Article
Biology
Jean-Philippe Defour, Emilie Leroy, Sharmila Dass, Thomas Balligand, Gabriel Levy, Ian C. Brett, Nicolas Papadopoulos, Celine Mouton, Lidvine Genet, Christian Pecquet, Judith Staerk, Steven O. Smith, Stefan N. Constantinescu, Lewis E. Kay
Summary: The study investigates the structural basis of activation for TpoR mutations S505N and W515K that induce myeloproliferative neoplasms. Ligand-independent activation of TpoR by TM asparagine (Asn) substitutions is shown to be proportional to the proximity of the Asn mutation to the intracellular membrane surface. The loss of helical structure in the juxtamembrane (JM) R/KWQFP motif and the effect of helical structure in the JM motif on receptor function are also investigated.
Article
Cell Biology
Luis Hernandez-Cano, Cristina Fernandez-Infante, Oscar Herranz, Pablo Berrocal, Francisco S. Lozano, Manuel A. Sanchez-Martin, Almudena Porras, Carmen Guerrero
Summary: C3G is a key factor in controlling platelet activation, aggregation, and the release of alpha-granule content, as well as promoting platelet-mediated angiogenesis and metastasis. It also plays a role in megakaryocyte maturation and platelet formation, and affects platelet production and internalization. These findings highlight the crucial role of C3G in regulating platelet functions and its involvement in pathological conditions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Monika Szabo, Wioleta Kowalczyk, Anna Tarasova, Jessica Andrade, Cheang Ly Be, Roger Mulder, Jacinta White, Adam G. Meyer, Kjiana E. Schwab, Kellie Cartledge, Tu C. Le, Anoja Wickrama Arachchilage, Xiaoli Wang, Ronald Hoffman, Susan K. Nilsson, David N. Haylock, David A. Winkler
Summary: Myelofibrosis is a life-threatening blood cancer, and current drugs only provide symptomatic relief without altering the course of the disease. Inhibition of thrombopoietin, an important cytokine for platelet production, shows promise in slowing or stopping MF progression. Computational modeling and rational residue substitutions have identified a lead cyclic peptide, 48, as essential for activity at the c-Mpl receptor. These peptides are significant tools for in vivo analysis and a step towards disease-modifying therapies for MF.
ADVANCED THERAPEUTICS
(2021)
Review
Cell Biology
Stefano Comazzetto, Bo Shen, Sean J. Morrison
Summary: This article presents an overview of the positioning of HSCs in the bone marrow and how their function is maintained, as well as discusses the regulatory role of niches in HSC function and hematopoiesis. Some important unresolved questions in this area have also been identified. The niches play a crucial role in maintaining HSC function and hematopoiesis.
DEVELOPMENTAL CELL
(2021)
Review
Peripheral Vascular Disease
Balasundaram Nandhini, Yacobu Sureshraj, Mohandass Kaviya, Thangavelu Sangeetha, Kathirvel Bharathi, Balasubramanian Balamuralikrishnan, Pappuswamy Manikantan, Meyyazhagan Arun, Kuchi Bhotla Haripriya, Pushparaj Karthika, Subramaniam Kalidass, Arumugam Vijaya Anand
Summary: Thrombocytes (platelets) play a role in hemostasis and thrombosis. They are produced from megakaryocytes through the action of thrombopoietin (TPO) protein encoded by the TPO gene. The interaction between TPO protein and c-Mpl receptor leads to the production of functional thrombocytes.
JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
(2023)
Article
Hematology
Nasrine Yahmi, Brahim Arkoun, Hana Raslova, William Vainchenker
Summary: Megakaryopoiesis is the process of platelet production from hematopoietic stem cells. It has several unique features compared to other hematopoietic cell differentiations. Recent advances have greatly improved our understanding of the different aspects of megakaryopoiesis and the regulation of platelet production. Furthermore, megakaryocytes can also be involved in hematopoietic regulation and immune response, and the lung is not only a site of platelet production but also a site of megakaryocyte differentiation.
Review
Biophysics
Wil Gardner, David A. Winkler, Benjamin W. Muir, Paul J. Pigram
Summary: Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging is a powerful label-free method for exploring organic, bioorganic, and biological systems. However, the complexity of the data produced by ToF-SIMS experiments makes interpretation and analysis challenging. Research has focused on applying multivariate analysis and machine learning techniques to find meaningful patterns and relationships in these datasets.
Article
Biochemistry & Molecular Biology
Sakshi Piplani, Puneet Singh, Nikolai Petrovsky, David A. Winkler
Summary: The urgent need for drugs to treat COVID-19 has led to a search for existing drugs and natural compounds that can be repurposed quickly. Researchers have developed a fast and robust computational process to screen large libraries of compounds, identifying potential inhibitors of the main protease of SARS-CoV-2. The top candidate compounds show promising activity against COVID-19 and provide leads for further experimental validation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Alexander Corletto, Amanda V. Ellis, Nick A. Shepelin, Marco Fronzi, David A. Winkler, Joseph G. Shapter, Peter C. Sherrell
Summary: Layered 2D crystals, with their unique properties and diversity, have great potential in energy conversion and harvesting devices. The synchronous multisource energy conversion enabled by these crystals offers a game-changing approach to device production and utilization in the future.
ADVANCED MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Suiying Ye, Nastaran Meftahi, Igor Lyskov, Tian Tian, Richard Whitfield, Sudhir Kumar, Andrew J. Christofferson, David A. Winkler, Chih-Jen Shih, Salvy Russo, Jean-Christophe Leroux, Yinyin Bao
Summary: In this study, a versatile and simple platform based on through-space charge transfer (TSCT) polymers was developed, which exhibited full-color-tunable emission and was aided by predictive machine learning models. By introducing electron donor groups containing simple polycyclic aromatic moieties (e.g., pyrene) through one-step copolymerization or end-group functionalization, continuous blue-to-red emission color tuning was easily achieved in solid polymers. Theoretical investigations confirmed the structurally dependent TSCT-induced emission redshifts. Additionally, the TSCT polymers were demonstrated to be a general design platform for solid-state stimuli-responsive materials, exemplified by their application in information encryption with high-contrast photochromic emission.
Article
Medicine, Research & Experimental
David Winkler, Ira Katz, Andrew Warden, Aaron Thornton, Geraldine Farjot
Summary: This study analyzed the dataset of protein-gas interactions, focusing on the potential clinical applications of xenon-protein interactions. A rational scoring method was used to generate a partial prioritized list of xenon protein targets. The study provides a preliminary analysis method for this massive dataset and emphasizes the importance of this dataset to the scientific community.
MEDICAL GAS RESEARCH
(2023)
Article
Nanoscience & Nanotechnology
Leonardo Contreas, Andrew L. Hook, David A. Winkler, Grazziela Figueredo, Paul Williams, Charles A. Laughton, Morgan R. Alexander, Philip M. Williams
Summary: Bacterial infections are becoming a greater concern due to antimicrobial resistance. The rational design of materials resistant to biofilm formation is a crucial strategy to prevent infections related to medical devices. Machine learning has been used to identify strong associations between bacterial adhesion and the physicochemical properties of polyacrylate libraries. However, the interpretability of nonlinear models is limited, making it challenging to understand the molecular interactions between materials and bacteria.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Analytical
Sarah E. Bamford, Dilek Yalcin, Wil Gardner, David A. Winkler, Thomas M. Kohl, Benjamin W. Muir, Shaun Howard, Eric A. Bruton, Paul J. Pigram
Summary: The self-organizing map with relational perspective mapping (SOM-RPM) is an unsupervised machine learning method used for visualizing and interpreting high-dimensional hyperspectral data. In this study, SOM-RPM was applied to stitched ToF-SIMS datasets to provide a direct comparison in both 2D and 3D. The quantitative assessment of annealing-induced chemical breakdown trends was conducted on spin-coated polyaniline (PANI) films, revealing differences in peak intensity ratios.
ANALYTICAL CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Xiliang Yan, Tongtao Yue, David A. A. Winkler, Yongguang Yin, Hao Zhu, Guibin Jiang, Bing Yan
Summary: Decades of nanotoxicology research have generated extensive and diverse data sets. However, data is not equal to information. This review discusses the role of artificial intelligence (AI) and molecular simulation in transforming nanotoxicity data into critical information, by constructing quantitative nanostructure-toxicity relationships and elucidating toxicity-related molecular mechanisms. Several obstacles must be overcome for AI and molecular simulation to have their full impact, including the lack of high-quality nanomaterials, standardized nanotoxicity data, model-friendly databases, specific and universal nanodescriptors, and realistic simulation of nanomaterials. The review also provides a comprehensive summary of current capability gaps and tools required to fill these gaps, as well as a perspective on future trends and challenges.
Article
Biochemistry & Molecular Biology
Sakshi Piplani, Puneet Singh, Nikolai Petrovsky, David A. A. Winkler
Summary: Drugs targeting novel targets are necessary for treating COVID-19 patients due to the rapid mutation of SARS-CoV-2. In silico simulations can quickly identify existing drugs with known safety profiles that can be repurposed for COVID-19 treatment. This study provides new insights into the SARS-CoV-2 spike protein and its potential regulation by endogenous hormones and drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
See Yoong Wong, Andrew L. Hook, Wil Gardner, Chien-Yi Chang, Ying Mei, Martyn C. Davies, Paul Williams, Morgan R. Alexander, Davide Ballabio, Benjamin W. Muir, David A. Winkler, Paul J. Pigram
Summary: Biofilm formation is a major problem in hospitals, and researching biofilm-resistant materials is critical. Polymer microarrays can efficiently discover new biofilm-resistant polymers. This study investigates bacterial attachment and surface chemistry on a polymer microarray to better understand Pseudomonas aeruginosa biofilm formation. Analyzing the data using linear multivariate analysis and a nonlinear self-organizing map reveals fragment ions associated with bacterial biofilm formation. Considering these insights, a second analysis is conducted that explicitly considers interactions between key fragments. This improved model provides chemical insights for designing materials that prevent pathogen attachment.
ADVANCED MATERIALS INTERFACES
(2023)
Article
Materials Science, Coatings & Films
Wil Gardner, David A. Winkler, David L. J. Alexander, Davide Ballabio, Benjamin W. Muir, Paul J. Pigram
Summary: In this study, two different ToF-SIMS imaging datasets were used to evaluate the impact of data preprocessing methods and SOM hyperparameters on the performance of SOM. It was found that preprocessing is generally more important than hyperparameter selection, and there are complex interactions between different parameters. The results of this study are important for understanding the effects of data processing on hyperspectral imaging data.
JOURNAL OF VACUUM SCIENCE & TECHNOLOGY A
(2023)
Article
Chemistry, Multidisciplinary
Alexander Corletto, Marco Fronzi, Alexis Krywula Joannidis, Peter C. Sherrell, Michael J. Ford, David A. Winkler, Joseph G. Shapter, James Bullock, Amanda V. Ellis
Summary: A new model is proposed to explain how the electrostatics and strain at the MoS2/metal interface influence the monolayer-selectivity of MME. The study demonstrates the significance of electrostatics in nanomaterial van der Waals interactions.
ADVANCED MATERIALS INTERFACES
(2023)
Editorial Material
Pharmacology & Pharmacy
David Alan Winkler
PHARMACEUTICAL SCIENCES
(2023)
Proceedings Paper
Computer Science, Artificial Intelligence
Aayush Kumar, Jimiama M. Mase, Divish Rengasamy, Benjamin Rothwell, Mercedes Torres Torres, David A. Winkler, Grazziela P. Figueredo
Summary: This paper presents an open-source Python toolbox called Ensemble Feature Importance (EFI) which provides robust and accurate feature importance quantification and reliable interpretation for prediction problems using fuzzy sets. EFI addresses uncertainties in feature importance quantification due to diverse machine learning algorithms and calculation methods, and it merges results from multiple models using decision fusion techniques.
MACHINE LEARNING, OPTIMIZATION, AND DATA SCIENCE, LOD 2022, PT II
(2023)
Article
Chemistry, Multidisciplinary
Xuying Li, Haoxin Mai, Junlin Lu, Xiaoming Wen, Tu C. Le, Salvy P. Russo, David A. Winkler, Dehong Chen, Rachel A. Caruso
Summary: This study used a combination of machine learning models and theoretical calculations to efficiently screen substitution elements that enhanced the photoactivity of Cs2AgBiBr6 perovskites. The results showed that d10-configured Zn2+ significantly boosted the photocatalytic activity. Experimental verification confirmed a 13-fold increase in toluene conversion compared to the unsubstituted counterpart. This research exemplifies the application of computational modeling in photocatalyst design and elucidating structure-property relationships.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
