Cholinergic modulation of intrinsic fibre-evoked excitatory transmission contains a nicotinic component in immature but not adult rat piriform cortex, in vitro

The piriform cortex (PC) is highly prone to epileptogenesis, particularly in immature animals, where decreased muscarinic modulation of PC intrinsic fibre excitatory neurotransmission is implicated as a likely cause. However, whether higher levels of acetylcholine (ACh) release occur in immature vs. adult PC remains unclear. We investigated this using in vitro extracellular electrophysiological recording techniques. Intrinsic fibre-evoked extracellular field potentials (EFPs) were recorded from layers II to III in PC brain slices prepared from immature (P14-18) and adult (P>40) rats. Adult and immature PC EFPs were suppressed by eserine (1muM) or neostigmine (1muM) application, with a greater suppression in immature ( approximately 40%) than adult ( approximately 30%) slices. Subsequent application of atropine (1muM) reversed EFP suppression, producing supranormal ( approximately 12%) recovery in adult slices, suggesting that suppression was solely muscarinic ACh receptor-mediated and that some 'basal' cholinergic 'tone' was present. Conversely, atropine only partially reversed anticholinesterase effects in immature slices, suggesting the presence of additional non-muscarinic modulation. Accordingly, nicotine (50muM) caused immature field suppression ( approximately 30%) that was further enhanced by neostigmine, whereas it had no effect on adult EFPs. Unlike atropine, nicotinic antagonists, mecamylamine and methyllycaconitine, induced immature supranormal field recovery ( approximately 20%) following anticholinesterase-induced suppression (with no effect on adult slices), confirming that basal cholinergic 'tone' was also present. We suggest that nicotinic inhibitory cholinergic modulation occurs in the immature rat PC intrinsic excitatory fibre system, possibly to complement the existing, weak muscarinic modulation, and could be another important developmentally regulated system governing immature PC susceptibility towards epileptogenesis.

A novel component of cannabis extract potentiates excitatory synaptic transmission in rat olfactory cortex in vitro

Cannabis is a potential treatment for epilepsy, although the few human studies supporting this use have proved inconclusive. Previously, we showed that a standardized cannabis extract (SCE), isolated Delta(9)-tetrahydrocannabinol (Delta(9)-THC), and even Delta(9)-THC-free SCE inhibited muscarinic agonist-induced epileptiform bursting in rat olfactory cortical brain slices, acting via CB1 receptors. The present work demonstrates that although Delta(9)-THC (1microM) significantly depressed evoked depolarizing postsynaptic potentials (PSPs) in rat olfactory cortex neurones, both SCE and Delta(9)-THC-free SCE significantly potentiated evoked PSPs (all results were fully reversed by the CB1 receptor antagonist SR141716A, 1microM); interestingly, the potentiation by Delta(9)-THC-free SCE was greater than that produced by SCE. On comparing the effects of Delta(9)-THC-free SCE upon evoked PSPs and artificial PSPs (aPSPs; evoked electrotonically following brief intracellular current injection), PSPs were enhanced, whereas aPSPs were unaffected, suggesting that the effect was not due to changes in background input resistance. Similar recordings made using CB1 receptor-deficient knockout mice (CB1(-/-)) and wild-type littermate controls revealed cannabinoid or extract-induced changes in membrane resistance, cell excitability and synaptic transmission in wild-type mice that were similar to those seen in rat neurones, but no effect on these properties were seen in CB1(-/-) cells. It appears that the unknown extract constituent(s) effects over-rode the suppressive effects of Delta(9)-THC on excitatory neurotransmitter release, which may explain some patients' preference for herbal cannabis rather than isolated Delta(9)-THC (due to attenuation of some of the central Delta(9)-THC side effects) and possibly account for the rare incidence of seizures in some individuals taking cannabis recreationally

Modelling European winter wind storm losses in current and future climate

Severe wind storms are one of the major natural hazards in the extratropics and inflict substantial economic damages and even casualties. Insured storm-related losses depend on (i) the frequency, nature and dynamics of storms, (ii) the vulnerability of the values at risk, (iii) the geographical distribution of these values, and (iv) the particular conditions of the risk transfer. It is thus of great importance to assess the impact of climate change on future storm losses. To this end, the current study employs—to our knowledge for the first time—a coupled approach, using output from high-resolution regional climate model scenarios for the European sector to drive an operational insurance loss model. An ensemble of coupled climate-damage scenarios is used to provide an estimate of the inherent uncertainties. Output of two state-of-the-art global climate models (HadAM3, ECHAM5) is used for present (1961–1990) and future climates (2071–2100, SRES A2 scenario). These serve as boundary data for two nested regional climate models with a sophisticated gust parametrizations (CLM, CHRM). For validation and calibration purposes, an additional simulation is undertaken with the CHRM driven by the ERA40 reanalysis. The operational insurance model (Swiss Re) uses a European-wide damage function, an average vulnerability curve for all risk types, and contains the actual value distribution of a complete European market portfolio. The coupling between climate and damage models is based on daily maxima of 10 m gust winds, and the strategy adopted consists of three main steps: (i) development and application of a pragmatic selection criterion to retrieve significant storm events, (ii) generation of a probabilistic event set using a Monte-Carlo approach in the hazard module of the insurance model, and (iii) calibration of the simulated annual expected losses with a historic loss data base. The climate models considered agree regarding an increase in the intensity of extreme storms in a band across central Europe (stretching from southern UK and northern France to Denmark, northern Germany into eastern Europe). This effect increases with event strength, and rare storms show the largest climate change sensitivity, but are also beset with the largest uncertainties. Wind gusts decrease over northern Scandinavia and Southern Europe. Highest intra-ensemble variability is simulated for Ireland, the UK, the Mediterranean, and parts of Eastern Europe. The resulting changes on European-wide losses over the 110-year period are positive for all layers and all model runs considered and amount to 44% (annual expected loss), 23% (10 years loss), 50% (30 years loss), and 104% (100 years loss). There is a disproportionate increase in losses for rare high-impact events. The changes result from increases in both severity and frequency of wind gusts. Considerable geographical variability of the expected losses exists, with Denmark and Germany experiencing the largest loss increases (116% and 114%, respectively). All countries considered except for Ireland (−22%) experience some loss increases. Some ramifications of these results for the socio-economic sector are discussed, and future avenues for research are highlighted. The technique introduced in this study and its application to realistic market portfolios offer exciting prospects for future research on the impact of climate change that is relevant for policy makers, scientists and economists.

Evaluating the risk of non-point source pollution from biosolids: integrated modelling of nutrient losses at field and catchment scales

A semi-distributed model, INCA, has been developed to determine the fate and distribution of nutrients in terrestrial and aquatic systems. The model simulates nitrogen and phosphorus processes in soils, groundwaters and river systems and can be applied in a semi-distributed manner at a range of scales. In this study, the model has been applied at field to sub-catchment to whole catchment scale to evaluate the behaviour of biosolid-derived losses of P in agricultural systems. It is shown that process-based models such as INCA, applied at a wide range of scales, reproduce field and catchment behaviour satisfactorily. The INCA model can also be used to generate generic information for risk assessment. By adjusting three key variables: biosolid application rates, the hydrological connectivity of the catchment and the initial P-status of the soils within the model, a matrix of P loss rates can be generated to evaluate the behaviour of the model and, hence, of the catchment system. The results, which indicate the sensitivity of the catchment to flow paths, to application rates and to initial soil conditions, have been incorporated into a Nutrient Export Risk Matrix (NERM).

Evolutionary bi-stability in pathogen transmission mode

Many pathogens transmit to new hosts by both infection (horizontal transmission) and transfer to the infected host's offspring (vertical transmission). These two transmission modes require speci®c adap- tations of the pathogen that can be mutually exclusive, resulting in a trade-off between horizontal and vertical transmission. We show that in mathematical models such trade-offs can lead to the simultaneous existence of two evolutionary stable states (evolutionary bi-stability) of allocation of resources to the two modes of transmission. We also show that jumping between evolutionary stable states can be induced by gradual environmental changes. Using quantitative PCR-based estimates of abundance in seed and vege- tative parts, we show that the pathogen of wheat, Phaeosphaeria nodorum, has jumped between two distinct states of transmission mode twice in the past 160 years, which, based on published evidence, we interpret as adaptation to environmental change. The ®nding of evolutionary bi-stability has impli- cations for human, animal and other plant diseases. An ill-judged change in a disease control programme could cause the pathogen to evolve a new, and possibly more damaging, combination of transmission modes. Similarly, environmental changes can shift the balance between transmission modes, with adverse effects on human, animal and plant health.

Threshold effects in price transmission: The case of Brazilian wheat, maize, and soya prices

Recent studies into price transmission have recognized the important role played by transport and transaction costs. Threshold models are one approach to accommodate such costs. We develop a generalized Threshold Error Correction Model to test for the presence and form of threshold behavior in price transmission that is symmetric around equilibrium. We use monthly wheat, maize, and soya prices from the United States, Argentina, and Brazil to demonstrate this model. Classical estimation of these generalized models can present challenges but Bayesian techniques avoid many of these problems. Evidence for thresholds is found in three of the five commodity price pairs investigated.

Transmission properties of Iranian wheat stripe virus

Transmission properties of Iranian wheat stripe virus (IWSV), a tentative member of the genus Tenuivirus, were studied. Results showed that similar to other tenuiviruses, IWSV multiplies in its vector, Unkanodes tanasijevici. In bioassay experiments, IWSV transmission rate by individual U. tanasijevici showed an increase with time after acquisition. IWSV was transovarially transmitted to 88-100% of progeny. The nymphs continued to be infective in the adult stage but with decreased efficiency. Males and females transmitted the virus with equal efficiency. Transmission properties of IWSV confirm the position of the virus in the genus Tenuivirus.