Article
Chemistry, Medicinal
Youchao Deng, Sunbin Deng, Yi-Hsun Ho, Sarah M. Gardner, Zhi Huang, Ronen Marmorstein, Rong Huang
Summary: The study designed and prepared a series of highly potent NatD bisubstrate inhibitors, showing high specificity towards NatD and strong competitive characteristics, providing a rational path for future inhibitor development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Plant Sciences
Hai-qing Liu, Ya-jie Zou, Xiao-feng Li, Lei Wu, Guang-qin Guo
Summary: Loss of function of auxiliary subunit CKRC3 and catalytic subunit NBC-1 of Arabidopsis NatB leads to defects in skotomorphogenesis and ethylene responses. Proteome profiling revealed significantly down-regulated activity of 1-amincyclopropane-1-carboxylate oxidase (ACO) in natb mutants, resulting in reduced endogenous ethylene content. The present results highlight a previously unknown co-translational protein level regulation mechanism for ethylene homeostasis mediated by NatB.
Article
Multidisciplinary Sciences
Yao Li, Yueling Zhao, Xiaojie Yan, Chen Ye, Sara Weirich, Bing Zhang, Xiaolu Wang, Lili Song, Chenhao Jiang, Albert Jeltsch, Cheng Dong, Wenyi Mi
Summary: The N-degron pathway is important for maintaining protein homeostasis. This study reveals that ZER1 and ZYG11B can recognize small N-terminal residues other than glycine. N-terminal serine, alanine, and cysteine undergo N-terminal acetylation, mediated by N-terminal acetyltransferase (NAT), which prevents their recognition by ZER1/ZYG11B. The crystal structures of ZER1 and ZYG11B bound to various non-acetylated small N-terminal residues provide insights into the mechanism of substrate recognition.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Shinki, Subhendu Sarkar
Summary: This study systematically investigates and compares the necessity of 3D versus 2D surface morphologies of SERS templates, finding that 2D structures exhibit better signal uniformity and reproducibility.
SURFACES AND INTERFACES
(2022)
Article
Cell & Tissue Engineering
Ping Duan, Hanyu Wang, Xinzeyu Yi, Hao Zhang, Hui Chen, Zhenyu Pan
Summary: This study investigated the epigenetic mechanism of intramedullary fat accumulation and continuous osteonecrosis in steroid-induced avascular necrosis of the femoral head (SANFH). The results showed that C/EBP alpha regulated PPAR gamma expression by acetylating histones and played a crucial role in the differentiation of BMSCs, leading to the development of SANFH.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Multidisciplinary Sciences
Michael Bonadonna, Sandro Altamura, Elisabeth Tybl, Gael Palais, Maria Qatato, Maria Polycarpou-Schwarz, Martin Schneider, Christina Kalk, Wibke Ruediger, Alina Ertl, Natasha Anstee, Ruzhica Bogeska, Dominic Helm, Michael D. Milsom, Bruno Galy
Summary: Iron plays a crucial role in hemoglobin synthesis in red blood cells, but recent studies have shown that it also has a broader role in hematopoiesis and immune system formation. Iron availability is regulated by iron-regulatory protein 1 and IRP2, which are essential for neutrophil development and differentiation. This study reveals the previously unrecognized importance of IRPs and iron metabolism in the formation of the innate immune system.
Article
Cell Biology
Wei Zhang, Wenqun Zhong, Beike Wang, Jiegang Yang, Jingbo Yang, Ziyan Yu, Zhiyuan Qin, Alex Shi, Wei Xu, Cathy Zheng, Lynn M. Schuchter, Giorgos C. Karakousis, Tara C. Mitchell, Ravi Amaravadi, Meenhard Herlyn, Haidong Dong, Phyllis A. Gimotty, George Daaboul, Xiaowei Xu, Wei Guo
Summary: This study reveals the co-localization of ICAM-1 and PD-L1 on exosomes, both of which are upregulated by interferon-y. The adhesion between TEVs and T cells mediated by ICAM-1-LFA-1 is crucial for exosomal PD-L1-mediated immune suppression.
DEVELOPMENTAL CELL
(2022)
Article
Hematology
Zachary C. Murphy, Kristin Murphy, Jacquelyn Myers, Michael Getman, Tyler Couch, Vincent P. Schulz, Kimberly Lezon-Geyda, Cal Palumbo, Hongxia Yan, Narla Mohandas, Patrick G. Gallagher, Laurie A. Steiner
Summary: The terminal maturation of human erythroblasts involves significant changes in histone marks associated with active transcription elongation, rather than heterochromatin accumulation. Regulation of RNA polymerase II activity and gene expression at the transcriptional level play a critical role in controlling the maturation process of erythroblasts.
Review
Biochemistry & Molecular Biology
Kritsanawan Sae-khow, Awirut Charoensappakit, Direkrit Chiewchengchol, Asada Leelahavanichkul
Summary: Vitamin C plays an important role in neutrophil function and has been studied in the treatment of sepsis. High-dose intravenous vitamin C (HDIVC) has been shown to improve neutrophil activity and microbial control, but long-term administration may have negative effects. Further studies are needed to determine the proper use of vitamin C in sepsis treatment.
Article
Chemistry, Medicinal
Katherine L. Jones, Dominic M. Beaumont, Sharon G. Bernard, Rino A. Bit, Simon P. Campbell, Chun-wa Chung, Leanne Cutler, Emmanuel H. Demont, Kate Dennis, Laurie Gordon, James R. Gray, Michael Haase, Antonia J. Lewis, Scott McCleary, Darren J. Mitchell, Susanne M. Moore, Nigel Parr, Olivia J. Robb, Nicholas Smithers, Peter E. Soden, Colin J. Suckling, Simon Taylor, Ann L. Walker, Robert J. Watson, Rab K. Prinjha
Summary: This study details the optimization process of the in vivo tool molecule I-BET151 towards I-BET282E, a molecule with properties suitable for clinical progression, in order to reduce the risk of compound attrition due to related toxicity findings.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Agricultural Engineering
Igor Vassilev, Paolo Dessi, Sebastia Puig, Marika Kokko
Summary: This review presents the role of cathodic biofilms in CO2 bio-reduction and provides insights into the formation and improvement of these biofilms in microbial electrosynthesis cells.
BIORESOURCE TECHNOLOGY
(2022)
Article
Microbiology
Owen A. Collars, Bradley S. Jones, Daniel D. Hu, Simon D. Weaver, Taylor A. Sherman, Matthew M. Champion, Patricia A. Champion
Summary: This study identified a NAT protein required for N-terminal acetylation and pathogenesis in Mycobacterium. Emp1 was found to be the sole responsible for EsxA acetylation in M. marinum and was also responsible for the acetylation of at least 22 additional proteins. Furthermore, loss of emp1 significantly reduced macrophage cytolysis and cell-to-cell spread of M. marinum during infection.
Review
Neurosciences
Aditya Iyer, Arshdeep Sidhu, Vinod Subramaniam
Summary: N-alpha-acetylation is a common post-translational modification in eukaryotic proteins, which has significant effects on protein regulation and function. However, the precise mechanisms and implications of N-alpha-acetylation of alpha-synuclein (alpha S) are not fully understood. This review provides an overview of current knowledge and discusses the impact of N-alpha-acetylation on the conformational, oligomeric, and fibrillar states of alpha S, as well as its relevance to Lewy body formation and synucleinopathies.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Miranda E. Clements, Lauren Holtslander, Courtney Edwards, Vera Todd, Samuel D. R. Dooyema, Kennady Bullock, Kensey Bergdorf, Cynthia A. Zahnow, Roisin M. Connolly, Rachelle W. Johnson
Summary: Histone deacetylase inhibitors (HDACi) have been shown to induce the expression of LIFR and activate a pro-dormancy program in breast cancer cells, slowing cell proliferation and reducing tumor growth. Clinical trial data suggests that HDACi treatment in breast cancer patients leads to increased LIFR levels and decreased proliferation rates in primary tumors, which is associated with prolonged patient survival.
Article
Chemistry, Multidisciplinary
Buyan Pan, Sarah M. Gardner, Kollin Schultz, Ryann M. Perez, Sunbin Deng, Marie Shimogawa, Kohei Sato, Elizabeth Rhoades, Ronen Marmorstein, E. James Petersson
Summary: N-terminal acetylation is a modification carried out by N-terminal acetyltransferases, and NatB is a major member of this enzyme family. NatB acetylates α-synuclein (αS), a protein involved in vesicle trafficking, and modulates its binding properties and fibril formation, which plays a role in Parkinson's disease. This study synthesized a bisubstrate inhibitor of NatB and characterized its structure using cryo-electron microscopy (cryo-EM). The study also revealed conformational changes in αS when bound to NatB through single molecule Förster resonance energy transfer (smFRET) and computational modeling, providing valuable strategies for studying challenging structural biology targets.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Conor J. Kearney, Stephin J. Vervoort, Kelly M. Ramsbottom, Izabela Todorovski, Emily J. Lelliott, Magnus Zethoven, Lizzy Pijpers, Ben P. Martin, Timothy Semple, Luciano Martelotto, Joseph A. Trapani, Ian A. Parish, Nichollas E. Scott, Jane Oliaro, Ricky W. Johnstone
Summary: SUGAR-seq is a novel method that enables simultaneous detection of N-linked glycosylation, extracellular epitopes, and the transcriptome at the single-cell level, providing insights into cellular differentiation states. Integrated analysis using SUGAR-seq and glycoproteome identified tumor-infiltrating T cells with unique surface glycan properties that reflect their epigenetic and functional state.
Review
Cell Biology
Anoushka Ashok Kumar Samat, Jolijn van der Geest, Sebastiaan J. Vastert, Jorg van Loosdregt, Femke van Wijk
Summary: The article summarizes the role of tissue-resident memory T cells (T-RM) in chronic inflammatory diseases, highlighting the presence of T-RM in both non-lymphoid tissue and circulation, and their potential significance in disease progression and treatment.
Article
Biochemistry & Molecular Biology
Stephin J. Vervoort, Sarah A. Welsh, Jennifer R. Devlin, Elisa Barbieri, Deborah A. Knight, Sarah Offley, Stefan Bjelosevic, Matteo Costacurta, Izabela Todorovski, Conor J. Kearney, Jarrod J. Sandow, Zheng Fan, Benjamin Blyth, Victoria McLeod, Joseph H. A. Vissers, Karolina Pavic, Ben P. Martin, Gareth Gregory, Elena Demosthenous, Magnus Zethoven, Isabella Y. Kong, Edwin D. Hawkins, Simon J. Hogg, Madison J. Kelly, Andrea Newbold, Kaylene J. Simpson, Otto Kauko, Kieran F. Harvey, Michael Ohlmeyer, Jukka Westermarck, Nathanael Gray, Alessandro Gardini, Ricky W. Johnstone
Summary: CDK9 regulates gene expression by controlling the pausing checkpoint during the transcription cycle, while PP2A counteracts CDK9-mediated phosphorylation. Loss of INTS6 leads to resistance to CDK9 inhibition-induced tumor cell death, and pharmacological activation of PP2A in combination with CDK9 inhibition provides therapeutic benefits in vivo.
Article
Pediatrics
Anouk Verwoerd, Wineke Armbrust, Katherine Cowan, Lotte van den Berg, Joke de Boer, Sanne Bookelman, Marjan Britstra, Jeannette Cappon, Maria Certan, Christine Dedding, Karin van den Haspel, Petra Hissink Muller, Karin Jongsma, Otto Lelieveld, Jorg van Loosdregt, Wendy Olsder, Johanna Rocha, Ellen Schatorje, Natasja Schouten, Joost F. Swart, Sebastiaan Vastert, Margot Walter, Casper G. Schoemaker
Summary: Involving end-users in setting research priorities is crucial to ensure research questions align with patient needs. This study aimed to generate a national research agenda for Juvenile Idiopathic Arthritis (JIA) with patients, caregivers, and clinicians. Through a nationwide survey and focus groups, the top 10 research priorities were identified, focusing on pain, fatigue, personalized treatment strategies, and etiology.
PEDIATRIC RHEUMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Gerdien Mijnheer, Lisanne Lutter, Michal Mokry, Marlot van der Wal, Rianne Scholman, Veerle Fleskens, Aridaman Pandit, Weiyang Tao, Mark Wekking, Stephin Vervoort, Ceri Roberts, Alessandra Petrelli, Janneke G. C. Peeters, Marthe Knijff, Sytze de Roock, Sebastiaan Vastert, Leonie S. Taams, Jorg van Loosdregt, Femke van Wijk
Summary: The study illustrates the effector characteristics of human Treg cells under inflammatory conditions and their epigenetic influences, indicating that inflammation-derived Treg cells have specific features and are fine-tuned by environmental adaptations.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Mayura Wagle, Stephin J. Vervoort, Madison J. Kelly, Willem Van der Byl, Timothy J. Peters, Ben P. Martin, Luciano G. Martelotto, Simone Nuessing, Kelly M. Ramsbottom, James R. Torpy, Deborah Knight, Sinead Reading, Kevin Thia, Lisa A. Miosge, Debbie R. Howard, Renee Gloury, Sarah S. Gabriel, Daniel T. Utzschneider, Jane Oliaro, Jonathan D. Powell, Fabio Luciani, Joseph A. Trapani, Ricky W. Johnstone, Axel Kallies, Christopher C. Goodnow, Ian A. Parish
Summary: Chronic antigenic stimulation induces the expression of EGR2, which in turn affects the epigenetic and transcriptional identity of exhausted T cells.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Emily J. Lelliott, Isabella Y. Kong, Magnus Zethoven, Kelly M. Ramsbottom, Luciano G. Martelotto, Deborah Meyran, Joe Jiang Zhu, Matteo Costacurta, Laura Kirby, Jarrod J. Sandow, Lydia Lim, Pilar M. Dominguez, Izabela Todorovski, Nicole M. Haynes, Paul A. Beavis, Paul J. Neeson, Edwin D. Hawkins, Grant A. McArthur, Ian A. Parish, Ricky W. Johnstone, Jane Oliaro, Karen E. Sheppard, Conor J. Kearney, Stephin J. Vervoort
Summary: Pharmacologic inhibitors of CDK4/6 have been shown to not only have well-defined tumor-intrinsic cytostatic mechanisms, but also promote the acquisition of immunologic T-cell memory. These insights significantly broaden the potential utility of CDK4/6 inhibitors as clinical tools to boost antitumor T-cell immunity.
Article
Dermatology
Chiara Angiolilli, Emmerik F. A. Leijten, Cornelis P. J. Bekker, Ella Eeftink, Barbara Giovannone, Michel Olde Nordkamp, Marlot van der Wal, Judith L. Thijs, Sebastiaan J. Vastert, Femke van Wijk, Timothy R. D. J. Radstake, Jorg van Loosdregt
Summary: Dermal fibroblasts in psoriatic skin are important producers of inflammatory mediators, and their cytokine production is regulated by ZFP36 family members. The expression of ZFP36 family proteins is reduced in chronic inflammatory conditions that mimic psoriatic skin.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Oncology
Lisa C. Wellinger, Simon J. Hogg, Dane M. Newman, Thomas Friess, Daniela Geiss, Jessica Michie, Kelly M. Ramsbottom, Marina Bacac, Tanja Fauti, Daniel Marbach, Laura Jarassier, Phillip Thienger, Axel Paehler, Leonie A. Cluse, Conor J. Kearney, Stephin J. Vervoort, Joseph A. Trapani, Jane Oliaro, Jake Shortt, Astrid Ruefli-Brasse, Daniel Rohle, Ricky W. Johnstone
Summary: Targeting chromatin binding proteins and modifying enzymes can enhance antitumor immunity and effectiveness of cancer immunotherapies by affecting tumor cell proliferation and survival. BET inhibitors sensitize tumor cells to TNF-induced cell death and suppress inflammatory gene expression, leading to enhanced tumor growth inhibition in combination with T-cell bispecific antibodies or immune-checkpoint blockade.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Rheumatology
Janneke G. C. Peeters, Arjan Boltjes, Rianne C. Scholman, Stephin J. Vervoort, Paul J. Coffer, Michal Mokry, Sebastiaan J. Vastert, Femke van Wijk, Jorg van Loosdregt
Summary: This study investigates the epigenetic changes in monocytes derived from inflamed joints of JIA patients and reveals the role of the local inflammatory environment in regulating these changes. The activation phenotype of synovial-derived monocytes is found to be regulated on the epigenetic level, with increased expression and epigenetic alterations in IFN signaling-associated genes. Treatment with the JAK inhibitor ruxolitinib transforms the activated enhancer landscape and reduces disease-associated gene expression, thus inhibiting the inflammatory phenotype.
Article
Immunology
Arjan Boltjes, Anoushka Ashok Kumar Samat, Maud Plantinga, Michal Mokry, Bas Castelijns, Joost F. Swart, Sebastiaan J. Vastert, Menno Creyghton, Stefan Nierkens, Jorg van Loosdregt, Femke van Wijk
Summary: This study indicates that human dendritic cells (DCs) have specific functional programming in chronic inflammatory conditions. Compared to other cell types, cDC1 remains relatively quiescent and unchanged at the site of inflammation, while cDC2 and monocytes show stronger inflammatory features and T cell activation ability.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anandhi Rajendiran, Sudheendra Hebbar Subramanyam, Patricia Klemm, Vera Jankowski, Jorg van Loosdregt, Bas Vastert, Kristina Vollbach, Norbert Wagner, Klaus Tenbrock, Kim Ohl
Summary: This study investigated the behavior of CD4+ T cells in the inflamed joints of patients with childhood rheumatism. It found that CD4+ T cells adapt to hypoxia, oxidative stress, and reduction in nutrients in the inflammatory environment, showing a high metabolic status and increased oxidative stress. The study also identified the potential role of NRF2 in regulating CD4+ T cells.
Article
Immunology
Lisanne Lutter, M. Marlot van der Wal, Eelco C. Brand, Patrick Maschmeyer, Sebastiaan Vastert, Mir-Farzin Mashreghi, Jorg van Loosdregt, Femke van Wijk
Summary: The study reveals a heterogeneous population of Tregs at the site of inflammation in patients with juvenile idiopathic arthritis. Synovial fluid Tregs differentiate into a classical eTreg profile, with some showing a more dominant suppressive or cytotoxic profile, while others differentiate into Tregs with unique features. Key regulators identified in driving Treg adaptation at inflamed joints may be potential targets for autoimmune or tumor interventions.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Simon J. Hogg, Olga Motorna, Leonie A. Cluse, Timothy M. Johanson, Hannah D. Coughlan, Ramya Raviram, Robert M. Myers, Matteo Costacurta, Izabela Todorovski, Lizzy Pijpers, Stefan Bjelosevic, Tobias Williams, Shannon N. Huskins, Conor J. Kearney, Jennifer R. Devlin, Zheng Fan, Jafar S. Jabbari, Ben P. Martin, Mohamed Fareh, Madison J. Kelly, Daphne Dupere-Richer, Jarrod J. Sandow, Breon Feran, Deborah Knight, Tiffany Khong, Andrew Spencer, Simon J. Harrison, Gareth Gregory, Vihandha O. Wickramasinghe, Andrew Webb, Phillippa C. Taberlay, Kenneth D. Bromberg, Albert Lai, Anthony T. Papenfuss, Gordon K. Smyth, Rhys S. Allan, Jonathan D. Licht, Dan A. Landau, Omar Abdel-Wahab, Jake Shortt, Stephin J. Vervoort, Ricky W. Johnstone
Summary: The study found that catalytic inhibition of P300/CBP dynamically disrupts steady-state acetylation kinetics and suppresses oncogenic transcriptional networks without changing chromatin accessibility. CRISPR-Cas9 screening identified NCOR1 and HDAC3 as the key antagonists of P300/CBP by counteracting acetylation turnover kinetics. Deacetylation of H3K27 provides nucleation sites for reciprocal methylation switching, which can be therapeutically exploited by simultaneous KDM6A and P300/CBP inhibition.
