Article
Biochemistry & Molecular Biology
Kazumasa Sakurai, Ryosuke Tomiyama
Summary: Beta 2-Microglobulin (beta 2m) is the causative protein of dialysis-related amyloidosis, and differences in folding/unfolding behavior between wild type and D76N mutant are mainly due to differences in activation energy and stability of the native state, resulting in faster accumulation of the IT state for D76N in the refolding process, leading to enhanced amyloidogenicity. Stabilization of the native state is suggested as an effective approach for suppressing amyloid fibril formation in the mutant.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Maria Celeste Maschio, Jacopo Fregoni, Carla Molteni, Stefano Corni
Summary: The protein beta(2)-microglobulin can aggregate in insoluble amyloid fibrils, which deposit in the skeletal muscle system of patients undergoing long-term haemodialysis. Research has shown that the isomerization of a specific proline (Pro32) in beta(2)-m plays a key role in stabilizing and destabilizing the two isomers.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Multidisciplinary Sciences
Walter Conca, Mayyadah Alabdely, Faisal Albaiz, Michael Warren Foster, Maha Alamri, Morad Alkaff, Futwan Al-Mohanna, Nicolaas Nagelkerke, Reem Saad Almaghrabi
Summary: The study suggests that elevated levels of beta(2)-microglobulin in Covid-19 patients may serve as an early indicator of disease severity and predict disease outcomes. Beta(2)-microglobulin levels were found to be a significant predictor of disease severity.
Article
Biochemistry & Molecular Biology
Jessica N. Rabuck-Gibbons, Dmitry Lyumkis, James R. Williamson
Summary: Single-particle cryo-EM allows characterization of macromolecular structural heterogeneity. We developed a workflow to quantitatively mine cryo-EM data for structures with maximal diversity.
Article
Multidisciplinary Sciences
Sara Linse, Pietro Sormanni, David J. O'Connell
Summary: In this study, phage display libraries were constructed and used to screen for inhibitors of A beta 40 and A beta 42 aggregation. Two SXkmers, SXkmer-YLTIRLM and SXkmer-VI-WI-DD, were identified as inhibitors of A beta 42 and A beta 40 aggregation, respectively. The findings suggest that SXkmer-YLTIRLM blocks secondary nucleation through an interaction with oligomeric intermediates.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Environmental Sciences
Supabhorn Yimthiang, Phisit Pouyfung, Tanaporn Khamphaya, David A. Vesey, Glenda C. Gobe, Soisungwan Satarug
Summary: The most common causes of chronic kidney disease, diabetes, and hypertension are significant public health issues worldwide. Exposure to cadmium, a heavy metal pollutant, has been associated with kidney damage and increased blood pressure, especially in diabetics. This study found that increased blood cadmium levels were significantly associated with higher blood pressure in diabetics, suggesting a potential link between cadmium exposure, kidney damage, and hypertension in diabetics.
Article
Urology & Nephrology
Sonoo Mizuiri, Yoshiko Nishizawa, Kazuomi Yamashita, Toshiki Doi, Aiko Okubo, Kenichi Morii, Koji Usui, Michiko Arita, Takayuki Naito, Kenichiro Shigemoto, Takao Masaki
Summary: In patients on Pre-OL-HDF, alpha 1-MG RRs ≥20% and beta 2-MG RRs ≥80% were associated with better survival, beta 2-MG RR ≥80% and pre- and postdialysis beta 2-MG levels were significant predictors of all-cause mortality, and alpha 1-MG RR ≥20% may predict mortality.
Article
Cell Biology
Zhenchao Wu, Mengdie Yan, Min Zhang, Nan Wu, Guoyuan Ma, Bingbing Wang, Youbo Fan, Xintong Du, Can Ding, Yi Liu
Summary: The expression of beta 2-microglobulin (β2M) is implicated in the progression of fibrosis in various organs. A retrospective study on COPD patients found that increased levels of β2M in serum were associated with pulmonary fibrosis development, including thickening of the alveolar wall/septum. This research suggests that β2M serum levels may serve as a potential indicator for evaluating lung function and severity of fibrosis in clinical settings and may offer a promising target for future treatment of pulmonary fibrosis.
Article
Chemistry, Multidisciplinary
Yan Liu, Fang-Zi Liu, Shi Li, Hua Liu, KaKing Yan
Summary: This study shows that transient and high-energy self-assembly intermediates in coordination self-assembly reactions can be obtained through ball-milling approaches. These intermediates, which are difficult to access in solution-based reactions, are successfully trapped in the solid state. The structures of these intermediates are determined using various characterization techniques. The results highlight the opportunity of using mechanochemistry to study coordination self-assembly reactions in a different chemical space compared to conventional solution-based approaches.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Medicinal
Anna Pavlova, Leda Bassit, Bryan D. Cox, Maksym Korablyov, Christophe Chipot, Dharmeshkumar Patel, Diane L. Lynch, Franck Amblard, Raymond F. Schinazi, James C. Gumbart
Summary: Interfering with the self-assembly of virus nucleo-capsids is a promising approach for the development of novel antiviral agents. Molecular dynamics simulations have revealed that distinct conformations of nucleocapsid assembly intermediates are induced depending on whether the bound CAM accelerates or misdirects assembly.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Nanoscience & Nanotechnology
Guming Zou, Xueling Wang, Hongmei Gao
Summary: The study found that nanoparticle-assisted polymerase chain reaction (nano-PCR) showed higher sensitivity in detecting alpha 1 and beta 2-microglobulin in urine samples, with greater specificity and ten-fold higher detection sensitivity compared to conventional methods. Nano-PCR also exhibited brighter bands and higher gene relative expression levels, surpassing the accuracy and sensitivity of nephelometry immunoassay. Nano-PCR may play a crucial role in the future detection of kidney diseases.
SCIENCE OF ADVANCED MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Ryosuke Tomiyama, Masatomo So, Keiichi Yamaguchi, Yohei Miyanoiri, Kazumasa Sakurai
Summary: β(2)-Microglobulin can form amyloid fibrils in acidic conditions. The presence of disulfide bonds affects the residual structure of the monomer, which influences the morphology of the fibrils.
Review
Polymer Science
Shiao-Wei Kuo
Summary: This review discusses the hydrogen bonding interactions in polymer/POSS nanomaterials and the synthesis of mono-, di-, and octa-functional POSS monomers and their corresponding polymers. The impact of hydrogen bonding interactions on the miscibility, physical properties, self-assembly, and secondary structures of polymers with POSS nanoparticles, including phenolic, polybenzoxazine, PVPh, PMMA, and polypeptide derivatives, is highlighted.
JOURNAL OF POLYMER RESEARCH
(2022)
Article
Clinical Neurology
Yi-Ming Huang, Ya-Hui Ma, Pei-Yang Gao, Zhi-Bo Wang, Liang-Yu Huang, Jia-Hui Hou, Lan Tan, Jin-Tai Yu
Summary: This study analyzed the link between plasma B2M and CSF AD biomarkers as well as cognition. The results showed that B2M levels were associated with cognitive impairment and changes in AD biomarkers. This suggests that B2M could be a potential biomarker for preclinical AD.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Materials Science, Multidisciplinary
Paula Loman-Cortes, Donald J. Jacobs, Juan L. Vivero-Escoto
Summary: Molecular dynamics simulations were used to study the aggregation of POSSP molecules in water, with different functional groups affecting the aggregation process and final morphology. It was observed that the isobutyl substituents drive the aggregation mainly through the hydrophobic effect, while the phenyl POSS unit self-assembles primarily through the hydrophobic effect with additional pi-pi and H-bonding interactions. The final morphology of the aggregates suggests significant implications for the optical properties of the molecules.
MATERIALS TODAY COMMUNICATIONS
(2021)
Editorial Material
Biochemistry & Molecular Biology
Jim E. Horne, Sheena E. Radford
Summary: New structures and experiments reveal that the 0-barrel assembly machinery (BAM) in bacteria utilizes the energy of membrane elastic tension to aid in the folding of 0-barrel outer membrane proteins.
Article
Multidisciplinary Sciences
Yong Xu, Roberto Maya-Martinez, Nicolas Guthertz, George R. Heath, Iain W. Manfield, Alexander L. Breeze, Frank Sobott, Richard Foster, Sheena E. Radford
Summary: This study applied chemical kinetics to investigate the assembly mechanism of hIAPP and discovered two small-molecule modulators that can regulate hIAPP assembly, which can serve as promising starting-points for research on hIAPP aggregation and the development of therapeutics for T2D.
NATURE COMMUNICATIONS
(2022)
Review
Neurosciences
Theodoros K. Karamanos, Arnout P. Kalverda, Sheena E. Radford
Summary: The early stages of protein misfolding and aggregation involve dynamic disorder and present challenges in capturing atomic level visualization. Identifying specific conformers on-pathway to aggregation within large pools of rapidly moving molecules is complex. This article describes experimental and computational approaches for studying the dynamic nature of protein misfolding and aggregation, and discusses challenges in describing these species due to ensemble averaging of experimental restraints. The potential of machine learning methods in extracting aggregation-relevant sub-ensembles is also explored.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Sarina Sanami, Tracey J. Purton, David P. Smith, Mick F. Tuite, Wei-Feng Xue
Summary: The division of amyloid fibril particles through fragmentation is related to the progression of neurodegenerative diseases. Controlled sonication can be used as a form of mechanical perturbation to assess the relative fragmentation stabilities of different amyloid fibril structures. Different polymorphs of alpha-synuclein fibrils displayed varied fragmentation stabilities, with A30P and A53T variants showing increased resistance compared to the wild-type.
Review
Biochemistry & Molecular Biology
Yong Xu, Roberto Maya-Martinez, Sheena E. Radford
Summary: The pathological assembly of intrinsically disordered proteins/peptides (IDPs) into amyloid fibrils is associated with various human pathologies. Discovering therapeutic agents for these diseases is challenging due to the diverse aggregation pathways and transient nature of IDPs.
ESSAYS IN BIOCHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Kevin Wu, Thomas C. Minshull, Sheena E. Radford, Antonio N. Calabrese, James C. A. Bardwell
Summary: Trigger factor plays a more active role in protein folding by binding to partially folded proteins, preventing non-productive self-association, and facilitating proteins to reach a native-like intermediate state before completing folding and acquiring enzymatic activity upon release.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Bob Schiffrin, Jonathan M. Machin, Theodoros K. Karamanos, Anastasia Zhuravleva, David J. Brockwell, Sheena E. Radford, Antonio N. Calabrese
Summary: This study reveals the crucial interaction between the OMP chaperone SurA and the OMP folding catalyst BAM, and proposes a model for OMP biogenesis.
COMMUNICATIONS BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Chalmers Chau, Fabio Marcuccio, Dimitrios Soulias, Martin Andrew Edwards, Andrew Tuplin, Sheena E. Radford, Eric Hewitt, Paolo Actis
Summary: This study presents a polymer-electrolyte solid-state nanopore system for analyzing biomolecular conformation under physiological conditions. By using specific salts, the system's performance is enhanced, allowing for the analysis of Chikungunya virus RNA conformation.
Review
Biochemistry & Molecular Biology
Laura E. Shippey, Susan G. Campbell, Andrew F. Hill, David P. Smith
Summary: Parkinson's disease is a common neurodegenerative condition that affects individuals worldwide, leading to debilitating motor and non motor symptoms. The aggregation of alpha-synuclein protein has been identified as the causative agent in neuronal degeneration. Extracellular vesicles are believed to play a role in the propagation of Parkinson's pathology, although the exact mechanism is not fully understood.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Roberto Maya-Martinez, Yong Xu, Nicolas Guthertz, Martin Walko, Theodoros K. Karamanos, Frank Sobott, Alexander L. Breeze, Sheena E. Radford
Summary: This study utilized NMR methods combined with photo-induced crosslinking to detect and structurally characterize transient dimers of D76N-112m. The results showed that these crosslinked dimers have different structures from previously characterized dimers and possess potent inhibitory effects on amyloid formation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Sabine M. Ulamec, Roberto Maya-Martinez, Emily J. Byrd, Katherine M. Dewison, Yong Xu, Leon F. Willis, Frank Sobott, George R. Heath, Patricija van Oosten Hawle, Vladimir L. Buchman, Sheena E. Radford, David J. Brockwell
Summary: In this study, the authors characterized the impact of amino acid substitution on alpha-synuclein aggregation. They found that residues 38 and 42 within the P1 region of alpha-synuclein influence amyloid formation.
NATURE COMMUNICATIONS
(2022)
Article
Education & Educational Research
Melissa M. Lacey, Hollie Shaw, Nikki Abbott, Caroline J. Dalton, David P. Smith
Summary: This study investigates the inspirations and aspirations of first year Biosciences and Chemistry undergraduates, and reveals the connection between career goals and ethnicity. The findings also highlight the importance of aligning course content with students' career aims for increased motivation and engagement.
EDUCATION SCIENCES
(2022)
Article
Microbiology
Melissa M. Lacey, David P. Smith
Summary: Artificial intelligence (AI) has become a tangible and disruptive force in education, particularly through the use of generative large language models (LLM) like OpenAI's ChatGPT. These AI models can perform tasks that traditionally require human thought, such as data analysis, understanding complex ideas, problem-solving, coding, and generating written outputs. The field of AI is advancing rapidly, with the emergence of new language models like GPT-4, Bard AI, and Bing AI, which have the ability to access real-time information, analyze images, and are being integrated into various applications.
MICROBIOLOGY AUSTRALIA
(2023)
Article
Nanoscience & Nanotechnology
Fabio Marcuccio, Dimitrios Soulias, Chalmers C. C. Chau, Sheena E. Radford, Eric Hewitt, Paolo Actis, Martin Andrew Edwards
Summary: In this study, the addition of poly(ethylene) glycol (PEG) to the external solution is shown to enhance the detection of biomolecules using solid-state nanopores. The researchers demonstrate that this addition creates an imbalance in the transport properties of cations and anions, which significantly affects the current response of the nanopore. The findings suggest that tuning the diffusion coefficients of ions could enhance the sensitivity of nanopore sensing.
ACS NANOSCIENCE AU
(2023)
Review
Chemistry, Multidisciplinary
Romany J. McLure, Sheena E. Radford, David J. Brockwell
Summary: Directed evolution is a powerful tool for engineering new functions in biomolecules and gaining insights into protein behavior. It accelerates the process of natural evolution through multiple rounds of gene diversification and selection.
TRENDS IN CHEMISTRY
(2022)