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61.
Xia M Hou C Demong D Pollack S Pan M Brackley J Singer M Matheis M Cavender D Wachter M 《Bioorganic & medicinal chemistry letters》2008,18(12):3562-3564
The synthesis and biological evaluation of a series of substituted dipiperidine alcohols are described. Structure-activity relationship studies led to the discovery of potent CCR2 antagonists displaying IC(50) values in the nanomolar or subnanomolar range. The cinnamoyl compounds had higher binding affinities than the corresponding urea analogs. 相似文献
62.
ABSTRACT: BACKGROUND: Lipase from Rhizopus chinensis is a versatile biocatalyst for various bioconversions and has been expressed at high-level in Pichia pastoris. However, the use of R. chinensis lipase in industrial applications is restricted by its low thermostability. Directed evolution has been proven to be a powerful and efficient protein engineering tool for improvement of biocatalysts. The present work describes improvement of the thermostability of R. chinensis lipase by directed evolution using P. pastoris as the host. RESULTS: An efficient, fast and highly simplified method was developed to create a mutant gene library in P. pastoris based on in vivo recombination, whose recombination efficiency could reach 2.3 x 105 /mug DNA. The thermostability of r27RCL was improved significantly by two rounds of error-prone PCR and two rounds of DNA shuffling in P. pastoris. The S4-3 variant was found to be the most thermostable lipase, under the conditions tested. Compared with the parent, the optimum temperature of S4-3 was two degrees higher, Tm was 22 degrees higher and half-lives at 60degreesC and 65degreesC were 46- and 23- times longer. Moreover, the catalytic efficiency kcat/Km of S4-3 was comparable to the parent. Stabilizing mutations probably increased thermostability by increasing the hydrophilicity and polarity of the protein surface and creating hydrophobic contacts inside the protein. CONCLUSIONS: P. pastoris was shown to be a valuable cell factory to improve thermostability of enzymes by directed evolution and it also could be used for improving other properties of enzymes. In this study, by using P. pastoris as a host to build mutant pool, we succeeded in obtaining a thermostable variant S4-3 without compromising enzyme activity and making it a highly promising candidate for future applications at high temperatures. 相似文献
63.
Larix principis-rupprechtii forest is an important vegetation formation and has a large distribution area in Luya Mountain Reserve, China. Spatial pattern
analysis on individual trees in different age-classes of Larix principis-rupprechtii was made in this paper. Here, we employed the technique of point pattern analysis, which could analyze patterns under all
scales along a gradient. It was based on spatial mapped points of individual distribution. The results of this study showed
that the densities of the five age-classes varied in the order: age-class 3 > age-class 4 > age-class 5 > age-class 2 > age-class
1. Although age-classes 1 and 2 have much fewer individuals than other three age-classes do, the population was stable at
present. However, it would be necessary to take some measures for improving population regeneration for a long-time view.
The individuals of all age-classes focused on clumping distribution in space; however, their distribution pattern varied with
the change of scale. This mainly depended on biological features of Larix principis-rupprechtii and forest environments, but it also meant that the scale was an important factor in controlling spatial distribution pattern
of tree individuals. The feature of clumping distribution became more significant with the increase of age. The relationships
between individuals in different age-classes were almost all significantly correlated with each other. These associations
became more significant within the older age-classes. This suggested that the individuals of different age-classes were interdistributed,
by which the population could get benefits in resource utilization. The technique of point pattern analysis is effective and
easy to be used in species pattern study. Its results are more closer to the reality, especially for community structure.
Translated from Acta Ecologica Sinica, 2004, 24(1): 35–40 [译自: 生态学报] 相似文献
64.
S.N. Wang P. Xu H.Z. Tang J. Meng X.L. Liu J. Huang H. Chen Y. Du H.D. Blankespoor 《Biotechnology letters》2005,26(19):1493-1496
A Pseudomonas sp. grew with nicotine optimally 3 g l–1 and at 30 °C and pH 7. Nicotine was fully degraded within 10 h. The resting cells degraded nicotine in tobacco solid waste completely within 6 h in 0.02 m sodium phosphate buffer (pH 7) at maximally 56 mg nicotine h–1 g dry cell–1. 相似文献
65.
Yiliang?LiuEmail authorView authors OrcID profile
return OK on get Yawen?Hua Anying?Yan Shuang?Wu Fanjie?Kong 《Journal of molecular modeling》2017,23(1):19
One-dimensional (1D) gold nanostructures have been extensively studied due to their potential applications in nanoelectronic devices. Using first-principles calculations, composites consisting of a well-defined linear Au n (n?=?2–4) chain encapsulated in a (9,0) single-walled carbon nanotube (SWCNT) were studied. The translational energy barrier of a single Au atom in a (9,0) SWCNT was found to be 0.03 eV. This low barrier guaranteed the formation of Au n @ (9,0) SWCNT (n?=?1–4) composites. Bond lengths, differential charge densities, and electronic band structures of the composites were studied. The average Au–Au bond lengths in the composites were found to be almost the same as those in the corresponding free-standing linear Au n . The average bond length increased as the number of Au atoms increased. Charge transfer in all of these composites was slight, although a few valence electrons were transferred from the (9,0) SWCNT and the Au chains to intercalations. The conductivities of the encapsulated linear Au n (n?=?2–4) chains were enhanced to some extent by encapsulating them in the SWCNT. 相似文献
66.
Background
Fructans – β-D-fructofuranosyl polymers with a sucrose starter unit – constitute a carbohydrate reservoir synthesised by a considerable number of bacteria and plant species. Biosynthesis of levan (αGlc(1–2)βFru [(2–6)βFru]n), an abundant form of bacterial fructan, is catalysed by levansucrase (sucrose:2,6-β-D-fructan-6-β-D-fructosyl transferase), utilizing sucrose as the sole substrate. Previously, we described the tertiary structure of Bacillus subtilis levansucrase in the ligand-free and sucrose-bound forms, establishing the mechanistic roles of three invariant carboxylate side chains, Asp86, Asp247 and Glu342, which are central to the double displacement reaction mechanism of fructosyl transfer. Still, the structural determinants of the fructosyl transfer reaction thus far have been only partially defined. 相似文献67.
Ran Liu Miao Yang Yanli Meng Juan Liao Jingyi Sheng Yuepu Pu Lihong Yin Sun Jung Kim 《PloS one》2013,8(10)
Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC) was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and invasion capability, as well as apoptosis. Luciferase reporter assay and Western blot analysis were performed to determine the target gene regulated by miR-139-5p. The mRNA level of NR5A2, the target gene of miR-139-5p, was determined in ESCC patients. Results showed that reduced miR-139-5p level was associated with lymph node metastases of ESCC. MiR-139-5p was investigated to induce cell cycle arrest in the G0/G1 phase and to suppress the invasive capability of esophageal carcinoma cells by targeting the 3′UTR of oncogenic NR5A2. Cyclin E1 and MMP9 were confirmed to participate in cell cycle arrest and invasive suppression induced by NR5A2, respectively. Pearson correlation analysis further confirmed the significantly negative correlation between miR-139-5p and NR5A2 expression. The results suggest that miR-139-5p exerts a growth- and invasiveness-suppressing function in human ESCCs, which demonstrates that miR-139-5p is a potential biomarker for early diagnosis and prognosis and is a therapeutic target for ESCC. 相似文献
68.
Solar Cells: Synergic Interface Optimization with Green Solvent Engineering in Mixed Perovskite Solar Cells (Adv. Energy Mater. 20/2017) 下载免费PDF全文
69.
Hai Hu Hong Li Feng Jiao Ting Han Meng Zhuo Jiujie Cui Yixue Li Liwei Wang 《Journal of hematology & oncology》2017,10(1):158
Background
Multiple primary cancers (MPC) have been identified as two or more cancers without any subordinate relationship that occur either simultaneously or metachronously in the same or different organs of an individual. Lynch syndrome is an autosomal dominant genetic disorder that increases the risk of many types of cancers. Lynch syndrome patients who suffer more than two cancers can also be considered as MPC; patients of this kind provide unique resources to learn how genetic mutation causes MPC in different tissues.Methods
We performed a whole genome sequencing on blood cells and two tumor samples of a Lynch syndrome patient who was diagnosed with five primary cancers. The mutational landscape of the tumors, including somatic point mutations and copy number alternations, was characterized. We also compared Lynch syndrome with sporadic cancers and proposed a model to illustrate the mutational process by which Lynch syndrome progresses to MPC.Results
We revealed a novel pathologic mutation on the MSH2 gene (G504 splicing) that associates with Lynch syndrome. Systematical comparison of the mutation landscape revealed that multiple cancers in the proband were evolutionarily independent. Integrative analysis showed that truncating mutations of DNA mismatch repair (MMR) genes were significantly enriched in the patient. A mutation progress model that included germline mutations of MMR genes, double hits of MMR system, mutations in tissue-specific driver genes, and rapid accumulation of additional passenger mutations was proposed to illustrate how MPC occurs in Lynch syndrome patients.Conclusion
Our findings demonstrate that both germline and somatic alterations are driving forces of carcinogenesis, which may resolve the carcinogenic theory of Lynch syndrome.70.