Ahmed, LA, Center, JR, Bjørnerem, Å, Bluic, D, Joakimsen, RM, Jørgensen, L, Meyer, HE, Nguyen, ND, Nguyen, TV, Omsland, TK, Størmer, J, Tell, GS, van Geel, TACM, Eisman, JA & Emaus, N 2013, 'Progressively increasing fracture risk with advancing age after initial incident fragility fracture: The Tromsø Study', Journal of Bone and Mineral Research, vol. 28, no. 10, pp. 2214-2221.
View/Download from: Publisher's site
View description>>
ABSTRACT The risk of subsequent fracture is increased after initial fractures; however, proper understanding of its magnitude is lacking. This population-based study examines the subsequent fracture risk in women and men by age and type of initial incident fracture. All incident nonvertebral fractures between 1994 and 2009 were registered in 27,158 participants in the Tromsø Study, Norway. The analysis included 3108 subjects with an initial incident fracture after the age of 49 years. Subsequent fracture (n = 664) risk was expressed as rate ratios (RR) and absolute proportions irrespective of death. The rates of both initial and subsequent fractures increased with age, the latter with the steepest curve. Compared with initial incident fracture rate of 30.8 per 1000 in women and 12.9 per 1000 in men, the overall age-adjusted RR of subsequent fracture was 1.3 (95% CI, 1.2–1.5) in women, and 2.0 (95% CI, 1.6–2.4) in men. Although the RRs decreased with age, the absolute proportions of those with initial fracture who suffered a subsequent fracture increased with age; from 9% to 30% in women and from 10% to 26% in men, between the age groups 50–59 to 80+ years. The type of subsequent fracture varied by age from mostly minor fractures in the youngest to hip or other major fractures in the oldest age groups, irrespective of type and severity of initial fracture. In women and men, 45% and 38% of the subsequent hip or other major fractures, respectively, were preceded by initial minor fractures. The risk of subsequent fracture is high in all age groups. At older age, severe subsequent fracture types follow both clinically severe and minor initial incident fractures. Any fragility fracture in the elderly reflects the need for specific osteoporosis management to reduce further fracture risk. © 2013 American Society for Bone and Mineral Research...
Al‐Hajjar, M, Fisher, J, Williams, S, Tipper, JL & Jennings, LM 2013, 'Effect of femoral head size on the wear of metal on metal bearings in total hip replacements under adverse edge‐loading conditions', Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 101B, no. 2, pp. 213-222.
View/Download from: Publisher's site
View description>>
AbstractMetal‐on‐metal (MoM) bearings have shown low‐wear rates under standard hip simulator conditions; however, retrieval studies have shown large variations in wear rates and mechanisms. High‐wear in vivo has caused catastrophic complications and has been associated with steep cup‐inclination angle (rotational malpositioning). However, increasing the cup‐inclination angle in vitro has not replicated the increases in wear to the same extent as those observed in retrievals. Clinically relevant wear rates, patterns, and particles were observed in vitro for ceramic‐on‐ceramic bearings when microseparation (translational malpositioning) conditions were introduced into the gait cycle. In the present study, 28 and 36‐mm MoM bearings were investigated under adverse conditions. Increasing the cup angle from 45° to 65° resulted in a significant increase in the wear rate of the 28 mm bearings. However, for the 36 mm bearings, head‐rim contact did not occur under the steep cup‐angle condition, and the wear rate did not increase. The introduction of microseparation to the gait cycle significantly increased the wear rate of the MoM bearings. Cup angle and head size did not influence the wear rate under microseparation conditions. This study indicated that high‐in vivo wear rates were associated with edge loading due to rotational malpositioning such as high‐cup‐inclination angle and translational malpositioning that could occur due to several surgical factors. Translational malpositioning had a more dominant effect on the wear rate. Preclinical simulation testing should be undertaken with translational and rotational malpositioning conditions as well as standard walking cycle conditions defined by the ISO standard. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.
Aquilina, P, Chamoli, U, Parr, WCH, Clausen, PD & Wroe, S 2013, 'Finite element analysis of three patterns of internal fixation of fractures of the mandibular condyle', British Journal of Oral and Maxillofacial Surgery, vol. 51, no. 4, pp. 326-331.
View/Download from: Publisher's site
Beck, D, Thoms, JAI, Perera, D, Schütte, J, Unnikrishnan, A, Knezevic, K, Kinston, SJ, Wilson, NK, O’Brien, TA, Göttgens, B, Wong, JWH & Pimanda, JE 2013, 'Genome-wide analysis of transcriptional regulators in human HSPCs reveals a densely interconnected network of coding and noncoding genes', Blood, vol. 122, no. 14, pp. e12-e22.
View/Download from: Publisher's site
View description>>
Key Points Genome-wide binding profiles of FLI1, ERG, GATA2, RUNX1, SCL, LMO2, and LYL1 in human HSPCs reveals patterns of combinatorial TF binding. Integrative analysis of transcription factor binding reveals a densely interconnected network of coding and noncoding genes in human HSPCs.
Behl, B, Papageorgiou, I, Brown, C, Hall, R, Tipper, JL, Fisher, J & Ingham, E 2013, 'Biological effects of cobalt-chromium nanoparticles and ions on dural fibroblasts and dural epithelial cells', Biomaterials, vol. 34, no. 14, pp. 3547-3558.
View/Download from: Publisher's site
Bliuc, D, Nguyen, ND, Nguyen, TV, Eisman, JA & Center, JR 2013, 'Compound risk of high mortality following osteoporotic fracture and refracture in elderly women and men', Journal of Bone and Mineral Research, vol. 28, no. 11, pp. 2317-2324.
View/Download from: Publisher's site
View description>>
ABSTRACT After fracture there is increased risk of refracture and premature mortality. These outcomes, particularly premature mortality following refracture, have not previously been studied together to understand overall mortality risk. This study examined the long-term cumulative incidence of subsequent fracture and total mortality with mortality calculated as a compound risk and separated according to initial and refracture. Community-dwelling participants aged 60+ years from Dubbo Osteoporosis Epidemiology Study with incident fractures, followed prospectively for further fractures and deaths from 1989 to 2010. Subsequent fracture and mortality ascertained using cumulative incidence competing risk models allowing four possible outcomes: death without refracture; death following refracture; refracture but alive, and event-free. There were 952 women and 343 men with incident fracture. Within 5 years following initial fracture, 24% women and 20% men refractured; and 26% women and 37% men died without refracture. Of those who refractured, a further 50% of women and 75% of men died, so that total 5-year mortality was 39% in women and 51% in men. Excess mortality was 24% in women and 27% in men. Although mortality following refracture occurred predominantly in the first 5 years post–initial fracture, total mortality (post-initial and refracture) was elevated for 10 years. Most of the 5-year to 10-year excess mortality was associated with refracture. The long-term (>10 years) refracture rate was reduced, particularly in the elderly as a result of their high mortality rate. The 30% alive beyond 10 years postfracture were at low risk of further adverse outcomes. Refractures contribute substantially to overall mortality associated with fracture. The majority of the mortality and refractures occurred in the first 5 years following the...
Chan, MY, Nguyen, ND, Center, JR, Eisman, JA & Nguyen, TV 2013, 'Quantitative ultrasound and fracture risk prediction in non-osteoporotic men and women as defined by WHO criteria', Osteoporosis International, vol. 24, no. 3, pp. 1015-1022.
View/Download from: Publisher's site
Croucher, DR, Hochgräfe, F, Zhang, L, Liu, L, Lyons, RJ, Rickwood, D, Tactacan, CM, Browne, BC, Ali, N, Chan, H, Shearer, R, Gallego-Ortega, D, Saunders, DN, Swarbrick, A & Daly, RJ 2013, 'Involvement of Lyn and the Atypical Kinase SgK269/PEAK1 in a Basal Breast Cancer Signaling Pathway', Cancer Research, vol. 73, no. 6, pp. 1969-1980.
View/Download from: Publisher's site
View description>>
Abstract Basal breast cancer cells feature high expression of the Src family kinase Lyn that has been implicated in the pathogenicity of this disease. In this study, we identified novel Lyn kinase substrates, the most prominent of which was the atypical kinase SgK269 (PEAK1). In breast cancer cells, SgK269 expression associated with the basal phenotype. In primary breast tumors, SgK269 overexpression was detected in a subset of basal, HER2-positive, and luminal cancers. In immortalized MCF-10A mammary epithelial cells, SgK269 promoted transition to a mesenchymal phenotype and increased cell motility and invasion. Growth of MCF-10A acini in three-dimensional (3D) culture was enhanced upon SgK269 overexpression, which induced an abnormal, multilobular acinar morphology and promoted extracellular signal–regulated kinase (Erk) and Stat3 activation. SgK269 Y635F, mutated at a major Lyn phosphorylation site, did not enhance acinar size or cellular invasion. We show that Y635 represents a Grb2-binding site that promotes both Stat3 and Erk activation in 3D culture. RNA interference–mediated attenuation of SgK269 in basal breast cancer cells promoted acquisition of epithelial characteristics and decreased anchorage-independent growth. Together, our results define a novel signaling pathway in basal breast cancer involving Lyn and SgK269 that offers clinical opportunities for therapeutic intervention. Cancer Res; 73(6); 1969–80. ©2012 AACR.
Deng, W, Xie, F, Baltar, HTMCM & Goldys, EM 2013, 'Metal-enhanced fluorescence in the life sciences: here, now and beyond', Physical Chemistry Chemical Physics, vol. 15, no. 38, pp. 15695-15695.
View/Download from: Publisher's site
Diffner, E, Beck, D, Gudgin, E, Thoms, JAI, Knezevic, K, Pridans, C, Foster, S, Goode, D, Lim, WK, Boelen, L, Metzeler, KH, Micklem, G, Bohlander, SK, Buske, C, Burnett, A, Ottersbach, K, Vassiliou, GS, Olivier, J, Wong, JWH, Göttgens, B, Huntly, BJ & Pimanda, JE 2013, 'Activity of a heptad of transcription factors is associated with stem cell programs and clinical outcome in acute myeloid leukemia', Blood, vol. 121, no. 12, pp. 2289-2300.
View/Download from: Publisher's site
View description>>
Key Points The ERG stem cell enhancer is active in acute myeloid leukemia and is regulated by a heptad of transcription factors. Expression signatures derived from ERG promoter–enhancer activity and heptad expression are associated with clinical outcome.
Emaus, N, Nguyen, ND, Almaas, B, Berntsen, GK, Center, JR, Christensen, M, Gjesdal, CG, Grimsgaard, AS, Nguyen, TV, Salomonsen, L, Eisman, JA & Fønnebø, VM 2013, 'Serum level of under-carboxylated osteocalcin and bone mineral density in early menopausal Norwegian women', European Journal of Nutrition, vol. 52, no. 1, pp. 49-55.
View/Download from: Publisher's site
View description>>
Serum level of under-carboxylated osteocalcin (ucOC) is considered a sensitive measure of vitamin K status, and ucOC levels are associated with bone mineral density (BMD) and fracture risk in elderly persons. The aim of this study was to assess the relationship between ucOC and BMD in early menopausal women. The data reported here come from the enrolment in a double-blinded placebo-controlled randomized trial comprising 334 healthy Norwegian women between 50 and 60 years, 1-5 years after menopause, not using warfarin or medication known to affect bone metabolism. Total hip, femoral neck, lumbar spine, and total body BMD and serum level of ucOC and total osteocalcin were measured, and information of lifestyle was collected through questionnaires. The association between ucOC and BMD at all measurement sites was assessed by multiple regression analyses adjusting for possible confounding variables. The absolute serum level of ucOC was significantly and negatively associated with BMD at all measurements sites, both in univariate analyses (p < 0.01) and in multivariate analyses adjusting for years since menopause, smoking status and weight (p < 0.01). However, serum ucOC, expressed as percentage of the total osteocalcin level, was not associated with BMD at any site. Achievement of adequate vitamin K nutritional intake is important, but ucOC expressed as percentage of total osteocalcin levels as reflection of vitamin K status does not seem to play a central role in determining BMD levels in early menopausal women.
Frost, SA, Nguyen, ND, Center, JR, Eisman, JA & Nguyen, TV 2013, 'Excess mortality attributable to hip-fracture: A relative survival analysis', Bone, vol. 56, no. 1, pp. 23-29.
View/Download from: Publisher's site
View description>>
Introduction: Individuals with hip fracture are at substantially increased risk of mortality. The aim of this study was to estimate the excess mortality attributable to hip fracture in elderly men and women. Methods: The Dubbo Osteoporosis Epidemiology Study was designed as a prospective epidemiologic investigation, in which more than 2000 men and women aged 60+ as of 1989 had been followed for 21 years. During the follow-up period, the incidence of atraumatic hip fractures was ascertained by X-ray reports, and mortality was ascertained by the New South Wales Birth, Death and Marriage Registry. Relative survival ratios were estimated by taking into account the age-and-sex specific expected survival in the general Australian population from 1989 to 2010. Results: During the follow-up period 151 women and 55 men sustained a hip fracture. Death occurred in 86 (57%) women and 36 (66%) men. In women, the cumulative relative survival post hip-fracture at 1, 5 and 10 years was 0.83 (95% confidence interval (CI) 0.76-0.89), 0.59 (95% CI 0.48-0.68), and 0.31 (95% Cl 0.20-0.43), respectively; in men, the corresponding estimates of relative survival were: 0.63 (95% CI 0.48-0.75), 0.48 (95% CI 0.32-0.63), and 0.36 (95% CI 0.18-0.56). On average post hip-fracture women died 4 years earlier (median: 4.1, inter-quartile range (IQR) 1.7-7.8) and men died 5 years earlier (median = 4.8, IQR 2.4-7.0) than expected. For every six women and for every three men with hip fracture one extra death occurred above that expected in the background population. Conclusion: Hip fracture is associated with reduced life expectancy, with men having a greater reduction than women, even after accounting for time-related changes in background mortality in the population. These data underscore that hip fracture is an independent clinical risk factor for mortality.
Gallego-Ortega, D, Oakes, SR, Lee, HJ, Piggin, CL & Ormandy, CJ 2013, 'ELF5, normal mammary development and the heterogeneous phenotypes of breast cancer', Breast Cancer Management, vol. 2, no. 6, pp. 489-498.
View/Download from: Publisher's site
View description>>
SUMMARY The ETS transcription factor ELF5 specifies the formation of the secretory cell lineage of the mammary gland during pregnancy, by directing cell fate decisions of the mammary progenitor cells. The decision-making activity continues in breast cancer, where in luminal breast cancer cells forced ELF5 expression suppresses estrogen sensitivity and shifts gene expression toward the basal molecular subtype. The development of anti-estrogen resistance in luminal breast cancer is accompanied by increased expression of ELF5 and acquired dependence on ELF5 for continued proliferation, providing a potential new therapeutic target or prognostic marker to improve the treatment of this stage of the disease. Forced ELF5 expression suppresses the mesenchymal phenotype, making cells more epithelial and producing lower rates of invasion and motility. Conversely, loss of ELF5 promotes metastasis, with a clear corollary in the claudin-low subtype of breast cancer, which does not express ELF5 and is highly metastatic, or during the final stages of tumor progression, where loss of ELF5 expression may be involved in the acquisition of the lethal phenotype. In circumstances where ELF5 expression increases in parallel with metastatic potential, such as anti-estrogen resistant luminal breast cancers and basal breast cancer, there is much more to be understood about ELF5 and metastasis.
Gentile, C, Muise-Helmericks, RC & Drake, CJ 2013, 'VEGF-mediated phosphorylation of eNOS regulates angioblast and embryonic endothelial cell proliferation', Developmental Biology, vol. 373, no. 1, pp. 163-175.
View/Download from: Publisher's site
Goldberg, L, Tijssen, MR, Birger, Y, Hannah, RL, Kinston, SJ, Schütte, J, Beck, D, Knezevic, K, Schiby, G, Jacob-Hirsch, J, Biran, A, Kloog, Y, Marcucci, G, Bloomfield, CD, Aplan, PD, Pimanda, JE, Göttgens, B & Izraeli, S 2013, 'Genome-scale expression and transcription factor binding profiles reveal therapeutic targets in transgenic ERG myeloid leukemia', Blood, vol. 122, no. 15, pp. 2694-2703.
View/Download from: Publisher's site
View description>>
Key PointsERG overexpression in transgenic mice induces a transcriptional leukemia stem cell program characteristic of human AML. PIM1 and RAS are relevant ERG therapeutic targets.
Gupta, B, Zhu, Y, Guan, B, Reece, PJ & Gooding, JJ 2013, 'Functionalised porous silicon as a biosensor: emphasis on monitoring cells in vivo and in vitro', The Analyst, vol. 138, no. 13, pp. 3593-3593.
View/Download from: Publisher's site
Ho-Pham, LT, Nguyen, ND & Nguyen, TV 2013, 'Quantification of the relative contribution of estrogen to bone mineral density in men and women', BMC Musculoskeletal Disorders, vol. 14, no. 1.
View/Download from: Publisher's site
View description>>
Background: The study quantified the relative contributions of estrogen (E2) and total testosterone (TT) to variation in bone mineral density in men and women. Methods: This was a cross-sectional study which involved 200 men and 415 women aged 18 to 89 years. BMD at the lumbar spine (LS) and femoral neck (FN) was measured by DXA. Serum levels of E2 and TT were measured by electrochemiluminescence immunoassays. The association between E2, TT, and BMD was analyzed by the multiple linear regression model, adjusting for age and BMI. The contribution of each hormone to the variation in BMD was quantified by the bootstrap method. Results: In women, higher serum levels of E2, but not TT, were significantly associated with greater BMD at the FN (P = 0.001) and LS (P < 0.0001). In men, higher serum levels of E2 were independently associated with greater FNBMD (P = 0.008) and LSBMD (P = 0.086). In the multiple linear regression model, age, body weight and E2 accounted for 50-55% variance in FNBMD, and 25% (in men) and 48% (in women) variance in LSBMD. Variation in E2 accounted for 2.5% (95% CI 0.4 - 7.8%) and 11.3% (95% CI 8.1 - 15.3%) variation in FNBMD in men and women, respectively. Moreover, E2 contributed 1.2% (95% CI 0.1 - 5.8%) and 11.7% (95% CI 8.5 - 15.9%) variation in LSBMD in men and women, respectively. Conclusions: Estrogen is more important than testosterone in the determination of age-related bone mineral density men and women of Vietnamese background. However, the relative contributions of estrogen to bone mineral density in men are likely modest
Hou, HW, Warkiani, ME, Khoo, BL, Li, ZR, Soo, RA, Tan, DS-W, Lim, W-T, Han, J, Bhagat, AAS & Lim, CT 2013, 'Isolation and retrieval of circulating tumor cells using centrifugal forces', Scientific Reports, vol. 3, no. 1, p. 1259.
View/Download from: Publisher's site
View description>>
Presence and frequency of rare circulating tumor cells (CTCs) in bloodstreams of cancer patients are pivotal to early cancer detection and treatment monitoring. Here, we use a spiral microchannel with inherent centrifugal forces for continuous, size-based separation of CTCs from blood (Dean Flow Fractionation (DFF)) which facilitates easy coupling with conventional downstream biological assays. Device performance was optimized using cancer cell lines (> 85% recovery), followed by clinical validation with positive CTCs enumeration in all samples from patients with metastatic lung cancer (n = 20; 5-88 CTCs per mL). The presence of CD133⁺ cells, a phenotypic marker characteristic of stem-like behavior in lung cancer cells was also identified in the isolated subpopulation of CTCs. The spiral biochip identifies and addresses key challenges of the next generation CTCs isolation assay including antibody independent isolation, high sensitivity and throughput (3 mL/hr); and single-step retrieval of viable CTCs.
Lee, HJ, Gallego-Ortega, D, Ledger, A, Schramek, D, Joshi, P, Szwarc, MM, Cho, C, Lydon, JP, Khokha, R, Penninger, JM & Ormandy, CJ 2013, 'Progesterone drives mammary secretory differentiation via RankL-mediated induction of Elf5 in luminal progenitor cells', Development, vol. 140, no. 7, pp. 1397-1401.
View/Download from: Publisher's site
View description>>
Progesterone-RankL paracrine signaling has been proposed as a driver of stem cell expansion in the mammary gland, and Elf5 is essential for the differentiation of mammary epithelial progenitor cells. We demonstrate that Elf5 expression is induced by progesterone and that Elf5 and progesterone cooperate to promote alveolar development. The progesterone receptor and Elf5 are expressed in a mutually exclusive pattern, and we identify RankL as the paracrine mediator of the effects of progesterone on Elf5 expression in CD61+ progenitor cells and their consequent differentiation. Blockade of RankL action prevented progesterone-induced side branching and the expansion of Elf5+ mature luminal cells. These findings describe a mechanism by which steroid hormones can produce the expansion of steroid hormone receptor-negative mammary epithelial cells.
Li, AD, Sun, ZZ, Zhou, M, Xu, XX, Ma, JY, Zheng, W, Zhou, HM, Li, L & Zheng, YF 2013, 'Electrospun Chitosan-graft-PLGA nanofibres with significantly enhanced hydrophilicity and improved mechanical property', Colloids and Surfaces B: Biointerfaces, vol. 102, pp. 674-681.
View/Download from: Publisher's site
Li, JJ, Gil, ES, Hayden, RS, Li, C, Roohani-Esfahani, S-I, Kaplan, DL & Zreiqat, H 2013, 'Multiple Silk Coatings on Biphasic Calcium Phosphate Scaffolds: Effect on Physical and Mechanical Properties and In Vitro Osteogenic Response of Human Mesenchymal Stem Cells', Biomacromolecules, vol. 14, no. 7, pp. 2179-2188.
View/Download from: Publisher's site
View description>>
Ceramic scaffolds such as biphasic calcium phosphate (BCP) have been widely studied and used for bone regeneration, but their brittleness and low mechanical strength are major drawbacks. We report the first systematic study on the effect of silk coating in improving the mechanical and biological properties of BCP scaffolds, including (1) optimization of the silk coating process by investigating multiple coatings, and (2) in vitro evaluation of the osteogenic response of human mesenchymal stem cells (hMSCs) on the coated scaffolds. Our results show that multiple silk coatings on BCP ceramic scaffolds can achieve a significant coating effect to approach the mechanical properties of native bone tissue and positively influence osteogenesis by hMSCs over an extended period. The silk coating method developed in this study represents a simple yet effective means of reinforcement that can be applied to other types of ceramic scaffolds with similar microstructure to improve osteogenic outcomes.
Ngalim, SH, Magenau, A, Zhu, Y, Tønnesen, L, Fairjones, Z, Gooding, JJ, Böcking, T & Gaus, K 2013, 'Creating Adhesive and Soluble Gradients for Imaging Cell Migration with Fluorescence Microscopy', Journal of Visualized Experiments, no. 74.
View/Download from: Publisher's site
Nguyen, TV & Eisman, JA 2013, 'Genetic profiling and individualized assessment of fracture risk', Nature Reviews Endocrinology, vol. 9, no. 3, pp. 153-161.
View/Download from: Publisher's site
View description>>
Osteoporosis and its consequence of fragility fracture impose a considerable demand on health-care services because fracture is associated with a series of adverse events, including re-fracture and mortality. One of the major priorities in osteoporosis care is the development of predictive models to identify individuals at high risk of fracture for early intervention and management. Existing predictive models include clinical factors and anthropometric characteristics but have not considered genetic variants in the prediction. Genome-wide association studies conducted in the past decade have identified several genetic variants relevant to fracture risk. These genetic variants are common in frequency but have very modest effect sizes. A remaining challenge is to use these genetic data to individualize fracture risk assessment on the basis of an individual's genetic risk profile. Empirical and simulation studies have shown that the usefulness of a single genetic variant for fracture risk assessment is very limited, but a profile of 50 genetic variants, each with odds ratio ranging from 1.02 to 1.15, could improve the accuracy of fracture prediction beyond that obtained by use of existing clinical risk factors. Thus, genetic profiling when integrated with existing risk assessment models could inform a more accurate prediction of fracture risk in an individual.
Nguyen, TV, Center, JR & Eisman, JA 2013, 'Individualized fracture risk assessment', Current Opinion in Rheumatology, vol. 25, no. 4, pp. 532-541.
View/Download from: Publisher's site
View description>>
Purpose of review Fragility fracture is a major public health burden, because it is associated with a substantial morbidity and mortality. Risk prediction models, including the Fracture Risk Assessment Tool (FRAX) and Garvan Fracture Risk Calculator (GFR
Ortiz-Padilla, C, Gallego-Ortega, D, Browne, BC, Hochgräfe, F, Caldon, CE, Lyons, RJ, Croucher, DR, Rickwood, D, Ormandy, CJ, Brummer, T & Daly, RJ 2013, 'Functional characterization of cancer-associated Gab1 mutations', Oncogene, vol. 32, no. 21, pp. 2696-2702.
View/Download from: Publisher's site
Parr, WCH, Chamoli, U, Jones, A, Walsh, WR & Wroe, S 2013, 'Finite element micro-modelling of a human ankle bone reveals the importance of the trabecular network to mechanical performance: New methods for the generation and comparison of 3D models', Journal of Biomechanics, vol. 46, no. 1, pp. 200-205.
View/Download from: Publisher's site
Remenyi, J, van den Bosch, MWM, Palygin, O, Mistry, RB, McKenzie, C, Macdonald, A, Hutvagner, G, Arthur, JSC, Frenguelli, BG & Pankratov, Y 2013, 'miR-132/212 Knockout Mice Reveal Roles for These miRNAs in Regulating Cortical Synaptic Transmission and Plasticity', PLoS ONE, vol. 8, no. 4, pp. e62509-e62509.
View/Download from: Publisher's site
View description>>
miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity. © 2013 Remenyi et al.
Roohani-Esfahani, SI, Dunstan, CR, Li, JJ, Lu, Z, Davies, B, Pearce, S, Field, J, Williams, R & Zreiqat, H 2013, 'Unique microstructural design of ceramic scaffolds for bone regeneration under load', Acta Biomaterialia, vol. 9, no. 6, pp. 7014-7024.
View/Download from: Publisher's site
View description>>
During the past two decades, research on ceramic scaffolds for bone regeneration has progressed rapidly; however, currently available porous scaffolds remain unsuitable for load-bearing applications. The key to success is to apply microstructural design strategies to develop ceramic scaffolds with mechanical properties approaching those of bone. Here we report on the development of a unique microstructurally designed ceramic scaffold, strontium-hardystonite-gahnite (Sr-HT-gahnite), with 85% porosity, 500μm pore size, a competitive compressive strength of 4.1±0.3MPa and a compressive modulus of 170±20MPa. The in vitro biocompatibility of the scaffolds was studied using primary human bone-derived cells. The ability of Sr-HT-gahnite scaffolds to repair critical-sized bone defects was also investigated in a rabbit radius under normal load, with β-tricalcium phosphate/hydroxyapatite scaffolds used in the control group. Studies with primary human osteoblast cultures confirmed the bioactivity of these scaffolds, and regeneration of rabbit radial critical defects demonstrated that this material induces new bone defect bridging, with clear evidence of regeneration of original radial architecture and bone marrow environment.
Sobala, A & Hutvagner, G 2013, 'Small RNAs derived from the 5′ end of tRNA can inhibit protein translation in human cells', RNA Biology, vol. 10, no. 4, pp. 553-563.
View/Download from: Publisher's site
View description>>
Recently, it has been shown that tRNA molecules can be processed into small RNAs that are derived from both the 5′ and 3′ termini. To date, the function of these tRNA fragments (tRFs) derived from the 5′ end of tRNAs has not been investigated in depth. We present evidence that conserved residues in tRNAs, present in all 5′ tRFs, can inhibit the process of protein translation without the need for complementary target sites in the mRNA. These results implicate 5′ tRFs in a new mechanism of gene regulation by small RNAs in human cells. © 2013 Landes Bioscience.
Stone, A, Cowley, MJ, Valdes-Mora, F, McCloy, RA, Sergio, CM, Gallego-Ortega, D, Caldon, CE, Ormandy, CJ, Biankin, AV, Gee, JMW, Nicholson, RI, Print, CG, Clark, SJ & Musgrove, EA 2013, 'BCL-2 Hypermethylation Is a Potential Biomarker of Sensitivity to Antimitotic Chemotherapy in Endocrine-Resistant Breast Cancer', Molecular Cancer Therapeutics, vol. 12, no. 9, pp. 1874-1885.
View/Download from: Publisher's site
View description>>
Abstract Overexpression of the antiapoptotic factor BCL-2 is a frequent feature of malignant disease and is commonly associated with poor prognosis and resistance to conventional chemotherapy. In breast cancer, however, high BCL-2 expression is associated with favorable prognosis, estrogen receptor (ER) positivity, and low tumor grade, whereas low expression is included in several molecular signatures associated with resistance to endocrine therapy. In the present study, we correlate BCL-2 expression and DNA methylation profiles in human breast cancer and in multiple cell models of acquired endocrine resistance to determine whether BCL-2 hypermethylation could provide a useful biomarker of response to cytotoxic therapy. In human disease, diminished expression of BCL-2 was associated with hypermethylation of the second exon, in a region that overlapped a CpG island and an ER-binding site. Hypermethylation of this region, which occurred in 10% of primary tumors, provided a stronger predictor of patient survival (P = 0.019) when compared with gene expression (n = 522). In multiple cell models of acquired endocrine resistance, BCL-2 expression was significantly reduced in parallel with increased DNA methylation of the exon 2 region. The reduction of BCL-2 expression in endocrine-resistant cells lowered their apoptotic threshold to antimitotic agents: nocodazole, paclitaxel, and the PLK1 inhibitor BI2536. This phenomenon could be reversed with ectopic expression of BCL-2, and rescued with the BCL-2 inhibitor ABT-737. Collectively, these data imply that BCL-2 hypermethylation provides a robust biomarker of response to current and next-generation cytotoxic agents in endocrine-resistant breast cancer, which may prove beneficial in directing therapeutic strategy for patients with nonresectable, metastatic disease. Mol Cancer Ther; 12(9); 1874–85. ©2013 AACR.
Styrkarsdottir, U, Thorleifsson, G, Sulem, P, Gudbjartsson, DF, Sigurdsson, A, Jonasdottir, A, Jonasdottir, A, Oddsson, A, Helgason, A, Magnusson, OT, Walters, GB, Frigge, ML, Helgadottir, HT, Johannsdottir, H, Bergsteinsdottir, K, Ogmundsdottir, MH, Center, JR, Nguyen, TV, Eisman, JA, Christiansen, C, Steingrimsson, E, Jonasson, JG, Tryggvadottir, L, Eyjolfsson, GI, Theodors, A, Jonsson, T, Ingvarsson, T, Olafsson, I, Rafnar, T, Kong, A, Sigurdsson, G, Masson, G, Thorsteinsdottir, U & Stefansson, K 2013, 'Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits', Nature, vol. 497, no. 7450, pp. 517-520.
View/Download from: Publisher's site
Tran, N & Hutvagner, G 2013, 'Biogenesis and the regulation of the maturation of miRNAs', Essays in Biochemistry, vol. 54, no. 1, pp. 17-28.
View/Download from: Publisher's site
View description>>
Regulation of gene expression is a fundamental process in both prokaryotic and eukaryotic organisms. Multiple regulatory mechanisms are in place to control gene expression at the level of transcription, post-transcription and post-translation to maintain optimal RNA and protein expressions in cells. miRNAs (microRNAs) are abundant short 21–23 nt non-coding RNAs that are key regulators of virtually all eukaryotic biological processes. The levels of miRNAs in an organism are crucial for proper development and sustaining optimal cell functions. Therefore the processing and regulation of the processing of these miRNAs are critical. In the present chapter we highlight the most important steps of miRNA processing, describe the functions of key proteins involved in the maturation of miRNAs, and discuss how the generation and the stability of miRNAs are regulated.
Tran, TS, Hirst, JE, Do, MAT, Morris, JM & Jeffery, HE 2013, 'Early Prediction of Gestational Diabetes Mellitus in Vietnam', Diabetes Care, vol. 36, no. 3, pp. 618-624.
View/Download from: Publisher's site
View description>>
OBJECTIVE We aimed to compare the discriminative power of prognostic models for early prediction of women at risk for the development of gestational diabetes mellitus (GDM) using four currently recommended diagnostic criteria based on the 75-g oral glucose tolerance test (OGTT). We also described the potential effect of application of the models into clinical practice. RESEARCH DESIGN AND METHODS A prospective cross-sectional study of 2,772 pregnant women was conducted at a referral maternity center in Vietnam. GDM was determined by the American Diabetes Association (ADA), International Association of the Diabetes and Pregnancy Study Groups (IADPSG), Australasian Diabetes in Pregnancy Society (ADIPS), and World Health Organization (WHO) criteria. Prognostic models were developed using the Bayesian model averaging approach, and discriminative power was assessed by area under the curve. Different thresholds of predicted risk of developing GDM were applied to describe the clinical impact of the diagnostic criteria. RESULTS The magnitude of GDM varied substantially by the diagnostic criteria: 5.9% (ADA), 20.4% (IADPSG), 20.8% (ADIPS), and 24.3% (WHO). The ADA prognostic model, consisting of age and BMI at booking, had the best discriminative power (area under the curve of 0.71) and the most favorable cost-effective ratio if implemented in clinical practice. Selective screening of women for GDM using the ADA model with a risk threshold of 3% gave 93% sensitivity for identification of women with GDM with a 27% reduction in the number of OGTTs required. ...
Warkiani, ME, Bhagat, AAS, Khoo, BL, Han, J, Lim, CT, Gong, HQ & Fane, AG 2013, 'Isoporous Micro/Nanoengineered Membranes', ACS Nano, vol. 7, no. 3, pp. 1882-1904.
View/Download from: Publisher's site
Wroe, S, Chamoli, U, Parr, WCH, Clausen, P, Ridgely, R & Witmer, L 2013, 'Comparative Biomechanical Modeling of Metatherian and Placental Saber-Tooths: A Different Kind of Bite for an Extreme Pouched Predator', PLoS ONE, vol. 8, no. 6, pp. e66888-e66888.
View/Download from: Publisher's site
Wu, J, Peng, Z & Tipper, J 2013, 'Investigation of three-dimensional surface topographies and mechanical properties of hypothesized biological active wear particles from artificial joints', Wear, vol. 301, no. 1-2, pp. 182-187.
View/Download from: Publisher's site
Wu, J, Peng, Z & Tipper, J 2013, 'Mechanical Properties and Three-Dimensional Topological Characterisation of Micron, Submicron and Nanoparticles from Artificial Joints', Tribology Letters, vol. 52, no. 3, pp. 449-460.
View/Download from: Publisher's site
Xu, XX, Ding, MH, Zhang, JX, Zheng, W, Li, L & Zheng, YF 2013, 'A novel copper/polydimethiylsiloxane nanocomposite for copper‐containing intrauterine contraceptive devices', Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 101, no. 8, pp. 1428-1436.
View/Download from: Publisher's site
View description>>
AbstractIn this article, a novel composite of copper (Cu) nanoparticles and polydimethiylsiloxane (PDMS) has been prepared and investigated for the potential application in Cu‐containing intrauterine device. The Cu/PDMS composite with various mass fraction of Cu nanoparticles was fabricated via the hot vulcanizing process. The chemical structures and surface morphologies of the Cu/PDMS composites were characterized confirming the physical interaction between Cu nanoparticles and PDMS. The surface morphology observation using scanning electron microscope and atomic force microscope showed the agglomeration of Cu nanoparticles in PDMS matrix and the distribution of the agglomerations was more uniform with increased amount of Cu nanoparticles. The cupric ion release behaviors of the Cu/PDMS composites with different amounts of Cu nanoparticles were investigated in simulated uterine fluid at 37°C for 150 days. The corrosion morphologies of the Cu/PDMS composites were also characterized. Both the burst release rate of the cupric ion in the first few days and the steady release rate after 30‐day immersion were improved. The cytotoxicity test has been done for the Cu/PDMS composites. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 101B: 1428–1436, 2013.
Yang, S, Nguyen, ND, Center, JR, Eisman, JA & Nguyen, TV 2013, 'Association Between Abdominal Obesity and Fracture Risk: A Prospective Study', The Journal of Clinical Endocrinology & Metabolism, vol. 98, no. 6, pp. 2478-2483.
View/Download from: Publisher's site
View description>>
Context: Higher body weight is associated with greater bone mineral density (BMD) and lower fracture risk. However, the relationship between abdominal fat mass (aFM) and fracture risk is unclear because of limited prospective data. The present study sought to examine the association between aFM, BMD, and fracture risk. Methods: The study was designed as a prospective investigation, in which a sample of 1126 participants (360 men and 766 women) aged 50 years or older had been continuously followed up for an average of 5 years. The mean age of participants was 71 years (range, 57–94 years). At baseline, BMD at the femoral neck and lumbar spine and aFM were measured by dual-energy X-ray absorptiometry. The incidence of low-trauma and nonpathological fractures was ascertained prospectively from X-ray reports. Results: During the follow-up period, 19 men and 107 women had sustained a fracture. In women, each 1-kg lower aFM was associated with a 50% higher risk of fracture (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.10–2.05) after adjustment for age, femoral neck BMD, falls, stature, physical activity, and prior fracture. Subgroup analysis by fracture type found that the association was mainly observed in clinical vertebral fracture (HR, 1.96; 95% CI, 1.22–3.13). In men, although there was no statistically significant association between aFM and fracture risk (HR, 1.15; 95% CI, 0.58–2.25), the strength of this finding is affected negatively by the low number of fractures. Conclusions:
Zhu, Y, Gupta, B, Guan, B, Ciampi, S, Reece, PJ & Gooding, JJ 2013, 'Photolithographic Strategy for Patterning Preformed, Chemically Modified, Porous Silicon Photonic Crystal Using Click Chemistry', ACS Applied Materials & Interfaces, vol. 5, no. 14, pp. 6514-6521.
View/Download from: Publisher's site