Publications

Warkiani, ME, Wu, L, Tay, AKP & Han, J 2015, Large-Volume Microfluidic Cell Sorting for Biomedical Applications, Annual Reviews.
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Microfluidic cell-separation technologies have been studied for almost two decades, but the limited throughput has restricted their impact and range of application. Recent advances in microfluidics enable high-throughput cell sorting and separation, and this has led to various novel diagnostic and therapeutic applications that previously had been impossible to implement using microfluidics technologies. In this review, we focus on recent progress made in engineering large-volume microfluidic cell-sorting methods and the new applications enabled by them.

Lu, Z, Li, JJ & Zreiqat, H 2015, 'Bone-Biomimetic Biomaterial and Cell Fate Determination' in Mechanical Engineering Series, Springer International Publishing, pp. 119-146.
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Ting, SRS, Min, EH, Cortie, MB, Nguyen, HT & Hutvagner, G 2015, 'Frontiers in Nanomedicine' in Bondì, M, Botto, C & Amore, E (eds), Frontiers in Nanomedicine, BENTHAM SCIENCE PUBLISHERS, UAE, pp. 222-255.
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The development of therapeutic nucleic acids has led to new strategies for treating various diseases. Non-viral, synthetic nano-vectors in gene therapy have attracted increasing attention due to their low immunogenicity and low toxicity compared to viral counterparts. Due to the molecular structure of nucleic acids, they are very prone to degradation in pH sensitive biological environments. Therefore, synthetic nano-vehicles for therapeutic delivery, known as ‘nano-vectors’, need to be cleverly designed and engineered to protect and deliver appropriate therapeutic nucleic acids to the targeted sites for action. In this chapter, a brief overview of various types of therapeutic nucleic acids is first provided, followed by analysis of the synthetic nanomaterials under development as delivery systems to carry nucleic acids. The nucleic acid-encapsulated nano-vectors discussed here open a window for a new generation of nanomedicine.

Aquilina, P, Parr, WCH, Chamoli, U & Wroe, S 2015, 'Finite Element Analysis of Patient-Specific Condyle Fracture Plates: A Preliminary Study', Craniomaxillofacial Trauma & Reconstruction, vol. 8, no. 2, pp. 111-116.
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Various patterns of internal fixation of mandibular condyle fractures have been proposed in the literature. This study investigates the stability of two patient-specific implants (PSIs) for the open reduction and internal fixation of a subcondylar fracture of the mandible. A subcondylar fracture of a mandible was simulated by a series of finite element models. These models contained approximately 1.2 million elements, were heterogeneous in bone material properties, and also modeled the muscles of mastication. Models were run assuming linear elasticity and isotropic material properties for bone. The stability and von Mises stresses of the simulated condylar fracture reduced with each of the PSIs were compared. The most stable of the plate configurations examined was PSI 1, which had comparable mechanical performance to a single 2.0 mm straight four-hole plate.

Asadnia, M, Kottapalli, AGP, Miao, J, Warkiani, ME & Triantafyllou, MS 2015, 'Artificial fish skin of self-powered micro-electromechanical systems hair cells for sensing hydrodynamic flow phenomena', Journal of The Royal Society Interface, vol. 12, no. 111, pp. 20150322-20150322.
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Using biological sensors, aquatic animals like fishes are capable of performing impressive behaviours such as super-manoeuvrability, hydrodynamic flow ‘vision’ and object localization with a success unmatched by human-engineered technologies. Inspired by the multiple functionalities of the ubiquitous lateral-line sensors of fishes, we developed flexible and surface-mountable arrays of micro-electromechanical systems (MEMS) artificial hair cell flow sensors. This paper reports the development of the MEMS artificial versions of superficial and canal neuromasts and experimental characterization of their unique flow-sensing roles. Our MEMS flow sensors feature a stereolithographically fabricated polymer hair cell mounted on Pb(Zr0.52Ti0.48)O3micro-diaphragm with floating bottom electrode. Canal-inspired versions are developed by mounting a polymer canal with pores that guide external flows to the hair cells embedded in the canal. Experimental results conducted employing our MEMS artificial superficial neuromasts (SNs) demonstrated a high sensitivity and very low threshold detection limit of 22 mV/(mm s−1) and 8.2 µm s−1, respectively, for an oscillating dipole stimulus vibrating at 35 Hz. Flexible arrays of such superficial sensors were demonstrated to localize an underwater dipole stimulus. Comparative experimental studies revealed a high-pass filtering nature of the canal encapsulated sensors with a cut-off frequency of 10 Hz and a flat frequency response of artificial SNs. Flexible arrays of self-powered, miniaturized, light-weight, low-cost and robust artificial lateral-line systems could enhance the capabilities of underwater vehicles.

Beckers, A, Van Peer, G, Carter, DR, Gartlgruber, M, Herrmann, C, Agarwal, S, Helsmoortel, HH, Althoff, K, Molenaar, JJ, Cheung, BB, Schulte, JH, Benoit, Y, Shohet, JM, Westermann, F, Marshall, GM, Vandesompele, J, De Preter, K & Speleman, F 2015, 'MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma', Cancer Letters, vol. 366, no. 1, pp. 123-132.
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Beckers, A, Van Peer, G, Carter, DR, Mets, E, Althoff, K, Cheung, BB, Schulte, JH, Mestdagh, P, Vandesompele, J, Marshall, GM, De Preter, K & Speleman, F 2015, 'MYCN-targeting miRNAs are predominantly downregulated during MYCN-driven neuroblastoma tumor formation', Oncotarget, vol. 6, no. 7, pp. 5204-5216.
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Bliuc, D, Alarkawi, D, Nguyen, TV, Eisman, JA & Center, JR 2015, 'Risk of Subsequent Fractures and Mortality in Elderly Women and Men with Fragility Fractures with and without Osteoporotic Bone Density: The Dubbo Osteoporosis Epidemiology Study', Journal of Bone and Mineral Research, vol. 30, no. 4, pp. 637-646.
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ABSTRACT   Half of fragility fractures occur in individuals with nonosteoporotic BMD (BMD T-score > –2.5); however, there is no information on postfracture adverse events of subsequent fracture and mortality for different BMD levels. The objective of this work was to determine the risk and predictors of subsequent fracture and excess mortality following initial fracture according to BMD. The subjects were community-dwelling participants aged 60+ years from the Dubbo Osteoporosis Epidemiology Study with incident fractures followed from 1989 to 2011. The outcome measurements were as follows: risk of subsequent fracture and mortality according to BMD categorized as normal (T-score < –1), osteopenia (T-score ≤ –1 and > –2.5), and osteoporosis (T-score ≤ –2.5). There were 528 low-trauma fractures in women and 187 in men. Of these, 12% occurred in individuals with normal BMD (38 women, 50 men) and 42% in individuals with osteopenia (221 women, 76 men). The relative risk (RR) of subsequent fracture was >2.0-fold for all levels of BMD (normal BMD: 2.0 [1.2 to 3.3] for women and 2.1 [1.2 to 3.8] for men; osteopenia: 2.1 [1.7 to 2.6] for women and 2.5 [1.6 to 4.1] for men; and osteoporosis 3.2 [2.7 to 3.9] for women and 2.1 [1.4 to 3.1] for men. The likelihood of falling and reduced quadriceps strength contributed to subsequent fracture risk in women with normal BMD. By contrast with subsequent fracture risk, postfracture mortality was increased particularly in individuals with low BMD (age-adjusted standardized mortality ratio [SMR] for osteopenia 1.3 [1.1 to 1.7] and 2.2 [1.7 to 2.9] for women and men, respectively, and osteoporosis 1.7 [1.5 to 2.0] and 2.7 [2.0 to 3.6] for women and men, respectively). This study demonstrates the high burden of subsequent fracture in individuals with normal BMD and osteopenia, and ...

Carter, DR, Murray, J, Cheung, BB, Gamble, L, Koach, J, Tsang, J, Sutton, S, Kalla, H, Syed, S, Gifford, AJ, Issaeva, N, Biktasova, A, Atmadibrata, B, Sun, Y, Sokolowski, N, Ling, D, Kim, PY, Webber, H, Clark, A, Ruhle, M, Liu, B, Oberthuer, A, Fischer, M, Byrne, J, Saletta, F, Thwe, LM, Purmal, A, Haderski, G, Burkhart, C, Speleman, F, De Preter, K, Beckers, A, Ziegler, DS, Liu, T, Gurova, KV, Gudkov, AV, Norris, MD, Haber, M & Marshall, GM 2015, 'Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma', Science Translational Medicine, vol. 7, no. 312.
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Histone chaperone FACT acts in a positive feedback loop with MYCN and is a therapeutic target in neuroblastoma.

Chamoli, U, Korkusuz, MH, Sabnis, AB, Manolescu, AR, Tsafnat, N & Diwan, AD 2015, 'Global and segmental kinematic changes following sequential resection of posterior osteoligamentous structures in the lumbar spine: An in vitro biomechanical investigation using pure moment testing protocols', Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, vol. 229, no. 11, pp. 812-821.
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Lumbar spinal surgeries may compromise the integrity of posterior osteoligamentous structures implicating mechanical stability. Circumstances necessitating a concomitant surgery to achieve restabilisation are not well understood. The main objective of this in vitro study was to quantify global and segmental (index and adjacent levels) kinematic changes in the lumbar spine following sequential resection of the posterior osteoligamentous structures using pure moment testing protocols. Six fresh frozen cadaveric kangaroo lumbar spines (T12–S1) were tested under a bending moment in flexion–extension, bilateral bending, and axial torsion in a 6-degree-of-freedom Kinematic Spine Simulator. Specimens were tested in the following order: intact state (D0), after interspinous and supraspinous ligaments transection between L4 and L5 (D1), further after a total bilateral facetectomy between L4 and L5 (D2). Segmental motions at the cephalad, damaged, and caudal levels were recorded using an infrared-based motion tracking device. Following D1, no significant change in the global range of motion was observed in any of the bending planes. Following D2, a significant increase in the global range of motion from the baseline (D0) was observed in axial torsion (median normalised change +20%). At the damaged level, D2resulted in a significant increase in the segmental range of motion in flexion–extension (+77%) and axial torsion (+492%). Additionally, a significant decrease in the segmental range of motion in axial torsion (−35%) was observed at the caudal level following D2. These results suggest that a multi-segment lumbar spine acts as a mechanism for transmitting motions, and that a compromised joint may significantly alter motion transfer to adjacent segments. We conclude that the interspinous an...

Cheung, BB, Tan, O, Koach, J, Liu, B, Shum, MSY, Carter, DR, Sutton, S, Po'uha, ST, Chesler, L, Haber, M, Norris, MD, Kavallaris, M, Liu, T, O'Neill, GM & Marshall, GM 2015, 'Thymosin‐β4 is a determinant of drug sensitivity for Fenretinide and Vorinostat combination therapy in neuroblastoma', Molecular Oncology, vol. 9, no. 7, pp. 1484-1500.
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AbstractRetinoids are an important component of neuroblastoma therapy at the stage of minimal residual disease, yet 40–50% of patients treated with 13‐cis‐retinoic acid (13‐cis‐RA) still relapse, indicating the need for more effective retinoid therapy. Vorinostat, or Suberoylanilide hydroxamic acid (SAHA), is a potent inhibitor of histone deacetylase (HDAC) classes I & II and has antitumor activity in vitro and in vivo. Fenretinide (4‐HPR) is a synthetic retinoid which acts on cancer cells through both nuclear retinoid receptor and non‐receptor mechanisms. In this study, we found that the combination of 4‐HPR + SAHA exhibited potent cytotoxic effects on neuroblastoma cells, much more effective than 13‐cis‐RA + SAHA. The 4‐HPR + SAHA combination induced caspase‐dependent apoptosis through activation of caspase 3, reduced colony formation and cell migration in vitro, and tumorigenicity in vivo. The 4‐HPR and SAHA combination significantly increased mRNA expression of thymosin‐beta‐4 (Tβ4) and decreased mRNA expression of retinoic acid receptor α (RARα). Importantly, the up‐regulation of Tβ4 and down‐regulation of RARα were both necessary for the 4‐HPR + SAHA cytotoxic effect on neuroblastoma cells. Moreover, Tβ4 knockdown in neuroblastoma cells increased cell migration and blocked the effect of 4‐HPR + SAHA on cell migration and focal adhesion formation. In primary human neuroblastoma tumor tissues, low expression of Tβ4 was associated with metastatic disease and predicted poor patient prognosis. Our findings demonstrate that Tβ4 is a novel therapeutic target in neuroblastoma, and that 4‐HPR + SAHA is a potential therapy for the disease.

Choudhury, MH, Ciampi, S, Yang, Y, Tavallaie, R, Zhu, Y, Zarei, L, Gonçales, VR & Gooding, JJ 2015, 'Connecting electrodes with light: one wire, many electrodes', Chemical Science, vol. 6, no. 12, pp. 6769-6776.
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The requirement of a wire to each electrode is central to the design of any electronic device but can also be a major restriction. Herein it is shown how electrodes can be connected using light such that a multielectrode device requires only a single physical wire.

Clement, S, Deng, W, Drozdowicz-Tomsia, K, Liu, D, Zachreson, C & Goldys, EM 2015, 'Bright, water-soluble CeF3 photo-, cathodo-, and X-ray luminescent nanoparticles', Journal of Nanoparticle Research, vol. 17, no. 1.
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© 2015, Springer Science+Business Media Dordrecht. Bright, water-soluble CeF3 nanoparticles with small size and narrow size distribution have been synthesized using a simple co-precipitation method without any ligands. Size control of nanoparticles from 13 ± 2 to 9 ± 2 nm was achieved by varying the reaction time. Colloidal properties have been found to vary with pH and, independently, with dilution. The photoluminescence of the as-synthesized nanoparticles shows a highly photostable UV/Visible fluorescence band due to allowed 5d–4f transitions, also observed in the X-ray luminescence spectrum. This band is suitable for X-ray excitation of a range of photosensitizers. The photoluminescence quantum yield of nanoparticles was also determined to be 31 %. Using the measured fluorescence decay time of 25 ns, the radiative lifetime of Ce in CeF3 was found to be 80.6 ns. Both photoluminescence and cathodoluminescence emission are affected by the reaction time and measurement temperature. Electron-beam-induced defect annealing is also observed.

Connerty, P, Ahadi, A & Hutvagner, G 2015, 'RNA Binding Proteins in the miRNA Pathway', International Journal of Molecular Sciences, vol. 17, no. 1, pp. 31-31.
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© 2015 by the authors; licensee MDPI, Basel, Switzerland. microRNAs (miRNAs) are short ~22 nucleotides (nt) ribonucleic acids which post-transcriptionally regulate gene expression. miRNAs are key regulators of all cellular processes, and the correct expression of miRNAs in an organism is crucial for proper development and cellular function. As a result, the miRNA biogenesis pathway is highly regulated. In this review, we outline the basic steps of miRNA biogenesis and miRNA mediated gene regulation focusing on the role of RNA binding proteins (RBPs). We also describe multiple mechanisms that regulate the canonical miRNA pathway, which depends on a wide range of RBPs. Moreover, we hypothesise that the interaction between miRNA regulation and RBPs is potentially more widespread based on the analysis of available high-throughput datasets.

Deng, W, Farnham, MMJ, Goldys, EM, Mohammed, S & Pilowsky, PM 2015, 'Gene Interference with Morpholinos in a Gold Nanoparticle-Based Delivery Platform in Rat PC12 Cells', Journal of Biomedical Nanotechnology, vol. 11, no. 12, pp. 2111-2123.
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Di Bartolo, BA, Cartland, SP, Prado‐Lourenco, L, Griffith, TS, Gentile, C, Ravindran, J, Azahri, NSM, Thai, T, Yeung, AWS, Thomas, SR & Kavurma, MM 2015, 'Tumor Necrosis Factor–Related Apoptosis‐Inducing Ligand (TRAIL) Promotes Angiogenesis and Ischemia‐Induced Neovascularization Via NADPH Oxidase 4 (NOX4) and Nitric Oxide–Dependent Mechanisms', Journal of the American Heart Association, vol. 4, no. 11.
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Background Tumor necrosis factor–related apoptosis‐inducing ligand ( TRAIL ) has the ability to inhibit angiogenesis by inducing endothelial cell death, as well as being able to promote pro‐angiogenic activity in vitro. These seemingly opposite effects make its role in ischemic disease unclear. Using Trail −/− and wildtype mice, we sought to determine the role of TRAIL in angiogenesis and neovascularization following hindlimb ischemia. Methods and Results Reduced vascularization assessed by real‐time 3‐dimensional Vevo ultrasound imaging and CD 31 staining was evident in Trail −/− mice after ischemia, and associated with reduced capillary formation and increased apoptosis. Notably, adenoviral TRAIL administration significantly improved limb perfusion, capillary density, and vascular smooth‐muscle cell content in both Trail −/− and wildtype mice. Fibroblast growth factor‐2, a potent angiogeni...

Dodd, JM, Ahmed, S, Karnon, J, Umberger, W, Deussen, AR, Tran, T, Grivell, RM, Crowther, CA, Turnbull, D, McPhee, AJ, Wittert, G, Owens, JA & Robinson, JS 2015, 'The cost-effectiveness of providing antenatal lifestyle advice for women who are overweight or obese: the LIMIT randomised trial', BMC Obesity, vol. 2, no. 1, p. 14.
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BACKGROUND: Overweight and obesity during pregnancy is common, although robust evidence about the economic implications of providing an antenatal dietary and lifestyle intervention for women who are overweight or obese is lacking. We conducted a health economic evaluation in parallel with the LIMIT randomised trial. Women with a singleton pregnancy, between 10(+0)-20(+0) weeks, and BMI ≥25 kg/m(2) were randomised to Lifestyle Advice (a comprehensive antenatal dietary and lifestyle intervention) or Standard Care. The economic evaluation took the perspective of the health care system and its patients, and compared costs encountered from the additional use of resources from time of randomisation until six weeks postpartum. Increments in health outcomes for both the woman and infant were considered in the cost-effectiveness analysis. Mean costs and effects in the treatment groups allocated at randomisation were compared, and incremental cost effectiveness ratios (ICERs) and confidence intervals (95%) calculated. Bootstrapping was used to confirm the estimated confidence intervals, and to generate acceptability curves representing the probability of the intervention being cost-effective at alternative monetary equivalent values for the outcomes avoiding high infant birth weight, and respiratory distress syndrome. Analyses utilised intention to treat principles. RESULTS: Overall, the increase in mean costs associated with providing the intervention was offset by savings associated with improved immediate neonatal outcomes, rendering the intervention cost neutral (Lifestyle Advice Group $11261.19±$14573.97 versus Standard Care Group $11306.70±$14562.02; p=0.094). Using a monetary value of $20,000 as a threshold value for avoiding an additional infant with birth weight above 4 kg, the probability that the antenatal intervention is cost-effective is 0.85, which increases to 0.95 when the threshold monetary value increases to $45,000. CONCLUSIONS: Providing an an...

Elson, KM, Fox, N, Tipper, JL, Kirkham, J, Hall, RM, Fisher, J & Ingham, E 2015, 'Non-destructive monitoring of viability in an ex vivo organ culture model of osteochondral tissue', European Cells and Materials, vol. 29, pp. 356-369.
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Gallego-Ortega, D, Ledger, A, Roden, DL, Law, AMK, Magenau, A, Kikhtyak, Z, Cho, C, Allerdice, SL, Lee, HJ, Valdes-Mora, F, Herrmann, D, Salomon, R, Young, AIJ, Lee, BY, Sergio, CM, Kaplan, W, Piggin, C, Conway, JRW, Rabinovich, B, Millar, EKA, Oakes, SR, Chtanova, T, Swarbrick, A, Naylor, MJ, O’Toole, S, Green, AR, Timpson, P, Gee, JMW, Ellis, IO, Clark, SJ & Ormandy, CJ 2015, 'ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells', PLOS Biology, vol. 13, no. 12, pp. e1002330-e1002330.
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Ho-Pham, LT, Lai, TQ, Mai, LD, Doan, MC, Pham, HN & Nguyen, TV 2015, 'Prevalence and Pattern of Radiographic Intervertebral Disc Degeneration in Vietnamese: A Population-Based Study', Calcified Tissue International, vol. 96, no. 6, pp. 510-517.
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Ho-Pham, LT, Lai, TQ, Nguyen, MTT & Nguyen, TV 2015, 'Relationship between Body Mass Index and Percent Body Fat in Vietnamese: Implications for the Diagnosis of Obesity', PLOS ONE, vol. 10, no. 5, pp. e0127198-e0127198.
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© 2015 Ho-Pham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background The burden of obesity in Vietnam has not been well defined because there is a lack of reference data for percent body fat (PBF) in Asians. This study sought to define the relationship between PBF and body mass index (BMI) in the Vietnamese population. Methods The study was designed as a comparative cross-sectional investigation that involved 1217 individuals of Vietnamese background (862 women) aged 20 years and older (average age 7 yr) who were randomly selected from the general population in Ho Chi Minh City. Lean mass (LM) and fat mass (FM) were measured by DXA (Hologic QDR 4500). PBF was derived as FM over body weight. Results Based on BMI 30, the prevalence of obesity was 1.1% and 1.3% for men and women, respectively. The prevalence of overweight and obesity combined (BMI 25) was ∼ 24% and ∼ 19% in men and women, respectively. Based on the quadratic relationship between BMI and PBF, the approximate PBF corresponding to the BMI threshold of 30 (obese) was 30.5 in men and 41 in women. Using the criteria of PBF >30 in men and PBF >40 in women, approximately 15% of men and women were considered obese. Conclusion These data suggest that body mass index underestimates the prevalence of obesity. We suggest that a PBF >30 in men or PBF >40 in women is used as criteria for the diagnosis of obesity in Vietnamese adults. Using these criteria, 15% of Vietnamese adults in Ho Chi Minh City was considered obese.

Ho-Pham, LT, Nguyen, SC, Tran, B & Nguyen, TV 2015, 'Contributions of Caucasian-associated bone mass loci to the variation in bone mineral density in Vietnamese population', Bone, vol. 76, pp. 18-22.
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Hyde, PJ, Tipper, J, Fisher, J & Hall, RM 2015, 'Wear and biological effects of a semi-constrained total disc replacement subject to modified ISO standard test conditions', Journal of the Mechanical Behavior of Biomedical Materials, vol. 44, pp. 43-52.
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Jing, D, Bhadri, VA, Beck, D, Thoms, JAI, Yakob, NA, Wong, JWH, Knezevic, K, Pimanda, JE & Lock, RB 2015, 'Opposing regulation of BIM and BCL2 controls glucocorticoid-induced apoptosis of pediatric acute lymphoblastic leukemia cells', BLOOD, vol. 125, no. 2, pp. 273-283.
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Jing, T, Ramji, R, Warkiani, ME, Han, J, Lim, CT & Chen, C-H 2015, 'Jetting microfluidics with size-sorting capability for single-cell protease detection', Biosensors and Bioelectronics, vol. 66, pp. 19-23.
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Junankar, S, Baker, LA, Roden, DL, Nair, R, Elsworth, B, Gallego-Ortega, D, Lacaze, P, Cazet, A, Nikolic, I, Teo, WS, Yang, J, McFarland, A, Harvey, K, Naylor, MJ, Lakhani, SR, Simpson, PT, Raghavendra, A, Saunus, J, Madore, J, Kaplan, W, Ormandy, C, Millar, EKA, O’Toole, S, Yun, K & Swarbrick, A 2015, 'ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype', Nature Communications, vol. 6, no. 1.
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Keam, S & Hutvagner, G 2015, 'tRNA-Derived Fragments (tRFs): Emerging New Roles for an Ancient RNA in the Regulation of Gene Expression', Life, vol. 5, no. 4, pp. 1638-1651.
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© 2015 by the authors; licensee MDPI, Basel, Switzerland. This review will summarise the recent discoveries and current state of research on short noncoding RNAs derived from tRNAs—known as tRNA-derived fragments (tRFs). It will describe the features of the known subtypes of these RNAs; including sequence characteristics, protein interactors, expression characteristics, biogenesis, and similarity to canonical miRNA pathways. Also their role in regulating gene expression; including mediating translational suppression, will be discussed. We also highlight their potential use as biomarkers, functions in gene regulation and links to disease. Finally, this review will speculate as to the origin and rationale for the conservation of this novel class of noncoding RNAs amongst both prokaryotes and eukaryotes.

Khoo, BL, Lee, SC, Kumar, P, Tan, TZ, Warkiani, ME, Ow, SGW, Nandi, S, Lim, CT & Thiery, JP 2015, 'Short-term expansion of breast circulating cancer cells predicts response to anti-cancer therapy', Oncotarget, vol. 6, no. 17, pp. 15578-15593.
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Circulating tumor cells (CTCs) are considered as surrogate markers for prognosticating and evaluating patient treatment responses. Here, 226 blood samples from 92 patients with breast cancer, including patients with newly diagnosed or metastatic refractory cancer, and 16 blood samples from healthy subjects were cultured in laser-ablated microwells. Clusters containing an increasing number of cytokeratin-positive (CK+) cells appeared after 2 weeks, while most blood cells disappeared with time. Cultures were heterogeneous and exhibited two distinct sub-populations of cells: 'Small' (≤ 25 μm; high nuclear/cytoplasmic ratio; CD45-) cells, comprising CTCs, and 'Large' (> 25 μm; low nuclear/cytoplasmic ratio; CD68+ or CD56+) cells, corresponding to macrophage and natural killer-like cells. The Small cell fraction also showed copy number increases in six target genes (FGFR1, Myc, CCND1, HER2, TOP2A and ZNF217) associated with breast cancer. These expanded CTCs exhibited different proportions of epithelial-mesenchymal phenotypes and were transferable for further expansion as spheroids in serum-free suspension or 3D cultures. Cluster formation was affected by the presence and duration of systemic therapy, and its persistence may reflect therapeutic resistance. This novel and advanced method estimates CTC clonal heterogeneity and can predict, within a relatively short time frame, patient responses to therapy.

Lambertz, I, Kumps, C, Claeys, S, Lindner, S, Beckers, A, Janssens, E, Carter, DR, Cazes, A, Cheung, BB, De Mariano, M, De Bondt, A, De Brouwer, S, Delattre, O, Gibbons, J, Janoueix-Lerosey, I, Laureys, G, Liang, C, Marchall, GM, Porcu, M, Takita, J, Trujillo, DC, Van Den Wyngaert, I, Van Roy, N, Van Goethem, A, Van Maerken, T, Zabrocki, P, Cools, J, Schulte, JH, Vialard, J, Speleman, F & De Preter, K 2015, 'Upregulation of MAPK Negative Feedback Regulators and RET in Mutant ALK Neuroblastoma: Implications for Targeted Treatment', Clinical Cancer Research, vol. 21, no. 14, pp. 3327-3339.
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Abstract Purpose: Activating ALK mutations are present in almost 10% of primary neuroblastomas and mark patients for treatment with small-molecule ALK inhibitors in clinical trials. However, recent studies have shown that multiple mechanisms drive resistance to these molecular therapies. We anticipated that detailed mapping of the oncogenic ALK-driven signaling in neuroblastoma can aid to identify potential fragile nodes as additional targets for combination therapies. Experimental Design: To achieve this goal, transcriptome profiling was performed in neuroblastoma cell lines with the ALKF1174L or ALKR1275Q hotspot mutations, ALK amplification, or wild-type ALK following pharmacologic inhibition of ALK using four different compounds. Next, we performed cross-species genomic analyses to identify commonly transcriptionally perturbed genes in MYCN/ALKF1174L double transgenic versus MYCN transgenic mouse tumors as compared with the mutant ALK-driven transcriptome in human neuroblastomas. Results: A 77-gene ALK signature was established and successfully validated in primary neuroblastoma samples, in a neuroblastoma cell line with ALKF1174L and ALKR1275Q regulable overexpression constructs and in other ALKomas. In addition to the previously established PI3K/AKT/mTOR, MAPK/ERK, and MYC/MYCN signaling branches, we identified that mutant ALK drives a strong upregulation of MAPK negative feedback regulators and upregulates RET and RET-driven sympathetic neuronal markers of the cholinergic lineage. Conclusions: We provide important novel insights into the transcriptional consequences and the complexity of mutant ALK signaling in this aggressive pediatric tumor. The negative feedback loop of MAPK pathway inhibitors may affect novel ALK inhibition therapies, whereas mutant ALK induced RET signaling can offer novel opportunit...

Lawson, J, Rasul, MG, Howard, P, Martin, F, Hadgraft, R & Jarman, R 2015, 'Getting it right: The case for supervisors assessing process in capstone projects', International Journal of Engineering Education, vol. 31, no. 6, pp. 1810-1818.
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Capstone projects represent the culmination of an undergraduate engineering degree and are typically the last checkpoint measure before students graduate and enter the engineering profession. In Australia there is a longstanding interest in and commitment to developing quality capstone experiences.Anational study into the supervision and assessment of capstone projects has determined that whilst there is relative consistency in terms of what project tasks are set and assessed, there is not comparable consistency in how these tasks or assignments are marked. Two interconnected areas of assessing process and the role of the supervisor in marking are identified as contentious. This paper presents some findings of a national case study and concludes that whilst further investigation is warranted, assessing process as well as project products is valuable as is the need for greater acceptance of project supervisors as capable of making informed, professional judgments when marking significant project work.

Li, JJ, Kim, K, Roohani-Esfahani, S-I, Guo, J, Kaplan, DL & Zreiqat, H 2015, 'A biphasic scaffold based on silk and bioactive ceramic with stratified properties for osteochondral tissue regeneration', Journal of Materials Chemistry B, vol. 3, no. 26, pp. 5361-5376.
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The developed biphasic scaffold featured a gradient of structural, mechanical and biological cues to match the segments of osteochondral tissue.

Li, R, Zhang, W, Su, QP, Xue, B & Sun, Y 2015, 'Structural and Functional Study of Midbody during Cytokinesis', Biophysical Journal, vol. 108, no. 2, pp. 631a-631a.
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Li, Y, Liu, Z, Zhang, Y, Su, QP, Xue, B, Shao, S, Zhu, Y, Xu, X, Wei, S & Sun, Y 2015, 'Live‐cell and super‐resolution imaging reveal that the distribution of wall‐associated protein A is correlated with the cell chain integrity of Streptococcus mutans', Molecular Oral Microbiology, vol. 30, no. 5, pp. 376-383.
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SummaryStreptococcus mutans is a primary pathogen responsible for dental caries. It has an outstanding ability to form biofilm, which is vital for virulence. Previous studies have shown that knockout of Wall‐associated protein A (WapA) affects cell chain and biofilm formation of S. mutans. As a surface protein, the distribution of WapA remains unknown, but it is important to understand the mechanism underlying the function of WapA. This study applied the fluorescence protein mCherry as a reporter gene to characterize the dynamic distribution of WapA in S. mutans via time‐lapse and super‐resolution fluorescence imaging. The results revealed interesting subcellular distribution patterns of WapA in single, dividing and long chains of S. mutans cells. It appears at the middle of the cell and moves to the poles as the cell grows and divides. In a cell chain, after each round of cell division, such dynamic relocation results in WapA distribution at the previous cell division sites, resulting in a pattern where WapA is located at the boundary of two adjacent cell pairs. This WapA distribution pattern corresponds to the breaking segmentation of wapA deletion cell chains. The dynamic relocation of WapA through the cell cycle increases our understanding of the mechanism of WapA in maintaining cell chain integrity and biofilm formation.

Liu, A, Richards, L, Bladen, CL, Ingham, E, Fisher, J & Tipper, JL 2015, 'The biological response to nanometre-sized polymer particles', Acta Biomaterialia, vol. 23, pp. 38-51.
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Lu, Z, Roohani-Esfahani, S-I, Li, J & Zreiqat, H 2015, 'Synergistic effect of nanomaterials and BMP-2 signalling in inducing osteogenic differentiation of adipose tissue-derived mesenchymal stem cells', Nanomedicine: Nanotechnology, Biology and Medicine, vol. 11, no. 1, pp. 219-228.
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The lack of complete understanding in the signalling pathways that control the osteogenic differentiation of mesenchymal stem cells hinders their clinical application in the reconstruction of large bone defects and non-union bone fractures. The aim of this study is to gain insight into the interactions of bone morphogenetic protein-2 (BMP-2) and bone biomimetic scaffolds in directing osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ASCs) and the underlying signalling pathways involved. We demonstrated that bioactive glass nanoparticles (nBG) incorporated polycaprolactone (PCL) coating on hydroxyapatite/β-tricalcium phosphate (HA/TCP) scaffold exerted a synergistic effect with 3days of BMP-2 treatment in promoting osteogenic gene expression levels (Runx-2, collagen I, osteopontin and bone sialoprotein) and alkaline phosphatase activity in ASCs. Furthermore, we revealed that the synergistic effect was mediated through a mechanism of activating β1-integrin and induction of Wnt-3a autocrine signalling pathways by nBG incorporated scaffold.

Mi, N, Chen, Y, Wang, S, Chen, M, Zhao, M, Yang, G, Ma, M, Su, Q, Luo, S, Shi, J, Xu, J, Guo, Q, Gao, N, Sun, Y, Chen, Z & Yu, L 2015, 'CapZ regulates autophagosomal membrane shaping by promoting actin assembly inside the isolation membrane', Nature Cell Biology, vol. 17, no. 9, pp. 1112-1123.
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© 2015 Macmillan Publishers Limited. A fundamental question regarding autophagosome formation is how the shape of the double-membrane autophagosomal vesicle is generated. Here we show that in mammalian cells assembly of an actin scaffold inside the isolation membrane (the autophagosomal precursor) is essential for autophagosomal membrane shaping. Actin filaments are depolymerized shortly after starvation and actin is assembled into a network within the isolation membrane. When formation of actin puncta is disrupted by an actin polymerization inhibitor or by knocking down the actin-capping protein CapZβ, isolation membranes and omegasomes collapse into mixed-membrane bundles. Formation of actin puncta is PtdIns(3)P dependent, and inhibition of PtdIns(3)P formation by treating cells with the PI(3)K inhibitor 3-MA, or by knocking down Beclin-1, abolishes the formation of actin puncta. Binding of CapZ to PtdIns(3)P, which is enriched in omegasomes, stimulates actin polymerization. Our findings illuminate the mechanism underlying autophagosomal membrane shaping and provide key insights into how autophagosomes are formed.

Nguyen, TV & Seeman, E 2015, 'Osteoporosis: Treat or Let Die Twice More Likely', Journal of Bone and Mineral Research, vol. 30, no. 9, pp. 1551-1552.
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Poulos, RC, Thoms, JAI, Shah, A, Beck, D, Pimanda, JE & Wong, JWH 2015, 'Systematic Screening of Promoter Regions Pinpoints Functional Cis-Regulatory Mutations in a Cutaneous Melanoma Genome', Molecular Cancer Research, vol. 13, no. 8, pp. 1218-1226.
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Abstract With the recent discovery of recurrent mutations in the TERT promoter in melanoma, identification of other somatic causal promoter mutations is of considerable interest. Yet, the impact of sequence variation on the regulatory potential of gene promoters has not been systematically evaluated. This study assesses the impact of promoter mutations on promoter activity in the whole-genome sequenced malignant melanoma cell line COLO-829. Combining somatic mutation calls from COLO-829 with genome-wide chromatin accessibility and histone modification data revealed mutations within promoter elements. Interestingly, a high number of potential promoter mutations (n = 23) were found, a result mirrored in subsequent analysis of TCGA whole-melanoma genomes. The impact of wild-type and mutant promoter sequences were evaluated by subcloning into luciferase reporter vectors and testing their transcriptional activity in COLO-829 cells. Of the 23 promoter regions tested, four mutations significantly altered reporter activity relative to wild-type sequences. These data were then subjected to multiple computational algorithms that score the cis-regulatory altering potential of mutations. These analyses identified one mutation, located within the promoter region of NDUFB9, which encodes the mitochondrial NADH dehydrogenase (ubiquinone) 1 beta subcomplex 9, to be recurrent in 4.4% (19 of 432) of TCGA whole-melanoma exomes. The mutation is predicted to disrupt a highly conserved SP1/KLF transcription factor binding motif and its frequent co-occurrence with mutations in the coding sequence of NF1 supports a pathologic role for this mutation in melanoma. Taken together, these data show the relatively high prevalence of promoter mutations in the COLO-829 melanoma genome, and indicate that a proportion of these significantly alter the regulatory potential of gene promoters. Implications: Genom...

Reales, E, Bernabé-Rubio, M, Casares-Arias, J, Rentero, C, Fernández-Barrera, J, Rangel, L, Correas, I, Enrich, C, Andrés, G & Alonso, MA 2015, 'The MAL protein is crucial for proper membrane condensation at the ciliary base, which is required for primary cilium elongation', Journal of Cell Science, vol. 128, no. 12, pp. 2261-2270.
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ABSTRACT The base of the primary cilium contains a zone of condensed membranes whose importance is not known. Here, we have studied the involvement of MAL, a tetraspanning protein that exclusively partitions into condensed membrane fractions, in the condensation of membranes at the ciliary base and investigated the importance of these membranes in primary cilium formation. We show that MAL accumulates at the ciliary base of epithelial MDCK cells. Knockdown of MAL expression resulted in a drastic reduction in the condensation of membranes at the ciliary base, the percentage of ciliated cells and the length of the cilia, but did not affect the docking of the centrosome to the plasma membrane or produce missorting of proteins to the pericentriolar zone or to the membrane of the remaining cilia. Rab8 (for which there are two isoforms, Rab8A and Rab8b), IFT88 and IFT20, which are important components of the machinery of ciliary growth, were recruited normally to the ciliary base of MAL-knockdown cells but were unable to elongate the primary cilium correctly. MAL, therefore, is crucial for the proper condensation of membranes at the ciliary base, which is required for efficient primary cilium extension.

Sercombe, TB, Xu, X, Challis, VJ, Green, R, Yue, S, Zhang, Z & Lee, PD 2015, 'Failure modes in high strength and stiffness to weight scaffolds produced by Selective Laser Melting', Materials & Design, vol. 67, pp. 501-508.
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The production of porous scaffold structures using additive manufacturing is becoming widespread, however a detailed understanding of the scaffold failure mechanisms is lacking. In this research, Selective Laser Melting (SLM) is used to produce Ti-6Al-4V scaffold structures consisting of a regular array of unit cells previously designed using topology optimisation. Interrupted compression testing and subsequent X-Ray Micro Tomography (XMT) characterisation is used to study the deformation and failure of the scaffolds for a range of solid fractions. Further, the XMT data of the unloaded scaffolds is used to generate meshes for finite element analysis which allowed direct comparison of desired and as built behaviour. Likely failure sites predicted from the finite element analysis compare favourably with the experimentally observed ones. Failure is initiated in areas that exhibit the greatest tensile stress, while the onset of the commonly observed layered failure occurs afterwards. The XMT of the unloaded scaffolds also highlights the inaccuracies in the SLM build process, which contributes to stress concentrations in the horizontal arms within the scaffolds. The results indicate that although the strength of the topology optimised structures is very high, further refinement in both the unit cell design and build quality would further increase the strength.

Shemesh, J, Jalilian, I, Shi, A, Heng Yeoh, G, Knothe Tate, ML & Ebrahimi Warkiani, M 2015, 'Flow-induced stress on adherent cells in microfluidic devices', Lab on a Chip, vol. 15, no. 21, pp. 4114-4127.
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The article describes flow-induced stress on adherent cells in microfluidics devices in light of ongoing discoveries in mechanobiology.

Shungin, D, Winkler, TW, Croteau-Chonka, DC, Ferreira, T, Locke, AE, Mägi, R, Strawbridge, RJ, Pers, TH, Fischer, K, Justice, AE, Workalemahu, T, Wu, JMW, Buchkovich, ML, Heard-Costa, NL, Roman, TS, Drong, AW, Song, C, Gustafsson, S, Day, FR, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, JC, Scherag, A, Vedantam, S, Wood, AR, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C-T, Schmidt, EM, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg-Gresham, JL, Buyske, S, Demirkan, A, Ehret, GB, Feitosa, MF, Goel, A, Jackson, AU, Johnson, T, Kleber, ME, Kristiansson, K, Mangino, M, Mateo Leach, I, Medina-Gomez, C, Palmer, CD, Pasko, D, Pechlivanis, S, Peters, MJ, Prokopenko, I, Stančáková, A, Ju Sung, Y, Tanaka, T, Teumer, A, Van Vliet-Ostaptchouk, JV, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, GM, Bandinelli, S, Barrett, A, Bellis, C, Bennett, AJ, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, DB, Caspersen, IH, Clarke, R, Warwick Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, ASF, Eklund, N, Erdos, MR, Estrada, K, Eury, E, Friedrich, N, Garcia, ME, Giedraitis, V, Gigante, B, Go, AS, Golay, A, Grallert, H, Grammer, TB, Gräßler, J, Grewal, J, Groves, CJ, Haller, T, Hallmans, G, Hartman, CA, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K-H, Helmer, Q, Hillege, HL, Holmen, O, Hunt, SC, Isaacs, A, Ittermann, T, James, AL, Johansson, I, Juliusdottir, T, Kalafati, I-P, Kinnunen, L, Koenig, W, Kooner, IK, Kratzer, W, Lamina, C, Leander, K, Lee, NR, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, PKE, Mahajan, A, McArdle, WL, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, KL, Mooijaart, SP, Mühleisen, TW, Mulas, A, Müller, G, Müller-Nurasyid, M, Nagaraja, R, Nalls, MA, Narisu, N, Glorioso, N, Nolte, IM, Olden, M, Rayner, NW, Renstrom, F, Ried, JS, Robertson, NR, Rose, LM, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, CM, Vernon Smith, A, Stirrups, K, Stringham, HM, Sundström, J, Swertz, MA, Swift, AJ, Syvänen, A-C, Tayo, BO, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, van Oort, FVA, Verweij, N, Vonk, JM, Waite, LL, Wennauer, R, Wilsgaard, T, Wojczynski, MK, Wong, A, Zhang, Q, Hua Zhao, J, Brennan, EP, Choi, M, Eriksson, P, Folkersen, L, Franco-Cereceda, A, Gharavi, AG, Hedman, ÅK & et al. 2015, 'New genetic loci link adipose and insulin biology to body fat distribution', Nature, vol. 518, no. 7538, pp. 187-196.
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© 2015, Macmillan Publishers Limited. All rights reserved. Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Sun, Y, Bell, JL, Carter, D, Gherardi, S, Poulos, RC, Milazzo, G, Wong, JWH, Al-Awar, R, Tee, AE, Liu, PY, Liu, B, Atmadibrata, B, Wong, M, Trahair, T, Zhao, Q, Shohet, JM, Haupt, Y, Schulte, JH, Brown, PJ, Arrowsmith, CH, Vedadi, M, MacKenzie, KL, Hüttelmaier, S, Perini, G, Marshall, GM, Braithwaite, A & Liu, T 2015, 'WDR5 Supports an N-Myc Transcriptional Complex That Drives a Protumorigenic Gene Expression Signature in Neuroblastoma', Cancer Research, vol. 75, no. 23, pp. 5143-5154.
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Abstract MYCN gene amplification in neuroblastoma drives a gene expression program that correlates strongly with aggressive disease. Mechanistically, trimethylation of histone H3 lysine 4 (H3K4) at target gene promoters is a strict prerequisite for this transcriptional program to be enacted. WDR5 is a histone H3K4 presenter that has been found to have an essential role in H3K4 trimethylation. For this reason, in this study, we investigated the relationship between WDR5-mediated H3K4 trimethylation and N-Myc transcriptional programs in neuroblastoma cells. N-Myc upregulated WDR5 expression in neuroblastoma cells. Gene expression analysis revealed that WDR5 target genes included those with MYC-binding elements at promoters such as MDM2. We showed that WDR5 could form a protein complex at the MDM2 promoter with N-Myc, but not p53, leading to histone H3K4 trimethylation and activation of MDM2 transcription. RNAi-mediated attenuation of WDR5 upregulated expression of wild-type but not mutant p53, an effect associated with growth inhibition and apoptosis. Similarly, a small-molecule antagonist of WDR5 reduced N-Myc/WDR5 complex formation, N-Myc target gene expression, and cell growth in neuroblastoma cells. In MYCN-transgenic mice, WDR5 was overexpressed in precancerous ganglion and neuroblastoma cells compared with normal ganglion cells. Clinically, elevated levels of WDR5 in neuroblastoma specimens were an independent predictor of poor overall survival. Overall, our results identify WDR5 as a key cofactor for N-Myc–regulated transcriptional activation and tumorigenesis and as a novel therapeutic target for MYCN-amplified neuroblastomas. Cancer Res; 75(23); 5143–54. ©2015 AACR.

Suñer, S, Joffe, R, Tipper, JL & Emami, N 2015, 'Ultra high molecular weight polyethylene/graphene oxide nanocomposites: Thermal, mechanical and wettability characterisation', Composites Part B: Engineering, vol. 78, pp. 185-191.
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Tran, TS, Center, JR, Seibel, MJ, Eisman, JA, Kushnir, MM, Rockwood, AL & Nguyen, TV 2015, 'Relationship between Serum Testosterone and Fracture Risk in Men: A Comparison of RIA and LC-MS/MS', Clinical Chemistry, vol. 61, no. 9, pp. 1182-1190.
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Abstract BACKGROUND Serum testosterone can be measured by LC-MS/MS and RIA. We investigated whether the testosterone–fracture relationship was affected by the method of measurement. METHODS We measured total testosterone (TT) by LC-MS/MS (TTLC-MS/MS) and RIA (TTRIA) in serum samples collected from 602 men whose incident fractures had been continuously ascertained by x-ray reports from 1989 to 2010. We measured bone mineral density (BMD) by dual-energy x-ray absorptiometry. The association between TT and fracture risk was assessed by the Cox proportional hazards model, taking into account the effect of age and BMD. RESULTS Mean TTLC-MS/MS was higher than TTRIA by 27 ng/dL (95% CI 13–41). The concordance correlation coefficient between TTLC-MS/MS and TTRIA was 0.72 (95% CI 0.68–0.76). The Deming regression equation linking the 2 measurements was ln(TTLC-MS/MS + 10) = 0.87 + 0.87 × ln(TTRIA + 10). The hazard ratio of fracture per SD decrease in TT was 1.32 (95% CI 1.12–1.54) for TTLC-MS/MS and 1.23 (1.06–1.43) for TTRIA. The correlation between predicted probabilities of fracture by TTLC-MS/MS and TTRIA was r = 0.96, with the mean difference being 0.01% (95% CI −6.1% to 6.2%). Slightly more patients were classified as having hypogonadism if TTRIA was used (29% vs 26%). CONCLUSIONS The concordance between LC-MS/MS and RIA in the measurement of serum TT was moderate. Moreover, the magnitude of association between testosterone and fracture risk in older me...

Tursky, ML, Beck, D, Thoms, JAI, Huang, Y, Kumari, A, Unnikrishnan, A, Knezevic, K, Evans, K, Richards, LA, Lee, E, Morris, J, Goldberg, L, Izraeli, S, Wong, JWH, Olivier, J, Lock, RB, MacKenzie, KL & Pimanda, JE 2015, 'Overexpression of ERG in cord blood progenitors promotes expansion and recapitulates molecular signatures of high ERG leukemias', Leukemia, vol. 29, no. 4, pp. 819-827.
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Wang, C, Du, W, Su, QP, Zhu, M, Feng, P, Li, Y, Zhou, Y, Mi, N, Zhu, Y, Jiang, D, Zhang, S, Zhang, Z, Sun, Y & Yu, L 2015, 'Dynamic tubulation of mitochondria drives mitochondrial network formation', Cell Research, vol. 25, no. 10, pp. 1108-1120.
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Mitochondria form networks. Formation of mitochondrial networks is important for maintaining mitochondrial DNA integrity and interchanging mitochondrial material, whereas disruption of the mitochondrial network affects mitochondrial functions. According to the current view, mitochondrial networks are formed by fusion of individual mitochondria. Here, we report a new mechanism for formation of mitochondrial networks through KIF5B-mediated dynamic tubulation of mitochondria. We found that KIF5B pulls thin, highly dynamic tubules out of mitochondria. Fusion of these dynamic tubules, which is mediated by mitofusins, gives rise to the mitochondrial network. We further demonstrated that dynamic tubulation and fusion is sufficient for mitochondrial network formation, by reconstituting mitochondrial networks in vitro using purified fusion-competent mitochondria, recombinant KIF5B, and polymerized microtubules. Interestingly, KIF5B only controls network formation in the peripheral zone of the cell, indicating that the mitochondrial network is divided into subzones, which may be constructed by different mechanisms. Our data not only uncover an essential mechanism for mitochondrial network formation, but also reveal that different parts of the mitochondrial network are formed by different mechanisms.

Wang, G, Li, Y, Wang, P, Liang, H, Cui, M, Zhu, M, Guo, L, Su, Q, Sun, Y, McNutt, MA & Yin, Y 2015, 'PTEN regulates RPA1 and protects DNA replication forks', Cell Research, vol. 25, no. 11, pp. 1189-1204.
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Wang, R, Xu, X, Zhang, Y, Chang, Z, Sun, Z & Dong, W-F 2015, 'Functionalized ZnO@TiO₂nanorod array film loaded with ZnIn_0.25Cu_0.02S_1.395solid-solution: synthesis, characterization and enhanced visible light driven water splitting', Nanoscale, vol. 7, no. 25, pp. 11082-11092.
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We have designed a novel semiconductor nanorod film, sensitized with a polymetallic sulfide, for solar energy conversion. Our results verify that it could be conveniently used in micro-nano photoelectronic devices.

Wargocki, P, Deng, W, Anwer, A & Goldys, E 2015, 'Medically Relevant Assays with a Simple Smartphone and Tablet Based Fluorescence Detection System', Sensors, vol. 15, no. 5, pp. 11653-11664.
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Warkiani, ME, Tay, AKP, Guan, G & Han, J 2015, 'Membrane-less microfiltration using inertial microfluidics', Scientific Reports, vol. 5, no. 1, p. 11018.
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AbstractMicrofiltration is a ubiquitous and often crucial part of many industrial processes, including biopharmaceutical manufacturing. Yet, all existing filtration systems suffer from the issue of membrane clogging, which fundamentally limits the efficiency and reliability of the filtration process. Herein, we report the development of a membrane-less microfiltration system by massively parallelizing inertial microfluidics to achieve a macroscopic volume processing rates (~ 500 mL/min). We demonstrated the systems engineered for CHO (10–20 μm) and yeast (3–5 μm) cells filtration, which are two main cell types used for large-scale bioreactors. Our proposed system can replace existing filtration membrane and provide passive (no external force fields), continuous filtration, thus eliminating the need for membrane replacement. This platform has the desirable combinations of high throughput, low-cost and scalability, making it compatible for a myriad of microfiltration applications and industrial purposes.

Warkiani, ME, Tay, AKP, Khoo, BL, Xiaofeng, X, Han, J & Lim, CT 2015, 'Malaria detection using inertial microfluidics', Lab on a Chip, vol. 15, no. 4, pp. 1101-1109.
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Diagnosis of malaria at the early stage of infection is challenging due to the difficulty in detecting low abundance parasites from blood.

Warkiani, ME, Wicaksana, F, Fane, AG & Gong, H-Q 2015, 'Investigation of membrane fouling at the microscale using isopore filters', Microfluidics and Nanofluidics, vol. 19, no. 2, pp. 307-315.
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Yang, S, Center, JR, Eisman, JA & Nguyen, TV 2015, 'Erratum to: Association between fat mass, lean mass, and bone loss: the Dubbo osteoporosis epidemiology study', Osteoporosis International, vol. 26, no. 6, pp. 1865-1866.
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Zarzour, P, Boelen, L, Luciani, F, Beck, D, Sakthianandeswaren, A, Mouradov, D, Sieber, OM, Hawkins, NJ, Hesson, LB, Ward, RL & Wong, JWH 2015, 'Single Nucleotide Polymorphism Array Profiling Identifies Distinct Chromosomal Aberration Patterns Across Colorectal Adenomas and Carcinomas', GENES CHROMOSOMES & CANCER, vol. 54, no. 5, pp. 303-314.
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Zhand, S, Karami, C, Hosseinzadeh Adli, A, Tabarraei, A, Khodabakhshi, B & Moradi, A 2015, 'Correlation Between Hepatitis B G1896A Precore Mutations and HBeAg in Chronic HBV Patients', Jundishapur Journal of Microbiology, vol. 8, no. 2.
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Zheng, H, Forgetta, V, Hsu, Y, Estrada, K, Rosello‐Diez, A, Leo, PJ, Dahia, CL, Park‐Min, KH, Tobias, JH, Kooperberg, C, Kleinman, A, Styrkarsdottir, U, Liu, C, Uggla, C, Evans, DS, Nielson, CM, Walter, K, Pettersson‐Kymmer, U, McCarthy, S, Eriksson, J, Kwan, T, Jhamai, M, Trajanoska, K, Memari, Y, Min, J, Huang, J, Danecek, P, Wilmot, B, Li, R, Chou, W, Mokry, LE, Moayyeri, A, Claussnitzer, M, Cheng, C, Cheung, W, Medina‐Gómez, C, Ge, B, Chen, S, Choi, K, Oei, L, Fraser, J, Kraaij, R, Hibbs, MA, Gregson, CL, Paquette, D, Hofman, A, Wibom, C, Tranah, GJ, Marshall, M, Gardiner, BB, Cremin, K, Auer, P, Hsu, L, Ring, S, Tung, JY, Thorleifsson, G, Enneman, AW, van Schoor, NM, de Groot, LCPGM, van der Velde, N, Melin, B, Kemp, JP, Christiansen, C, Sayers, A, Zhou, Y, Calderari, S, van Rooij, J, Carlson, C, Peters, U, Berlivet, S, Dostie, J, Uitterlinden, AG, Williams, SR, Farber, C, Grinberg, D, LaCroix, AZ, Haessler, J, Chasman, DI, Giulianini, F, Rose, LM, Ridker, PM, Eisman, JA, Nguyen, TV, Center, JR, Nogues, X, Garcia‐Giralt, N, Launer, LL, Gudnason, V, Mellström, D, Vandenput, L, Amin, N, van Duijn, CM, Karlsson, MK, Ljunggren, Ö, Svensson, O, Hallmans, G, Rousseau, F, Giroux, S, Bussière, J, Arp, PP, Koromani, F, Prince, RL, Lewis, JR, Langdahl, BL, Pernille Hermann, A, Jensen, JB, Kaptoge, S, Khaw, K, Reeve, J, Formosa, MM, Xuereb‐Anastasi, A, Åkesson, K, McGuigan, FE, Garg, G, Olmos, JM, Zarrabeitia, MT, Riancho, JA, Ralston, SH, Alonso, N, Jiang, X, Goltzman, D, Pastinen, T, Grundberg, E, Gauguier, D, Orwoll, ES, Karasik, D, Davey‐Smith, G, Smith, AV, Siggeirsdottir, K, Harris, TB, Carola Zillikens, M, van Meurs, JBJ, Thorsteinsdottir, U, Maurano, MT, Timpson, NJ, Soranzo, N, Durbin, R, Wilson, SG, Ntzani, EE, Brown, MA, Stefansson, K, Hinds, DA, Spector, T, Adrienne Cupples, L, Ohlsson, C, Greenwood, CMT, Jackson, RD, Rowe, DW, Loomis, CA, Evans, DM, Ackert‐Bicknell, CL, Joyner, AL, Duncan, EL, Kiel, DP, Rivadeneira, F & Richards, JB 2015, 'Whole‐genome sequencing identifies EN1 as a determinant of bone density and fracture', Nature, vol. 526, no. 7571, pp. 112-117.
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© 2015 Macmillan Publishers Limited. All rights reserved. The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10-14), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10-11; ncases = 98,742 and n controls = 409,511). Using an En1 cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10-11). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rat...

Zibellini, J, Seimon, RV, Lee, CMY, Gibson, AA, Hsu, MSH, Shapses, SA, Nguyen, TV & Sainsbury, A 2015, 'Does Diet-Induced Weight Loss Lead to Bone Loss in Overweight or Obese Adults? A Systematic Review and Meta-Analysis of Clinical Trials', Journal of Bone and Mineral Research, vol. 30, no. 12, pp. 2168-2178.
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ABSTRACT   Diet-induced weight loss has been suggested to be harmful to bone health. We conducted a systematic review and meta-analysis (using a random-effects model) to quantify the effect of diet-induced weight loss on bone. We included 41 publications involving overweight or obese but otherwise healthy adults who followed a dietary weight-loss intervention. The primary outcomes examined were changes from baseline in total hip, lumbar spine, and total body bone mineral density (BMD), as assessed by dual-energy X-ray absorptiometry (DXA). Secondary outcomes were markers of bone turnover. Diet-induced weight loss was associated with significant decreases of 0.010 to 0.015 g/cm2 in total hip BMD for interventions of 6, 12, or 24 (but not 3) months' duration (95% confidence intervals [CIs], –0.014 to –0.005, –0.021 to –0.008, and –0.024 to –0.000 g/cm2, at 6, 12, and 24 months, respectively). There was, however, no statistically significant effect of diet-induced weight loss on lumbar spine or whole-body BMD for interventions of 3 to 24 months' duration, except for a significant decrease in total body BMD (–0.011 g/cm2; 95% CI, –0.018 to –0.003 g/cm2) after 6 months. Although no statistically significant changes occurred in serum concentrations of N-terminal propeptide of type I procollagen (P1NP), interventions of 2 or 3 months in duration (but not of 6, 12, or 24 months' duration) induced significant increases in serum concentrations of osteocalcin (0.26 nmol/L; 95% CI, 0.13 to 0.39 nmol/L), C-terminal telopeptide of type I collagen (CTX) (4.72 nmol/L; 95% CI, 2.12 to 7.30 nmol/L) or N-terminal telopeptide of type I collagen (NTX) (3.70 nmol/L; 95% CI, 0.90 to 6.50 nmol/L bone collagen equivalents [BCEs]), indicating an early effect of diet-induced weight loss to promote bone breakdown. These data show that in overweight and obese indi...

Chandrakanthan, V, Jair, K, Oliver, R, Qiao, Q, Kang, YC, Zarzour, P, Beck, D, Boelen, L, Unnikrihnan, A, Villanueva, J, Nunez, A, Knezevic, K, Palu, C, Nasrallah, R, Hardy, P, Grey, S, Whan, R, Walkley, C, Purton, LE, Ward, R, Wong, J, Hesson, L, Ittner, L, Walsh, W & Pimanda, J 1970, 'PDGF-AB AND AZACITIDINE INDUCED REPROGRAMMING OF SOMATIC CELLS INTO TISSUE REGENERATIVE MULTNOTENT STEM CELLS', EXPERIMENTAL HEMATOLOGY, 44th Annual Scientific Meeting of the International-Society-for-Experimental-Hematology (ISEH), ELSEVIER SCIENCE INC, Kyoto, JAPAN, pp. S89-S89.
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Chung, C-Y, Warkiani, ME, Mesgari, S, Rosengarten, G & Taylor, R 1970, 'Thermoset polyester-based superhydrophobic microchannels for nanofluid heat transfer applications', SPIE Proceedings, SPIE Micro+Nano Materials, Devices, and Applications, SPIE, Sydney, AUSTRALIA.
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Gallego-Ortega, D, Ledger, A, Roden, D, Cho, C, Allerdice, SL, Lee, HJ, Valdes-Mora, F, Lee, B, Kaplan, W, Salomon, R, Piggin, C, Rabinovich, B, Millar, E, Chtanova, T, Swarbrick, A, Clark, SJ & Ormandy, CJ 1970, 'The ETS transcription factor Elf5 drives metastasis via angiogenesis and recruitment of Gr-1+CD11b+myeloid derived suppressor cells in luminal breast cancer', CLINICAL & EXPERIMENTAL METASTASIS, SPRINGER, pp. 203-203.

Ho-Le, TP, Center, JR, Eisman, JA, Nguyen, HT & Nguyen, TV 1970, 'POLYGENIC RISK SCORE IMPROVES FRACTURE RISK PREDICTION: THE DUBBO OSTEOPROROSIS EPIDEMIOLOGY STUDY', 25th Annual Scientific Meeting of the Australian New Zealand Bone and Mineral Society, Tasmania.
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Many genes for bone mineral density (BMD) have been identified in genomewide association studies. However, the contribution of these genes for fracture prediction is still unclear. This study sought to develop clinico-genetic models for predicting fracture risk in the elderly.The study was part of the Dubbo Osteoporosis Epidemiology Study, in which bone health of participants aged from 60 years had been monitored continuously since 1990. Fragility fracture was ascertained from X-ray reports. Femoral neck BMD was measured by dual-energy X-ray absorptiometry. Seventy-one BMD-associated genetic variants were genotyped. A weighted polygenic risk score (GRS) was derived from the variants. Three fracture risk models were constructed: (1) clinical factors only, (2) clinical factors and GRS, or (3) clinical factors and 71 variants.During the follow-up period, 230 fracture cases (36.4%) were observed. Each score increase in GRS was associated with an odds ratio of 1.47 (95%CI, 1.28 to 1.69) of fracture. The area under the curve (AUC) of model 1 (with age, sex, BMD, prior fracture, and fall) was 0.71 (95%CI, 0.67 to 0.75); when GRS was added to the model (P<0.001), the AUC was increased to 0.74 (95%CI, 0.70 to 0.78). When all 71 variants were considered together with the clinical risk factors, the AUC was increased to 0.78 (95%CI, 0.74 to 0.82), and net reclassification index was improved by 22%.These results indicate that BMD-associated genes could improve the performance of fracture prediction over and above that of clinical risk factors alone, and help stratify individuals by fracture status.

Kwon, T, Madziva, N, Oliveira, JD, Chandramohan, SK, Yin, L, Prentice, H, Warkiani, ME, Hamel, JFP & Han, J 1970, 'Long-term steady state perfusion culture of mammalian cells using a robust microfluidic cell retention device', MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences, pp. 108-110.
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Cell retention devices are used to retain cells in containers during perfusion culture. However, the conventional membrane-based filtration devices have challenges such as membrane fouling/clogging and increased contamination risk due to frequent filter replacements. To solve these challenges, we introduce a new microfluidic cell retention device based on inertial cell focusing. We demonstrated a long-term steady state perfusion culture of suspended CHO cells, where high density of cells (> 3×106 cells/mL) and viability (> 90%) were maintained for more than a week. Our membrane-less and clog-free cell retention device has unique advantage over the conventional filtration devices for perfusion culture.

Liu, Z, Xing, D, Peter Su, Q, Zhu, Y, Zhang, J, Kong, X, Xue, B, Wang, S, Sun, H, Tao, Y & Sun, Y 1970, 'Super Resolution Imaging and Tracking of Protein-Protein Interactions in Sub Diffraction Cellular Space', Biophysical Journal, Elsevier BV, pp. 36a-36a.
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Rasul, MG, Lawson, JJ, Howard, P, Martin, F & Hadgraft, R 1970, 'Learning and teaching approaches and methodologies of capstone final year engineering projects', International Journal of Engineering Education, Capstone Design Conference, TEMPUS PUBLICATIONS, Columbus, OH, pp. 1727-1735.
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The capstone final year engineering project (FYEP) is the culminating learning experience of engineering programs. It requires students to demonstrate that they can integrate knowledge, skills and professional graduate attributes developed during the program and perform at a standard expected of graduates. This paper reports on insight into the approaches and methodologies used for learning and teaching of the capstone FYEPs. National and international literature outlines a variety of information regarding the capstone FYEPs structures, elements of its assessment criteria, and methodologies of learning and teaching. More specifically, the study seeks to map processes, assessment and supervision practices of capstone FYEPs and to provide a set of guidelines and tools to ensure quality outcomes of capstone FYEPs. This study is intended to promote quality practice amongst supervisors and academics involved in learning, teaching and facilitating capstone FYEPs. Aquestionnaire was conducted to answer a broad research question: What is the current approach used in learning and teaching of capstone FYEPs? The questionnaire outcomes and a number of common issues, discrepancies and inconsistencies found are outlined in the paper. In supporting its claims, the paper offers some qualitative data to explore contentious issues around capstone learning and teaching. This is pertinent to those involved in the design and teaching of capstone projects.

Rostamian, G, Zhand, S, Tabarraei, A & Moradi, A 1970, 'Study of mutations in hepatitis B complete viral genome in chronic hepatitis B patients, from Southeast of Caspian Sea, Iran', JOURNAL OF VIRAL HEPATITIS, WILEY-BLACKWELL, pp. 45-45.

Shi, A, Shemesh, J, Asadnia, M, Robles, UA, Green, R, Yeoh, GH & Warkiani, ME 1970, 'A novel microfluidic patterning device for neuron-glia co-culture', MicroTAS 2015 - 19th International Conference on Miniaturized Systems for Chemistry and Life Sciences, pp. 633-635.
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Many biological processes in the body are regulated by synchronized activity between two cell types. To study cell-cell interactions, it is necessary to develop easy to use co-culture systems, where different cell types can be cultured within the same confined space. Designing a complete 3D biomimetic system to study these interactions in vitro requires complex protocols and use of non-conventional materials such as hydrogels. This paper reports development of a temporarily sealed microfluidic device which utilizes a novel valve design to directly and accurately co-culture two cell lines in alternating rows, allowing them to proliferate towards each other and then observe their interaction at the boundaries of their interface.

Ting, SS, Min, EH, Nguyen, HT, Stenzel, MH & Hutvagner, G 1970, 'Targeted delivery of siRNA using glycopolymer', 35th Australasian Polymer Symposium, 35th Australasian Polymer Symposium, Gold Coast, Australia.
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Liver is an essential part of the human biological system as it serves to detoxify, synthesize protein and produce biochemicals necessary for digestion. However, there have been common liver diseases namely, hepatitis (A, B, C, and E), fatty liver, cirrhosis and ultimately liver cancer. RNA interference (RNAi) mediated through double-stranded small interfering RNA (siRNA) pave the way to knockdown disease causing gene.1 Nevertheless, effective delivery of siRNA is an arduous task as they are very prone to degradation and are difficult to target specific cells. Glycopolymers are carbohydrates based polymers that recognise biological receptors on cells.2 This project focuses on the design of synthetic glycopolymer architectures using reversible addition-fragmentation transfer (RAFT) polymerization of sugar containing monomers for conjugations of siRNA. Galactose based monomer are selected here, as liver cancer cells over-expressed asialoglycoproteins, which are galactose recognising receptors. Moreover, synthetic delivery system has been reported to protect enzymatic degradation of therapeutics during delivery in the biological enviroment.3 Figure 1 shows the synthetic approach towards glycopolymers for the conjugation of siRNA by using a 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid (CPDT) RAFT agent, 4,4′-Azobis(4-cyanovaleric acid) (ACVA) initiator polymerized in dioxane. Figure 2 display the increased in molecular weights of polymers with increasing monomer conversions.

Zarepour, E, Hassan, M, Chou, CT, Adesina, AA & Warkiani, ME 1970, 'Reliability analysis of time-varying wireless nanoscale sensor networks', 2015 IEEE 15th International Conference on Nanotechnology (IEEE-NANO), 2015 IEEE 15th International Conference on Nanotechnology (IEEE-NANO), IEEE, ROME, ITALY, pp. 63-68.
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Zarepour, E, Hassan, N, Hassan, M, Tung Chou, C & Ebrahimi Warkiani, M 1970, 'Design and Analysis of a Wireless Nanosensor Network for Monitoring Human Lung Cells', Proceedings of the 10th EAI International Conference on Body Area Networks, 10th EAI International Conference on Body Area Networks, ICST.
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© 2015 ICST. Thanks to nanotechnology, it is now possible to fabricate sensor nodes below 100 nanometers in size. Although wireless communication at this scale has not been successfully demonstrated yet, simulations confirm that these sensor nodes would be able to communicate in the terahertz band using graphene as a transmission antenna. These developments suggest that deployment of wireless nanoscale sensor networks (WNSNs) inside human body could be a reality one day. In this paper, we design and analyse a WNSN for monitoring human lung cells. We find that respiration, i.e., the periodic inhalation and exhalation of oxygen and carbon dioxide, is the major process that inuences the terahertz channel inside lung cells. The channel is characterised as a two-state channel, where it periodically switches between good and bad states. Using real human respiratory data, we -nd that the channel absorbs terahertz signal much faster when it is in bad state compared to good state. Our simulation experiments confirm that we could reduce transmission power of the nanosensors, and hence the electromagnetic radiation inside lungs due to deployment of WNSN, by a factor of 20 if we could schedule all communication only during good channel states. We propose two duty cycling protocols along with a simple channel estimation algorithm that enables nanosensors to achieve such scheduling.

Zhand, S, Rostamian, G, Tabarraei, A & Moradi, A 1970, 'Cytotoxic T-lymphocytes and CD4 epitope mutations in pre-core/core region of hepatitis B virus in chronic hepatitis B patients in Northeast of Iran', JOURNAL OF VIRAL HEPATITIS, WILEY-BLACKWELL, pp. 46-46.