The double mutation ΔL6MW241F in PsbO, the photosystem II manganese stabilizing protein, yields insights into the evolution of its structure and function

The W241F mutation in spinach manganese-stabilizing protein (PsbO) decreases binding to photosystem II (PSII); its thermostability is increased and reconstituted activity is lower [Wyman et al. (2008) Biochemistry 47, 6490-6498]. The results reported here show that W241F cannot adopt a normal solution structure and fails to reconstitute efficient Cl⁻ retention by PSII. An N-terminal truncation of W241F, producing the ΔL6MW241F double mutant that resembles some features of cyanobacterial PsbO, significantly repairs the defects in W241F. Our data suggest that the C-terminal F → W mutation likely evolved in higher plants and green algae in order to preserve proper PsbO folding and PSII binding and assembly, which promotes efficient Cl⁻ retention in the oxygen-evolving complex.     

Scavenger receptor BI facilitates hepatic very low density lipoprotein production in mice

Scavenger receptor BI (SR-BI) is a selective uptake receptor for HDL cholesterol but is also involved in the catabolism of apolipoprotein (apo)B-containing lipoproteins. However, plasma levels of apoB-containing lipoproteins increase following hepatic SR-BI overexpression, suggesting that SR-BI not solely mediates their catabolism. We therefore tested the hypothesis that hepatic SR-BI impacts on VLDL production. On day 7 following adenovirus (Ad)-mediated overexpression of SR-BI, VLDL-triglyceride and VLDL-apoB production rates were significantly increased (P < 0.001), whereas VLDL production was significantly lower in SR-BI knockout mice compared with controls (P < 0.05). In mice injected with AdSR-BI, hepatic cholesterol content increased (P < 0.001), microsomal triglyceride transfer protein activity was higher (P < 0.01) and expression of sterol-regulatory element binding protein (SREBP)2 and its target genes was decreased (P < 0.01). Conversely, in SR-BI knockout mice, microsomal triglyceride transfer protein activity was lower and expression of SREBP2 target genes was increased (P < 0.01). Finally, we demonstrate in vitro in isolated primary hepatocytes as well as in vivo that cholesterol derived from HDL and taken up via SR-BI into the liver can be resecreted within VLDL. These data indicate that hepatic SR-BI expression is linked to VLDL production, and within liver, a metabolic shunt might exist that delivers HDL cholesterol, at least in part, to a pool from which cholesterol is mobilized for VLDL production. These results might have implications for HDL-based therapies against atherosclerotic cardiovascular disease, especially with SR-BI as target.     

Shifting fungal endophyte communities colonize Bouteloua gracilis: effect of host tissue and geographical distribution

Communities of root-associated fungi (RAF) commonly have been studied under the auspices of arbuscular mycorrhizal fungi (AMF) or ectomycorrhizal fungi. However many studies now indicate that other groups of endophytic RAF, including dark septate endophytes (DSE) are more abundant in some plants and environments. The common forage grass, Bouteloua gracilis, was used as a model to examine whether RAF also colonize different organs within the same plant and to compare RAF communities from sites across North America, spanning the latitudinal range of B. gracilis (from Canada to Mexico). We compared the RAF communities of organs within individual plants at one site and within plant roots among six sites. With the possible exception of one group related to genus Paraphaeosphaeria there was little evidence that RAF colonized vertically beyond the crowns. Furthermore, although there was some variation in the constitution of rare members of the RAF communities, several taxonomically related groups dominated the RAF community at all sites. These dominant taxa included members in the Pleosporales (related to the DSE, Paraphaeosphaeria spp.), Agaricales (related to Moniliophthora spp., or Campanella spp.) and Hypocreales (related to Fusarium spp.). AMF were notable by their near absence. Similar phylotypes from the dominant groups clustered around adjacent sites so that similarity of the RAF communities was negatively correlated to site inter-distance and the RAF communities appeared to group by country. These results increase the possibility that at least some of these common and widely distributed core members of the RAF community form important, intimate and long lasting relationships with grasses.     

Azabicyclic sulfonamides as potent 11β-HSD1 inhibitors

Inhibition of 11β-HSD1 has demonstrated potential in the treatment of various components of metabolic syndrome. We wish to report herein the discovery of novel azabicyclic sulfonamide based 11β-HSD1 inhibitors. Highly potent compounds exhibiting inhibitory activities at both human and mouse 11β-HSD1 were identified. Several compounds demonstrated significant in vivo activity in the mouse cortisone challenge assay.     

1,4-Dihydropyrazolo[4,3-d]imidazole phenyl derivatives: A novel type II Raf kinase inhibitors

The synthesis of a novel series of 1,4-dihydropyrazolo[4,3-d]imidazole phenyl derivatives 1a–b, 2a–v and their antiproliferative activities against A375P and WM3629 human melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, pyrazoloimidazole phenyl urea compounds 2a, 2d, 2g, 2i, 2t exhibited potent activities on WM3629 cell lines (IC₅₀ = 0.56–0.86 μM). Especially, 2t was found to be a potent and selective C-Raf inhibitor, showing a possibility as melanoma therapeutics.     

Similar patterns of rDNA evolution in synthetic and recently formed natural populations of <Emphasis Type="Italic">Tragopogon</Emphasis>(Asteraceae) allotetraploids

Background  

Tragopogon mirus and T. miscellus are allotetraploids (2n = 24) that formed repeatedly during the past 80 years in eastern Washington and adjacent Idaho (USA) following the introduction of the diploids T. dubius, T. porrifolius, and T. pratensis (2n = 12) from Europe. In most natural populations of T. mirus and T. miscellus, there are far fewer 35S rRNA genes (rDNA) of T. dubius than there are of the other diploid parent (T. porrifolius or T. pratensis). We studied the inheritance of parental rDNA loci in allotetraploids resynthesized from diploid accessions. We investigate the dynamics and directionality of these rDNA losses, as well as the contribution of gene copy number variation in the parental diploids to rDNA variation in the derived tetraploids.