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.

Using Comparative Constitutionalism in Human Rights Discourse:Ireland’s Past and Scotland’s Future

The article considers the use of comparisons in constitutional development, specifically the use of comparative reasoning in the context of debates about human rights in newly emerging independent states, using the examples of Ireland and Scotland.

Further evidence for a bifactor solution for the Consideration of Future Consequences Scale: Measurement and conceptual implications

The Consideration of Future Consequences construct has been found to relate meaningfully to several positive outcomes in temporal research. Researchers have proposed 1-factor, 2-factor, and bifactor solutions to the Consideration of Future Consequences Scale (CFCS). Using 313 British University undergraduates, we tested four competing models: (a) a 12-item unidimensional model, (b) a model fitted for two uncorrelated factors (CFC-Immediate and CFC-Future), (c) a model fitted for two correlated factors (CFC-I and CFC-F), and (d) a bifactor model. Results supported the bifactor model, suggesting that the two hypothesized factors are better understood as grouping factors. Accordingly, the present study supports the CFCS as a unidimensional global future orientation measure. These results have important implications for the study of future orientation using the CFCS. Researchers using the CFCS are encouraged to examine a bifactor solution for the scores.

The Muslim Brotherhood: the Arab Spring its Future Face

The Muslim Brotherhood is the most significant and enduring Sunni Islamist organization of the contemporary era. Its roots lie in the Middle East but it has grown into both a local and global movement, with its well-placed branches reacting effectively to take the opportunities for power and electoral competition offered by the Arab Spring.

Regarded by some as a force of moderation among Islamists, and by others as a façade hiding a terrorist fundamentalist threat, the potential influence of the Muslim Brotherhood on Middle Eastern politics remains ambiguous.The Muslim Brotherhood: The Arab Spring and its Future Face provides an essential insight into the organisation, with chapters devoted to specific cases where the Brotherhood has important impacts on society, the state and politics. Key themes associated with the Brotherhood, such as democracy, equality, pan-Islamism, radicalism, reform, the Palestine issue and gender, are assessed to reveal an evolutionary trend within the movement since its founding in Egypt in 1928 to its manifestation as the largest Sunni Islamist movement in the Middle East in the 21st century. The book addresses the possible future of the Muslim Brotherhood; whether it can surprise sceptics and effectively accommodate democracy and secular trends, and how its ascension to power through the ballot box might influence Western policy debates on their engagement with this manifestation of political Islam.

Drawing on a wide range of sources, this book presents a comprehensive study of a newly resurgent movement and is a valuable resource for students, scholars and policy makers focused on Middle Eastern Politics.