Genomic instability after targeted irradiation of human lymphocytes: Evidence for inter-individual differences under bystander conditions

Environmental (222)radon exposure is a human health concern, and many studies demonstrate that very low doses of high LET alpha-particle irradiation initiate deleterious genetic consequences in both radiated and non-irradiated bystander cells. One consequence, radiation-induced genomic instability (RIGI), is a hallmark of tumorigenesis and is often assessed by measuring delayed chromosomal aberrations We utilised a technique that facilitates transient immobilization of primary lymphocytes for targeted microbeam irradiation and have reported that environmentally relevant doses, e.g. a single He-3(2+) particle traversal to a single cell, are sufficient to Induce RIGI Herein we sought to determine differences in radiation response in lymphocytes isolated from five healthy male donors Primary lymphocytes were irradiated with a single particle per cell nucleus. We found evidence for inter-individual variation in radiation response (Rid, measured as delayed chromosome aberrations) Although this was not highly significant, it was possibly masked by high levels of intra-individual variation While there are many studies showing a link between genetic predisposition and RIGI, there are few studies linking genetic background with bystander effects in normal human lymphocytes In an attempt to investigate inter-individual variation in the induction of bystander effects, primary lymphocytes were irradiated with a single particle under conditions where fractions of the population were traversed We showed a marked genotype-dependent bystander response in one donor after exposure to 15% of the population The findings may also be regarded as a radiation-induced genotype-dependent bystander effect triggering an instability phenotype (C) 2010 Elsevier B.V. All rights reserved.

‘Governing (Through) Rights: Statistics as Technologies of Governmentality’

An increasing amount of attention is being given to the use of human rights measurement indicators in monitoring ‘progress’ in rights and there is consequently a growing focus on statistics and information. This article concentrates on the use of statistics in rights discourse, with reference to the new human rights institution for the European Union: the Fundamental Rights Agency. The article has two main objectives: first, to show that statistics operate as technologies of governmentality – by explaining that statistics both govern rights and govern through rights. Second, the article discusses the implications that this has for rights discourse – rights become a discourse of governmentality, that is a normalizing and regulating discourse. In doing so, the article stresses the importance of critique and questioning new socio-legal methodologies, which involve the collection and dissemination of information and data (statistics), in rights discourse.

‘Government(ality) By Experts: Human Rights as Governance’

The suggestion that the general economy of power in our societies is becoming a domain of security was made by Michel Foucault in the late 1970s. This paper takes inspiration from Foucault?s work to interpret human rights as technologies of governmentality, which make possible the safe and secure society. I examine, by way of illustration, the site of the European Union and its use of new modes of governance to regulate rights discourse – in particular via the emergence of a new Fundamental Rights Agency. „Governance? in the EU is constructed in an apolitical way, as a departure from traditional legal and juridical methods of governing. I argue, however, that the features of governance represent technologies of government(ality), a new form of both being governed through rights and of governing rights. The governance feature that this article is most interested in is experts. The article aims to show, first and foremost, how rights operate as technologies of governmentality via a new relation to expertise. Second, it considers the significant implications that this reading of rights has for rights as a regulatory and normalising discourse. Finally, it highlights how the overlap between rights and governance discourses can be problematic because (as the EU model illustrates) governance conceals the power relations of governmentality, allowing, for instance, the unproblematic representation of the EU as an international human rights actor

Metabolic and structural properties of human obestatin {1-23} and two fragment peptides

Obestatin is a peptide produced in the oxyntic mucosa of the stomach and co-localizes with ghrelin on the periphery of pancreatic islets. Several studies demonstrate that obestatin reduces food and water intake, decreases body weight gain, inhibits gastrointestinal motility, and modulates glucose-induced insulin secretion. In this study we evaluated the acute metabolic effects of human obestatin {1-23} and fragment peptides {1-10} or {11-23} in high-fat fed mice, and then investigated their solution structure by NMR spectroscopy and molecular modelling. Obestatins {1-23} and {11-23} significantly reduced food intake (86% and 90% respectively) and lowered glucose responses to feeding, whilst leaving insulin responses unchanged. No metabolic changes could be detected following the administration of obestatin (1-10). In aqueous solution none of the obestatin peptides possessed secondary structural features. However, in a 2,2,2-trifluoroethanol (TFE-d(3))-H2O solvent mixture, the structure of obestatin {1-23} was characterized by an a-helix followed by a single turn helix conformation between residues Pro(4) and Gln(15) and His(19) and Ala(22) respectively. Obestatin {1-10} showed no structural components whereas {11-23} contained an a-helix between residues Val(14) and Ser(20) in a mixed solvent. These studies are the first to elucidate the structure of human obestatin and provide clear evidence that the observed a-helical structures are critical for in vivo activity. Future structure/function studies may facilitate the design of novel therapeutic agents based on the obestatin peptide structure. (C) 2010 Elsevier Inc. All rights reserved.

In vivo and in vitro function of human UDP-galactose 4 '-epimerase variants

Type III galactosemia results from reduced activity of the enzyme UDP-galactose 4'-epimerase. Five disease-associated alleles (G90E, V94M, D103G, N34S and L183P) and three artificial alleles (Y105C, N268D, and M284K) were tested for their ability to alleviate galactose-induced growth arrest in a Saccharomyces cerevisiae strain which lacks endogenous UDP-galactose 4'-epimerase. For all of these alleles, except M284K, the ability to alleviate galactose sensitivity was correlated with the UDP-galactose 4'-epimerase activity detected in cell extracts. The M284K allele, however, was able to substantially alleviate galactose sensitivity, but demonstrated near-zero activity in cell extracts. Recombinant expression of the corresponding protein in Escherichia coil resulted in a protein with reduced enzymatic activity and reduced stability towards denaturants in vitro. This lack of stability may result from the introduction of an unpaired positive charge into a bundle of three alpha-helices near the surface of the protein. The disparities between the in vivo and in vitro data for M284K-hGALE further suggest that there are additional, stabilising factors present in the cell. Taken together, these results reinforce the need for care in the interpretation of in vitro, enzymatic diagnostic tests for type III galactosemia. (C) 2011 Elsevier Masson SAS. All rights reserved.

Book Review: Critical Perspectives on Human Rights and Disability Law

Book Review

Applying an International Human Rights Framework to State Budget Allocations: Rights and Resources

Human rights based budget analysis projects have emerged at a time when the United Nations has asserted the indivisibility of all human rights and attention is increasingly focused on the role of non-judicial bodies in promoting and protecting human rights. This book seeks to develop the human rights framework for such budget analyses, by exploring the international law obligations of the International Covenant on Economic, Social and Cultural Rights (ICESCR) in relation to budgetary processes. The book outlines international experiences and comparative practice in relation to economic and social rights budget analysis and budgeting.

The book sets out an ICESCR-based methodology for analysing budget and resource allocations and focuses on the legal obligation imposed on state parties by article 2(1) of ICESCR to progressively realise economic and social rights to 'the maximum of available resources'. Taking Northern Ireland as a key case study, the book demonstrates and promotes the use of a ‘rights-based’ approach in budgetary decision-making.

The book will be relevant to a global audience currently considering how to engage in the budget process from a human rights perspective. It will be of interest to students and researchers of international human rights law and public law, as well as economic and social rights advocacy and lobbying groups.

Amnesties in Transition: Punishment, Restoration, and the Governance of Mercy

Despite the much vaunted triumph of human rights, amnesties continue to be a frequently used technique of post-conflict transitional justice. For many critics, they are synonymous with unaccountability and injustice. This article argues that despite the rhetoric, there is no universal duty to prosecute under international law and that issues of selectivity and proportionality present serious challenges to the retributive rationale for punishment in international justice. It contends that many of the assumptions concerning the deterrent effect in the field are also oversold and poorly theorized. It also suggests that appropriately designed restorative amnesties can be both lawful and effective as routes to truth recovery, reconciliation, and a range of other peacemaking goals. Rather than mere instruments of impunity, amnesties should instead be seen as important institutions in the governance of mercy, the reassertion of state sovereignty and, if properly constituted, the return of law to a previously lawless domain.

Human Rights in Irish Prisons

Ireland is bound by several international instruments in the area of prisoners’ rights and penal policy and the ongoing reform in the Irish prison system means that the time is opportune to consider the extent to which these legal obligations are currently met and to evaluate what needs to be done to ensure greater compliance. The aim of this article is thus to examine Ireland’s record in prisoners’ rights against international standards and to determine where reform needs to take place in order to ensure full respect for the rights of prisoners in Irish law, policy and practice.