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3. STING activation in TET2-mutated hematopoietic stem/progenitor cells contributes to the increased self-renewal and neoplastic transformation

Author

Xie, Jiaying, Sheng, Mengyao, Rong, Shaoqin, Zhou, Dan, Wang, Chao, Wu, Wanling, Huang, Jingru, Sun, Yue, Wang, Yin, Chen, Pingyue, Wu, Yushuang, Wang, Yuanxian, Wang, Lan, Zhou, Bo O., Huang, Xinxin, Walsh, Colum P., Bohlander, Stefan K., Huang, Jian, Wang, Xiaoqin, Xu, Guo-Liang, Gao, Hai, and Shi, Yuheng

Published
2023
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4. Alterations in the steroid hormone receptor co-chaperone FKBPL are associated with male infertility: a case-control study

Author

Barton David, Hirst David, Downes CS, Campbell Alan, Scullion Catherine, Ward Michael, Kaluskar Soniya, Crowe Hannah, Miyagawa Yasushi, De León Johanny M, McDaid Jennifer R, Lagan Kevin, Hiripi Laszlo, Sunnotel Olaf, Mocanu Edgar, Tsujimura Akira, Cox Marc B, Robson Tracy, and Walsh Colum P

Subjects
Gynecology and obstetrics, RG1-991, Reproduction, QH471-489
Abstract

Abstract Background Male infertility is a common cause of reproductive failure in humans. In mice, targeted deletions of the genes coding for FKBP6 or FKBP52, members of the FK506 binding protein family, can result in male infertility. In the case of FKBP52, this reflects an important role in potentiating Androgen Receptor (AR) signalling in the prostate and accessory glands, but not the testis. In infertile men, no mutations of FKBP52 or FKBP6 have been found so far, but the gene for FKBP-like (FKBPL) maps to chromosome 6p21.3, an area linked to azoospermia in a group of Japanese patients. Methods To determine whether mutations in FKBPL could contribute to the azoospermic phenotype, we examined expression in mouse and human tissues by RNA array blot, RT-PCR and immunohistochemistry and sequenced the complete gene from two azoospermic patient cohorts and matching control groups. FKBPL-AR interaction was assayed using reporter constructs in vitro. Results FKBPL is strongly expressed in mouse testis, with expression upregulated at puberty. The protein is expressed in human testis in a pattern similar to FKBP52 and also enhanced AR transcriptional activity in reporter assays. We examined sixty patients from the Japanese patient group and found one inactivating mutation and one coding change, as well as a number of non-coding changes, all absent in fifty-six controls. A second, Irish patient cohort of thirty showed another two coding changes not present in thirty proven fertile controls. Conclusions Our results describe the first alterations in the gene for FKBPL in azoospermic patients and indicate a potential role in AR-mediated signalling in the testis.

Published
2010
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5. Reactivation of a silenced H19 gene in human rhabdomyosarcoma by demethylation of DNA but not by histone hyperacetylation

Author

Bestor Timothy H, Tycko Benjamin, Lynch Catherine A, and Walsh Colum P

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The active copy of the imprinted gene H19 is turned off by inappropriate methylation in several pediatric tumors including Wilms' Tumour and embryonal rhabdomyosarcoma. H19 controls in cis the linked Insulin-like Growth Factor 2 (IGF2) gene, encoding an important growth factor. Recent work has suggested that methylation of a gene may lead to deacetylation of its associated histones and that silenced genes can be reactivated by increasing histone acetylation levels. Results Treatment of a rhabdomyosarcoma cell line which has a silent, methylated H19 gene with histone deacetylase (HDAC) inhibitors under conditions which gave maximal hyperacetylation of histone 4, both globally and at the H19 gene itself could not reactivate H19 or affect the active Insulin-like Growth Factor 2 (IGF2) gene, but caused clear up-regulation of the Tissue-type Plasminogen Activator (TPA) gene, a non-imprinted gene known to respond to changes in histone acetylation. In contrast, mild treatment of the cells with the methylation inhibitor 5-AzaC-2'-deoxycytidine (AzaC) on its own was able to reactivate H19. Combining AzaC treatment with HDAC inhibitors gave a reduced rather than enhanced reactivation. These findings were confirmed in mouse primary liver and kidney explants which maintain normal imprinting, where we also found that the silent Igf2 gene could not be reactivated by HDAC inhibitors. Conclusion These results suggest that DNA methylation rather than histone acetylation is the primary determinant of silencing of H19 in rhabdomyosarcoma.

Published
2002
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15. BS43 Hyperglycaemia induces epigenetic dysregulation in human endothelial colony-forming cells which limits their vasoreparative and therapeutic potential

Author

O’Neill, Karla M, primary, Madishetti, Vinuthna Vani, additional, Edgar, Kevin, additional, Pedrini, Edoardo, additional, McLoughlin, Kiran J, additional, Pun, Shun Hay, additional, O’Neill, Christina, additional, Guduric-Fuchs, Jasenka, additional, Medina, Reinhold J, additional, Jurkowski, Tomasz, additional, Walsh, Colum P, additional, and Grieve, David J, additional

Published
2024
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16. Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial

Author

Caffrey, Aoife, McNulty, Helene, Rollins, Mark, Prasad, Girijesh, Gaur, Pramod, Talcott, Joel B., Witton, Caroline, Cassidy, Tony, Marshall, Barry, Dornan, James, Moore, Adrian J., Ward, Mary, Strain, J. J., Molloy, Anne M., McLaughlin, Marian, Lees-Murdock, Diane J., Walsh, Colum P., and Pentieva, Kristina

Published
2021
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17. Potential Plasma Proteins (LGALS9, LAMP3, PRSS8 and AGRN) as Predictors of Hospitalisation Risk in COVID-19 Patients.

Author

McLarnon, Thomas, McDaid, Darren, Lynch, Seodhna M., Cooper, Eamonn, McLaughlin, Joseph, McGilligan, Victoria E., Watterson, Steven, Shukla, Priyank, Zhang, Shu-Dong, Bucholc, Magda, English, Andrew, Peace, Aaron, O'Kane, Maurice, Kelly, Martin, Bhavsar, Manav, Murray, Elaine K., Gibson, David S., Walsh, Colum P., Bjourson, Anthony J., and Rai, Taranjit Singh

Subjects
MACHINE learning, SARS-CoV-2, SUPPORT vector machines, COVID-19 pandemic, BLOOD proteins, COVID-19
Abstract

Background: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has posed unprecedented challenges to healthcare systems worldwide. Here, we have identified proteomic and genetic signatures for improved prognosis which is vital for COVID-19 research. Methods: We investigated the proteomic and genomic profile of COVID-19-positive patients (n = 400 for proteomics, n = 483 for genomics), focusing on differential regulation between hospitalised and non-hospitalised COVID-19 patients. Signatures had their predictive capabilities tested using independent machine learning models such as Support Vector Machine (SVM), Random Forest (RF) and Logistic Regression (LR). Results: This study has identified 224 differentially expressed proteins involved in various inflammatory and immunological pathways in hospitalised COVID-19 patients compared to non-hospitalised COVID-19 patients. LGALS9 (p-value < 0.001), LAMP3 (p-value < 0.001), PRSS8 (p-value < 0.001) and AGRN (p-value < 0.001) were identified as the most statistically significant proteins. Several hundred rsIDs were queried across the top 10 significant signatures, identifying three significant SNPs on the FSTL3 gene showing a correlation with hospitalisation status. Conclusions: Our study has not only identified key signatures of COVID-19 patients with worsened health but has also demonstrated their predictive capabilities as potential biomarkers, which suggests a staple role in the worsened health effects caused by COVID-19. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Effect of continued folic acid supplementation beyond the first trimester of pregnancy on cognitive performance in the child: a follow-up study from a randomized controlled trial (FASSTT Offspring Trial)

Author

McNulty, Helene, Rollins, Mark, Cassidy, Tony, Caffrey, Aoife, Marshall, Barry, Dornan, James, McLaughlin, Marian, McNulty, Breige A., Ward, Mary, Strain, J. J., Molloy, Anne M., Lees-Murdock, Diane J., Walsh, Colum P., and Pentieva, Kristina

Published
2019
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22. DCK confers sensitivity of DCTD-positive cancer cells to oxidized methylcytidines

Author

Zhao, Ya-Hui, Jiang, Wei, Gao, Hai, Pang, Guo-Zheng, Wu, Yu-Shuang, Wang, Yuan-Xian, Sheng, Meng-Yao, Xie, Jia-Ying, Wu, Wan-Ling, Ji, Zhi-Jian, Du, Ya-Rui, Zhang, Lei, Wang, Xiao-Qin, Walsh, Colum P., Jiang, Hai, Xu, Guo-Liang, Zhou, Dan, Zhao, Ya-Hui, Jiang, Wei, Gao, Hai, Pang, Guo-Zheng, Wu, Yu-Shuang, Wang, Yuan-Xian, Sheng, Meng-Yao, Xie, Jia-Ying, Wu, Wan-Ling, Ji, Zhi-Jian, Du, Ya-Rui, Zhang, Lei, Wang, Xiao-Qin, Walsh, Colum P., Jiang, Hai, Xu, Guo-Liang, and Zhou, Dan

Published
2023
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29. Variations in psychological disorders, suicidality, and help-seeking behaviour among college students from different academic disciplines

Author

McLafferty, Margaret, primary, Brown, Natasha, additional, Brady, John, additional, McLaughlin, Jonathon, additional, McHugh, Rachel, additional, Ward, Caoimhe, additional, McBride, Louise, additional, Bjourson, Anthony J., additional, O’Neill, Siobhan M., additional, Walsh, Colum P., additional, and Murray, Elaine K., additional

Published
2022
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30. STING-dependent cytosolic DNA sensing pathway drives the progression to leukemia in TET2-mutated HSPCs

Author

Xie, Jiaying, primary, Sheng, Mengyao, additional, Rong, Shaoqin, additional, Wang, Chao, additional, Wu, Wanling, additional, Huang, Jingru, additional, Sun, Yue, additional, Chen, Pingyue, additional, Wu, Yushuang, additional, Wang, Yuanxian, additional, Wang, Lan, additional, Zhou, Bo O., additional, Huang, Xinxin, additional, Walsh, Colum P., additional, Bohlander, Stefan K., additional, Huang, Jian, additional, Wang, Xiaoqin, additional, Gao, Hai, additional, Zhou, Dan, additional, Shi, Yuheng, additional, and Xu, Guo-Liang, additional

Published
2022
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31. DCK confers sensitivity of DCTD-positive cancer cells to oxidized methylcytidines

Author

Zhao, Ya-Hui, primary, Jiang, Wei, additional, Gao, Hai, additional, Pang, Guo-Zheng, additional, Wu, Yu-Shuang, additional, Wang, Yuan-Xian, additional, Sheng, Meng-Yao, additional, Xie, Jia-Ying, additional, Wu, Wan-Ling, additional, Ji, Zhi-Jian, additional, Du, Ya-Rui, additional, Zhang, Lei, additional, Wang, Xiao-Qin, additional, Walsh, Colum P, additional, Jiang, Hai, additional, Xu, Guo-Liang, additional, and Zhou, Dan, additional

Published
2022
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33. Prognostic value of miR-21 for prostate cancer : a systematic review and meta-analysis

Author

Stafford, M. Y. Cynthia, Willoughby, Colin E., Walsh, Colum P., McKenna, Declan J., Stafford, M. Y. Cynthia, Willoughby, Colin E., Walsh, Colum P., and McKenna, Declan J.

Abstract

Elevated levels of miR-21 expression are associated with many cancers, suggesting it may be a promising clinical biomarker. In prostate cancer (PCa), however, there is still no consensus about the usefulness of miR-21 as an indicator of disease progression. This systematic review and meta-analysis was conducted to investigate the value of miR-21 expression as a prognostic measurement in PCa patients. Medline (Ovid), EMBASE, Web of Science, Scopus and Cochrane Library databases were systematically searched for relevant publications between 2010 to 2021. Studies exploring the relationship between miR-21 expression, PCa prognosis and clinicopathological factors were selected for review. Those reporting hazard ratio (HR) and 95% confidence intervals (CIs) were subject to meta-analyses. Fixed-effect models were employed to calculated pooled HRs and 95% CIs. Risk of bias in each study was assessed using QUIPS tool. Certainty of evidence in each meta-analysis was assessed using GRADE guidelines. A total of 64 studies were included in the systematic review. Of these, 11 were eligible for inclusion in meta-analysis. Meta-analyses revealed that high miR-21 expression was associated with poor prognosis: HR = 1.58 (95% CI = 1.19-2.09) for biochemical recurrence, MODERATE certainty; HR = 1.46 (95% CI = 1.06-2.01) for death, VERY LOW certainty; and HR = 1.26 (95% CI = 0.70-2.27) for disease progression, VERY LOW certainty. Qualitative summary revealed elevated miR-21 expression was significantly positively associated with PCa stage, Gleason score and risk groups. This systematic review and meta-analysis suggests that elevated levels of miR-21 are associated with poor prognosis in PCa patients. miR-21 expression may therefore be a useful prognostic biomarker in this disease.

Published
2022
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34. Variations in psychological disorders, suicidality, and help-seeking behaviour among college students from different academic disciplines

Author

McLafferty, Margaret, Brown, Natasha, Brady, John, McLaughlin, Jonathon, McHugh, Rachel, Ward, Caoimhe, McBride, Louise, Bjourson, Anthony J., O'Neill, Siobhan M., Walsh, Colum P., Murray, Elaine K., McLafferty, Margaret, Brown, Natasha, Brady, John, McLaughlin, Jonathon, McHugh, Rachel, Ward, Caoimhe, McBride, Louise, Bjourson, Anthony J., O'Neill, Siobhan M., Walsh, Colum P., and Murray, Elaine K.

Abstract

Background Elevated levels of suicidality, ADHD, mental ill-health and substance disorders are reported among college students globally, yet few receive treatment. Some faculties and courses appear to have more at-risk students than others. The current study aimed to determine if students commencing college in different academic disciplines were at a heightened risk for psychopathology, substance use disorders and suicidal behaviour, and examined variations in help-seeking behaviour. Materials and methods The study utilised data collected from 1,829 first-year undergraduate students as part of the Student Psychological Intervention Trial (SPIT) which commenced in September 2019 across four Ulster University campuses in Northern Ireland and an Institute of Technology, in the North-West of Ireland. The SPIT study is part of the World Mental Health International College Student Initiative (WMH-ICS) which uses the WMH-CIDI to identify 12-month and lifetime disorders. Results Students from Life and Health Sciences reported the lowest rates of a range of psychological problems in the year prior to commencing college, while participants studying Arts and Humanities displayed the highest levels (e.g. depression 20.6%; social anxiety 38.8%). However, within faculty variations were found. For example, psychology students reported high rates, while nursing students reported low rates. Variations in help seeking behaviour were also revealed, with male students less likely to seek help. Conclusions Detecting specific cohorts at risk of psychological disorders and suicidality is challenging. This study revealed that some academic disciplines have more vulnerable students than others, with many reluctant to seek help for their problems. It is important for educators to be aware of such issues and for colleges to provide information and support to students at risk. Tailored interventions and prevention strategies may be beneficial to address the needs of students from different dis

Published
2022
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36. Additional file 2 of Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms

Author

Ondičová, Miroslava, Irwin, Rachelle E., Thursby, Sara-Jayne, Hilman, Luke, Caffrey, Aoife, Cassidy, Tony, McLaughlin, Marian, Lees-Murdock, Diane J., Ward, Mary, Murphy, Michelle, Lamers, Yvonne, Pentieva, Kristina, McNulty, Helene, and Walsh, Colum P.

Abstract

Additional file 2. Table S1: Top 10 sites with differential methylation in response to folic acid also show neurodevelopmental associations. Table S2: Top 10 ranking gene body regions showing differential methylation.

Published
2022
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41. Additional file 1 of Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial

Author

Caffrey, Aoife, McNulty, Helene, Rollins, Mark, Girijesh Prasad, Gaur, Pramod, Talcott, Joel B., Witton, Caroline, Cassidy, Tony, Marshall, Barry, Dornan, James, Moore, Adrian J., Ward, Mary, J. J. Strain, Molloy, Anne M., McLaughlin, Marian, Lees-Murdock, Diane J., Walsh, Colum P., and Pentieva, Kristina

Subjects
behavioral disciplines and activities
Abstract

Additional file 1: Methods. Supplementary details in relation to magnetoencephalographic brain imaging. Table S1. Maternal characteristics during pregnancy in all FASSTT trial participants and in the sample whose children completed the FASSTT Offspring trial at 11 years. Table S2. Full Scale IQ, composite and subtest scores for the WISC-IV cognitive assessment in FASSTT Offspring trial participants. Table S3. Maternal characteristics during pregnancy in all FASSTT trial participants and in the sub-sample whose children completed the MEG assessment in the FASSTT Offspring trial.

Published
2021
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42. Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child:an 11-year follow-up from a randomised controlled trial

Author

Caffrey, Aoife, McNulty, Helene, Rollins, Mark, Prasad, Girijesh, Gaur, Pramod, Talcott, Joel B., Witton, Caroline, Cassidy, Tony, Marshall, Barry, Dornan, James, Moore, Adrian J., Ward, Mary, Strain, J. J., Molloy, Anne M., McLaughlin, Marian, Lees-Murdock, Diane J., Walsh, Colum P., Pentieva, Kristina, Caffrey, Aoife, McNulty, Helene, Rollins, Mark, Prasad, Girijesh, Gaur, Pramod, Talcott, Joel B., Witton, Caroline, Cassidy, Tony, Marshall, Barry, Dornan, James, Moore, Adrian J., Ward, Mary, Strain, J. J., Molloy, Anne M., McLaughlin, Marian, Lees-Murdock, Diane J., Walsh, Colum P., and Pentieva, Kristina

Published
2021

48. Cytosine methylation and mammalian development

Author

Walsh, Colum P. and Bestor, Timothy H.

Subjects
Cytosine -- Physiological aspects, Methylation -- Physiological aspects, Embryology -- Research, Genetic transcription -- Regulation, Biological sciences
Abstract

Programmed methylation and demethylation of regulatory sequences has been proposed to play a central role, in vertebrate development. The methylation status of 5' regions of a panel of tissue-specific genes has not been correlated with expression in tissues of fetal and newborn mice despite efforts to do so. A model in which cytosine methylation is a biochemical specialization of large genomes and participates in specialized biological functions, among them allele-specific gene expression and heritable transcriptional silencing of parasitic sequence elements. Cellular differentiation is regulated by conserved regulatory networks. These networks do not depend on covalent modification of the genome.

Published
1999

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