We explore the phylogenetic relationships among HIV sequences sampled from young adult black men who have sex with men (YAB-MSM), who are connected through peer referral/social ties and who attend common venues. Using 196 viral sequences sampled from the peripheral blood mononuclear cells of 10 individuals, our preliminary phylogenetic results indicate that these socially connected YAB-MSM are infected with distantly related viruses and provide no evidence for viral transmission between network members. Our results suggest that HIV-prevention strategies that target young adult MSM should extend beyond their network members and local community.
View Article and Find Full Text PDFObjectives: Regulatory T cells (Tregs) which may indicate operational tolerance provide a promising biomarker for individualization of immunosuppression. Naturally thymus-derived Tregs (nTregs) represent the major suppressive phenotype and can be identified by their demethylation status in the Tregs Specific Demethylated Region (TSDR) of the Forkhead-Box-P3 (FOXP3) gene using quantitative PCR (qPCR).
Design And Methods: The analytical performance of a TSDR demethylation qPCR assay was assessed in whole blood of healthy individuals (HI) and kidney transplant recipients (KTR).
Objective: The objective of this study is to determine whether adipose tissue functions as a reservoir for HIV-1.
Design: We examined memory CD4(+) T cells and HIV DNA in adipose tissue-stromal vascular fraction (AT-SVF) of five patients [four antiretroviral therapy (ART)-treated and one untreated]. To determine whether adipocytes stimulate CD4(+) T cells and regulate HIV production, primary human adipose cells were cocultured with HIV-infected CD4(+) T cells.
BMJ Open Diabetes Res Care
December 2014
Background: The transcription factor 7-like 2 (TCF7L2) gene has the strongest genetic association with type 2 diabetes. TCF7L2 also associates with latent autoimmune diabetes in adults, which often presents with a single islet autoantibody, but not with classical type 1 diabetes.
Methods: We aimed to test if TCF7L2 is associated with single islet autoantibody expression in pediatric type 1 diabetes.
Stochastic models of sequence evolution have been developed to reflect many biologically important processes, allowing for accurate phylogenetic reconstruction when an appropriate model is selected. However, commonly used models do not incorporate several potentially important biological processes. Spurious phylogenetic inference may result if these processes play an important role in the evolution of a dataset yet are not incorporated into assumed models.
View Article and Find Full Text PDFRecent developments of unique nucleotide probes have expanded our understanding of DNA polymerase function, providing many benefits to techniques involving next-generation sequencing (NGS) technologies. The cyclic reversible termination (CRT) method depends on efficient base-selective incorporation of reversible terminators by DNA polymerases. Most terminators are designed with 3'-O-blocking groups but are incorporated with low efficiency and fidelity.
View Article and Find Full Text PDFJ Exp Psychol Hum Percept Perform
June 2011
Recently, it was proposed that the Simon effect would result not only from two interfering processes, as classical dual-route models assume, but from three processes. It was argued that priming from the spatial code to the nonspatial code might facilitate the identification of the nonspatial stimulus feature in congruent Simon trials. In the present study, the authors provide evidence that the identification of the nonspatial information can be facilitated by the activation of an associated spatial code.
View Article and Find Full Text PDFWe describe a novel 3'-OH unblocked reversible terminator with the potential to improve accuracy and read-lengths in next-generation sequencing (NGS) technologies. This terminator is based on 5-hydroxymethyl-2'-deoxyuridine triphosphate (HOMedUTP), a hypermodified nucleotide found naturally in the genomes of numerous bacteriophages and lower eukaryotes. A series of 5-(2-nitrobenzyloxy)methyl-dUTP analogs (dU.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2010
Phylogenetic analysis has been widely used to test the a priori hypothesis of epidemiological clustering in suspected transmission chains of HIV-1. Among studies showing strong support for relatedness between HIV samples obtained from infected individuals, evidence for the direction of transmission between epidemiologically related pairs has been lacking. During transmission of HIV, a genetic bottleneck occurs, resulting in the paraphyly of source viruses with respect to those of the recipient.
View Article and Find Full Text PDFDemand has never been greater for revolutionary technologies that deliver fast, inexpensive and accurate genome information. This challenge has catalysed the development of next-generation sequencing (NGS) technologies. The inexpensive production of large volumes of sequence data is the primary advantage over conventional methods.
View Article and Find Full Text PDFThe Simon effect is mostly explained in terms of dual-route models, which imply unidirectional activation processes from stimulus features to response features. However, there is also evidence that these preactivated response features themselves prime corresponding stimulus features. From this perspective, the Simon effect should only occur whenever the response is unequivocally mapped to just 1 stimulus feature (one-to-one mapping).
View Article and Find Full Text PDFObjective: Ketosis-prone diabetes (KPD) is an emerging syndrome that encompasses several distinct phenotypic subgroups that share a predisposition to diabetic ketoacidosis. We investigated whether the A-beta- subgroup of KPD, characterized by complete insulin dependence, absent beta-cell functional reserve, lack of islet cell autoantibodies, and strong family history of type 2 diabetes, represents a monogenic form of diabetes.
Research Design And Methods: Over 8 years, 37 patients with an A-beta- phenotype were identified in our longitudinally followed cohort of KPD patients.
The Human Genome Project has facilitated the sequencing of many species, yet the current Sanger method is too expensive, labor intensive and time consuming to accomplish medical resequencing of human genomes en masse. Of the 'next-generation' technologies, cyclic reversible termination (CRT) is a promising method with the goal of producing accurate sequence information at a fraction of the cost and effort. The foundation of this approach is the reversible terminator (RT), its chemical and biological properties of which directly impact the performance of the sequencing technology.
View Article and Find Full Text PDFWe have designed fluorescent "through-bond energy-transfer cassettes" that can harvest energy of a relatively short wavelength (e.g., 490 nm), and emit it at appreciably longer wavelengths without significant loss of intensity.
View Article and Find Full Text PDFAfter the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far.
View Article and Find Full Text PDFHuman chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.
View Article and Find Full Text PDFDemand for DNA sequence information has never been greater, yet current Sanger technology is too costly, time consuming, and labor intensive to meet this ongoing demand. Applications span numerous research interests, including sequence variation studies, comparative genomics and evolution, forensics, and diagnostic and applied therapeutics. Several emerging technologies show promise of delivering next-generation solutions for fast and affordable genome sequencing.
View Article and Find Full Text PDFThe highly secretory Clara cells play a pivotal role in protecting the lung against inflammation and oxidative stress. This study reports the positional cloning of a novel protein required for Clara cell physiology in mouse lung development. The perinatal lethal N-ethyl-N-nitrosourea-induced l7Rn6(4234SB) allele contained a nonsense mutation in the previously hypothetical gene NM_026304 on chromosome 7.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
April 2005
We present an approach called pulsed multiline excitation (PME) for measurements of multicomponent, fluorescence species and demonstrate its application in capillary electrophoresis for DNA sequencing. To fully demonstrate the advantages of PME, a fluorescent dye set has been developed whose absorption maxima span virtually the entire visible spectrum. Unlike emission wavelength-dependent approaches for identifying fluorescent species, the removal of the spectral component in PME confers a number of advantages including higher and normalized signals from all dyes present in the assay, the elimination of spectral cross-talk between dyes, and higher signal collection efficiency.
View Article and Find Full Text PDFThe human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome.
View Article and Find Full Text PDFWe have sequenced the genome of a second Drosophila species, Drosophila pseudoobscura, and compared this to the genome sequence of Drosophila melanogaster, a primary model organism. Throughout evolution the vast majority of Drosophila genes have remained on the same chromosome arm, but within each arm gene order has been extensively reshuffled, leading to a minimum of 921 syntenic blocks shared between the species. A repetitive sequence is found in the D.
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