (Surveying the Agents of Galaxy Evolution in the Tidally Stripped, Low Metallicity Small Magellanic Cloud) Spitzer Legacy program with the specific goals of studying the amount and type of dust in the present interstellar medium, the sources of dust in the winds of evolved stars, and how much dust is consumed in star formation. This program mapped the full SMC (30 deg^2) including the body, wing, and tail in seven bands from 3.6 to 160 μm using IRAC and MIPS on the Spitzer Space Telescope. The data were reduced and mosaicked, and the point sources were measured using customized routines specific for large surveys. We have made the resulting mosaics and point-source catalogs available to the community. The infrared colors of the SMC are compared to those of other nearby galaxies and the 8 μm/24 μm ratio is somewhat lower than the average and the 70 μm/160 μm ratio is somewhat higher than the average. The global infrared spectral energy distribution (SED) shows that the SMC has approximately 1/3 the aromatic emission/polycyclic aromatic hydrocarbon abundance of most nearby galaxies. Infrared color-magnitude diagrams are given illustrating the distribution of different asymptotic giant branch stars and the locations of young stellar objects. Finally, the average SED of H II/star formation regions is compared to the equivalent Large Magellanic Cloud average H II/star formation region SED. These preliminary results will be expanded in detail in subsequent papers

Ankylosing Spondylitis: a trade Off of HLA-B27, ERAP, and pathogen interconnections? Focus on Sardinia

The frequency of HLA-B27 in patients with Ankylosing Spondylitis (AS) is over 85%. There are more than 170 recognized HLA-B27 alleles but the majority of them is not sufficiently represented for genetic association studies. So far only two alleles, the HLA-B*2706 in Asia and the HLA-B*2709 in Sardinia, have not been found to be associated with AS. The highly homogenous genetic structure of the Sardinian population has favored the search of relevant variants for disease-association studies. Moreover, malaria, once endemic in the island, has been shown to have contributed to shape the native population genome affecting the relative allele frequency of relevant genes. In Sardinia, the prevalence of HLA-B*2709, which differs from the strongly AS-associated B*2705 prototype for one amino acid (His/Asp116) in the F pocket of the peptide binding groove, is around 20% of all HLA-B27 alleles. We have previously hypothesized that malaria could have contributed to the establishment of this allele in Sardinia. Based on our recent findings, in this perspective article we speculate that the Endoplasmic Reticulum Amino Peptidases, ERAP1 and 2, associated with AS and involved in antigen presentation, underwent co-selection by malaria. These genes, besides shaping the immunopeptidome of HLA-class I molecules, have other biological functions that could also be involved in the immunosurveillance against malaria

The PTI Carbon Star Angular Size Survey: Effective Temperatures and Non-Sphericity

We report new interferometric angular diameter observations of 41 carbon stars observed with the Palomar Testbed Interferometer (PTI). Two of these stars are CH carbon stars and represent the first such measurements for this subtype. Of these, 39 have Yamashita (1972,1975) spectral classes and are of sufficiently high quality that we may determine the dependence of effective temperature on spectral type. We find that there is a tendency for the effective temperature to increase with increasing temperature index by ~120K per step, starting at T_EFF ~= 2500K for C3,y, although there is a large amount of scatter about this relationship. Overall, the median effective temperature for the carbon star sample is found to be 2800 +- 270K, and the median linear radius is 360 +- 100 R_SUN. We also find agreement on average within 15K with the T_EFF determinations of Bergeat (2001,2002a,b), and a refinement of carbon star angular size prediction based on V & K magnitudes is presented that is good to an rms of 12%. A subsample of our stars have sufficient {u,v} coverage to permit non-spherical modeling of their photospheres, and a general tendency for detection of statistically significant departures from sphericity with increasing signal-to-noise of the interferometric data is seen. The implications of most - and potentially all - carbon stars being non-spherical is considered in the context of surface inhomogeneities and a rotation-mass loss connection.Comment: 59 pages, 15 figures, 6 tables; accepted for publication in Ap

Analysis of the thin layer of Galactic warm ionized gas in the range 20 < l < 30 deg, -1.5 < b < +1.5 deg

We present an analysis of the thin layer of Galactic warm ionized gas at an angular resolution ~ 10'. This is carried out using radio continuum data at 1.4 GHz, 2.7 GHz and 5 GHz in the coordinate region 20 < l < 30 deg, -1.5 < b < +1.5 deg. For this purpose, we evaluate the zero level of the 2.7 and 5 GHz surveys using auxiliary data at 2.3 GHz and 408 MHz. The derived zero level corrections are T_{zero}(2.7 GHz)=0.15 +/- 0.06 K and T_{zero}(5 GHz)=0.1 +/- 0.05 K. We separate the thermal (free-free) and non-thermal (synchrotron) component by means of a spectral analysis performed adopting an antenna temperature spectral index -2.1 for the free-free emission, a realistic spatial distribution of indices for the synchrotron radiation and by fitting, pixel-by-pixel, the Galactic spectral index. We find that at 5 GHz, for |b| = 0 deg, the fraction of thermal emission reaches a maximum value of 82%, while at 1.4 GHz, the corresponding value is 68%. In addition, for the thermal emission, the analysis indicates a dominant contribution of the diffuse component relative to the source component associated with discrete HII regions.Comment: 9 pages, 9 figures, accepted to MNRA

The MIPSGAL View of Supernova Remnants in the Galactic Plane

We report the detection of Galactic supernova remnants (SNRs) in the mid-infrared (at 24 and 70 μm), in the coordinate ranges 10° < l < 65° and 285° < l < 350°, |b| < 1°, using MIPS aboard the Spitzer Space Telescope. We search for infrared counterparts to SNRs in Green's catalog and identify 39 out of 121, i.e., a detection rate of about 32%. Such a relatively low detection fraction is mainly due to confusion with nearby foreground/background sources and diffuse emission. The SNRs in our sample show a linear trend in [F_8/F_(24)] versus [F_(70)/F_(24)]. We compare their infrared fluxes with their corresponding radio flux at 1.4 GHz and find that most remnants have a ratio of 70 μm to 1.4 GHz which is similar to those found in previous studies of SNRs (with the exception of a few that have ratios closer to those of H II regions). Furthermore, we retrieve a slope close to unity when correlating infrared (24 and 70 μm) with 1.4 GHz emission. Our survey is more successful in detecting remnants with bright X-ray emission, which we find is well correlated with the 24 μm morphology. Moreover, by comparing the power emitted in the X-ray, infrared, and radio, we conclude that the energy released in the infrared is comparable to the cooling in the X-ray range

The Hi-GAL compact source catalogue – I. The physical properties of the clumps in the inner Galaxy (−71∘.0 < ℓ < 67∘0)

Hi-GAL (Herschel InfraRed Galactic Plane Survey) is a large-scale survey of the Galactic plane, performed with Herschel in five infrared continuum bands between 70 and 500 μm. We present a band-merged catalogue of spatially matched sources and their properties derived from fits to the spectral energy distributions (SEDs) and heliocentric distances, based on the photometric catalogues presented in Molinari et al., covering the portion of Galactic plane −71∘.0 < ℓ < 67∘.0. The band-merged catalogue contains 100 922 sources with a regular SED, 24 584 of which show a 70-μm counterpart and are thus considered protostellar, while the remainder are considered starless. Thanks to this huge number of sources, we are able to carry out a preliminary analysis of early stages of star formation, identifying the conditions that characterize different evolutionary phases on a statistically significant basis. We calculate surface densities to investigate the gravitational stability of clumps and their potential to form massive stars. We also explore evolutionary status metrics such as the dust temperature, luminosity and bolometric temperature, finding that these are higher in protostellar sources compared to pre-stellar ones. The surface density of sources follows an increasing trend as they evolve from pre-stellar to protostellar, but then it is found to decrease again in the majority of the most evolved clumps. Finally, we study the physical parameters of sources with respect to Galactic longitude and the association with spiral arms, finding only minor or no differences between the average evolutionary status of sources in the fourth and first Galactic quadrants, or between ‘on-arm’ and ‘interarm’ positions

An allelic variant in the intergenic region between ERAP1 and ERAP2 correlates with an inverse expression of the two genes

The Endoplasmatic Reticulum Aminopeptidases ERAP1 and ERAP2 are implicated in a variety of immune and non-immune functions. Most studies however have focused on their role in shaping the HLA class I peptidome by trimming peptides to the optimal size. Genome Wide Association Studies highlighted non-synonymous polymorphisms in their coding regions as associated with several immune mediated diseases. The two genes lie contiguous and oppositely oriented on the 5q15 chromosomal region. Very little is known about the transcriptional regulation and the quantitative variations of these enzymes. Here, we correlated the level of transcripts and proteins of the two aminopeptidases in B-lymphoblastoid cell lines from 44 donors harbouring allelic variants in the intergenic region between ERAP1 and ERAP2. We found that the presence of a G instead of an A at SNP rs75862629 in the ERAP2 gene promoter strongly influences the expression of the two ERAPs with a down-modulation of ERAP2 coupled with a significant higher expression of ERAP1. We therefore show here for the first time a coordinated quantitative regulation of the two ERAP genes, which can be relevant for the setting of specific therapeutic approaches