Heme oxygenase-1 induction may explain the antioxidant profile of pentaerythrityl trinitrate

The organic nitrate pentaerythrityl tetranitrate (PETN) is known to exert long-term antioxidant and antiatherogenic effects by as yet unidentified mechanisms. In cultured endothelial cells derived from human umbilical vein, the active PETN metabolite PETriN (0.01-1 mM) increased heme oxygenase (HO)-1 mRNA and protein levels in a concentration-dependent fashion. HO-1 induction was accompanied by a marked increase in catalytic activity of the enzyme as reflected by enhanced formation of carbon monoxide and bilirubin. Pretreatment with PETriN or bilirubin at low micromolar concentrations protected endothelial cells from hydrogen peroxide-mediated toxicity. HO-1 induction and endothelial protection by PETriN were not mimicked by isosorbide dinitrate, another long-acting nitrate. The present study demonstrates that PETriN stimulates mRNA and protein expression as well as enzymatic activity of the antioxidant defense protein HO-1 in endothelial cells. Increased HO-1 expression and ensuing formation of cytoprotective bilirubin may contribute to and explain the specific antioxidant and antiatherogenic actions of PETN.     

Ethanol production from native cassava starch by a mixed culture of Endomycopsis fibuligera and Zymomonas mobilis

The conversion of starch from unhydrolyzed cassava flour to ethanol by a pure culture of Endomycopsis fibuligera and by a co-culture of this amylolytic yeast and the bacterium Zymomonas mobilis was studied. The best overall results were obtained using the mixed culture. After 96 h of fermentation of a medium containing 150 g/l initial cassava starch, an ethanol concentration of 31.4 g/l, a productivity of 0.33 g ethanol/l × h and a yield of 0.21 g ethanol/g initial starch were reached. The highest yield (0.37 g/g) was obtained after 48 h when using a medium containing 50 g/l initial starch.     

Piperazine sulfonamide BACE1 inhibitors: Design,synthesis, and in vivo characterization

With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2′ sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral Aβ₄₀ in transgenic mice with a single subcutaneous dose.     

Synthesis and binding assays of novel 3,3-dimethylpiperidine derivatives with various lipophilicities as σ₁ receptor ligands

Starting from two carbocyclic analogs, a series of 3,3-dimethylpiperidine derivatives was prepared and tested in radioligand binding assays at σ(1) and σ(2) receptors, and at Δ(8)-Δ(7) sterol isomerase (SI) site. The novel compounds mostly bear heterocyclic rings or bicyclic nucleus of differing lipophilicities. Compounds 18a and 19a,b demonstrated the highest σ(1) affinity (K(i)=0.14-0.38 nM) with a good selectivity versus σ(2) binding. Among them, 18a had the lowest ClogD value (3.01) and only 19b was selective versus SI too. Generally, it was observed that more planar and hydrophilic heteronuclei conferred a decrease in affinity for both σ receptor subtypes.     

Inheritance of Fusarium head blight resistance in the soft red winter wheat Ernie

Fusarium head blight (FHB), caused by Fusarium graminearum Schwabe [telomorph:Gibberella zeae Schw. (Petch)], is an increasingly important disease of wheat (Triticum aestivum L.). Host-plant resistance is considered to be the most economical means of control, but a lack of unique sources of resistance has hindered efforts to breed resistant varieties. The soft red winter wheat, Ernie, has moderately high FHB resistance and is widely used in U.S. breeding programs; however, the genetics of resistance have not been studied. The objectives of this study were to estimate the genetic effects, gene numbers, and heritability for traits related to FHB resistance in Ernie through generation means analyses and variance analyses of 243 F₃-derived F₈ and F₉ recombinant inbred lines (RILs). Replicated experiments were grown in the greenhouse, inoculated with F. graminearum, and evaluated for disease spread and the FHB index (FHBI). The latter was calculated as the percentage of diseased spikelets in inoculated spikes and is often referred to as type-II resistance. Gene action for both disease spread and FHBI was primarily additive with partial dominance for low disease. Broad-sense heritabilities for spread and FHBI were 78.2% and 78.3%, respectively, while the narrow-sense heritabilities were 51.3% and 55.4%, respectively. Line-mean heritabilities from analyses of variance of RILs were 0.70 and 0.87 for spread and FHBI, respectively. A minimum of four genes conditioned both disease spread and FHBI. These results suggest that breeders should be able to enhance FHB resistance by combining the resistance in Ernie with other complementary additive sources of resistance.