Epigenetic Changes in Endothelial Progenitors as a Possible Cellular Basis for Glycemic Memory in Diabetic Vascular Complications

The vascular complications of diabetes significantly impact the quality of life and mortality in diabetic patients. Extensive evidence from various human clinical trials has clearly established that a period of poor glycemic control early in the disease process carries negative consequences, such as an increase in the development and progression of vascular complications that becomes evident many years later. Importantly, intensive glycemic control established later in the disease process cannot reverse or slow down the onset or progression of diabetic vasculopathy. This has been named the glycemic memory phenomenon. Scientists have successfully modelled glycemic memory using various in vitro and in vivo systems. This review emphasizes that oxidative stress and accumulation of advanced glycation end products are key factors driving glycemic memory in endothelial cells. Furthermore, various epigenetic marks have been proposed to closely associate with vascular glycemic memory. In addition, we comment on the importance of endothelial progenitors and their role as endogenous vasoreparative cells that are negatively impacted by the diabetic milieu and may constitute a "carrier" of glycemic memory. Considering the potential of endothelial progenitor-based cytotherapies, future studies on their glycemic memory are warranted to develop epigenetics-based therapeutics targeting diabetic vascular complications.

Quality Assurance for GCxGC-FID, Accreditation for TPH CWG Protocol

A new technological approach in the analysis and forensic interpretation of Total Hydrocarbons in soils and waters using 2D Gas Chromatography method (GC-GC) was developed alongside environmental forensic and the assessment models to provide better customer products for the environmental industry.
The objective was to develop an analytical methodology for TPH CWG. Raw data from this method is then to be evaluated for forensic interpretation and risk assessment modelling. Access will be made available to the expertise in methods of forensic tracing contaminant sources, transport modelling, human health risk modelling and detailed quantitative risk assessment.
The quantification of internal standards was key to the development of this method. As the laboratory does not test for TPH in 1D, it was requested during INAB ISO 17025 audit to individually map out where each compound falls chromatographically in the 2D. This was done through comparing carbon equivalent numbers to the n-alkane carbons. This proved e.g. 2-methylnaphthalene has 11 carbons in its structure; its carbon equivalent is 12.84 , the result of which falls within the band of Aromatic eC12-eC16 as opposed to expected eC10-eC12. This was carried out for all 16 PAH (polyaromatic hydrocarbons) and BTEX (benzene, toluene, ethylbenzene and o, m and p-xylenes). The n-alkanes were also assigned to their corresponding aliphatic bands e.g. nC8 would be expected to be in nC8-nC10.
The method was validated through a designated systematic experimental protocol and was challenged with spikes of known concentration of hydrocarbon parameters such as recoveries, precision, bias and linearity. The method was verified by testing a certified reference material which was used as a proficiency round of testing for numerous laboratories.
It is hoped that the method will be used in conjunction with the analysis through Bonn Agreement with their OSINet group. This is a panel of experts and laboratories (including CLS) who forensically identify oil spill contamination from a water source.
This method can prove itself to be a robust method and benefit the industry for contaminated land and water but the method needs to be seen as separate from the regular 1D chromatography. It will help identify contaminants and assist consultants, regulators, clients and scientists valuable information not seen in 1D

The molecular basis of galactosemia - Past, present and future

Galactosemia, an inborn error of galactose metabolism, was first described in the 1900s by von Ruess. The subsequent 100years has seen considerable progress in understanding the underlying genetics and biochemistry of this condition. Initial studies concentrated on increasing the understanding of the clinical manifestations of the disease. However, Leloir's discovery of the pathway of galactose catabolism in the 1940s and 1950s enabled other scientists, notably Kalckar, to link the disease to a specific enzymatic step in the pathway. Kalckar's work established that defects in galactose 1-phosphate uridylyltransferase (GALT) were responsible for the majority of cases of galactosemia. However, over the next three decades it became clear that there were two other forms of galactosemia: type II resulting from deficiencies in galactokinase (GALK1) and type III where the affected enzyme is UDP-galactose 4'-epimerase (GALE). From the 1970s, molecular biology approaches were applied to galactosemia. The chromosomal locations and DNA sequences of the three genes were determined. These studies enabled modern biochemical studies. Structures of the proteins have been determined and biochemical studies have shown that enzymatic impairment often results from misfolding and consequent protein instability. Cellular and model organism studies have demonstrated that reduced GALT or GALE activity results in increased oxidative stress. Thus, after a century of progress, it is possible to conceive of improved therapies including drugs to manipulate the pathway to reduce potentially toxic intermediates, antioxidants to reduce the oxidative stress of cells or use of "pharmacological chaperones" to stabilise the affected proteins.

In Pursuit of Human Dignity

The discussion of human dignity raises such complex issues, and the issues that current scholarship now considers central to its understanding are so daunting, that we are in danger of not being able to see the forest for the trees. This Introduction forms the first chapter of a book of essays (Christopher McCrudden (ed.), UNDERSTANDING HUMAN DIGNITY,
Proceedings of the British Academy/Oxford University Press, in press) by a multi-disciplinary group of historians, legal academics, judges, political scientists, theologians, and philosophers, arising from a Conference held in Rhodes House, Oxford In June 2012. The Introduction aims to provide a guide, a map, through the thicket of current dignity scholarship. It situates the subsequent chapters of the book within an overview of the terrain that currently constitutes debates about the use of dignity in these fields. I have not attempted to put forward my own
comprehensive account of dignity. Mostly based on the rich conversations that took place at the Conference, I have sought, rather, to probe the potential strengths and weaknesses of all of the principal positions identified, at least in some contexts taking on the role of a Devil’s Advocate.

Navigating Grounded Theory:A critical and reflective response to the challenges of using grounded theory in an education PhD

This paper offers a critical reflection upon the use of a grounded theory approach within a doctoral study. As well as providing an outline of grounded theory, it begins by noting the existence of some powerful critiques of a grounded theory approach, in particular around the key concepts of ‘theory’, ‘discovery’ and ‘ground’. It is argued that, in some cases, grounded theory struggles to counter these challenges, especially in its ‘purist’ forms. However, with reference to research carried out as part of a PhD study of sharing education in Northern Ireland which employed a grounded theory approach, a case is made for an open and critical grounded theory based upon three principles: pragmatism; research as practice; and reflexivity. It is concluded that a reasonable case can be made for grounded theory where: grounded theory researchers maintain a balance between belonging to and critique of the grounded theory community; where there is an emphasis upon theorizing rather than the discovery of theory; and where the strengths of grounded theory as 'practice' and 'craft' are maximised.

Interpreting signals from astrophysical transient experiments

Time domain astronomy has come of age with astronomers now able to monitor the sky at high cadence both across the electromagnetic spectrum and using neutrinos and gravitational waves. The advent of new observing facilities permits new science, but the ever increasing throughput of facilities demands efficient communication of coincident detections and better subsequent coordination among the scientific community so as to turn detections into scientific discoveries. To discuss the revolution occurring in our ability to monitor the Universe and the challenges it brings, on 2012 April 25-26 a group of scientists from observational and theoretical teams studying transients met with representatives of the major international transient observing facilities at the Kavli Royal Society International Centre, UK. This immediately followed the Royal Society Discussion meeting "New windows on transients across the Universe" held in London. Here we present a summary of the Kavli meeting at which the participants discussed the science goals common to the transient astronomy community and analysed how to better meet the challenges ahead as ever more powerful observational facilities come on stream.