Exendin-4 protects against post-myocardial infarction remodelling via specific actions on inflammation and the extracellular matrix

Glucagon-like peptide-1 (GLP-1) is an insulin-releasing hormone clinically exploited for glycaemic control in diabetes, which also confers acute cardioprotection and benefits in experimental/clinical heart failure. We specifically investigated the role of the GLP-1 mimetic, exendin-4, in post-myocardial infarction (MI) remodelling, which is a key contributor to heart failure. Adult female normoglycaemic mice underwent coronary artery ligation/sham surgery prior to infusion with exendin-4/vehicle for 4 weeks. Metabolic parameters and infarct sizes were comparable between groups. Exendin-4 protected against cardiac dysfunction and chamber dilatation post-MI and improved survival. Furthermore, exendin-4 modestly decreased cardiomyocyte hypertrophy/apoptosis but markedly attenuated interstitial fibrosis and myocardial inflammation post-MI. This was associated with altered extracellular matrix (procollagen IαI/IIIαI, connective tissue growth factor, fibronectin, TGF-β3) and inflammatory (IL-10, IL-1β, IL-6) gene expression in exendin-4-treated mice, together with modulation of both Akt/GSK-3β and Smad2/3 signalling. Exendin-4 also altered macrophage response gene expression in the absence of direct actions on cardiac fibroblast differentiation, suggesting cardioprotective effects occurring secondary to modulation of inflammation. Our findings indicate that exendin-4 protects against post-MI remodelling via preferential actions on inflammation and the extracellular matrix independently of its established actions on glycaemic control, thereby suggesting that selective targeting of GLP-1 signalling may be required to realise its clear therapeutic potential for post-MI heart failure.

Genetically Engineered Crops' Authorizations in the US and the EU: a Struggle Against the Clock

The regulation of genetically engineered crops is important for society: ensuring their safety for humans and the environment. Their authorization starts with a scientific step and ends with a political step. Trends in the time taken for their authorization in the European Union are that they are decreasing, but in the United States there is a break in the overall trend: initially it decreased until 1998 after which it increased.

Mobilizing against neoliberalism? Global affirmative action in context

This article uses the example of Northern Ireland to illustrate how political mobilization may
be deployed to challenge structural forms of inequality. The experience suggests that regulatory
models can be designed for particular contexts to shape approaches that present challenges to
dominant economic and political orthodoxies. The intention is not to overstate the significance
of this specific transitional context but simply to highlight elements that might feature in any
attempt to mobilize successfully around human rights and equality, and against aspects of neoliberal
thinking.

Man-up Against Suicide

Male suicide rates are high in Western countries including the US and Canada. Underpinned by men’s resistance to health help-seeking and challenges diagnosing mental illness including male depression, suicide ends the lives of many men amid inflicting pain and grief on the family and friends who are left behind. Fuelled by the discordant relationship between men’s low rates of depression and high rates of suicide we embarked on a unique and novel photovoice study title Man-Up Against Suicide. Specifically, men who have contemplated suicide in the past, and individuals (men and women) who have lost a male partner, family member or friend to suicide were invited to take photographs representing their experiences with men’s suicide with the ultimate goal of messaging ‘at risk’ men that there are alternatives to taking one’s life. Participants subsequently completed semi-structured individual interviews narrating the photographs and providing captions to accompany their selected images. In this presentation we share the preliminary study findings along with some participant photographs and narratives as a means to discussing; 1) men’s experiences of suicidal behaviours and their management strategies; and, 2) how men’s and women’s experiences of losing a male to suicide can de-stigmatize men’s mental illness and raise public awareness about male suicide.

Malware detection: program run length against detection rate

N-gram analysis is an approach that investigates the structure of a program using bytes, characters or text strings. This research uses dynamic analysis to investigate malware detection using a classification approach based on N-gram analysis. A key issue with dynamic analysis is the length of time a program has to be run to ensure a correct classification. The motivation for this research is to find the optimum subset of operational codes (opcodes) that make the best indicators of malware and to determine how long a program has to be monitored to ensure an accurate support vector machine (SVM) classification of benign and malicious software. The experiments within this study represent programs as opcode density histograms gained through dynamic analysis for different program run periods. A SVM is used as the program classifier to determine the ability of different program run lengths to correctly determine the presence of malicious software. The findings show that malware can be detected with different program run lengths using a small number of opcodes