Biophysics reports最新文献_第9页

Theoretical framework and experimental solution for the air-water interface adsorption problem in cryoEM. 低温电子显微镜中空气-水界面吸附问题的理论框架和实验解决方案。

Biophysics reports Pub Date : 2023-08-31 DOI: 10.52601/bpr.2023.230008

Joon S Kang, Xueting Zhou, Yun-Tao Liu, Kaituo Wang, Z Hong Zhou

{"title":"Theoretical framework and experimental solution for the air-water interface adsorption problem in cryoEM.","authors":"Joon S Kang, Xueting Zhou, Yun-Tao Liu, Kaituo Wang, Z Hong Zhou","doi":"10.52601/bpr.2023.230008","DOIUrl":"10.52601/bpr.2023.230008","url":null,"abstract":"As cryogenic electron microscopy (cryoEM) gains traction in the structural biology community as a method of choice for determining atomic structures of biological complexes, it has been increasingly recognized that many complexes that behave well under conventional negative-stain electron microscopy tend to have preferential orientation, aggregate or simply mysteriously \"disappear\" on cryoEM grids. However, the reasons for such misbehavior are not well understood, which limits systematic approaches to solving the problem. Here, we have developed a theoretical formulation that explains these observations. Our formulation predicts that all particles migrate to the air-water interface (AWI) to lower the total potential surface energy-rationalizing the use of surfactant, which is a direct solution to reduce the surface tension of the aqueous solution. By performing cryogenic electron tomography (cryoET) on the widely-tested sample, GroEL, we demonstrate that, in a standard buffer solution, nearly all particles migrate to the AWI. Gradually reducing the surface tension by introducing surfactants decreased the percentage of particles exposed to the surface. By conducting single-particle cryoEM, we confirm that suitable surfactants do not damage the biological complex, thus suggesting that they might provide a practical, simple, and general solution to the problem for high-resolution cryoEM. Applying this solution to a real-world AWI adsorption problem involving a more challenging membrane protein, namely, the ClC-1 channel, has resulted in its near-atomic structure determination using cryoEM.","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"9 4","pages":"215-229"},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186591","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

Xenopus cell-free extracts and their applications in cell biology study. 无细胞爪蟾提取物及其在细胞生物学研究中的应用。

Biophysics reports Pub Date : 2023-08-31 DOI: 10.52601/bpr.2023.230016

Junjun Liu, Chuanmao Zhang

{"title":"Xenopus cell-free extracts and their applications in cell biology study.","authors":"Junjun Liu, Chuanmao Zhang","doi":"10.52601/bpr.2023.230016","DOIUrl":"10.52601/bpr.2023.230016","url":null,"abstract":"Xenopus has proven to be a remarkably versatile model organism in the realm of biological research for numerous years, owing to its straightforward maintenance in laboratory settings and its abundant provision of ample-sized oocytes, eggs, and embryos. The cell cycle of these oocytes, eggs, and early embryos exhibits synchrony, and extracts derived from these cells serve various research purposes. Many fundamental concepts in biochemistry, cell biology, and development have been elucidated through the use of cell-free extracts derived from Xenopus cells. Over the past few decades, a wide array of cell-free extracts has been prepared from oocytes, eggs, and early embryos of different Xenopus species at varying cell cycle stages. Each of these extracts possesses distinct characteristics. This review provides a concise overview of the Xenopus species employed in laboratory research, the diverse types of cell-free extracts available, and their respective properties. Furthermore, this review delves into the extensive investigation of spindle assembly in Xenopus egg extracts, underscoring the versatility and potency of these cell-free systems in the realm of cell biology.","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"9 4","pages":"195-205"},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186588","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

Deep learning-enabled fast DNA-PAINT imaging in cells. 基于深度学习的细胞快速 DNA-PAINT 成像。

Biophysics reports Pub Date : 2023-08-31 DOI: 10.52601/bpr.2023.230014

Min Zhu, Luhao Zhang, Luhong Jin, Yunyue Chen, Haixu Yang, Baohua Ji, Yingke Xu

引用次数: 0

Tumor type classification and candidate cancer-specific biomarkers discovery via semi-supervised learning. 通过半监督学习发现肿瘤类型分类和候选癌症特异性生物标志物。

Biophysics reports Pub Date : 2023-04-30 DOI: 10.52601/bpr.2023.230005

Peng Chen, Zhenlei Li, Zhaolin Hong, Haoran Zheng, Rong Zeng

{"title":"Tumor type classification and candidate cancer-specific biomarkers discovery via semi-supervised learning.","authors":"Peng Chen, Zhenlei Li, Zhaolin Hong, Haoran Zheng, Rong Zeng","doi":"10.52601/bpr.2023.230005","DOIUrl":"10.52601/bpr.2023.230005","url":null,"abstract":"Identifying cancer-related differentially expressed genes provides significant information for diagnosing tumors, predicting prognoses, and effective treatments. Recently, deep learning methods have been used to perform gene differential expression analysis using microarray-based high-throughput gene profiling and have achieved good results. In this study, we proposed a new robust multiple-datasets-based semi-supervised learning model, MSSL, to perform tumor type classification and candidate cancer-specific biomarkers discovery across multiple tumor types and multiple datasets, which addressed the following long-lasting obstacles: (1) the data volume of the existing single dataset is not enough to fully exert the advantages of deep learning; (2) a large number of datasets from different research institutions cannot be effectively used due to inconsistent internal variances and low quality; (3) relatively uncommon cancers have limited effects on deep learning methods. In our article, we applied MSSL to The Cancer Genome Atlas (TCGA) and the Gene Expression Comprehensive Database (GEO) pan-cancer normalized-level3 RNA-seq data and got 97.6% final classification accuracy, which had a significant performance leap compared with previous approaches. Finally, we got the ranking of the importance of the corresponding genes for each cancer type based on classification results and validated that the top genes selected in this way were biologically meaningful for corresponding tumors and some of them had been used as biomarkers, which showed the efficacy of our method.","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"9 2","pages":"57-66"},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41168715","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

A basic phosphoproteomic-DIA workflow integrating precise quantification of phosphosites in systems biology. 一个基本的磷酸蛋白质组DIA工作流程，集成了系统生物学中磷酸位点的精确量化。

Biophysics reports Pub Date : 2023-04-30 DOI: 10.52601/bpr.2023.230007

Yi Di, Wenxue Li, Barbora Salovska, Qian Ba, Zhenyi Hu, Shisheng Wang, Yansheng Liu

{"title":"A basic phosphoproteomic-DIA workflow integrating precise quantification of phosphosites in systems biology.","authors":"Yi Di, Wenxue Li, Barbora Salovska, Qian Ba, Zhenyi Hu, Shisheng Wang, Yansheng Liu","doi":"10.52601/bpr.2023.230007","DOIUrl":"10.52601/bpr.2023.230007","url":null,"abstract":"Phosphorylation is one of the most important post-translational modifications (PTMs) of proteins, governing critical protein functions. Most human proteins have been shown to undergo phosphorylation, and phosphoproteomic studies have been widely applied due to recent advancements in high-resolution mass spectrometry technology. Although the experimental workflow for phosphoproteomics has been well-established, it would be useful to optimize and summarize a detailed, feasible protocol that combines phosphoproteomics and data-independent acquisition (DIA), along with follow-up data analysis procedures due to the recent instrumental and bioinformatic advances in measuring and understanding tens of thousands of site-specific phosphorylation events in a single experiment. Here, we describe an optimized Phos-DIA protocol, from sample preparation to bioinformatic analysis, along with practical considerations and experimental configurations for each step. The protocol is designed to be robust and applicable for both small-scale phosphoproteomic analysis and large-scale quantification of hundreds of samples for studies in systems biology and systems medicine.","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"9 2","pages":"82-98"},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41155098","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

Integrated proteomic and phosphoproteomic data-independent acquisition data evaluate the personalized drug responses of primary and metastatic tumors in colorectal cancer. 综合蛋白质组学和磷酸蛋白质组学数据独立采集数据评估癌症原发性和转移性肿瘤的个性化药物反应。

Biophysics reports Pub Date : 2023-04-30 DOI: 10.52601/bpr.2022.210048

Xumiao Li, Yiming Huang, Kuo Zheng, Guanyu Yu, Qinqin Wang, Lei Gu, Jingquan Li, Hui Wang, Wei Zhang, Yidi Sun, Chen Li

{"title":"Integrated proteomic and phosphoproteomic data-independent acquisition data evaluate the personalized drug responses of primary and metastatic tumors in colorectal cancer.","authors":"Xumiao Li, Yiming Huang, Kuo Zheng, Guanyu Yu, Qinqin Wang, Lei Gu, Jingquan Li, Hui Wang, Wei Zhang, Yidi Sun, Chen Li","doi":"10.52601/bpr.2022.210048","DOIUrl":"https://doi.org/10.52601/bpr.2022.210048","url":null,"abstract":"Mass spectrometry (MS)-based proteomics and phosphoproteomics are powerful methods to study the biological mechanisms, diagnostic biomarkers, prognostic analysis, and drug therapy of tumors. Data-independent acquisition (DIA) mode is considered to perform better than data-dependent acquisition (DDA) mode in terms of quantitative reproducibility, specificity, accuracy, and identification of low-abundance proteins. Mini patient derived xenograft (MiniPDX) model is an effective model to assess the response to antineoplastic drugs in vivo and is helpful for the precise treatment of cancer patients. Kinases are favorable spots for tumor-targeted drugs, and their functional completion relies on signaling pathways through phosphorylating downstream substrates. Kinase-phosphorylation networks or edge interactions are considered more credible and permanent for characterizing complex diseases. Here, we provide a workflow for personalized drug response assessment in primary and metastatic colorectal cancer (CRC) tumors using DIA proteomic data, DIA phosphoproteomic data, and MiniPDX models. Three kinase inhibitors, afatinib, gefitinib, and regorafenib, are tested pharmacologically. The process mainly includes the following steps: clinical tissue collection, sample preparation, hybrid spectral libraries establishment, MS data acquisition, kinase-substrate network construction, in vivo drug test, and elastic regression modeling. Our protocol gives a more direct data basis for individual drug responses, and will improve the selection of treatment strategies for patients without the druggable mutation.","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"9 2","pages":"67-81"},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41180699","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

A hydrogen-deuterium exchange mass spectrometry-based protocol for protein-small molecule interaction analysis. 一种基于氢-氘交换质谱法的蛋白质小分子相互作用分析方案。

Biophysics reports Pub Date : 2023-04-30 DOI: 10.52601/bpr.2023.230006

Qian Meng, Yuan-Li Song, Chen Zhou, Han He, Naixia Zhang, Hu Zhou

引用次数: 0

Insights into human eNOS, nNOS and iNOS structures and medicinal indications from statistical analyses of their interactions with bound compounds 通过统计分析人类eNOS、nNOS和iNOS与结合化合物的相互作用，了解它们的结构和药物适应症

Biophysics reports Pub Date : 2023-01-01 DOI: 10.52601/bpr.2023.210045

Jianshu Dong, Dié Li, Lei Kang, Chenbing Luo, Jiangyun Wang

{"title":"Insights into human eNOS, nNOS and iNOS structures and medicinal indications from statistical analyses of their interactions with bound compounds","authors":"Jianshu Dong, Dié Li, Lei Kang, Chenbing Luo, Jiangyun Wang","doi":"10.52601/bpr.2023.210045","DOIUrl":"https://doi.org/10.52601/bpr.2023.210045","url":null,"abstract":"83 Structures of human nNOS, 55 structures of human eNOS, 13 structures of iNOS, and about 126 reported NOS-bound compounds are summarized and analyzed. Structural and statistical analysis show that, at least one copy of each analyzed compound binds to the active site (the substrate arginine binding site) of human NOS. And binding features of the three isoforms show differences, but the binding preference of compounds is not in the way helpful for inhibitor design targeting nNOS and iNOS, or for activator design targeting eNOS. This research shows that there is a strong structural and functional similarity between oxygenase domains of human NOS isoforms, especially the architecture, residue composition, size, shape, and distribution profile of hydrophobicity, polarity and charge of the active site. The selectivity and efficacy of inhibitors over the rest of isoforms rely a lot on chance and randomness. Further increase of selectivity via rational improvement is uncertain, unpredictable and unreliable, therefore, to achieve high selectivity through targeting this site is complicated and requires combinative investigation. After analysis on the current two targeting sites in NOS, the highly conserved arginine binding pocket and H4B binding pocket, new potential drug-targeting sites are proposed based on structure and sequence profiling. This comprehensive analysis on the structure and interaction profiles of human NOS and bound compounds provides fresh insights for drug discovery and pharmacological research, and the new discovery here is practically applied to guide protein-structure based drug discovery.","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"293 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135444977","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: 0

Reconstitution of membrane contact by unilamellar vesicles 单层囊泡重建膜接触

Biophysics reports Pub Date : 2023-01-01 DOI: 10.52601/bpr.2023.230011

Shulin Li, Min Zhang, Liang Ge

引用次数: 0

Isolation and proteomic study of fish liver lipid droplets 鱼肝脂滴的分离与蛋白质组学研究

Biophysics reports Pub Date : 2023-01-01 DOI: 10.52601/bpr.2023.230004

Yuwei Sun, Jian Heng, Feng Liu, Shuyan Zhang, Pingsheng Liu

{"title":"Isolation and proteomic study of fish liver lipid droplets","authors":"Yuwei Sun, Jian Heng, Feng Liu, Shuyan Zhang, Pingsheng Liu","doi":"10.52601/bpr.2023.230004","DOIUrl":"https://doi.org/10.52601/bpr.2023.230004","url":null,"abstract":"Lipid droplets (LDs) are a neutral lipid storage organelle that is conserved in almost all species. Excessive storage of neutral lipids in LDs is directly associated with many metabolic syndromes. Zebrafish is a better model animal for the study of LD biology due to its transparent embryonic stage compared to other organisms. However, the study of LDs in fish has been difficult due to the lack of specific LD marker proteins and the limitation of purification technology. In this paper, the purification and proteomic analysis of liver LDs of fish including zebrafish and Carassius auratus were performed for the first time. 259 and 267 proteins were identified respectively. Besides most of the identified proteins were reported in previous LD proteomes of mammals, indicating the similarity between mammal and fish LDs. We also identified many unique proteins of liver LDs in fish that are involved in the regulation of LD dynamics. Through morphological and biochemical analysis, we found that the marker protein Plin2 of zebrafish LD was located on LDs in Huh7 cells. These results will facilitate further study of LDs in fish and liver metabolic diseases using fish as a model animal.","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"162 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135444973","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: 0