Chemistry & biology最新文献_第4页

XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans. XBP1s 将未折叠蛋白反应与成熟 N-聚糖的分子结构联系起来。

Chemistry & biology Pub Date : 2015-10-22 DOI: 10.1016/j.chembiol.2015.09.006

Mahender B Dewal, Andrew S DiChiara, Aristotelis Antonopoulos, Rebecca J Taylor, Chyleigh J Harmon, Stuart M Haslam, Anne Dell, Matthew D Shoulders

{"title":"XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans.","authors":"Mahender B Dewal, Andrew S DiChiara, Aristotelis Antonopoulos, Rebecca J Taylor, Chyleigh J Harmon, Stuart M Haslam, Anne Dell, Matthew D Shoulders","doi":"10.1016/j.chembiol.2015.09.006","DOIUrl":"10.1016/j.chembiol.2015.09.006","url":null,"abstract":"The molecular architecture of the mature N-glycome is dynamic, with consequences for both normal and pathologic processes. Elucidating cellular mechanisms that modulate the N-linked glycome is, therefore, crucial. The unfolded protein response (UPR) is classically responsible for maintaining proteostasis in the secretory pathway by defining levels of chaperones and quality control proteins. Here, we employ chemical biology methods for UPR regulation to show that stress-independent activation of the UPR's XBP1s transcription factor also induces a panel of N-glycan maturation-related enzymes. The downstream consequence is a distinctive shift toward specific hybrid and complex N-glycans on N-glycoproteins produced from XBP1s-activated cells, which we characterize by mass spectrometry. Pulse-chase studies attribute this shift specifically to altered N-glycan processing, rather than to changes in degradation or secretion rates. Our findings implicate XBP1s in a new role for N-glycoprotein biosynthesis, unveiling an important link between intracellular stress responses and the molecular architecture of extracellular N-glycoproteins. ","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 10","pages":"1301-12"},"PeriodicalIF":0.0,"publicationDate":"2015-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621487/pdf/nihms726150.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34180935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In-Depth High-Throughput Screening of Protein Engineering Libraries by Split-GFP Direct Crude Cell Extract Data Normalization. 利用Split-GFP直接粗细胞提取数据归一化技术深入筛选蛋白质工程文库。

Chemistry & biology Pub Date : 2015-10-22 Epub Date: 2015-10-01 DOI: 10.1016/j.chembiol.2015.08.014

Javier Santos-Aberturas, Mark Dörr, Geoffrey S Waldo, Uwe T Bornscheuer

{"title":"In-Depth High-Throughput Screening of Protein Engineering Libraries by Split-GFP Direct Crude Cell Extract Data Normalization.","authors":"Javier Santos-Aberturas, Mark Dörr, Geoffrey S Waldo, Uwe T Bornscheuer","doi":"10.1016/j.chembiol.2015.08.014","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.08.014","url":null,"abstract":"Here, we report a widely and generally applicable strategy to obtain reliable information in high-throughput protein screenings of enzyme mutant libraries. The method is based on the usage of the split-GFP technology for the normalization of the expression level of each individual protein variant combined with activity measurements, thus resolving the important problems associated with the different solubility of each mutant and allowing the detection of previously invisible variants. The small size of the employed protein tag (16 amino acids) required for the reconstitution of the GFP fluorescence reduces possible interferences such as enzyme activity variations or solubility disturbances to a minimum. Specific enzyme activity measurements without purification, in situ soluble protein expression monitoring, and data normalization are the powerful outputs of this methodology, thus enabling the accurate identification of improved protein variants during high-throughput screening by substantially reducing the occurrence of false negatives and false positives. ","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 10","pages":"1406-14"},"PeriodicalIF":0.0,"publicationDate":"2015-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.08.014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34235991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 32

Development of Potent and Selective Tissue Transglutaminase Inhibitors: Their Effect on TG2 Function and Application in Pathological Conditions. 高效和选择性组织转谷氨酰胺酶抑制剂的开发:对TG2功能的影响及其在病理条件下的应用。

Chemistry & biology Pub Date : 2015-10-22 Epub Date: 2015-10-09 DOI: 10.1016/j.chembiol.2015.08.013

Eduard Badarau, Zhuo Wang, Dan L Rathbone, Andrea Costanzi, Thomas Thibault, Colin E Murdoch, Said El Alaoui, Milda Bartkeviciute, Martin Griffin

{"title":"Development of Potent and Selective Tissue Transglutaminase Inhibitors: Their Effect on TG2 Function and Application in Pathological Conditions.","authors":"Eduard Badarau, Zhuo Wang, Dan L Rathbone, Andrea Costanzi, Thomas Thibault, Colin E Murdoch, Said El Alaoui, Milda Bartkeviciute, Martin Griffin","doi":"10.1016/j.chembiol.2015.08.013","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.08.013","url":null,"abstract":"Potent-selective peptidomimetic inhibitors of tissue transglutaminase (TG2) were developed through a combination of protein-ligand docking and molecular dynamic techniques. Derivatives of these inhibitors were made with the aim of specific TG2 targeting to the intra- and extracellular space. A cell-permeable fluorescently labeled derivative enabled detection of in situ cellular TG2 activity in human umbilical cord endothelial cells and TG2-transduced NIH3T3 cells, which could be enhanced by treatment of cells with ionomycin. Reaction of TG2 with this fluorescent inhibitor in NIH3T3 cells resulted in loss of binding of TG2 to cell surface syndecan-4 and inhibition of translocation of the enzyme into the extracellular matrix, with a parallel reduction in fibronectin deposition. In human umbilical cord endothelial cells, this same fluorescent inhibitor also demonstrated a reduction in fibronectin deposition, cell motility, and cord formation in Matrigel. Use of the same inhibitor in a mouse model of hypertensive nephrosclerosis showed over a 40% reduction in collagen deposition. ","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 10","pages":"1347-61"},"PeriodicalIF":0.0,"publicationDate":"2015-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.08.013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34247658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 31

Elucidation of DnaE as the Antibacterial Target of the Natural Product, Nargenicin. 天然产物Nargenicin抑菌靶点DnaE的研究。

Chemistry & biology Pub Date : 2015-10-22 Epub Date: 2015-10-08 DOI: 10.1016/j.chembiol.2015.08.015

Ronald E Painter, Gregory C Adam, Marta Arocho, Edward DiNunzio, Robert G K Donald, Karen Dorso, Olga Genilloud, Charles Gill, Michael Goetz, Nichelle N Hairston, Nicholas Murgolo, Bakela Nare, David B Olsen, Maryann Powles, Fred Racine, Jing Su, Francisca Vicente, Douglas Wisniewski, Li Xiao, Milton Hammond, Katherine Young

{"title":"Elucidation of DnaE as the Antibacterial Target of the Natural Product, Nargenicin.","authors":"Ronald E Painter, Gregory C Adam, Marta Arocho, Edward DiNunzio, Robert G K Donald, Karen Dorso, Olga Genilloud, Charles Gill, Michael Goetz, Nichelle N Hairston, Nicholas Murgolo, Bakela Nare, David B Olsen, Maryann Powles, Fred Racine, Jing Su, Francisca Vicente, Douglas Wisniewski, Li Xiao, Milton Hammond, Katherine Young","doi":"10.1016/j.chembiol.2015.08.015","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.08.015","url":null,"abstract":"Resistance to existing classes of antibiotics drives the need for discovery of novel compounds with unique mechanisms of action. Nargenicin A1, a natural product with limited antibacterial spectrum, was rediscovered in a whole-cell antisense assay. Macromolecular labeling in both Staphylococcus aureus and an Escherichia coli tolC efflux mutant revealed selective inhibition of DNA replication not due to gyrase or topoisomerase IV inhibition. S. aureus nargenicin-resistant mutants were selected at a frequency of ∼1 × 10(-9), and whole-genome resequencing found a single base-pair change in the dnaE gene, a homolog of the E. coli holoenzyme α subunit. A DnaE single-enzyme assay was exquisitely sensitive to inhibition by nargenicin, and other in vitro characterization studies corroborated DnaE as the target. Medicinal chemistry efforts may expand the spectrum of this novel mechanism antibiotic. ","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 10","pages":"1362-73"},"PeriodicalIF":0.0,"publicationDate":"2015-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.08.015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34247657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 28

Three Redundant Synthetases Secure Redox-Active Pigment Production in the Basidiomycete Paxillus involutus. 三种冗余合成酶保证担子菌氧化还原活性色素的生产。

Chemistry & biology Pub Date : 2015-10-22 DOI: 10.1016/j.chembiol.2015.08.016

Jana Braesel, Sebastian Götze, Firoz Shah, Daniel Heine, James Tauber, Christian Hertweck, Anders Tunlid, Pierre Stallforth, Dirk Hoffmeister

{"title":"Three Redundant Synthetases Secure Redox-Active Pigment Production in the Basidiomycete Paxillus involutus.","authors":"Jana Braesel, Sebastian Götze, Firoz Shah, Daniel Heine, James Tauber, Christian Hertweck, Anders Tunlid, Pierre Stallforth, Dirk Hoffmeister","doi":"10.1016/j.chembiol.2015.08.016","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.08.016","url":null,"abstract":"The symbiotic fungus Paxillus involutus serves a critical role in maintaining forest ecosystems, which are carbon sinks of global importance. P. involutus produces involutin and other 2,5-diarylcyclopentenone pigments that presumably assist in the oxidative degradation of lignocellulose via Fenton chemistry. Their precise biosynthetic pathways, however, remain obscure. Using a combination of biochemical, genetic, and transcriptomic analyses, in addition to stable-isotope labeling with synthetic precursors, we show that atromentin is the key intermediate. Atromentin is made by tridomain synthetases of high similarity: InvA1, InvA2, and InvA5. An inactive atromentin synthetase, InvA3, gained activity after a domain swap that replaced its native thioesterase domain with that of InvA5. The found degree of multiplex biosynthetic capacity is unprecedented with fungi, and highlights the great importance of the metabolite for the producer. ","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 10","pages":"1325-34"},"PeriodicalIF":0.0,"publicationDate":"2015-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.08.016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34113643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 40

Nuclear Pore Complex: From Structural View to Chemical Tools. 核孔复合物:从结构角度到化学工具。

Chemistry & biology Pub Date : 2015-10-22 DOI: 10.1016/j.chembiol.2015.10.001

Richard W Wong

引用次数: 15

Characterization of the Biosynthetic Gene Cluster for Benzoxazole Antibiotics A33853 Reveals Unusual Assembly Logic. 苯并恶唑类抗生素A33853生物合成基因簇的表征揭示了不同寻常的组装逻辑。

Chemistry & biology Pub Date : 2015-10-22 DOI: 10.1016/j.chembiol.2015.09.005

Meinan Lv, Junfeng Zhao, Zixin Deng, Yi Yu

{"title":"Characterization of the Biosynthetic Gene Cluster for Benzoxazole Antibiotics A33853 Reveals Unusual Assembly Logic.","authors":"Meinan Lv, Junfeng Zhao, Zixin Deng, Yi Yu","doi":"10.1016/j.chembiol.2015.09.005","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.09.005","url":null,"abstract":"A33853, which shows excellent bioactivity against Leishmania, is a benzoxazole-family compound formed from two moieties of 3-hydroxyanthranilic acid and one 3-hydroxypicolinic acid. In this study, we have identified the gene cluster responsible for the biosynthesis of A33853 in Streptomyces sp. NRRL12068 through genome mining and heterologous expression. Bioinformatics analysis and functional characterization of the orfs contained in the gene cluster revealed that the biosynthesis of A33853 is directed by a group of unusual enzymes. In particular, BomK, annotated as a ketosynthase, was found to catalyze the amide bond formation between 3-hydroxypicolinic and 3-hydroxyanthranilic acid during the assembly of A33853. BomJ, a putative ATP-dependent coenzyme A ligase, and BomN, a putative amidohydrolase, were further proposed to be involved in the benzoxazole formation in A33853 according to gene deletion experiments. Finally, we have successfully utilized mutasynthesis to generate two analogs of A33853, which were reported previously to possess excellent anti-leishmanial activity. ","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 10","pages":"1313-24"},"PeriodicalIF":0.0,"publicationDate":"2015-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.09.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34180934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 35

MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish. MEK抑制剂逆转斑马鱼camp介导的焦虑。

Chemistry & biology Pub Date : 2015-10-22 Epub Date: 2015-09-17 DOI: 10.1016/j.chembiol.2015.08.010

Pia R Lundegaard, Corina Anastasaki, Nicola J Grant, Rowland R Sillito, Judith Zich, Zhiqiang Zeng, Karthika Paranthaman, Anders Peter Larsen, J Douglas Armstrong, David J Porteous, E Elizabeth Patton

{"title":"MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish.","authors":"Pia R Lundegaard, Corina Anastasaki, Nicola J Grant, Rowland R Sillito, Judith Zich, Zhiqiang Zeng, Karthika Paranthaman, Anders Peter Larsen, J Douglas Armstrong, David J Porteous, E Elizabeth Patton","doi":"10.1016/j.chembiol.2015.08.010","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.08.010","url":null,"abstract":"Altered phosphodiesterase (PDE)-cyclic AMP (cAMP) activity is frequently associated with anxiety disorders, but current therapies act by reducing neuronal excitability rather than targeting PDE-cAMP-mediated signaling pathways. Here, we report the novel repositioning of anti-cancer MEK inhibitors as anxiolytics in a zebrafish model of anxiety-like behaviors. PDE inhibitors or activators of adenylate cyclase cause behaviors consistent with anxiety in larvae and adult zebrafish. Small-molecule screening identifies MEK inhibitors as potent suppressors of cAMP anxiety behaviors in both larvae and adult zebrafish, while causing no anxiolytic behavioral effects on their own. The mechanism underlying cAMP-induced anxiety is via crosstalk to activation of the RAS-MAPK signaling pathway. We propose that targeting crosstalk signaling pathways can be an effective strategy for mental health disorders, and advance the repositioning of MEK inhibitors as behavior stabilizers in the context of increased cAMP. ","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 10","pages":"1335-46"},"PeriodicalIF":0.0,"publicationDate":"2015-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.08.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34020127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 32

Fluorinated Sterols Are Suicide Inhibitors of Ergosterol Biosynthesis and Growth in Trypanosoma brucei. 氟化甾醇是布氏锥虫麦角甾醇合成和生长的自杀抑制剂。

Chemistry & biology Pub Date : 2015-10-22 DOI: 10.1016/j.chembiol.2015.08.017

David J Leaver, Presheet Patkar, Ujjal K Singha, Matthew B Miller, Brad A Haubrich, Minu Chaudhuri, W David Nes

{"title":"Fluorinated Sterols Are Suicide Inhibitors of Ergosterol Biosynthesis and Growth in Trypanosoma brucei.","authors":"David J Leaver, Presheet Patkar, Ujjal K Singha, Matthew B Miller, Brad A Haubrich, Minu Chaudhuri, W David Nes","doi":"10.1016/j.chembiol.2015.08.017","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.08.017","url":null,"abstract":"Trypanosoma brucei, the causal agent for sleeping sickness, depends on ergosterol for growth. Here, we describe the effects of a mechanism-based inhibitor, 26-fluorolanosterol (26FL), which converts in vivo to a fluorinated substrate of the sterol C24-methyltransferase essential for sterol methylation and function of ergosterol, and missing from the human host. 26FL showed potent inhibition of ergosterol biosynthesis and growth of procyclic and bloodstream forms while having no effect on cholesterol biosynthesis or growth of human epithelial kidney cells. During exposure of cloned TbSMT to 26-fluorocholesta-5,7,24-trienol, the enzyme is gradually killed as a consequence of the covalent binding of the intermediate C25 cation to the active site (kcat/kinact = 0.26 min(-1)/0.24 min(-1); partition ratio of 1.08), whereas 26FL is non-productively bound. These results demonstrate that poisoning of ergosterol biosynthesis by a 26-fluorinated Δ(24)-sterol is a promising strategy for developing a new treatment for trypanosomiasis. ","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":"22 10","pages":"1374-83"},"PeriodicalIF":0.0,"publicationDate":"2015-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.08.017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34113644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

Small-Molecule Reactivation of Mutant p53 to Wild-Type-like p53 through the p53-Hsp40 Regulatory Axis. 通过p53- hsp40调控轴，突变型p53小分子再激活为野生型p53。

Chemistry & biology Pub Date : 2015-09-17 Epub Date: 2015-08-27 DOI: 10.1016/j.chembiol.2015.07.016

Masatsugu Hiraki, So-Young Hwang, Shugeng Cao, Timothy R Ramadhar, Sanguine Byun, Kyoung Wan Yoon, Jung Hyun Lee, Kiki Chu, Aditi U Gurkar, Vihren Kolev, Jianming Zhang, Takushi Namba, Maureen E Murphy, David J Newman, Anna Mandinova, Jon Clardy, Sam W Lee

{"title":"Small-Molecule Reactivation of Mutant p53 to Wild-Type-like p53 through the p53-Hsp40 Regulatory Axis.","authors":"Masatsugu Hiraki, So-Young Hwang, Shugeng Cao, Timothy R Ramadhar, Sanguine Byun, Kyoung Wan Yoon, Jung Hyun Lee, Kiki Chu, Aditi U Gurkar, Vihren Kolev, Jianming Zhang, Takushi Namba, Maureen E Murphy, David J Newman, Anna Mandinova, Jon Clardy, Sam W Lee","doi":"10.1016/j.chembiol.2015.07.016","DOIUrl":"https://doi.org/10.1016/j.chembiol.2015.07.016","url":null,"abstract":"TP53 is the most frequently mutated gene in human cancer, and small-molecule reactivation of mutant p53 function represents an important anticancer strategy. A cell-based, high-throughput small-molecule screen identified chetomin (CTM) as a mutant p53 R175H reactivator. CTM enabled p53 to transactivate target genes, restored MDM2 negative regulation, and selectively inhibited the growth of cancer cells harboring mutant p53 R175H in vitro and in vivo. We found that CTM binds to Hsp40 and increases the binding capacity of Hsp40 to the p53 R175H mutant protein, causing a potential conformational change to a wild-type-like p53. Thus, CTM acts as a specific reactivator of the p53 R175H mutant form through Hsp40. These results provide new insights into the mechanism of reactivation of this specific p53 mutant.","PeriodicalId":9772,"journal":{"name":"Chemistry & biology","volume":" ","pages":"1206-16"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.chembiol.2015.07.016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33963732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 57