Journal of Molecular Biology最新文献

{"title":"Translation Complex Profile Sequencing Allows Discrimination of Leaky Scanning and Reinitiation in Upstream Open Reading Frame-controlled Translation","authors":"Dmitri E. Andreev ,&nbsp;Jack A.S. Tierney ,&nbsp;Pavel V. Baranov","doi":"10.1016/j.jmb.2024.168850","DOIUrl":"10.1016/j.jmb.2024.168850","url":null,"abstract":"<div><div>Upstream open reading frames (uORFs) are a class of translated regions (translons) in mRNA 5′ leaders. uORFs are believed to be pervasive regulators of the translation of mammalian mRNAs. Some uORFs are highly repressive but others have little or no impact on downstream mRNA translation either due to inefficient recognition of their start codon(s) or/and due to efficient reinitiation after uORF translation. While experiments with uORF reporter constructs proved to be instrumental in the investigation of uORF-mediated mechanisms of translation control, they can have serious limitations as manipulations with uORF sequences can yield various artefacts. Here we propose a general approach for using translation complex profiling (TCP-seq) data for exploring uORF regulatory characteristics. Using several examples, we show how TCP-seq could be used to estimate both repressiveness and modes of action of individual uORFs. We demonstrate how this approach could be used to assess the mechanisms of uORF-mediated translation control in the mRNA of several human genes, including <em>EIF5</em>, <em>IFRD1</em>, <em>MDM2</em>, <em>MIEF1</em>, <em>PPP1R15B</em>, <em>TAF7,</em> and <em>UCP2</em>.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168850"},"PeriodicalIF":4.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563952","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":"HulaCCR1, a pump-like cation channelrhodopsin discovered in a lake microbiome","authors":"Shunki Takaramoto ,&nbsp;Shai Fainsod ,&nbsp;Takashi Nagata ,&nbsp;Andrey Rozenberg ,&nbsp;Oded Béjà ,&nbsp;Keiichi Inoue","doi":"10.1016/j.jmb.2024.168844","DOIUrl":"10.1016/j.jmb.2024.168844","url":null,"abstract":"<div><div>Channelrhodopsins are light-gated ion channels consisting of seven transmembrane helices and a retinal chromophore, which are used as popular optogenetic tools for modulating neuronal activity. Cation channelrhodopsins (CCRs), first recognized as the photoreceptors in the chlorophyte <em>Chlamydomonas reinhardtii</em>, have since been identified in diverse species of green algae, as well in other unicellular eukaryotes. The CCRs from non-chlorophyte species are commonly referred to as bacteriorhodopsin-like cation channelrhodopsins, or BCCRs, as most of them feature the three characteristic amino acid residues of the “DTD motif” in the third transmembrane helix (TM3 or helix C) matching the canonical DTD motif of the well-studied archaeal light-driven proton pump bacteriorhodopsin. Here, we report characterization of HulaCCR1, a novel BCCR identified through metatranscriptomic analysis of a unicellular eukaryotic community in Lake Hula, Israel. Interestingly, HulaCCR1 has an ETD motif in which the first residue of the canonical motif is substituted for glutamate. Electrophysiological measurements of the wild-type and a mutant with a DTD motif of HulaCCR1 suggest the critical role of the first glutamate in spectral tuning and channel gating. Additionally, HulaCCR1 exhibits long extensions at the N- and C-termini. Photocurrents recorded from a truncated variant without the signal peptide predicted at the N-terminus were diminished, and membrane localization of the truncated variant significantly decreased, indicating that the signal peptide is important for membrane trafficking of HulaCCR1. These characteristics of HulaCCR1 would be related to a new biological significance in the original unidentified species, distinct from those known for other BCCRs.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168844"},"PeriodicalIF":4.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Hsp90 Molecular Chaperone as a Global Modifier of the Genotype-Phenotype-Fitness Map: An Evolutionary Perspective","authors":"José Aguilar-Rodríguez ,&nbsp;Christopher M. Jakobson ,&nbsp;Daniel F. Jarosz","doi":"10.1016/j.jmb.2024.168846","DOIUrl":"10.1016/j.jmb.2024.168846","url":null,"abstract":"<div><div>Global modifier genes influence the mapping of genotypes onto phenotypes and fitness through their epistatic interactions with genetic variants on a massive scale. The first such factor to be identified, Hsp90, is a highly conserved molecular chaperone that plays a central role in protein homeostasis. Hsp90 is a “hub of hubs” that chaperones proteins engaged in many key cellular and developmental regulatory networks. These clients, which are enriched in kinases, transcription factors, and E3 ubiquitin ligases, drive diverse cellular functions and are themselves highly connected. By contrast to many other hub proteins, the abundance and activity of Hsp90 changes substantially in response to shifting environmental conditions. As a result, Hsp90 modifies the functional impact of many genetic variants simultaneously in a manner that depends on environmental stress. Studies in diverse organisms suggest that this coupling between Hsp90 function and challenging environments exerts a substantial impact on what parts of the genome are visible to natural selection, expanding adaptive opportunities when most needed. In this Perspective, we explore the multifaceted role of Hsp90 as global modifier of the genotype-phenotype-fitness map as well as its implications for evolution in nature and the clinic.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168846"},"PeriodicalIF":4.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556806","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":"DTA-GTOmega: Enhancing Drug-Target Binding Affinity Prediction with Graph Transformers Using OmegaFold Protein Structures.","authors":"Lijun Quan, Jian Wu, Yelu Jiang, Deng Pan, Lyu Qiang","doi":"10.1016/j.jmb.2024.168843","DOIUrl":"10.1016/j.jmb.2024.168843","url":null,"abstract":"<p><p>Understanding drug-protein interactions is crucial for elucidating drug mechanisms and optimizing drug development. However, existing methods have limitations in representing the three-dimensional structure of targets and capturing the complex relationships between drugs and targets. This study proposes a new method, DTA-GTOmega, for predicting drug-target binding affinity. DTA-GTOmega utilizes OmegaFold to predict protein three-dimensional structure and construct target graphs, while processing drug SMILES sequences with RDKit to generate drug graphs. By employing multi-layer graph transformer modules and co-attention modules, this method effectively integrates atomic-level features of drugs and residue-level features of targets, accurately modeling the complex interactions between drugs and targets, thereby significantly improving the accuracy of binding affinity predictions. Our method outperforms existing techniques on benchmark datasets such as KIBA, Davis, and BindingDB_Kd under cold-start setting. Moreover, DTA-GTOmega demonstrates competitive performance in real-world DTI scenarios involving DrugBank data and drug-target interactions related to cardiovascular and nervous system-related diseases, highlighting its robust generalization capabilities. Additionally, the introduced DTI evaluation metrics further validate DTA-GTOmega's potential in handling imbalanced data.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168843"},"PeriodicalIF":4.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556805","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":"Conformational Differences in the Light Chain Constant Domain of Immunoglobulin G and Free Light Chain May Influence Proteolysis in AL Amyloidosis","authors":"Elena S. Klimtchuk ,&nbsp;Tatiana Prokaeva ,&nbsp;Brian H. Spencer ,&nbsp;Sherry Wong ,&nbsp;Shreya Ghosh ,&nbsp;Angela Urdaneta ,&nbsp;Gareth Morgan ,&nbsp;Thomas E. Wales ,&nbsp;Olga Gursky","doi":"10.1016/j.jmb.2024.168837","DOIUrl":"10.1016/j.jmb.2024.168837","url":null,"abstract":"<div><div>Immunoglobulin light chain amyloidosis (AL) is a life-threatening disease caused by the deposition of light chain (LC) and its fragments containing variable (V_L) and portions of constant (C_L) domains. AL patients feature either monoclonal free LCs (FLCs) circulating as covalent and noncovalent homodimers, or monoclonal immunoglobulin (Ig) wherein the LC and heavy chain (HC) form disulfide-linked heterodimers, or both. The role of full-length Ig in AL amyloidosis is unclear as prior studies focused on FLC or V_L domain. We used a mammalian cell-based expression system to generate four AL patient-derived full-length IgGs, two non-AL IgG controls, and six corresponding FLC proteins derived from an <em>IGLV6-57</em> germline precursor. Comparison of proteins’ secondary structure, thermal stability, proteolytic susceptibility, and disulfide link reduction suggested the importance of local <em>vs.</em> global conformational stability. Analysis of IgGs <em>vs.</em> corresponding FLCs using hydrogen–deuterium exchange mass spectrometry revealed major differences in the local conformation/dynamics of the C_L domain. In all IgGs <em>vs.</em> FLCs, segments containing β-strand and α-helix βA_C-αA_CB_C were more dynamic/exposed while segment βD_C-βE_C was less dynamic/exposed. Notably, these segments overlapped proteolysis-prone regions whose <em>in vivo</em> cleavage generates LC fragments found in AL deposits. Altogether, the results suggest that preferential cleavage in segments βA_C-αA_CB_C of FLC or βD_C-βE_C of LC in IgG helps generate amyloid protein precursors. We propose that protecting these segments using small-molecule stabilizers, which bind to the interfacial cavities C_L-C_L in FLC and/or C_L-C_H1 in IgG, is a potential therapeutic strategy to complement current approaches targeting V_L-V_L or V_L-C_L stabilization of LC dimer.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168837"},"PeriodicalIF":4.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566743","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":"Regulated Proteolysis Induces Aberrant Phase Transition of Biomolecular Condensates into Aggregates: A Protective Role for the Chaperone Clusterin","authors":"Janine Kamps ,&nbsp;Patricia Yuste-Checa ,&nbsp;Fatemeh Mamashli ,&nbsp;Matthias Schmitz ,&nbsp;Maria Georgina Herrera ,&nbsp;Susana Margarida da Silva Correia ,&nbsp;Kalpshree Gogte ,&nbsp;Verian Bader ,&nbsp;Inga Zerr ,&nbsp;F. Ulrich Hartl ,&nbsp;Andreas Bracher ,&nbsp;Konstanze F. Winklhofer ,&nbsp;Jörg Tatzelt","doi":"10.1016/j.jmb.2024.168839","DOIUrl":"10.1016/j.jmb.2024.168839","url":null,"abstract":"<div><div>Several proteins associated with neurodegenerative diseases, such as the mammalian prion protein (PrP), undergo liquid–liquid phase separation (LLPS), which led to the hypothesis that condensates represent precursors in the formation of neurotoxic protein aggregates. However, the mechanisms that trigger aberrant phase separation are incompletely understood. In prion diseases, protease-resistant and infectious amyloid fibrils are composed of N-terminally truncated PrP, termed C2-PrP. C2-PrP is generated by regulated proteolysis (β-cleavage) of the cellular prion protein (PrP^C) specifically upon prion infection, suggesting that C2-PrP is a misfolding-prone substrate for the propagation of prions. Here we developed a novel assay to investigate the role of both LLPS and β-cleavage in the formation of C2-PrP aggregates. We show that β-cleavage induces the formation of C2-PrP aggregates, but only when full-length PrP had formed biomolecular condensates via LLPS before proteolysis. In contrast, C2-PrP remains soluble after β-cleavage of non-phase-separated PrP. To investigate whether extracellular molecular chaperones modulate LLPS of PrP and/or misfolding of C2-PrP, we focused on Clusterin. Clusterin does not inhibit LLPS of full-length PrP, however, it prevents aggregation of C2-PrP after β-cleavage of phase-separated PrP. Furthermore, Clusterin interferes with the <em>in vitro</em> amplification of infectious human prions isolated from Creutzfeldt-Jakob disease patients. Our study revealed that regulated proteolysis triggers aberrant phase transition of biomolecular condensates into aggregates and identified Clusterin as a component of the extracellular quality control pathway to prevent the formation and propagation of pathogenic PrP conformers.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168839"},"PeriodicalIF":4.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryo-EM Structures of the Plasmodium falciparum Apicoplast DNA Polymerase","authors":"Chen-Yu Lo ,&nbsp;Adron R. Ung ,&nbsp;Tirthankar Koley ,&nbsp;Scott W. Nelson ,&nbsp;Yang Gao","doi":"10.1016/j.jmb.2024.168842","DOIUrl":"10.1016/j.jmb.2024.168842","url":null,"abstract":"<div><div>The apicoplast DNA polymerase (apPol) from Plasmodium falciparum is essential for the parasite’s survival, making it a prime target for antimalarial therapies. Here, we present cryo-electron microscopy structures of the apPol in complex with DNA and incoming nucleotide, offering insights into its molecular mechanisms. Our structural analysis reveals that apPol contains critical residues for high-fidelity DNA synthesis, but lacks certain structural elements to confer processive DNA synthesis during replication, suggesting the presence of additional accessory factors. The enzyme exhibits large-scale conformational changes upon DNA and nucleotide binding, particularly within the fingers and thumb subdomains. These movements reveal potential allosteric sites that could serve as targets for drug design. Our findings provide a foundation for advancing the understanding of apPol’s unique functional mechanisms and potentially offering new avenues for the development of novel inhibitors and therapeutic interventions against malaria.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168842"},"PeriodicalIF":4.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566746","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":"Identification of a Non-canonical Function of Prefoldin Subunit 5 in Proteasome Assembly","authors":"Somayeh Shahmoradi Ghahe ,&nbsp;Krzysztof Drabikowski ,&nbsp;Monika Stasiak ,&nbsp;Ulrike Topf","doi":"10.1016/j.jmb.2024.168838","DOIUrl":"10.1016/j.jmb.2024.168838","url":null,"abstract":"<div><div>The prefoldin complex is a heterohexameric, evolutionarily conserved co-chaperone that assists in folding of polypeptides downstream of the protein translation machinery. Loss of prefoldin function leads to impaired solubility of cellular proteins. The degradation of proteins by the proteasome is an integral part of protein homeostasis. Failure of regulated protein degradation can lead to the accumulation of misfolded and defective proteins. We show that prefoldin subunit 5 is required for proteasome activity by contributing to the assembly of the 26S proteasome. In particular, we found that absence of the prefoldin subunit 5 impairs formation of the Rpt ring subcomplex of the proteasome. Concomitant deletion of <em>PFD5</em> and <em>HSM3</em>, a chaperone for assembly of the ATPase subunits comprising the Rpt ring, exacerbates this effect, suggesting a synergistic relationship between the two factors in proteasome assembly. Thus, our findings reveal a regulatory mechanism wherein prefoldin subunit 5 plays a crucial role in maintaining proteasome integrity, thereby influencing the degradation of proteins.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168838"},"PeriodicalIF":4.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566753","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":"The HSP90/R2TP Quaternary Chaperone Scaffolds Assembly of the TSC Complex","authors":"Claire Abéza ,&nbsp;Philipp Busse ,&nbsp;Ana C.F. Paiva ,&nbsp;Marie-Eve Chagot ,&nbsp;Justine Schneider ,&nbsp;Marie-Cécile Robert ,&nbsp;Franck Vandermoere ,&nbsp;Christine Schaeffer ,&nbsp;Bruno Charpentier ,&nbsp;Pedro M.F. Sousa ,&nbsp;Tiago M. Bandeiras ,&nbsp;Xavier Manival ,&nbsp;Sarah Cianferani ,&nbsp;Edouard Bertrand ,&nbsp;Céline Verheggen","doi":"10.1016/j.jmb.2024.168840","DOIUrl":"10.1016/j.jmb.2024.168840","url":null,"abstract":"<div><div>The R2TP chaperone is composed of the RUVBL1/RUVBL2 AAA+ ATPases and two adapter proteins, RPAP3 and PIH1D1. Together with HSP90, it functions in the assembly of macromolecular complexes that are often involved in cell proliferation. Here, proteomic experiments using the isolated PIH domain reveals additional R2TP partners, including the Tuberous Sclerosis Complex (TSC) and many transcriptional complexes. The TSC is a key regulator of mTORC1 and is composed of TSC1, TSC2 and TBC1D7. We show a direct interaction of TSC1 with the PIH phospho-binding domain of PIH1D1, which is, surprisingly, phosphorylation independent. Via the use of mutants and KO cell lines, we observe that TSC2 makes independent interactions with HSP90 and the TPR domains of RPAP3. Moreover, inactivation of PIH1D1 or the RUVBL1/2 ATPase activity inhibits the association of TSC1 with TSC2. Taken together, these data suggest a model in which the R2TP recruits TSC1 via PIH1D1 and TSC2 via RPAP3 and HSP90, and use the chaperone-like activities of RUVBL1/2 to stimulate their assembly.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168840"},"PeriodicalIF":4.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GEMimp: An Accurate and Robust Imputation Method for Microbiome Data Using Graph Embedding Neural Network","authors":"Ziwei Sun,&nbsp;Kai Song","doi":"10.1016/j.jmb.2024.168841","DOIUrl":"10.1016/j.jmb.2024.168841","url":null,"abstract":"<div><div>Microbiome research has increasingly underscored the profound link between microbial compositions and human health, with numerous studies establishing a strong correlation between microbiome characteristics and various diseases. However, the analysis of microbiome data is frequently compromised by inherent sparsity issues, characterized by a substantial presence of observed zeros. These zeros not only skew the abundance distribution of microbial species but also undermine the reliability of scientific conclusions drawn from such data. Addressing this challenge, we introduce GEMimp, an innovative imputation method designed to infuse robustness into microbiome data analysis. GEMimp leverages the node2vec algorithm, which incorporates both Breadth-First Search (BFS) and Depth-First Search (DFS) strategies in its random walks sampling process. This approach enables GEMimp to learn nuanced, low-dimensional representations of each taxonomic unit, facilitating the reconstruction of their similarity networks with unprecedented accuracy.</div><div>Our comparative analysis pits GEMimp against state-of-the-art imputation methods including SAVER, MAGIC and mbImpute. The results unequivocally demonstrate that GEMimp outperforms its counterparts by achieving the highest Pearson correlation coefficient when compared to the original raw dataset. Furthermore, GEMimp shows notable proficiency in identifying significant taxa, enhancing the detection of disease-related taxa and effectively mitigating the impact of sparsity on both simulated and real-world datasets, such as those pertaining to Type 2 Diabetes (T2D) and Colorectal Cancer (CRC). These findings collectively highlight the strong effectiveness of GEMimp, allowing for better analysis on microbial data. With alleviation of sparsity issues, it could be greatly facilitated in downstream analyses and even in the field of microbiology.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"436 23","pages":"Article 168841"},"PeriodicalIF":4.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566750","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}