A preclinical model for the ATLL lymphoma subtype with insights into the role of microenvironment in HTLV-1-mediated lymphomagenesis

Abstract \uef7f View references (83) Adult T cell Leukemia/Lymphoma (ATLL) is a mature T cell malignancy associated with Human T cell Leukemia Virus type 1 (HTLV-1) infection. Among its four main clinical subtypes, the prognosis of acute and lymphoma variants remains poor. The long latency (3-6 decades) and low incidence (3-5%) of ATLL imply the involvement of viral and host factors in full-blown malignancy. Despite multiple preclinical and clinical studies, the contribution of the stromal microenvironment in ATLL development is not yet completely unraveled. The aims of this study were to investigate the role of the host microenvironment, and specifically fibroblasts, in ATLL pathogenesis and to propose a murine model for the lymphoma subtype. Here we present evidence that the oncogenic capacity of HTLV-1-immortalized C91/PL cells is enhanced when they are xenotransplanted together with human foreskin fibroblasts (HFF) in immunocompromised BALB/c Rag2-/-\u3b3c -/-mice. Moreover, cell lines derived from a developed lymphoma and their subsequent in vivo passages acquired the stable property to induce aggressive T cell lymphomas. In particular, one of these cell lines, C91/III cells, consistently induced aggressive lymphomas also in NOD/SCID/IL2R\u3b3c KO (NSG) mice. To dissect the mechanisms linked to this enhanced tumorigenic ability, we quantified 45 soluble factors released by these cell lines and found that 21 of them, mainly pro-inflammatory cytokines and chemokines, were significantly increased in C91/III cells compared to the parental C91/PL cells. Moreover, many of the increased factors were also released by human fibroblasts and belonged to the known secretory pattern of ATLL cells. C91/PL cells co-cultured with HFF showed features reminiscent of those observed in C91/III cells, including a similar secretory pattern and a more aggressive behavior in vivo. On the whole, our data provide evidence that fibroblasts, one of the major stromal components, might enhance tumorigenesis of HTLV-1-infected and immortalized T cells, thus throwing light on the role of microenvironment contribution in ATLL pathogenesis. We also propose that the lymphoma induced in NSG mice by injection with C91/III cells represents a new murine preclinical ATLL model that could be adopted to test novel therapeutic interventions for the aggressive lymphoma subtype

Market Competition, Institutions, and Contracting Outcomes: Preliminary Model and Experimental Results

Contracts, Competition, Market Power, Enforcement, Institutions, Agribusiness, Industrial Organization, Institutional and Behavioral Economics, Production Economics, C91, D02, D43, D86,

Optimal Timing of Farmland Investment - An Experimental Study on Farmers' Decision Behavior -

Replaced with revised version of paper 5/26/11.Experimental Economics, Investment, Real Options, Agribusiness, Agricultural Finance, Farm Management, Financial Economics, Institutional and Behavioral Economics, Risk and Uncertainty, C91, D81, D92,

Glycyl-L-proline hemihydrate at 298 K

The crystal structure of glycyl-L-proline (GLY-PRO) hemihydrate, C(7)H(12)N(2)O(3)(.)0.5H(2)O, has two molecules of GLY-PRO in the asymmetric unit; one molecule adopts the cis configuration at the peptide bond and the other adopts the trans configuration.</p

New catalogue of Wolf-Rayet galaxies and high-excitation extra-galactic HII regions

We present a new compilation of Wolf-Rayet (WR) galaxies and extra-galactic HII regions showing BROAD HeII emission drawn from the literature. Relevant information on the presence of other broad emission lines (NIII 4640, CIV 5808 and others) from WR stars of WN and WC subtypes, and other existing broad nebular lines is provided. In total we include 139 known WR galaxies. Among these, 57 objects show both broad HeII and CIV features. In addition to the broad (stellar) HeII emission, a NEBULAR HeII component is well established (suspected) in 44 (54) objects. We find 19 extra-galatic HII regions without WR detections showing nebular HeII emission. The present sample can be used for a variety of studies on massive stars, interactions of massive stars with the ISM, stellar populations, starburst galaxies etc. The data is accessible electronically and will be updated periodicaly.Comment: Accepted for publication in A&AS. LaTeX, 19 pages including 3 tables. Database and paper available at http://www.obs-mip.fr/omp/astro/people/schaerer/ (minor corrections to references

High Resolution Mid-Infrared Imaging of Ultraluminous Infrared Galaxies

Observations of ultraluminous infrared galaxies (ULIRGs) with an achieved resolution approaching the diffraction limit in the mid-infrared from 8 - 25 $\mu$m using the Keck Telescopes are reported. We find extremely compact structures, with spatial scales of $< 0.3''$ (diameter) in six of the seven ULIRGs observed. These compact sources emit between 30% and 100% of the mid-infrared energy from these galaxies. We have utilized the compact mid-infrared structures as a diagnostic of whether an AGN or a compact (100 -- 300 pc) starburst is the primary power source in these ULIRGs. In Markarian 231, the upper limit on the diameter of the 12.5 $\mu$m source, 0.13$''$, shows that the size of the infrared source must increase with increasing wavelength, consistent with AGN models. In IRAS 05189-2524 and IRAS 08572+3915 there is strong evidence that the source size increases with increasing wavelength. This suggests heating by a central source rather than an extended luminosity source, consistent with the optical classification as an AGN. The compact mid-infrared sources seen in the other galaxies cannot be used to distinguish the ultimate luminosity source. If these ULIRGs are powered by compact starbursts, the star formation rates seen in the central few hundred parsecs far exceed the global rates seen in nearby starburst galaxies, and approach the surface brightness of individual clusters in nearby starburst galaxies.Comment: 33pages, 6 tables, 5 figures, Accepted for publication in A

Unstable Individual Bids and Stable Market Demand

We explore preference stability at the individual and market level. We examine individual bidding behavior among 116 French consumers who participated in experimental auctions conducted seven months apart for five types of fish. We reject preference stability at the individual level, but not at the aggregate market level.aggregation, consumer preferences, demand, experimental auctions, food choice, Marketing, C91, D12, Q13,