Few alterations in clinical pathology and histopathology observed in a CYP2C18&19 humanized mice model

<p>Abstract</p> <p>Background</p> <p>This study was performed to characterize a gene-addition transgenic mouse containing a BAC (bacterial artificial chromosome) clone spanning the human CYP2C18&19 genes (tg-CYP2C18&19).</p> <p>Methods</p> <p>Hemizygous tg-CYP2C18&19, 11 week old mice were compared with wild-type littermates to obtain information regarding clinical status, clinical pathology and anatomical pathology. After one week of clinical observations, blood samples were collected, organs weighed, and tissues collected for histopathology.</p> <p>Results</p> <p>In males, the tissue weights were lower in tg-CYP2C18&19 than in wild-type mice for brain (<it>p </it>≤ 0.05), adrenal glands (<it>p </it>≤ 0.05) and brown fat deposits (<it>p </it>≤ 0.001) while the heart weight was higher (<it>p </it>≤ 0.001). In female tg-CYP2C18&19, the tissue weights were lower for brain (<it>p </it>≤ 0.001) and spleen (<it>p </it>≤ 0.001) compared to wild-type females. Male tg-CYP2C18&19 had increased blood glucose levels (<it>p </it>≤ 0.01) while females had decreased blood triglyceride levels (<it>p </it>≤ 0.01).</p> <p>Conclusion</p> <p>Despite the observed alterations, tg-CYP2C18&19 did not show any macroscopic or microscopic pathology at the examined age. Hence, these hemizygous transgenic mice were considered to be viable and healthy animals.</p

Furan in heat-treated foods: Formation, exposure, toxicity, and aspects of risk assessment

Furan is formed in a variety of heat-treated foods through thermal degradation of natural food constituents. Relatively high levels of furan contamination are found in ground roasted coffee, instant coffee, and processed baby foods. European exposure estimates suggest that mean dietary exposure to furan may be as high as 1.23 and 1.01 μg/kg bw/day for adults and 3- to 12-month-old infants, respectively. Furan is a potent hepatotoxin and hepatocarcinogen in rodents, causing hepatocellular adenomas and carcinomas in rats and mice, and high incidences of cholangiocarcinomas in rats at doses ≥2 mg/kg bw. There is therefore a relatively low margin of exposure between estimated human exposure and doses that cause a high tumor incidence in rodents. Since a genotoxic mode of action cannot be excluded for furan-induced tumor formation, the present exposures may indicate a risk to human health and need for mitigation. This review summarizes the current knowledge on mechanisms of furan formation in food, human dietary exposure to furan, and furan toxicity, and highlights the need to establish the risk resulting from the genotoxic and carcinogenic properties of furan at doses lower than 2 mg/kg bw. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Leads in Arctic pack ice enable early phytoplankton blooms below snow-covered sea ice

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 7 (2017): 40850, doi:10.1038/srep40850.The Arctic icescape is rapidly transforming from a thicker multiyear ice cover to a thinner and largely seasonal first-year ice cover with significant consequences for Arctic primary production. One critical challenge is to understand how productivity will change within the next decades. Recent studies have reported extensive phytoplankton blooms beneath ponded sea ice during summer, indicating that satellite-based Arctic annual primary production estimates may be significantly underestimated. Here we present a unique time-series of a phytoplankton spring bloom observed beneath snow-covered Arctic pack ice. The bloom, dominated by the haptophyte algae Phaeocystis pouchetii, caused near depletion of the surface nitrate inventory and a decline in dissolved inorganic carbon by 16 ± 6 g C m−2. Ocean circulation characteristics in the area indicated that the bloom developed in situ despite the snow-covered sea ice. Leads in the dynamic ice cover provided added sunlight necessary to initiate and sustain the bloom. Phytoplankton blooms beneath snow-covered ice might become more common and widespread in the future Arctic Ocean with frequent lead formation due to thinner and more dynamic sea ice despite projected increases in high-Arctic snowfall. This could alter productivity, marine food webs and carbon sequestration in the Arctic Ocean.This study was supported by the Centre for Ice, Climate and Ecosystems (ICE) at the Norwegian Polar Institute, the Ministry of Climate and Environment, Norway, the Research Council of Norway (projects Boom or Bust no. 244646, STASIS no. 221961, CORESAT no. 222681, CIRFA no. 237906 and AMOS CeO no. 223254), and the Ministry of Foreign Affairs, Norway (project ID Arctic), the ICE-ARC program of the European Union 7th Framework Program (grant number 603887), the Polish-Norwegian Research Program operated by the National Centre for Research and Development under the Norwegian Financial Mechanism 2009–2014 in the frame of Project Contract Pol-Nor/197511/40/2013, CDOM-HEAT, and the Ocean Acidification Flagship program within the FRAM- High North Research Centre for Climate and the Environment, Norway

Leads in Arctic pack ice enable early phytoplankton blooms below snow-covered sea ic

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Risks for public health related to the presence of furan and methylfurans in food

EFSA wishes to thank the hearing experts: Diana Doell and Ruud Woutersen and EFSA staff member: José Cortinas Abrahantes for the support provided to this scientific output. The CONTAM Panel acknowledges all European competent institutions and other stakeholders that provided occurrence data on furan and methylfurans in food, and supported the data collection for the Comprehensive European Food Consumption Database. Adopted: 20 September 2017Peer reviewedPublisher PD

Regulation of Human CYP2C18 and CYP2C19 in Transgenic Mice: Influence of Castration, Testosterone, and Growth HormoneS⃞

The hormonal regulation of human CYP2C18 and CYP2C19, which are expressed in a male-specific manner in liver and kidney in a mouse transgenic model, was examined. The influence of prepubertal castration in male mice and testosterone treatment of female mice was investigated, as was the effect of continuous administration of growth hormone (GH) to transgenic males. Prepubertal castration of transgenic male mice suppressed the expression of CYP2C18 and CYP2C19 in liver and kidney to female levels, whereas expression was increased for the endogenous female-specific mouse hepatic genes Cyp2c37, Cyp2c38, Cyp2c39, and Cyp2c40. Testosterone treatment of female mice increased CYP2C18 and CYP2C19 expression in kidney, and to a lesser extent in liver, but was without effect in brain or small intestine, where gene expression was not gender-dependent. Continuous GH treatment of transgenic males for 7 days suppressed hepatic expression of CYP2C19 (>90% decrease) and CYP2C18 (∼50% decrease) but had minimal effect on the expression of these genes in kidney, brain, or small intestine. Under these conditions, continuous GH induced all four female-specific mouse liver Cyp2c genes in males to normal female levels. These studies indicate that the human CYP2C18 and CYP2C19 genes contain regulatory elements that respond to the endogenous mouse hormonal profiles, with androgen being the primary regulator of male-specific expression in kidney, whereas the androgen-dependent pituitary GH secretory pattern is the primary regulator of male-specific expression in liver in a manner that is similar to the regulation of the endogenous gender-specific hepatic genes

Mid-winter freeze experiment in the Arctic Ocean: Norwegian Young sea ICE cruise (N-ICE2015)

In mid-January 2015, RV Lance will freeze into the ice north of Svalbard, Arctic Ocean at around 83.25°N 30°E, and passively drift with the ice as part of the Norwegian Young sea ICE cruise (N-ICE2015). Judging from historic sea ice drift trajectories, it is likely that RV Lance will drift in a SW direction and the ship will probably be freed from the ice in mid spring after about two to three months of drift. Thereafter, RV Lance will return to her starting position and start a new drift. Under all circumstances, the ice drift project will end in late June 2015. Throughout the cruise the focus will be on the interaction of the atmosphere-ice-ocean system and the response of the marine ecosystem to the thinner ice regime. The overall goal of the project team is to improve our understanding of the role of the younger ice pack in the Arctic on greenhouse gas fluxes and to ultimately assess whether the Arctic Ocean is a sink or source of greenhouse gases. We plan to conduct long-term synchronous observations of Arctic snow and sea ice biogeochemistry and physics and fluxes of carbon dioxide, methane, nitrous oxide and bromoform. This work targets at filling a crucial gap in our understanding of the role of Arctic sea ice in the climate system. This is done by conducting state of the art observations on Arctic sea ice in the polar night, when observations are basically non-existent. Further we are focusing on the new thinner ice regime, which is even less documented. We aim to understand how the thinner sea ice in the Arctic basin contributes (i) to important greenhouse gas exchange between the atmosphere and ocean and (ii) to aerosol formation, that contribute to the radiative balance of the planet. This work will increase direct collaboration between Japanese and European scientists in the Arctic, and combines complimentary expertise and experience from several international partners to carry out the interdisciplinary work proposed