Dissection of human MiRNA regulatory influence to subpathway

The global insight into the relationships between miRNAs and their regulatory influences remains poorly understood. And most of complex diseases may be attributed to certain local areas of pathway (subpathway) instead of the entire pathway. Here, we reviewed the studies on miRNA regulations to pathways and constructed a bipartite miRNAs and subpathways network for systematic analyzing the miRNA regulatory influences to subpathways. We found that a small fraction of miRNAs were global regulators, environmental information processing pathways were preferentially regulated by miRNAs, and miRNAs had synergistic effect on regulating group of subpathways with similar function. Integrating the disease states of miRNAs, we also found that disease miRNAs regulated more subpathways than nondisease miRNAs, and for all miRNAs, the number of regulated subpathways was not in proportion to the number of the related diseases. Therefore, the study not only provided a global view on the relationships among disease, miRNA and subpathway, but also uncovered the function aspects of miRNA regulations and potential pathogenesis of complex diseases. A web server to query, visualize and download for all the data can be freely accessed at http://bioinfo.hrbmu.edu.cn/miR2Subpath.     

Recognition of H3K9me1 by maize RNA-directed DNA methylation factor SHH2

RNA-directed DNA methylation (RdDM) is a plant-specific de novo DNA methylation pathway, which has extensive cross-talk with histone modifications. Here, we report that the maize RdDM regulator SAWADEE HOMEODOMAIN HOMOLOG 2 (SHH2) is an H3K9me1 reader. Our structural studies reveal that H3K9me1 recognition is achieved by recognition of the methyl group via a classic aromatic cage and hydrogen-bonding and salt-bridge interactions with the free protons of the mono-methyllysine. The di- and tri-methylation states disrupt the polar interactions, decreasing the binding affinity. Our study reveals a mono-methyllysine recognition mechanism which potentially links RdDM to H3K9me1 in maize.     

Apoplastic hydrogen peroxide and superoxide anion exhibited different regulatory functions in salt-induced oxidative stress in wheat leaves

The present work aimed to investigate the mechanisms of nitric oxide (NO) and reactive oxygen species (ROS) generations and to explore their roles in the regulation of antioxidative responses in the wheat leaves under salinity. Except for an insignificant change of NO content and nitrate reductase (NR) activity due to 50 mM NaCl, NO, hydrogen peroxide, superoxide anion (O₂^?-), hydroxyl radical (?OH), chlorophyll and malondialdehyde content, as well as activities of nitric oxide synthase, NR, peroxidases (POD), catalase (CAT), and ascorbate peroxidase rose in response to different NaCl concentrations. Meanwhile, leaf superoxide dismutase activity lowered only at 50 mM NaCl. NaCl-stimulatory effects on NO content as well as POD and CAT activities could be partly alleviated by the application of 2-phenyl-4,4,5,5-tetrame-thylimidazoline-3-oxide-1-oxyl (PTIO, NO scavenger), exogenous CAT, or diphenylene iodonium (DPI, NADPH oxidase inhibitor). Native polyacrylamide gel electrophoresis also showed that the amount of POD (especially POD4, POD5, and POD7) and CAT (especially CAT1, CAT2, and CAT3) isozymes increased with increasing salinity but decreased by application of PTIO, CAT, or DPI. Furthermore, histochemical staining showed a similar change of O₂^?- generation. In addition, the inhibition of diamineoxidase (DAO), polyamine oxidase (PAO), and cell wall-bound POD (cw-POD) activities in NaCl-stressed seedlings seemed to be insensitive to the application of PTIO or DPI. Taken together, salinity-induced NO, H₂O₂, and O₂^?- generation influenced each other and played different roles in the regulation of antioxidant enzyme activities in the leaves of wheat seedlings under NaCl treatment.     

ROCK1 induces ERK nuclear translocation in PDGF-BB-stimulated migration of rat vascular smooth muscle cells

It has been known that Rho-associated protein kinase (ROCK) signaling regulates the migration of vascular smooth muscle cells (VSMCs). However, the isoform-specific roles of ROCK and its underlying mechanism in VSMC migration are not well understood. The current study thus aimed to investigate the roles of ROCK1/2 and their relationship to the MAPK signaling pathway in platelet-derived growth factor (PDGF)-induced rat aorta VSMC migration by manipulating ROCK gene expression. The results revealed that ROCK1 small interfering ribonucleic acid (siRNA) rather than ROCK2 siRNA decreased PDGF-BB-generated VSMC migration, and upregulation of ROCK1 expression via transfection of constructed pEGFP-C1/ROCK1 plasmid further increased the migration of PDGF-BB-treated VSMCs. In PDGF-treated VSMCs, ROCK1 siRNA did not affect the phosphorylation levels of ERK and p38 in the cytoplasm, but decreased the level of ERK phosphorylation in the nucleus. These findings demonstrate that activated ROCK1 can promote VSMC migration through facilitating phosphorylation and nuclear translocation of ERK protein.     

Effects of habitat fragmentation on genetic diversity and gene flow among the Homidia socia (Collembola: Entomobryidae) populations in the Thousand Island Lake

In the present study, partial sequences of the mitochondrial cytochrome oxidase subunit I (COI) gene of 22 island populations of the springtail Homidia socia in the Thousand Island Lake were sequenced. Across all sequences, 37 haplotypes were identified for the 510‐bp mitochondrial (mt) DNA COI gene. Haplotype 2 was the most common, and was distributed in the most of the 22 island populations. Haplotype diversity ranged from 0.065 to 0.733, and the total genetic diversity was 0.56216. The genetic characteristics of the 22 island populations were analyzed using the fixation index and gene flow, with values of 0.00043–0.94900 and 0.02703–703.72540, respectively. Comparison between (island area and isolations) with population genetic diversity revealed that there were no significant correlations between them, except for a significant correlation between the number of haplotypes and island area. Mantel tests showed that there was no significant correlation between geographic distance and genetic distance among various groups. All the results indicated that there were no obvious relationships between island characteristics and the genetic diversity of the springtails. We consider that the low dispersal capacity of springtails and the island patches surrounded by water in the Thousand Island Lake are the major factors affecting the genetic diversity of H. socia.     

Enhanced Healing of Rat Calvarial Critical Size Defect with Selenium-Doped Lamellar Biocomposites

A 3D porous lamellar selenium-containing nano-hydroxyapatite (SeHAN)/chitosan (CS) biocomposite was synthesized. The selenium-containing hydroxyapatite (HA) grains of 150～200 nm in length and 20～30 nm in width were observed by dynamic light scattering and transmission electron microscopy. A combination of X-ray diffraction, Fourier-transform infrared spectroscopy, and SEM indicated that HA particles were uniformly dispersed in chitosan matrix and there was a chemical interaction between chitosan and HA. Then, a standard critical size calvarial bone defect was created in Wistar rats. In group 1, no implant was made in the defect. In groups 2 and 3, HA nanoparticles (HAN)/CS biocomposite and SeHAN/CS biocomposite were implanted into the defect, respectively. After 4 weeks, the histological assessment clearly exhibited no significant changes, only found some living cells anchored in the periphery of the implants. After 8 and 12 weeks, most newly formed osteoid tissue was found in the SeHAN/CS implant group. Additionally, the newly formed osteoid tissue, both at the edge and in the center of implants, was bioactive and neovascularized. Microfocus computerized tomography measurements also confirmed the much better quality of the newly formed bone tissue in SeHAN/CS implant group than that in HAN/CS implant group (p?<?0.01). Collectively, the SeHAN/CS biocomposite, as a bioactive bone grafting substitute, significantly enhanced the repair of bone defect.     

Mechanisms of Metabonomic for a Gateway Drug: Nicotine Priming Enhances Behavioral Response to Cocaine with Modification in Energy Metabolism and Neurotransmitter Level

Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned place preference (CPP) models in mice. In threshold dose model, mice were pretreated with nicotine, followed by cocaine treatment at the dose of 2 mg/kg, a threshold dose of cocaine to induce CPP in mice. In high-dose model, mice were only treated with 20 mg/kg cocaine, which induced a significant CPP. ¹H nuclear magnetic resonance based on metabonomics was used to investigate metabolic profiles of the nucleus accumbens (NAc) and striatum. We found that nicotine pretreatment dramatically increased CPP induced by 2 mg/kg cocaine, which was similar to 20 mg/kg cocaine-induced CPP. Interestingly, metabolic profiles showed considerable overlap between these two models. These overlapped metabolites mainly included neurotransmitters as well as the molecules participating in energy homeostasis and cellular metabolism. Our results show that the reinforcing effect of nicotine on behavioral response to cocaine may attribute to the modification of some specific metabolites in NAc and striatum, thus creating a favorable metabolic environment for enhancing conditioned rewarding effect of cocaine. Our findings provide an insight into the effect of cigarette smoking on cocaine dependence and the underlying mechanism.