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39 results on '"Geary, Bethany"'

1. PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons

Author

Milioto, Carmelo, Carcolé, Mireia, Giblin, Ashling, Coneys, Rachel, Attrebi, Olivia, Ahmed, Mhoriam, Harris, Samuel S., Lee, Byung Il, Yang, Mengke, Ellingford, Robert A., Nirujogi, Raja S., Biggs, Daniel, Salomonsson, Sally, Zanovello, Matteo, de Oliveira, Paula, Katona, Eszter, Glaria, Idoia, Mikheenko, Alla, Geary, Bethany, Udine, Evan, Vaizoglu, Deniz, Anoar, Sharifah, Jotangiya, Khrisha, Crowley, Gerard, Smeeth, Demelza M., Adams, Mirjam L., Niccoli, Teresa, Rademakers, Rosa, van Blitterswijk, Marka, Devoy, Anny, Hong, Soyon, Partridge, Linda, Coyne, Alyssa N., Fratta, Pietro, Alessi, Dario R., Davies, Ben, Busche, Marc Aurel, Greensmith, Linda, Fisher, Elizabeth M. C., and Isaacs, Adrian M.

Published
2024
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6. Determining the rates of protein synthesis in the zebrafish heart in response to chronic unpredictable stress

Author

Geary, Bethany, Doherty, Mary, and Whitfield, Phil

Subjects
597, Zebra danio, Heart, Proteins, Proteomics
Abstract

The proteome is in constant flux and therefore it is important to understand the contribution of protein dynamics to the function of an organism. The zebrafish (Danio rerio) is a recognised model organism that is widely used to investigate physiological processes. The focus of this thesis was to develop a method to calculate the rates of synthesis of heart proteins of zebrafish on a proteome-wide scale. The initial stage of the project involved the optimisation of a method to characterise the protein complement of individual zebrafish hearts. It was concluded that for the rapid screening of proteins 1-dimensional gel electrophoresis in conjunction with high resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) was the most appropriate experimental approach. In order to determine the rates of protein synthesis, zebrafish were administered with a stable isotope-labelled amino acid ([2H7] L-leucine) via the diet and its incorporation into heart proteins was monitored over an 8 week time course. Using this method it was possible to calculate the synthesis rates of over 600 proteins. The experimental strategy was then applied to define the changes in protein synthesis rates in hearts from zebrafish that were subjected to chronic unpredictable stress (CUS). A variety of stressors on zebrafish comprising air emersion, net chasing or net confinement were employed to model CUS. These approaches were validated by a parallel behavioural analysis. The results revealed that glycolytic and gluconeogenic enzymes as well as proteins involved in hypoxia had significantly altered synthesis rates in response to induced stress. This thesis describes for the first time a proteomics approach to determine the rates of synthesis of individual proteins in the zebrafish and its application to investigate the effects of stress conditions on heart proteome dynamics.

Published
2016

9. EVI1 phosphorylation at S436 regulates interactions with CtBP1 and DNMT3A and promotes self-renewal

Author

Paredes, Roberto, Kelly, James R., Geary, Bethany, Almarzouq, Batool, Schneider, Marion, Pearson, Stella, Narayanan, Prakrithi, Williamson, Andrew, Lovell, Simon C., Wiseman, Daniel H., Chadwick, John A., Jones, Nigel J., Kustikova, Olga, Schambach, Axel, Garner, Terence, Amaral, Fabio M. R., Pierce, Andrew, Stevens, Adam, Somervaille, Tim C. P., Whetton, Anthony D., and Meyer, Stefan

Published
2020
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10. PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature inC9orf72ALS/FTD neurons

Author

Milioto, Carmelo, primary, Carcolé, Mireia, additional, Giblin, Ashling, additional, Coneys, Rachel, additional, Attrebi, Olivia, additional, Ahmed, Mhoriam, additional, Harris, Samuel S., additional, Lee, Byung Il, additional, Yang, Mengke, additional, Nirujogi, Raja S., additional, Biggs, Daniel, additional, Salomonsson, Sally, additional, Zanovello, Matteo, additional, Oliveira, Paula De, additional, Katona, Eszter, additional, Glaria, Idoia, additional, Mikheenko, Alla, additional, Geary, Bethany, additional, Udine, Evan, additional, Vaizoglu, Deniz, additional, Rademakers, Rosa, additional, van Blitterswijk, Marka, additional, Devoy, Anny, additional, Hong, Soyon, additional, Partridge, Linda, additional, Fratta, Pietro, additional, Alessi, Dario R., additional, Davies, Ben, additional, Busche, Marc Aurel, additional, Greensmith, Linda, additional, Fisher, Elizabeth M.C., additional, and Isaacs, Adrian M., additional

Published
2023
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11. A Novel Blood Proteomic Signature for Prostate Cancer

Author

Muazzam, Ammara, primary, Spick, Matt, additional, Cexus, Olivier N. F., additional, Geary, Bethany, additional, Azhar, Fowz, additional, Pandha, Hardev, additional, Michael, Agnieszka, additional, Reed, Rachel, additional, Lennon, Sarah, additional, Gethings, Lee A., additional, Plumb, Robert S., additional, Whetton, Anthony D., additional, Geifman, Nophar, additional, and Townsend, Paul A., additional

Published
2023
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12. PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72ALS/FTD neurons

Author

Milioto, Carmelo, Carcolé, Mireia, Giblin, Ashling, Coneys, Rachel, Attrebi, Olivia, Ahmed, Mhoriam, Harris, Samuel S., Lee, Byung Il, Yang, Mengke, Ellingford, Robert A., Nirujogi, Raja S., Biggs, Daniel, Salomonsson, Sally, Zanovello, Matteo, de Oliveira, Paula, Katona, Eszter, Glaria, Idoia, Mikheenko, Alla, Geary, Bethany, Udine, Evan, Vaizoglu, Deniz, Anoar, Sharifah, Jotangiya, Khrisha, Crowley, Gerard, Smeeth, Demelza M., Adams, Mirjam L., Niccoli, Teresa, Rademakers, Rosa, van Blitterswijk, Marka, Devoy, Anny, Hong, Soyon, Partridge, Linda, Coyne, Alyssa N., Fratta, Pietro, Alessi, Dario R., Davies, Ben, Busche, Marc Aurel, Greensmith, Linda, Fisher, Elizabeth M. C., and Isaacs, Adrian M.

Abstract

Dipeptide repeat proteins are a major pathogenic feature of C9orf72amyotrophic lateral sclerosis (C9ALS)/frontotemporal dementia (FTD) pathology, but their physiological impact has yet to be fully determined. Here we generated C9orf72dipeptide repeat knock-in mouse models characterized by expression of 400 codon-optimized polyGR or polyPR repeats, and heterozygous C9orf72reduction. (GR)400 and (PR)400 knock-in mice recapitulate key features of C9ALS/FTD, including cortical neuronal hyperexcitability, age-dependent spinal motor neuron loss and progressive motor dysfunction. Quantitative proteomics revealed an increase in extracellular matrix (ECM) proteins in (GR)400 and (PR)400 spinal cord, with the collagen COL6A1 the most increased protein. TGF-β1 was one of the top predicted regulators of this ECM signature and polyGR expression in human induced pluripotent stem cell neurons was sufficient to induce TGF-β1 followed by COL6A1. Knockdown of TGF-β1 or COL6A1 orthologues in polyGR model Drosophilaexacerbated neurodegeneration, while expression of TGF-β1 or COL6A1 in induced pluripotent stem cell-derived motor neurons of patients with C9ALS/FTD protected against glutamate-induced cell death. Altogether, our findings reveal a neuroprotective and conserved ECM signature in C9ALS/FTD.

Published
2024
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13. Identification of curaxin as a potential new therapeutic for JAK2 V617F mutant patients.

Author

Pearson, Stella, Blance, Rognvald, Yan, Fei, Hsieh, Ya-Ching, Geary, Bethany, Amaral, Fabio M. R., Somervaille, Tim C. P., Kirschner, Kristina, Whetton, Anthony D., and Pierce, Andrew

Subjects
MYELOPROLIFERATIVE neoplasms, PROGENITOR cells, HEART cells, MYELOFIBROSIS, DRUG repositioning
Abstract

Myelofibrosis is a myeloproliferative neoplasm (MPN) which typically results in reduced length and quality of life due to systemic symptoms and blood count changes arising from fibrotic changes in the bone marrow. While the JAK2 inhibitor ruxolitinib provides some clinical benefit, there remains a substantial unmet need for novel targeted therapies to better modify the disease process or eradicate the cells at the heart of myelofibrosis pathology. Repurposing drugs bypasses many of the hurdles present in drug development, such as toxicity and pharmacodynamic profiling. To this end we undertook a re-analysis of our pre-existing proteomic data sets to identify perturbed biochemical pathways and their associated drugs/inhibitors to potentially target the cells driving myelofibrosis. This approach identified CBL0137 as a candidate for targeting Jak2 mutation-driven malignancies. CBL0137 is a drug derived from curaxin targeting the Facilitates Chromatin Transcription (FACT) complex. It is reported to trap the FACT complex on chromatin thereby activating p53 and inhibiting NF-kB activity. We therefore assessed the activity of CBL0137 in primary patient samples and murine models of Jak2-mutated MPN and found it preferentially targets CD34+ stem and progenitor cells from myelofibrosis patients by comparison with healthy control cells. Further we investigate its mechanism of action in primary haemopoietic progenitor cells and demonstrate its ability to reduce splenomegaly and reticulocyte number in a transgenic murine model of myeloproliferative neoplasms. [ABSTRACT FROM AUTHOR]

Published
2023
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14. THOC5 Complexes With DDX5, DDX17 and CDK12 Are Essential in Primitive Cell Survival to Regulate R Loop Structures and Transcription Elongation Rate

Author

Polenkowski, Mareike, primary, Allister, Aldrige Bernardus, additional, de Lara, Sebastian Burbano, additional, Pierce, Andrew, additional, Geary, Bethany, additional, El Bounkari, Omar, additional, Wiehlmann, Lutz, additional, Hoffmann, Andrea, additional, Whetton, Anthony D., additional, Tamura, Teruko, additional, and Tran, Doan Duy Hai, additional

Published
2022
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19. Changes in the Proteome Profile of People Achieving Remission of Type 2 Diabetes after Bariatric Surgery

Author

Iqbal, Zohaib, primary, Fachim, Helene A., additional, Gibson, J. Martin, additional, Baricevic-Jones, Ivona, additional, Campbell, Amy E., additional, Geary, Bethany, additional, Donn, Rachelle P., additional, Hamarashid, Dashne, additional, Syed, Akheel, additional, Whetton, Anthony D., additional, Soran, Handrean, additional, and Heald, Adrian H., additional

Published
2021
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24. Analysis of the brain palmitoyl-proteome using both acyl-biotin exchange and acyl-resin-assisted capture methods

Author

Edmonds, Matthew J., Geary, Bethany, Doherty, Mary K., and Morgan, Alan

Subjects
Proteomics, Proteome, Acylation, Lipoylation, Science, Palmitic Acid, technology, industry, and agriculture, Biotin, Brain, Article, Mass Spectrometry, Rats, Resins, Synthetic, Animals, Medicine, lipids (amino acids, peptides, and proteins)
Abstract

Palmitoylation is a reversible post-translational protein modification in which palmitic acid is added to cysteine residues, allowing association with different cellular membranes and subdomains. Recently, techniques have been developed to identify palmitoylation on a proteome-wide scale in order to reveal the full cellular complement of palmitoylated proteins. However, in the studies reported to date, there is considerable variation between the sets of identified palmitoyl-proteins and so there remains some uncertainty over what constitutes the definitive complement of palmitoylated proteins even in well-studied tissues such as brain. To address this issue, we used both acyl-biotin exchange and acyl-resin-assisted capture approaches using rat brain as a common protein source. The palmitoyl-proteins identified from each method by mass spectrometry were then compared with each other and previously published studies. There was generally good agreement between the two methods, although many identifications were unique to one method, indicating that at least some of the variability in published palmitoyl proteomes is due to methodological differences. By combining our new data with previous publications using mammalian cells/tissues, we propose a high confidence set of bona fide palmitoylated proteins in brain and provide a resource to help researchers prioritise candidate palmitoyl-proteins for investigation.

Published
2017

25. Additional file 1 of Application of SWATH mass spectrometry in the identification of circulating proteins does not predict future weight gain in early psychosis

Author

Heald, Adrian, Azadbakht, Narges, Geary, Bethany, Conen, Silke, Fachim, Helene, Lee, Dave Chi Hoo, Nophar Geifman, Farman, Sanam, Howes, Oliver, Whetton, Anthony, and Deakin, Bill

Abstract

Additional file 1: Figure S1. Heatmap of BeneMin baseline proteomics data for male vs female participants. Heatmap of BeneMin baseline proteomics data for (a) 60 male participants and (b) 23 female participants in all four weight change categories. The dendrograms above and to the left side of the heatmap correspond to the results of hierarchical clustering analysis (HCA) for samples and proteins, respectively (the distance matrix of which was computed using the Euclidean method and clustering using the complete linkage method). The bars below the top dendrogram are coloured according to the type of treatment (minocycline vs placebo) and the category of weight change from baseline measured at follow-up. Heatmap was plotted using the pheatmap R package with row scaling.

Published
2020
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26. Additional file 3 of Application of SWATH mass spectrometry in the identification of circulating proteins does not predict future weight gain in early psychosis

Author

Heald, Adrian, Azadbakht, Narges, Geary, Bethany, Conen, Silke, Fachim, Helene, Lee, Dave Chi Hoo, Nophar Geifman, Farman, Sanam, Howes, Oliver, Whetton, Anthony, and Deakin, Bill

Abstract

Additional file 3: Figure S3. Principal component analysis (PCA) of BeneMin baseline proteomics data for male vs female participants. Principal component analysis (PCA) of BeneMin baseline proteomics data for (a) 60 male participants and (b) 23 female participants in all four weight change categories. Results were illustrated using the ggbiplot R package and are coloured according to the category of weight change from baseline measured at follow-up.

Published
2020
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27. Additional file 4 of Application of SWATH mass spectrometry in the identification of circulating proteins does not predict future weight gain in early psychosis

Author

Heald, Adrian, Azadbakht, Narges, Geary, Bethany, Conen, Silke, Fachim, Helene, Lee, Dave Chi Hoo, Nophar Geifman, Farman, Sanam, Howes, Oliver, Whetton, Anthony, and Deakin, Bill

Abstract

Additional file 4: Figure S4. Principal component analysis (PCA) of BeneMin baseline proteomics data for minocycline vs placebo treatment groups. Principal component analysis (PCA) of BeneMin baseline proteomics data for (a) 39 participants treated with minocycline and (b) 44 participants treated with placebo as adjunctive treatment, in all four weight change categories. Results were illustrated using the ggbiplot R package and are coloured according to the category of weight change from baseline measured at follow-up.

Published
2020
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28. Additional file 2 of Application of SWATH mass spectrometry in the identification of circulating proteins does not predict future weight gain in early psychosis

Author

Heald, Adrian, Azadbakht, Narges, Geary, Bethany, Conen, Silke, Fachim, Helene, Lee, Dave Chi Hoo, Nophar Geifman, Farman, Sanam, Howes, Oliver, Whetton, Anthony, and Deakin, Bill

Abstract

Additional file 2: Figure S2. Heatmap of BeneMin baseline proteomics data for minocycline vs placebo treatment groups. Heatmap of BeneMin baseline proteomics data for (a) 39 participants treated with minocycline and (b) 44 participants treated with placebo as adjunctive treatment, in all four weight change categories. The dendrograms above and to the left side of the heatmap correspond to the results of hierarchical clustering analysis (HCA) for samples and proteins, respectively (the distance matrix of which was computed using the Euclidean method and clustering using the complete linkage method). The bars below the top dendrogram are coloured according to gender and the category of weight change from baseline measured at follow-up. Heatmap was plotted using the pheatmap R package with row scaling.

Published
2020
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29. The use of missing values in proteomic data-independent acquisition mass spectrometry to enable disease activity discrimination

Author

McGurk, Kathryn A, primary, Dagliati, Arianna, primary, Chiasserini, Davide, primary, Lee, Dave, primary, Plant, Darren, primary, Baricevic-Jones, Ivona, primary, Kelsall, Janet, primary, Eineman, Rachael, primary, Reed, Rachel, primary, Geary, Bethany, primary, Unwin, Richard D, primary, Nicolaou, Anna, primary, Keavney, Bernard D, primary, Barton, Anne, primary, Whetton, Anthony D, primary, and Geifman, Nophar, primary

Published
2019
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31. Identification of a Biomarker Panel for Early Detection of Lung Cancer Patients

Author

Geary, Bethany, primary, Walker, Michael J., additional, Snow, Joseph T., additional, Lee, David C. H., additional, Pernemalm, Maria, additional, Maleki-Dizaji, Saeedeh, additional, Azadbakht, Narges, additional, Apostolidou, Sophia, additional, Barnes, Julie, additional, Krysiak, Piotr, additional, Shah, Rajesh, additional, Booton, Richard, additional, Dive, Caroline, additional, Crosbie, Philip A., additional, and Whetton, Anthony D., additional

Published
2019
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33. Data Independent Acquisition Mass Spectrometry Can Identify Circulating Proteins That Predict Future Weight Loss with a Diet and Exercise Programme

Author

Malipatil, Nagaraj, primary, Fachim, Helene A., additional, Siddals, Kirk, additional, Geary, Bethany, additional, Wark, Gwen, additional, Porter, Nick, additional, Anderson, Simon, additional, Donn, Rachelle, additional, Harvie, Michelle, additional, Whetton, Anthony D., additional, Gibson, Martin J., additional, and Heald, Adrian, additional

Published
2019
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34. The use of missing values in proteomic data-independent acquisition mass spectrometry to enable disease activity discrimination.

Author

McGurk, Kathryn A, Dagliati, Arianna, Chiasserini, Davide, Lee, Dave, Plant, Darren, Baricevic-Jones, Ivona, Kelsall, Janet, Eineman, Rachael, Reed, Rachel, Geary, Bethany, Unwin, Richard D, Nicolaou, Anna, Keavney, Bernard D, Barton, Anne, Whetton, Anthony D, and Geifman, Nophar

Subjects
PROTEOMICS, LONGITUDINAL method, FORECASTING, MACHINE learning, MASS spectrometry
Abstract

Motivation Data-independent acquisition mass spectrometry allows for comprehensive peptide detection and relative quantification than standard data-dependent approaches. While less prone to missing values, these still exist. Current approaches for handling the so-called missingness have challenges. We hypothesized that non-random missingness is a useful biological measure and demonstrate the importance of analysing missingness for proteomic discovery within a longitudinal study of disease activity. Results The magnitude of missingness did not correlate with mean peptide concentration. The magnitude of missingness for each protein strongly correlated between collection time points (baseline, 3 months, 6 months; R  = 0.95–0.97, confidence interval = 0.94–0.97) indicating little time-dependent effect. This allowed for the identification of proteins with outlier levels of missingness that differentiate between the patient groups characterized by different patterns of disease activity. The association of these proteins with disease activity was confirmed by machine learning techniques. Our novel approach complements analyses on complete observations and other missing value strategies in biomarker prediction of disease activity. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Published
2020
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36. Identification and Verification of a Biomarker Panel for Early Diagnosis of Lung Cancer Patients

Author

Geary, Bethany, primary, Walker, Michael J., additional, Snow, Joseph T., additional, Lee, David C. H., additional, Pernemalm, Maria, additional, Maleki-Dizaji, Saeedeh, additional, Azadbakht, Narges, additional, Apostolidou, Sophia, additional, Barnes, Julie, additional, Krysiak, Piotr, additional, Shah, Rajesh, additional, Booton, Richard, additional, Dive, Caroline, additional, Crosbie, Philip A., additional, and Whetton, Anthony, additional

Published
2018
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