A whole-genome scan for recurrent airway obstruction in Warmblood sport horses indicates two positional candidate regions

Recurrent airway obstruction (RAO), or heaves, is a naturally occurring asthma-like disease that is related to sensitisation and exposure to mouldy hay and has a familial basis with a complex mode of inheritance. A genome-wide scanning approach using two half-sibling families was taken in order to locate the chromosome regions that contribute to the inherited component of this condition in these families. Initially, a panel of 250 microsatellite markers, which were chosen as a well-spaced, polymorphic selection covering the 31 equine autosomes, was used to genotype the two half-sibling families, which comprised in total 239 Warmblood horses. Subsequently, supplementary markers were added for a total of 315 genotyped markers. Each half-sibling family is focused around a severely RAO-affected stallion, and the phenotype of each individual was assessed for RAO and related signs, namely, breathing effort at rest, breathing effort at work, coughing, and nasal discharge, using an owner-based questionnaire. Analysis using a regression method for half-sibling family structures was performed using RAO and each of the composite clinical signs separately; two chromosome regions (on ECA13 and ECA15) showed a genome-wide significant association with RAO at P < 0.05. An additional 11 chromosome regions showed a more modest association. This is the first publication that describes the mapping of genetic loci involved in RAO. Several candidate genes are located in these regions, a number of which are interleukins. These are important signalling molecules that are intricately involved in the control of the immune response and are therefore good positional candidates.

How political economies affect immigrants' socio-economic incorporation. A comparative analysis of immigrants’ poverty risks across advanced industrialised countries

Immigration and the resulting increasing ethnic diversity have become an important characteristic of advanced industrialised countries. At the same time, the majority of the countries in question are confronted with structural transformation such as deindustrialisation and changes in family structures as well as economic downturn, which limit the capacities of nation-states in addressing rising inequality and supporting those individuals at the margins of the society. This paper addresses both issues, immigration and inequality, by focusing on immigrants’ socio-economic incorporation into the receiving societies of advanced industrialised countries. The aim of this paper is to explain cross-national variation in immigrants’ poverty risks. Drawing on the political economy as well as the migration literature, the paper develops a theoretical framework that considers how the impact of the national labour market and welfare system on immigrants’ poverty risks is moderated by the integration policies, which regulate immigrants’ access to the labour market and social programs (or immigrants’ economic and social rights). The empirical analysis draws on income surveys as well as a newly collected data set on economic and social rights of immigrants in 19 advanced industrialised countries, including European countries as well as Australia, and North America, for the year 2007. As the results from multilevel analysis show, integration policies concerning immigrants’ access to the labour market and social programs can partly explain cross-national variations in immigrants’ poverty risks. In line with the hypothesis, stricter labour market regulations such as minimum wage setting reduce immigrants’ poverty risks stronger in countries where they are granted easier access to the labour market. However, concerning the impact of more generous social programs the reductive poverty effect is stronger in countries with less inclusive access of immigrants to social programs. The paper concludes by discussing possible explanations for this puzzling finding.

One size does not fit all: Entrepreneurial families’ reliance on family offices

Family offices are organisations dedicated to the management of entrepreneurial families’ private wealth. Based on agency theory, we analyse types of family offices with regard to the families’ goals and the control mechanisms used to ensure goal achievement. Family-dominant management and private client structures involve stronger emphasis on non-financial goals in single and multi-family offices than in non-family-dominant management and open client structures. Variations in family involvement, ranging from family dominance to the complete absence of family ownership and/or management, and diverse client structures justify the differential reliance on formal and informal control mechanisms.

The SLC1 high-affinity glutamate and neutral amino acid transporter family

Glutamate transporters play important roles in the termination of excitatory neurotransmission and in providing cells throughout the body with glutamate for metabolic purposes. The high-affinity glutamate transporters EAAC1 (SLC1A1), GLT1 (SLC1A2), GLAST (SLC1A3), EAAT4 (SLC1A6), and EAAT5 (SLC1A7) mediate the cellular uptake of glutamate by the co-transport of three sodium ions (Na(+)) and one proton (H(+)), with the counter-transport of one potassium ion (K(+)). Thereby, they protect the CNS from glutamate-induced neurotoxicity. Loss of function of glutamate transporters has been implicated in the pathogenesis of several diseases, including amyotrophic lateral sclerosis and Alzheimer's disease. In addition, glutamate transporters play a role in glutamate excitotoxicity following an ischemic stroke, due to reversed glutamate transport. Besides glutamate transporters, the SLC1 family encompasses two transporters of neutral amino acids, ASCT1 (SLC1A4) and ASCT2 (SLC1A5). Both transporters facilitate electroneutral exchange of amino acids in neurons and/or cells of the peripheral tissues. Some years ago, a high resolution structure of an archaeal homologue of the SLC1 family was determined, followed by the elucidation of its structure in the presence of the substrate aspartate and the inhibitor d,l-threo-benzyloxy aspartate (d,l-TBOA). Historically, the first few known inhibitors of SLC1 transporters were based on constrained glutamate analogs which were active in the high micromolar range but often also showed off-target activity at glutamate receptors. Further development led to the discovery of l-threo-β-hydroxyaspartate derivatives, some of which effectively inhibited SLC1 transporters at nanomolar concentrations. More recently, small molecule inhibitors have been identified whose structures are not based on amino acids. Activators of SLC1 family members have also been discovered but there are only a few examples known.

New insights on the role of paired membrane structures in coronavirus replication.

The replication of coronaviruses, as in other positive-strand RNA viruses, is closely tied to the formation of membrane-bound replicative organelles inside infected cells. The proteins responsible for rearranging cellular membranes to form the organelles are conserved not just among the Coronaviridae family members, but across the order Nidovirales. Taken together, these observations suggest that the coronavirus replicative organelle plays an important role in viral replication, perhaps facilitating the production or protection of viral RNA. However, the exact nature of this role, and the specific contexts under which it is important have not been fully elucidated. Here, we collect and interpret the recent experimental evidence about the role and importance of membrane-bound organelles in coronavirus replication.