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排序方式: 共有247条查询结果,搜索用时 8 毫秒
121.
将大鼠酰胺化酶的信号肽及前导肽编码序列引入昆虫核多角体病毒转移表达载体,构建PABChGRF(Gly)、PABCIGFI融合基因的昆虫细胞分泌表达质粒pBacPAG2、pBacPAI,并与经修饰的银纹夜蛾核多角体病毒BacPAK6线性化DNA共转染秋粘虫细胞Sf21,通过同源重组、筛选和鉴定,得到它们的重组病毒BacPAG、BacPAI。将重组病毒感染Sf21细胞,PABChGRF(Gly)和PABCIGFI均得到有效外泌表达,表达产物通过IgGSepharose柱可获得快速纯化。 相似文献
122.
The NMDA receptor (NMDAR) family of l-glutamate receptors are well known to have diverse roles in CNS function as well as in various neuropathological and psychiatric conditions. Until recently, the types of agents available to pharmacologically regulate NMDAR function have been quite limited in terms of mechanism of action and subtype selectivity. This has changed significantly in the past two years. The purpose of this review is to summarize the many drug classes now available for modulating NMDAR activity. Previously, this included competitive antagonists at the l-glutamate and glycine binding sites, high and low affinity channel blockers, and GluN2B-selective N-terminal domain binding site antagonists. More recently, we and others have identified new classes of NMDAR agents that are either positive or negative allosteric modulators (PAMs and NAMs, respectively). These compounds include the pan potentiator UBP646, the GluN2A-selective potentiator/GluN2C and GluN2D inhibitor UBP512, the GluN2D-selective potentiator UBP551, the GluN2C/GluN2D-selective potentiator CIQ as well as the new NMDAR-NAMs such as the pan-inhibitor UBP618, the GluN2C/GluN2D-selective inhibitor QZN46 and the GluN2A inhibitors UBP608 and TCN201. These new agents do not bind within the l-glutamate or glycine binding sites, the ion channel pore or the N-terminal regulatory domain. Collectively, these new allosteric modulators appear to be acting at multiple novel sites on the NMDAR complex. Importantly, these agents display improved subtype-selectivity and as NMDAR PAMs and NAMs, they represent a new generation of potential NMDAR therapeutics. 相似文献
123.
Pongsak Khunrae Madeleine Dahlbäck Morten A. Nielsen Sisse B. Ditlev Vera V. Pinto Matthew K. Higgins 《Journal of molecular biology》2010,397(3):826-1133
Plasmodium falciparum malaria remains one of the world's leading causes of human suffering and poverty. Each year, the disease takes 1-3 million lives, mainly in sub-Saharan Africa. The adhesion of infected erythrocytes (IEs) to vascular endothelium or placenta is the key event in the pathogenesis of severe P. falciparum infection. In pregnant women, the parasites express a single and unique member of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family named VAR2CSA, which is associated with the ability of the IEs to adhere specifically to chondroitin sulphate A (CSA) in the placenta. Several Duffy-binding-like domains from VAR2CSA molecules have been shown in vitro to bind to CSA, but it has also been demonstrated that Duffy-binding-like domains from PfEMP1 proteins other than VAR2CSA can bind CSA. In addition, the specificity of the binding of VAR2CSA domains to glycosaminoglycans does not match that of VAR2CSA-expressing IEs. This has led to speculation that the domains of native VAR2CSA need to come together to form a specific binding site or that VAR2CSA might bind to CSA through a bridging molecule. Here, we describe the expression and purification of the complete extracellular region of VAR2CSA secreted at high yields from insect cells. Using surface plasmon resonance, we demonstrate that VAR2CSA alone binds with nanomolar affinity to human chondroitin sulphate proteoglycan and with significantly weaker affinity to other glycosaminoglycans, showing a specificity similar to that observed for IEs. Antibodies raised against full-length VAR2CSA completely inhibit recombinant VAR2CSA binding, as well as parasite binding to chondroitin sulphate proteoglycan. This is the first study to describe the successful production and functionality of a full-length PfEMP1. The specificity of the binding and anti-adhesion potency of induced IgG, together with high-yield production, encourages the use of full-length PfEMP1 in vaccine development strategies. 相似文献
124.
猪圆环病毒2型与猪细小病毒共感染对猪肺泡巨噬细胞吞噬功能及其干扰素表达水平的影响 总被引:1,自引:0,他引:1
【目的】分析猪圆环病毒2型(PCV2)与猪细小病毒(PPV)共感染对猪肺泡巨噬细胞(PAM)吞噬功能及其干扰素表达水平的影响,为进一步阐明猪断奶后多系统衰减综合征的发病机制提供实验依据。【方法】将48头5周龄健康仔猪随机分为PCV2组、PPV组、PCV2/PPV组和对照组,每组12头。PCV2和PPV组经口鼻途径分别接种PCV2或PPV,PCV2/PPV组同时接种PCV2和PPV,对照组接种细胞营养液。感染后3、7、14和35d(dpi)从每组随机选择3头剖杀,检测PAM的存活率、吞噬活性及其α1型干扰素(IFN-α1)、γ干扰素(IFN-γ)mRNA的表达水平。【结果】PCV2组和PCV2/PPV组PAM的存活率于3、7、14dpi均低于对照组,35dpi均与对照组PAM的存活率接近,PCV2与PCV2/PPV两组之间差异不显著(P>0.05);3个病毒感染组PAM的吞噬功能均显著下降(P<0.01),其中PCV2/PPV组的吞噬功能低于PCV2组(P<0.05);PCV2/PPV组PAM中IFN-α1和IFN-γ mRNA的水平持续低于PCV2、PPV组和对照组的水平(P<0.01)。【结论】PCV2与PPV共感染没有引起PAM的活力进一步下降,但导致其吞噬功能及IFN-α1和IFN-γmRNA的表达水平持续降低。 相似文献
125.
F.Gevaert A.Creach D.Davoult A.-C.Holl L.Seuront & Y.Lemoine 《Plant, cell & environment》2002,25(7):859-872
Laminaria saccharina (Lamouroux) form the largest, most abundant and conspicuous seaweed populations along the French coast of the eastern English Channel. As they are located in the intertidal zone, they are exposed to considerable irradiance variations, mainly related to tidal cycles. The response of these macro‐algae to light variations over a simulated daily tidal cycle was investigated in the laboratory during spring, autumn and winter using chlorophyll fluorescence and pigment analysis. The maximum quantum yield of photosystem II (PSII) photochemistry (Fv/Fm) and the operating PSII efficiency (ΦPSII) showed clear daily cycles according to the irradiance variation throughout the 12 h simulated tidal cycle, whereas the pattern of the relative photosynthetic electron transport rate (rETR) was not so obvious. The algae reacted to the light increase by developing photoprotective mechanisms able to dissipate the excess energy reaching PSII by the de‐epoxidation of violaxanthin into zeaxanthin. Because of their better acclimation to strong irradiance, spring populations were less affected by this light treatment than were winter populations. In particular, L. saccharina showed more pigments of the xanthophyll cycle in spring to cope with strong irradiance exposure. Alternatively, they developed their antenna complexes in winter to harvest a maximum of light. 相似文献
126.
规律成簇的间隔短回文重复序列(clustered regularly interspaced short palindromic repeats,CRISPR)是原核生物的适应性免疫系统,对抗外来遗传物质(如质粒和噬菌体)的攻击。近年来,科学家们发现了一种新型基因编辑工具,一种强大的分子剪刀CRISPR/Cas12a系统,该系统在对靶标DNA进行切割的同时还具有对体系内单链DNA进行任意切割的活性,并将其转移到体外检测系统。本文对CRISPR/Cas12a系统组成、结构、Cas12a与Cas9的对比和CRISPR/Cas12a系统在核酸检测中的应用进行了综述。 相似文献
127.
N. G. A. Ekelund C. A. Nygård R. Nordström A. M. Gylle 《Journal of applied phycology》2008,20(5):751-756
The brown alga Fucus vesiculous is one of the few marine species in the Baltic Sea. Fucus vesiculosus shows high morphological and physiological variability as a response to its environmental conditions. The salinity in the
Baltic Sea is 4–5 psu, compared to 35 psu in the Atlantic. Photosynthesis of algae is usually measured after collection and
transportation to constant culture conditions. However, in this study, relative photosynthetic electron transport rates, calculated
from chlorophyll a fluorescence parameters were compared in algae collected from 1 and 4 m depths by SCUBA divers. Measurements of light response
curves from the same individuals of F. vesiculosus at different depths and times of the year have, to our knowledge, not been made previously. Measurements were performed on
four different occasions during the spring of 2005 (25 February, 3 and 29 April, and 26 May) in the Baltic Sea, using rapid
light curves generated with a Diving PAM. In addition, samples were collected for photoinhibition studies in the laboratory.
The light response curves obtained in situ at 1 and 4 m depths for F. vesiculosus showed lower values of light saturation with depth. When algae from 1 and 4 m depths were exposed to high irradiances of
photosynthetically active radiation (1,400 μmol photons m−2 s−1), algae from 1 m depth showed a higher degree of photoinhibition in comparison to algae from 4 m depth. 相似文献
128.
Lamb JP Engers DW Niswender CM Rodriguez AL Venable DF Conn PJ Lindsley CW 《Bioorganic & medicinal chemistry letters》2011,21(9):2711-2714
This Letter describes a chemical lead optimization campaign directed at a weak mGlu5 NAM discovered while developing SAR for the mGlu5 PAM, ADX-47273. An iterative parallel synthesis effort discovered multiple, subtle molecular switches that afford potent mGlu5 NAMs, mGlu5 PAMs as well as mGlu5 partial antagonists. 相似文献
129.
《Bioorganic & medicinal chemistry letters》2019,29(21):126678
This Letter details our efforts to replace the 2,4-dimethylquinoline carboxamide core of our previous M4 PAM series, which suffered from high predicted hepatic clearance and protein binding. A scaffold hopping exercise identified a novel 3,4-dimethylcinnoline carboxamide core that provided good M4 PAM activity and improved clearance and protein binding profiles. 相似文献
130.
Jae-Sam Hwang Jin-Sung Lee Tae-Won Goo Eun-Young Yun Kwang-Sik Lee Yong-Sung Kim Byung-Rae Jin Sang-Mong Lee Keun-Young Kim Seok-Woo Kang Dong-Sang Suh 《Biotechnology letters》2001,23(16):1321-1326
The nucleotide sequences containing an entire genomic region and 5 upstream region of Antheraea yamamai fibroin gene have been determined. The gene consists of an initial exon encoding 14 amino acids, an intron (150 bp), and a long second exon coding for 2641 amino acids. The fibroin coding sequence shows a specialized organization with a highly repetitive region flanked by non repetitive 5 and 3 ends. Northern blot analyses confirmed that fibroin gene is actively expressed in the posterior silk gland of the final instar larvae of Antheraea yamamai. 相似文献