Polypeptide Modulators of TRPV1 Produce Analgesia without Hyperthermia

Transient receptor potential vanilloid 1 receptors (TRPV1) play a significant physiological role. The study of novel TRPV1 agonists and antagonists is essential. Here, we report on the characterization of polypeptide antagonists of TRPV1 based on in vitro and in vivo experiments. We evaluated the ability of APHC1 and APHC3 to inhibit TRPV1 using the whole-cell patch clamp approach and single cell Ca²⁺ imaging. In vivo tests were performed to assess the biological effects of APHC1 and APHC3 on temperature sensation, inflammation and core body temperature. In the electrophysiological study, both polypeptides partially blocked the capsaicin-induced response of TRPV1, but only APHC3 inhibited acid-induced (pH 5.5) activation of the receptor. APHC1 and APHC3 showed significant antinociceptive and analgesic activity in vivo at reasonable doses (0.01–0.1 mg/kg) and did not cause hyperthermia. Intravenous administration of these polypeptides prolonged hot-plate latency, blocked capsaicin- and formalin-induced behavior, reversed CFA-induced hyperalgesia and produced hypothermia. Notably, APHC3’s ability to inhibit the low pH-induced activation of TRPV1 resulted in a reduced behavioural response in the acetic acid-induced writhing test, whereas APHC1 was much less effective. The polypeptides APHC1 and APHC3 could be referred to as a new class of TRPV1 modulators that produce a significant analgesic effect without hyperthermia.     

Decadal changes of the Western Arabian sea ecosystem

Historical data from oceanographic expeditions and remotely sensed data on outgoing longwave radiation, temperature, wind speed and ocean color in the western Arabian Sea (1950–2010) were used to investigate decadal trends in the physical and biochemical properties of the upper 300 m. 72 % of the 29,043 vertical profiles retrieved originated from USA and UK expeditions. Increasing outgoing longwave radiation, surface air temperatures and sea surface temperature were identified on decadal timescales. These were well correlated with decreasing wind speeds associated with a reduced Siberian High atmospheric anomaly. Shoaling of the oxycline and nitracline was observed as well as acidification of the upper 300 m. These physical and chemical changes were accompanied by declining chlorophyll-a concentrations, vertical macrofaunal habitat compression, declining sardine landings and an increase of fish kill incidents along the Omani coast.     

Introducing host‐plant resistance to anthracnose in Kyrgyz common bean through inoculation‐based and marker‐aided selection

Common bean (Phaseolus vulgaris L.) is one of the most important legume crops for human consumption. However, its grain yield can be reduced by up to 90% by the seedborne disease, anthracnose. Fungicide treatment is costly and time‐consuming. The introduction of host plant resistance against this disease appears, therefore, to be crucial for enhancing the productivity of this crop in Kyrgyzstan. The use of DNA‐based markers in backcrossing programmes may help speed up the breeding for resistance. In this study, we used a combination of inoculation tests and a DNA marker (SCAreoli marker) to track the transfer of host‐plant resistance (Co‐2 gene) from two donor cultivars, ‘Vaillant’ and ‘Flagrano’, to susceptible Kyrgyz cultivars ‘Ryabaya’, ‘Kytayanka’ and ‘Lopatka’, which are widely grown in the country. The segregating offspring were evaluated to test the reliability of the SCAreoli marker as selection aid for host‐plant resistance to anthracnose. Our study showed that a co‐dominant DNA marker can successfully be used in backcross breeding to distinguish segregating material in different market classes of common bean.     

Can highly saline irrigation water improve sodicity and alkalinity in sodic clayey subsoils?

Purpose

The concept of irrigating crops with saline irrigation water is not new, but impacts of this practice on soil properties remain debatable, particularly the use of highly saline water. In this work, key soil chemical properties were assessed to a depth of 300 cm following 2.5 years of application of highly saline irrigation to a sodic texture-contrast soil (Brown Sodosol) in south-eastern Tasmania, Australia.

Materials and methods

Control plots (rainfall only) were compared to irrigation treatments of low (0.8 dS/m) and high salinity (16 dS/m) waters at application rates of both 200 and 800 mm/year.

Results and discussion

Whilst significant increases in both electrical conductivity and chloride concentration occurred throughout the soil profile in the high salinity treatment, these values were well below those of the irrigation water, indicating effective deep leaching. In the upper soil profile, 0–50 cm, of the high salinity treatments both the exchangeable Na⁺ and its ratio to total base cations (ESP) were significantly increased whilst the lower soil profile between 50 and 200 cm, was improved via both reduced alkalinity and sodicity. Leaching of the exchangeable base cations Ca²⁺, Mg²⁺ and K⁺ was significant in the upper soil profile (0–50 cm). As expected, the low salinity treatment (0.8 dS/m) had minimal impacts on soil chemical properties. The upper topsoil (0–10 cm) total organic carbon was significantly reduced in the high salinity plots and was negatively correlated with Cl^? concentration.

Conclusions

The data confirms the general concerns about application of saline irrigation, namely increased whole profile salinisation and upper soil profile (0–50 cm) sodicity, but they also show unexpected and desirable reductions in the lower soil profile (>?50 cm) alkalinity and sodicity. It appears the Na⁺ ions present in the saline waters led to differential leaching of base cations from the rooting zone, especially Ca²⁺ which then ameliorate the alkalinity and sodicity deeper in the soil profile (>?50 cm). Thus, surface application of gypsum may help sustain the application of highly saline waters; alternatively, subsurface irrigation above the sodic clayey subsoils could be trailed.

     

Multifaceted Clinical Effects of Echinochrome

The marine drug histochrome is a special natural antioxidant. The active substance of the drug is echinochrome A (Ech A, 7-ethyl-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone), the most abundant quinonoid pigment in sea urchins. The medicine is clinically used in cardiology and ophthalmology based on the unique properties of Ech A, which simultaneously block various links of free radical reactions. In the last decade, numerous studies have demonstrated the effectiveness of histochrome in various disease models without adverse effects. Here, we review the data on the various clinical effects and modes of action of Ech A in ophthalmic, cardiovascular, cerebrovascular, inflammatory, metabolic, and malignant diseases.     

Isoflavonoid composition of a callus culture of the relict tree Maackia amurensis Rupr. et Maxim

Isoflavonoids, an interesting and restricted group of secondary metabolites of legumes, exhibit estrogenic, antiangiogenic, and anticancer activities and are now popular as dietary supplements. Plant cell cultures that possess an increased ability to synthesize these metabolites were examined. During the investigation, cell cultures of the Far Eastern relict tree Maackia amurensis (Leguminosae) were established. A selection of seed-derived cell aggregates yielded the callus line designated A-18. This culture produces 20 isoflavonoids, namely, the isoflavones genistein, daidzein, formononetin, calycosin, derrone, and pseudobaptigenin and their glycosylated conjugates genistin, 6'-O-malonylgenistin, ononin, 6'-O-malonylononin, daidzin, 3'-methoxydaidzin, 4'-O-beta-D-glucopyranosyldaidzin, 4'-O-beta-D-glucopyranosylgenistin, and 7-O-beta-D-glucopyranosylcalycosin; the pterocarpans maackiain and medicarpin and their glycosylated conjugates 6'-O-malonyl-3-O-beta-D-glucopyranosylmaackiain and 6'-O-malonyl-3-O-beta-D-glucopyranosylmedicarpin; and the new pterocarpan glucoside 6'-O-malonyl-3-O-beta-D-glucopyranosyl-6,6a-dehydromaackiain. These isoflavonoids, possessing a hepatoprotective activity, were stably produced by the A-18 calli for prolonged periods of observation.     

Fluctuating fine-scale spatial genetic structure in the common shrews (Eulipotyphla,Mammalia)

The spatial genetic structure is a topical issue in the studies of various aspects of ecology and evolution. Using the multilocus autocorrelation method with hypervariable microsatellite genetic markers, we investigated a fine-scale pattern of genetic structure in 5 local populations of the common shrew Sorex araneus separated by distances of 300–1000 m (the Moscow chromosomal race). Spatial genetic autocorrelation analysis based on 5 microsatellite loci (expected heterozygosity >0.79) with 90 alleles revealed a consistent pattern of significant positive genetic structure. By testing the autocorrelation at multiple scales from 25 to 500 m, we found that positive spatial genetic structure is detectable in distance classes of <500 m. The weaker spatial genetic structure positively correlated with a higher ratio of nonresident individuals to residents’ activity (number of captures). In contrast to nonresident animals, the residents demonstrated prominent genetic structure. Genetic difference (F_ST) between the populations was significant (0.016–0.051) and comparable with that between populations of different races analyzed previously (0.016–0.038). F_ST was not associated with geographic distance. These demographic patterns allowed us to propose a scheme of genetic-structure dynamics involving periodic appearance of more related local groups and renewal of allelic profiles from а common pool where the alleles are mixed. The scheme predicts fluctuating genetic structure and random similar differences among local populations.     

Effect of replacement of pyruvate/lactate in culture medium with glucose on preimplantation development of porcine embryos in vitro

The effect of glucose supplementation at different times in in vitro culture on the developmental competence of in vitro produced (IVP) porcine embryos was examined. In Experiment 1, when IVP embryos were cultured in modified NCSU-37 supplemented with pyruvate and lactate (IVC-pyr/lac) for 0 h, 24 h, 48 h, 72 h, 96 h, or 118 h and subsequently in modified NCSU-37 supplemented with glucose (IVC-glu) until Day 6 (Day 0=day of in vitro fertilization), the rates of blastocyst formation were significantly higher in embryos cultured in IVC-pyr/lac for 24 or 48 h (24.4% and 23.0%, respectively) than in embryos cultured in IVC-pyr/lac for the whole culture period (14.5%). However, there were no significant differences between embryos obtained after the energy source replacement and embryos cultured in IVC-glu for the whole culture period on the rates (15.2%-24.4%, and 16.8% respectively). Replacement of pyruvate/lactate with glucose at 58 h of culture in Experiment 2 significantly enhanced the rate (31.3%) compared to those after replacement at 48 h, 53 h and 63 h of culture (20.6%, 20.8%, and 21.1%, respectively). In conclusion, replacement of pyruvate/lactate with glucose as the energy substrate was optimal at 58 h of culture for the development of porcine embryos to the blastocyst stage.