Molecular Alterations in Asbestos-Related Lung Cancer

Background: Asbestos is a well known cancer-causing mineral fibre, which has a synergistic effect on lung cancer risk in combination with tobacco smoking. Several in vitro and in vivo experiments have demonstrated that asbestos can evoke chromosomal damage and cause alterations as well as gene expression changes. Lung tumours, in general, have very complex karyotypes with several recurrently gained and lost chromosomal regions and this has made it difficult to identify specific molecular changes related primarily to asbestos exposure. The main aim of these studies has been to characterize asbestos-related lung cancer at a molecular level. Methods: Samples from asbestos-exposed and non-exposed lung cancer patients were studied using array comparative genomic hybridization (aCGH) and fluorescent in situ hybridization (FISH) to detect copy number alterations (CNA) as well as microsatellite analysis to detect allelic imbalance (AI). In addition, asbestos-exposed cell lines were studied using gene expression microarrays. Results: Eighteen chromosomal regions showing differential copy number in the lung tumours of asbestos-exposed patients compared to those of non-exposed patients were identified. The most significant differences were detected at 2p21-p16.3, 5q35.3, 9q33.3-q34.11, 9q34.13-q34.3, 11p15.5, 14q11.2 and 19p13.1-p13.3 (p<0.005). The alterations at 2p and 9q were validated and characterized in detail using AI and FISH analysis in a larger study population. Furthermore, in vitro studies were performed to examine the early gene expression changes induced by asbestos in three different lung cell lines. The results revealed specific asbestos-associated gene expression profiles and biological processes as well as chromosomal regions enriched with genes believed to contribute to the common asbestos-related responses in the cell lines. Interestingly, the most significant region enriched with asbestos-response genes was identified at 2p22, close to the previously identified region showing asbestos-related CNA in lung tumours. Additionally, in this thesis, the dysregulated biological processes (Gene Ontology terms) detected in the cell line experiment were compared to dysregulated processes identified in patient samples in a later study (Ruosaari et al., 2008a). Commonly affected processes such as those related to protein ubiquitination, ion transport and surprisingly sensory perception of smell were identified. Conclusions: The identification of specific CNA and dysregulated biological processes shed some light on the underlying genes acting as mediators in asbestos-related lung carcinogenesis. It is postulated that the combination of several asbestos-specific molecular alterations could be used to develop a diagnostic method for the identification of asbestos-related lung cancer.

Transfunctional living walls-designing living walls for environmental and social benefits

Greater attention is being directed towards incorporating greenery into the built environment as increasing global urbanisation drives the search for sustainable urbanism. This research takes a parametric approach to studying living wall dynamics using three methods to cover a diversity of design parameters and performance criteria. The findings led to a functional typology for living walls based on a range of design, context and performance parameters wider than previously identified. Such parametric studies offer valuable insights into 'transfunctional' living walls for homes, schools and public spaces.

Carabid beetles (Coleoptera, Carabidae) as indicators of environmental change in Ranomafana National Park, Madagascar

Growing human populations and increasing exploitation of natural resources threaten nature all over the world. Tropical countries are especially vulnerable to human impact because of the high number of species, most of these endemic and still unknown. Madagascar is one of the centers of high biodiversity and renowned for its unique species. However, during the last centuries many endemic species have gone extinct and more are endangered. Because of high natural values, Madagascar is one of the global conservation priorities. The establishment of Ranomafana National Park (RNP) was intended to preserve the unique nature of Madagascar. Containing several endemic and threatened species, Ranomafana has been selected as one of UNESCO’s World Natural Heritage sites. However, due to strong human pressures the region immediately surroundings the protected area has severely degraded. Aims of this thesis were to inventory carabid fauna in RNP and evaluate their use as indicators of the environmental change. Carabid beetles were collected from protected area (secondary and primary forests) and from its degraded surrounding area. Collecting was mostly conducted by hand during years 2000-2005. Species compositions between the protected area and its surroundings were compared, and species habitat preferences and seasonal variations were studied. In total, 4498 individuals representing 127 carabid species (of which 38 are new species) were collected. Species compositions within and outside of the protected area were markedly different. Most of the species preferred forest as their primary habitat and were mainly collected from trees and bushes. Their value as indicators is based on their different habitat requirements and sensitivity to environmental variables. Some of the species were found only in the protected forest, some occupied also the degraded forests and some preferred open areas. Carabid fauna is very species rich in Ranomafana and there are still many species to be found. Most of the species are arboreal and probably cannot survive in the deforested areas outside the park. This is very likely also the case for other species. Establishment and continued protection of RNP is probably the only way to conserve this globally important area. However, new occupations and land use methods are urgently needed by the local people for improving their own lives while maintaining the forest intact.

Novel Molecular Mechanisms of Arabidopsis Disease Resistance

Plants are capable of recognizing phytopathogens through the perception of pathogen-derived molecules or plant cell-wall degradation products due to the activities of pathogen-secreted enzymes. Such elicitor recognition events trigger an array of inducible defense responses involving signal transduction networks and massive transcriptional re-programming. The outcome of a pathogen infection relies on the balance between different signaling pathways, which are integrated by regulatory proteins. This thesis characterized two key regulatory components: a damage control enzyme, chlorophyllase 1 (AtCHL1), and a transcription factor, WRKY70. Their roles in defense signaling were then investigated. The Erwinia-derived elicitors rapidly activated the expression of AtCLH1 and WRKY70 through different signaling pathways. The expression of the AtCHL1 gene was up-regulated by jasmonic acid (JA) but down-regulated by salicylic acid (SA), whereas WRKY70 was activated by SA and repressed by JA. In order to elucidate the functions of AtCLH1 and WRKY70 in plant defense, stable transgenic lines were produced where these genes were overexpressed or silenced. Additionally, independent knockout lines were also characterized. Bacterial and fungal pathogens were then used to assess the contribution of these genes to the Arabidopsis disease resistance. The transcriptional modulation of AtCLH1 by either the constitutive over-expression or RNAi silencing caused alterations in the chlorophyll-to-chlorophyllide ratio, supporting the claim that chlorophyllase 1 has a role in the chlorophyll degradation pathway. Silencing of this gene led to light-dependent over-accumulation of the reactive oxygen species (ROS) in response to infection by Erwinia carotovora subsp. carotovora SCC1. This was followed by an enhanced induction of SA-dependent defense genes and an increased resistance to this pathogen. Interestingly, little effect on the pathogen-induced SA accumulation at the early infection was observed, suggesting that action of ROS might potentiate SA signaling. In contrast, the pathogen-induced JA production was significantly reduced in the RNAi silenced plants. Moreover, JA signaling and resistance to Alternaria brassicicola were impaired. These observations provide support for the argument that the ROS generated in chloroplasts might have a negative impact on JA signaling. The over-expression of WRKY70 resulted in an enhanced resistance to E. carotovora subsp. carotovora SCC1, Pseudomonas syringae pv. tomato DC3000 and Erysiphe cichoracearum UCSC1, whilst an antisense suppression or an insertional inactivation of WRKY70 led to a compromised resistance to E. carotovora subsp. carotovora SCC1 and to E. cichoracearum UCSC1 but not to P. syringae pv. tomato DC3000. Gene expression analysis revealed that WRKY70 activated many known defense-related genes associated with the SAR response but suppressed a subset of the JA-responsive genes. In particular, I was able to show that both the basal and the induced expression of AtCLH1 was enhanced by the antisense silencing or the insertional inactivation of WRKY70, whereas a reduction in AtCLH1 expression was observed in the WRKY70 over-expressors following an MeJA application or an A. brassicicola infection. Moreover, the SA-induced suppression of AtCLH1 was relieved in wrky70 mutants. These results indicate that WRKY70 down-regulates AtCLH1. An epistasis analysis suggested that WRKY70 functions downstream of the NPR1 in an SA-dependent signaling pathway. When challenged with A. brassicicola, WRKY70 over-expressing plants exhibited a compromised disease resistance while wrky70 mutants had the opposite effect. These results confirmed the WRKY70-mediated inhibitory effects on JA signaling. Furthermore, the WRKY70-controlled suppression of A. brassicicola resistance was mainly through an NPR1-dependent mechanism. Taking all the data together, I suggest that the pathogen-responsive transcription factor WRKY70 is a common component in both SA- and JA-dependent pathways and plays a crucial role in the SA-mediated suppression of JA signaling.

Maternal perception of weight status in first-born Australian toddlers aged 12–16 months – the NOURISH and SAIDI cohorts

Background The preference amongst parents for heavier infants is in contrast to obesity prevention efforts worldwide. Parents are poor at identifying overweight in older children, but few studies have investigated maternal perception of weight status amongst toddlers and none in the Australian setting. Methods Mothers (n = 290) completed a self-administered questionnaire at child age 12–16 months, defining their child's weight status as underweight, normal weight, somewhat overweight or very overweight. Weight-for-length z-score was derived from measured weight and length, and children categorized as underweight, normal weight, at risk overweight or obese (WHO standards). Objective classification was compared with maternal perception of weight status. Mean weight-for-length z-score was compared across categories of maternal perception using one-way ANOVA. Multinomial logistic regression was used to determine child or maternal characteristics associated with inaccurate weight perception. Results Most children (83%) were perceived as normal weight. Twenty nine were described as underweight, although none were. Sixty-six children were at risk of overweight, but 57 of these perceived as normal weight. Of the 14 children who were overweight, only 4 were identified as somewhat overweight by their mother. Compared with mothers who could accurately classify their normal weight child, mothers who were older had higher odds of perceiving their normal weight child as underweight, while mothers with higher body mass index had slightly higher odds of describing their overweight/at risk child as normal weight. Conclusion The leaner but healthy weight toddler was perceived as underweight, while only the heaviest children were recognized as overweight. Mothers unable to accurately identify children at risk are unlikely to act to prevent further excess weight gain. Practitioners can lead a shift in attitudes towards weight in infants and young children, promoting routine growth monitoring and adequate but not rapid weight gain.

LbL Fabricated Poly(Styrene Sulfonate)/TiO2 Multilayer Thin Films for Environmental Applications

Fabrication of multilayer ultrathin composite films composed of nanosized titanium dioxide particles (P25, Degussa) and polyelectrolytes (PELs), such as poly(allyl amine hydrochloride) (PAH) and poly(styrene sulfonate sodium salt) (PSS), on glass substrates using the layer-by-layer (LbL) assembly technique and its potentia application for the photodegradation of rhodamine B under ultraviolet (UV) irradiation has been reported. The polyelectrolytes and TiO2 were deposited on glass substrates at pH 2.5 and the growth of the multilayers was studied using UV/vis speccrophotometer. Thicknes measurements of the films showed a linear increase in film thickness with increase in number of bilayers. The surface microstructure of the thin films was characterized by field emission scanning electron microscope. The ability of the catalysts immobilized by this technique was compared with TiO2 films prepared by drop casting and spin coating methods. Comparison has been made in terms of film stability and photodegradation of rhodamine B. Process variables such as the effect of surface area of the multilayers, umber of bilayers, and initial dye concentration on photodegradation of rhodamine B were studied. Degradation efficiency increased with increase in number of catalysts (total surface area) and bilayers. Kinetics analysis indicated that the photodegradation rates follow first order kinetics. Under maximum loading of TiO2, with five catalyst slides having 20 bilayers of polyelectrolyte/TiO2 on each, 100 mL of 10 mg/L dye solution could be degraded completely in 4 h. The same slides could be reused with the same efficiency for several cycles. This study demonstrates that nanoparticles can be used in wastewater treatment using a simple immobilization technique. This makes the process an attractive option for scale up.

Content-based birdcall retrieval from environmental audio

This research investigates techniques to analyse long duration acoustic recordings to help ecologists monitor birdcall activities. It designs a generalized algorithm to identify a broad range of bird species. It allows ecologists to search for arbitrary birdcalls of interest, rather than restricting them to just a very limited number of species on which the recogniser is trained. The algorithm can help ecologists find sounds of interest more efficiently by filtering out large volumes of unwanted sounds and only focusing on birdcalls.

Social and environmental reporting practices of organisations operating in, or sourcing products from, a developing country : evidence from Bangladesh

This research consists of a broad study in three parts of the social and environmental reporting practices of organisations operating in or sourcing products from a developing country, in this case Bangladesh. The first part of this study explores the social and environmental disclosure practices of the Bangladesh Garment Manufacturers and Exporters Association (BGMEA), the body responsible for organising the activities of 4,200 entities involved in the export of garments from Bangladesh. By way of interview, this part documents the opinions of numerous senior executives from the BGMEA with regard to any changes in the degree of social and environmental pressures since 1985. Utilising a complementary theoretical perspective that includes legitimacy theory, stakeholder theory and institutional theory this part then performs an analysis of the BGMEA's annual reports (1987-2005), t o explore the link between the perceived pressures and changes entailed therein and the social and environmental disclosure practices of the BGMEA across the period of analysis. The results show that the disclosure practices of BGMEA appear to be directly driven by the changing expectations of multinational buying companies- the group deemed to be the most powerful stakeholder group. This section is the first known study to interview managers from a large organisation in a developing country about shifting stakeholder expectations and then to link these changing expectations to annual report disclosures across an extended period of analysis. The findings then directly lead to the second major part of this thesis which investigates the social and environmental disclosure practices of two major multinational buying companies: Nike and H&M. Adopting a joint consideration of legitimacy theory and media agenda setting theory, this second part investigates the linkage between negative media attention and positive corporate social and environmental disclosures over a 19 year period. The results support the view that for those industry-related social and environmental issues that attract the greatest amount of negative media attention, these companies react by providing positive social and environmental disclosures. The results were particularly significant in relation to labour practices in developing countries-the issue that attracts the greatest amount of negative media attention for the companies in question. While the second part demonstrates that the media influences particular disclosure practices, the third part of the thesis shows what drives the media. Based on the speculation provided in the second part, the third part tests the proposition that the media is an important ally of NGOs in their quest to influence change in corporate accountabilities. Through the use of interviews, the results of this part of the study provide evidence to support previously untested perspectives about NGOs' utilisation of the m edia. The results reveal that NGOs use the media because the media is responsible for creating real changes in the operations and disclosure policies of organisations sourcing products from Bangladesh. The various pressures impacting the activities of organisations operating in or sourcing products from developing countries constitutes a fascinating area of investigation, and it is hoped that this study will motivate further research in this area.

Protocol for assessing maternal, environmental and epigenetic risk factors for dental caries in children

Background Expenditure on dental and oral health services in Australia is $3.4 billion AUD annually. This is the sixth highest health cost and accounts for 7 % of total national health expenditure. Approximately 49 % of Australian children aged 6 years have caries experience in their deciduous teeth and this is rising. The aetiology of dental caries involves a complex interplay of individual, behavioural, social, economic, political and environmental conditions, and there is increasing interest in genetic predisposition and epigenetic modification. Methods The Oral Health Sub-study; a cross sectional study of a birth cohort began in November 2012 by examining mothers and their children who were six years old by the time of initiation of the study, which is ongoing. Data from detailed questionnaires of families from birth onwards and data on mothers’ knowledge, attitudes and practices towards oral health collected at the time of clinical examination are used. Subjects’ height, weight and mid-waist circumference are taken and Body Mass Index (BMI) computed, using an electronic Bio-Impedance balance. Dental caries experience is scored using the International Caries Detection and Assessment System (ICDAS). Saliva is collected for physiological measures. Salivary Deoxyribose Nucleic Acid (DNA) is extracted for genetic studies including epigenetics using the SeqCap Epi Enrichment Kit. Targets of interest are being confirmed by pyrosequencing to identify potential epigenetic markers of caries risk. Discussion This study will examine a wide range of potential determinants for childhood dental caries and evaluate inter-relationships amongst them. The findings will provide an evidence base to plan and implement improved preventive strategies.

Biological and environmental determinants

This chapter describes biological and environmental determinants of the health of Australians, providing a background to the development of successful public health activity. You will recall from the introduction to Section 2 that health determinants are the biomedical, genetic, behavioural, socioeconomic and environmental factors that impact on health and wellbeing. These determinants can be influenced by interventions and by resources and systems (Australian Institute of Health and Welfare (AIHW) AIHW 2012a). Many factors combine to affect the health of individuals and communities. People’s circumstances and the environment determine whether a population is healthy or not. Factors such as where people live, the state of their environment, genetics, their education level and income, and their relationships with friends and family are all likely to impact on their health. The determinants of population health reflect the context of people’s lives; however, people have limited control over many of these determinants (WHO 2007).

Microbiological, environmental and proteolytic aspects in chronic rhinosinusitis with nasal polyposis

Chronic rhinosinusitis is one of the most common chronic respiratory tract diseases affecting up to 15% of the adult population in the Western world. It may be perpetuated by factors predisposing to sinus ostial obstruction together with inflammatory changes in the sinus mucosa. Chronic rhinosinusitis is associated with asthma, and it may represent the same disease process. Chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma share also the characteristic inflammatory features and histopathologic feature of airway remodelling. Remodelling is considered as a key event in the pathogenesis of asthma. It is controlled by a delicate balance between the matrix metalloproteinases (MMPs) and their regulators. The purpose of the present study was to evaluate the microbiological findings, inflammatory features and MMP and tissue inhibitor of metalloproteinases-1 (TIMP-1) expression in CRSwNP. The results were related to the patient history, exposure to moisture and clinical outcome in order to find out possible explanations for the etiology and chronicity of CRSwNP. Bacterial culture results were similar in patients and in controls and do not explain the chronic course of CRSwNP. The presence of fungi seems to be more common in CRSwNP than chronic rhinosinusitis in general, and they should be actively searched for using microbiological as well as histological methods. Typical outdoor fungal species were found in nasal lavage samples taken from controls in the autumn but not in the winter, reflecting environmental exposure. Exposure to moisture was reported by 46% of the CRSwNP patients, which is in accordance to the Finnish general population. Exposed patients did not differ significantly from non-exposed subjects with regards to microbiological findings, tissue eosinophilia and clinical outcome. Significantly elevated levels of collagenase-2 (MMP-8) and interleukin (IL)-8 but not tumour necrosis factor-α were found in CRSwNP patients. In particular, the activation of mesenchymal-type MMP-8 but not polymorphonuclear-type MMP-8 was associated with elevated IL-8 levels. IL-8 and MMP-8 may form an inductive cytokine-proteinase cascade in CRSwNP pathogenesis and provide a target for novel therapies and a diagnostic tool for monitoring CRSwNP treatment. The proteolytic spectrum is different in eosinophilic and non-eosinophilic CRSwNP with the up-regulation of MMP-8 and MMP-9 in non-eosinophilic CRSwNP, suggesting different pathophysiology in these subgroups. The lack of MMP up-regulation was associated with a poor prognostic factor and worse clinical outcome, representing a possible synergic anti-inflammatory function of MMP-8 and MMP-9 in CRSwNP. This study provides new information about possible immunologic mechanisms in the pathogenesis of CRSwNP. The recently discovered anti-inflammatory/ defensive properties of MMP-8 and MMP-9 in animal models are reported for the first time in a clinical setting in human inflammatory diseases.

Student perception of a new integrated anatomy practical program: Does students' prior learning make a difference?

While there is evidence that science and non-science background students display small differences in performance in basic and clinical sciences, early in a 4-year, graduate entry medical program, this lessens with time. With respect to anatomy knowledge, there are no comparable data as to the impact previous anatomy experience has on the student perception of the anatomy practical learning environment. A study survey was designed to evaluate student perception of the anatomy practical program and its impact on student learning, for the initial cohort of a new medical school. The survey comprised 19 statements requiring a response using a 5-point Likert scale, in addition to a free text opportunity to provide opinion of the perceived educational value of the anatomy practical program. The response rate for a total cohort of 82 students was 89%. The anatomy practical program was highly valued by the students in aiding their learning of anatomy, as indicated by the high mean scores for all statements (range: 4.04-4.7). There was a significant difference between the students who had and had not studied a science course prior to entering medicine, with respect to statements that addressed aspects of the course related to its structure, organization, variety of resources, linkage to problem-based learning cases, and fairness of assessment. Nonscience students were more positive compared to those who had studied science before (P levels ranging from 0.004 to 0.035). Students less experienced in anatomy were more challenged in prioritizing core curricular knowledge. © 2011 Wiley-Liss, Inc.

Extending visual perception with haptic exploration for improved scene understanding

Scene understanding has been investigated from a mainly visual information point of view. Recently depth has been provided an extra wealth of information, allowing more geometric knowledge to fuse into scene understanding. Yet to form a holistic view, especially in robotic applications, one can create even more data by interacting with the world. In fact humans, when growing up, seem to heavily investigate the world around them by haptic exploration. We show an application of haptic exploration on a humanoid robot in cooperation with a learning method for object segmentation. The actions performed consecutively improve the segmentation of objects in the scene.