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71.
Miles JJ Elhassen D Borg NA Silins SL Tynan FE Burrows JM Purcell AW Kjer-Nielsen L Rossjohn J Burrows SR McCluskey J 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(6):3826-3834
MHC class I molecules generally present peptides of 8-10 aa long, forming an extended coil in the HLA cleft. Although longer peptides can also bind to class I molecules, they tend to bulge from the cleft and it is not known whether the TCR repertoire has sufficient plasticity to recognize these determinants during the antiviral CTL response. In this study, we show that unrelated individuals infected with EBV generate a significant CTL response directed toward an HLA-B*3501-restricted, 11-mer epitope from the BZLF1 Ag. The 11-mer determinant adopts a highly bulged conformation with seven of the peptide side chains being solvent-exposed and available for TCR interaction. Such a complex potentially creates a structural challenge for TCR corecognition of both HLA-B*3501 and the peptide Ag. Surprisingly, unrelated B*3501 donors recognizing the 11-mer use identical or closely related alphabeta TCR sequences that share particular CDR3 motifs. Within the small number of dominant CTL clonotypes observed, each has discrete fine specificity for the exposed side chain residues of the peptide. The data show that bulged viral peptides are indeed immunogenic but suggest that the highly constrained TCR repertoire reflects a limit to TCR diversity when responding to some unusual MHC peptide ligands. 相似文献
72.
We study a model of the chemostat with two species competing for two perfectly substitutable resources in the case of linear
functional response. Lyapunov methods are used to provide sufficient conditions for the global asymptotic stability of the
coexistence equilibrium. Then, using compound matrix techniques, we provide a global analysis in a subset of parameter space.
In particular, we show that each solution converges to an equilibrium, even in the case that the coexistence equilibrium is
a saddle. Finally, we provide a bifurcation analysis based on the dilution rate. In this context, we are able to provide a
geometric interpretation that gives insight into the role of the other parameters in the bifurcation sequence.
Funding was provided by the National Science Foundation-funded ADVANCE Institutional Transformation Program at New Mexico
State University, fund # NSF0123690.
Research partially supported by the Natural Science and Engineering Research Council of Canada. 相似文献
73.
A convenient assay to score repeat-induced point mutation (RIP) inNeurospora employs theerg-3 locus as a mutagenesis target. Using this assay we screened 132 wild-isolatedNeurospora crassa strains for ability to dominantly suppress RIP. RIP was exceptionally inefficient in crosses with the wild isolates Sugartown
(P0854) and Adiopodoume-7 (P4305), thereby suggesting the presence of dominant RIP suppressors in these strains. In other
experiments, we found no evidence for dominant RIP suppression by theSpore killer haplotypesSk-2 andSk-3. 相似文献
74.
75.
76.
Conn McCluskey 《BMJ (Clinical research ed.)》1946,2(4481):791-792
77.
78.
Frederique M Moret Cornelis E Hack Kim MG van der Wurff-Jacobs Wilco de Jager Timothy RDJ Radstake Floris PJG Lafeber Joel AG van Roon 《Arthritis research & therapy》2013,15(5):R155
Introduction
Myeloid dendritic cells (mDCs) are potent T cell-activating antigen-presenting cells that have been suggested to play a crucial role in the regulation of immune responses in many disease states, including rheumatoid arthritis (RA). Despite this, studies that have reported on the capacity of naturally occurring circulating mDCs to regulate T cell activation in RA are still lacking. This study aimed to evaluate the phenotypic and functional properties of naturally occurring CD1c (BDCA-1)+ mDCs from synovial fluid (SF) compared to those from peripheral blood (PB) of RA patients.Methods
CD1c+ mDC numbers and expression of costimulatory molecules were assessed by fluorescence-activated cell sorting (FACS) analysis in SF and PB from RA patients. Ex vivo secretion of 45 inflammatory mediators by mDCs from SF and PB of RA patients was determined by multiplex immunoassay. The capacity of mDCs from SF to activate autologous CD4+ T cells was measured.Results
CD1c+ mDC numbers were significantly increased in SF versus PB of RA patients (mean 4.7% vs. 0.6%). mDCs from SF showed increased expression of antigen-presenting (human leukocyte antigen (HLA) class II, CD1c) and costimulatory molecules (CD80, CD86 and CD40). Numerous cytokines were equally abundantly produced by mDCs from both PB and SF (including IL-12, IL-23, IL-13, IL-21). SF mDCs secreted higher levels of interferon γ-inducible protein-10 (IP-10), monokine induced by interferon γ (MIG) and, thymus and activation-regulated chemokine (TARC), but lower macrophage-derived chemokine (MDC) levels compared to mDCs from PB. mDCs from SF displayed a strongly increased capacity to induce proliferation of CD4+ T cells associated with a strongly augmented IFNγ, IL-17, and IL-4 production.Conclusions
This study suggests that increased numbers of CD1c+ mDCs in SF are involved in the inflammatory cascade intra-articularly by the secretion of specific T cell-attracting chemokines and the activation of self-reactive T cells. 相似文献79.
Kubicek CP Herrera-Estrella A Seidl-Seiboth V Martinez DA Druzhinina IS Thon M Zeilinger S Casas-Flores S Horwitz BA Mukherjee PK Mukherjee M Kredics L Alcaraz LD Aerts A Antal Z Atanasova L Cervantes-Badillo MG Challacombe J Chertkov O McCluskey K Coulpier F Deshpande N von Döhren H Ebbole DJ Esquivel-Naranjo EU Fekete E Flipphi M Glaser F Gómez-Rodríguez EY Gruber S Han C Henrissat B Hermosa R Hernández-Oñate M Karaffa L Kosti I Le Crom S Lindquist E Lucas S Lübeck M Lübeck PS Margeot A 《Genome biology》2011,12(4):R40
Background
Mycoparasitism, a lifestyle where one fungus is parasitic on another fungus, has special relevance when the prey is a plant pathogen, providing a strategy for biological control of pests for plant protection. Probably, the most studied biocontrol agents are species of the genus Hypocrea/Trichoderma.Results
Here we report an analysis of the genome sequences of the two biocontrol species Trichoderma atroviride (teleomorph Hypocrea atroviridis) and Trichoderma virens (formerly Gliocladium virens, teleomorph Hypocrea virens), and a comparison with Trichoderma reesei (teleomorph Hypocrea jecorina). These three Trichoderma species display a remarkable conservation of gene order (78 to 96%), and a lack of active mobile elements probably due to repeat-induced point mutation. Several gene families are expanded in the two mycoparasitic species relative to T. reesei or other ascomycetes, and are overrepresented in non-syntenic genome regions. A phylogenetic analysis shows that T. reesei and T. virens are derived relative to T. atroviride. The mycoparasitism-specific genes thus arose in a common Trichoderma ancestor but were subsequently lost in T. reesei.Conclusions
The data offer a better understanding of mycoparasitism, and thus enforce the development of improved biocontrol strains for efficient and environmentally friendly protection of plants. 相似文献80.
Mark Tarleton Lauren Dyson Jayne Gilbert Jennette A. Sakoff Adam McCluskey 《Bioorganic & medicinal chemistry》2013,21(1):333-347
With our lead compound (E)-3-(4-chlorophenyl)-2-(1H-pyrrole-2-carbonyl)acrylonitrile (1) inducing 50% growth inhibition of 11 cancer cell lines at 27–61 μM, potency enhancements were rapidly established through the synthesis of a series of focused compound libraries. Six highly focused libraries (46 compounds in total) were synthesised. Each library allowed the identification of a new lead compound, viz Library A identified (E)-3-(pentafluorophenyl)-2-(1H-pyrrole-2-carbonyl)acrylonitrile (11) and (E)-3-(1H-indol-3-yl)-2-(1H-pyrrole-2-carbonyl)acrylonitrile (13) as inhibitors with improved cytotoxicity. Synthesis of discrete libraries of amidoacrylamide analogues (Ar–CC(CN)–Ar?Ar–CC(CN)–C(O)NH)–Ar) resulted in a series of analogues significantly more potent that the lead, 1. Three furan three analogues: (E)-3-(5-chlorofuran-2-yl)-2-cyano-N-(4-methoxybenzyl)acrylamide (33), (E)-3-(5-bromofuran-2-yl)-2-cyano-N-(4-methoxybenzyl)acrylamide (34) and (E)-2-cyano-3-(furan-3-yl)-N-(4-methoxybenzyl)acrylamide (37) returned broad spectrum growth inhibition (GI50 values of 5–16 μM). Replacement of the furan moiety with simple aromatics gave an additional three analogues: (E)-2-cyano-N-(4-methoxybenzyl)-3-phenylacrylamide (39), (E)-3-(4-chlorophenyl)-2-cyano-N-(4-methoxybenzyl)acrylamide (41) and (E)-2-cyano-N-(4-methoxyphenyl)-3-(naphthalen-1-yl)acrylamide (45) with GI50 values of 7–24 μM. The final library retained the aromatic substituents but introduced a 3,4-dichlorbenzylamine moiety to afford the 1-naphthyl substituted 52, which was the most potent broad spectrum cytotoxic analogue produced here in with an average GI50 = 8.6 μM. This represents a fivefold potency enhancement relative to 1 and a new cytotoxic scaffold suitable for further development. 相似文献