Article
Chemistry, Physical
Lucas W. Henderson, Edie M. Sharon, Amit K. S. Gautam, Adam J. Anthony, Martin F. Jarrold, David H. Russell, Andreas Matouschek, David E. Clemmer
Summary: Mass spectrometry studies show that the stability of S. cerevisiae 20S proteasome undergoes related configurations and transitions during temperature changes, possibly linked to the opening of the proteolytic core. The study indicates that the proteasome remains intact and all transitions are reversible. Three types of structures are identified based on thermodynamic analysis: energetically stabilized closed configurations, high-entropy precursor states, and open pore structures. Opening of the 20S pore in the absence of the regulatory unit involves a charge-priming process. However, only a small fraction of precursor configurations actually open to expose the catalytic cavity.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Medicine, Research & Experimental
Zongang Liu, Mengnan Zhao, Xizi Jiang, Yao Zhang, Suning Zhang, Yitong Xu, Hongjiu Ren, Hongbo Su, Huanxi Wang, Xueshan Qiu
Summary: This study elucidates the role of KLHL17 in the development and progression of NSCLC using clinical samples and NSCLC cell lines. The results show that upregulated KLHL17 in NSCLC promotes the proliferation and migration of tumor by activating Ras/MAPK signaling pathway, and suggest that KLHL17 may be a novel therapeutic target for the treatment of NSCLC.
LABORATORY INVESTIGATION
(2022)
Article
Immunology
Duygu Eryavuz Onmaz, Abdullah Sivrikaya, Kevser Isik, Sedat Abusoglu, Ilknur Albayrak Gezer, Fatma Humeyra Yerlikaya, Gulsum Abusoglu, Ali Unlu, Dilek Tezcan
Summary: The study found altered kynurenine pathway metabolism in AS patients. Conventional therapy and anti-TNF-alpha therapy are effective in reducing the Kynurenine/Tryptophan ratio and CRP levels.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Immunology
Daniele Mauro, Archita Srinath, Giuliana Guggino, Vicky Nicolaidou, Stefania Raimondo, Jonathan J. Ellis, Jessica Whyte, Maria Maddalena Nicoletti, Marco Romano, Tony John Kenna, Juan D. Canete, Riccardo Alessandro, Aroldo Rizzo, Matthew Arthur Brown, Nicole J. Horwood, Nigil Haroon, Francesco Ciccia
Summary: Ankylosing spondylitis (AS) is an inflammatory disease that leads to spine ankylosis. The mechanisms of new bone formation in AS are not fully understood, but Single Nucleotide Polymorphisms (SNPs) in the PTGER4 gene have been associated with AS. This study found that the PGE2-EP4 axis, which is involved in inflammation and bone metabolism, may contribute to radiographic progression in AS. Baseline serum PGE2 levels and the PTGER4 SNP rs6896969 were found to predict progression in AS patients. Increased expression of EP4/PTGER4 was observed in immune cells, synovial tissue, and bone marrow of AS patients. The PGE2/EP4 axis also induced bone formation when monocytes were cocultured with mesenchymal stem cells.
CLINICAL IMMUNOLOGY
(2023)
Article
Genetics & Heredity
Chenxing Zhou, Tuo Liang, Jie Jiang, Zide Zhang, Jiarui Chen, Tianyou Chen, Liyi Chen, Xuhua Sun, ShengSheng Huang, Jichong Zhu, Shaofeng Wu, Xinli Zhan, Chong Liu
Summary: This study identified the miRNA-mRNA interaction network and immune cell infiltration-related hub genes associated with Ankylosing Spondylitis (AS). The immune-related gene LYN correlated with immune cell infiltration in AS patients, and counts of monocytes and neutrophils were found to be independent diagnostic factors for AS.
FRONTIERS IN GENETICS
(2022)
Article
Medicine, Research & Experimental
Xinzhe Feng, Shanbang Zhu, Junjie Qiao, Zhou Ji, Bole Zhou, Weidong Xu
Summary: The up-regulated CX3CL1 promotes M1-type macrophage polarization and osteoclast differentiation through the NF-κB signaling pathway. Inhibition of this pathway and blocking CX3CL1 can alleviate inflammation and bone destruction in AS.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Biotechnology & Applied Microbiology
Xiao-lin Zhong, Bang-Ping Qian, Ji-chen Huang, Shi-zhou Zhao, Yao Li, Yong Qiu
Summary: This study aimed to characterize the association of heterotopic ossification (HO) with ankylosing spondylitis (AS) through gene expression profiling. Key genes TCP1 and PSMC1 were identified in AS-induced HO, and further validation of these genes could help elucidate their role in the complex association of AS and HO. Quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry were used for experimental validation of genes.
Article
Biochemistry & Molecular Biology
Pinduo Liu, Anping Wu, Hui Li, Jun Zhang, Junjun Ni, Zhenzhen Quan, Hong Qing
Summary: This study revealed the degradation pathways of Rab21 protein through the ubiquitin-proteasome pathway and the autophagy-lysosome pathway, and demonstrated increased ubiquitination of Rab21 protein in the AD model. Moreover, the study suggested the involvement of the autophagy-lysosome pathway in maintaining the protein level of Rab21.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Yu-Ping Zhang, Xing Wang, Li-Gang Jie, Yuan Qu, Xiao-Tong Zhu, Jing Wu, Qing-Hong Yu
Summary: This study explored the shared molecular mechanisms between psoriatic arthritis and ankylosing spondylitis, and identified potential diagnostic markers and therapeutic targets. The mRNA surveillance pathway and immune processes were found to be involved in the osteoarticular involvement of psoriasis and AS. PUM1 and ZFP91 were identified as potential biomarkers for diagnosing and treating AS and Ps patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Lihang Wang, Yun Wang, Yang Jiang, Ming Chen, Zhuhai Li, Kai Wang, Chunshan Luo, Ning Ning, Jiancheng Zeng, Zongke Zhou, Yueming Song, Fan Yang, Shi-shu Huang, Yunfeng Lin
Summary: The treatment with tetrahedral framework nucleic acids (tFNAs) has been found to inhibit inflammatory responses and heterotopic ossification in ankylosing spondylitis (AS), suggesting its potential as a nonsurgical remedy for the disease.
Article
Immunology
Adam J. Berlinberg, Emilie H. Regner, Andrew Stahly, Ana Brar, Julie A. Reisz, Mark E. Gerich, Blair P. Fennimore, Frank I. Scott, Alison E. Freeman, Kristine A. Kuhn
Summary: The study identified significant alterations in tryptophan pathway metabolites, including an expansion of indole-3-acetate (IAA) and indole-3-acetaldehyde (I3Ald), in patients with axial spondyloarthritis (SpA) compared to other disease groups and healthy controls, suggesting a possible specificity in the development of axSpA. This indicates that tryptophan metabolism into I3Ald and then IAA may be a mechanism through which the gut microbiome potentially influences the pathophysiology of axSpA.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Yusuke Nishimura, Jitpisute Chunthorng-Orn, Samuel Lord, Ibrahim Musa, Peter Dawson, Lars Holm, Yu-Chiang Lai
Summary: In this study, the researchers showed that Atrogin-1 and MuRF1 protein contents are regulated by different mechanisms, specifically the downstream of Akt, and that Atrogin-1 protein content can be regulated by the rapamycin-sensitive mTOR-S6K1-dependent signaling pathway.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jin-Taek Hwang, Ahyoung Lee, Changwon Kho
Summary: Post-translational modification (PTM) is an essential mechanism for enhancing the functional diversity of proteins and adjusting their signaling networks. The reversible conjugation of ubiquitin (Ub) and ubiquitin-like proteins (Ubls) to cellular proteins is among the most prevalent PTM, which modulates various cellular and physiological processes by altering the activity, stability, localization, trafficking, or interaction networks of its target molecules. The dysregulation of Ub/Ubl modifications is associated with various diseases, providing new targets for drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Alireza Rezaiemanesh, Mahdi Mahmoudi, Ali Akbar Amirzargar, Mahdi Vojdanian, Farhad Babaie, Jila Mahdavi, Misagh Rajabinejad, Ahmad Reza Jamshidi, Mohammad Hossein Nicknam
Summary: ER stress in macrophages from AS patients plays a role in the increased production of IL-23. The autophagy pathway is not involved in the modulation of IL-23 production by AS macrophages.
Article
Microbiology
Priyadharshini Ramachandran, J. Beslin Joshi, Julie A. Maupin-Furlow, Sivakumar Uthandi
Summary: Plant pathogenic Gram-negative bacteria evade the host plant immune system by secreting Type III and Type IV effector proteins, which mimic components of the ubiquitin-265 proteasome system to control plant cellular activities and establish pathogenicity.
MICROBIOLOGICAL RESEARCH
(2021)
Article
Surgery
Rebecca H. Vaughan, Jean-Claude Kresse, Louise K. Farmer, Marie L. Thezenas, Benedikt M. Kessler, Jan H. N. Lindeman, Edward J. Sharples, Gavin Welsh, Rikke Norregaard, Rutger J. Ploeg, Maria Kaisar
Summary: The study reveals that cytoskeletal proteins in brain death donor kidneys are susceptible to proteolytic cleavage, which may cause posttransplant dysfunction. Specific proteolytic fragments were detected in brain death kidneys but not in other types of donor kidneys.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Review
Biochemistry & Molecular Biology
George Vere, Md Rashadul Alam, Sam Farrar, Rachel Kealy, Benedikt M. Kessler, Darragh P. O'Brien, Adan Pinto-Fernandez
Summary: This review discusses potential therapeutic intervention points in COVID-19 treatment, including PLpro, USP18, TRIM25, CYLD, A20, and others, which may be effective in combating current and future vaccine-resistant variants of the virus.
Article
Biochemistry & Molecular Biology
Zhuoyao Chen, Rafael M. Ioris, Stacey Richardson, Ava N. Van Ess, Iolanda Vendrell, Benedikt M. Kessler, Francesca M. Buffa, Luca Busino, Steven C. Clifford, Alex N. Bullock, Vincenzo D'Angiolella
Summary: Medulloblastoma is a common malignant brain tumor in children, and it has been found to have different subtypes based on genomic studies. WNT and SHH signaling pathway alterations are known to be the main causes for their subtypes, but the causes for non-WNT/non-SHH tumors are still largely unknown. Recent studies have identified KBTBD4 gene mutations as important drivers in group 3 and group 4 medulloblastomas. These mutations promote significant changes in chromatin accessibility and transcriptional programs, leading to increased stemness of cancer cells.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Hannah B. L. Jones, Raphael Heilig, Simon Davis, Roman Fischer, Benedikt M. Kessler, Adan Pinto-Fernandez
Summary: Activity-based protein profiling (ABPP) is an important method for characterizing specific enzymes, and has proven invaluable in drug discovery and pharmacodynamic studies. In this study, an improved ABPP-HT method was developed, combining state-of-the-art MS analysis tools to achieve high throughput and improved data accuracy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Tehmina Bharucha, Bevin Gangadharan, Abhinav Kumar, Ashleigh C. Myall, Nazli Ayhan, Boris Pastorino, Anisone Chanthongthip, Manivanh Vongsouvath, Mayfong Mayxay, Onanong Sengvilaipaseuth, Ooyanong Phonemixay, Sayaphet Rattanavong, Darragh P. O'Brien, Iolanda Vendrell, Roman Fischer, Benedikt Kessler, Lance Turtle, Xavier de Lamballerie, Audrey Dubot-Peres, Paul N. Newton, Nicole Zitzmann, SEAe Consortium
Summary: A diagnostic signature consisting of nine proteins for Japanese encephalitis was developed using liquid chromatography and tandem mass spectrometry techniques. The accuracy of the signature was tested and validated, showing 82% accuracy. Further research and validation can help refine the signature for rapid diagnosis of Japanese encephalitis.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Larissa Dietz, Cara J. Ellison, Carlos Riechmann, C. Keith Cassidy, F. Daniel Felfoldi, Adan Pinto-Fernandez, Benedikt M. Kessler, Paul R. Elliott
Summary: Certain members of the inhibitor of apoptosis (IAP) family, including BIRC6, regulate cell death by inhibiting caspases, while SMAC antagonizes IAPs and promotes cell death. BIRC6 directly inhibits caspase-3 and-7 and ubiquitinates caspase-3,-7, and-9, working with noncanonical E1, UBA6. SMAC suppresses both mechanisms by competitively displacing caspases.
Article
Cell Biology
Cyriel Sebastiaan Olie, Adan Pinto-Fernandez, Andreas Damianou, Iolanda Vendrell, Hailiang Mei, Bianca den Hamer, Erik van der Wal, Jessica C. de Greef, Vered Raz, Benedikt M. Kessler
Summary: The ubiquitin proteasomal system plays a critical role in muscle physiology, but the function of deubiquitinating enzymes (DUBs) in muscle cells remains poorly understood. Through a genetic screen, we discovered that the depletion of USP18, a DUB, affects muscle cell differentiation. USP18 regulates differentiation initiation and maintenance independently of ISG15 and the ISG response. Alterations in gene networks and protein expression profiles were observed in the absence of USP18, leading to disrupted calcium homeostasis and reduced contractile force.
CELL DEATH & DISEASE
(2023)
Article
Microbiology
Chanel A. Mosby, Mariola J. Edelmann, Melissa K. Jones
Summary: Outer membrane vesicles (OMVs) serve as a means of communication for Gram-negative bacteria. Interaction with norovirus induces changes in OMV content, particularly in lipid accumulation and metabolite content, which may be linked to a shift in the mechanism of vesicle biogenesis.
MICROBIOLOGY SPECTRUM
(2023)
Correction
Microbiology
Austin E. F. Sheppe, John Santelices, Daniel M. Czyz, Mariola J. Ferraro
MICROBIOLOGY SPECTRUM
(2023)
Article
Pharmacology & Pharmacy
L. Leonie van Leeuwen, Mitchel J. R. Ruigrok, Benedikt M. Kessler, Henri G. D. Leuvenink, Peter Olinga
Summary: This study demonstrates the value of machine perfusion for administering antifibrotic drugs such as galunisertib and proves the effectiveness of ex vivo administration.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hannah C. Scott, Simeon D. Draganov, Zhanru Yu, Benedikt M. Kessler, Adan Pinto-Fernandez
Summary: Bioactive lipids play important roles in cellular signaling events and are associated with human diseases. A liquid chromatography-dynamic multiple reaction monitoring-targeted mass spectrometry (LC-dMRM-MS) approach has been optimized for the analysis of eicosanoids and fatty acids in biological samples. By studying a cellular model of chronic myeloid leukemia (CML), it was found that immunomodulation by type I interferon (IFN-I) caused changes in the levels of specific lipids, potentially indicating their relevance in cancer inflammation and CML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Dedrick Kok Hong Chan, Amit Mandal, Svenja Hester, Zhanru Yu, Geoff Stuart Higgins, Benedikt Mathias Kessler, Roman Fischer, Simon James Alexander Buczacki
Summary: This study found that FBXW7 gene mutation in colorectal cancer cells leads to DNA damage in neighboring wildtype cells. The study also discovered that FBXW7 mutant cells induce DNA damage through the secretion of AKAP8 protein. These findings highlight the importance of understanding the local effects of cancer driver mutations between subclonal populations.
CELL DEATH DISCOVERY
(2023)
Article
Multidisciplinary Sciences
Dannielle Wellington, Zixi Yin, Zhanru Yu, Raphael Heilig, Simon Davis, Roman Fischer, Suet Ling Felce, Elie Antoun, Philip Hublitz, Ryan Beveridge, Danning Dong, Guihai Liu, Xuan Yao, Yanchun Peng, Benedikt M. Kessler, Tao Dong
Summary: This study reveals that mutations in flanking regions of SARS-CoV-2 epitopes can affect proteasomal processing and T cell activation, leading to immune escape or enhancement. These findings have important implications for the design of COVID-19 vaccines.
Article
Biochemistry & Molecular Biology
Elizabeth R. Dellar, Iolanda Vendrell, Kevin Talbot, Benedikt M. Kessler, Roman Fischer, Martin R. Turner, Alexander G. Thompson
Summary: This study used mass spectrometry with library-free data-independent acquisition to analyze the CSF proteome of ALS patients. It identified proteins correlated with clinical variables and strengthened the candidacy of CHIT1 and UCHL1 as biomarkers for ALS. The study also highlighted inflammatory and endoplasmic reticulum proteins as potential prognostic biomarkers.
JOURNAL OF NEUROCHEMISTRY
(2023)
Meeting Abstract
Oncology
Zhuoyao Chen, Rafael Ioris, Stacey Richardson, Ava Van Ess, Iolanda Vendrell, Benedikt Kessler, Francesca Buffa, Luca Busino, Steven Clifford, Alex Bullock, Vincenzo D'Angiolella