83 results on '"Fogarty R"'
Search Results
2. Molecular dynamics study of structure and reactions at the hydroxylated Mg(0001)/bulk water interface.
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Fogarty, R. M. and Horsfield, A. P.
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MOLECULAR dynamics , *DENSITY functional theory , *AUTOMOBILE parts , *METASTABLE states , *HYDROGEN bonding - Abstract
A molecular level understanding of the aqueous Mg corrosion mechanism will be essential in developing improved alloys for battery electrodes, automobile parts, and biomedical implants. The structure and reactivity of the hydroxylated surface is expected to be key to the overall mechanism because (i) it is predicted to be the metastable surface state (rather than the bare surface) under a range of conditions and (ii) it provides a reasonable model for the outer corrosion film/water interface. We investigate the structure, interactions, and reactivity at the hydroxylated Mg(0001)/water interface using a combination of static Density Functional Theory calculations and second-generation Car–Parrinello ab initio molecular dynamics. We carry out detailed structural analyses into, among other properties, near-surface water orientations, favored adsorption sites, and near-surface hydrogen bonding behavior. Despite the short timescale (tens of ps) of our molecular dynamics run, we observe a cathodic water splitting event; the rapid timescale for this reaction is explained in terms of near-surface water structuring lowering the reaction barrier. Furthermore, we observe oxidation of an Mg surface atom to effectively generate a univalent Mg species (Mg+). Results are discussed in the context of understanding the Mg corrosion mechanism: For example, our results provide an explanation for the catalytic nature of the Mg corrosion film toward water splitting and a feasible mechanism for the generation of the univalent Mg species often proposed as a key intermediate. [ABSTRACT FROM AUTHOR]
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- 2022
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3. Structure and interactions at the Mg(0001)/water interface: An ab initio study.
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Fogarty, R. M., Li, B. X., Harrison, N. M., and Horsfield, A. P.
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ATOMIC structure , *METALWORK , *ATOMIC charges , *DENSITY functional theory , *MINIMAL surfaces - Abstract
A molecular level understanding of metal/bulk water interface structure is key for a wide range of processes, including aqueous corrosion, which is our focus, but their buried nature makes experimental investigation difficult and we must mainly rely on simulations. We investigate the Mg(0001)/water interface using second generation Car–Parrinello molecular dynamics (MD) to gain structural information, combined with static density functional theory calculations to probe the atomic interactions and electronic structure (e.g., calculating the potential of zero charge). By performing detailed structural analyses of both metal–surface atoms and the near-surface water, we find that, among other insights: (i) water adsorption causes significant surface roughening (the planar distribution for top-layer Mg has two peaks separated by ≈ 0.6 A ̊ ), (ii) strongly adsorbed water covers only ≈ 1 4 of available surface sites, and (iii) adsorbed water avoids clustering on the surface. Static calculations are used to gain a deeper understanding of the structuring observed in MD. For example, we use an energy decomposition analysis combined with calculated atomic charges to show that adsorbate clustering is unfavorable due to Coulombic repulsion between adsorption site surface atoms. Results are discussed in the context of previous simulations carried out on other metal/water interfaces. The largest differences for the Mg(0001)/water system appear to be the high degree of surface distortion and the minimal difference between the metal work function and metal/water potential of zero charge (at least compared to other interfaces with similar metal–water interaction strengths). The structural information, in this paper, is important for understanding aqueous Mg corrosion, as the Mg(0001)/water interface is the starting point for key reactions. Furthermore, our focus on understanding the driving forces behind this structuring leads to important insights for general metal/water interfaces. [ABSTRACT FROM AUTHOR]
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- 2022
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4. RNA Sequencing of Lens Capsular Epithelium Implicates Novel Pathways in Pseudoexfoliation Syndrome.
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Mullany, S, Marshall, H, Zhou, T, Thomson, D, Schmidt, JM, Qassim, A, Knight, LSW, Hollitt, G, Berry, EC, Nguyen, T, To, M-S, Dimasi, D, Kuot, A, Dubowsky, J, Fogarty, R, Sun, M, Chehade, L, Kuruvilla, S, Supramaniam, D, Breen, J, Sharma, S, Landers, J, Lake, S, Mills, RA, Hassall, MM, Chan, WO, Klebe, S, Souzeau, E, Siggs, OM, Craig, JE, Mullany, S, Marshall, H, Zhou, T, Thomson, D, Schmidt, JM, Qassim, A, Knight, LSW, Hollitt, G, Berry, EC, Nguyen, T, To, M-S, Dimasi, D, Kuot, A, Dubowsky, J, Fogarty, R, Sun, M, Chehade, L, Kuruvilla, S, Supramaniam, D, Breen, J, Sharma, S, Landers, J, Lake, S, Mills, RA, Hassall, MM, Chan, WO, Klebe, S, Souzeau, E, Siggs, OM, and Craig, JE
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PURPOSE: Pseudoexfoliation syndrome (PEX) is a common systemic disease that results in severe and often irreversible vision loss. Despite considerable research effort, PEX remains incompletely understood. This study sought to perform the first RNAseq study in elucidate the pathophysiology of PEX, and contribute a publicly available transcriptomic data resource for future research. METHODS: Human ocular lens capsular epithelium samples were collected from 25 patients with PEX and 39 non-PEX controls undergoing cataract surgery. RNA extracted from these specimens was subjected to polyadenylated (mRNA) selection and deep bulk RNA sequencing. Differential expression analysis investigated protein-coding gene transcripts. Exploratory analyses used pathway analysis tools, and curated class- and disease-specific gene sets. RESULTS: Differential expression analysis demonstrated that 2882 genes were differentially expressed according to PEX status. Genes associated with viral gene expression pathways were among the most upregulated, alongside genes encoding ribosomal and mitochondrial respiratory transport chain proteins. Cell adhesion protein transcripts including type 4 collagen subunits were downregulated. CONCLUSIONS: This comparative transcriptomic dataset highlights novel and previously recognized pathogenic pathways in PEX and provides the first comprehensive transcriptomic resource, adding an additional layer to build further understanding of PEX pathophysiology.
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- 2022
5. 409 The Impact of Level Loading in a Large Academic Medical System
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Dilip, M., Su, H., Zhang, W., Meng, L., Tuffuor, K., Pham, L., Fogarty, R., Venkatesh, A., Pinker, E., and Sangal, R.
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- 2024
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6. Resonant X-ray photoelectron spectroscopy: identification of atomic contributions to valence states
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Seymour, J. M., primary, Gousseva, E., additional, Bennett, R. A., additional, Large, A. I., additional, Held, G., additional, Hein, D., additional, Wartner, G., additional, Quevedo, W., additional, Seidel, R., additional, Kolbeck, C., additional, Clarke, C. J., additional, Fogarty, R. M., additional, Bourne, R. A., additional, Palgrave, R. G., additional, Hunt, P. A., additional, and Lovelock, K. R. J., additional
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- 2022
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7. Beyond two-center tight binding: Models for Mg and Zr
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Fogarty, R. M., primary, Smutna, J., additional, Wenman, M. R., additional, and Horsfield, A. P., additional
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- 2020
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8. Systematic development of ab initio tight-binding models for hexagonal metals
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Smutna, J., primary, Fogarty, R. M., additional, Wenman, M. R., additional, and Horsfield, A. P., additional
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- 2020
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9. Metal removal by immobilised and non-immobilised Azolla filiculoides
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Fogarty, R. V., Dostalek, P., Patzak, M., Votruba, J., Tel-Or, E., and Tobin, J. M.
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- 1999
10. A one-pot-one-reactant synthesis of platinum compounds at the nanoscale
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Stoppiello, C. T., Biskupek, J., Li, Z. Y., Rance, G. A., Botos, A., Fogarty, R. M., Bourne, R. A., Yuan, J., Lovelock, K. R. J., Thompson, P., Fay, M. W., Kaiser, U., Chamberlain, T. W., and Khlobystov, A. N.
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The preparation of inorganic nanomaterials with a desired structure and specific properties requires the ability to strictly control their size, shape and composition. A series of chemical reactions with platinum compounds carried out within the 1.5 nm wide channel of single-walled carbon nanotubes (SWNTs) have demonstrated the ability of SWNTs to act as both a very effective reaction vessel and a template for the formation of nanocrystals of platinum di-iodide and platinum di-sulphide, materials that are difficult to synthesise in the form of nanoparticles by traditional synthetic methods. The stepwise synthesis inside nanotubes has enabled the formation of Pt compounds to be monitored at each step of the reaction by aberration-corrected high resolution transmission electron microscopy (AC-HRTEM), verifying the atomic structures of the products, and by an innovative combination of fluorescence-detected X-ray absorption spectroscopy (FD-XAS) and Raman spectroscopy, monitoring the oxidation states of the platinum guest-compounds within the nanotube and the vibrational properties of the host-SWNT, respectively. This coupling of complementary spectroscopies reveals that electron transfer between the guest-compound and the host-SWNT can occur in either direction depending on the composition and structure of the guest. A new approach for nanoscale synthesis in nanotubes developed in this study utilises the versatile coordination chemistry of Pt which has enabled the insertion of the required chemical elements (e.g. metal and halogens or chalcogens) into the nanoreactor in the correct proportions for the controlled formation of PtI2 and PtS2 with the correct stoichiometry.
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- 2017
11. FDIONIC18 atomic charges of sulfur in ionic liquids: experiments and calculations
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Fogarty, R, Rowe, R, Matthews, R, Clough, M, Ashworth, C, Brandt, A, Corbett, P, Palgrave, R, Smith, E, Bourne, R, Chamberlain, T, Thompson, P, Hunt, P, and Lovelock, K
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Physics::Atomic and Molecular Clusters ,Physics::Atomic Physics - Abstract
Experimental near edge X-ray absorption fine structure (NEXAFS) spectra, X-ray photoelectron (XP) spectra and Auger electron spectra are reported for sulfur in ionic liquids (ILs) with a range of chemical structures. These values provide experimental measures of the atomic charge in each IL and enable evaluation of the suitability of NEXAFS spectroscopy and XPS for probing relative atomic charge of sulfur. In addition, we use Auger electron spectroscopy to show that when XPS binding energies differ by less than 0.5 eV, conclusions on atomic charge should be treated with caution. Our experimental data provides a benchmark for calculations of atomic charge of sulfur obtained using different methods. Atomic charges were computed for lone ions and ion pairs, both in the gas phase (GP) and in a solvation model based on density (SMD), with a wide range of ion pair conformers considered. Three methods were used to compute atomic charges: charges from electrostatic potential using a grid based method (ChelpG), natural bond orbital (NBO) population analysis and Bader’s atoms in molecules (AIM) approach. By comparing experimental and calculated measures of atomic charge of sulfur, we provide an order for the sulfur atoms, ranging from most negative to most positive atomic charge. Furthermore, we show that both ChelpG and NBO are reasonable methods for calculating atomic charge of sulfur in ILs, based on agreement with both XPS and NEXAFS spectroscopy results. However, atomic charges of sulfur derived from ChelpG are found to display significant, non-physical conformational dependence. Only small differences in individual atomic charge of sulfur were observed between lone ion (GP) and ion pair IL(SMD) model systems, indicating that ion–ion interactions do not strongly influence individual atomic charges.
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- 2017
12. Implicit and explicit host effects on excitons in pentacene derivatives
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Charlton, R. J., primary, Fogarty, R. M., additional, Bogatko, S., additional, Zuehlsdorff, T. J., additional, Hine, N. D. M., additional, Heeney, M., additional, Horsfield, A. P., additional, and Haynes, P. D., additional
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- 2018
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13. The PHF21B gene is associated with major depression and modulates the stress response
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Wong, M-L, Arcos-Burgos, M, Liu, S, Velez, JI, Yu, C, Baune, BT, Jawahar, MC, Arolt, V, Dannlowski, U, Chuah, A, Huttley, GA, Fogarty, R, Lewis, MD, Bornstein, SR, Licinio, J, Wong, M-L, Arcos-Burgos, M, Liu, S, Velez, JI, Yu, C, Baune, BT, Jawahar, MC, Arolt, V, Dannlowski, U, Chuah, A, Huttley, GA, Fogarty, R, Lewis, MD, Bornstein, SR, and Licinio, J
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Major depressive disorder (MDD) affects around 350 million people worldwide; however, the underlying genetic basis remains largely unknown. In this study, we took into account that MDD is a gene-environment disorder, in which stress is a critical component, and used whole-genome screening of functional variants to investigate the 'missing heritability' in MDD. Genome-wide association studies (GWAS) using single- and multi-locus linear mixed-effect models were performed in a Los Angeles Mexican-American cohort (196 controls, 203 MDD) and in a replication European-ancestry cohort (499 controls, 473 MDD). Our analyses took into consideration the stress levels in the control populations. The Mexican-American controls, comprised primarily of recent immigrants, had high levels of stress due to acculturation issues and the European-ancestry controls with high stress levels were given higher weights in our analysis. We identified 44 common and rare functional variants associated with mild to moderate MDD in the Mexican-American cohort (genome-wide false discovery rate, FDR, <0.05), and their pathway analysis revealed that the three top overrepresented Gene Ontology (GO) processes were innate immune response, glutamate receptor signaling and detection of chemical stimulus in smell sensory perception. Rare variant analysis replicated the association of the PHF21B gene in the ethnically unrelated European-ancestry cohort. The TRPM2 gene, previously implicated in mood disorders, may also be considered replicated by our analyses. Whole-genome sequencing analyses of a subset of the cohorts revealed that European-ancestry individuals have a significantly reduced (50%) number of single nucleotide variants compared with Mexican-American individuals, and for this reason the role of rare variants may vary across populations. PHF21b variants contribute significantly to differences in the levels of expression of this gene in several brain areas, including the hippocampus. Furthermore, u
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- 2017
14. Name It! Store It! Protect It!: A Systems Approach to Managing Data in Research Core Facilities
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DeVries, Matthew, primary, Fenchel, Matthew, additional, Fogarty, R. E., additional, Kim, Byong-Do, additional, Timmons, Daniel, additional, and White, A. Nicole, additional
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- 2017
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15. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error
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Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), Makela, K.M. (Kari Matti), Fan, Q. (Qiao), Verhoeven, V.J.M. (Virginie), Wojciechowski, R. (Robert), Barathi, V.A. (Veluchamy), Hysi, P.G. (Pirro), Guggenheim, J. (Jean), Höhn, R. (René), Vitart, V. (Veronique), Khawaja, A.P. (Anthony P.), Yamashiro, K. (Kenji), Hosseini, S.M. (S Mohsen), Lehtimäki, T. (Terho), Lu, Y. (Yi), Haller, T. (Toomas), Xie, J. (Jing), Delcourt, C. (Cécile), Pirastu, M. (Mario), Wedenoja, J. (Juho), Gharahkhani, P. (Puya), Venturini, C. (Cristina), Miyake, M. (Masahiro), Hewit, A.W. (Alex), Guo, X. (Xiaobo), Mazur, J. (Johanna), Huffman, J.E. (Jenifer E.), Williams, K.M. (Katie M.), Polasek, O. (Ozren), Campbell, H. (Harry), Rudan, I. (Igor), Vatavuk, Z. (Zoran), Wilson, J.F. (James F), Joshi, P.K. (Peter), Mcmahon, G. (George), St Pourcain, B. (Beate), Evans, D.M. (David), Simpson, C.L. (Claire), Schwantes-An, T.-H. (Tae-Hwi), Igo Jr., R.P. (Robert), Mirshahi, A. (Alireza), Cougnard-Grégoire, A. (Audrey), Bellenguez, C. (Céline), Blettner, M. (Maria), Raitakari, O. (Olli), Kähönen, M. (Mika), Seppälä, I. (Ilkka), Zeller, T. (Tanja), Meitinger, T. (Thomas), Ried, J.S. (Janina), Gieger, C. (Christian), Portas, L. (Laura), Leeuwen, E.M. (Elisa) van, Amin, N. (Najaf), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Hofman, A. (Albert), Vingerling, J.R. (Hans), Wang, Y. (Ying), Wang, X. (Xu), Tai-Hui Boh, E. (Eileen), Ikram, M.K. (Kamran), Sabanayagam, C. (Charumathi), Gupta, P. (Preeti), Tan, V. (Vincent), Zhou, L. (Lei), Ho, C.E.H. (Candice E. H.), Lim, W. (Wan'E), Beuerman, R.W. (Roger W.), Siantar, R. (Rosalynn), Tai, E.-S. (E-Shyong), Vithana, E.N. (Eranga), Mihailov, E. (Evelin), Khor, C.C., Hayward, C. (Caroline), Luben, R.N. (Robert), Foster, P.J. (Paul), Klein, B.E.K. (Barbara), Klein, R. (Ronald), Wong, H.-S. (Hoi-Suen), Mitchell, P. (Paul), Metspalu, A. (Andres), Aung, T. (Tin), Young, T.L. (Terri L.), He, M. (Mingguang), Pärssinen, O. (Olavi), Duijn, C.M. (Cornelia) van, Jin Wang, J. (Jie), Williams, C. (Cathy), Jonas, J.B. (Jost B.), Teo, Y.Y. (Yik Ying), Mackey, D.A. (David), Oexle, K. (Konrad), Yoshimura, N., Paterson, A.D. (Andrew D.), Pfeiffer, N. (Norbert), Wong, T.Y. (Tien Yin), Baird, P.N. (Paul), Stambolian, D. (Dwight), Wilson, J.E.B. (Joan E. Bailey), Cheng, C-Y. (Ching-Yu), Hammond, C.J. (Christopher J.), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Rahi, J.S. (Jugnoo), Korobelnik, J.-F. (Jean-François), Kemp, J.P. (John), Timpson, N.J. (Nicholas), Smith, A.V. (Davey), Craig, J.E. (Jamie E.), Burdon, K.P. (Kathryn P.), Fogarty, R. (Rhys), Iyengar, S.K. (Sudha), Chew, E.Y. (Emily), Janmahasatian, S. (Sarayut), Martin, N.G. (Nicholas), MacGregor, S. (Stuart), Xu, L. (Liang), Schache, M. (Maria), Nangia, M. (Monika), Panda-Jonas, S. (Songhomitra), Wright, A.F. (Alan), Fondran, J.R. (Jeremy R.), Lass, J.H. (Jonathan H.), Feng, S. (Sheng), Zhao, J.H. (Jing Hua), Khaw, K.T., Wareham, N.J. (Nick), Rantanen, T. (Taina), Kaprio, J. (Jaakko), Pang, C.P. (Chi Pui), Chen, L.J. (Li Jia), Tam, P.O. (Pancy O.), Jhanji, V. (Vishal), Young, A.L. (Alvin L.), Döring, A. (Angela), Raffel, L.J. (Leslie), Cotch, M.-F. (Mary-Frances), Li, X. (Xiaohui), Yip, S.P. (Shea Ping), Yap, M.K.H. (Maurice K.H.), Biino, G. (Ginevra), Vaccargiu, S. (Simona), Fossarello, M. (Maurizio), Fleck, B. (Brian), Yazar, S. (Seyhan), Tideman, J.W.L. (Willem), Tedja, M. (Milly), Léveillard, T. (Thierry), Morrison, M.A. (Margaux A.), Farrer, L.A. (Lindsay), Zhou, X. (Xiangtian), Chen, W. (Wei), Mizuki, N. (Nobuhisa), Meguro, A. (Akira), and Makela, K.M. (Kari Matti)
- Abstract
Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10-5), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.
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- 2016
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16. The PHF21B gene is associated with major depression and modulates the stress response
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Wong, M-L, primary, Arcos-Burgos, M, additional, Liu, S, additional, Vélez, J I, additional, Yu, C, additional, Baune, B T, additional, Jawahar, M C, additional, Arolt, V, additional, Dannlowski, U, additional, Chuah, A, additional, Huttley, G A, additional, Fogarty, R, additional, Lewis, M D, additional, Bornstein, S R, additional, and Licinio, J, additional
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- 2016
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17. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma
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Hysi, P.G. (Pirro), Cheng, C-Y. (Ching-Yu), Springelkamp, H. (Henriët), MacGregor, S. (Stuart), Bailey, J.N.C. (Jessica N. Cooke), Wojciechowski, R. (Robert), Vitart, V. (Veronique), Nag, A. (Abhishek), Hewit, A.W. (Alex), Höhn, R. (René), Venturini, C. (Cristina), Mirshahi, A. (Alireza), Ramdas, W.D. (Wishal), Thorleifsson, G. (Gudmar), Vithana, E.N. (Eranga), Khor, C.C., Stefansson, A.B. (Arni B.), Liao, J. (Jie), Haines, J.L. (Jonathan), Amin, N. (Najaf), Wang, Y. (Ying), Wild, P.S. (Philipp S.), Ozel, A.B. (Ayse), Li, J., Fleck, B.W. (Brian W.), Zeller, T. (Tanja), Staffieri, S.E. (Sandra E.), Teo, Y.Y. (Yik Ying), Cuellar-Partida, G. (Gabriel), Luo, X. (Xiaoyan), Allingham, R.R. (R Rand), Richards, J.E. (Julia), Senft, A. (Andrea), Karssen, L.C. (Lennart), Zheng, Y. (Yingfeng), Bellenguez, C. (Céline), Xu, L. (Liang), Iglesias González, A.I. (Adriana), Wilson, J.F. (James F), Kang, J.H. (Jae), Leeuwen, E.M. (Elisa) van, Jonsson, V. (Vesteinn), Thorsteinsdottir, U. (Unnur), Despriet, D.D.G. (Dominique), Ennis, S. (Sarah), Moroi, S.E. (Sayoko), Martin, N.G. (Nicholas), Jansonius, N.M. (Nomdo), Yazar, S. (Seyhan), Tai, E.S. (Shyong), Amouyel, P. (Philippe), Kirwan, J. (James), Koolwijk, L.M.E. (Leonieke) van, Hauser, M.A. (Michael), Jonasson, F. (Fridbert), Leo, P.J. (Paul), Loomis, S.J. (Stephanie J.), Fogarty, R. (Rhys), Rivadeneira Ramirez, F. (Fernando), Kearns, L.S. (Lisa S.), Lackner, K.J. (Karl), Jong, P.T.V.M. (Paulus) de, Simpson, C.L. (Claire), Pennell, C.E. (Craig), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Saw, S-M. (Seang-Mei), Lotery, A.J. (Andrew), Bailey-Wilson, J.E. (Joan E.), Hofman, A. (Albert), Vingerling, J.R. (Hans), Maubaret, C. (Cécilia), Pfeiffer, A.F.H. (Andreas), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Young, T.L. (Terri), Pasquale, L.R. (Louis), Delcourt, C. (Cécile), Spector, T.D. (Timothy), Klaver, C.C.W. (Caroline), Small, K.S. (Kerrin), Burdon, K.P. (Kathryn), Zwart, J-A. (John-Anker), Wong, T.Y. (Tien Yin), Viswanathan, A.C. (Ananth), Mackey, D.A. (David), Craig, J.E. (Jamie), Wiggs, J.L. (Janey), Duijn, C.M. (Cornelia) van, Hammond, C.J. (Christopher), Aung, T. (Tin), Hysi, P.G. (Pirro), Cheng, C-Y. (Ching-Yu), Springelkamp, H. (Henriët), MacGregor, S. (Stuart), Bailey, J.N.C. (Jessica N. Cooke), Wojciechowski, R. (Robert), Vitart, V. (Veronique), Nag, A. (Abhishek), Hewit, A.W. (Alex), Höhn, R. (René), Venturini, C. (Cristina), Mirshahi, A. (Alireza), Ramdas, W.D. (Wishal), Thorleifsson, G. (Gudmar), Vithana, E.N. (Eranga), Khor, C.C., Stefansson, A.B. (Arni B.), Liao, J. (Jie), Haines, J.L. (Jonathan), Amin, N. (Najaf), Wang, Y. (Ying), Wild, P.S. (Philipp S.), Ozel, A.B. (Ayse), Li, J., Fleck, B.W. (Brian W.), Zeller, T. (Tanja), Staffieri, S.E. (Sandra E.), Teo, Y.Y. (Yik Ying), Cuellar-Partida, G. (Gabriel), Luo, X. (Xiaoyan), Allingham, R.R. (R Rand), Richards, J.E. (Julia), Senft, A. (Andrea), Karssen, L.C. (Lennart), Zheng, Y. (Yingfeng), Bellenguez, C. (Céline), Xu, L. (Liang), Iglesias González, A.I. (Adriana), Wilson, J.F. (James F), Kang, J.H. (Jae), Leeuwen, E.M. (Elisa) van, Jonsson, V. (Vesteinn), Thorsteinsdottir, U. (Unnur), Despriet, D.D.G. (Dominique), Ennis, S. (Sarah), Moroi, S.E. (Sayoko), Martin, N.G. (Nicholas), Jansonius, N.M. (Nomdo), Yazar, S. (Seyhan), Tai, E.S. (Shyong), Amouyel, P. (Philippe), Kirwan, J. (James), Koolwijk, L.M.E. (Leonieke) van, Hauser, M.A. (Michael), Jonasson, F. (Fridbert), Leo, P.J. (Paul), Loomis, S.J. (Stephanie J.), Fogarty, R. (Rhys), Rivadeneira Ramirez, F. (Fernando), Kearns, L.S. (Lisa S.), Lackner, K.J. (Karl), Jong, P.T.V.M. (Paulus) de, Simpson, C.L. (Claire), Pennell, C.E. (Craig), Oostra, B.A. (Ben), Uitterlinden, A.G. (André), Saw, S-M. (Seang-Mei), Lotery, A.J. (Andrew), Bailey-Wilson, J.E. (Joan E.), Hofman, A. (Albert), Vingerling, J.R. (Hans), Maubaret, C. (Cécilia), Pfeiffer, A.F.H. (Andreas), Wolfs, R.C.W. (Roger), Lemij, H.G. (Hans), Young, T.L. (Terri), Pasquale, L.R. (Louis), Delcourt, C. (Cécile), Spector, T.D. (Timothy), Klaver, C.C.W. (Caroline), Small, K.S. (Kerrin), Burdon, K.P. (Kathryn), Zwart, J-A. (John-Anker), Wong, T.Y. (Tien Yin), Viswanathan, A.C. (Ananth), Mackey, D.A. (David), Craig, J.E. (Jamie), Wiggs, J.L. (Janey), Duijn, C.M. (Cornelia) van, Hammond, C.J. (Christopher), and Aung, T. (Tin)
- Abstract
Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 × 10 '8 for rs6445055), two on chromosome 9 (P = 2.80 × 10 '11 for rs2472493 near ABCA1 and P = 6.39 × 10 '11 for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 10 '11 for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.
- Published
- 2014
- Full Text
- View/download PDF
18. Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma
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Gharahkhani, P, Burdon, KP, Fogarty, R, Sharma, S, Hewitt, AW, Martin, S, Law, MH, Cremin, K, Bailey, JNC, Loomis, SJ, Pasquale, LR, Haines, JL, Hauser, MA, Viswanathan, AC, McGuffin, P, Topouzis, F, Foster, PJ, Graham, SL, Casson, RJ, Chehade, M, White, AJ, Zhou, T, Souzeau, E, Landers, J, Fitzgerald, JT, Klebe, S, Ruddle, JB, Goldberg, I, Healey, PR, Mills, RA, Wang, JJ, Montgomery, GW, Martin, NG, Radford-Smith, G, Whiteman, DC, Brown, MA, Wiggs, JL, Mackey, DA, Mitchell, P, MacGregor, S, Craig, JE, Gharahkhani, P, Burdon, KP, Fogarty, R, Sharma, S, Hewitt, AW, Martin, S, Law, MH, Cremin, K, Bailey, JNC, Loomis, SJ, Pasquale, LR, Haines, JL, Hauser, MA, Viswanathan, AC, McGuffin, P, Topouzis, F, Foster, PJ, Graham, SL, Casson, RJ, Chehade, M, White, AJ, Zhou, T, Souzeau, E, Landers, J, Fitzgerald, JT, Klebe, S, Ruddle, JB, Goldberg, I, Healey, PR, Mills, RA, Wang, JJ, Montgomery, GW, Martin, NG, Radford-Smith, G, Whiteman, DC, Brown, MA, Wiggs, JL, Mackey, DA, Mitchell, P, MacGregor, S, and Craig, JE
- Abstract
Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10(-19)), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10(-10)) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10(-10)). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.
- Published
- 2014
19. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma
- Author
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Hysi, PG, Cheng, C-Y, Springelkamp, H, Macgregor, S, Bailey, JNC, Wojciechowski, R, Vitart, V, Nag, A, Hewitt, AW, Hohn, R, Venturini, C, Mirshahi, A, Ramdas, WD, Thorleifsson, G, Vithana, E, Khor, C-C, Stefansson, AB, Liao, J, Haines, JL, Amin, N, Wang, YX, Wild, PS, Ozel, AB, Li, JZ, Fleck, BW, Zeller, T, Staffieri, SE, Teo, Y-Y, Cuellar-Partida, G, Luo, X, Allingham, RR, Richards, JE, Senft, A, Karssen, LC, Zheng, Y, Bellenguez, C, Xu, L, Iglesias, AI, Wilson, JF, Kang, JH, van Leeuwen, EM, Jonsson, V, Thorsteinsdottir, U, Despriet, DDG, Ennis, S, Moroi, SE, Martin, NG, Jansonius, NM, Yazar, S, Tai, E-S, Amouyel, P, Kirwan, J, van Koolwijk, LME, Hauser, MA, Jonasson, F, Leo, P, Loomis, SJ, Fogarty, R, Rivadeneira, F, Kearns, L, Lackner, KJ, de Jong, PTVM, Simpson, CL, Pennell, CE, Oostra, BA, Uitterlinden, AG, Saw, S-M, Lotery, AJ, Bailey-Wilson, JE, Hofman, A, Vingerling, JR, Maubaret, C, Pfeiffer, N, Wolfs, RCW, Lemij, HG, Young, TL, Pasquale, LR, Delcourt, C, Spector, TD, Klaver, CCW, Small, KS, Burdon, KP, Stefansson, K, Wong, T-Y, Viswanathan, A, Mackey, DA, Craig, JE, Wiggs, JL, van Duijn, CM, Hammond, CJ, Aung, T, Hysi, PG, Cheng, C-Y, Springelkamp, H, Macgregor, S, Bailey, JNC, Wojciechowski, R, Vitart, V, Nag, A, Hewitt, AW, Hohn, R, Venturini, C, Mirshahi, A, Ramdas, WD, Thorleifsson, G, Vithana, E, Khor, C-C, Stefansson, AB, Liao, J, Haines, JL, Amin, N, Wang, YX, Wild, PS, Ozel, AB, Li, JZ, Fleck, BW, Zeller, T, Staffieri, SE, Teo, Y-Y, Cuellar-Partida, G, Luo, X, Allingham, RR, Richards, JE, Senft, A, Karssen, LC, Zheng, Y, Bellenguez, C, Xu, L, Iglesias, AI, Wilson, JF, Kang, JH, van Leeuwen, EM, Jonsson, V, Thorsteinsdottir, U, Despriet, DDG, Ennis, S, Moroi, SE, Martin, NG, Jansonius, NM, Yazar, S, Tai, E-S, Amouyel, P, Kirwan, J, van Koolwijk, LME, Hauser, MA, Jonasson, F, Leo, P, Loomis, SJ, Fogarty, R, Rivadeneira, F, Kearns, L, Lackner, KJ, de Jong, PTVM, Simpson, CL, Pennell, CE, Oostra, BA, Uitterlinden, AG, Saw, S-M, Lotery, AJ, Bailey-Wilson, JE, Hofman, A, Vingerling, JR, Maubaret, C, Pfeiffer, N, Wolfs, RCW, Lemij, HG, Young, TL, Pasquale, LR, Delcourt, C, Spector, TD, Klaver, CCW, Small, KS, Burdon, KP, Stefansson, K, Wong, T-Y, Viswanathan, A, Mackey, DA, Craig, JE, Wiggs, JL, van Duijn, CM, Hammond, CJ, and Aung, T
- Abstract
Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 × 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 × 10(-11) for rs2472493 near ABCA1 and P = 6.39 × 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 10(-11) for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.
- Published
- 2014
20. Pteropid bats are confirmed as the reservoir hosts of henipaviruses: A comprehensive experimental study of virus transmission
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Halpin, K., Hyatt, A. D., Fogarty, R., Middleton, D., Bingham, J., Epstein, J. H., Rahman, S. A., Hughes, T., Smith, C., Field, H. E., Daszak, P., Halpin, K., Hyatt, A. D., Fogarty, R., Middleton, D., Bingham, J., Epstein, J. H., Rahman, S. A., Hughes, T., Smith, C., Field, H. E., and Daszak, P.
- Abstract
Bats of the genus Pteropus have been identified as the reservoir hosts for the henipaviruses Hendra virus (HeV) and Nipah virus (NiV). The aim of these studies was to assess likely mechanisms for henipaviruses transmission from bats. In a series of experiments, Pteropus bats from Malaysia and Australia were inoculated with NiV and HeV, respectively, by natural routes of infection. Despite an intensive sampling strategy, no NiV was recovered from the Malaysian bats and HeV was reisolated from only one Australian bat; no disease was seen. These experiments suggest that opportunities for henipavirus transmission may be limited; therefore, the probability of a spillover event is low. For spillover to occur, a range of conditions and events must coincide. An alternate assessment framework is required if we are to fully understand how this reservoir host maintains and transmits not only these but all viruses with which it has been associated. Copyright © 2011 by The American Society of Tropical Medicine and Hygiene.
- Published
- 2011
21. Robot RAL-ly international - Promoting STEM in elementary school across international boundaries using remote access technology
- Author
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Maxwell, A., primary, Fogarty, R., additional, Gibbings, P., additional, Noble, K., additional, Kist, A. A., additional, and Midgley, W., additional
- Published
- 2013
- Full Text
- View/download PDF
22. Effect of s-methylmethionine sulphonium chloride on oesophagogastric ulcers in pigs
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Kopinski, J.S., Fogarty, R., McVeigh, J., Kopinski, J.S., Fogarty, R., and McVeigh, J.
- Abstract
Objective: To assess the value of s-methylmethionine sulphonium chloride (SMMSC) (200 mg/kg) on nutritional performance of pigs and as prevention or therapy for oesophagogastric ulcers. Design: Sixty pigs from a high health status herd with continuing oesophagogastric ulcer problems were endoscopically assessed for the presence or absence of oesophagogastric ulcers. Forty-eight pigs were then selected and allocated according to an initial oesophagogastric epithelial (ulcer score) classification to replicated treatment groups in a 2 × 2 factorial design. Weight gain and feed intake were measured over 49 d, after which pigs were killed and stomachs were collected, re-examined and scored for oesophagogastric ulceration. Results: There was no difference over the 49 d in weight gain, feed intake and backfat in pigs with and without SMMSC supplementation between pigs with or without fully developed oesophagogastric ulcers at the start of the study. In pigs with an initially low ulcer score, feeding SMMSC did not prevent further oesophagogastric ulcer development. No significant effect of SMMSC was apparent when final mean oesophagogastric ulcer scores were compared in pigs with existing high ulcer score. However, further analysis of the changes in individual pig oesophagogastric ulcer scores during the experiment showed that the observed reductions in scores of the high ulcer group was significantly different from all other groups. Conclusion: This study has indicated that supplementation of pig diets with SMMSC cannot be justified unless the slight ulcer score improvement observed could be translated to some commercial production advantage such as a reduction in pig mortalities due to oesophagogastric ulcers. This study has further confirmed the benefit of endoscopy as a tool to enable objective assessment of oesophageal gastric health.
- Published
- 2007
23. Religious Inventions in America: New Religious Movements
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Fogarty, R. S., primary
- Published
- 2008
- Full Text
- View/download PDF
24. Effect of s‐methylmethionine sulphonium chloride on oesophagogastric ulcers in pigs
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Kopinski, JS, primary, Fogarty, R, additional, and McVeigh, J, additional
- Published
- 2007
- Full Text
- View/download PDF
25. 133. Ultrafine Particle Counting Method to Track Pressure-Differential Driven Pollutant Transport in Commercial and School Buildings
- Author
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Halvorsen, T., primary, McNattin, S., additional, and Fogarty, R., additional
- Published
- 2001
- Full Text
- View/download PDF
26. Isolation of Haemophilus Taxon “minor group” from pigs
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BLACKALL, PJ, primary, MERCY, AR, additional, BULLER, N, additional, DICKSON, J, additional, FOGARTY, R, additional, and JAMESON, D, additional
- Published
- 1991
- Full Text
- View/download PDF
27. Practical experience with commercial embryo transfer in pigs.
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CAMERON, RDA., DURACK, M., FOGARTY, R., PUTRA, DKH., and McVEIGH, J.
- Published
- 1989
- Full Text
- View/download PDF
28. Real-time sonar beamforming on high-performance distributed computers
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George, A. D., Markwell, J., and Fogarty, R.
- Published
- 2000
- Full Text
- View/download PDF
29. Ten ways to integrate curriculum.
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Fogarty, R.
- Subjects
- *
CURRICULUM , *INTERDISCIPLINARY education , *CURRICULUM enrichment , *TEACHERS , *CURRICULUM planning , *TEACHER-student relationships , *SCHOOL children , *CURRICULUM change - Abstract
Offers models that give school faculties a solid foundation for designing curriculums that help their students make valuable connections while learning. Overview of various models; Focus on moving toward an integrated curriculum; How a faculty can easily work with the models over time to develop an integrated curriculum throughout the school; Role of the teacher.
- Published
- 1991
30. Ways to integrate curriculum.
- Author
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Fogarty, R.
- Subjects
- *
CURRICULUM - Abstract
Describes ten models designed to facilitate the integration of different types of school curriculum. Explorations within single disciplines; Models that cover several disciplines; Models that employ networks of learners; Various views of the curriculum.
- Published
- 1992
31. Fungal melanins and their interactions with metals
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Fogarty, R. V. and Tobin, J. M.
- Published
- 1996
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- View/download PDF
32. The PHF21B gene is associated with major depression and modulates the stress response
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Udo Dannlowski, Julio Licinio, Martin Lewis, Jorge I. Vélez, Aaron Chuah, Chenglong Yu, Stefan R. Bornstein, Rhys Fogarty, Sha Liu, Magdalene C. Jawahar, Gavin A. Huttley, Mauricio Arcos-Burgos, Bernhard T. Baune, V. Arolt, Ma-Li Wong, Wong, ML, Arcos-Burgos, M, Liu, S, Vélez, JI, Yu, C, Baune, BT, Jawahar, MC, Arolt, V, Dannlowski, U, Chuah, A, Huttley, GA, Fogarty, R, Lewis, MD, Bornstein, SR, and Licinio, J
- Subjects
Male ,single nucleotide ,Immobilization stress ,Genome-wide association study ,California ,Sensory perception test ,Missing heritability problem ,Mexican Americans ,Haplotype ,Major depression ,Chronic stress ,Innate immunity ,Phd finger protein 21b ,major depressive disorder (MDD) ,Psychiatry and Mental health ,Clinical trial (topic) ,Cohort ,Trpm2 gene ,Cohort analysis ,Human ,Immigrant ,Ubiquitin protein ligase ,Genotype environment interaction ,Case control study ,Single-nucleotide polymorphism ,Major clinical study ,European ,White People ,Article ,03 medical and health sciences ,whole-genome screening ,Genetics ,Humans ,Animal experiment ,Polymorphism ,Molecular Biology ,Genetic association ,Aged ,Depressive Disorder, Major ,Depressive disorder ,Genetic predisposition ,stress response ,medicine.disease ,030104 developmental biology ,Mood disorders ,Risk factors ,Case-Control Studies ,Phf21b gene ,Whole genome sequencing ,Rat ,Gene expression ,Risk factor ,Mexican american ,0301 basic medicine ,Unclassified drug ,Gene Expression ,major ,Gene locus ,Hippocampus ,Animal tissue ,Risk Factors ,Middle aged ,Priority journal ,Mexican americans ,Middle Aged ,Brain region ,Los Angeles ,Mental stress ,Transient receptor potential channel m2 ,Los angeles ,Major depressive disorder ,Original Article ,Female ,Psychology ,Clinical psychology ,Adult ,Genetic predisposition to disease ,Case-control studies ,Caucasian ,Stress ,Polymorphism, Single Nucleotide ,Heritability ,Cellular and Molecular Neuroscience ,medicine ,Genetic Predisposition to Disease ,Disease severity ,Molecular pathology ,Glutamate receptor ,Nonhuman ,Single nucleotide polymorphism ,Gene ontology ,Genetic variability ,psychological ,Controlled study ,Stress, Psychological ,Genome-Wide Association Study ,European continental ancestry group - Abstract
Major depressive disorder (MDD) affects around 350 million people worldwide; however, the underlying genetic basis remains largely unknown. In this study, we took into account that MDD is a gene-environment disorder, in which stress is a critical component, and used whole-genome screening of functional variants to investigate the â missing heritability' in MDD. Genome-wide association studies (GWAS) using single- A nd multi-locus linear mixed-effect models were performed in a Los Angeles Mexican-American cohort (196 controls, 203 MDD) and in a replication European-ancestry cohort (499 controls, 473 MDD). Our analyses took into consideration the stress levels in the control populations. The Mexican-American controls, comprised primarily of recent immigrants, had high levels of stress due to acculturation issues and the European-ancestry controls with high stress levels were given higher weights in our analysis. We identified 44 common and rare functional variants associated with mild to moderate MDD in the Mexican-American cohort (genome-wide false discovery rate, FDR, less than 0.05), and their pathway analysis revealed that the three top overrepresented Gene Ontology (GO) processes were innate immune response, glutamate receptor signaling and detection of chemical stimulus in smell sensory perception. Rare variant analysis replicated the association of the PHF21B gene in the ethnically unrelated European-ancestry cohort. The TRPM2 gene, previously implicated in mood disorders, may also be considered replicated by our analyses. Whole-genome sequencing analyses of a subset of the cohorts revealed that European-ancestry individuals have a significantly reduced (50%) number of single nucleotide variants compared with Mexican-American individuals, and for this reason the role of rare variants may vary across populations. PHF21b variants contribute significantly to differences in the levels of expression of this gene in several brain areas, including the hippocampus. Furthermore, using an animal model of stress, we found that Phf21b hippocampal gene expression is significantly decreased in animals resilient to chronic restraint stress when compared with non-chronically stressed animals. Together, our results reveal that including stress level data enables the identification of novel rare functional variants associated with MDD. © 2017 Macmillan Publishers Limited.
- Published
- 2017
33. Navigating challenges and workarounds: A qualitative study of healthcare and support workers' perceptions on providing care to people seeking sanctuary.
- Author
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Khanom A, Evans BA, Alanazy W, Couzens L, Fagan L, Fogarty R, John A, Khan T, Kingston MR, Moyo S, Porter A, Richardson G, Rungua G, Williams V, and Snooks H
- Subjects
- Humans, Wales, Female, Male, Attitude of Health Personnel, State Medicine, Adult, Qualitative Research, Health Personnel psychology, Interviews as Topic
- Abstract
Background: Healthcare and support workers play a pivotal role in delivering quality services and support to people seeking sanctuary who have experienced poor physical and mental health linked to previous trauma, relocation and loss of freedoms. However, they often encounter various challenges in their daily work, ranging from communication barriers to resource constraints. This qualitative study seeks to delve into the perspectives of healthcare and support workers' experience of workarounds, employed to overcome barriers to providing care., Aim: This study aims to describe healthcare providers', practitioners' and health and third sector support workers' views on barriers and workarounds to providing care for people seeking sanctuary, to inform policy and practice., Design: A qualitative study was carried out using semi-structured telephone interviews., Setting: This study focused on primary, secondary, community and specialist National Health Service (NHS) support services for people seeking sanctuary in Wales, United Kingdom (2018)., Method: We interviewed 32 healthcare providers, practitioners and support workers employed by primary care and third sector organisations. Our approach involved obtaining verbal informed consent before digitally recording and transcribing all interviews. To analyse the data, we used the Four Levels of Change for Improving Quality model as a guiding framework for interpretation., Results: Our study findings reveal that certain respondents expressed challenges in meeting the needs of people seeking sanctuary; notably, their experience of delivering care differed by care settings. Specifically, those involved in providing specialist NHS care believed that there was room for improvement. Mainstream primary, secondary and community health practitioners faced limitations due to resource constraints and lacked tailored information to address the unique circumstances and needs of sanctuary seekers. To address these gaps, workarounds emerged at both individual and local levels (team/departmental and organisational level). These included establishing informal communication channels between providers, fostering cross service collaboration to fill gaps and adapting existing services to enhance accessibility., Conclusion: Understanding healthcare providers', practitioners' and support workers' perspectives offers invaluable insights into ways to enhance healthcare delivery to sanctuary seekers. Acknowledging challenges and harnessing innovative workarounds can foster a more effective and compassionate service for this vulnerable population., Patient or Public Contribution: The HEAR study actively involved public contributors in the design, delivery and dissemination of the research. Two public contributors (S. M. and G. R.) who had personal experience of seeking asylum served as study co-applicants. They played pivotal roles in shaping the research by participating in its development and securing funding. Alongside other co-applicants, S. M. and G. R. formed the Research Management Group, overseeing study delivery. Their contributions extended to strategic decision-making and specific feedback at critical junctures, including participant recruitment, data collection, analysis and reporting. Additionally, S. M. and G. R. were instrumental in recruiting and supporting a team of peer researchers, enhancing respondent participation among people seeking sanctuary. To facilitate effective public involvement, we provided named contacts for support (A. K. and R. F.), research training, honoraria, reimbursement of expenses and accessible information in line with best practice., (© 2024 The Authors. Health Expectations published by John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
34. Classifying Malignancy in Prostate Glandular Structures from Biopsy Scans with Deep Learning.
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Fogarty R, Goldgof D, Hall L, Lopez A, Johnson J, Gadara M, Stoyanova R, Punnen S, Pollack A, Pow-Sang J, and Balagurunathan Y
- Abstract
Histopathological classification in prostate cancer remains a challenge with high dependence on the expert practitioner. We develop a deep learning (DL) model to identify the most prominent Gleason pattern in a highly curated data cohort and validate it on an independent dataset. The histology images are partitioned in tiles (14,509) and are curated by an expert to identify individual glandular structures with assigned primary Gleason pattern grades. We use transfer learning and fine-tuning approaches to compare several deep neural network architectures that are trained on a corpus of camera images (ImageNet) and tuned with histology examples to be context appropriate for histopathological discrimination with small samples. In our study, the best DL network is able to discriminate cancer grade (GS3/4) from benign with an accuracy of 91%, F
1 -score of 0.91 and AUC 0.96 in a baseline test (52 patients), while the cancer grade discrimination of the GS3 from GS4 had an accuracy of 68% and AUC of 0.71 (40 patients).- Published
- 2023
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35. RNA Sequencing of Lens Capsular Epithelium Implicates Novel Pathways in Pseudoexfoliation Syndrome.
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Mullany S, Marshall H, Zhou T, Thomson D, Schmidt JM, Qassim A, Knight LSW, Hollitt G, Berry EC, Nguyen T, To MS, Dimasi D, Kuot A, Dubowsky J, Fogarty R, Sun M, Chehade L, Kuruvilla S, Supramaniam D, Breen J, Sharma S, Landers J, Lake S, Mills RA, Hassall MM, Chan WO, Klebe S, Souzeau E, Siggs OM, and Craig JE
- Subjects
- Epithelium metabolism, Humans, Sequence Analysis, RNA, Cataract Extraction, Exfoliation Syndrome genetics, Exfoliation Syndrome pathology, Lens, Crystalline metabolism
- Abstract
Purpose: Pseudoexfoliation syndrome (PEX) is a common systemic disease that results in severe and often irreversible vision loss. Despite considerable research effort, PEX remains incompletely understood. This study sought to perform the first RNAseq study in elucidate the pathophysiology of PEX, and contribute a publicly available transcriptomic data resource for future research., Methods: Human ocular lens capsular epithelium samples were collected from 25 patients with PEX and 39 non-PEX controls undergoing cataract surgery. RNA extracted from these specimens was subjected to polyadenylated (mRNA) selection and deep bulk RNA sequencing. Differential expression analysis investigated protein-coding gene transcripts. Exploratory analyses used pathway analysis tools, and curated class- and disease-specific gene sets., Results: Differential expression analysis demonstrated that 2882 genes were differentially expressed according to PEX status. Genes associated with viral gene expression pathways were among the most upregulated, alongside genes encoding ribosomal and mitochondrial respiratory transport chain proteins. Cell adhesion protein transcripts including type 4 collagen subunits were downregulated., Conclusions: This comparative transcriptomic dataset highlights novel and previously recognized pathogenic pathways in PEX and provides the first comprehensive transcriptomic resource, adding an additional layer to build further understanding of PEX pathophysiology.
- Published
- 2022
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36. Asylum seekers' and refugees' experiences of accessing health care: a qualitative study.
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Khanom A, Alanazy W, Couzens L, Evans BA, Fagan L, Fogarty R, John A, Khan T, Kingston MR, Moyo S, Porter A, Rhydderch M, Richardson G, Rungua G, Russell I, and Snooks H
- Abstract
Background: Asylum seekers and refugees (ASRs) often experience poor health in host countries. The United Nations High Commissioner for Refugees (UNHCR) requires hosts to ensure these sanctuary seekers have access to basic health care., Aim: To identify barriers and facilitators that affect access to health care by ASRs in Wales., Design & Setting: Participatory research approach using qualitative focus groups across Wales, which hosts 10 000 refugees., Method: Eight focus groups were undertaken with ASRs, support workers, and volunteers ( n = 57)., Results: Specialist NHS-funded services and grant-aided non-governmental organisations (NGOs) facilitated access to health care, including primary care. Most ASRs understood the role of general practice in providing and coordinating care, but were unaware of out-of-hours services. Reported barriers included: language difficulties, health literacy, unrecognised needs, and the cost of travel to appointments. Participants recognised the importance of mental health, but were disappointed by the state of mental health care. Some feared seeking support for mental health from their GP, and few were aware they had the right to move practice if they were unhappy. Written information about health care was not as accessible to refugees as to asylum seekers (ASs). While some participants read such material before consulting, others struggled to access information when in need. Few participants were aware of health prevention services. Even when they knew about services, such as smoking cessation, these services' difficulty in accommodating ASRs was a barrier., Conclusion: The main barriers identified were: availability of interpreters; knowledge about entitlements; and access to specialist services., (Copyright © 2021, The Authors.)
- Published
- 2021
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37. Influence of scan body design and digital implant analogs on implant replica position in additively manufactured casts.
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Revilla-León M, Fogarty R, Barrington JJ, Zandinejad A, and Özcan M
- Subjects
- Computer-Aided Design, Dental Impression Materials, Dental Impression Technique, Humans, Models, Dental, Dental Implants, Mouth, Edentulous
- Abstract
Statement of Problem: Additive manufacturing (AM) technologies can be used to fabricate definitive casts for implant-supported restorations. However, information regarding the accuracy of the implant replica position on the polymeric AM cast generated with different scan bodies and digital implant replica systems is lacking., Purpose: The purpose of this in vitro study was to compare with a conventional stone cast the linear and angular discrepancies of the implant analog positions in a polymeric AM cast obtained from 3 different scan body and digital implant replica systems., Material and Methods: A partially edentulous maxillary typodont with 3 implant replicas (Implant replica RP Branemark system; Nobel Biocare) was prepared. Two duplicating methods were evaluated: conventional (CNV group) and AM (AM group) procedures. For the CNV group, polyvinyl siloxane open-tray implant impressions (CNV) were made at room temperature (23 °C). The AM group was further divided into the subgroups Elos Medtech, Nt-Trading, and Dynamic Abutment. For the Elos Medtech subgroup, the corresponding scan bodies were placed on each implant, and the typodont was digitized by using a laboratory scanner (E3 scanner; 3Shape A/S). The same procedure was repeated with the remaining subgroups. All the AM polymer casts were fabricated at once by using the same 3D printer (Eden 500V; Stratasys). Ten specimens of each group were obtained (n=10). A coordinate-measuring machine (CMM) was used to measure the position of each implant replica, and distortion was calculated for each system at the x-, y-, and z-axes and 3D distortion measurement (3D=x
2 +y2 +z2 ). The Shapiro-Wilk test revealed that the data were not normally distributed. The Kruskal-Wallis and pairwise Mann-Whitney U tests (α=.05) were used for the analysis., Results: The CNV group presented significantly higher linear discrepancy than the Dynamic Abutment group on the x- and y-axes. On the z-axis, however, the CNV group showed significantly lower linear discrepancy than the Nt-Trading and Dynamic Abutment groups. The 3D linear discrepancy was 12 ±12 μm for the CNV group, 4 ±100 μm for the Elos Medtech group, 8 ±52 μm for the Nt-Trading group, and 5 ±19 μm for the Dynamic Abutment. The CNV group demonstrated a significantly higher angle than the Nt-Trading group but a significantly smaller angle than the Elos Medtech and Dynamic Abutment groups., Conclusions: The AM groups had lower 3D discrepancies than the CNV group. The Dynamic Abutment group had significantly better accuracy for the mesiodistal and buccolingual implant replica positions than the CNV group, but the conventional procedures had significantly better results for the apicocoronal implant replica position. Scan body and digital implant replica design systems only influenced the accuracy of the angular implant replica position on the AM casts., (Copyright © 2019 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
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38. A one-pot-one-reactant synthesis of platinum compounds at the nanoscale.
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Stoppiello CT, Biskupek J, Li ZY, Rance GA, Botos A, Fogarty RM, Bourne RA, Yuan J, Lovelock KRJ, Thompson P, Fay MW, Kaiser U, Chamberlain TW, and Khlobystov AN
- Abstract
The preparation of inorganic nanomaterials with a desired structure and specific properties requires the ability to strictly control their size, shape and composition. A series of chemical reactions with platinum compounds carried out within the 1.5 nm wide channel of single-walled carbon nanotubes (SWNTs) have demonstrated the ability of SWNTs to act as both a very effective reaction vessel and a template for the formation of nanocrystals of platinum di-iodide and platinum di-sulphide, materials that are difficult to synthesise in the form of nanoparticles by traditional synthetic methods. The stepwise synthesis inside nanotubes has enabled the formation of Pt compounds to be monitored at each step of the reaction by aberration-corrected high resolution transmission electron microscopy (AC-HRTEM), verifying the atomic structures of the products, and by an innovative combination of fluorescence-detected X-ray absorption spectroscopy (FD-XAS) and Raman spectroscopy, monitoring the oxidation states of the platinum guest-compounds within the nanotube and the vibrational properties of the host-SWNT, respectively. This coupling of complementary spectroscopies reveals that electron transfer between the guest-compound and the host-SWNT can occur in either direction depending on the composition and structure of the guest. A new approach for nanoscale synthesis in nanotubes developed in this study utilises the versatile coordination chemistry of Pt which has enabled the insertion of the required chemical elements (e.g. metal and halogens or chalcogens) into the nanoreactor in the correct proportions for the controlled formation of PtI
2 and PtS2 with the correct stoichiometry.- Published
- 2017
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39. The PHF21B gene is associated with major depression and modulates the stress response.
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Wong ML, Arcos-Burgos M, Liu S, Vélez JI, Yu C, Baune BT, Jawahar MC, Arolt V, Dannlowski U, Chuah A, Huttley GA, Fogarty R, Lewis MD, Bornstein SR, and Licinio J
- Subjects
- Adult, Case-Control Studies, Female, Gene Expression, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Humans, Los Angeles, Male, Mexican Americans genetics, Middle Aged, Polymorphism, Single Nucleotide genetics, Risk Factors, Stress, Psychological, White People genetics, Depressive Disorder, Major genetics
- Abstract
Major depressive disorder (MDD) affects around 350 million people worldwide; however, the underlying genetic basis remains largely unknown. In this study, we took into account that MDD is a gene-environment disorder, in which stress is a critical component, and used whole-genome screening of functional variants to investigate the 'missing heritability' in MDD. Genome-wide association studies (GWAS) using single- and multi-locus linear mixed-effect models were performed in a Los Angeles Mexican-American cohort (196 controls, 203 MDD) and in a replication European-ancestry cohort (499 controls, 473 MDD). Our analyses took into consideration the stress levels in the control populations. The Mexican-American controls, comprised primarily of recent immigrants, had high levels of stress due to acculturation issues and the European-ancestry controls with high stress levels were given higher weights in our analysis. We identified 44 common and rare functional variants associated with mild to moderate MDD in the Mexican-American cohort (genome-wide false discovery rate, FDR, <0.05), and their pathway analysis revealed that the three top overrepresented Gene Ontology (GO) processes were innate immune response, glutamate receptor signaling and detection of chemical stimulus in smell sensory perception. Rare variant analysis replicated the association of the PHF21B gene in the ethnically unrelated European-ancestry cohort. The TRPM2 gene, previously implicated in mood disorders, may also be considered replicated by our analyses. Whole-genome sequencing analyses of a subset of the cohorts revealed that European-ancestry individuals have a significantly reduced (50%) number of single nucleotide variants compared with Mexican-American individuals, and for this reason the role of rare variants may vary across populations. PHF21b variants contribute significantly to differences in the levels of expression of this gene in several brain areas, including the hippocampus. Furthermore, using an animal model of stress, we found that Phf21b hippocampal gene expression is significantly decreased in animals resilient to chronic restraint stress when compared with non-chronically stressed animals. Together, our results reveal that including stress level data enables the identification of novel rare functional variants associated with MDD.
- Published
- 2017
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40. Genetic Association at the 9p21 Glaucoma Locus Contributes to Sex Bias in Normal-Tension Glaucoma.
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Ng SK, Burdon KP, Fitzgerald JT, Zhou T, Fogarty R, Souzeau E, Landers J, Mills RA, Casson RJ, Ridge B, Graham SL, Hewitt AW, Mackey DA, Healey PR, Wang JJ, Mitchell P, MacGregor S, and Craig JE
- Subjects
- Adult, Aged, Australia, Female, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, New Zealand, Risk Factors, Sex Factors, Chromosomes, Human, Pair 9 genetics, Genetic Predisposition to Disease genetics, Low Tension Glaucoma genetics, Polymorphism, Single Nucleotide
- Abstract
Purpose: Many genome-wide association studies have identified common single nucleotide polymorphisms (SNPs) at the 9p21 glaucoma locus (CDKN2B/CDKN2B-AS1) to be significantly associated with primary open-angle glaucoma (POAG), with association being stronger in normal tension glaucoma (NTG) and advanced glaucoma. We aimed to determine whether any observed differences in genetic association at the 9p21 locus are influenced by sex., Methods: Sex was assessed as a risk factor for POAG for 2241 glaucoma participants from the Australian and New Zealand Registry of Advanced Glaucoma, the Glaucoma Inheritance Study in Tasmania, and the Flinders Medical Centre. A total of 3176 controls were drawn from the Blue Mountains Eye Study and South Australia: 1523 advanced POAG and 718 nonadvanced POAG cases were genotyped along with 3176 controls. We selected 13 SNPs at the 9p21 locus, and association results were subanalyszd by sex for high-tension glaucoma (HTG) and NTG. Odds ratios (ORs) between sexes were compared., Results: A sex bias was present within advanced NTG cases (57.1% female versus 42.9% male, P = 0.0026). In all POAG cases, the strongest associated SNP at 9p21 was rs1063192 (OR, 1.43; P = 4 × 10-18). This association was stronger in females (OR, 1.5; P = 5 × 10-13) than in males (OR, 1.35; P = 7 × 10-7), with a statistically significant difference in female to male OR comparison (P = 1.0 × 10-2). An NTG to HTG subanalysis yielded statistically significant results only in females (OR, 1.63; P = 1.5 × 10-4) but not in males (OR, 1.15; P = 2.8 × 10-1), with a statistically significant difference in female to male OR comparison (P = 1.4 × 10-4)., Conclusions: This study demonstrated that female sex is a risk factor for developing advanced NTG. The stronger genetic signals at the 9p21 locus among females may contribute at least in part to the observed sex bias for NTG.
- Published
- 2016
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41. Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma.
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Gharahkhani P, Burdon KP, Fogarty R, Sharma S, Hewitt AW, Martin S, Law MH, Cremin K, Bailey JNC, Loomis SJ, Pasquale LR, Haines JL, Hauser MA, Viswanathan AC, McGuffin P, Topouzis F, Foster PJ, Graham SL, Casson RJ, Chehade M, White AJ, Zhou T, Souzeau E, Landers J, Fitzgerald JT, Klebe S, Ruddle JB, Goldberg I, Healey PR, Mills RA, Wang JJ, Montgomery GW, Martin NG, RadfordSmith G, Whiteman DC, Brown MA, Wiggs JL, Mackey DA, Mitchell P, MacGregor S, and Craig JE
- Subjects
- ATP Binding Cassette Transporter 1 metabolism, Aged, Aged, 80 and over, Australia, Cohort Studies, Female, Gene Expression, Gene Frequency, Genotype, Glaucoma, Open-Angle metabolism, Humans, Immunoblotting, Male, Meta-Analysis as Topic, Microfilament Proteins metabolism, Middle Aged, Reverse Transcriptase Polymerase Chain Reaction, Risk Factors, United States, ATP Binding Cassette Transporter 1 genetics, Genetic Predisposition to Disease genetics, Glaucoma, Open-Angle genetics, Hydro-Lyases genetics, Microfilament Proteins genetics, Polymorphism, Single Nucleotide
- Abstract
Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10(-19)), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10(-10)) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10(-10)). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.
- Published
- 2014
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42. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma.
- Author
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Hysi PG, Cheng CY, Springelkamp H, Macgregor S, Bailey JNC, Wojciechowski R, Vitart V, Nag A, Hewitt AW, Höhn R, Venturini C, Mirshahi A, Ramdas WD, Thorleifsson G, Vithana E, Khor CC, Stefansson AB, Liao J, Haines JL, Amin N, Wang YX, Wild PS, Ozel AB, Li JZ, Fleck BW, Zeller T, Staffieri SE, Teo YY, Cuellar-Partida G, Luo X, Allingham RR, Richards JE, Senft A, Karssen LC, Zheng Y, Bellenguez C, Xu L, Iglesias AI, Wilson JF, Kang JH, van Leeuwen EM, Jonsson V, Thorsteinsdottir U, Despriet DDG, Ennis S, Moroi SE, Martin NG, Jansonius NM, Yazar S, Tai ES, Amouyel P, Kirwan J, van Koolwijk LME, Hauser MA, Jonasson F, Leo P, Loomis SJ, Fogarty R, Rivadeneira F, Kearns L, Lackner KJ, de Jong PTVM, Simpson CL, Pennell CE, Oostra BA, Uitterlinden AG, Saw SM, Lotery AJ, Bailey-Wilson JE, Hofman A, Vingerling JR, Maubaret C, Pfeiffer N, Wolfs RCW, Lemij HG, Young TL, Pasquale LR, Delcourt C, Spector TD, Klaver CCW, Small KS, Burdon KP, Stefansson K, Wong TY, Viswanathan A, Mackey DA, Craig JE, Wiggs JL, van Duijn CM, Hammond CJ, and Aung T
- Subjects
- ABO Blood-Group System genetics, ATP Binding Cassette Transporter 1 genetics, Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, Pair 3 genetics, Chromosomes, Human, Pair 9 genetics, Cohort Studies, Female, Fibronectins genetics, Genotype, Glaucoma, Open-Angle genetics, Humans, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Young Adult, Genetic Loci genetics, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Glaucoma genetics, Intraocular Pressure genetics
- Abstract
Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 × 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 × 10(-11) for rs2472493 near ABCA1 and P = 6.39 × 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 10(-11) for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.
- Published
- 2014
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43. Genetic study of diabetic retinopathy: recruitment methodology and analysis of baseline characteristics.
- Author
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Kaidonis G, Abhary S, Daniell M, Gillies M, Fogarty R, Petrovsky N, Jenkins A, Essex R, Chang JH, Pal B, Hewitt AW, Burdon KP, and Craig JE
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Body Mass Index, Case-Control Studies, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 2 complications, Female, Fluorescein Angiography, Gene-Environment Interaction, Genetic Predisposition to Disease, Glycated Hemoglobin metabolism, Humans, Male, Middle Aged, Young Adult, Diabetic Retinopathy genetics, Genome-Wide Association Study, Macular Edema genetics, Patient Selection
- Abstract
Background: Diabetic retinopathy (DR) is a blinding disease of increasing prevalence that is caused by a complex interplay of genetic and environmental factors. Here we describe the patient recruitment methodology, case and control definitions, and clinical characteristics of a study sample to be used for genome-wide association analysis to detect genetic risk variants of DR., Methods: One thousand six hundred sixty-nine participants with either type 1 (T1) or type 2 (T2) diabetes mellitus (DM) aged 18 to 95 years were recruited in Australian hospital clinics. Individuals with T2DM had disease duration of at least 5 years and were taking oral hypoglycaemic medication, and/or insulin therapy. Participants underwent ophthalmic examination. Medical history and biochemistry results were collected. Venous blood was obtained for genetic analysis., Results: Six hundred eighty-three diabetic cases (178 T1DM and 505 T2DM participants) with sight-threatening DR, defined as severe non-proliferative DR, proliferative DR or diabetic macular oedema were included in this analysis. Eight hundred twelve individuals with DM but no DR or minimal non-proliferative DR were recruited as controls (191 with T1DM and 621 with T2DM). The presence of sight-threatening DR was significantly correlated with DM duration, hypertension, nephropathy, neuropathy, HbA1C and body mass index. Diabetic macular oedema was associated with T2DM (P < 0.001), whereas proliferative DR was associated with T1DM (P < 0.001)., Conclusions: Adoption of a case-control study design involving extremes of the DR phenotype makes this a suitable cohort, for a well-powered genome-wide association study to detect genetic risk variants for DR., (© 2013 Royal Australian and New Zealand College of Ophthalmologists.)
- Published
- 2014
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44. Phonetic measures of reduced tongue movement correlate with negative symptom severity in hospitalized patients with first-episode schizophrenia-spectrum disorders.
- Author
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Covington MA, Lunden SL, Cristofaro SL, Wan CR, Bailey CT, Broussard B, Fogarty R, Johnson S, Zhang S, and Compton MT
- Subjects
- Adult, Female, Hospitalization, Humans, Male, Psychiatric Status Rating Scales, Psychotic Disorders diagnosis, Retrospective Studies, Schizophrenia diagnosis, Severity of Illness Index, Video Recording, Young Adult, Movement Disorders diagnosis, Movement Disorders etiology, Movement Disorders pathology, Phonetics, Psychotic Disorders complications, Schizophrenia complications, Schizophrenic Psychology, Tongue physiopathology
- Abstract
Background: Aprosody, or flattened speech intonation, is a recognized negative symptom of schizophrenia, though it has rarely been studied from a linguistic/phonological perspective. To bring the latest advances in computational linguistics to the phenomenology of schizophrenia and related psychotic disorders, a clinical first-episode psychosis research team joined with a phonetics/computational linguistics team to conduct a preliminary, proof-of-concept study., Methods: Video recordings from a semi-structured clinical research interview were available from 47 first-episode psychosis patients. Audio tracks of the video recordings were extracted, and after review of quality, 25 recordings were available for phonetic analysis. These files were de-noised and a trained phonologist extracted a 1-minute sample of each patient's speech. WaveSurfer 1.8.5 was used to create, from each speech sample, a file of formant values (F0, F1, F2, where F0 is the fundamental frequency and F1 and F2 are resonance bands indicating the moment-by-moment shape of the oral cavity). Variability in these phonetic indices was correlated with severity of Positive and Negative Syndrome Scale negative symptom scores using Pearson correlations., Results: A measure of variability of tongue front-to-back position-the standard deviation of F2-was statistically significantly correlated with the severity of negative symptoms (r=-0.446, p=0.03)., Conclusion: This study demonstrates a statistically significant and meaningful correlation between negative symptom severity and phonetically measured reductions in tongue movements during speech in a sample of first-episode patients just initiating treatment. Further studies of negative symptoms, applying computational linguistics methods, are warranted., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2012
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45. Pteropid bats are confirmed as the reservoir hosts of henipaviruses: a comprehensive experimental study of virus transmission.
- Author
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Halpin K, Hyatt AD, Fogarty R, Middleton D, Bingham J, Epstein JH, Rahman SA, Hughes T, Smith C, Field HE, and Daszak P
- Subjects
- Animals, Australia, Female, Genome, Viral, Hendra Virus genetics, Hendra Virus immunology, Malaysia, Nipah Virus genetics, Nipah Virus immunology, Pregnancy, Chiroptera classification, Chiroptera virology, Disease Reservoirs veterinary, Hendra Virus isolation & purification, Henipavirus Infections transmission, Nipah Virus isolation & purification
- Abstract
Bats of the genus Pteropus have been identified as the reservoir hosts for the henipaviruses Hendra virus (HeV) and Nipah virus (NiV). The aim of these studies was to assess likely mechanisms for henipaviruses transmission from bats. In a series of experiments, Pteropus bats from Malaysia and Australia were inoculated with NiV and HeV, respectively, by natural routes of infection. Despite an intensive sampling strategy, no NiV was recovered from the Malaysian bats and HeV was reisolated from only one Australian bat; no disease was seen. These experiments suggest that opportunities for henipavirus transmission may be limited; therefore, the probability of a spillover event is low. For spillover to occur, a range of conditions and events must coincide. An alternate assessment framework is required if we are to fully understand how this reservoir host maintains and transmits not only these but all viruses with which it has been associated.
- Published
- 2011
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46. Homozygous mutations in PXDN cause congenital cataract, corneal opacity, and developmental glaucoma.
- Author
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Khan K, Rudkin A, Parry DA, Burdon KP, McKibbin M, Logan CV, Abdelhamed ZI, Muecke JS, Fernandez-Fuentes N, Laurie KJ, Shires M, Fogarty R, Carr IM, Poulter JA, Morgan JE, Mohamed MD, Jafri H, Raashid Y, Meng N, Piseth H, Toomes C, Casson RJ, Taylor GR, Hammerton M, Sheridan E, Johnson CA, Inglehearn CF, Craig JE, and Ali M
- Subjects
- Animals, Base Sequence, Cataract pathology, Cornea metabolism, Cornea pathology, Corneal Opacity pathology, Extracellular Matrix Proteins chemistry, Extracellular Matrix Proteins metabolism, Glaucoma pathology, Humans, Mice, Microscopy, Fluorescence, Molecular Sequence Data, Mutation genetics, Pedigree, Peroxidase chemistry, Peroxidase metabolism, Sequence Analysis, DNA, Peroxidasin, Cataract genetics, Corneal Opacity genetics, Extracellular Matrix Proteins genetics, Genetic Predisposition to Disease genetics, Glaucoma genetics, Models, Molecular, Peroxidase genetics
- Abstract
Anterior segment dysgenesis describes a group of heterogeneous developmental disorders that affect the anterior chamber of the eye and are associated with an increased risk of glaucoma. Here, we report homozygous mutations in peroxidasin (PXDN) in two consanguineous Pakistani families with congenital cataract-microcornea with mild to moderate corneal opacity and in a consanguineous Cambodian family with developmental glaucoma and severe corneal opacification. These results highlight the diverse ocular phenotypes caused by PXDN mutations, which are likely due to differences in genetic background and environmental factors. Peroxidasin is an extracellular matrix-associated protein with peroxidase catalytic activity, and we confirmed localization of the protein to the cornea and lens epithelial layers. Our findings imply that peroxidasin is essential for normal development of the anterior chamber of the eye, where it may have a structural role in supporting cornea and lens architecture as well as an enzymatic role as an antioxidant enzyme in protecting the lens, trabecular meshwork, and cornea against oxidative damage., (Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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47. Gene expression microarray analysis of early oxygen-induced retinopathy in the rat.
- Author
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Tea M, Fogarty R, Brereton HM, Michael MZ, Van der Hoek MB, Tsykin A, Coster DJ, and Williams KA
- Abstract
Different inbred strains of rat differ in their susceptibility to oxygen-induced retinopathy (OIR), an animal model of human retinopathy of prematurity. We examined gene expression in Sprague-Dawley (susceptible) and Fischer 344 (resistant) neonatal rats after 3 days exposure to cyclic hyperoxia or room air, using Affymetrix rat Genearrays. False discovery rate analysis was used to identify differentially regulated genes. Such genes were then ranked by fold change and submitted to the online database, DAVID. The Sprague-Dawley list returned the term "response to hypoxia," absent from the Fischer 344 output. Manual analysis indicated that many genes known to be upregulated by hypoxia-inducible factor-1alpha were downregulated by cyclic hyperoxia. Quantitative real-time RT-PCR analysis of Egln3, Bnip3, Slc16a3, and Hk2 confirmed the microarray results. We conclude that combined methodologies are required for adequate dissection of the pathophysiology of strain susceptibility to OIR in the rat. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12177-009-9041-7) contains supplementary material, which is available to authorized users.
- Published
- 2009
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48. Henipavirus susceptibility to environmental variables.
- Author
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Fogarty R, Halpin K, Hyatt AD, Daszak P, and Mungall BA
- Subjects
- Animals, Chiroptera virology, Chlorocebus aethiops, Desiccation, Fruit chemistry, Fruit virology, Half-Life, Hendra Virus growth & development, Henipavirus Infections transmission, Horse Diseases virology, Horses virology, Humans, Hydrogen-Ion Concentration, Nipah Virus growth & development, Temperature, Urine chemistry, Urine virology, Vero Cells, Virus Cultivation, Zoonoses, Hendra Virus physiology, Henipavirus Infections veterinary, Henipavirus Infections virology, Nipah Virus physiology
- Abstract
The routes of henipavirus transmission between hosts are poorly understood. The purpose of this study was to measure the persistence of henipaviruses under various environmental conditions and thereby gain an insight into likely mechanisms of transmission. Henipaviruses survived for more than 4 days at 22 degrees C in pH-neutral fruit bat urine but were sensitive to higher temperatures and pH changes. On mango flesh, survival time varied depending on temperature and fruit pH, ranging from 2h to more than 2 days. Desiccation of viruses substantially reduced survival time to less than 2h. The sensitivity of henipaviruses to pH, temperature and desiccation indicates a need for close contact between hosts for transmission to occur, although under ideal conditions henipaviruses can persist for extended periods facilitating vehicle-borne transmission.
- Published
- 2008
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49. Antisense inhibition of IGF receptor expression in HaCaT keratinocytes: a model for antisense strategies in keratinocytes.
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White PJ, Fogarty RD, Werther GA, and Wraight CJ
- Subjects
- Cell Line, Transformed, Cell Nucleus drug effects, Cell Nucleus metabolism, Cytoplasm metabolism, Drug Carriers, Growth Inhibitors pharmacology, Humans, Keratinocytes cytology, Keratinocytes drug effects, Microscopy, Confocal, Microscopy, Fluorescence, Models, Biological, Oligodeoxyribonucleotides, Antisense chemistry, Oligodeoxyribonucleotides, Antisense metabolism, Phosphatidylethanolamines chemistry, Phosphatidylethanolamines metabolism, RNA, Messenger antagonists & inhibitors, RNA, Messenger biosynthesis, RNA, Messenger metabolism, Receptor, IGF Type 1 genetics, Trypan Blue, Keratinocytes metabolism, Oligodeoxyribonucleotides, Antisense pharmacology, Receptor, IGF Type 1 antagonists & inhibitors, Receptor, IGF Type 1 biosynthesis
- Abstract
Antisense strategies targeting skin conditions are attractive in concept, with a number of possible pathologic conditions, such a psoriasis, apparently suitable for such an approach. Because in vitro screening of candidate sequences is usually desirable, we have attempted to use a range of new generation cationic lipids to produce significant antisense oligodeoxynucleotide (ODN) uptake in an immortalized keratinocyte cell line (HaCaT). A large number of commercially available lipids were screened for the ability to induce nuclear ODN localization: Tfx-50, Tfx-20, Tfx-10, Superfect, Cytofectin GSV, Perfect lipids 1-8, Lipofectin, and Lipofectamine. All lipids were used at a range of concentrations (1-20 microg/ml) and with a range of ODN concentrations (1-1000) nM). Of all lipids used, only Cytofectin GSV and Superfect produced significant (>30% of cells) levels of nuclear positive cells, with Superfect also producing significant toxicity at the effective concentration used. Only two treatments produced a significant reduction in target mRNA: insulin-like growth factor-1 receptor (IGF-1R)-ODN 64 complexed with Cytofectin GSV (27.1% +/- 3.5% of IGF-1R mRNA in untreated cells,p < 0.01) and ODN 64 complexed with 10 microg/ml Lipofectin (62.2% +/- 3.4% of IGF-1R mRNA in untreated cells, p < 0.05). Only one treatment, ODN 64 complexed with Cytofectin GSV, produced a reduction in cell growth and survival as assessed by amido black assay. These results demonstrate that in HaCaT keratinocytes, Cytofectin GSV alone of all commercially available cationic lipids was effective in delivering antisense ODN into cell nuclei such that a profound antisense effect could be demonstrated.
- Published
- 2000
- Full Text
- View/download PDF
50. Reversal of epidermal hyperproliferation in psoriasis by insulin-like growth factor I receptor antisense oligonucleotides.
- Author
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Wraight CJ, White PJ, McKean SC, Fogarty RD, Venables DJ, Liepe IJ, Edmondson SR, and Werther GA
- Subjects
- Animals, Humans, Hyperplasia, Injections, Intradermal, Keratinocytes cytology, Keratinocytes drug effects, Mice, Mice, Inbred CBA, Mice, Nude, RNA, Messenger isolation & purification, Receptor, IGF Type 1 analysis, Skin Transplantation, Transplantation, Heterologous, Epidermis pathology, Oligonucleotides, Antisense therapeutic use, Psoriasis drug therapy, Receptor, IGF Type 1 genetics
- Abstract
Epidermal hyperplasia is a key feature of the common skin disorder psoriasis. Stimulation of epidermal keratinocytes by insulin-like growth factor I (IGF-I) is essential for cell division, and increased sensitivity to IGF-I may occur in psoriasis. We hypothesized that inhibition of IGF-I receptor expression in the psoriasis lesion would reverse psoriatic epidermal hyperplasia by slowing the rate of keratinocyte cell division. Here we report the use of C5-propynyl-dU,dC-phosphorothioate antisense oligonucleotides to inhibit IGF-I receptor expression in keratinocytes. We identified several inhibitory antisense oligonucleotides and demonstrated IGF-I receptor inhibition in vitro through an mRNA targeting mechanism. Repeated injection of these oligonucleotides into human psoriasis lesions, grafted onto nude mice, caused a dramatic normalization of the hyperplastic epidermis. The findings indicate that IGF-I receptor stimulation is a rate-limiting step in psoriatic epidermal hyperplasia and that IGF-I receptor targeting by cutaneous administration of antisense oligonucleotides forms the basis of a potential new psoriasis therapy.
- Published
- 2000
- Full Text
- View/download PDF
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