ASU Scholarship Showcase

Swinging arms are a key functional component of multistep catalytic transformations in many naturally occurring multi-enzyme complexes. This arm is typically a prosthetic chemical group that is covalently attached to the enzyme complex via a flexible linker, allowing the direct transfer of substrate molecules between multiple active sites within the complex. Mimicking this method of substrate channelling outside the cellular environment requires precise control over the spatial parameters of the individual components within the assembled complex. DNA nanostructures can be used to organize functional molecules with nanoscale precision and can also provide nanomechanical control. Until now, protein–DNA assemblies have been used to organize cascades of enzymatic reactions by controlling the relative distance and orientation of enzymatic components or by facilitating the interface between enzymes/cofactors and electrode surfaces. Here, we show that a DNA nanostructure can be used to create a multi-enzyme complex in which an artificial swinging arm facilitates hydride transfer between two coupled dehydrogenases. By exploiting the programmability of DNA nanostructures, key parameters including position, stoichiometry and inter-enzyme distance can be manipulated for optimal activity.

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.

Background: Counselor behaviors that mediate the efficacy of motivational interviewing (MI) are not well understood, especially when applied to health behavior promotion. We hypothesized that client change talk mediates the relationship between counselor variables and subsequent client behavior change.

Methods: Purposeful sampling identified individuals from a prospective randomized worksite trial using an MI intervention to promote firefighters’ healthy diet and regular exercise that increased dietary intake of fruits and vegetables (n = 21) or did not increase intake of fruits and vegetables (n = 22). MI interactions were coded using the Motivational Interviewing Skill Code (MISC 2.1) to categorize counselor and firefighter verbal utterances. Both Bayesian and frequentist mediation analyses were used to investigate whether client change talk mediated the relationship between counselor skills and behavior change.

Results: Counselors’ global spirit, empathy, and direction and MI-consistent behavioral counts (e.g., reflections, open questions, affirmations, emphasize control) significantly correlated with firefighters’ total client change talk utterances (rs = 0.42, 0.40, 0.30, and 0.61, respectively), which correlated significantly with their fruit and vegetable intake increase (r = 0.33). Both Bayesian and frequentist mediation analyses demonstrated that findings were consistent with hypotheses, such that total client change talk mediated the relationship between counselor’s skills—MI-consistent behaviors [Bayesian mediated effect: αβ = .06 (.03), 95% CI = .02, .12] and MI spirit [Bayesian mediated effect: αβ = .06 (.03), 95% CI = .01, .13]—and increased fruit and vegetable consumption.

Conclusion: Motivational interviewing is a resource- and time-intensive intervention, and is currently being applied in many arenas. Previous research has identified the importance of counselor behaviors and client change talk in the treatment of substance use disorders. Our results indicate that similar mechanisms may underlie the effects of MI for dietary change. These results inform MI training and application by identifying those processes critical for MI success in health promotion domains.

Background: The Nike + Fuelband is a commercially available, wrist-worn accelerometer used to track physical activity energy expenditure (PAEE) during exercise. However, validation studies assessing the accuracy of this device for estimating PAEE are lacking. Therefore, this study examined the validity and reliability of the Nike + Fuelband for estimating PAEE during physical activity in young adults. Secondarily, we compared PAEE estimation of the Nike + Fuelband with the previously validated SenseWear Armband (SWA).

Methods: Twenty-four participants (n = 24) completed two, 60-min semi-structured routines consisting of sedentary/light-intensity, moderate-intensity, and vigorous-intensity physical activity. Participants wore a Nike + Fuelband and SWA, while oxygen uptake was measured continuously with an Oxycon Mobile (OM) metabolic measurement system (criterion).

Results: The Nike + Fuelband (ICC = 0.77) and SWA (ICC = 0.61) both demonstrated moderate to good validity. PAEE estimates provided by the Nike + Fuelband (246 ± 67 kcal) and SWA (238 ± 57 kcal) were not statistically different than OM (243 ± 67 kcal). Both devices also displayed similar mean absolute percent errors for PAEE estimates (Nike + Fuelband = 16 ± 13 %; SWA = 18 ± 18 %). Test-retest reliability for PAEE indicated good stability for Nike + Fuelband (ICC = 0.96) and SWA (ICC = 0.90).

Conclusion: The Nike + Fuelband provided valid and reliable estimates of PAEE, that are similar to the previously validated SWA, during a routine that included approximately equal amounts of sedentary/light-, moderate- and vigorous-intensity physical activity.

Background: Little research has explored who responds better to an automated vs. human advisor for health behaviors in general, and for physical activity (PA) promotion in particular. The purpose of this study was to explore baseline factors (i.e., demographics, motivation, interpersonal style, and external resources) that moderate intervention efficacy delivered by either a human or automated advisor.

Methods: Data were from the CHAT Trial, a 12-month randomized controlled trial to increase PA among underactive older adults (full trial N = 218) via a human advisor or automated interactive voice response advisor. Trial results indicated significant increases in PA in both interventions by 12 months that were maintained at 18-months. Regression was used to explore moderation of the two interventions.

Results: Results indicated amotivation (i.e., lack of intent in PA) moderated 12-month PA (d = 0.55, p < 0.01) and private self-consciousness (i.e., tendency to attune to one’s own inner thoughts and emotions) moderated 18-month PA (d = 0.34, p < 0.05) but a variety of other factors (e.g., demographics) did not (p > 0.12).

Conclusions: Results provide preliminary evidence for generating hypotheses about pathways for supporting later clinical decision-making with regard to the use of either human- vs. computer-delivered interventions for PA promotion.

Although previous research has studied power in mediation models, the extent to which the inclusion of a mediator will increase power has not been investigated. To address this deficit, in a first study we compared the analytical power values of the mediated effect and the total effect in a single-mediator model, to identify the situations in which the inclusion of one mediator increased statistical power. The results from this first study indicated that including a mediator increased statistical power in small samples with large coefficients and in large samples with small coefficients, and when coefficients were nonzero and equal across models. Next, we identified conditions under which power was greater for the test of the total mediated effect than for the test of the total effect in the parallel two-mediator model. These results indicated that including two mediators increased power in small samples with large coefficients and in large samples with small coefficients, the same pattern of results that had been found in the first study. Finally, we assessed the analytical power for a sequential (three-path) two-mediator model and compared the power to detect the three-path mediated effect to the power to detect both the test of the total effect and the test of the mediated effect for the single-mediator model. The results indicated that the three-path mediated effect had more power than the mediated effect from the single-mediator model and the test of the total effect. Practical implications of these results for researchers are then discussed.

Investigation into the causes underlying the rapid, global amphibian decline provides critical insight into the effects of changing ecosystems. Hypothesized and confirmed links between amphibian declines, disease, and environmental changes are increasingly represented in published literature. However, there are few long-term amphibian studies that include data on population size, abnormality/injury rates, disease, and habitat variables to adequately assess changes through time. We cultured and identified microorganisms isolated from abnormal/injured and repressed tissue regeneration sites of the endangered Ozark Hellbender, Cryptobranchus alleganiensis bishopi, to discover potential causative agents responsible for their significant decline in health and population. This organism and our study site were chosen because the population and habitat of C. a. bishopi have been intensively studied from 1969–2009, and the abnormality/injury rate and apparent lack of regeneration were established.

Although many bacterial and fungal isolates recovered were common environmental organisms, several opportunistic pathogens were identified in association with only the injured tissues of C.a. bishopi. Bacterial isolates included Aeromonas hydrophila, a known amphibian pathogen, Granulicetella adiacens, Gordonai terrae, Stenotrophomonas maltophilia, Aerococcus viridans, Streptococcus pneumoniae and a variety of Pseudomonads, including Pseudomonas aeruginosa, P. stutzeri, and P. alcaligenes. Fungal isolates included species in the genera Penicillium, Acremonium, Cladosporium, Curvularia, Fusarium, Streptomycetes, and the Class Hyphomycetes. Many of the opportunistic pathogens identified are known to form biofilms. Lack of isolation of the same organism from all wounds suggests that the etiological agent responsible for the damage to C. a. bishopi may not be a single organism. To our knowledge, this is the first study to profile the external microbial consortia cultured from a Cryptobranchid salamander. The incidence of abnormalities/injury and retarded regeneration in C. a. bishopi may have many contributing factors including disease and habitat degradation. Results from this study may provide insight into other amphibian population declines.

Mobile devices are a promising channel for delivering just-in-time guidance and support for improving key daily health behaviors. Despite an explosion of mobile phone applications aimed at physical activity and other health behaviors, few have been based on theoretically derived constructs and empirical evidence. Eighty adults ages 45 years and older who were insufficiently physically active, engaged in prolonged daily sitting, and were new to smartphone technology, participated in iterative design development and feasibility testing of three daily activity smartphone applications based on motivational frames drawn from behavioral science theory and evidence. An “analytically” framed custom application focused on personalized goal setting, self-monitoring, and active problem solving around barriers to behavior change. A “socially” framed custom application focused on social comparisons, norms, and support.

An “affectively” framed custom application focused on operant conditioning principles of reinforcement scheduling and emotional transference to an avatar, whose movements and behaviors reflected the physical activity and sedentary levels of the user. To explore the applications' initial efficacy in changing regular physical activity and leisure-time sitting, behavioral changes were assessed across eight weeks in 68 participants using the CHAMPS physical activity questionnaire and the Australian sedentary behavior questionnaire. User acceptability of and satisfaction with the applications was explored via a post-intervention user survey. The results indicated that the three applications were sufficiently robust to significantly improve regular moderate-to-vigorous intensity physical activity and decrease leisure-time sitting during the 8-week behavioral adoption period. Acceptability of the applications was confirmed in the post-intervention surveys for this sample of midlife and older adults new to smartphone technology. Preliminary data exploring sustained use of the applications across a longer time period yielded promising results. The results support further systematic investigation of the efficacy of the applications for changing these key health-promoting behaviors.

Background: Worksites are important locations for interventions to promote health. However, occupational programs with documented efficacy often are not used, and those being implemented have not been studied. The research in this report was funded through the American Reinvestment and Recovery Act Challenge Topic 'Pathways for Translational Research,' to define and prioritize determinants that enable and hinder translation of evidenced-based health interventions in well-defined settings.

Methods: The IGNITE (investigation to guide new insights for translational effectiveness) trial is a prospective cohort study of a worksite wellness and injury reduction program from adoption to final outcomes among 12 fire departments. It will employ a mixed methods strategy to define a translational model. We will assess decision to adopt, installation, use, and outcomes (reach, individual outcomes, and economic effects) using onsite measurements, surveys, focus groups, and key informant interviews. Quantitative data will be used to define the model and conduct mediation analysis of each translational phase. Qualitative data will expand on, challenge, and confirm survey findings and allow a more thorough understanding and convergent validity by overcoming biases in qualitative and quantitative methods used alone.

Discussion: Findings will inform worksite wellness in fire departments. The resultant prioritized influences and model of effective translation can be validated and manipulated in these and other settings to more efficiently move science to service.

This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans–induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance.

Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the low fluid-shear environment of microgravity is relevant to physical forces encountered by pathogens during the infection process, insights gained from this study could identify novel infectious disease mechanisms, with downstream benefits for the general public.