968 research outputs found

    Performance of the Syva Direct Fluorescent Antibody Assay for Chlamydia in a Low-Prevalence Population

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    Chlamydia trachomatis is the most common reportable sexually transmitted disease (STD) in the United States. In the 1980s, rapid diagnostic tests for chlamydia began to replace more cumbersome tissue culture methods. Current data on rapid antigen detection assays demonstrate acceptable sensitivity, specificity, and predictive values in populations with a high prevalence of chlamydia. Few studies report the performance of these assays in a low-prevalence obstetric and gynecologic (Ob/Gyn) population, This study compares the most commonly used direct fluorescent antibody (DFA) assay (Syva Microtrak) with tissue culture (TC) in a low-prevalence population. Endocervical specimens (775) were tested from women at risk for chlamydia infection, and the prevalence was found to be 7.7%. The DFA assay demonstrated a sensitivity of 80% and a specificity of 97% compared with TC. The positive and negative predictive values were 72% and 98%, respectively. The results of this study indicate that the Syva DFA assay lacks the sensitivity and positive predictive value for routine use in Ob/Gyn populations with a lowprevalence of C. trachomatis

    P53 is active in murine stem cells and alters the transcriptome in a manner that is reminiscent of mutant p53

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    Since it was found that p53 is highly expressed in murine embryonic stem cells, it remained a mystery whether p53 is active in this cell type. We show that a significant part of p53 is localised in the nucleus of murine embryonic stem cells and that the majority of this nuclear p53 is bound to DNA. According to its nuclear localisation, we show that p53 alters the transcriptional program of stem cells. Nevertheless, the anti-proliferative activity of p53 is compromised in stem cells, and this control is due, at least in part, to the high amount of MdmX that is present in embryonic stem cells and bound to p53. Instead of the anti-proliferative activity that p53 has in differentiated cells, p53 controls transcription of pro-proliferative genes in embryonic stem cells including c-myc and c-jun. The impeded anti-proliferative activity of p53 and the induction of certain proto-oncogenes by p53 in murine embryonic stem cells can explain why stem cells proliferate efficiently despite having high levels of p53

    Chloroplast Genome Sequence of the Moss Torula ruralis: Gene Content, Polymorphism, and Structural Arrangement Relative to Other Green Plant Chloroplast Genomes

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    Background Tortula ruralis, a widely distributed species in the moss family Pottiaceae, is increasingly used as a model organism for the study of desiccation tolerance and mechanisms of cellular repair. In this paper, we present the chloroplast genome sequence of T. ruralis, only the second published chloroplast genome for a moss, and the first for a vegetatively desiccation-tolerant plant. Results The Tortula chloroplast genome is ~123,500 bp, and differs in a number of ways from that of Physcomitrella patens, the first published moss chloroplast genome. For example, Tortula lacks the ~71 kb inversion found in the large single copy region of the Physcomitrella genome and other members of the Funariales. Also, the Tortula chloroplast genome lacks petN, a gene found in all known land plant plastid genomes. In addition, an unusual case of nucleotide polymorphism was discovered. Conclusions Although the chloroplast genome of Tortula ruralis differs from that of the only other sequenced moss, Physcomitrella patens, we have yet to determine the biological significance of the differences. The polymorphisms we have uncovered in the sequencing of the genome offer a rare possibility (for mosses) of the generation of DNA markers for fine-level phylogenetic studies, or to investigate individual variation within population

    The role of amelogenin during enamel-crystallite growth and organization in vivo: Amelogenin and enamel-crystallite formation

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    Amelogenin is critical for enamel formation and human AMELX gene mutations cause hypoplastic and/or hypomaturation enamel phenotypes. The Amelx null (AKO) mouse has a severe hypoplastic phenotype. This study evaluated the effect of amelogenin loss on enamel formation and crystallite morphology. Enamel from AKO and wild type (WT) mice was used. AKO mice were mated with transgenic mice expressing the most abundant known amelogenin isoform TgM180-87 to rescue (KOM180-87) the enamel crystallite phenotype. Molar enamel was embedded, sectioned with a diamond microtome and photographed using transmission electron microscopy. Crystallite sizes from multiple sections were measured using Image J. Crystallite mean thicknesses were (WT = 26 nm, AKO = 16 nm, KOm180-87 = 25 nm) and the mean widths were (WT = 96 nm, AKO = 59 nm, KOm180-87 = 85 nm). Despite a complete loss of amelogenin in AKO mice, a mineralized enamel layer with well-defined and organized crystallites forms. Enamel crystallites forming in the absence of amelogenin were reduced in thickness and width. For the first time we show that introduction of the m180 amelogenin isoform into the AKO mouse through crossbreeding rescues the crystallite phenotype. We conclude that amelogenin is essential for the development of normal crystallite size

    A gene expression signature distinguishes innate response and resistance to proteasome inhibitors in multiple myeloma

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    Extensive interindividual variation in response to chemotherapy is a major stumbling block in achieving desirable efficacy in the treatment of cancers, including multiple myeloma (MM). In this study, our goal was to develop a gene expression signature that predicts response specific to proteasome inhibitor (PI) treatment in MM. Using a well-characterized panel of human myeloma cell lines (HMCLs) representing the biological and genetic heterogeneity of MM, we created an in vitro chemosensitivity profile in response to treatment with the four PIs bortezomib, carfilzomib, ixazomib and oprozomib as single agents. Gene expression profiling was performed using next-generation high-throughput RNA-sequencing. Applying machine learning-based computational approaches including the supervised ensemble learning methods Random forest and Random survival forest, we identified a 42-gene expression signature that could not only distinguish good and poor PI response in the HMCL panel, but could also be successfully applied to four different clinical data sets on MM patients undergoing PI-based chemotherapy to distinguish between extraordinary (good and poor) outcomes. Our results demonstrate the use of in vitro modeling and machine learning-based approaches to establish predictive biomarkers of response and resistance to drugs that may serve to better direct myeloma patient treatment options

    Liver Enzyme Abnormalities and Associated Risk Factors in HIV Patients on Efavirenz-Based HAART with or without Tuberculosis Co-Infection in Tanzania.

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    To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection. A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS). Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week), being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7 per 1000 person-week) than those receiving HAART alone (5.9%, 6.3 per 1000 person-week). Frequency of CYP2B6*6 allele (p = 0.03) and CYP2B6*6/*6 genotype (p = 0.06) was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI. Antiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians

    Rescue of the murine amelogenin null phenotype with two amelogenin transgenes

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    The amelogenin proteins are required for normal enamel development; the most abundant amelogenins expressed from alternatively spliced mRNAs are M180 and leucine rich amelogenin protein (LRAP). The Amelx null (KO) mouse has an enamel defect similar to human X-linked amelogenesis imperfecta. The disorganized enamel layer in KO mice is 10–20% the thickness of wild-type (WT) enamel and lacks prismatic structures. When the KO mice were mated with mice that express TgM180-87, partial rescue of the phenotype was observed such that enamel thickness, volume and density increased. A second transgene was introduced by mating the TgM180KO mice with TgLRAP mice, and male offspring were characterized for genotype and tooth phenotype was evaluated by SEM. TgM180LRAPKO molar enamel thickness further increased, and the structure was improved, with a more defined decussation pattern compared to singly rescued mice. We conclude that TgM180 provides significant rescue of the KO phenotype. Although the effectiveness of TgLRAP to rescue by itself is less obvious, the addition of TgLRAP to TgM180 in KO enamel leads to added improvement in both amount and structure and thus these transgenes function in a complementary manner. Together the two most abundant amelogenins lead to formation of obvious enamel decussation patterns
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