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排序方式: 共有586条查询结果,搜索用时 15 毫秒
31.
Cheng Guo Peter R. Guzzo Mark Hadden Bruce J. Sargent Larry Yet Yanqing Kan Oksana Palyha Theresa M. Kelly Xiaoming Guan Kim Rosko Karen Gagen Joseph M. Metzger Jasminka Dragovic Kathryn Lyons Linus S. Lin Ravi P. Nargund 《Bioorganic & medicinal chemistry letters》2010,20(9):2785-2789
The original structure of a high-throughput screening hit obtained from an external vendor was revised based on multiple NMR studies. The active compound was re-synthesized via a novel route and its structure and biological activity as a BRS-3 agonist were unambiguously confirmed. Multi-gram quantities of the hit were prepared for pharmacokinetic and efficacy studies. The synthetic strategy allowed for the preparation of multiple analogs for SAR exploration. 相似文献
32.
Hom RA Vora M Regner M Subach OM Cho W Verkhusha VV Stahelin RV Kutateladze TG 《Journal of molecular biology》2007,373(2):412-423
Epsin and AP180 are essential components of the endocytotic machinery, which controls internalization of protein receptors and other macromolecules at the cell surface. Epsin and AP180 are recruited to the plasma membrane by their structurally and functionally related N-terminal ENTH and ANTH domains that specifically recognize PtdIns(4,5)P2. Here, we show that membrane anchoring of the ENTH and ANTH domains is regulated by the acidic environment. Lowering the pH enhances PtdIns(4,5)P2 affinity of the ENTH and ANTH domains reinforcing their association with lipid vesicles and monolayers. The pH dependency is due to the conserved histidine residues of the ENTH and ANTH domains, protonation of which is necessary for the strong PtdIns(4,5)P2 recognition, as revealed by liposome binding, surface plasmon resonance, NMR, monolayer surface tension and mutagenesis experiments. The pH sensitivity of the ENTH and ANTH domains is reminiscent to the pH dependency of the FYVE domain suggesting a common regulatory mechanism of membrane anchoring by a subset of the PI-binding domains. 相似文献
33.
Serum soluble Fas ligand (sFasL) in patients with primary squamous cell carcinoma of the esophagus 总被引:1,自引:0,他引:1
Kozlowski M Kowalczuk O Sulewska A Dziegielewski P Lapuc G Laudanski W Niklinska W Chyczewski L Niklinski J Laudanski J 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2007,45(3):199-204
Esophageal carcinomas have been shown to express Fas ligand (FasL) and down-regulate Fas to escape from host immune surveillance. Circulating soluble FasL (sFasL) has been suggested to provide protection from Fas-mediated apoptosis. The aim of this study was to assess serum sFasL levels in esophageal cancer. The pretreatment levels of sFasL in the serum of 100 patients with esophageal squamous cell cancer and 41 healthy volunteers were determined by ELISA. Probability of survival was calculated according to the method of Kaplan-Meier. The prognostic influence of high and low level of sFasL was analyzed with the log-rank test. The mean serum level of sFasL in patients with esophageal cancer was significantly higher than that in healthy donors (1.567+/-1.786 vs 0.261+/-0.435, p<0.0001). The levels of serum sFasL were significantly higher in advanced stages (II vs IV p<0.034; III vs IV p<0.041; except II vs III p=0.281), patients with lymph node (N0 vs N1 p<0.0389) or distant (M0 vs. M1 p<0.0388) metastases and significantly lower in patients with well differentiated tumors (G1 vs G2 p<0.0272). The serum levels of soluble FasL were not related to gender, age, tumor size, T-stage, tobacco smoking and history of chronic alcohol intake. The survival difference between pretreatment high and low level of sFasL in surgery and chemio- and/or radiotherapy group was not statistically significant (p=0.525; p=0.840). Our results indicate that elevated serum sFasL levels might be associated with a disease progression in patients with esophageal squamous cell carcinoma. 相似文献
34.
Non-CpG methylation occurring in the context of CNG sequences is found in plants at a large number of genomic loci. However, there is still little information available about non-CpG methylation in mammals. Efficient methods that would allow detection of scarcely localized methylated sites in small quantities of DNA are required to elucidate the biological role of non-CpG methylation in both plants and animals. In this study, we tested a new whole genome approach to identify sites of CCWGG methylation (W is A or T), a particular case of CNG methylation, in genomic DNA. This technique is based on digestion of DNAs with methylation-sensitive restriction endonucleases EcoRII-C and AjnI. Short DNAs flanking methylated CCWGG sites (tags) are selectively purified and assembled in tandem arrays of up to nine tags. This allows high-throughput sequencing of tags, identification of flanking regions, and their exact positions in the genome. In this study, we tested specificity and efficiency of the approach. 相似文献
35.
Lunina NA Agafonova EV Chekanovskaya LA Dvortsov IA Berezina OV Shedova EN Kostrov SV Velikodvorskaya GA 《Protein expression and purification》2007,54(1):18-23
A cluster of Thermotoga neapolitana genes participating in starch degradation includes the malG gene of sugar transport protein and the aglB gene of cyclomaltodextrinase. The start and stop codons of these genes share a common overlapping sequence, aTGAtg. Here, we compared properties of expression products of three different constructs with aglB from T. neapolitana. The first expression vector contained the aglB gene linked to an upstream 90-bp 3'-terminal region of the malG gene with the stop codon overlapping with the start codon of aglB. The second construct included the isolated coding sequence of aglB with two tandem potential start codons. The expression product of this construct in Escherichia coli had two tandem Met residues at its N terminus and was characterized by low thermostability and high tendency to aggregate. In contrast, co-expression of aglB and the 3'-terminal region of malG (the first construct) resulted in AglB with only one N-terminal Met residue and a much higher specific activity of cyclomaltodextrinase. Moreover, the enzyme expressed by such a construct was more thermostable and less prone to aggregation. The third construct was the same as the second one except that it contained only one ATG start codon. The product of its expression had kinetic and other properties similar to those of the enzyme with only one N-terminal Met residue. 相似文献
36.
Studneva Irina M. Veselova Oksana M. Dobrokhotov Igor V. Serebryakova Larisa I. Palkeeva Marina E. Molokoedov Alexander S. Azmuko Andrey A. Ovchinnikov Michael V. Sidorova Maria V. Pisarenko Oleg I. 《Biochemistry. Biokhimii?a》2022,87(4):346-355
Biochemistry (Moscow) - Neuropeptide galanin and its N-terminal fragments reduce the generation of reactive oxygen species and normalize metabolic and antioxidant states of myocardium in... 相似文献
37.
38.
Roldan M de Guia Adam J Rose Anke Sommerfeld Oksana Seibert Daniela Strzoda Annika Zota Yvonne Feuchter Anja Krones‐Herzig Tjeerd Sijmonsma Milen Kirilov Carsten Sticht Norbert Gretz Geesje Dallinga‐Thie Sven Diederichs Nora Klöting Matthias Blüher Mauricio Berriel Diaz Stephan Herzig 《The EMBO journal》2015,34(3):344-360
In mammals, glucocorticoids (GCs) and their intracellular receptor, the glucocorticoid receptor (GR), represent critical checkpoints in the endocrine control of energy homeostasis. Indeed, aberrant GC action is linked to severe metabolic stress conditions as seen in Cushing's syndrome, GC therapy and certain components of the Metabolic Syndrome, including obesity and insulin resistance. Here, we identify the hepatic induction of the mammalian conserved microRNA (miR)‐379/410 genomic cluster as a key component of GC/GR‐driven metabolic dysfunction. Particularly, miR‐379 was up‐regulated in mouse models of hyperglucocorticoidemia and obesity as well as human liver in a GC/GR‐dependent manner. Hepatocyte‐specific silencing of miR‐379 substantially reduced circulating very‐low‐density lipoprotein (VLDL)‐associated triglyceride (TG) levels in healthy mice and normalized aberrant lipid profiles in metabolically challenged animals, mediated through miR‐379 effects on key receptors in hepatic TG re‐uptake. As hepatic miR‐379 levels were also correlated with GC and TG levels in human obese patients, the identification of a GC/GR‐controlled miRNA cluster not only defines a novel layer of hormone‐dependent metabolic control but also paves the way to alternative miRNA‐based therapeutic approaches in metabolic dysfunction. 相似文献
39.
40.
Leonid Fedorenko Sergey Mamykin Oksana Lytvyn Yulia Burlachenko Boris Snopok 《Plasmonics (Norwell, Mass.)》2011,6(2):363-371
The physical mechanisms of metallic nanoparticles formation by laser technology were studied. The system air/Au film/glass
was irradiated by laser at the conditions of surface plasmon resonance. A surface electromagnetic wave was excited in Kretchmann
configuration by the fundamental and second harmonics of the Q-switched YAG/Nd+3 laser with pulse power density close to the threshold of melting. Nanostructuring of Au film was observed only for the second
harmonic (λ = 0.532 μm) irradiation at the surface plasmon polariton resonance (SPR) conditions. Estimations were done using the interference
model of the differently directed plasmon polariton waves excited by a surface electromagnetic wave on the metal surface.
It was shown that a regular pattern of locally heated spots can be formed in a metallic film by pulsed laser irradiation.
The spatial distribution of this pattern is close to the period of interference. The observed effect of laser nanofragmentation
is explained by the self-organization of plasmon polariton subsystem in the process of Au nanoparticles formation at high
laser intensity levels. These methods open new possibilities for nanostructured surfaces formation utilizing simple self-organization
processes. 相似文献