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1.

Background

The Step trial raised the possibility that uncircumcised men with pre-existing Ad5 neutralizing antibodies carried an increased risk of HIV infection after vaccination. Thus, understanding Ad seropositivity in humans is important to the development of an AIDS vaccine. Here, we analyze the impact of different Ad5-specific neutralizing antibodies on immune function and clinical outcome.

Methods and Findings

Ad seropositivity in the Step trial volunteers was analyzed using chimeric rAd5/35 vectors to characterize their specificity for Ad5 fiber and non-fiber external (capsid) proteins. Immune responses and HIV seropositivity were correlated with the specificity of Ad5-neutralizing antibodies. Neutralizing antibodies induced by the vaccine in Ad5 seronegative subjects were directed preferentially to Ad5 capsid proteins, although some fiber-neutralizing antibodies could be detected. Pre-vaccination Ad5 serostatus did not affect the capsid-directed response after three vaccinations. In contrast, anti-fiber antibody titers were significantly higher in volunteers who were Ad5 seropositive prior to vaccination. Those Ad5 seropositive subjects who generated anti-capsid responses showed a marked reduction in vaccine-induced CD8 responses. Unexpectedly, anti-vector immunity differed qualitatively in Ad5 seropositive participants who became HIV-1 infected compared to uninfected case controls; Ad5 seropositive participants who later acquired HIV had lower neutralizing antibodies to capsid. Moreover, Ad35 seropositivity was decreased in HIV-infected subjects compared with uninfected case controls, while seroprevalence for other serotypes including Ad14, Ad28 and Ad41 was similar in both groups.

Conclusions

Together, these findings suggest that the case subjects were less immunologically responsive prior to infection. Subjects infected during the Step trial had qualitative differences in immunity that increased their risk of HIV-1 infection independent of vaccination.  相似文献   
2.

Background  

We recently described a mini-intein in the PRP8 gene of a strain of the basidiomycete Cryptococcus neoformans, an important fungal pathogen of humans. This was the second described intein in the nuclear genome of any eukaryote; the first nuclear encoded intein was found in the VMA gene of several saccharomycete yeasts. The evolution of eukaryote inteins is not well understood. In this report we describe additional PRP8 inteins (bringing the total of these to over 20). We compare and contrast the phylogenetic distribution and evolutionary history of the PRP8 intein and the saccharomycete VMA intein, in order to derive a broader understanding of eukaryote intein evolution. It has been suggested that eukaryote inteins undergo horizontal transfer and the present analysis explores this proposal.  相似文献   
3.
? Premise of the study: Plants and animals may experience reproductive Allee effects in fragmented populations, and obligate pollination mutualisms may be especially sensitive to extinction risk via this density-dependent process. In this study we examine how a shift from within-crown reproductive synchrony to asynchrony influences reproductive assurance through contributions to selfing and outcrossing in small, spatially isolated populations of Ficus. ? Methods: The research focuses on the monoecious fig F. petiolaris and consists of phenological analyses and genetic assessments of selfing and outcrossing for populations located in Baja California's Sonoran Desert. ? Key results: Phenological censuses of eight populations revealed within-crown asynchrony in 44% of reproducing trees, with 16% having sufficient overlap of male and female flowering phases to permit selfing via the cycling of pollinating fig wasps within natal trees. In mating system analyses of two of these populations, however, multilocus outcrossing rates (t(m)) were indistinguishable from 1. This result, combined with low levels of inbreeding, indicates selfing to be absent or at best a minor contributor to reproductive assurance. ? Conclusions: The results indicate that the fitness benefits of within-crown asynchrony lie not with selfing, as commonly asserted, but with increased opportunities for outcross pollen transmission and receipt, changing our understanding of the mechanisms by which reproduction is facilitated and extinction risk minimized in naturally fragmented Ficus populations. Given the role of fig fruit as a keystone food resource in many tropical environments, trait variation leading to reproductive assurance in figs, such as within-crown asynchrony, has broader ecosystem-level implications.  相似文献   
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6.
Development of cell surface saccharides on embryonic pancreatic cells   总被引:3,自引:2,他引:1  
Using a battery of seven lectin-ferritin conjugates as probes for cell surface glycoconjugates, we have studied the pattern of plasmalemmal differentiation of cells in the embryonic rat pancreas from day 15 in utero to the early postpartum stage. Our results indicate that differentiation of plasmalemmal glycoconjugates on acinar, endocrine, and centroacinar cells is temporally correlated with development and is unique for each cell type, as indicated by lectin-ferritin binding. Specifically, (a) expression of adult cell surface saccharide phenotype can be detected on presumptive acinar cells as early as 15 d in utero, as indicated by soybean agglutinin binding, and precedes development of intracellular organelles characteristic of mature acinar cells; (b) maturation of the plasmalemma of acinar cells is reached after intracellular cytodifferentiation is completed, as indicated by appearance of Con A and fucoselectin binding sites only at day 19 of development; conversely, maturation of the endocrine cell plasmalemma is accompanied by "loss" (masking) of ricinus communis II agglutinin receptors; and (c) binding sites for fucose lectins and for soybean agglutinin are absent on endocrine and centroacinar cells at all stages examined. We conclude that acinar, centroacinar, and endocrine cells develop from a common progenitor cell(s) whose plasmalemmal carbohydrate composition resembles most closely that of the adult centroacinar cell. Finally, appearance of acinar lumina beginning at approximately 17 d in utero is accompanied by differenetiation of apical and basolateral plasmalemmal domains of epithelial cells, as indicated by enhanced binding of several lectin-ferritin conjugates to the apical plasmalemmal, a pattern that persists from this stage through adult life.  相似文献   
7.
The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889–90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics.
“The war is over – and I must go” Egon Schiele, 1890–1918.
  相似文献   
8.
Cell-free extracts of tomato leaves from plants grown on media individually deficient in each of the micronutrient elements showed marked changes in enzymatic constitution. Each deficiency caused an alteration in the over-all enzyme pattern which was characteristic of the micronutrient element in question. The metallo-enzymes such as polyphenol oxidase, ascorbic acid oxidase, and peroxidase lost approximately half their activity in plants deficient in the specific metal concerned. In the cases of all other metal deficiencies, however, polyphenol oxidase and peroxidase were elevated in concentration at least two to six times that of the control. Ascorbic acid oxidase was doubled in zinc- and manganese-deficient material. Glycolic acid dehydrogenase and lactic acid dehydrogenase showed smaller parallel rises averaging a one and a half fold increase in content in zinc- and manganese-deficient plants. Reduced diphosphopyridine nucleotide diaphorase was doubled by copper and manganese deficiencies and was increased to almost one and a half fold by zinc deficiency. Endogenous oxygen uptake in boron-deficient, copper-deficient, and manganese-deficient leaf homogenates was increased, and almost lacking in molybdenum-deficient material.  相似文献   
9.
Exposure of pronghorns (Antilocapra americana) in western Nebraska in 1983 to selected livestock pathogens was examined by serology and attempted virus isolation. Antibodies were present to the agents of bluetongue, epizootic hemorrhagic disease, and bovine respiratory syncytial virus. There were no serologic reactors to Brucella, and attempts to isolate the viruses of bluetongue and epizootic hemorrhagic disease were negative.  相似文献   
10.
We developed seven nuclear intron markers for Euphorbia lomelii. New exon-primed intron-crossing (EPIC) oligonucleotides were used for initial amplification and sequencing, then locus-specific primers and restriction-fragment-length polymorphism genotyping assays were designed. Loci showed no significant deviation from Hardy–Weinberg and linkage equilibrium, and they cross-amplify in at least three congeneric species. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.  相似文献   
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