In silico identification of natural product inhibitors for γ-secretase activating protein,a therapeutic target for Alzheimer's disease

Alzheimer's disease (AD) is clinically characterized by the aggregation of neurotoxic amyloid-β (Aβ) peptides in the brain. γ-Secretase catalyzes the reaction of Aβ formation. Inhibition of γ-secretase activating protein (GSAP) reduces Aβ production without disrupting other molecular functions and serves as a promising therapeutic target for lowering Aβ and curing AD. Till date, no proven drug is available for curing AD because of the nonexistence of crystal/NMR structure of GSAP. Thus in the present study, for the first time, we adopted in silico method to predict the 3D structure of GSAP via comparative modeling and studied the architecture and function of GSAP through simulation studies. Docking studies with 4153 phytochemicals revealed that GSAP having a better binding affinity with macaflavanone C, (E)-1-[2,4-dihydroxy-3-(3-methylbut-2-enyl)phenyl]-3-(2,2-dimethyl-8-hydroxy-2H-benzopyran-6-yl)prop-2-en-1-one, and monachosorin B as compared with the standard drug, imatinib. Further, the molecular dynamics analysis suggested that only two phytochemicals, namely, macaflavanone C and (E)-1-[2,4-dihydroxy-3-(3-methylbut-2-enyl)phenyl]-3-(2,2-dimethyl-8-hydroxy-2H-benzopyran-6-yl)prop-2-en-1-one) significantly disrupt the original property of GSAP and also cleared the absorption, distribution, metabolism, and excretion test. These natural compounds may be utilized in future for curing AD after further investigations.     

Fungicide Resistance Phenotypes of Botrytis cinerea Isolates from Commercial Vineyards in South West Germany

Fungicide resistance frequencies of Botrytis cinerea populations in the German Wine Road region were determined for 4 years. Strains showing specific resistance against carbendazim, iprodione or fenhexamid were found to occur wide‐spread, but at low frequencies. In contrast, cyprodinil resistance increased from 5.4% in 2006 to 21.9% in 2008 and 16% in 2009, and strains resistant to boscalid increased from 2% in 2006 to 26.7% in 2009. Strains with multidrug resistance (MDR) phenotypes were found at high frequencies. One of the three MDR phenotypes, MDR1, with reduced sensitivity to cyprodinil and fludioxonil, was dominating, representing 19% to 35% of the total population. Strains with a combination of cyprodinil resistance and MDR1 were found to be strongly increasing in 2008 and 2009.     

Seasonal variation in the response of Hagberg falling and liquefaciton numbers to propiconazole fungicide in wheat

The hypothesis was tested that seasonal differences in the response to propiconazole fungicide of hagberg failling and liquefaction numbers are related to grain drying rate, as indicated by potential evaportranspiration. The response of Hagberg failling and liquefaciton numbers to late-season applicaitions of propiconazole was calculated using data from a field experiments in each of the years 1981 to 1990 on winter wheat (Triticum aestivum) cv. Agalong grown with similar husbandry at one site. Cumulative potential evapotranspiration was calculated over seven different periods during grain ripening. No visible sprouting occurred in any experiment and Hagberg falling number was above 250 s in nine of the 10 years. Disease severity on the flag leaf was less than 7% in nine of the 10 years, and diseases were generally controlled well by propiconazole. There were no significant relationships between the response of Hagberg falling number and any of the potential evapotranspiration variables. The response of liquefaction number was exponentially related to each of three cumulative potential evapotranspiration variables which covered periods before the estimated date of 40% moisture content. Years with lower cumulative potential evapotranspiration gave the greater responses, but the relationships were considerably influenced by the two lowest potential evapotranspiration years. It was concluded that these data provide indirect evidence that the response of Hagberg falling number (when transformed to liquefaction number) to fungicide is mediated through grain drying rate, and furthermore that the results are compatible with the hypothesis that pre-maturity alpha-amylase activity is stimulated by slow grain drying.     

Assessment of winter wheat cultivars for changes in straw composition and digestibility in response to fungicide and growth regulator treatments

The effects of a combined fungicide and growth regulator treatment on the composition and dry matter digestibility of straw samples of winter wheat cultivars, Beaver, Brigadier, Hussar, Mercia, Riband, Genesis, Hunter, Spark, Cadenza and Flame, were compared. The samples were analysed for nitrogen, ash, fibre fractions and minerals. Nitrogen content of treated samples was reduced compared to the untreated control samples and in contrast the proportion of ash increased for all the treated samples. All samples were analysed by derivative thermogravimetry (DTG) to determine changes in fibre composition. Only six cultivars were analysed by chemical fractionation methods to determine changes in lignin, cellulose and hemicellulose content. The results from the two methods of fibre analysis were broadly similar. K, Ca, Mg and Na concentrations of the treated straw samples were found to be different to the untreated samples. Increase in dry matter digestibility (DMD) of treated straw was observed for all cultivars; the effects on Beaver, Brigadier, Mercia, Riband, Genesis, Hunter and Cadenza were most pronounced, but were less for Hussar, Spark and Flame. The potential impact of these changes in straw quality on organic mushroom compost preparation is briefly discussed.     

Interactive effects of pesticide exposure and pathogen infection on bee health – a critical analysis

Bees are fundamentally important for pollination services and declines in populations could have significant economic and environmental implications. Pesticide exposure and pathogen infection are recognised as potential stressors impacting upon bee populations and recently there has been a surge in research on pesticide–disease interactions to reflect environmentally realistic scenarios better. We critically analyse the findings on pesticide–disease interactions, including effects on the survival, pathogen loads and immunity of bees, and assess the suitability of various endpoints to inform our mechanistic understanding of these interactions. We show that pesticide exposure and pathogen infection have not yet been found to interact to affect worker survival under field‐realistic scenarios. Colony‐level implications of pesticide effects on Nosema infections, viral loads and honey bee immunity remain unclear as these effects have been observed in a laboratory setting only using a small range of pesticide exposures, generally exceeding those likely to occur in the natural environment, and assessing a highly selected series of immune‐related endpoints. Future research priorities include the need for a better understanding of pesticide effects on the antimicrobial peptide (AMP) component of an individual's immune response and on social defence behaviours. Interactions between pesticide exposure and bacterial and fungal infections have yet to be addressed. The paucity of studies in non‐Apis bee species is a further major knowledge gap.     

Effects of successive applications of fosetyl-Al on growth ofAllium cepa L. associated with endomycorrhizal fungi

The effect of successive applications (0 to 4) of fosetyl-Al on the growth of mycorrhizal (M) and nonmycorrhizal (NM) onion plants and on the residual quantity of the fungicide in the root was studied for 6 weeks under growth chamber conditions. Fosetyl-Al was applied as foliar spray at a concentration of 3 mg ml^–1. The successive applications of fosetyl-Al did not affect the dry mass of root or shoot of M plants. NM plants sprayed only once with fosetyl-Al had a higher root mass than plants sprayed 0, 2, 3 and 4 times. The quantity of phosphorous acid, the only residue detected, was positively correlated with the number of fosetyl-Al applications. It showed a positive partial correlation coefficient with the shoot (r=0.41) and the root dry mass (r=0.40) of NM and M plants.Contribution no 344, Station de recherches, Agriculture Canada, Sainte-Foy.     

Secondary ion mass spectrometry analysis of the copper distribution in Drosophila melanogaster chronically intoxicated with Bordeaux mixture

The fungicides used intensively in agriculture may affect non-target organisms. The concentrations of copper sulfate-based fungicide, Bordeaux mixture, normally used in agriculture, can significantly reduce both the life span and breeding rate of Drosophila melanogaster. The present study examines the distribution of copper in organ sections of fruit flies intoxicated with Bordeaux mixture, by secondary ion mass spectrometry. The organs of most control flies contained no copper. In contrast, copper accumulated in the cytoplasm of all the mesenteron and Malpighian tubule epithelial cells of the treated flies. There were also copper deposits in the fat body and the epithelia of the seminal receptacle and accessory glands of some flies, but there was little or no copper in the ovaries. The mesenteron and Malpighian tubules are generally responsible for detoxification by accumulation of ingested metal salts in insects. The high concentration of Bordeaux mixture used saturated these organs and resulted in excess copper being deposited in other sites, such as the fat body and the reproductive system.     

Leucocyanidin: Synthesis and properties of (2R,3S,4R)-(+)-3,4,5,7,3′,4′-hexahydroxyflavan

An isomer of leucocyanidin, (2R,3S,4R)-(+)-3,4,5,7,3′,4′-hexahydroxyflavan has been synthesized from (+)-taxifolin, isolated in its phe     

The phytochemistry of proanthocyanidin polymers

The structures of 38 proanthocyanidin polymers (condensed tannins) from 14 widely distributed families of plants are described. The polymers have been isolated from a wide variety of tissues including fruit (ripe and unripe), leaves, bark and phloem. They are all based on a common 4-8 (or 6) linked polyflavan-3-ol structure, analogous to B-type proanthocyanidin dimers.     

Antifungals: Mold control and safe levels in artificial media forTrichogramma [Hymenoptera: Trichogrammatidae]

Ten chemicals known to be fungicides are tested in artificial media forTrichogramma dendrolimi Matsu. [Hymenoptera: Trichogrammatidae]. Tests are performed in France by using artificial host egg capsules. Most of the fungicides cannot control fungus or are toxic forTrichogramma at effective levels. Geneticin, Amphotericin B and Nystatin, used at proper levels are able to control molds efficiently without modifyingTrichogramma development. These antifungals are also tested in actual conditions of mass production, in Guangzhou (China).