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61.
Mucocutaneous leishmaniasis is caused by infections with intracellular parasites of the Leishmania Viannia subgenus, including Leishmania guyanensis. The pathology develops after parasite dissemination to nasopharyngeal tissues, where destructive metastatic lesions form with chronic inflammation. Currently, the mechanisms involved in lesion development are poorly understood. Here we show that metastasizing parasites have a high Leishmania RNA virus-1 (LRV1) burden that is recognized by the host Toll-like receptor 3 (TLR3) to induce proinflammatory cytokines and chemokines. Paradoxically, these TLR3-mediated immune responses rendered mice more susceptible to infection, and the animals developed an increased footpad swelling and parasitemia. Thus, LRV1 in the metastasizing parasites subverted the host immune response to Leishmania and promoted parasite persistence.  相似文献   
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Tropical Animal Health and Production - Intake, digestion and nitrogen retention were measured in fifteen 1-year-old Black Belly rams that had an average weight of 35.3...  相似文献   
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Receptor tyrosine kinase genes were sequenced in non-small cell lung cancer (NSCLC) and matched normal tissue. Somatic mutations of the epidermal growth factor receptor gene EGFR were found in 15of 58 unselected tumors from Japan and 1 of 61 from the United States. Treatment with the EGFR kinase inhibitor gefitinib (Iressa) causes tumor regression in some patients with NSCLC, more frequently in Japan. EGFR mutations were found in additional lung cancer samples from U.S. patients who responded to gefitinib therapy and in a lung adenocarcinoma cell line that was hypersensitive to growth inhibition by gefitinib, but not in gefitinib-insensitive tumors or cell lines. These results suggest that EGFR mutations may predict sensitivity to gefitinib.  相似文献   
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The distribution of chemical elements in primitive meteorites (chondrites), as building blocks of terrestrial planets, provides insight into the formation and early differentiation of Earth. The processes that resulted in the depletion of some elements [such as chromium (Cr)] in the bulk silicate Earth relative to chondrites, however, remain debated between leading candidate causes: volatility versus core partitioning. We show through high-precision measurements of Cr stable isotopes in a range of meteorites, which deviate by up to ~0.4 per mil from those of the bulk silicate Earth, that Cr depletion resulted from its partitioning into Earth's core, with a preferential enrichment in light isotopes. Ab initio calculations suggest that the isotopic signature was established at mid-mantle magma ocean depth as Earth accreted planetary embryos and progressively became more oxidized.  相似文献   
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Binding of Sonic Hedgehog (Shh) to Patched (Ptc) relieves the latter's tonic inhibition of Smoothened (Smo), a receptor that spans the cell membrane seven times. This initiates signaling which, by unknown mechanisms, regulates vertebrate developmental processes. We find that two molecules interact with mammalian Smo in an activation-dependent manner: G protein-coupled receptor kinase 2 (GRK2) leads to phosphorylation of Smo, and beta-arrestin 2 fused to green fluorescent protein interacts with Smo. These two processes promote endocytosis of Smo in clathrin-coated pits. Ptc inhibits association of beta-arrestin 2 with Smo, and this inhibition is relieved in cells treated with Shh. A Smo agonist stimulated and a Smo antagonist (cyclopamine) inhibited both phosphorylation of Smo by GRK2 and interaction of beta-arrestin 2 with Smo. beta-Arrestin 2 and GRK2 are thus potential mediators of signaling by activated Smo.  相似文献   
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Leaching of soluble compounds from pelleted feeds is an issue for the aquaculture industry through increased environmental impact and reduced ingestion essential components. This study was undertaken to examine the leaching rates of taurine, a non‐protein amino acid with critical physiological roles in teleosts. To this end we adapted a new liquid chromatography mass spectrometry (LC‐MS) method for quantifying taurine. Twelve different feeds (4 mm dia.) varying in protein source and taurine levels were examined. Fishmeal content ranged from 0.0% to 45.5% with taurine supplementation ranging from 0.0% to 5.0%. Taurine was extracted and quantified from individual pellets in triplicate at six time points (0, 1, 5, 10, 20 and 40 min). Leaching rates ranged from 0.026 ± 0.005 to 0.826 ± 0.121 mg min?1 over 40 min at 27°C and were strongly correlated to initial taurine content of the feeds (for distilled water n = 12, P < 0.001, R2 = 0.91 for artificial seawater, 25 ppt, n = 4, P = 0.020, R2 = 0.96). Loss of taurine from feeds was 59.5 ± 16.5% after 40 min. This study shows that a significant amount of taurine is lost over time from uneaten feed and that taurine supplementation should exceed requirement levels for slow consumers or feed being delivered as multiple additions.  相似文献   
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