Spectroscopy of Pluto, 380-930 Nm at Six Longitudes

We have obtained spectra of the Pluto-Charon pair (unresolved) in the wavelength range 380-930 nm with resolution approx..450 at six roughly equally spaced longitudes. The data were taken in May and June, 2014, with the 4.2-m Isaac Newton Telescope at Roque de Los Muchachos Observatory in the Canary Islands, using the ACAM (auxiliary-port camera) in spectrometer mode, and using two solar analog stars. The new spectra clearly show absorption bands of solid CH4 at 620, 728, and 850-910 nm, which were known from earlier work. The 620-nm CH4 band is intrinsically very weak, and its appearance indicates a long optical path-length through the ice. This is especially true if it arises from CH4 dissolved in N2 ice. Earlier work (Owen et al. Science 261, 745, 1993) on the near-infrared spectrum of Pluto (1-2.5 microns) has shown that the CH4 bands are shifted to shorter wavelengths because the CH4 occurs as a solute in beta-phase crystalline N2. The optical path-length through the N2 crystals must be on the order of several cm to produce the N2 band observed at 2.15 microns. The new spectra exhibit a pronounced red slope across the entire wavelength range; the slope is variable with longitude, and differs in a small but significant way from that measured at comparable longitudes by Grundy & Fink (Icarus 124, 329, 1996) in their 15-year study of Pluto's spectrum (500-1000 nm). The new spectra will provide an independent means for calibrating the color filter bands on the Multispectral Visible Imaging Camera (MVIC) (Reuter et al. Space Sci. Rev. 140, 129, 2008) on the New Horizons spacecraft, which will encounter the Pluto-Charon system in mid-2015. They will also form the basis of modeling the spectrum of Pluto at different longitudes to help establish the nature of the non-ice component(s) of Pluto's surface. It is presumed that the non-ice component is the source of the yellow-red coloration of Pluto, which is known to be variable across the surface

E-cadherin expression and blunted interferon response in blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive neoplasm derived from plasmacytoid dendritic cells (pDCs). In this study, we investigated by immunohistochemical analysis the expression of E-cadherin (EC) on pDCs in reactive lymph nodes and tonsils, bone marrow, and in BPDCN. We compared the expression of EC in BPDCN to that in leukemia cutis (LC) and cutaneous lupus erythematosus (CLE), the latter typically featuring pDC activation. In BPDCN, we also assessed the immunomodulatory activity of malignant pDCs through the expression of several type I interferon (IFN-I) signaling effectors and downstream targets, PD-L1/CD274, and determined the extent of tumor infiltration by CD8-expressing T cells. In reactive lymph nodes and tonsils, pDCs expressed EC, whereas no reactivity was observed in bone marrow pDCs. BPDCN showed EC expression in the malignant pDCs in the vast majority of cutaneous (31/33 cases, 94%), nodal, and spleen localizations (3/3 cases, 100%), whereas it was more variable in the bone marrow (5/13, 38,5%), where tumor cells expressed EC similarly to the skin counterpart in 4 cases and differently in other 4. Notably, EC was undetectable in LC (n=30) and in juxta-epidermal pDCs in CLE (n=31). Contrary to CLE showing robust expression of IFN-I-induced proteins MX1 and ISG5 in 20/23 cases (87%), and STAT1 phosphorylation, BPDCN biopsies showed inconsistent levels of these proteins in most cases (85%). Expression of IFN-I-induced genes, IFI27, IFIT1, ISG15, RSAD2, and SIGLEC1, was also significantly (P\u3c0.05) lower in BPDCN as compared with CLE. In BPDCN, a significantly blunted IFN-I response correlated with a poor CD8+T-cell infiltration and the lack of PD-L1/CD274 expression by the tumor cells. This study identifies EC as a novel pDC marker of diagnostic relevance in BPDCN. The results propose a scenario whereby malignant pDCs through EC-driven signaling promote the blunting of IFN-I signaling and, thereby, the establishment of a poorly immunogenic tumor microenvironment

Occurrence of nodular lymphocyte-predominant hodgkin lymphoma in hermansky-pudlak type 2 syndrome is associated to natural killer and natural killer T cell defects

Hermansky Pudlak type 2 syndrome (HPS2) is a rare autosomal recessive primary immune deficiency caused by mutations on b3A gene (AP3B1 gene). The defect results in the impairment of the adaptor protein 3 (AP-3) complex, responsible for protein sorting to secretory lysosomes leading to oculo-cutaneous albinism, bleeding disorders and immunodeficiency. We have studied peripheral blood and lymph node biopsies from two siblings affected by HPS2. Lymph node histology showed a nodular lymphocyte predominance type Hodgkin lymphoma (NLPHL) in both HPS2 siblings. By immunohistochemistry, CD8 T-cells from HPS2 NLPHL contained an increased amount of perforin (Prf) + suggesting a defect in the release of this granules-associated protein. By analyzing peripheral blood immune cells we found a significant reduction of circulating NKT cells and of CD56brightCD162 Natural Killer (NK) cells subset. Functionally, NK cells were defective in their cytotoxic activity against tumor cell lines including Hodgkin Lymphoma as well as in IFN-c production. This defect was associated with increased baseline level of CD107a and CD63 at the surface level of unstimulated and IL-2-activated NK cells. In summary, these results suggest that a combined and profound defect of innate and adaptive effector cells might explain the susceptibility to infections and lymphoma in these HPS2 patients.peer-reviewe

Targeting the Endothelin-1 Receptors Curtails Tumor Growth and Angiogenesis in Multiple Myeloma

The endothelin-1 (ET-1) receptors were recently found to mediate pro-survival functions in multiple myeloma (MM) cells in response to autocrine ET-1. This study investigated the effectiveness of macitentan, a dual ET-1 receptor antagonist, in MM treatment, and the mechanisms underlying its activities. Macitentan affected significantly MM cell (RPMI-8226, U266, KMS-12-PE) survival and pro-angiogenic cytokine release by down-modulating ET-1-activated MAPK/ERK and HIF-1 alpha pathways, respectively. HIF-1 alpha silencing abrogated the ET-1 mediated induction of genes encoding for pro-angiogenic cytokines such as VEGF-A, IL-8, Adrenomedullin, and ET-1 itself. Upon exposure to macitentan, MM cells cultured in the presence of the hypoxia-mimetic agent CoCl2, exogenous ET-1, or CoCl2 plus ET-1, down-regulated HIF-1 alpha and the transcription and release of downstream pro-angiogenic cytokines. Consistently, macitentan limited significantly the basal pro-angiogenic activity of RPMI-8226 cells in chorioallantoic membrane assay. In xenograft mouse models, established by injecting NOG mice either via intra-caudal vein with U266 or subcutaneously with RPMI-8226 cells, macitentan reduced effectively the number of MM cells infiltrating bone marrow, and the size and microvascular density of subcutaneous MM tumors. ET-1 receptors targeting by macitentan represents an effective anti-proliferative and anti-angiogenic therapeutic approach in preclinical settings of MM