Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability

Epilepsy is the most common neurological disorder, with over 50 million people worldwide affected. Recent evidence suggests that the transient receptor potential cation channel subfamily V member 1 (TRPV1) may contribute to the onset and progression of some forms of epilepsy. Since the two nonpsychotropic cannabinoids cannabidivarin (CBDV) and cannabidiol (CBD) exert anticonvulsant activity in vivo and produce TRPV1-mediated intracellular calcium elevation in vitro, we evaluated the effects of these two compounds on TRPV1 channel activation and desensitization and in an in vitro model of epileptiform activity. Patch clamp analysis in transfected HEK293 cells demonstrated that CBD and CBDV dose-dependently activate and rapidly desensitize TRPV1, as well as TRP channels of subfamily V type 2 (TRPV2) and subfamily A type 1 (TRPA1). TRPV1 and TRPV2 transcripts were shown to be expressed in rat hippocampal tissue. When tested on epileptiform neuronal spike activity in hippocampal brain slices exposed to a Mg2+-free solution using multielectrode arrays (MEAs), CBDV reduced both epileptiform burst amplitude and duration. The prototypical TRPV1 agonist, capsaicin, produced similar, although not identical effects. Capsaicin, but not CBDV, effects on burst amplitude were reversed by IRTX, a selective TRPV1 antagonist. These data suggest that CBDV antiepileptiform effects in the Mg2+-free model are not uniquely mediated via activation of TRPV1. However, TRPV1 was strongly phosphorylated (and hence likely sensitized) in Mg2+-free solution-treated hippocampal tissue, and both capsaicin and CBDV caused TRPV1 dephosphorylation, consistent with TRPV1 desensitization. We propose that CBDV effects on TRP channels should be studied further in different in vitro and in vivo models of epilepsy.

The impact of monsoon intraseasonal variability on renewable power generation in India

India is increasingly investing in renewable technology to meet rising energy demands, with hydropower and other renewables comprising one-third of current installed capacity. Installed wind-power is projected to increase 5-fold by 2035 (to nearly 100GW) under the International Energy Agency’s New Policies scenario. However, renewable electricity generation is dependent upon the prevailing meteorology, which is strongly influenced by monsoon variability. Prosperity and widespread electrification are increasing the demand for air conditioning, especially during the warm summer. This study uses multi-decadal observations and meteorological reanalysis data to assess the impact of intraseasonal monsoon variability on the balance of electricity supply from wind-power and temperature-related demand in India. Active monsoon phases are characterised by vigorous convection and heavy rainfall over central India. This results in lower temperatures giving lower cooling energy demand, while strong westerly winds yield high wind-power output. In contrast, monsoon breaks are characterised by suppressed precipitation, with higher temperatures and hence greater demand for cooling, and lower wind-power output across much of India. The opposing relationship between wind-power supply and cooling demand during active phases (low demand, high supply) and breaks (high demand, low supply) suggests that monsoon variability will tend to exacerbate fluctuations in the so-called demand-net-wind (i.e., electrical demand that must be supplied from non-wind sources). This study may have important implications for the design of power systems and for investment decisions in conventional schedulable generation facilities (such as coal and gas) that are used to maintain the supply/demand balance. In particular, if it is assumed (as is common) that the generated wind-power operates as a price-taker (i.e., wind farm operators always wish to sell their power, irrespective of price) then investors in conventional facilities will face additional weather-volatility through the monsoonal impact on the length and frequency of production periods (i.e. their load-duration curves).

First-principles study of the inversion thermodynamics and electronic structure of FeM2X4 (thio)spinels (M = Cr, Mn, Co, Ni; X = O, S)

FeM2X4 spinels, where M is a transition metal and X is oxygen or sulfur, are candidate materials for spin filters, one of the key devices in spintronics. We present here a computational study of the inversion thermodynamics and the electronic structure of these (thio)spinels for M = Cr, Mn, Co, Ni, using calculations based on the density functional theory with on-site Hubbard corrections (DFT+U). The analysis of the configurational free energies shows that different behaviour is expected for the equilibrium cation distributions in these structures: FeCr2X4 and FeMn2S4 are fully normal, FeNi2X4 and FeCo2S4 are intermediate, and FeCo2O4 and FeMn2O4 are fully inverted. We have analyzed the role played by the size of the ions and by the crystal field stabilization effects in determining the equilibrium inversion degree. We also discuss how the electronic and magnetic structure of these spinels is modified by the degree of inversion, assuming that this could be varied from the equilibrium value. We have obtained electronic densities of states for the completely normal and completely inverse cation distribution of each compound. FeCr2X4, FeMn2X4, FeCo2O4 and FeNi2O4 are half-metals in the ferrimagnetic state when Fe is in tetrahedral positions. When M is filling the tetrahedral positions, the Cr-containing compounds and FeMn2O4 are half-metallic systems, while the Co and Ni spinels are insulators. The Co and Ni sulfide counterparts are metallic for any inversion degree together with the inverse FeMn2S4. Our calculations suggest that the spin filtering properties of the FeM2X4 (thio)spinels could be modified via the control of the cation distribution through variations in the synthesis conditions.

A review of biochars’ potential role in the remediation, revegetation and restoration of contaminated soils

Biochars are biological residues combusted under low oxygen conditions, resulting in a porous, low density carbon rich material. Their large surface areas and cation exchange capacities, determined to a large extent by source materials and pyrolysis temperatures, enables enhanced sorption of both organic and inorganic contaminants to their surfaces, reducing pollutant mobility when amending contaminated soils. Liming effects or release of carbon into soil solution may increase arsenic mobility, whilst low capital but enhanced retention of plant nutrients can restrict revegetation on degraded soils amended only with biochars; the combination of composts, manures and other amendments with biochars could be their most effective deployment to soils requiring stabilisation by revegetation. Specific mechanisms of contaminant-biochar retention and release over time and the environmental impact of biochar amendments on soil organisms remain somewhat unclear but must be investigated to ensure that the management of environmental pollution coincides with ecological sustainability.

Controlled variation of monomer sequence-distribution in the synthesis of aromatic poly(ether ketone)s

The effects of varying the alkali metal cation in the high-temperature nucleophilic synthesis of a semi-crystalline, aromatic poly(ether ketone) have been systematically investigated, and striking variations in the sequence-distributions and thermal characteristics of the resulting polymers were found. Polycondensation of 4,4'-dihydroxybenzophenone with 1,3-bis(4-fluorobenzoyl)benzene in diphenylsulfone as solvent, in the presence of an alkali metal carbonate M2CO3 (M= Li, Na, K, or Rb) as base, affords a range of different polymers that vary in the distribution pattern of 2-ring and 3-ring monomer units along the chain. Lithium carbonate gives an essentially alternating and highly crystalline polymer, but the degree of sequence-randomisation increases progressively as the alkali metal series is descended, with rubidium carbonate giving a fully random and non-thermally-crystallisable polymer. Randomisation during polycondensation is shown to result from reversible cleavage of the ether linkages in the polymer by fluoride ions, and an isolated sample of alternating-sequence polymer is thus converted to a fully randomised material on heating with rubidium fluoride.

Ecological traits affect the sensitivity of bees to land-use pressures in European agricultural landscapes

1. Bees are a functionally important and economically valuable group, but are threatened byland-use conversion and intensification. Such pressures are not expected to affect all species identically; rather, they are likely to be mediated by the species’ ecological traits. 2. Understanding which types of species are most vulnerable under which land uses is an important step towards effective conservation planning.3. We collated occurrence and abundance data for 257 bee species at 1584 European sites from surveys reported in 30 published papers (70 056 records) and combined them with species-level ecological trait data. We used mixed-effects models to assess the importance of land use (land-use class, agricultural use-intensity and a remotely-sensed measure of vegetation),traits and trait 9 land-use interactions, in explaining species occurrence and abundance.4. Species’ sensitivity to land use was most strongly influenced by flight season duration and foraging range, but also by niche breadth, reproductive strategy and phenology, with effects that differed among cropland, pastoral and urban habitats.5. Synthesis and applications. Rather than targeting particular species or settings, conservation action s may be more effective if focused on mitigating situations where species’ traits strongly and negatively interact with land-use pressures. We find evidence that low-intensity agriculture can maintain relatively diverse bee communities; in more intensive settings, added floral resources may be beneficial, but will require careful placement with respect to foraging ranges of smaller bee species. Protection of semi-natural habitats is essential, however; in particular, conversion to urban environments could have severe effects on bee diversity and pollination services. Our results highlight the importance of exploring how ecological traits mediate species responses to human impacts, but further research is needed to enhance the predictive ability of such analyses.

Detection of the phosphorylation of the estrogen receptor alpha as an outcome of GPR30 activation

Phosphorylation of the serine residues in estrogen receptor (ER) α is important in transcriptional activation. Hence, methods to detect such posttranslational modifi cation events are valuable. We describe, in detail, the analysis of the phosphorylated ERα by electrophoretic separation of proteins and subsequent immuno-blotting techniques. In particular, phosphorylation of the ERα is one possible outcome of activation of the putative membrane estrogen receptor (mER), GPR30. Hence, phosphorylation represents a cross talk event between GPR30 and ERα and may be important in estrogen-regulated physiology.