Discovery of a novel series of quinolone α7 nicotinic acetylcholine receptor agonists

High throughput screening led to the identification of a novel series of quinolone α7 nicotinic acetylcholine receptor (nAChR) agonists. Optimization of an HTS hit (1) led to 4-phenyl-1-(quinuclidin-3-ylmethyl)quinolin-2(1H)-one, which was found to be potent and selective. Poor brain penetrance in this series was attributed to transporter-mediated efflux, which was in turn due to high pK_a. A novel 4-fluoroquinuclidine significantly lowered the pK_a of the quinuclidine moiety, reducing efflux as measured by a Caco-2 assay.     

Identification and mapping of leaf, stem and stripe rust resistance quantitative trait loci and their interactions in durum wheat

Leaf rust (Puccinia triticina Eriks.), stripe rust (Puccinia striiformis f. tritici Eriks.) and stem rust (Puccinia graminis f. sp. tritici) cause major production losses in durum wheat (Triticum turgidum L. var. durum). The objective of this research was to identify and map leaf, stripe and stem rust resistance loci from the French cultivar Sachem and Canadian cultivar Strongfield. A doubled haploid population from Sachem/Strongfield and parents were phenotyped for seedling reaction to leaf rust races BBG/BN and BBG/BP and adult plant response was determined in three field rust nurseries near El Batan, Obregon and Toluca, Mexico. Stripe rust response was recorded in 2009 and 2011 nurseries near Toluca and near Njoro, Kenya in 2010. Response to stem rust was recorded in field nurseries near Njoro, Kenya, in 2010 and 2011. Sachem was resistant to leaf, stripe and stem rust. A major leaf rust quantitative trait locus (QTL) was identified on chromosome 7B at Xgwm146 in Sachem. In the same region on 7B, a stripe rust QTL was identified in Strongfield. Leaf and stripe rust QTL around DArT marker wPt3451 were identified on chromosome 1B. On chromosome 2B, a significant leaf rust QTL was detected conferred by Strongfield, and at the same QTL, a Yr gene derived from Sachem conferred resistance. Significant stem rust resistance QTL were detected on chromosome 4B. Consistent interactions among loci for resistance to each rust type across nurseries were detected, especially for leaf rust QTL on 7B. Sachem and Strongfield offer useful sources of rust resistance genes for durum rust breeding.     

Unique sympatric quartet of limnetic,benthic, profundal and piscivorous brown trout populations resolved by 3D sampling and focused molecular marker selection

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Metal Removal from Water Discharges by a Constructed Treatment Wetland

A full‐scale constructed wetland treatment system consisting of four pairs of wetland cells (3.2 ha total area) with water flowing through a pair of cells in series prior to discharge was investigated. A retention basin provided stable water flow to the system. Water retention time in the wetland system was approximately 48 hours, and the wetland cells operated at circumneutral pH. Vegetation development within the cells has been excellent. Copper removal efficiency was greater than 75 % from the start‐up of the system, while mercury efficiency improved with maturation of the treatment cells. Sampling of the water course through the wetlands conducted during the fourth year of operation validated continued performance, and assessed the fate of a larger suite of metals present in the water. Copper and mercury removal efficiencies were still very high, both in excess of 80 % removal from the water after passage through the wetland system. Mercury removal continued along the entire water course through the system, while copper was removed almost immediately upon entering the wetland cells. Lead removal from the water by the system was 83 %, zinc removal was 60 %, and nickel was generally unaffected. Organic carbon in the water was also increased by the system and reduced the bioavailability of some metals. Operation and maintenance of the system continued to be minimal, and mainly consisted of checking for growth of the vegetation and free flow of the water through the system. The system was entirely passive, relying on gravity as the power source of water flow. No reportable permit exceedances have been experienced since the wetland began treating an outfall discharge.     

Effect of Dipyridamole on Membrane Energization and Energy Transfer in Chromatophores of Rba. sphaeroides

Biochemistry (Moscow) - Effect of dipyridamole (DIP) at concentrations up to 1 mM on fluorescent characteristics of light-harvesting complexes LH2 and LH1, as well as on conditions of...     

Immunocytochemical localization of water-soluble glycoproteins, including Group 1 allergen, in pollen of ryegrass,Lolium perenne, using ferritin-labelled antibody

Summary The cellular sites of the glycoproteins Group 1 allergen (glycoprotein 1) and Antigen A (glycoprotein 2) in mature ryegrass pollen have been investigated by immunoelectron microscopy. Radioimmunoassays confirm previous findings of cross-reactivity between the purified glycoprotein antigens at the high immunoglobulin G (IgG) concentrations used for localization.Freeze-drying of anthers followed by anhydrous processing has been employed because of the water solubility and mobility of the glycoproteins. A double-embedding technique has been developed. This involves, first, embedding anthers in the water-soluble plastic resin JB-4, sectioning and incubating in ferritin-labelled antisera by the indirect method. The sections are then embedded in Spurr's resin for ultra-thin sectioning. Both glycoproteins are found in the following sites: (1) exine and intine wall layers; (2) pollen cytoplasm; (3) the orbicules and anther loculus; and (4) the anther cuticle. In the exine arcades and surface and in the anther loculus, the ferritin label is bound to pollenkitt. The finding that the glycoproteins are in similar sites is predictable in view of the cross-specificity of the antisera. The extent of antibody penetration of the plastic sections has been examined; labelling is confined to cut grains and absent from intact grains.     

Temporal Stability and the Effects of Training on Saccade Latency in “Express Saccade Makers”

The temporal stability of saccade latency, and the effects of training, particularly in “express saccade makers” (ESMs), has received little attention. ESMs are healthy, naïve, adults, who persist in executing very many low latency “express saccades” (ES; saccades with latency of 80 ms to 130 ms), in conditions designed to suppress such responses. We investigated the stability of ES production (%ES) in 59 ESM and 54 non-ESM participants in overlap tasks. Within a single session, the intraclass correlation coefficient (ICC) for %ES in two runs of 200 trials was 0.97 (p<0.001); participants in whom >30% of saccades over the two runs were ES, were classified as ESMs. For 60 participants tested over two sessions 12 weeks apart, and 30 participants tested in three sessions over approximately six months, the ICC for %ES was uniformly high (0.95, p<0.001 and 0.97, p<0.001 respectively) and participants behaved consistently with their initial classification. Fourteen participants (7 ESMs) were then exposed to training consisting of either gap or overlap tasks. Training increased %ES in both groups. However, when tested in overlap tasks, it was not sufficient to transform Normal participants into ESMs. We conclude that the pattern of saccade behaviour exhibited by ESMs constitutes a stable and distinct oculomotor phenotype.