Article
Biochemistry & Molecular Biology
Alon Ben David, Ada Barnea, Eran Diamant, Eyal Dor, Arieh Schwartz, Amram Torgeman, Ran Zichel
Summary: A high-throughput screening assay for receptor-binding inhibitors against BoNT/A was developed, leading to the identification of several potentially effective compounds. One compound, ATA, provided 92% protection in mice exposed to a lethal dose of BoNT/A. The study suggests that receptor-binding inhibitors may serve as next generation therapeutics for botulism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Yongliang Fang, Andrew Y. Chang, Deeptak Verma, Shin-Ichiro Miyashita, Susan Eszterhas, Pyung-Gang Lee, Yi Shen, Lydia R. Davis, Min Dong, Chris Bailey-Kellogg, Karl E. Griswold
Summary: In this study, a new library of botulinum neurotoxin serotype A (BoNT/A) light chains (BoNT/A-LC) was computationally designed and screened for reduced T cell epitope content and immunogenicity. High-speed fluorescence-activated cell sorting (FACS) was used to identify variants with wild-type-like enzyme kinetics. Some of these variants exhibited decreased immunogenicity in mice and demonstrated in vivo paralytic activity. One variant achieved near wild-type potency and a 300% reduction in antidrug antibody response. This study demonstrates a successful strategy for deimmunization of BoNT/A-LC and holds promise for deimmunizing other biologics with complex superstructures and mechanisms of action.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Xuan Wei, Lu Li, Yiwen Wu, Jia Liu
Summary: Engineered BoNTA proteins fused with cell-penetrating peptides (CPPs), particularly zinc finger protein, have shown improved cellular uptake and intramuscular therapeutic index, providing insights for developing next-generation neuromuscular modulators using CPP fusion.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Chemistry, Medicinal
Martin Amezcua, Ricardo S. Cruz, Alex Ku, Wilfred Moran, Marcos E. Ortega, Nicholas T. Salzameda
Summary: Botulinum neurotoxin is the most lethal toxin known to man, causing flaccid paralysis and potentially death. Dipeptides inhibitors can inhibit BoNT/A LC through a competitive mechanism, playing a crucial role in its action.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Food Science & Technology
Kyle S. Gregory, Tejaswini B. Mahadeva, Sai Man Liu, K. Ravi Acharya
Summary: Botulinum neurotoxins are toxic substances that can cause botulism, but they can also be used to treat neuromuscular conditions. This study reveals the crystal structures of the cell binding domain of botulinum neurotoxin A2 and its interactions with the receptor ganglioside GD1a. The findings provide important insights into the binding mechanism between the toxin and its receptor.
Review
Chemistry, Multidisciplinary
Xabier Rodriguez-Martinez, Enrique Pascual-San-Jose, Mariano Campoy-Quiles
Summary: The discovery of novel high-performing materials in organic solar cells has rapidly increased efficiency, but traditional experimentation methods are unable to evaluate the vast catalog of materials efficiently. High-throughput experimental and computational methods are being utilized to accelerate the discovery of new materials, with machine-learning algorithms playing a key role in retrieving quantitative structure-activity relationships.
ENERGY & ENVIRONMENTAL SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Jianxin Wang, Yuelin Wu, Deyan Luo, Chunlin Zhuang, Nianzhi Ning, Yanming Zhang, Zhili He, Jie Gao, Zhanying Hong, Xiguo Xv, Wannian Zhang, Tao Li, Zhenyuan Miao, Hui Wang
Summary: Researchers identified a novel scaffold, 2-thionicotinate, through high-throughput virtual screening to inhibit the activity of BoNT/A light chain. They synthesized and evaluated a series of derivatives, with compound ZM299 showing promising anti-BoNT/A activity and therapeutic efficacy in vivo, suggesting its potential as a drug candidate for botulism treatment.
CHINESE JOURNAL OF CHEMISTRY
(2022)
Review
Microbiology
Ghuncha Ambrin, Shuowei Cai, Bal Ram Singh
Summary: The study on botulinum neurotoxins (BoNTs) has rapidly evolved in understanding their structure and functions. It is currently used as a tool for understanding neurocellular activity and treating neurological disorders. Sensitive assays are crucial for biochemical, physiological, and pharmacological studies. The mechanism of crossing the epithelial cell barrier is also important. Cell-based assays have been developed and provide a comprehensive platform for studying the cellular interaction and activities of BoNT.
CRITICAL REVIEWS IN MICROBIOLOGY
(2023)
Review
Food Science & Technology
Kyle S. Gregory, K. Ravi Acharya
Summary: Botulinum neurotoxins (BoNTs) are highly potent neurotoxins that cause neuromuscular paralysis by cleaving SNARE complex proteins. They have high affinity and specificity for neuromuscular junctions. This review focuses on the structural analysis of the cell-binding domain of different BoNT subtypes, providing insights into their functions and potential therapeutic applications.
Article
Food Science & Technology
Kyle S. Gregory, Otsile O. Mojanaga, Sai Man Liu, K. Ravi Acharya
Summary: Botulinum neurotoxins (BoNT) are highly toxic proteins that cause botulism by proteolysis of a SNARE protein. They consist of three domains, with the H-C domain responsible for neuronal specificity. Some BoNTs have been commercialized for treating various neuromuscular conditions.
Article
Biochemistry & Molecular Biology
Kyle S. Gregory, Anna R. Newell, Otsile O. Mojanaga, Sai Man Liu, K. Ravi Acharya
Summary: This study determined the crystal structure of botulinum neurotoxin A6 cell binding domain (H-C/A6) in complex with GD1a and presented a new crystal form of wild type H-C/A6 (crystal form II), revealing the degree of conformational flexibility exhibited by H-C/A6.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Phuc Nguyen, Sylvia Chien, Jin Dai, Raymond J. Monnat, Pamela S. Becker, Hao Yuan Kueh
Summary: UPSIDE is a machine learning approach for discovering cell types and states from time-resolved live cell imaging data, capable of distinguishing different blood cell types and identifying clinical disease-related cell states. By utilizing deep learning technology, this method provides a unbiased tool for analyzing cell types and state transitions in biology and medicine.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Chemistry, Analytical
Sang-Yun Lee, Hyun Ju Hwang, Bosung Ku, Dong Woo Lee
Summary: The use of the CPRE 3D-HTS model improves the correlation of EGFR-targeting drugs compared to 2D cell-based HTS. In breast cancer cell lines, the CPRE 3D-HTS model shows a greater difference in the expression of HER2 protein between HER2-positive and HER2-negative cells. Alginate was selected as the extracellular matrix to enhance cell proliferation receptor expression in the CPRE 3D-HTS model.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
James Carthew, Hazem H. Abdelmaksoud, Karla J. Cowley, Margeaux Hodgson-Garms, Roey Elnathan, Joachim P. Spatz, Juergen Brugger, Helmut Thissen, Kaylene J. Simpson, Nicolas H. Voelcker, Jessica E. Frith, Victor J. Cadarso
Summary: The novel technology developed allows for direct imprint of micro- and nanoscaled topographical features onto the base of conventional cell cultureware, making it compatible with standard biological techniques and methods of analysis. High-throughput screening across five distinct cell types interrogated the effects of 12 surface topographies, demonstrating unique cell specific responses to behavior and cell morphological characteristics. This technology provides new insights into how surface topographies can regulate key image descriptors to drive cell fate determination in various fields in the life sciences.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Review
Pharmacology & Pharmacy
Fabio Stossi, Pankaj K. Singh, Kazem Safari, Michela Marini, Demetrio Labate, Michael A. Mancini
Summary: Measuring single cell responses to chemicals is crucial for human health, and high throughput, microscopy-based assays coupled with multi-dimensional single cell analysis methods are being used to address this problem. This article summarizes efforts in this field, focusing on environmental toxicology and drug screening, and discusses the advantages and limitations of high throughput assays.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Immunology
Kelly L. Warfield, Katie A. Howell, Hong Vu, Joan Geisbert, Gary Wong, Sergey Shulenin, Stephanie Sproule, Frederick W. Holtsberg, Daisy W. Leung, Gaya K. Amarasinghe, Dana L. Swenson, Sina Bavari, Gary P. Kobinger, Thomas W. Geisbert, M. Javad Aman
JOURNAL OF INFECTIOUS DISEASES
(2018)
Article
Chemistry, Medicinal
Jelena Konstantinovic, Erkan Kiris, Krishna P. Kota, Johanny Kugelman-Tonos, Milica Videnovic, Lisa H. Cazares, Natasa Terzic Jovanovic, Tatjana Z. Verbic, Boban Andjelkovic, Allen J. Duplantier, Sina Bavari, Bogdan A. Solaja
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Biochemical Research Methods
Krishnamurthy Konduru, Amy C. Shurtleff, Sina Bavari, Gerardo Kaplan
JOURNAL OF VIROLOGICAL METHODS
(2018)
Article
Microbiology
Maria Eugenia Loureiro, Andre Luiz Zorzetto-Fernandes, Sheli Radoshitzky, Xiaoli Chi, Simone Dallari, Nuha Marooki, Psylvia Leger, Sabrina Foscaldi, Vince Harjono, Sonia Sharma, Brian M. Zid, Nora Lopez, Juan Carlos de la Torre, Sina Bavari, Elina Zuniga
Article
Medicine, General & Internal
Jessica G. Shantha, John G. Mattia, Augustine Goba, Kayla G. Barnes, Faiqa K. Ebrahim, Colleen S. Kraft, Brent R. Hayek, Jessica N. Hartnett, Jeffrey G. Shaffer, John S. Schieffelin, John D. Sandi, Mambu Momoh, Simbirie Jalloh, Donald S. Grant, Kerry Dierberg, Joyce Chang, Sharmistha Mishra, Adrienne K. Chan, Rob Fowler, Tim O'Dempsey, Erick Kaluma, Taylor Hendricks, Roger Reiners, Melanie Reiners, Lowell A. Gess, Kwame ONeill, Sarian Kamara, Alie Wurie, Mohamed Mansaray, Nisha R. Acharya, William J. Liu, Sina Bavari, Gustavo Palacios, Moges Teshome, Ian Crozier, Paul E. Farmer, Timothy M. Uyeki, Daniel G. Bausch, Robert F. Garry, Matthew J. Vandy, Steven Yeh
Article
Microbiology
Kayla M. Coffin, Jun Liu, Travis K. Warren, Candace D. Blancett, Kathleen A. Kuehl, Donald K. Nichols, Jeremy J. Bearss, Christopher W. Schellhase, Cary J. Retterer, Jessica M. Weidner, Sheli R. Radoshitzky, Jennifer M. Brannan, Anthony P. Cardile, John M. Dye, Gustavo Palacios, Mei G. Sun, Jens H. Kuhn, Sina Bavari, Xiankun Zeng
CELL HOST & MICROBE
(2018)
Article
Virology
Piet Maes, Gaya K. Amarasinghe, Maria A. Ayllon, Christopher F. Basler, Sina Bavari, Kim R. Blasdell, Thomas Briese, Paul A. Brown, Alexander Bukreyev, Anne Balkema-Buschmann, Ursula J. Buchholz, Kartik Chandran, Ian Crozier, Rik L. de Swart, Ralf G. Dietzgen, Olga Dolnik, Leslie L. Domier, Jan F. Drexler, Ralf Duerrwald, William G. Dundon, W. Paul Duprex, John M. Dye, Andrew J. Easton, Anthony R. Fooks, Pierre B. H. Formenty, Ron A. M. Fouchier, Juliana Freitas-Astua, Elodie Ghedin, Anthony Griffiths, Roger Hewson, Masayuki Horie, Julia L. Hurwitz, Timothy H. Hyndman, Daohong Jiang, Gary P. Kobinger, Hideki Kondo, Gael Kurath, Ivan V. Kuzmin, Robert A. Lamb, Benhur Lee, Eric M. Leroy, Jianrong Li, Shin-Yi L. Marzano, Elke Muhlberger, Sergey V. Netesov, Norbert Nowotny, Gustavo Palacios, Bernadett Palyi, Janusz T. Paweska, Susan L. Payne, Bertus K. Rima, Paul Rota, Dennis Rubbenstroth, Peter Simmonds, Sophie J. Smither, Qisheng Song, Timothy Song, Kirsten Spann, Mark D. Stenglein, David M. Stone, Ayato Takada, Robert B. Tesh, Keizo Tomonaga, Noel Tordo, Jonathan S. Towner, Bernadette van den Hoogen, Nikos Vasilakis, Victoria Wahl, Peter J. Walker, David Wang, Lin-Fa Wang, Anna E. Whitfield, John V. Williams, Gongyin Ye, F. Murilo Zerbini, Yong-Zhen Zhang, Jens H. Kuhn
ARCHIVES OF VIROLOGY
(2019)
Article
Chemistry, Medicinal
Zivota Selakovic, Julie P. Tran, Krishna P. Kota, Marija Lazic, Cary Retterer, Robert Besh, Rekha G. Panchal, Veronica Soloveva, Vantongreen A. Sean, Wells B. Jay, Aleksandar Pavic, Tatjana Verbic, Branka Vasiljevic, Kathleen Kuehl, Allen J. Duplantier, Sina Bavari, Rajini Mudhasani, Bogdan A. Solaja
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Biochemical Research Methods
Michael D. Ward, Ernst E. Brueggemann, Tara Kenny, Raven E. Reitstetter, Christopher R. Mahone, Sylvia Trevino, Kelly Wetzel, Ginger C. Donnelly, Cary Retterer, Robert B. Norgren, Rekha G. Panchal, Travis K. Warren, Sina Bavari, Lisa H. Cazares
CLINICAL PROTEOMICS
(2019)
Article
Immunology
Melek M. E. Sunay, Karen A. O. Martins, Jesse T. Steffens, Melissa Gregory, Sean A. Vantongeren, Neal Van Hoeven, Preston G. Games, Sina Bavari
Article
Cell & Tissue Engineering
Onur Can Begentas, Dilara Koc, Sukran Yurtogullari, Musa Temel, Kamil Can Akcali, Seref Demirkaya, Erkan Kiris
Summary: A new iPSC line was established from a 25-year-old male with RRMS, demonstrating normal male karyotype, pluripotency markers expression, and ability to differentiate into three germ layers. This iPSC line serves as a valuable resource for investigating molecular mechanisms underlying RRMS.
STEM CELL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Edanur Sen, Krishna P. Kota, Rekha G. Panchal, Sina Bavari, Erkan Kiris
Summary: BoNT/A is the most studied serotype responsible for most cases of human botulism. Studies have shown that E3 ligase HECTD2 and deubiquitinase VCIP135 play crucial roles in the degradation of BoNT/A, potentially as drug targets for countermeasures against botulism.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Psychiatry
Sudhirkumar Yanpallewar, Francesco Tomassoni-Ardori, Mary Ellen Palko, Zhenyi Hong, Erkan Kiris, Jodi Becker, Gianluca Fulgenzi, Lino Tessarollo
Summary: Recent research suggests that the use of cognitive enhancers in conjunction with exposure-based therapy may be beneficial for individuals with post-traumatic stress disorder (PTSD). This study used a genetic strategy to increase cholinergic activity and found that it led to a reduction in fear response and fear expression. Additionally, enhancing cholinergic signaling with a drug promoted extinction learning in a model of PTSD-like behavior.
TRANSLATIONAL PSYCHIATRY
(2022)
Letter
Immunology
Ronald B. Reisler, Colleen S. Kraft, Sina Bavari, Anthony P. Cardile
CLINICAL INFECTIOUS DISEASES
(2018)