Article
Automation & Control Systems
Chunxiang Wang, Mingsi Tong, Liqun Zhao, Xinghu Yu, Songlin Zhuang, Huijun Gao
Summary: The study introduces DanioSense (DS), an automatic tracker for group larval zebrafish, that overcomes challenges such as similar appearances, frequent occlusions, and highly discontinuous kinematics through the integration of a light convolutional neural network and a centerline extraction algorithm. DS is capable of localizing individuals even in occlusion cases where object identities are prone to switch, providing detailed quantitative data for a large-scale larvae group in nearly real time.
IEEE TRANSACTIONS ON AUTOMATION SCIENCE AND ENGINEERING
(2022)
Article
Biology
Gefei Zhang, Xinghu Yu, Gang Huang, Dongxu Lei, Mingsi Tong
Summary: This paper presents an improved high-throughput imaging system for zebrafish larvae, which enhances reliability and automation through optimized loading strategy, dynamic model establishment, and automated rotation method. The improvements significantly reduce human intervention and increase efficiency and success rates of larva imaging.
COMPUTERS IN BIOLOGY AND MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Menglei Xia, XinYao Yan, Zehui Zan, Fan Yang, Mengjiao Liu, Danni Xue, Yanbing Shen, Min Wang
Summary: The study successfully obtained a high-efficiency Arthrobacter simplex strain with C1(2) dehydrogenation ability through a new screening strategy and optimized model, achieving high substrate conversion rates.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Xi He, Shuo Quan, Min Xu, Silveria Rodriguez, Shih Lin Goh, Jiajie Wei, Arthur Fridman, Kenneth A. Koeplinger, Steve S. Carroll, Jay A. Grobler, Amy S. Espeseth, David B. Olsen, Daria J. Hazuda, Dai Wang
Summary: This study successfully constructed a noninfectious SARS-CoV-2 reporter replicon for deciphering viral replication mechanisms and evaluating antiviral drugs, and developed a high-throughput antiviral assay. Significant differences in the potencies of several SARS-CoV-2 inhibitors in different cell lines were observed, highlighting the importance of testing compounds in multiple cell culture models for discovering antivirals capable of inhibiting viral replication in vivo.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Alexandra Lubin, Jason Otterstrom, Yvette Hoade, Ivana Bjedov, Eleanor Stead, Matthew Whelan, Gaia Gestri, Yael Paran, Elspeth Payne
Summary: Zebrafish offer a unique opportunity for drug screening in living animals, but the limited availability of imaging and analysis platforms has restricted their use. Researchers developed an easy-to-use automated screening procedure for high-throughput phenotype-based screens of live zebrafish, utilizing AI and brightfield/fluorescent imaging. The system was validated for various assays and proved to be a broadly applicable and rapidly customizable platform for high-content screening in zebrafish.
Article
Pharmacology & Pharmacy
Nikunj M. Shukla, Fumi Sato-Kaneko, Shiyin Yao, Minya Pu, Michael Chan, Fitzgerald S. Lao, Yukiya Sako, Tetsuya Saito, Karen Messer, Tomoko Hayashi, Howard B. Cottam, Maripat Corr, Dennis A. Carson
Summary: Extracellular vesicles play a crucial role in intercellular communication and immune regulation. Researchers have identified small molecule compounds that can enhance the immunogenicity of vaccines by increasing the release of extracellular vesicles. The compounds were screened and validated through multiple assays, leading to the discovery of potential vaccine adjuvants.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Katja F. Hellendahl, Maryke Fehlau, Sebastian Hans, Peter Neubauer, Anke Kurreck
Summary: The study introduces a luciferase-based assay for the detection of NK activity, which was validated in a 96-well plate format. The high-throughput assay showed comparable results to HPLC analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Applied
Ines Fuster Fernandez, Michael Kickstein, Wolf-Dieter Fessner
Summary: This article reports the generation of metal chelating compounds by the transketolase from Geobacillus stearothermophilus, which can be used for high-throughput screening of TKgst and its variants. The colorimetric assay in both solid- and liquid-phase formats validated the specificity and sensitivity of the assays. This method is important for engineering the TKgst enzyme towards improved conversion of aromatic aldehydes.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Multidisciplinary Sciences
Chance M. Carbaugh, William H. van der Schalie, Mark W. Widder
Summary: Engineered nanomaterials with unique properties may pose health and environmental concerns. A study using zebrafish PMR test for toxicity evaluation, along with automated dechorionation, showed improved bioavailability of nanomaterials. Behavioral and toxicological responses were measured at 30-31 hours and 120 hours, revealing behavioral responses for 13 nanomaterials and acute toxicity levels below the maximum test concentration for 9 nanomaterials.
Article
Pharmacology & Pharmacy
Ningning Tang, Ling Li, Fei Xie, Ying Lu, Zifan Zuo, Hao Shan, Quan Zhang, Lianwen Zhang
Summary: Inhibition of cellular O-GlcNAcylation can suppress proliferation and migration of cancer cells, leading to a new avenue for cancer therapy. A cell-based fluorescent reporter was developed to sense changes in cellular O-GlcNAcylation, allowing for identification of natural compounds such as sesamin that inhibit O-GlcNAcylation and migration of cancer cells.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2021)
Article
Chemistry, Multidisciplinary
Anqi Yang, Xiang Lin, Zijian Liu, Xin Duan, Yurou Yuan, Jiaxuan Zhang, Qilin Liang, Xianglin Ji, Nannan Sun, Huajun Yu, Weiwei He, Lili Zhu, Bingzhe Xu, Xudong Lin
Summary: A novel in vivo screening strategy combining hierarchically structured biohybrid triboelectric nano-generators (HB-TENGs) arrays with computational bioinformatics analysis for high-throughput pharmacological evaluation using Caenorhabditis elegans is described. The animals' behaviors are efficiently converted into friction deformation through HB-TENGs, and the resulting triboelectric signals are extracted for various bioinformation of the screened compounds. The information-rich electrical readouts are sufficient to predict a drug's identity by multiple-Gaussian-kernels-based machine learning methods.
Article
Chemistry, Medicinal
Brittney J. Mills, Malika P. Godamudunage, Siyuan Ren, Malabika Laha
Summary: This study evaluated the biophysical properties of two ADCs in 16 formulation conditions using high-throughput techniques and verified the predictive capabilities of the screening methods through stability studies. The results showed that high-throughput stability indicators, such as Tagg and B22, have similar ranking abilities as traditional methods like SEC data in assessing aggregate formation, while conformational stability indicators (Tm) are less predictive. Additionally, the high-throughput assays effectively identified poor performing formulation conditions, which is the ultimate goal of screening assays.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Parisa Shiri, Veronica Lai, Tara Zepel, Daniel Griffin, Jonathan Reifman, Sean Clark, Shad Grunert, Lars P. E. Yunker, Sebastian Steiner, Henry Situ, Fan Yang, Paloma L. Prieto, Jason E. Hein
Summary: Solubility screening is essential but labor intensive. By developing a flexible robotic system with computer vision and iterative feedback, researchers can successfully measure solubility in multiple solvents autonomously, saving time and resources.
Article
Chemistry, Multidisciplinary
Huiming Yuan, Zhongpeng Dai, Xiaodan Zhang, Baofeng Zhao, Hongwei Chu, Lihua Zhang, Yukui Zhang
Summary: This study introduces a FAST method for efficient and thorough proteome analysis, which significantly outperforms previous methods in terms of speed and sample quantity. By combining FAST with nanoLC-ESI-MS/MS, a highly reproducible and precise platform for label-free quantification of proteome was established, marking a major advance in high throughput sample treatment and quantitative analysis of proteomes.
SCIENCE CHINA-CHEMISTRY
(2021)
Article
Developmental Biology
Elisabeth C. Kugler, James Frost, Vishmi Silva, Karen Plant, Karishma Chhabria, Tim J. A. Chico, Paul A. Armitage
Summary: Zebrafish vasculature quantification (ZVQ) is a image analysis workflow that allows for the 3D quantification of zebrafish brain vasculature. It enables assessment of vascular anatomy, extraction of quantitative parameters, and study of vascular biology.
Article
Biochemical Research Methods
Abigail Sharrock, Timothy S. Mulligan, Kelsi R. Hall, Elsie M. Williams, David T. White, Liyun Zhang, Kevin Emmerich, Frazer Matthews, Saumya Nimmagadda, Selena Washington, Katherine D. Le, Danielle Meir-Levi, Olivia L. Cox, Meera T. Saxena, Anne L. Calof, Martha E. Lopez-Burks, Arthur D. Lander, Ding Ding, Hongkai Ji, David F. Ackerley, Jeff S. Mumm
Summary: Researchers have developed an improved NTR 2.0 variant through rational engineering and cross-species screening, which significantly enhances cell-specific ablation efficacy without the need for toxic prodrug treatment. This discovery allows for enhanced investigations into cell function, stem cell niche regenerative capacity, and chronic degenerative diseases.
Article
Developmental Biology
Christopher J. Hall, Jonathan W. Astin, Jeff S. Mumm, David F. Ackerley
Summary: This article investigates a new approach to target neutrophils using an improved variant of NTR, showing that it is more effective than current treatment regimens.
Article
Cell & Tissue Engineering
Bria L. Macklin, Ying-Yu Lin, Kevin Emmerich, Emily Wisniewski, Brian M. Polster, Konstantinos Konstantopoulos, Jeff S. Mumm, Sharon Gerecht
Summary: Human-induced pluripotent stem cell-derived endothelial cells (iECs) have angiogenic potential and their phenotype is regulated by epigenetics, indicating their potential therapeutic applications.
NPJ REGENERATIVE MEDICINE
(2022)
Article
Neurosciences
Joseph Fogerty, Ping Song, Patrick Boyd, Sarah E. Grabinski, Thanh Hoang, Adrian Reich, Lauren T. Cianciolo, Seth Blackshaw, Jeff S. Mumm, David R. Hyde, Brian D. Perkins
Summary: Zebrafish has the ability to regenerate retinal neurons and restore visual function, which is not permanent in mammals. However, in zebrafish models of retinal degeneration, photoreceptor death does not induce the regeneration of lost cells. Both MG reprogramming and proliferation of retinal progenitor cells require reactive microglia and associated inflammatory signaling.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Ziva Zajec, Jaka Dernovsek, Martin Distel, Martina Gobec, Tihomir Tomasic
Summary: In this article, a new class of allosteric Hsp90 C-terminal domain (CTD) inhibitors based on the virtual screening hit TVS24 is reported, which showed anti-proliferative activity in the SK-N-MC Ewing sarcoma cell line. The optimized compounds exhibited enhanced anticancer activity in the SK-N-MC cell line. Exposure to the most potent analogue 11c depleted critical Hsp90 client proteins involved in cancer pathways without inducing a heat shock response. This study highlights Hsp90 CTD inhibitors as promising new agents for the treatment of Ewing sarcoma.
BIOORGANIC CHEMISTRY
(2023)
Article
Oncology
Sarah Grissenberger, Caterina Sturtzel, Andrea Wenninger-Weinzierl, Branka Radic-Sarikas, Eva Scheuringer, Lisa Bierbaumer, Vesnie Etienne, Fariba Nemati, Susana Pascoal, Marcus Toetzl, Eleni M. Tomazou, Martin Metzelder, Eva M. Putz, Didier Decaudin, Olivier Delattre, Didier Surdez, Heinrich Kovar, Florian Halbritter, Martin Distel
Summary: High-throughput drug screening using zebrafish xenografts identified dual inhibition of anti-apoptotic proteins MCL-1 and BCL-XL as an effective strategy against Ewing sarcoma cells. The combination treatment showed enhanced efficacy compared to single agents in both zebrafish and mouse models, suggesting a promising therapeutic approach for Ewing sarcoma.
Article
Biochemistry & Molecular Biology
Khadija Hassan, Blondelle Matio Kemkuignou, Marco Kirchenwitz, Kathrin Wittstein, Monique Rascher-Albaghdadi, Clara Chepkirui, Josphat C. Matasyoh, Cony Decock, Reinhard W. Koster, Theresia E. B. Stradal, Marc Stadler
Summary: This study investigated the neurotrophic properties of compounds isolated from two types of mushrooms. The results showed that some of these compounds can stimulate the expression of neurotrophic factors and enhance neurite outgrowth. These findings suggest that these compounds have potential as therapeutic agents for neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Karin Schelch, Sebastian Eder, Benjamin Zitta, Monica Phimmachanh, Thomas G. Johnson, Dominik Emminger, Andrea Wenninger-Weinzierl, Caterina Sturtzel, Hugo Poplimont, Alexander Ries, Konrad Hoetzenecker, Mir A. Hoda, Walter Berger, Martin Distel, Balazs Dome, Glen Reid, Michael Grusch
Summary: Pleural mesothelioma (PM) is a highly aggressive cancer with limited treatment options. The oncoprotein Y-box-binding protein-1 (YB-1) is overexpressed in cancer and has been shown to promote cancer cell migration. This study investigates the role of YB-1 in PM cell behavior and identifies snail as a critical regulator of YB-1-mediated cell motility. The findings provide insights into the mechanism underlying PM's aggressive nature and highlight the importance of YB-1 in this cancer.
MOLECULAR ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Johanna Klughammer, Daria Romanovskaia, Amelie Nemc, Annika Posautz, Charlotte A. Seid, Linda C. Schuster, Melissa C. Keinath, Juan Sebastian Lugo Ramos, Lindsay Kosack, Ann Evankow, Dieter Printz, Stefanie Kirchberger, Bekir Erguener, Paul Datlinger, Nikolaus Fortelny, Christian Schmidl, Matthias Farlik, Kaja Skjaerven, Andreas Bergthaler, Miriam Liedvogel, Denise Thaller, Pamela A. Burger, Marcela Hermann, Martin Distel, Daniel L. Distel, Anna Kuebber-Heiss, Christoph Bock
Summary: This study maps DNA methylation in 535 vertebrates and 45 invertebrates and establishes a reference dataset for cross-species analysis. It quantifies the association between DNA methylation and genomic DNA sequence throughout vertebrate evolution and reveals a deeply conserved association of DNA methylation with tissue type. The study also identifies evolutionary changes in DNA methylation at gene promoters for orthologous genes.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Ossia M. Eichhoff, Corinne I. Stoffel, Jan Kasler, Luzia Briker, Patrick Turko, Gergely Karsai, Nina Zila, Verena Paulitschke, Phil F. Cheng, Alexander Leitner, Andrea Bileck, Nicola Zamboni, Anja Irmisch, Zsolt Balazs, Aizhan Tastanova, Susana Pascoal, Pal Johansen, Rebekka Wegmann, Julien Mena, Alaa Othman, Vasanthi S. Viswanathan, Judith Wenzina, Andrea Aloia, Annalisa Saltari, Andreas Dzung, Michael Krauthammer, Stuart L. Schreiber, Thorsten Hornemann, Martin Distel, Berend Snijder, Reinhard Dummer, Mitchell P. Levesque
Summary: The clinical management of NRAS-mutated melanomas is challenging due to resistance that arises through genetic, transcriptional, and metabolic adaptation. However, the adoption of a mesenchymal phenotype with a quiescent metabolic program in NRAS-mutated melanoma cells confers sensitivity to reactive oxygen species (ROS) induction, which can be inhibited by ROS inducers in combination with MAPK pathway inhibitors. The findings suggest that targeting both metabolic reprogramming and MAPK signaling could improve patient treatment in melanoma and other cancers.
Article
Medicine, General & Internal
Jana Block, Christina Rashkova, Irinka Castanon, Samaneh Zoghi, Jessica Platon, Rico C. Ardy, Mitsuhiro Fujiwara, Beatriz Chaves, Rouven Schoppmeyer, Caspar I. van der Made, Raul Jimenez Heredia, Frederike L. Harms, Samin Alavi, Laia Alsina, Paula Sanchez Moreno, Rainiero Avila Polo, Rocio Cabrera-Perez, Sevgi Kostel Bal, Laurene Pfajfer, Bernhard Ransmayr, Anna-Katharina Mautner, Ryohei Kondo, Anna Tinnacher, Michael Caldera, Michael Schuster, Cecilia Dominguez Conde, Rene Platzer, Elisabeth Salzer, Thomas Boyer, Han G. Brunner, Judith E. Nooitgedagt-Frons, Estibaliz Iglesias, Angela Deya-Martinez, Marisol Camacho-Lovillo, Joerg Menche, Christoph Bock, Johannes B. Huppa, Winfried F. Pickl, Martin Distel, Jeffrey A. Yoder, David Traver, Karin R. Engelhardt, Tobias Linden, Leo Kager, J. Thomas Hannich, Alexander Hoischen, Sophie Hambleton, Sabine Illsinger, Lydie Da Costa, Kerstin Kutsche, Zahra Chavoshzadeh, Jaap D. van Buul, Jordi Anton, Joan Calzada-Hernandez, Olaf Neth, Julien Viaud, Akihiko Nishikimi, Loic Dupre, Kaan Boztug
Summary: This study reveals that DOCK11 regulates T-cell shape and migration as well as erythroid development. Inherited loss-of-function variants in DOCK11 resulted in early-onset severe immune dysregulation and normocytic anemia.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Oncology
C. Sturtzel, S. Grissenberger, P. Bozatzi, E. Scheuringer, A. Wenninger-Weinzierl, Z. Zajec, J. Dernovsek, S. Pascoal, V. Gehl, A. Kutsch, A. Granig, F. Rifatbegovic, M. Carre, A. Lang, I. Valtingojer, J. Moll, D. Loetsch, F. Erhart, G. Widhalm, D. Surdez, O. Delattre, N. Andre, J. Stampfl, T. Tomasic, S. Taschner-Mandl, M. Distel
Summary: Zebrafish xenotransplantation models are increasingly used for phenotypic drug screening in precision oncology. This study presents a robust workflow for drug screening in zebrafish xenografts using high-content imaging. The authors established methods for embedding xenografts in 96-well format and provided strategies for automated imaging and analysis. The assay enables quantification of small compound efficacy in large cohorts of a vertebrate model system in vivo.
NPJ PRECISION ONCOLOGY
(2023)
Article
Biology
Kevin Emmerich, David T. T. White, Siva P. P. Kambhampati, Grace L. L. Casado, Tian-Ming Fu, Zeeshaan Chunawala, Arpan Sahoo, Saumya Nimmagadda, Nimisha Krishnan, Meera T. T. Saxena, Steven L. L. Walker, Eric Betzig, Rangaramanujam M. M. Kannan, Jeff S. S. Mumm
Summary: Analyzing microglial activity in a zebrafish model, the study shows the immunosuppressive effect of dexamethasone in vivo and the enhanced photoreceptor regeneration when conjugated to dendrimer nanoparticles. The study also discusses the potential mechanisms by which dexamethasone accelerates retinal regeneration and the effects of dendrimer-based targeting. Intravital time-lapse imaging revealed that post-injury dexamethasone inhibited microglia reactivity, and the dendrimer-conjugated formulation decreased toxicity and improved regeneration enhancing effects.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Tori R. Tucker, Courtney A. Knitter, Deena M. Khoury, Sheida Eshghi, Sophia Tran, Abigail Sharrock, Travis J. Wiles, David F. Ackerley, Jeff S. Mumm, Michael J. Parsons
Summary: Expression of Escherichia coli nitroreductase (NTR1.0) driven by a transgene makes animal cells susceptible to metronidazole (MTZ). Although NTR1.0/MTZ tools have been used in zebrafish studies, they are not suitable for chronic cell loss modeling due to the harmful effects of prolonged MTZ application. By using a more active nitroreductase (NTR2.0) that requires lower MTZ dose, the researchers established two new zebrafish lines for acute & beta;-cell ablation without MTZ-associated intestinal pathology. This study paves the way for modeling diabetes and related pathologies.
DISEASE MODELS & MECHANISMS
(2023)
Article
Biochemical Research Methods
Hanbin Zhang, Stavrini Papadaki, Xiaoting Sun, Xinyue Wang, Mikhail Drobizhev, Luxia Yao, Michel Rehbock, Reinhard W. Koester, Lianfeng Wu, Kazuhiko Namikawa, Kiryl D. Piatkevich
Summary: Recent progress in the development of fluorescent proteins has led to the creation of a wide range of near-infrared fluorescent proteins (NIR FPs), which are increasingly being used in various imaging applications. However, the diversity of NIR FPs presents a challenge for end-users in selecting the most suitable one for a specific application. In this study, we conducted a systematic and quantitative assessment of 22 NIR FPs in cultured mammalian cells and primary mouse neurons, and identified a set of top-performing FPs that can cover a majority of imaging applications.