The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa. Heredity (2010) 104, 148-154; doi:10.1038/hdy.2009.84; published online 29 July 2009

The Essential Role of Human Databases for Learning in and Validation of Affectively Competent Agents.

This output is an invited and refereed chapter in the second of the two book length outputs resulting from the EU HUMAINE grant and follow-on grants. The book is in the OUP Affective Science Series and is intended to provide a theoretically oriented state of the art model for those working in the area of affective computing. Each chapter provides a synthesis of a specific area and presents new data/findings/approaches developed by the author(s) which take the area further. This chapter is in the section on ‘Approaches to developing expression corpora and databases.’ The chapter provides a critical synthesis of the issues involved in databases for affective computing and introduces the SEMAINE SAL Database, developed as an integral part of the EU SEMAINE Project (The Sensitive Agent Project 2008-2011) which is an interdisciplinary project. The project aimed to develop a computer interface that would allow a human to interact with an artificial agent in an emotional manner.

Identification of different specificity requirements between SGK1 and PKB alpha

NDRG1 is phosphorylated by SGK1 (but not PKB) in vivo at three residues each contained within three nonapeptide repeats. Here, we demonstrate that this nonapeptide, like the NDRG1 protein, is phosphorylated by SGK1, but not by PKBalpha or RSK1 in vitro. The inability of PKBa and RSK1 to phosphorylate the nonapeptide was traced to residues n + 1, n + 2 and n - 4 (where n is the phosphorylation site). Changing them from Ser, Glu and Ser to Phe, Ala and Pro, respectively, transformed the nonapeptide into an excellent substrate for PKBalpha and RSK1. Our results identify a specific substrate for SGK1 and may facilitate detection of additional physiological substrates for this enzyme. (C) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Sexual division of antibacterial resource defence in breeding burying beetles, Nicrophorus vespilloides

A key component of parental care involves defending resources destined for offspring from a diverse array of potential interspecific competitors, such as social parasites, fungi and bacteria. 2. Just as with other aspects of parental care, such as offspring provisioning or brood defence, sexual conflict between parents may arise over how to share the costs of this form of care. There has been little previous work, however, to investigate how this particular burden might be shared. 3. Here, we describe a hitherto uncharacterized form of parental care in burying beetles Nicrophorus vespilloides, a species which prepares carrion for its young and faces competition from microbes for this resource. We found that parents defend the carcass with antibacterial anal exudates, and that the antibacterial activity of these exudates is only upregulated following the discovery of a corpse. At the same time, phenoloxidase activity in the anal exudates is downregulated, indicating parallels with the internal insect immune system. 4. In unmanipulated breeding pairs, females had higher antibacterial activity in their anal exudates than males, suggesting sex-specific roles in this aspect of parental care. 5. When we experimentally widowed males, we found that they increased levels of antibacterial activity in their anal exudates. Experimentally widowing females, however, led them to decrease levels of antibacterial activity in their anal exudates. Widowed beetles of each sex thus produced anal exudates of comparable antibacterial activity. We suggest that this flexible division of antibacterial activity may be coordinated by Juvenile Hormone. © 2009 British Ecological Society.

The European Court of Human Rights and Domestic Violence

Domestic violence is an issue that affects vast numbers of women throughout the world. It seems to constitute a clear violation of at least three articles of the European Convention on Human Rights, however it has only been recognised as being a human rights issue relatively recently. Indeed, until 2007 domestic violence had not been directly addressed by the European Court of Human Rights. However, the Court has now addressed the issue in a series of recent cases. This paper discusses what positive obligations states parties to the Convention now have in relation to the issue of domestic violence. It proceeds to discuss the gaps in the Court’s jurisprudence in this area at present and how the case law of the Court may develop in the future.

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.

Why do they go? Empirical evidence of employees' motives for seeking or accepting relocation

This study addresses one of the shortcomings apparent in previous research on expatriate job-transfers, namely the lack of exploratory, empirical groundwork into the motives of expatriates to seek or accept international assignments. The relocatee population of a large German MNC was surveyed for their motives to seek or accept their transfer, using an open-response format. Responses were content analysed in order to arrive at an empirically grounded set of motives. The findings provide a very detailed picture of employees' motives to seek or accept international assignments and thus an important interim result that, when used as input in subsequent investigations, promises highly relevant results due to established content validity.