Low and High Resolution GC-MS Detection of N2, 3-Ethenoguanine in Livers of Vinyl Chloride Exposed Sprague-Dawley Rats and of Unexposed Mammals

Vinyl chloride (VC) is a known human and animal carcinogen requiring metabolic activation by cytochrome P450-dependent monooxygenases. The metabolic products of vinyl chloride, chloroethylene oxide and chloroacetaldehyde, react with deoxyribonucleic acids to form DNA adducts. The formation and persistence of DNA adducts have been previously reported in preweanling Sprague-Dawley rats and dams exposed to vinyl chloride by inhalation. In the present study, adult male Sprague-Dawley rats were exposed to 500 ppm VC by inhalation for 1, 2, 4, or 8 weeks (4 hrs/day, 5 days/week). The quantitation of N^2,3-ethenoguanine (ɛG) was accomplished by low resolution gas chromatography-negative ion chemical ionization-mass spectrometry (GC-MS) monitoring of the [M-181]" fragment of ɛG's dipentafluorobenzyl derivative, 3,5-PFB[2]-ɛG. ɛG concentrations, expressed as μmol adduct/μmol unmodified guanine, were 0.57±0.06, 1.3±0.54, 1.4±0.21, and 2.0±0.91 following 1, 2, 4, or 8 weeks of VC exposure, respectively. To verify the low resolution GC-MS, a high resolution GC-MS method was applied to provide both a highly sensitive and highly specific method for quantitating ɛG. Whereas low resolution could selectively monitor single ion masses of m/z 354±0.5 for PFB-ɛG and m/z 358±0.5 for PFB-[13Cc]ɛG, the high resolution method could detect exact masses (10,000 resolution power) of the ɛG analyte and its 13C-labeled analog, [13C4]-ɛG. The relative response ratios of the ɛG analyte to its internal standard, [13C4-ɛG, were comparable between low resolution and high resolution GC-MS. The concentrations of ɛG using high resolution GC-MS were 0.45±0.07, 1.1±0.61, 1.5±0.43, and 1.7±0.79 following 1, 2, 4, or 8 weeks of VC exposure, respectively. In addition, the amounts of endogenous ɛG were analyzed in liver DNA from untreated Sprague-Dawley rats (53-week old), Sprague-Dawley rats (8-week old), Fischer 344 rats, and human samples. The ɛG concentrations detected by low resolution were 0.27±0.07, 0.57±0.48, 0.16±0.02, and 0.56±0. 35 μmol eɛ/μmol guanine for Sprague-Dawley rats, Fischer 344 rats, and humans. Comparable levels (0.02[n=l], 0.32±0.17, 0.06±0.07, and 0.81±0.97μmol ɛG/μmolG) were measured by high resolution. While the sources of endogenous ɛG are presently unknown, the application of high resolution GC-MS to its detection left little doubt as to its identity. Since ɛG is one of the most promutagenic DNA adducts formed by exogenous alkylating agents, this endogenous DNA adduct may be of importance in human cancer. Our findings that ɛG increased in an exposure-related manner in DNA from rats exposed to vinyl chloride, and was also present in unexposed animals present important new data for VC-induced carcinogenesis.Master of Science in Public Healt

Healthcare Barriers of Residents at a Subsidized Housing Community

Introduction: Despite expanded healthcare programs, the low income and elderly lack coverage of vision, hearing, and dental services. Community services are often asked to fill these gaps. To evaluate the situation in Burlington, VT, we surveyed staff and residents in Burlington Housing Authority (BHA) subsidized housing to (1) identify gaps in healthcare coverage and (2) assess barriers to accessing those services in this population.https://scholarworks.uvm.edu/comphp_gallery/1207/thumbnail.jp

Impact of Missing Data for Body Mass Index in an Epidemiologic Study

To assess the potential impact of missing data on body mass index (BMI) on the association between prepregnancy obesity and specific birth defects

Imprints, Vol. 2

Imprints is the official publication for Sigma Tau Delta, the honorary English fraternity. The editors welcome creative works submitted by contributors and also publish winners of the annual T. E. Ferguson Writing Contest. Especially welcome are poems, fiction pieces and essays of no more than 5,000 words in length. At this time we would like to express our gratitude to David Whitescarver, Sigma Tau Delta faculty advisor, for his unrelenting optimism and valuable help in the preparation of this journal

Artificial Light Increases Local Predator Abundance, Predation Rates, and Herbivory.

Human activity is rapidly increasing the radiance and geographic extent of artificial light at night (ALAN) leading to alterations in the development, behavior, and physiological state of many organisms. A limited number of community-scale studies investigating the effects of ALAN have allowed for spatial aggregation through positive phototaxis, the commonly observed phenomenon of arthropod movement toward light. We performed an open field study (without restricted arthropod access) to determine the effects of ALAN on local arthropod community composition, plant traits, and local herbivory and predation rates. We found strong positive phototaxis in 10 orders of arthropods, with increased (159% higher) overall arthropod abundance under ALAN compared to unlit controls. The arthropod community under ALAN was more diverse and contained a higher proportion of predaceous arthropods (15% vs 8%). Predation of immobilized flies occurred 3.6 times faster under ALAN; this effect was not observed during the day. Contrary to expectations, we also observed a 6% increase in herbivory under ALAN. Our results highlight the importance of open experimental field studies in determining community-level effects of ALAN

Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms’ Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8–1.4 x 106). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients

Differentiated function and localisation of SPO11-1 and PRD3 on the chromosome axis during meiotic DSB formation in Arabidopsis thaliana

During meiosis, DNA double-strand breaks (DSBs) occur throughout the genome, a subset of which are repaired to form reciprocal crossovers between chromosomes. Crossovers are essential to ensure balanced chromosome segregation and to create new combinations of genetic variation. Meiotic DSBs are formed by a topoisomerase-VI-like complex, containing catalytic (e.g. SPO11) proteins and auxiliary (e.g. PRD3) proteins. Meiotic DSBs are formed in chromatin loops tethered to a linear chromosome axis, but the interrelationship between DSB-promoting factors and the axis is not fully understood. Here, we study the localisation of SPO11-1 and PRD3 during meiosis, and investigate their respective functions in relation to the chromosome axis. Using immunocytogenetics, we observed that the localisation of SPO11-1 overlaps relatively weakly with the chromosome axis and RAD51, a marker of meiotic DSBs, and that SPO11-1 recruitment to chromatin is genetically independent of the axis. In contrast, PRD3 localisation correlates more strongly with RAD51 and the chromosome axis. This indicates that PRD3 likely forms a functional link between SPO11-1 and the chromosome axis to promote meiotic DSB formation. We also uncovered a new function of SPO11-1 in the nucleation of the synaptonemal complex protein ZYP1. We demonstrate that chromosome co-alignment associated with ZYP1 deposition can occur in the absence of DSBs, and is dependent on SPO11-1, but not PRD3. Lastly, we show that the progression of meiosis is influenced by the presence of aberrant chromosomal connections, but not by the absence of DSBs or synapsis. Altogether, our study provides mechanistic insights into the control of meiotic DSB formation and reveals diverse functional interactions between SPO11-1, PRD3 and the chromosome axis

Strained tetragonal states and Bain paths in metals

Paths of tetragonal states between two phases of a material, such as bcc and fcc, are called Bain paths. Two simple Bain paths can be defined in terms of special imposed stresses, one of which applies directly to strained epitaxial films. Each path goes far into the range of nonlinear elasticity and reaches a range of structural parameters in which the structure is inherently unstable. In this paper we identify and analyze the general properties of these paths by density functional theory. Special examples include vanadium, cobalt and copper, and the epitaxial path is used to identify an epitaxial film as related uniquely to a bulk phase.Comment: RevTeX, 4 pages, 4 figures, submitted to Phys. Rev. Let

Center Variation in the Delivery of Indicated Late Preterm Births

Evidence for optimal timing of delivery for some pregnancy complications at late preterm gestation is limited. The purpose of this study was to identify center variation of indicated late preterm births

The transcriptional profile of coronary arteritis in Kawasaki disease.

BACKGROUND: Kawasaki Disease (KD) can cause potentially life-threatening coronary arteritis in young children, and has a likely infectious etiology. Transcriptome profiling is a powerful approach to investigate gene expression in diseased tissues. RNA sequencing of KD coronary arteries could elucidate the etiology and the host response, with the potential to improve KD diagnosis and/or treatment. METHODS: Deep RNA sequencing was performed on KD (n = 8) and childhood control (n = 7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Non-human RNA sequences were subjected to a microbial discovery bioinformatics platform, and microbial sequences were analyzed by Metastats for association with KD. RESULTS: T lymphocyte activation, antigen presentation, immunoglobulin production, and type I interferon response were significantly upregulated in KD arteritis, while the tumor necrosis factor α pathway was not differentially expressed. Transcripts from known infectious agents were not specifically associated with KD coronary arteritis. CONCLUSIONS: The immune transcriptional profile in KD coronary artery tissues has features of an antiviral immune response such as activated cytotoxic T lymphocyte and type I interferon-induced gene upregulation. These results provide new insights into the pathogenesis of KD arteritis that can guide selection of new immunomodulatory therapies for high-risk KD patients, and provide direction for future etiologic studies