ASU Scholarship Showcase

Although insulin resistance in skeletal muscle is well-characterized, the role of circulating whole blood in the metabolic syndrome phenotype is not well understood. We set out to test the hypothesis that genes involved in inflammation, insulin signaling and mitochondrial function would be altered in expression in the whole blood of individuals with metabolic syndrome. We further wanted to examine whether similar relationships that we have found previously in skeletal muscle exist in peripheral whole blood cells. All subjects (n=184) were Latino descent from the Arizona Insulin Resistance registry. Subjects were classified based on the metabolic syndrome phenotype according to the National Cholesterol Education Program’s Adult Treatment Panel III. Of the 184 Latino subjects in the study, 74 were classified with the metabolic syndrome and 110 were without. Whole blood gene expression profiling was performed using the Agilent 4x44K Whole Human Genome Microarray. Whole blood microarray analysis identified 1,432 probes that were altered in expression ≥1.2 fold and P<0.05 after Benjamini-Hochberg in the metabolic syndrome subjects. KEGG pathway analysis revealed significant enrichment for pathways including ribosome, oxidative phosphorylation and MAPK signaling (all Benjamini-Hochberg P<0.05). Whole blood mRNA expression changes observed in the microarray data were confirmed by quantitative RT-PCR. Transcription factor binding motif enrichment analysis revealed E2F1, ELK1, NF-kappaB, STAT1 and STAT3 significantly enriched after Bonferroni correction (all P<0.05). The results of the present study demonstrate that whole blood is a useful tissue for studying the metabolic syndrome and its underlying insulin resistance although the relationship between blood and skeletal muscle differs.

Background: Although the effect of the fat mass and obesity-associated (FTO) gene on adiposity is well established, there is a lack of evidence whether physical activity (PA) modifies the effect of FTO variants on obesity in Latino populations. Therefore, the purpose of this study was to examine PA influences and interactive effects between FTO variants and PA on measures of adiposity in Latinos.

Results: After controlling for age and sex, participants who did not engage in regular PA exhibited higher BMI, fat mass, HC, and WC with statistical significance (P < 0.001). Although significant associations between the three FTO genotypes and adiposity measures were found, none of the FTO genotype by PA interaction assessments revealed nominally significant associations. However, several of such interactive influences exhibited considerable trend towards association.

Conclusions: These data suggest that adiposity measures are associated with PA and FTO variants in Latinos, but the impact of their interactive influences on these obesity measures appear to be minimal. Future studies with large sample sizes may help to determine whether individuals with specific FTO variants exhibit differential responses to PA interventions.

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.

Introduction: Decreased insulin sensitivity blunts the normal increase in gene expression from skeletal muscle after exercise. In addition, chronic inflammation decreases insulin sensitivity. Chronic kidney disease (CKD) is an inflammatory state. How CKD and, subsequently, kidney transplantation affects skeletal muscle gene expression after exercise are unknown.

Methods: Study cohort: non-diabetic male/female 4/1, age 52±2 years, with end-stage CKD who underwent successful kidney transplantation. The following were measured both pre-transplant and post-transplant and compared to normals: Inflammatory markers, euglycemic insulin clamp studies determine insulin sensitivity, and skeletal muscle biopsies performed before and within 30 minutes after an acute exercise protocol. Microarray analyses were performed on the skeletal muscle using the 4x44K Whole Human Genome Microarrays. Since nuclear factor of activated T cells (NFAT) plays an important role in T cell activation and calcineurin inhibitors are mainstay immunosuppression, calcineurin/NFAT pathway gene expression was compared at rest and after exercise. Log transformation was performed to prevent skewing of data and regression analyses comparing measures pre- and post-transplant performed.

Result: Markers of inflammation significantly improved post-transplantation. Insulin infusion raised glucose disposal slightly lower post-transplant compared to pre-transplant, but not significantly, thus concluding differences in insulin sensitivity were similar. The overall pattern of gene expression in response to exercise was reduced both pre-and post-transplant compared to healthy volunteers. Although significant changes were observed among NFAT/Calcineurin gene at rest and after exercise in normal cohort, there were no significant differences comparing NFAT/calcineurin pathway gene expression pre- and post-transplant.

Conclusions: Despite an improvement in serum inflammatory markers, no significant differences in glucose disposal were observed post-transplant. The reduced skeletal muscle gene expression, including NFAT/calcineurin gene expression, in response to a single bout of exercise was not improved post-transplant. This study suggests that the improvements in inflammatory mediators post-transplant are unrelated to changes of NFAT/calcineurin gene expression.

International trade networks are manifestations of a complex combination of diverse underlying factors, both natural and social. Here we apply social network analytics to the international trade network of agricultural products to better understand the nature of this network and its relation to patterns of international development. Using a network tool known as triadic analysis we develop triad significance profiles for a series of agricultural commodities traded among countries. Results reveal a novel network “superfamily” combining properties of biological information processing networks and human social networks. To better understand this unique network signature, we examine in more detail the degree and triadic distributions within the trade network by country and commodity. Our results show that countries fall into two very distinct classes based on their triadic frequencies. Roughly 165 countries fall into one class while 18, all highly isolated with respect to international agricultural trade, fall into the other. Only Vietnam stands out as a unique case. Finally, we show that as a country becomes less isolated with respect to number of trading partners, the country's triadic signature follows a predictable trajectory that may correspond to a trajectory of development.

Governing common pool resources (CPR) in the face of disturbances such as globalization and climate change is challenging. The outcome of any CPR governance regime is the influenced by local combinations of social, institutional, and biophysical factors, as well as cross-scale interdependencies. In this study, we take a step towards understanding multiple-causation of CPR outcomes by analyzing 1) the co-occurrence of Design Principles (DP) by activity (irrigation, fishery and forestry), and 2) the combination(s) of DPs leading to social and ecological success. We analyzed 69 cases pertaining to three different activities: irrigation, fishery, and forestry. We find that the importance of the design principles is dependent upon the natural and hard human made infrastructure (i.e. canals, equipment, vessels etc.). For example, clearly defined social boundaries are important when the natural infrastructure is highly mobile (i.e. tuna fish), while monitoring is more important when the natural infrastructure is more static (i.e. forests or water contained within an irrigation system). However, we also find that congruence between local conditions and rules and proportionality between investment and extraction are key for CPR success independent from the natural and human hard made infrastructure. We further provide new visualization techniques for co-occurrence patterns and add to qualitative comparative analysis by introducing a reliability metric to deal with a large meta-analysis dataset on secondary data where information is missing or uncertain.

Includes supplemental materials and appendices publications in International Journal of the Commons 2016 Special Issue. Volume 10 - Issue 2 - 2016

Cities around the world are facing an ever-increasing variety of challenges that seem to make more sustainable urban futures elusive. Many of these challenges are being driven by, and exacerbated by, increases in urban populations and climate change. Novel solutions are needed today if our cities are to have any hope of more sustainable and resilient futures. Because most of the environmental impacts of any project are manifest at the point of design, we posit that this is where a real difference in urban development can be made. To this end, we present a transformative model that merges urban design and ecology into an inclusive, creative, knowledge-to-action process. This design-ecology nexus—an ecology for cities—will redefine both the process and its products. In this paper we: (1) summarize the relationships among design, infrastructure, and urban development, emphasizing the importance of joining the three to achieve urban climate resilience and enhance sustainability; (2) discuss how urban ecology can move from an ecology of cities to an ecology for cities based on a knowledge-to-action agenda; (3) detail our model for a transformational urban design-ecology nexus, and; (4) demonstrate the efficacy of our model with several case studies.

The purpose of applying social-ecological resilience thinking to food systems is twofold: First, to define those factors that help achieve a state in which food security for all and at all scales is possible. Second, to provide insights into how to maintain the system in this desirable regime. However, the resilience of food systems is distinct from the broader conceptualizations of resilience in social-ecological systems because of the fundamentally normative nature of food systems: humans need food to survive, and thus system stability is typically a primary policy objective for food system management. With that being said, society also needs food systems that can intensify sustainably i.e., feed everybody equitably, provide livelihoods and avoid environmental degradation while responding flexibly to shocks and uncertainty. Today’s failure in meeting food security objectives can be interpreted as the lack of current governance arrangements to consider the full and differential dimensions of food system functions – economic, ecological and social – at appropriate scales: in other words, the multifunctionality of food.

We focus on functional and response diversity as two key attributes of resilient, multifunctional food systems; respectively, the number of different functional groups and the diversity of types of responses to disturbances within a functional group. Achieving food security will require functional redundancy and enhanced response diversity, creating multiple avenues to fulfill all food system objectives. We use the 2013-15 drought in California to unpack the potential differences between managing for a single function – economic profit – and multiple functions. Our analysis emphasizes how the evolution of the Californian food system has reduced functional and response diversity and created vulnerabilities. Managing for the resilience of food systems will require a shift in priorities from profit maximization to the management for all functions that create full food security at multiple scales.

This article identifies equity outcomes associated with three biofuel systems in Brazil, Ethiopia and Guatemala. Acknowledging that winners and losers are socially and politically generated, the article identifies some of the factors behind the distribution of winners and losers along different stages of three sugarcane-ethanol supply chains. Analysing the outcomes for equity within each case study reveals an uneven distribution that we argue is related to the procedure and structure of the given sugarcane-ethanol system, and the recognition of the impacts on different actors within those structures. Increasing equity in sugarcane-ethanol systems will require greater openness in decision making processes, in order that multiple voices are taken into account in the promotion, production and consumption of biofuels – particularly those of smaller and less powerful actors.

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.