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Metformin escape in prostate cancer by activating the PTGR1 transcriptional program through a novel super-enhancer

Signal Transduction and Targeted Therapy 2023年第9期8卷 4365-4379页

作者： Jianheng Ye Shanghua Cai Yuanfa Feng Jinchuang Li Zhiduan Cai Yulin Deng Ren Liu Xuejin Zhu Jianming Lu Yangjia Zhuo Yingke Liang Jianjiang Xie Yanqiong Zhang Huichan He Zhaodong Han Zhenyu Jia Weide Zhong Department of Urology Guangzhou First People’s HospitalSouth China University of Technology510180 GuangzhouGuangdongChina Urology Key Laboratory of Guangdong Province The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical University510230 GuangzhouGuangdongChina Guangzhou National Laboratory No.9 XingDaoHuanBei RoadGuangzhou International Bio Island510005 GuangzhouGuangdongChina Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences100700 BeijingChina Department of Botany and Plant Sciences University of CaliforniaRiversideCA 92507USA Graduate Program in Genetics Genomics&BioinformaticsUniversity of CaliforniaRiversideCA 92507USA State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyTaipa999078 MacaoChina

The therapeutic efficacy of metformin in prostate cancer(PCa)appears uncertain based on various clinical *** treatment failure may be attributed to the high frequency of transcriptional dysregulation,which leads to drug ***,the underlying mechanism is still *** this study,we found evidences that metformin resistance in PCa cells may be linked to cell cycle ***-enhancers(SEs),crucial regulatory elements,have been shown to be associated with drug resistance in various *** analysis of SEs in metformin-resistant(MetR)PCa cells revealed a correlation with Prostaglandin Reductase 1(PTGR1)expression,which was identified as significantly increased in a cluster of cells with metformin resistance through single-cell transcriptome *** functional experiments showed that PTGR1 overexpression accelerated cell cycle progression by promoting progression from the G0/G1 to the S and G2/M phases,resulting in reduced sensitivity to ***,we identified key transcription factors that significantly increase PTGR1 expression,such as SRF and RUNX3,providing potential new targets to address metformin resistance in *** conclusion,our study sheds new light on the cellular mechanism underlying metformin resistance and the regulation of the SE-TFs-PTGR1 axis,offering potential avenues to enhance metformin’s therapeutic efficacy in PCa.

关键词： RUNX3 cancer offering

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Decomposition of dynamic transcriptomic responses during effector-triggered immunity reveals conserved responses in two distinct plant cell populations

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Plant Communications 2024年第8期5卷 1-17页

作者： Xiaotong Liu Daisuke Igarashi Rachel A.Hillmer Thomas Stoddard You Lu Kenichi Tsuda Chad L.Myers Fumiaki Katagiri Department of Plant and Microbial Biology University of Minnesota-Twin CitiesSt PaulMN 55108USA Department of Computer Science and Engineering University of Minnesota-Twin CitiesMinneapolisMN 55455USA Bioinformatics and Computational Biology Graduate Program University of Minnesota-Twin CitiesMinneapolisMN 55455USA Institute for Innovation Ajinomoto Co.Inc.KawasakiJapan State Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryHubei Key Lab of Plant PathologyCollege of Plant Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China Present address:225 S 6th St MinneapolisMN 55402USA Present address:Biotalys Inc.2520 Meridian Parkway Suite 480DurhamNC 27713USA Present address:Life Sciences Institute and Department of Cell and Developmental Biology University of Michigan Medical SchoolAnn ArborMI 48109USA

Rapid plant immune responses in the appropriate cells are needed for effective defense against *** transcriptome analysis is often used to describe overall immune responses,collection of transcriptome data with sufficient resolution in both space and time is *** reanalyzed public Arabidopsis time-course transcriptome data obtained after low-dose inoculation with a Pseudomonas syringae strain expressing the effector AvrRpt2,which induces effector-triggered immunity in ***-peak time-course patterns are prevalent among thousands of upregulated *** implemented a multicompartment modeling approach to decompose the double-peak pattern into two single-peak patterns for each *** decomposed peaks reveal an“echoing”pattern:the peak times of the first and second peaks correlate well across most upregulated *** demonstrated that the two peaks likely represent responses of two distinct cell populations that respond either cell autonomously or indirectly to ***,the peak decomposition has extracted spatial information from the time-course *** echoing pattern also indicates a conserved transcriptome response with different initiation times between the two cell populations despite different elicitor types.A gene set highly overlapping with the conserved gene set is also upregulated with similar kinetics during pattern-triggered *** of a WRKY network via different entry-point WRKYs can explain the similar but not identical transcriptome responses elicited by different elicitor *** discuss potential benefits of the properties of the WRKY activation network as an immune signaling network in light of pressure from rapidly evolving pathogens.

关键词： Arabidopsis Pseudomonas syringae plant immune response multi-compartment model WRKY transcription factors resilient immune signaling network

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Unsupervised Neural Tracing In Densely Labeled Multispectral Brainbow Images

Unsupervised Neural Tracing In Densely Labeled Multispectral...

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IEEE International Symposium on Biomedical Imaging

作者： Bin Duan Logan A Walker Douglas H Roossien Fred Y Shen Dawen Cai Yan Yan Illinois Institute of Technology Biophysics University of Michigan Bioinformatics Ball State University Neuroscience Graduate Program Cell and Developmental Biology Michigan Medicine

ISBN: (纸本)9781665412469;9781665429474

Recent advances in imaging technologies for generating large quantities of high-resolution 3D images, especially multispectral labeling technology such as Brainbow, permits unambiguous differentiation of neighboring neurons in a densely labeled brain. This enables, for the first time, the possibility of studying the connectivity between many neurons from a light microscopy image. The lack of reliable automated neuron morphology reconstruction, however, makes data analysis the bottleneck of extracting rich informatics in neuroscience. Supervoxel-based neuron segmentation methods have been proposed to solve this problem, however, previous approaches have been impeded by the large numbers of errors which arise in the final segmentation. In this paper, we present a novel unsupervised approach to trace neurons from multispectral Brainbow images, which prevents segmentation errors and tracing continuity errors using two innovations: First, we formulate a Gaussian mixture model-based clustering strategy to improve the separation of segmented color channels that provides accurate skeletons for the next steps. Then, a skeleton graph approach is proposed to allow the identification and correction of discontinuities in the neuron tree topology. We find that these innovations allow better performance over current state-of-the-art approaches, which results in more accurate neuron tracing results close to human expert annotation.

关键词： Image segmentation Technological innovation Three-dimensional displays Neuroscience Microscopy Neurons Morphology

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Clustering Analysis of a Spatiotemporal Dataset with a Novel Kernel Density Estimator

Clustering Analysis of a Spatiotemporal Dataset with a Novel...

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International Conference on Machine Learning and Cybernetics (ICMLC)

作者： Jen-Chien Yu Chun-Chieh Yang John Reuben Gilbert Rou-Jun Liu Yen-Jen Oyang Meng-Han Yang Department of Computer Science and Information Engineering National Kaohsiung University of Science and Technology Kaohsiung City Taiwan ROC Master Program in Statistics National Taiwan University Taipei Taiwan ROC Department of Computer Science & Information Engineering National Taiwan University Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University

A vast number of spatiotemporal datasets collected from a wide range of sources has motivated scientists to develop effective approaches to identify interesting patterns hidden in these datasets. In this respect, kernel density estimators, which belong to a class of non-parametric estimators in statistics, have been widely exploited in recent years. With this background, we have developed a novel kernel density estimator aiming to provide accurate analysis results. According to the evaluation with a real spatiotemporal dataset, which collected emergency medical service records in a county in the United States, the proposed kernel density estimator can approximate the probability density function significantly more accurately than a conventional kernel density estimator. Furthermore, we have exploited the proposed kernel density estimator to identify interesting patterns hidden in the real spatiotemporal dataset.

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Automatic Smart Crawling on Twitter for Weather Information in Indonesia

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Procedia Computer Science 2023年 227卷 795-804页

作者： Kartika Purwandari Reza Bayu Perdana Join W.C. Sigalingging Reza Rahutomo Bens Pardamean Bioinformatics and Data Science Research Center Bina Nusantara University Jakarta 11480 Indonesia Database Center Division of BMKG Meteorological Climatological and Geophysical Agency Jakarta 10720 Indonesia Information Systems Department School of Information Systems Bina Nusantara University Jakarta 11480 Indonesia Computer Science Department BINUS Graduate Program – Master of Computer Science Bina Nusantara University Jakarta 11480 Indonesia

Although Twitter is a popular platform for social interaction analysis and text data mining, it faces challenges with geolocation automation. To address this problem, the researchers propose the utilization of a Support Vector Machine (SVM) model to develop an automated Twitter crawling system. The system aims to collect data related to weather in Indonesia by employing Twin, a Python-based Twitter scraping software. To overcome null geolocations, the study incorporates aliases created based on the common practice of Indonesian users mentioning the country's location in tweets. The results demonstrate that the SVM model, combined with automated smart crawling, achieves an 85% accuracy rate.

关键词： Social media Twitter SVM smart crawling weather

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Confidentiality. Integrity, and Availability (CIA) Approach for Private Dataset Management System Design

Confidentiality. Integrity, and Availability (CIA) Approach ...

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Information Technology and Digital Applications (ICITDA), IEEE International Conference on

作者： Mahmud Isnan Gregorius Natanael Elwirehardja Dedy Ariansyah Reza Rahutomo Bens Pardamean Computer Science Department School of Computer Science Bina Nusantara University Jakarta Indonesia Bioinformatics and Data Science Research Center Bina Nusantara University Jakarta Indonesia Information Systems Department School of Information Systems Bina Nusantara University Jakarta Indonesia Computer Science Department BINUS Graduate Program - Master of Computer Science Bina Nusantara University Jakarta Indonesia

ISBN: (数字)9798331510732

ISBN: (纸本)9798331510749

Dataset management systems are essential for assisting research and development (R&D) organizations in applying data governance protocols, especially in managing the utilization of datasets. In R&D, datasets are vital sources for producing analysis, machine learning prediction, and supporting decision-making. As such, it is important to deploy dataset management systems with considerations regarding the aspects of Confidentiality, Integrity, and Availability (CIA) which is a design principle that emphasized information protection and collaboration facilitation among dataset users. The study proposed an analysis and a design for a dataset management system that takes CIA aspects into account. In the future, the proposed design will be utilized as a benchmark for building a dataset management system. In this study, the Waterfall method was adopted. A use case diagram, an ERD (Entity Relationship Diagram), and an activity diagram were constructed in the design stage. In the project implementation stage, the Laravel framework including Laravel Jetstream was considered to be used.

关键词： Protocols Data security Decision making Organizations Machine learning Encryption Protection Information technology Research and development System analysis and design

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Pseudomonas aeruginosa-derived DnaJ induces TLR2 expression through TLR10-mediated activation of the PI3K-SGK1 pathway in macrophages

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Microbes and Infection 2025年 105481页

作者： Lee, Jaehoo Jin, Yongxin Wu, Weihui Lee, Yeji Ha, Un-Hwan Department of Biotechnology and Bioinformatics Korea University Sejong 30019 South Korea Interdisciplinary Graduate Program for Artificial Intelligence Smart Convergence Technology Korea University Sejong 30019 South Korea State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education Department of Microbiology Nankai University Tianjin 300071 China

TLR2 is a key component of the innate immune system, responsible for recognizing Gram-positive bacterial components and initiating inflammatory signaling cascades that activate defense responses. However, little is known about the regulatory effects of Pseudomonas aeruginosa (P. aeruginosa) on TLR2 expression. In this study, we investigated the potential link between P. aeruginosa-derived DnaJ and TLR2 expression in macrophages, as well as the activation of downstream signaling pathways. Our findings revealed that DnaJ significantly induced TLR2 expression in a dose- and time-dependent manner, predominantly affecting TLR2 with minimal impact on other TLRs, such as TLR4 and TLR5, which detect bacterial PAMPs. The DnaJ-mediated TLR2 induction was driven by activation of the PI3K-SGK1 signaling pathway, with TLR10 playing a crucial role in facilitating these effects. This increase in TLR2 expression led to enhanced production of inflammatory cytokines in response to secondary Staphylococcus aureus infections, indicating a role in boosting host defense mechanisms. In conclusion, these findings suggest that P. aeruginosa-derived DnaJ promotes TLR2 expression via TLR10-mediated activation of the PI3K-SGK1 pathway, thereby enhancing host immune responses against Gram-positive bacterial infections. © 2025 Institut Pasteur

关键词： DnaJ Pseudomonas aeruginosa SGK1 TLR10 TLR2

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Twitter-based text classification using svm for weather information system 6

Twitter-based text classification using svm for weather info...

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6th International Conference on Information Management and Technology, ICIMTech 2021

作者： Purwandari, Kartika Rahutomo, Reza Sigalingging, Join W. C. Ajy Kusuma, Mahisa Prasetyo, Aji Pardamean, Bens Research Center Bina Nusantara University Bioinformatics and Data Science Jakarta11480 Indonesia BMKG Meteorological Climatological and Geophysical Agency Database Center Division Jakarta10720 Indonesia Bina Nusantara University BINUS Graduate Program - Master of Computer Science Computer Science Department Jakarta11480 Indonesia

ISBN: (纸本)9781665449373

The popularity of social media amplified the amount of text data that is used to enrich text classification research with machine learning approach. The modernization in weather information system is needed to produce real-time weather information using the involvement of Twitter users. GetOldTweets was used to cover data acquisition from Twitter. Support Vector Machine (SVM) was deployed as a machine learning model for text classification. The result was delivered in Esri Maps features. It facilitated a social sensing for Indonesia weather information system by using Twitter posts from Indonesian users with 93% accuracy. © 2021 IEEE.

关键词： Data acquisition

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Dual-targeting compounds possessing enhanced anticancer activity via microtubule disruption and histone deacetylase inhibition

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European Journal of Medicinal Chemistry 2024年 265卷 116042页

作者： Tseng, Yu-Wei Yang, Tsung-Jung Hsu, Yuan-Ling Liu, Jyung-Hurng Tseng, Yin-Chen Hsu, Tse-Wei Lu, Yueh Pan, Szu-Hua Cheng, Ting-Jen Rachel Fang, Jim-Min Department of Chemistry National Taiwan University Taipei 106 Taiwan Graduate Institute of Medical Genomics and Proteomics College of Medicine National Taiwan University Taipei 100 Taiwan Graduate Institute of Genomics and Bioinformatics College of Life Sciences National Chung Hsing University Taichung 40227 Taiwan The Genomics Research Center Academia Sinica Taipei 115 Taiwan Doctoral Degree Program of Translational Medicine National Taiwan University Taipei 100 Taiwan Genome and Systems Biology Degree Program National Taiwan University and Academia Sinica Taipei 100 Taiwan

Dual-targeting anticancer agents 4–29 are designed by combining the structural features of purine-type microtubule-disrupting compounds and HDAC inhibitors. A library of the conjugate compounds connected by appropriate linkers was synthesized and found to possess HDACs inhibitory activity and render microtubule fragmentation by activating katanin, a microtubule-severing protein. Among various zinc-binding groups, hydroxamic acid shows the highest inhibitory activity of Class I HDACs, which was also reconfirmed by three-dimensional quantitative structure-activity relationship (3D-QSAR) pharmacophore prediction. The purine–hydroxamate conjugates exhibit enhanced cytotoxicity against MDA-MB231 breast cancer cells, H1975 lung cancer cells, and various clinical isolated non-small-cell lung cancer cells with different epidermal growth factor receptor (EGFR) status. Pyridyl substituents could be used to replace the C2 and N9 phenyl moieties in the purine-type scaffold, which can help to improve the solubility under physiological conditions, thus increasing cytotoxicity. In mice treated with the purine–hydroxamate conjugates, the tumor growth rate was significantly reduced without causing toxic effects. Our study demonstrates the potential of the dual-targeting purine–hydroxamate compounds for cancer monotherapy. © 2023 Elsevier Masson SAS

关键词： Breast cancer Histidine deacetylase Hydroxamate Katanin Lung cancer Microtubule Purine-type conjugate

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Targeting protein-protein interaction interfaces with antiviral N protein inhibitor in SARS-CoV-2

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Biophysical Journal 2024年第4期123卷 478-488页

作者： Hong, Jhen-Yi Lin, Shih-Chao Kehn-Hall, Kylene Zhang, Kai-Min Luo, Shun-Yuan Wu, Hung-Yi Chang, Sui-Yuan Hou, Ming-Hon Institute of Genomics and Bioinformatics and Department of Life Sciences National Chung Hsing University Taichung Taiwan Bachelor Degree Program in Marine Biotechnology College of Life Sciences National Taiwan Ocean University Keelung Taiwan Department of Biomedical Sciences and Pathobiology Virginia-Maryland College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg VA United States Center for Emerging Zoonotic and Arthropod-borne Pathogens Virginia Polytechnic Institute and State University Blacksburg VA United States Department of Chemistry National Chung Hsing University Taichung Taiwan Graduate Institute of Veterinary Pathobiology College of Veterinary Medicine National Chung Hsing University. Taichung Taiwan Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine National Taiwan University Taipei Taiwan PhD Program in Medical Biotechnology National Chung Hsing University Taichung Taiwan Biotechnology Center National Chung Hsing University Taichung Taiwan

Coronaviruses not only pose significant global public health threats but also cause extensive damage to livestock-based industries. Previous studies have shown that 5-benzyloxygramine (P3) targets the Middle East respiratory syndrome coronavirus (MERS-CoV) nucleocapsid (N) protein N-terminal domain (N-NTD), inducing non-native protein-protein interactions (PPIs) that impair N protein function. Moreover, P3 exhibits broad-spectrum antiviral activity against CoVs. The sequence similarity of N proteins is relatively low among CoVs, further exhibiting notable variations in the hydrophobic residue responsible for non-native PPIs in the N-NTD. Therefore, to ascertain the mechanism by which P3 demonstrates broad-spectrum anti-CoV activity, we determined the crystal structure of the SARS-CoV-2 N-NTD:P3 complex. We found that P3 was positioned in the dimeric N-NTD via hydrophobic contacts. Compared with the interfaces in MERS-CoV N-NTD, P3 had a reversed orientation in SARS-CoV-2 N-NTD. The Phe residue in the MERS-CoV N-NTD:P3 complex stabilized both P3 moieties. However, in the SARS-CoV-2 N-NTD:P3 complex, the Ile residue formed only one interaction with the P3 benzene ring. Moreover, the pocket in the SARS-CoV-2 N-NTD:P3 complex was more hydrophobic, favoring the insertion of the P3 benzene ring into the complex. Nevertheless, hydrophobic interactions remained the primary stabilizing force in both complexes. These findings suggested that despite the differences in the sequence, P3 can accommodate a hydrophobic pocket in N-NTD to mediate a non-native PPI, enabling its effectiveness against various CoVs. © 2024 Biophysical Society

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