Journal of Biological Chemistry最新文献

{"title":"High-affinity ELR+ chemokine ligands show G protein bias over β-arrestin recruitment and receptor internalization in CXCR1 signalling.","authors":"Katrijn Boon, Nathan Vanalken, Martyna Szpakowska, Andy Chevigné, Dominique Schols, Tom Van Loy","doi":"10.1016/j.jbc.2024.108044","DOIUrl":"https://doi.org/10.1016/j.jbc.2024.108044","url":null,"abstract":"<p><p>The human CXC chemokine receptor 1 (CXCR1), a G protein-coupled receptor (GPCR), plays significant roles in inflammatory diseases and cancer. While CXCL8 is a well-established high-affinity ligand for CXCR1, there is no consensus regarding the binding ability of the other ELR+ chemokines (CXCL1-3 and CXCL5-8). Since research has predominantly focused on CXCL8-mediated CXCR1 signalling, insight into potential signalling bias induced by different CXCR1 ligands is lacking. Therefore, in this study we first compared and clarified the binding ability of all ELR+ chemokines using a competition binding assay. In this assay CXCL1-3 and CXCL5 behaved as low-affinity ligands while CXCL6-8 were high affinity ligands. We further investigated potential ligand bias within the CXCR1 signalling system. Using NanoBRET-based assays heterotrimeric G protein dissociation, β-arrestin recruitment and receptor internalisation induced by chemokine binding to CXCR1 were investigated. A quantitative and qualitative investigation of ligand bias showed that the high-affinity ELR+ chemokines were biased towards G protein activation over β-arrestin recruitment and receptor internalisation, when CXCL8 was used as a reference ligand.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108044"},"PeriodicalIF":4.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphorylation of Lamin A/C regulates structural integrity of the nuclear envelope.","authors":"Shuaiyu Liu, Fangyuan Xiong, Zhen Dou, Lingluo Chu, Yihan Yao, Ming Wang, Xuebiao Yao, Xing Liu, Zhikai Wang","doi":"10.1016/j.jbc.2024.108033","DOIUrl":"https://doi.org/10.1016/j.jbc.2024.108033","url":null,"abstract":"<p><p>Dynamic disassembly and reconstruction of the nuclear lamina during entry and exit of mitosis, respectively, are pivotal steps in proliferation of higher eukaryotic cells. Although numerous post-translational modifications of lamin proteins have been identified, key factors driving the nuclear lamina dynamics remain elusive. Here we identified CDK1-elicited phosphorylation sites on endogenous Lamin A/C and characterized their functions in regulation of the nuclear lamina. Specifically, mass spectrometry revealed CDK1-mediated phosphorylation of Lamin A/C at the N-terminal Thr19/Ser22 and the C-terminal Ser390/Ser392 during mitosis. Importantly, the phospho-mimicking 4D mutant T19D/S22D/S390D/S392D completely disrupted Lamin A filamentous structure in interphase cells. Conversely, the non-phosphorylatable mutant T19A/S22A and especially the 4A mutant T19A/S22A/S390A/S392A protected Lamin A from depolymerization during mitosis. These results suggest that phosphorylation and dephosphorylation of both N- and C-terminal sites regulate the nuclear lamina dynamics. Engineering the non-phosphorylatable mutant T19A/S22A into the endogenous LMNA gene resulted in nuclear abnormalities and micronucleus formation during telophase. Perturbation of the Lamin A phosphorylation is shown to prevent proper nuclear envelope dynamics and impair nuclear integrity. These findings reveal a previously undefined link between the CDK1-elicited Lamin A phosphorylation dynamics, nuclear envelope plasticity, and genomic stability during the cell cycle.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108033"},"PeriodicalIF":4.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small molecule-based regulation of gene expression in human astrocytes switching on and off the G-quadruplex control systems.","authors":"Vijay Kumar M J, Jérémie Mitteaux, Zi Wang, Ellery Wheeler, Nitin Tandon, Sung Yun Jung, Robert H E Hudson, David Monchaud, Andrey S Tsvetkov","doi":"10.1016/j.jbc.2024.108040","DOIUrl":"https://doi.org/10.1016/j.jbc.2024.108040","url":null,"abstract":"<p><p>A great deal of attention is being paid to strategies seeking to uncover the biology of the four-stranded nucleic acid structure G-quadruplex (G4) via their stabilization in cells with G4-specific ligands. The conventional definition of chemical biology implies that a complete assessment of G4 biology can only be achieved by implementing a complementary approach involving destabilization of cellular G4s by ad hoc molecular effectors. We report here on an unprecedented comparison of the cellular consequences of G4 chemical stabilization by pyridostatin (PDS) and destabilization by phenylpyrrolocytosine (PhpC) at both transcriptome- and proteome-wide scales in patient-derived primary human astrocytes. Our results show that the stabilization of G4s by PDS triggers the dysregulation of many cellular circuitries, the most drastic effects originating in downregulation of 354 transcripts and 158 proteins primarily involved in RNA transactions. In contrast, destabilization of G4s by PhpC modulates the G4 landscapes in a far more focused manner with upregulation of 295 proteins, mostly involved in RNA transactions as well, thus mirroring the effects of PDS. Our study is the first of its kind to report the extent of G4-associated cellular circuitries in human cells by systematically pitting the effect of G4 stabilization against destabilization in a direct and unbiased manner.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108040"},"PeriodicalIF":4.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biased constitutive signalling of the G protein-coupled receptor GPR35 suppresses gut barrier permeability.","authors":"Tezz Quon, Li-Chiung Lin, Amlan Ganguly, Brian D Hudson, Andrew B Tobin, Graeme Milligan","doi":"10.1016/j.jbc.2024.108035","DOIUrl":"https://doi.org/10.1016/j.jbc.2024.108035","url":null,"abstract":"<p><p>Agonist-independent, or constitutive, activity is an integral feature of G protein-coupled receptors but its relevance in patho-physiological settings is generally poorly explored. GPR35 is a therapeutic target in inflammatory diseases of the lower gut. In colonic organoids from a human GPR35a-expressing transgenic mouse line the GPR35 inverse agonist CID-2745687 increased barrier permeability substantially, indicating that constitutive receptor activity contributes to maintaining epithelial barrier integrity. High constitutive activity of GPR35 was also observed in both HT-29 and HEPG2 cells that express GPR35 endogenously. Mechanistic investigations in recombinant in vitro systems revealed that constitutive activity of GPR35a was biased and not equivalent across signalling pathways. Hence, no constitutive interactions of the receptor with arrestin-adaptor proteins or activation of Gα_o-containing G protein heterotrimers were detected whilst, even at low GPR35a expression levels, substantial constitutive activation of heterotrimers containing either Gα₁₂ or Gα₁₃ was observed. Similar biased constitutive activity was observed for the human GPR35b isoform. The extent of constitutive and agonist-mediated activity was dependent on receptor expression level. At high receptor levels constitutive activation of Gα₁₂ or Gα₁₃ masked any agonist-induced effects whilst low expression levels with low constitutive activity allowed measurement of agonist-induced responses. These results highlight roles, selectivity and the extent of constitutive activity of GPR35 in cells and tissues that express this receptor endogenously and highlight the contribution of its constitutive activity to maintaining the colonic epithelial barrier, potentially limiting the development of inflammatory bowel diseases.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108035"},"PeriodicalIF":4.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombin confers chemotherapeutic resistance by promoting transcriptional induction and post-translational stabilization of pro-survival MCL1 in TNBC.","authors":"Subhojit Paul, Akash Chatterjee, Kaushik Das, Anushka Ray, Abhimanyu Basu, Soma Mukhopadhyay, Prosenjit Sen","doi":"10.1016/j.jbc.2024.108025","DOIUrl":"10.1016/j.jbc.2024.108025","url":null,"abstract":"<p><p>The association between idiopathic venous thrombosis and occult cancer is widely recognized. However, the comprehensive understanding of how thrombin, generated during the process of thrombosis, possesses the potential to augment the malignant phenotype is still not well understood. The coagulation protease thrombin mediates its effects by cleaving protease-activated receptor 1 (PAR1), a receptor abundantly expressed on the surface of triple-negative breast cancer (TNBC) cells. While emerging evidence implicates coagulation proteases in facilitating cancer progression, the precise molecular pathways underlying thrombin-mediated induction of chemoresistance remain poorly defined. Here, we demonstrate that thrombin-induced PAR1 activation in TNBC cells promotes the development of a multidrug-resistant phenotype, mechanistically linked to the upregulation of the pro-survival protein MCL1. Genetic ablation of MCL1 sensitizes TNBC cells to cytotoxic drugs despite thrombin exposure, affirming MCL1's functional importance. Chromatin immunoprecipitation analyses reveal thrombin triggers protein kinase A-dependent phosphorylation of serine 133 residues of cAMP-responsive element-binding protein (CREB), enhancing CREB's affinity for the co-activators CBP and p300. Furthermore, thrombin treatment induces the nuclear translocation of CREB-regulated transcription coactivator 2 (CRTC2) in a calcium-dependent manner, which collectively interacts with CREB/CBP-P300. The coordinated action of these transcriptional co-activators facilitates the transcriptional induction of MCL1. We further report that PAR1 activation augments MCL1 binding to the deubiquitinase USP9X, reducing MCL1 turnover. Our pre-clinical breast cancer murine model also shows that genetic deletion of PAR1 sensitizes breast cancer cells to chemotherapeutic drugs in vivo. Collectively, these findings emphasize the thrombin-PAR1 axis as a novel driver of chemoresistance. Utilizing FDA-approved oral anticoagulants for selective blocking of thrombin action may serve as a potential therapeutic adjunct for the treatment of triple-negative breast cancer.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108025"},"PeriodicalIF":4.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E2F1 and E2F7 regulate gastric cancer cell proliferation, respectively, through transcriptional activation and transcriptional repression of MYBL2.","authors":"Tianyi Wu, Fengli Jiang, Fan Wu, Guoliang Zheng, Yang Li, Lizhao Wu","doi":"10.1016/j.jbc.2024.108027","DOIUrl":"10.1016/j.jbc.2024.108027","url":null,"abstract":"<p><p>Gastric cancer (GC) is the most common malignant tumor of the digestive tract. However, the molecular pathogenesis is not well understood. Through bioinformatic analysis and analyzing clinical tissue samples, we found that E2F1 and E2F7 as well as their potential downstream target MYBL2 were all upregulated in GC tissues and that their expressions correlated with patient prognosis. While knockdown of E2F1 or MYBL2 inhibited cell proliferation and promoted apoptosis, knockdown of E2F7 promoted cell proliferation but had no effects on apoptosis. Chromatin immunoprecipitation and dual luciferase reporter assays demonstrated that MYBL2 was transcriptionally activated and repressed by E2F1 and E2F7, respectively. Importantly, in vitro and ex vivo experiments demonstrated that the effects of E2F1 and E2F7 on GC cell proliferation were significantly attenuated by reversely modulating MYBL2 expression, indicating that MYBL2 is a direct and functionally relevant target of E2F1 and E2F7 in GC cells. Furthermore, the effects of E2F1 and E2F7 on GC cell proliferation through transcriptional regulation of MYBL2 can be mediated by the PI3K/AKT signaling pathway. Interestingly, we found differential nucleocytoplasmic distribution of E2F7 in GC cells with functional relevance. Taken together, our data suggest that targeted therapies of GC may be achieved from three different angles, E2F1, E2F7, and MYBL2 themselves, E2F1/E2F7 expression balance, and E2F7 nuclear localization.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108027"},"PeriodicalIF":4.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chelerythrine triggers the prolongation of QT interval and induces cardiotoxicity by promoting the degradation of hERG channels.","authors":"Fang Wang, Baoqiang Wang, Xiwei Gu, Xiaoxu Li, Xinyu Liu, Baoxin Li","doi":"10.1016/j.jbc.2024.108023","DOIUrl":"10.1016/j.jbc.2024.108023","url":null,"abstract":"<p><p>Cardiotoxicity is a serious adverse reaction during drug treatment. The cardiac human ether-a-go-go-related gene (hERG) channels play a crucial role in driving cardiac action potential repolarization and are a key target for drug-induced cardiac toxicity. Chelerythrine (CHE) has anticancer effects on various human cancer cells. But little is known about its drug safety currently. The purpose of this study is to explore the key mechanism of cardiac toxicity induced by CHE under pathological conditions. CHE and hypoxia prolonged QT interval and action potential duration compared with control group in guinea pigs, as measured by BL-420S biological acquisition and processing system in conjunction with optical mapping technology. hERG current was measured by patch-clamp technique, and the interaction between ubiquitin molecules and hERG channels was assessed using immunoprecipitation method at the molecular level. The colocalization of proteins and the function of lysosomes were determined via confocal laser scanning microscopy. Further research indicates that CHE enhances the ubiquitination process of hERG proteins by catalyzing the formation of K63 ubiquitin chains, the ubiquitination modification disrupts hERG channel homeostasis, and promotes the degradation of the channel. Mechanistically, CHE accelerates the degradation of hERG channels through lysosomes via HDAC6, which may easily induce cardiotoxicity caused by prolonged QT interval under hypoxic conditions.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108023"},"PeriodicalIF":4.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purification of micrococcal nuclease for use in ribosomal profiling of high-salinity extremophiles.","authors":"Pavlina Gregorova, Matthew Isada, Jocelyne DiRuggiero, L Peter Sarin","doi":"10.1016/j.jbc.2024.108020","DOIUrl":"10.1016/j.jbc.2024.108020","url":null,"abstract":"<p><p>Nucleases, that is, enzymes that catalyze the hydrolysis of phosphodiester bonds in nucleic acids, are essential tools in molecular biology and biotechnology. Staphylococcus aureus nuclease is particularly interesting due to its thermostability and Ca²⁺ dependence, making it the prime choice for applications where nuclease modulation is critical, such as ribosome profiling in bacteria and halophilic archaea. The latter poses a technical and economical challenge: high salt reaction conditions are essential for maintaining ribosome integrity but negatively impact the micrococcal nuclease (MNase) activity, necessitating using large amounts of nuclease to achieve efficient cleavage. Here, we set out to generate an optimized production protocol for two forms of MNase-fully processed MNaseA and the 19 amino acid propeptide-containing MNaseB-and to biochemically benchmark them against a commercial nuclease. Our results show that both MNases are highly active in normal reaction conditions, but MNaseA maintains higher enzymatic activity in high salt concentrations than MNaseB. MNaseA also retains >90% of its activity after multiple freeze-thaw cycles when stored at -80 °C in a buffer containing 5% glycerol. Importantly, ribosome profiling experiments in the haloarchaeon Haloferax volcanii demonstrated that MNaseA produces ribosome footprints and hallmarks of active translation highly comparable to those obtained with the commercial nuclease, making it a suitable alternative for high-salt ribosome profiling applications. In conclusion, our method can be easily implemented for efficient MNaseA production, thereby providing access to an effective, robust, and cost-efficient alternative to commercial nucleases, as well as facilitating future translation studies into halophilic organisms.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108020"},"PeriodicalIF":4.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Independent evolution of plant natural products: Formation of benzoxazinoids in Consolida orientalis (Ranunculaceae).","authors":"Matilde Florean, Hedwig Schultz, Jens Wurlitzer, Sarah E O'Connor, Tobias G Köllner","doi":"10.1016/j.jbc.2024.108019","DOIUrl":"https://doi.org/10.1016/j.jbc.2024.108019","url":null,"abstract":"<p><p>Benzoxazinoids (BXDs) are important defense compounds produced by a number of species from different, evolutionarily unrelated plant families. While BXD biosynthesis has been extensively studied in the grasses (monocots) and core eudicots, the mechanism of BXD synthesis in the basal eudicots is still unclear. We used an integrated metabolomics and transcriptomics approach to elucidate the BXD pathway in Consolida orientalis, a Ranunculaceae species known to produce the BXD DIBOA-Glc. Overexpression of candidate genes in Nicotiana benthamiana identified a flavin-dependent monooxygenase (CoBX2-3) and two cytochrome P450 enzymes (CoBX4 and CoBX5) that catalyze the oxidation steps that transform indole into DIBOA. Co-expression of CoBx2-3, CoBx4, and CoBx5 with the previously described indole synthase gene CoBx1 and the UDP-glucosyltransferase gene CoBx8 in N. benthamiana resulted in the reconstitution of a fully active BXD pathway. The fact that CoBX2-3, CoBX4, and CoBX5 are not phylogenetically related to their counterparts in the grasses and core eudicots suggests independent evolution of benzoxazinoids biosynthesis in these three angiosperm lineages.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108019"},"PeriodicalIF":4.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Energy metabolism in osteoprogenitors and osteoblasts: Role of the pentose phosphate pathway.","authors":"Sarah E Catheline, Charles O Smith, Matthew McArthur, Chen Yu, Paul S Brookes, Roman A Eliseev","doi":"10.1016/j.jbc.2024.108016","DOIUrl":"10.1016/j.jbc.2024.108016","url":null,"abstract":"<p><p>Bioenergetic preferences of osteolineage cells, including osteoprogenitors and osteoblasts (OBs), are a matter of intense debate. Early studies pointed to OB reliance on glucose and aerobic glycolysis while more recent works indicated the importance of glutamine as a mitochondrial fuel. Aiming to clarify this issue, we performed metabolic tracing of ¹³C-labeled glucose and glutamine in human osteolineage cells: bone marrow stromal (a.k.a. mesenchymal stem) cells and bone marrow stromal cell-derived OBs. Glucose tracing showed noncanonical direction of glucose metabolism with high labeling of early glycolytic steps and the pentose phosphate pathway (PPP) but very low labeling of late glycolytic steps and the Krebs cycle. Labeling of Krebs cycle and late steps of glycolysis was primarily from glutamine. These data suggest that in osteolineage cells, glucose is metabolized primarily via the PPP while glutamine is metabolized in the mitochondria, also feeding into the late steps of glycolysis likely via the malate-aspartate shuttle. This metabolic setup did not change after induction of differentiation. To evaluate the importance of this setup for osteolineage cells, we used the inhibitors of either PPP or malate-aspartate shuttle and observed a significant reduction in both cell growth and ability to differentiate. In sum, we observed a distinct metabolic wiring in osteolineage cells with high flux of glucose through the PPP and glutamine flux fueling both mitochondria and late steps of glycolysis. This wiring likely reflects their unique capacity to rapidly proliferate and produce extracellular matrix, e.g., after bone fracture.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108016"},"PeriodicalIF":4.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}