The genetic basis of human height : the role of estrogen

Height is a complex physical trait that displays strong heritability. Adult height is related to length of the long bones, which is determined by growth at the epiphyseal growth plate. Longitudinal bone growth occurs via the process of endochondral ossification, where bone forms over the differentiating cartilage template at the growth plate. Estrogen plays a major role in regulating longitudinal bone growth and is responsible for inducing the pubertal growth spurt and fusion of the epiphyseal growth plate. However, the mechanism by which estrogen promotes epiphyseal fusion is poorly understood. It has been hypothesised that estrogen functions to regulate growth plate fusion by stimulating chondrocyte apoptosis, angiogenesis and bone cell invasion in the growth plate. Another theory has suggested that estrogen exposure exhausts the proliferative capacity of growth plate chondrocytes, which accelerates the process of chondrocyte senescence, leading to growth plate fusion. The overall objective of this study was to gain a greater understanding of the molecular mechanisms behind estrogen-mediated growth and height attainment by examining gene regulation in chondrocytes and the role of some of these genes in normal height inheritance. With the heritability of height so well established, the initial hypothesis was that genetic variation in candidate genes associated with longitudinal bone growth would be involved in normal adult height variation. The height-related genes FGFR3, CBFA1, ER and CBFA1 were screened for novel polymorphisms using denaturing HPLC and RFLP analysis. In total, 24 polymorphisms were identified. Two SNPs in ER (rs3757323 C>T and rs1801132 G>C) were strongly associated with adult male height and displayed an 8 cm and 9 cm height difference between homozygous genotypes, respectively. The TC haplotype of these SNPs was associated with a 6 cm decrease in height and remarkably, no homozygous carriers of the TC haplotype were identified in tall subjects. No significant associations with height were found for polymorphisms in the FGFR3, CBFA1 or VDR genes. In the epiphyseal growth plate, chondrocyte proliferation, matrix synthesis and chondrocyte hypertrophy are all major contributors to long bone growth. As estrogen plays such a significant role in both growth and final height attainment, another hypothesis of this study was that estrogen exerted its effects in the growth plate by influencing chondrocyte proliferation and mediating the expression of chondrocyte marker genes. The examination of genes regulated by estrogen in chondrocyte-like cells aimed to identify potential regulators of growth plate fusion, which may further elucidate mechanisms involved in the cessation of linear growth. While estrogen did not dramatically alter the proliferation of the SW1353 cell line, gene expression experiments identified several estrogen regulated genes. Sixteen chondrocyte marker genes were examined in response to estrogen concentrations ranging from 10-12 M to 10-8 M over varying time points. Of the genes analysed, IHH, FGFR3, collagen II and collagen X were not readily detectable and PTHrP, GHR, ER, BMP6, SOX9 and TGF1 mRNAs showed no significant response to estrogen treatments. However, the expression of MMP13, CBFA1, BCL-2 and BAX genes were significantly decreased. Interestingly, the majority of estrogen regulated genes in SW1353 cells are expressed in the hypertrophic zone of the growth plate. Estrogen is also known to regulate systemic GH secretion and local GH action. At the molecular level, estrogen functions to inhibit GH action by negatively regulating GH signalling. GH treated SW1353 cells displayed increases in MMP9 mRNA expression (4.4-fold) and MMP13 mRNA expression (64-fold) in SW1353 cells. Increases were also detected in their respective proteins. Treatment with AG490, an established JAK2 inhibitor, blocked the GH mediated stimulation of both MMP9 and MMP13 mRNA expression. The application of estrogen and GH to SW1353 cells attenuated GH-stimulated MMP13 levels, but did not affect MMP9 levels. Investigation of GH signalling revealed that SW1353 cells have high levels of activated JAK2 and exposure to GH, estrogen, AG490 and other signalling inhibitors did not affect JAK2 phosphorylation. Interestingly, AG490 treatment dramatically decreased ERK2 signalling, although GH did stimulate ERK2 phosphorylation above control levels. AG490 also decreased CBFA1 expression, a transcription factor known to activate MMP9 and MMP13. Finally, GH and estrogen treatment increased expression of SOCS3 mRNA, suggesting that SOCS3 may regulate JAK/STAT signalling in SW1353 cells. The modulation of GH-mediated MMP expression by estrogen in SW1353 cells represents a potentially novel mechanism by which estrogen may regulate longitudinal bone growth. However, further investigation is required in order to elucidate the precise mechanisms behind estrogen and GH regulation of MMP13 expression in SW1353 cells. This study has provided additional evidence that estrogen and the ER gene are major factors in the regulation of growth and the determination of adult height. Newly identified polymorphisms in the ER gene not only contribute to our understanding of the genetic basis of human height, but may also be useful in association studies examining other complex traits. This study also identified several estrogen regulated genes and indicated that estrogen modifies the expression of genes which are primarily expressed in the hypertrophic region of the epiphyseal growth plate. Furthermore, synergistic studies incorporating GH and estrogen have revealed the ability of estrogen to attenuate the effects of GH on MMP13 expression, revealing potential pathways by which estrogen may modulate growth plate fusion, longitudinal bone growth and even arthritis.

Patterns of fitting cosmetically tinted contact lenses

Cosmetically tinted soft contact lenses are an attractive option for contact lens wearers. Data that we have gathered from annual contact lens fitting surveys demonstrate that those wearing tinted lenses are more likely to be female (4.6% of all soft lenses fitted vs. 1.6% for males; p < 0.0001) and younger (27 11 years vs. 33 13 years for those wearing non-tinted lenses; p < 0.0001). Tinted lenses tend to be worn more on a part-time basis and are replaced less frequently than non-tinted lenses. The decline in fitting tinted lenses over the past 12 years may be due to (a) the current limited availability of tinted lenses in silicone hydrogel materials and daily disposable replacement frequencies, which together represent a significant majority (78%) of new soft lenses fits today, (b) growing concerns among lens wearers and practitioners relating to the risks of complications associated with the wearing of tinted lenses, and (c) reduced promotion of such lenses by the contact lens industry.

Members abroad - Australia : Paul Sanders

I have been an academic since joining the University of Natal in 1998 and, following a period as a visiting lecturer in Brisbane in 2001, I joined the staff at QUT on an ongoing basis in 2003. I was appointed as Architecture Co-ordinator in 2006, and this role involves the leadership of the architectur discipline of 17 full time academics. I am currently enrolled in a PhD course in the field of urban morphology. This research proposes a theory on the relevance of mapping the evolutionary aspects of historical urban form to develop a measure for evaluating architecural elements and deriving parameters for new buildings. My participation in a QUT design team contributed to a recent successful invited competition bid for an Urban Transit Centre in Hangzhou, China. The Centre will include retail, business, entertainment, residential and service components at the heart of the Binjiang district on the 11.5ha core area with 32ha surrounding urban design precinct. The project has received the approval to commence and is to be implemented over the next three years!

Examining the use of bid information in predicting the contractor’s performance

Purpose – The purpose of this paper is to examine the use of bid information, including both price and non-price factors in predicting the bidder’s performance. Design/methodology/approach – The practice of the industry was first reviewed. Data on bid evaluation and performance records of the successful bids were then obtained from the Hong Kong Housing Department, the largest housing provider in Hong Kong. This was followed by the development of a radial basis function (RBF) neural network based performance prediction model. Findings – It is found that public clients are more conscientious and include non-price factors in their bid evaluation equations. With the input variables used the information is available at the time of the bid and the output variable is the project performance score recorded during work in progress achieved by the successful bidder. It was found that past project performance score is the most sensitive input variable in predicting future performance. Research limitations/implications – The paper shows the inadequacy of using price alone for bid award criterion. The need for a systemic performance evaluation is also highlighted, as this information is highly instrumental for subsequent bid evaluations. The caveat for this study is that the prediction model was developed based on data obtained from one single source. Originality/value – The value of the paper is in the use of an RBF neural network as the prediction tool because it can model non-linear function. This capability avoids tedious ‘‘trial and error’’ in deciding the number of hidden layers to be used in the network model. Keywords Hong Kong, Construction industry, Neural nets, Modelling, Bid offer spreads Paper type Research paper

Human brain regions required for the dividing and switching of attention between two features of a single object

This combined PET and ERP study was designed to identify the brain regions activated in switching and divided attention between different features of a single object using matched sensory stimuli and motor response. The ERP data have previously been reported in this journal [64]. We now present the corresponding PET data. We identified partially overlapping neural networks with paradigms requiring the switching or dividing of attention between the elements of complex visual stimuli. Regions of activation were found in the prefrontal and temporal cortices and cerebellum. Each task resulted in different prefrontal cortical regions of activation lending support to the functional subspecialisation of the prefrontal and temporal cortices being based on the cognitive operations required rather than the stimuli themselves.

Further evidence for a deficit in switching attention in schizophrenia

In this study, sustained, selective, divided, and switching attention, and reloading of working memory were investigated in schizophrenia by using a newly developed Visual Attention Battery (VAB). Twenty-four outpatients with schizophrenia and 24 control participants were studied using the VAB. Performance on VAB components was correlated with performance of standard tests. Patients with schizophrenia were significantly impaired on VAB tasks that required switching of attention and reloading of working memory but had normal performance on tasks involving sustained attention or attention to multiple stimulus features. Switching attention and reloading of working memory were highly correlated with Trails (B - A) score for patients. The decline in performance on the switching-attention task in patients with schizophrenia met criteria for a differential deficit in switching attention. Future research should examine the neurophysiological basis of the switching deficit and its sensitivity and specificity to schizophrenia.

Spatial Science News from QUT, Urban Development, November 2009.

Brief overview of topics/issues of interest end of 2009, including Spatial Science Students undertake Variety of Research Projects; labs and offices on the move again); Congratulations to Surveying Student Project- QSEA awards.

Mobile phone use while driving : an investigation of the beliefs influencing drivers’ hands-free and hand-held mobile phone use.

This study explored the psychological influences of hands-free and hand-held mobile phone use while driving. Participants were 796 Australian drivers aged 17 to 76 years who owned mobile phones. A cross-sectional survey assessed frequency of calling and text messaging while driving (overall, hands-free, hand-held) as well as drivers’ behavioural, normative, and control beliefs relating to mobile phone use while driving. Irrespective of handset type, 43% of drivers reported answering calls while driving on a daily basis, followed by making calls (36%), reading text messages (27%), and sending text messages (18%). In total, 63.9% of drivers did not own hands-free kits and, of the drivers that owned hand-free kits, 32% did not use it most or all of the time. Significant differences were found in the behavioural, normative, and control beliefs of frequent and infrequent users of both types of handset while driving. As expected, frequent users reported more advantages of, more approval from others for, and fewer barriers that would prevent them from, using either a hands-free or a hand-held mobile phone while driving than infrequent users. Campaigns to reduce mobile phone use while driving should attempt to minimise the perceived benefits of the behaviour and highlight the risks of this unsafe driving practice.

A Reliable Basis for Approximate Association Rules

For most of the work done in developing association rule mining, the primary focus has been on the efficiency of the approach and to a lesser extent the quality of the derived rules has been emphasized. Often for a dataset, a huge number of rules can be derived, but many of them can be redundant to other rules and thus are useless in practice. The extremely large number of rules makes it difficult for the end users to comprehend and therefore effectively use the discovered rules and thus significantly reduces the effectiveness of rule mining algorithms. If the extracted knowledge can’t be effectively used in solving real world problems, the effort of extracting the knowledge is worth little. This is a serious problem but not yet solved satisfactorily. In this paper, we propose a concise representation called Reliable Approximate basis for representing non-redundant approximate association rules. We prove that the redundancy elimination based on the proposed basis does not reduce the belief to the extracted rules. We also prove that all approximate association rules can be deduced from the Reliable Approximate basis. Therefore the basis is a lossless representation of approximate association rules.

Diffuse reflectance near infrared spectroscopy can distinguish normal from enzymatically digested cartilage

A non-destructive, diffuse reflectance near infrared spectroscopy (DR-NIRS)approach is considered as a potential tool for determining the component-level structural properties of articular cartilage. To this end, DR-NIRS was applied in vitro to detect structural changes, using principal component analysis as the statistical basis for characterization. The results show that this technique, particularly with first-derivative pretreatment, can distinguish normal, intact cartilage from enzymatically digested cartilage. Further, this paper establishes that the use of DR-NIRS enables the probing of the full depth of the uncalcified cartilage matrix, potentially allowing the assessment of degenerative changes in joint tissue, independent of the site of initiation of the osteoarthritic process.

Concentrations of polybrominated diphenyl ethers (PBDEs) in matched samples of human milk, dust and indoor air

Polybrominated diphenyl ethers (PBDEs) are lipophilic, persistent pollutants found worldwide in environmental and human samples. Exposure pathways for PBDEs remain unclear but may include food, air and dust. The aim of this study was to conduct an integrated assessment of PBDE exposure and human body burden using 10 matched samples of human milk, indoor air and dust collected in 2007–2008 in Brisbane, Australia. In addition, temporal analysis was investigated comparing the results of the current study with PBDE concentrations in human milk collected in 2002–2003 from the same region. PBDEs were detected in all matrices and the median concentrations of BDEs -47 and -209 in human milk, air and dust were: 4.2 and 0.3 ng/g lipid; 25 and 7.8 pg/m3; and 56 and 291 ng/g dust, respectively. Significant correlations were observed between the concentrations of BDE-99 in air and human milk (r = 0.661, p = 0.038) and BDE-153 in dust and BDE-183 in human milk (r = 0.697, p = 0.025). These correlations do not suggest causal relationships — there is no hypothesis that can be offered to explain why BDE-153 in dust and BDE-183 in milk are correlated. The fact that so few correlations were found in the data could be a function of the small sample size, or because additional factors, such as sources of exposure not considered or measured in the study, might be important in explaining exposure to PBDEs. There was a slight decrease in PBDE concentrations from 2002–2003 to 2007–2008 but this may be due to sampling and analytical differences. Overall, average PBDE concentrations from these individual samples were similar to results from pooled human milk collected in Brisbane in 2002–2003 indicating that pooling may be an efficient, cost-effective strategy of assessing PBDE concentrations on a population basis. The results of this study were used to estimate an infant's daily PBDE intake via inhalation, dust ingestion and human milk consumption. Differences in PBDE intake of individual congeners from the different matrices were observed. Specifically, as the level of bromination increased, the contribution of PBDE intake decreased via human milk and increased via dust. As the impacts of the ban of the lower brominated (penta- and octa-BDE) products become evident, an increased use of the higher brominated deca-BDE product may result in dust making a greater contribution to infant exposure than it does currently. To better understand human body burden, further research is required into the sources and exposure pathways of PBDEs and metabolic differences influencing an individual's response to exposure. In addition, temporal trend analysis is necessary with continued monitoring of PBDEs in the human population as well as in the suggested exposure matrices of food, dust and air.

Are combination forecasts of S&P 500 volatility statistically superior?

Forecasting volatility has received a great deal of research attention, with the relative performances of econometric model based and option implied volatility forecasts often being considered. While many studies find that implied volatility is the pre-ferred approach, a number of issues remain unresolved, including the relative merit of combining forecasts and whether the relative performances of various forecasts are statistically different. By utilising recent econometric advances, this paper considers whether combination forecasts of S&P 500 volatility are statistically superior to a wide range of model based forecasts and implied volatility. It is found that a combination of model based forecasts is the dominant approach, indicating that the implied volatility cannot simply be viewed as a combination of various model based forecasts. Therefore, while often viewed as a superior volatility forecast, the implied volatility is in fact an inferior forecast of S&P 500 volatility relative to model-based forecasts.

Best basis-based intelligent machine fault diagnosis

The wavelet packet transform decomposes a signal into a set of bases for time–frequency analysis. This decomposition creates an opportunity for implementing distributed data mining where features are extracted from different wavelet packet bases and served as feature vectors for applications. This paper presents a novel approach for integrated machine fault diagnosis based on localised wavelet packet bases of vibration signals. The best basis is firstly determined according to its classification capability. Data mining is then applied to extract features and local decisions are drawn using Bayesian inference. A final conclusion is reached using a weighted average method in data fusion. A case study on rolling element bearing diagnosis shows that this approach can greatly improve the accuracy ofdiagno sis.

Creating and sustaining a basis for life-long learning in tertiary dancer training

This paper acknowledges the influences that a generation Y population brings to dance training methodologies and examines this impact in a tertiary context. Over the last 4 years, Queensland University of Technology has been modifying their curriculum for new students transitioning from the private dance studio into the prevocational university environment. An intensive training program was designed to empower the student creating effective entry points for common understandings in the learning and teaching of dance techniques with improved and accelerated learning outcomes. This paper shares these philosophies and practices in training for life-long learning that prepare the young dancer for longevity in the industry.