Marine bis-γ-pyrone polypropionates of onchidione family and their effects on the XBP1 gene expression

Two additional new members of the onchidione family, 16-epi-onchidione (1) and 4-epi-onchidione (2), co-occurring with six previously reported bis-γ-pyrone polypropionates including onchidione (3), were isolated from the marine pulmonate Onchidium sp. Their structures were determined by extensive spectroscopic analysis and by comparison with 3 and onchidione-related derivatives. The absolute configuration of 1 was established by X-ray diffraction analysis employing graphite monochromated Cu K_α radiation (λ?=?0.71073?Å) with small Flack parameter 0.08. In addition, the absolute stereochemistry of previously reported onchidionol (6) was confirmed by the X-ray diffraction analysis. Some of the isolated compounds showed significant activation effects on the splicing of XBP1 mRNA as ER stress modulators to inhibit the growth of tumors.     

Simultaneous automated measurement of total ‘antioxidant’ (reducing) capacity and ascorbic acid concentration

Summary

Biochemical tests of antioxidant status may be useful in measuring oxidative stress, however the time, skills and resources required for most such tests have limited their application and evaluation. In this study, newly available tests for two indices of antioxidant status, ferric reducing ability of plasma (FRAP) and ascorbic acid, were combined in one simple, rapid, automated test, referred to as FRASC.

Results are available within 5 min of sample/reagent mixing. Linear dose-response is seen over a wide concentration range for both parameters. In- and between- run CVs were <1.0% and <3.0% respectively at 900–1800 μmol/l FRAP, and <5.0% for both at 20–400 μmol/l ascorbic acid. Mean (SD) FRAP values and ascorbic acid concentrations of fasting plasma from 130 healthy adults were 1018 (198) and 51 (18) μmol/l respectively.

This combined test is straightforward and inexpensive, and lends itself to the measurement of ‘antioxidant’ (reducing) capacity and ascorbic acid concentrations of various biological fluids, as well as extracts of drugs and foodstuffs. FRASC will, therefore, facilitate experimental and clinical studies of pro-oxidant: antioxidant balance and oxidative stress-related disease.     

Increasingly ice-free winters and their effects on water quality in Sweden’s largest lakes

Mean global air temperatures have steadily increased during recent decades, resulting in an earlier timing of lake ice breakup. In Sweden’s largest lakes, Vänern and Vättern, the breakup of ice has occurred considerably earlier since 1979 and ice-free winters have become more frequent. Comparison between the years when the lakes were ice covered with those when they remained ice-free in terms of 37 lake variables revealed significant differences in water temperatures, sulphate concentrations and the biomass of diatoms in May after ice breakup (P < 0.01). In particular, the biomass of the genus Aulacoseira increased significantly, which may explain increasing complaints about algae that clog fishing-nets, filter-beds and micro-strainers in waterworks in Vänern and Vättern. We assume that Aulacoseira is mainly affected by changes in climate-driven water circulation patterns. In contrast, other observed water quality changes such as changes in sulphate concentration might rather be attributed to changes in atmospheric deposition. To explain water quality changes in Sweden’s largest lakes it is important to consider changes in both climate and atmospheric deposition as well as catchment measures.     

Tissue pharmacokinetics and pharmacodynamics of AmBisome® (L-AmBis) in uninfected and infected animals and their effects on dosing regimens

Abstract

By selecting a unique combination of lipids and amphotericin B, the liposome composition for AmBisome® (L-AmBis) has been optimized resulting in a formulation that is minimally toxic, targets to fungal cell walls, and distributes into and remains for days to weeks in various host tissues at drug levels above the MIC for many fungi. Procedures have been standardized to ensure that large scale production of the drug retains the drug’s low toxicity profile, favorable pharmacokinetics and antifungal efficacy. Tissue accumulation and clearance with single or multiple intravenous administration is similar in uninfected and infected animal species, with tissue accumulation being dose-dependent and the liver and spleen retaining the most drug. The efficacy in animals appears to be correlated with drug tissue levels although the amount needed in a given organ varies depending upon the type of infection. The long-term tissue retention of bioactive L-AmBis in different organs suggests that for some indications, prophylactic and intermittent drug dosing would be efficacious reducing the cost and possible toxic side-effects. In addition, preliminary preclinical studies using non-intravenous routes of delivery, such as aerosolized L-AmBis, catheter lock therapy, and intravitreal administration, suggest that alternative routes could possibly provide additional therapeutic applications for this antifungal drug.     

Fluorescence ‘turn-off–on’ assays for neomycin sulphate and K+ ions with orange-red fluorescent molybdenum nanoclusters

Fluorescent metal nanoclusters (MNCs) have found extensive application in recognizing molecular species. Here, orange-red fluorescent Arg–A. paniculata–MoNCs were synthesized using Andrographis paniculata leaf extract, arginine as a ligand, and MoCl₅ as a metal precursor. The Arg–A. paniculata–MoNCs complex exhibited a quantum yield (QY) of 16.91% and excitation/emission wavelengths of 400/665 nm. The synthesized Arg–A. paniculata–MoNCs successfully acted as a probe for assaying neomycin sulphate (NS) via fluorescence turn-off and K⁺ ions via fluorescence turn-on mechanisms, respectively. Moreover, the developed probe was effectively used to develop a cellulose paper strip-based sensor for detection of NS and K⁺ ions. Arg–A. paniculata–MoNCs demonstrated great potential for sensing NS and K⁺ ions, with concentration ranges of 0.1–80 and 0.25–110 μM for NS and K⁺ ions, respectively. The as-synthesized Arg–A. paniculata–MoNCs efficiently detected NS and K⁺ ions in food and biofluid samples, respectively.     

Growth stimulation effects of smoke-water and vermicompost leachate on greenhouse grown-tissue-cultured ‘Williams’ bananas

A common problem often experienced by both small and large scale banana farmers is the reduction in quality and yield of bananas due to soil moisture deficits and declining soil fertility. To overcome this, mechanisms of improving yield without compromising environmental integrity or public health are being embraced. Globally, researchers have continued to evaluate the competence of environmental-friendly organic fertilizers and smoke solutions to improve the growth, yield and quality of various crops. In the present study, the effect of smoke-water (1:1,000; 1:500 and 1:250 dilutions) and vermicompost leachate (1:20; 1:10 and 1:5 dilutions) treatments on the growth of greenhouse grown bananas was evaluated. Soil drenching (smoke-water and vermicompost leachate) and foliar application (smoke-water) were tested on 1-month-old tissue-cultured banana seedlings under greenhouse conditions. After 3 months, growth parameters such as number and length of roots and shoots; number of leaves and leaf area as well as their fresh and dry weights were analyzed. Soil drenching with smoke-water significantly increased the root length (1:1,000 and 1:500 dilutions) as well as fresh and dry weight (1:1,000; 1:500 and 1:250 dilutions) when compared to foliar application. Vermicompost leachate (1:10 and 1:5 dilutions) significantly enhanced the shoot length, root length, leaf area and dry weights. Vermicompost leachate (1:20; 1:10 and 1:5 dilutions) also significantly increased the number of off-shoots. The positive effect on rooting is beneficial for acclimatization and establishment of tissue-cultured banana plantlets in nurseries and subsequent transfer to the field. Moreover, the high cost of inorganic fertilizers as well as environmental safety concerns makes the use of smoke-water and vermicompost leachate potential alternatives to improving the growth and cultivation of bananas.     

Pervasive and strong effects of plants on soil chemistry: a meta-analysis of individual plant ‘Zinke’ effects

Plant species leave a chemical signature in the soils below them, generating fine-scale spatial variation that drives ecological processes. Since the publication of a seminal paper on plant-mediated soil heterogeneity by Paul Zinke in 1962, a robust literature has developed examining effects of individual plants on their local environments (individual plant effects). Here, we synthesize this work using meta-analysis to show that plant effects are strong and pervasive across ecosystems on six continents. Overall, soil properties beneath individual plants differ from those of neighbours by an average of 41%. Although the magnitudes of individual plant effects exhibit weak relationships with climate and latitude, they are significantly stronger in deserts and tundra than forests, and weaker in intensively managed ecosystems. The ubiquitous effects of plant individuals and species on local soil properties imply that individual plant effects have a role in plant–soil feedbacks, linking individual plants with biogeochemical processes at the ecosystem scale.     

Morphological, anatomical and chemical characterization of white spruce ( Picea glauca ‘Conica’) differently aged needles and hypotheses on their influence on Oligonychus ununguis infestation

Our investigations suggest that the usually observed avoidance by O. ununguis of current year’s twigs of P. glauca ‘Conica’ as a place for feeding and development may be connected with their morphological and anatomical structure as well their biochemical composition. Needles of the current year’s twigs were covered with a thicker layer of wax and formed more extensive epidermis cell walls, in comparison with needles of 1-year-old twigs. Young needles also showed lower concentration of reducing sugars and soluble proteins, which might additionally reduce their nutritional suitability for mite development. Differences were also found between the 1-year-old growth and current growth in contribution of essential oils and a range of other compounds. Further analyses of the effect of these compounds on mite behavior may provide additional explanation of the feeding preferences of the mite.

Synthetic studies and pharmacological evaluations on the MDMA (‘Ecstasy’) antagonist nantenine

The naturally occurring aporphine alkaloid nantenine, has been shown to antagonize behavioral and physiological effects of MDMA in mice. We have synthesized (±)-nantenine via an oxidative cyclization reaction with PIFA and evaluated its binding profile against a panel of CNS targets. To begin to understand the importance of the chiral center of nantenine with regards to its capacity to antagonize the effects of MDMA in vivo, (R)- and (S)-nantenine were prepared and evaluated in a food-reinforced operant task in rats. Pretreatment with either nantenine enantiomer (0.3 mg/kg ip) completely blocked the behavioral suppression induced upon administration of 3.0 mg/kg MDMA. (±)-Nantenine displayed high affinity and selectivity for the α_1A adrenergic receptor among several other receptors suggesting that this α₁ subtype may be significantly involved in the anti-MDMA effects of the enantiomers.     

The effects of ‘gibberellin-insensitive’ dwarfing alleles in wheat on grain weight and protein content

Summary Three series of near-isogenic wheat lines differing in dwarfing alleles, in the varietal backgrounds of Maris Huntsman, Maris Widgeon and Bersee, and the F₂ grain on intravarietal F₁ hybrids, produced with a chemical hybridising agent, were examined for grain size and protein content. Individual F₂ grains from Rht1/rht, Rht2/rht and Rht3/rht F₁ spikes were classified for Rht genotype by assaying embryo half grains in a gibberellic acid seedling response test, while the remaining half was used for protein determination. Mean grain weight and protein percentage were lower in all homozygous isogenic lines and the Rht/rht F₁ hybrids than in the respective tall lines, in an allele dose-dependent manner. In all the hybrids, the Rht genotype of individual F₂ grains, which segregated within the spikes of F₁ plants, had no significant effects on grain weight or protein. Consequently, the pleiotropic effects of the Rht alleles on these yield and quality components must be attributed to their presence in maternal plant tissues rather than in the endosperm or embryo tissues of individual grains.     

Isolation and identification of entomopathogenic nematodes and their symbiotic bacteria from Hérault and Gard (Southern France)

Isolation and identification of native nematode-bacterial associations in the field are necessary for successful control of endemic pests in a particular location. No study has yet been undertaken to recover and identify EPN in metropolitan France. In the present paper, we provide results of a survey of EPN and their symbiotic bacteria conducted in Hérault and Gard regions in Southern France. Molecular characterization of isolated nematodes depicted three different Steinernema species and one Heterorhabditis species, H. bacteriophora. Steinernema species recovered were identified as: S. feltiae and S. affine and an undescribed species. Xenorhabdus symbionts were identified as X. bovienii for both S. feltiae and S. affine. Phylogenetic analysis placed the new undescribed Steinernema sp. as closely related to S. arenarium but divergent enough to postulate that it belongs to a new species within the “glaseri-group”. The Xenorhabdus symbiont from this Steinernema sp. was identified as X. kozodoii. All Heterorhabditis isolates recovered were diagnosed as H. bacteriophora and their bacterial symbionts were identified as Photorhabdus luminescens. Molecular characterization of these nematodes enabled the distinction of two different H. bacteriophora strains. Bacterial symbiontic strains of these two H. bacteriophora strains were identified as P. luminescens ssp. kayaii and P. luminescens ssp. laumondii.     

Differential effects of foods traditionally regarded as ‘heating’ and ‘cooling’ on prostaglandin E2 production by a macrophage cell line

Some components of natural foods may enhance or inhibit prostaglandin formation and potentially affect the inflammation condition. A macrophage cell line, RAW264.7, was employed to examine the effects of foods traditionally regarded as heating or cooling on the production of PGE₂, a well-known proinflammatory mediator. Foods traditionally regarded as heating (litchi, longan, and dried longan) or cooling (chrysanthemum flower, bitter gourd, and lotus seed plumule) were extracted sequentially with water and ethyl acetate. The water extracts (WE) and ethyl acetate extracts (EAE) were applied to RAW264.7 macrophages in the presence or absence of LPS (lipopolysaccharide). In the absence of LPS, the WEs from the heating foods, litchi, longan, or dried longan had a dose-dependent enhancing effect on PGE₂ production, with respective EC₅₀s of 8.4, 16, and 11 mg/ml. This effect was accompanied by significant induction of COX-2 protein expression, as shown by Western blot analysis. In contrast, LPS-induced PGE₂ production was inhibited in a dose-dependent manner by the WEs of the cooling foods, chrysanthemum flower, bitter gourd, and lotus seed plumule, with respective IC₅₀s of 0.6, 0.13, and 0.08 mg/ml. At the concentrations tested, none of the EAEs had any effect on basal PGE₂ production, while LPS-induced PGE₂ production was inhibited or increased by the EAE from bitter gourd and longan, respectively. Water-soluble extracts of foods traditionally regarded as heating enhanced basal PGE₂ production, while those from cooling foods significantly inhibited LPS-induced PGE₂ production by the macrophage cell line. This subject merits further study to determine whether appropriate food selection may help patients suffering from chronic inflammatory conditions.     

Fluorescence ‘off–on’ probe for lead (II) detection based on Atractylodes III CQDs and bioimaging

In this work, a type of carbon quantum dots (CQDs) with bright blue emission was readily fabricated through one-step hydrothermal treatment from Atractylodes III. We explored the surface morphology and optical properties of the CQDs using transmission electron microscopy, X-ray diffraction patterns, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy and ultraviolet–visible light spectrophotometry. The obtained CQDs possessed good photoluminescence properties, water solubility, and biocompatibility. The fluorescence quantum yield of these was 3.72%. It was found that the fluorescence intensity of CQDs was quenched by picric acid. After adding lead (II), the fluorescence could be effectively recovered. Therefore, an ‘off–on’ fluorescence probe was designed to detect lead (II) in the range 0–580 μM and the limit of detection was 0.068 μM. In addition, the experiments showed that the CQDs could be successfully used in bioimaging and as a hidden fluorescent ink.     

Proteinase-activated receptors (PARs) – focus on receptor-receptor-interactions and their physiological and pathophysiological impact

Proteinase-activated receptors (PARs) are a subfamily of G protein-coupled receptors (GPCRs) with four members, PAR₁, PAR₂, PAR₃ and PAR₄, playing critical functions in hemostasis, thrombosis, embryonic development, wound healing, inflammation and cancer progression. PARs are characterized by a unique activation mechanism involving receptor cleavage by different proteinases at specific sites within the extracellular amino-terminus and the exposure of amino-terminal “tethered ligand“ domains that bind to and activate the cleaved receptors. After activation, the PAR family members are able to stimulate complex intracellular signalling networks via classical G protein-mediated pathways and beta-arrestin signalling. In addition, different receptor crosstalk mechanisms critically contribute to a high diversity of PAR signal transduction and receptor-trafficking processes that result in multiple physiological effects.In this review, we summarize current information about PAR-initiated physical and functional receptor interactions and their physiological and pathological roles. We focus especially on PAR homo- and heterodimerization, transactivation of receptor tyrosine kinases (RTKs) and receptor serine/threonine kinases (RSTKs), communication with other GPCRs, toll-like receptors and NOD-like receptors, ion channel receptors, and on PAR association with cargo receptors. In addition, we discuss the suitability of these receptor interaction mechanisms as targets for modulating PAR signalling in disease.     

Presence of ‘PSI free’ LHCI and monomeric LHCII and subsequent effects on fluorescence characteristics in lincomycin treated maize

The cause of the strong non-photochemical fluorescence quenching was examined in maize (Zea mays L.) plants that were treated with lincomycin during the 72 h period of greening. They were deficient in core complexes but seemed to contain the full complement of antennae. The following results were obtained: (1) High F _o could not be attributed to the dark reduction of Q _A but to the presence of a high amount of not properly organized antenna complexes due to the inhibited synthesis of reaction centres. (2) On illumination fluorescence intensity dropped considerably below F _o within 20 s, and reached a steady state still below F _o . (3) Slowly relaxing part of non-photochemical quenching was significantly higher than in control plants. (4) De-epoxidation state was constant, and corresponded to the maximal value of the control. (5) Free Lhca1/4 dimers could be detected in all submembrane fractions, including the grana, obtained by digitonin fractionation. (6) Increase in the 679 and 700 nm fluorescence emissions could be attributed to the monomerisation of part of LHCII and to the presence of free Lhca2 or LHCII aggregates, respectively. (7) LHCII or PSII+LHCII and Lhca1/4 interaction may contribute to the increase of long-wavelength fluorescence in the granal fraction. We assume that the elevated fluorescence quenching of monomeric LHCII as well as the interaction between LHCII or PSII+LHCII and Lhca1/4 can be considered as an explanation for the extensive non-photochemical fluorescence quenching in lincomycin treated plants. The permanent presence of zeaxanthin may have contributed to the fast formation of quenching.