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.

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.

Missions and Institutions: Henri-Philippe Junod, Anthropology, Human Rights and Academia between Africa and Switzerland, 1921–1966

Drawing on a cultural, transnational and genealogical approach, this article studies the work of a Swiss missionary, Henri-Philippe Junod, between Europe and Africa. It tries not to look at what he brought to Africa, or brought back from Africa, but to see how his back-and-forth movement contributed to the formation of new ideas and institutions globally. The article looks at Junod’s contribution in three domains in particular, namely anthropology, human rights worldwide, and African studies in Switzerland.

Article 6 ECHR, Civil Rights and the Enduring Role of the Common Law

This article examines the role that the common law has played in Human Rights Act 1998 case law on the protection of 'civil rights' within the meaning of Article 6 ECHR. Focusing on Article 6 ECHR's 'disclosure' and 'full jurisdiction' requirements, it highlights an increasingly nuanced relationship between the ECHR and common law in cases under and outside the Human Rights Act 1998. Although the general pattern within the case law has been one of domestic court fidelity to the ECHR - something that is wholly consistent with section 2 of the Human Rights Act 1998 - the article notes areas in which the courts have been reluctant to adapt common law principles, as well as instances of common law protections exceeding those available under Article 6 ECHR. The article suggests that such lines of reasoning reveal a robustness within the common law that brings a multi-dimensional quality to the Human Rights Act 1998. It also suggests that such robustness can be analysed with reference to 'common law constitutionalism' and a corresponding imagery of 'dialogue' between the domestic courts and European Court of Human Rights.

Human Rights and the United Kingdom Supreme Court

After setting the scene by explaining the constraints which are placed on the Justices of the UK Supreme Court, this book considers how human rights are conceptualized by the Court in general and how in particular the procedural questions thrown up by the Human Rights Act have been dealt with so far. It then examines on a right-by-right basis the Justices' position on all the European Convention rights and some additional international human rights standards incorporated into UK law.

Constitutive expression of human keratin 14 gene in mouse lung induces premalignant lesions and squamous differentiation

Squamous cell carcinoma accounts for 20% of all human lung cancers and is strongly linked to cigarette smoking. It develops through premalignant changes that are characterized by high levels of keratin 14 (K14) expression in the airway epithelium and evolve through basal cell hyperplasia, squamous metaplasia and dysplasia to carcinoma in situ and invasive carcinoma. In order to explore the impact of K14 in the pulmonary epithelium that normally lacks both squamous differentiation and K14 expression, human keratin 14 gene hK14 was constitutively expressed in mouse airway progenitor cells using a mouse Clara cell specific 10 kDa protein (CC10) promoter. While the lungs of CC10-hK14 transgenic mice developed normally, we detected increased expression of K14 and the molecular markers of squamous differentiation program such as involucrin, loricrin, small proline-rich protein 1A, transglutaminase 1 and cholesterol sulfotransferase 2B1. In contrast, wild-type lungs were negative. Aging CC10-hK14 mice revealed multifocal airway cell hyperplasia, occasional squamous metaplasia and their lung tumors displayed evidence for multidirectional differentiation. We conclude that constitutive expression of hK14 initiates squamous differentiation program in the mouse lung, but fails to promote squamous maturation. Our study provides a novel model for assessing the mechanisms of premalignant lesions in vivo by modifying differentiation and proliferation of airway progenitor cells. © The Author 2008. Published by Oxford University Press. All rights reserved.

Truth Recovery and Transitional Justice: Deferring human rights issues

This book investigates why some societies defer the solution of transitional justice issues, such as the disappeared/missing, even after successful democratic consolidation. It also explains why the same societies finally decide to deal with these human rights issues. In short, it considers the interesting and understudied phenomenon of post-transitional justice. The prolonged silences in Spain, Cyprus and Greece contradict the experience of other countries -- such as South Africa, Bosnia, and Guatemala -- where truth recovery for disappeared/missing persons was a central element of the transition to peace and democracy. Despite democratization, the exhumation of mass graves containing the victims from the violence in Cyprus (1963-1974) and the Spanish civil war (1936-1939) was delayed until the early 2000s, when both countries suddenly decided to revisit the past. Cyprus and Spain are not alone: this is an increasing trend among countries trying to come to terms with past violence. Interestingly, despite similar background conditions, Greece is resisting the trend, challenging both theory and regional experience. Truth Recovery and Transitional Justice considers three interrelated issues. First, what factors can explain prolonged silence on the issue of missing persons in some transitional settings? Second, which processes can address the occasional yet puzzling transformation of victims’ groups from opponents of truth recovery to vocal pro-reconciliation pressure groups? Third, under which conditions is it better to tie victims’ rights to an overall political settlement? The book looks at Spain and Cyprus to show how they have attempted to bring closure to deep trauma by exhuming and identifying their missing, albeit under considerably different conditions. It then probes the generalizability of the conclusions on Spain and Cyprus by looking at the Greek experience; oddly, despite similar background conditions, Greece remains resistant to post-transitional justice norms. Interestingly, each case study takes a different approach to transitional justice.

Relatively Absolute? The Undermining of Article 3 ECHR in Ahmad v UK

The recent decision of the European Court of Human Rights in Ahmad v UK dangerously undermines the well-established case law of the Court on counter-terrorism and non-refoulement towards torture, inhuman and degrading treatment or punishment. Although ostensibly rejecting the ‘relativist’ approach to Article 3 ECHR adopted by the House of Lords in Wellington v Secretary of State for the Home Department, the Court appeared to accept that what is a breach of Article 3 in a domestic context may not be a breach in an extradition or expulsion context. This statement is difficult to reconcile with the jurisprudence constante of the Court in the last fifteen years, according to which Article 3 ECHR is an absolute right in all its applications, including non-refoulement, regardless of who the potential victim of torture, inhuman or degrading treatment is, what she may have done, or where the treatment at issue would occur.

The Human Rights Act 1998 – Future Prospects

It is now over fifteen years since the Human Rights Act was enacted in November 1998. Although in legal terms it is difficult to argue with the proposition that the Act is working in an effective manner, in political terms the Act remains one of the most highly debated pieces of legislation on the UK statute books. In recent years there have been numerous calls for the repeal of the Act, and for its replacement with a ‘UK Bill of Rights’. Such calls led to the establishment of a Commission on a Bill of Rights, which issued its final report in December 2012. Little progress has since been made on the issue. One notable occurrence however was the introduction of the Human Rights Act 1998 (Repeal and Substitution) Bill, a Private Member’s Bill which was eventually withdrawn in March 2013. This article seeks to assess the current situation regarding the bill of rights debate, and ultimately the question of the future prospects of the Human Rights Act, an issue of immense legal significance. Overall, it will be questioned whether the enactment of a UK Bill of Rights would constitute an improvement on the current position under the Human Rights Act.

The European Convention on Human Rights Act 2003 – Ten Years On

The European Convention on Human Rights Act 2003 has now been in force in Ireland for ten years. This article analyses the Act itself and the impact which it has had on the Irish courts during the first decade of its operation. The use of the European Convention on Human Rights in the Irish courts prior to the enactment of the legislation is discussed, as are the reasons for the passing of the Act. The relationship between the Act and the Irish Constitution is examined, as is the jurisprudence of the Irish courts towards the interpretative obligation found in section 2(1), and the duty placed upon organs of the State by section 3(1). The article ends with a number of observations regarding the impact which the Act has had on the Irish courts at a more general level. Comparisons will be drawn with the UK’s Human Rights Act 1998 throughout the discussion.