ASU Scholarship Showcase

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.

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.

A structurally and compositionally well-defined and spectrally tunable artificial light-harvesting system has been constructed in which multiple organic dyes attached to a three-arm-DNA nanostructure serve as an antenna conjugated to a photosynthetic reaction center isolated from Rhodobacter sphaeroides 2.4.1. The light energy absorbed by the dye molecules is transferred to the reaction center, where charge separation takes place. The average number of DNA three-arm junctions per reaction center was tuned from 0.75 to 2.35. This DNA-templated multichromophore system serves as a modular light-harvesting antenna that is capable of being optimized for its spectral properties, energy transfer efficiency, and photostability, allowing one to adjust both the size and spectrum of the resulting structures. This may serve as a useful test bed for developing nanostructured photonic systems.

This paper considers the changes in education and capacity building that are needed in response to environmental and social challenges of the 21st Century. We argue that such changes will require more than adjustments in current educational systems, research funding strategies, and interdisciplinary collaborations. Instead, it calls for a deeper questioning of the assumptions and beliefs that frame both problems and solutions. We first discuss the challenges of transforming education and capacity building within five key arenas: interdisciplinary research; university education systems; primary and secondary education systems; researchers from the developing world; and the public at large and politicians. Our starting point is that any type of revolution that is proposed in response to global change is likely to reflect the educational perspectives and paradigms of those calling for the revolution. We differentiate between a circular revolution (as in the "plan-do-check-act cycle" often used in change management) versus an axial revolution (moving to a different way of thinking about the issues), arguing that the latter is a more appropriate response to the complex transdisciplinary challenges posed by global environmental change. We present some potential tools to promote an axial revolution, and consider the limits to this approach. We conclude that rather than promoting one large and ideologically homogenous revolution in education and capacity building, there is a need for a revolution in the way that leaders working with education and capacity building look at systems and processes of change. From this perspective, transformative learning may not only be desirable, but critical in responding to the challenges posed by global environmental change.

We present a microarray nonlinear calibration (MiNC) method for quantifying antibody binding to the surface of protein microarrays that significantly increases the linear dynamic range and reduces assay variation compared with traditional approaches. A serological analysis of guinea pig Mycobacterium tuberculosis models showed that a larger number of putative antigen targets were identified with MiNC, which is consistent with the improved assay performance of protein microarrays. MiNC has the potential to be employed in biomedical research using multiplex antibody assays that need quantitation, including the discovery of antibody biomarkers, clinical diagnostics with multi-antibody signatures, and construction of immune mathematical models.

Time-resolved fluorescence spectroscopy was used to explore the pathway and kinetics of energy transfer in photosynthetic membrane vesicles (chromatophores) isolated from Rhodobacter (Rba.) sphaeroides cells harvested 2, 4, 6 or 24 hours after a transition from growth in high to low level illumination. As previously observed, this light intensity transition initiates the remodeling of the photosynthetic apparatus and an increase in the number of light harvesting 2 (LH2) complexes relative to light harvesting 1 (LH1) and reaction center (RC) complexes. It has generally been thought that the increase in LH2 complexes served the purpose of increasing the overall energy transmission to the RC. However, fluorescence lifetime measurements and analysis in terms of energy transfer within LH2 and between LH2 and LH1 indicate that, during the remodeling time period measured, only a portion of the additional LH2 generated are well connected to LH1 and the reaction center. The majority of the additional LH2 fluorescence decays with a lifetime comparable to that of free, unconnected LH2 complexes. The presence of large LH2-only domains has been observed by atomic force microscopy in Rba. sphaeroides chromatophores (Bahatyrova et al., Nature, 2004, 430, 1058), providing structural support for the existence of pools of partially connected LH2 complexes. These LH2-only domains represent the light-responsive antenna complement formed after a switch in growth conditions from high to low illumination, while the remaining LH2 complexes occupy membrane regions containing mixtures of LH2 and LH1–RC core complexes. The current study utilized a multi-parameter approach to explore the fluorescence spectroscopic properties related to the remodeling process, shedding light on the structure-function relationship of the photosynthetic assembles. Possible reasons for the accumulation of these largely disconnected LH2-only pools are discussed.

Throughout the long history of virus-host co-evolution, viruses have developed delicate strategies to facilitate their invasion and replication of their genome, while silencing the host immune responses through various mechanisms. The systematic characterization of viral protein-host interactions would yield invaluable information in the understanding of viral invasion/evasion, diagnosis and therapeutic treatment of a viral infection, and mechanisms of host biology. With more than 2,000 viral genomes sequenced, only a small percent of them are well investigated. The access of these viral open reading frames (ORFs) in a flexible cloning format would greatly facilitate both in vitro and in vivo virus-host interaction studies. However, the overall progress of viral ORF cloning has been slow. To facilitate viral studies, we are releasing the initiation of our panviral proteome collection of 2,035 ORF clones from 830 viral genes in the Gateway® recombinational cloning system. Here, we demonstrate several uses of our viral collection including highly efficient production of viral proteins using human cell-free expression system in vitro, global identification of host targets for rubella virus using Nucleic Acid Programmable Protein Arrays (NAPPA) containing 10,000 unique human proteins, and detection of host serological responses using micro-fluidic multiplexed immunoassays. The studies presented here begin to elucidate host-viral protein interactions with our systemic utilization of viral ORFs, high-throughput cloning, and proteomic technologies. These valuable plasmid resources will be available to the research community to enable continued viral functional studies.

The effects of urbanization on ozone levels have been widely investigated over cities primarily located in temperate and/or humid regions. In this study, nested WRF-Chem simulations with a finest grid resolution of 1 km are conducted to investigate ozone concentrations O₃ due to urbanization within cities in arid/semi-arid environments. First, a method based on a shape preserving Monotonic Cubic Interpolation (MCI) is developed and used to downscale anthropogenic emissions from the 4 km resolution 2005 National Emissions Inventory (NEI05) to the finest model resolution of 1 km. Using the rapidly expanding Phoenix metropolitan region as the area of focus, we demonstrate the proposed MCI method achieves ozone simulation results with appreciably improved correspondence to observations relative to the default interpolation method of the WRF-Chem system. Next, two additional sets of experiments are conducted, with the recommended MCI approach, to examine impacts of urbanization on ozone production: (1) the urban land cover is included (i.e., urbanization experiments) and, (2) the urban land cover is replaced with the region's native shrubland. Impacts due to the presence of the built environment on O₃ are highly heterogeneous across the metropolitan area. Increased near surface O₃ due to urbanization of 10–20 ppb is predominantly a nighttime phenomenon while simulated impacts during daytime are negligible. Urbanization narrows the daily O₃ range (by virtue of increasing nighttime minima), an impact largely due to the region's urban heat island. Our results demonstrate the importance of the MCI method for accurate representation of the diurnal profile of ozone, and highlight its utility for high-resolution air quality simulations for urban areas.

Rho GTPases are frequent targets of virulence factors as they are keystone signaling molecules. Herein, we demonstrate that AMPylation of Rho GTPases by VopS is a multifaceted virulence mechanism that counters several host immunity strategies. Activation of NFκB, Erk, and JNK kinase signaling pathways were inhibited in a VopS-dependent manner during infection with Vibrio parahaemolyticus. Phosphorylation and degradation of IKBα were inhibited in the presence of VopS as was nuclear translocation of the NFκB subunit p65. AMPylation also prevented the generation of superoxide by the phagocytic NADPH oxidase complex, potentially by inhibiting the interaction of Rac and p67. Furthermore, the interaction of GTPases with the E3 ubiquitin ligases cIAP1 and XIAP was hindered, leading to decreased degradation of Rac and RhoA during infection. Finally, we screened for novel Rac1 interactions using a nucleic acid programmable protein array and discovered that Rac1 binds to the protein C1QA, a protein known to promote immune signaling in the cytosol. Interestingly, this interaction was disrupted by AMPylation. We conclude that AMPylation of Rho Family GTPases by VopS results in diverse inhibitory consequences during infection beyond the most obvious phenotype, the collapse of the actin cytoskeleton.

Studies in both terrestrial and aquatic ecosystems have documented the potential importance of consumers on ecosystem-level nutrient dynamics. This is especially true when aggregations of organisms create biogeochemical hotspots through nutrient consumption, assimilation, and remineralization via excretion and egestion. Here, we focused on aggregations of humans in cities to examine how diet and waste management interact to drive nitrogen- (N) and phosphorus- (P) fluxes into nutrient pollution, inert forms, and nutrient recycling. We constructed six diet patterns (five US-based and one developing nation) to examine N- and P-consumption and excretion, and explored their implications for human health. Next, we constructed six waste-management patterns (three US and three for developing nations) to model how decisions at household and city scales determine the eventual fates of N and P. When compared to the US Recommended Daily Intake, all US diet patterns exceeded N and P requirements. Other than the “enriched CO₂ environment scenario” diet, the typical US omnivore had the greatest excess (37% N and 62% P). Notably, P from food additives could account for all of the excess P found in US omnivore and vegetarian diets. Across all waste-management approaches, a greater proportion of P was stored or recycled (0 to > 100% more P than N) and a greater proportion of N was released as effluent (20 to > 100% more N than P) resulting in pollution enriched with N and a recycling stream enriched with P. In developing nations, 60% of N and 50% of P from excreta entered the environment as pollution because of a lack of sanitation infrastructure. Our study demonstrates a novel addition to modeling sustainable scenarios for urban N- and P-budgets by linking human diets and waste management through socio-ecological systems.