295 research outputs found
Spatial Bioaccumulation Modeling in a Network of Bayous
A software system, Spatial Network Bioaccumulation Model (SNBM), was developed to model the bioaccumulation of polycyclic aromatic hydrocarbons (PAHs) in aquatic food webs. The SNBM uses a geographic information system as an engine to: (i) store the spatial representation of input parameters (the data related to the ecosystem), (ii) transfer input and output data to and from the food-web bioaccumulation model, and (iii) display the predicted food-web organism concentrations over a base map of the field site. The bioaccumulation model is a time-dependent, set of first-order ordinary differential equations that are solved numerically. Many sampling locations can be analyzed using the SNBM in one individual run. We demonstrate the system for a steady-state simulation of three PAHs, naphthalene, phenanthrene and benzanthracene in a food web for spotted gar (Lepisosteus oculatus) from the LaBranche Wetlands, Louisiana, USA. The predicted food-web organism concentrations are plotted at their respective sampling location
Gene expression responses in male fathead minnows exposed to binary mixtures of an estrogen and antiestrogen
<p>Abstract</p> <p>Background</p> <p>Aquatic organisms are continuously exposed to complex mixtures of chemicals, many of which can interfere with their endocrine system, resulting in impaired reproduction, development or survival, among others. In order to analyze the effects and mechanisms of action of estrogen/anti-estrogen mixtures, we exposed male fathead minnows (<it>Pimephales promelas</it>) for 48 hours via the water to 2, 5, 10, and 50 ng 17α-ethinylestradiol (EE<sub>2</sub>)/L, 100 ng ZM 189,154/L (a potent antiestrogen known to block activity of estrogen receptors) or mixtures of 5 or 50 ng EE<sub>2</sub>/L with 100 ng ZM 189,154/L. We analyzed gene expression changes in the gonad, as well as hormone and vitellogenin plasma levels.</p> <p>Results</p> <p>Steroidogenesis was down-regulated by EE<sub>2 </sub>as reflected by the reduced plasma levels of testosterone in the exposed fish and down-regulation of genes in the steroidogenic pathway. Microarray analysis of testis of fathead minnows treated with 5 ng EE<sub>2</sub>/L or with the mixture of 5 ng EE<sub>2</sub>/L and 100 ng ZM 189,154/L indicated that some of the genes whose expression was changed by EE<sub>2 </sub>were blocked by ZM 189,154, while others were either not blocked or enhanced by the mixture, generating two distinct expression patterns. Gene ontology and pathway analysis programs were used to determine categories of genes for each expression pattern.</p> <p>Conclusion</p> <p>Our results suggest that response to estrogens occurs via multiple mechanisms, including canonical binding to soluble estrogen receptors, membrane estrogen receptors, and other mechanisms that are not blocked by pure antiestrogens.</p
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Incremental Lifetime Cancer Risks Computed for Benzo[A]Pyrene and Two Tobacco-Specific N-Nitrosamines in Mainstream Cigarette Smoke Compared with Lung Cancer Risks Derived from Epidemiologic Data
The manner in which humans smoke cigarettes is an important determinant of smoking risks. Of the few investigators that have predicted cancer risks from smoking on a chemical-specific basis, most used mainstream cigarette smoke (MCS) carcinogen emissions obtained via machine smoking protocols that only approximate human smoking conditions. Here we use data of Djordjevic et al. [Djordjevic, M.V., Stellman, S.D., Zang, E., 2000. Doses of nicotine and lung carcinogens delivered to cigarette smokers. J. Natl. Cancer Inst. 92, 106–111] for MCS emissions of three carcinogens measured under human smoking conditions to compute probability distributions of incremental lifetime cancer risk (ILCR) values using Monte Carlo simulations. The three carcinogens considered are benzo[a]pyrene, N ′-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Computed NNK ILCR values were compared with lifetime risks of lung cancer (ILCR*((obsΣ/CMD)-lung)) derived from American Cancer Society Cancer Prevention Studies (CPS) I and II. Within the Monte Carlo simulation results, NNK was responsible for the greatest ILCR values for all cancer endpoints: median ILCR values for NNK were ~18-fold and 120-fold higher than medians for NNN and benzo[a]pyrene, respectively. For “regular” cigarettes, the NNK median ILCR for lung cancer was lower than ILCR*((obsΣ/CMD)-lung) from CPS-I and II by less than 90-fold for men and less than 4-fold for women. Given what is known about chemical carcinogens in MCS, this study shows that there is a higher incidence of lung cancer from exposure to MCS than can be predicted with current risk assessment methods using available toxicity and emission data
Separated twins or just siblings? A multi-planet system around an M dwarf including a cool sub-Neptune
We report the discovery of two TESS sub-Neptunes orbiting the early M dwarf
TOI-904 (TIC 261257684). Both exoplanets, TOI-904 b and c, were initially
observed in TESS sector 12 with twin sizes of 2.49R and
2.31R, respectively. Through observations in five additional sectors
in the TESS primary mission and the first and second extended missions, the
orbital periods of both planets were measured to be 10.8870.001 and
83.9990.001 days, respectively. Reconnaissance radial velocity
measurements (taken with EULER/CORALIE) and high resolution speckle imaging
with adaptive optics (obtained from SOAR/HRCAM and Gemini South/ZORRO) show no
evidence of an eclipsing binary or a nearby companion, which together with the
low false positive probabilities calculated with the statistical validation
software TRICERATOPS establish the planetary nature of these candidates. The
outer planet, TOI-904 c, is the longest-period M dwarf exoplanet found by TESS,
with an estimated equilibrium temperature of 217K. As the three other validated
planets with comparable host stars and orbital periods were observed by Kepler
around much dimmer stars (J 12), TOI-904 c, orbiting a brighter
star (J 9.6), is the coldest M dwarf planet easily accessible for
atmospheric follow-up. Future mass measurements and transmission spectroscopy
of the similar sized planets in this system could determine whether they are
also similar in density and composition, suggesting a common formation pathway,
or whether they have distinct origins.Comment: 18 pages, 6 figures, Accepted by the Astrophysical Journal Letter
The state of the Martian climate
60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes
A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): Study protocol for a randomised controlled trial
Background: Malignant pleural mesothelioma is an incurable cancer caused by exposure to asbestos. The United Kingdom has the highest death rate from mesothelioma in the world and this figure is increasing. Median survival is 8 to 12 months, and most patients have symptoms at diagnosis. The fittest patients may be offered chemotherapy with palliative intent. For patients not fit for systemic anticancer treatment, best supportive care remains the mainstay of management. A study from the United States examining advanced lung cancer showed that early specialist palliative care input improved patient health related quality of life and depression symptoms 12 weeks after diagnosis. While mesothelioma and advanced lung cancer share many symptoms and have a poor prognosis, oncology and palliative care services in the United Kingdom, and many other countries, vary considerably compared to the United States. The aim of this trial is to assess whether regular early symptom control treatment provided by palliative care specialists can improve health related quality of life in patients newly diagnosed with mesothelioma. Methods: This multicentre study is an non-blinded, randomised controlled, parallel group trial. A total of 174 patients with a new diagnosis of malignant pleural mesothelioma will be minimised with a random element in a 1:1 ratio to receive either 4weekly regular early specialist symptom control care, or standard care. The primary outcome is health related quality of life for patients at 12 weeks. Secondary outcomes include health related quality of life for patients at 24 weeks, carer health related quality of life at 12 and 24 weeks, patient and carer mood at 12 and 24 weeks, overall survival and analysis of healthcare utilisation and cost. Discussion: Current practice in the United Kingdom is to involve specialist palliative care towards the final weeks or months of a life-limiting illness. This study aims to investigate whether early, regular specialist care input can result in significant health related quality of life gains for patients with mesothelioma and if this change in treatment model is cost-effective. The results will be widely applicable to many institutions and patients both in the United Kingdom and internationally. Trial registration: Current controlled trials ISRCTN18955704.Date ISRCTN assigned: 31 January 2014
QLT0267, a small molecule inhibitor targeting integrin-linked kinase (ILK), and docetaxel can combine to produce synergistic interactions linked to enhanced cytotoxicity, reductions in P-AKT levels, altered F-actin architecture and improved treatment outcomes in an orthotopic breast cancer model
Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains
BACKGROUND: Despite multiple causes, Chronic Kidney Disease is commonly associated with proteinuria. A previous study on Non Obese Diabetic mice (NOD), which spontaneously develop type 1 diabetes, described histological and gene expression changes incurred by diabetes in the kidney. Because proteinuria is coincident to diabetes, the effects of proteinuria are difficult to distinguish from those of other factors such as hyperglycemia. Proteinuria can nevertheless be induced in mice by peritoneal injection of Bovine Serum Albumin (BSA). To gain more information on the specific effects of proteinuria, this study addresses renal changes in diabetes resistant NOD-related mouse strains (NON and NOD.B10) that were made to develop proteinuria by BSA overload. METHODS: Proteinuria was induced by protein overload on NON and NOD.B10 mouse strains and histology and microarray technology were used to follow the kidney response. The effects of proteinuria were assessed and subsequently compared to changes that were observed in a prior study on NOD diabetic nephropathy. RESULTS: Overload treatment significantly modified the renal phenotype and out of 5760 clones screened, 21 and 7 kidney transcripts were respectively altered in the NON and NOD.B10. Upregulated transcripts encoded signal transduction genes, as well as markers for inflammation (Calmodulin kinase beta). Down-regulated transcripts included FKBP52 which was also down-regulated in diabetic NOD kidney. Comparison of transcripts altered by proteinuria to those altered by diabetes identified mannosidase 2 alpha 1 as being more specifically induced by proteinuria. CONCLUSION: By simulating a component of diabetes, and looking at the global response on mice resistant to the disease, by virtue of a small genetic difference, we were able to identify key factors in disease progression. This suggests the power of this approach in unraveling multifactorial disease processes
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