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Dana Jones

Publications and source records attributed to Dana Jones.

8 recordsLinked to original sources
PubMed2007

Life without water: expression of plant LEA genes by an anhydrobiotic arthropod.

Anhydrobiotic animals protect cellular architecture and metabolic machinery in the dry state, yet the molecular repertoire supporting this profound dehydration tolerance is not fully understood. For the desiccation-tolerant crustacean, Artemia franciscana, we report differential expression of two distinct mRNAs encoding for proteins that share sequence similarities and structural features with late-embryogenesis abundant (LEA) proteins originally discovered in plants. Bioinformatic analyses support assignment of the LEA proteins from A. franciscana to group 3. This eucoelomate species is the most highly evolved animal for which LEA gene expression has been reported. It is becoming clear that an ensemble of micromolecules and macromolecules is important for establishing the physical conditions required for cellular stabilization during drying in nature.

Amino Acid Sequence↗
PubMed2006

Phenotypic drug resistance patterns in subtype A HIV-1 clones with nonnucleoside reverse transcriptase resistance mutations.

We analyzed the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) susceptibility of 29 subtype A HIV-1 clones isolated from 10 Ugandan women after single-dose nevirapine (NVP) administration. Six clones had no NNRTI resistance-associated mutations ("wild type"), eight had K103N, nine had Y181C, five had G190A, and one had Y181S. Three clones displayed unexpected phenotypic drug susceptibility/resistance based on their RT genotypes. One wild-type clone had reduced susceptibility to NVP, delavirdine (DLV), and efavirenz (EFV), one clone with K103N was susceptible to all three NNRTIs, and one clone with G190A had extreme hypersusceptibility to DLV. Three unusual HIV-1 RT amino acid substitutions may have contributed to the unexpected phenotypes of the clones: I31T, N136S, and N265D. These polymorphisms were rarely detected among 47,900 HIV-1 genotypes from clinical samples of predominantly United States origin. Further studies are needed to define the genetic correlates of antiretroviral drug resistance in nonsubtype B HIV-1.

Alkynes↗
PubMed2006

Sensitivity of the ViroSeq HIV-1 genotyping system for detection of the K103N resistance mutation in HIV-1 subtypes A, C, and D.

The US Food and Drug Administration-cleared ViroSeq HIV-1 Genotyping System (ViroSeq) and other population sequencing-based human immunodeficiency virus type 1 (HIV-1) genotyping methods detect antiretroviral drug resistance mutations present in the major viral population of a test sample. These assays also detect some mutations in viral variants that are present as mixtures. We compared detection of the K103N nevirapine resistance mutation using ViroSeq and a sensitive, quantitative point mutation assay, LigAmp. The LigAmp assay measured the percentage of K103N-containing variants in the viral population (percentage of K103N). We analyzed 305 samples with HIV-1 subtypes A, C, and D collected from African women after nevirapine administration. ViroSeq detected K103N in 100% of samples with >20% K103N, 77.8% of samples with 10 to 20% K103N, 71.4% of samples with 5 to 10% K103N, and 16.9% of samples with 1 to 5% K103N. The sensitivity of ViroSeq for detection of K103N was similar for subtypes A, C, and D. These data indicate that the ViroSeq system reliably detects the K103N mutation at levels above 20% and frequently detects the mutation at lower levels. Further studies are needed to compare the sensitivity of different assays for detection of HIV-1 drug resistance mutations and to determine the clinical relevance of HIV-1 minority variants.

Anti-HIV Agents↗
PubMed2005

Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012.

BACKGROUND: The HIV Network for Prevention Trials (HIVNET) 012 trial showed that NVP resistance (NVPR) emerged in some women and children after the administration of single-dose nevirapine (SD-NVP). We tested whether K103N-containing human immunodeficiency virus (HIV)-1 variants persisted in women and infants 1 year or more after the administration of SD-NVP. METHODS: We analyzed samples from 9 women and 5 infants in HIVNET 012 who had NVPR 6-8 weeks after the administration of SD-NVP. Samples were analyzed with the ViroSeq system and with 2 sensitive resistance assays, LigAmp and TyHRT. RESULTS: ViroSeq detected the K103N mutation in 8 of 9 women and in 2 of 5 infants. LigAmp detected the K103N mutation at low levels in 8 of 9 women and in 4 of 5 infants. K103N was not detected by ViroSeq 12-24 months after the administration of SD-NVP but was detected by LigAmp in 3 of 9 women and in 1 of 5 infants. K103N was also detected in those samples by use of the TyHRT assay. CONCLUSIONS: K103N-containing variants persist in some women and infants for 1 year or more after the administration of SD-NVP. Sensitive resistance assays may provide new insight into the impact of antiretroviral drug exposure on HIV-1 evolution.

Anti-HIV Agents↗
PubMed2005

Genetic linkage of nevirapine resistance mutations in HIV type 1 seven days after single-dose nevirapine.

The HIVNET 012 trial in Uganda demonstrated that a regimen of single-dose nevirapine (NVP) can prevent HIV-1 mother-to-child transmission. Previous studies show that HIV-1 with one or more NVP resistance (NVPR) mutations can be selected in many women as early as 7 days after single-dose NVP. We evaluated the genetic linkage of NVPR mutations in plasma from women in HIVNET 012 collected 7 days after single-dose NVP administration. The HIV-1 pol region was amplified and cloned from 20 plasma samples (16 with NVPR mutations detected by population sequencing and 4 with no NVPR mutations detected), and 10 clones from each sample were sequenced. Up to five different NVPR mutations were detected in clones from a single sample. K103N and Y181C were the most common mutations detected. Clones with two genetically linked mutations were detected in four samples. Different combinations of NVPR mutations were linked in individual clones, but none of the clones contained both K103N and Y181C. Further studies are needed to evaluate whether selection of minority variants with one or more NVPR mutations after single-dose NVP is clinically relevant.

Amino Acid Substitution↗
PubMed2004

LigAmp for sensitive detection of single-nucleotide differences.

We developed the LigAmp assay for sensitive detection and accurate quantification of viruses and cells with single-base mutations. In LigAmp, two oligonucleotides are hybridized adjacently to a DNA template. One oligonucleotide matches the target sequence and contains a probe sequence. If the target sequence is present, the oligonucleotides are ligated together and detected using real-time PCR. LigAmp detected KRAS2 mutant DNA at 0.01% in mixtures of different cell lines. KRAS2 mutations were also detected in pancreatic duct juice from patients with pancreatic cancer. LigAmp detected the K103N HIV-1 drug resistance mutation at 0.01% in plasmid mixtures and at approximately 0.1% in DNA amplified from plasma HIV-1. Detection in both systems is linear over a broad dynamic range. Preliminary evidence indicates that reactions can be multiplexed. This assay may find applications in the diagnosis of genetic disorders and the management of patients with cancer and infectious diseases.

Biomarkers, Tumor↗
PubMed2004

Prospective studies of Bartonella of rodents. Part II. Diverse infections in a single rodent community.

The genetic diversity of Bartonella species within a small mammal community and in individual cotton rats (Sigmodon hispidus) was examined by trapping, capturing, sampling, and releasing of marked animals over a 17-month interval. Based on sequence analyses of the Bartonella gltA gene, amplicons separated into four genogroups (A, B, C, and Pin) containing 11 variants. Although the prevalence of bacteremia due to different genogroups/variants of Bartonella was temporally variable, variants of genogroup A predominated during each sampling period. Multiple gltA variants were often (20.5% of individuals) isolated from a single cotton rat blood sample; a maximum of five variants was recovered from an individual during its sampling history. Among 92 cotton rats bacteremic at two or more sampling dates, 34 rats retained a single genetic variant, alone or in mixed infection, throughout their sampling history. The temporal course of individual infections was complex as the succession of gltA variants was variable and detectable bacteremia was often intermittent. No antibodies (titer of >1:8) were detected to homologous strains of Bartonella recovered from individual cotton rats during their sampling history. The temporal course of Bartonella infections could result from a single, persistent, and potentially multi-genogroup/variant infection, during which variants differentially dominate the detectable bacteremia.

Animals↗