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Ryan K. Cheu Andrew T. Gustin Christina Lee Luca Schifanella Charlene J. Miller Avie Ha Casey Kim Violeta J. Rodriguez Margaret Fischl Adam D. Burgener Kelly B. Arnold Maria L. Alcaide Nichole R. Klatt 《PLoS pathogens》2020,16(12)
Despite the efficacy of antiretroviral-based pre-exposure prophylactics (PrEP) in men who have sex with men, studies in women have produced widely varying outcomes. Recent evidence demonstrates that vaginal microbial communities are associated with increased HIV acquisition risk and may impact PrEP efficacy. Here, we investigate the mechanisms underlying how vaginal bacteria alter PrEP drug levels and impact HIV infection rates ex vivo. Using cervicovaginal lavages (CVLs) from women with or without bacterial vaginosis (BV), we identified microbial metabolism of PrEP drugs in BV samples through LC-MS/MS analysis of soluble drug levels and metabolite formation in dual T-cell cultures. CVL samples were assessed for microbiome analysis using sequencing of bacterial 16S rRNA genes. We also observed non-Lactobacillus bacteria that are associated with BV may potentially impact PrEP efficacy through increased HIV infection rates in co-cultures containing Lactobacillus or BV bacteria, PrEP drugs, CEM-GFP cells, and HIV-1LAI virus. Finally, we used these data to develop a novel predictive mathematical simulation modeling system to predict these drug interactions for future trials. These studies demonstrate how dysbiotic vaginal microbiota may impact PrEP drugs and provides evidence linking vaginal bacteria to PrEP efficacy in women. 相似文献
63.
Andrew Leask 《Journal of cell communication and signaling》2010,4(2):109-110
The role of CCN proteins in vivo is only just becoming understood. A prototypical member of the CCN family, CCN3 suppresses proliferation. In a study in press, Shimoyama and colleagues show that mice lacking CCN3 have a hyperproliferative response to vascular injury. These data, along with other recent observations, suggest that CCN3 may represent a novel therapy for hyperproliferative diseases. 相似文献
64.
The impact of ticks on pheasant territoriality 总被引:1,自引:0,他引:1
Pheasants are competent reservoir hosts for the Lyme disease spirochaete, Borrelia burgdorferi s.l., and carry large, but highly over-dispersed, infestations of the vector ticks, Ixodes ricinus . The effects of experimental reduction of tick infestation levels on the survival and territorial behaviour of male pheasants were studied. Over three years in two woodlands in southern England, birds were marked individually and half were fitted with a slow-release acaricide, which substantially reduced their tick burdens from March to August. Acaricide treatment affected reproductive success but had no discernible impact on the survival rates of male pheasants. The degree of wattle inflation by males, an indicator of territorial status and a correlate of harem acquisition, was significantly greater among treated males. In each year, a significantly higher proportion of treated (overall 44%) than control (22%) males acquired harems. Males that acquired females ranged over small areas on field edges. By contrast, those with no females ranged more widely in woods and the adjoining fields, increasing their exposure to questing ticks. The relative contribution of such roving males to tick-borne pathogen transmission may thus increase. 相似文献
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66.
The chloroplast genome is now known to be more variable than was once thought. Reports of RFLP (restriction fragment length polymorphism) and sequence variation, as well as variation in chloroplast microsatellites, are common. Here, data are presented on the variability of a minisatellite sequence in the chloroplast genome of Sorbus species. RFLP analysis of a PCR product comprising the region between the trnM and rbcL genes of nine Sorbus species identified seven size variants. Sequencing revealed the observed size polymorphism to be due to differences in the number of copies of an imperfect 9-bp motif. A more intensive survey of the variability of the minisatellite was undertaken in populations of Sorbus aucuparia. The potential uses of such regions in chloroplast DNA are discussed and a possible mechanism for the evolution of the minisatellite is presented. 相似文献
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Analysis of the distribution and structure of integrated Banana streak virus DNA in a range of Musa cultivars 总被引:2,自引:0,他引:2
Andrew D. W. Geering Neil E. Olszewski Ganesh Dahal John E. Thomas Benham E. L. Lockhart 《Molecular Plant Pathology》2001,2(4):207-213
Banana streak virus strain OL (BSV-OL) commonly infects new Musa hybrids, and this infection is thought to arise de novo from integrated virus sequences present in the nuclear genome of the plant. Integrated DNA (Musa6+8 sequence) containing the whole genome of the virus has previously been cloned from cv. Obino l’Ewai (Musa AAB group), a parent of many of the hybrids. Using a Southern blot hybridization assay, we have examined the distribution and structure of integrated BSV-OL sequences in a range of Musa cultivars. For cv. Obino l’Ewai, almost every restriction fragment hybridizing to BSV-OL was predicted from the Musa6+8 sequence, suggesting that this is the predominant type of BSV-OL integrant in the genome. Furthermore, since only two junction fragments of Musa/BSV sequence were detected, and the Musa6+8 sequence is believed to be integrated as multiple copies in a tandem array, then the internal Musa spacer sequences must be highly conserved. Similarly sized restriction fragments were detected in four BB group cultivars, but not in six AA or AAA group cultivars, suggesting that the BSV-OL sequences are linked to the B-genome of Musa. We also provide evidence that cv. Williams (Musa AAA group) contains a distinct badnavirus integrant that is closely related to the ‘dead’ virus integrant previously characterized from Calcutta 4 (Musa acuminata ssp. burmannicoides). Our results suggest that the virus integrant from cv. Williams is linked to the A-genome, and the complexity of the hybridization patterns suggest multiple sites of integration and/or variation in sequence and structure of the integrants. 相似文献
69.
70.
A stable carbon isotope study of dissolved inorganic carbon cycling in a softwater lake 总被引:3,自引:0,他引:3
Andrew L. Herczeg 《Biogeochemistry》1987,4(3):231-263
The dissolved inorganic carbon (DIC) cycle in a softwater lake was studied using natural variations of the stable isotopes of carbon,12C and13C. During summer stratification there was a progressive decrease in epilimnion DIC concentration with a concomitant increase in 13CDIC), due to preferential uptake of12C by phytoplankton and a change in the dominant CO2 source from inflow andin situ oxidation to invasion from the atmosphere. There was an increase in hypolimnion DIC concentration throughout summer with a concomitant general decrease in 13CDIC from oxidation of the isotopically light particulate organic carbon that sank down through the thermocline from the epilimnion.Mass balance calculations of DI12C and DI13C in the epilimnion for the summer (June 23–September 25) yield a mean rate of net conversion of DIC to organic carbon (Corg) of 430 ± 150 moles d-1 (6.5 ± 1.8 m moles m-2 d-1. Net CO2 invasion from the atmosphere was 420 ± 120 moles d-1 (6.2 ± 1.8 m moles m-2 d-1) with an exchange coefficient of 0.6 ± 0.3m d-1. These results imply that at least for the summer months the phytoplankton obtained about 90% of their carbon from atmosphere CO2. About 50% of CO2 invasion and conversion to Corg for the summer occurred during a two week interval in mid-summer.DIC concentration increased in the hypolimnion at a rate of 350 ± 70 moles DIC d-1 during summer stratification. The amount of DIC added to the hypolimnion was equivalent to 75 ± 20% of net conversion of DIC to Corg in the euphotic zone over spring and summer implying rapid degradation of POC in the hypolimnion. The 13C of DIC added to the deep water (-22.) was too heavy to have been derived from oxidation of particulate organic carbon alone. About 20% of the added DIC must have diffused from hypolimnetic sediments where relatively heavy CO2 (-7) was produced by a combination of POC oxidation and as a by-product of methanogenesis. 相似文献