Article
Neurosciences
Taro Inoue, Bisei Ohkawara, Samira Bushra, Shunsuke Kanbara, Hiroaki Nakashima, Hiroyuki Koshimizu, Hiroyuki Tomita, Mikako Ito, Akio Masuda, Naoki Ishiguro, Shiro Imagama, Kinji Ohno
Summary: Zonisamide enhances agrin-dependent AChR clustering by upregulating the Nrg1/ErbB signaling pathways at the NMJ.
Article
Engineering, Biomedical
Ji Hyun Kim, In Kap Ko, Myung Jae Jeon, Ickhee Kim, Margaret Maria Vanschaayk, Anthony Atala, James J. Yoo
Summary: Efficient innervation is crucial for successful grafting and functional recovery of bioengineered skeletal muscle constructs. In this study, a 3D bioprinted human skeletal muscle construct with pre-formed AChR clusters is developed and shown to accelerate innervation in vivo, leading to functional muscle reconstruction in a rat model of pelvic floor muscle injury.
ACTA BIOMATERIALIA
(2021)
Article
Neurosciences
Qiao Ding, Kaamini Kesavan, Kah Meng Lee, Elyse Wimberger, Thomas Robertson, Melinder Gill, Dominique Power, Jeryn Chang, Atefeh T. Fard, Jessica C. Mar, Robert D. Henderson, Susan Heggie, Pamela A. McCombe, Rosalind L. Jeffree, Michael J. Colditz, Massimo A. Hilliard, Dominic C. H. Ng, Frederik J. Steyn, William D. Phillips, Ernst J. Wolvetang, Shyuan T. Ngo, Peter G. Noakes
Summary: A defect in the n-agrin-LRP4-MuSK signaling pathway has been identified in muscle from MND patients for the first time. This signaling pathway plays a crucial role in maintaining the stability of the neuromuscular junction. These findings provide a potential therapeutic target for prolonging muscle function in MND patients.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Geriatrics & Gerontology
Kuniyasu Kamiya, Takahiro Tachiki, Yuho Sato, Katsuyasu Kouda, Etsuko Kajita, Junko Tamaki, Sadanobu Kagamimori, Masayuki Iki
Summary: This study found that CAF110 was associated with the presence and incidence of low muscle mass, but not low muscle strength.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Cell Biology
Jakob Proemer, Cinzia Barresi, Ruth Herbst
Summary: Muscle-specific kinase (MuSK) is the key regulator of neuromuscular junction development and its activation and signaling are tightly regulated. Recent studies using omics techniques have contributed to a better understanding of MuSK signaling. Impaired MuSK signaling causes muscle weakness, but the underlying pathophysiology is often unclear. This review focuses on recent advances in deciphering MuSK activation and downstream signaling, as well as the role of MuSK in non-muscle tissue.
CELLULAR SIGNALLING
(2023)
Article
Developmental Biology
Lauren J. Walker, Rebecca A. Roque, Maria F. Navarro, Michael Granato
Summary: Using a zebrafish pectoral fin model, the study shows similarities in the development of neuromuscular synapses between axial and appendicular muscles, but differences in the MuSK, Agrin, and Lrp4 signaling pathways. This highlights distinct differences between axial and appendicular synapse development.
Article
Clinical Neurology
Zheng Yu, Meiying Zhang, Hongyang Jing, Peng Chen, Rangjuan Cao, Jinxiu Pan, Bin Luo, Yue Yu, Brandy M. Quarles, Wencheng Xiong, Michael H. Rivner, Lin Mei
Summary: The study aimed to investigate the pathogenic role of human anti-LRP4/agrin antibodies in mice and found that the antibodies led to MG symptoms in the mice. The antibodies impaired neuromuscular junction function and disrupted agrin-dependent LRP4-MuSK interaction, providing insights into the pathogenic mechanisms of these antibodies.
Article
Clinical Neurology
Zheng Yu, Meiying Zhang, Hongyang Jing, Peng Chen, Rangjuan Cao, Jinxiu Pan, Bin Luo, Yue Yu, Brandy M. Quarles, Wencheng Xiong, Michael H. Rivner, Lin Mei
Summary: The study found that antibodies against LRP4/agrin from a patient with MG can induce MG symptoms in mice, including weight loss and muscle weakness. These antibodies impair the neuromuscular junction by interfering with agrin-dependent LRP4-MuSK interaction, leading to compromised neuromuscular transmission and fragmentation of the neuromuscular junction.
Article
Developmental Biology
Jun Yu, Marilyn Janice Oentaryo, Chi Wai Lee
Summary: The study demonstrates the essential role of local protein synthesis in presynaptic differentiation at developing neuromuscular junctions. Newly synthesized proteins play a crucial role at agrin bead-neurite contacts. Axonal MT1-MMP translation is shown to be vital in mediating agrin-induced presynaptic differentiation, in addition to the recognized long-range transport of MT1-MMP proteins.
Review
Biochemistry & Molecular Biology
Ellya A. Bukharaeva, Andrey Skorinkin, Dmitry Samigullin, Alexey M. Petrov
Summary: Effective transmission of excitation in neuromuscular junctions requires a certain level of depolarization to trigger action potential spreading. The amplitude of end-plate potential, which depends on the synchronization and release rate of acetylcholine quanta, is influenced by presynaptic autoreceptors. The timing characteristics of neurotransmitter release play a crucial role in the plasticity and efficacy of synaptic transmission.
Review
Neurosciences
Xinying Huang, Junjian Jiang, Jianguang Xu
Summary: Understanding the degeneration and regeneration mechanisms of neuromuscular junctions after denervation and reinnervation is clinically valuable and may lead to the development of therapies for maintaining or protecting the structures and functions of NMJs.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Cell & Tissue Engineering
Katarina Stoklund Dittlau, Emily N. Krasnow, Laura Fumagalli, Tijs Vandoorne, Pieter Baatsen, Axelle Kerstens, Giorgia Giacomazzi, Benjamin Pavie, Elisabeth Rossaert, Jimmy Beckers, Maurilio Sampaolesi, Philip Van Damme, Ludo Van den Bosch
Summary: This study established a versatile and reproducible in vitro model of a human motor unit to investigate the effects of ALS-causing mutations. It was observed that ALS-causing FUS mutations resulted in reduced neurite outgrowth, impaired neurite regrowth, and reduced NMJ numbers. Interestingly, the selective HDAC6 inhibitor Tubastatin A improved these outcomes, suggesting HDAC6 inhibition as a potential therapeutic strategy for ALS.
Article
Zoology
Wen-Yo Tu, Wentao Xu, Jianmin Zhang, Shuyuan Qi, Lei Bai, Chengyong Shen, Kejing Zhang
Summary: Amyotrophic lateral sclerosis (ALS) is a devastating motoneuron disease characterized by the loss of control of skeletal muscles. Degeneration of neuromuscular junctions (NMJs) is an early event in ALS. Poly-GA, the most abundant form of DPR in C9-ALS, is released from cells and impairs NMJs through inhibiting Agrin-MuSK signaling.
ZOOLOGICAL RESEARCH
(2023)
Article
Geriatrics & Gerontology
Jedd Pratt, Giuseppe De Vito, Marco Narici, Ricardo Segurado, Ludmilla Pessanha, Jackie Dolan, Judith Conroy, Colin Boreham
Summary: This study confirms the relevance of plasma CAF as a biomarker for sarcopenia, showing significant associations with muscle mass and elevated levels in sarcopenic individuals. Gender differences were observed, with males showing elevated CAF levels in low grip strength or low ALM, while only low ALM in females had significantly raised CAF concentrations compared to healthy controls.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Article
Neurosciences
Matheus P. S. Magalhaes-Gomes, Wallace Camargos, Priscila A. C. Valadao, Rubens S. Garcias, Hermann A. Rodrigues, Jessica N. Andrade, Vanessa P. Teixeira, Ligia A. Naves, Walter L. G. Cavalcante, Marcia Gallaci, Silvia Guatimosim, Vania F. Prado, Marco A. M. Prado, Cristina Guatimosim
Summary: Increased VAChT expression leads to higher levels of ACh release, but may have detrimental effects on the structure and function of the neuromuscular system, including impaired synaptic vesicle cycle and structural alterations of NMJs.
Article
Orthopedics
R. Y. Nigel Kour, Shanyuanye Guan, Michelle M. Dowsey, Peter F. Choong, Marcus G. Pandy
Summary: The study aimed to compare the knee joint motion of three different total knee arthroplasty implant designs during daily activities, and found that the medial-stabilized design had motion patterns closer to a healthy knee joint.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2023)
Article
Cell & Tissue Engineering
Serena Duchi, Sam L. Francis, Carmine Onofrillo, Cathal D. O'Connell, Peter Choong, Claudia Di Bella
Summary: This study demonstrates the possibility of repairing critical size articular cartilage defects using a surgical streamlined procedure with optimized conditions.
TISSUE ENGINEERING AND REGENERATIVE MEDICINE
(2023)
Article
Materials Science, Biomaterials
Alexandre Xavier Mendes, Adriana Teixeira do Nascimento, Serena Duchi, Anita F. Quigley, Lilith Caballero M. Aguilar, Chaitali Dekiwadia, Robert M. I. Kapsa, Saimon Moraes Silva, Simon E. Moulton
Summary: The development of electroactive cell-laden hydrogels has attracted attention in neural tissue engineering research. These hydrogels have inherent electrical properties that can regulate cell behavior and promote cell growth and proliferation when combined with electrically conducting materials. Different electrical stimulation protocols have been found to impact neuronal cells' survival and proliferation, providing new options for electroactive hydrogels and electrical stimulation in neural tissue engineering research.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Article
Biochemistry & Molecular Biology
Yuen Yi Lam, Angel Tan, Cameron J. Nowell, Kristian Kempe, Ben J. Boyd
Summary: Metabolic oligosaccharide engineering (MOE) allows the introduction of functionality to cell membranes through synthetic monosaccharides. MOE enables the expression of unnatural sugars (e.g., peracetylated mannose-azide) on cell surfaces, and the azide group can participate in a copper-free click reaction with an alkyne probe (e.g., dibenzocyclooctyne, DBCO), providing insights into monosaccharide metabolism in cells.
Article
Engineering, Biomedical
Manuela A. Boos, Frances A. Ryan, Felix Linnenschmidt, Manula S. B. Rathnayake, Cameron J. Nowell, Shireen R. Lamande, Kathryn S. Stok
Summary: This paper presents the design and validation of a custom device called FELIX, which enables non-destructive image-guided micromechanical evaluation of biological tissues and tissue-engineered constructs. The results show that FELIX can accurately measure biomechanical properties with high repeatability and reproducibility compared to a commercial device. It also allows for longitudinal studies at the cell and tissue level. In conclusion, FELIX provides reliable and biocompatible measurements for studying the structure-function relationships of cartilage.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2023)
Article
Biochemical Research Methods
Michelle Palmieri, Bruno Catimel, Dmitri Mouradov, Anuratha Sakthianandeswaren, Eugene Kapp, Ching-Seng Ang, Nicholas A. Williamson, Cameron J. Nowell, Michael Christie, Jayesh Desai, Peter Gibbs, Antony W. Burgess, Oliver M. Sieber
Summary: The nuclear translocation of PI3K alpha regulates the subcellular levels of PtdIns(3,4,5)P3 in colorectal cancer cell lines, and 867 potential nuclear PtdIns(3,4,5)P3 effector proteins have been identified. These effector proteins are mainly involved in RNA metabolism and may play a role in modulating pre-mRNA splicing. These findings suggest that nuclear PI3K alpha signaling through PtdIns(3,4,5)P3 effector proteins is important for CRC development.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Medicine, Research & Experimental
Alina D. Lam, Ian K. Styles, Danielle Senyschyn, Enyuan Cao, Abel Anshabo, Mohammad Abdallah, Reyaj Mikrani, Cameron J. Nowell, Christopher J. H. Porter, Orlagh M. Feeney, Natalie L. Trevaskis
Summary: Changes in immune cells within the joint-draining lymphatics contribute to the progression of inflammatory arthritis. There is an expansion of pathogenic B cells in the joint-draining lymph node, which inhibit lymph flow and reduce clearance of inflammatory fluid and cells. Localized delivery of B-cell depleting therapies to the joint-draining lymph nodes has the potential to improve treatment efficacy and reduce side effects.
MOLECULAR PHARMACEUTICS
(2023)
Article
Cell Biology
Aeson Chang, Edoardo Botteri, Ryan D. Gillis, Lukas Lofling, Caroline P. Le, Alexandra I. Ziegler, Ni-Chun Chung, Matthew C. Rowe, Stewart A. Fabb, Brigham J. Hartley, Cameron J. Nowell, Sasagu Kurozumi, Sara Gandini, Elisabetta Munzone, Emilia Montagna, Nina Eikelis, Sarah E. Phillips, Chikako Honda, Kei Masuda, Ayaka Katayama, Tetsunari Oyama, Steve W. Cole, Gavin W. Lambert, Adam K. Walker, Erica K. Sloan
Summary: We found a relationship between beta-blocker use and anthracycline chemotherapy in protecting against TNBC progression, disease recurrence, and mortality. Beta-blockade improved the efficacy of anthracycline chemotherapy in TNBC mouse models by reducing metastatic development. Anthracycline chemotherapy increased sympathetic nerve fiber activity and norepinephrine concentration in mammary tumors, but this effect can be overcome by inhibiting beta 2-adrenergic signaling in the tumor microenvironment.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Health Care Sciences & Services
Daniel J. Gould, Michelle M. Dowsey, Marion Glanville-Hearst, Tim Spelman, James A. Bailey, Peter F. M. Choong, Samantha Bunzli
Summary: This study explored the understanding and attitudes of patients who underwent knee replacement surgery regarding AI in the context of risk prediction for shared clinical decision-making. The study found that patients had varied levels of familiarity with AI and diverse conceptualizations of its definitions and capabilities. The study suggests that educating patients about AI through non-technical explanations and illustrative scenarios could help inform their decision to use it in the shared decision-making process with their surgeon.
JOURNAL OF MEDICAL INTERNET RESEARCH
(2023)
Article
Cell & Tissue Engineering
Tajanka Mladenovska, Peter F. Choong, Gordon G. Wallace, Cathal D. O'Connell
Summary: New developments in additive manufacturing and regenerative medicine have the potential to disrupt traditional therapy development and medical device manufacture. Regulators face challenges in adapting traditional regulatory frameworks for bespoke solutions and incorporating living cells in 3D bioprinting. This perspective discusses the regulatory challenges of 3D bioprinting in comparison to existing cell therapies and custom-made medical devices, including classification, risk, standardization, and quality control.
REGENERATIVE MEDICINE
(2023)
Review
Materials Science, Biomaterials
Elizabeth Footner, Kate Firipis, Emily Liu, Chris Baker, Peter Foley, Robert M. I. Kapsa, Elena Pirogova, Cathal O'Connell, Anita Quigley
Summary: In vitro human skin models have great potential in the study of skin biology and disorders, as well as drug testing and safety assessment. Recent advances in biofabrication techniques and biomaterials have enabled the creation of complex skin models that accurately mimic native human skin, allowing for more precise testing and modeling of skin behavior and response.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2023)
Article
Orthopedics
Yangqi Xu, Tony B. Huang, Michael A. Schuetz, Peter F. M. Choong
Summary: Prosthetic joint infection (PJI) is a devastating complication following arthroplasty, with higher mortality rate, reduced quality of life, and increased healthcare resource utilization. Improving preventative and treatment strategies is crucial for patients and the healthcare system.
EFORT OPEN REVIEWS
(2023)
Article
Rheumatology
Lyndon J. Hawke, Nora Shields, Michelle M. Dowsey, Peter F. M. Choong, Nicholas F. Taylor
Summary: The study aimed to determine if a consumer co-designed infographic could increase knowledge of physical activity and self-efficacy for exercise after total knee joint replacement surgery. The results showed that the infographic did not improve knowledge of physical activity, but may have had a short-term positive effect on self-efficacy for exercise.
MUSCULOSKELETAL CARE
(2023)
Article
Engineering, Biomedical
Tianshi Yu, Alireza Mohammadi, Ying Tan, Peter Choong, Denny Oetomo
Summary: A Human-Prosthetic Interface (HPI) is used to estimate and implement the desired limb pose by the user through sensors worn on the body. Unlike conventional methods, which map each degree of freedom to one or a pair of sensors, recent studies have shown that HPI can map multi-joint limb poses to multiple sensors. This approach requires systematic sensor selection to optimize system accuracy and minimize the complexity of the prosthetic system. This paper proposes an algorithm called Sensor Selection with Composite Features (SS-CF) to solve the sensor selection problem.
IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING
(2023)
Article
Engineering, Biomedical
Dave Hill, Tom Williamson, Chow Yin Lai, Martin Leary, Milan Brandt, Peter Choong
Summary: This study describes an automated approach for generating conformal bone tumor resection plans. The method optimizes the resection geometry, defined by the convex hull of the tumor, to minimize the volume of healthy bone collaterally resected with the tumor. The results show significant improvements compared to manual methods in reducing the collateral resection of healthy bone.
INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY
(2023)
