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901.
Ren‐Hua Chen Yi‐Gang Li Kun‐Li Jiao Peng‐Pai Zhang Yu Sun Li‐Ping Zhang Xiang‐Fei Fong Wei Li Yi Yu 《Journal of cellular and molecular medicine》2013,17(5):608-616
The expression of the chemorepellent Sema3a is inversely related to sympathetic innervation. We investigated whether overexpression of Sema3a in the myocardial infarction (MI) border zone could attenuate sympathetic hyper‐innervation and decrease the vulnerability to malignant ventricular tachyarrhythmia (VT) in rats. Survived MI rats were randomized to phosphate buffered saline (PBS, n = 12); mock lentivirus (MLV, n = 13) and lentivirus‐mediated overexpression of Sema3a (SLV, n = 13) groups. Sham‐operated rats served as control group (CON, n = 20). Cardiac function and electrophysiological study (PES) were performed at 1 week later. Blood and tissue samples were collected for histological analysis, epinephrine (EPI), growth‐associated factor 43 (GAP43) and tyrosine hydroxylase (TH) measurements. QTc intervals were significantly shorter in SLV group than in PBS and MLV groups (168.6 ± 7.8 vs. 178.1 ± 9.5 and 180.9 ± 8.2 ms, all P < 0.01). Inducibility of VT by PES was significantly lower in the SLV group [30.8% (4/13)] than in PBS [66.7% (8/12)] and MLV [61.5% (8/13)] groups (P < 0.05). mRNA and protein expressions of Sema3a were significantly higher and the protein expression of GAP43 and TH was significantly lower at 7 days after transduction in SLV group compared with PBS, MLV and CON groups. Myocardial EPI in the border zone was also significantly lower in SLV group than in PBS and MLV group (8.73 ± 1.30 vs. 11.94 ± 1.71 and 12.24 ± 1.54 μg/g protein, P < 0.001). Overexpression of Sema3a in MI border zone could reduce the inducibility of ventricular arrhythmias by reducing sympathetic hyper‐reinnervation after infarction. 相似文献
902.
Interplay between human microglia and neural stem/progenitor cells in an allogeneic co‐culture model
Mingqin Zhu Cinzia Calzarossa Eva‐Britt Samuelsson Marianne Schultzberg Elisabet Åkesson 《Journal of cellular and molecular medicine》2013,17(11):1434-1443
Experimental neural cell therapies, including donor neural stem/progenitor cells (NPCs) have been reported to offer beneficial effects on the recovery after an injury and to counteract inflammatory and degenerative processes in the central nervous system (CNS). The interplay between donor neural cells and the host CNS still to a large degree remains unclear, in particular in human allogeneic conditions. Here, we focused our studies on the interaction of human NPCs and microglia utilizing a co‐culture model. In co‐cultures, both NPCs and microglia showed increased survival and proliferation compared with mono‐cultures. In the presence of microglia, a larger subpopulation of NPCs expressed the progenitor cell marker nestin, whereas a smaller group of NPCs expressed the neural markers polysialylated neural cell adhesion molecule, A2B5 and glial fibrillary acidic protein compared with NPC mono‐cultures. Microglia thus hindered differentiation of NPCs. The presence of human NPCs increased microglial phagocytosis of latex beads. Furthermore, we observed that the expression of CD200 molecules on NPCs and the CD200 receptor protein on microglia was enhanced in co‐cultures, whereas the release of transforming growth factor‐β was increased suggesting anti‐inflammatory features of the co‐cultures. To conclude, the interplay between human allogeneic NPCs and microglia, significantly affected their respective proliferation and phenotype. Neural cell therapy including human donor NPCs may in addition to offering cell replacement, modulate host microglial phenotypes and functions to benefit neuroprotection and repair. 相似文献
903.
Tingxiu Xiang Lili Li Xuedong Yin Lan Zhong Weiyan Peng Zhu Qiu Guosheng Ren Qian Tao 《Journal of cellular and molecular medicine》2013,17(10):1236-1246
Dickkopf‐related protein 3 (DKK3) is an antagonist of Wnt ligand activity. Reduced DKK3 expression has been reported in various types of cancers, but its functions and related molecular mechanisms in breast tumorigenesis remain unclear. We examined the expression and promoter methylation of DKK3 in 10 breast cancer cell lines, 96 primary breast tumours, 43 paired surgical margin tissues and 16 normal breast tissues. DKK3 was frequently silenced in breast cell lines (5/10) by promoter methylation, compared with human normal mammary epithelial cells and tissues. DKK3 methylation was detected in 78% of breast tumour samples, whereas only rarely methylated in normal breast and surgical margin tissues, suggesting tumour‐specific methylation of DKK3 in breast cancer. Ectopic expression of DKK3 suppressed cell colony formation through inducing G0/G1 cell cycle arrest and apoptosis of breast tumour cells. DKK3 also induced changes of cell morphology, and inhibited breast tumour cell migration through reversing epithelial‐mesenchymal transition (EMT) and down‐regulating stem cell markers. DKK3 inhibited canonical Wnt/β‐catenin signalling through mediating β‐catenin translocation from nucleus to cytoplasm and membrane, along with reduced active‐β‐catenin, further activating non‐canonical JNK signalling. Thus, our findings demonstrate that DKK3 could function as a tumour suppressor through inducing apoptosis and regulating Wnt signalling during breast tumorigenesis. 相似文献
904.
Qiong Wu Chunhong Yang Yong Pan Fang Xiang Zhichao Liu Weihua Zhu Heming Xiao 《Journal of molecular modeling》2013,19(12):5159-5170
Periodic first-principles calculations have been performed to study the effect of high pressure on the geometric, electronic, and absorption properties of 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) under hydrostatic pressures of 0–50 GPa. Obvious irregular changes in lattice constants, unit-cell angles, bond lengths, bond angles, and band gaps showed that crystalline LLM-105 undergoes four structural transformations at 8, 17, 25, and 42 GPa, respectively. The intramolecular H-bonds were strong at pressures of 0–41 GPa but weakened in the range 42–50 GPa. The lengths of the intermolecular H-bonds (<1.47 Å) indicated that these H-bonds have covalent character and tend to induce the formation of a new twelve-membered ring. Analysis of the DOS showed that the interactions between electrons, especially the valence electrons, strengthen under the influence of pressure. The p states play a very important role in chemical reactions of LLM-105. The absorption spectrum of LLM-105 displayed more bands—as well as stronger bands—in the fundamental absorption region when the pressure was high rather than low. A new absorption peak due to O–H stretching appeared at 18.3 eV above 40 GPa, indicating that covalent O–H bonds and a new twelve-membered ring are present in LLM-105. 相似文献
905.
X.‐R. Liu M. Wu N. He H. Meng L. Wen J.‐L. Wang M.‐P. Zhang W.‐B. Li X. Mao J.‐M. Qin B.‐M. Li B. Tang Y.‐H. Deng Y.‐W. Shi T. Su Y.‐H. Yi B.‐S. Tang W.‐P. Liao 《Genes, Brain & Behavior》2013,12(2):234-240
Paroxysmal dyskinesias (PDs) are a group of episodic movement disorders with marked variability in clinical manifestation and potential association with epilepsy. PRRT2 has been identified as a causative gene for PDs, but the phenotypes and inheritance patterns of PRRT2 mutations need further clarification. In this study, 10 familial and 21 sporadic cases with PDs and PDs‐related phenotypes were collected. Genomic DNA was screened for PRRT2 mutations by direct sequencing. Seven PRRT2 mutations were identified in nine (90.0%) familial cases and in six (28.6%) sporadic cases. Five mutations are novel: two missense mutations (c.647C>G/p.Pro216Arg and c.872C>T/p.Ala291Val) and three truncating mutations (c.117delA/p.Val41TyrfsX49, c.510dupT/p.Leu171SerfsX3 and c.579dupA/p.Glu194ArgfsX6). Autosomal dominant inheritance with incomplete penetrance was observed in most of the familial cases. In the sporadic cases, inheritance was heterogeneous including recessive inheritance with compound heterozygous mutations, inherited mutations with incomplete parental penetrance and de novo mutation. Variant phenotypes associated with PRRT2 mutations, found in 36.0% of the affected cases, included febrile convulsions, epilepsy, infantile non‐convulsive seizures (INCS) and nocturnal convulsions (NC). All patients with INCS or NC, not reported previously, displayed abnormalities on electroencephalogram (EEG). No EEG abnormalities were recorded in patients with classical infantile convulsions and paroxysmal choreoathetosis (ICCA)/paroxysmal kinesigenic dyskinesia (PKD). Our study further confirms that PRRT2 mutations are the most common cause of familial PDs, displaying both dominant and recessive inheritance. Epilepsy may occasionally occur in ICCA/PKD patients with PRRT2 mutations. Variant phenotypes INCS or NC differ from classical ICCA/PKD clinically and electroencephalographically. They have some similarities with, but not identical to epilepsy, possibly represent an overlap between ICCA/PKD and epilepsy . 相似文献
906.
Wentao Wang Weihua Zhu Jinshan Li Bibo Cheng Heming Xiao 《Journal of molecular modeling》2013,19(1):305-314
A detailed study of the structural, electronic, and optical absorption properties of crystalline 1,4-dinitrofurazano[3,4-b]piperazine (DNFP) under hydrostatic pressures of 0–100 GPa was performed using periodic density functional theory. As the pressure increases, the lattice constants and cell volumes calculated by LDA gradually approach those obtained by GGA-PW91. It was found that the structure of DNFP is much stiffer in the b direction than along the a and c axes, indicating that the compressibility of the crystal is anisotropic. As the pressure increases, the band gap gradually decreases, and this decrease is more pronounced in the low-pressure range than in the high-pressure region. An analysis of the density of states showed that the electronic delocalization in DNFP gradually increases under the influence of pressure. DNFP exhibits relatively high optical activity at high pressure. As the pressure increases, the bands in the fundamental absorption region of the absorption spectrum of DNFP become more numerous and intense. 相似文献
907.
Molecular dynamics study on the correlation between structure and sensitivity for defective RDX crystals and their PBXs 总被引:1,自引:0,他引:1
Ji Jun Xiao Song Yuan Li Jun Chen Guang Fu Ji Wei Zhu Feng Zhao Qiang Wu He Ming Xiao 《Journal of molecular modeling》2013,19(2):803-809
Molecular dynamics simulation was applied to investigate the sensitivities of perfect and defective RDX (cyclotrimethylene trinitramine) crystals, as well as their PBXs (polymer-bonded explosives) with the polymeric binder F2311, in the NPT (constant number of particles, constant pressure, constant temperature) ensemble using the COMPASS force field. Five kinds of defects—two dislocations, one vacancy, and two types of doping—were considered separately. The bond length distribution and the maximum (L max) and average (L ave) bond lengths of the N–NO2 trigger bonds in RDX were obtained and their relationships to the sensitivities of RDX and PBXs are discussed. L max was found to be an important structural parameter for judging the relative sensitivity, and defects were observed to have little effect on the sensitivities of PBXs, due to the strong desensitizing effect of the polymer F2311. 相似文献
908.
In the synthesis of cyanuric acid from NH3 and CO2, urea and isocyanic acid OCNH are two pivotal intermediates. Based on density functional theory (DFT) calculations, the synthesis mechanism of cyanuric acid from NH3 + CO2 was investigated systematically. Urea can be synthesized from NH3 and CO2, and cyanuric acid can be obtained from urea or NH3 + CO2. In the stepwise mechanism of cyanuric acid from urea or NH3 + CO2, the energy barriers are relatively high, and the condition of high pressure and temperature does not decrease the energy barriers. Our theoretical model shows that cyanuric acid is actually acquired from OCNH via a one-step cycloaddition reaction. Figure
The synthesis mechanism of cyanuric acid from NH3 and CO2 was revealed systematically with density functional theory methods relative to 3NH3 + 3CO2 相似文献
909.
Yingtao Liu Zhijian Xu Zhuo Yang Kaixian Chen Weiliang Zhu 《Journal of molecular modeling》2013,19(11):5015-5030
Halogen bonding, a non-covalent interaction between the halogen σ-hole and Lewis bases, could not be properly characterized by majority of current scoring functions. In this study, a knowledge-based halogen bonding scoring function, termed XBPMF, was developed by an iterative method for predicting protein-ligand interactions. Three sets of pairwise potentials were derived from two training sets of protein-ligand complexes from the Protein Data Bank. It was found that two-dimensional pairwise potentials could characterize appropriately the distance and angle profiles of halogen bonding, which is superior to one-dimensional pairwise potentials. With comparison to six widely used scoring functions, XBPMF was evaluated to have moderate power for predicting protein-ligand interactions in terms of “docking power”, “ranking power” and “scoring power”. Especially, it has a rather satisfactory performance for the systems with typical halogen bonds. To the best of our knowledge, XBPMF is the first halogen bonding scoring function that is not dependent on any dummy atom, and is practical for high-throughput virtual screening. Therefore, this scoring function should be useful for the study and application of halogen bonding interactions like molecular docking and lead optimization. Figure
Heat map of 2D XB potentials for OA-Cl 相似文献
910.
Jonathan Griffin Darren C. Watters Hunan Yi Ahmed Iraqi David Lidzey Alastair R. Buckley 《Liver Transplantation》2013,3(7):903-908
Bulk heterojunction solar cells containing molybdenum oxide hole extracting anode contacts have been fabricated with varying stoicheometry using radio frequency reactive sputtering from a Molybdenum metal target. A blend of the newly synthesised conjugated polymer poly[9‐(heptadecan‐9‐yl)‐9H‐carbazole‐2,7‐diyl‐alt‐(5,6‐bis(octyloxy)‐4,7‐di(thiophen‐2‐yl)benzo[c][1,2,5]thiadiazole)‐5,5‐diyl] (PCDTBT‐8) and fullerene [6,6]‐Phenyl‐C71‐butyric acid methyl ester (PC70BM) was used as the photoactive layer and device results show that anodes with greater than 98% Molybdenum (VI) oxide result in peak power conversion efficiencies of 3.7%.The presence of up to 28% of Mo (V) results in no significant reduction in efficiency, however the presence of metallic Mo (IV) and lower oxidation states lead to severe reductions in device performance due to a combination of a large hole extraction energy barrier of approximately 0.9eV and reduced device stability. 相似文献