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131.
Genyan Liu Huaguang Li Jiaying Shi Wenjie Wang Kenjiro Furuta Di Liu Chunqing Zhao Fumiyo Ozoe Xiulian Ju Yoshihisa Ozoe 《Bioorganic & medicinal chemistry》2019,27(2):416-424
Competitive antagonists (CAs) of ionotropic GABA receptors (GABARs) reportedly exhibit insecticidal activity and have potential for development as novel insecticides for overcoming emerging resistance to traditional GABAR-targeting insecticides. Our previous studies demonstrated that 4,5-disubstituted 3-isoxazolols or 3-isothiazolols are an important class of insect GABAR CAs. In the present study, we synthesized a series of 4-aryl-5-carbamoyl-3-isoxazolols and examined their antagonism of insect GABARs expressed in Xenopus oocytes. Several of these 3-isoxazolols exhibited potent antagonistic activities against housefly and common cutworm GABARs, with IC50 values in the low-micromolar range in both receptors. 4-(3-Amino-4-methylphenyl)-5-carbamoyl-3-isoxazolol (3u) displayed the highest antagonism, with IC50 values of 2.0 and 0.9?μM in housefly and common cutworm GABARs, respectively. Most of the synthesized 3-isoxazolols showed moderate larvicidal activities against common cutworms, with more than 50% mortality at 100?μg/g. These results indicate that 4-monocyclic aryl-5-carbamoyl-3-isoxazolol is a promising scaffold for insect GABAR CA discovery and provide important information for the design and development of GABAR-targeting insecticides with a novel mode of action. 相似文献
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133.
Qingping Xu Matthew Biancalana Joanna C. Grant Hsiu‐Ju Chiu Lukasz Jaroszewski Mark W. Knuth Scott A. Lesley Adam Godzik Marc‐Andr Elsliger Ashley M. Deacon Ian A. Wilson 《Protein science : a publication of the Protein Society》2019,28(9):1676-1689
Free‐standing single‐layer β‐sheets are extremely rare in naturally occurring proteins, even though β‐sheet motifs are ubiquitous. Here we report the crystal structures of three homologous, single‐layer, anti‐parallel β‐sheet proteins, comprised of three or four twisted β‐hairpin repeats. The structures reveal that, in addition to the hydrogen bond network characteristic of β‐sheets, additional hydrophobic interactions mediated by small clusters of residues adjacent to the turns likely play a significant role in the structural stability and compensate for the lack of a compact hydrophobic core. These structures enabled identification of a family of secreted proteins that are broadly distributed in bacteria from the human gut microbiome and are putatively involved in the metabolism of complex carbohydrates. A conserved surface patch, rich in solvent‐exposed tyrosine residues, was identified on the concave surface of the β‐sheet. These new modular single‐layer β‐sheet proteins may serve as a new model system for studying folding and design of β‐rich proteins. 相似文献
134.
Guofeng Yang Yanqin Ju Shangfeng Liu Shouliang Zhao 《Cell biology international》2019,43(11):1276-1285
NG2+ cells have been proven to differentiate into odontoblasts in vivo, and their contribution to odontoblasts is significantly increased, especially after tooth injury. However, their characteristics in vitro, especially under an inflammatory environment, are still not fully understood. Therefore, this study aimed to explore their proliferation, migration, and odontoblastic differentiation ability after treatment with lipopolysaccharide (LPS) in vitro. In our study, NG2 + cells were isolated from the human dental pulp by magnetic‐activated cell sorting, and these isolated cells were proven to be NG2 + by immunostaining. When compared with human dental pulp cells (hDPCs), the NG2 + cells showed no significant differences in cell migration with or without LPS incubation, but their proliferative ability was weaker. When treated with LPS, NG2 + cells expressed elevated levels of pro‐inflammatory cytokines including interleukin‐1β (IL‐1β), IL‐6, IL‐8, and tumor necrosis factor‐α, and among these, the expression of IL‐1β and IL‐6 were higher than that of hDPCs. Their multipotent differentiation potential was confirmed by the induction of odontoblastic and adipogenic differentiation, and LPS increased their odontoblastic differentiation capacity. In the odontoblastic differentiation process, Wnt5a, BMP2, and BMP7 mRNA were increased, while the canonical Wnt‐related genes were decreased. In conclusion, the LPS stimulation promotes the migration, proliferative, and odontoblastic differentiation ability of NG2 + cells from the human dental pulp in vitro, and bone morphogenetic protein and the noncanonical Wnt pathway may be involved in their odontoblastic differentiation. These results indicated their special roles in tooth injury repair and potential application in pulp regeneration. 相似文献
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136.
Yuqiu Wei Guicheng Zhang Ju Chen Jing Wang Changling Ding Xiaodong Zhang Jun Sun 《Ecology and evolution》2019,9(8):5003-5017
Picophytoplankton were investigated during spring 2015 and 2016 extending from near‐shore coastal waters to oligotrophic open waters in the eastern Indian Ocean (EIO). They were typically composed of Prochlorococcus (Pro), Synechococcus (Syn), and picoeukaryotes (PEuks). Pro dominated most regions of the entire EIO and were approximately 1–2 orders of magnitude more abundant than Syn and PEuks. Under the influence of physicochemical conditions induced by annual variations of circulations and water masses, no coherent abundance and horizontal distributions of picophytoplankton were observed between spring 2015 and 2016. Although previous studies reported the limited effects of nutrients and heavy metals around coastal waters or upwelling zones could constrain Pro growth, Pro abundance showed strong positive correlation with nutrients, indicating the increase in nutrient availability particularly in the oligotrophic EIO could appreciably elevate their abundance. The exceptional appearance of picophytoplankton with high abundance along the equator appeared to be associated with the advection processes supported by the Wyrtki jets. For vertical patterns of picophytoplankton, a simple conceptual model was built based upon physicochemical parameters. However, Pro and PEuks simultaneously formed a subsurface maximum, while Syn generally restricted to the upper waters, significantly correlating with the combined effects of temperature, light, and nutrient availability. The average chlorophyll a concentrations (Chl a) of picophytoplankton accounted for above 49.6% and 44.9% of the total Chl a during both years, respectively, suggesting that picophytoplankton contributed a significant proportion of the phytoplankton community in the whole EIO. 相似文献
137.
The diphenyleneiodonium (DPI) is widely used as an inhibitor of flavoenzymes, particularly NADPH oxidase. In this study, we investigated the effect of DPI on the apoptosis of human RPE cells. DPI treatment in ARPE-19 cells evoked a dose- and time-dependent growth inhibition, and also induced DNA fragmentation and protein content of the proapoptotic factor Bax. In addition, DPI significantly induced the expression and phosphorylation of p53, which induces proapoptotic genes in response to DNA damage or irreparable cell cycle arrest. ROS have been implicated as a key factor in the activation of p53 by many chemotherapeutic drugs. Recent data on the regulation of intracellular ROS by DPI are controversial. Therefore, we analyzed whether DPI could contribute to the generation of intracellular ROS. Although there was increase in ROS level from cells treated for 24h with DPI, it was not detectable at early time points, required to induce p53 expression. And DPI-induced p53 expression was not affected by the ROS scavenger NAC. We conclude that DPI induces the expression of p53 by ROS-independent mechanism in ARPE-19 cells, and renders cells sensitive to drug-induced apoptosis by induction of p53 expression. 相似文献
138.
Glycine is an inhibitory neurotransmitter in the spinal cord and brain stem, where it acts on strychnine-sensitive glycine receptors, and is also an excitatory neurotransmitter throughout the brain and spinal cord, where it acts on the N-methyl-d-aspartate family of receptors. There are two Na(+)/Cl(-)-dependent glycine transporters, GLYT1 and GLYT2, which control extracellular glycine concentrations and these transporters show differences in substrate selectivity and blocker sensitivity. A bacterial Na(+)-dependent leucine transporter (LeuT(Aa)) has recently been crystallized and its structure determined. When the amino acid residues within the leucine binding site of LeuT(Aa) are aligned with residues of the two glycine transporters there are a number of identical residues and also some key differences. In this report, we demonstrate that the LeuT(Aa) structure represents a good working model of the Na(+)/Cl(-)-dependent neurotransmitters and that differences in substrate selectivity can be attributed to a single difference of a glycine residue in transmembrane domain 6 of GLYT1 for a serine residue at the corresponding position of GLYT2. 相似文献
139.
本文旨在探讨分子佐剂C3d3与hCGβ融合在基因免疫中增强抗hCGβ体液免疫效应的机制。分别用质粒pCMV4-hCGB-C3d3、pCMV4-hCGβ和pCMV4免疫BALB/c小鼠,间接ELISA法检测免疫小鼠外周血IgG/IgA类抗hCGβ抗体水平;ELISPOT分析免疫鼠脾脏组织IgG/IgA类抗体分泌细胞水平(ASC);RT-PCR分析免疫鼠脾脏B细胞趋化因子受体表达,RT-PCR和FCM分析CXCR4表达水平;RT-PCR和ELISA检测脾脏组织CXCL12表达水平。结果显示,pCMV4- hCGβ-C3d3免疫组外周血IgG类抗hCGβ抗体水平明显高于pCMV4-hCGβ免疫组;而IgA类抗hCGβ抗体水平在两组间无明显差异。pCMV4-hCGβ-C3d3免疫组脾脏组织IgG类ASCs水平明显高于pCMV4-hCGβ组;两组间IgA类ASCs水平无明显差异。经pCMV4-hCGB、pCMV4-hCGβ- C3d3免疫鼠脾脏B细胞CXCR4表达明显高于对照组;且pCMV4-hCGβ-C3d3组明显高于pCMV4-hCGβ免疫组。CXCR4~ 细胞与ASCs呈正相关,r=0.966,(P<0.05)。pCMV4-hCGβ-C3d3和pCMV4-hCGβ组脾脏组织CXC L12表达均显著高于对照组。结果表明,分子佐剂C3d3与hCGβ基因融合,在基因免疫小鼠后能够显著升调节脾脏ASCs CXCR4表达,从而可能增强抗hcGβ基因疫苗的体液免疫效应。 相似文献
140.
太空诱变玉米核不育材料花粉败育的细胞学观察(简报) 总被引:1,自引:0,他引:1
玉米是最早利用雄性不育系生产杂交种的作物之一。在玉米T型细胞质雄性不育杂交种遭受毁灭性病害侵袭之后,科学家认识到利用细胞质雄性不育制种存在潜在的遗传脆弱性,从此试图通过多种途径来创造新的雄性不育.并对雄性不育材料的遗传多样性进行研究。空间诱变育种是80年代于我国发展起来的新技术,在农作物品种改良和种质创新上已初见成效。[第一段] 相似文献