Article
Chemistry, Physical
Alex Berlaga, Anatoly B. Kolomeisky
Summary: This article investigates the molecular translocation mechanisms of antiporters and symporters in cellular membrane channels, and discovers that despite the differing transport flux directions, their molecular mechanisms are drastically different. The authors propose chemical-kinetic models to explain this phenomenon, and find that antiporters primarily utilize single-site transportation for translocation, while symporters require simultaneous association of two different molecules for translocation.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Review
Biochemistry & Molecular Biology
Tania Henriquez, Larissa Wirtz, Dan Su, Heinrich Jung
Summary: The solute/sodium symporter family consists of integral membrane proteins that use a sodium gradient for uphill transport. Members of this family are found in all three kingdoms of life, with some playing key roles in diseases and bacterial-host interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Soumajit Dutta, Balaji Selvam, Diwakar Shukla
Summary: This study uses molecular dynamic simulations to investigate the binding of sodium ions in the cannabinoid receptors CB1 and CB2. The simulations reveal that sodium ions bind to the primary binding site from different extracellular sites for CB1 and CB2, with CB1 also having a distinct secondary binding site. Additionally, simulations show that intracellular sodium ions can bind to the binding site in CB1.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Christopher J. Draper-Joyce, Rebecca Bhola, Jinan Wang, Apurba Bhattarai, Anh T. N. Nguyen, India Cowie-Kent, Kelly O'Sullivan, Ling Yeong Chia, Hariprasad Venugopal, Celine Valant, David M. Thal, Denise Wootten, Nicolas Panel, Jens Carlsson, Macdonald J. Christie, Paul J. White, Peter Scammells, Lauren T. May, Patrick M. Sexton, Radostin Danev, Yinglong Miao, Alisa Glukhova, Wendy L. Imlach, Arthur Christopoulos
Summary: The study demonstrates that a positive allosteric modulator of the A(1) receptor, MIPS521, exhibits analgesic efficacy in rats with neuropathic pain by modulating endogenous adenosine levels in the spinal cord. This provides proof of concept for structure-based allosteric drug design specific to disease contexts.
Review
Biochemistry & Molecular Biology
Andrei Mironenko, Ulrich Zachariae, Bert L. de Groot, Wojciech Kopec
Summary: Potassium channels play critical roles in physiological processes by providing a selective permeation route for K+ ions. The structure of the selectivity filter has been determined at atomic resolution, but the molecular mechanism of K+ ions permeation remains unclear. Various proposed mechanisms of ion permeation are discussed, with critical evaluation against available data.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Energy & Fuels
Maike Willke, Nils-Eric Rahm, Stephan Kabelac
Summary: Thermoelectric energy converters based on galvanic cells offer the potential to convert low-temperature waste heat into electrical energy, increasing overall energy conversion efficiency.
Article
Multidisciplinary Sciences
Janik B. Hedderich, Margherita Persechino, Katharina Becker, Franziska M. Heydenreich, Torben Gutermuth, Michel Bouvier, Moritz Buenemann, Peter Kolb
Summary: Researchers computationally describe alternative allosteric pockets in G-protein-coupled receptors, identifying nine previously untargeted sites for synthetic ligands. They further investigate the potential of modulating receptor function through ligand binding to these sites.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Alexander O. Shpakov
Summary: Allosteric regulation plays a critical role in the functioning of GPCRs and their signaling pathways. The complexity of allosteric effects caused by various regulators determines the multiplicity and topology of allosteric sites in GPCRs. These sites are involved in the regulation of receptor activity, GPCR-complex formation, and endocytosis. They are also targets for synthetic allosteric regulators and modulators. The review provides an overview of the principles and mechanisms of GPCRs allosteric regulation, the diversity of allosteric sites, and the endogenous and synthetic allosteric regulators.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Pedro Renault, Jesus Giraldo
Summary: Computational tools have been used to estimate the druggability of allosteric sites in GPCRs, but predicting hydrophobic sites remains challenging. This study introduces a dynamics-based approach using experimental structures, normal mode analysis, and molecular dynamics simulations to identify allosteric sites in beta 2AR, GCGR, and M2 receptors, showing promising predictive value.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Green & Sustainable Science & Technology
Zechuan Peng, Yang Zhou, Jiawei Wang, Luchuan Chen, Changwen Miao
Summary: In this study, sodium lactate was added into SSC mixtures to enhance their hydration performance. The presence of lactates was found to decrease the release of hydration heat and delay the hydration of SSC at the early stage, which is beneficial for maintaining workability. In the long term, lactates were observed to accelerate the dissolution of slag and improve the mechanical properties of SSC.
JOURNAL OF CLEANER PRODUCTION
(2022)
Article
Engineering, Chemical
Kim R. Kristiansen, Oivind Wilhelmsen, Signe Kjelstrup
Summary: This study presents a non-equilibrium thermodynamics approach for analyzing transport mechanisms in direct-contact membrane distillation. By incorporating the properties of the membrane, membrane interfaces, and temperature polarization layers, a unified framework is established to assess mass and heat transfer. The approach reveals that the temperature difference across the membrane is the true driving force of mass transfer, and simplifying models can disregard certain effects.
Article
Chemistry, Multidisciplinary
Antonella Ciancetta, Amandeep Kaur Gill, Tianyi Ding, Dmitry S. Karlov, George Chalhoub, Peter J. McCormick, Irina G. Tikhonova
Summary: This study developed a probe confined dynamic mapping protocol to predict allosteric sites on GPCRs, demonstrating the advantage of specific probes derived from GPCR allosteric ligand structures over commonly used cosolvents in allosteric site mapping. The protocol was successfully validated retrospectively on selected receptors and prospectively on the D-2 dopamine receptor, confirming the prediction through subsequent mutagenesis. It provides a fast and efficient prediction of key amino acid residues surrounding allosteric sites in membrane proteins, aiding in the design of allosteric modulators based on protein structure.
ACS CENTRAL SCIENCE
(2021)
Review
Biophysics
George Khelashvili, Anant K. Menon
Summary: The rapid flip-flop of phospholipids across the two leaflets of biological membranes is crucial for many aspects of cellular life. G protein-coupled receptors (GPCRs), such as opsins, exhibit constitutive scramblase activity in vitro, with opsins scrambling lipids at a unitary rate of >100,000 per second. This review discusses the physiological significance of GPCR scramblase activity and its regulation in cells.
ANNUAL REVIEW OF BIOPHYSICS
(2022)
Article
Physiology
Antonio G. Soares, Jorge Contreras, Crystal R. Archer, Elena Mironova, Rebecca Berdeaux, James D. Stockand, Tarek Mohamed Abd El-Aziz
Summary: The study demonstrates that targeted activation of Gs signaling exclusively in renal principal cells (PC) is sufficient to increase ENaC activity and decrease urinary sodium excretion in live animals.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Cell Biology
Javier Encinar del Dedo, Isabel Maria Fernandez-Golbano, Laura Pastor, Paula Meler, Cristina Ferrer-Orta, Elena Rebollo, Maria Isabel Geli
Summary: The study reveals the formation of ERSESs (ER sterol exit sites) within cellular membranes, where the sterol transporter Osh2 extracts sterols. Coupling of the sterol synthesis and transport machineries is essential for endocytosis in mother cells, but not in daughters.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Computer Science, Interdisciplinary Applications
Tu Mai Anh Do, Loic Pottier, Silvina Caino-Lores, Rafael Ferreira da Silva, Michel A. Cuendet, Harel Weinstein, Trilce Estrada, Michela Taufer, Ewa Deelman
Summary: Performance evaluation is crucial for understanding the behavior of scientific workflows, especially in dealing with in situ workflows. By proposing a lightweight metric, the resource usage efficiency of in situ workflow execution can be assessed, analyzing the tradeoffs of various configurable parameters and evaluating different execution scenarios.
JOURNAL OF COMPUTATIONAL SCIENCE
(2021)
Article
Biophysics
George Khelashvili, Ambrose Plante, Milka Doktorova, Harel Weinstein
Summary: Studies have shown that the fusion peptide (FP) of coronaviruses requires binding of Ca2+ ions to enhance penetration, but the mechanisms of membrane insertion and destabilization remain unclear.
BIOPHYSICAL JOURNAL
(2021)
Article
Biochemical Research Methods
Hector Carrillo-Cabada, Jeremy Benson, Asghar M. Razavi, Brianna Mulligan, Michel A. Cuendet, Harel Weinstein, Michela Taufer, Trilce Estrada
Summary: To successfully predict a protein's function, techniques that maintain its 3D information while performing at scale are necessary. Researchers extended a protein representation and neural network architecture, demonstrating applicability in protein function prediction and detection of conformational changes in protein trajectories.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Ambrose Plante, Harel Weinstein
Summary: Molecular Dynamics (MD) simulations are vital tools for ligand discovery and design, but the challenges of handling large datasets and rare events in complex molecular machines remain. A protocol called Rare Event Detection (RED) has been developed to efficiently detect functionally relevant responses to ligand binding, offering new insights into drug activity.
Article
Multidisciplinary Sciences
George R. Heath, Ekaterina Kots, Janice L. Robertson, Shifra Lansky, George Khelashvili, Harel Weinstein, Simon Scheuring
Summary: This study introduces a new technique called localization AFM (LAFM) that overcomes traditional AFM resolution limits by applying localization image reconstruction algorithms, allowing for structural analysis of biomolecules at the single-molecule level.
Correction
Multidisciplinary Sciences
David Froelicher, Juan R. Troncoso-Pastoriza, Jean Louis Raisaro, Michel A. Cuendet, Joao Sa Sousa, Hyunghoon Cho, Bonnie Berger, Jacques Fellay, Jean-Pierre Hubaux
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
David Froelicher, Juan R. Troncoso-Pastoriza, Jean Louis Raisaro, Michel A. Cuendet, Joao Sa Sousa, Hyunghoon Cho, Bonnie Berger, Jacques Fellay, Jean-Pierre Hubaux
Summary: The authors propose a federated analytics system based on multiparty homomorphic encryption to protect patient privacy and ensure accurate results in biomedical research. They demonstrate the system's effectiveness in various essential biomedical analysis tasks. This work represents a key step towards enabling multi-centric scientific collaborations and overcoming privacy obstacles.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Veronica Aedo-Lopez, Camille L. Gerard, Sarah Boughdad, Bianca Gautron Moura, Gregoire Berthod, Antonia Digklia, Krisztian Homicsko, Niklaus Schaefer, Rafael Duran, Michel A. Cuendet, Olivier Michielin
Summary: This retrospective study evaluated the safety and efficacy of sequential treatment with Ipilimumab plus Nivolumab and selective internal radiation therapy (SIRT) in patients with metastatic uveal melanoma. The results showed that this treatment approach is well-tolerated and has promising survival rates.
Article
Oncology
Bianca Gautron Moura, Camille L. Gerard, Nathalie Testart, Marian Caikovski, Alexandre Wicky, Veronica Aedo-Lopez, Gregoire Berthod, Krisztian Homicsko, John O. Prior, Clarisse Dromain, Lana E. Kandalaft, Michel A. Cuendet, Olivier Michielin
Summary: In stage IV melanoma, the combination of ipilimumab and nivolumab significantly improves outcomes but has a major financial impact on healthcare. This study analyzes the costs associated with ipilimumab-nivolumab combination, focusing on immune-related adverse events (irAE). Surprisingly, toxicity costs are insignificant compared to the total treatment costs, and patients with higher toxicity grades have lower costs and better outcomes. These findings provide important information for clinicians and healthcare organizations making treatment decisions in immunotherapy.
Article
Oncology
Michel A. Cuendet, Roberto Gatta, Alexandre Wicky, Camille L. Gerard, Margaux Dalla-Vale, Erica Tavazzi, Gregoire Michielin, Julie Delyon, Nabila Ferahta, Julien Cesbron, Sebastien Lofek, Alexandre Huber, Jeremy Jankovic, Rita Demicheli, Hasna Bouchaab, Antonia Digklia, Michel Obeid, Solange Peters, Manuela Eicher, Sylvain Pradervand, Olivier Michielin
Summary: This study utilized Process Mining to analyze the therapeutic pathways of cancer patients following COVID-19 infection, introducing Differential Process Mining tool to compare patient strata and quantify hospital adaptation to the pandemic, as well as to understand the impact of cancer and its treatment on COVID-19 outcomes.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Alexandre Wicky, Roberto Gatta, Sofiya Latifyan, Rita De Micheli, Camille Gerard, Sylvain Pradervand, Olivier Michielin, Michel A. Cuendet
Summary: The increasing availability of clinical real-world data (RWD) provides an opportunity to supplement evidence from randomized clinical trials and explore treatment outcomes in real-life conditions. Process mining is a suitable methodology for analyzing treatment paths and outcomes. In this study, an interactive application was implemented to compare treatment sequences based on overall survival, progression-free survival, and best overall response. The application was used to conduct a descriptive analysis of RWD in advanced melanoma patients and explore the outcomes of different treatment choices. Results showed long-term survival benefits from immune-checkpoint inhibitors rechallenge, suggesting potential implications for treatment guidelines.
FRONTIERS IN ONCOLOGY
(2023)
Article
Health Care Sciences & Services
Andre Manuel da Silva Lopes, Sara Colomer-Lahiguera, Celia Darnac, Stellio Giacomini, Sebastien Bugeia, Garance Gutknecht, Gilliosa Spurrier-Bernard, Michel Cuendet, Fanny Muet, Veronica Aedo-Lopez, Nuria Mederos, Olivier Michielin, Alfredo Addeo, Sofiya Latifyan, Manuela Eicher
Summary: This study aims to shorten the time between symptomatic immune-related adverse events (IrAEs) onset and clinician detection through remote patient monitoring and symptom management. The study plans to recruit 198 cancer patients receiving immune checkpoint inhibitors (ICIs) and randomize them into an intervention group and a control group. The results will make a significant impact on the routine care of patients treated with ICIs.
JMIR RESEARCH PROTOCOLS
(2023)
Article
Oncology
Lisa Haas, Anais Elewaut, Camille L. Gerard, Christian Umkehrer, Lukas Leiendecker, Malin Pedersen, Izabela Krecioch, David Hoffmann, Maria Novatchkova, Mario Kuttke, Tobias Neumann, Ines Pires da Silva, Harriet Witthock, Michel A. Cuendet, Sebastian Carotta, Kevin J. Harrington, Johannes Zuber, Richard A. Scolyer, Georgina Long, James S. Wilmott, Olivier Michielin, Sakari Vanharanta, Thomas Wiesner, Anna C. Obenauf
Summary: The study reveals that tumors relapsing after targeted therapy show cross-resistance to immunotherapies due to an immunosuppressive tumor microenvironment lacking CD103(+) dendritic cells. Cross-resistance is not a result of immune response pressure during resistance evolution, but stems from the MAPK pathway's increased transcriptional output driving immune evasion. Restoring CD103(+) dendritic cells can resensitize tumors to immunotherapy.
Meeting Abstract
Biophysics
George Khelashvili, Harel Weinstein
BIOPHYSICAL JOURNAL
(2021)