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排序方式: 共有163条查询结果,搜索用时 171 毫秒
61.
Lisa Kish Naomi Hotte Gilaad G. Kaplan Renaud Vincent Robert Tso Michael G?nzle Kevin P. Rioux Aducio Thiesen Herman W. Barkema Eytan Wine Karen L. Madsen 《PloS one》2013,8(4)
Background
Particulate matter (PM) is a key pollutant in ambient air that has been associated with negative health conditions in urban environments. The aim of this study was to examine the effects of orally administered PM on the gut microbiome and immune function under normal and inflammatory conditions.Methods
Wild-type 129/SvEv mice were gavaged with Ottawa urban PM10 (EHC-93) for 7–14 days and mucosal gene expression analyzed using Ingenuity Pathways software. Intestinal permeability was measured by lactulose/mannitol excretion in urine. At sacrifice, segments of small and large intestine were cultured and cytokine secretion measured. Splenocytes were isolated and incubated with PM10 for measurement of proliferation. Long-term effects of exposure (35 days) on intestinal cytokine expression were measured in wild-type and IL-10 deficient (IL-10−/−) mice. Microbial composition of stool samples was assessed using terminal restriction fragment length polymorphism. Short chain fatty acids were measured in caecum.Results
Short-term treatment of wild-type mice with PM10 altered immune gene expression, enhanced pro-inflammatory cytokine secretion in the small intestine, increased gut permeability, and induced hyporesponsiveness in splenocytes. Long-term treatment of wild-type and IL-10−/− mice increased pro-inflammatory cytokine expression in the colon and altered short chain fatty acid concentrations and microbial composition. IL-10−/− mice had increased disease as evidenced by enhanced histological damage.Conclusions
Ingestion of airborne particulate matter alters the gut microbiome and induces acute and chronic inflammatory responses in the intestine. 相似文献62.
Recently, Bennett and Riedel (BR) (http://arxiv.org/abs/1303.7435v1) argued that thermodynamics is not essential in the Kirchhoff-law–Johnson-noise (KLJN) classical physical cryptographic exchange method in an effort to disprove the security of the KLJN scheme. They attempted to demonstrate this by introducing a dissipation-free deterministic key exchange method with two batteries and two switches. In the present paper, we first show that BR''s scheme is unphysical and that some elements of its assumptions violate basic protocols of secure communication. All our analyses are based on a technically unlimited Eve with infinitely accurate and fast measurements limited only by the laws of physics and statistics. For non-ideal situations and at active (invasive) attacks, the uncertainly principle between measurement duration and statistical errors makes it impossible for Eve to extract the key regardless of the accuracy or speed of her measurements. To show that thermodynamics and noise are essential for the security, we crack the BR system with 100% success via passive attacks, in ten different ways, and demonstrate that the same cracking methods do not function for the KLJN scheme that employs Johnson noise to provide security underpinned by the Second Law of Thermodynamics. We also present a critical analysis of some other claims by BR; for example, we prove that their equations for describing zero security do not apply to the KLJN scheme. Finally we give mathematical security proofs for each BR-attack against the KLJN scheme and conclude that the information theoretic (unconditional) security of the KLJN method has not been successfully challenged. 相似文献
63.
Wang W Devasthale P Wang A Harrity T Egan D Morgan N Cap M Fura A Klei HE Kish K Weigelt C Sun L Levesque P Li YX Zahler R Kirby MS Hamann LG 《Bioorganic & medicinal chemistry letters》2011,21(22):6646-6651
Design, synthesis, and SAR of 7-oxopyrrolopyridine-derived DPP4 inhibitors are described. The preferred stereochemistry of these atropisomeric biaryl analogs has been identified as Sa. Compound (+)-3t, with a K(i) against DPP4, DPP8, and DPP9 of 0.37 nM, 2.2, and 5.7 μM, respectively, showed a significant improvement in insulin response after single doses of 3 and 10 μmol/kg in ob/ob mice. 相似文献
64.
Dyckman AJ Li T Pitt S Zhang R Shen DR McIntyre KW Gillooly KM Shuster DJ Doweyko AM Sack JS Kish K Kiefer SE Newitt JA Zhang H Marathe PH McKinnon M Barrish JC Dodd JH Schieven GL Leftheris K 《Bioorganic & medicinal chemistry letters》2011,21(15):4633-4637
Pyrrolo[2,1-f][1,2,4]triazine based inhibitors of p38α have been prepared exploring functional group modifications at the C6 position. Incorporation of aryl and heteroaryl ketones at this position led to potent inhibitors with efficacy in in vivo models of acute and chronic inflammation. 相似文献
65.
Gentles RG Sheriff S Beno BR Wan C Kish K Ding M Zheng X Chupak L Poss MA Witmer MR Morin P Wang YK Rigat K Lemm J Voss S Liu M Pelosi L Roberts SB Gao M Kadow JF 《Bioorganic & medicinal chemistry letters》2011,21(8):2212-2215
Structure based rationales for the activities of potent N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamide inhibitors of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select examples from this series with NS5B are reported. Comparison of co-crystal structures of a potent analog with both NS5B genotype 1a and genotype 1b provides a possible explanation for the genotype-selectivity observed with this compound class and suggests opportunities for the further optimization of the series. 相似文献
66.
X-ray crystal structures of human immunodeficiency virus type 1 protease mutants complexed with atazanavir
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Klei HE Kish K Lin PF Guo Q Friborg J Rose RE Zhang Y Goldfarb V Langley DR Wittekind M Sheriff S 《Journal of virology》2007,81(17):9525-9535
Atazanavir, which is marketed as REYATAZ, is the first human immunodeficiency virus type 1 (HIV-1) protease inhibitor approved for once-daily administration. As previously reported, atazanavir offers improved inhibitory profiles against several common variants of HIV-1 protease over those of the other peptidomimetic inhibitors currently on the market. This work describes the X-ray crystal structures of complexes of atazanavir with two HIV-1 protease variants, namely, (i) an enzyme optimized for resistance to autolysis and oxidation, referred to as the cleavage-resistant mutant (CRM); and (ii) the M46I/V82F/I84V/L90M mutant of the CRM enzyme, which is resistant to all approved HIV-1 protease inhibitors, referred to as the inhibitor-resistant mutant. In these two complexes, atazanavir adopts distinct bound conformations in response to the V82F substitution, which may explain why this substitution, at least in isolation, has yet to be selected in vitro or in the clinic. Because of its nearly symmetrical chemical structure, atazanavir is able to make several analogous contacts with each monomer of the biological dimer. 相似文献
67.
Characterization of a petunia acetyltransferase involved in the biosynthesis of the floral volatile isoeugenol 总被引:1,自引:0,他引:1
Dexter R Qualley A Kish CM Ma CJ Koeduka T Nagegowda DA Dudareva N Pichersky E Clark D 《The Plant journal : for cell and molecular biology》2007,49(2):265-275
Petunia flower petals emit large amounts of isoeugenol, which has been shown to be synthesized by isoeugenol synthase (PhIGS1) from an ester of coniferyl alcohol, hypothesized to be coniferyl acetate. This paper describes the identification and characterization of a novel petunia gene encoding an enzyme belonging to the BAHD acyltransferase family whose expression correlates with isoeugenol biosynthesis. RNAi suppression of this gene results in inhibition of isoeugenol biosynthesis. Biochemical characterization of the protein encoded by this gene showed that it has acetyltransferase activity and is most efficient with coniferyl alcohol among the alcohol substrates tested. Overall, these data support the conclusion that coniferyl acetate is the substrate of isoeugenol synthase. 相似文献
68.
Bézière N Decroos C Mkhitaryan K Kish E Richard F Bigot-Marchand S Durand S Cloppet F Chauvet C Corvol MT Rannou F Xu-Li Y Mansuy D Peyrot F Frapart YM 《Molecular imaging》2012,11(3):220-228
Although laboratory data clearly suggest a role for oxidants (dioxygen and free radicals derived from dioxygen) in the pathogenesis of many age-related and degenerative diseases (such as arthrosis and arthritis), methods to image such species in vivo are still very limited. This methodological problem limits physiopathologic studies about the role of those species in vivo, the effects of their regulation using various drugs, and the evaluation of their levels for diagnosis of degenerative diseases. In vivo electron paramagnetic resonance (EPR) imaging and spectroscopy are unique, noninvasive methods used to specifically detect and quantify paramagnetic species. However, two problems limit their application: the anatomic location of the EPR image in the animal body and the relative instability of the EPR probes. Our aim is to use EPR imaging to obtain physiologic and pathologic information on the mouse knee joint. This article reports the first in vivo EPR image of a small tissue, the mouse knee joint, with good resolution (≈ 160 μm) after intra-articular injection of a triarylmethyl radical EPR probe. It was obtained by combining EPR and x-ray micro-computed tomography for the first time and by taking into account the disappearance kinetics of the EPR probe during image acquisition to reconstruct the image. This multidisciplinary approach opens the way to high-resolution EPR imaging and local metabolism studies of radical species in vivo in different physiologic and pathologic situations. 相似文献
69.
The genome of the halophilic archaeon Halobacterium sp. strain NRC-1 encodes homologs of the eukaryotic Mre11 and Rad50 proteins, which are involved in the recognition and end processing of DNA double-strand breaks in the homologous recombination repair pathway. We have analyzed the phenotype of Halobacterium deletion mutants lacking mre11 and/or rad50 after exposure to UV-C radiation, an alkylating agent (N-methyl-N'-nitro-N-nitrosoguanidine), and gamma radiation, none of which resulted in a decrease in survival of the mutant strains compared to that of the background strain. However, a decreased rate of repair of DNA double-strand breaks in strains lacking the mre11 gene was observed using pulsed-field gel electrophoresis. These observations led to the hypothesis that Mre11 is essential for the repair of DNA double-strand breaks in Halobacterium, whereas Rad50 is dispensable. This is the first identification of a Rad50-independent function for the Mre11 protein, and it represents a shift in the Archaea away from the eukaryotic model of homologous recombination repair of DNA double-strand breaks. 相似文献
70.
Sylvain Charlat Anne Duplouy Emily A Hornett Emily A Dyson Neil Davies George K Roderick Nina Wedell Gregory DD Hurst 《BMC evolutionary biology》2009,9(1):64-9