21 research outputs found
Comparative determination of HIV-1 co-receptor tropism by Enhanced Sensitivity Trofile, gp120 V3-loop RNA and DNA genotyping
BACKGROUND: Trofile is the prospectively validated HIV-1 tropism assay. Its use is limited by high costs, long turn-around time, and inability to test patients with very low or undetectable viremia. We aimed at assessing the efficiency of population genotypic assays based on gp120 V3-loop sequencing for the determination of tropism in plasma viral RNA and in whole-blood viral DNA. Contemporary and follow-up plasma and whole-blood samples from patients undergoing tropism testing via the enhanced sensitivity Trofile (ESTA) were collected. Clinical and clonal geno2pheno[coreceptor] (G2P) models at 10% and at optimised 5.7% false positive rate cutoff were evaluated using viral DNA and RNA samples, compared against each other and ESTA, using Cohen's kappa, phylogenetic analysis, and area under the receiver operating characteristic (AUROC).
RESULTS: Both clinical and clonal G2P (with different false positive rates) showed good performances in predicting the ESTA outcome (for V3 RNA-based clinical G2P at 10% false positive rate AUROC = 0.83, sensitivity = 90%, specificity = 75%). The rate of agreement between DNA- and RNA-based clinical G2P was fair (kappa = 0.74, p < 0.0001), and DNA-based clinical G2P accurately predicted the plasma ESTA (AUROC = 0.86). Significant differences in the viral populations were detected when comparing inter/intra patient diversity of viral DNA with RNA sequences.
CONCLUSIONS: Plasma HIV RNA or whole-blood HIV DNA V3-loop sequencing interpreted with clinical G2P is cheap and can be a good surrogate for ESTA. Although there may be differences among viral RNA and DNA populations in the same host, DNA-based G2P may be used as an indication of viral tropism in patients with undetectable plasma viremia
The impact of sex-role reversal on the diversity of the major histocompatibility complex: Insights from the seahorse (Hippocampus abdominalis)
Background: Both natural and sexual selection are thought to influence genetic diversity, but the study of the relative importance of these two factors on ecologically-relevant traits has traditionally focused on species with conventional sex-roles, with male-male competition and female-based mate choice. With its high variability and significance in both immune function and olfactory-mediated mate choice, the major histocompatibility complex(MHC/MH) is an ideal system in which to evaluate the relative contributions of these two selective forces to genetic diversity. Intrasexual competition and mate choice are both reversed in sex-role reversed species, and sexrelated differences in the detection and use of MH-odor cues are expected to influence the intensity of sexual selection in such species. The seahorse, Hippocampus abdominalis, has an exceptionally highly developed form of male parental care, with female-female competition and male mate choice. Results: Here, we demonstrate that the sex-role reversed seahorse has a single MH class II beta-chain gene and that the diversity of the seahorse MHIIb locus and its pattern of variation are comparable to those detected in species with conventional sex roles. Despite the presence of only a single gene copy, intralocus MHIIb allelic diversity in this species exceeds that observed in species with multiple copies of this locus. The MHIIb locus of the seahorse exhibits a novel expression domain in the male brood pouch. Conclusions: The high variation found at the seahorse MHIIb gene indicates that sex-role reversed species are capable of maintaining the high MHC diversity typical in most vertebrates. Whether such species have evolved the capacity to use MH-odor cues during mate choice is presently being investigated using mate choice experiments. If this possibility can be rejected, such systems would offer an exceptional opportunity to study the effects of natural selection in isolation, providing powerful comparative models for understanding the relative importance of selective factors in shaping patterns of genetic variation
Incidence of AIDS-Defining Opportunistic Infections in a Multicohort Analysis of HIV-infected Persons in the United States and Canada, 2000–2010
Background. There are few recent data on the rates of AIDS-defining opportunistic infections (OIs) among human immunodeficiency virus (HIV)–infected patients in care in the United States and Canada
End-Stage Renal Disease Among HIV-Infected Adults in North America
Background. Human immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks
Principal Variance Component Analysis of Crop Composition Data: A Case Study on Herbicide-Tolerant Cotton
Compositional
studies on genetically modified (GM) and non-GM crops
have consistently demonstrated that their respective levels of key
nutrients and antinutrients are remarkably similar and that other
factors such as germplasm and environment contribute more to compositional
variability than transgenic breeding. We propose that graphical and
statistical approaches that can provide meaningful evaluations of
the relative impact of different factors to compositional variability
may offer advantages over traditional frequentist testing. A case
study on the novel application of principal variance component analysis
(PVCA) in a compositional assessment of herbicide-tolerant GM cotton
is presented. Results of the traditional analysis of variance approach
confirmed the compositional equivalence of the GM and non-GM cotton.
The multivariate approach of PVCA provided further information on
the impact of location and germplasm on compositional variability
relative to GM
Investigation of Biochemical Diversity in a Soybean Lineage Representing 35 Years of Breeding
This
paper reports an assessment of seed biochemical and metabolite
variability and diversity in a series of nine soybean varieties; all
lines share the same genetic lineage but represent ∼35 years
of breeding (launch years 1972–2008) and differing yield potentials.
These varieties, including six conventional and three glyphosate-tolerant
lines, were grown concurrently at two replicated field sites in the
United States during the 2011 growing season, and seeds were harvested
at maturity. A compositional assessment included measurement of proximates,
amino acids, fatty acids, tocopherols, isoflavones, saccharides, organic
acids, and selected phytohormones. Statistical analysis included application
of principal variance component analysis (PVCA) to investigate the
interrelationships among compositional components from these soybean
varieties and the impacts of location (environment) and pedigree on
variability of these components. Results demonstrated that (i) some
biochemical analytes showed trends (either increased or decreased)
with launch year and/or yield, (ii) some analytes varied according
to variety but showed no trend with launch year and/or yield, and
(iii) almost all analytes showed extensive variation within and across
sites. In summary, varietal development of high-yielding soybean,
as represented in this study, has been accompanied by compositional
changes but these are typically modest relative to environmental
factors