Acta crystallographica. Section D, Biological crystallography最新文献

{"title":"Structural basis for the sequestration of the anti-σ(70) factor Rsd from σ(70) by the histidine-containing phosphocarrier protein HPr.","authors":"Young Ha Park,&nbsp;Si Hyeon Um,&nbsp;Saemee Song,&nbsp;Yeong Jae Seok,&nbsp;Nam Chul Ha","doi":"10.1107/S1399004715013759","DOIUrl":"https://doi.org/10.1107/S1399004715013759","url":null,"abstract":"<p><p>Histidine-containing phosphocarrier protein (HPr) is a general component of the bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS) involved in the phosphorylation-coupled transport of numerous sugars called PTS sugars. HPr mainly exists in a dephosphorylated form in the presence of PTS sugars in the medium, while its phosphorylation increases in the absence of PTS sugars. A recent study revealed that the dephosphorylated form of HPr binds and antagonizes the function of the antisigma factor Rsd. This anti-sigma factor sequesters the housekeeping sigma factor σ(70) to facilitate switching of the sigma subunit on RNA polymerase from σ(70) to the stress-responsive sigma factor σ(S) in stationary-phase cells. In this study, the structure of the complex of Rsd and HPr was determined at 2.1 Å resolution and revealed that the binding site for HPr on the surface of Rsd partly overlaps with that for σ(70). The localization of the phosphorylation site on HPr at the binding interface for Rsd explains why phosphorylation of HPr abolishes its binding to Rsd. The mutation of crucial residues involved in the HPr-Rsd interaction significantly influenced the competition between HPr and σ(70) for binding to Rsd both in vitro and in vivo. The results provide a structural basis for the linkage of global gene regulation to nutrient availability in the external environment.</p>","PeriodicalId":7047,"journal":{"name":"Acta crystallographica. Section D, Biological crystallography","volume":"71 Pt 10","pages":"1998-2008"},"PeriodicalIF":0.0,"publicationDate":"2015-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34146659","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}

{"title":"Structure of RC1339/APRc from Rickettsia conorii, a retropepsin-like aspartic protease.","authors":"Mi Li, Alla Gustchina, Rui Cruz, Marisa Simões, Pedro Curto, Juan Martinez, Carlos Faro, Isaura Simões, Alexander Wlodawer","doi":"10.1107/S1399004715013905","DOIUrl":"10.1107/S1399004715013905","url":null,"abstract":"<p><p>The crystal structures of two constructs of RC1339/APRc from Rickettsia conorii, consisting of either residues 105-231 or 110-231 followed by a His tag, have been determined in three different crystal forms. As predicted, the fold of a monomer of APRc resembles one-half of the mandatory homodimer of retroviral pepsin-like aspartic proteases (retropepsins), but the quaternary structure of the dimer of APRc differs from that of the canonical retropepsins. The observed dimer is most likely an artifact of the expression and/or crystallization conditions since it cannot support the previously reported enzymatic activity of this bacterial aspartic protease. However, the fold of the core of each monomer is very closely related to the fold of retropepsins from a variety of retroviruses and to a single domain of pepsin-like eukaryotic enzymes, and may represent a putative common ancestor of monomeric and dimeric aspartic proteases.</p>","PeriodicalId":7047,"journal":{"name":"Acta crystallographica. Section D, Biological crystallography","volume":"71 Pt 10","pages":"2109-18"},"PeriodicalIF":0.0,"publicationDate":"2015-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601372/pdf/d-71-02109.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34079245","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}

{"title":"Comparison of epsilon- and delta-class glutathione S-transferases: the crystal structures of the glutathione S-transferases DmGSTE6 and DmGSTE7 from Drosophila melanogaster.","authors":"Michele Scian, Isolde Le Trong, Aslam M A Mazari, Bengt Mannervik, William M Atkins, Ronald E Stenkamp","doi":"10.1107/S1399004715013929","DOIUrl":"10.1107/S1399004715013929","url":null,"abstract":"Cytosolic glutathione transferases (GSTs) comprise a large family of enzymes with canonical structures that diverge functionally and structurally among mammals, invertebrates and plants. Whereas mammalian GSTs have been characterized extensively with regard to their structure and function, invertebrate GSTs remain relatively unstudied. The invertebrate GSTs do, however, represent potentially important drug targets for infectious diseases and agricultural applications. In addition, it is essential to fully understand the structure and function of invertebrate GSTs, which play important roles in basic biological processes. Invertebrates harbor delta- and epsilon-class GSTs, which are not found in other organisms. Drosophila melanogaster GSTs (DmGSTs) are likely to contribute to detoxication or antioxidative stress during development, but they have not been fully characterized. Here, the structures of two epsilon-class GSTs from Drosophila, DmGSTE6 and DmGSTE7, are reported at 2.1 and 1.5 Å resolution, respectively, and are compared with other GSTs to identify structural features that might correlate with their biological functions. The structures of DmGSTE6 and DmGSTE7 are remarkably similar; the structures do not reveal obvious sources of the minor functional differences that have been observed. The main structural difference between the epsilon- and delta-class GSTs is the longer helix (A8) at the C-termini of the epsilon-class enzymes.","PeriodicalId":7047,"journal":{"name":"Acta crystallographica. Section D, Biological crystallography","volume":"71 Pt 10","pages":"2089-98"},"PeriodicalIF":0.0,"publicationDate":"2015-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1107/S1399004715013929","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34146667","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}

{"title":"Structural basis for amino-acid recognition and transmembrane signalling by tandem Per-Arnt-Sim (tandem PAS) chemoreceptor sensory domains.","authors":"Yu C Liu,&nbsp;Mayra A Machuca,&nbsp;Simone A Beckham,&nbsp;Menachem J Gunzburg,&nbsp;Anna Roujeinikova","doi":"10.1107/S139900471501384X","DOIUrl":"https://doi.org/10.1107/S139900471501384X","url":null,"abstract":"<p><p>Chemotaxis, mediated by methyl-accepting chemotaxis protein (MCP) receptors, plays an important role in the ecology of bacterial populations. This paper presents the first crystallographic analysis of the structure and ligand-induced conformational changes of the periplasmic tandem Per-Arnt-Sim (PAS) sensing domain (PTPSD) of a characterized MCP chemoreceptor. Analysis of the complex of the Campylobacter jejuni Tlp3 PTPSD with isoleucine (a chemoattractant) revealed that the PTPSD is a dimer in the crystal. The two ligand-binding sites are located in the membrane-distal PAS domains on the faces opposite to the dimer interface. Mutagenesis experiments show that the five strongly conserved residues that stabilize the main-chain moiety of isoleucine are essential for binding, suggesting that the mechanism by which this family of chemoreceptors recognizes amino acids is highly conserved. Although the fold and mode of ligand binding of the PTPSD are different from the aspartic acid receptor Tar, the structural analysis suggests that the PTPSDs of amino-acid chemoreceptors are also likely to signal by a piston displacement mechanism. The PTPSD fluctuates between piston (C-terminal helix) `up' and piston `down' states. Binding of an attractant to the distal PAS domain locks it in the closed form, weakening its association with the proximal domain and resulting in the transition of the latter into an open form, concomitant with a downward (towards the membrane) 4 Å piston displacement of the C-terminal helix. In vivo, this movement would generate a transmembrane signal by driving a downward displacement of the transmembrane helix 2 towards the cytoplasm.</p>","PeriodicalId":7047,"journal":{"name":"Acta crystallographica. Section D, Biological crystallography","volume":"71 Pt 10","pages":"2127-36"},"PeriodicalIF":0.0,"publicationDate":"2015-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1107/S139900471501384X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34079247","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}

{"title":"Nicotinamide mononucleotide adenylyltransferase displays alternate binding modes for nicotinamide nucleotides.","authors":"Roland Pfoh, Emil F Pai, Vivian Saridakis","doi":"10.1107/S1399004715015497","DOIUrl":"10.1107/S1399004715015497","url":null,"abstract":"<p><p>Nicotinamide mononucleotide adenylyltransferase (NMNAT) catalyzes the biosynthesis of NAD(+) and NaAD(+). The crystal structure of NMNAT from Methanobacterium thermoautotrophicum complexed with NAD(+) and SO4(2-) revealed the active-site residues involved in binding and catalysis. Site-directed mutagenesis was used to further characterize the roles played by several of these residues. Arg11 and Arg136 were implicated in binding the phosphate groups of the ATP substrate. Both of these residues were mutated to lysine individually. Arg47 does not interact with either NMN or ATP substrates directly, but was deemed to play a role in binding as it is proximal to Arg11 and Arg136. Arg47 was mutated to lysine and glutamic acid. Surprisingly, when expressed in Escherichia coli all of these NMNAT mutants trapped a molecule of NADP(+) in their active sites. This NADP(+) was bound in a conformation that was quite different from that displayed by NAD(+) in the native enzyme complex. When NADP(+) was co-crystallized with wild-type NMNAT, the same structural arrangement was observed. These studies revealed a different conformation of NADP(+) in the active site of NMNAT, indicating plasticity of the active site.</p>","PeriodicalId":7047,"journal":{"name":"Acta crystallographica. Section D, Biological crystallography","volume":"71 Pt 10","pages":"2032-9"},"PeriodicalIF":0.0,"publicationDate":"2015-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1107/S1399004715015497","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34146662","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}

{"title":"An alternative RNA polymerase I structure reveals a dimer hinge.","authors":"Dirk Kostrewa,&nbsp;Claus-D Kuhn,&nbsp;Christoph Engel,&nbsp;Patrick Cramer","doi":"10.1107/S1399004715012651","DOIUrl":"https://doi.org/10.1107/S1399004715012651","url":null,"abstract":"<p><p>RNA polymerase I (Pol I) is the central, 14-subunit enzyme that synthesizes the ribosomal RNA (rRNA) precursor in eukaryotic cells. The recent crystal structure of Pol I at 2.8 Å resolution revealed two novel elements: the `expander' in the active-centre cleft and the `connector' that mediates Pol I dimerization [Engel et al. (2013), Nature (London), 502, 650-655]. Here, a Pol I structure in an alternative crystal form that was solved by molecular replacement using the original atomic Pol I structure is reported. The resulting alternative structure lacks the expander but still shows an expanded active-centre cleft. The neighbouring Pol I monomers form a homodimer with a relative orientation distinct from that observed previously, establishing the connector as a hinge between Pol I monomers. </p>","PeriodicalId":7047,"journal":{"name":"Acta crystallographica. Section D, Biological crystallography","volume":"71 Pt 9","pages":"1850-5"},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1107/S1399004715012651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34034511","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}

{"title":"Responses to Crystallography and chemistry should always go together: a cautionary tale of protein complexes with cisplatin and carboplatin.","authors":"Todd O Yeates","doi":"10.1107/S1399004715014704","DOIUrl":"https://doi.org/10.1107/S1399004715014704","url":null,"abstract":"Responses to Crystallography and chemistry should always go together: a cautionary tale of protein complexes with cisplatin and carboplatin In this issue of Acta Cryst. D, Shabalin et al. (2015) critique and re-evaluate dozens of crystal structures in the PDB in which proteins are bound to the platinum compounds cisplatin or carboplatin. Investigators whose structures were critiqued were contacted and several wrote comments in response. Through all those comments there was much agreement with certain sentiments expressed by Shabalin et al., including the idea that identification and refinement of metal ligands (and other unanticipated molecules in a crystal) is often extremely difficult. There was a shared opinion that greater vigilance and further tools for validation are needed. Shabalin et al. offer challenges to previous structural interpretations that vary in their severity. One end of the spectrum concerns cases where difficult decisions were required about whether or not to model a ligand into relatively weak features in an electron-density map. For example, in one protein that was reexamined (SOD), Shabalin et al. conclude that a missing fourth ligand to one of the Pt atoms should have been included but was not, and that a ligand to another Pt atom was included where the electron density was too weak for accurate modeling. They express similar opinions in their re-examination of RNase. Responses to Shabalin et al. in these two cases by A. Merlino, L. Messori, V. Calderone and S. Mangani include concessions on at least one point, that platinum is four-coordinated in the SOD structure; its omission by the original authors was a modeling decision or oversight not intended to convey that platinum was actually three-coordinated. In addressing other challenges such as whether reported ligands to platinum were reliably modeled, the responders maintained that their original assignments reflect plausible interpretations of electron density. At the other end of the critique spectrum, Shabalin et al. identify specific errors and arrive at alternate interpretations after re-refining the crystal structures of some other proteins bound to platinum compounds. These include ATOX1 and hen egg-white lysozyme. Here, Shabalin et al. offer challenges to the assignment of electron-density features to platinum atoms versus other metals, the identification of the ligands to platinum, and the modeling of various buffer constituents in the crystal structures. Owing to the specific re-interpretations offered by Shabalin et al. in these two cases, responses from the original investigators are published in this issue …","PeriodicalId":7047,"journal":{"name":"Acta crystallographica. Section D, Biological crystallography","volume":"71 Pt 9","pages":"1980-1"},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1107/S1399004715014704","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33967366","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}

{"title":"Response from Boal and Rosenzweig to Crystallography and chemistry should always go together: a cautionary tale of protein complexes with cisplatin and carboplatin.","authors":"Amie K Boal,&nbsp;Amy C Rosenzweig","doi":"10.1107/S1399004715014352","DOIUrl":"https://doi.org/10.1107/S1399004715014352","url":null,"abstract":"Response from Boal and Rosenzweig to Crystallography and chemistry should always go together: a cautionary tale of protein complexes with cisplatin and carboplatin In this issue of Acta Cryst. D, Shabalin et al. (2015) reinterpret diffraction data for a series of protein complexes with cisplatin (cis-Pt) and related drugs, an attractive target for study because of the possibility of drawing upon the extensive knowledge of the chemical and biological properties of platinum-based anticancer therapeutics (Berners-Price, 2000; Arnesano et al., 2009). cis-Pt and associated drugs bind avidly to duplex DNA inside the cell to form intrastrand crosslinks, driven in large part by the bonding preferences of Pt II , and typically distort the structure of the biomolecule significantly (Johnstone et al., 2015). The clinical importance of cisplatin interaction with proteins, however, is far less well understood. Association of Pt II compounds with these targets can be slow and more non-specific than corresponding interactions with nucleic acids (Peleg-Shulman et al., 2002). These properties are perhaps reflected in the findings of the study here in which low occupancies and heterogeneity in the structure and location of cis-Pt binding sites give rise to unique challenges in crystallographic modeling. The authors examined two structures we solved in 2009 of cis-Pt adducts with a human copper chaperone, Atox1 (Boal & Rosenzweig, 2009b). Of the structures discussed in the paper, these are perhaps the most biologically relevant owing to the implication of human copper transport proteins in clinical platinum resistance (Howell et al., 2010), although it remains unknown whether this correlation is a direct consequence of Pt II-protein association in vivo or simply an indirect effect. Our crystallographic study showed that cis-Pt is capable of binding to a Cys-XX-Cys site normally occupied by copper in these proteins, suggesting they are at least capable of trafficking or inactivating platinum-based drugs. In one of these structures, in which cis-Pt is likely first modified by a phos-phine reductant (TCEP) included to reduce the Cys ligands, Pt II interacts with a single Atox1 monomer and maintains a square planar coordination environment that distorts the structure of the Cys-XX-Cys motif. In a second structure obtained afterwards in which the reductant was removed under anaerobic conditions prior to Pt II exposure, the metal binds at the same location but instead bridges an Atox1 dimer, similar to what is observed upon interaction with the native substrate Cu I (Boal & Rosenzweig, 2009a). Interestingly, Pt …","PeriodicalId":7047,"journal":{"name":"Acta crystallographica. Section D, Biological crystallography","volume":"71 Pt 9","pages":"1984-6"},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1107/S1399004715014352","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33967368","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}

{"title":"Accounting for partiality in serial crystallography using ray-tracing principles.","authors":"Loes M J Kroon-Batenburg, Antoine M M Schreurs, Raimond B G Ravelli, Piet Gros","doi":"10.1107/S1399004715011803","DOIUrl":"10.1107/S1399004715011803","url":null,"abstract":"<p><p>Serial crystallography generates `still' diffraction data sets that are composed of single diffraction images obtained from a large number of crystals arbitrarily oriented in the X-ray beam. Estimation of the reflection partialities, which accounts for the expected observed fractions of diffraction intensities, has so far been problematic. In this paper, a method is derived for modelling the partialities by making use of the ray-tracing diffraction-integration method EVAL. The method estimates partialities based on crystal mosaicity, beam divergence, wavelength dispersion, crystal size and the interference function, accounting for crystallite size. It is shown that modelling of each reflection by a distribution of interference-function weighted rays yields a `still' Lorentz factor. Still data are compared with a conventional rotation data set collected from a single lysozyme crystal. Overall, the presented still integration method improves the data quality markedly. The R factor of the still data compared with the rotation data decreases from 26% using a Monte Carlo approach to 12% after applying the Lorentz correction, to 5.3% when estimating partialities by EVAL and finally to 4.7% after post-refinement. The merging R(int) factor of the still data improves from 105 to 56% but remains high. This suggests that the accuracy of the model parameters could be further improved. However, with a multiplicity of around 40 and an R(int) of ∼50% the merged still data approximate the quality of the rotation data. The presented integration method suitably accounts for the partiality of the observed intensities in still diffraction data, which is a critical step to improve data quality in serial crystallography.</p>","PeriodicalId":7047,"journal":{"name":"Acta crystallographica. Section D, Biological crystallography","volume":"71 Pt 9","pages":"1799-811"},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34034507","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}

{"title":"Structure of the JmjC domain-containing protein NO66 complexed with ribosomal protein Rpl8.","authors":"Chengliang Wang, Qiongdi Zhang, Tianrong Hang, Yue Tao, Xukai Ma, Minhao Wu, Xuan Zhang, Jianye Zang","doi":"10.1107/S1399004715012948","DOIUrl":"10.1107/S1399004715012948","url":null,"abstract":"<p><p>The JmjC domain-containing proteins belong to a large family of oxygenases possessing distinct substrate specificities which are involved in the regulation of different biological processes, such as gene transcription, RNA processing and translation. Nucleolar protein 66 (NO66) is a JmjC domain-containing protein which has been reported to be a histone demethylase and a ribosome protein 8 (Rpl8) hydroxylase. The present biochemical study confirmed the hydroxylase activity of NO66 and showed that oligomerization is required for NO66 to efficiently catalyze the hydroxylation of Rpl8. The structures of NO66(176-C) complexed with Rpl8(204-224) in a tetrameric form and of the mutant protein M2 in a dimeric form were solved. Based on the results of structural and biochemical analyses, the consensus sequence motif NHXH recognized by NO66 was confirmed. Several potential substrates of NO66 were found by a BLAST search according to the consensus sequence motif. When binding to substrate, the relative positions of each subunit in the NO66 tetramer shift. Oligomerization may facilitate the motion of each subunit in the NO66 tetramer and affect the catalytic activity. </p>","PeriodicalId":7047,"journal":{"name":"Acta crystallographica. Section D, Biological crystallography","volume":"71 Pt 9","pages":"1955-64"},"PeriodicalIF":0.0,"publicationDate":"2015-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1107/S1399004715012948","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33965230","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}