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2. Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning

Author

Neag, Georgiana, Lewis, Jonathan, Turner, Jason D., Manning, Julia E., Dean, Isaac, Finlay, Melissa, Poologasundarampillai, Gowsihan, Woods, Jonathan, Sahu, Muhammad Arham, Khan, Kabir A., Begum, Jenefa, McGettrick, Helen M., Bellantuono, Ilaria, Heath, Victoria, Jones, Simon W., Buckley, Christopher D., Bicknell, Roy, and Naylor, Amy J.

Published
2024
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6. Therapeutic avenues in bone repair: Harnessing an anabolic osteopeptide, PEPITEM, to boost bone growth and prevent bone loss

Author

Lewis, Jonathan W., Frost, Kathryn, Neag, Georgiana, Wahid, Mussarat, Finlay, Melissa, Northall, Ellie H., Abudu, Oladimeji, Kemble, Samuel, Davis, Edward T., Powell, Emily, Palmer, Charlotte, Lu, Jinsen, Rainger, G. Ed, Iqbal, Asif J., Chimen, Myriam, Mahmood, Ansar, Jones, Simon W., Edwards, James R., Naylor, Amy J., and McGettrick, Helen M.

Published
2024
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7. Onboard evolution of human-understandable behaviour trees for robot swarms

Author

Jones, Simon W. and Hauert, Sabine

Subjects
629.8, swarm robotics, behaviour trees, understandable controller, evolutionary robotics
Abstract

Swarm robotics, inspired by swarms in nature, has great potential. The resilience, scalability, robustness and redundancy of having many robots collectively perform tasks such as mapping, disaster recovery, pollution control, and cleaning make for a compelling vision. To achieve this, we need to design swarm robot systems to have a desired collective behaviour, but the design of controllers for the individual robots of a swarm such that this behaviour emerges from the interaction of the individual robots is difficult. Current solutions often use off-line automatic discovery by artificial evolution of robot controllers, which are then transferred into the swarm. This is problematic for two important reasons. Firstly, since there is the need for additional supporting infrastructure, both to evolve the new controllers and to communicate them to the swarm, the swarm is not self-sufficient. Secondly, the evolved controllers are often opaque and hard to understand, an important consideration for safety and explainability reasons. In this work we tackle both of these issues. We build a swarm of robots with very high computing performance using recently available mobile computation devices. This high performance allows us to move the evolutionary process, dependent on processing power for simulation, into the swarm. Because the computational power of the swarm grows with the size of the swarm, it is both autonomous and scalable. We use behaviour trees as the individual robot controller architecture. They are modular, hierarchical and human readable. By developing automatic tools to simplify large evolved trees, we can understand, explain, and even improve the evolved controllers. By moving the evolutionary process into the swarm, and by using understandable controllers, we make the swarm autonomous, scalable, and understandable, necessary steps towards their real-world deployment.

Published
2020

9. A detailed methodology for the long-term in vitro culture and analysis of three-dimensional, self-structuring bone models generated from cell lines or primary osteoblastic cell populations

Author

Finlay, Melissa, primary, Hill, Laurence A, additional, Neag, Georgiana, additional, Patel, Binal, additional, Chipara, Miruna, additional, Lamont, Hannah C, additional, Frost, Kathryn, additional, Patrick, Kieran, additional, Lewis, Jonathan W, additional, Nicholson, Thomas, additional, Edwards, James, additional, Jones, Simon W, additional, Grover, Liam M, additional, and Naylor, Amy J, additional

Published
2024
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10. Pre-Operative Adiposity and Synovial Fluid Inflammatory Biomarkers Provide a Predictive Model for Post-Operative Outcomes Following Total Joint Replacement Surgery in Osteoarthritis Patients.

Author

Nanus, Dominika E., Davis, Edward T., and Jones, Simon W.

Subjects
ARTIFICIAL joints, ANALGESIA, SYNOVIAL fluid, HEALTH status indicators, PREDICTION models, OSTEOARTHRITIS
Abstract

A proportion of osteoarthritis (OA) patients are unsatisfied with post-operative outcomes following total joint replacement surgery (TJR), with insufficient pain relief or poor functional improvement. Predicting those who will have poor outcomes would be beneficial for patients and clinicians. The aim of this study was to determine the relationship between baseline anthropometric data and the concentration of pre-operative serum and peri-operative synovial fluid (SF) cytokines and 7-month post-operative outcomes in a cohort of knee and hip OA patients. 160 OA patients were recruited who were scheduled for TJR. The concentration of 24 cytokines was measured in blood and SF by multiplex assay. EQ5D index health status was assessed pre-operatively and at 7 months post-operatively. 13% of patients were identified as non-responders based on EQ5D index. Compared to responders, non-responders were of higher body mass index (BMI), had greater waist and hip circumference, and had higher levels of SF leptin but lower levels of SF resistin (p < 0.05). Linear regression analysis found a significant but weak relationship between pre-operative body weight and post-operative response (ΔEQ5D index; r = 0.222, p = 0.049). The combination of body weight with SF amphiregulin and SF IL-6 provided an improved predictive model of post-operative response (r = 0.470, p = 0.035). [ABSTRACT FROM AUTHOR]

Published
2024
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16. Obesity defined molecular endotypes in the synovium of patients with osteoarthritis provides a rationale for therapeutic targeting of fibroblast subsets

Author

Wijesinghe, Susanne N., primary, Badoume, Amel, additional, Nanus, Dominika E., additional, Sharma‐Oates, Archana, additional, Farah, Hussein, additional, Certo, Michelangelo, additional, Alnajjar, Fawzeyah, additional, Davis, Edward T., additional, Mauro, Claudio, additional, Lindsay, Mark A., additional, and Jones, Simon W., additional

Published
2023
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20. The role of extracellular vesicle miRNAs and tRNAs in synovial fibroblast senescence

Author

Wijesinghe, Susanne N., primary, Anderson, James, additional, Brown, Thomas J., additional, Nanus, Dominika E., additional, Housmans, Bas, additional, Green, Jonathan A., additional, Hackl, Matthias, additional, Choi, Katie K., additional, Arkill, Kenton P., additional, Welting, Tim, additional, James, Victoria, additional, Jones, Simon W., additional, and Peffers, Mandy J., additional

Published
2022
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25. 11β-Hydroxysteroid Dehydrogenase Type 1 within Osteoclasts Mediates the Bone Protective Properties of Therapeutic Corticosteroids in Chronic Inflammation

Author

Fenton, Chloe G., primary, Crastin, Ana, additional, Martin, Claire S, additional, Suresh, Saicharan, additional, Montagna, Isabella, additional, Hussain, Bismah, additional, Naylor, Amy J., additional, Jones, Simon W., additional, Hansen, Morten S, additional, Gorvin, Caroline M., additional, Price, Maria, additional, Filer, Andrew, additional, Cooper, Mark S., additional, Lavery, Gareth G., additional, Raza, Karim, additional, and Hardy, Rowan S., additional

Published
2022
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27. Inflammation causes remodeling of mitochondrial cytochrome c oxidase mediated by the bifunctional gene C15orf48

Author

Clayton, Sally A., primary, Daley, Kalbinder K., additional, MacDonald, Lucy, additional, Fernandez-Vizarra, Erika, additional, Bottegoni, Giovanni, additional, O’Neil, John D., additional, Major, Triin, additional, Griffin, Daniel, additional, Zhuang, Qinqin, additional, Adewoye, Adeolu B., additional, Woolcock, Kieran, additional, Jones, Simon W., additional, Goodyear, Carl, additional, Elmesmari, Aziza, additional, Filer, Andrew, additional, Tennant, Daniel A., additional, Alivernini, Stefano, additional, Buckley, Christopher D., additional, Pitceathly, Robert D. S., additional, Kurowska-Stolarska, Mariola, additional, and Clark, Andrew R., additional

Published
2021
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31. Global Deletion of 11β-HSD1 Prevents Muscle Wasting Associated with Glucocorticoid Therapy in Polyarthritis

Author

Webster, Justine M., primary, Sagmeister, Michael S., additional, Fenton, Chloe G., additional, Seabright, Alex P., additional, Lai, Yu-Chiang, additional, Jones, Simon W., additional, Filer, Andrew, additional, Cooper, Mark S., additional, Lavery, Gareth G., additional, Raza, Karim, additional, Langen, Ramon, additional, and Hardy, Rowan S., additional

Published
2021
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36. Onboard Evolution of Human-Understandable Behaviour Trees for Robot Swarms

Author

Jones, Simon W and Jones, Simon W

Abstract

Swarm robotics, inspired by swarms in nature, has great potential. The resilience, scalability, robustness and redundancy of having many robots collectively perform tasks such as mapping, disaster recovery, pollution control, and cleaning make for a compelling vision. To achieve this, we need to design swarm robot systems to have a desired collective behaviour, but the design of controllers for the individual robots of a swarm such that this behaviour emerges from the interaction of the individual robots is difficult. Current solutions often use off-line automatic discovery by artificial evolution of robot controllers, which are then transferred into the swarm. This is problematic for two important reasons. Firstly, since there is the need for additional supporting infrastructure, both to evolve the new controllers and to communicate them to the swarm, the swarm is not self-sufficient. Secondly, the evolved controllers are often opaque and hard to understand, an important consideration for safety and explainability reasons. In this work we tackle both of these issues. We build a swarm of robots with very high computing performance using recently available mobile computation devices. This high performance allows us to move the evolutionary process, dependent on processing power for simulation, into the swarm. Because the computational power of the swarm grows with the size of the swarm, it is both autonomous and scalable. We use behaviour trees as the individual robot controller architecture. They are modular, hierarchical and human readable. By developing automatic tools to simplify large evolved trees, we can understand, explain, and even improve the evolved controllers. By moving the evolutionary process into the swarm, and by using understandable controllers, we make the swarm autonomous, scalable, and understandable, necessary steps towards their real-world deployment.

Published
2020

39. Protein‐carbohydrate ingestion alters Vps34 cellular localization independent of changes in kinase activity in human skeletal muscle

Author

Hodson, Nathan, primary, Dent, Jessica R., additional, Song, Zhe, additional, O'Leary, Mary F., additional, Nicholson, Thomas, additional, Jones, Simon W., additional, Murray, James T., additional, Jeromson, Stewart, additional, Hamilton, D. Lee, additional, Breen, Leigh, additional, and Philp, Andrew, additional

Published
2020
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41. circSamd4 represses myogenic transcriptional activity of PUR proteins

Author

Pandey, Poonam R, primary, Yang, Jen-Hao, primary, Tsitsipatis, Dimitrios, primary, Panda, Amaresh C, primary, Noh, Ji Heon, primary, Kim, Kyoung Mi, primary, Munk, Rachel, primary, Nicholson, Thomas, primary, Hanniford, Douglas, primary, Argibay, Diana, primary, Yang, Xiaoling, primary, Martindale, Jennifer L, primary, Chang, Ming-Wen, primary, Jones, Simon W, primary, Hernando, Eva, primary, Sen, Payel, primary, De, Supriyo, primary, Abdelmohsen, Kotb, primary, and Gorospe, Myriam, primary

Published
2020
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43. IL-6 secretion in osteoarthritis patients is mediated by chondrocyte-synovial fibroblast cross-talk and is enhanced by obesity

Author

Pearson, Mark J., Herndler-Brandstetter, Dietmar, Tariq, Mohammad A., Nicholson, Thomas A., Philp, Ashleigh M., Smith, Hannah L., Davis, Edward T., Jones, Simon W., and Lord, Janet M.

Subjects
Science, Medicine
Abstract

Increasing evidence suggests that inflammation plays a central role in driving joint pathology in certain patients with osteoarthritis (OA). Since many patients with OA are obese and increased adiposity is associated with chronic inflammation, we investigated whether obese patients with hip OA exhibited differential pro-inflammatory cytokine signalling and peripheral and local lymphocyte populations, compared to normal weight hip OA patients. No differences in either peripheral blood or local lymphocyte populations were found between obese and normal-weight hip OA patients. However, synovial fibroblasts from obese OA patients were found to secrete greater amounts of the pro-inflammatory cytokine IL-6, compared to those from normal-weight patients (p

Published
2017

44. Obese subcutaneous adipose tissue impairs human myogenesis, particularly in old skeletal muscle, via resistin-mediated activation of NF?B

Author

Wallace, Graham R., Davis, Edward T., Murphy, David P., Nicholson, Thomas, Bennett, Andrew J., Tsintzas, Kostas, and Jones, Simon W.

Subjects
Multidisciplinary
Abstract

Adiposity and adipokines are implicated in the loss of skeletal muscle mass with age and in several chronic disease states. The aim of this study was to determine the effects of human obese and lean subcutaneous adipose tissue secretome on myogenesis and metabolism in skeletal muscle cells derived from both young (18–30 yr) and elderly (>65 yr) individuals. Obese subcutaneous adipose tissue secretome impaired the myogenesis of old myoblasts but not young myoblasts. Resistin was prolifically secreted by obese subcutaneous adipose tissue and impaired myotube thickness and nuclear fusion by activation of the classical NFκB pathway. Depletion of resistin from obese adipose tissue secretome restored myogenesis. Inhibition of the classical NFκB pathway protected myoblasts from the detrimental effect of resistin on myogenesis. Resistin also promoted intramyocellular lipid accumulation in myotubes and altered myotube metabolism by enhancing fatty acid oxidation and increasing myotube respiration and ATP production. In conclusion, resistin derived from human obese subcutaneous adipose tissue impairs myogenesis of human skeletal muscle, particularly older muscle, and alters muscle metabolism in developing myotubes. These findings may have important implications for the maintenance of muscle mass in older people with chronic inflammatory conditions, or older people who are obese or overweight.

Published
2018

46. Metabolic dysfunction and inflammatory disease: the role of stromal fibroblasts.

Author

Farah, Hussein, Young, Stephen P., Mauro, Claudio, and Jones, Simon W.

Subjects
FIBROBLASTS, METABOLIC disorders, CHRONIC kidney failure, PULMONARY fibrosis, DISEASE progression, INFLAMMATION
Abstract

Mesenchymal stromal fibroblasts have emerged as key mediators of the inflammatory response and drivers of localised inflammation, in part through their interactions with resident and circulating immune cells at inflammatory sites. As such, they have been implicated in a number of chronic inflammatory conditions as well as in tumour progression through modifying the microenvironment. The connection between metabolic changes and altered phenotype of fibroblasts in inflammatory microenvironments has clear implications for our understanding of how chronic inflammation is regulated and for the development of new anti‐inflammatory therapeutics. In this review, we consider the evidence that changes to fibroblast metabolic state underpin chronic inflammation. We examine recent research on fibroblast metabolism in inflammatory microenvironments and consider their involvement in inflammation, providing insight into the role of fibroblasts and metabolism in mediating inflammatory disease progression namely cancer, arthritis and fibrotic disorders including chronic kidney disease, pulmonary fibrosis, heart disease and liver disease. [ABSTRACT FROM AUTHOR]

Published
2021
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47. The role of microRNAs in glucocorticoid action - literature review

Author

Clayton, Sally A., Jones, Simon W., Kurowska-Stolarska, Mariola, and Clark, Andrew R.

Subjects
hormones, hormone substitutes, and hormone antagonists
Abstract

Glucocorticoids (GCs) are steroids with profound anti-inflammatory and immunomodulatory activities. Synthetic GCs are widely used for managing chronic inflammatory and autoimmune conditions, as immunosuppressants in transplantation, and as antitumor agents in certain hematological cancers. However, prolonged GC exposure can cause adverse effects. A detailed understanding of GCs' mechanisms of action may enable harnessing of their desirable actions while minimizing harmful effects. Here, we review the impact on GC biology of microRNAs, small noncoding RNAs that posttranscriptionally regulate gene expression. Emerging evidence indicates that microRNAs modulate GC production by the adrenal glands and cells' responses to GCs. Furthermore, GCs influence cell proliferation, survival, and function at least in part by regulating microRNA expression. We propose that the beneficial effects of GCs may be enhanced through combination with reagents targeting specific microRNAs.

Published
2018

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