Aquilina, P, Parr, WCH, Chamoli, U, Wroe, S & Clausen, P 2014, 'A Biomechanical Comparison of Three 1.5-mm Plate and Screw Configurations and a Single 2.0-mm Plate for Internal Fixation of a Mandibular Condylar Fracture', Craniomaxillofacial Trauma & Reconstruction, vol. 7, no. 3, pp. 218-223.
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The most stable pattern of internal fixation for mandibular condyle fractures is an area of ongoing discussion. This study investigates the stability of three patterns of plate fixation using readily available, commercially pure titanium implants. Finite element models of a simulated mandibular condyle fracture were constructed. The completed models were heterogeneous in bone material properties, contained approximately 1.2 million elements and incorporated simulated jaw adducting musculature. Models were run assuming linear elasticity and isotropic material properties for bone. No human subjects were involved in this investigation. The stability of the simulated condylar fracture reduced with the different implant configurations, and the von Mises stresses of a 1.5-mm X-shaped plate, a 1.5-mm rectangular plate, and a 1.5-mm square plate (all Synthes (Synthes GmbH, Zuchwil, Switzerland) were compared. The 1.5-mm X plate was the most stable of the three 1.5-mm profile plate configurations examined and had comparable mechanical performance to a single 2.0-mm straight four-hole plate. This study does not support the use of rectangular or square plate patterns in the open reduction and internal fixation of mandibular condyle fractures. It does provide some support for the use of a 1.5-mm X plate to reduce condylar fractures in selected clinical cases.
Bajan, S & Hutvagner, G 2014, 'Regulation of miRNA Processing and miRNA Mediated Gene Repression in Cancer', MicroRNA, vol. 3, no. 1, pp. 10-17.
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The majority of human protein-coding genes are predicted to be targets of miRNA-mediated post-transcriptional regulation. The widespread influence of miRNAs is illustrated by their essential roles in all biological processes. Regulated miRNA expression is essential for maintaining cellular differentiation; therefore alterations in miRNA expression patterns are associated with several diseases, including various cancers. High-throughput sequencing technologies revealed low level expressing miRNA isoforms, termed isomiRs. IsomiRs may differ in sequence, length, target preference and expression patterns from their parental miRNA and can arise from differences in miRNA biosynthesis, RNA editing, or SNPs inherent to the miRNA gene. The association between isomiR expression and disease progression is largely unknown. Misregulated miRNA expression is thought to contribute to the formation and/or progression of cancer. However, due to the diversity of targeted transcripts, miRNAs can function as both tumor-suppressor genes and oncogenes as defined by cellular context. Despite this, miRNA profiling studies concluded that the differential expression of particular miRNAs in diseased tissue could aid the diagnosis and treatment of some cancers.
Brandl, MB, Pasquier, E, Li, F, Beck, D, Zhang, S, Zhao, H, Kavallaris, M & Wong, STC 2014, 'Computational analysis of image-based drug profiling predicts synergistic drug combinations: Applications in triple-negative breast cancer', MOLECULAR ONCOLOGY, vol. 8, no. 8, pp. 1548-1560.
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An imaged-based profiling and analysis system was developed to predict clinically effective synergistic drug combinations that could accelerate the identification of effective multi-drug therapies for the treatment of triple-negative breast cancer and other challenging malignancies. The identification of effective drug combinations for the treatment of triple-negative breast cancer (TNBC) was achieved by integrating high-content screening, computational analysis, and experimental biology. The approach was based on altered cellular phenotypes induced by 55 FDA-approved drugs and biologically active compounds, acquired using fluorescence microscopy and retained in multivariate compound profiles. Dissimilarities between compound profiles guided the identification of 5 combinations, which were assessed for qualitative interaction on TNBC cell growth. The combination of the microtubule-targeting drug vinblastine with KSP/Eg5 motor protein inhibitors monastrol or ispinesib showed potent synergism in 3 independent TNBC cell lines, which was not substantiated in normal fibroblasts. The synergistic interaction was mediated by an increase in mitotic arrest with cells demonstrating typical ispinesib-induced monopolar mitotic spindles, which translated into enhanced apoptosis induction. The antitumour activity of the combination vinblastine/ispinesib was confirmed in an orthotopic mouse model of TNBC. Compared to single drug treatment, combination treatment significantly reduced tumour growth without causing increased toxicity. Image-based profiling and analysis led to the rapid discovery of a drug combination effective against TNBC in vitro and in vivo, and has the potential to lead to the development of new therapeutic options in other hard-to-treat cancers.
Brzozowska, MM, Bliuc, D, Hong, A, Jorgensen, J, Talbot, M, Travers, V, Rigas, G, Chen, W, Tran, T, Pocock, NA, Eisman, JA, White, CP, Baldock, P & Center, JR 2014, 'Long term skeletal changes following different types of bariatric surgery', Obesity Research & Clinical Practice, vol. 8, pp. 11-11.
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Carter, DR, Buckle, AD, Tanaka, K, Perdomo, J & Chong, BH 2014, 'Art27 Interacts with GATA4, FOG2 and NKX2.5 and Is a Novel Co-Repressor of Cardiac Genes', PLoS ONE, vol. 9, no. 4, pp. e95253-e95253.
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Chacon, D, Beck, D, Perera, D, Wong, JWH & Pimanda, JE 2014, 'BloodChIP: a database of comparative genome-wide transcription factor binding profiles in human blood cells', Nucleic Acids Research, vol. 42, no. D1, pp. D172-D177.
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The BloodChIP database (http://www.med.unsw.edu.au/CRCWeb.nsf/page/ BloodChIP) supports exploration and visualization of combinatorial transcription factor (TF) binding at a particular locus in human CD34-positive and other normal and leukaemic cells or retrieval of target gene sets for user-defined combinations of TFs across one or more cell types. Increasing numbers of genome-wide TF binding profiles are being added to public repositories, and this trend is likely to continue. For the power of these data sets to be fully harnessed by experimental scientists, there is a need for these data to be placed in context and easily accessible for downstream applications. To this end, we have built a user-friendly database that has at its core the genome-wide binding profiles of seven key haematopoietic TFs in human stem/progenitor cells. These binding profiles are compared with binding profiles in normal differentiated and leukaemic cells. We have integrated these TF binding profiles with chromatin marks and expression data in normal and leukaemic cell fractions. All queries can be exported into external sites to construct TF-gene and protein-protein networks and to evaluate the association of genes with cellular processes and tissue expression. © 2013 The Author(s). Published by Oxford University Press.
Challis, VJ, Xu, X, Zhang, LC, Roberts, AP, Grotowski, JF & Sercombe, TB 2014, 'High specific strength and stiffness structures produced using selective laser melting', Materials & Design, vol. 63, pp. 783-788.
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Selective Laser Melting (SLM) was used to fabricate scaffolds using the titanium alloy Ti-6Al-4V. Two types of high porosity open-cell structures were manufactured: the first built from topology optimised designs with maximised stiffness, and the second from gyroid labyrinths. In mechanical compression tests the scaffolds demonstrate exceptional strength- and stiffness-to-weight ratios. In particular, for densities in the range 0.2-0.8g/cm3 the topology optimised scaffolds have specific strength and stiffness that are superior to those of comparable materials in the literature. In addition, the optimised scaffolds have the benefit of being elastically isotropic. The results of finite element calculations accurately match the measured stiffness of the scaffolds. Calculated strain energy distributions provide insight into how the high stiffness and strength of the optimised designs is connected to their efficient distribution of load.
Chamoli, U, Chen, AS & Diwan, AD 2014, 'Interpedicular kinematics in an in vitro biomechanical assessment of a bilateral lumbar spondylolytic defect', Clinical Biomechanics, vol. 29, no. 10, pp. 1108-1115.
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Chamoli, U, Chen, AS & Diwan, AD 2014, 'Letters', Spine, vol. 39, no. 11, pp. 921-921.
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Chamoli, U, Diwan, AD & Tsafnat, N 2014, 'Pedicle screw‐based posterior dynamic stabilizers for degenerative spine: In vitro biomechanical testing and clinical outcomes', Journal of Biomedical Materials Research Part A, vol. 102, no. 9, pp. 3324-3340.
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AbstractDynamic stabilization in a degenerate symptomatic spine may be advantageous compared with conventional fusion procedures, as it helps preserve motion and minimizes redistribution of loads at instrumented and adjacent segments. This article presents a systematic review of biomechanical and clinical evidence available on some of the pedicle screw based posterior dynamic stabilization (PDS) devices. Using Medline, Embase, and Scopus online databases, we identified four pedicle‐screw‐PDS devices for which both, biomechanical testing and clinical follow‐up data are available: Graf artificial ligaments, Isobar TTL, Polyetheretherketone rods, and Dynesys. The current state‐of‐the‐art of pedicle‐screw‐PDS devices is far from achieving its desired biomechanical efficacy, which has resulted in a weak support for the posited clinical benefits. Although pedicle‐screw‐PDS devices are useful in salvaging a moderately degenerate functionally suboptimal disc, for severe disc degeneration cases fusion is still the preferred choice. We conclude that a pedicle‐screw‐PDS device should aim at restoring load sharing amongst spinal elements while preserving the qualitative and quantitative nature of spinal motion, especially minimize posterior shift of the helical axis of motion. More precise and objective assessment techniques need to be standardized for in vivo evaluation of intervertebral motion and load sharing amongst spinal elements across different pedicle‐screw‐PDS devices. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3324–3340, 2014.
Chan, MY, Center, JR, Eisman, JA & Nguyen, TV 2014, 'Bone mineral density and association of osteoarthritis with fracture risk', Osteoarthritis and Cartilage, vol. 22, no. 9, pp. 1251-1258.
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Chan, MY, Frost, SA, Center, JR, Eisman, JA & Nguyen, TV 2014, 'Relationship Between Body Mass Index and Fracture Risk Is Mediated by Bone Mineral Density', Journal of Bone and Mineral Research, vol. 29, no. 11, pp. 2327-2335.
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ABSTRACT The relationship between body mass index (BMI) and fracture risk is controversial. We sought to investigate the effect of collinearity between BMI and bone mineral density (BMD) on fracture risk, and to estimate the direct and indirect effect of BMI on fracture with BMD being the mediator. The study involved 2199 women and 1351 men aged 60 years or older. BMI was derived from baseline weight and height. Femoral neck BMD was measured by dual-energy X-ray absorptiometry (DXA; GE-LUNAR, Madison, WI, USA). The incidence of fragility fracture was ascertained by X-ray reports from 1991 through 2012. Causal mediation analysis was used to assess the mediated effect of BMD on the BMI-fracture relationship. Overall, 774 women (35% of total women) and 258 men (19%) had sustained a fracture. Approximately 21% of women and 20% of men were considered obese (BMI ≥ 30). In univariate analysis, greater BMI was associated with reduced fracture risk in women (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.85 to 0.99) and in men (HR 0.77; 95% CI, 0.67 to 0.88). After adjusting for femoral neck BMD, higher BMI was associated with greater risk of fracture in women (HR 1.21; 95% CI, 1.11 to 1.31) but not in men (HR 0.96; 95% CI, 0.83 to 1.11). Collinearity had minimal impact on the BMD-adjusted results (variance inflation factor [VIF] = 1.2 for men and women). However, in mediation analysis, it was found that the majority of BMI effect on fracture risk was mediated by femoral neck BMD. The overall mediated effect estimates were −0.048 (95% CI, −0.059 to −0.036; p < 0.001) in women and −0.030 (95% CI, −0.042 to −0.018; p < 0.001) in men. These analyses suggest that there is no significant direct effect of BMI on fracture, and that the observed association between BMI and fracture risk is mediated by femoral neck BMD in both m...
Deng, W & Goldys, EM 2014, 'Chemical sensing with nanoparticles as optical reporters: from noble metal nanoparticles to quantum dots and upconverting nanoparticles', The Analyst, vol. 139, no. 21, pp. 5321-5334.
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Deng, W, Goldys, EM, Farnham, MMJ & Pilowsky, PM 2014, 'Optogenetics, the intersection between physics and neuroscience: light stimulation of neurons in physiological conditions', American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, vol. 307, no. 11, pp. R1292-R1302.
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Neuronal stimulation by light is a novel approach in the emerging field of optogenetics, where genetic engineering is used to introduce light-activated channels. However, light is also capable of stimulating neurons even in the absence of genetic modifications through a range of physical and biological mechanisms. As a result, rigorous design of optogenetic experiments needs to take note of alternative and parallel effects of light illumination of neuronal tissues. Thus all matters relating to light penetration are critical to the development of studies using light-activated proteins. This paper discusses ways to quantify light, light penetration in tissue, as well as light stimulation of neurons in physiological conditions. We also describe the direct effect of light on neurons investigated at different sites.
Diffner, E, Beck, D, Gudgin, E, Thoms, JAI, Knezevic, K, Pridans, C, Foster, S, Goode, D, Khong Lim, W, Boelen, L, Metzeler, KH, Micklem, G, Bohlander, SK, Buske, C, Burnett, A, Ottersbach, K, Vassiliou, GS, Olivier, J, Wong, JWH, Gottgens, B, Huntly, BJ & Pimanda, JE 2014, 'Diffner E, Beck D, Gudgin E, et al. Activity of a heptad of transcription factors is associated with stem cell programs and clinical outcome in acute myeloid leukemia. Blood. 2013;121(12):2289-2300.', Blood, vol. 123, no. 18, pp. 2901-2901.
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Galougahi, KK, Liu, C, Gentile, C, Kok, C, Nunez, A, Garcia, A, Fry, NAS, Davies, MJ, Hawkins, CL, Rasmussen, HH & Figtree, GA 2014, 'Glutathionylation Mediates Angiotensin II–Induced eNOS Uncoupling, Amplifying NADPH Oxidase‐Dependent Endothelial Dysfunction', Journal of the American Heart Association, vol. 3, no. 2.
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Background Glutathionylation of endothelial nitric oxide synthase ( eNOS ) “uncouples” the enzyme, switching its function from nitric oxide (NO) to O 2 •− generation. We examined whether this reversible redox modification plays a role in angiotensin II (Ang II)‐induced endothelial dysfunction. Methods and Results Ang II increased eNOS glutathionylation in cultured human umbilical vein endothelial cells (HUVECs), rabbit aorta, and human arteries in vitro. This was associated with decreased NO bioavailability and eNOS activity as well as increased O 2 •− generation. Ang II‐induced decrease in eNOS activity was mediated by glutathionylation, as shown by restoration of function by glutaredoxin‐1. Moreover, Ang II‐induced increase in O 2 •− and decrease in NO were abolished in HUVECs transiently transfected, with mutant eNOS rendered resistant to glutathionylation. Ang II effects were nicotinamide adenine dinucleotide phosphate (NADPH) oxidase dependent because preincubation with gp 91ds‐tat, an inh...
Ganda, K, Nguyen, TV & Pocock, N 2014, 'Gender disparity in BMD conversion: a comparison between Lunar and Hologic densitometers', Archives of Osteoporosis, vol. 9, no. 1, pp. 1-8.
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Female-derived inter-conversion and standardised BMD equations at the lumbar spine and hip have not been validated in men. This study of 110 male subjects scanned on Hologic and Lunar densitometers demonstrates that published equations may not applicable to men at the lumbar spine. Male inter-conversion equations have also been derived.Currently, available equations for inter-manufacturer conversion of bone mineral density (BMD) and calculation of standardised BMD (sBMD) are used in both males and females, despite being derived and validated only in women. Our aim was to test the validity of the published equations in men.One hundred ten men underwent lumbar spine (L2-4), femoral neck (FN) and total hip (TH) dual X-ray absorptiometry (DXA) using Hologic and Lunar scanners. Hologic BMD was converted to Lunar using published equations derived from women for L2-4 and FN. Actual Lunar BMD (A-Lunar) was compared to converted (Lunar equivalent) Hologic BMD values (H-Lunar). sBMD was calculated separately using Hologic (sBMD-H) and Lunar BMD (sBMD-L) at L2-4, FN and TH. Conversion equations in men for Hologic to Lunar BMD were derived using Deming regression analysis.There was a strong linear correlation between Lunar and Hologic BMD at all skeletal sites. A-Lunar BMD was however significantly higher than derived H-Lunar BMD (p < 0.001) at L2-L4 (mean difference, 0.07 g/cm(2)). There was no significant difference at the FN (mean difference, 0.01 g/cm(2)). sBMD-L at the spine was significantly higher than sBMD-H (mean difference, 0.06 g/cm(2), p < 0.001), whilst there was little difference at the FN and TH (mean difference, 0.01 g/cm(2)).Published conversion equations for Lunar BMD to Hologic BMD, and formulae for lumbar spine sBMD, derived in women may not be applicable to men.
Gentile, C, Drake, CJ, Figtree, G & Davies, MJ 2014, 'Post-Transcriptional Regulation of eNOS and SNitrosylation of Cell Cycle-Related Proteins in Human Endothelial Cells', Free Radical Biology and Medicine, vol. 76, pp. S43-S44.
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Goh, EG, Xu, X & McCormick, PG 2014, 'Effect of particle size on the UV absorbance of zinc oxide nanoparticles', Scripta Materialia, vol. 78-79, pp. 49-52.
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The effect of particle size on the UV absorption of zinc oxide nanoparticles has been investigated in the size range above the quantum limit. The results show that the absorbance increases with increasing size for particle sizes of 15-40 nm. The results are evaluated in terms of intrinsic particle absorption and the number concentration of particles. It is shown that the particles become opaque for particle sizes greater than 70 nm. For larger sizes the absorbance decreases with increasing size due to the decrease in particle concentration. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Ho-Pham, LT, Lai, TQ, Mai, LD, Doan, MC, Pham, HN & Nguyen, TV 2014, 'Prevalence of Radiographic Osteoarthritis of the Knee and Its Relationship to Self-Reported Pain', PLoS ONE, vol. 9, no. 4, pp. e94563-e94563.
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Background and Aim: Osteoarthritis (OA) of the knee is one of the most common skeletal disorders, yet little data are available in Asian populations. We sought to assess the prevalence and pattern of radiographic OA of the knee, and its relationship to s
Keam, SP, Sobala, A, Humphreys, DT, Suter, CM & Hutvagner, G 2014, 'Computational Analysis, Biochemical Purification, and Detection of tRNA-Derived Small RNA Fragments', Methods in Molecular Biology, vol. 1173, pp. 157-167.
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© Springer Science+Business Media New York 2014. The rapidly growing list of small RNA species generated by next-generation sequencing technologies has accelerated the development of new bioinformatics tools for their detection. Small RNAs generated from tRNAs, transfer RNA-derived fragments (tRFs), represent a novel challenge in accurately identifying and distinguishing them from random degradation products of tRNAs. Here, we describe a bioinformatics approach to detect tRFs in next-generation sequencing libraries. We also present a biochemical purification protocol for enriching 5′ tRFs and separating them from miRNAs. And finally, we suggest reliable methods for detecting and quantifying tRFs.
Keam, SP, Young, PE, McCorkindale, AL, Dang, THY, Clancy, JL, Humphreys, DT, Preiss, T, Hutvagner, G, Martin, DIK, Cropley, JE & Suter, CM 2014, 'The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells', NUCLEIC ACIDS RESEARCH, vol. 42, no. 14, pp. 8984-8995.
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The Piwi-piRNA pathway is active in animal germ cells where its functions are required for germ cell maintenance and gamete differentiation. Piwi proteins and piRNAs have been detected outside germline tissue in multiple phyla, but activity of the pathway in mammalian somatic cells has been little explored. In particular, Piwi expression has been observed in cancer cells, but nothing is known about the piRNA partners or the function of the system in these cells. We have surveyed the expression of the three human Piwi genes, Hiwi, Hili and Hiwi2, in multiple normal tissues and cancer cell lines. We find that Hiwi2 is ubiquitously expressed; in cancer cells the protein is largely restricted to the cytoplasm and is associated with translating ribosomes. Immunoprecipitation of Hiwi2 from MDAMB231 cancer cells enriches for piRNAs that are predominantly derived from processed tRNAs and expressed genes, species which can also be found in adult human testis. Our studies indicate that a Piwi-piRNA pathway is present in human somatic cells, with an uncharacterised function linked to translation. Taking this evidence together with evidence from primitive organisms, we propose that this somatic function of the pathway predates the germline functions of the pathway in modern animals. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
Khoo, BL, Warkiani, ME, Tan, DSW, Bhagat, AAS & Irwin, D 2014, 'Erratum: Clinical validation of an ultra high-throughput spiral microfluidics for the detection and enrichment of viable circulating tumor cells (PLoS ONE 9(7) e99409). doi:10.1371/journal.pone.0099409', PLoS ONE, vol. 9, no. 10.
Khoo, BL, Warkiani, ME, Tan, DS-W, Bhagat, AAS, Irwin, D, Lau, DP, Lim, AST, Lim, KH, Krisna, SS, Lim, W-T, Yap, YS, Lee, SC, Soo, RA, Han, J & Lim, CT 2014, 'Clinical Validation of an Ultra High-Throughput Spiral Microfluidics for the Detection and Enrichment of Viable Circulating Tumor Cells', PLoS ONE, vol. 9, no. 7, pp. e99409-e99409.
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BACKGROUND: Circulating tumor cells (CTCs) are cancer cells that can be isolated via liquid biopsy from blood and can be phenotypically and genetically characterized to provide critical information for guiding cancer treatment. Current analysis of CTCs is hindered by the throughput, selectivity and specificity of devices or assays used in CTC detection and isolation. METHODOLOGY/PRINCIPAL FINDINGS: Here, we enriched and characterized putative CTCs from blood samples of patients with both advanced stage metastatic breast and lung cancers using a novel multiplexed spiral microfluidic chip. This system detected putative CTCs under high sensitivity (100%, n = 56) (Breast cancer samples: 12-1275 CTCs/ml; Lung cancer samples: 10-1535 CTCs/ml) rapidly from clinically relevant blood volumes (7.5 ml under 5 min). Blood samples were completely separated into plasma, CTCs and PBMCs components and each fraction were characterized with immunophenotyping (Pan-cytokeratin/CD45, CD44/CD24, EpCAM), fluorescence in-situ hybridization (FISH) (EML4-ALK) or targeted somatic mutation analysis. We used an ultra-sensitive mass spectrometry based system to highlight the presence of an EGFR-activating mutation in both isolated CTCs and plasma cell-free DNA (cf-DNA), and demonstrate concordance with the original tumor-biopsy samples. CONCLUSIONS/SIGNIFICANCE: We have clinically validated our multiplexed microfluidic chip for the ultra high-throughput, low-cost and label-free enrichment of CTCs. Retrieved cells were unlabeled and viable, enabling potential propagation and real-time downstream analysis using next generation sequencing (NGS) or proteomic analysis.
Kim, PY, Tan, O, Diakiw, SM, Carter, D, Sekerye, EO, Wasinger, VC, Liu, T, Kavallaris, M, Norris, MD, Haber, M, Chesler, L, Dolnikov, A, Trahair, TN, Cheung, N-K, Marshall, GM & Cheung, BB 2014, 'Identification of plasma Complement C3 as a potential biomarker for neuroblastoma using a quantitative proteomic approach', Journal of Proteomics, vol. 96, pp. 1-12.
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Li, J, Mei, H, Zheng, W, Pan, P, Sun, XJ, Li, F, Guo, F, Zhou, HM, Ma, JY, Xu, XX & Zheng, YF 2014, 'A novel hydrogen peroxide biosensor based on hemoglobin-collagen-CNTs composite nanofibers', Colloids and Surfaces B: Biointerfaces, vol. 118, pp. 77-82.
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Li, JJ, Kaplan, DL & Zreiqat, H 2014, 'Scaffold-based regeneration of skeletal tissues to meet clinical challenges', J. Mater. Chem. B, vol. 2, no. 42, pp. 7272-7306.
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Scaffold-based tissue engineering strategies are being explored for the management and reconstruction of damaged or diseased skeletal tissues, the effective treatment of which has remained a significant global healthcare challenge.
Liu, A, Ingham, E, Fisher, J & Tipper, JL 2014, 'Generation of a large volume of clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles for cell culture studies', Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, vol. 228, no. 4, pp. 418-426.
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It has recently been shown that the wear of ultra-high-molecular-weight polyethylene in hip and knee prostheses leads to the generation of nanometre-sized particles, in addition to micron-sized particles. The biological activity of nanometre-sized ultra-high-molecular-weight polyethylene wear particles has not, however, previously been studied due to difficulties in generating sufficient volumes of nanometre-sized ultra-high-molecular-weight polyethylene wear particles suitable for cell culture studies. In this study, wear simulation methods were investigated to generate a large volume of endotoxin-free clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles. Both single-station and six-station multidirectional pin-on-plate wear simulators were used to generate ultra-high-molecular-weight polyethylene wear particles under sterile and non-sterile conditions. Microbial contamination and endotoxin levels in the lubricants were determined. The results indicated that microbial contamination was absent and endotoxin levels were low and within acceptable limits for the pharmaceutical industry, when a six-station pin-on-plate wear simulator was used to generate ultra-high-molecular-weight polyethylene wear particles in a non-sterile environment. Different pore-sized polycarbonate filters were investigated to isolate nanometre-sized ultra-high-molecular-weight polyethylene wear particles from the wear test lubricants. The use of the filter sequence of 10, 1, 0.1, 0.1 and 0.015 µm pore sizes allowed successful isolation of ultra-high-molecular-weight polyethylene wear particles with a size range of < 100 nm, which was suitable for cell culture studies.
Liu, Z, Xing, D, Su, QP, Zhu, Y, Zhang, J, Kong, X, Xue, B, Wang, S, Sun, H, Tao, Y & Sun, Y 2014, 'Super-resolution imaging and tracking of protein–protein interactions in sub-diffraction cellular space', Nature Communications, vol. 5, no. 1, pp. 1-8.
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AbstractImaging the location and dynamics of individual interacting protein pairs is essential but often difficult because of the fluorescent background from other paired and non-paired molecules, particularly in the sub-diffraction cellular space. Here we develop a new method combining bimolecular fluorescence complementation and photoactivated localization microscopy for super-resolution imaging and single-molecule tracking of specific protein–protein interactions. The method is used to study the interaction of two abundant proteins, MreB and EF-Tu, in Escherichia coli cells. The super-resolution imaging shows interesting distribution and domain sizes of interacting MreB–EF-Tu pairs as a subpopulation of total EF-Tu. The single-molecule tracking of MreB, EF-Tu and MreB–EF-Tu pairs reveals intriguing localization-dependent heterogonous dynamics and provides valuable insights to understanding the roles of MreB–EF-Tu interactions.
Marshall, GM, Carter, DR, Cheung, BB, Liu, T, Mateos, MK, Meyerowitz, JG & Weiss, WA 2014, 'The prenatal origins of cancer', Nature Reviews Cancer, vol. 14, no. 4, pp. 277-289.
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Moradi, A, Zhand, S, Ghaemi, A, Javid, N, Bazouri, M & Tabarraei, A 2014, 'Mutations in pre-core and basal-core promoter regions of hepatitis B virus in chronic HBV patients from Golestan, Iran.', Iran J Basic Med Sci, vol. 17, no. 5, pp. 370-377.
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OBJECTIVES: It has been reported that the mutation of the pre-core (PC) and basal-core promoter (BCP) may play an important role in the development of HBV-related hepatocellular carcinoma (HCC). In this study the PC and BCP mutations were investigated in chronic HBV patients. MATERIALS AND METHODS: In this study, 120 chronic HBV patients from Golestan, Northeast of Iran who were not vaccinated against HBV, were recruited from the year 2008 to 2012. HBV-DNA extraction from plasma and PCR were performed and positive PCR products were subjected to automated sequencing. RESULTS: One hundred out of 120 (83.3%) patients were HBeAg negative. Comparison of our nucleotide sequences with reference sequence showed high rate mutation in BCP and PC region (96.66%). Frame shift mutation was found in 78 (65%) of patients in BCP region, among them 8 (6.6%) patients showed mutation in PC region. CONCLUSION: Our results demonstrated high rate of mutations in BCP and PC regions among HBV chronic patients in Northeast of Iran.
Nguyen, TV 2014, 'Osteoarthritis in southeast Asia', International Journal of Clinical Rheumatology, vol. 9, no. 5, pp. 405-408.
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Osteoarthritis (OA) is a multifactorial and
complex disease that involves change in
articular bone and cartilage structure. The
multifactorial nature of OA is that the disease
is not a single entity, but encompasses
many entities, including the the loss of cartilage
within synovial joints, hypertrophy
of bone, and thickening of the capsule. The
complexity is in the causality and etiology
of the disease as its risk is determined by
multiple, and probably interactive, effects of
genetic and environmental factors.
Oakes, SR, Gallego-Ortega, D & Ormandy, CJ 2014, 'The mammary cellular hierarchy and breast cancer', Cellular and Molecular Life Sciences, vol. 71, no. 22, pp. 4301-4324.
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Papageorgiou, I, Abberton, T, Fuller, M, Tipper, J, Fisher, J & Ingham, E 2014, 'Biological Effects of Clinically Relevant CoCr Nanoparticles in the Dura Mater: An Organ Culture Study', Nanomaterials, vol. 4, no. 2, pp. 485-504.
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Papageorgiou, I, Marsh, R, Tipper, JL, Hall, RM, Fisher, J & Ingham, E 2014, 'Interaction of micron and nano‐sized particles with cells of the dura mater', Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 102, no. 7, pp. 1496-1505.
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AbstractIntervertebral total disc replacements (TDR) are used in the treatment of degenerative spinal disc disease. There are, however, concerns that they may be subject to long‐term failure due to wear. The adverse effects of TDR wear have the potential to manifest in the dura mater and surrounding tissues. The aim of this study was to investigate the physiological structure of the dura mater, isolate the resident dural epithelial and stromal cells and analyse the capacity of these cells to internalise model polymer particles. The porcine dura mater was a collagen‐rich structure encompassing regularly arranged fibroblastic cells within an outermost epithelial cell layer. The isolated dural epithelial cells had endothelial cell characteristics (positive for von Willebrand factor, CD31, E‐cadherin and desmoplakin) and barrier functionality whereas the fibroblastic cells were positive for collagen I and III, tenascin and actin. The capacity of the dural cells to take up model particles was dependent on particle size. Nanometer sized particles readily penetrated both types of cells. However, dural fibroblasts engulfed micron‐sized particles at a much higher rate than dural epithelial cells. The study suggested that dural epithelial cells may offer some barrier to the penetration of micron‐sized particles but not nanometer sized particles. © 2014 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1496–1505, 2014.
Perera, D, Chacon, D, Thoms, JAI, Poulos, RC, Shlien, A, Beck, D, Campbell, PJ, Pimanda, JE & Wong, JWH 2014, 'OncoCis: annotation of cis-regulatory mutations in cancer', GENOME BIOLOGY, vol. 15, no. 10, pp. 1-14.
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Whole genome sequencing has enabled the identification of thousands of somatic mutations within non-coding genomic regions of individual cancer samples. However, identification of mutations that potentially alter gene regulation remains a major challenge. Here we present OncoCis, a new method that enables identification of potential cis-regulatory mutations using cell type-specific genome and epigenome-wide datasets along with matching gene expression data. We demonstrate that the use of cell type-specific information and gene expression can significantly reduce the number of candidate cis-regulatory mutations compared with existing tools designed for the annotation of cis-regulatory SNPs.
Roohani-Esfahani, S-I, Wong, KY, Lu, Z, Juan Chen, Y, Li, JJ, Gronthos, S, Menicanin, D, Shi, J, Dunstan, C & Zreiqat, H 2014, 'Fabrication of a novel triphasic and bioactive ceramic and evaluation of its in vitro and in vivo cytocompatibility and osteogenesis', Journal of Materials Chemistry B, vol. 2, no. 13, pp. 1866-1866.
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We report, for the first time, the synthesis of a novel triphasic and crystalline bioactive ceramic (MSM-10) with the ability to simultaneously release three types of bioactive ions (strontium (Sr), silicon (Si) and magnesium (Mg)) to the surrounding microenvironment. An MSM-10 powder with a nominal composition (wt%) of 54 Mg2SiO4, 36 Si3Sr5 and 10 MgO was prepared by the sol-gel method and fabricated as porous scaffolds using the foam replication method. The effects of the different amounts of the phases in the ceramics on the mechanical and physical properties of the scaffolds as well as their in vitro and in vivo behaviors were comprehensively investigated. Biphasic calcium phosphate (BCP, β-tricalcium phosphate (60 wt%)/hydroxyapatite (40 wt%)) scaffolds were used as the control material. The attachment, morphology, proliferation and differentiation of primary human osteoblasts (HOBs) were investigated after cell culturing on the various scaffolds. In vitro cytotoxicity (ISO/EN 10993-5) results not only indicated the biocompatibility of MSM-10, but also its positive effects on inducing the proliferation of HOBs. Our results showed significant enhancement in osteogenic gene expression levels (Runx2, osteocalcin, osteopontin and bone sialoprotein), when HOBs were cultured on MSM-10, compared to those for BCP and other generated ceramic scaffolds. For the in vivo studies, the different types of the materials were seeded with cultured human mesenchymal stem cells (hMSC) and then subcutaneously transplanted into the dorsal surface of eight-week-old immunocompromised (NOD/SCID) mice. MSM-10 demonstrated a significant amount of new bone formation compared to the other groups tested with no macroscopic signs of inflammation or toxicity in the tissue surrounding the implants. The novel MSM-10 ceramic presents promising potential for bone regeneration in orthopaedic and maxillofacial applications.
Song, R, Liu, Q, Hutvagner, G, Nguyen, H, Ramamohanarao, K, Wong, L & Li, J 2014, 'Rule discovery and distance separation to detect reliable miRNA biomarkers for the diagnosis of lung squamous cell carcinoma', BMC GENOMICS, vol. 15.
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© 2014 Song et al. Background: Altered expression profiles of microRNAs (miRNAs) are linked to many diseases including lung cancer. miRNA expression profiling is reproducible and miRNAs are very stable. These characteristics of miRNAs make them ideal biomarker candidates. Method: This work is aimed to detect 2-and 3-miRNA groups, together with specific expression ranges of these miRNAs, to form simple linear discriminant rules for biomarker identification and biological interpretation. Our method is based on a novel committee of decision trees to derive 2-and 3-miRNA 100%-frequency rules. This method is applied to a data set of lung miRNA expression profiles of 61 squamous cell carcinoma (SCC) samples and 10 normal tissue samples. A distance separation technique is used to select the most reliable rules which are then evaluated on a large independent data set. Results: We obtained four 2-miRNA and three 3-miRNA top-ranked rules. One important rule is that: If the expression level of miR-98 is above 7.356 and the expression level of miR-205 is below 9.601 (log2 quantile normalized MirVan miRNA Bioarray signals), then the sample is normal rather than cancerous with specificity and sensitivity both 100%. The classification performance of our best miRNA rules remarkably outperformed that by randomly selected miRNA rules. Our data analysis also showed that miR-98 and miR-205 have two common predicted target genes FZD3 and RPS6KA3, which are actually genes associated with carcinoma according to the Online Mendelian Inheritance in Man (OMIM) database. We also found that most of the chromosomal loci of these miRNAs have a high frequency of genomic alteration in lung cancer. On the independent data set (with balanced controls), the three miRNAs miR-126, miR-205 and miR-182 from our best rule can separate the two classes of samples at the accuracy of 84.49%, sensitivity of 91.40% and specificity of 77.14%. Conclusion: Our results indicate that rule discovery foll...
Suñer, S, Bladen, CL, Gowland, N, Tipper, JL & Emami, N 2014, 'Investigation of wear and wear particles from a UHMWPE/multi-walled carbon nanotube nanocomposite for total joint replacements', Wear, vol. 317, no. 1-2, pp. 163-169.
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Sutton, SK, Koach, J, Tan, O, Liu, B, Carter, DR, Wilmott, JS, Yosufi, B, Haydu, LE, Mann, GJ, Thompson, JF, Long, GV, Liu, T, McArthur, G, Zhang, XD, Scolyer, RA, Cheung, BB & Marshall, GM 2014, 'TRIM16 inhibits proliferation and migration through regulation of interferon beta 1 in melanoma cells', Oncotarget, vol. 5, no. 20, pp. 10127-10139.
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High basal or induced expression of the tripartite motif protein, TRIM16, leads to reduce cell growth and migration of neuroblastoma and skin squamous cell carcinoma cells. However, the role of TRIM16 in melanoma is currently unknown. TRIM16 protein levels were markedly reduced in human melanoma cell lines, compared with normal human epidermal melanocytes due to both DNA methylation and reduced protein stability. TRIM16 knockdown strongly increased cell migration in normal human epidermal melanocytes, while TRIM16 overexpression reduced cell migration and proliferation of melanoma cells in an interferon beta 1 (IFNβ1)-dependent manner. Chromatin immunoprecipitation assays revealed TRIM16 directly bound the IFNβ1 gene promoter. Low level TRIM16 expression in 91 melanoma patient samples, strongly correlated with lymph node metastasis, and, predicted poor patient prognosis in a separate cohort of 170 melanoma patients with lymph node metastasis. The BRAF inhibitor, vemurafenib, increased TRIM16 protein levels in melanoma cells in vitro, and induced growth arrest in BRAF-mutant melanoma cells in a TRIM16-dependent manner. High levels of TRIM16 in melanoma tissues from patients treated with Vemurafenib correlated with clinical response. Our data, for the first time, demonstrates TRIM16 is a marker of cell migration and metastasis, and a novel treatment target in melanoma.
Tran, B, Nguyen, ND, Center, JR, Eisman, JA & Nguyen, TV 2014, 'Association between fat‐mass‐and‐obesity‐associated (FTO) gene and hip fracture susceptibility', Clinical Endocrinology, vol. 81, no. 2, pp. 210-217.
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SummaryObjectiveCommon variants in the fat‐mass‐and‐obesity‐associated (FTO) gene are related to body mass index (BMI), which is a predictor of hip fracture risk. This study sought to examine the association between variants in the FTO gene and hip fracture risk.Design and participantsThis is a prospective study including 934 postmenopausal women aged 60 years and above living in Dubbo, Australia (Dubbo Osteoporosis Epidemiology Study), followed up between 1989 and 2007.MeasurementsSix single nucleotide polymorphisms (SNPs) (rs1421085, rs1558902, rs1121980, rs17817449, rs9939609 and rs9930506) of the FTO gene were genotyped using Taqman assay. Bone mineral density at the lumbar spine and femoral neck was measured by DXA (GE‐Lunar) at baseline. Incidence of hip fractures during the follow‐up was ascertained by reviewing X‐ray reports. We used Cox's models to estimate the association between the genetic variants and hip fracture risk. We also utilized Bayes factor to evaluate the association.ResultsOne hundred and two women (11%) had sustained a hip fracture. The incidence of hip fracture was greater in women homozygous for the minor allele of all SNP
Warkiani, ME, Guan, G, Luan, KB, Lee, WC, Bhagat, AAS, Kant Chaudhuri, P, Tan, DS-W, Lim, WT, Lee, SC, Chen, PCY, Lim, CT & Han, J 2014, 'Slanted spiral microfluidics for the ultra-fast, label-free isolation of circulating tumor cells', Lab Chip, vol. 14, no. 1, pp. 128-137.
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Warkiani, ME, Khoo, BL, Tan, DS-W, Bhagat, AAS, Lim, W-T, Yap, YS, Lee, SC, Soo, RA, Han, J & Lim, CT 2014, 'An ultra-high-throughput spiral microfluidic biochip for the enrichment of circulating tumor cells', The Analyst, vol. 139, no. 13, pp. 3245-3255.
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We demonstrate the high-throughput and high-resolution separation of rare circulating tumor cells (CTCs) from blood using a multiplexed spiral microfluidic device.
Wilkinson, DJC, Crespigny, L, Lees, C, Savulescu, J, Thiele, P, Tran, T & Watkins, A 2014, 'Perinatal management of trisomy 18: a survey of obstetricians in Australia, New Zealand and the UK', Prenatal Diagnosis, vol. 34, no. 1, pp. 42-49.
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Yagoub, D, Wilkins, MR, Lay, AJ, Kaczorowski, DC, Hatoum, D, Bajan, S, Hutvagner, G, Lai, JH, Wu, W, Martiniello-Wilks, R, Xia, P & McGowan, EM 2014, 'Sphingosine Kinase 1 Isoform-Specific Interactions in Breast Cancer', MOLECULAR ENDOCRINOLOGY, vol. 28, no. 11, pp. 1899-1915.
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© 2014 by the Endocrine Society. Sphingosine kinase 1 (SK1) is a signaling enzyme that catalyzes the formation of sphingosine-1-phosphate. Overexpression of SK1 is causally associated with breast cancer progression and resistance to therapy. SK1 inhibitors are currently being investigated as promising breast cancer therapies. Two major transcriptional isoforms, SK143kDa and SK151kDa, have been identified; however, the 51kDa variant is predominant in breast cancer cells. No studies have investigated the protein-protein interactions of the 51kDa isoform and whether the two SK1 isoforms differ significantly in their interactions. Seeking an understanding of the regulation and role of SK1, we used a triple-labeling stable isotope labeling by amino acids in cell culture-based approach to identify SK1-interacting proteins common and unique to both isoforms. Of approximately 850 quantified proteins in SK1 immunopre-cipitates, a high-confidence list of 30 protein interactions with each SK1 isoform was generated via a meta-analysis of multiple experimental replicates. Many of the novel identified SK1 interaction partners such assupervillin, drebrin, and the myristoylated alanine-rich C-kinase substrate-related protein supported and highlighted previously implicated roles of SK1 in breast cancer cell migration, adhesion, and cytoskeletal remodeling. Of these interactions, several were found to be exclusive to the 43kDa isoform of SK1, including the protein phosphatase 2A, a previously identified SK1-interacting protein. Other proteins such as allograft inflammatory factor 1-like protein, the latent-transforming growth factor β-binding protein, and dipeptidyl peptidase 2 were found to associate exclusively with the 51kDa isoform of SK1. In this report, we have identified common and isoform-specificSK1-interacting partners that provide insight into the molecular mechanisms that drive SK1-mediated oncogenicity.
Yang, S, Nguyen, ND, Center, JR, Eisman, JA & Nguyen, TV 2014, 'Association between hypertension and fragility fracture: a longitudinal study', Osteoporosis International, vol. 25, no. 1, pp. 97-103.
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Hypertension is an independent risk factor for osteoporosis and osteoporotic fracture in postmenopausal women.Although hypertension has been suggested to be associated with increased fracture risk, it is not clear whether the association is independent of bone mineral density (BMD). The present study sought to examine the interrelationships between hypertension, BMD, and fracture risk.The study included 1,032 men and 1,701 women aged 50 years and older who were participants in the Dubbo Osteoporosis Epidemiology Study. BMD at the femoral neck and lumbar spine was measured by dual energy X-ray absorptiometry (GE-LUNAR Corp., Madison, WI, USA). The presence of hypertension was ascertained by direct interview and verification through clinical history. The incidence of fragility fractures was ascertained by X-ray report during the follow-up period (1989-2008). The Cox proportional hazards model was used to assess the association between hypertension and fracture risk.Women with hypertension had lower BMD at the femoral neck (0.79 versus 0.82 g/cm(2), P = 0.02) than those without the disease. After adjusting for BMD and covariates, hypertension was an independent risk factor for fragility fracture [hazard ratio (HR), 1.49; 95% CI, 1.13-1.96]. In men, hypertension was associated with higher femoral neck BMD (0.94 versus 0.92 g/cm(2), P = 0.02), but the association between hypertension and fracture risk did not reach statistical significance.Hypertension is associated with increased fracture risk in women, and the association is independent of BMD.
Yoshizaki, K, Hu, L, Nguyen, T, Sakai, K, He, B, Fong, C, Yamada, Y, Bikle, DD & Oda, Y 2014, 'Ablation of Coactivator Med1 Switches the Cell Fate of Dental Epithelia to That Generating Hair', PLoS ONE, vol. 9, no. 6, pp. e99991-e99991.
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Cell fates are determined by specific transcriptional programs. Here we provide evidence that the transcriptional coactivator, Mediator 1 (Med1), is essential for the cell fate determination of ectodermal epithelia. Conditional deletion of Med1 in vivo converted dental epithelia into epidermal epithelia, causing defects in enamel organ development while promoting hair formation in the incisors. We identified multiple processes by which hairs are generated in Med1 deficient incisors: 1) dental epithelial stem cells lacking Med 1 fail to commit to the dental lineage, 2) Sox2-expressing stem cells extend into the differentiation zone and remain multi-potent due to reduced Notch1 signaling, and 3) epidermal fate is induced by calcium as demonstrated in dental epithelial cell cultures. These results demonstrate that Med1 is a master regulator in adult stem cells to govern epithelial cell fate.
Zhang, L, Zheng, X, Deng, W, Lu, Y, Lechevallier, S, Ye, Z, Goldys, EM, Dawes, JM, Piper, JA, Yuan, J, Verelst, M & Jin, D 2014, 'Practical Implementation, Characterization and Applications of a Multi-Colour Time-Gated Luminescence Microscope', Scientific Reports, vol. 4, no. 1, pp. 1-6.
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AbstractTime-gated luminescence microscopy using long-lifetime molecular probes can effectively eliminate autofluorescence to enable high contrast imaging. Here we investigate a new strategy of time-gated imaging for simultaneous visualisation of multiple species of microorganisms stained with long-lived complexes under low-background conditions. This is realized by imaging two pathogenic organisms (Giardia lamblia stained with a red europium probe and Cryptosporidium parvum with a green terbium probe) at UV wavelengths (320–400 nm) through synchronization of a flash lamp with high repetition rate (1 kHz) to a robust time-gating detection unit. This approach provides four times enhancement in signal-to-background ratio over non-time-gated imaging, while the average signal intensity also increases six-fold compared with that under UV LED excitation. The high sensitivity is further confirmed by imaging the single europium-doped Y2O2S nanocrystals (150 nm). We report technical details regarding the time-gating detection unit and demonstrate its compatibility with commercial epi-fluorescence microscopes, providing a valuable and convenient addition to standard laboratory equipment.
