Creating conservation strategies with value-focused thinking.

Biodiversity and human well-being strategies are only as good as the set of ideas people think about. We evaluated value-focused thinking (VFT), a framework that emphasizes creating objectives and strategies that are responsive to the objectives. We performed a proof-of-concept study of VFT with 6 conservation planning teams at a global conservation organization. We developed a package of materials related to VFT, including meeting-session agendas, a virtual facilitation template, facilitator's guide, and evaluation questionnaires. We used these materials to test whether VFT applied in a group setting resulted in high-quality conservation strategies and participant satisfaction and whether our materials were scalable, meaning that someone newly trained in VFT could facilitate planning meetings that resulted in high-quality strategies and participant satisfaction, as compared with an experienced VFT facilitator. Net response indicated positive compelling, feasible, creative, and representative ratings for the conservation strategies per team. Participants indicated satisfaction overall, although satisfaction was greater for objectives than for strategies. Among the participants with previous conservation planning experience, all were at least as satisfied with their VFT strategies compared with previously developed strategies, and none were less satisfied (p = 0.001). Changes in participant satisfaction were not related to facilitator type (experienced or inexperienced with VFT) (p > 0.10). Some participants had a preconceived sense of shared understanding of important values and interests before participating in the study, which VFT strengthened. Our results highlight the advantages of structuring the development and evaluation of conservation planning frameworks around VFT.

Creación de estrategias de conservación con el pensamiento orientado a valores Resumen Las estrategias para la biodiversidad y el bienestar humano son tan buenas como el conjunto de ideas en el que piensan las personas. Evaluamos el pensamiento orientado a valores (POV), un marco que promueve la creación de objetivos y estrategias responsivas a los objetivos. Realizamos un estudio de prueba de concepto del POV con seis equipos de planeación de la conservación en una organización mundial de conservación. Desarrollamos un paquete de materiales relacionado con el POV que incluyó orden del día de las reuniones, una plantilla de asesoramiento virtual, una guía para el facilitador y cuestionarios de evaluación. Usamos estos materiales para probar si el POV aplicado en un entorno de grupo da como resultado estrategias de conservación de gran calidad y la satisfacción de los participantes. También probamos si nuestros materiales podían ampliarse, es decir, si alguien con entrenamiento reciente de POV podría facilitar la planeación de reuniones para que resultaran en estrategias de gran calidad y la satisfacción de los participantes en comparación con un facilitador experimentado. Por equipo, la respuesta neta indicó calificaciones positivas, convincentes, factibles, creativas y representativas para las estrategias de conservación. Los participantes indicaron una satisfacción generalizada, aunque ésta fue mayor para los objetivos que para las estrategias. Entre los participantes con experiencia previa en la planeación de la conservación, todos estuvieron satisfechos al menos con sus estrategias de POV en comparación con las estrategias previas y ninguno estuvo menos satisfecho (p= 0.001). Los cambios en la satisfacción de los participantes no estuvieron relacionados con el tipo de facilitador (con o sin experiencia en POV) (p> 0.10). Antes de participar en el estudio, algunos participantes ya tenían un sentido preconcebido del entendimiento compartido de los valores e intereses importantes, lo que el POV fortaleció. Nuestros resultados resaltan las ventajas de la estructuración del desarrollo y la evaluación en torno al POV de los marcos de planeación de la conservación.

Using Structured Decision Making to Evaluate Wetland Restoration Opportunities in the Chesapeake Bay Watershed.

Wetland restoration is an important water quality and climate resilience strategy. Wetland restoration rarely considers tradeoffs at large spatial and temporal scales, which limits capacity to aid decision makers. High resolution data can reveal hundreds to thousands of possible restoration options across a landscape, but guidance for setting restoration targets at these scales is limited. This study uses structured decision making (SDM) as a process for evaluating the desirability of numerous restoration options, with a case study on the Outer Coastal Plain of the Chesapeake Bay watershed, USA. The Nature Conservancy, in partnership with federal, state, and nonprofit organizations, evaluated a decision to target large-scale wetland restoration based on two fundamental objectives: improve water quality and enhance climate resilience. A total of 964 potentially restorable alternatives were delineated across the study area. The alternatives were evaluated on seven water quality and climate resilience criteria. High-priority alternatives were mapped based on multi-criteria ranking methods and principal component analysis. Sensitivity analysis included varying nutrient load data, implementing multiple ranking methods with different assumptions, and varying criteria weights. The maps revealed seven distinct regions of restoration opportunities. Tradeoffs were evaluated to distinguish between desirable and less desirable regions. Results indicated that three regions were promising choices to initiate landowner engagement and outreach. This study highlights the advantages of SDM to structure large-scale restoration decisions. In doing so, our work offers a roadmap toward further developing SDM in future applied restoration contexts.

Alignment of Biological Sequences with Jalview.

In this chapter, we introduce core functionality of the Jalview interactive platform for the creation, analysis, and publication of multiple sequence alignments. A workflow is described based on Jalview's core functions: from data import to figure generation, including import of alignment reliability scores from T-Coffee and use of Jalview from the command line. The accompanying notes provide background information on the underlying methods and discuss additional options for working with Jalview to perform multiple sequence alignment, functional site analysis, and publication of alignments on the web.

A Multiarmed Bandit Approach to Adaptive Water Quality Management.

Nonpoint source water quality management is challenged with allocating uncertain management actions and monitoring their performance in the absence of state-dependent decision making. This adaptive management context can be expressed as a multiarmed bandit problem. Multiarmed bandit strategies attempt to balance the exploitation of actions that appear to maximize performance with the exploration of uncertain, but potentially better, actions. We performed a test of multiarmed bandit strategies to inform adaptive water quality management in Massachusetts, USA. Conservation and restoration practitioners were tasked with allocating household wastewater treatments to minimize N inputs to impaired waters. We obtained time series of N monitoring data from 3 wastewater treatment types and organized them chronologically and randomly. The chronological data set represented nonstationary performance based on recent monitoring data, whereas the random data set represented stationary performance. We tested 2 multiarmed bandit strategies in hypothetical experiments to sample from the treatment data through 20 sequential decisions. A deterministic probability-matching strategy allocated treatments with the highest probability of success regarding their performance at each decision. A randomized probability-matching strategy randomly allocated treatments according to their probability of success at each decision. The strategies were compared with a nonadaptive strategy that equally allocated treatments at each decision. Results indicated that equal allocation is useful for learning in nonstationary situations but tended to overexplore inferior treatments and thus did not maximize performance when compared with the other strategies. Deterministic probability matching maximized performance in many stationary situations, but the strategy did not adequately explore treatments and converged on inferior treatments in nonstationary situations. Randomized probability matching balanced performance and learning in stationary situations, but the strategy could converge on inferior treatments in nonstationary situations. These findings provide evidence that probability-matching strategies are useful for adaptive management. Integr Environ Assess Manag 2020;16:841-852. © 2020 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Assessment of a portable quadrupole-based gas chromatography mass spectrometry for seized drug analysis.

The cutting agents, classified as diluents (pharmacologically inactive) or adulterants (pharmacologically active), are substances commonly used to cut drugs of abuse to increase profits. These substances are constantly changing over time, increasing the risks to the user's health caused by the compounds' potential individual toxicities as well as their drug-drug interactions. This work aimed to develop and validate a screening method using a portable quadrupole-based gas chromatography mass spectrometer (FLIR Griffin™ G510) to identify drugs of abuse and adulterants in seized material, and compare it with a well validated standard technology, gas chromatography mass spectrometry (GC-MS). The method was validated for the identification of alprazolam, amphetamine, aminopyrine, benzocaine, caffeine, cocaine, codeine, diltiazem, ephedrine, fentanyl, fenethylline, furanylfentanyl, heroin, hydroxyzine, levamisole, lidocaine, methamphetamine, morphine, noramidopyrine (a marker of metamizole), phencyclidine, phenacetin, procaine, strychnine and xylazine. The targeted substances were chosen based on current intelligence regarding prevalent adulterants observed in multiple jurisdictions. Interference, precision, robustness and carryover were evaluated. The method was successfully validated and proved to be suitable to detect and identify the 24 target compounds proposed. The reliability of the instrument for detecting the presence of targeted compounds was analyzed by using Receiver Operating Characteristic (ROC) analysis. The portable quadrupole-based gas chromatography mass spectrometer was considered suitable for use in forensic analysis as a screening method.

Young Adults Performance of Unipedal Dynamic Balance with Various Footwear Conditions.

Wearing barefoot-style (minimalist) shoes is suggested as a transition between wearing shoes and barefoot running. Some sources equate wearing Vibram FiveFingers™(VFFs), a brand of barefoot shoes, with running/walking barefoot. Static and dynamic balance exercises are recommended. Little information is available on the effects barefoot shoes may have on dynamic balance. This study's purpose was to examine dynamic balance when participants wore VFFs, athletic shoes, or went barefoot (BF). To test dynamic balance, participants used a modified version of the Star Excursion Balance Test (SEBT), in which the reaching leg followed only three spokes of the test: the anterior, posteromedial and posterolateral. For the timed test, participants touched down as quickly as possible in both directions using all 8 spokes. Thirty participants (ages 24.1+/-3.71 years) without lower extremity injury or experience wearing minimalist shoes were tested using the modified SEBT and a timed test wearing VFFs™, athletic shoes, or BF. Three trials for each footwear were completed for three reaching positions: anterior, posterolateral, posteromedial. The timed test measured (seconds) one counterclockwise and one clockwise direction of the 8-spoke figure. A repeated measures analysis of variance determined if any differences existed between footwear type and studied variables. Anterior reach was significantly greater when wearing shoes than with VFF or BF. Posteromedial reach was greater with shoes than BF. Time trials were not significantly different. Because no difference was found in any measured variables between VFF and BF, the results suggest wearing VFFS™ provided similar dynamic balance as going barefoot.

Incorporating uncertainty and risk into decision making to reduce nitrogen inputs to impaired waters.

This article aims to understand decision making under uncertainty and risk, with a case study on Cape Cod, Massachusetts. Decision makers need to consider imperfect information on the cost and effectiveness of advanced nitrogen-removing on-site wastewater treatment systems as options to mitigate water quality degradation. Research included modeling nitrogen load reduction to impaired coastal waters from seven treatment system technologies and eliciting expert knowledge on their costs. Predictions of nitrogen load removal and cost for each technology incorporated variation in effectiveness and uncertainty in household water use, costs, and expert confidence in costs. The predictions were evaluated using the Pareto efficiency concept to reveal tradeoffs between cost and effectiveness. The stochastic dominance index was used to identify preferred technologies for risk-averse decision making, assuming no further learning is possible. Lastly, the predictions were combined into a cost-effectiveness metric to estimate the expected payoff of implementing the best treatment system in the face of uncertainty and the expected payoff of learning which treatment systems are most cost-effective over time. The expected value of perfect information was calculated as the difference between the expected payoffs. Three technologies revealed Pareto efficient tradeoffs between cost and effectiveness, whereas one technology was the preferred risk-averse option in the absence of future learning. There was a high expected value of perfect information, which could motivate adaptive management on Cape Cod. This research demonstrated decision analysis methods to guide future research and decision making toward meeting water quality objectives and reducing uncertainty.

Detection of Cutting Agents in Drug-Positive Seized Exhibits within the United States.

The following report summarizes a study performed on seized drug exhibits collected in two U.S. states to evaluate the presence and identification of cutting agents. Aliquots of seized drug materials from Kentucky (n = 200) and Vermont (n = 315) were prepared using a dilute-and-shoot procedure. Initial analysis was performed using gas chromatography-mass spectrometry (GC-MS) followed by analysis using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF). Active compounds detected overall included caffeine (31.0%), quinine/quinidine (24.7%), levamisole (11.6%), acetaminophen, (8.2%) and procaine (8.2%). These compounds were found with several drugs of abuse, such as heroin, fentanyl, methamphetamine, and cocaine. This novel information about cutting agents used to dilute or alter drugs of abuse is important to criminal investigations and in the management of acute intoxications at health centers. However, common methodologies for analysis and standard reporting practices frequently do not include cutting agents, resulting in lacking or inadequate information regarding prevalence of these substances.

Structured Decision Making to Meet a National Water Quality Mandate.

Water quality criteria are necessary to ensure protection of ecological and human health conditions, but compliance can require complex decisions. We use structured decision making to consider multiple stakeholder objectives in a water quality management process, with a case study in the Three Bays watershed on Cape Cod, Massachusetts. We set a goal to meet or exceed a nitrogen load reduction target for the watershed and four key objectives: minimizing economic costs of implementing management actions, minimizing the complexity of permitting management actions, maximizing stakeholder acceptability of the management actions, and maximizing the provision of ecosystem services (recreational opportunity, erosion and flood control, socio-cultural amenity). We used multi-objective optimization and sensitivity analysis to generate many possible solutions that implement different combinations of nitrogen-removing management actions and reflect tradeoffs between the objectives. Results show that technological advances in controlling household nitrogen sources could provide lower cost solutions and positive impacts to ecosystem services. Although this approach is demonstrated with Cape Cod data, the decision-making process is not specific to any watershed and could be easily applied elsewhere.

Combining ecosystem services assessment with structured decision making to support ecological restoration planning.

Accounting for ecosystem services in environmental decision making is an emerging research topic. Modern frameworks for ecosystem services assessment emphasize evaluating the social benefits of ecosystems, in terms of who benefits and by how much, to aid in comparing multiple courses of action. Structured methods that use decision analytic-approaches are emerging for the practice of ecological restoration. In this article, we combine ecosystem services assessment with structured decision making to estimate and evaluate measures of the potential benefits of ecological restoration with a case study in the Woonasquatucket River watershed, Rhode Island, USA. We partnered with a local watershed management organization to analyze dozens of candidate wetland restoration sites for their abilities to supply five ecosystem services-flood water retention, scenic landscapes, learning opportunities, recreational opportunities, and birds. We developed 22 benefit indicators related to the ecosystem services as well as indicators for social equity and reliability that benefits will sustain in the future. We applied conceptual modeling and spatial analysis to estimate indicator values for each candidate restoration site. Lastly, we developed a decision support tool to score and aggregate the values for the organization to screen the restoration sites. Results show that restoration sites in urban areas can provide greater social benefits than sites in less urban areas. Our research approach is general and can be used to investigate other restoration planning studies that perform ecosystem services assessment and fit into a decision-making process.

A resilience framework for chronic exposures: water quality and ecosystem services in coastal social-ecological systems.

Water quality degradation is a chronic problem which influences the resilience of a social-ecological system differently than acute disturbances, such as disease or storms. Recognizing this, we developed a tailored resilience framework that applies ecosystem service concepts to coastal social-ecological systems affected by degraded water quality. We present the framework as a mechanism for coordinating interdisciplinary research to inform long-term community planning decisions pertaining to chronic challenges in coastal systems. The resulting framework connects the ecological system to the social system via ecological production functions and ecosystem services. The social system then feeds back to the ecological system via policies and interventions to address declining water quality. We apply our resilience framework to the coastal waters and communities of Cape Cod (Barnstable County, Massachusetts, USA) which are affected by nitrogen over-enrichment. This approach allowed us to design research to improve the understanding of the effectiveness and acceptance of water quality improvement efforts and their effect on the delivery of ecosystem services. This framework is intended to be transferable to other geographical settings and more generally applied to systems exposed to chronic disturbances in order to coordinate interdisciplinary research planning and inform coastal management.

Developing qualitative ecosystem service relationships with the Driver-Pressure-State-Impact-Response framework: A case study on Cape Cod, Massachusetts.

Understanding the effects of environmental management strategies on society and the environment is critical for evaluating their effectiveness, but is often impeded by limited data availability. In this article, we present a method that can help scientists to support resource managers' thinking about social-ecological relationships in coupled human and natural systems. Our method aims to model qualitative cause-effect relationships between management strategies and ecosystem services, using information provided by knowledgeable participants, and the tradeoffs between strategies. Social, environmental, and cultural indicators are organized using the Driver-Pressure-State-Impact-Response, or DPSIR, framework. The relationships between indicators are evaluated using a decision tree and numerical representations of interaction strength. We use a matrix multiplication procedure to model direct and indirect interaction effects, and we provide guidelines for combining effects. Results include several data tables from which information can be visualized to understand the plausible interaction effects of implementing management strategies on ecosystem services. We illustrate our method with a water quality management case study on Cape Cod, Massachusetts.

Learning anatomy through Thiel- vs. formalin-embalmed cadavers: Student perceptions of embalming methods and effect on functional anatomy knowledge.

Thiel-embalmed cadavers, which have been adopted for use in anatomy teaching in relatively few universities, show greater flexibility and color retention compared to formalin-embalmed cadavers, properties which might be considered advantageous for anatomy teaching. This study aimed to investigate student attitudes toward the dissection experience with Thiel- compared to formalin/ethanol-embalmed cadavers. It also aimed to determine if one embalming method is more advantageous in terms of learning functional anatomy through the comparison of student anterior forearm functional anatomy knowledge. Student opinions and functional anatomy knowledge were obtained through use of a questionnaire from students at two medical schools, one using Thiel-, and one using more traditional formalin/ethanol-embalmed cadavers. Both the Thiel group and the formalin group of students were surveyed shortly after completing an anterior forearm dissection session. Significant differences (P-values <0.01) in some attitudes were found toward the dissection experience between cohorts using Thiel- vs. formalin-embalmed cadavers. The Thiel group of students felt more confident about recognizing anatomy in the living individual, found it easier to identify and dissect anatomical structures, and indicated more active exploration of functional anatomy due to the retained flexibility of the cadaver. However, on testing, no significant difference in functional anatomy knowledge was found between the two cohorts. Overall, although Thiel embalming may provide an advantageous learning experience in some investigated areas, more research needs to be carried out, especially to establish whether student perception is based on reality, at least in terms of structure identification. Anat Sci Educ 11: 166-174. © 2017 American Association of Anatomists.

Ecological restoration should be redefined for the twenty-first century.

Forty years ago, ecological restoration was conceptualized through a natural science lens. Today, ecological restoration has evolved into a social and scientific concept. The duality of ecological restoration is acknowledged in guidance documents on the subject but is not apparent in its definition. Current definitions reflect our views about what ecological restoration does but not why we do it. This viewpoint does not give appropriate credit to contributions from social sciences, nor does it provide compelling goals for people with different motivating rationales to engage in or support restoration. In this study, I give a concise history of the conceptualization and definition of ecological restoration, and I propose an alternative definition and corresponding viewpoint on restoration goal-setting to meet twenty-first century scientific and public inquiry.

Oxygen Mass Transport in Stented Coronary Arteries.

Oxygen deficiency, known as hypoxia, in arterial walls has been linked to increased intimal hyperplasia, which is the main adverse biological process causing in-stent restenosis. Stent implantation has significant effects on the oxygen transport into the arterial wall. Elucidating these effects is critical to optimizing future stent designs. In this study the most advanced oxygen transport model developed to date was assessed in two test cases and used to compare three coronary stent designs. Additionally, the predicted results from four simplified blood oxygen transport models are compared in the two test cases. The advanced model showed good agreement with experimental measurements within the mass-transfer boundary layer and at the luminal surface; however, more work is needed in predicting the oxygen transport within the arterial wall. Simplifying the oxygen transport model within the blood flow produces significant errors in predicting the oxygen transport in arteries. This study can be used as a guide for all future numerical studies in this area and the advanced model could provide a powerful tool in aiding design of stents and other cardiovascular devices.

Prevalence of drug and alcohol use in urban Afghanistan: epidemiological data from the Afghanistan National Urban Drug Use Study (ANUDUS).

BACKGROUND: Previous attempts to assess the prevalence of drug use in Afghanistan have focused on subgroups that are not generalisable. In the Afghanistan National Urban Drug Use Study, we assessed risk factors and drug use in Afghanistan through self-report questionnaires that we validated with laboratory test confirmation using analysis of hair, urine, and saliva. METHODS: The study took place between July 13, 2010, to April 25, 2012, in 11 Afghan provinces. 2187 randomly selected households completed a survey, representing 19 025 household members. We completed surveys with the female head of the household about past and current drug use among members of their household. We also obtained hair, urine, and saliva samples from 5236 people in these households and tested them for metabolites of 13 drugs. FINDINGS: Of 2170 households with biological samples tested, 247 (11·4%) tested positive for any drug. Overall, opioids were the most prevalent drug in the biological samples (5·6%), although prescription drugs (prescription pain pills, sedatives, and tranquilliser) were the most commonly reported in the past 30 days in the questionnaires (7·6%). Of individuals testing positive for at least one substance, opioids accounted for more than 50% of substance use in women and children, but only a third of substances in men, who predominantly tested positive for cannabinoids. After controlling for age with direct standardisation, individual prevalence of substance use (from laboratory tests) was 7·2% (95% CI 6·1-8·3) in men and 3·1% (2·5-3·7) in women-with a national prevalence of 5·1% (4·4-5·8) and a prevalence of 5·0% (4·1-5·8) in Kabul. Concordance between laboratory test results and self-reports was high. INTERPRETATION: These data suggest the female head of household to be a knowledgeable informant for household substance use. They also might provide insight into new avenues for targeted behavioural interventions and prevention messages.

Computational fluid dynamics analysis of balloon-expandable coronary stents: influence of stent and vessel deformation.

In many computational fluid dynamics (CFD) studies of stented vessel haemodynamics, the geometry of the stented vessel is described using non-deformed (NDF) geometrical models. These NDF models neglect complex physical features, such as stent and vessel deformation, which may have a major impact on the haemodynamic environment in stented coronary arteries. In this study, CFD analyses were carried out to simulate pulsatile flow conditions in both NDF and realistically-deformed (RDF) models of three stented coronary arteries. While the NDF models were completely idealised, the RDF models were obtained from nonlinear structural analyses and accounted for both stent and vessel deformation. Following the completion of the CFD analyses, major differences were observed in the time-averaged wall shear stress (TAWSS), time-averaged wall shear stress gradient (TAWSSG) and oscillatory shear index (OSI) distributions predicted on the luminal surface of the artery for the NDF and RDF models. Specifically, the inclusion of stent and vessel deformation in the CFD analyses resulted in a 32%, 30% and 31% increase in the area-weighted mean TAWSS, a 3%, 7% and 16% increase in the area-weighted mean TAWSSG and a 21%, 13% and 21% decrease in the area-weighted mean OSI for Stents A, B and C, respectively. These results suggest that stent and vessel deformation are likely to have a major impact on the haemodynamic environment in stented coronary arteries. In light of this observation, it is recommended that these features are considered in future CFD studies of stented vessel haemodynamics.

Global quantitative SILAC phosphoproteomics reveals differential phosphorylation is widespread between the procyclic and bloodstream form lifecycle stages of Trypanosoma brucei.

We report a global quantitative phosphoproteomic study of bloodstream and procyclic form Trypanosoma brucei using SILAC labeling of each lifecycle stage. Phosphopeptide enrichment by SCX and TiO2 led to the identification of a total of 10096 phosphorylation sites on 2551 protein groups and quantified the ratios of 8275 phosphorylation sites between the two lifecycle stages. More than 9300 of these sites (92%) have not previously been reported. Model-based gene enrichment analysis identified over representation of Gene Ontology terms relating to the flagella, protein kinase activity, and the regulation of gene expression. The quantitative data reveal that differential protein phosphorylation is widespread between bloodstream and procyclic form trypanosomes, with significant intraprotein differential phosphorylation. Despite a lack of dedicated tyrosine kinases, 234 phosphotyrosine residues were identified, and these were 3-4 fold over-represented among site changing >10-fold between the two lifecycle stages. A significant proportion of the T. brucei kinome was phosphorylated, with evidence that MAPK pathways are functional in both lifecycle stages. Regulation of gene expression in T. brucei is exclusively post-transcriptional, and the extensive phosphorylation of RNA binding proteins observed may be relevant to the control of mRNA stability in this organism.

Tumorigenic fragments of APC cause dominant defects in directional cell migration in multiple model systems.

Nonsense mutations that result in the expression of truncated, N-terminal, fragments of the adenomatous polyposis coli (APC) tumour suppressor protein are found in most sporadic and some hereditary colorectal cancers. These mutations can cause tumorigenesis by eliminating ß-catenin-binding sites from APC, which leads to upregulation of ß-catenin and thereby results in the induction of oncogenes such as MYC. Here we show that, in three distinct experimental model systems, expression of an N-terminal fragment of APC (N-APC) results in loss of directionality, but not speed, of cell motility independently of changes in ß-catenin regulation. We developed a system to culture and fluorescently label live pieces of gut tissue to record high-resolution three-dimensional time-lapse movies of cells in situ. This revealed an unexpected complexity of normal gut cell migration, a key process in gut epithelial maintenance, with cells moving with spatial and temporal discontinuity. Quantitative comparison of gut tissue from wild-type mice and APC heterozygotes (APC(Min/+); multiple intestinal neoplasia model) demonstrated that cells in precancerous epithelia lack directional preference when moving along the crypt-villus axis. This effect was reproduced in diverse experimental systems: in developing chicken embryos, mesoderm cells expressing N-APC failed to migrate normally; in amoeboid Dictyostelium, which lack endogenous APC, expressing an N-APC fragment maintained cell motility, but the cells failed to perform directional chemotaxis; and multicellular Dictyostelium slug aggregates similarly failed to perform phototaxis. We propose that N-terminal fragments of APC represent a gain-of-function mutation that causes cells within tissue to fail to migrate directionally in response to relevant guidance cues. Consistent with this idea, crypts in histologically normal tissues of APC(Min/+) intestines are overpopulated with cells, suggesting that a lack of migration might cause cell accumulation in a precancerous state.