Beck, D, Brandl, MB, Boelen, L, Unnikrishnan, A, Pimanda, JE & Wong, JWH 2012, 'Signal analysis for genome-wide maps of histone modifications measured by ChIP-seq', Bioinformatics, vol. 28, no. 8, pp. 1062-1069.
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Abstract Motivation: Chromatin structure, including post-translational modifications of histones, regulates gene expression, alternative splicing and cell identity. ChIP-seq is an increasingly used assay to study chromatin function. However, tools for downstream bioinformatics analysis are limited and are only based on the evaluation of signal intensities. We reasoned that new methods taking into account other signal characteristics such as peak shape, location and frequencies might reveal new insights into chromatin function, particularly in situation where differences in read intensities are subtle. Results: We introduced an analysis pipeline, based on linear predictive coding (LPC), which allows the capture and comparison of ChIP-seq histone profiles. First, we show that the modeled signal profiles distinguish differentially expressed genes with comparable accuracy to signal intensities. The method was robust against parameter variations and performed well up to a signal-to-noise ratio of 0.55. Additionally, we show that LPC profiles of activating and repressive histone marks cluster into distinct groups and can be used to predict their function. Availability and implementation: http://www.cancerresearch.unsw.edu.au/crcweb.nsf/page/LPCHP A Matlab implementation along with usage instructions and an example input file are available from: http://www.cancerresearch.unsw.edu.au/crcweb.nsf/page/LPCHP Contact: d.beck@student.unsw.edu.au; jpimanda@unsw.edu.au; jason.wong@unsw.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.
Carroll, AP, Tran, N, Tooney, PA & Cairns, MJ 2012, 'Alternative mRNA fates identified in microRNA-associated transcriptome analysis', BMC Genomics, vol. 13, no. 1, pp. 1-19.
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AbstractBackgroundMicroRNA (miRNA) are small non-coding RNA molecules which function as nucleic acid-based specificity factors in the universal RNA binding complex known as the RNA induced silencing complex (RISC). In the canonical gene-silencing pathway, these activated RISC particles are associated with RNA decay and gene suppression, however, there is evidence to suggest that in some circumstances they may also stabilise their target RNA and even enhance translation. To further explore the role of miRNA in this context, we performed a genome-wide expression analysis to investigate the molecular consequences of bidirectional modulation of the disease-associated miRNAs miR-181b and miR-107 in multiple human cell lines.ResultsThis data was subjected to pathways analysis and correlated against miRNA targets predicted through seed region homology. This revealed a large number of both conserved and non-conserved miRNA target genes, a selection of which were functionally validated through reporter gene assays. Contrary to expectation we also identified a significant proportion of predicted target genes with both conserved and non-conserved recognition elements that were positively correlated with the modulated miRNA. Finally, a large proportion of miR-181b associated genes devoid of the corresponding miRNA recognition element, were enriched with binding motifs for the E2F1 transcription factor, which is encoded by a miR-181b target gene.ConclusionsThese findings suggest that miRNA regulate target genes directly through interactions with both conserved and non-conserved target recognition elements, and can lead to both a decrease and increase in transcript abundance. They also multiply their influence through interaction with transcription factor genes exemplified by ...
Chan, MY, Nguyen, ND, Center, JR, Eisman, JA & Nguyen, TV 2012, 'Absolute Fracture-Risk Prediction by a Combination of Calcaneal Quantitative Ultrasound and Bone Mineral Density', Calcified Tissue International, vol. 90, no. 2, pp. 128-136.
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Abstract Quantitative ultrasound measurement (QUS) and bone mineral density (BMD) have each been shown to predict fracture risk in women. The present study examined whether a combination of QUS and BMD could improve the predictive accuracy of fracture risk. This is a population- based prospective study which involved 454 women and 445 men aged 6289 years. Femoral neck BMD (FNBMD) was measured by DXA and calcaneal QUS was measured as broadband ultrasound attenuation (BUA) by a CUBA sonometer. Fragility fracture was ascertained by X-ray reports during the follow-up period, which took place between mid-1989 and 2009. During the follow-up period (median 13 years, range 1115), 75 men and 154 women sustained a fragility fracture. In women, the model with FNBMD and BUA had a higher AUC compared to that without BUA (0.73 vs. 0.71 for any fracture, 0.81 vs. 0.77 for hip fracture, and 0.72 vs. 0.70 for vertebral fracture). Reclassification analysis yielded a total net reclassification improvement of 7.3%, 11.1%, and 5.2% for any, hip, and vertebral fractures, respectively. For men, the addition of BUA to FNBMD did not improve the predictive power for any, hip, or vertebral fracture. These results suggest that calcaneal QUS is an independent predictor of fracture risk and that a combination of QUS and BMD measurement could improve the predictive accuracy of fracture risk in elderly women.
Ciampi, S, Guan, B, Darwish, NA, Zhu, Y, Reece, PJ & Justin Gooding, J 2012, 'A multimodal optical and electrochemical device for monitoring surface reactions: redox active surfaces in porous silicon Rugate filters', Physical Chemistry Chemical Physics, vol. 14, no. 47, pp. 16433-16433.
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Deng, W & Goldys, EM 2012, 'Plasmonic Approach to Enhanced Fluorescence for Applications in Biotechnology and the Life Sciences', Langmuir, vol. 28, no. 27, pp. 10152-10163.
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Ellison, P, Tipper, JL, Jennings, LM & Fisher, J 2012, 'Biological activity of polyethylene wear debris produced in the patellofemoral joint', Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, vol. 226, no. 5, pp. 377-383.
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Polyethylene wear is considered a threat to the long term survival of total knee replacements. The aim of this study was to investigate the contribution that resurfacing the patella makes to wear debris-induced osteolysis following total knee replacement. Ultra-high molecular-weight polyethylene wear particles were isolated from simulator lubricant. Particle shape, size, and volume distributions were recorded allowing the osteolytic potential of the wear debris produced in the patellofemoral joint to be estimated using the concept of specific biological activity and functional biological activity. Values were compared with those reported for the tibiofemoral joint. Specific biological activity for the patellofemoral joint was not significantly different from the values for the tibiofemoral joint of total knee replacement devices, and therefore, has a similar potential to stimulate osteolytic cytokine release from macrophages. Functional biological activity was significantly lower for the patellofemoral joint compared with the tibiofemoral joint. Functional biological activity was significantly lower for the patellofemoral joint compared with the fixed bearing and rotating platform total knee replacement devices. However, as patellar resurfacing is commonly fitted as part of a total knee replacement system, this results in a 20% increase in overall functional biological activity for the system. Therefore, implanting a patellar resurfacing will increase the potential for osteolysis in the knee.
Engels, B, Jannot, G, Remenyi, J, Simard, MJ & Hutvagner, G 2012, 'Polypyrimidine Tract Binding Protein (hnRNP I) Is Possibly a Conserved Modulator of miRNA-Mediated Gene Regulation', PLoS ONE, vol. 7, no. 3, pp. e33144-e33144.
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MiRNAs can regulate gene expression through versatile mechanisms that result in increased or decreased expression of the targeted mRNA and it could effect the expression of thousands of protein in a particular cell. An increasing body of evidence suggest that miRNAs action can be modulated by proteins that bind to the same 3′UTRs that are targeted by miRNAs, suggesting that other factors apart from miRNAs and their target sites determine miRNA-modulation of gene expression. We applied an affinity purification protocol using biotinylated let-7 miRNA inhibitor to isolate proteins that are involved in let-7 mediated gene regulation that resulted in an affinity purification of Polypyrimidine Tract Binding protein (PTB). Here we show that PTB interacts with miRNAs and human Argonaute 2 (hAgo2) through RNA as well as identified potential mammalian cellular targets that are co-regulated by PTB and hAgo2. In addition, using genetic approach, we have demonstrated that PTB genetically interacts with Caenorhabditis elegans let-7 indicating a conserved role for PTB in miRNA-mediated gene regulation. © 2012 Engels et al.
Estrada, K, Styrkarsdottir, U, Evangelou, E, Hsu, Y-H, Duncan, EL, Ntzani, EE, Oei, L, Albagha, OME, Amin, N, Kemp, JP, Koller, DL, Li, G, Liu, C-T, Minster, RL, Moayyeri, A, Vandenput, L, Willner, D, Xiao, S-M, Yerges-Armstrong, LM, Zheng, H-F, Alonso, N, Eriksson, J, Kammerer, CM, Kaptoge, SK, Leo, PJ, Thorleifsson, G, Wilson, SG, Wilson, JF, Aalto, V, Alen, M, Aragaki, AK, Aspelund, T, Center, JR, Dailiana, Z, Duggan, DJ, Garcia, M, Garcia-Giralt, N, Giroux, S, Hallmans, G, Hocking, LJ, Husted, LB, Jameson, KA, Khusainova, R, Kim, GS, Kooperberg, C, Koromila, T, Kruk, M, Laaksonen, M, Lacroix, AZ, Lee, SH, Leung, PC, Lewis, JR, Masi, L, Mencej-Bedrac, S, Nguyen, TV, Nogues, X, Patel, MS, Prezelj, J, Rose, LM, Scollen, S, Siggeirsdottir, K, Smith, AV, Svensson, O, Trompet, S, Trummer, O, van Schoor, NM, Woo, J, Zhu, K, Balcells, S, Brandi, ML, Buckley, BM, Cheng, S, Christiansen, C, Cooper, C, Dedoussis, G, Ford, I, Frost, M, Goltzman, D, González-Macías, J, Kähönen, M, Karlsson, M, Khusnutdinova, E, Koh, J-M, Kollia, P, Langdahl, BL, Leslie, WD, Lips, P, Ljunggren, Ö, Lorenc, RS, Marc, J, Mellström, D, Obermayer-Pietsch, B, Olmos, JM, Pettersson-Kymmer, U, Reid, DM, Riancho, JA, Ridker, PM, Rousseau, F, lagboom, PES, Tang, NLS, Urreizti, R, Van Hul, W, Viikari, J, Zarrabeitia, MT, Aulchenko, YS, Castano-Betancourt, M, Grundberg, E, Herrera, L, Ingvarsson, T, Johannsdottir, H, Kwan, T, Li, R, Luben, R, Medina-Gómez, C, Th Palsson, S, Reppe, S, Rotter, JI, Sigurdsson, G, van Meurs, JBJ, Verlaan, D, Williams, FMK, Wood, AR, Zhou, Y, Gautvik, KM, Pastinen, T, Raychaudhuri, S, Cauley, JA, Chasman, DI, Clark, GR, Cummings, SR, Danoy, P, Dennison, EM, Eastell, R, Eisman, JA, Gudnason, V, Hofman, A, Jackson, RD, Jones, G, Jukema, JW, Khaw, K-T, Lehtimäki, T, Liu, Y, Lorentzon, M, McCloskey, E, Mitchell, BD, Nandakumar, K, Nicholson, GC, Oostra, BA, Peacock, M, Pols, HAP, Prince, RL, Raitakari, O, Reid, IR, Robbins, J, Sambrook, PN, Sham, PC, Shuldiner, AR, Tylavsky, FA, van Duijn, CM, Wareham, NJ, Cupples, LA, Econs, MJ, Evans, DM, Harris, TB, Kung, AWC, Psaty, BM, Reeve, J, Spector, TD, Streeten, EA, Zillikens, MC, Thorsteinsdottir, U, Ohlsson, C, Karasik, D, Richards, JB, Brown, MA, Stefansson, K, Uitterlinden, AG, Ralston, SH, Ioannidis, JPA, Kiel, DP & Rivadeneira, F 2012, 'Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture', Nature Genetics, vol. 44, no. 5, pp. 491-501.
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Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10 -8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10 -4, Bonferroni corrected), of which six reached P < 5 × 10 -8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility. © 2012 Nature America, Inc. All rights reserved.
Fisher, J, Al Hajjar, M, Williams, S, Tipper, J, Ingham, E & Jennings, L 2012, '(v) Simulation and measurement of wear in metal-on-metal bearings in vitro- understanding the reasons for increased wear', Orthopaedics and Trauma, vol. 26, no. 4, pp. 253-258.
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A new Stratified Approach For Enhanced Reliability (SAFER) pre-clinical simulation testing of joint prostheses has been described in a preceding paper in this volume. The application of SAFER in vitro simulation and testing to metal-on-metal bearings is described in this review paper. The review aims to provide further understanding of the reasons for, and causes of, increased wear in metal-on-metal hips in a proportion of patients. Variation in positioning (mal-positioning) of the head and cup in hip prostheses results in the head contacting the rim of the cup and producing increased wear. Variation in both translational and rotational positioning has been investigated. Variation in translational positioning of the centres of the head and cup, which is not detected on radiographs, is a frequent occurrence clinically and can result in a substantial increase in wear rate. The variation in translational positioning acts synergistically with variation in rotational positioning to produce substantial increases in wear. These recent findings are consistent with the wear mechanisms and formation of stripe wear reported for ceramic-on-ceramic bearings over a decade ago, and provide insight into the reasons for the variation and increases in the wear rate found clinically in metal-on-metal hips in specific patients, which may cause premature failure. © 2012 Elsevier Ltd.
Gentile, C, Muise-Helmericks, R & Drake, CJ 2012, 'Abstract 237: VEGF-Mediated Phosphorylation of eNOS Regulates Angioblast and Endothelial Cell Proliferation', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. suppl_1.
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To evaluate when nitric oxide (NO) is first expressed in the EC lineage, the expression pattern of eNOS, phosphorylated eNOS (P-eNOS), and key proteins that define the endothelial lineage (i.e., Flk-1, TAL-1, CD31) were assessed in 7.0-8.5dpc mouse embryos. Immunohistochemical analyses revealed that embryonic endothelial cells (Flk-1 + /TAL-1 + / CD31 + ) expressed eNOS prior to their investment by smooth muscle cells while isolated angioblasts (Flk-1 + /TAL-1 + / CD31 - ) did not express eNOS. Based on eNOS expression we identified a cell type, transitional angioblasts ( eNOS + / FLK-1 + /TAL-1 + / CD31 - ), intermediate between embryonic endothelial cells (EECs) and angioblasts. Transitional angioblasts are further distinguished from angioblasts by their initiation of cell-cell contacts with other eNOS + Flk-1 + /TAL-1 + /CD31 - cells or with EECs. Analysis of P-eNOS and phospho-histone H3 expression in transitional angioblasts and EECs showed a tight correlation between P-eNOS expression and cell proliferation. This correlation was also observ...
Gracey, DM, Fernando, M, Ziegler, J, White, CP & Post, JJ 2012, 'An unrecognised case of tenofovir‐associated Fanconi syndrome', Medical Journal of Australia, vol. 196, no. 2, pp. 111-112.
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Gracey, DM, Fernando, M, Ziegler, J, White, CP & Post, JJ 2012, 'Importance of screening for renal disease among the human immunodeficiency virus‐infected patient population', Internal Medicine Journal, vol. 42, no. 8, pp. 954-955.
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Ho-Pham, LT, Mai, LD, Pham, HN, Nguyen, ND & Nguyen, TV 2012, 'Reference ranges for vertebral heights and prevalence of asymptomatic (undiagnosed) vertebral fracture in Vietnamese men and women', Archives of Osteoporosis, vol. 7, no. 1-2, pp. 257-266.
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Summary Based on quantitative measurements of vertebral heights, the prevalence of undiagnosed vertebral fracture in Vietnamese men and women aged 50 years and older was 23 and 26 %, respectively Background The present study sought to develop reference ranges for vertebral heights and to determine the prevalence of asymptomatic vertebral fracture in Vietnamese men and women. Methods The study included 312 men and 657 women aged over 18 who were randomly selected from the community. The ImageJ software program was used to measure anterior height (Ha), middle height (Hm), and posterior height (Hp) for each vertebra (T4 to T12 and L1 to L5). Four vertebral ratios were determined: Ha/Hp, Hm/Hp, Hp/Hp+1, and Hp/Hp -1. Reference ranges for the ratios were then developed by the method of Winsorized mean. Vertebral fracture was diagnosed as a ratio lower than three standard deviations from the normal mean. Results For any given vertebra, Ha, Hm, and Hp in men were higher than in women. In both sexes, Ha and Hm increased in a stepwise fashion from T4 to L3 and then gradually reduced in L4L5. Vertebral heights for T4T9 tended to decrease, while vertebral height for T10L5 tended to increase with advancing age. Among those aged over 50 years, the prevalence of vertebral fracture in men was 23.3 % (95 % confidence interval (CI) 16.831.3 %) which was lower than that in women (26.5 %; 95 % CI 22.431.1 %). The prevalence increased with advancing age, such that from the age of over 70, 41 % of men and 42 % women had at least one vertebral fracture. Conclusion One fourth of Vietnamese men and women aged 50 years and older have a symptomatic vertebral fracture. This prevalence is equivalent to that in Caucasian populations.
Ho-Pham, LT, Vu, BQ, Lai, TQ, Nguyen, ND & Nguyen, TV 2012, 'Vegetarianism, bone loss, fracture and vitamin D: a longitudinal study in Asian vegans and non-vegans', European Journal of Clinical Nutrition, vol. 66, no. 1, pp. 75-82.
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Background/Objectives:The effect of vegan diet on bone loss has not been studied. The aim of this study was to examine the association between veganism and bone loss in postmenopausal women.Subjects/Methods:The study was designed as a prospective longitudinal investigation with 210 women, including 105 vegans and 105 omnivores. Femoral neck (FN) bone mineral density (BMD) was measured in 2008 and 2010 by dual-energy X-ray absorptiometry (Hologic QDR4500). The incidence of vertebral fracture was ascertained by X-ray report. Serum levels of C-terminal telopeptide of type I collagen (ΒCTX) and N-terminal propeptide of type I procollagen (PINP) were measured by Roche Elecsys assays. Serum concentration of 25-hydroxyvitamin D and parathyroid hormone were measured by electrochemiluminescence.Results:Among the 210 women who initially participated in the study in 2008, 181 women had completed the study and 29 women were lost to follow-up. The rate of loss in FN BMD was -1.91±3.45%/year in omnivores and -0.86±3.81%/year (P=0.08) in vegans. Lower body weight, higher intakes of animal protein and lipid, and corticosteroid use were associated with greater rate of bone loss. The 2-year incidence of fracture was 5.7% (n5/88) in vegans, which was not significantly different from omnivores (5.4%, n6/93). There were no significant differences in ΒCTX and PINP between vegans and omnivores. The prevalence of vitamin D insufficiency in vegans was higher than in omnivores (73% versus 46%; P=0.0003).Conclusions:Vegan diet did not have adverse effect on bone loss and fracture. Corticosteroid use and high intakes of animal protein and animal lipid were negatively associated with bone loss. © 2012 Macmillan Publishers Limited All rights reserved.
Jennings, LM, Al-Hajjar, M, Brockett, CL, Williams, S, Tipper, JL, Ingham, E & Fisher, J 2012, '(iv) Enhancing the safety and reliability of joint replacement implants', Orthopaedics and Trauma, vol. 26, no. 4, pp. 246-252.
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A new Stratified Approach For Enhanced Reliability (SAFER) pre-clinical simulation testing of joint prostheses is presented in this article. The aim of this approach is preclinical systematic testing of wear performance in the much wider envelope of conditions found clinically rather than relying only on the standard testing conditions that are currently used. The approach includes variations in surgical delivery, variations in kinematics, variations in the patient population and degradation of the biomaterial properties. Clinical experience of existing prostheses has been used to validate the new in vitro methods. © 2012 Elsevier Ltd.
Kalyuga, M, Gallego-Ortega, D, Lee, HJ, Roden, DL, Cowley, MJ, Caldon, CE, Stone, A, Allerdice, SL, Valdes-Mora, F, Launchbury, R, Statham, AL, Armstrong, N, Alles, MC, Young, A, Egger, A, Au, W, Piggin, CL, Evans, CJ, Ledger, A, Brummer, T, Oakes, SR, Kaplan, W, Gee, JMW, Nicholson, RI, Sutherland, RL, Swarbrick, A, Naylor, MJ, Clark, SJ, Carroll, JS & Ormandy, CJ 2012, 'ELF5 Suppresses Estrogen Sensitivity and Underpins the Acquisition of Antiestrogen Resistance in Luminal Breast Cancer', PLoS Biology, vol. 10, no. 12, pp. e1001461-e1001461.
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Lu, Z, Roohani-Esfahani, S-I, Wang, G & Zreiqat, H 2012, 'Bone biomimetic microenvironment induces osteogenic differentiation of adipose tissue-derived mesenchymal stem cells', Nanomedicine: Nanotechnology, Biology and Medicine, vol. 8, no. 4, pp. 507-515.
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Martiniello-Wilks, R, Suurbach, JH, Tran, N, Mcgowan, EM, Simpson, A, Larsen, SR & Russell, PJ 2012, 'Cellular and genetic medicines advancing the treatment of prostate cancer', JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, vol. 6, pp. 289-289.
McGowan, EM, Tran, N, Alling, N, Yagoub, D, Sedger, LM & Martiniello-Wilks, R 2012, 'p14ARF Post-Transcriptional Regulation of Nuclear Cyclin D1 in MCF-7 Breast Cancer Cells: Discrimination between a Good and Bad Prognosis?', PLOS ONE, vol. 7, no. 7, pp. 1-16.
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As part of a cell's inherent protection against carcinogenesis, p14ARF is upregulated in response to hyperproliferative signalling to induce cell cycle arrest. This property makes p14ARF a leading candidate for cancer therapy. This study explores the consequences of reactivating p14ARF in breast cancer and the potential of targeting p14ARF in breast cancer treatment. Our results show that activation of the p14ARF-p53-p21-Rb pathway in the estrogen sensitive MCF-7 breast cancer cells induces many hallmarks of senescence including a large flat cell morphology, multinucleation, senescence-associated-β-gal staining, and rapid G1 and G2/M phase cell cycle arrest. P14ARF also induces the expression of the proto-oncogene cyclin D1, which is most often associated with a transition from G1-S phase and is highly expressed in breast cancers with poor clinical prognosis. In this study, siRNA knockdown of cyclin D1, p21 and p53 show p21 plays a pivotal role in the maintenance of high cyclin D1 expression, cell cycle and growth arrest post-p14ARF induction. High p53 and p14ARF expression and low p21/cyclin D1 did not cause cell-cycle arrest. Knockdown of cyclin D1 stops proliferation but does not reverse senescence-associated cell growth. Furthermore, cyclin D1 accumulation in the nucleus post-p14ARF activation correlated with a rapid loss of nucleolar Ki-67 protein and inhibition of DNA synthesis. Latent effects of the p14ARF-induced cellular processes resulting from high nuclear cyclin D1 accumulation included a redistribution of Ki-67 into the nucleoli, aberrant nuclear growth (multinucleation), and cell proliferation. Lastly, downregulation of cyclin D1 through inhibition of ER abrogated latent recurrence. The mediation of these latent effects by continuous expression of p14ARF further suggests a novel mechanism whereby dysregulation of cyclin D1 could have a double-edged effect. Our results suggest that p14ARF induced-senescence is related to late-onset breast c...
Meng, ZX, Zeng, QT, Sun, ZZ, Xu, XX, Wang, YS, Zheng, W & Zheng, YF 2012, 'Immobilizing natural macromolecule on PLGA electrospun nanofiber with surface entrapment and entrapment-graft techniques', Colloids and Surfaces B: Biointerfaces, vol. 94, pp. 44-50.
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Mitra, A, Barua, P, Zaman, S & Banerjee, K 2012, 'Analysis of Trace Metals in Commercially Important Crustaceans Collected from UNESCO Protected World Heritage Site of Indian Sundarbans', Turkish Journal of Fisheries and Aquatic Sciences, vol. 12, no. 1, pp. 49-61.
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Montavon, C, Gloss, BS, Warton, K, Barton, CA, Statham, AL, Scurry, JP, Tabor, B, Nguyen, TV, Qu, W, Samimi, G, Hacker, NF, Sutherland, RL, Clark, SJ & O'Brien, PM 2012, 'Prognostic and diagnostic significance of DNA methylation patterns in high grade serous ovarian cancer', Gynecologic Oncology, vol. 124, no. 3, pp. 582-588.
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Objective. Altered DNA methylation patterns hold promise as cancer biomarkers. In this study we selected a panel of genes which are commonly methylated in a variety of cancers to evaluate their potential application as biomarkers for prognosis and diagnosis in high grade serous ovarian carcinoma (HGSOC); the most common and lethal subtype of ovarian cancer. Methods. The methylation patterns of 10 genes (BRCA1, EN1, DLEC1, HOXA9, RASSF1A, GATA4, GATA5, HSULF1, CDH1, SFN) were examined and compared in a cohort of 80 primary HGSOC and 12 benign ovarian surface epithelium (USE) samples using methylation-specific headloop suppression PCR. Results. The genes were variably methylated in primary HGSOC, with HOXA9 methylation observed in 95% of cases. Most genes were rarely methylated in benign USE, with the exception of SFN which was methylated in all HGSOC and benign USE samples examined. Methylation of DLEC1 was associated with disease recurrence, independent of tumor stage and suboptimal surgical debulking (HR 3.5 (95% CI:1.10-11.07), p=0.033). A combination of the methylation status of HOXA9 and EN1 could discriminate HGSOC from benign USE with a sensitivity of 98.8% and a specificity of 91.7%, which increased to 100% sensitivity with no loss of specificity when pre-operative CA125 levels were also incorporated. Conclusions. This study provides further evidence to support the feasibility of detecting altered DNA methylation patterns as a potential diagnostic and prognostic approach for HGSOC.
Nguyen, HT, Pourian, M, Bystrom, B, Dahlin, I, Duc, PT, Nguyen, TV, von Schoultz, B & Hirschberg, AL 2012, 'Low aglycone content in commercial soy drink products.', Asia Pac J Clin Nutr, vol. 21, no. 1, pp. 52-56.
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The effectiveness of soy isoflavones to prevent bone loss in postmenopausal women is controversial. While consumption of soy in Vietnam is very high, we recently reported a prevalence of osteoporosis comparable to that of many Western populations. In the present study, we analyzed the isoflavone content of soy drink products commercially available in Vietnam and Sweden, and we also compared these products to 'home-made' soy drink from beans of different origin. The amounts of the bioactive aglycones (daidzein, glycitein and genistein) and their glycoside isomers were quantified by high-pressure liquid chromatography. We found that the total isoflavone content was low in all preparations, around 70-100 mg/L and of this only 10% were bioactive aglycones. Of these, the Vietnamese products contained significantly lower levels of glycitein than the products from Sweden and 'home-made' soy drink preparations. The results show that consumption of several liters of soy drink per day would be needed to achieve threshold levels for a protective effect on bone. There was no significant association between total protein and isoflavone content in different products. Accurate labeling of soy drink and other products eg of aglycone and glycoside content would allow health professionals and researchers to better explore the possible benefits of soy in dietary intervention studies.
Nguyen, HTT, von Schoultz, B, Nguyen, TV, Dzung, DN, Duc, PTM, Thuy, VT & Hirschberg, AL 2012, 'Vitamin D deficiency in northern Vietnam: Prevalence, risk factors and associations with bone mineral density', Bone, vol. 51, no. 6, pp. 1029-1034.
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Purpose: Vitamin D deficiency has been linked to osteoporosis and also to the risk of cancer, autoimmune disorders and cardiovascular diseases. This study sought to determine the prevalence of, and risk factors for, vitamin D deficiency and its relationship with bone mineral density (BMD) in a Vietnamese population. Methods: This cross-sectional study involved 269 women and 222 men aged 13-83. years, who were randomly selected from urban and rural areas in northern Vietnam. Serum concentrations of 25-hydroxy-vitamin D [25(OH)D] and parathyroid hormone (PTH) were measured by electrochemiluminescence immunoassay. Vitamin D deficiency was defined as serum 25(OH)D levels below 20. ng/mL. BMD was measured by dual X-ray absorptiometry. Results: The prevalence of vitamin D deficiency in women was 30%, almost two-fold higher than in men (16%). Significant predictors of vitamin D deficiency in women were urban residency (p < 0.01) and age less than 30. years (p < 0.01), whereas use of contraceptive pills was protective (p < 0.01). In men, winter season was the only significant predictor of vitamin D deficiency (p < 0.01). In multiple linear regression analysis, serum levels of 25(OH)D were positively associated with BMD in both women (p < 0.001) and men (p < 0.001). Conclusions: These data suggest that the prevalence of vitamin D deficiency is high in the Vietnamese population, and that part of this prevalence could be explained by low exposure to sunlight (urban residency and winter season). The high prevalence of vitamin D deficiency should raise the awareness of potentially important health issues such as osteoporosis within the Vietnamese society. © 2012 Elsevier Inc.
Nguyen, TV & Eisman, JA 2012, 'Genetics and the Individualized Prediction of Fracture', Current Osteoporosis Reports, vol. 10, no. 3, pp. 236-244.
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Recent genome-wide association studies have identified many genetic variants associated with fracture risk. These genetic variants are common in the general population but have very modest effect sizes. A remaining challenge is to translate these genetic variant discoveries to better predict the risk of fracture based on an individual's genetic profile (ie, individualized risk assessment). Empirical and simulation studies have shown that 1) the utility of a single genetic variant for fracture risk assessment is very limited; but 2) a profile of 50 genetic variants, each with odds ratio ranging from 1.02 to 1.15, can improve the accuracy of fracture prediction and classification beyond that obtained by conventional clinical risk factors. These results are consistent with the view that genetic profiling, when integrated in existing risk assessment models, can inform a more accurate prediction of fracture risk in an individual.
Nguyen, TV, Eisman, JA, Center, JR, Pocock, NA, Jones, G, March, L, Clifton-Bligh, R, Naganathan, V & Seibel, MJ 2012, 'In Memoriam: Philip Neil Sambrook', Osteoporosis International, vol. 23, no. 7, pp. 1835-1836.
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Perdomo, J, Jiang, X-M, Carter, DR, Khachigian, LM & Chong, BH 2012, 'SUMOylation Regulates the Transcriptional Repression Activity of FOG-2 and Its Association with GATA-4', PLoS ONE, vol. 7, no. 11, pp. e50637-e50637.
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Roohani-Esfahani, SI, Dunstan, CR, Davies, B, Pearce, S, Williams, R & Zreiqat, H 2012, 'Repairing a critical-sized bone defect with highly porous modified and unmodified baghdadite scaffolds', Acta Biomaterialia, vol. 8, no. 11, pp. 4162-4172.
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Roohani-Esfahani, SI, Lu, ZF, Li, JJ, Ellis-Behnke, R, Kaplan, DL & Zreiqat, H 2012, 'Effect of self-assembled nanofibrous silk/polycaprolactone layer on the osteoconductivity and mechanical properties of biphasic calcium phosphate scaffolds', Acta Biomaterialia, vol. 8, no. 1, pp. 302-312.
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We here present the first successful report on combining nanostructured silk and poly(ε-caprolactone) (PCL) with a ceramic scaffold to produce a composite scaffold that is highly porous (porosity ∼85%, pore size ∼500 μm, ∼100% interconnectivity), strong and non-brittle with a surface that resembles extracellular matrix (ECM). The ECM-like surface was developed by self-assembly of nanofibrous structured silk (20-80 nm diameter, similar to native collagen found in ECM) over a thin PCL layer which is coated on biphasic calcium phosphate (BCP) scaffolds. The effects of different concentrations of silk solution on the mechanical and physical properties of the scaffolds were also comprehensively examined. Our results showed that using silk only (irrespective of concentration) for the modification of ceramic scaffolds could drastically reduce the compressive strength of the modified scaffolds in aqueous media, and the modification made a limited contribution to improving scaffold toughness. Using PCL/nanostructured silk the compressive strength and modulus of the modified scaffolds reached 0.42 MPa (compared with 0.07 MPa for BCP) and ∼25 MPa (compared with 5 MPa for BCP), respectively. The failure strain of the modified scaffold increased more than 6% compared with a BCP scaffold (failure strain of less than 1%), indicating a transformation from brittle to elastic behavior. The cytocompatibility of ECM-like composite scaffolds was investigated by studying the attachment, morphology, proliferation and bone-related gene expression of primary human bone-derived cells. Cells cultured on the developed scaffolds for 7 days had significant up-regulation of cell proliferation (∼1.6-fold higher, P<0.001) and osteogenic gene expression levels (collagen type I, osteocalcin and bone sialoprotein) compared with the other groups tested.
Roohani-Esfahani, SI, Nouri-Khorasani, S, Lu, ZF, Fathi, MH, Razavi, M, Appleyard, RC & Zreiqat, H 2012, 'Modification of porous calcium phosphate surfaces with different geometries of bioactive glass nanoparticles', Materials Science and Engineering: C, vol. 32, no. 4, pp. 830-839.
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Shen, Z, Bi, J, Shi, B, Nguyen, D, Xian, CJ, Zhang, H & Dai, S 2012, 'Exploring thermal reversible hydrogels for stem cell expansion in three-dimensions', Soft Matter, vol. 8, no. 27, pp. 7250-7250.
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Shi, B, Deng, L, Shi, X, Dai, S, Zhang, H, Wang, Y, Bi, J & Guo, M 2012, 'The enhancement of neural stem cell survival and growth by coculturing with expanded sertoli cells in vitro', Biotechnology Progress, vol. 28, no. 1, pp. 196-205.
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AbstractSertoli cells (SCs) have been described as the “nurse cells” of testis to provide essential growth factors and to create a proper environment for the development of other cells (e.g., germinal and neural stem cell). However, the physiological functions of the SCs obtained from different culture conditions are different in a coculturing system, and thus the optimal SC culturing condition should be investigated in vitro. In this paper, primary Sertoli cells were isolated from a 12‐day‐old mouse and expanded in two different culture conditions: a two dimensional (2D) plastic tissue disc and a three dimensional (3D) microcarrier culture system. They were then cocultured with neural stem cells (NSCs) isolated from 14‐day‐old mouse embryos. The metabolic activities of SCs2D(SCs in 2D) and SCs3D(SCs in 3D) and the amount of proteins secreted from two culturing systems were compared. The results show that the metabolic activity and the amount of secreted proteins from SCs3Dwere higher than both from SCs2D. Three coculturing groups: NSCs+SC2D, NSCs+SC3D, and NSCs +SC‐conditioned medium (SCCM, control group) were also compared regarding cell morphology and the numbers of neurons, neural outgrowths and neurospheres. The quantity of neurons, neural outgrowths and neurospheres were the highest in the NSCs+SC3Dgroup. SCs cultured in the 3D system had a strong trophic effect on NSCs and enhanced their survival and growth. Besides, the mRNA of trophic and nutritive factors such as Glial‐cell‐line‐derived neurotrophic factor (GDNF) and Interleukin‐1 α (IL‐1 α) secreted by the SCs from both 2D and 3D culture system were analyzed by real time‐PCR and gel assay. The mRNA transcription of GDNF and IL‐1α is more apparent in the 3D culture system than that from the 2D one. The coculturing sy...
Shi, B, Shen, Z, Zhang, H, Bi, J & Dai, S 2012, 'Exploring N-Imidazolyl-O-Carboxymethyl Chitosan for High Performance Gene Delivery', Biomacromolecules, vol. 13, no. 1, pp. 146-153.
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Suñer, S, Tipper, JL & Emami, N 2012, 'Biological effects of wear particles generated in total joint replacements: trends and future prospects', Tribology - Materials, Surfaces & Interfaces, vol. 6, no. 2, pp. 39-52.
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Joint replacements have considerably improved the quality of life of patients with joints damaged by disease or trauma. However, problems associated with wear particles generated due to the relative motion between the components of the bearing are still present and can lead to the eventual failure of the implant. The biological response to wear debris affects directly the longevity of the prosthesis. The identification of the mechanisms by which cells respond to wear debris and how particles distribute into the human body may provide valuable information for the long term success of artificial joints. During the last few decades, orthopaedic research has been focused on predicting the in vivo performance of joint replacements. However, the exact relationship between material physicochemical properties and inflammatory response has not been fully understood. Laboratory wear simulators provide an accurate prediction of implant wear performance. Though, particles generated from such wear simulators require validation to compare them with particles extracted from peri-implant tissues. This review focuses initially on the current status of total joint replacements (hard on soft and hard on hard bearings) as well as on the tribological behaviour of the potential materials currently under investigation. Then, the correspondence between particles observed in vivo and those generated in vitro to predict the cellular response to wear debris is discussed. Finally, the biological effects of the degradation products generated by wear and corrosion are described. © 2012 W. S. Maney & Son Ltd.
Suurbach, JH, McGowan, EM, Simpson, A, Tran, N & Martiniello-Wilks, R 2012, 'A unique bioluminescent prostate cancer mouse model for the evaluation of stem-cell based gene therapy', JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, vol. 6, pp. 288-288.
Tavakoli, J, Miar, S, Majid Zadehzare, M & Akbari, H 2012, 'Evaluation of effectiveness of herbal medication in cancer care: a review study.', Iran J Cancer Prev, vol. 5, no. 3, pp. 144-156.
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Based on a common belief, herbal medicine with the least possible side effects should be the center of attention in cancer care; however, in many cases they have not been properly studied with reliable clinical trials in human subjects. In this review, it was attempted to identify the available evidence on the use and clinical effects of herbs in cancer care. The research consists of two major parts including immunomodulator and chemopreventive herbal compounds whose mechanism, biological response, anticancer element of extract and related benefits were completely studied. Also, the safety of herbal anticancer compounds was discussed. Although the use of herbal medicines in treating cancer shows less chemotherapy-induced, toxicity, more researches are required to reach their full therapeutic potentials.
Vicars, R, Prokopovich, P, Brown, TD, Tipper, JL, Ingham, E, Fisher, J & Hall, RM 2012, 'The Effect of Anterior-Posterior Shear on the Wear of CHARITÉ Total Disc Replacement', Spine, vol. 37, no. 9, pp. E528-E534.
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Wang, G, Lu, Z, Xie, KY, Lu, WY, Roohani-Esfahani, SI, Kondyurin, A & Zreiqat, H 2012, 'A facile method to in situ formation of hydroxyapatite single crystal architecture for enhanced osteoblast adhesion', Journal of Materials Chemistry, vol. 22, no. 36, pp. 19081-19081.
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Warkiani, ME, Lou, C-P, Liu, H-B & Gong, H-Q 2012, 'A high-flux isopore micro-fabricated membrane for effective concentration and recovering of waterborne pathogens', Biomedical Microdevices, vol. 14, no. 4, pp. 669-677.
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Waterloo, S, Ahmed, LA, Center, JR, Eisman, JA, Morseth, B, Nguyen, ND, Nguyen, T, Sogaard, AJ & Emaus, N 2012, 'Prevalence of vertebral fractures in women and men in the population-based Tromsø Study', BMC Musculoskeletal Disorders, vol. 13, no. 1, pp. 1-9.
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BACKGROUND: Osteoporotic vertebral fractures are, as the hip fractures, associated with increased morbidity and mortality. Norway has one of the highest reported incidences of hip fractures in the world. Because of methodological challenges, vertebral fractures are not extensively studied. The aim of this population based study was to describe, for the first time, the age- and sex specific occurrence of osteoporotic vertebral fractures in Norway. METHODS: Data was collected in the Tromso Study, 2007/8 survey. By the use of dual x-ray absorptiometry (GE Lunar Prodigy) vertebral fracture assessments were performed in 2887 women and men aged from 38 to 87 years, in addition to measurements of bone mineral density at the femoral sites. Information on lifestyle was collected through questionnaires. Comparisons between fractures and non-fractures were done sex stratified, by univariate analyses, adjusting for age when relevant. RESULTS: The prevalence of vertebral fractures varied from about 3% in the age group below 60 to about 19% in the 70+ group in women, and from 7.5% to about 20% in men, with an overall prevalence of 11.8% in women and 13.8% in men (p = 0.07). Among those with fractures, only one fracture was the most common; two and more fractures were present in approximately 30% of the cases. Fractures were seen from the fourth lumbar to the fifth thoracic vertebrae, most common between first lumbar and sixth thoracic vertebrae. The most common type of fracture was the wedge type in both sexes. Bone mineral density at the hip differed significantly according to type of fracture, being highest in those with wedge fractures and lowest in those with compression fractures. CONCLUSIONS: The prevalence of vertebral fractures increased by age in women and men, but the overall prevalence was lower than expected, considering the high prevalence of hip and forearm fractures in Norway. In both sexes, the wedge type was the fracture type most frequently observed and most ...
Waterloo, S, Nguyen, T, Ahmed, LA, Center, JR, Morseth, B, Nguyen, ND, Eisman, JA, Søgaard, AJ & Emaus, N 2012, 'Important risk factors and attributable risk of vertebral fractures in the population-based Tromsø study', BMC Musculoskeletal Disorders, vol. 13, no. 1.
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Background: Vertebral fractures, the most common type of osteoporotic fractures, are associated with increased risk of subsequent fracture, morbidity, and mortality. The aim of this study was to examine the contribution of important risk factors to the variability in vertebral fracture risk. Methods. Vertebral fracture was ascertained by VFA method (DXA, GE Lunar Prodigy) in 2887 men and women, aged between 38 and 87 years, in the population-based Tromsø Study 2007/2008. Bone mineral density (BMD; g/cm2) at the hip was measured by DXA. Lifestyle information was collected by questionnaires. Multivariable logistic regression model, with anthropometric and lifestyle factors included, was used to assess the association between each or combined risk factors and vertebral fracture risk. Population attributable risk was estimated for combined risk factors in the final multivariable model. Results: In both sexes, age (odds ratio [OR] per 5 year increase: 1.32; 95% CI 1.19-1.45 in women and 1.21; 95% CI 1.10-1.33 in men) and BMD (OR per SD decrease: 1.60; 95% CI 1.34-1.90 in women and1.40; 95% CI 1.18-1.67 in men) were independent risk factors for vertebral fracture. At BMD levels higher than 0.85 g/cm2, men had a greater risk of fracture than women (OR 1.52; 95% CI 1.14-2.04), after adjusting for age. In women and men, respectively, approximately 46% and 33% of vertebral fracture risk was attributable to advancing age (more than 70 years) and low BMD (less than 0.85 g/cm 2), with the latter having a greater effect than the former. Conclusions: These data confirm that age and BMD are major risk factors for vertebral fracture risk. However, in both sexes the two factors accounted for less than half of fracture risk. The identification of individuals with vertebral fracture is still a challenge
Xu, X, Yang, H & Liu, Y 2012, 'Self-assembled structures of CuO primary crystals synthesized from Cu(CH3COO)2–NaOH aqueous systems', CrystEngComm, vol. 14, no. 16, pp. 5289-5289.
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Xu, XX, Nie, FL, Wang, YB, Zhang, JX, Zheng, W, Li, L & Zheng, YF 2012, 'Effective inhibition of the early copper ion burst release with ultra-fine grained copper and single crystal copper for intrauterine device application', Acta Biomaterialia, vol. 8, no. 2, pp. 886-896.
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Yang, S, Nguyen, ND, Eisman, JA & Nguyen, TV 2012, 'Association between beta-blockers and fracture risk: A Bayesian meta-analysis', Bone, vol. 51, no. 5, pp. 969-974.
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Background: The association between beta-blockers (BB) and fracture risk is controversial, due largely to conflicting findings from previous studies. The present study sought to evaluate the effect of BB on fracture risk by using a Bayesian meta-analysis approach. Methods and results: We systematically retrieved 13 observational studies on the association between BB use and fracture risk. This meta-analysis involved more than 907.000 men and women with mean/median age of individual studies ranging from 43 to 81 years. We used a hierarchical Bayesian random effects model to synthesize the results. BB use was associated with an average 17% reduction in the risk of any fracture (risk ratio [RR] 0.83: 95% credible interval [Crl]: 0.71-0.93), hip fracture (RR 0.83: 95% Crl: 0.70-0.92) and vertebral fracture (RR 0.81:95% Crl: 0.61-0.99). The probability that BB use reduces fracture risk by at least 10% was 0.91. Conclusions: Beta-blockers are associated with reduced risk of fracture in older adults, but the effect size is likely to be modest. (C) 2012 Elsevier Inc. All rights reserved.
