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11.
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Diminished proliferation of human immunodeficiency virus-specific CD4+ T cells is associated with diminished interleukin-2 (IL-2) production and is recovered by exogenous IL-2 总被引:11,自引:0,他引:11 下载免费PDF全文
Iyasere C Tilton JC Johnson AJ Younes S Yassine-Diab B Sekaly RP Kwok WW Migueles SA Laborico AC Shupert WL Hallahan CW Davey RT Dybul M Vogel S Metcalf J Connors M 《Journal of virology》2003,77(20):10900-10909
Virus-specific CD4(+) T-cell function is thought to play a central role in induction and maintenance of effective CD8(+) T-cell responses in experimental animals or humans. However, the reasons that diminished proliferation of human immunodeficiency virus (HIV)-specific CD4(+) T cells is observed in the majority of infected patients and the role of these diminished responses in the loss of control of replication during the chronic phase of HIV infection remain incompletely understood. In a cohort of 15 patients that were selected for particularly strong HIV-specific CD4(+) T-cell responses, the effects of viremia on these responses were explored. Restriction of HIV replication was not observed during one to eight interruptions of antiretroviral therapy in the majority of patients (12 of 15). In each case, proliferative responses to HIV antigens were rapidly inhibited during viremia. The frequencies of cells that produce IFN-gamma in response to Gag, Pol, and Nef peptide pools were maintained during an interruption of therapy. In a subset of patients with elevated frequencies of interleukin-2 (IL-2)-producing cells, IL-2 production in response to HIV antigens was diminished during viremia. Addition of exogenous IL-2 was sufficient to rescue in vitro proliferation of DR0101 class II Gag or Pol tetramer(+) or total-Gag-specific CD4(+) T cells. These observations suggest that, during viremia, diminished in vitro proliferation of HIV-specific CD4(+) T cells is likely related to diminished IL-2 production. These results also suggest that relatively high frequencies of HIV-specific CD4(+) T cells persist in the peripheral blood during viremia, are not replicatively senescent, and proliferate when IL-2 is provided exogenously. 相似文献
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Xu L Renaud L Müller JG Baicu CF Bonnema DD Zhou H Kappler CS Kubalak SW Zile MR Conway SJ Menick DR 《The Journal of biological chemistry》2006,281(45):34430-34440
The Na+-Ca2+ exchanger (NCX1) is up-regulated in hypertrophy and is often found up-regulated in end-stage heart failure. Studies have shown that the change in its expression contributes to contractile dysfunction. We have previously shown that the 1831-bp Ncx1 H1 (1831Ncx1) promoter directs cardiac-specific expression of the exchanger in both development and in the adult, and is sufficient for the up-regulation of Ncx1 in response to pressure overload. Here, we utilized adenoviral mediated gene transfer and transgenics to identify minimal regions and response elements that mediate Ncx1 expression in the heart. We demonstrate that the proximal 184 bp of the Ncx1 H1 (184Ncx1) promoter is sufficient for expression of reporter genes in adult cardiomyocytes and for the correct spatiotemporal pattern of Ncx1 expression in development but not for up-regulation in response to pressure overload. Mutational analysis revealed that both the -80 CArG and the -50 GATA elements were required for expression in isolated adult cardiomyocytes. Chromatin immunoprecipitation assays in adult cardiocytes demonstrate that SRF and GATA4 are associated with the proximal region of the endogenous Ncx1 promoter. Transgenic lines were established for the 1831Ncx1 promoter-luciferase containing mutations in the -80 CArG or -50 GATA element. No luciferase activity was detected during development, in the adult, or after pressure overload in any of the -80 CArG transgenic lines. The Ncx1 -50 GATA mutant promoter was sufficient for driving the normal spatiotemporal pattern of Ncx1 expression in development and for up-regulation in response to pressure overload but importantly, expression was no longer cardiac restricted. This work is the first in vivo study that demonstrates which cis elements are important for Ncx1 regulation. 相似文献
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Lambers Hans Wright Ian J. Guilherme Pereira Caio Bellingham Peter J. Bentley Lisa Patrick Boonman Alex Cernusak Lucas A. Foulds William Gleason Sean M. Gray Emma F. Hayes Patrick E. Kooyman Robert M. Malhi Yadvinder Richardson Sarah J. Shane Michael W. Staudinger Christiana Stock William D. Swarts Nigel D. Turner Benjamin L. Turner John Veneklaas Erik J. Wasaki Jun Westoby Mark Xu Yanggui 《Plant and Soil》2021,461(1-2):43-61
Plant and Soil - Root-released carboxylates enhance the availability of manganese (Mn), which enters roots through transporters with low substrate specificity. Leaf Mn concentration ([Mn]) has been... 相似文献
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Yanmin Hu Alexander Liu James Vaudrey Brigita Vaiciunaite Christiana Moigboi Sharla M. McTavish Angela Kearns Anthony Coates 《PloS one》2015,10(2)
Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87–89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections. 相似文献
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Christiana M. A. Faria Eugenia Zarza Víctor H. Reynoso Brent C. Emerson 《Conservation Genetics》2010,11(5):1645-1652
Because of female-biased illegal harvesting, knowledge about the genetic mating system of the black spiny-tailed iguana Ctenosaura pectinata is of primary interest for the conservation of this threatened species. Based on the high levels of multiple paternity found
in clutches of many other reptiles, particularly in lizards, it is hypothesised that multiple paternity may also be common
in black iguanas. This was investigated by using microsatellite DNA to estimate the number of males siring nine litters (9
mothers, 121 offspring genotyped at ten polymorphic loci) of black iguanas. Contrary to expectations, only 11% of sampled
black iguana females produced litters consistent with being sired by multiple males. These data are the first evidence for
the predominance of single paternity within an iguanid lizard, and suggest that black iguana may be more susceptible to loss
of genetic variation in the face of gender-biased over-hunting pressure than previously thought. 相似文献
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The secreted glycoprotein vascular endothelial growth factor A (VEGF or VEGFA) affects many different cell types and modifies a wide spectrum of cellular behaviors in tissue culture models, including proliferation, migration, differentiation and survival. The versatility of VEGF signaling is reflected in the complex composition of its cell surface receptors and their ability to activate a variety of different downstream signaling molecules. A major challenge for VEGF research is to determine which of the specific signaling pathways identified in vitro control development and homeostasis of tissues containing VEGF-responsive cell types in vivo. 相似文献
20.
Weigert C Brodbeck K Staiger H Kausch C Machicao F Häring HU Schleicher ED 《The Journal of biological chemistry》2004,279(23):23942-23952