Editorial Material
Chemistry, Multidisciplinary
Takeharu Nagai, Mitsuru Hattori
Summary: Ten years ago, the engineering breakthrough of NanoLuc, a small luciferase, overcame a common limitation in bioluminescence. It is currently the brightest known bioluminescent protein and has been widely used for measurements in single cells and whole living organisms.
NATURE REVIEWS CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Soroush Moasses Ghafary, Paula M. Soriano-Teruel, Shima Lotfollahzadeh, Monica Sancho, Eva Serrano-Candelas, Fatemeh Karami, Stephen J. Barigye, Ivan Fernandez-Perez, Rafael Gozalbes, Maryam Nikkhah, Mar Orzaez, Saman Hosseinkhani
Summary: This study identified QM380 and QM381 as inhibitors of NLRP3(PYD) homo-oligomerization, which interfere with the formation of inflammasomes and reduce inflammatory responses. Spectroscopic techniques and computational docking analyses confirmed the experimental results and predicted possible mechanisms underlying the inhibition of NLRP3(PYD) homo-interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Qiankun Wang, Hongbo Gao, Kolin M. Clark, Christian Shema Mugisha, Keanu Davis, Jack P. Tang, Gray H. Harlan, Carl J. DeSelm, Rachel M. Presti, Sebla B. Kutluay, Liang Shan
Summary: HIV-1's rapid evolution and high mutation rates enable it to evade the host immune system, but intervention targeting the protease activity with the inflammasome sensor CARD8 has shown promise in clearing latent HIV-1 infection.
Article
Pharmacology & Pharmacy
Sorina Andreea Anghel, Rodica Aura Badea, Gabriela Chiritoiu, David Sebastian Patriche, Petruta Ramona Alexandru, Florentina Pena
Summary: GLP-1 secretion plays a crucial role in controlling blood glucose levels. A newly developed cell line allowed for rapid assessment of GLP-1 secretion. The discovery of quercetin as a potent GLP-1 secretagogue opens up possibilities for developing alternative glucose-lowering therapies.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jittima Phonbuppha, Ruchanok Tinikul, Yoshihiro Ohmiya, Pimchai Chaiyen
Summary: In this study, we constructed a gene reporter system based on Flavin Luciferase from Vibrio campbellii (Vc) (FLUXVc), which can generate powerful bioluminescence signals in mammalian cells. The signal intensity of FLUXVc is over 400-fold higher than the nonengineered version.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Neurosciences
Dianne Marquez Lopez, Connor J. Maltby, Hannah Warming, Nullin Divecha, Mariana Vargas-Caballero, Mark J. Coldwell, Katrin Deinhardt
Summary: In Alzheimer's disease, tau pathology is spread through neuronal networks via a prion-like mechanism. The secretion of tau protein, both healthy and pathological, remains not fully understood. This study found that both wild-type and mutant tau were secreted in basal conditions, with mutant tau being more robustly secreted. Pharmacological stimulation of neuronal activity increased tau secretion, while inhibition of activity had no effect. Heparin sulfate proteoglycans (HSPGs) were found to play a crucial role in the secretion of tau, regardless of activity dependence.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Chemistry, Analytical
Mina Oliayi, Rahman Emamzadeh, Mojgan Rastegar, Mahboobeh Nazari
Summary: For many years, researchers have been using protein-fragment complementation assay (PCA) approaches to study protein-protein interactions in various areas. NanoLuc (NLuc), a smaller and brighter engineered luciferase, has emerged as a beneficial reporter in PCA. Two split NLuc systems, including binary and ternary NLuc, have been reported. While the binary NLuc system NanoBiT® has been extensively used, the application of the ternary NLuc has been limited. However, the ternary NLuc has the potential to become a multifunctional and powerful tool, despite its drawbacks and challenges. This review focuses on various aspects of the ternary NLuc and provides a brief comparison with NanoBiT®.
ANALYTICAL METHODS
(2023)
Article
Environmental Sciences
Lili Xin, Jianshu Wang, Jiaojiao Sun, Chen Zhang, Xing Tong, Jianmei Wan, Jialiang Feng, Hailin Tian, Zengli Zhang
Summary: Exposure to PM(2.5) can have adverse health outcomes, particularly when it comes from traffic tunnels. The study found that PM(2.5) from traffic tunnels had the most significant negative effects on cells, including oxidative stress, cytotoxicity, genotoxicity, inflammation, and activation of stress-responsive genes. Cytokine expression was correlated with endotoxin content, while other toxic effects were mainly linked to PM(2.5)-bound metals and polycyclic aromatic hydrocarbons (PAHs).
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2021)
Article
Microbiology
Heather M. Froggatt, Kaitlyn N. Burke, Ryan R. Chaparian, Hector A. Miranda, Xinyu Zhu, Benjamin S. Chambers, Nicholas S. Heaton
Summary: Influenza A viruses are capable of utilizing RNA splicing to expand their coding capacity, with a higher tolerance for splicing than previously thought. Inserting an artificial intron did not significantly affect viral fitness, and incorporating a reporter gene allowed for high levels of protein expression without major impacts on viral replication or disease-causing abilities. This knowledge can be used to develop viral genetic platforms with biotechnology applications.
Article
Veterinary Sciences
Peng-Fei Fu, Xuan Cheng, Bing-Qian Su, Li-Fang Duan, Cong-Rong Wang, Xin-Rui Niu, Jiang Wang, Guo-Yu Yang, Bei-Bei Chu
Summary: A double reporter PRV was constructed using gene editing technology for virology studies and antiviral agent evaluation, providing valuable insights for understanding the virulence enhancement of variant PRV and potential treatment options.
VETERINARY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Frederic A. Fellouse, Shane Miersch, Chao Chen, Stephen W. Michnick
Summary: Recombinant antibodies against the SARS-CoV-2 virus show promise for COVID-19 treatment and diagnostic assays. A Protein-fragment Complementation Assay (PCA) detector was developed using two antibodies coupled to complementary N- and C-terminal fragments of Gaussia luciferase to detect SARS-CoV-2 antigen with high specificity. This design can be applied to develop reporters for virtually any protein with sufficient available structural details.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Cell Biology
Natalya Kaverina, R. Allen Schweickart, Gek Cher Chan, Joseph C. Maggiore, Diana G. Eng, Yuting Zeng, Sierra R. McKinzie, Hannah S. Perry, Adilijiang Ali, Christopher O'Connor, Beatriz Maria Veloso Pereira, Ashleigh B. Theberge, Joshua C. Vaughan, Carol J. Loretz, Anthony Chang, Neil A. Hukriede, Markus Bitzer, Jeffrey W. Pippin, Oliver Wessely, Stuart J. Shankland
Summary: The lifespan and health-span of podocytes in healthy aging kidneys decrease, leading to changes in their structure, physiology, and function. The ability to reverse these changes becomes important when disease occurs in an aged kidney. RNA-sequencing of podocytes in middle-aged mice and humans revealed an upregulation of inflammatory pathways, including the NLRP3 inflammasome, which is associated with aging. Inhibition of NLRP3 showed promising results in reducing podocyte senescence and improving their lifespan, suggesting a critical role for NLRP3 in podocyte and liver aging.
Article
Biochemical Research Methods
Joshua Philippe Olorocisimo, Jeric Briones, Kiyotaka Sasagawa, Makito Haruta, Hironari Takehara, Hiroyuki Tashiro, Norihiro Ishida-Kitagawa, Yasumasa Bessho, Jun Ohta
Summary: The study aims to develop smaller, more cost-effective, and versatile imaging capabilities for gene expression analysis compared with conventional devices. By using a bioluminescence reporter-based approach and micro-CMOS image sensors, the researchers achieved lower dark current, lower temporal noise, and higher sensitivity in imaging living mammalian cells. These improvements make it possible to measure bioluminescence reporter-based gene expression and potentially use the device for in vivo applications like simultaneous gene expression imaging, behavioral analysis, and optogenetic modulation.
JOURNAL OF BIOMEDICAL OPTICS
(2021)
Article
Microbiology
Kevin Chiem, Jun-Gyu Park, Desarey Morales Vasquez, Richard K. Plemper, Jordi B. Torrelles, James J. Kobie, Mark R. Walter, Chengjin Ye, Luis Martinez-Sobrido
Summary: Despite the availability of vaccines and antivirals, the SARS-CoV-2 virus continues to cause the COVID-19 pandemic, affecting healthcare institutions worldwide. Previous studies have generated replicable forms of the virus that express fluorescent or luciferase reporter proteins to track viral infection in vitro and/or in vivo. However, the limitations of these approaches have prevented their use in specific assays or studies. In this study, researchers engineered a new form of the virus that expresses both fluorescent (mCherry) and luciferase (Nluc) reporter genes, allowing for better understanding of the virus's behavior in vitro and in vivo. This new model was successfully used to study viral infection and transmission in rodent models using in vivo imaging systems.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biochemical Research Methods
Eduardo Gonzalez-Grandio, Gozde S. Demirer, Wenhe Ma, Siobhan Brady, Markita P. Landry
Summary: Transcriptional reporter assays are crucial in plant synthetic biology for constructing complex genetic circuits and understanding gene expression control. The dual color luciferase ratiometric reporter system developed in this study offers advantages including speed, cost-effectiveness, and reduced variability.
ACS SYNTHETIC BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Nathaniel L. Hepowit, Carl-Christian Kolbe, Sarah R. Zelle, Eicke Latz, Jason A. MacGurn
Summary: The regulatory influence of ubiquitin in cellular processes is vast, with phosphorylation playing a key role in enhancing the complexity of the ubiquitin code. Phosphorylation can affect the function of ubiquitin at different sites and its crosstalk with other modifiers.
Article
Neurosciences
Frederic Brosseron, Anne Maass, Luca Kleineidam, Kishore Aravind Ravichandran, Pablo Garcia Gonzalez, Roisin M. McManus, Christina Ising, Francesco Santarelli, Carl-Christian Kolbe, Lisa M. Haesler, Steffen Wolfsgruber, Marta Marquie, Merce Boada, Adelina Orellana, Itziar de Rojas, Sandra Roeske, Oliver Peters, Nicoleta-Carmen Cosma, Arda Cetindag, Xiao Wang, Josef Priller, Eike J. Spruth, Slawek Altenstein, Anja Schneider, Klaus Fliessbach, Jens Wiltfang, Bjorn H. Schott, Katharina Buerger, Daniel Janowitz, Martin Dichgans, Robert Perneczky, Boris-Stephan Rauchmann, Stefan Teipel, Ingo Kilimann, Doreen Goerss, Christoph Laske, Matthias H. Munk, Emrah Duzel, Renat Yakupov, Laura Dobisch, Coraline D. Metzger, Wenzel Glanz, Michael Ewers, Peter Dechent, John Dylan Haynes, Klaus Scheffler, Nina Roy, Ayda Rostamzadeh, Charlotte E. Teunissen, Natalie L. Marchant, Annika Spottke, Mathias Jucker, Eicke Latz, Michael Wagner, David Mengel, Matthis Synofzik, Frank Jessen, Alfredo Ramirez, Agustin Ruiz, Michael T. Heneka
Summary: Understanding neuroinflammation in Alzheimer's disease is crucial, as evident from the analysis of inflammatory biomarkers in pre-dementia individuals showing close interactions between inflammation and accumulating neurodegeneration. Additionally, higher levels of specific biomarkers are associated with larger brain structure and stable cognitive outcomes at follow-up.
Review
Rheumatology
Susan MacLauchlan, Katherine A. Fitzgerald, Ellen M. Gravallese
Summary: Evidence has shown that DNA plays a unique role in distinguishing between endogenous and foreign DNA, posing a challenge in disease discrimination. Autoinflammatory diseases resulting from gene mutations or DNA sensing pathway activation provide insight into the role of DNA in inflammation. This review discusses the current understanding of intracellular DNA sensing and its relevance to various diseases, as well as the development of therapies targeting these pathways.
ARTHRITIS & RHEUMATOLOGY
(2022)
Review
Immunology
Christine Wuebben, Eva Bartok, Gunther Hartmann
Summary: The success of RNA applications, such as mRNA vaccines and RNA therapeutics, holds great promise for future drug development. Understanding innate RNA sensing can lead to further improvements in mRNA vaccines and RNA therapeutics.
CURRENT OPINION IN IMMUNOLOGY
(2022)
Correction
Immunology
Nina Kessler, Susanne F. Viehmann, Calvin Krollmann, Karola Mai, Katharina M. Kirschner, Hella Luksch, Prasanti Kotagiri, Alexander M. C. Boehner, Dennis Huugen, Carina C. de Oliveira Mann, Simon Otten, Stefanie A. I. Weiss, Thomas Zillinger, Kristiyana Dobrikova, Dieter E. Jenne, Rayk Behrendt, Andrea Ablasser, Eva Bartok, Gunther Hartmann, Karl-Peter Hopfner, Paul A. Lyons, Peter Boor, Angela Roesen-Wolff, Lino L. Teichmann, Peter Heeringa, Christian Kurts, Natalio Garbi
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Review
Cell Biology
John S. S. Mattick, Paulo P. P. Amaral, Piero Carninci, Susan Carpenter, Howard Y. Y. Chang, Ling-Ling Chen, Runsheng Chen, Caroline Dean, Marcel E. E. Dinger, Katherine A. A. Fitzgerald, Thomas R. R. Gingeras, Mitchell Guttman, Tetsuro Hirose, Maite Huarte, Rory Johnson, Chandrasekhar Kanduri, Philipp Kapranov, Jeanne B. B. Lawrence, Jeannie T. T. Lee, Joshua T. T. Mendell, Timothy R. R. Mercer, Kathryn J. J. Moore, Shinichi Nakagawa, John L. L. Rinn, David L. L. Spector, Igor Ulitsky, Yue Wan, Jeremy E. E. Wilusz, Mian Wu
Summary: Genes encoding lncRNAs are abundant in complex organisms and are transcribed by RNA polymerase I, II, and III, as well as processed introns. The classification and annotation of lncRNAs are challenging due to their various functions, isoforms, and interactions with other genes. These lncRNAs evolve rapidly, are cell type-specific, and regulate multiple cellular processes, including gene expression and translation control.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Editorial Material
Immunology
Michelle A. Kelliher, Katherine A. Fitzgerald
Summary: Resistance mechanisms have hindered the effectiveness of immune checkpoint blockade therapies, but inhibition of TBK1 can restore their efficacy by sensitizing tumors to RIPK1 kinase-dependent cell death.
TRENDS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Silke Lambing, Yu Pan Tan, Paraskevi Vasileiadou, Stefan Holdenrieder, Patrick Mueller, Christian Hagen, Stephan Garbe, Rayk Behrendt, Martin Schlee, Jasper G. van den Boorn, Eva Bartok, Marcel Renn, Gunther Hartmann
Summary: Radiotherapy induces DNA damage and activates cell death pathways, but its effectiveness is limited in radioresistant tumors such as melanoma. This study shows that activation of the immune sensing receptor RIG-I can enhance irradiation-induced tumor cell death, leading to improved survival in melanoma models. The results suggest that combining RIG-I ligands with radiotherapy may be a promising approach for treating radioresistant tumors with functional p53 pathways, such as melanoma.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Matthew S. J. Mangan, Friederike Gorki, Karoline Krause, Alexander Heinz, Anne Pankow, Thomas Ebert, Dieter Jahn, Karsten Hiller, Veit Hornung, Marcus Maurer, Florian Schmidt, Ralf Gerhard, Eicke Latz
Summary: This study reveals that human monocyte-derived macrophages (hMDM) have a different regulation of Pyrin activation compared to monocytes and murine macrophages. Unlike the latter, hMDM fail to activate Pyrin in response to known Pyrin activators and require prolonged priming and increased Pyrin expression for Pyrin inflammasome response. However, FMF mutations lift the requirement for prolonged priming, enabling Pyrin activation without additional inflammatory signals. Additionally, the study unexpectedly finds that TcdB can activate the NLRP3 inflammasome in hMDM even without a Pyrin response.
Article
Cell Biology
Gabor Zsurka, Maximilian L. T. Appel, Maximilian Nastaly, Kerstin Hallmann, Niels Hansen, Daniel Nass, Tobias Baumgartner, Rainer Surges, Gunther Hartmann, Eva Bartok, Wolfram S. Kunz
Summary: This study reports on a family with three affected individuals exhibiting symptoms resembling a neurodevelopmental disorder. Whole-exome sequencing identified a homozygous stop-gain mutation in the BATF2 gene, which is predominantly expressed in macrophages and monocytes and plays a role in modulating pro-inflammatory responses. Transcriptome analysis showed altered expression of interferon-stimulated genes and elevated responses to innate immune stimuli in the patients' blood. These findings suggest that BATF2 may be a novel disease-associated gene candidate for severe epilepsy and mental retardation related to dysregulation of immune responses, highlighting the importance of neuroinflammation in epilepsy.
Editorial Material
Cell Biology
Kevin MingJie Gao, Katherine A. Fitzgerald
Summary: Endoplasmic-reticulum-associated degradation of the adaptor STING by SEL1L-HRD1 regulates steady-state STING levels to limit STING-driven inflammation, according to the study by Jie et al.
NATURE CELL BIOLOGY
(2023)
Article
Rheumatology
Jonathan J. J. Miner, Katherine A. A. Fitzgerald
Summary: Next-generation sequencing has revolutionized the field of genetics and has allowed for the discovery of rare autoinflammatory diseases and their corresponding mutations. This has opened up opportunities for personalized medicine and has shed light on more common forms of autoimmunity and autoinflammation. The rapid and cost-effective sequencing of individual genomes is changing the practice of rheumatology.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Adham Abuelola Mohamed, Sofia Soler, Julia Wegner, Eva Bartok, Sanda Stankovic, Andrew G. G. Brooks, Martin Schlee
Summary: NK cell activation in response to Influenza A virus infection depends on the cytosolic RNA receptor RIG-I, and activation of RIG-I enhances both the antiviral defense and cytotoxic effector function of NK cells against target cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Respiratory System
Konrad Peukert, Folkert Steinhagen, Mario Fox, Caroline Feuerborn, Susanne Schulz, Benjamin Seeliger, Patrick Schuss, Matthias Schneider, Stilla Frede, Andrea Sauer, Christian Putensen, Eicke Latz, Christoph Wilhelm, Christian Bode
Summary: The study found that tetracycline can reduce silica-induced lung injury and fibrosis associated with chronic silicosis by inhibiting caspase-1 activation and the production of IL-1 beta. Tetracycline may be an effective treatment for patients with silicosis and other diseases involving silicotic inflammation.
RESPIRATORY RESEARCH
(2022)
Review
Medicine, General & Internal
Marcus J. Moeller, Rafael Kramann, Twan Lammers, Bernd Hoppe, Eicke Latz, Isis Ludwig-Portugall, Peter Boor, Juergen Floege, Christian Kurts, Ralf Weiskirchen, Tammo Ostendorf
Summary: Organ fibrogenesis, characterized by a common pathophysiological final pathway, independent of the progressive disease, offers potential therapeutic targets. The SFB/TRR57 consortium successfully identified new mechanisms and established novel therapeutic approaches to interfere with hepatic and renal fibrosis. This review focuses on the consortium's key findings related to renal fibrosis, addressing new relevant mechanisms, immunological contributors, and modulation strategies.
FRONTIERS IN MEDICINE
(2022)