Between-strand disulfides: Forbidden disulfides linking adjacent ß-Strands

Between-strand disulfides (BSDs) connect cysteine (Cys) residues across adjacent strands of β-sheets. There are four BSD types which can be found in regular β-structure: CSDs, which link residues immediately opposite each other in the β-structure (residues i and j); ETDs, which connect Cys out of register by one residue (i and j ± 1); BDDs, which join Cys at positions i and j ± 2; and BFDs, which link residues i and j ± 3. Formation of these disulfides was initially predicted to be forbidden, producing too much local strain in the protein fold. However, BSDs do exist in nature. Significantly, their high levels of strain allow them to be involved in redox processes under physiological conditions. Here we characterise BSD motifs found in the Protein Data Bank (PDB), discussing important intrinsic factors, such as the disulfide conformation and torsional strain, and extrinsic factors, such as the influence of the β-sheet environment on the disulfide and vice versa. We also discuss the biological importance of BSDs, including the prevalence of non-homologous examples in the PDB, the conservation of BSD motifs amongst related proteins (BSD clusters) and experimental evidence for BSD redox activity. For clusters of homologous BSDs we present detailed data of the disulfide properties and the variations of these properties amongst the “redundant” structures. Identification of disulfides with the potential to be involved in biological redox processes via the analysis of these data will provide important insights into the function and mechanism of BSD-containing proteins. Characterisation of thiol-based redox signalling pathways will lead to significant breakthroughs in understanding the molecular basis of oxidative stress and associated pathways, such as ageing and neurodegenerative diseases

Isospecific Polymerization of Racemic Epoxides: a Catalyst System for the Synthesis of Highly Isotactic Polyethers

A highly active bimetallic cobalt catalyst system is reported for the polymerization of racemic terminal epoxides to yield isotactic polyethers.We acknowledge the NSF (CHE-0809778) and the King Abdullah University of Science and Technology (KAUST; Award No. KUS-C1-018-02) for support of this research. The authors are grateful for the help of T. Mourey at Kodak for polymer molecular weight determinatio

Bimetallic Catalysts For Enantioselective Epoxide Polymerization: Establishing And Using Mechanistic Hypotheses To Develop Enhanced Catalyst Systems

In 2008, the Coates group reported a bimetallic cobalt catalyst that enantioselectively polymerized terminal epoxides to form highly isotactic polyethers and enantiopure epoxides. The complex catalyst system, which consisted of the catalyst and a cocatalyst, was extremely difficult to study due to the paramagnetism of the catalyst, short reaction times, exothermic nature of the reaction, induction periods, and precipitation of polyether during polymerization. Despite these challenges, a viable mechanistic hypothesis for the enchainment of epoxides was established using experimental observations and theoretical calculations focused on the structural features of the catalyst, the oxidation state of the metal center, the role of the cocatalyst, and free-energy changes during propagation of epoxide. The mechanistic insight gained was used to develop enhanced catalysts through systematic ligand variations, enabling higher activity and selectivity for isotactic polyether synthesis under milder and more controlled reaction conditions

Outsourcing: Opportunities and challenges for India and the USA

The global outsourcing of services has become increasingly important in the debate over globalization. In India, the most high profile services exporter, GDP per capita increased rapidly between 2001 and 2006 in a climate of increasing services trade, with the export-oriented services sector responsible for greater shares of GDP growth. Despite its contributions to aggregate economic growth, there is no empirical examination of how these gains are distributed across the economy. At the same time, there are many fears in the USA that greater services imports will have detrimental effects on US wages and employment by displacing occupations whose activities are currently not tradable, but could become tradable in the future. While economic theory is useful in conceptualizing the problem of outsourcing, purely analytical approaches have not been able to address the questions being posed by policy makers. Therefore empirical methods are necessary. A global general equilibrium model was used to examine how the historical changes in India’s services trade affected factor incomes across different industries. The analysis concludes that factors of production in the urban-based services sector benefited from the services trade growth. At the same time outsourcing has hurt the incomes of the owners of capital in the rural and suburban based agriculture and manufacturing sectors, indicative of a widening of income inequality. Shifting the analysis to the USA, a panel data econometric analysis of US manufacturing industries between 1998 and 2004 found that historically, services imports have only had a small influence on the demand for skilled workers. Moving past historical changes, a USA focused specific-factors general equilibrium model was used to analyze how wages of different occupational groups will be affected if outsourcing increases enough to displace the maximum possible share of US employment. The US economy as a whole would grow, although most occupations that could be classified as tradable would suffer from wage declines. Legal workers would be an exception, and experience wage increases instead. Several nontradable occupational groups would benefit through wage gains, although a handful of labor types, including construction and transportation workers are projected to suffer from the growth of outsourcing

The Impact of Liberalizing Labor Mobility in the Pacific Region

Due to the lack of political consensus at the previous General Agreement on Trade on Services (GATS), negotiations on the temporary movement of natural persons (Mode 4) have stagnated. The growth in the economic literature surrounding this issue has also been lackluster; despite the large welfare gains that have been demonstrated to result from relatively small multilateral liberalizations on such transitory movements. This paper implements a CGE model of bilateral migration flows to quantify the benefits of liberalising GATS Mode 4 in the Pacific region. The results indicate that an increase in the labor forces of Australia and New Zealand from elsewhere within the Pacific region would raise welfare in both Australia and New Zealand. However the results show that while the Pacific Islands economies could gain substantially from the movement of unskilled workers, the loss of scarce skilled workers could lead to significant declines in the welfare of those remaining. Agreements regarding the movement of unskilled labor could therefore potentially constitute significant development policies which warrant further attention from policy makers

What price tolerance?

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