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- Jax, Elinor, et al.
(author)
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Comparative Genomics of the Waterfowl Innate Immune System
- 2022
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In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 39:8
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Journal article (peer-reviewed)abstract
- Animal species differ considerably in their ability to fight off infections. Finding the genetic basis of these differences is not easy, as the immune response is comprised of a complex network of proteins that interact with one another to defend the body against infection. Here, we used population- and comparative genomics to study the evolutionary forces acting on the innate immune system in natural hosts of the avian influenza virus (AIV). For this purpose, we used a combination of hybrid capture, next- generation sequencing and published genomes to examine genetic diversity, divergence, and signatures of selection in 127 innate immune genes at a micro- and macroevolutionary time scale in 26 species of waterfowl. We show across multiple immune pathways (AIV-, toll-like-, and RIG-I -like receptors signalling pathways) that genes involved genes in pathogen detection (i.e., toll-like receptors) and direct pathogen inhibition (i.e., antimicrobial peptides and interferon-stimulated genes), as well as host proteins targeted by viral antagonist proteins (i.e., mitochondrial antiviral-signaling protein, [MAVS]) are more likely to be polymorphic, genetically divergent, and under positive selection than other innate immune genes. Our results demonstrate that selective forces vary across innate immune signaling signalling pathways in waterfowl, and we present candidate genes that may contribute to differences in susceptibility and resistance to infectious diseases in wild birds, and that may be manipulated by viruses. Our findings improve our understanding of the interplay between host genetics and pathogens, and offer the opportunity for new insights into pathogenesis and potential drug targets.
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- Long, F., et al.
(author)
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A low-carbohydrate diet induces hepatic insulin resistance and metabolic associated fatty liver disease in mice
- 2023
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In: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 69
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Journal article (peer-reviewed)abstract
- Objectives: Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease that can range from hepatic steatosis to non-alcoholic steatohepatitis (NASH), which can lead to fibrosis and cirrhosis. Recently, ketogenic diet (KD), a low carbohydrate diet, gained popularity as a weight-loss approach, although it has been reported to induce hepatic insulin resistance and steatosis in animal model systems via an undefined mechanism. Herein, we investigated the KD metabolic benefits and its contribution to the pathogenesis of NASH.Methods: Using metabolic, biochemical and omics approaches, we identified the effects of a KD on NASH and investigated the mechanisms by which KD induces hepatic insulin resistance and steatosis.Results: We demonstrate that KD can induce fibrosis and NASH regardless of body weight loss compared to high-fat diet (HFD) fed mice at thermoneutrality. At ambient temperature (23 degrees C), KD-fed mice develop a severe hepatic injury, inflammation, and steatosis. In addition, KD increases liver cholesterol, IL-6, and p-JNK and aggravates diet induced-glucose intolerance and hepatic insulin resistance compared to HFD. Pharmacological inhibition of IL-6 and JNK reverses KD-induced glucose intolerance, and hepatic steatosis and restores insulin sensitivity.Conclusions: Our studies uncover a new mechanism for KD-induced hepatic insulin resistance and NASH potentially via IL-6-JNK signaling and provide a new NASH mouse model.C 2023 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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- Stoustrup, Peter, et al.
(author)
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Management of orofacial manifestations of juvenile idiopathic arthritis : Interdisciplinary consensus-based recommendations.
- 2023
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In: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 75:1, s. 4-14
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Research review (peer-reviewed)abstract
- OBJECTIVES: Involvement of the temporomandibular joint (TMJ) is common in juvenile idiopathic arthritis (JIA). TMJ arthritis can lead to orofacial symptoms, dysfunction and dentofacial deformity with negative impact on quality of life. Management involves interdisciplinary collaboration. No current recommendations exist to guide clinical management.OBJECTIVES: 1) To develop consensus-based interdisciplinary recommendations for management of orofacial manifestations of JIA. 2) To create a future research agenda related to management of TMJ arthritis in children with JIA.METHODS: The recommendations were developed using online surveying of relevant stakeholders, systematic literature review, evidence-informed generation of recommendations during two consensus-meetings, and Delphi study iterations involving external experts. The process included disciplines involved in the care of orofacial manifestations of JIA: Pediatric rheumatology, radiology, orthodontics, oral and maxillofacial surgery, orofacial pain specialists and pediatric dentistry. Recommendations were accepted if agreement was >80% during a final Delphi study.RESULTS: Three overarching management principles and 12 recommendations for interdisciplinary management of orofacial manifestations of JIA were outlined. The 12 recommendations pertained to: diagnosis (n=4), treatment of TMJ arthritis (active TMJ inflammation) (n=2), treatment of TMJ dysfunction and symptoms (n=3), treatment of arthritis-related dentofacial deformity (n=2), and other related aspects to JIA (n=1). Additionally, a future interdisciplinary research agenda was developed.CONCLUSIONS: These are the first interdisciplinary recommendations to guide clinical management of TMJ JIA. The 3 overarching principles and 12 recommendations fill an important gap in current clinical practice. They emphasize the importance of an interdisciplinary approach to diagnosis and management of orofacial manifestations of JIA. This article is protected by copyright. All rights reserved.
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- Stoustrup, Peter, et al.
(author)
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Standardizing Terminology and Assessment for Orofacial Conditions in Juvenile Idiopathic Arthritis : International, Multidisciplinary Consensus-based Recommendations
- 2019
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In: Journal of Rheumatology. - : Journal Of Rheumatology Publishing Co., Ltd.. - 0315-162X .- 1499-2752. ; 46:5, s. 518-522
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Journal article (peer-reviewed)abstract
- Objective. To propose multidisciplinary, consensus-based, standardization of operational terminology and method of assessment for temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA). Methods. Using a sequential expert group-defined terminology and methods-of-assessment approach by (1) establishment of task force, (2) item generation, (3) working group consensus, (4) external expert content validity testing, and (5) multidisciplinary group of experts final Delphi survey consensus. Results. Seven standardized operational terms were defined: TMJ arthritis, TMJ involvement, TMJ arthritis management, dentofacial deformity, TMJ deformity, TMJ symptoms, and TMJ dysfunction. Conclusion. Definition of 7 operational standardized terms provides an optimal platform for communication across healthcare providers involved in JIA-TMJ arthritis management.
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