ASU Scholarship Showcase

Many drugs are effective in the early stage of treatment, but patients develop drug resistance after a certain period of treatment, causing failure of the therapy. An important example is Herceptin, a popular monoclonal antibody drug for breast cancer by specifically targeting human epidermal growth factor receptor 2 (Her2). Here we demonstrate a quantitative binding kinetics analysis of drug-target interactions to investigate the molecular scale origin of drug resistance. Using a surface plasmon resonance imaging, we measured the in situ Herceptin-Her2 binding kinetics in single intact cancer cells for the first time, and observed significantly weakened Herceptin-Her2 interactions in Herceptin-resistant cells, compared to those in Herceptin-sensitive cells. We further showed that the steric hindrance of Mucin-4, a membrane protein, was responsible for the altered drug-receptor binding. This effect of a third molecule on drug-receptor interactions cannot be studied using traditional purified protein methods, demonstrating the importance of the present intact cell-based binding kinetics analysis.

Groundwater is a common-pool resource that is subject to depletion in many places around the world as a result of increased use of irrigation and water-demanding cash crops. Where state capacity to control groundwater use is limited, collective action is important to increase recharge and restrict highly water-consumptive crops. We present results of field experiments in hard rock areas of Andhra Pradesh, India, to examine factors affecting groundwater use. Two nongovernmental organizations (NGOs) ran the games in communities where they were working to improve watershed and water management. Results indicate that, when the links between crop choice and groundwater depletion is made explicit, farmers can act cooperatively to address this problem. Longer NGO involvement in the villages was associated with more cooperative outcomes in the games. Individuals with more education and higher perceived community social capital played more cooperatively, but neither gender nor method of payment had a significantly effect on individual behavior. When participants could repeat the game with communication, similar crop choice patterns were observed. The games provided an entry point for discussion on the understanding of communities of the interconnectedness of groundwater use and crop choice.

Environmental niche modeling (ENM) is commonly used to develop probabilistic maps of species distribution. Among available ENM techniques, MaxEnt has become one of the most popular tools for modeling species distribution, with hundreds of peer-reviewed articles published each year. MaxEnt’s popularity is mainly due to the use of a graphical interface and automatic parameter configuration capabilities. However, recent studies have shown that using the default automatic configuration may not be always appropriate because it can produce non-optimal models; particularly when dealing with a small number of species presence points. Thus, the recommendation is to evaluate the best potential combination of parameters (feature classes and regularization multiplier) to select the most appropriate model. In this work we reviewed 244 articles published between 2013 and 2015 to assess whether researchers are following recommendations to avoid using the default parameter configuration when dealing with small sample sizes, or if they are using MaxEnt as a “black box tool.” Our results show that in only 16% of analyzed articles authors evaluated best feature classes, in 6.9% evaluated best regularization multipliers, and in a meager 3.7% evaluated simultaneously both parameters before producing the definitive distribution model. We analyzed 20 articles to quantify the potential differences in resulting outputs when using software default parameters instead of the alternative best model. Results from our analysis reveal important differences between the use of default parameters and the best model approach, especially in the total area identified as suitable for the assessed species and the specific areas that are identified as suitable by both modelling approaches. These results are worrying, because publications are potentially reporting over-complex or over-simplistic models that can undermine the applicability of their results. Of particular importance are studies used to inform policy making. Therefore, researchers, practitioners, reviewers and editors need to be very judicious when dealing with MaxEnt, particularly when the modelling process is based on small sample sizes.

Course-based undergraduate research experiences (CUREs) meet national recommendations for integrating research experiences into life science curricula. As such, CUREs have grown in popularity and many research studies have focused on student outcomes from CUREs. Institutional change literature highlights that understanding faculty is also key to new pedagogies succeeding. To begin to understand faculty perspectives on CUREs, we conducted semi-structured interviews with 61 faculty who teach CUREs regarding why they teach CUREs, what the outcomes are, and how they would discuss a CURE with a colleague. Using grounded theory, participant responses were coded and categorized as tangible or intangible, related to both student and faculty-centered themes. We found that intangible themes were prevalent, and that there were significant differences in the emphasis on tangible themes for faculty who have developed their own independent CUREs when compared with faculty who implement pre-developed, national CUREs. We focus our results on the similarities and differences among the perspectives of faculty who teach these two different CURE types and explore trends among all participants. The results of this work highlight the need for considering a multi-dimensional framework to understand, promote, and successfully implement CUREs.

We recommend using backward design to develop course-based undergraduate research experiences (CUREs). The defining hallmark of CUREs is that students in a formal lab course explore research questions with unknown answers that are broadly relevant outside the course. Because CUREs lead to novel research findings, they represent a unique course design challenge, as the dual nature of these courses requires course designers to consider two distinct, but complementary, sets of goals for the CURE: 1) scientific discovery milestones (i.e., research goals) and 2) student learning in cognitive, psychomotor, and affective domains (i.e., pedagogical goals). As more undergraduate laboratory courses are re-imagined as CUREs, how do we thoughtfully design these courses to effectively meet both sets of goals? In this Perspectives article, we explore this question and outline recommendations for using backward design in CURE development.

Background: Vulnerability mapping based on vulnerability indices is a pragmatic approach for highlighting the areas in a city where people are at the greatest risk of harm from heat, but the manner in which vulnerability is conceptualized influences the results.

Objectives: We tested a generic national heat-vulnerability index, based on a 10-variable indicator framework, using data on heat-related hospitalizations in Phoenix, Arizona. We also identified potential local risk factors not included in the generic indicators.

Methods: To evaluate the accuracy of the generic index in a city-specific context, we used factor scores, derived from a factor analysis using census tract–level characteristics, as independent variables, and heat hospitalizations (with census tracts categorized as zero-, moderate-, or high-incidence) as dependent variables in a multinomial logistic regression model. We also compared the geographical differences between a vulnerability map derived from the generic index and one derived from actual heat-related hospitalizations at the census-tract scale.

Results: We found that the national-indicator framework correctly classified just over half (54%) of census tracts in Phoenix. Compared with all census tracts, high-vulnerability tracts that were misclassified by the index as zero-vulnerability tracts had higher average income and higher proportions of residents with a duration of residency < 5 years.

Conclusion: The generic indicators of vulnerability are useful, but they are sensitive to scale, measurement, and context. Decision makers need to consider the characteristics of their cities to determine how closely vulnerability maps based on generic indicators reflect actual risk of harm.

Social-ecological organization is a multidimensional phenomenon that combines material and symbolic processes. However, the coupling between social and ecological subsystem is often conceptualized as purely material, thus reducing the symbolic dimension to its behavioral and actionable expressions. In this paper I conceptualize social-ecological systems as doubly coupled. On the one hand, material expressions of socio-cultural processes affect and are affected by ecological dynamics. On the other hand, coupled social-ecological material dynamics are concurrently coupled with subjective dynamics via coding, decoding, personal experience, and human agency. This second coupling operates across two organizationally heterogeneous dimensions: material and symbolic. Although resilience thinking builds on the recognition of organizational asymmetry between living and nonliving systems, it has overlooked the equivalent asymmetry between ecological and socio-cultural subsystems.

Three guiding concepts are proposed to formalize double coupling. The first one, social-ecological asymmetry, expands on past seminal work on ecological self-organization to incorporate reflexivity and subjectivity in social-ecological modeling. Organizational asymmetry is based in the distinction between social rules, which are symbolically produced and changed through human agents’ reflexivity and purpose, and biophysical rules, which are determined by functional relations between ecological components. The second guiding concept, conscious power, brings to the fore human agents’ distinctive capacity to produce our own subjective identity and the consequences of this capacity for social-ecological organization. The third concept, congruence between subjective and objective dynamics, redefines sustainability as contingent on congruent relations between material and symbolic processes. Social-ecological theories and analyses based on these three guiding concepts would support the integration of current structuralist-functionalist methods, which sufficiently and appropriately characterize ecological organization, with ethnographic and narrative methods exploring human intentionality, reflexivity, and biographical development.

There is an increasing demand in higher education institutions for training in complex environmental problems. Such training requires a careful mix of conventional methods and innovative solutions, a task not always easy to accomplish. In this paper we review literature on this theme, highlight relevant advances in the pedagogical literature, and report on some examples resulting from our recent efforts to teach complex environmental issues. The examples range from full credit courses in sustainable development and research methods to project-based and in-class activity units. A consensus from the literature is that lectures are not sufficient to fully engage students in these issues. A conclusion from the review of examples is that problem-based and project-based, e.g., through case studies, experiential learning opportunities, or real-world applications, learning offers much promise. This could greatly be facilitated by online hubs through which teachers, students, and other members of the practitioner and academic community share experiences in teaching and research, the way that we have done here.

Background: Microalgae are promising feedstock for production of lipids, sugars, bioactive compounds and in particular biofuels, yet development of sensitive and reliable phylotyping strategies for microalgae has been hindered by the paucity of phylogenetically closely-related finished genomes.

Results: Using the oleaginous eustigmatophyte Nannochloropsis as a model, we assessed current intragenus phylotyping strategies by producing the complete plastid (pt) and mitochondrial (mt) genomes of seven strains from six Nannochloropsis species. Genes on the pt and mt genomes have been highly conserved in content, size and order, strongly negatively selected and evolving at a rate 33% and 66% of nuclear genomes respectively. Pt genome diversification was driven by asymmetric evolution of two inverted repeats (IRa and IRb): psbV and clpC in IRb are highly conserved whereas their counterparts in IRa exhibit three lineage-associated types of structural polymorphism via duplication or disruption of whole or partial genes. In the mt genomes, however, a single evolution hotspot varies in copy-number of a 3.5 Kb-long, cox1-harboring repeat. The organelle markers (e.g., cox1, cox2, psbA, rbcL and rrn16_mt) and nuclear markers (e.g., ITS2 and 18S) that are widely used for phylogenetic analysis obtained a divergent phylogeny for the seven strains, largely due to low SNP density. A new strategy for intragenus phylotyping of microalgae was thus proposed that includes (i) twelve sequence markers that are of higher sensitivity than ITS2 for interspecies phylogenetic analysis, (ii) multi-locus sequence typing based on rps11_mt-nad4, rps3_mt and cox2-rrn16_mt for intraspecies phylogenetic reconstruction and (iii) several SSR loci for identification of strains within a given species.

Conclusion: This first comprehensive dataset of organelle genomes for a microalgal genus enabled exhaustive assessment and searches of all candidate phylogenetic markers on the organelle genomes. A new strategy for intragenus phylotyping of microalgae was proposed which might be generally applicable to other microalgal genera and should serve as a valuable tool in the expanding algal biotechnology industry.

Major progress has been made in the past decade towards understanding of the biosynthesis of red carotenoid astaxanthin and its roles in stress response while exploiting microalgae-based astaxanthin as a potent antioxidant for human health and as a coloring agent for aquaculture applications. In this review, astaxanthin-producing green microalgae are briefly summarized with Haematococcus pluvialis and Chlorella zofingiensis recognized to be the most popular astaxanthin-producers. Two distinct pathways for astaxanthin synthesis along with associated cellular, physiological, and biochemical changes are elucidated using H. pluvialis and C. zofingiensis as the model systems. Interactions between astaxanthin biosynthesis and photosynthesis, fatty acid biosynthesis and enzymatic defense systems are described in the context of multiple lines of defense mechanisms working in concert against photooxidative stress. Major pros and cons of mass cultivation of H. pluvialis and C. zofingiensis in phototrophic, heterotrophic, and mixotrophic culture modes are analyzed. Recent progress in genetic engineering of plants and microalgae for astaxanthin production is presented. Future advancement in microalgal astaxanthin research will depend largely on genome sequencing of H pluvialis and C. zofingiensis and genetic toolbox development. Continuous effort along the heterotrophic-phototrophic culture mode could lead to major expansion of the micro algal astaxanthin industry.