Abstract:The mechanism of the organism to repair DNA damage has been studied in reasonable detail. In contrast, the agents of damage to DNA also cause RNA damage have not been widely recognized. This is mainly due to aberrant RNAs are generally assumed to be degraded rather than repaired. With the discovery of RNA repair systems, the RNA damage of the organism may preferentially be repaired. Based on the latest findings, the phage-type RNA repair system, bacterial-type RNA repair system, yeast-type RNA repair system and human RNA damage repair system are reviewed and discussed in this paper.

Abstract:The development of solid tumor is often accompanied by extracellular matrix abnormal deposition, cross-linking and stiffening. Extracellular matrix stiffening and tumor cell softening contribute to the mechanical heterogeneity of tumor microenvironment. Matrix mechanics regulates tumorigenesis, malignancy, metastasis of tumor by affecting tumor cells proliferation, migration, epithelial-mesenchymal transition, properties of cancer stem cells and drug resistance. To study the effect of matrix mechanics on cancer development can not only deepen the understanding of cancer development, but also provide theoretical basis for developing new treatment strategy. In this paper, the research advances in the effect of extracellular matrix mechanical characteristics on tumor development and tumor cell biological behavior was summarized and its development prospect was also discussed.

Abstract:The evolution makes bats have abilities of flying, echolocating and highly adaptating to living surroundings. Bats, as the only true flying mammals, belong to the Chiroptera, ranking the second order of the mammals with more than 1000 species. They are classified into Megachiroptera and Microchiroptera according to their size and morphological characteristics of the body. Because bats share some basic principles with human in auditory perception, the researches of bats can provide helpful information to understand the hearing of human. The echolocation signals emitted by bats are regular and can be easily imitated to study the mechanism of the signal processing in the central auditory system, especially in the processing of complex acoustic signals, bats is an excellent model animal. Moreover, the biosonar system of echolocation bats with very high temporal and spatial resolution has very important value in bionics, which is a very interesting topic. The study on auditory structure and function of CF-FM ( constant frequency-frequency modulation) bats has gone through a considerable time and achieved numerous new understanding, some adaptive mechanisms of the acute auditory system to echolocation behavior are also revealed. Therefore，the research progress in relation to the auditory system and echolocation of CF-FM bats are briefly introduced and reviewed in this article.

Abstract:The Global First theory considers the global properties of objects could be described as topological invariants, with the earliest detection and highest priority in visual processing. The theory is supported by accumulating evidence in conscious vision, but remains unclear in implicit perception, the perception in the absence of awareness, whose mechanism and application have been studied a lot in cognition research for years. In the present study we probed into the processing of global properties in implicit perception by means of a variant of binocular rivalry called continuous flash suppression, in which our target stimuli were suppressed by dynamic mosaic noise patterns in order to achieve subconscious vision. The number of holes, a crucial topological invariant of an object, is the target of this study. In Exp1, the disk, the S and the O shape were used as target stimuli, the shapes might change or not after being suppressed, subjects reported the breakthrough of suppressed figures by keypress, we measured the suppression time of the figures, and found stimuli of topological changes(changes of numbers of holes in stimuli) took significantly less time to get into dominance, comparing with those of non-topological changes or unchanged. In Exp2, disks with different amount of holes or similar arcs were used as target stimuli, subjects were required to perform a 2AFC task after a 3s display in which the suppressed figures might be presented in the upper or lower visual field, the detection accuracy were compared, which indicated that the topological changes have a higher chance to be detected during suppression. The result strongly supported Global First in implicit perception, and revealed the high priority of topological properties in human visual processing, meanwhile it suggested the possible subcortical visual processing of topological properties.

Abstract:IL-24 and Smac are the important candidate genes for the targeting multi-genes therapy of cancer. In the construction of IL-24 and Smac dual gene expression vector, a stable and efficient linker is critical. We use three different linkers such as IETD, EEED and F2A to obtain three eukaryotic expression plasmids which are pcDNA3.1(+)-IL-24-IETD-Smac, pcDNA3.1( )-IL-24-EEED-Smac, pcDNA3.1( )-IL-24-F2A-Smac, and then combined with 5-fluorouracil (5-FU) treatment to study the cleavage efficiency of the three linker peptides. The results showed that among three IL-24-linker-Smac dual gene expression vectors, the F2A linker is superior to IETD and EEED linkers. In addition, its cleavage efficiency is positively correlated with activated caspases. Moreover, the fusion protein mediated by both IETD and EEED linker also can be cleaved,but their upstream IL-24 protein with 4 additional amino acid residues derived from IETD or EEED linker was detected with obvious degradation regulated by the ubiquitin-proteasome system. This study will provides a reference for the construction of dual-gene or muti-gene expression vector in cancer therapy.

Abstract:proEMAPⅡ/p43 was originally described as a scaffolding protein that is a component of the multi-aminoacyl-tRNA synthetase complex. Recently, proEMAPⅡ/p43 was found to be a cytokine as well as an endogenic anti-angiogenic protein. The p43 protein is thought to be a precursor of endothelial monocyte-activating polypeptideⅡ (EMAPⅡ). p43 showed higher biological activity than EMAPⅡ, making it a promising anti-angiogenesis inhibitors for cancer therapy. However, the structure of p43 and its function in angiogenesis remain unknown. Here, we constructed p43-like proteins with low molecular mass and high activity. We also determined the functional domains for the anti-angiogenic activity of p43. First, we predicted the secondary structure of p43 using a bioinformatics method, and then constructed 10 p43 truncated mutants. We compared the anti-angiogenic activity of the full-length p43 with the activities of the truncated proteins. We found that all the truncated proteins inhibited the migration of endothelial cells and prevent tubule formation. The deletion of up to 79 amino acids at the N-terminus or 47 amino acids at the C-terminus of p43 increased the activity to 2～3 times that of full-length p43. We identified three p43 truncations with lower molecular mass and higher activity than the full-length p43. These findings will help improve our understanding of the structure and function of p43, which, in turn, will be helpful to the further studies on the possible clinical applications of p43-like drugs.

Abstract:MicroRNAs (miRNAs) array results have shown that the expression of miR-30b is downregulated in heart tissues from patients with familial hypertrophic cardiomyopathy who were carriers of missense mutations in the MYH7, and also in a murine heart failure model, implying that miR-30b might play an important role in heart diseases. To study miR-30b in vivo function, we generated a transgenic mouse line overexpressing miR-30b under the control of the 5.5 kb promoter of α-myosin heavy chain (α-MHC). qRT-PCR results demonstrated that miR-30b was significantly increased in the heart tissues of miR-30b transgenic mice (P < 0.05). miR-30b transgenic mice did not exhibit significant heart/body weight and left ventricular(LV)/body weight changes and abnormal myocardium structure. At present, little is known about how miR-30b regulates myocardial infarction. We constructed I/R models by the coronary artery ligation method and sham-operated mice were used as controls. Biochemical detection results and TTC-Evans blue results showed that after ischemia-reperfusion, these transgenic mice had lower releases of LDH, CK and cTnⅠ(P < 0.05)and their hearts exhibited a smaller infarct size compared to those from control mice(P < 0.05). Echocardiographic results indicated that cardiac function of transgenic mice was markedly improved compared to that of control mice. In conclusion, miR-30b has protective effect upon ischemic-reperfusion injury. And it may provide a new therapeutic approach for preventing and treating myocardial infarction.

Abstract:In our previous work, the 9-(4-chlorophenyloxycarbonyl)-10-methylacridinium triflate ester (CPOCMA) was used as a chemiluminescent substrate for determination of serum arylesterase activity successfully. Based on CPOCMA, a chemiluminescent method was developed for assessing drugs' effect on this enzyme activity. The method was first validated with a UV method based on phenyl acetate by using trinitroglycerine as a model drug. The inhibitory effects of drugs were then exemplified by three anti-inflammatory drugs (including indometacin, aspirin and acetaminophen). It was observed that the serum-mediated CPOCMA hydrolysis slowed down due to addition of the drugs individually. It means that all the three drugs were PON inhibitors. The IC₅₀ values of indometacin, aspirin and acetaminophen were 0.254, 0.564 and 0.656 mmol/L, respectively; and their average inhibitory constants were 0.154, 1.38, and 2.98 mmol/L, respectively. Competitive inhibitory type was observed for all the three drugs by plotting the Lineweaver-Burk curves. According to the kinetics of the hydrolysis, IC₅₀ values, inhibitory constants, and Michaelis constants, the inhibitory abilities of the three drugs were ranked as: indometacin>aspirin>acetaminophen. This chemiluminescent method is especially valuable for evaluation of those drugs which the UV method cannot work for.

Abstract:HDAC1, HDAC2 and RbAp46, RbAp48 are core subunits of several important functional molecular complexes, such as NuRD, Sin3. The four subunits interact with each other, forming a complex which has enzyme activity of deacetylation. However, little is known about the overall structure of this core complex and the influences of its structure to the chromatin deacetylation and remodeling activities. Here, we purified the HDAC1/2-RbAp46/48 core complex from the Sf9 cells infected with baculoviruses containing the genes of HDAC1, HDAC2, RbAp46, and RbAp48, and reconstructed the three dimensional architecture of the core complex using negative stain electron microscopic single particle analysis. It is found that the four subunits (HDAC1, HDAC2, RbAp46 RbAp48) can form a stable and uniform complex, but not all of the subunits exist in the form of a single copy or a proportion way in the the complex. It is shown that HDAC1/2-RbAp46/48 core complex presents an asymmetric saddle shape with a triangle shape back bulging. There is a groove, approximately 6 nm in width, in the middle of the wings of the saddle. We hypothesize that the groove is the binding site of the nucleosome, although further analysis is needed. The work reported here sheds a light on the overall structure of the HDAC1/2-RbAp46/48 complex and its interaction with nucleosome and chromatin, and the mechanism of deactylation enzyme activity of this core complex.

Abstract:The p28 peptide, derived from the blue copper protein azurin, is known to enhance the anticancer capabilities of the tumor suppressor p53 likely binding to its DNA-binding domain (DBD). The p28-p53 DBD complex has been investigated by steered molecular dynamics in order to characterize the unbinding process at atomic resolution. We found that the unbinding of the complex follows a candidate pathway with a well-defined detaching sequence between the partners. The analysis of the unbinding force and the calculation of the irreversible work done along several unbinding paths have allowed us to extract information on the energy landscape regulating the unbinding process.

Abstract:Bistable perception to ambiguous figure is an intriguing visual phenomenon. The underlying mechanisms, however, remain largely unclear. We addressed the issue by recording eye saccade and pupillary reflex in the perceptual responses of human subjects to the ambiguous figure and disambiguous figure (control) generated from the structure-from-motion stimuli. Their pupils dilated when the subjects reported the perceptual reversal between the two mutually exclusive states to both the ambiguous figure and disambiguous figure. The pupillary dilation reached the peak after the perceptual reversal. In contrast to the disambiguous figure, before reported the reversal to the ambiguous figure, the pupils were smaller than the mean size, while after the peak of pupillary dilation occurred, the pupils were still larger than the mean size. These results illustrate that the pupillary dilation posterior to the perceptual report can be regarded as an indication of the perceptual reversal that had occurred, while the differences in pupillary reflex to the ambiguous figure and disambiguous figure prior to the perceptual report probably reflects the intrinsic neural trace of the perceptual reversal and of the perceptual states. Additionally, in the process of perceiving structure-from-motion stimuli, the distribution in directions of eye saccades of subjects changed with the change in the motion axis of the stimuli. The change fashions were accordant between the ambiguous figure and disambiguous figure. This suggests that subjects have the same perception to the ambiguous figure and disambiuous figure and that the correlation of the pupillary reflex changes with the perceptual reversals to the bistable figure of structure-from-motion is reliable. The study casts new light on the visual mechanisms for bistable perception to ambiguous figure.

Abstract:RNA-binding proteins (RBPs) function importantly in RNA synthesis and metabolism by interacting with specific RNAs. The identification of RNA-protein interactions is required for understanding the cellular function mechanisms. A new technique, PAR-CLIP (photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation), has been used to determine the target transcripts of a few RBPs and map the RNA binding sites in a genome-wide fashion. In this study, a rapid and effective method was developed on the basis of PAR-CLIP to detect the RNA binding activity of putative RBPs and their complexes, termed UV cross-linking and tandem affinity purification (CLiTAP). The improvements include: (1) Tandem affinity purification was performed to purify RNA-protein complexes efficiently; (2) Sypro Ruby staining and autoradiography were used sequentially to determine which protein(s) possessing RNA-binding activities. CLiTAP was used to analyze the RNA binding activity of three kinds of CCCH-type zinc finger proteins, TbZC3H7, TbZC3H34 and TbZC3H5, in Trypanosoma brucei. TbZC3H7, a core component of RNA cap-binding complex, showed a strong RNA-binding ability. TbZC3H34, a hypothetical protein, displayed a weak RNA-binding activity, while one of its interacting proteins showed a strong activity. In contrast, TbZC3H5 and all its interacting proteins did not show any RNA binding activity. These results indicated that CLiTAP is an efficient method and can be used to experimentally identify the RBPs in a protein complex, which provide a basis for further mapping the RNA binding sites and investigating the structure and mechanism of RBPs.