SAR inspired by aldehyde oxidase (AO) metabolism: Discovery of novel,CNS penetrant tricyclic M4 PAMs

This letter describes progress towards an M₄ PAM preclinical candidate inspired by an unexpected aldehyde oxidase (AO) metabolite of a novel, CNS penetrant thieno[2,3-c]pyridine core to an equipotent, non-CNS penetrant thieno[2,3-c]pyrdin-7(6H)-one core. Medicinal chemistry design efforts yielded two novel tricyclic cores that enhanced M₄ PAM potency, regained CNS penetration, displayed favorable DMPK properties and afforded robust in vivo efficacy in reversing amphetamine-induced hyperlocomotion in rats.     

Selection for genetics‐based architecture traits in a native cottonwood negatively affects invasive tamarisk in a restoration field trial

Climate change and competition from invasive species remain two important challenges in restoration. We examined the hypothesis that non‐native tamarisk (Tamarix spp.) reestablishment after aboveground removal is affected by genetics‐based architecture of native Fremont cottonwood (Populus fremontii) used in restoration. As cottonwood architecture (height, canopy width, number of stems, and trunk diameter) is, in part, determined by genetics, we predicted that trees from different provenances would exhibit different architecture, and mean annual maximum temperature transfer distance from the provenances would interact with the architecture to affect tamarisk. In a common garden in Chevelon, AZ, U.S.A. (elevation 1,496 m), with cottonwoods from provenances spanning its elevation distribution, we measured the performance of both cottonwoods and tamarisk. Several key findings emerged. On average, cottonwoods from higher elevations were (1) two times taller and wider, covered approximately 3.5 times more basal area, and were less shrubby in appearance, by exhibiting four times fewer number of stems than cottonwoods from lower elevations; (2) had 50% fewer tamarisk growing underneath, which were two times shorter and covered 6.5 times less basal area than tamarisk growing underneath cottonwoods of smaller stature; and (3) the number of cottonwood stems did not affect tamarisk growth, possibly because the negative relationship between cottonwood stems and basal area. In combination, these findings argue that cottonwood architecture is affected by local conditions that interact with genetics‐based architecture. These interactions can negatively affect the growth of reinvading tamarisk and enhance restoration success. Our study emphasizes the importance of incorporating genetic and environmental interactions of plants used in restoration.     

Assessment of a large number of empirical plant species niche models by elicitation of knowledge from two national experts

Quantitative models play an increasing role in exploring the impact of global change on biodiversity. To win credibility and trust, they need validating. We show how expert knowledge can be used to assess a large number of empirical species niche models constructed for the British vascular plant and bryophyte flora. Key outcomes were (a) scored assessments of each modeled species and niche axis combination, (b) guidance on models needing further development, (c) exploration of the trade‐off between presenting more complex model summaries, which could lead to more thorough validation, versus the longer time these take to evaluate, (d) quantification of the internal consistency of expert opinion based on comparison of assessment scores made on a random subset of models evaluated by both experts. Overall, the experts assessed 39% of species and niche axis combinations to be “poor” and 61% to show a degree of reliability split between “moderate” (30%), “good” (25%), and “excellent” (6%). The two experts agreed in only 43% of cases, reaching greater consensus about poorer models and disagreeing most about models rated as better by either expert. This low agreement rate suggests that a greater number of experts is required to produce reliable assessments and to more fully understand the reasons underlying lack of consensus. While area under curve (AUC) statistics showed generally very good ability of the models to predict random hold‐out samples of the data, there was no correspondence between these and the scores given by the experts and no apparent correlation between AUC and species prevalence. Crowd‐sourcing further assessments by allowing web‐based access to model fits is an obvious next step. To this end, we developed an online application for inspecting and evaluating the fit of each niche surface to its training data.     

Assessing factors associated with changes in the numbers of birds visiting gardens in winter: Are predators partly to blame?

The factors governing the recent declines observed in many songbirds have received much research interest, in particular whether increases of avian predators have had a negative effect on any of their prey species. In addition, further discussion has centered on whether or not the choice of model formulation has an effect on model inference. The study goal was to evaluate changes in the number of 10 songbird species in relation to a suite of environmental covariates, testing for any evidence in support of a predator effect using multiple model formulations to check for consistency in the results. We compare two different approaches to the analysis of long‐term garden bird monitoring data. The first approach models change in the prey species between 1970 and 2005 as a function of environmental covariates, including the abundance of an avian predator, while the second uses a change–change approach. Significant negative relationships were found between Eurasian Sparrowhawk Accipiter nisus and three of the 10 species analyzed, namely house Sparrow Passer domesticus, starling Sturnus vulgaris, and blue tit Cyanistes caeruleus. The results were consistent under both modeling approaches. It is not clear if this is a direct negative impact on the overall populations of these species or a behavioral response of the prey species to avoid feeding stations frequented by Sparrowhawks (which may in turn have population consequences, by reducing available resources). The species showing evidence of negative effects of Sparrowhawks were three of the four species most at risk to Sparrowhawk predation according to their prevalence in the predator's diet. The associations could be causal in nature, although in practical terms the reduction in the rate of change in numbers visiting gardens accredited to Sparrowhawks is relatively small, and so unlikely to be the main driver of observed population declines.     

Authors need to be prudent when assigning names to microbial isolates

Antonie van Leeuwenhoek -     

Amsterdam urban canals contain novel niches for methane-cycling microorganisms

Urbanised environments have been identified as hotspots of anthropogenic methane emissions. Especially urban aquatic ecosystems are increasingly recognised as important sources of methane. However, the microbiology behind these emissions remains unexplored. Here, we applied microcosm incubations and molecular analyses to investigate the methane-cycling community of the Amsterdam canal system in the Netherlands. The sediment methanogenic communities were dominated by Methanoregulaceae and Methanosaetaceae, with co-occurring methanotrophic Methanoperedenaceae and Methylomirabilaceae indicating the potential for anaerobic methane oxidation. Methane was readily produced after substrate amendment, suggesting an active but substrate-limited methanogenic community. Bacterial 16S rRNA gene amplicon sequencing of the sediment revealed a high relative abundance of Thermodesulfovibrionia. Canal wall biofilms showed the highest initial methanotrophic potential under oxic conditions compared to the sediment. During prolonged incubations the maximum methanotrophic rate increased to 8.08 mmol g_DW⁻¹ d⁻¹ that was concomitant with an enrichment of Methylomonadaceae bacteria. Metagenomic analysis of the canal wall biofilm lead to the recovery of a single methanotroph metagenome-assembled genome. Taxonomic analysis showed that this methanotroph belongs to the genus Methyloglobulus. Our results underline the importance of previously unidentified and specialised environmental niches at the nexus of the natural and human-impacted carbon cycle.     

Validated predictive modelling of the environmental resistome

Multi-drug-resistant bacteria pose a significant threat to public health. The role of the environment in the overall rise in antibiotic-resistant infections and risk to humans is largely unknown. This study aimed to evaluate drivers of antibiotic-resistance levels across the River Thames catchment, model key biotic, spatial and chemical variables and produce predictive models for future risk assessment. Sediment samples from 13 sites across the River Thames basin were taken at four time points across 2011 and 2012. Samples were analysed for class 1 integron prevalence and enumeration of third-generation cephalosporin-resistant bacteria. Class 1 integron prevalence was validated as a molecular marker of antibiotic resistance; levels of resistance showed significant geospatial and temporal variation. The main explanatory variables of resistance levels at each sample site were the number, proximity, size and type of surrounding wastewater-treatment plants. Model 1 revealed treatment plants accounted for 49.5% of the variance in resistance levels. Other contributing factors were extent of different surrounding land cover types (for example, Neutral Grassland), temporal patterns and prior rainfall; when modelling all variables the resulting model (Model 2) could explain 82.9% of variations in resistance levels in the whole catchment. Chemical analyses correlated with key indicators of treatment plant effluent and a model (Model 3) was generated based on water quality parameters (contaminant and macro- and micro-nutrient levels). Model 2 was beta tested on independent sites and explained over 78% of the variation in integron prevalence showing a significant predictive ability. We believe all models in this study are highly useful tools for informing and prioritising mitigation strategies to reduce the environmental resistome.     

Implications of land‐use change to Short Rotation Forestry in Great Britain for soil and biomass carbon

Land‐use change can have significant impacts on soil and aboveground carbon (C) stocks and there is a clear need to identify sustainable land uses which maximize C mitigation potential. Land‐use transitions from agricultural to bioenergy crops are increasingly common in Europe with one option being Short Rotation Forestry (SRF). Research on the impact on C stocks of the establishment of SRF is limited, but given the potential for this bioenergy crop in temperate climates, there is an evident knowledge gap. Here, we examine changes in soil C stock following the establishment of SRF using combined short (30 cm depth) and deep (1 m depth) soil cores at 11 sites representing 29 transitions from agriculture to SRF. We compare the effects of tree species including 9 coniferous, 16 broadleaved and 4 Eucalyptus transitions. SRF aboveground and root biomass were also estimated in 15 of the transitions using tree mensuration data allowing assessments of changes in total ecosystem C stock. Planting coniferous SRF, compared to broadleaved and Eucalyptus SRF, resulted in greater accumulation of litter and overall increased soil C stock relative to agricultural controls. Though broadleaved SRF had no overall effect on soil C stock, it showed the most variable response suggesting species‐specific effects and interactions with soil types. While Eucalyptus transitions induced a reduction in soil C stocks, this was not significant unless considered on a soil mass basis. Given the relatively young age and limited number of Eucalyptus plantations, it is not possible to say whether this reduction will persist in older stands. Combining estimates of C stocks from different ecosystem components (e.g., soil, aboveground biomass) reinforced the accumulation of C under coniferous SRF, and indicates generally positive effects of SRF on whole‐ecosystem C. These results fill an important knowledge gap and provide data for modelling of future scenarios of LUC.     

Ecological restoration of rich fens in Europe and North America: from trial and error to an evidence‐based approach

Fens represent a large array of ecosystem services, including the highest biodiversity found among wetlands, hydrological services, water purification and carbon sequestration. Land‐use change and drainage has severely damaged or annihilated these services in many parts of North America and Europe; restoration plans are urgently needed at the landscape level. We review the major constraints on the restoration of rich fens and fen water bodies in agricultural areas in Europe and disturbed landscapes in North America: (i) habitat quality problems: drought, eutrophication, acidification, and toxicity, and (ii) recolonization problems: species pools, ecosystem fragmentation and connectivity, genetic variability, and invasive species; and here provide possible solutions. We discuss both positive and negative consequences of restoration measures, and their causes. The restoration of wetland ecosystem functioning and services has, for a long time, been based on a trial‐and‐error approach. By presenting research and practice on the restoration of rich fen ecosystems within agricultural areas, we demonstrate the importance of biogeochemical and ecological knowledge at different spatial scales for the management and restoration of biodiversity, water quality, carbon sequestration and other ecosystem services, especially in a changing climate. We define target processes that enable scientists, nature managers, water managers and policy makers to choose between different measures and to predict restoration prospects for different types of deteriorated fens and their starting conditions.