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2. Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes

Author

Baxter, Melissa, Withey, Sarah, Harrison, Sean, Segeritz, Charis-Patricia, Zhang, Fang, Atkinson-Dell, Rebecca, Rowe, Cliff, Gerrard, Dave T., Sison-Young, Rowena, Jenkins, Roz, Henry, Joanne, Berry, Andrew A., Mohamet, Lisa, Best, Marie, Fenwick, Stephen W., Malik, Hassan, Kitteringham, Neil R., Goldring, Chris E., Piper Hanley, Karen, Vallier, Ludovic, and Hanley, Neil A.

Published
2015
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6. Streptococcal toxic shock syndrome caused by Group G Streptococcus, United Kingdom

Author

Baxter, Melissa and Morgan, Marina

Subjects
Mortality -- United Kingdom, Toxic shock syndrome -- Care and treatment -- Health aspects, Infection -- Care and treatment -- Health aspects, Health
Abstract

Streptococcal toxic shock syndrome (STSS) was defined in 1993 as the isolation of group A Streptococcus (GAS) with parameters indicative of multiorgan dysfunction (1). STSS remains associated with high mortality [...]

Published
2017
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9. MicroRNA-122: A Novel Hepatocyte-Enriched in vitro Marker of Drug-Induced Cellular Toxicity

Author

Kia, Richard, Kelly, Lorna, Sison-Young, Rowena L. C., Zhang, Fang, Pridgeon, Chris S., Heslop, James A., Metcalfe, Pete, Kitteringham, Neil R., Baxter, Melissa, Harrison, Sean, Hanley, Neil A., Burke, Zoë D., Storm, Mike P., Welham, Melanie J., Tosh, David, Küppers-Munther, Barbara, Edsbagge, Josefina, Starkey Lewis, Philip J., Bonner, Frank, Harpur, Ernie, Sidaway, James, Bowes, Joanne, Fenwick, Stephen W., Malik, Hassan, Goldring, Chris E. P., and Park, B. Kevin

Published
2015
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16. PlantFAdb: a resource for exploring hundreds of plant fatty acid structures synthesized by thousands of plants and their phylogenetic relationships

Author

Ohlrogge, John, primary, Thrower, Nick, additional, Mhaske, Vandana, additional, Stymne, Sten, additional, Baxter, Melissa, additional, Yang, Weili, additional, Liu, Jinjie, additional, Shaw, Kathleen, additional, Shorrosh, Basil, additional, Zhang, Meng, additional, Wilkerson, Curtis, additional, and Matthäus, Bertrand, additional

Published
2018
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17. MicroRNA-122: A Novel Hepatocyte-Enriched in vitro Marker of Drug-Induced Cellular Toxicity

Author

Kia, Richard, Kelly, Lorna, Sison-Young, Rowena L C, Zhang, Fang, Pridgeon, Chris S, Heslop, James A, Metcalfe, Pete, Kitteringham, Neil R, Baxter, Melissa, Harrison, Sean, Hanley, Neil A, Burke, Zoë D, Storm, Mike P, Welham, Melanie J, Tosh, David, Küppers-Munther, Barbara, Edsbagge, Josefina, Starkey Lewis, Philip J, Bonner, Frank, Harpur, Ernie, Sidaway, James, Bowes, Joanne, Fenwick, Stephen W, Malik, Hassan, Goldring, Chris E P, and Park, B Kevin

Subjects
Genetic Markers, Male, bridging biomarker, Diclofenac, Time Factors, Cell Survival, Induced Pluripotent Stem Cells, MicroRNA-122 as A Biomarker of Liver Injury, Adenosine Triphosphate, cell-specific biomarker, Humans, Embryonic Stem Cells, Acetaminophen, Aged, microRNA, Dose-Response Relationship, Drug, L-Lactate Dehydrogenase, in vitro model, Cell Differentiation, Hep G2 Cells, Middle Aged, Culture Media, MicroRNAs, Hepatocytes, cytotoxicity, Female, Chemical and Drug Induced Liver Injury, drug-induced liver injury
Abstract

Emerging hepatic models for the study of drug-induced toxicity include pluripotent stem cell-derived hepatocyte-like cells (HLCs) and complex hepatocyte-non-parenchymal cellular coculture to mimic the complex multicellular interactions that recapitulate the niche environment in the human liver. However, a specific marker of hepatocyte perturbation, required to discriminate hepatocyte damage from non-specific cellular toxicity contributed by non-hepatocyte cell types or immature differentiated cells is currently lacking, as the cytotoxicity assays routinely used in in vitro toxicology research depend on intracellular molecules which are ubiquitously present in all eukaryotic cell types. In this study, we demonstrate that microRNA-122 (miR-122) detection in cell culture media can be used as a hepatocyte-enriched in vitro marker of drug-induced toxicity in homogeneous cultures of hepatic cells, and a cell-specific marker of toxicity of hepatic cells in heterogeneous cultures such as HLCs generated from various differentiation protocols and pluripotent stem cell lines, where conventional cytotoxicity assays using generic cellular markers may not be appropriate. We show that the sensitivity of the miR-122 cytotoxicity assay is similar to conventional assays that measure lactate dehydrogenase activity and intracellular adenosine triphosphate when applied in hepatic models with high levels of intracellular miR-122, and can be multiplexed with other assays. MiR-122 as a biomarker also has the potential to bridge results in in vitro experiments to in vivo animal models and human samples using the same assay, and to link findings from clinical studies in determining the relevance of in vitro models being developed for the study of drug-induced liver injury.

Published
2014

18. Point prevalence of penicillin allergy in hospital inpatients.

Author

Baxter, M., Bethune, C., Powell, R., Morgan, M., Baxter, Melissa, Bethune, Claire, Powell, Roy, and Morgan, Marina

Abstract

Ten percent of the general population believe themselves to be allergic to beta-lactams, many erroneously. Alternative, broader-spectrum antibiotics are associated with increased drug costs and colonization with resistant organisms. A point prevalence study of hospital inpatients determined the local reported rate of penicillin allergy, the nature of allergy described, evidence of antimicrobial resistance and antimicrobial regimens used as a result. Of the 583 patients assessed, the overall rate of penicillin allergy was 13.7% [95% confidence interval (CI) 11-17%]. Rash was the most commonly reported reaction (27.5%, 95% CI 18-39%). Details of the nature of the penicillin allergy were poorly recorded on drug charts. Significantly higher rates of meticillin-resistant Staphylococcus aureus were seen in the allergic cohort (P=0.0065) compared with those without a label of penicillin allergy; this was also seen for vancomycin-resistant enterococci, but this did not reach significance. This study demonstrates an increase in detection of resistant organisms in penicillin-allergic patients which may result from use of broader-spectrum antibiotics in this group. [ABSTRACT FROM AUTHOR]

Published
2020
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19. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines

Author

Mullish, Benjamin H., primary, Quraishi, Mohammed Nabil, additional, Segal, Jonathan P., additional, McCune, Victoria L., additional, Baxter, Melissa, additional, Marsden, Gemma L., additional, Moore, David, additional, Colville, Alaric, additional, Bhala, Neeraj, additional, Iqbal, Tariq H., additional, Settle, Christopher, additional, Kontkowski, Graziella, additional, Hart, Ailsa L., additional, Hawkey, Peter M., additional, Williams, Horace RT, additional, and Goldenberg, Simon D., additional

Published
2018
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20. The use of faecal microbiota transplant as treatment for recurrent or refractoryClostridium difficileinfection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines

Author

Mullish, Benjamin H, primary, Quraishi, Mohammed Nabil, additional, Segal, Jonathan P, additional, McCune, Victoria L, additional, Baxter, Melissa, additional, Marsden, Gemma L, additional, Moore, David J, additional, Colville, Alaric, additional, Bhala, Neeraj, additional, Iqbal, Tariq H, additional, Settle, Christopher, additional, Kontkowski, Graziella, additional, Hart, Ailsa L, additional, Hawkey, Peter M, additional, Goldenberg, Simon D, additional, and Williams, Horace R T, additional

Published
2018
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21. Integrin-Associated Focal Adhesion Kinase Protects Human Embryonic Stem Cells from Apoptosis, Detachment, and Differentiation

Author

Vitillo, Loriana, Baxter, Melissa, Iskender, Banu, Whiting, Paul, and Kimber, Susan

Subjects
Human Embryonic Stem Cells, Apoptosis, Report, Cell Adhesion, Humans, lcsh:QH301-705.5, reproductive and urinary physiology, Cell Aggregation, Cell Nucleus, lcsh:R5-920, Integrin beta1, Cell Differentiation, Proto-Oncogene Proteins c-mdm2, equipment and supplies, Anoikis, Extracellular Matrix, lcsh:Biology (General), Cytoprotection, Caspases, Focal Adhesion Protein-Tyrosine Kinases, embryonic structures, biological phenomena, cell phenomena, and immunity, Tumor Suppressor Protein p53, lcsh:Medicine (General), Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract

Summary Human embryonic stem cells (hESCs) can be maintained in a fully defined niche on extracellular matrix substrates, to which they attach through integrin receptors. However, the underlying integrin signaling mechanisms, and their contribution to hESC behavior, are largely unknown. Here, we show that focal adhesion kinase (FAK) transduces integrin activation and supports hESC survival, substrate adhesion, and maintenance of the undifferentiated state. After inhibiting FAK kinase activity we show that hESCs undergo cell detachment-dependent apoptosis or differentiation. We also report deactivation of FAK downstream targets, AKT and MDM2, and upregulation of p53, all key players in hESC regulatory networks. Loss of integrin activity or FAK also induces cell aggregation, revealing a role in the cell-cell interactions of hESCs. This study provides insight into the integrin signaling cascade activated in hESCs and reveals in FAK a key player in the maintenance of hESC survival and undifferentiated state., Graphical Abstract, Highlights • Integrin activation in hESCs is transduced by FAK kinase • FAK protects hESCs from anoikis upstream of the AKT/MDM2/p53 cascade • FAK is required for maintenance of low contractility and attachment of hESCs • Prolonged inhibition of FAK induces non-biased hESCs differentiation, In this research, Kimber and colleagues reveal the critical role of the extracellular matrix-dependent signaling in controlling human embryonic stem cell behavior. Such cues are principally mediated by focal adhesion kinase signaling, which links to intrinsic pluripotent stem cell regulators, such as AKT and p53, preventing detachment, apoptosis, and differentiation.

Published
2016

22. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

Author

Mullish, Benjamin H., Quraishi, Mohammed Nabil, Segal, Jonathan P., McCune, Victoria L., Baxter, Melissa, Marsden, Gemma L., Moore, David J., Colville, Alaric, Bhala, Neeraj, Iqbal, Tariq H., Settle, Christopher, Kontkowski, Graziella, Hart, Ailsa L., Hawkey, Peter M., Goldenberg, Simon D., and Williams, Horace R. T.

Subjects
GUIDELINES, FECAL microbiota transplantation, CLOSTRIDIOIDES difficile, EVIDENCE-based medicine, GASTROENTEROLOGY, MICROBIOLOGY, THERAPEUTICS
Published
2018
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25. Concise Review: Workshop Review: Understanding and Assessing the Risks of Stem Cell-Based Therapies

Author

Heslop, James A., primary, Hammond, Thomas G., additional, Santeramo, Ilaria, additional, Tort Piella, Agnès, additional, Hopp, Isabel, additional, Zhou, Jing, additional, Baty, Roua, additional, Graziano, Enrique I., additional, Proto Marco, Bernabé, additional, Caron, Alexis, additional, Sköld, Patrik, additional, Andrews, Peter W., additional, Baxter, Melissa A., additional, Hay, David C., additional, Hamdam, Junnat, additional, Sharpe, Michaela E., additional, Patel, Sara, additional, Jones, David R., additional, Reinhardt, Jens, additional, Danen, Erik H.J., additional, Ben-David, Uri, additional, Stacey, Glyn, additional, Björquist, Petter, additional, Piner, Jacqueline, additional, Mills, John, additional, Rowe, Cliff, additional, Pellegrini, Giovanni, additional, Sethu, Swaminathan, additional, Antoine, Daniel J., additional, Cross, Michael J., additional, Murray, Patricia, additional, Williams, Dominic P., additional, Kitteringham, Neil R., additional, Goldring, Chris E.P., additional, and Park, B. Kevin, additional

Published
2015
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26. The Increase in Maternal Expression of axin1 and axin2 Contribute to the Zebrafish Mutant Ichabod Ventralized Phenotype

Author

Valenti, Fabio, primary, Ibetti, Jessica, additional, Komiya, Yuko, additional, Baxter, Melissa, additional, Lucchese, Anna Maria, additional, Derstine, Lauren, additional, Covaciu, Claudia, additional, Rizzo, Valeria, additional, Vento, Renza, additional, Russo, Giuseppe, additional, Macaluso, Marcella, additional, Cotelli, Franco, additional, Castiglia, Daniele, additional, Gottardi, Cara J., additional, Habas, Raymond, additional, Giordano, Antonio, additional, and Bellipanni, Gianfranco, additional

Published
2015
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27. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficileinfection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines

Author

Mullish, Benjamin H, Quraishi, Mohammed Nabil, Segal, Jonathan P, McCune, Victoria L, Baxter, Melissa, Marsden, Gemma L, Moore, David J, Colville, Alaric, Bhala, Neeraj, Iqbal, Tariq H, Settle, Christopher, Kontkowski, Graziella, Hart, Ailsa L, Hawkey, Peter M, Goldenberg, Simon D, and Williams, Horace R T

Abstract

Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory Clostridium difficileinfection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.

Published
2018
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30. Comparative Proteomic Analysis of Supportive and Unsupportive Extracellular Matrix Substrates for Human Embryonic Stem Cell Maintenance

Author

Soteriou, Despina, primary, Iskender, Banu, additional, Byron, Adam, additional, Humphries, Jonathan D., additional, Borg-Bartolo, Simon, additional, Haddock, Marie-Claire, additional, Baxter, Melissa A., additional, Knight, David, additional, Humphries, Martin J., additional, and Kimber, Susan J., additional

Published
2013
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40. Retrovirally mediated correction of bone marrow–derived mesenchymal stem cells from patients with mucopolysaccharidosis type I

Author

Baxter, Melissa A., primary, Wynn, Robert F., additional, Deakin, Jonathan A., additional, Bellantuono, Ilaria, additional, Edington, Kirsten G., additional, Cooper, Alan, additional, Besley, Guy T. N., additional, Church, Heather J., additional, Wraith, J. Ed, additional, Carr, Trevor F., additional, and Fairbairn, Leslie J., additional

Published
2002
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41. Can executive search firms help propel women into the boardroom?

Author

Baxter, Melissa

Subjects
EMPLOYEE recruitment, CONSULTING firms
Abstract

A letter to the editor is presented in response to the article about the lower ratio of women working in recruitment consultancy firm boards as compared to men in the March 2014 issue.

Published
2014

43. Serotonin neuromodulation directs optic nerve regeneration.

Author

Saied-Santiago K, Baxter M, Mathiaparanam J, and Granato M

Abstract

Optic nerve (ON) regeneration in mammalian systems is limited by an overshadowing dominance of inhibitory factors. This has severely hampered the identification of pro-regenerative pathways. Here, we take advantage of the regenerative capacity of larval zebrafish to identify pathways that promote ON regeneration. From a small molecule screen, we identified modulators of serotonin (5-HT) signaling that inhibit ON regeneration. We find several serotonin type-1 receptor genes are expressed in RGC neurons during regeneration and that inhibiting 5-HT1 receptors or components of the 5-HT pathway selectively impedes ON regeneration. We show that 5-HT1 receptor signaling is dispensable during ON development yet is critical for regenerating axons to emerge from the injury site. Blocking 5-HT receptors once ON axons have crossed the chiasm does not inhibit regeneration, suggesting a selective role for 5-HT receptor signaling early during ON regeneration. Finally, we show that agonist-mediated activation of 5-HT1 receptors leads to enhanced and ectopic axonal regrowth. Combined, our results provide evidence for mechanisms through which serotonin-dependent neuromodulation directs ON regeneration in vivo., Competing Interests: Competing Interest The authors have declared no competing interest.

Published
2024
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44. Assaying Optic Nerve Regeneration in Larval Zebrafish.

Author

Harvey BM, Baxter M, and Granato M

Subjects
Animals, Biological Assay, Central Nervous System, Larva, Nerve Regeneration, Zebrafish, Axons
Abstract

Zebrafish have a remarkable capacity for spontaneously regenerating their central nervous system. Larval zebrafish are optically transparent and therefore are widely used to dynamically visualize cellular processes in vivo, such as nerve regeneration. Regeneration of retinal ganglion cell (RGC) axons within the optic nerve has been previously studied in adult zebrafish. In contrast, assays of optic nerve regeneration have previously not been established in larval zebrafish. In order to take advantage of the imaging capabilities in the larval zebrafish model, we recently developed an assay to physically transect RGC axons and monitor optic nerve regeneration in larval zebrafish. We found that RGC axons rapidly and robustly regrow to the optic tectum. Here, we describe the methods for performing the optic nerve transections, as well as methods for visualizing RGC regeneration in larval zebrafish., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2023
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