Article
Oncology
Lamis Yehia, Charis Eng
Summary: The study of characteristics of breast cancer in young women has important implications for personalized genomics-driven management.
CLINICAL CANCER RESEARCH
(2022)
Review
Microbiology
Ayush Kumar, Georgia Stavrakis, Andrew H. Karaba
Summary: Herpesviruses are common DNA viruses that cause lifelong infections and are associated with various diseases. While they can evade the immune system, they are recognized by the innate immune system, leading to inflammation. Recent studies have found that inflammasome signaling plays a role in herpesvirus innate immune activation and impacts disease outcomes.
Review
Microbiology
Ayush Kumar, Georgia Stavrakis, Andrew H. Karaba
Summary: Herpesviruses are common DNA viruses that cause lifelong infections and are associated with various diseases. They activate the innate immune system by inflammasome signaling, leading to inflammation and potential disease outcomes.
Article
Obstetrics & Gynecology
Lan N. Vuong
Summary: Freeze-all strategy has emerged as an alternative approach in in vitro fertilization (IVF) to reduce the negative effects of controlled ovarian stimulation. However, current studies have inconsistent results and a personalized approach should be taken based on individual patient characteristics and preference.
HUMAN REPRODUCTION
(2022)
Review
Ophthalmology
Mohit Parekh, Davide Romano, Rintra Wongvisavavit, Giulia Coco, Giuseppe Giannaccare, Stefano Ferrari, Carlos Rocha-de-Lossada, Hannah J. Levis, Francesco Semeraro, Marina Rodriguez Calvo-de-Mora, Vincenzo Scorcia, Vito Romano
Summary: Descemet membrane endothelial keratoplasty (DMEK) is a popular surgical procedure for treating Fuchs endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK). The size of the graft is crucial for the success of the procedure, with smaller grafts being preferred. However, larger diameter grafts pose challenges due to higher detachment rates.
ACTA OPHTHALMOLOGICA
(2023)
Article
Psychiatry
Elias Langeland, Ingvild Faxvaag Johnsen, Kaja Kastrup Somme, Arne Magnus Morken, Eilin Kristine Erevik, Eirin Kolberg, Jakob Jonsson, Rune Aune Mentzoni, Stale Pallesen
Summary: This study examined whether gambling loss limits should be income-specific and found that income does moderate empirically derived gambling loss limits. The lowest income group had the lowest loss limits, while the highest income group had the highest loss limits. Income-based gambling loss limits may have higher applied value for preventing gambling related harm compared to general loss limits.
FRONTIERS IN PSYCHIATRY
(2022)
Review
Cell Biology
Cristiana Barone, Roberto Orsenigo, Raffaella Meneveri, Silvia Brunelli, Emanuele Azzoni
Summary: Our understanding of the complexity of the developing hematopoietic system has greatly increased in recent decades. We now know that multiple HSC-independent progenitor populations during fetal development play vital roles that can affect adult physiology and lead to disease. Ontogeny has been shown to be a primary determinant of the function of critical cell types.
Article
Computer Science, Hardware & Architecture
Xiaomeng Zhai, Hong Zhang, Xu Huang, Shouhua Zhang
Summary: This paper focuses on the problem of graph partitioning in distributed graph computing. The existing graph partitioning methods do not consider the relationship between partition strategies and graph algorithm characteristics, resulting in significant performance differences. To address this issue, the paper proposes a distributed graph partitioning framework based on program analysis, which can select the optimal partitioning strategy based on the characteristics of the graph algorithm. Additionally, the paper introduces a triangle-based partitioning strategy and redesigns the PageRank algorithm to reduce shuffling operations. Experimental results show that the proposed adaptive graph partitioning framework outperforms the original framework, especially in triangle counting and PageRank algorithms, on both real-world and synthetic graphs.
JOURNAL OF SUPERCOMPUTING
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Tolga Aksu, Carlos A. Morillo, Richard Sutton
Summary: This article describes a practical decision pathway for managing vasovagal syncope, including the locations of autonomic ganglia and methods for evaluating the response to treatment.
EUROPEAN HEART JOURNAL
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Dirk Van Raemdonck, Laurens J. Ceulemans, Robin Vos, Geert M. Verleden
Summary: Lung transplantation may involve lobar transplantation and graft reduction to better match the recipient. Some patients may be given priority for transplantation based on their condition.
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2021)
Article
Neurosciences
Pavel Prado, Sebastian Moguilner, Jhony A. Mejia, Agustin Sainz-Ballesteros, Monica Otero, Agustina Birba, Hernando Santamaria-Garcia, Agustina Legaz, Sol Fittipaldi, Josephine Cruzat, Enzo Tagliazucchi, Mario Parra, Ruben Herzog, Agustin Ibanez
Summary: Brain functional connectivity in dementia has been assessed using various EEG connectivity metrics, and joint analyses integrating information from different metrics can provide a more comprehensive characterization of brain interactions. In this study, rsEEG was recorded in individuals with AD, bvFTD, and HCs, and whole-brain functional connectivity was estimated using 101 different types of connectivity metrics. The multi-metric analysis revealed patterns of hypoconnectivity in frontotemporal regions in both patient groups, which were differently captured by frequency- and time-domain metrics. These joint analyses contribute to a more reliable and interpretable description of atypical functional connectivity in neurodegeneration.
NEUROBIOLOGY OF DISEASE
(2023)
Editorial Material
Rheumatology
Andreas Kronbichler, Milena Bond, Christian Dejaco
Summary: This editorial discusses the reclassification of previously diagnosed GPA patients using the 2022 ACR/EULAR classification criteria.
Editorial Material
Biochemistry & Molecular Biology
Izhar Karbat, Eitan Reuveny
Summary: Ion channels can adjust their activity by incorporating auxiliary subunits, and this study reveals that a voltage-gated K+ channel auxiliary subunit can also modulate the gating of Ca2+-activated Cl- channels.
Editorial Material
Biochemistry & Molecular Biology
Nancy E. Sealover, Robert L. Kortum
Summary: The specific amino acid substitution substantially affects the biological activity and oncogenicity of mutant KRAS, creating challenges for the development of effective treatments for RAS-mutated cancers.
Article
Gastroenterology & Hepatology
Camille Danne, Nathalie Rolhion, Harry Sokol
Summary: Faecal microbiota transplantation (FMT) shows varying efficacy in treating different diseases. Sokol and colleagues discuss the relevance of recipient factors, such as inflammation, immunity, and genetics, in influencing the success of FMT.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Chemistry, Medicinal
Fergus Boyles, Charlotte M. Deane, Garrett M. Morris
Summary: Machine learning scoring functions for protein-ligand binding affinity perform better on crystal structures than on docked poses, but a hybrid scoring function combining structure-based and ligand-based features shows comparable performance on docked poses to purely structure-based scoring functions trained on crystal poses. However, the hybrid scoring function may not always generalize well to protein targets not represented in the training set, indicating the need for improved scoring functions and additional validation benchmarks.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Hannah T. Baddock, Sanja Brolih, Yuliana Yosaatmadja, Malitha Ratnaweera, Marcin Bielinski, Lonnie P. Swift, Abimael Cruz-Migoni, Haitian Fan, Jeremy R. Keown, Alexander P. Walker, Garrett M. Morris, Jonathan M. Grimes, Ervin Fodor, Christopher J. Schofield, Opher Gileadi, Peter J. McHugh
Summary: The nsp14-nsp10 complex of SARS-CoV-2 has been found to possess RNase activity and is capable of digesting various RNA structures. Its activity is enhanced by the viral RNA-dependent RNA polymerase complex nsp12-7-8. Inhibitors of nsp14-nsp10, including ebselen and raltegravir, have been identified and may have potential use in the treatment of COVID-19.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Lucy Kate Ladefoged, Rebekka Koch, Philip C. Biggin, Birgit Schiott
Summary: Studying the action of multimodal antidepressant drug vortioxetine (VXT) on different receptors can provide insights into the mechanisms of agonist-antagonist dual behavior and activation without polar interaction with helix 5.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Chemistry, Physical
Zhiyi Wu, Philip C. Biggin
Summary: Absolute binding free-energy calculations play a crucial role in drug design, but accuracy is of utmost importance. This study explores the most suitable approach for simulation boxes containing lipid bilayers, and introduces the Rocklin correction method for lipid bilayer systems.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Biochemistry & Molecular Biology
Harold Grosjean, Mehtap Isik, Anthony Aimon, David Mobley, John Chodera, Frank von Delft, Philip C. Biggin
Summary: A novel crystallographic fragment screening data set was generated and used in the SAMPL7 challenge for protein-ligands. The results show that there is room for improvement in the development of computational tools particularly when applied to fragment-based drug design.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2022)
Article
Physiology
Adamo S. Mancino, William G. Glass, Yuhao Yan, Philip C. Biggin, Derek Bowie
Summary: Using electrophysiology and molecular dynamics simulations, this study highlights the role of two alternatively spliced residues in the DI S3-S4 linker in channel activation of Nav1.5 and suggests a conserved function in Nav1.4 isoform. Understanding the structural mechanisms of alternative splicing in gating properties of voltage-gated ion channels can provide insights into therapeutic target identification and drug development for related cardiac disorders.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Angelina R. Sekirnik, Jessica K. Reynolds, Larissa See, Joseph P. Bluck, Amy R. Scorah, Cynthia Tallant, Bernadette Lee, Katarzyna B. Leszczynska, Rachel L. Grimley, R. Ian Storer, Marta Malattia, Sara Crespillo, Sofia Caria, Stephanie Duclos, Ester M. Hammond, Stefan Knapp, Garrett M. Morris, Fernanda Duarte, Stuart J. Conway, Philip C. Biggin
Summary: This study investigates the differences between the two isoforms of TRIM33, TRIM33δ and TRIM33γ, using structural and biophysical approaches. It is found that both isoforms have similar affinities for methylated lysine and acetylated lysine, providing a starting point for further investigation into the cellular function of TRIM33.
ACS CHEMICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
An Goto, Raul Rodriguez-Esteban, Sebastian H. Scharf, Garrett M. Morris
Summary: Drug resistance caused by mutations is a significant public health threat. This study provides a comprehensive perspective on Hepatitis B virus mutations by combining clinical research and genetic data from scientific literature, identifying mutational hotspots and a common mutation position related to anti-HBV drug binding.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Physical
Simon M. Lichtinger, Philip C. Biggin
Summary: The structure of proteins holds the key to understanding their function, but studying the conformational transitions is challenging. The traditional molecular dynamics simulation suffers from starting-state dependence, while the new MEMENTO method provides a solution.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Multidisciplinary Sciences
Eric Gibbs, Emily Klemm, David Seiferth, Arvind Kumar, Serban L. Ilca, Philip C. Biggin, Sudha Chakrapani
Summary: In this study, cryo-EM structures of the α1βGlyR in the presence of an antagonist, agonist, and agonist with a positive allosteric modulator were determined. The structures revealed distinct pore conformations with varying degrees of asymmetry, and the receptors were found to be in closed or desensitized states. Subunit-specific features and characteristics of the extracellular and intracellular domains were also identified. These findings provide a framework for further investigations into the function of this physiologically important channel.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Suleyman Selim Cinaroglu, Philip C. Biggin
Summary: Understanding the thermodynamic signature of protein-peptide binding events is a major challenge in computational chemistry. This study computed the enthalpy of binding for protein-peptide complexes using available experimental data and identified key sampling problems that can be addressed to improve the agreement with experiments. The results show the potential of computational calorimetry in predicting protein-peptide binding enthalpy.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Sueleyman Selim Cinaroglu, Philip C. C. Biggin
Summary: The enthalpic and entropic components of ligand-protein binding free energy are challenging to predict accurately. Recent advances in predicting relative and absolute binding free energies have been successful, but predicting the enthalpic contributions remains challenging. A study evaluating the performance of absolute enthalpy of binding calculations for inhibitors against a bromodomain protein showed good agreement with experimental data and revealed the importance of considering conformational dynamics of a specific loop in improving accuracy.
Article
Chemistry, Physical
David Seiferth, Stephen J. Tucker, Philip C. Biggin
Summary: Transmembrane anion transport by synthetic ionophores is important for understanding endogenous anion transport and has potential therapeutic implications. Computational studies using non-polarizable and polarizable force fields provide insights into the binding properties of anions. The results show solvent dependency and the importance of electrostatics and oxidation status in anion recognition.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Multidisciplinary
Martin Buttenschoen, Garrett M. Morris, Charlotte M. Deane
Summary: In recent years, there have been significant developments in deep learning-based protein-ligand docking methods, offering great potential in terms of speed and accuracy. However, these methods often produce physically implausible molecular structures despite claims of state-of-the-art performance. It is crucial to evaluate them not only based on crystallographic RMSD but also on steric and energetic criteria. We introduce PoseBusters, a Python package that performs standard quality checks, and use it to compare different docking methods. The results show that classical docking tools currently outperform deep learning-based methods in terms of physical plausibility and generalization ability.
Article
Chemistry, Multidisciplinary
Daniel Crusius, Jason R. Schnell, Flaviu Cipcigan, Philip C. Biggin
Summary: Knowing the solution structures of cyclic peptides is crucial for predicting the pharmacokinetic properties in drug discovery. In this study, we introduced the MacroConf dataset and computational workflows to evaluate the performance of current in silico methods in reproducing experimental cyclic peptide solution structures. Our findings show that enhanced sampling molecular dynamics methods, like Gaussian accelerated MD, performed well in reproducing experimental results. Conventional MD suffered from limited sampling, especially for compounds with proline isomerization. Cheminformatics-based conformer generators generated diverse and plausible structures that matched the sampling observed in MD-based methods, but did not provide thermodynamic insights. The presented computational workflow can be easily extended to include new compounds or different simulation methods, serving as a benchmark to improve cyclic peptide conformer generators.