BRCA1 deficiency exacerbates estrogen-induced DNA damage and genomic instability

Germline mutations in BRCA1 predispose carriers to a high incidence of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through critical roles in DNA repair, cell cycle arrest and transcriptional control. A major question has been why BRCA1 loss or mutation leads to tumors mainly in estrogen-regulated tissues, given that BRCA1 has essential functions in all cell types. Here we report that estrogen and estrogen metabolites can cause DNA double strand breaks (DSB) in estrogen receptor-α negative breast cells and that BRCA1 is required to repair these DSBs to prevent metabolite-induced genomic instability. We found that BRCA1 also regulates estrogen metabolism and metabolite-mediated DNA damage by repressing the transcription of estrogen-metabolising enzymes, such as CYP1A1, in breast cells. Lastly, we used a knock-in human cell model with a heterozygous BRCA1 pathogenic mutation to show how BRCA1 haploinsufficiency affects these processes. Our findings provide pivotal new insights into why BRCA1 mutation drives the formation of tumours in estrogen-regulated tissues, despite the general role of BRCA1 in DNA repair in all cell types.

Turbulence and Mixing in the Environment: Multi-Device Study in a Sub-tropical Estuary

In an estuary, mixing and dispersion result from a combination of large-scale advection and smallscale turbulence, which are complex to estimate. The predictions of scalar transport and mixing are often inferred and rarely accurate, due to inadequate understanding of the contributions of these difference scales to estuarine recirculation. A multi-device field study was conducted in a small sub-tropical estuary under neap tide conditions with near-zero fresh water discharge for about 48 hours. During the study, acoustic Doppler velocimeters (ADV) were sampled at high frequency (50 Hz), while an acoustic Doppler current profiler (ADCP) and global positioning system (GPS) tracked drifters were used to obtain some lower frequency spatial distribution of the flow parameters within the estuary. The velocity measurements were complemented with some continuous measurement of water depth, conductivity, temperature and some other physiochemical parameters. Thorough quality control was carried out by implementation of relevant error removal filters on the individual data set to intercept spurious data. A triple decomposition (TD) technique was introduced to access the contributions of tides, resonance and ‘true’ turbulence in the flow field. The time series of mean flow measurements for both the ADCP and drifter were consistent with those of the mean ADV data when sampled within a similar spatial domain. The tidal scale fluctuation of velocity and water level were used to examine the response of the estuary to tidal inertial current. The channel exhibited a mixed type wave with a typical phase-lag between 0.035π– 0.116π. A striking feature of the ADV velocity data was the slow fluctuations, which exhibited large amplitudes of up to 50% of the tidal amplitude, particularly in slack waters. Such slow fluctuations were simultaneously observed in a number of physiochemical properties of the channel. The ensuing turbulence field showed some degree of anisotropy. For all ADV units, the horizontal turbulence ratio ranged between 0.4 and 0.9, and decreased towards the bed, while the vertical turbulence ratio was on average unity at z = 0.32 m and approximately 0.5 for the upper ADV (z = 0.55 m). The result of the statistical analysis suggested that the ebb phase turbulence field was dominated by eddies that evolved from ejection type process, while that of the flood phase contained mixed eddies with significant amount related to sweep type process. Over 65% of the skewness values fell within the range expected of a finite Gaussian distribution and the bulk of the excess kurtosis values (over 70%) fell within the range of -0.5 and +2. The TD technique described herein allowed the characterisation of a broader temporal scale of fluctuations of the high frequency data sampled within the durations of a few tidal cycles. The study provides characterisation of the ranges of fluctuation required for an accurate modelling of shallow water dispersion and mixing in a sub-tropical estuary.

Making things happen: How the environment triggers action

Innovative research conducted by Dr Jan Golembiewski from Medical Architectures Australasia-Pacific, in the area of environmental design for mental healthcare helps us reflect, through experiential storytelling, on the importance of paying attention to positive environmental ‘triggers for action’ when designing physical spaces to help manage particular patients’ conditions. This article is written about the mental health experience specifically, however environmental design is an issue we can all relate to in our everyday lives (at home, at work, social spots or in places such as hospitals or retreats) when we instinctively notice a connection between our mental health and our surroundings or a healthy sense of place.

Biomarkers of exercise-induced myocardial stress in relation to inflammatory and oxidative stress

Increased concentrations of biomarkers reflecting myocardial stress such as cardiac troponin I and T and brain natriuretic peptide (BNP) have been observed following strenuous, long-lasting endurance exercise. The pathophysiological mechanisms are still not fully elucidated and the interpretations of increased post-exercise concentrations range from (i) evidence for exercise-induced myocardial damage to (ii) non-relevant spurious troponin elevations, presumably caused by assay imprecision or heterophilic antibodies. Several lines of evidence suggest that inflammatory processes or oxidative stress could be involved in the rise of NT-proBNP and Troponin observed in critically ill patients with sepsis or burn injury. We tested the hypothesis that inflammatory or oxidative stress is also responsible for exercise-induced cardiomyocyte strain in a large cohort of triathletes following an Ironman triathlon. However, the post-race increase in cardiac troponin T and NT-proBNP was not associated with several markers of exercise-induced inflammation, oxidative stress or antioxidant vitamins. Therefore, we clearly need more studies with other inflammatory markers and different designs to elucidate the scientific background for increases in myocardial stress markers following strenuous endurance events.

Exercise-induced DNA damage: Is there a relationship with inflammatory responses?

Both a systemic inflammatory response as well as DNA damage has been observed following exhaustive endurance exercise. Hypothetically, exercise-induced DNA damage might either be a consequence of inflammatory processes or causally involved in inflammation and immunological alterations after strenuous prolonged exercise (e.g. by inducing lymphocyte apoptosis and lymphocytopenia). Nevertheless, up to now only few studies have addressed this issue and there is hardly any evidence regarding a direct relationship between DNA or chromosomal damage and inflammatory responses in the context of exercise. The most conclusive picture that emerges from available data is that reactive oxygen and nitrogen species (RONS) appear to be the key effectors which link inflammation with DNA damage. Considering the time-courses of inflammatory and oxidative stress responses on the one hand and DNA effects on the other the lack of correlations between these responses might also be explained by too short observation periods. This review summarizes and discusses the recent findings on this topic. Furthermore, data from our own study are presented that aimed to verify potential associations between several endpoints of genome stability and inflammatory, immune-endocrine and muscle damage parameters in competitors of an Ironman triathlon until 19 days into recovery. The current results indicate that DNA effects in lymphocytes are not responsible for exercise-induced inflammatory responses. Furthermore, this investigation shows that inflammatory processes, vice versa, do not promote DNA damage, neither directly nor via an increased formation of RONS derived from inflammatory cells. Oxidative DNA damage might have been counteracted by training- and exercise-induced antioxidant responses. However, further studies are needed that combine advanced -omics based techniques (transcriptomics, proteomics) with state-of-the-art biochemical biomarkers to gain more insights into the underlying mechanisms.

Recognising paediatric deterioration in a simulated environment

This thesis examined the impact of high fidelity patient simulation on paediatric critical care nurses' self-efficacy and knowledge for recognising and responding to paediatric deterioration. This research highlights the positive effect simulation education can have on nursing learning outcomes which may influence patient safety through the timely recognition and management of the deteriorating child.

Eating for health and the environment: Australian regulatory responses for dietary change

The Australian food system significantly contributes to a range of key environmental issues including harmful greenhouse gas emissions, air pollution, soil desertification, biodiversity loss and water scarcity. At the same time, the Australian s food system is a key cause of public health nutrition issues that stem from the co-existence of over- and under-consumption of dietary energy and nutrients. Within these challenges lie synergies and opportunities because a diet that has a lower environmental impact generally aligns with good nutrition. Australian State and Federal initiatives to influence food consumption patterns focus on individual body weight and ‘soft law’ interventions. These regulatory approaches, by focusing on select symptoms of food system failures, are fragmented, reductionist and inefficient. In order to illustrate this point, this paper will explore Australian regulatory responses to diet-related illnesses. The analysis will support the argument that only when regulatory responses to diets become embedded within reform of the current food system will substantial improvements to human and planetary health be achieved.

Understanding pressures on the future of roads: A sustainable built environment National Research Centre Discussion Paper

According to the Australian Government, when combined with expected population growth and internal migration, expected changes in temperature and rainfall are expected to increase road maintenance costs by over 30 percent by 2100. This presents a significant future economic risk, in response, this paper will discuss the potential for roads to improve their resilience to the impacts of climate change and other key pressures. The paper will also highlight how such measures can inform state and national main road infrastructure planning and reduce future associated risks and costs.

Good for the environment good for health

“First do no harm”. This phrase, attributed to the 19th century surgeon, Thomas Inman, 1 reflects an equivalent phrase found in Epidemics, Book I of the Hippocratic School, “Practise two things in your dealings with disease: either help or do not harm the patient”. Pharmacists have played, and continue to play, an important role in reducing patient harm from medication misadventures. Now, they have a new role to play. The delivery of pharmaceutical care contributes to climate change (e.g. through the embedded carbon in the manufacture and distribution of medicines, disposal of waste, and energy and water use),2 which in turn has a negative impact on health. 3,4 This paradox argues a moral and ethical obligation by pharmacists, to deliver pharmaceutical care more sustainably – do no harm. Sustainability “…. is concerned, on one hand, with resources and how we can preserve them, and, on the other hand, with waste products and how we can best reduce or dispose of them.” 5(p.37) It is about preserving and nurturing Earth’s resources and systems for this generation and future generations to enjoy. Pharmacists play an important role in preventative health strategies such as smoking cessation, promotion of healthier lifestyles and vaccination/immunisation programmes and have the potential to also play a significant role in delivering pharmaceutical care more sustainably. Sustainable pharmaceutical care may be considered a virtuous cycle - what is good for the environment is also good for our health. 5 The good news for community pharmacy owners and managers is that implementing sustainability initiatives in the pharmacy can also have significant financial co-benefits.

Intellectual property, innovation, and the environment (2014) edited by Peter Menell and Sarah Tran: A review

Peter S. Menell and Sarah M. Tran (ed.), Intellectual Property, Innovation and the Environment, Cheltenham (UK) and Northampton (MA): Edward Elgar, 2014, 756 pp Hardback 978 1 78195 160 6, http://www.e-elgar.com/bookentry_main.lasso?id=15063 There has been a longstanding deadlock over intellectual property and clean technologies in international climate talks. The United States — and other developed countries such as Japan, Denmark Germany, the United Kingdom, Australia, and New Zealand — have pushed for stronger and longer protection of intellectual property rights related to clean technologies. BASIC countries — such as Brazil, South Africa, India, and China — have pushed for greater flexibilities in respect of intellectual property for the purpose of addressing climate change and global warming. Small island states, least developed countries, and nations vulnerable to climate change have called for climate-adaptation and climate-mitigation technologies to be available in the public domain. In the lead-up to the United Nations Climate Summit in New York on the 23rd September 2014, it is timely to consider the debate over intellectual property, innovation, the environment, and climate change.

Submission on the Hawke Interim Review of the Environment Protection and Biodiversity Conservation Act 1999 (Cth)

There are currently no regulatory mechanisms, laws or policies that specifically provide rights to Indigenous peoples over their Indigenous knowledge and intellectual property. We strongly recommend that the commonwealth take the lead to ensure that national sui generis laws are developed (perhaps to operate initially in areas of Cth jurisdiction, such as IPAs and national parks). The development of such laws should be in tandem with practical guidelines to assist their implementation. A comprehensive, nationally consistent scheme for access to genetic resources, which offers meaningful protection of traditional knowledge and substantive benefit-sharing with Indigenous communities, has to be developed. There are already a range of reports/resources that urge these same reforms and that we direct the Enquiry to again; these include the Voumard Report (2000) – especially Fourmile’s Appendix 10 – “Indigenous Interests”, and Terri Jankes “Our Culture, Our Future (1998).

A comparison land-water environment of maximal voluntary isometric contraction during manual muscle testing through surface electromyography

Background The aim of this study was to compare through surface electromyographic (sEMG) recordings of the maximum voluntary contraction (MVC) on dry land and in water by manual muscle test (MMT). Method Sixteen healthy right-handed subjects (8 males and 8 females) participated in measurement of muscle activation of the right shoulder. The selected muscles were the cervical erector spinae, trapezius, pectoralis, anterior deltoid, middle deltoid, infraspinatus and latissimus dorsi. The MVC test conditions were random with respect to the order on the land/in water. Results For each muscle, the MVC test was performed and measured through sEMG to determine differences in muscle activation in both conditions. For all muscles except the latissimus dorsi, no significant differences were observed between land and water MVC scores (p = 0.063–0.679) and precision (%Diff = 7–10%) were observed between MVC conditions in the muscles trapezius, anterior deltoid and middle deltoid. Conclusions If the procedure for data collection is optimal, under MMT conditions it appears that comparable MVC sEMG values were achieved on land and in water and the integrity of the EMG recordings were maintained during wáter immersion.

Understanding the performance of green commercial buildings: a Sustainable Built Environment National Research Centre (SBEnrc) briefing report

Efforts to reduce carbon emissions in the buildings sector have been focused on encouraging green design, construction and building operation; however, the business case is not very compelling if considering the energy cost savings alone. In recent years green building has been driven by a sense that it will improve the productivity of occupants,something with much greater economic returns than energy savings. Reducing energy demand in green commercial buildings in a way that encourages greater productivity is not yet well understood as it involves a set of complex and interdependent factors. This project investigates these factors and focuses on the performance of and interaction between: green design elements, internal environmental quality, occupant experience, tenant/leasing agreements, and building regulation and management. This paper suggests six areas of strategic research that are needed to understand how conditions can be created to support productivity in green buildings, and deliver significant energy consumption reductions.

Considering the application of biophilic urbanism: A Sustainable Built Environment National Research Centre discussion paper

Biophilic urbanism, or urban design which refl ects human’s innate need for nature in and around and on top of our buildings, stands to make signifi cant contributions to a range of national, state and local government policies related to climate change mitigation and adaptation. Potential benefi ts include reducing the heat island effect, reducing energy consumption for thermal control, enhancing urban biodiversity, improving well being and productivity, improving water cycle management, and assisting in the response to growing needs for densifi cation and revitalisation of cities. This discussion paper will give an overview of the concept of biophilia and consider enablers and disablers to its application to urban planning and design. The paper will present findings from stakeholder engagement related to a consideration of the economics of the use of biophilic elements (direct and indirect). The paper outlines eight strategic areas being considered in the project, including how a ‘daily minimum dose’ of nature can be received through biophilic elements, and how planning and policy can underpin effective biophilic urbanism.

Implementing process views in the web service environment

Web service and business process technologies are widely adopted to facilitate business automation and collaboration. Given the complexity of business processes, it is a sought-after feature to show a business process with different views to cater for the diverse interests, authority levels, etc., of different users. Aiming to implement such flexible process views in the Web service environment, this paper presents a novel framework named FlexView to support view abstraction and concretisation of WS-BPEL processes. In the FlexView framework, a rigorous view model is proposed to specify the dependency and correlation between structural components of process views with emphasis on the characteristics of WS-BPEL, and a set of rules are defined to guarantee the structural consistency between process views during transformations. A set of algorithms are developed to shift the abstraction and concretisation operations to the operational level. A prototype is also implemented for the proof-of-concept purpose. © 2010 Springer Science+Business Media, LLC.