INFLUENCE OF NOX4 NADPH OXIDASE ON GENERATION AND ANGIOGENIC FUNCTION OF INDUCED PLURIPOTENT STEM CELL-DERIVED ENDOTHELIAL CELLS

Human induced pluripotent stem (iPS) cell-derived endothelial cells (ECs) hold clear potential for therapeutic angiogenesis as a novel strategy for ischaemic disease. Recently, we have developed a novel method for direct reprogramming of partial iPS (PiPS) cells, which unlike iPS cells, are generated before pluripotency so do not form tumours, and may be differentiated into ECs with characteristic morphology and pro-angiogenic actions. Our previous work showed that PiPS-derived ECs are capable of forming vascular-like tubes both in vitro and in vivo and promoting re-endothelialisation of ischemic tissue, with greater effectiveness versus mature ECs.

Interestingly, our preliminary data demonstrate that Nox NADPH oxidases, which are reported to influence stem cell function, are progressively induced during PiPs/PiPS-EC differentiation and in response to hypoxia, with Nox4 demonstrating highest expression. As this isoform is an established regulator of angiogenesis, we hypothesize that Nox4 plays a key role in modulating PiPS-EC generation and angiogenic function.

The aim of this project is therefore to investigate: (1) the specific role of Nox4 in direct reprogramming of PiPS cells and differentiation to PiPS-ECs; (2) whether genetic manipulation of Nox4 influences in vitro function of PiPs-ECs and their ability to promote in vivo angiogenesis. This will be achieved by employing established in vitro functional assays and an experimental model of hindlimb ischaemia with assessment of relevant end-points. Identification of a key role for Nox4 in regulating PiPS-EC generation/function may inform selective targeting of this isoform to enhance the efficiency of PiPS-EC differentiation and their capacity to treat ischemic disease.

Mitochondrial Transfer via Tunneling Nanotubes (TNT) is an Important Mechanism by which Mesenchymal Stem Cells Enhance Macrophage Phagocytosis in the in vitro and in vivo Models of ARDS

Mesenchymal stromal cells (MSC) have been reported to improve bacterial clearance in pre-clinical models of Acute Respiratory Distress Syndrome (ARDS) and sepsis. The mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the anti-microbial effect of MSC in vivo depends on their modulation of macrophage phagocytic activity which occurs through mitochondrial transfer. We established that selective depletion of alveolar macrophages (AM) with intranasal (IN) administration of liposomal clodronate resulted in complete abrogation of MSC anti-microbial effect in the in vivo model of E.coli pneumonia. Furthermore, we showed that MSC administration was associated with enhanced AM phagocytosis in vivo. We showed that direct co-culture of MSC with monocyte-derived macrophages (MDMs) enhanced their phagocytic capacity. By fluorescent imaging and flow cytometry we demonstrated extensive mitochondrial transfer from MSC to macrophages which occurred at least partially through TNT-like structures. We also detected that lung macrophages readily acquire MSC mitochondria in vivo, and macrophages which are positive for MSC mitochondria display more pronounced phagocytic activity. Finally, partial inhibition of mitochondrial transfer through blockage of TNT formation by MSC resulted in failure to improve macrophage bioenergetics and complete abrogation of the MSC effect on macrophage phagocytosis in vitro and the anti-microbial effect of MSC in vivo.

Collectively, this work for the first time demonstrates that mitochondrial transfer from MSC to innate immune cells leads to enhancement in phagocytic activity and reveals an important novel mechanism for the anti-microbial effect of MSC in ARDS.

Philosophy and Political Engagement: Reflection in the Public Sphere

Do philosophers have a responsibility to their society that is distinct from their responsibility to it as citizens? This edited volume explores both what type of contribution philosophy can make and what type of reasoning is appropriate when addressing public matters now. These questions are posed by leading international scholars working in the fields of moral and political philosophy. Each contribution also investigates the central issue of how to combine critical, rational analysis with a commitment to politically relevant public engagement. The contributions to this volume analyse issues raised in practical ethics, including abortion, embryology, and assisted suicide. They consider the role of ethical commitment in the philosophical analysis of contemporary political issues, and engage with matters of public policy such as poverty, the arts, meaningful work, as well as the evidence base for policy. They also examine the normative legitimacy of power, including the use of violence.

Laser Surface Treatment of Polyamide and NiTi Alloy and the Effects on Mesenchymal Stem Cell Response

Mesenchymal stem cells (MSCs) are known to play important roles in development, post-natal growth, repair, and regeneration of mesenchymal tissues. What is more, surface treatments are widely reported to affect the biomimetic nature of materials. This paper will detail, discuss and compare laser surface treatment of polyamide (Polyamide 6,6), using a 60 W CO2 laser, and NiTi alloy, using a 100 W fiber laser, and the effects of these treatments on mesenchymal stem cell response. The surface morphology and composition of the polyamide and NiTi alloy were studied by scanning electron microscopy (SEM) and X-ray photoemission spectroscopy (XPS), respectively. MSC cell morphology cell counting and viability measurements were done by employing a haemocytometer and MTT colorimetric assay. The success of enhanced adhesion and spreading of the MSCs on each of the laser surface treated samples, when compared to as-received samples, is evidenced in this work. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

An evaluation of the Socrative (personal response system) app for increasing student engagement and learning in an undergraduate psychology curriculum.

Personal response systems using hardware such as 'clickers' have been around for some time, however their use is often restricted to multiple choice questions (MCQs) and they are therefore used as a summative assessment tool for the individual student. More recent innovations such as 'Socrative' have removed the need for specialist hardware, instead utilising web-based technology and devices common to students, such as smartphones, tablets and laptops. While improving the potential for use in larger classrooms, this also creates the opportunity to pose more engaging open-response questions to students who can 'text in' their thoughts on questions posed in class. This poster will present two applications of the Socrative system in an undergraduate psychology curriculum which aimed to encourage interactive engagement with course content using real-time student responses and lecturer feedback. Data is currently being collected and result will be presented at the conference.
The first application used Socrative to pose MCQs at the end of two modules (a level one Statistics module and level two Individual Differences Psychology module, class size N≈100), with the intention of helping students assess their knowledge of the course. They were asked to rate their self-perceived knowledge of the course on a five-point Likert scale before and after completing the MCQs, as well as their views on the value of the revision session and any issues that had with using the app. The online MCQs remained open between the lecture and the exam, allowing students to revisit the questions at any time during their revision.
This poster will present data regarding the usefulness of the revision MCQs, the metacognitive effect of the MCQs on student's judgements of learning (pre vs post MCQ testing), as well as student engagement with the MCQs between the revision session and the examination. Student opinions on the use of the Socrative system in class will also be discussed.
The second application used Socrative to facilitate a flipped classroom lecture on a level two 'Conceptual Issues in Psychology' module, class size N≈100). The content of this module requires students to think critically about historical and contemporary conceptual issues in psychology and the philosophy of science. Students traditionally struggle with this module due to the emphasis on critical thinking skills, rather than simply the retention of concrete knowledge. To prepare students for the written examination, a flipped classroom lecture was held at the end of the semester. Students were asked to revise their knowledge of a particular area of Psychology by assigned reading, and were told that the flipped lecture would involve them thinking critically about the conceptual issues found in this area. They were informed that questions would be posed by the lecturer in class, and that they would be asked to post their thoughts using the Socrative app for a class discussion. The level of preparation students engaged in for the flipped lecture was measured, as well as qualitative opinions on the usefulness of the session. This poster will discuss the level of student engagement with the flipped lecture, both in terms of preparation for the lecture, and engagement with questions posed during the lecture, as well as the lecturer's experience in facilitating the flipped classroom using the Socrative platform.

Linking Family Engagement with a Rights Perspective: Macro Factors Influencing Practice

While child welfare practitioners in many countries are struggling to develop methods of effective family engagement, they operate within different national and cultural contexts which influence, both positively and negatively, the ability to engage with families. Increasingly, international comparisons are necessary to further understanding of the development of social work practice. This is particularly necessary because most countries utilize international frameworks (such as the United National Convention on the Rights of the Child) to provide guidance in the development of policies, programs, and interventions. Each country (and locality) struggles to advance practice to be more effective and humane. Our paper offers a comparative analysis focused on family-oriented and rights-based frameworks of different countries. Based on a review of current national policies and a review of the literature regarding family based practices, we examine similarities and differences among four countries: the United Kingdom, Sweden, the United States, and South Korea. These countries were selected because they have some similarities (advanced industrialized democracies, professional social work, formal child protection systems) but have some differences in their social welfare systems (policies, specific practices, socio-cultural context). These differences can be utilized to advance understanding regarding the promise and potential for family engagement strategies. We then discuss the utility of this comparison for theory-building in the arena of child care practice and conclude by identifying the challenges and limitations of this work.