AIMER: A SNP-independent software for identifying imprinting-like allelic methylated regions from DNA methylome.

Genomic imprinting is essential for mammalian growth and embryogenesis. High-throughput bisulfite sequencing accompanied with parental haplotype-specific information allows analysis of imprinted genes and imprinting control regions (ICRs) on a large scale. Currently, although several allelic methylated regions (AMRs) detection software were developed, methods for detecting imprinted AMRs is still limited. Here, we developed a SNP-independent statistical approach, AIMER, to detect imprinting-like AMRs. By using the mouse frontal cortex methylome as input, we demonstrated that AIMER performs very well in detecting known germline ICRs compared with other methods. Furthermore, we found the putative parental AMRs AIMER detected could be distinguished from sequence-dependent AMRs. Finally, we found a novel germline imprinting-like AMR using WGBS data from 17 distinct mouse tissue samples. The results indicate that AIMER is a good choice for detecting imprinting-like (parent-of-origin-dependent) AMRs. We hope this method will be helpful for future genomic imprinting studies. The Python source code for our project is now publicly available on both GitHub (https://github.com/ZhaoLab-TMU/AIMER) and Gitee (https://gitee.com/zhaolab_tmu/AIMER).

Rif1 and Hmgn3 regulate the conversion of murine trophoblast stem cells.

The appearance of trophectoderm (TE) is a hallmark event in preimplantation development during murine embryogenesis. However, little is known about the mechanisms underlying TE specification. We find that the depletion of Rif1 breaks down the barrier to the transition from embryonic stem cells (ESCs) to trophoblast stem cells (TSCs). Rif1-null-induced TSCs show typical TE properties and the potential to differentiate into terminal trophoblast lineages. Global transcriptome analysis reveal that Rif1 deletion activates 2-cell embryo (2C)-related genes and induces a totipotent-like state. Chimeric assays further confirm that Rif1-null ESCs contribute to the functional placenta in addition to the fetus on embryonic day 12.5. Furthermore, we show overexpression of Hmgn3, one of the key upregulated gene in Rif1-null ESCs, facilitates the induction of TSCs. Therefore, we report two key genes regulating the conversion of TSCs and provide insights for investigating TE specification.

Toxicity of ionic liquids on the growth, reproductive ability, and ATPase activity of earthworm.

To evaluate the toxicity of the ionic liquid 1-methyl-3-octylimidazolium bromide ([C(8)mim]Br) to Eisenia foetida, effects of [C(8)mim]Br on the growth, reproductive ability, and adenosine triphosphatase (ATPase) activity of earthworms were determined under laboratory conditions using artificial soil as substrate. The results showed that [C(8)mim]Br in high concentrations significantly inhibited the growth of the earthworms. These effects were enhanced with prolonged exposure to and increasing concentration of [C(8)mim]Br. E. foetida's reproductive ability was significantly inhibited after 42d of subchronic exposure to [C(8)mim]Br at a concentration >or=5 mg kg(-1) artificial soil (dry weight). During acute exposure, a high concentration of [C(8)mim]Br >or=40 mg kg(-1) artificial soil (dry weight) inhibited the activities of Na(+)-K(+)-ATPase and Mg(++)-ATPase after 3 and 7d of exposure. After 42d of subchronic exposure, the activity of both ATPases was inhibited in groups exposed to >or=5mg[C(8)mim]Brkg(-1) artificial soil (dry weight). These results indicate that treatment with the ionic liquid [C(8)mim]Br affects the growth, reproductive ability, and ATPase activity of earthworms E. foetida.

Effects of 1-methyl-3-octylimidazolium bromide on the anti-oxidant system of earthworm.

The activity changes of anti-oxidant enzymes and the levels of glutathione and malondialdehyde were determined when Eisenia foetida were exposed to different concentrations of 1-methyl-3-octylimidazolium bromide for 14d. The results showed catalase activity in all treatment groups was elevated significantly after 1d of exposure, and superoxide dismutase activity in higher-dosage groups (120 and 160mgkg(-1)) was increased at 3d post-exposure. On the 7thd, the activity of glutathione-S-transferase in the 20 and 40mgkg(-1) dosage groups was inhibited while increased in the 80 and 160mgkg(-1) groups compared with the control groups. During exposure, the level of intracellular glutathione in all treatment groups was much higher than that of the control groups. Changes in malondialdehyde indicate that [C(8)mim]Br may lead to cellular lipid peroxidation in earthworm. Our results suggest that exposure to [C(8)mim]Br induce the formation of reactive oxygen species in earthworms.

The toxic effects of ionic liquids on the activities of acetylcholinesterase and cellulase in earthworms.

The earthworm Eisenia foetida was exposed to different concentrations of imidazolium ionic liquids with varying chain lengths according to the method of OECD [OECD, 1984. (The Current Organization of Economic and Cooperative Development Acute Earthworm Toxicity Test) Guidelines for the Testing of Chemicals, No. 207. Earthworm Acute Toxicity Tests]. The acute and subchronic toxic effects of [C(8)mim]Br on the activities of acetylcholinesterase (AChE) and cellulase in earthworms were determined under an artificial soil condition. Using filter paper contact tests, the 48 h-LC(50) values of [C(4)mim]Br, [C(6)mim]Br, [C(8)mim]Br, [C(10)mim]Br and [C(12)mim]Br on the earthworm were 73.33, 28.25, 2.69, 0.37 and 0.02 microg cm(-2), respectively. The 7 d-LC(50) of [C(8)mim]Br was 206.8 mg kg(-1) artificial soil (dry weight) and the 14 d-LC(50) was 159.4 mg kg(-1) artificial soil (dry weight), under the condition of artificial soil. After 1 d and 3 d of acute exposure, the activity of AChE was markedly inhibited when compared to the control, while it was increased at 7d. The cellulase activity was elevated significantly in the treatment groups of 20-160 mg kg(-1) after 3 and 7d of acute exposure. The activity of cellulase was also promoted under the subchronic exposure condition in the 10 and 20 mg kg(-1) groups. The experimental results suggest that [C(8)mim]Br may interfere with the nervous function of the earthworms and increase their cellulase activity. These results indicate that [C(8)mim]Br-exposure can affect the metabolized enzyme activity of earthworms at low concentrations and can even cause worm death at high doses, both of which have potential impacts on the soil environment.

Effects of the 1-alkyl-3-methylimidazolium bromide ionic liquids on the antioxidant defense system of Daphnia magna.

This study examined the antioxidant responses of Daphnia magna following exposure to different concentrations of the ionic liquid (IL) 1-octyl-3-methylimidazolium bromide and the 50% LC(50) concentrations of methylimidazolium bromide ILs with different alkyl-chain lengths. Activities of antioxidant defense enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase) and levels of the antioxidant glutathione and the lipid peroxidation by-product malondialdehyde were measured using traditional methods or commercial kits. The concentration and the alkyl-chain length of ILs were found to strongly influence the antioxidant system of D. magna following IL exposure, and exposure to higher IL concentrations and to ILs with longer alkyl chains generally increased the enzyme activities and biomarker levels examined. Therefore, the present study suggests that oxidative stress is involved in the mechanism of IL-induced toxicity in D. magna.

The developmental toxicity of 1-methyl-3-octylimidazolium bromide on Daphnia magna.

The developmental toxicity of 1-methyl-3-octylimidazolium bromide ([C(8)mim]Br) on Daphnia magna was investigated. The 24 and 48 h LC(50) values for [C(8)mim]Br in D. magna were 1.99 and 0.95 mg/L, respectively. A series of multigenerational toxicity tests were then used to explore [C(8)mim]Br effects in D. magna. [C(8)mim]Br significantly inhibited the body lengths of the F0 and F1 1st generations. After 21 days of exposure, [C(8)mim]Br lowered the reproductive ability of the F0 and F1 1st generations. In F1 3rd generation, 21 days of [C(8)mim]Br exposure prolonged the time to bear the first egg and the time to the first brood compared with the control, but the number of first-brood offspring and the number of broods produced by these animals were reduced. After the recovery period all the reproductive parameters returned to normal in F1 1st generation except for the number of broods. The dead neonates increased with prolonged exposure and increasing concentrations, and the dead neonates of the F1 3rd generation went far beyond that of the F1 1st and F0 generations. The intrinsic rate of natural increase (r) values of the three D. magna generations significantly decreased after exposure to higher concentrations of [C(8)mim]Br compared with control groups. Collectively, these results suggest that [C(8)mim]Br exerts a toxic effect on the development of D. magna. This study also highlights the importance of systematically evaluating the potential effects of aquatic ecosystems of ionic liquids that may be released into bodies of water.

[The effect of swimming training on the expression of cardiovascular CGRPmRNA in rats].

AIM: Rats cardiovascular expression of CGRPmRNA surveyed after an eight-week swimming training, and molecular mechanism of exercise-induced adaptation were studied. METHODS: 24 purebred male SD rats were divided randomly into three groups (n = 8): control (CR), exhaust (ER), train (TR). After swimming training left ventricular muscle and main artery arch were extracted, we inspected the expression of CGRPmRNA by RT-PCR. RESULTS: (1) Comparing with the control group, once exhausting exercise had no significant effect on cardiovascular expression of CGRPmRNA. (2) Comparing with the control group, long-term aerobic swimming training upregulated significantly cardiac expression of CGRPmRNA. CONCLUSION: Long-term aerobic training induced benign cardiac adaptation in molecular level. Long-term aerobic swimming training had no significant effect on vascular expression of CGRPmRNA.