Expression cloning and cDNA sequencing of the Na+/glucose co-transporter

Organic substrates (sugars, amino acids, carboxylic acids and neutrotransmitters) are actively transported into eukaryotic cells by Na+ co-transport. Some of the transport proteins have been identified--for example, intestinal brush border Na+/glucose and Na+/proline transporters and the brain Na+/CI-/GABA transporter--and progress has been made in locating their active sites and probing their conformational states. The archetypical Na+-driven transporter is the intestinal brush border Na+/glucose co-transporter (see ref. 8), and a defect in the co-transporter is the origin of the congenital glucose-galactose malabsorption syndrome. Here we describe cloning of this co-transporter by a method new to membrane proteins. We have sequenced the cloned DNA and have found no homology between the Na+/glucose co-transporter and either the mammalian facilitated glucose carrier or the bacterial sugar transport proteins. This suggests that the mammalian Na+-driven transporter has no evolutionary relationship to the other sugar transporters.     

Subjective confidence in forecasts: A response to fischhoff and MacGregor

Here we evaluate the generalizability of calibration studies which have used general knowledge questions, and argue that on conceptual, methodological and empirical grounds the results have limited applicability to judgemental forecasting. We also review evidence which suggests that judgemental forecast probabilities are influenced by variables such as the desirability, imminence, time period and perceived controllability of the event to be forecast. As these variables do not apply to judgement in the domain of general knowledge, a need for research recognizing and exploring the psychological processes underlying uncertainty about the future is apparent.     

Novel reactions of rotenone

Summary Novel reactions of rotenone are described. Demethylation of rotenone under mild conditions was observed. A compound with oxidation state between rotenone and rotenonone was isolated.     

Ocean circulation off east Antarctica affects ecosystem structure and sea-ice extent

Sea ice and oceanic boundaries have a dominant effect in structuring Antarctic marine ecosystems. Satellite imagery and historical data have identified the southern boundary of the Antarctic Circumpolar Current as a site of enhanced biological productivity. Meso-scale surveys off the Antarctic peninsula have related the abundances of Antarctic krill (Euphausia superba) and salps (Salpa thompsoni) to inter-annual variations in sea-ice extent. Here we have examined the ecosystem structure and oceanography spanning 3,500 km of the east Antarctic coastline, linking the scales of local surveys and global observations. Between 80 degrees and 150 degrees E there is a threefold variation in the extent of annual sea-ice cover, enabling us to examine the regional effects of sea ice and ocean circulation on biological productivity. Phytoplankton, primary productivity, Antarctic krill, whales and seabirds were concentrated where winter sea-ice extent is maximal, whereas salps were located where the sea-ice extent is minimal. We found enhanced biological activity south of the southern boundary of the Antarctic Circumpolar Current rather than in association with it. We propose that along this coastline ocean circulation determines both the sea-ice conditions and the level of biological productivity at all trophic levels.     

A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis

Psoriasis (OMIM 177900) is a chronic inflammatory skin disorder of unknown pathogenesis affecting approximately 2% of the Western population. It occurs more frequently in individuals with human immunodeficiency virus, and 20-30% of individuals with psoriasis have psoriatic arthritis. Psoriasis is associated with HLA class I alleles, and previous linkage analysis by our group identified a second psoriasis locus at 17q24-q25 (PSORS2; ref. 7). Linkage to this locus was confirmed with independent family sets. Additional loci have also been proposed to be associated with psoriasis. Here we describe two peaks of strong association with psoriasis on chromosome 17q25 separated by 6 Mb. Associated single-nucleotide polymorphisms (SNPs) in the proximal peak lie in or near SLC9A3R1 (also called EBP50 and NHERF1) and NAT9, a new member of the N-acetyltransferase family. SLC9A3R1 is a PDZ domain-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family and is implicated in diverse aspects of epithelial membrane biology and immune synapse formation in T cells. The distal peak of association is in RAPTOR (p150 target of rapamycin (TOR)-scaffold protein containing WD-repeats). Expression of SLC9A3R1 is highest in the uppermost stratum Malpighi of psoriatic and normal skin and in inactive versus active T cells. A disease-associated SNP lying between SLC9A3R1 and NAT9 leads to loss of RUNX1 binding. This is the second example of loss of a RUNX1 binding site associated with susceptibility to an autoimmune disease. It also suggests defective regulation of SLC9A3R1 or NAT9 by RUNX1 as a susceptibility factor for psoriasis.