Article
Multidisciplinary Sciences
Masayuki Iwamoto, Masayuki Morito, Shigetoshi Oiki, Yudai Nishitani, Daisuke Yamamoto, Nobuaki Matsumori
Summary: The study reveals that dianionic cardiolipin (CL) has higher affinity for KcsA and can bind to both the N-terminal M0 helix and a specific site, while monoanionic lipids primarily interact with the M0 helix. This suggests the presence of an alternative CL-binding site in the transmembrane domain. Furthermore, CL enhances the channel opening independently of the M0 helix, while the action of monoanionic lipids is mediated solely by the M0 helix.
Article
Chemistry, Physical
Yukina Suzuki, Keisuke Hirata, James M. Lisy, Shun-ichi Ishiuchi, Masaaki Fujii
Summary: The conformation of the K+ - peptide complex shows significant variation with temperature, indicating greater flexibility and lower barrier heights when complexed with K+ compared to other metal-peptide complexes. The variability of the conformational distribution with temperature for the ions follows the same order of ion permeability of a K+ channel. This study highlights the power of using an additional temperature-controlled ion trap to explore the conformational landscape of flexible molecular systems.
JOURNAL OF PHYSICAL CHEMISTRY A
(2021)
Article
Biochemical Research Methods
Brennica Marlow, Georg Kuenze, Jens Meiler, Julia Koehler Leman
Summary: Lipid molecules, such as cholesterol, interact with integral membrane proteins (IMP) in a different way compared to drug-like molecules. The RosettaCholesterol protocol, developed in this study, improves the sampling and scoring of native poses of protein-cholesterol complexes. It also quantifies the specificity of cholesterol binding sites, providing a basis for further experimental validation and modeling.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Matthew J. Ryan, Lujia Gao, Francis I. Valiyaveetil, Martin T. Zanni, Alexei A. Kananenka
Summary: The potassium ion configurations in the selectivity filter of the KcsA ion channel protein were investigated using 2D IR spectroscopy. The study found that in the closed conductive state of the KcsA channel, K+ ions do not occupy adjacent binding sites. The experimental data supported the soft-knock ion configurations rather than the hard-knock ion configurations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Przemyslaw Borys, Paulina Trybek, Beata Dworakowska, Piotr Bednarczyk, Agata Wawrzkiewicz-Jalowiecka
Summary: The patch-clamp technique is a powerful tool for real-time observation of transport protein activity; the proposed simplified mathematical method in this study can assess distinct conformational substates of the channel.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Multidisciplinary
Amitava Chandra, Ankona Datta
Summary: Anionic phospholipids play a key role in cell signaling, and developing fluorescent sensors that can detect them in living cells is important. Cell-permeable sensors allow rapid detection and tracking of intracellular anionic phospholipids. This peptide-based sensor can enter cells via endosomal machinery or lipofection to detect anionic phospholipids in the cell membrane. Colocalization studies confirm its ability to detect intracellular anionic phospholipids.
Article
Physiology
Evan C. Ray, Rolando Carrisoza-Gaytan, Mohammad Al-Bataineh, Allison L. Marciszyn, Lubika J. Nkashama, Jingxin Chen, Aaliyah Winfrey, Shawn Griffiths, Tracey R. Lam, Daniel Flores, Peng Wu, WenHui Wang, Chou-Long Huang, Arohan R. Subramanya, Thomas R. Kleyman, Lisa M. Satlin
Summary: The large-conductance K+ (BK) channels in intercalated cells (ICs) are increased by a high-K+ diet, with the long isoform of with-no-lysine kinase 1 (L-WNK1) playing a role in enhancing BK channel expression and activity. Mice with IC-selective deletion of L-WNK1 on a high-K+ diet showed higher blood K+ concentration and reduced IC BK channel activity, indicating the involvement of IC L-WNK1 in renal adaptation to a high-K+ diet.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Dian Ding, Jing-Xiang Wu, Xinli Duan, Songling Ma, Lipeng Lai, Lei Chen
Summary: ATP-sensitive potassium channels (K-ATP) composed of Kir6 and SUR subunits convert the metabolic status of the cell into electrical signals. The authors present cryo-EM structures of SUR2A and SUR2B subunits in complex with two vasodilators, P1075 and levcromakalim, uncovering the mechanisms of these drugs.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Adam Lewis, Vilius Kurauskas, Marco Tonelli, Katherine Henzler-Wildman
Summary: The selectivity filter (SF) in NaK is dynamic, with structural differences between Na+ and K+-bound states, determining efficient conduction of ions. The SF structure communicates with the pore-lining helices, supporting multiple conformations involved in non-selective conduction. Allosteric coupling between the SF and pore-lining helices is demonstrated, similar to that in K+-selective channels, indicating a general model for ion channel function.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Vikas Arige, Lara E. Terry, Larry E. Wagner, Sundeep Malik, Mariah R. Baker, Guizhen Fan, Suresh K. Joseph, Irina I. Serysheva, David I. Yule
Summary: Inositol 1,4,5-trisphosphate receptors (IP3Rs) initiate physiological responses by regulating intracellular calcium signals. This study identifies Ca2+ binding sites and acidic residues that regulate IP3Rs channel activity, providing insights into their regulatory mechanism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Jie Xu, Yan-Tian Lv, Xiao-Yun Zhao, Jing-Jing Wang, Zhong-Shan Shen, Jian Li, Fei-Fei Zhang, Jing Liu, Xiao-Hui Wang, Yun Xu, Qi Geng, Yi-Tong Ding, Jing-Jing Xu, Meng-Jiao Tan, Zhi-Xiao Li, Ran Wang, Jian Chen, Wen Sun, Meng Cui, Diomedes E. Logothetis, Jun-li Cao, Qiong-Yao Tang, Zhe Zhang
Summary: In this study, two potential sodium-sensitive sites were identified in the C-terminal domain of the rat Slack channel, and R379 was determined to be a chloride interaction site. These findings contribute to a better understanding of the sodium gating mechanism and the regulation of Slack channel function.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Jintao Wang, Huan Liu, Zhuolin Sun, Xinyi Zou, Zixuan Zhang, Xiaofeng Wei, Lanying Pan, Antony Stalin, Wei Zhao, Yuan Chen
Summary: In this study, the TWIK1 current was increased by using a high concentration of ammonium solution. The inhibitory effect of magnolol on TWIK1 was observed, and it was found that G229 and T225 on the P2-pore helix play an important role in TWIK1 inhibition.
Article
Chemistry, Medicinal
Xiaoyu Wang, Xinyuan Zhang, Jie Zhou, Weiping Wang, Xiaoliang Wang, Bailing Xu
Summary: In this study, an in silico model of Kv2.1 tetramer structure was constructed using deep learning methods, and multiple receptor conformations were generated for analysis. The binding sites of two inhibitors were identified through experiments, and important amino acid residues contributing to the binding affinity were discovered. These findings provide a theoretical basis for the development of novel Kv2.1 inhibitors.
MOLECULAR INFORMATICS
(2023)
Article
Neurosciences
Xin-Shen Wu, Shobana Subramanian, Yalan Zhang, Bo Shi, Jessica Xia, Tiansheng Li, Xiaoli Guo, Lynda El-Hassar, Klara Szigeti-Buck, Jorge Henao-Mejia, Richard A. Flavell, Tamas L. Horvath, Elizabeth A. Jonas, Leonard K. Kaczmarek, Ling-Gang Wu
Summary: Potassium channels play a crucial role in endocytosis and vesicle mobilization by organizing the F-actin cytoskeleton, in addition to their traditional role in ion conductance. Mutations in potassium channels that impair these non-conducting functions may contribute to various neurological disorders.
Article
Biology
Go Kasuya, Koichi Nakajo
Summary: In this study, the researchers investigated the interaction between KCNE3 and KCNQ1 voltage sensors in the KCNQ1-KCNE3-calmodulin complex. They found that the distance between the S1 segment and KCNE3 is optimized to achieve constitutive activity. In addition, they identified mutant pairs of KCNQ1 and KCNE3 that partially restored constitutive activity when expressed together.
Article
Chemistry, Analytical
Yu Zhang, Ziyun Wang, Declan New, Michele Zagnoni
Summary: Microsystem technologies offer miniaturized, high-throughput capabilities for microemulsion- and microdroplet-based assays in analytical chemistry, biology, and synthetic biology. Many of these methods have been implemented using microfluidic and lab-on-a-chip technologies, but the microfabrication of such devices often requires expensive equipment and time-consuming methods. This study demonstrates a cost-effective and easily fabricated alternative approach for manipulating water-in-oil microdroplets using polymeric microtube modules, providing versatile and functional droplet operations without the need for laborious microfabrication protocols.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Analytical
Anastasia Kapara, Karla A. Findlay Paterson, Valerie G. Brunton, Duncan Graham, Michele Zagnoni, Karen Faulds
Summary: Breast cancer is a leading cause of cancer death in women. Functionalized nanoparticles were utilized to detect ERα expression, providing insights into the efficiency of targeted nanotags.
ANALYTICAL CHEMISTRY
(2021)
Article
Biology
Elise L. Malavasi, Aniket Ghosh, Daniel G. Booth, Michele Zagnoni, Diane L. Sherman, Peter J. Brophy
Summary: Recent research suggests that the assembly of 'early clusters' of nodal proteins in the murine axonal membrane precedes heminode formation. These early clusters are essential for node assembly, as they are mobile and their proteins are dynamically recruited by lateral diffusion.
Article
Engineering, Manufacturing
Roger Domingo-Roca, Lauren Gilmour, Oana Dobre, Stylianos Sarrigiannidis, Mairi E. Sandison, Richard O'Leary, Joseph C. Jackson-Camargo, Helen E. Mulvana
Summary: The ability to create cell-laden fluidic models that mimic the geometries and physical properties of vascularized tissue would be extremely beneficial to the study of disease etiologies and future therapies. Engineered systems, such as hydrogel-based systems, offer an alternative approach to animal studies and can accurately reproduce the complex features of microvasculature.
3D PRINTING AND ADDITIVE MANUFACTURING
(2023)
Article
Materials Science, Multidisciplinary
Laura McShea, Harjot S. Kambo, Michelle Maclean, Maki E. Sandison
Summary: Healthcare-associated infection through transmission of pathogenic bacteria poses a huge threat to public health. This study investigates the potential to enhance the antimicrobial efficacy of 405 nm light for surface decontamination through use of a photocatalytic TiO2-doped elastomer. Results suggest that this doping and etching strategy shows significant potential for facilitating decontamination of elastomer-based biomaterials.
MATERIALS RESEARCH EXPRESS
(2022)
Article
Engineering, Biomedical
Hugo Bissig, Oliver Buker, Krister Stolt, Elsa Batista, Joana Afonso, Michele Zagnoni, Rozan Vroman, Henrik Kjeldsen, Anders Niemann, Joerg Schroeter
Summary: This article discusses an application in medical treatment involving very small flow rates - the usage of an insulin pump. The pump delivers doses of insulin at constant cycle times, playing a crucial role in diabetes management. The article describes the calibration of the basal rates using gravimetric or optical methods, and introduces an improved approach to determine the discrete doses and corresponding basal rates. The calibration results of different basal rates and bolus deliveries are presented.
BIOMEDICAL ENGINEERING-BIOMEDIZINISCHE TECHNIK
(2023)
Article
Engineering, Biomedical
E. Smith, M. Zagnoni, M. E. Sandison
Summary: Microengineering technologies provide customized tools for single-cell studies, including microarray approaches. This study presents a medium throughput cellular microarray to track single vascular smooth muscle cells (vSMCs) as they undergo phenotypic modulation in vitro. The microarray enables long-term characterization of multiple phenotypic characteristics of vSMCs and the identification of new cellular sub-populations.
BIOMEDICAL MICRODEVICES
(2023)
Article
Cell Biology
Caroline Busch, Theresa Mulholland, Michele Zagnoni, Matthew Dalby, Catherine Berry, Helen Wheadon
Summary: This study demonstrates the importance of the BMP signaling pathway in the survival of CML cells. Targeting SRC, ABL, and ALK kinases is more effective than ABL inhibition alone, as shown in both 2D and 3D cell cultures. Combinatorial therapies are necessary to combat LSC persistence.
CELL COMMUNICATION AND SIGNALING
(2023)
Correction
Endocrinology & Metabolism
Emily J. Kay, Karla Paterson, Carla Riera-Domingo, David Sumpton, J. Henry M. Dabritz, Saverio Tardito, Claudia Boldrini, Juan R. Hernandez-Fernaud, Dimitris Athineos, Sandeep Dhayade, Ekaterina Stepanova, Enio Gjerga, Lisa J. Neilson, Sergio Lilla, Ann Hedley, Grigorios Koulouras, Grace McGregor, Craig Jamieson, Radia Marie Johnson, Morag Park, Kristina Kirschner, Crispin Miller, Jurre J. Kamphorst, Fabricio Loayza-Puch, Julio Saez-Rodriguez, Massimiliano Mazzone, Karen Blyth, Michele Zagnoni, Sara Zanivan
Article
Endocrinology & Metabolism
Emily J. Kay, Karla Paterson, Carla Riero-Domingo, David Sumpton, J. Henry M. Dabritz, Saverio Tardito, Claudia Boldrini, Juan R. Hernandez-Fernaud, Dimitris Athineos, Sandeep Dhayade, Ekaterina Stepanova, Enio Gjerga, Lisa J. Neilson, Sergio Lilla, Ann Hedley, Grigorios Koulouras, Grace McGregor, Craig Jamieson, Radia Marie Johnson, Morag Park, Kristina Kirschner, Crispin Miller, Jurre J. Kamphorst, Fabricio Loayza-Puch, Julio Saez-Rodriguez, Massimiliano Mazzone, Karen Blyth, Michele Zagnoni, Sara Zanivan
Summary: The study reveals that the newly synthesized proline in CAFs promotes the production of tumor collagen in breast cancer xenografts, and reducing PYCR1 levels can inhibit tumor growth and metastasis. Additionally, the synthesis of collagen and proline in CAFs is epigenetically regulated by increased pyruvate dehydrogenase-derived acetyl-CoA levels.
Article
Engineering, Biomedical
Karla Paterson, Sarah Paterson, Theresa Mulholland, Seth B. Coffelt, Michele Zagnoni
Summary: CAR-T cell therapy is effective against hematological malignancies, but faces challenges when used for solid tumors. Microfluidic technologies offer a solution to assess CAR-T therapies in more realistic 3D models for preclinical evaluation.
IEEE OPEN JOURNAL OF ENGINEERING IN MEDICINE AND BIOLOGY
(2022)
Article
Biochemical Research Methods
D. Megarity, R. Vroman, M. Kriek, P. Downey, T. J. Bushell, M. Zagnoni
Summary: Disorders of the central nervous system (CNS) are a global health challenge. Traditional in vitro and animal models have limited validity in simulating the CNS environment. Microfluidic and organ-on-chip technologies offer the opportunity to develop more relevant and complex in vitro models. We introduce a modular platform for creating bespoke culture environments and conducting functional analysis to enhance our understanding of CNS disease mechanisms.
Review
Biochemical Research Methods
K. Paterson, S. Zanivan, R. Glasspool, S. B. Coffelt, M. Zagnoni
Summary: Immunotherapy is an effective cancer treatment that uses the body's immune system to target and eliminate cancer cells, showing success in treating hematological malignancies and melanoma. However, challenges arise in tackling solid tumors due to the immunosuppressive tumor microenvironment. Microfluidics and lab-on-a-chip technologies offer opportunities to study cancer-immune cell interactions and test immunotherapies in solid tumors with higher translational value.
Article
Biochemical Research Methods
Anna Desalvo, Faith Bateman, Edward James, Hywel Morgan, Tim Elliott