Time and dose-dependent effects of phenobarbital on the rat liver miRNAome.

In a previous study we had shown that treatment of male Fischer rats with exogenous chemicals for three months resulted in prominent, mode-of-action dependent effects on liver microRNA (miRNA) (Koufaris et al., 2012). Here we investigated how the effects of chemicals on liver miRNA in male Fischer rats relate to the length and dose of exposure to phenobarbital (PB), a drug with multiple established hepatic effects. Importantly, although acute PB treatment (1-7 days) had significant effects on liver mRNA and the expected effects on the liver phenotype (transient hyperplasia, hepatomegaly, cytochrome P450 induction), limited effects on liver miRNA were observed. However, at 14 days of PB treatment clear dose-dependent effects on miRNA were observed. The main effect of PB treatment from days 1 to 90 on liver miRNA was found to be the persistent, progressive, and highly correlated induction of the miR-200a/200b/429 and miR-96/182 clusters, occurring after the termination of the xenobiotic-induced transient hyperplasia. Moreover, in agreement with their reported functions in the literature we found associations between perturbations of miR-29b and miR-200a/200b by PB with global DNA methylation and zeb1/zeb2 proteins respectively. Our data suggest that miRNA are unlikely to play an important role in the acute responses of the adult rodent liver to PB treatment. However, the miRNA responses to longer PB exposures suggest a potential role for maintaining liver homeostasis in response to sub-chronic and chronic xenobiotic-induced perturbations. Similar studies for more chemicals are needed to clarify whether the temporal and dose pattern of miRNA-toxicant interaction identified here for PB are widely applicable to other xenobiotics. © 2013 Elsevier Ireland Ltd

Bringing genetics into primary care: findings from a national evaluation of pilots in England

Objectives: Developments in genetic knowledge and clinical applications are seen as rendering traditional modes of organizing genetics provision increasingly inappropriate. In common with a number of developed world countries the UK has sought to increase the role of primary care in delivering such services. However, efforts to reconfigure service delivery face multiple challenges associated with divergent policy objectives, organizational boundaries and professional cultures. This paper presents findings from an evaluation of an English initiative to integrate genetics into 'mainstream' clinical provision in the National Health Service. Methods: Qualitative research in 11 case-study sites focusing on attempts by pilots funded by the initiative to embed knowledge and provision within primary care illustrating barriers faced and the ways in which these were surmounted. Results: Lack of intrinsic interest in clinical genetics among primary care staff was compounded by national targets that focused their attention elsewhere and by service structures that rendered genetics a peripheral concern demanding minimal engagement. Established divisions between the commissioning of mainstream and specialist services, along with the pressures of shorter-term targets, impeded ongoing funding. Conclusions: More wide-ranging policy and organizational support is required if the aim of entrenching genetics knowledge and practice across the Health Service is to be realized

Laser beam pointing tests

Laser beam pointing tests for lunar communication and rangefinding and tracking using Surveyor 7 vidicon camer

The far field diffraction pattern for corner reflectors with complex reflection coefficients

The far field diffraction pattern of a geometrically perfect corner reflector is examined analytically for normally incident monochromatic light. The states of polarization and the complex amplitudes of the emerging light are expressed through transformation matrices in terms of those of the original incident light for each sextant of the face in a single coordinate system. The analytic expression of the total diffraction pattern is obtained for a circular face. This expression consists of three component functions in addition to the basic Airy function. The coefficient of each function is expressed in terms of complex coefficients of reflectance of the reflecting surface. Some numerical results for different reflecting surfaces, including total internal reflection, are presented. The iso-intensity contours of the diffraction pattern evaluated from the analytical expressions for an uncoated solid corner reflector are also presented along with the photographs of the pattern

Hepatic microRNA profiles offer predictive and mechanistic insights after exposure to genotoxic and epigenetic hepatocarcinogens.

In recent years, accumulating evidence supports the importance of microRNAs in liver physiology and disease; however, few studies have examined the involvement of these noncoding genes in chemical hepatocarcinogenesis. Here, we examined the liver microRNA profile of male Fischer rats exposed through their diet to genotoxic (2-acetylaminofluorene) and epigenetic (phenobarbital, diethylhexylphthalate, methapyrilene HCL, monuron, and chlorendic acid) chemical hepatocarcinogens, as well as to non-hepatocarcinogenic treatments (benzophenone, and diethylthiourea) for 3 months. The effects of these treatments on liver pathology, plasma clinical parameters, and liver mRNAs were also determined. All hepatocarcinogens affected the expression of liver mRNAs, while the hepatic microRNA profiles were associated with the mode of action of the chemical treatments and corresponded to chemical carcinogenicity. The three nuclear receptor-activating chemicals (phenobarbital, benzophenone, and diethylhexylphthalate) were characterized by the highly correlated induction of the miR-200a/200b/429, which is involved in protecting the epithelial status of cells and of the miR-96/182 clusters. The four non-nuclear receptor-activating hepatocarcinogens were characterized by the early, persistent induction of miR-34, which was associated with DNA damage and oxidative stress in vivo and in vitro. Repression of this microRNA in a hepatoma cell line led to increased cell growth; thus, miR-34a could act to block abnormal cell proliferation in cells exposed to DNA damage or oxidative stress. This study supports the proposal that hepatic microRNA profiles could assist in the earlier evaluation and identification of hepatocarcinogens, especially those acting by epigenetic mechanisms. © The Author 2012. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved

The effect of maternal iron deficiency on zinc and copper levels and on genes of zinc and copper metabolism during pregnancy in the rat

Fe deficiency is relatively common in pregnancy and has both short- and long-term consequences. However, little is known about the effect on the metabolism of other micronutrients. A total of fifty-four female rats were fed control (50 mg Fe/kg) or Fe-deficient diets (7·5 mg/kg) before and during pregnancy. Maternal liver, placenta and fetal liver were collected at day 21 of pregnancy for Cu and Zn analysis and to measure expression of the major genes of Cu and Zn metabolism. Cu levels increased in the maternal liver (P=0·002) and placenta (P=0·018) of Fe-deficient rats. Zn increased (P&lt;0·0001) and Cu decreased (P=0·006) in the fetal liver. Hepatic expression of the Cu chaperones antioxidant 1 Cu chaperone (P=0·042) and cytochrome c oxidase Cu chaperone (COX17, P=0·020) decreased in the Fe-deficient dams, while the expression of the genes of Zn metabolism was unaltered. In the placenta, Fe deficiency reduced the expression of the chaperone for superoxide dismutase 1, Cu chaperone for superoxide dismutase (P=0·030), ceruloplasmin (P=0·042) and Zn transport genes, ZRT/IRT-like protein 4 (ZIP4, P=0·047) and Zn transporter 1 (ZnT1, P=0·012). In fetal liver, Fe deficiency increased COX17 (P=0·020), ZRT/IRT-like protein 14 (P=0·036) and ZnT1 (P=0·0003) and decreased ZIP4 (P=0·004). The results demonstrate that Fe deficiency during pregnancy has opposite effects on Cu and Zn levels in the fetal liver. This may, in turn, alter metabolism of these nutrients, with consequences for development in the fetus and the neonate.</p

Ubiquitous energy storage

This paper presents a vision of a future power system with "ubiquitous energy storage", where storage would be utilized at all levels of the electricity system. The growing requirement for storage is reviewed, driven by the expansion of distributed generation. The capabilities and existing applications of various storage technologies are presented, providing a useful review of the state of the art. Energy storage will have to be integrated with the power system and there are various ways in which this may be achieved. Some of these options are discussed, as are commercial and regulatory issues. In two case studies, the costs and benefits of some storage options are assessed. It is concluded that electrical storage is not cost effective but that thermal storage offers attractive opportunities

The Evolution of Circumstellar Disks Surrounding Intermediate Mass Stars: IC 1805

We report the results of a study of the intermediate and high mass stars in the young, rich star-forming complex IC 1805, based on a combination of optical, near-infrared, and mid-infrared photometry, and classification spectra. These data provide the basis for characterizing the masses and ages for stars more massive than ~2 Msun and enable a study of the frequency and character of circumstellar disks associated with intermediate- and high-mass stars. Optically thick accretion disks among stars with masses 2 < M/Msun <4 are rare (~2% of members) and absent among more massive stars. A larger fraction (~10%) of stars with masses 2 < M/Msun < 4 appear to be surrounded by disks that have evolved from the initial optically thick accretion phase. We identify four classes of such disks. These classes are based on spectral energy distributions (SEDs) of excess emsission above photospheric levels: disks that are (1) optically thin based on the magnitude of the observed excess emission from 2 to 24 um; (2) optically thin in their inner regions (r< 20 AU) and optically thick in their outer regions; (3) exhibit empty inner regions (r < 10 AU) and optically thin emission in their outer regions; and (4) exhibit empty inner regions and optically thick outer regions. We discuss, and assess the merits and liabilities of, proposed explanations for disks exhibiting these SED types and suggest additional observations that would test these proposals.Comment: Accepted to Ap