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siRNA-directed inhibition of HIV-1 infection 总被引:133,自引:0,他引:133
Novina CD Murray MF Dykxhoorn DM Beresford PJ Riess J Lee SK Collman RG Lieberman J Shankar P Sharp PA 《Nature medicine》2002,8(7):681-686
RNA interference silences gene expression through short interfering 21 23-mer double-strand RNA segments that guide mRNA degradation in a sequence-specific fashion. Here we report that siRNAs inhibit virus production by targeting the mRNAs for either the HIV-1 cellular receptor CD4, the viral structural Gag protein or green fluorescence protein substituted for the Nef regulatory protein. siRNAs effectively inhibit pre- and/or post-integration infection events in the HIV-1 life cycle. Thus, siRNAs may have potential for therapeutic intervention in HIV-1 and other viral infections. 相似文献
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Smith GD Zhou L Rowe LR Jarboe EA Collins BT Bentz JS Wittwer CT Chadwick BE 《Acta cytologica》2011,55(6):576-583
Objective: To detect BRAF V600E mutation in thyroid fine-needle aspiration (FNA) slides and needle rinses (NR). Study Design: Tumor-enriched DNA was extracted from FNA smears, formalin-fixed paraffin-embedded (FFPE) sections, or NR specimens from 37 patients with confirmed papillary thyroid carcinoma or benign findings. An allele-specific primer selectively amplified the 1799 T>A BRAF mutation while simultaneously blocking amplification of wild-type (WT) BRAF with an unlabeled probe during PCR. Mutation detection was accomplished by melting analysis of the probe. Results: Allele-specific/blocking probe PCR confirmed the BRAF mutation status for 20 of 24 paired FNA/FFPE samples previously tested by fluorescent probe real-time PCR. For the other 4 cases, the sensitive PCR method detected the BRAF mutation in all paired FNA/FFPE samples. Previously, the mutation had been detected in only the FFPE samples. The BRAF mutation was also detected in some NR specimens. Conclusion: Treatment of patients with thyroid nodules is guided by FNA biopsy, which can be scantly cellular, necessitating a sensitive test that can detect low levels of BRAF V600E mutation in a WT background. We report increased detection of BRAF V600E in FNA specimens using allele-specific/blocking probe PCR, which has an analytical sensitivity of 0.01%. 相似文献
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Down-regulation of light-saturated photosynthesis (Asat) at elevated atmospheric CO2 concentration, [CO2], has been demonstrated for many C3 species and is often associated with inability to utilize additional photosynthate and/or nitrogen limitation. In soybean, a nitrogen-fixing species, both limitations are less likely than in crops lacking an N-fixing symbiont. Prior studies have used controlled environment or field enclosures where the artificial environment can modify responses to [CO2]. A soybean free air [CO2] enrichment (FACE) facility has provided the first opportunity to analyze the effects of elevated [CO2] on photosynthesis under fully open-air conditions. Potential ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) carboxylation (Vc,max) and electron transport through photosystem II (Jmax) were determined from the responses of Asat to intercellular [CO2] (Ci) throughout two growing seasons. Mesophyll conductance to CO2 (gm) was determined from the responses of Asat and whole chain electron transport (J) to light. Elevated [CO2] increased Asat by 15–20% even though there was a small, statistically significant, decrease in Vc,max. This differs from previous studies in that Vc,max/Jmax decreased, inferring a shift in resource investment away from Rubisco. This raised the Ci at which the transition from Rubisco-limited to ribulose-1,5-bisphosphate regeneration-limited photosynthesis occurred. The decrease in Vc,max was not the result of a change in gm, which was unchanged by elevated [CO2]. This first analysis of limitations to soybean photosynthesis under fully open-air conditions reveals important differences to prior studies that have used enclosures to elevate [CO2], most significantly a smaller response of Asat and an apparent shift in resources away from Rubisco relative to capacity for electron transport.Abbreviations FACE Free air [CO2] enrichment - Rubisco Ribulose-1,5-bisphosphate carboxylase/oxygenase - RuBP Ribulose-1,5-bisphosphate - SoyFACE Soybean free air [CO2] enrichment - VPD Vapor pressure deficit 相似文献
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Backbone relationships within the large eupolypod II clade, which includes nearly a third of extant fern species, have resisted elucidation by both molecular and morphological data. Earlier studies suggest that much of the phylogenetic intractability of this group is due to three factors: (i) a long root that reduces apparent levels of support in the ingroup; (ii) long ingroup branches subtended by a series of very short backbone internodes (the "ancient rapid radiation" model); and (iii) significantly heterogeneous lineage-specific rates of substitution. To resolve the eupolypod II phylogeny, with a particular emphasis on the backbone internodes, we assembled a data set of five plastid loci (atpA, atpB, matK, rbcL, and trnG-R) from a sample of 81 accessions selected to capture the deepest divergences in the clade. We then evaluated our phylogenetic hypothesis against potential confounding factors, including those induced by rooting, ancient rapid radiation, rate heterogeneity, and the Bayesian star-tree paradox artifact. While the strong support we inferred for the backbone relationships proved robust to these potential problems, their investigation revealed unexpected model-mediated impacts of outgroup composition, divergent effects of methods for countering the star-tree paradox artifact, and gave no support to concerns about the applicability of the unrooted model to data sets with heterogeneous lineage-specific rates of substitution. This study is among few to investigate these factors with empirical data, and the first to compare the performance of the two primary methods for overcoming the Bayesian star-tree paradox artifact. Among the significant phylogenetic results is the near-complete support along the eupolypod II backbone, the demonstrated paraphyly of Woodsiaceae as currently circumscribed, and the well-supported placement of the enigmatic genera Homalosorus, Diplaziopsis, and Woodsia. 相似文献
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Hybridization between sympatric species provides unique opportunities to examine the contrast between mechanisms that promote hybridization and maintain species integrity. We surveyed hybridization between sympatric coastal steelhead (Oncorhynchus mykiss irideus) and coastal cutthroat trout (O. clarki clarki) from two streams in Washington State, Olsen Creek (256 individuals sampled) and Jansen Creek (431 individuals sampled), over a 3-year period. We applied 11 O. mykiss-specific nuclear markers, 11 O. c. clarki-specific nuclear markers and a mitochondrial DNA marker to assess spatial partitioning among species and hybrids and determine the directionality of hybridization. F1 and post-F1 hybrids, respectively, composed an average of 1.2% and 33.6% of the population sampled in Jansen Creek, and 5.9% and 30.4% of the population sampled in Olsen Creek. A modest level of habitat partitioning among species and hybrids was detected. Mitochondrial DNA analysis indicated that all F1 hybrids (15 from Olsen Creek and five from Jansen Creek) arose from matings between steelhead females and cutthroat males implicating a sneak spawning behaviour by cutthroat males. First-generation cutthroat backcrosses contained O. c. clarki mtDNA more often than expected suggesting natural selection against F1 hybrids. More hybrids were backcrossed toward cutthroat than steelhead and our results indicate recurrent hybridization within these creeks. Age analysis demonstrated that hybrids were between 1 and 4 years old. These results suggest that within sympatric salmonid hybrid zones, exogenous processes (environmentally dependent factors) help to maintain the distinction between parental types through reduced fitness of hybrids within parental environments while divergent natural selection promotes parental types through distinct adaptive advantages of parental phenotypes. 相似文献
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To promote their survival, intracellular pathogens must confront microbicidal activities induced by interferons. In this issue of Cell Host & Microbe, Fentress et?al. show that Toxoplasma gondii evades intracellular killing by deploying a virulence determinant, ROP18, which acts by directly phosphorylating and disabling an IFN-γ-inducible immunity-related GTPase involved in pathogen clearance. 相似文献
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Maochun Qin Biao Liu Jeffrey M Conroy Carl D Morrison Qiang Hu Yubo Cheng Mitsuko Murakami Adekunle O Odunsi Candace S Johnson Lei Wei Song Liu Jianmin Wang 《BMC bioinformatics》2015,16(1)