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Adeyemi T. Kayode Kazeem Akano Fehintola V. Ajogbasile Jessica N. Uwanibe Paul E. Oluniyi Bolajoko E. Bankole Philomena J. Eromon Akintunde Sowunmi Onikepe A. Folarin Sarah K. Volkman Bronwyn McInnis Pardis Sabeti Dyann F. Wirth Christian T. Happi 《International journal for parasitology》2021,51(4):301-310
The emergence and spread of Plasmodium falciparum parasites resistant to artemisinin derivatives and their partners in southeastern Asia threatens malaria control and elimination efforts, and heightens the need for an alternative therapy. We have explored the distribution of P. falciparum chloroquine resistance transporter (Pfcrt) and multidrug-resistant gene 1 (Pfmdr-1) haplotypes 10 years following adoption of artemisinin-based combination therapies in a bid to investigate the possible re-emergence of Chloroquine-sensitive parasites in Nigeria, and investigated the effect of these P. falciparum haplotypes on treatment outcomes of patients treated with artemisinin-based combination therapies. A total of 271 children aged <5 years with uncomplicated falciparum malaria were included in this study. Polymorphisms on codons 72–76 of the Pfcrt gene and codon 86 and 184 of Pfmdr-1 were determined using the high resolution melting assay. Of 240 (88.6%) samples successfully genotyped with HRM for Pfcrt, wildtype C72M74N75K76 (42.9%) and mutant C72I74E75T76 (53.8%) were observed. Also, wildtype N86Y184 (62.9%) and mutant N86F184 (21.1%), Y86Y184 (6.4%), and Y86F184 (0.4%) haplotypes of Pfmdr-1 were observed. Measures of responsiveness to ACTs were similar in children infected with P. falciparum crt haplotypes (C72I74E75T76 and C72M74N75K76) and major mdr-1 haplotypes (N86Y184, N86F184 and Y86Y184). Despite a 10 year gap since the malaria treatment policy changed to ACTs, over 50% of the P. falciparum parasites investigated in this study harboured the Chloroquine-resistant C72I74E75T76 haplotype, however this did not compromise the efficacy of artemisinin-based combination therapies. Should complete artemisinin resistance emerge from or spread to Nigeria, chloroquine might not be a good alternative therapy. 相似文献
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Hussein Melhem Pardis Simon Layla Beouch Fabrice Goubard Mourad Boucharef Catherine Di Bin Yann Leconte Bernard Ratier Nathalie Herlin‐Boime Johann Bouclé 《Liver Transplantation》2011,1(5):908-916
A crucial issue regarding emerging nanotechnologies remains the up‐scaling of new functional nanostructured materials towards their implementation in high performance applications on a large scale. In this context, we demonstrate high efficiency solid‐state dye‐sensitized solar cells prepared from new porous TiO2 photoanodes based on laser pyrolysis nanocrystals. This strategy exploits a reduced number of processing steps as well as non‐toxic chemical compounds to demonstrate highly porous TiO2 films. The possibility to easily tune the TiO2 nanocrystal physical properties allows us to demonstrate all solid‐state dye‐sensitized devices based on a commercial benchmark materials (organic indoline dye and molecular hole transporter) presenting state‐of‐the‐art performance comparable with reference devices based on a commercial TiO2 paste. In particular, a drastic improvement in pore infiltration, which is found to balance a relatively lower surface area compared to the reference electrode, is evidenced using laser‐synthesized nanocrystals resulting in an improved short‐circuit current density under full sunlight. Transient photovoltage decay measurements suggest that charge recombination kinetics still limit device performance. However, the proposed strategy emphasizes the potentialities of the laser pyrolysis technique for up‐scaling nanoporous TiO2 electrodes for various applications, especially for solar energy conversion. 相似文献
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Saeedi P Moosaabadi JM Sebtahmadi SS Behmanesh M Mehrabadi JF 《Biotechnology letters》2012,34(3):455-462
Bacteriorhodopsin (BR) mutagenesis plays an important role in the development of BR-based materials and tools with enhanced
optical and electrical properties. Previously reported protocols for generating BR mutations are inefficient for the preparation
and purification of mutant proteins. Therefore, a series of BR mutations were generated by using improved methods, which are
described in further detail. The functional activity of the recombinant proteins was confirmed by spectroscopic and electrochemical
assays. Modified proteins with different wavelengths and activities form a foundation for color-sensitive sensors and can
be utilized to produce unique bioelectrical and biotechnological tools and materials. The proton-pumping activity of the generated
mutant D85E was normal, indicating that the mutant could be used in light batteries. However, mutants D85Q and D85N were almost
inactive; and D85N had a prolonged M state, suggesting that it could be utilized in light memories. 相似文献
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Churchward MA Rogasevskaia T Brandman DM Khosravani H Nava P Atkinson JK Coorssen JR 《Biophysical journal》2008,94(10):3976-3986
The Ca2+-triggered merger of two apposed membranes is the defining step of regulated exocytosis. CHOL is required at critical levels in secretory vesicle membranes to enable efficient, native membrane fusion: CHOL-sphingomyelin enriched microdomains organize the site and regulate fusion efficiency, and CHOL directly supports the capacity for membrane merger by virtue of its negative spontaneous curvature. Specific, structurally dissimilar lipids substitute for CHOL in supporting the ability of vesicles to fuse: diacylglycerol, αT, and phosphatidylethanolamine support triggered fusion in CHOL-depleted vesicles, and this correlates quantitatively with the amount of curvature each imparts to the membrane. Lipids of lesser negative curvature than cholesterol do not support fusion. The fundamental mechanism of regulated bilayer merger requires not only a defined amount of membrane-negative curvature, but this curvature must be provided by molecules having a specific, critical spontaneous curvature. Such a local lipid composition is energetically favorable, ensuring the necessary “spontaneous” lipid rearrangements that must occur during native membrane fusion—Ca2+-triggered fusion pore formation and expansion. Thus, different fusion sites or vesicle types can use specific alternate lipidic components, or combinations thereof, to facilitate and modulate the fusion pore. 相似文献
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Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparum population divergence
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Daniel E Neafsey Stephen F Schaffner Sarah K Volkman Daniel Park Philip Montgomery Danny A Milner Jr Amanda Lukens David Rosen Rachel Daniels Nathan Houde Joseph F Cortese Erin Tyndall Casey Gates Nicole Stange-Thomann Ousmane Sarr Daouda Ndiaye Omar Ndir Soulyemane Mboup Marcelo U Ferreira Sandra do Lago Moraes Aditya P Dash Chetan E Chitnis Roger C Wiegand Daniel L Hartl Bruce W Birren Eric S Lander Pardis C Sabeti Dyann F Wirth 《Genome biology》2008,9(12):R171-16
Background
The malaria parasite Plasmodium falciparum exhibits abundant genetic diversity, and this diversity is key to its success as a pathogen. Previous efforts to study genetic diversity in P. falciparum have begun to elucidate the demographic history of the species, as well as patterns of population structure and patterns of linkage disequilibrium within its genome. Such studies will be greatly enhanced by new genomic tools and recent large-scale efforts to map genomic variation. To that end, we have developed a high throughput single nucleotide polymorphism (SNP) genotyping platform for P. falciparum.Results
Using an Affymetrix 3,000 SNP assay array, we found roughly half the assays (1,638) yielded high quality, 100% accurate genotyping calls for both major and minor SNP alleles. Genotype data from 76 global isolates confirm significant genetic differentiation among continental populations and varying levels of SNP diversity and linkage disequilibrium according to geographic location and local epidemiological factors. We further discovered that nonsynonymous and silent (synonymous or noncoding) SNPs differ with respect to within-population diversity, inter-population differentiation, and the degree to which allele frequencies are correlated between populations.Conclusions
The distinct population profile of nonsynonymous variants indicates that natural selection has a significant influence on genomic diversity in P. falciparum, and that many of these changes may reflect functional variants deserving of follow-up study. Our analysis demonstrates the potential for new high-throughput genotyping technologies to enhance studies of population structure, natural selection, and ultimately enable genome-wide association studies in P. falciparum to find genes underlying key phenotypic traits. 相似文献27.
Sabeti PC Walsh E Schaffner SF Varilly P Fry B Hutcheson HB Cullen M Mikkelsen TS Roy J Patterson N Cooper R Reich D Altshuler D O'Brien S Lander ES 《PLoS biology》2005,3(11):e378
The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14%) in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5), they imply that the pattern of genetic variation seen at CCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome. 相似文献
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Michael Lauck Adam L. Bailey Kristian G. Andersen Tony L. Goldberg Pardis C. Sabeti David H. O'Connor 《Journal of virology》2015,89(4):2425-2429
In 49 patients with known Ebola virus disease outcomes during the ongoing outbreak in Sierra Leone, 13 were coinfected with the immunomodulatory pegivirus GB virus C (GBV-C). Fifty-three percent of these GBV-C+ patients survived; in contrast, only 22% of GBV-C− patients survived. Both survival and GBV-C status were associated with age, with older patients having lower survival rates and intermediate-age patients (21 to 45 years) having the highest rate of GBV-C infection. Understanding the separate and combined effects of GBV-C and age on Ebola virus survival may lead to new treatment and prevention strategies, perhaps through age-related pathways of immune activation. 相似文献