Article
Multidisciplinary Sciences
Alice Coillard, Lea Guyonnet, Alba De Juan, Adeline Cros, Elodie Segura
Summary: Monocytes are recruited to inflamed tissues where they encounter a broad range of microbial motifs, leading to differentiation into mo-mac or mo-DC. Viruses promote mo-mac differentiation via TLR signaling, while Mycobacteria favor mo-DC differentiation through NOD signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Clovis H. T. Seumen, Tanja M. Grimm, Christof R. Hauck
Summary: Toll-like receptors (TLRs) play a crucial role in immune response, but exaggerated activation can lead to inflammatory diseases. This review discusses the impact of protein phosphorylation on TLR signaling, highlighting the role of phosphatases as negative regulators. Understanding phosphatase-mediated regulation could offer new approaches to modulate immune signaling.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Immunology
Katharina Radakovics, Claire Battin, Judith Leitner, Sabine Geiselhart, Wolfgang Paster, Johannes Stoeckl, Karin Hoffmann-Sommergruber, Peter Steinberger
Summary: Toll-like receptors (TLRs) are essential for recognizing microbial components and initiating immune responses. Although impurities containing TLR ligands can be problematic, this study developed a highly sensitive platform for detecting TLR ligands. By using specific reporter cell lines, the study demonstrated high specificity and sensitivity in detecting various TLR ligands. This system can be used to characterize different TLR ligands, including complex samples like bacterially expressed proteins or allergen extracts, and can help define the structural requirements for TLR agonists.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ziying Sun, Qianqian Liu, Zhongyang Lv, Jiawei Li, Xingquan Xu, Heng Sun, Maochun Wang, Kuoyang Sun, Tianshu Shi, Zizheng Liu, Guihua Tan, Wenqiang Yan, Rui Wu, Yannick Xiaofan Yang, Shiro Ikegawa, Qing Jiang, Yang Sun, Dongquan Shi
Summary: The study revealed that inhibiting M1 macrophage polarization can slow down the progression of osteoarthritis, with SHP099 potentially being a promising therapeutic strategy for OA treatment.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Biochemistry & Molecular Biology
Julia Maria Coronas-Serna, Elba del Val, Jonathan C. Kagan, Maria Molina, Victor J. Cid
Summary: Toll-like receptor signaling plays a key role in detecting pathogens and initiating inflammation through supramolecular organizing centers (SMOCs), which rely on protein-protein interactions involving Toll Interleukin-1 Receptor (TIR) and Death Domain (DD).
Article
Immunology
Yan Liu, Li Liu, Wanying Xing, Yan Sun
Summary: Anesthetics have dual effects on inflammation and neuronal injury, with potential immune-modulation mechanisms involving TLR-mediated signaling regulation and nc RNA modulations. The review focuses on the immunomodulatory functions of anesthetics and the roles of nc RNAs in regulating TLR signaling induced by anesthetics.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Social Sciences, Interdisciplinary
J. M. Sanne, H. Matschke Ekholm, M. Rahmberg
Summary: Resilience approaches offer capabilities beyond traditional methods to respond to hazards and threats, with opportunities to enhance resilience by learning and improving performance. Challenges of contextualizing resilience indicators for specific critical infrastructures and designing comprehensive multidimensional approaches highlight the importance of modular methods and iterative indicator design processes in collaboration with stakeholders.
JOURNAL OF RISK RESEARCH
(2021)
Article
Hematology
Ruth Shiloh, Ruth Lubin, Odeya David, Ifat Geron, Elimelech Okon, Idit Hazan, Marketa Zaliova, Gil Amarilyo, Yehudit Birger, Yael Borovitz, Dafna Brik, Arnon Broides, Sarit Cohen-Kedar, Liora Harel, Eyal Kristal, Daria Kozlova, Galina Ling, Mika Shapira Rootman, Noa Shefer Averbuch, Shiri Spielman, Jan Trka, Shai Izraeli, Simon Yona, Sarah Elitzur
Summary: In this study, the molecular pathway leading to histiocytosis and inflammation in H syndrome, a genetic disorder, was revealed through analysis of primary cells from patients. Loss of function of ENT3 was found to activate nucleoside-sensing toll-like receptors and downstream MAPK signaling, inducing cytokine secretion and inflammation. MEK inhibitor therapy showed effectiveness in resolving histiocytosis and inflammation in a patient with H syndrome.
Article
Biochemistry & Molecular Biology
Patrick Haider, Julia B. Kral-Pointner, Manuel Salzmann, Florian Moik, Sonja Bleichert, Waltraud C. Schrottmaier, Christoph Kaun, Mira Brekalo, Michael B. Fischer, Walter S. Speidl, Christian Hengstenberg, Bruno K. Podesser, Kurt Huber, Ingrid Pabinger, Sylvia Knapp, Frank Brombacher, Christine Brostjan, Cihan Ay, Johann Wojta, Philipp J. Hohensinner
Summary: IL-4R alpha plays a homeostatic role in regulating the lifespan of monocytes, and its absence leads to a reduction in monocyte numbers and affects the occurrence of inflammatory responses.
Review
Pharmacology & Pharmacy
Zhen Zhang, Hong Zhao, Chu Chu, Xiaoxiao Fu, Yonglin Liu, Li Wang, Ran Wei, Ke Xu, Lihua Li, Xia Li
Summary: Ovarian cancer is fatal to women with a high mortality rate, and efforts to identify diagnostic and intervention strategies are ongoing with limited success. Inflammation plays a crucial role in the initiation and progression of ovarian cancer, triggered by various stimuli and innate immune system related receptors like Toll-like receptors and cyclic GMP-AMP synthase. The complexity of pathogenesis poses challenges in effectively managing ovarian cancer.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Adam L. Viens, Kyle D. Timmer, Natalie J. Alexander, Rana Barghout, Jelena Milosevic, Alex Hopke, Natalie J. Atallah, Allison K. Scherer, David B. Syke, Daniel Irimia, Michael K. Mansour
Summary: In this study, TLR signaling is found to be an alternative activation pathway that can partially restore neutrophil effector function against Candida albicans in a Syk-independent manner. The findings suggest that modulation of TLR signaling may be a potential therapeutic strategy for patients with impaired neutrophil response to fungal infections.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Kang Mi Lee, Qiang Fu, Guoli Huai, Kevin Deng, Ji Lei, Lisa Kojima, Divyansh Agarwal, Peter van Galen, Shoko Kimura, Naoki Tanimine, Laura Washburn, Heidi Yeh, Ali Naji, Charles G. Rickert, Christian LeGuern, James F. Markmann
Summary: B lymphocytes play important roles in adaptive immunity and self-tolerance. Activated B cells through TLR4/TLR9 receptors acquire regulatory properties, inhibiting T cell proliferation and preventing allograft rejection.
Review
Parasitology
Francis M. Kobia, Kaushik Maiti, Moses M. Obimbo, Roger Smith, Jesse Gitaka
Summary: Complications from placental malaria affect pregnancy outcomes, but recent studies suggest that fetal innate immune responses may play a positive role in improving outcomes. Pharmacologic modulation shows promise for better placental malaria outcomes.
TRENDS IN PARASITOLOGY
(2022)
Article
Virology
V. Douglas Landers, Daniel W. Wilkey, Michael L. Merchant, Thomas C. Mitchell, Kevin J. Sokoloski
Summary: This study examines the protein-protein interactions of Sindbis virus capsid protein using a BioID2 biotin ligase system and identifies novel host-pathogen interactions, including the conserved interaction between the alphavirus capsid protein and host IRAK1 protein. The research demonstrates that the alphaviral capsid protein inhibits IRAK1-dependent signaling, providing insight into how alphaviruses may evade innate immune detection.
Article
Immunology
Parveen Kumar, Mikita Patel, Robert A. Oster, Vidhush Yarlagadda, Adam Ambrosetti, Dean G. Assimos, Tanecia Mitchell
Summary: This study found that dietary oxalate loading may impact monocyte metabolism and immune response in healthy adults, but the responses are variable. Further research is needed to understand oxalate-mediated mechanisms on circulating monocytes and how this potentially influences CaOx kidney stone formation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Yurong Cheng, Pascal Schlosser, Johannes Hertel, Peggy Sekula, Peter J. Oefner, Ute Spiekerkoetter, Johanna Mielke, Daniel F. Freitag, Miriam Schmidts, Florian Kronenberg, Kai-Uwe Eckardt, Ines Thiele, Yong Li, Anna Koettgen
Summary: This study explores the cumulative contribution of rare, exonic genetic variants on urine metabolite levels and identifies 30 genes related to inborn errors of metabolism, with shared expression in liver and kidney. By using in silico constraint-based modeling, the study correctly predicts the direction of metabolite changes, emphasizing the potential of linking population genetics to modeling.
NATURE COMMUNICATIONS
(2021)
Article
Environmental Sciences
Simon Mills, Anna Christine Trego, John Ward, Juan Castilla-Archilla, Johannes Hertel, Ines Thiele, Piet N. L. Lens, Umer Zeeshan Ijaz, Gavin Collins
Summary: This study utilized laboratory-scale bioreactors to investigate the formation, maturation, disintegration, and re-formation of new granules. The findings highlighted distinct morphological features of granule sizes and biofilm development stages, which are important for maximizing bioreactor performance.
JOURNAL OF ENVIRONMENTAL MANAGEMENT
(2021)
Article
Mathematical & Computational Biology
Almut Heinken, Johannes Hertel, Ines Thiele
Summary: Inflammatory bowel diseases, such as Crohn's Disease, are characterized by changes in blood and fecal metabolites and alterations in gut microbiome composition. A systems biology framework was used to connect microbial strains and fecal metabolites, revealing differences in metabolite contributions and diversity between healthy and dysbiotic microbiomes, leading to potential novel therapeutic and dietary interventions.
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2021)
Article
Biochemical Research Methods
Almut Heinken, Stefania Magnusdottir, Ronan M. T. Fleming, Ines Thiele
Summary: DEMETER is a tool that can efficiently refine thousands of draft genome-scale reconstructions simultaneously, ensuring adherence to quality standards, agreement with available experimental data, and refinement of pathways based on manually refined genome annotations.
Article
Biochemical Research Methods
Leo Zhu, William Pei, Ines Thiele, Radhakrishnan Mahadevan
Summary: Ethanol, a widely used recreational substance, is responsible for over 3.3 million deaths annually due to abuse. Genetic variations play a crucial role in the metabolism of ethanol and its primary metabolite, acetaldehyde, highlighting the importance of understanding the impact of these variations on individual responses to alcohol. By integrating a whole-body genome-scale model with traditional pharmacokinetic modeling, the study shows a personalized approach to pharmacokinetic modeling that can enhance precision medicine.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Biochemical Research Methods
Almut Heinken, Ines Thiele
Summary: This study improved the computation speed and scalability of the constraint-based microbiome modeling and analysis approach, and added additional functionalities for analysis and visualization.
Article
Biochemistry & Molecular Biology
Johannes Hertel, Daniel Faessler, Almut Heinken, Frank U. Weiss, Malte Ruehlemann, Corinna Bang, Andre Franke, Kathrin Budde, Ann-Kristin Henning, Astrid Petersmann, Uwe Voelker, Henry Voelzke, Ines Thiele, Hans-Joergen Grabe, Markus M. Lerch, Matthias Nauck, Nele Friedrich, Fabian Frost
Summary: Microbial metabolites measured using NMR can serve as markers for host-microbe interactions and mediate the beneficial effects of microbiome diversity. This study analyzed gut microbiome data and urine NMR metabolome from a large population cohort, identifying novel markers and metabolic pathways associated with microbial diversity and health. The findings suggest a role of benzoate metabolism in the positive associations between high microbial alpha diversity and healthy states.
Article
Biochemical Research Methods
Ines Thiele, German Preciat, Ronan M. T. Fleming
Summary: This study aims to expand the coverage of metabolite annotation by using various databases and chemoinformatic approaches. The researchers developed a tool called MetaboAnnotator to comprehensively annotate metabolites and perform cross-mapping between reconstructions.
Article
Biotechnology & Applied Microbiology
Bronson R. Weston, Ines Thiele
Summary: The optimization of animal feeds and cell culture media is challenging due to the complexity of metabolic systems. A nutrition algorithm utilizing linear programming is developed to identify the most efficient changes to nutrition for desired metabolic outcomes. This algorithm has been successfully applied to Atlantic salmon and CHO cell metabolism models, providing predictions that align with experimental findings and offering new insights into feeding strategies.
METABOLIC ENGINEERING
(2023)
Article
Microbiology
William F. F. Kindschuh, Federico Baldini, Martin C. C. Liu, Jingqiu Liao, Yoli Meydan, Harry H. H. Lee, Almut Heinken, Ines Thiele, Christoph A. A. Thaiss, Maayan Levy, Tal Korem
Summary: The study discovers multiple associations between vaginal metabolites and subsequent preterm birth, suggesting the potential of vaginal metabolites as early biomarkers of sPTB. Using metabolic and machine learning models, they accurately predict sPTB risk with higher accuracy than microbiome-based and maternal covariates-based models. These findings highlight exogenous exposures as potential risk factors for prematurity.
NATURE MICROBIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Arianna Basile, Almut Heinken, Johannes Hertel, Larry Smarr, Weizhong Li, Laura Treu, Giorgio Valle, Stefano Campanaro, Ines Thiele
Summary: This study employs constraint-based microbial community modeling to investigate an individual with episodic inflammation of the gastrointestinal tract. The individual has well-documented colonic inflammatory biomarkers and metagenomically-sequenced fecal time series. Results show time-correlated microbial species and metabolites in the individual's microbial ecology during the disease state. Dysbiosis in the gut microbiome affects metabolite production and has consequences on other organs in the body.
Article
Biochemistry & Molecular Biology
Tim Hensen, Daniel Faessler, Liam O'Mahony, Werner C. Albrich, Beatrice Barda, Christian Garzoni, Gian-Reto Kleger, Urs Pietsch, Noemie Suh, Johannes Hertel, Ines Thiele
Summary: This study characterized the serum metabolomic changes in hospitalized COVID-19 patients and identified potential biomarkers for disease severity. The findings showed significant alterations in metabolite concentrations related to hospitalization, physiological functioning, and disease progression. These results provide insights into monitoring the course of COVID-19 and offer a wide range of potential biomarkers for further study.
Article
Biochemical Research Methods
Ronan M. T. Fleming, Hulda S. Haraldsdottir, Le Hoai Minh, Phan Tu Vuong, Thomas Hankemeier, Ines Thiele
Summary: Several applications in constraint-based modelling can be formulated as cardinality optimization problems involving the minimization or maximization of the number of nonzeros in a vector. By approximating the zero-norm with nonconvex continuous functions, a set of cardinality optimization problems in constraint-based modelling is reformulated into a difference of convex functions. Novel algorithms are implemented and numerically tested, demonstrating their efficiency and practical utility in various biochemical networks.
Article
Biochemistry & Molecular Biology
Almut Heinken, Arianna Basile, Ines Thiele
Summary: This article provides a comprehensive overview of the applications of microbial multispecies models at the microbiome scale and the role of computational modeling in discovering novel biological knowledge. Constraint-based microbiome modeling complements experimental approaches and has valuable applications in ecology, human health, industry, and environmental conservation.
CURRENT OPINION IN SYSTEMS BIOLOGY
(2021)
Review
Gastroenterology & Hepatology
F. Hosseinkhani, A. Heinken, I Thiele, P. W. Lindenburg, A. C. Harms, T. Hankemeier
Summary: This review discusses the impact of bacterial metabolites on immune signaling pathways in non-communicable diseases and reviews recent advancements in designing microbial therapeutics. Using a metabolomics-based system biology platform to understand the interactions between host and gut microbiota metabolism promises to reveal fundamental mechanisms underlying metabolic predispositions to disease and suggests new avenues for microbial therapeutic opportunities in the treatment and prevention of non-communicable diseases.