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991.
锌指核酸酶技术在基因定点修饰中具有效率高和特异性好等特点,并成功应用于数十种生物。目前,该技术是否能应用羊上尚未报道。为了敲除转基因山羊标记基因 (EGFP),构建了一对针对EGFP外显子上的锌指核酸酶表达载体,将其电转染至转EGFP基因胎儿成纤维细胞中,研究了锌指核酸酶突变EGFP基因的效率和方式,利用基因显微注射单细胞获得获得的转基因 (EGFP) 细胞系作为锌指核酸酶的靶细胞。结果显示,通过锌指核酸酶的突变作用,转染后的细胞发绿色荧光比例下降,测序结果显示在EGFP外显子中插入1个碱基G,导致编码EGFP基因的阅读框改变,从而起到基因突变的作用。结果表明,文中构建的锌指核酸酶对EGFP基因有突变作用,可以为以后获得无标记基因供核细胞进行体细胞核移植生产克隆羊奠定基础。 相似文献
992.
Xiao Wang Zhong-Wei Zhang Shi-Hua Tu Wen-Qiang Feng Fei Xu Feng Zhu Da-Wei Zhang Jun-Bo Du Shu Yuan Hong-Hui Lin 《Biologia》2013,68(1):74-81
Cadmium (Cd) has been identified as a significant pollutant due to its high solubility in water and soil and high toxicity to plants and animals. Rice, as one of the most important food crops, is grown in soils with variable levels of Cd and therefore, is important to discriminate the Cd tolerance of different rice cultivars to determine their suitability for cultivation in Cd-contaminated soils. This study investigates the primary mechanisms employed by four rice cultivars in attaining Cd tolerance. HA63 cultivar reduces Cd uptake by increasing Fe absorption through activation of phytosiderophores. T3028 cultivar accumulates the highest level of Cd in leaves while also activating its reactive oxygen species (ROS) scavenging system, including antioxidant enzymes and phytochelatins. In some rice cultivars (such as HA63), a cyanide-resistant respiration mechanism, important in Cd detoxification, was also promoted under the Cd stress. In conclusion, different rice cultivars may adopt different biochemical strategies and respond with different efficiency to Cd stress. 相似文献
993.
Xiao‐Bin Li Fei Xie Shan‐Shan Liu Ying Li Jin‐Chuan Zhou Yong‐Qing Liu Hui‐Qing Yuan Hong‐Xiang Lou 《化学与生物多样性》2013,10(7):1193-1201
Bioactivity‐guided fractionation of the cytotoxic extract of Aspergillus niger, an endophytic fungus from the Chinese liverwort Heteroscyphus tener (Steph .) Schiffn ., afforded five new naphtho‐γ‐pyrones, rubrofusarin‐6‐O‐α‐D ‐ribofuranoside ( 1 ), (R)‐10‐(3‐succinimidyl)‐TMC‐256A1 ( 2 ), asperpyrone E ( 3 ), isoaurasperone A ( 4 ), and isoaurasperone F ( 5 ), as well as four known ones, dianhydroaurasperone C ( 6 ), aurasperone D ( 7 ), asperpyrone D ( 8 ), and asperpyrone A ( 9 ), together with a cytotoxic cyclic pentapeptide, malformin A1 ( 10 ). Their structures were determined by extensive spectroscopic analysis. The absolute configurations of dimeric naphtho‐γ‐pyrones 3 – 9 were also determined by analysis of their respective CD spectra. 相似文献
994.
Li‐Na Zhu Cai‐Yun Fu Shi‐Fu Zhang Wei Chen Yuan‐Ting Jin Fu‐Kun Zhao 《Journal of peptide science》2013,19(9):566-574
Anoplin is a recently discovered antimicrobial peptide (AMP) isolated from the venom sac of the spider wasp Anoplius samariensis, and it is one of the shortest α‐helical AMP found naturally to date consisting of only ten amino acids. Previous results showed that anoplin exhibits potent antimicrobial activity but little hemolytic activity. In this study, we synthesized anoplin, studied its cytotoxicity in Friend virus‐induced leukemia cells [murine erythroleukemia (MEL) cells], and proposed its possible mechanism. Our results showed that anoplin could inhibit the proliferation of MEL cells in a dose‐dependent and time‐dependent manner via disrupting the integrity of cell membrane, which indicated that anoplin exerts its cytotoxicity efficacy. In addition, the cell cycle distribution of MEL cells was arrested in the G0/G1 phase significantly. However, anoplin could not induce obvious apoptosis in MEL cells, as well as anoplin could not induce visible changes on morphology and quantity in the bone marrow cells isolated from normal mice. All of these results indicate that anoplin, as generally believed, is a selective AMP, a value characteristic in the design of safe therapeutic agents. The cytotoxicity of anoplin on MEL cells was mainly attributable to the plasma membrane perturbation and also to the intracellular events such as the arrest of cell cycle. Although this is an initial study that explored the activity of anoplin in vitro rather than in vivo, with the increasing resistance of conventional chemotherapy, there is no doubt that anoplin has desirable feature to be developed as a novel and selective anticancer agent. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
995.
Larval settlement of the barnacle Balanus amphitrite Darwin (Cirripedia, Balanidae) is influenced by natural biofilms. In previous work by others, discriminatory settlement of aged cyprids has been observed in response to biofilms of different age. This study extends prior work by considering the effect of the age of cyprids on the outcome of settlement assays. Settlement was investigated with 0‐day‐old (newly metamorphosed) and 5‐day‐old cyprids. Biofilms under investigation were developed in the field for periods of 5 d and 1 month, and were subsequently included in laboratory settlement assays with a choice between a filmed and an unfilmed substratum. The bioassay was modified from the conventional horizontal dish design in order to generate a low water surface‐to‐volume ratio, which served to suppress larval entrapment in an organic layer on the water surface. Irrespective of cyprid age, a clear discrimination between a filmed and an unfilmed substrata was observed, and the preference for filmed or unfilmed substratum was dependent on the age of the cyprids. Settlement of 0‐day‐old cyprids was inhibited by a biofilmed substratum whereas induction occurred with aged cyprids. This pattern of settlement was independent of biofilm age. Bacterial abundance on unfilmed substrata in treatments and controls was significantly lower than that on biofilmed surfaces, confirming that bacterial contamination did not change the qualitative option during the assay. 相似文献
996.
997.
Tao Zhang Jianbing Mo Qiong Shi Xianfeng Zhang Maochun Yuan Long Chen Xueqiang Mao Rutong Yu Xiuping Zhou 《Journal of neurochemistry》2013,125(5):698-712
Geranylgeranyltransferase I (GGT) is a prenyltransferase that mediates lipid modification of Rho small GTPases, such as Rho, Rac, and Cdc42, which are important for neuronal synaptogenesis. Although GGT is expressed in brain extensively, the function of GGT in central nerves system is largely unknown so far. We have previously demonstrated that GGT promotes the basal and neuronal activity and brain‐derived neurotrophic factor (BDNF)‐induced dendritic morphogenesis of cultured hippocampal neurons and cerebellar slices. This study is to explore the function and mechanism of GGT in neuronal synaptogenesis. We found that the protein level and activity of GGT gradually increased in rat hippocampus from P7 to P28 and subcellular located at synapse of neurons. The linear density of Synapsin 1 and post‐synaptic density protein 95 increased by over‐expression of GGT β, while reduced by inhibition or down‐regulation of GGT. In addition, GGT and its known substrate Rac was activated by BDNF, which promotes synaptogenesis in cultured hippocampal neurons. Furthermore, BDNF‐induced synaptogenesis was eliminated by GGT inhibition or down‐regulation, as well as by non‐prenylated Rac1 over‐expression. Together, our data suggested that GGT mediates BDNF‐induced neuronal synaptogenesis through Rac1 activation. 相似文献
998.
Yanmei Zou Shuo Yao Xiuqiong Chen Dian Liu Jianhua Wang Xun Yuan Jie Rao Huihua Xiong Shiying Yu Xianglin Yuan Feng Zhu Guohong Hu Yihua Wang Hua Xiong 《European journal of cell biology》2018,97(5):369-378
Object
This study aimed to investigate the role of lncRNA OIP5-AS1 in regulating radioresistance of colorectal cancer (CRC) cells.Methods
Microarray analysis was used to screen out lncRNAs differentially expressed in radio-resistant CRC cell lines. Expression levels of OIP5-AS1, miR-369-3p and DYRK1A in CRC cell lines were measured by qRT-PCR. Protein expression of DYRK1A was determined by western blot. The target relationships among OIP5-AS1, miR-369-3p and DYRK1A were validated by dual luciferase reporter assay. Impacts of OIP5-AS1 or DYRK1A on CRC cellular activity and apoptosis were investigated by MTT assay, clonogenic survival assay and flow cytometry to analyze OIP5-AS1 or DYRK1A’s effect on radioresistance of CRC cells.Results
LncRNA OIP5-AS1 and DYRK1A were down-regulated in radio-resistant CRC cell lines. OIP5-AS1 suppressed the expression of miR-369-3p, thus up-regulating DYRK1A, the downstream gene of miR-369-3p. OIP5-AS1 and DYRK1A impaired cell clonogenic survival and promoted cell apoptosis after irradiation, improving radiosensitivity of CRC cells.Conclusion
LncRNA OIP5-AS1 suppressed cell viability, promoted radio-induced apoptosis, and enhanced the radiosensitivity of CRC cells by regulating DYRK1A expression through miR-369-3p. 相似文献999.
Jun-Jun Huang Zhi-Han Zhang Fei He Xia-Wen Liu Xing-Jie Xu Li-Jun Dai Qi-Meng Liu Mu Yuan 《Bioorganic & medicinal chemistry letters》2018,28(4):547-551
α1-Adrenoceptor (α1-AR) antagonists are considered to be the most effective monotherapy agents for lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). In this study, we synthesized compounds 2–17, which are novel piperazine derivatives that contain methyl phenylacetate. We then evaluated the vasodilatory activities of these compounds. Among them, we found that compounds 2, 7, 12, which contain 2-OCH3, 2-CH3 or 2, 5-CH3, respectively, exhibited potent α1-blocking activity similar to protype drug naftopidil (1). The antagonistic effects of 2, 7, and 12 on the (?)-noradrenaline-induced contractile response of isolated rat prostatic vas deferens (α1A), spleen (α1B) and thoracic aorta (α1D) were further characterized to assess the sub receptor selectivity. Compared with naftopidil (1) and terazosin, compound 12 showed the most desirable α1D/1A subtype selectivity, especially improved α1A subtype selectivity, and the ratios pA2 (α1D)/pA2 (α1B) and pA2 (α1A)/pA2 (α1B) were 17.0- and 19.5-fold, respectively, indicating less cardiovascular side effects when used to treat LUTS/BPH. Finally, we investigated the chiral pharmacology of 12. We found, however, that the activity of enantiomers (R)-12 and (S)-12 are not significantly different from that of rac-12. 相似文献
1000.
Biao Lu Song Huang Jingsong Cao Qiyue Hu Ru Shen Hong Wan Dan Wang Jijun Yuan Lei Zhang Jiayin Zhang Minsheng Zhang Weikang Tao Lianshan Zhang 《Bioorganic & medicinal chemistry》2018,26(3):581-589
A novel series of benzodihydrofuran derivatives was developed as potent MEK inhibitors through scaffold hopping based on known clinical compounds. Further SAR exploration and optimization led to another benzofuran series with good oral bioavailability in rats. One of the compounds EBI-1051 (28d) demonstrated excellent in vivo efficacy in colo-205 tumor xenograft models in mouse and is suitable for pre-clinical development studies for the treatment of melanoma and MEK associated cancers. Compared to AZD6244, EBI-1051 showed superior potency in some cancer cell lines such as colon-205, A549 and MDA-MB-231. 相似文献