• Adjusting for age improves identification of gut microbiome alterations in multiple diseases.

      Ghosh, Tarini S; Das, Mrinmoy; Jeffery, Ian B; O'Toole, Paul W (2020-03-11)
    • Age at period cessation and trajectories of cardiovascular risk factors across mid and later life.

      O'Keeffe, Linda Marie; Kuh, Diana; Fraser, Abigail; Howe, Laura D; Lawlor, Debbie; Hardy, Rebecca (2020-02-25)
    • An analysis of the attitudes of dental patients attending general dental practice in Galway

      Hayes, Martina; Burke, Francis; McKenna, Gerald; Madden, Jamie; Cronin, Michael (Journal of the Irish Dental Association, 2013-08)
    • Antifungal Peptides as Therapeutic Agents.

      Fernández de Ullivarri, Miguel; Arbulu, Sara; Garcia-Gutierrez, Enriqueta; Cotter, Paul D (2020-03-17)
    • Antiproliferation Activity and Mechanism of c9, t11, c15-CLNA and t9, t11, c15-CLNA from ZS2058 on Colon Cancer Cells.

      Ren, Qing; Yang, Bo; Zhu, Guangzhen; Wang, Shunyu; Fu, Chengli; Zhang, Hao; Ross, R Paul; Stanton, Catherine; Chen, Haiqin; Chen, Wei (2020-03-09)
      Conjugated linolenic acid (CLNA) is a type of ω-3 fatty acid which has been proven to have a series of benefits. However, there is no study about the function of Lactobacillus-derived CLNA isomer. Lactobacillus plantarum ZS2058 has been proven to manifest comprehensive functions and can produce CLNA. To investigate the specific functions of CLNA produced by this probiotic bacterium, two different conjugated α-linolenic acid (CLNA) isomers were successfully isolated. These isoforms, CLNA1 (c9, t11, c15-CLNA, purity 97.48%) and CLNA2 (c9, t11, t15-CLNA, purity 99.00%), both showed the ability to inhibit the growth of three types of colon cancer cells in a time- and concentration-dependent manner. In addition, the expression of MDA in Caco-2 cells was increased by CLNA1 or CLNA2, which indicated that lipid peroxidation was related to the antiproliferation activity of CLNAs. An examination of the key protein of pyroptosis showed that CLNA1 induced the cleavage of caspase-1 and gasdermin-D, while CLNA2 induced the cleavage of caspase-4, 5 and gasdermin-D. The addition of relative inhibitors could alleviate the pyroptosis by CLNAs. CLNA1 and CLNA2 showed no effect on caspase-3, 7, 9 and PARP-1, which were key proteins associated with apoptosis. No sub-diploid apoptotic peak appeared in the result of PI single staining test. In conclusion, CLNA1 activated caspase-1 and induced Caco-2 cell pyroptosis, whereas CLNA2 induced pyroptosis through the caspase-4/5-mediated pathway. The inhibition of Caco-2 cells by the two isomers was not related to apoptosis. This is the first study on the function of Lactobacillus-derived CLNA isomer. The inhibition pathway of Lactobacillus-derived CLNA isomer on colon cancer cells were proved.
    • Assessing Autophagy in Archived Tissue or How to Capture Autophagic Flux from a Tissue Snapshot.

      Humbert, Magali; Morán, María; de la Cruz-Ojeda, Patricia; Muntané, Jordi; Wiedmer, Tabea; Apostolova, Nadezda; McKenna, Sharon L; Velasco, Guillermo; Balduini, Walter; Eckhart, Leopold; et al. (2020-03-21)
    • Assessment of the Prognostic Value of Radiomic Features in F-FMISO PET Imaging of Hypoxia in Postsurgery Brain Cancer Patients: Secondary Analysis of Imaging Data from a Single-Center Study and the Multicenter ACRIN 6684 Trial.

      Muzi, Mark; Wolsztynski, Eric; Fink, James R; O'Sullivan, Janet N; O'Sullivan, Finbarr; Krohn, Kenneth A; Mankoff, David A (2020-03)
      Hypoxia is associated with resistance to radiotherapy and chemotherapy in malignant gliomas, and it can be imaged by positron emission tomography with 18F-fluoromisonidazole (18F-FMISO). Previous results for patients with brain cancer imaged with 18F-FMISO at a single center before conventional chemoradiotherapy showed that tumor uptake via T/Bmax (tissue SUVmax/blood SUV) and hypoxic volume (HV) was associated with poor survival. However, in a multicenter clinical trial (ACRIN 6684), traditional uptake parameters were not found to be prognostically significant, but tumor SUVpeak did predict survival at 1 year. The present analysis considered both study cohorts to reconcile key differences and examine the potential utility of adding radiomic features as prognostic variables for outcome prediction on the combined cohort of 72 patients with brain cancer (30 University of Washington and 42 ACRIN 6684). We used both 18F-FMISO intensity metrics (T/Bmax, HV, SUV, SUVmax, SUVpeak) and assessed radiomic measures that determined first-order (histogram), second-order, and higher-order radiomic features of 18F-FMISO uptake distributions. A multivariate model was developed that included age, HV, and the intensity of 18F-FMISO uptake. HV and SUVpeak were both independent predictors of outcome for the combined data set (P < .001) and were also found significant in multivariate prognostic models (P < .002 and P < .001, respectively). Further model selection that included radiomic features showed the additional prognostic value for overall survival of specific higher order texture features, leading to an increase in relative risk prediction performance by a further 5%, when added to the multivariate clinical model..
    • Association between phospholipid metabolism in plasma and spontaneous preterm birth: a discovery lipidomic analysis in the cork pregnancy cohort.

      Morillon, Aude-Claire; Yakkundi, Shirish; Thomas, Gregoire; Gethings, Lee A; Langridge, James I; Baker, Philip N; Kenny, Louise C; English, Jane A; McCarthy, Fergus P (2020-01-24)
    • Association of distinct type 1 bone morphogenetic protein receptors with different molecular pathways and survival outcomes in neuroblastoma.

      Alshangiti, Amnah M; Wyatt, Sean L; McCarthy, Erin; Collins, Louise M; Hegarty, Shane V; Sullivan, Aideen M; O'Keeffe, Gerard W (2020-04-23)
      Neuroblastoma (NB) is a paediatric cancer that arises in the sympathetic nervous system. Patients with stage 4 tumours have poor outcomes and 20% of high-risk cases have MYCN amplification. The bone morphogenetic proteins (BMPs) play roles in sympathetic neuritogenesis, by signalling through bone morphogenetic protein receptor (BMPR)2 and either BMPR1A or BMPR1B. Alterations in BMPR2 expression have been reported in NB; it is unknown if the expression of BMPR1A or BMPR1B is altered. We report lower BMPR2 and BMPR1B, and higher BMPR1A, expression in stage 4 and in MYCN-amplified NB. Kaplan-Meier plots showed that high BMPR2 or BMPR1B expression was linked to better survival, while high BMPR1A was linked to worse survival. Gene ontology enrichment and pathway analyses revealed that BMPR2 and BMPR1B co-expressed genes were enriched in those associated with NB differentiation. BMPR1A co-expressed genes were enriched in those associated with cell proliferation. Moreover, the correlation between BMPR2 and BMPR1A was strengthened, while the correlation between BMPR2 and BMPR1B was lost, in MYCN-amplified NB. This suggested that differentiation should decrease BMPR1A and increase BMPR1B expression. In agreement, nerve growth factor treatment of cultured sympathetic neurons decreased Bmpr1a expression and increased Bmpr1b expression. Overexpression of dominant negative BMPR1B, treatment with a BMPR1B inhibitor and treatment with GDF5, which signals via BMPR1B, showed that BMPR1B signalling is required for optimal neuritogenesis in NB cells, suggesting that loss of BMPR1B may alter neuritogenesis. The present study shows that expression of distinct BMPRs is associated with different survival outcomes in NB.
    • Bifidobacterium breve UCC2003 Induces a Distinct Global Transcriptomic Program in Neonatal Murine Intestinal Epithelial Cells.

      Kiu, Raymond; Treveil, Agatha; Harnisch, Lukas C; Caim, Shabhonam; Leclaire, Charlotte; van Sinderen, Douwe; Korcsmaros, Tamas; Hall, Lindsay J (2020-07-02)
    • A bioinformatics approach to identify novel long, non-coding RNAs in breast cancer cell lines from an existing RNA-sequencing dataset.

      Zaheed, Oza; Samson, Julia; Dean, Kellie (2020-02-24)
      Breast cancer research has traditionally centred on genomic alterations, hormone receptor status and changes in cancer-related proteins to provide new avenues for targeted therapies. Due to advances in next generation sequencing technologies, there has been the emergence of long, non-coding RNAs (lncRNAs) as regulators of normal cellular events, with links to various disease states, including breast cancer. Here we describe our bioinformatic analyses of a previously published RNA sequencing (RNA-seq) dataset to identify lncRNAs with altered expression levels in a subset of breast cancer cell lines. Using a previously published RNA-seq dataset of 675 cancer cell lines, a subset of 18 cell lines was selected for our analyses that included 16 breast cancer lines, one ductal carcinoma in situ line and one normal-like breast epithelial cell line. Principal component analysis demonstrated correlation with well-established categorisation methods of breast cancer (i.e. luminal A/B, HER2 enriched and basal-like A/B). Through detailed comparison of differentially expressed lncRNAs in each breast cancer sub-type with normal-like breast epithelial cells, we identified 15 lncRNAs with consistently altered expression, including three uncharacterised lncRNAs. Utilising data from The Cancer Genome Atlas (TCGA) and The Genotype Tissue Expression (GETx) project via Gene Expression Profiling Interactive Analysis (GEPIA2), we assessed clinical relevance of several identified lncRNAs with invasive breast cancer. Lastly, we determined the relative expression level of six lncRNAs across a spectrum of breast cancer cell lines to experimentally confirm the findings of our bioinformatic analyses. Overall, we show that the use of existing RNA-seq datasets, if re-analysed with modern bioinformatic tools, can provide a valuable resource to identify lncRNAs that could have important biological roles in oncogenesis and tumour progression.
    • Birth as a neuro-psycho-social event: An integrative model of maternal experiences and their relation to neurohormonal events during childbirth.

      Olza, Ibone; Uvnas-Moberg, Kerstin; Ekström-Bergström, Anette; Leahy-Warren, Patricia; Karlsdottir, Sigfridur Inga; Nieuwenhuijze, Marianne; Villarmea, Stella; Hadjigeorgiou, Eleni; Kazmierczak, Maria; Spyridou, Andria; et al. (2020-07-28)
    • Breast Milk, a Source of Beneficial Microbes and Associated Benefits for Infant Health.

      Lyons, Katríona E; Ryan, C Anthony; Dempsey, Eugene M; Ross, R Paul; Stanton, Catherine (2020-04-09)
    • Breast milk-derived human milk oligosaccharides promote Bifidobacterium interactions within a single ecosystem.

      Lawson, Melissa A E; O'Neill, Ian J; Kujawska, Magdalena; Gowrinadh Javvadi, Sree; Wijeyesekera, Anisha; Flegg, Zak; Chalklen, Lisa; Hall, Lindsay J (2019-11-18)
      Diet-microbe interactions play an important role in modulating the early-life microbiota, with Bifidobacterium strains and species dominating the gut of breast-fed infants. Here, we sought to explore how infant diet drives distinct bifidobacterial community composition and dynamics within individual infant ecosystems. Genomic characterisation of 19 strains isolated from breast-fed infants revealed a diverse genomic architecture enriched in carbohydrate metabolism genes, which was distinct to each strain, but collectively formed a pangenome across infants. Presence of gene clusters implicated in digestion of human milk oligosaccharides (HMOs) varied between species, with growth studies indicating that within single infants there were differences in the ability to utilise 2'FL and LNnT HMOs between strains. Cross-feeding experiments were performed with HMO degraders and non-HMO users (using spent or 'conditioned' media and direct co-culture). Further 1H-NMR analysis identified fucose, galactose, acetate, and N-acetylglucosamine as key by-products of HMO metabolism; as demonstrated by modest growth of non-HMO users on spend media from HMO metabolism. These experiments indicate how HMO metabolism permits the sharing of resources to maximise nutrient consumption from the diet and highlights the cooperative nature of bifidobacterial strains and their role as 'foundation' species in the infant ecosystem. The intra- and inter-infant bifidobacterial community behaviour may contribute to the diversity and dominance of Bifidobacterium in early life and suggests avenues for future development of new diet and microbiota-based therapies to promote infant health.
    • Capacity challenges in water quality monitoring: understanding the role of human development.

      Kirschke, Sabrina; Avellán, Tamara; Bärlund, Ilona; Bogardi, Janos J; Carvalho, Laurence; Chapman, Deborah; Dickens, Chris W S; Irvine, Kenneth; Lee, SungBong; Mehner, Thomas; et al. (2020-04-19)
    • Characteristics of Upper Limb Impairment Related to Degenerative Cervical Myelopathy: Development of a Sensitive Hand Assessment (Graded Redefined Assessment of Strength, Sensibility, and Prehension Version Myelopathy).

      Kalsi-Ryan, Sukhvinder; Riehm, Lauren E; Tetreault, Lindsay; Martin, Allan R; Teoderascu, Florentina; Massicotte, Eric; Curt, Armin; Verrier, Mary C; Velstra, Inge-Marie; Fehlings, Michael G
    • The class II histone deacetylases as therapeutic targets for Parkinson's disease.

      Mazzocchi, Martina; Collins, Louise M; Sullivan, Aideen M; O'Keeffe, Gerard W (2020-06-09)
    • Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease.

      Ryan, F J; Ahern, A M; Fitzgerald, R S; Laserna-Mendieta, E J; Power, E M; Clooney, A G; O'Donoghue, K W; McMurdie, P J; Iwai, S; Crits-Christoph, A; et al. (2020-03-23)
    • Community profiling and health needs assessment: a practical guide for public health nurses

      Mulcahy, Helen; Downey, Joanna (University College Cork, Health Service Executive, 2021-06)