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

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

Terrestrial Zone Debris Disk Candidates in h and chi Persei

We analyze 8 sources with strong mid-infrared excesses in the 13 Myr-old double cluster h and chi Persei. New optical spectra and broadband SEDs (0.36-8 mu_m) are consistent with cluster membership. We show that material with T ~ 300-400 K and Ld/Lstar ~ 10^-4-10^-3 produces the excesses in these sources. Optically-thick blackbody disk models - including those with large inner holes - do not match the observed SEDs. The SEDs of optically-thin debris disks produced from terrestrial planet formation calculations match the observations well. Thus, some h and chi Persei stars may have debris from terrestrial zone planet formation.Comment: 5 pages, 3 figures, Matched to published version, Astrophysical Journal Letters, in press: 2007, ApJL, 663, 10

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

Socioeconomic inequalities in childhood exposure to secondhand smoke before and after smoke-free legislation in three UK countries

Background: Secondhand smoke (SHS) exposure is higher among lower socioeconomic status (SES) children. Legislation restricting smoking in public places has been associated with reduced childhood SHS exposure and increased smoke-free homes. This paper examines socioeconomic patterning in these changes.&lt;p&gt;&lt;/p&gt; Methods: Repeated cross-sectional survey of 10 867 schoolchildren in 304 primary schools in Scotland, Wales and Northern Ireland. Children provided saliva for cotinine assay, completing questionnaires before and 12 months after legislation.&lt;p&gt;&lt;/p&gt; Results: SHS exposure was highest, and private smoking restrictions least frequently reported, among lower SES children. Proportions of saliva samples containing &lt;0.1 ng/ml (i.e. undetectable) cotinine increased from 31.0 to 41.0%. Although across the whole SES spectrum, there was no evidence of displacement of smoking into the home or increased SHS exposure, socioeconomic inequality in the likelihood of samples containing detectable levels of cotinine increased. Among children from the poorest families, 96.9% of post-legislation samples contained detectable cotinine, compared with 38.2% among the most affluent. Socioeconomic gradients at higher exposure levels remained unchanged. Among children from the poorest families, one in three samples contained &gt; 3 ng/ml cotinine. Smoking restrictions in homes and cars increased, although socioeconomic patterning remained.&lt;p&gt;&lt;/p&gt; Conclusions Urgent action is needed to reduce inequalities in SHS exposure. Such action should include emphasis on reducing smoking in cars and homes

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

Suffix conjugates for a class of morphic subshifts

Let A be a finite alphabet and f: A^* --> A^* be a morphism with an iterative fixed point f^\omega(\alpha), where \alpha{} is in A. Consider the subshift (X, T), where X is the shift orbit closure of f^\omega(\alpha) and T: X --> X is the shift map. Let S be a finite alphabet that is in bijective correspondence via a mapping c with the set of nonempty suffixes of the images f(a) for a in A. Let calS be a subset S^N be the set of infinite words s = (s_n)_{n\geq 0} such that \pi(s):= c(s_0)f(c(s_1)) f^2(c(s_2))... is in X. We show that if f is primitive and f(A) is a suffix code, then there exists a mapping H: calS --> calS such that (calS, H) is a topological dynamical system and \pi: (calS, H) --> (X, T) is a conjugacy; we call (calS, H) the suffix conjugate of (X, T). In the special case when f is the Fibonacci or the Thue-Morse morphism, we show that the subshift (calS, T) is sofic, that is, the language of calS is regular