Intrinsically photosensitive melanopsin retinal ganglion cell contributions to the post-illumination pupil response and circadian rhythm

Intrinsically photosensitive retinal ganglion cells (ipRGCs) in the eye transmit the environmental light level, projecting to the suprachiasmatic nucleus (SCN) (Berson, Dunn & Takao, 2002; Hattar, Liao, Takao, Berson & Yau, 2002), the location of the circadian biological clock, and the olivary pretectal nucleus (OPN) of the pretectum, the start of the pupil reflex pathway (Hattar, Liao, Takao, Berson & Yau, 2002; Dacey, Liao, Peterson, Robinson, Smith, Pokorny, Yau & Gamlin, 2005). The SCN synchronizes the circadian rhythm, a cycle of biological processes coordinated to the solar day, and drives the sleep/wake cycle by controlling the release of melatonin from the pineal gland (Claustrat, Brun & Chazot, 2005). Encoded photic input from ipRGCs to the OPN also contributes to the pupil light reflex (PLR), the constriction and recovery of the pupil in response to light. IpRGCs control the post-illumination component of the PLR, the partial pupil constriction maintained for > 30 sec after a stimulus offset (Gamlin, McDougal, Pokorny, Smith, Yau & Dacey, 2007; Kankipati, Girkin & Gamlin, 2010; Markwell, Feigl & Zele, 2010). It is unknown if intrinsic ipRGC and cone-mediated inputs to ipRGCs show circadian variation in their photon-counting activity under constant illumination. If ipRGCs demonstrate circadian variation of the pupil response under constant illumination in vivo, when in vitro ipRGC activity does not (Weng, Wong & Berson, 2009), this would support central control of the ipRGC circadian activity. A preliminary experiment was conducted to determine the spectral sensitivity of the ipRGC post-illumination pupil response under the experimental conditions, confirming the successful isolation of the ipRGC response (Gamlin, et al., 2007) for the circadian experiment. In this main experiment, we demonstrate that ipRGC photon-counting activity has a circadian rhythm under constant experimental conditions, while direct rod and cone contributions to the PLR do not. Intrinsic ipRGC contributions to the post-illumination pupil response decreased 2:46 h prior to melatonin onset for our group model, with the peak ipRGC attenuation occurring 1:25 h after melatonin onset. Our results suggest a centrally controlled evening decrease in ipRGC activity, independent of environmental light, which is temporally synchronized (demonstrates a temporal phase-advanced relationship) to the SCN mediated release of melatonin. In the future the ipRGC post-illumination pupil response could be developed as a fast, non-invasive measure of circadian rhythm. This study establishes a basis for future investigation of cortical feedback mechanisms that modulate ipRGC activity.

Common variation in the fibroblast growth factor receptor 2 gene is not associated with endometriosis risk

BACKGROUND Endometriosis is a polygenic disease with a complex and multifactorial aetiology that affects 8-10% of women of reproductive age. Epidemiological data support a link between endometriosis and cancers of the reproductive tract. Fibroblast growth factor receptor 2 (FGFR2) has recently been implicated in both endometrial and breast cancer. Our previous studies on endometriosis identified significant linkage to a novel susceptibility locus on chromosome 10q26 and the FGFR2 gene maps within this linkage region. We therefore hypothesized that variation in FGFR2 may contribute to the risk of endometriosis. METHODS We genotyped 13 single nucleotide polymorphisms (SNPs) densely covering a 27 kb region within intron 2 of FGFR2 including two SNPs (rs2981582 and rs1219648) significantly associated with breast cancer and a total 40 tagSNPs across 150 kb of the FGFR2 gene. SNPs were genotyped in 958 endometriosis cases and 959 unrelated controls. RESULTS We found no evidence for association between endometriosis and FGFR2 intron 2 SNPs or SNP haplotypes and no evidence for association between endometriosis and variation across the FGFR2 gene. CONCLUSIONS Common variation in the breast-cancer implicated intron 2 and other highly plausible causative candidate regions of FGFR2 do not appear to be a major contributor to endometriosis susceptibility in our large Australian sample.

The threat to scientific integrity in environmental and occupational medicine

Over the last century, environmental and occupational medicine has played a significant role in the protection and improvement of public health. However, scientific integrity in this field has been increasingly threatened by pressure from some industries and governments. For example, it has been reported that the tobacco industry manipulated eminent scientists to legitimise their industrial positions, irresponsibly distorted risk and deliberately subverted scientific processes, and influenced many organisations in receipt of tobacco funding. Many environmental whistleblowers were sued and encountered numerous personal attacks. In some countries, scientific findings have been suppressed and distorted, and scientific advisory committees manipulated for political purposes by government agencies. How to respond to these threats is an important challenge for environmental and occupational medicine professionals and their societies. The authors recommend that professional organisations adopt a code of ethics that requires openness from public health professionals; that they not undertake research or use data where they do not have freedom to publish their results if these data have public health implications; that they disclose all possible conflicts; that the veracity of their research results should not be compromised; and that their research independence be protected through professional and legal support. The authors furthermore recommend that research funding for public health not be directly from the industry to the researcher. An independent, intermediate funding scheme should be established to ensure that there is no pressure to analyse data and publish results in bad faith. Such a funding system should also provide equal competition for funds and selection of the best proposals according to standard scientific criteria.

Early childhood education : the natural starting point for environmental education

Young children are most vulnerable to, and most at risk from, environmental and sustainability challenges. Early education investments aimed at addressing such issues, until recently however, have been neglected or under-rated. Fortunately, this is changing. A groundswell of practitioner interest in early childhood environmental education/ education for sustainability is emerging, in contrast to the ‘patches of green’ that have characterised previous decades. Indeed, an international coalition for early childhood education for sustainability (ECEfS) is beginning to develop, evidenced by The Gothenburg Recommendations on Education for Sustainable Development (2008) that identifies early childhood, within a framework of lifelong learning, as a ‘natural starting point’ for all ongoing education for sustainability. This document is important as it is the first international statement to explicitly identify ECEfS as contributing to education for sustainability. The next challenge for ECEfS is for practitioner mobilisation to be matched by research activity aimed at broadening and deepening practice-based responses. This is the next exciting frontier in the legitimisation of ECEfS.

Exploring the parameter space of a rabbit ventricular action potential model to investigate the effect of variation on action potential and calcium transients

Computational models for cardiomyocyte action potentials (AP) often make use of a large parameter set. This parameter set can contain some elements that are fitted to experimental data independently of any other element, some elements that are derived concurrently with other elements to match experimental data, and some elements that are derived purely from phenomenological fitting to produce the desired AP output. Furthermore, models can make use of several different data sets, not always derived for the same conditions or even the same species. It is consequently uncertain whether the parameter set for a given model is physiologically accurate. Furthermore, it is only recently that the possibility of degeneracy in parameter values in producing a given simulation output has started to be addressed. In this study, we examine the effects of varying two parameters (the L-type calcium current (I(CaL)) and the delayed rectifier potassium current (I(Ks))) in a computational model of a rabbit ventricular cardiomyocyte AP on both the membrane potential (V(m)) and calcium (Ca(2+)) transient. It will subsequently be determined if there is degeneracy in this model to these parameter values, which will have important implications on the stability of these models to cell-to-cell parameter variation, and also whether the current methodology for generating parameter values is flawed. The accuracy of AP duration (APD) as an indicator of AP shape will also be assessed.

The influence of cultural selection on strategic communication

Strategic communication is held to be a key process by which organisations respond to environmental uncertainty. In the received view articulated in the literatures of organisational communication and public relations, strategic communication results from collaborative efforts by organisational members to create shared understanding about environmental uncertainty and, as a result of this collective understanding, formulate appropriate communication responses. In this study, I explore how such collaborative efforts towards the development of strategic communication are derived from, and bounded by, culturally shared values and assumptions. Study of the influences of an organisation‟s culture on the formulation of strategic communication is a fundamental conceptual challenge for public relations and, to date, a largely unaddressed area of research. This thesis responds to this challenge by describing a key property of organisational culture – the action of cultural selection (Durham, 1992). I integrate this property of cultural selection to extend and refine the descriptive range of Weick‟s (1969, 1979) classic sociocultural model of organizing. From this integration I propose a new model, the Cultural Selection of Strategic Communication (CSSC). Underpinning the CSSC model is the central proposition that because of the action of cultural selection during organizing processes, the inherently conservative properties of an organisation‟s culture constrain development of effective strategic communication in ways that may be unrelated to the outcomes of “environmental scanning” and other monitoring functions heralded by the public relations literature as central to organisational adaptation. Thus, by examining the development of strategic communication, I describe a central conservative influence on the social ecology of organisations. This research also responds to Butschi and Steyn‟s (2006) call for the development of theory focusing on strategic communication as well as Grunig (2006) and Sriramesh‟s (2007) call for research to further understand the role of culture in public relations practice. In keeping with the explorative and descriptive goals of this study, I employ organisational ethnography to examine the influence of cultural selection on the development of strategic communication. In this methodological approach, I use the technique of progressive contextualisation to compare data from two related but distinct cultural settings. This approach provides a range of descriptive opportunities to permit a deeper understanding of the work of cultural selection. Findings of this study propose that culture, operating as a system of shared and socially transmitted social knowledge, acts through the property of cultural selection to influence decision making, and decrease conceptual variation within a group. The findings support the view that strategic communication, as a cultural product derived from the influence of cultural selection, is an essential feature to understand the social ecology of an organisation.

The right to be green: using human rights law to achieve environmental protection

The relationship between the environment and human rights has long been recognised. It is now largely accepted that a ‘good’ environment is a necessary precondition for the enjoyment of a wide range of human rights, including the right to health, the right to an adequate standard of living, and even the right to life. It has even been suggested that as humans we all possess a right to live in an environment of a certain standard, based on the intrinsic value of the natural world to all human beings. In this context much has been written regarding the important role that the environment plays in human lives. This paper looks at the flip-side of this discussion, and examines what human rights can do for the environment. It is argued that, while there are valid criticisms for linking environmental protection too strongly to human needs, there is nonetheless much to be gained from using human rights law as a framework to achieve environmental protection.