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971.
The ability of an oligomeric human immunodeficiency virus type 1 (HIV-1) envelope antigen to elicit neutralizing antibodies against primary HIV-1 isolates is improved following partial deletion of the second hypervariable region 总被引:8,自引:0,他引:8
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Barnett SW Lu S Srivastava I Cherpelis S Gettie A Blanchard J Wang S Mboudjeka I Leung L Lian Y Fong A Buckner C Ly A Hilt S Ulmer J Wild CT Mascola JR Stamatatos L 《Journal of virology》2001,75(12):5526-5540
Partial deletion of the second hypervariable region from the envelope of the primary-like SF162 virus increases the exposure of certain neutralization epitopes and renders the virus, SF162DeltaV2, highly susceptible to neutralization by clade B and non-clade B human immunodeficiency virus (HIV-positive) sera (L. Stamatatos and C. Cheng-Mayer, J. Virol. 78:7840-7845, 1998). This observation led us to propose that the modified, SF162DeltaV2-derived envelope may elicit higher titers of cross-reactive neutralizing antibodies than the unmodified SF162-derived envelope. To test this hypothesis, we immunized rabbits and rhesus macaques with the gp140 form of these two envelopes. In rabbits, both immunogens elicited similar titers of binding antibodies but the modified immunogen was more effective in eliciting neutralizing antibodies, not only against the SF162DeltaV2 and SF162 viruses but also against several heterologous primary HIV type 1 (HIV-1) isolates. In rhesus macaques both immunogens elicited potent binding antibodies, but again the modified immunogen was more effective in eliciting the generation of neutralizing antibodies against the SF162DeltaV2 and SF162 viruses. Antibodies capable of neutralizing several, but not all, heterologous primary HIV-1 isolates tested were elicited only in macaques immunized with the modified immunogen. The efficiency of neutralization of these heterologous isolates was lower than that recorded against the SF162 isolate. Our results strongly suggest that although soluble oligomeric envelope subunit vaccines may elicit neutralizing antibody responses against heterologous primary HIV-1 isolates, these responses will not be broad and potent unless specific modifications are introduced to increase the exposure of conserved neutralization epitopes. 相似文献
972.
Assessment of clone identity and sequence fidelity for 1189 IMAGE cDNA clones 总被引:11,自引:2,他引:9
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This report documents the error rate in a commercially distributed subset of the IMAGE Consortium mouse cDNA clone collection. After isolation of plasmid DNA from 1189 bacterial stock cultures, only 62.2% were uncontaminated and contained cDNA inserts that had significant sequence identity to published data for the ordered clones. An agarose gel electrophoresis pre-screening strategy identified 361 stock cultures that appeared to contain two or more plasmid species. Isolation of individual colonies from these stocks demonstrated that 7.1% of the original 1189 stocks contained both a correct and an incorrect plasmid. 5.9% of the original 1189 stocks contained multiple, distinct, incorrect plasmids, indicating the likelihood of multiple contaminating events. While only 739 of the stocks purchased contained the desired cDNA clone, agarose gel pre-screening, colony isolation and similarity searching of dbEST allowed for the identification of an additional 420 clones that would have otherwise been discarded. Considering the high error rate in this subset of the IMAGE cDNA clone set, the use of sequence verified clones for cDNA microarray construction is warranted. When this is not possible, pre-screening non-sequence verified clones with agarose gel electrophoresis provides an inexpensive and efficient method to eliminate contaminated clones from the probe set. 相似文献
973.
Subramaniam N Leong GM Cock TA Flanagan JL Fong C Eisman JA Kouzmenko AP 《The Journal of biological chemistry》2001,276(19):15741-15746
1,25-Dihydroxyvitamin D(3) (vitamin D) and transforming growth factor-beta (TGF-beta) regulate diverse biological processes including cell proliferation and differentiation through modulation of the expression of target genes. Members of the Smad family of proteins function as effectors of TGF-beta signaling pathways whereas the vitamin D receptor (VDR) confers vitamin D signaling. We investigated the molecular mechanisms by which TGF-beta and vitamin D signaling pathways interact in the regulation of the human osteocalcin promoter. Synergistic activation of the osteocalcin gene promoter by TGF-beta and vitamin D was observed in transient transfection experiments. However, in contrast to a previous report by Yanagisawa, J., Yanagi, Y., Masuhiro, Y., Suzawa, M., Watanabe, M., Kashiwagi, K., Toriyabe, T., Kawabata, M., Miyazono, K., and Kato, S. (1999) Science, 283, 1317-1321, synergistic activation was not detectable when the osteocalcin vitamin D response element (VDRE) alone was linked to a heterologous promoter. Inclusion of the Smad binding elements (SBEs) with the VDRE in the heterologous promoter restored synergistic activation. Furthermore, this synergy was dependent on the spacing between VDRE and SBEs. The Smad3-Smad4 heterodimer was found to bind in gel shift assay to two distinct DNA segments of the osteocalcin promoter: -1030 to -989 (SBE3) and -418 to -349 (SBE1). Deletion of SBE1, which is proximal to the VDRE, but not the distal SBE3 in this promoter reporter abolished TGF-beta responsiveness and eliminated synergistic co-activation with vitamin D. Thus the molecular mechanism, whereby Smad3 and VDR mediate cross-talk between the TGF-beta and vitamin D signaling pathways, requires both a VDRE and a SBE located in close proximity to the target promoter. 相似文献
974.
Upward cascading effects of nutrients: shifts in a benthic microalgal community and a negative herbivore response 总被引:3,自引:0,他引:3
We evaluated the effects of nutrient addition on interactions between the benthic microalgal community and a dominant herbivorous gastropod, Cerithidea californica (California horn snail), on tidal flats in Mugu Lagoon, southern California, USA. We crossed snail and nutrient (N and P) addition treatments in enclosures on two tidal flats varying from 71 to 92% sand content in a temporally replicated experiment (summer 2000, fall 2000, spring 2001). Diatom biomass increased slightly (~30%) in response to nutrient treatments but was not affected by snails. Blooms of cyanobacteria (up to 200%) and purple sulfur bacteria (up to 400%) occurred in response to nutrient enrichment, particularly in the sandier site, but only cyanobacterial biomass decreased in response to snail grazing. Snail mortality was 2–5 times higher in response to nutrient addition, especially in the sandier site, corresponding to a relative increase in cyanobacterial biomass. Nutrient-related snail mortality occurred only in the spring and summer, when the snails were most actively feeding on the microalgal community. Inactive snails in the fall showed no response to nutrient-induced cyanobacterial growths. This study demonstrated strongly negative upward cascading effects of nutrient enrichment through the food chain. The strength of this upward cascade was closely linked to sediment type and microalgal community composition. 相似文献
975.
976.
Constituents of the stems of Macrococculus pomiferus and their inhibitory activities against cyclooxygenases-1 and -2 总被引:4,自引:0,他引:4
Su BN Jones WP Cuendet M Kardono LB Ismail R Riswan S Fong HH Farnsworth NR Pezzuto JM Kinghorn AD 《Phytochemistry》2004,65(21):2861-2866
As part of our program directed towards the discovery of new cancer chemopreventive agents from plants, the EtOAc-soluble extract of the stems of M. pomiferus was found to inhibit the enzyme cyclooxygenase-2 (COX-2). Bioassay-directed fractionation of this extract led to the isolation of two dibenzylbutyrolactone lignans, (8R,8'R)-3'-O-demethyl-5-hydroxymatairesinol (1) and (8R,8'R)-3'-O-demethyl-5-methoxymatairesinol (2), as well as seven known compounds, (-)-5'-methoxyyatein (3), blumenol A, (-)-deoxypodophyllotoxin (anthricin), (-)-deoxypodorhizone, 2,6-dimethoxyhydroquinone, 4-hydroxybenzaldehyde, and beta-sitosterol glucoside. The structures of compounds 1 and 2 were determined using spectroscopic data (1D and 2D NMR, and HREIMS), and the 8R and 8'R absolute stereochemistry was established for both 1 and 2 on the basis of their CD spectra. All isolates obtained in the present study were evaluated for their inhibitory effects with both COX-1 and -2. Of these, only 5'-methoxyyatein (3) showed weak activity against COX-2, while all other compounds isolated were inactive. The COX-2 inhibitory activity of the EtOAc extract was also traced to the presence of several common fatty acids by LC-MS. 相似文献
977.
Elevated nutrient content of tropical macroalgae increases rates of herbivory in coral,seagrass, and mangrove habitats 总被引:3,自引:0,他引:3
We explored the role of food quality in herbivore preference for macroalgae by comparing consumption of Acanthophora spicifera with and without elevated tissue nitrogen and phosphorus concentrations. Algal enrichment effects on herbivory were examined in coral, seagrass, and mangrove habitats along a sparsely populated Honduran island protected from fishing. Nutrient enrichment led to significantly increased grazing by herbivores across habitats. Consumption of enriched algae increased by 91% compared to controls among the mangrove roots, where herbivory rates were generally lowest. In the heavily grazed seagrass and coral habitats, nutrient enrichment increased consumption by 30 and 20%, respectively, with the effect more spatially variable than among the mangrove roots. We suggest that, at least on the local scale, intact herbivore populations may be able to compensate for effects of increased nutrient supply by locating and consuming nutrient-enriched algae, but that the importance of this mechanism varies both among and within habitats.Communicated by: R. C. Carpenter 相似文献
978.
High resolution magnetic images of planar wave fronts reveal bidomain properties of cardiac tissue
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We magnetically imaged the magnetic action field and optically imaged the transmembrane potentials generated by planar wavefronts on the surface of the left ventricular wall of Langendorff-perfused isolated rabbit hearts. The magnetic action field images were used to produce a time series of two-dimensional action current maps. Overlaying epifluorescent images allowed us to identify a net current along the wavefront and perpendicular to gradients in the transmembrane potential. This is in contrast to a traditional uniform double-layer model where the net current flows along the gradient in the transmembrane potential. Our findings are supported by numerical simulations that treat cardiac tissue as a bidomain with unequal anisotropies in the intra- and extracellular spaces. Our measurements reveal the anisotropic bidomain nature of cardiac tissue during plane wave propagation. These bidomain effects play an important role in the generation of the whole-heart magnetocardiogram and cannot be ignored. 相似文献
979.
980.
We have determined the abilities of (E)-ferulic acid, (E)-p-coumaric acid and (E,E)-5-5-dehydrodiferulic acid to protect against different types of mutation in a simple bacterial model. These antimutagenic properties were compared with those of the related compound curcumin, and also with those of an extract containing hydroxycinnamic acids obtained by the saponification of the cell walls of wheat coleoptiles. Three known mutagens, bleomycin, hydrogen peroxide and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) were used to chemically induce reversion mutation, while the known antimutagen Trolox was used as a positive control. Both the pure hydroxycinnamic acids and the extract from the cell walls showed antimutagenic properties. It is known that hydroxycinnamic acids ester-linked to plant cell walls can be released in the human colon by the action of microbial esterases. Providing the current data extrapolate to mammalian cells, they suggest that antimutagenic properties of hydroxycinnamic acids released from plant cell walls could play a role in dietary fibre protection against cancer. 相似文献