Fan Shi, Tong Zhang, Juan Li, Chaowei Shi, Shengqi Xiang
{"title":"Studying large biomolecules as sedimented solutes with solid-state NMR.","authors":"Fan Shi, Tong Zhang, Juan Li, Chaowei Shi, Shengqi Xiang","doi":"10.52601/bpr.2024.240014","DOIUrl":"https://doi.org/10.52601/bpr.2024.240014","url":null,"abstract":"<p><p>Sedimentation solid-state NMR is a novel method for sample preparation in solid-state NMR (ssNMR) studies. It involves the sedimentation of soluble macromolecules such as large protein complexes. By utilizing ultra-high centrifugal forces, the molecules in solution are driven into a high-concentrated hydrogel, resulting in a sample suitable for solid-state NMR. This technique has the advantage of avoiding the need for chemical treatment, thus minimizing the loss of sample biological activity. Sediment ssNMR has been successfully applied to a variety of non-crystalline protein solids, significantly expanding the scope of solid-state NMR research. In theory, using this method, any biological macromolecule in solution can be transferred into a sedimented solute appropriate for solid-state NMR analysis. However, specialized equipment and careful handling are essential for effectively collecting and loading the sedimented solids to solid-state NMR rotors. To improve efficiency, we have designed a series of loading tools to achieve the loading process from the solution to the rotor in one step. In this paper, we illustrate the sample preparation process of sediment NMR using the H1.4-NCP<sup>167</sup> complex, which consists of linker histone H1.4 and nucleosome core particle, as an example.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 4","pages":"201-212"},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303329","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":"The brain network hub degeneration in Alzheimer's disease.","authors":"Suhui Jin, Jinhui Wang, Yong He","doi":"10.52601/bpr.2024.230025","DOIUrl":"https://doi.org/10.52601/bpr.2024.230025","url":null,"abstract":"<p><p>Alzheimer's disease (AD) has been conceptualized as a syndrome of brain network dysfunction. Recent imaging connectomics studies have provided unprecedented opportunities to map structural and functional brain networks in AD. By reviewing molecular, imaging, and computational modeling studies, we have shown that highly connected brain hubs are primarily distributed in the medial and lateral prefrontal, parietal, and temporal regions in healthy individuals and that the hubs are selectively and severely affected in AD as manifested by increased amyloid-beta deposition and regional atrophy, hypo-metabolism, and connectivity dysfunction. Furthermore, AD-related hub degeneration depends on the imaging modality with the most notable degeneration in the medial temporal hubs for morphological covariance networks, the prefrontal hubs for structural white matter networks, and in the medial parietal hubs for functional networks. Finally, the AD-related hub degeneration shows metabolic, molecular, and genetic correlates. Collectively, we conclude that the brain-network-hub-degeneration framework is promising to elucidate the biological mechanisms of network dysfunction in AD, which provides valuable information on potential diagnostic biomarkers and promising therapeutic targets for the disease.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 4","pages":"213-229"},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303330","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":"Unlocking the secrets of TGR5: a new dawn in treating diabetic cardiomyopathy.","authors":"Jin Li, He Huang","doi":"10.52601/bpr.2024.240907","DOIUrl":"https://doi.org/10.52601/bpr.2024.240907","url":null,"abstract":"","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 4","pages":"254-256"},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303331","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":"Streamlined process for effective and strand-selective mitochondrial base editing using mitoBEs.","authors":"Xiaoxue Zhang, Zongyi Yi, Wei Tang, Wensheng Wei","doi":"10.52601/bpr.2024.240010","DOIUrl":"https://doi.org/10.52601/bpr.2024.240010","url":null,"abstract":"<p><p>Mitochondrial base editing tools hold great promise for the investigation and treatment of mitochondrial diseases. Mitochondrial DNA base editors (mitoBEs) integrate a programmable transcription-activator-like effector (TALE) protein with single-stranded DNA deaminase (TadA8e-V106W, APOBEC1, <i>etc</i>.) and nickase (MutH, Nt.BspD6I(C), <i>etc</i>.) to achieve heightened precision and efficiency in mitochondrial base editing. This innovative mitochondrial base editing tool exhibits a number of advantages, including strand-selectivity for editing, high efficiency, and the capacity to perform diverse types of base editing on the mitochondrial genome by employing various deaminases. In this context, we provide a detailed experimental protocol for mitoBEs to assist others in achieving proficient mitochondrial base editing.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 4","pages":"191-200"},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303328","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":"Decoder-seq: a technology for high sensitivity, high resolution, and low-cost spatial RNA sequencing.","authors":"Siquan Li, Jin Li, He Huang","doi":"10.52601/bpr.2024.240903","DOIUrl":"10.52601/bpr.2024.240903","url":null,"abstract":"","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 3","pages":"172-174"},"PeriodicalIF":0.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725293","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":"Developing ChatGPT for biology and medicine: a complete review of biomedical question answering.","authors":"Qing Li, Lei Li, Yu Li","doi":"10.52601/bpr.2024.240004","DOIUrl":"10.52601/bpr.2024.240004","url":null,"abstract":"<p><p>ChatGPT explores a strategic blueprint of question answering (QA) to deliver medical diagnoses, treatment recommendations, and other healthcare support. This is achieved through the increasing incorporation of medical domain data via natural language processing (NLP) and multimodal paradigms. By transitioning the distribution of text, images, videos, and other modalities from the general domain to the medical domain, these techniques have accelerated the progress of medical domain question answering (MDQA). They bridge the gap between human natural language and sophisticated medical domain knowledge or expert-provided manual annotations, handling large-scale, diverse, unbalanced, or even unlabeled data analysis scenarios in medical contexts. Central to our focus is the utilization of language models and multimodal paradigms for medical question answering, aiming to guide the research community in selecting appropriate mechanisms for their specific medical research requirements. Specialized tasks such as unimodal-related question answering, reading comprehension, reasoning, diagnosis, relation extraction, probability modeling, and others, as well as multimodal-related tasks like vision question answering, image captioning, cross-modal retrieval, report summarization, and generation, are discussed in detail. Each section delves into the intricate specifics of the respective method under consideration. This paper highlights the structures and advancements of medical domain explorations against general domain methods, emphasizing their applications across different tasks and datasets. It also outlines current challenges and opportunities for future medical domain research, paving the way for continued innovation and application in this rapidly evolving field. This comprehensive review serves not only as an academic resource but also delineates the course for future probes and utilization in the field of medical question answering.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 3","pages":"152-171"},"PeriodicalIF":0.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725294","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}
Hui Peng, Yashuo Zhang, Qun Luo, Xinyu Wang, Huijuan You
{"title":"Unfolding rates of 1:1 and 2:1 complex of CX-5461 and c-<i>MYC</i> promoter G-quadruplexes revealed by single-molecule force spectroscopy.","authors":"Hui Peng, Yashuo Zhang, Qun Luo, Xinyu Wang, Huijuan You","doi":"10.52601/bpr.2024.240018","DOIUrl":"10.52601/bpr.2024.240018","url":null,"abstract":"<p><p>CX-5461, also known as pidnarulex, is a strong G4 stabilizer and has received FDA fast-track designation for BRCA1- and BRCA2- mutated cancers. However, quantitative measurements of the unfolding rates of CX-5461-G4 complexes which are important for the regulation function of G4s, remain lacking. Here, we employ single-molecule magnetic tweezers to measure the unfolding force distributions of c-<i>MYC</i> G4s in the presence of different concentrations of CX-5461. The unfolding force distributions exhibit three discrete levels of unfolding force peaks, corresponding to three binding modes. In combination with a fluorescent quenching assay and molecular docking to previously reported ligand-c-<i>MYC</i> G4 structure, we assigned the ~69 pN peak corresponding to the 1:1 (ligand:G4) complex where CX-5461 binds at the G4's 5'-end. The ~84 pN peak is attributed to the 2:1 complex where CX-5461 occupies both the 5' and 3'. Furthermore, using the Bell-Arrhenius model to fit the unfolding force distributions, we determined the zero-force unfolding rates of 1:1, and 2:1 complexes to be (2.4 ± 0.9) × 10<sup>-8</sup> s<sup>-1</sup> and (1.4 ± 1.0) × 10<sup>-9</sup> s<sup>-1</sup> respectively. These findings provide valuable insights for the development of G4-targeted ligands to combat c-<i>MYC</i>-driven cancers.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 3","pages":"180-189"},"PeriodicalIF":0.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725298","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":"Digital counting of force accumulation during mechanotransduction.","authors":"Xinyu Zhang, Bei Liu","doi":"10.52601/bpr.2024.240905","DOIUrl":"10.52601/bpr.2024.240905","url":null,"abstract":"","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 3","pages":"178-179"},"PeriodicalIF":0.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725295","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":"Foundation models in molecular biology.","authors":"Yunda Si, Jiawei Zou, Yicheng Gao, Guohui Chuai, Qi Liu, Luonan Chen","doi":"10.52601/bpr.2024.240006","DOIUrl":"10.52601/bpr.2024.240006","url":null,"abstract":"<p><p>Determining correlations between molecules at various levels is an important topic in molecular biology. Large language models have demonstrated a remarkable ability to capture correlations from large amounts of data in the field of natural language processing as well as image generation, and correlations captured from data using large language models can also be applicable to solving a wide range of specific tasks, hence large language models are also referred to as foundation models. The massive amount of data that exists in the field of molecular biology provides an excellent basis for the development of foundation models, and the recent emergence of foundation models in the field of molecular biology has really pushed the entire field forward. We summarize the foundation models developed based on RNA sequence data, DNA sequence data, protein sequence data, single-cell transcriptome data, and spatial transcriptome data respectively, and further discuss the research directions for the development of foundation models in molecular biology.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 3","pages":"135-151"},"PeriodicalIF":0.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725296","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}