A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1

We report the design and characterization of UNC3866, a potent antagonist of the methyllysine (Kme) reading function of the Polycomb CBX and CDY families of chromodomains. Polycomb CBX proteins regulate gene expression by targeting Polycomb repressive complex 1 (PRC1) to sites of H3K27me3 via their chromodomains. UNC3866 binds the chromodomains of CBX4 and CBX7 most potently, with a K d of â ∼1/4100 nM for each, and is 6-to 18-fold selective as compared to seven other CBX and CDY chromodomains while being highly selective over >250 other protein targets. X-ray crystallography revealed that UNC3866's interactions with the CBX chromodomains closely mimic those of the methylated H3 tail. UNC4195, a biotinylated derivative of UNC3866, was used to demonstrate that UNC3866 engages intact PRC1 and that EED incorporation into PRC1 is isoform dependent in PC3 prostate cancer cells. Finally, UNC3866 inhibits PC3 cell proliferation, consistent with the known ability of CBX7 overexpression to confer a growth advantage, whereas UNC4219, a methylated negative control compound, has negligible effects

SARS-CoV-2 variants of interest and concern naming scheme conducive for global discourse

A group convened and led by the Virus Evolution Working Group of the World Health Organization reports on its deliberations and announces a naming scheme that will enable clear communication about SARS-CoV-2 variants of interest and concern.Molecular basis of virus replication, viral pathogenesis and antiviral strategie

A unifying approach for evaluating the condition of wetland plant communities and identifying related stressors

Assessment of vegetation is an important part of evaluating wetland condition, but it is complicated by the variety of plant communities that are naturally present in freshwater wetlands. We present an approach to evaluate wetland condition consisting of: (1) a stratified random sample representing the entire range of anthropogenic stress, (2) field data representing a range of water depths within the wetlands sampled, (3) nonmetric multidimensional scaling (MDS) to determine a biological condition gradient across the wetlands sampled, (4) hierarchical clustering to interpret the condition results relative to recognizable plant communities, (5) classification and regression tree (CART) analysis to relate biological condition to natural and anthropogenic environmental drivers, and (6) mapping the results to display their geographic distribution. We applied this approach to plant species data collected at 90 wetlands of the U.S. Great Lakes coast that support a variety of plant communities, reflecting the diverse physical environment and anthropogenic stressors present within the region. Hierarchical cluster analysis yielded eight plant communities at a minimum similarity of 25%. Wetlands that clustered botanically were often geographically clustered as well, even though location was not an input variable in the analysis. The eight vegetation clusters corresponded well with the MDS configuration of the data, in which the first axis was strongly related (R2 = 0.787, P < 0.001) with floristic quality index (FQI) and the second axis was related to the Great Lake of occurrence. CART models using FQI and the first MDS axis as the response variables explained 75% and 82% of the variance in the data, resulting in 6-7 terminal groups spanning the condition gradient. Initial CART splits divided the region based on growing degree-days and cumulative anthropogenic stress; only after making these broad divisions were wetlands distinguished by more local characteristics. Agricultural and urban development variables were important correlates of wetland biological condition, generating optimal or surrogate splits at every split node of the MDS CART model. Our findings provide a means of using vegetation to evaluate a range of wetland condition across a broad and diverse geographic region

Partitioning vegetation response to anthropogenic stress to develop multi-taxa wetland indicators

Emergent plants can be suitable indicators of anthropogenic stress in coastal wetlands if their responses to natural environmental variation can be parsed from their responses to human activities in and around wetlands. We used hierarchical partitioning to evaluate the independent influence of geomorphology, geography, and anthropogenic stress on common wetland plants of the U.S. Great Lakes coast and developed multi-taxa models indicating wetland condition. A seven-taxon model predicted condition relative to watershed-derived anthropogenic stress, and a four-taxon model predicted condition relative to within-wetland anthropogenic stressors that modified hydrology. The Great Lake on which the wetlands occurred explained an average of about half the variation in species cover, and subdividing the data by lake allowed us to remove that source of variation. We developed lake-specific multi-taxa models for all of the Great Lakes except Lake Ontario, which had no plant species with significant independent effects of anthropogenic stress. Plant responses were both positive (increasing cover with stress) and negative (decreasing cover with stress), and plant taxa incorporated into the lake-specific models differed by Great Lake. The resulting models require information on only a few taxa, rather than all plant species within a wetland, making them easier to implement than existing indicators

Nutrient limitation and botanical diversity in wetlands: Can fertilisation raise species richness?

The 'resource balance hypothesis' proposes that the species richness of grassland vegetation is potentially highest when the N:P ratio of plant tissues is 10-15 (co-limitation), so that species richness could be raised by fertilisation with N or P at sites with lower or higher N:P ratios, respectively. Here we use data from field surveys in Swiss, Dutch and American fens or wet grasslands to analyse what changes in N:P ratios might produce noticeable changes in species richness. Plant species numbers, above-ground biomass, tissue N and P concentrations and soil pH were recorded in plots of 0.06-4 m2. In each data set, plots with intermediate tissue N:P ratios (6-20) were on average most species-rich, but N:P ratios explained only 5-37% of the variation in species richness. Moreover, these effects were partially confounded with those of vegetation biomass and/or soil pH. The unique effects of N:P ratios (excluding those shared with biomass and pH) explained 11-17% of variation in species richness. The relationship between species richness and N:P ratios was asymmetric: plots with high N:P ratios were more species-poor than those with low N:P ratios. This was paralleled by a smaller species pool size at high N:P ratios (estimated from species numbers in multiple records), suggesting that fewer species are adapted to P-limited conditions than to N-limited conditions. According to these data, species richness in wetlands may possibly be raised by P-fertilisation when the initial N:P ratio of the vegetation is well above 20, but this option is not recommended for nature conservation as it might promote common species at the expense of rare one

Plant species indicators of physical environment in Great Lakes coastal wetlands

Plant taxa identified in 90 U.S. Great Lakes coastal emergent wetlands were evaluated as indicators of physical environment. Canonical correspondence analysis using the 40 most common taxa showed that water depth and tussock height explained the greatest amount of species-environment interaction among ten environmental factors measured as continuous variables (water depth, tussock height, latitude, longitude, and six ground cover categories). Indicator species analysis was used to identify species-environment interactions with categorical variables of soil type (sand, silt, clay, organic) and hydrogeomorphic type (Open-Coast Wetlands, River-Influenced Wetlands, Protected Wetlands). Of the 169 taxa that occurred in a minimum of four study sites and ten plots, 48 were hydrogeomorphic indicators and 90 were soil indicators. Most indicators of Protected Wetlands were bog and fen species which were also organic soil indicators. Protected Wetlands had significantly greater average coefficient of conservatism (C) values than did Open-Coast Wetlands and River-Influenced Wetlands, but average C values did not differ significantly by soil type. Open-Coast and River-Influenced hydrogeomorphic types tended to have sand or silt soils. Clay soils were found primarily in areas with Quaternary glaciolacustrine deposits or clay-rich tills. A fuller understanding of how the physical environment influences plant species distribution will improve our ability to detect the response of wetland vegetation to anthropogenic activities