Psychosis as a disorder of muscarinic signalling: psychopathology and pharmacology.

Dopaminergic receptor antagonism is a crucial component of all licensed treatments for psychosis, and dopamine dysfunction has been central to pathophysiological models of psychotic symptoms. Some clinical trials, however, indicate that drugs that act through muscarinic receptor agonism can also be effective in treating psychosis, potentially implicating muscarinic abnormalities in the pathophysiology of psychosis. Here, we discuss understanding of the central muscarinic system, and we examine preclinical, behavioural, post-mortem, and neuroimaging evidence for its involvement in psychosis. We then consider how altered muscarinic signalling could contribute to the genesis and maintenance of psychotic symptoms, and we review the clinical evidence for muscarinic agents as treatments. Finally, we discuss future research that could clarify the relationship between the muscarinic system and psychotic symptoms.

Climate change effects on denitrification performance of woodchip bioreactors treating agricultural tile drainage.

Denitrifying woodchip bioreactors (WBRs) are a nature-based technology that are increasingly used to control nonpoint source nitrate (NO3-) pollution in agricultural catchments. The treatment effectiveness of WBRs depends on temperature and hydraulic retention time (HRT), both of which are affected by climate change. Warmer temperatures will increase microbial denitrification rates, but the extent to which the resulting benefits to treatment performance may be offset by intensified precipitation and shorter HRTs is not clear. Here, we use three years of monitoring data from a WBR in Central New York State to train an integrated hydrologic-biokinetic model describing links among temperature, precipitation, bioreactor discharge, denitrification kinetics, and NO3- removal efficiencies. Effects of climate warming are assessed by first training a stochastic weather generator with eleven years of weather data from our field site, and then adjusting the distribution of precipitation intensities according to the Clausius-Clapeyron relationship between water vapor and temperature. Modeling results indicate, in our system, faster denitrification rates will outweigh the influence of intensified precipitation and discharge under warming, leading to net improvements in NO3- load reductions. Median cumulative NO3- load reductions at our study site from May - October are projected to increase from 21.7% (interquartile range 17.4%-26.1%) under baseline hydro-climate to 41.0% (interquartile range 32.6-47.1%) with a + 4 °C change in mean air temperature. This improved performance under climate warming is driven by strong nonlinear dependence of NO3- removal rates on temperature. Temperature sensitivity may increase with woodchip age and lead to stronger temperature-response in systems like this one with a highly aged woodchip matrix. While the impacts of hydro-climatic change on WBR performance will depend on site-specific properties, this hydrologic-biokinetic modeling approach provides a framework for assessing climate impacts on the effectiveness of WBRs and other denitrifying nature-based systems.

Oxic-anoxic cycling promotes coupling between complex carbon metabolism and denitrification in woodchip bioreactors.

Denitrifying woodchip bioreactors (WBRs) are increasingly used to manage the release of non-point source nitrogen (N) by stimulating microbial denitrification. Woodchips serve as a renewable organic carbon (C) source, yet the recalcitrance of organic C in lignocellulosic biomass causes many WBRs to be C-limited. Prior studies have observed that oxic-anoxic cycling increased the mobilization of organic C, increased nitrate (NO3 - ) removal rates, and attenuated production of nitrous oxide (N2 O). Here, we use multi-omics approaches and amplicon sequencing of fungal 5.8S-ITS2 and prokaryotic 16S rRNA genes to elucidate the microbial drivers for enhanced NO3 - removal and attenuated N2 O production under redox-dynamic conditions. Transient oxic periods stimulated the expression of fungal ligninolytic enzymes, increasing the bioavailability of woodchip-derived C and stimulating the expression of denitrification genes. Nitrous oxide reductase (nosZ) genes were primarily clade II, and the ratio of clade II/clade I nosZ transcripts during the oxic-anoxic transition was strongly correlated with the N2 O yield. Analysis of metagenome-assembled genomes revealed that many of the denitrifying microorganisms also have a genotypic ability to degrade complex polysaccharides like cellulose and hemicellulose, highlighting the adaptation of the WBR microbiome to the ecophysiological niche of the woodchip matrix.

Nitrous Oxide and Methane Dynamics in Woodchip Bioreactors: Effects of Water Level Fluctuations on Partitioning into Trapped Gas Phases.

Woodchip bioreactors (WBRs) are low-cost, passive systems for nonpoint source nitrogen removal at terrestrial-aquatic interfaces. The greenhouse gases nitrous oxide (N2O) and methane (CH4) can be produced within WBRs, and efforts to reduce N2O and CH4 emissions from WBR systems require improved understanding of the biogeochemical and physical-chemical mechanisms regulating their production, transport, and release. This study evaluates the impact of trapped gas-filled void volumes as sinks of dissolved gases from water and as sources of episodic fluxes when water levels fall. Dissolved gas tracer experiments in a laboratory bioreactor were used to parameterize nonequilibrium advection-dispersion-gas transfer models and quantify trapping of gas-filled voids as a function of antecedent hydrological conditions. Experiments following a water-level rise revealed that up to 24% of the WBR pore volume was occupied by trapped gas phases, which were primarily located in pore spaces inside woodchips. This finding was confirmed with X-ray-computed microtomography. N2O (3.3-10%) and CH4 (4.3-14%) injected into the reactor following a water table rise partitioned into gas-filled voids and were released when water tables fell. In the case of N2O, partitioning into trapped gas phases makes N2O unavailable for enzymatic reduction, potentially enhancing N2O fluxes under fluctuating water levels.

MR imaging of infrapatellar plica injury.

OBJECTIVE: Injury to the infrapatellar plica (ligamentum mucosum) has not been previously described in the radiology literature to our knowledge. This article shows the MR imaging appearance of injury to the infrapatellar plica. CONCLUSION: Injury to the infrapatellar plica is uncommon but should be considered as a potential source of knee pain, especially if no other evidence indicates internal derangement. MR imaging can reveal a typical appearance for infrapatellar plica injury.