Mechanisms of peroxisome proliferator-induced DNA hypomethylation in rat liver

Genomic hypomethylation is a consistent finding in both human and animal tumors and mounting experimental evidence suggests a key role for epigenetic events in tumorigenesis. Furthermore, it has been suggested that early changes in DNA methylation and histone modifications may serve as sensitive predictive markers in animal testing for carcinogenic potency of environmental agents. Alterations in metabolism of methyl donors, disturbances in activity and/or expression of DNA methyltransferases, and presence of DNA single-strand breaks could contribute to the loss of cytosine methylation during carcinogenesis; however, the precise mechanisms of genomic hypomethylation induced by chemical carcinogens remain largely unknown. This study examined the mechanism of DNA hypomethylation during hepatocarcinogenesis induced by peroxisome proliferators WY-14,643 (4-chloro-6-(2,3-xylidino)-pyrimidynylthioacetic acid) and DEHP (di-(2-ethylhexyl)phthalate), agents acting through non-genotoxic mode of action. In the liver of male Fisher 344 rats exposed to WY-14,643 (0.1% (w/w), 5 months), the level of genomic hypomethylation increased by approximately 2-fold, as compared to age-matched controls, while in the DEHP group (1.2% (w/w), 5 months) DNA methylation did not change. Global DNA hypomethylation in livers from WY-14,643 group was accompanied by the accumulation of DNA single-strand breaks, increased cell proliferation, and diminished expression of DNA methyltransferase 1, while the metabolism of methyl donors was not affected. In contrast, none of these parameters changed significantly in rats fed DEHP. Since WY-14,643 is much more potent carcinogen than DEHP, we conclude that the extent of loss of DNA methylation may be related to the carcinogenic potential of the chemical agent, and that accumulation of DNA single-strand breaks coupled to the increase in cell proliferation and altered DNA methyltransferase expression may explain genomic hypomethylation during peroxisome proliferator-induced carcinogenesis.     

Mutants for photosystem I subunit D of Arabidopsis thaliana: effects on photosynthesis, photosystem I stability and expression of nuclear genes for chloroplast functions

In Arabidopsis thaliana, the D-subunit of photosystem I (PSI-D) is encoded by two functional genes, PsaD1 and PsaD2, which are highly homologous. Knock-out alleles for each of the loci have been identified by a combination of forward and reverse genetics. The double mutant psad1-1 psad2-1 is seedling-lethal, high-chlorophyll-fluorescent and deficient for all tested PSI subunits, indicating that PSI-D is essential for photosynthesis. In addition, psad1-1 psad2-1 plants show a defect in the accumulation of thylakoid multiprotein complexes other than PSI. Of the single-gene mutations, psad2 plants behave like wild-type (WT) plants, whereas psad1-1 markedly affects the accumulation of PsaD mRNA and protein, and photosynthetic electron flow. Additional effects of the psad1-1 mutation include a decrease in growth rate under greenhouse conditions and downregulation of the mRNA expression of most genes involved in the light phase of photosynthesis. In the same mutant, a marked decrease in the levels of PSI and PSII polypeptides is evident, as well as a light-green leaf coloration and increased photosensitivity. Increased dosage of PsaD2 in the psad1-1 background restores the WT phenotype, indicating that PSI-D1 and PSI-D2 have redundant functions.     

Molecular basis of inherited predispositions for tumors

On the basis of literature data and own experience the authors review the current knowledge about the molecular basis of inherited predispositions for tumors. They hypothesize that in the near perspective 5-10 years studies using existing registry data/material and the latest novel technology will allow the identification of the molecular background for the majority of hereditary cancers which will have enormous practical consequences especially for the prevention of malignancies.     

Cardiovascular events in early RA are a result of inflammatory burden and traditional risk factors: a five year prospective study

Introduction  

Co-morbidity and mortality due to cardiovascular disease (CVD) are increased in patients with rheumatoid arthritis (RA). Most published studies in this field are retrospective or cross sectional. We investigated the presence of traditional and disease related risk factors for CVD at the onset of RA and during the first five years following diagnosis. We also evaluated their potential for predicting a new cardiovascular event (CVE) during the five-year follow-up period and the modulatory effect of pharmacological treatment.     

Lionfish in the eastern Pacific: a cellular automaton approach to assessing invasion risk

The lionfish invasion in the Atlantic and Caribbean has proceeded with vigor since their introduction in the 1980s or early 1990s. Lionfish affect recruitment of juvenile fish to reefs due to predation and are found in densities far surpassing that of their native Indo-Pacific. There is concern that the lionfish may become introduced and proliferate (through aquarium releases, transport on floating debris, or passage through the Panama Canal in ship ballast water) in the eastern tropical and north Pacific. This study presents the first known prediction of the potential for establishment of lionfish in the eastern Pacific Ocean. Through computational modeling, we compare and contrast the dynamics of random hypothetical introductions of lionfish into the eastern Pacific and Atlantic Oceans in order to highlight the different potentials for invasion in both basins. Connectivity between discrete regions (precincts) in both the Atlantic and eastern Pacific are examined and settlement densities are calculated to indicate possible locations of establishment of breeding lionfish populations. Our results suggest that lionfish, which are successful invaders in the Atlantic, may not be as successful in the eastern Pacific due to weak mesoscale connectivity which reduces the rapid spread of lionfish larvae.     

A genome-wide association analysis for porcine serum lipid traits reveals the existence of age-specific genetic determinants

Background

The genetic determinism of blood lipid concentrations, the main risk factor for atherosclerosis, is practically unknown in species other than human and mouse. Even in model organisms, little is known about how the genetic determinants of lipid traits are modulated by age-specific factors. To gain new insights into this issue, we have carried out a genome-wide association study (GWAS) for cholesterol (CHOL), triglyceride (TRIG) and low (LDL) and high (HDL) density lipoprotein concentrations measured in Duroc pigs at two time points (45 and 190 days).

Results

Analysis of data with mixed-model methods (EMMAX, GEMMA, GenABEL) and PLINK showed a low positional concordance between trait-associated regions (TARs) for serum lipids at 45 and 190 days. Besides, the proportion of phenotypic variance explained by SNPs at these two time points was also substantially different. The four analyses consistently detected two regions on SSC3 (124 Mb, CHOL and LDL at 190 days) and SSC6 (135 Mb, CHOL and TRIG at 190 days) with highly significant effects on the porcine blood lipid profile. Moreover, we have found that SNP variation within SSC3, SSC6, SSC10, SSC13 and SSC16 TARs is associated with the expression of several genes mapping to other chromosomes and related to lipid metabolism.

Conclusions

Our data demonstrate that the effects of genomic determinants influencing lipid concentrations in pigs, as well as the amount of phenotypic variance they explain, are influenced by age-related factors.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-758) contains supplementary material, which is available to authorized users.     

Behavioural and Physiological Effects of Finely Balanced Decision-Making in Chickens

In humans, more difficult decisions result in behavioural and physiological changes suggestive of increased arousal, but little is known about the effect of decision difficulty in other species. A difficult decision can have a number of characteristics; we aimed to monitor how finely balanced decisions, compared to unbalanced ones, affected the behaviour and physiology of chickens. An unbalanced decision was one in which the two options were of unequal net value (1 (Q1) vs. 6 (Q6) pieces of sweetcorn with no cost associated with either option); a finely balanced decision was one in which the options were of equal net value (i.e. hens were "indifferent" to both options). To identify hens'' indifference, a titration procedure was used in which a cost (electromagnetic weight on an access door) was applied to the Q6 option, to find the individual point at which hens chose this option approximately equally to Q1 via a non-weighted door. We then compared behavioural and physiological indicators of arousal (head movements, latency to choose, heart-rate variability and surface body temperature) when chickens made decisions that were unbalanced or finely balanced. Significant physiological (heart-rate variability) and behavioural (latency to pen) differences were found between the finely balanced and balanced conditions, but these were likely to be artefacts of the greater time and effort required to push through the weighted doors. No other behavioural and physiological measures were significantly different between the decision categories. We suggest that more information is needed on when best to monitor likely changes in arousal during decision-making and that future studies should consider decisions defined as difficult in other ways.     

Are chlorella viruses a rich source of ion channel genes?

Plaque-forming dsDNA (>330 kb) viruses that infect certain unicellular, eukaryotic chlorella-like green algae contain approximately 375 protein-encoding genes. These proteins include a 94 amino acid K+ channel protein, called Kcv, as well as two putative ligand-gated ion channels. The viruses also encode other proteins that could be involved in the assembly and/or function of ion channels, including protein kinases and a phosphatase, polyamine biosynthetic enzymes and histamine decarboxylase.