Transplantation of human amnion epithelial cells reduces hepatic fibrosis in immunocompetent CCl4-treated mice

Chronic liver injury and inflammation lead to hepatic fibrosis, cirrhosis, and liver failure. Embryonic and mesenchymal stem cells have been shown to reduce experimental liver fibrosis but have potential limitations, including the formation of dysplastic precursors, tumors, and profibrogenic cells. Other stem-like cells may reduce hepatic inflammation and fibrosis without tumor and profibrogenic cell formation. To test this hypothesis we transplanted human amnion epithelial cells (hAEC), isolated from term delivered placenta, into immunocompetent C57/BL6 mice at week 2 of a 4-week regimen of carbon tetrachloride (CCl4) exposure to induce liver fibrosis. Two weeks following hAEC infusion, intact cells expressing the human-specific markers inner mitochondrial membrane protein and human leukocyte antigen-G were found in mouse liver without evidence of host rejection of the transplanted cells. Human albumin, known to be produced by hAEC, was detected in sera of hAEC-treated mice. Human DNA was detected in mouse liver and also spleen, lungs, and heart of some animals. Following hAEC transplantation, CCl4-treated animals showed decreased serum ALT levels and reduced hepatocyte apoptosis, compared to controls. hAEC-treated mouse liver had lower TNF-α and IL-6 protein levels and higher IL-10 compared to animals given CCl4 alone. Compared to CCl4 controls, hAEC-treated mice showed fewer activated collagen-producing hepatic stellate cells and less fibrosis area and collagen content. Reduced hepatic TGF-β levels in conjunction with a twofold increase in the active form of the collagen-degrading enzyme matrix metalloproteinase-2 in hAEC-treated mice compared to CCl4 controls may account for the reduction in fibrosis. hAEC transplantation into immunocompetent mice leads to cell engraftment, reduced hepatocyte apoptosis, and decreased hepatic inflammation and fibrosis.

Triphasic pattern in the ex vivo response of human proliferative phase endometrium to oestrogens

The aim of this study was to evaluate the ex vivo oestrogen responsiveness of human proliferative phase endometrium using short-term explant cultures. The effects of oestrogen (17beta-E2) on proliferation and the expression of oestrogen-responsive genes known to be involved in regulating endometrial function were evaluated. Three distinct response patterns could be distinguished: (1) the menstrual (M) phase pattern (cycle days 2-5), which is characterised by a complete lack in the proliferative response to 17beta-E2, while an increased expression of AR (2.6-fold, P<0.01), PR (2.7-fold, P<0.01) and COX-2 (3.5-fold, P<0.01) at the mRNA level was observed and a similar upregulation was also found for AR, PR and COX-2 at the protein level; (2) the early proliferative (EP) phase pattern (cycle days 6-10) with 17beta-E2 enhanced proliferation in the stroma (1.7-fold, P<0.05), whereas the expression of AR, PR and COX-2 were not affected at the mRNA and protein levels and ER-a mRNA and protein levels were significantly reduced by 17beta-E2; (3) the late proliferative (LP) phase pattern (cycle days 11-14), which is characterised by a moderate stimulation of proliferation (1.4-fold, P<0.05) and PR mRNA expression (1.7-fold, P<0.01) by 17beta-E2. In conclusion, three distinct response patterns to 17beta-E2 could be identified with respect to proliferation and the expression of known oestrogen-responsive genes in human proliferative phase endometrium explant cultures.

Incorporating human-factors in car-following models : a review of recent developments and research needs

Over the past decades there has been a considerable development in the modeling of car-following (CF) behavior as a result of research undertaken by both traffic engineers and traffic psychologists. While traffic engineers seek to understand the behavior of a traffic stream, traffic psychologists seek to describe the human abilities and errors involved in the driving process. This paper provides a comprehensive review of these two research streams. It is necessary to consider human-factors in {CF} modeling for a more realistic representation of {CF} behavior in complex driving situations (for example, in traffic breakdowns, crash-prone situations, and adverse weather conditions) to improve traffic safety and to better understand widely-reported puzzling traffic flow phenomena, such as capacity drop, stop-and-go oscillations, and traffic hysteresis. While there are some excellent reviews of {CF} models available in the literature, none of these specifically focuses on the human factors in these models. This paper addresses this gap by reviewing the available literature with a specific focus on the latest advances in car-following models from both the engineering and human behavior points of view. In so doing, it analyses the benefits and limitations of various models and highlights future research needs in the area.

Informal caring networks for people at end of life: Building social capital in Australian communities

The care of a person living at home near the end of their life is predominantly provided by family carers with the support of health services such as palliative care. In addition, informal caring networks also contribute at times to the support to the dying person and their carer. In this way, these networks can promote social capital in the communities from which they are drawn. This social approach to end of life care enhances community capacity to provide support to those dying at home and their carers. This article examines relevant published literature to explore the conceptual foundations of informal caring networks, examining the place of social capital and community development in the provision of end of life care at home, particularly in the Australian context.

Optics of the human eye in diabetes

This study compared optics of eyes in people with diabetes with those age-balanced controls. Relative to the control group, the diabetes group demonstrated greater lens thickness, more curved lens shapes, smaller lens diameters, higher light scatter, greater lens yellowing, and poorer focusing ability. While the optics of the people with diabetes made them appear as older eyes than those of people of the same age without diabetes, the differences did not increase significantly with age. It was concluded that age-related changes in eyes of people with diabetes need not be accelerated if the diabetes is well controlled.

Fully validated LC–MS/MS method for quantification of homocysteine concentrations in samples of human serum : a new approach

Reported homocysteine (HCY) concentrations in human serum show poor concordance amongst laboratories due to endogenous HCY in the matrices used for assay calibrators and QCs. Hence, we have developed a fully validated LC–MS/MS method for measurement of HCY concentrations in human serum samples that addresses this issue by minimising matrix effects. We used small volumes (20 μL) of 2% Bovine Serum Albumin (BSA) as surrogate matrix for making calibrators and QCs with concentrations adjusted for the endogenous HCY concentration in the surrogate matrix using the method of standard additions. To aliquots (20 μL) of human serum samples, calibrators or QCs, were added HCY-d4 (internal standard) and tris-(2-carboxyethyl) phosphine hydrochloride (TCEP) as reducing agent. After protein precipitation, diluted supernatants were injected into the LC–MS/MS. Calibration curves were linear; QCs were accurate (5.6% deviation from nominal), precise (CV% ≤ 9.6%), stable for four freeze–thaw cycles, and when stored at room temperature for 5 h or at −80 °C (27 days). Recoveries from QCs in surrogate matrix or pooled human serum were 91.9 and 95.9%, respectively. There was no matrix effect using 6 different individual serum samples including one that was haemolysed. Our LC–MS/MS method has satisfied all of the validation criteria of the 2012 EMA guideline.

An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss

Background Environmental factors can influence obesity by epigenetic mechanisms. Adipose tissue plays a key role in obesity-related metabolic dysfunction, and gastric bypass provides a model to investigate obesity and weight loss in humans. Results Here, we investigate DNA methylation in adipose tissue from obese women before and after gastric bypass and significant weight loss. In total, 485,577 CpG sites were profiled in matched, before and after weight loss, subcutaneous and omental adipose tissue. A paired analysis revealed significant differential methylation in omental and subcutaneous adipose tissue. A greater proportion of CpGs are hypermethylated before weight loss and increased methylation is observed in the 3′ untranslated region and gene bodies relative to promoter regions. Differential methylation is found within genes associated with obesity, epigenetic regulation and development, such as CETP, FOXP2, HDAC4, DNMT3B, KCNQ1 and HOX clusters. We identify robust correlations between changes in methylation and clinical trait, including associations between fasting glucose and HDAC4, SLC37A3 and DENND1C in subcutaneous adipose. Genes investigated with differential promoter methylation all show significantly different levels of mRNA before and after gastric bypass. Conclusions This is the first study reporting global DNA methylation profiling of adipose tissue before and after gastric bypass and associated weight loss. It provides a strong basis for future work and offers additional evidence for the role of DNA methylation of adipose tissue in obesity.

FGF-2 induces the proliferation of human periodontal ligament cells and modulates their osteoblastic phenotype by affecting Runx2 expression in the presence and absence of osteogenic inducers

The exact phenotype of human periodontal ligament cells (hPDLCs) remains a controversial area. Basic fibroblast growth factor (FGF‑2) exhibits various functions and its effect on hPDLCs is also controversial. Therefore, the present study examined the effect of FGF‑2 on the growth and osteoblastic phenotype of hPDLCs with or without osteogenic inducers (dexamethasone and β‑glycerophosphate). FGF‑2 was added to defined growth culture medium and osteogenic inductive culture medium. Cell proliferation, osteogenic differentiation and mineralization were measured. The selected differentiation markers, Runx2, collagen type Ⅰ, α1 (Col1a1), osteocalcin (OCN) and epidermal growth factor receptor (EGFR), were investigated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Runx2 and OCN protein expression was measured by western blotting. FGF‑2 significantly increased the proliferation of hPDLCs, but did not affect alkaline phosphatase activity. RT‑qPCR analysis revealed enhanced mRNA expression of Runx2, OCN and EGFR, but suppressed Col1a1 gene expression in the absence of osteogenic inducers, whereas all these gene levels had no clear trend in their presence. The Runx2 protein expression was clearly increased, but the OCN protein level showed no evident trend. The mineralization assay demonstrated that FGF‑2 inhibited mineralized matrix deposition with osteogenic inducers. These results suggested that FGF‑2 induces the growth of immature hPDLCs, which is a competitive inhibitor of epithelial downgrowth, and suppresses their differentiation into mineralized tissue by affecting Runx2 expression. Therefore, this may lead to the acceleration of periodontal regeneration.

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.

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.

Computational analysis of epigenetic information in human DNA sequences

Over the last few years, investigations of human epigenetic profiles have identified key elements of change to be Histone Modifications, stable and heritable DNA methylation and Chromatin remodeling. These factors determine gene expression levels and characterise conditions leading to disease. In order to extract information embedded in long DNA sequences, data mining and pattern recognition tools are widely used, but efforts have been limited to date with respect to analyzing epigenetic changes, and their role as catalysts in disease onset. Useful insight, however, can be gained by investigation of associated dinucleotide distributions. The focus of this paper is to explore specific dinucleotides frequencies across defined regions within the human genome, and to identify new patterns between epigenetic mechanisms and DNA content. Signal processing methods, including Fourier and Wavelet Transformations, are employed and principal results are reported.

Folk conceptions of humanness: Beliefs about distinctive and core human characteristics in Australia, Italy, and China

The present research explores cultural understandings of what it means to be human. We used open-ended responses to examine whether the most culturally salient aspects of humanness are captured by two theoretical dimensions: human uniqueness (HU) and human nature (HN). Australians, Italians, and Chinese (N = 315) showed differences in the characteristics considered human and in the emphasis placed on HU and HN. These findings contribute to developing cross-cultural folk psychological models of humanness.

A matter of style? Driver attributional 'style' in accounting for the driving of others as protective or as predisposing drivers towards retaliatory aggressive driving

Driver cognitions about aggressive driving of others are potentially important to the development of evidence-based interventions. Previous research has suggested that perceptions that other drivers are intentionally aggressive may influence recipient driver anger and subsequent aggressive responses. Accordingly, recent research on aggressive driving has attempted to distinguish between intentional and unintentional motives in relation to problem driving behaviours. This study assessed driver cognitive responses to common potentially provocative hypothetical driving scenarios to explore the role of attributions in driver aggression. A convenience sample of 315 general drivers 16–64 yrs (M = 34) completed a survey measuring trait aggression (Aggression Questionnaire AQ), driving anger (Driving Anger Scale, DAS), and a proxy measure of aggressive driving behaviour (Australian Propensity for Angry Driving AusPADS). Purpose designed items asked for drivers’ ‘most likely’ thought in response to AusPADS scenarios. Response options were equivalent to causal attributions about the other driver. Patterns in endorsements of attribution responses to the scenarios suggested that drivers tended to adopt a particular perception of the driving of others regardless of the depicted circumstances: a driving attributional style. No gender or age differences were found for attributional style. Significant differences were detected between attributional styles for driving anger and endorsement of aggressive responses to driving situations. Drivers who attributed the on-road event to the other being an incompetent or dangerous driver had significantly higher driving anger scores and endorsed significantly more aggressive driving responses than those drivers who attributed other driver’s behaviour to mistakes. In contrast, drivers who gave others the ‘benefit of the doubt’ endorsed significantly less aggressive driving responses than either of these other two groups, suggesting that this style is protective.

Unspeakably present: The (un)acknowledgment of diverse sexuality and gender human rights in Australian youth justice systems

A number of international human rights frameworks protect the rights of young people in contact with the criminal justice system in states parties, including Australia. These frameworks inform youth justice policy in Australia’s jurisdictions. While the frameworks protect young people’s right to non-discrimination on the grounds of ‘race’, religion and political opinion, the rights of young people to non-discrimination on the grounds of sexuality and gender diversity are not explicitly protected. This is problematic given that lesbian, gay, bisexual, trans, intersex and queer (LGBTIQ) young people appear over-represented in youth justice systems. This article argues that the exclusion of this group from human rights frameworks has an important flow-on effect: the marginalisation of the right of LGBTIQ young people to non-discrimination in policy and discourse that is informed by international human rights frameworks. After outlining the relevant frameworks, this article examines the evidence about LGBTIQ young people’s interactions with youth justice agencies, particularly police. The evidence indicates that the human rights of LGBTIQ young people are frequently breached in these interactions. We conclude by arguing that it is timely to consider how best to protect the human rights of LBGTIQ young people and keep their rights on the agenda.