DNA molecules and human therapeutics

Nucleic acid molecules are championing a new generation of reverse engineered biopharmaceuticals. In terms of potential application in gene medicine, plasmid DNA (pDNA) vectors have exceptional therapeutic and immunological profiles as they are free from safety concerns associated with viral vectors, display non-toxicity and are simpler to develop. This review addresses the potential applications of pDNA molecules in vaccine design/development and gene therapy via recombinant DNA technology as well as a staged delivery mechanism for the introduction of plasmid-borne gene to target cells via the nasal route.

Elucidating the host-pathogen interactions between in vitro human cells and enterovirus 71 in Hand, Foot and Mouth Disease (HFMD)

This study has provided further understanding of the pathogenesis of EV71, one of the major etiological agents associated with significant mortality in Hand, Foot and Mouth disease. Elucidating the host-pathogen interaction and the mechanism that the virus uses to bypass host defence systems to establish infection will aid in the development of potential antiviral therapeutics against EV71.

Cytokine secretion in macrophages : SNAREs, Rabs and membrane trafficking

Macrophages have the capacity to rapidly secrete a wide range of inflammatory mediators that influence the development and extent of an inflammatory response. Newly synthesized and/or preformed stored cytokines and other inflammatory mediators are released upon stimulation, the timing, and volume of which is highly regulated. To finely tune this process, secretion is regulated at many levels; at the level of transcription and translation and post-translationally at the endoplasmic reticulum (ER), Golgi, and at or near the cell surface. Here, we discuss recent advances in deciphering these cytokine pathways in macrophages, focusing on recent discoveries regarding the cellular machinery and mechanisms implicated in the synthesis, trafficking, and secretion of cytokines. The specific roles of trafficking machinery including chaperones, GTPases, cytoskeletal proteins, and SNARE membrane fusion proteins will be discussed.

Tropomyosin Tm5NM1 spatially restricts src kinase activity through perturbation of rab11 vesicle trafficking

In order for cells to stop moving, they must synchronously stabilize actin filaments and their associated focal adhesions. How these two structures are coordinated in time and space is not known. We show here that the actin association protein Tm5NM1, which induces stable actin filaments, concurrently suppresses the trafficking of focal-adhesion-regulatory molecules. Using combinations of fluorescent biosensors and fluorescence recovery after photobleaching (FRAP), we demonstrate that Tm5NM1 reduces the level of delivery of Src kinase to focal adhesions, resulting in reduced phosphorylation of adhesion-resident Src substrates. Live imaging of Rab11-positive recycling endosomes that carry Src to focal adhesions reveals disruption of this pathway. We propose that tropomyosin synchronizes adhesion dynamics with the cytoskeleton by regulating actin-dependent trafficking of essential focal-adhesion molecules.

The United Nations Guiding Principles on Business and Human Rights : Putting Accounting for Human Rights into Practice

The “Guiding Principles on Business and Human Rights: Implementing the United Nations ‘Protect, Respect and Remedy Framework’” (the Guiding Principles), endorsed by The United Nations Human Rights Council on 16 June 2011, outline obligations for nation states that currently exist under international law and provide the first authoritative reference point for corporations’ human rights responsibilities. Of the 30 principles endorsed, half relate directly to business. The Guiding Principles have far-reaching implications for all businesses, both small and large, and represent one of the most significant developments in corporate governance this century. In response to a recognition of the potential impacts of the Guiding Principles on corporate governance, the Institute of Chartered Accountants in Australia provided La Trobe Business School with grant funding to undertake groundbreaking research on the implications of the Guiding Principles for management and accounting systems within corporate Australia. This report represents the outcome of the study.

Attributing human uniqueness and human nature to cultural groups : distinct forms of subtle dehumanization

Research on subtle dehumanization has focused on the attribution of human uniqueness to groups (infrahumanization), but has not examined another sense of humanness, human nature. Additionally, research has not extended far beyond Western cultures to examine the universality of these forms of dehumanization. Hence, the attribution of both forms of humanness was examined in three cross-cultural studies. Anglo-Australian and ethnic Chinese attributed values and traits (Study 1, N = 200) and emotions (Study 2, N = 151) to Australian and Chinese groups, and rated these characteristics on human uniqueness and human nature. Both studies found evidence of complementary attributions of humanness for Australians, who denied Chinese human nature but attributed them with greater human uniqueness. Chinese denied Australians human uniqueness, but their attributions of human nature varied for traits, values, and emotions. Study 3 (N = 54) demonstrated similar forms of dehumanization using an implicit method. These results and their implications for dehumanization and prejudice suggest the need to broaden investigation and theory to encompass both forms of humanness, and examine the attribution of both lesser and greater humanness to outgroups.

Balancing the books : an assessment of financial stress associated with social work and human service student placements

This report presents the findings from a study of the financial impact of work-integrated learning commonly referred to as 'placement' among social work and human services students. Based on a survey of 214 respondants, 14 in-depth interviews and two focus groups, the findings indicate that two thirds of the surveyed group felt tired and anxious about their experience of balancing paid work and placement, with 2 in 5 reporting their learning experience was compromised as a result. The significant implications and potential solutions are also discussed.

Autologous human kidney proximal tubule epithelial cells (PTEC) modulate dendritic cell (DC), T cell and B cell responses

This is a comprehensive study of human kidney proximal tubular epithelial cells (PTEC) which are known to respond to and mediate the pathological process of a range of kidney diseases. It identifies various molecules expressed by PTEC and how these molecules participate in down-regulating the inflammatory process, thereby highlighting the clinical potential of these molecules to treat various kidney diseases. In the disease state, PTEC gain the ability to regulate the immune cell responses present within the interstitium. This down-regulation is a complex interaction of contact dependent/independent mechanisms involving various immuno-regulatory molecules including PD-L1, sHLA-G and IDO. The overall outcome of this down-regulation is suppressed DC maturation, decreased number of antibody producing B cells and low T cell responses. These manifestations within a clinical setting are expected to dampen the ongoing inflammation, preventing the damage caused to the kidney tissue.

The 'gourmet' sausage factory: Keeping it human

Whilst tertiary institutions continue to invest heavily in the technological aspects of online Teaching & Learning (T&L), there does not appear to have been a commensurate investment in the “human” aspects of the use of the technology. Despite the broad recognition that teaching and learning materials need to be adapted for and to the onscreen medium, little attention appears to have been paid thus far to the actual people who are delivering it – who equally need to “adapt themselves” to that medium, in order to maximise the benefit of the technology by maximising the human communication skills of those using the online medium – as distinct from the technical skills required to drive and deliver the bits and bytes. The REdelivery Initiative was a direct response to that notion. This paper details – by way of a narrative of one of the workshop participants – that part of the process involving the professional development of academics specifically in and specifically for the digital, online, T&L context, in order to both illuminate and maximise the potential and opportunities afforded by the technology.

The effect of autonomy transparency in human-robot interactions : a preliminary study on operator cognitive workload and situation awareness in multiple heterogeneous UAV management

The autonomous capabilities in collaborative unmanned aircraft systems are growing rapidly. Without appropriate transparency, the effectiveness of the future multiple Unmanned Aerial Vehicle (UAV) management paradigm will be significantly limited by the human agent’s cognitive abilities; where the operator’s CognitiveWorkload (CW) and Situation Awareness (SA) will present as disproportionate. This proposes a challenge in evaluating the impact of robot autonomous capability feedback, allowing the human agent greater transparency into the robot’s autonomous status - in a supervisory role. This paper presents; the motivation, aim, related works, experiment theory, methodology, results and discussions, and the future work succeeding this preliminary study. The results in this paper illustrates that, with a greater transparency of a UAV’s autonomous capability, an overall improvement in the subjects’ cognitive abilities was evident, that is, with a confidence of 95%, the test subjects’ mean CW was demonstrated to have a statistically significant reduction, while their mean SA was demonstrated to have a significant increase.

Temporal characteristics of melanopsin inputs to the human pupil light reflex

Rods, cones and melanopsin containing intrinsically photosensitive retinal ganglion cells (ipRGCs) operate in concert to regulate pupil diameter. The temporal properties of intrinsic ipRGC signalling are distinct to those of rods and cones, including longer latencies and sustained signalling after light offset. We examined whether the melanopsin mediated post-illumination pupil response (PIPR) and pupil constriction were dependent upon the inter-stimulus interval (ISI) between successive light pulses and the temporal frequency of sinusoidal light stimuli. Melanopsin excitation was altered by variation of stimulus wavelength (464 nm and 638 nm lights) and irradiance (11.4 and 15.2 log photons cm(-2) s(-1)). We found that 6s PIPR amplitude was independent of ISI and temporal frequency for all melanopsin excitation levels, indicating complete summation. In contrast to the PIPR, the maximum pupil constriction increased with increasing ISI with high and low melanopsin excitation, but time to minimum diameter was slower with high melanopsin excitation only. This melanopsin response to briefly presented pulses (16 and 100 ms) slows the temporal response of the maximum pupil constriction. We also demonstrate that high melanopsin excitation attenuates the phasic peak-trough pupil amplitude compared to conditions with low melanopsin excitation, indicating an interaction between inner and outer retinal inputs to the pupil light reflex. We infer that outer retina summation is important for rapidly controlling pupil diameter in response to short timescale fluctuations in illumination and may occur at two potential sites, one that is presynaptic to extrinsic photoreceptor input to ipRGCs, or another within the pupil control pathway if ipRGCs have differential temporal tuning to extrinsic and intrinsic signalling.

Teleoperation of a 7 DOF humanoid robot arm using human arm accelerations and EMG signals

We present our work on tele-operating a complex humanoid robot with the help of bio-signals collected from the operator. The frameworks (for robot vision, collision avoidance and machine learning), developed in our lab, allow for a safe interaction with the environment, when combined. This even works with noisy control signals, such as, the operator’s hand acceleration and their electromyography (EMG) signals. These bio-signals are used to execute equivalent actions (such as, reaching and grasping of objects) on the 7 DOF arm.

Polybrominated diphenyl ether (PBDE) human half lives estimated from North Americans moving to Australia

Human half-lives of PentaBDE congeners have been estimated from the decline in serum concentrations measured over a 6-12 month period for a population of exchange students moving from North America to Australia. Australian serum PBDE concentrations are typically between 5 -10 times lower than in North America and we can therefore hypothesize that if the biological half-life is sufficiently short we would observe a decline in serum concentration with length of residence in Australia. Thirty students were recruited over a period of 3 years from whom serum were archived every 2 months during their stay in Australia. Australian residents (n=22) were also sampled longitudinally to estimate general population background levels. All serum samples were analyzed by gas chromatography high resolution mass spectrometry. Key findings confirmed that BDE-47 concentrations in the Australians (median 2.3;

Polybrominated diphenyl ethers and age: analysis of pooled human blood serum from birth to over 60 years

Polybrominated diphenyl ethers (PBDEs) are considered to be a cost effective and efficient way to reduce flammability therefore reducing harm caused by fires. PBDEs are incorporated into a variety of manufactured products and are found worldwide in biological and environmental samples (e.g. Hites et al. 2004). Unlike other persistent organic pollutants there is limited data on PBDE concentrations by age and/or other population specific factors. Some studies have shown no variation in adult serum PBDE concentrations with age (e.g. Mazdai et al., 2003, Meironyte Guvenius et al., 2003) while Petreas et al. (2003) and Schecter et al. (2005) found results to be suggestive of an age trend in adult data but no statistically significant correlation was found. In addition to the data on adult concentrations there is limited data which investigates the levels of PBDEs in infants and young children. Fangström et al. (2005) showed that in seven year olds there was no difference in PBDE concentration when compared to adult concentrations. While Thomsen et al. (2002, 2005) found the concentration of PBDEs in pooled samples of blood serum from a 0-4 years age group to be higher than other age groups (4 to > 60 years). In addition, a family of four was studied in the U.S. and the concentrations were found to be greatest in the 18-month-old infant followed by the 5 year old child, then the mother and father (Fischer et al., 2006). The objectives of this study were to assess age, gender and regional trends of PBDE concentrations in a representative sample of the Australian population.