Alkylamine-tethered molecules recruit FBXO22 for targeted protein degradation.

Targeted protein degradation (TPD) relies on small molecules to recruit proteins to E3 ligases to induce their ubiquitylation and degradation by the proteasome. Only a few of the approximately 600 human E3 ligases are currently amenable to this strategy. This limits the actionable target space and clinical opportunities and thus establishes the necessity to expand to additional ligases. Here we identify and characterize SP3N, a specific degrader of the prolyl isomerase FKBP12. SP3N features a minimal design, where a known FKBP12 ligand is appended with a flexible alkylamine tail that conveys degradation properties. We found that SP3N is a precursor and that the alkylamine is metabolized to an active aldehyde species that recruits the SCFFBXO22 ligase for FKBP12 degradation. Target engagement occurs via covalent adduction of Cys326 in the FBXO22 C-terminal domain, which is critical for ternary complex formation, ubiquitylation and degradation. This mechanism is conserved for two recently reported alkylamine-based degraders of NSD2 and XIAP, thus establishing alkylamine tethering and covalent hijacking of FBXO22 as a generalizable TPD strategy.

Comparison of coral reef communities in proximity to ocean effluent pipes off the north coast of Puerto Rico.

Coral reefs are declining globally as a result of multiple stressors, including land-based stressors, such as sedimentation and pollution, and those that are related to a changing climate, such as increases in ocean acidification. Degradation of US Caribbean coral reef biota has been associated with exposure to sewage effluent from wastewater treatment plants (WWTPs). The Puerto Rico Aqueduct and Sewer Authority (PRASA) maintains WWTPs on the north coast of Puerto Rico, which release effluent into the marine environment in the vicinity of coral reefs. Using data collected by PRASA surveys conducted from 1999 to 2013, we examined coral reef condition at survey sites to identify potential changes or differences in reefs with respect to their proximity to the WWTP effluent pipes (e.g., upstream, downstream). The proportion of coverage represented by all coral, sensitive taxa, and tolerant taxa were compared across sites located upstream and downstream of WWTP effluent pipes using multivariate approaches and analysis of variance. The proportion of healthy, sensitive coral species and invasive or tolerant coral species were not different at sites downstream of the WWTP effluent pipe compared to upstream. These results are caveated by the limited sampling design, highly variable communities across WWTP locations, and the sparsity or absence of well-developed coral reef communities at most stations. We evaluate the strengths and weaknesses of the survey design and provide recommendations for future coral reef surveys investigating potential impacts of WWTP effluent.

A biological condition gradient for Caribbean coral reefs: Part II. Numeric rules using sessile benthic organisms.

The Biological Condition Gradient (BCG) is a conceptual model used to describe incremental changes in biological condition along a gradient of increasing anthropogenic stress. As coral reefs collapse globally, scientists and managers are focused on how to sustain the crucial structure and functions, and the benefits that healthy coral reef ecosystems provide for many economies and societies. We developed a numeric (quantitative) BGC model for the coral reefs of Puerto Rico and the US Virgin Islands to transparently facilitate ecologically meaningful management decisions regarding these fragile resources. Here, reef conditions range from natural, undisturbed conditions to severely altered or degraded conditions. Numeric decision rules were developed by an expert panel for scleractinian corals and other benthic assemblages using multiple attributes to apply in shallow-water tropical fore reefs with depths <30 m. The numeric model employed decision rules based on metrics (e.g., % live coral cover, coral species richness, pollution-sensitive coral species, unproductive and sediment substrates, % cover by Orbicella spp.) used to assess coral reef condition. Model confirmation showed the numeric BCG model predicted the panel's median site ratings for 84% of the sites used to calibrate the model and 89% of independent validation sites. The numeric BCG model is suitable for adaptive management applications and supports bioassessment and criteria development. It is a robust assessment tool that could be used to establish ecosystem condition that would aid resource managers in evaluating and communicating current or changing conditions, protect water and habitat quality in areas of high biological integrity, or develop restoration goals with stakeholders and other public beneficiaries.

A biological condition gradient for coral reefs in the US Caribbean Territories: Part I. Coral narrative rules.

As coral reef condition and sustainability continue to decline worldwide, losses of critical habitat and their ecosystem services have generated an urgency to understand and communicate reef response to management actions, environmental contamination, and natural disasters. Increasingly, coral reef protection and restoration programs emphasize the need for robust assessment tools for protecting high-quality waters and establishing conservation goals. Of equal importance is the need to communicate assessment results to stakeholders, beneficiaries, and the public so that environmental consequences of decisions are understood. The Biological Condition (BCG) model provides a structure to evaluate the condition of a coral reef in increments of change along a gradient of human disturbance. Communication of incremental change, regardless of direction, is important for decision makers and the public to better understand what is gained or lost depending on what actions are taken. We developed a narrative (qualitative) Biological Condition Gradient (BCG) from the consensus of a diverse expert panel to provide a framework for coral reefs in US Caribbean Territories. The model uses narrative descriptions of biological attributes for benthic organisms to evaluate reefs relative to undisturbed or minimally disturbed conditions. Using expert elicitation, narrative decision rules were proposed and deliberated to discriminate among six levels of change along a gradient of increasing anthropogenic stress. Narrative rules for each of the BCG levels are presented to facilitate the evaluation of benthic communities in coral reefs and provide specific narrative features to detect changes in coral reef condition and biological integrity. The BCG model can be used in the absence of numeric, or quantitative metrics, to evaluate actions that may encroach on coral reef ecosystems, manage endangered species habitat, and develop and implement management plans for marine protected areas, watersheds, and coastal zones. The narrative BCG model is a defensible model and communication tool that translates scientific results so the nontechnical person can understand and support both regulatory and non-regulatory water quality and natural resource programs.

What is it about coral reefs? Translation of ecosystem goods and services relevant to people and their well-being.

There is an astonishing diversity of ways in which people benefit from coral reefs. They provide recreation, resource extraction, inspirational, and educational opportunities, among many others as well as being valued just for their existence. As the condition of coral reef ecosystems decline, so do their ability to provide these benefits. Prudent management of coral reefs and the benefits they provide are important as some predict most coral reefs globally will be lost by the mid-21st century. Meanwhile, coral reef managers have limited tools and relevant data to design and implement effective environmental management practices that will enable coral reefs to provide benefits demanded by society. We demonstrate an approach to identify and measure environmental components of coral reefs that directly benefit human well-being. The approach views ecosystems through the lens of a specific set of beneficiaries and the biophysical features directly relevant to each. We call these biophysical features Final Ecosystem Goods and Services (FEGS). In our demonstration, we (1) identify a range of beneficiaries of coral reefs; (2) identify metrics of FEGS for those beneficiaries; and (3) describe how data quantifying those biophysical metrics might be used to facilitate greater economic and social understanding.

Development of a reef fish biological condition gradient model with quantitative decision rules for the protection and restoration of coral reef ecosystems.

Coral reef ecosystems are declining due to multiple interacting stressors. A bioassessment framework focused on stressor-response associations was developed to help organize and communicate complex ecological information to support coral reef conservation. This study applied the Biological Condition Gradient (BCG), initially developed for freshwater ecosystems, to fish assemblages of U.S. Caribbean coral reef ecosystems. The reef fish BCG describes how biological conditions changed incrementally along a gradient of increasing anthropogenic stress. Coupled with physical and chemical water quality data, the BGC forms a scientifically defensible basis to prioritize, protect and restore water bodies containing coral reefs. Through an iterative process, scientists from across the U.S. Caribbean used fishery-independent survey data and expert knowledge to develop quantitative decision rules to describe six levels of coral reef ecosystem condition. The resultant reef fish BCG provides an effective tool for identifying healthy and degraded coral reef ecosystems and has potential for global application.