B cells from rheumatoid arthritis patients show important alterations in the expression of CD86 and FcγRIIb, which are modulated by anti-tumor necrosis factor therapy

Introduction: Several molecules help preserve peripheral B cell tolerance, but when altered, they may predispose to autoimmunity. This work studied the expression of the costimulatory molecule CD86 and the inhibitory receptor for IgG immune complexes FcγRIIb (CD32b), on B cells from rheumatoid arthritis (RA) patients, and the influence of anti-tumor necrosis factor (TNF) therapy.Methods: Peripheral B cells from 18 RA patients and 13 healthy donors were characterized using flow cytometry. Eleven patients who underwent a six-month adalimumab therapy were further assessed for phenotypic changes on their B cells.Results: RA patients exhibited a high percentage of naïve and memory B cells expressing CD86. In contrast, expression of FcγRIIb was significantly reduced on RA memory B cells and plasmablasts as compared to healthy donors, probably due to downregulation of this receptor when differentiating from naïve to memory cells. These alterations on FcγRIIb were associated with high levels

Dexamethasone Preconditioning Improves the Response of Collagen-Induced Arthritis to Treatment with Short-Term Lipopolysaccharide-Stimulated Collagen-Loaded Dendritic Cells

Background. Pharmacologically modulated dendritic cells (DCs) have been shown to restore tolerance in type II collagen-(CII-) induced arthritis (CIA). We examined the effect of dexamethasone (DXM) administration as a preconditioning agent, followed by an injection of lipopolysaccharide-(LPS-) stimulated and CII-loaded DCs on the CIA course. Methods. After CIA induction, mice pretreated with DXM were injected with 4-hour LPS-stimulated DCs loaded with CII (DXM/4hLPS/CII/DCs). Results. Mice injected with DXM/4hLPS/CII/DCs displayed significantly less severe clinical disease compared to animals receiving 4hLPS/CII/DCs alone or those in which only DXM was administered. Cytokine profile evaluation showed that CD4+ T cells from DXM/4hLPS/CII/DCs and 4hLPS/CII/DCs groups release higher IL-10 levels than those from mice receiving DXM alone or CIA mice. CD4+ T cells from all DC-treated groups showed less IL-17 release when compared to the CIA group. On the contrary, CD4+ T cells from DXM/4hLPS/CII/DCs and 4hLPS/CII/DCs groups released higher IFN-γ levels than those from CIA group. Conclusion. A combined treatment, including DXM preconditioning followed by an inoculation of short-term LPS-stimulated CII-loaded DCs, provides an improved strategy for attenuating CIA severity. Our results suggest that this benefit is driven by a modulation in the cytokine profile secreted by CD4+ T cells

Isolation of HLA-DR-naturally presented peptides identifies T-cell epitopes for rheumatoid arthritis

Objective Rheumatoid arthritis (RA) immunopathogenesis revolves around the presentation of poorly characterised self-peptides by human leucocyte antigen (HLA)-class II molecules on the surface of antigen-presenting cells to autoreactive CD4 +T cells. Here, we analysed the HLA-DR-Associated peptidome of synovial tissue (ST) and of dendritic cells (DCs) pulsed with synovial fluid (SF) or ST, to identify potential T-cell epitopes for RA. Methods HLA-DR/peptide complexes were isolated from RA ST samples (n=3) and monocyte-derived DCs, generated from healthy donors carrying RA-Associated shared epitope positive HLA-DR molecules and pulsed with RA SF (n=7) or ST (n=2). Peptide sequencing was performed by high-resolution mass spectrometry. The immunostimulatory capacity of selected peptides was evaluated on peripheral blood mononuclear cells from patients with RA (n=29) and healthy subjects (n=12) by flow cytometry. Results We identified between 103 and 888 HLA-DR-naturally presented peptides per sample. We selected 37 native and six citrullinated (cit)-peptides for stimulation assays. Six of these peptides increased the expression of CD40L on CD4 +T cells patients with RA, and specifically triggered IFN-γexpression on RA CD4 +T cells compared with healthy subjects. Finally, the frequency of IFN- 3-producing CD4 +T cells specific for a myeloperoxidase-derived peptide showed a positive correlation with disease activity. Conclusions We significantly expanded the peptide repertoire presented by HLA-DR molecules in a physiologically relevant context, identifying six new epitopes recognised by CD4 +T cells from patients with RA. This information is important for a better understanding of the disease immunopathology, as well as for designing tolerising antigen-specific immunotherapies.This study was funded by the following grants: Fondecyt 1181853, Fondef-IDeA ID15I10080; Fondef-IDeA ID15I20080, Fondef-IDeA ID18I10243, and REDES 180028, from ANID, Chile; and by Project RTI2018-097414-B-I00 from the Spanish Ministry of Science. Doctoral training of JM was supported by ANID-PFCHA/National Doctoral Scholarship 2018/No 21181538

Large-Scale Temperature Changes across the Southern Andes: 20th-Century Variations in the Context of the Past 400 Years

Long-term trends of temperature variations across the southern Andes (37–55° S) are examined using a combination of instrumental and tree-ring records. A critical appraisal of surface air temperature from station records is presented for southern South America during the 20th century. For the interval 1930–1990, three major patterns in temperature trends are identified. Stations along the Pacific coast between 37 and 43° S are characterized by negative trends in mean annual temperature with a marked cooling period from 1950 to the mid-1970s. A clear warming trend is observed in the southern stations (south of 46°S), which intensifies at higher latitudes. No temperature trends are detected for the stations on the Atlantic coast north of 45° S. In contrast to higher latitudes in the Northern Hemisphere where annual changes in temperature are dominated by winter trends, both positive and negative trends in southern South America are due to mostly changes in summer (December to February) temperatures. Changes in the Pacific Decadal Oscillation (PDO) around 1976 are felt in summer temperatures at most stations in the Pacific domain, starting a period with increased temperature across the southern Andes and at higher latitudes.Tree-ring records from upper-treeline were used to reconstruct past temperature fluctuations for the two dominant patterns over the southern Andes. These reconstructions extend back to 1640 and are based on composite tree-ring chronologies that were processed to retain as much low-frequency variance as possible. The resulting reconstructions for the northern and southern sectors of the southern Andes explain 55% and 45% ofthe temperature variance over the interval 1930–1989, respectively. Cross-spectral analysis of actual and reconstructed temperatures over the common interval 1930–1989, indicates that most of the explained varianceis at periods >10 years in length. At periods >15 years, the squaredcoherency between actual and reconstructed temperatures ranges between 0.6 and 0.95 for both reconstructions. Consequently, these reconstructions are especially useful for studying multi-decennial temperature variations in the South American sector of the Southern Hemisphere over the past 360 years. As a result, it is possible to show that the temperatures during the 20thcentury have been anomalously warm across the southern Andes. The mean annual temperatures for the northern and southern sectors during the interval 1900–1990 are 0.53 °C and 0.86 °C above the1640–1899 means, respectively. These findings placed the current warming in a longer historical perspective, and add new support for the existence of unprecedented 20th century warming over much of the globe. The rate of temperature increase from 1850 to 1920 was the highest over the past 360 years, a common feature observed in several proxy records from higher latitudes in the Northern Hemisphere.Local temperature regimes are affected by changes in planetary circulation, with in turn are linked to global sea surface temperature (SST) anomalies. Therefore, we explored how temperature variations in the southern Andes since 1856 are related to large-scale SSTs on the South Pacific and South Atlantic Oceans. Spatial correlation patterns between the reconstructions and SSTs show that temperature variations in the northern sector of the southern Andes are strongly connected with SST anomalies in the tropical and subtropical Pacific. This spatial correlation pattern resembles the spatial signature of the PDO mode of SST variability over the South Pacific and is connected with the Pacific-South American (PSA) atmospheric pattern in the Southern Hemisphere. In contrast, temperature variations in the southern sector of the southern Andes are significantly correlated with SST anomalies over most of the South Atlantic, and in less degree, over the subtropical Pacific. This spatial correlation field regressed against SST resembles the `Global Warming' mode of SST variability, which in turn, is linked to the leading mode of circulation in the Southern Hemisphere. Certainly, part of the temperature signal present in the reconstructions can be expressed as a linear combination of four orthogonal modes of SST variability. Rotated empirical orthogonal function analysis, performed on SST across the South Pacific and South Atlantic Oceans, indicate that four discrete modes of SST variability explain a third, approximately, of total variance in temperature fluctuations across the southern Andes.Fil: Villalba, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Lara, Antonio. Universidad Austral de Chile; ChileFil: Boninsegna, Jose Armando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Masiokas, Mariano Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Delgado, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Aravena, Juan C.. Universidad de Chile; ChileFil: Roig Junent, Fidel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Schmelter, Andrea. Universitaet Bonn; AlemaniaFil: Wolodarsky, Alexia. Universidad Austral de Chile; ChileFil: Ripalta, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentin

Mid-infrared Galaxy Morphology from the Spitzer Survey of Stellar Structure in Galaxies (S^4G): The Imprint of the De Vaucouleurs Revised Hubble-Sandage Classification System at 3.6 μm

Spitzer Space Telescope Infrared Array Camera imaging provides an opportunity to study all known morphological types of galaxies in the mid-IR at a depth significantly better than ground-based near-infrared and optical images. The goal of this study is to examine the imprint of the de Vaucouleurs classification volume in the 3.6 μm band, which is the best Spitzer waveband for galactic stellar mass morphology owing to its depth and its reddening-free sensitivity mainly to older stars. For this purpose, we have prepared classification images for 207 galaxies from the Spitzer archive, most of which are formally part of the Spitzer Survey of Stellar Structure in Galaxies (S^4G), a Spitzer post-cryogenic ("warm") mission Exploration Science Legacy Program survey of 2331 galaxies closer than 40 Mpc. For the purposes of morphology, the galaxies are interpreted as if the images are blue light, the historical waveband for classical galaxy classification studies. We find that 3.6 μm classifications are well correlated with blue-light classifications, to the point where the essential features of many galaxies look very similar in the two very different wavelength regimes. Drastic differences are found only for the most dusty galaxies. Consistent with a previous study by Eskridge et al., the main difference between blue-light and mid-IR types is an ≈1 stage interval difference for S0/a to Sbc or Sc galaxies, which tend to appear "earlier" in type at 3.6 μm due to the slightly increased prominence of the bulge, the reduced effects of extinction, and the reduced (but not completely eliminated) effect of the extreme population I stellar component. We present an atlas of all of the 207 galaxies analyzed here and bring attention to special features or galaxy types, such as nuclear rings, pseudobulges, flocculent spiral galaxies, I0 galaxies, double-stage and double-variety galaxies, and outer rings, that are particularly distinctive in the mid-IR

Holocene tephrochronology around Cochrane (~47° S), southern Chile

Two Holocene tephras encountered in outcrops, cores and trenches in bogs, and lake cores in the area around Cochrane, southern Chile, are identified (based on their age, tephra glass color and morphology, mineralogy, and both bulk and glass chemistry) as H1 derived from Hudson volcano, and MEN1 derived from Mentolat volcano. New AMS radiocarbon ages indicate systematic differences between those determined in lake cores (MEN1=7,689 and H1=8,440 cal yrs BP) and surface deposits (MEN1=7,471 and H1=7,891 cal yrs BP), with the lake cores being somewhat older. H1 tephra layers range from 8 to 18 cm thick, suggesting that both the area of the 10 cm isopach and the volume of this eruption were larger than previously suggested, but not greatly, and that the direction of maximum dispersion was more to the south. MEN1 tephra layers range from 1-4 cm in thickness, indicating that this was probably a reasonably large (&gt;5 km3) eruption. Some of the lake cores also contain thin layers (&lt; 2 cm) of late Holocene H2 tephra and the recent H3 (1991 AD) tephra, both derived from the Hudson volcano. No tephra evidence has been observed for any late Pleistocene tephra, nor for the existence of the supposed Arenales volcano, proposed to be located west of Cochrane.</p

Mapping soil organic carbon content in Patagonian forests based on climate, topography and vegetation metrics from satellite imagery

Soil organic carbon (SOC) content supports several ecosystem services. Quantifying SOC requires: (i) accurate C estimates of forest components, and (ii) soil estimates. However, SOC is difficult to measure, so predictive models are needed. Our objective was to model SOC stocks within 30 cm depth in Patagonian forests based on climatic, topographic and vegetation productivity measures from satellite images, including Dynamic Habitat Indices and Land Surface Temperature derived from Landsat-8. We used data from 1320 stands of different forest types in Patagonia, and random forest regression to map SOC. The model captured SOC variability well (R2 = 0.60, RMSE = 22.1%), considering the huge latitudinal extension (36.4◦ to 55.1◦ SL) and the great diversity of forest types. Mean SOC was 134.4 ton C ha−1 ± 25.2, totaling 404.2 million ton C across Patagonia. Overall, SOC values were highest in valleys of the Andes mountains and in southern Tierra del Fuego, ranging from 53.5 to 277.8 ton C ha−1 for the whole Patagonia region. Soil organic carbon is a metric relevant to many applications, connecting major issues such as forest management, conservation, and livestock production, and having spatially explicit estimates of SOC enables managers to fulfil the international agreements that Argentina has joined.EEA EsquelFil: Martínez Pastur, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas (CADIC). Laboratorio de Recursos Agroforestales; ArgentinaFil: Aravena Acuña, Marie Claire. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas (CADIC). Laboratorio de Recursos Agroforestales; ArgentinaFil: Silveira, Eduarda M. O. University of Wisconsin. Department of Forest and Wildlife Ecology. SILVIS Lab.; Estados UnidosFil: von Müller, Axel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agroforestal Esquel; ArgentinaFil: La Manna, Ludmila. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: La Manna, Ludmila. Universidad Nacional de la Patagonia San Juan Bosco. Facultad de Ingeniería. Centro de Estudios Ambientales Integrados; ArgentinaFil: González Polo, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: González Polo, Marina. Universidad Nacional del Comahue. Instituto de Investigaciones en Biodiversidad y Medioambiente (INIBIOMA); ArgentinaFil: Chaves, Jimena E. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas (CADIC). Laboratorio de Recursos Agroforestales; ArgentinaFil: Cellini, Juan M. Universidad Nacional de La Plata. Laboratorio de Investigaciones en Maderas (LIMAD); ArgentinaFil: Lencinas, María V. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas (CADIC). Laboratorio de Recursos Agroforestales; ArgentinaFil: Radeloff, Volker C. University of Wisconsin. Department of Forest and Wildlife Ecology. SILVIS Lab.; Estados UnidosFil: Pidgeon, Anna M. University of Wisconsin. Department of Forest and Wildlife Ecology. SILVIS Lab.; Estados UnidosFil: Peri, Pablo Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

The Spitzer Survey of Stellar Structure in Galaxies (S^4G)

The Spitzer Survey of Stellar Structure in Galaxies S^4G is an Exploration Science Legacy Program approved for the Spitzer post-cryogenic mission. It is a volume-, magnitude-, and size-limited (d < 40 Mpc, |b| > 30 degrees, m_(Bcorr) < 15.5, D25>1') survey of 2,331 galaxies using IRAC at 3.6 and 4.5 microns. Each galaxy is observed for 240 s and mapped to > 1.5 x D25. The final mosaicked images have a typical 1 sigma rms noise level of 0.0072 and 0.0093 MJy / sr at 3.6 and 4.5 microns, respectively. Our azimuthally-averaged surface brightness profile typically traces isophotes at mu_3.6 (AB) (1 sigma) ~ 27 mag arcsec^-2, equivalent to a stellar mass surface density of ~ 1 Msun pc^-2. S^4G thus provides an unprecedented data set for the study of the distribution of mass and stellar structures in the local Universe. This paper introduces the survey, the data analysis pipeline and measurements for a first set of galaxies, observed in both the cryogenic and warm mission phase of Spitzer. For every galaxy we tabulate the galaxy diameter, position angle, axial ratio, inclination at mu_3.6 (AB) = 25.5 and 26.5 mag arcsec^-2 (equivalent to ~ mu_B (AB) =27.2 and 28.2 mag arcsec^-2, respectively). These measurements will form the initial S^4G catalog of galaxy properties. We also measure the total magnitude and the azimuthally-averaged radial profiles of ellipticity, position angle, surface brightness and color. Finally, we deconstruct each galaxy using GALFIT into its main constituent stellar components: the bulge/spheroid, disk, bar, and nuclear point source, where necessary. Together these data products will provide a comprehensive and definitive catalog of stellar structures, mass and properties of galaxies in the nearby Universe.Comment: Accepted for Publication in PASP, 14 pages, 13 figure

Phylogeography and population genetics of Vicugna vicugna: evolution in the arid Andean high plateau

The vicuña (Vicugna vicugna) is the most representative wild ungulate of the high Andes of South America with two recognized morphological subspecies, V. v. mensalis in the north and V. v. vicugna in the south of its distribution. Current vicuña population size (460,000–520,000 animals) is the result of population recovery programs established in response to 500 years of overexploitation. Despite the vicuña’s ecosystemic, economic and social importance, studies about their genetic variation and history are limited and geographically restricted. Here, we present a comprehensive assessment of the genetic diversity of vicuña based on samples collected throughout its distribution range corresponding to eleven localities in Peru and five in Chile representing V. v. mensalis, plus four localities each in Argentina and Chile representing V. v. vicugna. Analysis of mitochondrial DNA and microsatellite markers show contrasting results regarding differentiation between the two vicuña types with mitochondrial haplotypes supporting subspecies differentiation, albeit with only a few mutational steps separating the two subspecies. In contrast, microsatellite markers show that vicuña genetic variation is best explained as an isolation by distance pattern where populations on opposite ends of the distribution present different allelic compositions, but the intermediate populations present a variety of alleles shared by both extreme forms. Demographic characterization of the species evidenced a simultaneous and strong reduction in the effective population size in all localities supporting the existence of a unique, large ancestral population (effective size ∼50,000 individuals) as recently as the mid-Holocene. Furthermore, the genetic variation observed across all localities is better explained by a model of gene flow interconnecting them rather than only by genetic drift. Consequently, we propose space “continuous” Management Units for vicuña as populations exhibit differentiation by distance and spatial autocorrelation linked to sex biased dispersal instead of population fragmentation or geographical barriers across the distribution