Moral judgments, gender, and antisocial preferences : an experimental study

Peer reviewedPostprin

The Kunitz-Like Modulatory Protein Haemangin Is Vital for Hard Tick Blood-Feeding Success

Ticks are serious haematophagus arthropod pests and are only second to mosquitoes as vectors of diseases of humans and animals. The salivary glands of the slower feeding hard ticks such as Haemaphysalis longicornis are a rich source of bioactive molecules and are critical to their biologic success, yet distinct molecules that help prolong parasitism on robust mammalian hosts and achieve blood-meals remain unidentified. Here, we report on the molecular and biochemical features and precise functions of a novel Kunitz inhibitor from H. longicornis salivary glands, termed Haemangin, in the modulation of angiogenesis and in persistent blood-feeding. Haemangin was shown to disrupt angiogenesis and wound healing via inhibition of vascular endothelial cell proliferation and induction of apoptosis. Further, this compound potently inactivated trypsin, chymotrypsin, and plasmin, indicating its antiproteolytic potential on angiogenic cascades. Analysis of Haemangin-specific gene expression kinetics at different blood-feeding stages of adult ticks revealed a dramatic up-regulation prior to complete feeding, which appears to be functionally linked to the acquisition of blood-meals. Notably, disruption of Haemangin-specific mRNA by a reverse genetic tool significantly diminished engorgement of adult H. longicornis, while the knock-down ticks failed to impair angiogenesis in vivo. To our knowledge, we have provided the first insights into transcriptional responses of human microvascular endothelial cells to Haemangin. DNA microarray data revealed that Haemangin altered the expression of 3,267 genes, including those of angiogenic significance, further substantiating the antiangiogenic function of Haemangin. We establish the vital roles of Haemangin in the hard tick blood-feeding process. Moreover, our results provide novel insights into the blood-feeding strategies that enable hard ticks to persistently feed and ensure full blood-meals through the modulation of angiogenesis and wound healing processes

Topological Analysis of MAPK Cascade for Kinetic ErbB Signaling

Ligand-induced homo- and hetero-dimer formation of ErbB receptors results in different biological outcomes irrespective of recruitment and activation of similar effector proteins. Earlier experimental research indicated that cells expressing both EGFR (epidermal growth factor receptor) and the ErbB4 receptor (E1/4 cells) induced E1/4 cell-specific B-Raf activation and higher extracellular signal-regulated kinase (ERK) activation, followed by cellular transformation, than cells solely expressing EGFR (E1 cells) in Chinese hamster ovary (CHO) cells. Since our experimental data revealed the presence of positive feedback by ERK on upstream pathways, it was estimated that the cross-talk/feedback pathway structure of the Raf-MEK-ERK cascade might affect ERK activation dynamics in our cell system. To uncover the regulatory mechanism concerning the ERK dynamics, we used topological models and performed parameter estimation for all candidate structures that possessed ERK-mediated positive feedback regulation of Raf. The structure that reliably reproduced a series of experimental data regarding signal amplitude and duration of the signaling molecules was selected as a solution. We found that the pathway structure is characterized by ERK-mediated positive feedback regulation of B-Raf and B-Raf-mediated negative regulation of Raf-1. Steady-state analysis of the estimated structure indicated that the amplitude of Ras activity might critically affect ERK activity through ERK-B-Raf positive feedback coordination with sustained B-Raf activation in E1/4 cells. However, Rap1 that positively regulates B-Raf activity might be less effective concerning ERK and B-Raf activity. Furthermore, we investigated how such Ras activity in E1/4 cells can be regulated by EGFR/ErbB4 heterodimer-mediated signaling. From a sensitivity analysis of the detailed upstream model for Ras activation, we concluded that Ras activation dynamics is dominated by heterodimer-mediated signaling coordination with a large initial speed of dimerization when the concentration of the ErbB4 receptor is considerably high. Such characteristics of the signaling cause the preferential binding of the Grb2-SOS complex to heterodimer-mediated signaling molecules

Sense of Coherence and Gambling: Exploring the Relationship Between Sense of Coherence, Gambling Behaviour and Gambling-Related Harm

Understanding why some people experience problems with gambling whilst others are able to restrict gambling to recreational levels is still largely unexplained. One potential explanation is through salutogenesis, which is a health promotion approach of understanding factors which move people towards health rather than disease. An important aspect of salutogenesis is sense of coherence. Individuals with stronger sense of coherence perceive their environment as comprehensible, manageable and meaningful. The present study examined the relationship of individuals’ sense of coherence on their gambling behaviour and experience of gambling related harm. This exploratory study utilised an archival dataset (n = 1236) from an online, cross sectional survey of people who had experienced negative consequences from gambling. In general, a stronger sense of coherence was related to lower problem gambling severity. When gambling behaviour was controlled for, sense of coherence was significantly related to the experience of individual gambling harms. A strong sense of coherence can be seen as a protective factor against problematic gambling behaviour, and subsequent gambling related harms. These findings support the value of both primary and tertiary prevention strategies that strengthen sense of coherence as a harm minimisation strategy. The present study demonstrates the potential value of, and provides clear direction for, considering sense of coherence in order to understand gambling-related issues.This study was funded by the Victorian Responsible Gambling Foundation, Grant VRGF1-13

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Embedding cultural competence in faculty : a mixed-methods evaluation of an applied Indigenous proficiency workshop

One of the most pressing issues in Australian society is the gap between Indigenous and non-Indigenous health and life expectancies (Marmot, 2017). Australia agreed with the World Health Organisation’s 2008 Closing the Gap in a Generation report (WHO, 2008), spending approximately 5.6% of government expenditure towards ameliorating this gap (Gardiner-Garden & Simon-Davies, 2012), yet there have been only minimal positive outcomes (Alford, 2015; Gannon, 2018). In applied terms, this means Indigenous people are still dying younger (Anderson et al., 2016), scoring higher on psychological distress (Markwick, Ansari, Sullivan, & McNeil, 2015) and suffering poorer indices on all chronic diseases (e.g. Walsh & Kangaharan, 2016; Thompson, Talley, & Kong, 2017). The level of complexity involved in addressing these “wicked” or seemingly “impossible to solve” health problems is made worse by the lack of any pan-national strategic planning and/or intervention evaluation (Lokuge et al., 2017), even though there has been a plethora of programs and projects designed to improve Indigenous health (see for example, AGPC, 2016). Leaders in health and educational institutions must consider why there is a lack of progress in closing the gap in Indigenous health and life expectancies. Addressing the inequities in Indigenous health requires a determinant of health approach (Mitrou et al., 2014), as 39% of the gap in health outcomes can be explained by social determinates (AIHW, 2017; Markwick, Ansari, Sullivan, Parsons, & McNeil, 2014). The social determinant considered to most reliably predict Indigenous poor health is racism (Kelaher, Ferdinand, & Paradies, 2014; Paradies, 2006; Paradies & Cunningham, 2009; Paradies et al., 2015; Paradies, Truong, & Priest, 2014)

Experimental Design

AbstractThis chapter covers various issues related to the experimental design, a statistical technique at the core of a discrete choice experiment. Specifically, it focuses on the dimensionality of a choice experiment and the statistical techniques used to allocate attribute levels to choice tasks. Among others, the pros and cons of orthogonal designs, optimal orthogonal in the differences designs as well as efficient designs are addressed. The last section shows how a simulation exercise can help to test the appropriateness of the experimental design

Developing the Questionnaire

AbstractThis chapter outlines the essential topics for developing and testing a questionnaire for a discrete choice experiment survey. It addresses issues such as the description of the environmental good, pretesting of the survey, incentive compatibility, consequentiality or mitigation of hypothetical bias. For the latter, cheap talk scripts, opt-out reminders or an oath script are discussed. Moreover, the use of instructional choice sets, the identification of protest responses and strategic bidders are considered. Finally, issues related to the payment vehicle and the cost vector design are the subject of this section

Infidelity-Revealing Snapchat Messages Arouse Different Levels of Jealousy Depending on Sex, Type of Message and Identity of the Opposite Sex Rival

Research highlighting sex-differentiated jealousy resulting from imagined scenarios has now been reaffirmed when the infidelity-revealing message is discovered on a social media platform. Participants in the current study were presented with both sexually and emotionally charged infidelity-revealing scenarios featuring a same-sex sibling, a friend and a stranger in the format of a ‘Snapchat’ message. Men indicated significantly higher jealousy to sexual as opposed to emotional messages with the reverse pattern evident in women. Sex differences were also evident in the extent of jealousy elicited by ‘third-party’ identity. Women were significantly more jealous when the imagined infidelity occurred between their sister compared to both a best friend and a stranger with males showing significantly lower jealousy directed towards their brother compared to a stranger. These findings are supportive not only of a parental investment (PI) interpretation of sex differences in jealousy but also an interpretation consistent with aspects of inclusive fitness theory