Regulation and consequences of differential gene expression in diabetic kidney disease

DIN (diabetic nephropathy) is the leading cause of end-stage renal disease worldwide and develops in 25-40% of patients with Type 1 or Type 2 diabetes mellitus. Elevated blood glucose over long periods together with glomerular hypertension leads to progressive glomerulosclerosis and tubulointerstitial fibrosis in susceptible individuals. Central to the pathology of DIN are cytokines and growth factors such as TGF-beta (transforming growth factor beta) superfamily members, including BMPs (bone morphogenetic protein) and TGF-beta 1, which play key roles in fibrogenic responses of the kidney, including podocyte loss, mesangial cell hypertrophy, matrix accumulation and tubulointerstitial fibrosis. Many of these responses can be mimicked in in vitro models of cells cultured in high glucose. We have applied differential gene expression technologies to identify novel genes expressed in in vitro and in vivo models of DN and, importantly, in human renal tissue. By mining these datasets and probing the regulation of expression and actions of specific molecules, we have identified novel roles for molecules such as Gremlin, IHG-1 (induced in high glucose-1) and CTGF (connective tissue growth factor) in DIN and potential regulators of their bioactions.

A statistical framework for the design of microarray experiments and effective detection of differential gene expression

Motivation: Microarray experiments generate a high data volume. However, often due to financial or experimental considerations, e.g. lack of sample, there is little or no replication of the experiments or hybridizations. These factors combined with the intrinsic variability associated with the measurement of gene expression can result in an unsatisfactory detection rate of differential gene expression (DGE). Our motivation was to provide an easy to use measure of the success rate of DGE detection that could find routine use in the design of microarray experiments or in post-experiment assessment.

Community participation and inclusion: People with disabilities defining their place

Disability-related public policy currently emphasises reducing the number of people experiencing exclusion from the spaces of the social and economic majority as being the pre-eminent indicator of inclusion. Twenty-eight adult, New Zealand vocational service users collaborated in a participatory action research project to develop shared understandings of community participation. Analysis of their narratives suggests that spatial indices of inclusion are quiet in potentially oppressive ways about the ways mainstream settings can be experienced by people with disabilities and quiet too about the alternative, less well sanctioned communities to which people with disabilities have always belonged. Participants identified five key attributes of place as important qualitative antecedents to a sense of community belonging. The potential of these attributes and other self-authored approaches to inclusion are explored as ways that people with disabilities can support the policy objective of effecting a transformation from disabling to inclusive communities.

Are rural development programmes socially inclusive? Social inclusion, civic engagement, participation, and social capital: Exploring the differences

Considerable importance is attached to social exclusion/inclusion in recent EU rural development programmes. At the national/regional operation of these programmes groups of people who are not participating are often identified as ‘socially excluded groups’. This article contends that rural development programmes are misinterpreting the social processes of participation and consequently labelling some groups as socially excluded when they are not. This is partly because of the interchangeable and confused use of the concepts social inclusion, social capital and civic engagement, and partly because of the presumption that to participate is the default position. Three groups identified as socially excluded groups in Northern Ireland are considered. It is argued that a more careful analysis of what social inclusion means, what civic engagement means, and why participation is presumed to be the norm, leads to a different conclusion about who is excluded. This has both theoretical and policy relevance for the much used concept of social inclusion.

Teachers’ understandings of reconciliation and inclusion in four troubled societies.

In this article, the authors examine how teachers in four troubled societies – Israel, Cyprus, Northern Ireland and South Africa – understand and implement reconciliation in light of the increasing diversity of these societies. The authors particularly pay attention to a dialogical encounter between reconciliation and inclusion, as they look for ways to contemplate how each might be of mutual benefit in educational theory and practice. In the first part of the article, the authors give an overview of current thinking on reconciliation and its role in education, and suggest that the notion of inclusiveness can enrich it. The context of the research is then provided by looking briefly at the socio-political and educational settings in which the study was conducted, followed by a discussion of the research methodology. The findings from the study are then presented with the main themes identified as arising across the four research locations. These themes concern understandings of reconciliation and inclusion, student diversity, teachers’ challenges, helping students deal with conflict, and teachers’ development. Finally, whilst acknowledging the exploratory nature of these findings, the authors discuss what policy makers, school leaders and teachers might change about policies and practices for reconciliation education in the four settings studied and, by implication, other comparable settings.

Towards Educational Inclusion in a Transforming Society: Some Lessons from Community Relations and Special Needs Education in Northern Ireland

This paper takes an original approach to an important aspect of educational research and its role in transforming societies, namely that of educational inclusion. It brings together what some might consider two rather strange bedfellows i.e. community relations and special needs education. It also draws upon new tools for theorising educational inclusion, which give a central role to the discursive nature of human conduct and which take a view of human behaviour as socially embedded and meaningful.

Towards Educational Inclusion in a Contested Society: From Critical Reflection to Cultural Action

This paper is written by democratic educators who stand for the idea that is it worth developing, through classrooms and schools, a socially just (egalitarian), anti-discriminatory society where interdependent relationships are valued. This paper significantly develops some of the ideas explored in the authors’ earlier contribution concerned with progress in Northern Ireland towards educational inclusion, and how this might more effectively advance in a post-conflict transforming society. In particular, the paper poses the ‘so what’ question, and it responds by exploring the practical implications of six key ideas thought essential for transforming learning environments supportive of cultural diversity, equity and excellence for all. In addition, it includes examples of how school staff, along with collaborating partners, might utilize these key principles in order to facilitate school improvement.

Differential Effect of IL-27 on Developing versus Committed Th17 Cells

IIL-27 counters the effect of TGF-beta+IL-6 on naive CD4(+) T cells, resulting in near complete inhibition of de novo Th17 development. In contrast, little is known about the effect of IL-27 on already differentiated Th17 cells. A better understanding of how IL-27 regulates these cells is needed to evaluate the therapeutic potential of IL-27 in Th17 cells-associated diseases. In this study, we show that IL-27 had surprisingly little effect on committed Th17 cells, despite its expression of a functional IL-27R. Contrary to de novo differentiation of Th17 cells, IL-27 did not suppress expression of retinoid-related orphan receptor (ROR)gammat or RORalpha in committed Th17 cells. Consistent with this finding, the frequency of committed Th17 cells and their cytokine secretion remained unaffected by IL-27. Both memory Th17 cells (CD4(+)CD25(-)CD62L(low)) that developed in vivo and encephalitogenic Th17 cells infiltrating the CNS of mice developing experimental autoimmune encephalomyelitis produced similar amounts of IL-17A when reactivated with IL-23 in the absence and presence of exogenous IL-27. Finally, IL-27 failed to suppress encephalitogenicity of Th17 cells in an adoptive transfer of experimental autoimmune encephalomyelitis. Analysis ex vivo of transferred Th17 cells in the spleen and CNS of recipient mice showed that cells retained similar phenotype irrespective of whether cells were treated or not with IL-27. Our data demonstrate that in contrast to inhibition of de novo differentiation of Th17 cells, IL-27 has little or no effect on committed Th17 cells. These findings indicate that therapeutic applications of IL-27 might have a limited efficacy in inflammatory conditions where aggressive Th17 responses have already developed.