The influence of social identity on attitudes toward wildlife.

Wildlife conservation depends on supportive social as well as biophysical conditions. Social identities such as hunter and nonhunter are often associated with different attitudes toward wildlife. However, it is unknown whether dynamics within and among these identity groups explain how attitudes form and why they differ. To investigate how social identities help shape wildlife-related attitudes and the implications for wildlife policy and conservation, we built a structural equation model with survey data from Montana (USA) residents (n = 1758) that tested how social identities affect the relationship between experiences with grizzly bears (Ursus arctos horribilis) and attitudes toward the species. Model results (r2  = 0.51) demonstrated that the hunter identity magnified the negative effect of vicarious property damage on attitudes toward grizzly bears (ß = -0.381, 95% confidence interval [CI]: -0.584 to -0.178, p < 0.001), which in turn strongly influenced acceptance (ß = -0.571, 95% CI: -0.611 to -0.531, p < 0.001). Our findings suggested that hunters' attitudes toward grizzly bears likely become more negative primarily because of in-group social interactions about negative experiences, and similar group dynamics may lead nonhunters to disregard the negative experiences that out-group members have with grizzly bears. Given the profound influence of social identity on human cognitions and behaviors in myriad contexts, the patterns we observed are likely important in a variety of wildlife conservation situations. To foster positive conservation outcomes and minimize polarization, management strategies should account for these identity-driven perceptions while prioritizing conflict prevention and promoting positive wildlife narratives within and among identity groups. This study illustrates the utility of social identity theory for explaining and influencing human-wildlife interactions.

La influencia de la identidad social sobre la actitud hacia la fauna Resumen La conservación de la fauna depende de condiciones de apoyo tanto sociales como biofísicas. La identidad social, como ser cazador o no, con frecuencia está asociada a las diferentes actitudes hacia la fauna. Sin embargo, no sabemos si las dinámicas dentro y entre estos grupos de identidad explican cómo las actitudes se forman y porqué son diferentes. Construimos un modelo de ecuación estructural con información de encuestas realizadas a 1,758 residentes de Montana (Estados Unidos) para conocer cómo la identidad social ayuda a formar la actitud relacionada con la fauna y las implicaciones que tiene para la conservación y políticas de fauna. El modelo analizó cómo la identidad social afecta la relación entre las experiencias con osos pardos (Ursus arctos horribilis) y la actitud hacia la especie. Los resultados del modelo (r2 = 0.51) demostraron que la identidad de cazador aumentaba el efecto negativo del daño indirecto a la propiedad sobre la actitud hacia los osos (ß=-0.381, 95% CI -0.584 a -0.178, p<0.001), lo cual en cambio tenía una gran influencia sobre la aceptación (ß=-0.571, 95% CI -0.611 a -0.531, p<0.001). Nuestros descubrimientos sugieren que la actitud de los cazadores hacia los osos probablemente se vuelve más negativa principalmente debido a las interacciones sociales del endogrupo en torno a las experiencias negativas; las dinámicas similares pueden llevar a los no cazadores a menospreciar las experiencias negativas que los miembros del exogrupo han tenido con los osos. Dada la influencia profunda que tiene la identidad social sobre la cognición humana y el comportamiento en una miríada de contextos, los patrones que observamos probablemente sean importantes en una variedad de situaciones de conservación de fauna. Para promover los resultados positivos de conservación y minimizar la polarización, las estrategias de manejo deberían considerar estas percepciones influenciadas por la identidad mientras se prioriza la prevención de conflictos y se promueven narrativas positivas de fauna dentro y entre los grupos de identidad. Este estudio demuestra la utilidad que tiene la teoría de identidad social para explicar e influenciar las interacciones humano-fauna.

Isotopically nonstationary 13C metabolic flux analysis in resting and activated human platelets.

Platelet metabolism is linked to platelet hyper- and hypoactivity in numerous human diseases. Developing a detailed understanding of the link between metabolic shifts and platelet activation state is integral to improving human health. Here, we show the first application of isotopically nonstationary 13C metabolic flux analysis to quantitatively measure carbon fluxes in both resting and thrombin activated platelets. Metabolic flux analysis results show that resting platelets primarily metabolize glucose to lactate via glycolysis, while acetate is oxidized to fuel the tricarboxylic acid cycle. Upon activation with thrombin, a potent platelet agonist, platelets increase their uptake of glucose 3-fold. This results in an absolute increase in flux throughout central metabolism, but when compared to resting platelets they redistribute carbon dramatically. Activated platelets decrease relative flux to the oxidative pentose phosphate pathway and TCA cycle from glucose and increase relative flux to lactate. These results provide the first report of reaction-level carbon fluxes in platelets and allow us to distinguish metabolic fluxes with much higher resolution than previous studies.

Differentiating Sources of Fecal Contamination to Wilderness Waters Using Droplet Digital PCR and Fecal Indicator Bacteria Methods.

INTRODUCTION: Human activity in wilderness areas has the potential to affect aquatic ecosystems, including through the introduction of microorganisms associated with fecal contamination. We examined fecal microorganism contamination in water sources (lake outlets, snowmelt streams) in the popular Absaroka Beartooth Wilderness in the United States. Although the region is remote, increasing human visitation has the potential to negatively affect water quality, with particular concern about human-derived microorganism fecal contaminants. METHODS: We used standard fecal indicator bacterial assays that quantified total coliform bacteria and Escherichia coli concentrations, together with more specific polymerase chain reaction-based microbial assays that identified possible human sources of fecal microorganisms in these waters. RESULTS: Total coliforms were detected at all lake outlets (21 of 21 sites), and E coli was detected at 11 of 21 sites. Droplet digital polymerase chain reaction assays revealed the presence of human feces-derived microorganisms, albeit at abundances below the limit of detection (<10 gene copies per milliliter of water) at all but 1 of the sampling sites. CONCLUSIONS: Our results suggest low prevalence of water-borne pathogens (specifically E coli and human-derived Bacteroides) in this popular wilderness area. However, widespread detection of total coliforms, Bacteroides, and E coli highlight the importance of purifying water sources in wilderness areas before consumption. Specific sources of total coliforms and E coli in these waters remain unknown but could derive from wild or domesticated animals that inhabit or visit the Absaroka Beartooth Wilderness. Hence, although contamination by human fecal microorganisms appears minimal, human visitation could indirectly influence fecal contamination through domesticated animals.

Promoting Healthy Decision-Making via Natural Environment Exposure: Initial Evidence and Future Directions.

Research within psychology and other disciplines has shown that exposure to natural environments holds extensive physiological and psychological benefits. Adding to the health and cognitive benefits of natural environments, evidence suggests that exposure to nature also promotes healthy human decision-making. Unhealthy decision-making (e.g., smoking, non-medical prescription opioid misuse) and disorders associated with lack of impulse control [e.g., tobacco use, opioid use disorder (OUD)], contribute to millions of preventable deaths annually (i.e., 6 million people die each year of tobacco-related illness worldwide, deaths from opioids from 2002 to 2017 have more than quadrupled in the United States alone). Impulsive and unhealthy decision-making also contributes to many pressing environmental issues such as climate change. We recently demonstrated a causal link between visual exposure to nature (e.g., forests) and improved self-control (i.e., decreased impulsivity) in a laboratory setting, as well as the extent to which nearby nature and green space exposure improves self-control and health decisions in daily life outside of the experimental laboratory. Determining the benefits of nearby nature for self-controlled decision-making holds theoretical and applied implications for the design of our surrounding environments. In this article, we synergize the overarching results of recent research endeavors in three domains including the effects of nature exposure on (1) general health-related decision-making, (2) health and decision-making relevant for application to addiction related processes (e.g., OUD), and (3) environmentally relevant decision-making. We also discuss key future directions and conclusions.

Enhancing predictions of patient conveyance using emergency call handler free text notes for unconscious and fainting incidents reported to the London Ambulance Service.

OBJECTIVE: Pre-hospital emergency medical services use clinical decision support systems (CDSS) to triage calls. Call handlers often supplement this by making free text notes covering key incident information. We investigate whether machine learning approaches using features from such free text notes can improve prediction of unconscious patients who require conveyance. MATERIALS AND METHODS: We analysed a subset of all London Ambulance Service calls that were triaged through the Medical Priority Dispatch System (MPDS) as involving an unconscious or fainting patient in 2018. We use and compare two machine learning algorithms: random forest (RF) and gradient boosting machine (GBM). For each incident, we predict whether the patient will be conveyed to a hospital emergency department or equivalent using as features 1) the MPDS code, 2) the free text notes and 3) the two together. We evaluate model performance using the area under the curve (AUC) metric. Given the imbalance of outcomes (patient conveyed 71 %, not conveyed 29 %), we also consider sensitivity and specificity. RESULTS: Using only the MPDS code resulted in an AUC of 0.57. Using the text notes gave an improved AUC score of 0.63 and combining the two gave an AUC score of 0.64 (scores were similar for RF and GBM). GBM models scored better on sensitivity (0.93 vs 0.62 for RF in the combined model), but specificity was lower (0.17 vs. 0.56 for RF in the combined model). CONCLUSIONS: Using information contained in the free text notes made by call handlers in combination with MPDS improves prediction of unconscious and fainting patients requiring conveyance to a hospital emergency department (or equivalent) when compared with machine learning models using MPDS codes only. This suggests there is some useful information in unstructured data captured by emergency call handlers that complements MPDS codes. Quantifying this gain can help inform emergency medical service policy when evaluating the decision to expand or augment existing CDSS.

Integrating Subjective and Objective Dimensions of Resilience in Fire-Prone Landscapes.

Resilience has become a common goal for science-based natural resource management, particularly in the context of changing climate and disturbance regimes. Integrating varying perspectives and definitions of resilience is a complex and often unrecognized challenge to applying resilience concepts to social-ecological systems (SESs) management. Using wildfire as an example, we develop a framework to expose and separate two important dimensions of resilience: the inherent properties that maintain structure, function, or states of an SES and the human perceptions of desirable or valued components of an SES. In doing so, the framework distinguishes between value-free and human-derived, value-explicit dimensions of resilience. Four archetypal scenarios highlight that ecological resilience and human values do not always align and that recognizing and anticipating potential misalignment is critical for developing effective management goals. Our framework clarifies existing resilience theory, connects literature across disciplines, and facilitates use of the resilience concept in research and land-management applications.

Considering weed management as a social dilemma bridges individual and collective interests.

Weeds pose severe threats to agricultural and natural landscapes worldwide. One major reason for the failure to effectively manage weeds at landscape scales is that current Best Management Practice guidelines, and research on how to improve such guidelines, focus too narrowly on property-level management decisions. Insufficiently considered are the aggregate effects of individual actions to determine landscape-scale outcomes, or whether there are collective practices that would improve weed management outcomes. Here, we frame landscape-scale weed management as a social dilemma, where trade-offs occur between individual and collective interests. We apply a transdisciplinary system approach-integrating the perspectives of ecologists, evolutionary biologists and agronomists into a social science theory of social dilemmas-to four landscape-scale weed management challenges: (i) achieving plant biosecurity, (ii) preventing weed seed contamination, (iii) maintaining herbicide susceptibility and (iv) sustainably using biological control. We describe how these four challenges exhibit characteristics of 'public good problems', wherein effective weed management requires the active contributions of multiple actors, while benefits are not restricted to these contributors. Adequate solutions to address these public good challenges often involve a subset of the eight design principles developed by Elinor Ostrom for 'common pool social dilemmas', together with design principles that reflect the public good nature of the problems. This paper is a call to action for scholars and practitioners to broaden our conceptualization and approaches to weed management problems. Such progress begins by evaluating the public good characteristics of specific weed management challenges and applying context-specific design principles to realize successful and sustainable weed management.

Microtargeting for conservation.

Widespread human action and behavior change is needed to achieve many conservation goals. Doing so at the requisite scale and pace will require the efficient delivery of outreach campaigns. Conservation gains will be greatest when efforts are directed toward places of high conservation value (or need) and tailored to critical actors. Recent strategic conservation planning has relied primarily on spatial assessments of biophysical attributes, largely ignoring the human dimensions. Elsewhere, marketers, political campaigns, and others use microtargeting-predictive analytics of big data-to identify people most likely to respond positively to particular messages or interventions. Conservationists have not yet widely capitalized on these techniques. To investigate the effectiveness of microtargeting to improve conservation, we developed a propensity model to predict restoration behavior among 203,645 private landowners in a 5,200,000 ha study area in the Chesapeake Bay Watershed (U.S.A.). To isolate the additional value microtargeting may offer beyond geospatial prioritization, we analyzed a new high-resolution land-cover data set and cadastral data to identify private owners of riparian areas needing restoration. Subsequently, we developed and evaluated a restoration propensity model based on a database of landowners who had conducted restoration in the past and those who had not (n = 4978). Model validation in a parallel database (n = 4989) showed owners with the highest scorers for propensity to conduct restoration (i.e., top decile) were over twice as likely as average landowners to have conducted restoration (135%). These results demonstrate that microtargeting techniques can dramatically increase the efficiency and efficacy of conservation programs, above and beyond the advances offered by biophysical prioritizations alone, as well as facilitate more robust research of many social-ecological systems.

Micro-focalización para la Conservación Resumen Se necesitan acciones humanas diseminadas y un cambio en el comportamiento para lograr muchos objetivos de conservación. Que se logre esto a la escala y al ritmo requerido requerirá de la entrega eficiente de las campañas de participación. Las ganancias de la conservación serán mayores cuando los esfuerzos estén dirigidos hacia sitios con un alto valor (o necesidad) de conservación y estén personalizados para los actores más importantes. La reciente planeación estratégica de la conservación ha dependido principalmente de las evaluaciones espaciales de los atributos biofísicos, ignorando generalmente las dimensiones humanas. En otros ámbitos, los mercadólogos, las campañas políticas, así como otros, usan la micro-focalización - el análisis predictivo de datos masivos - para identificar a las personas con mayor probabilidad de responder positivamente a mensajes o intervenciones particulares. Los conservacionistas todavía no han capitalizado extensamente estas técnicas. Desarrollamos un modelo de tendencia para predecir el comportamiento de restauración entre 203,645 terratenientes privados en un área de estudio de 5,200,000 ha en la cuenca de la Bahía de Chesapeake (E.U.A.) y así investigar la eficiencia de la micro-focalización en el aumento de la conservación. Para aislar el valor adicional que puede ofrecer la micro-focalización más allá de la priorización geoespacial, analizamos un nuevo conjunto de alta resolución de datos sobre la cobertura del suelo y datos catastrales para identificar a los terratenientes privados de áreas ribereñas que necesitan restauración. Después de esto, desarrollamos y evaluamos el modelo de tendencia a la restauración basado en una base de datos de terratenientes que han realizado restauraciones en el pasado y aquellos que no (n = 4,978). La validación del modelo en una base de datos paralela (n = 4,989) mostró que los terratenientes con los puntajes más altos para la tendencia a la restauración (es decir, el decil superior) tenían el doble de probabilidad de haber realizado acciones de conservación que el terrateniente promedio (135%). Estos resultados muestran que las técnicas de micro-focalización pueden incrementar dramáticamente la eficiencia y la eficacia de los programas de conservación, más allá de los avances ofrecidos sólo por las priorizaciones biofísicas, así como facilitar la investigación más sólida sobre muchos sistemas socio-ecológicos.

The challenge and potential of photosynthesis: unique considerations for metabolic flux measurements in photosynthetic microorganisms.

Photosynthetic microorganisms have the potential for sustainable production of chemical feedstocks and products but have had limited success due to a lack of tools and deeper understanding of metabolic pathway regulation. The application of instationary metabolic flux analysis (INST-MFA) to photosynthetic microorganisms has allowed researchers to quantify fluxes and identify bottlenecks and metabolic inefficiencies to improve strain performance or gain insight into cellular physiology. Additionally, flux measurements can also highlight deviations between measured and predicted fluxes, revealing weaknesses in metabolic models and highlighting areas where a lack of understanding still exists. In this review, we outline the experimental steps necessary to successfully perform photosynthetic flux experiments and analysis. We also discuss the challenges unique to photosynthetic microorganisms and how to account for them, including: light supply, quenching, concentration, extraction, analysis, and flux calculation. We hope that this will enable a larger number of researchers to successfully apply isotope assisted metabolic flux analysis (13C-MFA) to their favorite photosynthetic organism.

Opportunities for better use of collective action theory in research and governance for invasive species management.

Controlling invasive species presents a public-good dilemma. Although environmental, social, and economic benefits of control accrue to society, costs are borne by only a few individuals and organizations. For decades, policy makers have used incentives and sanctions to encourage or coerce individual actors to contribute to the public good, with limited success. Diverse, subnational efforts to collectively manage invasive plants, insects, and animals provide effective alternatives to traditional command-and-control approaches. Despite this work, there has been little systematic evaluation of collective efforts to determine whether there are consistent principles underpinning success. We reviewed 32 studies to identify the extent to which collective-action theories from related agricultural and environmental fields explain collaborative invasive species management approaches; describe and differentiate emergent invasive species collective-action efforts; and provide guidance on how to enable more collaborative approaches to invasive species management. We identified 4 types of collective action aimed at invasive species-externally led, community led, comanaged, and organizational coalitions-that provide blueprints for future invasive species management. Existing collective-action theories could explain the importance attributed to developing shared knowledge of the social-ecological system and the need for social capital. Yet, collection action on invasive species requires different types of monitoring, sanctions, and boundary definitions. We argue that future government policies can benefit from establishing flexible boundaries that encourage social learning and enable colocated individuals and organizations to identify common goals, pool resources, and coordinate efforts.

Oportunidades para un Mejor Uso de la Teoría de Acción Colectiva en la Investigación y el Control del Manejo de Especies Invasoras Resumen El control de especies invasoras es un dilema para el bien público. Aunque los beneficios ambientales, sociales y económicos del control se acoplan a la sociedad, los costos los resuelven unos cuantos individuos y organizaciones. Durante décadas, los legisladores han utilizado incentivos y sanciones para alentar y forzar a los actores individuales a contribuir con el bien público, aunque con un éxito limitado. Los diversos esfuerzos sub-nacionales para manejar colectivamente plantas, insectos y otros animales proporcionan alternativas efectivas a las estratégicas tradicionales de comando y control. A pesar de esta labor, ha habido una evaluación sistemática mínima de los esfuerzos colectivos para determinar si hay principios congruentes que estén respaldando el éxito. Revisamos 32 estudios para identificar la extensión a la cual las teorías de acción colectiva a partir de los campos agrícolas y ambientales relacionados explican las estrategias colaborativas de manejo de especies invasoras; describen y diferencian los esfuerzos de acción colectiva para especies invasoras emergentes; y proporcionan una guía sobre cómo posibilitar estrategias más colaborativas para el manejo de especies invasoras. Identificamos cuatro tipos de acción colectiva enfocada en las especies invasoras - guiada externamente, guiada por la comunidad, co-manejada, y coaliciones organizacionales - que proporcionan los planos para el manejo futuro de especies invasoras. Las teorías existentes de acción colectiva podrían explicar la importancia que se le atribuye al conocimiento compartido en desarrollo sobre los sistemas socio-ecológicos y la necesidad de capital social. Aun así, la acción colectiva sobre las especies invasoras requiere de diferentes tipos de monitoreo, sanciones y definición de los límites. Argumentamos que las próximas políticas gubernamentales pueden beneficiarse del establecimiento de límites flexibles que alientan el aprendizaje social y permiten que individuos y organizaciones colocadas identifiquen objetivos en común, acumulen y compartan recursos y coordinen esfuerzos.

How does nature exposure make people healthier?: Evidence for the role of impulsivity and expanded space perception.

Nature exposure has been linked to a plethora of health benefits, but the mechanism for this effect is not well understood. We conducted two studies to test a new model linking the health benefits of nature exposure to reduced impulsivity in decision-making (as measured by delay discounting) via psychologically expanding space perception. In study 1 we collected a nationwide U.S. sample (n = 609) to determine whether nature exposure was predictive of health outcomes and whether impulsive decision-making mediated the effect. Results indicated that Nature Accessibility and Nature Exposure From Home significantly predicted reduced scores on the Depression, Anxiety, Stress Scales (DASS) (p < .001, p = .03, respectively) and improved general health and wellbeing (p < .001, p < .01, respectively). Nature Accessibility also predicted reduced impulsive decision-making (p < .01), and Nature Accessibility showed significant indirect effects through impulsive decision-making on both the DASS (p = .02) and general health and wellbeing (p = .04). In Study 2, a lab-based paradigm found that nature exposure expanded space perception (p < .001), and while the indirect effect of nature exposure through space perception on impulsive decision-making did not meet conventional standards of significance (p < .10), the pattern was consistent with hypotheses. This combination of ecologically-valid and experimental methods offers promising support for an impulsivity-focused model explaining the nature-health relationship.

Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing.

PURPOSE: Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations. PATIENTS AND METHODS: Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS). RESULTS: Tumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative. A combination of MMR IHC plus MLH1 methylation testing in women younger than 60 years of age at diagnosis provided the highest positive predictive value for the identification of mutation carriers at 46% versus ≤ 41% for any other criteria considered. CONCLUSION: Population-level identification of patients with MMR mutation-positive endometrial cancer is optimized by stepwise testing for tumor MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation.

Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of germline mismatch repair gene mutation status: a literature review.

Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can be caused by either germline mutations in mismatch repair (MMR) genes, or non-inherited transcriptional silencing of the MLH1 promoter. A correlation between MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has been reported in CRC studies. Germline MMR mutations also greatly increase risk of endometrial cancer (EC), but no systematic review has been undertaken to determine if these tumour markers may be useful predictors of MMR mutation status in EC patients. Endometrial cancer cohorts meeting review inclusion criteria encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11 studies for MLH1 methylation testing. BRAF V600E mutations were reported in 4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were 7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15. Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in 48/51 (94%) of tumours. We have also detailed specific examples that show the importance of MLH1 promoter region, assay design, and quantification of methylation. This review shows that BRAF mutations occurs so infrequently in endometrial tumours they can be discounted as a useful marker for predicting MMR-negative mutation status, and further studies of endometrial cohorts with known MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter methylation as a marker of negative germline MMR mutation status in EC patients.

A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway.

Sequence polymorphisms linked to human diseases and phenotypes in genome-wide association studies often affect noncoding regions. A SNP within an intron of the gene encoding Interferon Regulatory Factor 4 (IRF4), a transcription factor with no known role in melanocyte biology, is strongly associated with sensitivity of skin to sun exposure, freckles, blue eyes, and brown hair color. Here, we demonstrate that this SNP lies within an enhancer of IRF4 transcription in melanocytes. The allele associated with this pigmentation phenotype impairs binding of the TFAP2A transcription factor that, together with the melanocyte master regulator MITF, regulates activity of the enhancer. Assays in zebrafish and mice reveal that IRF4 cooperates with MITF to activate expression of Tyrosinase (TYR), an essential enzyme in melanin synthesis. Our findings provide a clear example of a noncoding polymorphism that affects a phenotype by modulating a developmental gene regulatory network.