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.

Mild Cognitive Impairment (MCI) is a transitional stage between normal aging and dementia and people with MCI are at high risk of progression to dementia. MCI is attracting increasing attention, as it offers an opportunity to target the disease process during an early symptomatic stage. Structural magnetic resonance imaging (MRI) measures have been the mainstay of Alzheimer's disease (AD) imaging research, however, ventricular morphometry analysis remains challenging because of its complicated topological structure. Here we describe a novel ventricular morphometry system based on the hyperbolic Ricci flow method and tensor-based morphometry (TBM) statistics. Unlike prior ventricular surface parameterization methods, hyperbolic conformal parameterization is angle-preserving and does not have any singularities. Our system generates a one-to-one diffeomorphic mapping between ventricular surfaces with consistent boundary matching conditions. The TBM statistics encode a great deal of surface deformation information that could be inaccessible or overlooked by other methods. We applied our system to the baseline MRI scans of a set of MCI subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI: 71 MCI converters vs. 62 MCI stable). Although the combined ventricular area and volume features did not differ between the two groups, our fine-grained surface analysis revealed significant differences in the ventricular regions close to the temporal lobe and posterior cingulate, structures that are affected early in AD. Significant correlations were also detected between ventricular morphometry, neuropsychological measures, and a previously described imaging index based on fluorodeoxyglucose positron emission tomography (FDG-PET) scans. This novel ventricular morphometry method may offer a new and more sensitive approach to study preclinical and early symptomatic stage AD.

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.

Although emerging evidence indicates that deep-sea water contains an untapped reservoir of high metabolic and genetic diversity, this realm has not been studied well compared with surface sea water. The study provided the first integrated meta-genomic and -transcriptomic analysis of the microbial communities in deep-sea water of North Pacific Ocean. DNA/RNA amplifications and simultaneous metagenomic and metatranscriptomic analyses were employed to discover information concerning deep-sea microbial communities from four different deep-sea sites ranging from the mesopelagic to pelagic ocean. Within the prokaryotic community, bacteria is absolutely dominant (~90%) over archaea in both metagenomic and metatranscriptomic data pools. The emergence of archaeal phyla Crenarchaeota, Euryarchaeota, Thaumarchaeota, bacterial phyla Actinobacteria, Firmicutes, sub-phyla Betaproteobacteria, Deltaproteobacteria, and Gammaproteobacteria, and the decrease of bacterial phyla Bacteroidetes and Alphaproteobacteria are the main composition changes of prokaryotic communities in the deep-sea water, when compared with the reference Global Ocean Sampling Expedition (GOS) surface water. Photosynthetic Cyanobacteria exist in all four metagenomic libraries and two metatranscriptomic libraries. In Eukaryota community, decreased abundance of fungi and algae in deep sea was observed. RNA/DNA ratio was employed as an index to show metabolic activity strength of microbes in deep sea. Functional analysis indicated that deep-sea microbes are leading a defensive lifestyle.

Background: Interaction in the form of cooperation, communication, and friendly competition theoretically precede the development of group cohesion, which often precedes adherence to health promotion programs. The purpose of this manuscript was to explore longitudinal relationships among dimensions of group cohesion and group-interaction variables to inform and improve group-based strategies within programs aimed at promoting physical activity.

Methods: Ethnic minority women completed a group dynamics-based physical activity promotion intervention (N = 103; 73% African American; 27% Hispanic/Latina; mage = 47.89 + 8.17 years; mBMI = 34.43+ 8.07 kg/m[superscript 2]) and assessments of group cohesion and group-interaction variables at baseline, 6 months (post-program), and 12 months (follow-up).

Results: All four dimensions of group cohesion had significant (ps < 0.01) relationships with the group-interaction variables. Competition was a consistently strong predictor of cohesion, while cooperation did not demonstrate consistent patterns of prediction.

Conclusions: Facilitating a sense of friendly competition may increase engagement in physical activity programs by bolstering group cohesion.

Background: Latino preschoolers (3-5 year old children) have among the highest rates of obesity. Low levels of physical activity (PA) are a risk factor for obesity. Characterizing what Latino parents do to encourage or discourage their preschooler to be physically active can help inform interventions to increase their PA. The objective was therefore to develop and assess the psychometrics of a new instrument: the Preschooler Physical Activity Parenting Practices (PPAPP) among a Latino sample, to assess parenting practices used to encourage or discourage PA among preschool-aged children.

Methods: Cross-sectional study of 240 Latino parents who reported the frequency of using PA parenting practices. 95% of respondents were mothers; 42% had more than a high school education. Child mean age was 4.5 (±0.9) years (52% male). Test-retest reliability was assessed in 20%, 2 weeks later. We assessed the fit of a priori models using Confirmatory factor analyses (CFA). In a separate sub-sample (35%), preschool-aged children wore accelerometers to assess associations with their PA and PPAPP subscales.

Results: The a-priori models showed poor fit to the data. A modified factor structure for encouraging PPAPP had one multiple-item scale: engagement (15 items), and two single-items (have outdoor toys; not enroll in sport-reverse coded). The final factor structure for discouraging PPAPP had 4 subscales: promote inactive transport (3 items), promote screen time (3 items), psychological control (4 items) and restricting for safety (4 items). Test-retest reliability (ICC) for the two scales ranged from 0.56-0.85. Cronbach’s alphas ranged from 0.5-0.9. Several sub-factors correlated in the expected direction with children’s objectively measured PA.

Conclusion: The final models for encouraging and discouraging PPAPP had moderate to good fit, with moderate to excellent test-retest reliabilities. The PPAPP should be further evaluated to better assess its associations with children’s PA and offers a new tool for measuring PPAPP among Latino families with preschool-aged children.

Background: To combat the disproportionately higher risk of childhood obesity in Latino preschool-aged children, multilevel interventions targeting physical (in) activity are needed. These require the identification of environmental and psychosocial determinants of physical (in) activity for this ethnic group. The objectives were to examine differences in objectively-measured physical activity and sedentary behavior across objectively-determined types of locations in Latino preschool-aged children; and determine whether the differences in physical activity by location were greater in children of parents with higher neighborhood-safety perceptions and physical activity-supportive parenting practices.

Methods: An observational field study was conducted in Houston (Texas, USA) from August 2011 to April 2012. A purposive sample of Latino children aged 3–5 years and one of their parents (n = 84) were recruited from Census block groups in Houston (Texas) stratified by objectively-assessed high vs. low traffic and crime safety. Seventy-three children provided valid data. Time spent outdoors/indoors tagged with geographic locations was coded into location types based on objective data collected using Global Positioning Systems units that children wore >8 hr/day for a week. Physical activity parenting practices, perceived neighborhood-safety, and demographics were reported by parents. Time spent in sedentary behavior and moderate-to-vigorous physical activity was measured based on objective data collected using accelerometers (motion sensors) that children wore >8 hr/day for a week.

Results: The odds of children engaging in moderate-to-vigorous physical activity were 43 % higher when outdoors than indoors (95 % confidence interval: 1.30, 1.58), and the odds of being sedentary were 14 % lower when outdoors compared to indoors (95 % confidence intervals: 0.81, 0.91). This difference depended on parental neighborhood-safety perceptions and parenting practices. Children were most active in parks/playgrounds (30 % of the time spent in moderate-to-vigorous physical activity) and least active in childcare/school settings (8 % of the time spent in moderate-to-vigorous physical activity).

Conclusions: Objectively-assessed time spent in specific locations is correlated with physical activity and sedentary behavior in Latino preschoolers. Interventions and policies should identify ways to engage Latino preschool-aged children in more physical activity and less sedentary behavior while in childcare, and encourage parents to spend more time with their young children in parks/playgrounds and other safe outdoor places.

The purpose of this review was to determine the degree to which physical activity interventions for Latin American populations reported on internal and external validity factors using the RE-AIM framework (reach & representativeness, effectiveness, adoption, implementation, maintenance). We systematically identified English (PubMed; EbscoHost) and Spanish (SCIELO; Biblioteca Virtual en Salud) language studies published between 2001 and 2012 that tested physical activity, exercise, or fitness promotion interventions in Latin American populations. Cross-sectional/descriptive studies, conducted in Brazil or Spain, published in Portuguese, not including a physical activity/fitness/exercise outcome, and with one time point assessment were excluded. We reviewed 192 abstracts and identified 46 studies that met the eligibility criteria (34 in English, 12 in Spanish). A validated 21-item RE-AIM abstraction tool was used to determine the quality of reporting across studies (0-7 = low, 8-14 = moderate, and 15-21 = high). The number of indicators reported ranged from 3–14 (mean = 8.1 ± 2.6), with the majority of studies falling in the moderate quality reporting category. English and Spanish language articles did not differ on the number of indicators reported (8.1 vs. 8.3, respectively). However, Spanish articles reported more across reach indicators (62% vs. 43% of indicators), while English articles reported more across effectiveness indicators (69% vs 62%). Across RE-AIM dimensions, indicators for reach (48%), efficacy/effectiveness (67%), and implementation (41%) were reported more often than indicators of adoption (25%) and maintenance (10%). Few studies reported on the representativeness of participants, staff that delivered interventions, or the settings where interventions were adopted. Only 13% of the studies reported on quality of life and/or potential negative outcomes, 20% reported on intervention fidelity, and 11% on cost of implementation. Outcomes measured after six months of intervention, information on continued delivery and institutionalization of interventions, were also seldom reported. Regardless of language of publication, physical activity intervention research for Latin Americans should increase attention to and measurement of external validity and cost factors that are critical in the decision making process in practice settings and can increase the likelihood of translation into community or clinical practice.

Background: Carriers of the APOE ε4 allele are at increased risk of developing Alzheimer’s disease (AD), and have been shown to have reduced cerebral metabolic rate of glucose (CMRgl) in the same brain areas frequently affected in AD. These individuals also exhibit reduced plasma levels of apolipoprotein E (apoE) attributed to a specific decrease in the apoE4 isoform as determined by quantification of individual apoE isoforms in APOE ε4 heterozygotes. Whether low plasma apoE levels are associated with structural and functional brain measurements and cognitive performance remains to be investigated.

Methods: Using quantitative mass spectrometry we quantified the plasma levels of total apoE and the individual apoE3 and apoE4 isoforms in 128 cognitively normal APOE ε3/ε4 individuals included in the Arizona APOE cohort. All included individuals had undergone extensive neuropsychological testing and 25 had in addition undergone FDG-PET and MRI to determine CMRgl and regional gray matter volume (GMV).

Results: Our results demonstrated higher apoE4 levels in females versus males and an age-dependent increase in the apoE3 isoform levels in females only. Importantly, a higher relative ratio of apoE4 over apoE3 was associated with GMV loss in the right posterior cingulate and with reduced CMRgl bilaterally in the anterior cingulate and in the right hippocampal area. Additional exploratory analysis revealed several negative associations between total plasma apoE, individual apoE isoform levels, GMV and CMRgl predominantly in the frontal, occipital and temporal areas. Finally, our results indicated only weak associations between apoE plasma levels and cognitive performance which further appear to be affected by sex.

Conclusions: Our study proposes a sex-dependent and age-dependent variation in plasma apoE isoform levels and concludes that peripheral apoE levels are associated with GMV, CMRgl and possibly cognitive performance in cognitively healthy individuals with a genetic predisposition to AD.

Background: We introduced a hypometabolic convergence index (HCI) to characterize in a single measurement the extent to which a person’s fluorodeoxyglucose positron emission tomogram (FDG PET) corresponds to that in Alzheimer’s disease (AD). Apolipoprotein E ε4 (APOE ε4) gene dose is associated with three levels of risk for late-onset AD. We explored the association between gene dose and HCI in cognitively normal ε4 homozygotes, heterozygotes, and non-carriers.

Methods: An algorithm was used to characterize and compare AD-related HCIs in cognitively normal individuals, including 36 ε4 homozygotes, 46 heterozygotes, and 78 non-carriers.

Results: These three groups differed significantly in their HCIs (ANOVA, p = 0.004), and there was a significant association between HCIs and gene dose (linear trend, p = 0.001).

Conclusions: The HCI is associated with three levels of genetic risk for late-onset AD. This supports the possibility of using a single FDG PET measurement to help in the preclinical detection and tracking of AD.