Interactions Between Rhinanthus minor and Its Hosts: A Review of Water, Mineral Nutrient and Hormone Flows and Exchanges in the Hemiparasitic Association

At the ecological level, the effects of the facultative root hemiparasite Rhinanthus minor on the structure and functioning of its host communities are relative well described; yet until recently, the mechanistic basis for parasitic plant-driven community change and the physiological basis for the host-parasite interaction were poorly understood. Empirical incremental flow models, based on the increase in water, mineral nutrients, carbon assimilates or phytohormones between two defined time points, have been successfully employed to investigate the physiology of resource acquisition by- and distribution within host-parasitic plant associations. In this study we review the application of these empirical flow models to Rhinanthus-host associations showing the extent of and physiological basis of resource abstraction from the host and how this is profoundly influenced by soil nutrient status. We show that Rhinanthus primarily abstracts water and mineral nutrients via the apoplastic pathway through direct lumen-lumen connections with little resource acquisition via symplastic pathways. Nutrient status of the soil is shown to significantly influence the resource acquisition. We also investigate the hormonal regulation of resource acquisition by Rhinanthus showing pivotal roles for the key for the phytohormones abscisic acid (ABA) and cytokinins.     

Identification of NBS-Type Resistance Gene Homologs in Tobacco Genome

Tobacco (Nicotiana tabacum) is an important cash crop and an ideal experimental system for studies on plant–pathogen interaction. The sequenced tobacco genome provides an opportunity for examining resistance gene homologs (RGHs) in the tobacco genome. Thirty nucleotide-binding site-type RGHs were annotated from genomic data, and another 281 putative RGHs were identified via PCR amplification from wild and cultivated tobacco. The newly identified RGHs are similar to other known RGHs, and some were categorized into new groups or branches that are different from known Nicotiana R genes or RGHs. Of the 281RGHs, 146 were identified from a single tobacco genome. We did not find any polymorphism at the RGHs in cultivated accessions, implying that strong domestication selection and/or demographic effects might have caused a sharp reduction in nucleotide diversity. Three positive selection sites were found in several RGH groups, while purifying selection is pervasive in the RGH family. Our results provide a primary RGH pool and several positively selected sites for the further functional validation of resistance genes in tobacco.     

Carnosine protects against permanent cerebral ischemia in histidine decarboxylase knockout mice by reducing glutamate excitotoxicity

Recently, we showed that carnosine protects against NMDA-induced excitotoxicity in differentiated PC12 cells through a histaminergic pathway. However, whether the protective effect of the carnosine metabolic pathway also occurs in ischemic brain is unknown. Utilizing the model of permanent middle cerebral artery occlusion (pMCAO) in mice, we found that carnosine significantly improved neurological function and decreased infarct size in both histidine decarboxylase knockout and the corresponding wild-type mice to the same extent. Carnosine decreased the glutamate levels and preserved the expression of glutamate transporter-1 (GLT-1) but not the glutamate/aspartate transporter in astrocytes exposed to ischemia in vivo and in vitro. It suppressed the dissipation of ΔΨ_m and generation of mitochondrial reactive oxygen species (ROS) induced by oxygen–glucose deprivation in astrocytes. Furthermore, carnosine also decreased the mitochondrial ROS and reversed the decrease in GLT-1 induced by rotenone. These findings are the first to demonstrate that the mechanism of carnosine action in pMCAO may not be mediated by the histaminergic pathway, but by reducing glutamate excitotoxicity through the effective regulation of the expression of GLT-1 in astrocytes due to improved mitochondrial function. Thus, our study reveals a novel antiexcitotoxic agent in ischemic injury.     

Determination of the absolute configurations of synthetic daunorubicin analogues using vibrational circular dichroism spectroscopy and density functional theory

The absolute configurations of three synthesized anthracycline analogues have been determined using vibrational circular dichroism (VCD) spectroscopy and the density functional theory (DFT) calculations. The experimental VCD spectra of the three compounds have been measured for the first time in the film state, prepared from their CDCl₃ solutions. Conformational searches for the monomers and some dimers of the three compounds have been performed at the DFT level using the B3LYP functional and the 6‐311G** and 6‐311++G** basis sets. The corresponding vibrational absorption and VCD spectra have been calculated. The good agreement between the experimental and the calculated spectra allows one to assign the absolute configurations of the three compounds with high confidence. In addition, the dominant conformers of the three compounds have also been identified. Chirality, 2010. © 2010 Wiley‐Liss, Inc.     

Clinical application of the SurePath liquid-based Pap test in cytological screening of bronchial brushing for the diagnosis of lung cancer

The SurePath liquid-based Pap test (LPT) is successfully and widely used to assess sputum cytology. This study aimed to compare the cytological findings and diagnostic sensitivity of LPT with those of the conventional Pap smear (CPS) method for diagnosing lung cancer. Bronchial brushing specimens from 204 patients diagnosed with lung cancer were studied. LPT slides showed decreased areas of cell monolayers, a clearer background and distinct, stereoscopic cytological features. The LPT had a significantly higher diagnostic sensitivity for lung cancer (71.6%) than the CPS method (57.8%, p < 0.05), particularly for small cell lung carcinoma and >2 cm lesions (p < 0.05). Combination of the LPT with the CPS method showed obviously higher diagnostic sensitivity for the detection of adenocarcinoma (63.6%), central lesions (85.0%) and >2 cm lesions (81.4%) compared with the CPS method alone (p < 0.05, p < 0.01). Thus, LPT is a useful and easily performed technique that can be widely applied, and is suitable for the early diagnosis of lung cancer.     

l-Tryptophan exhibits therapeutic function in a porcine model of dextran sodium sulfate (DSS)-induced colitis

Conventional therapies for the treatment of inflammatory bowel disease (IBD) have demonstrated limited efficacy and potential toxicity; therefore, there is a need for novel therapies that can safely and effectively treat IBD. Recent evidence has indicated that amino acids may play a role in maintaining gut health. l-Tryptophan has been shown to reduce oxidative stress and improve neurological states. The objective of this study was to assess the therapeutic effects of l-tryptophan in a porcine model of dextran sodium sulfate (DSS)-induced colitis. DSS was administered to piglets via intragastric catheter for 5 days followed by tryptophan administration at 80% of the daily recommended intake. The severity of colitis was assessed macroscopically and histopathologically, and intestinal permeability was monitored in vivo by d-mannitol analysis. The effect of tryptophan on the local expression of key mediators of inflammation and IBD pathogenesis was examined at the protein and gene expression levels. Supplementation with tryptophan ameliorated clinical symptoms and improved weight gain to feed intake conversion ratios. Histological scores and measurements were also improved, and gut permeability was notably reduced in tryptophan-supplemented animals. Moreover, tryptophan reduced the expression of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, interferon (IFN)-γ, IL-12p40, IL-1β and IL-17, as well as IL-8 and intracellular adhesion molecule-1, and resulted in increased expression of apoptosis initiators caspase-8 and Bax. These results demonstrate that l-tryptophan supplementation can reduce inflammation and enhance the rate of recovery in DSS-induced colitis and may be an effective immunomodulating agent for the treatment of IBD.     

Biological origins of normal-chain hydrocarbons: a pathway model based on cuticular wax analyses of maize silks

Long-chain normal hydrocarbons (e.g. alkanes, alkenes and dienes) are rare biological molecules and their biosynthetic origins are obscure. Detailed analyses of the surface lipids that accumulate on maize silks have revealed that these hydrocarbons constitute a large portion (>90%) of the cuticular waxes that coat this organ, which contrasts with the situation on maize seedling leaves, where the cuticular waxes are primary alcohols and aldehydes. The normal hydrocarbons that occur on silks are part of a homologous series of alkanes, alkenes and dienes of odd-number carbon atoms, ranging between 19 and 33 in number. The alkenes and dienes consist of a homologous series, each of which has double bonds situated at defined positions of the alkyl chains: alkenes have double bonds situated at the sixth, ninth or 12th positions, and dienes have double bonds situated at the sixth and ninth, or ninth and twelfth positions. Finding a homologous series of unsaturated aldehydes and fatty acids suggests that these alkenes and dienes are biosynthesized by a series of parallel pathways of fatty-acid elongation and desaturation reactions, which are followed by sequential reduction and decarbonylation. In addition, the silk cuticular waxes contain metabolically related unsaturated long-chain methylketones, which probably arise via a decarboxylation mechanism. Finally, metabolite profiling analyses of the cuticular waxes of two maize inbred lines (B73 and Mo17), and their genetic hybrids, have provided insights into the genetic control network of these biosynthetic pathways, and that the genetic regulation of these pathways display best-parent heterotic effects.     

Design and synthesis of aminohydantoins as potent and selective human β-secretase (BACE1) inhibitors with enhanced brain permeability

The identification of small molecule aminohydantoins as potent and selective human β-secretase inhibitors is reported. These analogs exhibit good brain permeability (40-70%), low nanomolar potency for BACE1, and demonstrate >100-fold selectivity for the structurally related aspartyl proteases cathepsin D, renin and pepsin. Alkyl and alkoxy groups at the meta-position of the P1 phenyl, which extend toward the S3 region of the enzyme, have contributed to the ligand's reduced affinity for the efflux transporter protein P-gp, and decreased topological polar surface area, thus resulting in enhanced brain permeability. A fluorine substitution at the para-position of the P1 phenyl has contributed to 100-fold decrease of CYP3A4 inhibition and enhancement of compound metabolic stability. The plasma and brain protein binding properties of these new analogs are affected by substitutions at the P1 phenyl moiety. Higher compound protein binding was observed in the brain than in the plasma. Two structurally diverse potent BACE1 inhibitors (84 and 89) reduced 30% plasma Aβ40 in the Tg2576 mice in vivo model at 30 mg/kg p.o..     

Discovery and initial optimization of 5,5′-disubstituted aminohydantoins as potent β-secretase (BACE1) inhibitors

8,8-Diphenyl-2,3,4,8-tetrahydroimidazo[1,5-a]pyrimidin-6-amine (1) was identified through HTS, as a weak (micromolar) inhibitor of BACE1. X-Ray crystallographic studies indicate the 2-aminoimidazole ring forms key H-bonding interactions with Asp32 and Asp228 in the catalytic site of BACE1. Lead optimization using structure-based focused libraries led to the identification of low nanomolar BACE1 inhibitors such as 20b with substituents which extend from the S₁ to the S₃ pocket.