An analysis of regional climate simulations for Western Australia's wine regions-model evaluation and future climate projections

The Weather Research and Forecasting (WRF) Model is evaluated as a regional climate model for the simulation of climate indices that are relevant to viticulture in Western Australia's wine regions at a 5-km resolution under current and future climate. WRF is driven with ERA-Interim reanalysis for the current climate and three global climate models (GCMs) for both current and future climate. The focus of the analysis is on a selection of climate indices that are commonly used in climate-viticulture research. Simulations of current climate are evaluated against an observational dataset to quantify model errors over the 1981-2010 period. Changes to the indices under future climate based on the SRES A2 emissions scenario are then assessed through an analysis of future (2030-59) minus present (1970-99) climate. Results show that when WRF is driven with ERA-Interim there is generally good agreement with observations for all of the indices although there is a noticeable negative bias for the simulation of precipitation. The results for the GCM-forced simulations were less consistent. Namely, while the GCM-forced simulations performed reasonably well for the temperature indices, all simulations performed inconsistently for the precipitation index. Climate projections showed significant warming for both of the temperature indices and indicated potential risks to Western Australia's wine growing regions under future climate, particularly in the north. There was disagreement between simulations with regard to the projections of the precipitation indices and hence greater uncertainty as to how these will be characterized under future climate

Acetylcholinesterase Inhibition of Diversely Functionalized Quinolinones for Alzheimer's Disease Therapy

In this communication, wereport the synthesis and cholinesterase (ChE)/monoamine oxidase (MAO) inhibition of 19 quinolinones (QN1-19) and 13 dihydroquinolinones (DQN1-13) designed as potential multitarget small molecules (MSM) for Alzheimer¿s disease therapy. Contrary to our expectations, none of them showed significant human recombinant MAO inhibition, but compounds QN8, QN9, and DQN7 displayed promising human recombinant acetylcholinesterase (hrAChE) and butyrylcholinesterase (hrBuChE) inhibition. In particular, molecule QN8 was found to be a potent and quite selective non-competitive inhibitor of hrAChE (IC50 = 0.29 M), with Ki value in nanomolar range (79 nM). Pertinent docking analysis confirmed this result, suggesting that this ligand is an interesting hit for further investigation.R.A., M.S., P.B., and K.M. were supported by European Regional Development Fund/European Social Fund (ERDF/ESF, project PharmaBrain, no. CZ.02.1.01/0.0/0.0/16_025/0007444), University of Hradec Kralove (no. SV2113-2019, VT2019-2021), and EU COST action CA15135 MuTaLig. J.M.C. thanks Ministerio de Economía (MINECO, SAF2015-65586-R) and Universidad Camilo José Cela (UCJC, grants UCJC 2020-03, and UCJC 2020-33) for support

Evidence for transitional and mildly alkalic eruptions during Hawai\u27i\u27s dominantly tholeiitic shield-building stage: Insights from the Kulanaokuaiki Tephra (≥1.0 ka) at Kīlauea Volcano, HI

Vitric clasts from a marker horizon in the Kulanaokuaiki Tephra, deposited on the summit and flanks of Kīlauea Volcano, HI, during a prolonged period of explosive eruptions and low magma supply \u3e1.0 ka, show unusual enrichments in alkalis relative to silica and in incompatible elements, in contrast with the volcano\u27s dominantly tholeiitic shield-building lavas. The clasts are transitional basalts, with compositions near the tholeiitic-alkalic boundary (Macdonald and Katsura, 1964). Nearly uniform in composition across ∼200 km2, the clasts are the most proximal to the summit among rare occurrences of transitional and mildly alkalic shield-stage eruptions at Kīlauea. In contrast with the volcano\u27s effusive shield-building style, stratigraphic evidence suggests the clasts were deposited in one of Kīlauea\u27s most vigorous explosive eruptions in the past 2.5 ka—an episode punctuated by high fountaining along with an ∼12 km-tall ash plume. The tephra\u27s composition is consistent with those of five unusual shield-stage Kīlauea lavas. All contain \u3c50.0 wt% SiO2 and 3.0–4.0 wt% Na2O + K2O. All but one contain ≥0.70 wt% K2O, ≥3.0 wt% TiO2, and \u3e 0.30 wt% P2O5. The transitional Kulanaokuaiki clasts also display elevated abundances and ratios of incompatible trace elements (e.g., ∼19 ppm La, La/Yb ∼ 8.6). Compositionally, these early shield-stage clasts and lavas resemble those erupted at the end of shield building at older Hawaiian volcanoes, attributed to lower degrees of partial mantle melting. Chemical constraints and extrinsic circumstances suggest that similar episodes of transitional and mildly alkalic volcanism will likely recur throughout shield building

Evaluating reanalysis-driven CORDEX regional climate models over Australia: model performance and errors

The ability of regional climate models (RCMs) to accurately simulate current and future climate is increasingly important for impact assessment. This is the first evaluation of all reanalysis-driven RCMs within the CORDEX Australasia framework [four configurations of the Weather Forecasting and Research (WRF) model, and single configurations of COSMO-CLM (CCLM) and the Conformal-Cubic Atmospheric Model (CCAM)] to simulate the historical climate of Australia (1981–2010) at 50 km resolution. Simulations of near-surface maximum and minimum temperature and precipitation were compared with gridded observations at annual, seasonal, and daily time scales. The spatial extent, sign, and statistical significance of biases varied markedly between the RCMs. However, all RCMs showed widespread, statistically significant cold biases in maximum temperature which were the largest during winter. This bias exceeded − 5 K for some WRF configurations, and was the lowest for CCLM at ± 2 K. Most WRF configurations and CCAM simulated minimum temperatures more accurately than maximum temperatures, with biases in the range of ± 1.5 K. RCMs overestimated precipitation, especially over Australia’s populous eastern seaboard. Strong negative correlations between mean monthly biases in precipitation and maximum temperature suggest that the maximum temperature cold bias is linked to precipitation overestimation. This analysis shows that the CORDEX Australasia ensemble is a valuable dataset for future impact studies, but improving the representation of land surface processes, and subsequently of surface temperatures, will improve RCM performance. The varying RCM capabilities identified here serve as a foundation for the development of future regional climate projections and impact assessments for Australia

Image1_Investigating role of ASIC2 in synaptic and behavioral responses to drugs of abuse.tiff

Drugs of abuse produce rearrangements at glutamatergic synapses thought to contribute to drug-reinforced behaviors. Acid-Sensing Ion Channels (ASICs) have been suggested to oppose these effects, largely due to observations in mice lacking the ASIC1A subunit. However, the ASIC2A and ASIC2B subunits are known to interact with ASIC1A, and their potential roles in drugs of abuse have not yet been investigated. Therefore, we tested the effects of disrupting ASIC2 subunits in mice exposed to drugs of abuse. We found conditioned place preference (CPP) to both cocaine and morphine were increased in Asic2−/− mice, which is similar to what was observed in Asic1a−/− mice. Because nucleus accumbens core (NAcc) is an important site of ASIC1A action, we examined expression of ASIC2 subunits there. By western blot ASIC2A was readily detected in wild-type mice, while ASIC2B was not, suggesting ASIC2A is the predominant subunit in nucleus accumbens core. An adeno-associated virus vector (AAV) was used to drive recombinant ASIC2A expression in nucleus accumbens core of Asic2−/− mice, resulting in near normal protein levels. Moreover, recombinant ASIC2A integrated with endogenous ASIC1A subunits to form functional channels in medium spiny neurons (MSNs). However, unlike ASIC1A, region-restricted restoration of ASIC2A in nucleus accumbens core was not sufficient to affect cocaine or morphine conditioned place preference, suggesting effects of ASIC2 differ from those of ASIC1A. Supporting this contrast, we found that AMPA receptor subunit composition and the ratio of AMPA receptor-mediated current to NMDA receptor-mediated current (AMPAR/NMDAR) were normal in Asic2−/− mice and responded to cocaine withdrawal similarly to wild-type animals. However, disruption of ASIC2 significantly altered dendritic spine morphology, and these effects differed from those reported previously in mice lacking ASIC1A. We conclude that ASIC2 plays an important role in drug-reinforced behavior, and that its mechanisms of action may differ from ASIC1A.</p

Image2_Investigating role of ASIC2 in synaptic and behavioral responses to drugs of abuse.tiff

Drugs of abuse produce rearrangements at glutamatergic synapses thought to contribute to drug-reinforced behaviors. Acid-Sensing Ion Channels (ASICs) have been suggested to oppose these effects, largely due to observations in mice lacking the ASIC1A subunit. However, the ASIC2A and ASIC2B subunits are known to interact with ASIC1A, and their potential roles in drugs of abuse have not yet been investigated. Therefore, we tested the effects of disrupting ASIC2 subunits in mice exposed to drugs of abuse. We found conditioned place preference (CPP) to both cocaine and morphine were increased in Asic2−/− mice, which is similar to what was observed in Asic1a−/− mice. Because nucleus accumbens core (NAcc) is an important site of ASIC1A action, we examined expression of ASIC2 subunits there. By western blot ASIC2A was readily detected in wild-type mice, while ASIC2B was not, suggesting ASIC2A is the predominant subunit in nucleus accumbens core. An adeno-associated virus vector (AAV) was used to drive recombinant ASIC2A expression in nucleus accumbens core of Asic2−/− mice, resulting in near normal protein levels. Moreover, recombinant ASIC2A integrated with endogenous ASIC1A subunits to form functional channels in medium spiny neurons (MSNs). However, unlike ASIC1A, region-restricted restoration of ASIC2A in nucleus accumbens core was not sufficient to affect cocaine or morphine conditioned place preference, suggesting effects of ASIC2 differ from those of ASIC1A. Supporting this contrast, we found that AMPA receptor subunit composition and the ratio of AMPA receptor-mediated current to NMDA receptor-mediated current (AMPAR/NMDAR) were normal in Asic2−/− mice and responded to cocaine withdrawal similarly to wild-type animals. However, disruption of ASIC2 significantly altered dendritic spine morphology, and these effects differed from those reported previously in mice lacking ASIC1A. We conclude that ASIC2 plays an important role in drug-reinforced behavior, and that its mechanisms of action may differ from ASIC1A.</p