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81.
82.
Stephanie Ringeissen Susan C. Connor H. Roger Brown Brian C. Sweatman Mark P. Hodson Steve P. Kenny 《Biomarkers》2013,18(3-4):240-271
This study identified two potential novel biomarkers of peroxisome proliferation in the rat. Three peroxisome proliferator-activated receptor (PPAR) ligands, chosen for their high selectivity towards the PPARα, -δ and -γ subtypes, were given to rats twice daily for 7 days at doses known to cause a pharmacological effect or peroxisome proliferation. Fenofibrate was used as a positive control. Daily treatment with the PPARα and -δ agonists produced peroxisome proliferation and liver hypertrophy. 1H nuclear magnetic resonance spectroscopy and multivariate statistical data analysis of urinary spectra from animals given the PPARα and -δ agonists identified two new potential biomarkers of peroxisome proliferation - N-methylnicotinamide (NMN) and N-methyl-4-pyridone-3-carboxamide (4PY) - both endproducts of the tryptophan-nicotinamide adenine dinucleotide (NAD+) pathway. After 7 days, excretion of NMN and 4PY increased 24- and three-fold, respectively, following high doses of fenofibrate. The correlation between total NMN excretion over 7 days and the peroxisome count was r=0.87 (r2=0.76). Plasma NMN, measured using a sensitive high performance liquid chromatography method, was increased up to 61-fold after 7 days' treatment with high doses of fenofibrate. Hepatic gene expression of aminocarboxymuconate-semialdehyde decarboxylase (EC 4.1.1.45) was downregulated following treatment with the PPARα and -δ agonists. The decrease was up to 11-fold compared with controls in the groups treated with high doses of fenofibrate. This supports the link between increased NMN and 4PY excretion and regulation of the tryptophan-NAD+ pathway in the liver. In conclusion, NMN, and possibly other metabolites in the pathway, are potential non-invasive surrogate biomarkers of peroxisome proliferation in the rat. 相似文献
83.
Loai M. Alnemer Raed I. Seetan Filippo M. Bassi Charith Chitraranjan Adam Helsene Paul Loree Steve Bou Goshn Yong Q. Gu Ming-Cheng Luo M. Javed Iqbal Gerard R. Lazo Anne M. Denton Shahryar F. Kianian 《Functional & integrative genomics》2013,13(1):11-17
In the course of evolution, the genomes of grasses have maintained an observable degree of gene order conservation. The information available for already sequenced genomes can be used to predict the gene order of nonsequenced species by means of comparative colinearity studies. The “Wheat Zapper” application presented here performs on-demand colinearity analysis between wheat, rice, Sorghum, and Brachypodium in a simple, time efficient, and flexible manner. This application was specifically designed to provide plant scientists with a set of tools, comprising not only synteny inference, but also automated primer design, intron/exon boundaries prediction, visual representation using the graphic tool Circos 0.53, and the possibility of downloading FASTA sequences for downstream applications. Quality of the “Wheat Zapper” prediction was confirmed against the genome of maize, with good correlation (r?>?0.83) observed between the gene order predicted on the basis of synteny and their actual position on the genome. Further, the accuracy of “Wheat Zapper” was calculated at 0.65 considering the “Genome Zipper” application as the “gold” standard. The differences between these two tools are amply discussed, making the point that “Wheat Zapper” is an accurate and reliable on-demand tool that is sure to benefit the cereal scientific community. The Wheat Zapper is available at http://wge.ndsu.nodak.edu/wheatzapper/. 相似文献
84.
85.
Darren Boone Susan Mallett Shihua Zhu Guiqing Lily Yao Nichola Bell Alex Ghanouni Christian von Wagner Stuart A. Taylor Douglas G. Altman Richard Lilford Steve Halligan 《PloS one》2013,8(12)
Purpose
To establish the relative weighting given by patients and healthcare professionals to gains in diagnostic sensitivity versus loss of specificity when using CT colonography (CTC) for colorectal cancer screening.Materials and Methods
Following ethical approval and informed consent, 75 patients and 50 healthcare professionals undertook a discrete choice experiment in which they chose between “standard” CTC and “enhanced” CTC that raised diagnostic sensitivity 10% for either cancer or polyps in exchange for varying levels of specificity. We established the relative increase in false-positive diagnoses participants traded for an increase in true-positive diagnoses.Results
Data from 122 participants were analysed. There were 30 (25%) non-traders for the cancer scenario and 20 (16%) for the polyp scenario. For cancer, the 10% gain in sensitivity was traded up to a median 45% (IQR 25 to >85) drop in specificity, equating to 2250 (IQR 1250 to >4250) additional false-positives per additional true-positive cancer, at 0.2% prevalence. For polyps, the figure was 15% (IQR 7.5 to 55), equating to 6 (IQR 3 to 22) additional false-positives per additional true-positive polyp, at 25% prevalence. Tipping points were significantly higher for patients than professionals for both cancer (85 vs 25, p<0.001) and polyps (55 vs 15, p<0.001). Patients were willing to pay significantly more for increased sensitivity for cancer (p = 0.021).Conclusion
When screening for colorectal cancer, patients and professionals believe gains in true-positive diagnoses are worth much more than the negative consequences of a corresponding rise in false-positives. Evaluation of screening tests should account for this. 相似文献86.
This study investigates the long term economic impact of severe obstetric complications for women and their children in Burkina Faso, focusing on measures of food security, expenditures and related quality of life measures. It uses a hospital based cohort, first visited in 2004/2005 and followed up four years later. This cohort of 1014 women consisted of two main groups of comparison: 677 women who had an uncomplicated delivery and 337 women who experienced a severe obstetric complication which would have almost certainly caused death had they not received hospital care (labelled a “near miss” event). To analyze the impact of such near miss events as well as the possible interaction with the pregnancy outcome, we compared household and individual level indicators between women without a near miss event and women with a near miss event who either had a live birth, a perinatal death or an early pregnancy loss. We used propensity score matching to remove initial selection bias. Although we found limited effects for the whole group of near miss women, the results indicated negative impacts: a) for near miss women with a live birth, on child development and education, on relatively expensive food consumption and on women’s quality of life; b) for near miss women with perinatal death, on relatively expensive foods consumption and children’s education and c) for near miss women who had an early pregnancy loss, on overall food security. Our results showed that severe obstetric complications have long lasting consequences for different groups of women and their children and highlighted the need for carefully targeted interventions. 相似文献
87.
María Díez-León Jeff Bowman Steve Bursian Hélène Filion David Galicia Jeannette Kanefsky Angelo Napolitano Rupert Palme Albrecht Schulte-Hostedde Kim Scribner Georgia Mason 《PloS one》2013,8(11)
Wild carnivores in zoos, conservation breeding centres, and farms commonly live in relatively small, unstimulating enclosures. Under these captive conditions, in a range of species including giant pandas, black-footed ferrets, and European mink, male reproductive abilities are often poor. Such problems have long been hypothesized to be caused by these animals'' housing conditions. We show for the first time that rearing under welfare-improving (i.e., highly valued and stress-reducing) environmental enrichments enhances male carnivores'' copulatory performance: in mate choice competitions, enriched male American mink (Neovison vison) mated more often than non-enriched males. We screened for several potential mediators of this effect. First was physiological stress and its impact on reproductive physiology; second, stress-mediated changes in morphology and variables related to immunocompetence that could influence male attractiveness; and third, behavioural changes likely to affect social competence, particularly autistic-like excessive routine and repetition (‘perseveration’) as is reflected in the stereotypies common in captive animals. Consistent with physiological stress, excreted steroid metabolites revealed that non-enriched males had higher cortisol levels and lower androgen levels than enriched conspecifics. Their os penises (bacula) also tended to be less developed. Consistent with reduced attractiveness, non-enriched males were lighter, with comparatively small spleens and a trend to greater fluctuating asymmetry. Consistent with impaired social competence, non-enriched males performed more stereotypic behaviour (e.g., pacing) in their home cages. Of all these effects, the only significant predictor of copulation number was stereotypy (a trend suggesting that low bodyweights may also be influential): highly stereotypic males gained the fewest copulations. The neurophysiological changes underlying stereotypy thus handicap males sexually. We hypothesise that such males are abnormally perseverative when interacting with females. Investigating similar problems in other taxa would be worthwhile, since many vertebrates, wild and domestic, live in conditions that cause stereotypic behaviour and/or impair neurological development. 相似文献
88.
Furaha Mramba Francis Oloo Mechtilda Byamungu Thomas Kr?ber Andrew McMullin Steve Mihok Patrick M. Guerin 《PLoS neglected tropical diseases》2013,7(2)
Background
Here we set out to standardize long-lasting, visually-attractive devices for Glossina swynnertoni, a vector of both human and animal trypanosomiasis in open savannah in Tanzania and Kenya, and in neighbouring conservation areas used by pastoralists. The goal was to determine the most practical device/material that would induce the strongest landing response in G. swynnertoni for use in area-wide population suppression of this fly with insecticide-impregnated devices.Methods and Findings
Trials were conducted in wet and dry seasons in the Serengeti and Maasai Mara to measure the performance of traps and targets of different sizes and colours, with and without chemical baits, at different population densities and under different environmental conditions. Adhesive film was used as a simple enumerator at these remote locations to compare trapping efficiencies of devices. Independent of season or presence of chemical baits, targets in phthalogen blue or turquoise blue cloth with adhesive film were the best devices for capturing G. swynnertoni in all situations, catching up to 19 times more flies than pyramidal traps. Baiting with chemicals did not affect the relative performance of devices. Fly landings were two times higher on 1 m2 blue-black targets as on pyramidal traps when equivalent areas of both were covered with adhesive film. Landings on 1 m2 blue-black targets were compared to those on smaller phthalogen blue 0.5 m2 all-blue or blue-black-blue cloth targets, and to landings on all-blue plastic 0.32–0.47 m2 leg panels painted in phthalogen blue. These smaller targets and leg panels captured equivalent numbers of G. swynnertoni per unit area as bigger targets.Conclusions
Leg panels and 0.5 m2 cloth targets show promise as cost effective devices for management of G. swynnertoni as they can be used for both control (insecticide-impregnated cloth) and for sampling (rigid plastic with insect glue or adhesive film) of populations. 相似文献89.
Xiaofei Chang Eugene Izumchenko Luisa M. Solis Myoung Sook Kim Aditi Chatterjee Shizhang Ling Constance L. Monitto Paul M. Harari Manuel Hidalgo Steve N. Goodman Ignacio I. Wistuba Atul Bedi David Sidransky 《PloS one》2013,8(7)
The sensitivity of only a few tumors to anti-epidermal growth factor receptor EGFR tyrosine kinase inhibitors (TKIs) can be explained by the presence of EGFR tyrosine kinase (TK) domain mutations. In addition, such mutations were rarely found in tumor types other than lung, such as pancreatic and head and neck cancer. In this study we sought to elucidate mechanisms of resistance to EGFR-targeted therapies in tumors that do not harbor TK sensitizing mutations in order to identify markers capable of guiding the decision to incorporate these drugs into chemotherapeutic regimens. Here we show that EGFR activity was markedly decreased during the evolution of resistance to the EGFR tyrosine kinase inhibitor (TKI) erlotinib, with a concomitant increase of mitogen-inducible gene 6 (Mig6), a negative regulator of EGFR through the upregulation of the PI3K-AKT pathway. EGFR activity, which was more accurately predicted by the ratio of Mig6/EGFR, highly correlated with erlotinib sensitivity in panels of cancer cell lines of different tissue origins. Blinded testing and analysis in a prospectively followed cohort of lung cancer patients treated with gefitinib alone demonstrated higher response rates and a marked increased in progression free survival for patients with a low Mig6/EGFR ratio (approximately 100 days, P = 0.01). 相似文献
90.
Cécilia G. Maubaret Klelia D. Salpea Casey E. Romanoski Lasse Folkersen Jackie A. Cooper Coralea Stephanou Ka Wah Li Jutta Palmen Anders Hamsten Andrew Neil Jeffrey W. Stephens Aldons J. Lusis Per Eriksson Philippa J. Talmud Steve E. Humphries the Simon Broome Research Group the EARSII consortium 《PloS one》2013,8(12)