Genotoxicity of inorganic mercury salts based on disturbed microtubule function

This study investigated the hypothesis that the chromosomal genotoxicity of inorganic mercury results from interaction(s) with cytoskeletal proteins. Effects of Hg2+ salts on functional activities of tubulin and kinesin were investigated by determining tubulin assembly and kinesin-driven motility in cell-free systems. Hg2+ inhibits microtubule assembly at concentrations above 1 μM, and inhibition is complete at about 10 μM. In this range, the tubulin assembly is fully (up to 6 μM) or partially (∼6-10 μM) reversible. The inhibition of tubulin assembly by mercury is independent of the anion, chloride or nitrate. The no-observed-effect- concentration for inhibition of microtubule assembly in vitro was 1 μM Hg2+, the IC50 5.8 μM. Mercury(II) salts at the IC 50 concentrations partly inhibiting tubulin assembly did not cause the formation of aberrant microtubule structures. Effects of mercury salts on the functionality of the microtubule motility apparatus were studied with the motor protein kinesin. By using a "gliding assay" mimicking intracellular movement and transport processes in vitro, HgCl2 affected the gliding velocity of paclitaxel-stabilised microtubules in a clear dose-dependent manner. An apparent effect is detected at a concentration of 0.1 μM and a complete inhibition is reached at 1 μM. Cytotoxicity of mercury chloride was studied in V79 cells using neutral red uptake, showing an influence above 17 μM HgCl2. Between 15 and 20 μM HgCl2 there was a steep increase in cell toxicity. Both mercury chloride and mercury nitrate induced micronuclei concentration-dependently, starting at concentrations above 0.01 μM. CREST analyses on micronuclei formation in V79 cells demonstrated both clastogenic (CREST-negative) and aneugenic effects of Hg2+, with some preponderance of aneugenicity. A morphological effect of high Hg2+ concentrations (100 μM HgCl2) on the microtubule cytoskeleton was verified in V79 cells by immuno-fluorescence staining. The overall data are consistent with the concept that the chromosomal genotoxicity could be due to interaction of Hg2+ with the motor protein kinesin mediating cellular transport processes. Interactions of Hg 2+ with the tubulin shown by in vitro investigations could also partly influence intracellular microtubule functions leading, together with the effects on the kinesin, to an impaired chromosome distribution as shown by the micronucleus test.

Using the Driver Behaviour Questionnaire to predict crashes and demerit point loss : does it get better with larger sample sizes?

The Driver Behaviour Questionnaire (DBQ) continues to be the most widely utilised self-report scale globally to assess crash risk and aberrant driving behaviours among motorists. However, the scale also attracts criticism regarding its perceived limited ability to accurately identify those most at risk of crash involvement. This study reports on the utilisation of the DBQ to examine the self-reported driving behaviours (and crash outcomes) of drivers in three separate Australian fleet samples (N = 443, N = 3414, & N = 4792), and whether combining the samples increases the tool’s predictive ability. Either on-line or paper versions of the questionnaire were completed by fleet employees in three organisations. Factor analytic techniques identified either three or four factor solutions (in each of the separate studies) and the combined sample produced expected factors of: (a) errors, (b) highway-code violations and (c) aggressive driving violations. Highway code violations (and mean scores) were comparable across the studies. However, across the three samples, multivariate analyses revealed that exposure to the road was the best predictor of crash involvement at work, rather than DBQ constructs. Furthermore, combining the scores to produce a sample of 8649 drivers did not improve the predictive ability of the tool for identifying crashes (e.g., 0.4% correctly identified) or for demerit point loss (0.3%). The paper outlines the major findings of this comparative sample study in regards to utilising self-report measurement tools to identify “at risk” drivers as well as the application of such data to future research endeavours.

Phosphorylation of caveolin-1 is anti-apoptotic and promotes cell attachment during oxidative stress of kidney cells

Aims: Caveolin-1 (cav1) is reported to have both cell survival and pro-apoptotic characteristics. This may be explained by its localisation or phosphorylation in injured cells. This study investigated the role of cav1 in kidney cells of different nephron origin and developmental state after oxidative stress. Methods: Renal MCDK distal tubular, HK2 proximal tubular epithelial cells and HEK293T renal embryonic cells were treated with 1mM hydrogen peroxide. Apoptosis, loss of cell adhesion, and cell survival were compared with expression of cav1 in its non-phosphorylated and phosphorylated (p-cav1) forms. Cav1 was transfected into the HEK293T cells, or caveolae were disrupted with filipin or nystatin in HK2 cells, to investigate functions of cav1 and p-cav1. Results: Oxidative stress induced more apoptosis in HK2s than MDCKs (p<0.05). HK2s had lower endogenous cav1 and p-cav1 than MDCKs (p<0.05). Both cell lines had increased p-cav1, but not cav1, with oxidative stress. This increase was greatest in MDCKs (p<0.01). Cav1 was located mainly in the plasma membrane of untreated cells and translocated to the cytoplasm with oxidative stress in both cell lines, more so in MDCKs. Disruption of caveolae caused cytoplasmic translocation of cav1 in HK2s, but did not alter high levels of oxidative stress-induced apoptosis. When HEK293Ts lacking endogenous cav1 were transfected with cav1, oxidant-induced apoptosis and loss of cell adhesion was decreased (p<0.01), and p-cav1 was induced by treatment. Conclusion: Cav1 expression and localisation in kidney cells is not anti-apoptotic, but increased expression of p-cav1 may promote cell survival after oxidative stress. © 2008 Royal College of Pathologists of Australasia.

A frontier functions approach to optimal scales of sustainable production

This paper translates the concepts of sustainable production to three dimensions of economic, environmental and ecological sustainability to analyze optimal production scales by solving optimizing problems. Economic optimization seeks input-output combinations to maximize profits. Environmental optimization searches for input-output combinations that minimize the polluting effects of materials balance on the surrounding environment. Ecological optimization looks for input-output combinations that minimize the cumulative destruction of the entire ecosystem. Using an aggregate space, the framework illustrates that these optimal scales are often not identical because markets fail to account for all negative externalities. Profit-maximizing firms normally operate at the scales which are larger than optimal scales from the viewpoints of environmental and ecological sustainability; hence policy interventions are favoured. The framework offers a useful tool for efficiency studies and policy implication analysis. The paper provides an empirical investigation using a data set of rice farms in South Korea.

Functions and therapeutic roles of exosomes in cancer

The role of exosomes in cancer development has become the focus of much research, due to the many emerging roles possessed by exosomes. These micro-vesicles that are ubiquitously released in to the extracellular milieu, have been found to regulate immune system function, particularly in tumorigenesis, as well as conditioning future metastatic sites for the attachment and growth of tumor tissue. Through an interaction with a range of host tissue, exosomes are able to generate a pro-tumor environment that is essential for carcinogenesis. Herein, we discuss the contents of exosomes and their contribution to tumorigenesis, as well as their role in chemotherapeutic resistance and the development of novel cancer treatments and the identification of cancer biomarkers.

Critical linguistics in the early years : exploring functions of language through sophisticated picture books and process drama strategies

In this chapter we describe a critical fairytales unit taught to 4.5 to 5.5 year olds in a context of intensifying pressure to raise literacy achievement. The unit was infused with lessons on reinterpreted fairytales followed by process drama activities built around a sophisticated picture book, Beware of the Bears (MacDonald, 2004). The latter entailed a text analytic approach to critical literacy derived from systemic functional linguistics (Halliday, 1978; Halliday & Matthiessen, 2004). This approach provides a way of analysing how words and discourse are used to represent the world in a particular way and shape reader relations with the author in a particular field (Janks, 2010).

Consumer misbehavior: a concurrent look at the impact that the size of the victim and size of the loss have on opinions regarding the acceptance or unacceptance of 12 questionable consumer actions

This study examines the role that the size of a victimised organisation and the size of the victim’s loss have on attitudes regarding the acceptance or unacceptance of 12 questionable consumer actions. A sample of 815 American adults rated each scenario on a scale anchored by very acceptable and very unacceptable. It was shown that the size of the victimised organisation tends to influence consumers’ opinions with more disdain directed towards consumers who take advantage of smaller businesses. Similarly, the respondents tended to be more critical of these actions when the loss incurred by the victimised organisation was large. A 2x2 matrix concurrently delineated the nature of the extent to which opinions regarding the 12 actions differed depending upon the mediating variable under scrutiny.

CORR Insights® : loss of cement-bone interlock in retrieved tibial components from total knee arthroplasties

Most surgeons cement the tibial component in total knee replacement surgery. Mid-term registry data from a number of countries, including those from the United Kingdom and Australia, support the excellent survivorship of cemented tibial components. In spite of this success, results can always be improved, and cementing technique can play a role. Cementing technique on the tibia is not standardized, and surgeons still differ about the best ways to deliver cement into the cancellous bone of the upper tibia. Questions remain regarding whether to use a gun or a syringe to inject the cement into the cancellous bone of the tibial plateau . The ideal cement penetration into the tibial plateau is debated, though most reports suggest that 4 mm to 10 mm is ideal. Thicker mantles are thought to be dangerous due to the risk of bone necrosis, but there is little in the literature to support this contention...

Improving treatment for obese women with early stage cancer of the uterus : rationale and design of the levonorgestrel intrauterine device ±Metformin ±weight loss in endometrial cancer (feMME) trial

Purpose Endometrial adenocarcinoma (EC) is the most common gynaecologic cancer. Up to 90% of EC patients are obese which poses a health threat to patients post-treatment. Standard treatment for EC includes hysterectomy, although this has significant side effects for obese women at high risk of surgical complications and for women of childbearing age. This trial investigates the effectiveness of non-surgical or conservative treatment options for obese women with early stage EC. The primary aim is to determine the efficacy of: levonorgestrel intrauterine device (LNG-IUD); with or without metformin (an antidiabetic drug); and with or without a weight loss intervention to achieve a pathological complete response (pCR) in EC at six months from study treatment initiation. The secondary aim is to enhance understanding of the molecular processes and to predict a treatment response by investigating EC biomarkers. Methods An open label, three-armed, randomised, phase-II, multi-centre trial of LNG-IUD ± metformin ± weight loss intervention. 165 participants from 28 centres are randomly assigned in a 3:3:5 ratio to the treatment arms. Clinical, quality of life and health behavioural data will be collected at baseline, six weeks, three and six months. EC biomarkers will be assessed at baseline, three and six months. Conclusions There is limited prospective evidence for conservative treatment for EC. Trial results could benefit patients and reduce health system costs through a reduction in hospitalisations and through lower incidence of adverse events currently observed with standard treatment.

Insomnia : A Self Help Handbook

This book is a practical and useful tool for getting your sleep back on track. Even if you have suffered from insomnia for many years, this book contains simple, easy to learn strategies to manage your sleep loss through evidence-based techniques such as cognitive therapy and stimulus control. Dr. Sacre will guide you through these approaches and explain how they work and why they are recommended above other approaches. There is a chapter on special populations that tells you what to do if you are a shift worker, long distance traveller, parent, older adult, woman (including pregnancy and menopause) or an elite athlete. If you want to enjoy natural, healthy and satisfying sleep again, this handbook gives you all the tools you need to achieve it. You only need to have the motivation and discipline to apply the strategies and stick to them over time. This handbook first explains what normal sleep is all about and challenges some myths about sleep and insomnia. Then you will be guided through a thorough sleep assessment. Insomnia is then described in detail including different types of insomnia and the kinds of factors that contribute to sleep loss. Through the following chapters, you will be shown step-by-step what to do to bring about change in your sleeping patterns and habits, through addressing the factors that perpetuate poor sleep. These factors mainly revolve around unhelpful thinking, compensatory behaviors, poor sleep hygiene and environmental influences. These are all things that are within your control and Dr. Sacre will show you how. Dr. Sacre has worked in the fields of sleep health, mental health and addictive disorders for 25 years and over that time, she has encountered hundreds of people who have struggled with insomnia and sleep loss due to other causes. She currently heads the Therapy Programs department at Belmont Private Hospital in Brisbane, Australia, where there is an emphasis on Cognitive Behavioral Therapy, including a Cognitive Behavioral Therapy for Insomnia (CBT-i) program. A psychologist and nurse, Dr. Sacre is a long-time member of the Australasian Sleep Association and the Australian Psychological Society. She has conducted research into the function of dreaming, online sleep surveys and the usefulness of sleep self-help guides for students, older adults and carers of people with dementia. She has also published on diverse topics, including the management of nightmares in war veterans. She is an Adjunct Associate Professor at Queensland University of Technology, Brisbane and lectures professionals, including psychologists, school counselors and psychiatrists, on sleep disorders and their management as well as Cognitive Behavioral Therapy.

Examining the predictive value of combining the theory of planned behaviour and the volunteer functions inventory

The functions of the volunteer functions inventory were combined with the constructs of the theory of planned behaviour (i.e., attitudes, subjective norms, and perceived behavioural control) to establish whether a stronger, single explanatory model prevailed. Undertaken in the context of episodic, skilled volunteering by individuals who were retired or approaching retirement (N = 186), the research advances on prior studies which either examined the predictive capacity of each model independently or compared their explanatory value. Using hierarchical regression analysis, the functions of the volunteer functions inventory (when controlling for demographic variables) explained an additional 7.0% of variability in individuals’ willingness to volunteer over and above that accounted for by the theory of planned behaviour. Significant predictors in the final model included attitudes, subjective norms and perceived behavioural control from the theory of planned behaviour and the understanding function from the volunteer functions inventory. It is proposed that the items comprising the understanding function may represent a deeper psychological construct (e.g., self-actualisation) not accounted for by the theory of planned behaviour. The findings highlight the potential benefit of combining these two prominent models in terms of improving understanding of volunteerism and providing a single parsimonious model for raising rates of this important behaviour.