New perspectives on neoplasia and the RNA world

<p>Key tenets of modern biology are the central place of protein in cell regulation and the flow of genetic information from DNA to RNA to protein. However, it is becoming increasingly apparent that genomes are much more complex than hitherto thought with remarkably complex regulatory systems. The notion that the fraction of the genome involved in coding protein is all that matters is increasingly being questioned as the roles of non-coding RNA (ncRNA) in cellular systems becomes recognised. The RNA world, including microRNA (miRNA), small inhibitory RNA (siRNA) and other RNA species, are now recognised as being crucial for the regulation of chromatin structure, gene expression, mRNA processing and splicing, mRNA stability and translational control. Furthermore such ncRNA systems may be perturbed in disease states and most notably in neoplasia, including in haematological malignancies. Here the burgeoning evidence for a role of miRNA in neoplasia is reviewed and the importance of understanding the RNA world emphasised. Copyright (c) 2005 John Wiley &amp; Sons, Ltd.</p>

UK National Report on Asylum and the Status of Non-EU Aliens

(with G. Anthony)

A multiple-radical model for radiation action on DNA and the dependence of OER on LET

We have a developed a multiple-radical model of the chemical modification reactions involving oxygen and thiols relevant to the interactions of ionizing radiations with DNA. The treatment is based on the Alper and Howard-Flanders equation but considers the case where more than one radical may be involved in the production of lesions in DNA. This model makes several predictions regarding the induction of double strand breaks in DNA by ionizing radiation and the role of sensitizers such as oxygen and protectors such as thiols which act at the chemical phase of radiation action via the involvement of free radicals. The model predicts a decreasing OER with increasing LET on the basis that as radical multiplicity increases so will the probability that, even under hypoxia, damage will be fixed and lead to lesion production. The model can be considered to provide an alternative hypothesis to those of 'interacting radicals' or of 'oxygen-in-the-track'.

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.

On Extraterritoriality and the Gazprom case

In September 2012 the European Commission opened a formal investigation of Gazprom’s business practices in the EU. The Gazprom investigation raises a number of questions. One of them is the issue of jurisdiction—whether EU competition law applies to Gazprom, a foreign company. A day after the opening of the proceeding, in a press note and alongside other issues, Gazprom raised the question of jurisdiction, noting that it complies with laws of the countries in which it operates and that is it ‘registered outside the jurisdiction of the EU’. This statement, possibly, prompted some commentators to consider the applicability of EU law in this case.<br/>In a piece in the ECLR, entitled ‘Iron Curtain at the border: Gazprom and the Russian blocking order to prevent the extraterritoriality of EU competition law’, Sean Morris offered his views on some of the aspects of the Gazprom case, including the issue of jurisdiction. Morris discussed also the blocking Order issued by the Russian President in response to the European Commission’s investigation, and its possible effects in the Gazprom case.<br/>This article seeks to add a few important and relevant issues of law relating to extraterritoriality and the reach of EU law generally and in particular— in the context of the Gazprom investigation and in the light of the Morris article. This piece also sheds some light on the considerations which might have informed Russia’s hastily enactment of the Blocking Order.

Deconstructing Victim and offender Identities in Discourses on Child Sexual Abuse: Hierarchies, Blame and the Good/Evil Dialectic

Contemporary social and political constructions of victimhood and offending behaviour lie at the heart of regulatory policies on child sexual abuse. Legislation is named after specific child victims of high profile cases, and a burgeoning range of pre-emptive measures are enacted to protect an amorphous class of ‘all potential victims’ from the risk sex offenders are seen as posing. Such policies are also heavily premised on the omnipresent predatory stranger. These constructed identities, however, are at odds with the actual identities of victims and offenders of such crimes. Drawing on a range of literatures, the core task of this article is to confront some of the complexities and tensions surrounding constructions of the victim/offender dyad within the specific context of sexual offending against children. In particular, the article argues that discourses on ‘blame’ – and the polarised notions of ‘innocence’ and ‘guilt’ – inform respective hierarchies of victimhood and offending concerning ‘legitimate’ victim and offender status. Based on these insights, the article argues for the need to move beyond such monochromatic understandings of victims and offenders of sexual crime and to reframe the politics of risk accordingly.

Pre-intravitrael injection preparation: endophthalmitis prevention and the importance of povidone-iodine

Despite adherence to strict standards of care in preparation for intravitreal injections, endophthalmitis can still occur. This article focuses on endophthalmitis and the importance of povidone-iodine in pre-procedure antisepsis. An overview of endophthalmitis and an examination of the benefits of povidone-iodine in ocular aseptic technique for the prevention of post-procedure endophthalmitis are provided. The misconceptions that patients and health practitioners may have in relation to povidone-iodine hypersensitivity are also explored.

Nutrition and the eye

The topic "nutrition and the eye" cannot adequately be covered in a single review article; indeed, dozens of books and hundreds of articles have been written on the subject. This review concentrates on three areas in which specific nutrients are known or theorized to have a major impact on vision and the visual system: vitamin A deficiency; antioxidants and their proposed role in the prevention of age-related cataract and macular degeneration; and nutritional optic neuropathies, including those of the recent Cuban epidemic. In addition, this article touches on nutritional treatments that have been suggested for several less common eye diseases and, finally, considers several less prevalent conditions in which deficiency of or excess exposure to a particular nutrient has been associated with ocular pathology.