ASU Scholarship Showcase

Objective: This cross sectional study aims to determine the effects of gender and parental perception of safety at school on children’s physical activity (PA) levels.

Materials and Methods: Parents of school aged Mexican children residing in Guadalajara, Mexico City, and Puerto Vallarta, completed surveys about their children’s PA measures. The physical activity indicators were evaluated using linear and logistical regression models.

Results: Analysis did not indicate that gender moderated the relationship between parental perception of safety and PA measures, but significant gender issues exist with girls participating less than boys in the three measures of PA in this study (p<0.001).

Conclusion: Results suggest the need for additional interventions promoting physical activity in girls in Mexico.

Background: The discovery of genetic associations is an important factor in the understanding of human illness to derive disease pathways. Identifying multiple interacting genetic mutations associated with disease remains challenging in studying the etiology of complex diseases. And although recently new single nucleotide polymorphisms (SNPs) at genes implicated in immune response, cholesterol/lipid metabolism, and cell membrane processes have been confirmed by genome-wide association studies (GWAS) to be associated with late-onset Alzheimer's disease (LOAD), a percentage of AD heritability continues to be unexplained. We try to find other genetic variants that may influence LOAD risk utilizing data mining methods.

Methods: Two different approaches were devised to select SNPs associated with LOAD in a publicly available GWAS data set consisting of three cohorts. In both approaches, single-locus analysis (logistic regression) was conducted to filter the data with a less conservative p-value than the Bonferroni threshold; this resulted in a subset of SNPs used next in multi-locus analysis (random forest (RF)). In the second approach, we took into account prior biological knowledge, and performed sample stratification and linkage disequilibrium (LD) in addition to logistic regression analysis to preselect loci to input into the RF classifier construction step.

Results: The first approach gave 199 SNPs mostly associated with genes in calcium signaling, cell adhesion, endocytosis, immune response, and synaptic function. These SNPs together with APOE and GAB2 SNPs formed a predictive subset for LOAD status with an average error of 9.8% using 10-fold cross validation (CV) in RF modeling. Nineteen variants in LD with ST5, TRPC1, ATG10, ANO3, NDUFA12, and NISCH respectively, genes linked directly or indirectly with neurobiology, were identified with the second approach. These variants were part of a model that included APOE and GAB2 SNPs to predict LOAD risk which produced a 10-fold CV average error of 17.5% in the classification modeling.

Conclusions: With the two proposed approaches, we identified a large subset of SNPs in genes mostly clustered around specific pathways/functions and a smaller set of SNPs, within or in proximity to five genes not previously reported, that may be relevant for the prediction/understanding of AD.

Background: Glioblastoma is the most aggressive primary central nervous tumor and carries a very poor prognosis. Invasion precludes effective treatment and virtually assures tumor recurrence. In the current study, we applied analytical and bioinformatics approaches to identify a set of microRNAs (miRs) from several different human glioblastoma cell lines that exhibit significant differential expression between migratory (edge) and migration-restricted (core) cell populations. The hypothesis of the study is that differential expression of miRs provides an epigenetic mechanism to drive cell migration and invasion.

Results: Our research data comprise gene expression values for a set of 805 human miRs collected from matched pairs of migratory and migration-restricted cell populations from seven different glioblastoma cell lines. We identified 62 down-regulated and 2 up-regulated miRs that exhibit significant differential expression in the migratory (edge) cell population compared to matched migration-restricted (core) cells. We then conducted target prediction and pathway enrichment analysis with these miRs to investigate potential associated gene and pathway targets. Several miRs in the list appear to directly target apoptosis related genes. The analysis identifies a set of genes that are predicted by 3 different algorithms, further emphasizing the potential validity of these miRs to promote glioblastoma.

Conclusions: The results of this study identify a set of miRs with potential for decreased expression in invasive glioblastoma cells. The verification of these miRs and their associated targeted proteins provides new insights for further investigation into therapeutic interventions. The methodological approaches employed here could be applied to the study of other diseases to provide biomedical researchers and clinicians with increased opportunities for therapeutic interventions.

Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467) completed questionnaires on the social environment, psychosocial factors (stress, depressive symptoms, and racial discrimination), and mental health. Multiple-mediator models were used to assess direct and indirect effects of the social environment on mental health. Low social status in the community (p < .001) and U.S. (p < .001) and low social support (p < .001) were associated with poor mental health. Psychosocial factors significantly jointly mediated the relationship between the social environment and mental health in multiple-mediator models. Low social status and social support were associated with greater perceived stress, depressive symptoms, and perceived racial discrimination, which were associated with poor mental health. Results suggest the relationship between the social environment and mental health is mediated by psychosocial factors and revealed potential mechanisms through which social status and social support influence the mental health of African American men and women. Findings from this study provide insight into the differential effects of stress, depression and discrimination on mental health. Ecological approaches that aim to improve the social environment and psychosocial mediators may enhance health-related quality of life and reduce health disparities in African Americans.

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: Obesity is a metabolic disease caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are incompletely understood. The aim of our study was to investigate the role of skeletal muscle DNA methylation in combination with transcriptomic changes in obesity.

Results: Muscle biopsies were obtained basally from lean (n = 12; BMI = 23.4 ± 0.7 kg/m[superscript 2]) and obese (n = 10; BMI = 32.9 ± 0.7 kg/m[superscript 2]) participants in combination with euglycemic-hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing (RRBS) next-generation methylation and microarray analyses on DNA and RNA isolated from vastus lateralis muscle biopsies. There were 13,130 differentially methylated cytosines (DMC; uncorrected P < 0.05) that were altered in the promoter and untranslated (5' and 3'UTR) regions in the obese versus lean analysis. Microarray analysis revealed 99 probes that were significantly (corrected P < 0.05) altered. Of these, 12 genes (encompassing 22 methylation sites) demonstrated a negative relationship between gene expression and DNA methylation. Specifically, sorbin and SH3 domain containing 3 (SORBS3) which codes for the adapter protein vinexin was significantly decreased in gene expression (fold change −1.9) and had nine DMCs that were significantly increased in methylation in obesity (methylation differences ranged from 5.0 to 24.4 %). Moreover, differentially methylated region (DMR) analysis identified a region in the 5'UTR (Chr.8:22,423,530–22,423,569) of SORBS3 that was increased in methylation by 11.2 % in the obese group. The negative relationship observed between DNA methylation and gene expression for SORBS3 was validated by a site-specific sequencing approach, pyrosequencing, and qRT-PCR. Additionally, we performed transcription factor binding analysis and identified a number of transcription factors whose binding to the differentially methylated sites or region may contribute to obesity.

Conclusions: These results demonstrate that obesity alters the epigenome through DNA methylation and highlights novel transcriptomic changes in SORBS3 in skeletal muscle.

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: 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.

Background: Our publication of the BitTorious portal [1] demonstrated the ability to create a privatized distributed data warehouse of sufficient magnitude for real-world bioinformatics studies using minimal changes to the standard BitTorrent tracker protocol. In this second phase, we release a new server-side specification to accept anonymous philantropic storage donations by the general public, wherein a small portion of each user’s local disk may be used for archival of scientific data. We have implementated the server-side announcement and control portions of this BitTorrent extension into v3.0.0 of the BitTorious portal, upon which compatible clients may be built.

Results: Automated test cases for the BitTorious Volunteer extensions have been added to the portal’s v3.0.0 release, supporting validation of the “peer affinity” concept and announcement protocol introduced by this specification. Additionally, a separate reference implementation of affinity calculation has been provided in C++ for informaticians wishing to integrate into libtorrent-based projects.

Conclusions: The BitTorrent “affinity” extensions as provided in the BitTorious portal reference implementation allow data publishers to crowdsource the extreme storage prerequisites for research in “big data” fields. With sufficient awareness and adoption of BitTorious Volunteer-based clients by the general public, the BitTorious portal may be able to provide peta-scale storage resources to the scientific community at relatively insignificant financial cost.

Background: Centralized silos of genomic data are architecturally easier to initially design, develop and deploy than distributed models. However, as interoperability pains in EHR/EMR, HIE and other collaboration-centric life sciences domains have taught us, the core challenge of networking genomics systems is not in the construction of individual silos, but the interoperability of those deployments in a manner embracing the heterogeneous needs, terms and infrastructure of collaborating parties. This article demonstrates the adaptation of BitTorrent to private collaboration networks in an authenticated, authorized and encrypted manner while retaining the same characteristics of standard BitTorrent.

Results: The BitTorious portal was sucessfully used to manage many concurrent domestic Bittorrent clients across the United States: exchanging genomics data payloads in excess of 500GiB using the uTorrent client software on Linux, OSX and Windows platforms. Individual nodes were sporadically interrupted to verify the resilience of the system to outages of a single client node as well as recovery of nodes resuming operation on intermittent Internet connections.

Conclusions: The authorization-based extension of Bittorrent and accompanying BitTorious reference tracker and user management web portal provide a free, standards-based, general purpose and extensible data distribution system for large ‘omics collaborations.