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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

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.

ContributorsTangen, Samantha (Author) / Tsinajinnie, Darwin (Author) / Nunez, Martha (Author) / Shaibi, Gabriel (Author) / Mandarino, Lawrence (Author) / Coletta, Dawn (Author) / College of Liberal Arts and Sciences (Contributor)
Created2013-12-17
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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

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.

ContributorsKim, Joon Young (Author) / DeMenna, Jacob (Author) / Puppala, Sobha (Author) / Chittoor, Geetha (Author) / Schneider, Jennifer (Author) / Duggirala, Ravindranath (Author) / Mandarino, Lawrence (Author) / Shaibi, Gabriel (Author) / Coletta, Dawn (Author) / College of Health Solutions (Contributor)
Created2016-02-24
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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

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.

ContributorsDay, Samantha (Author) / Coletta, Rich (Author) / Kim, Joon Young (Author) / Campbell, Latoya (Author) / Benjamin, Tonya R. (Author) / Roust, Lori R. (Author) / De Filippis, Elena A. (Author) / Dinu, Valentin (Author) / Shaibi, Gabriel (Author) / Mandarino, Lawrence J. (Author) / Coletta, Dawn (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-07-18
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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

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.

ContributorsColetta, Dawn (Author) / Campbell, Latoya (Author) / Well, Jennifer (Author) / Kaplan, Bruce (Author) / Clarkson, Marie (Author) / Finlayson, Jean (Author) / Mandarino, Lawrence (Author) / Chakkera, Harini A. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-08-12
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In 2013, the community of mathematical scientists and educators focused its collective attention on the mathematics of planet Earth. In the course of the year, a grassroots organization grew into an international partnership of more than 150 scientific societies, universities, research institutes, and organizations. The project, known as “Mathematics of

In 2013, the community of mathematical scientists and educators focused its collective attention on the mathematics of planet Earth. In the course of the year, a grassroots organization grew into an international partnership of more than 150 scientific societies, universities, research institutes, and organizations. The project, known as “Mathematics of Planet Earth 2013” (MPE2013), received the patronage of UNESCO and was a truly unique event. It brought the challenges facing our planet to the attention of the mathematics research community in numerous lectures, seminars, workshops, and special sessions at conferences of the professional societies; it sponsored the development of curriculum materials for all educational levels; it organized many outreach activities, including an international juried exhibit of virtual and physical displays for use in museums and schools; and it presented a series of public lectures by renowned scientists showing the public how mathematics contributes to our understanding of planet Earth, the nature of the challenges our planet is facing, and how mathematicians contribute to their solution. At the end of the year, MPE2013 morphed into “Mathematics of Planet Earth” (MPE).

ContributorsAnderies, John (Author) / Kaper, Hans G. (Author) / Shuckburgh, Emily F. (Author) / Zagaris, Antonios (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-03-01
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Urban environmental measurements and observational statistics should reflect the properties generated over an adjacent area of adequate length where homogeneity is usually assumed. The determination of this characteristic source area that gives sufficient representation of the horizontal coverage of a sensing instrument or the fetch of transported quantities is of

Urban environmental measurements and observational statistics should reflect the properties generated over an adjacent area of adequate length where homogeneity is usually assumed. The determination of this characteristic source area that gives sufficient representation of the horizontal coverage of a sensing instrument or the fetch of transported quantities is of critical importance to guide the design and implementation of urban landscape planning strategies. In this study, we aim to unify two different methods for estimating source areas, viz. the statistical correlation method commonly used by geographers for landscape fragmentation and the mechanistic footprint model by meteorologists for atmospheric measurements. Good agreement was found in the intercomparison of the estimate of source areas by the two methods, based on 2-m air temperature measurement collected using a network of weather stations. The results can be extended to shed new lights on urban planning strategies, such as the use of urban vegetation for heat mitigation. In general, a sizable patch of landscape is required in order to play an effective role in regulating the local environment, proportional to the height at which stakeholders’ interest is mainly concerned.

ContributorsWang, Zhi-Hua (Author) / Fan, Chao (Author) / Myint, Soe (Author) / Wang, Chenghao (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-11-10
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Climate change and its interactions with complex socioeconomic dynamics dictate the need for decision makers to move from incremental adaptation toward transformation as societies try to cope with unprecedented and uncertain change. Developing pathways toward transformation is especially difficult in regions with multiple contested resource uses and rights, with diverse

Climate change and its interactions with complex socioeconomic dynamics dictate the need for decision makers to move from incremental adaptation toward transformation as societies try to cope with unprecedented and uncertain change. Developing pathways toward transformation is especially difficult in regions with multiple contested resource uses and rights, with diverse decision makers and rules, and where high uncertainty is generated by differences in stakeholders’ values, understanding of climate change, and ways of adapting. Such a region is the Murray-Darling Basin, Australia, from which we provide insights for developing a process to address these constraints. We present criteria for sequencing actions along adaptation pathways: feasibility of the action within the current decision context, its facilitation of other actions, its role in averting exceedance of a critical threshold, its robustness and resilience under diverse and unexpected shocks, its effect on future options, its lead time, and its effects on equity and social cohesion. These criteria could potentially enable development of multiple stakeholder-specific adaptation pathways through a regional collective action process. The actual implementation of these multiple adaptation pathways will be highly uncertain and politically difficult because of fixity of resource-use rights, unequal distribution of power, value conflicts, and the likely redistribution of benefits and costs. We propose that the approach we outline for building resilient pathways to transformation is a flexible and credible way of negotiating these challenges.

ContributorsAbel, Nick (Author) / Wise, Russell M. (Author) / Colloff, Matthew J. (Author) / Walker, Brian H. (Author) / Butler, James R. A. (Author) / Ryan, Paul (Author) / Norman, Chris (Author) / Langston, Art (Author) / Anderies, John (Author) / Gorddard, Russell (Author) / Dunlop, Michael (Author) / O'Connell, Deborah (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016
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Globalization, the process by which local social-ecological systems (SESs) are becoming linked in a global network, presents policy scientists and practitioners with unique and difficult challenges. Although local SESs can be extremely complex, when they become more tightly linked in the global system, complexity increases very rapidly as multi-scale and

Globalization, the process by which local social-ecological systems (SESs) are becoming linked in a global network, presents policy scientists and practitioners with unique and difficult challenges. Although local SESs can be extremely complex, when they become more tightly linked in the global system, complexity increases very rapidly as multi-scale and multi-level processes become more important. Here, we argue that addressing these multi-scale and multi-level challenges requires a collection of theories and models. We suggest that the conceptual domains of sustainability, resilience, and robustness provide a sufficiently rich collection of theories and models, but overlapping definitions and confusion about how these conceptual domains articulate with one another reduces their utility. We attempt to eliminate this confusion and illustrate how sustainability, resilience, and robustness can be used in tandem to address the multi-scale and multi-level challenges associated with global change.

ContributorsAnderies, John (Author) / Folke, Carl (Author) / Walker, Brian (Author) / Ostrom, Elinor (Author) / College of Liberal Arts and Sciences (Contributor)
Created2013
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The net storage heat flux (ΔQ[subscript S]) is important in the urban surface energy balance (SEB) but its determination remains a significant challenge. The hysteresis pattern of the diurnal relation between the ΔQ[subscript S] and net all-wave radiation (Q[superscript ∗]) has been captured in the Objective Hysteresis Model (OHM) parameterization

The net storage heat flux (ΔQ[subscript S]) is important in the urban surface energy balance (SEB) but its determination remains a significant challenge. The hysteresis pattern of the diurnal relation between the ΔQ[subscript S] and net all-wave radiation (Q[superscript ∗]) has been captured in the Objective Hysteresis Model (OHM) parameterization of ΔQ[subscript S]. Although successfully used in urban areas, the limited availability of coefficients for OHM hampers its application. To facilitate use, and enhance physical interpretations of the OHM coefficients, an analytical solution of the one-dimensional advection–diffusion equation of coupled heat and liquid water transport in conjunction with the SEB is conducted, allowing development of AnOHM (Analytical Objective Hysteresis Model). A sensitivity test of AnOHM to surface properties and hydrometeorological forcing is presented using a stochastic approach (subset simulation). The sensitivity test suggests that the albedo, Bowen ratio and bulk transfer coefficient, solar radiation and wind speed are most critical. AnOHM, driven by local meteorological conditions at five sites with different land use, is shown to simulate the ΔQ[subscript S] flux well (RMSE values of ∼ 30 W m[superscript −2]). The intra-annual dynamics of OHM coefficients are explored. AnOHM offers significant potential to enhance modelling of the surface energy balance over a wider range of conditions and land covers.

ContributorsSun, Ting (Author) / Wang, Zhi-Hua (Author) / Oechel, Walter C. (Author) / Grimmond, Sue (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2017-07-27
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Social roles are thought to play an important role in determining the capacity for collective action in a community regarding the use of shared resources. Here we report on the results of a study using a behavioral experimental approach regarding the relationship between social roles and the performance of social-ecological

Social roles are thought to play an important role in determining the capacity for collective action in a community regarding the use of shared resources. Here we report on the results of a study using a behavioral experimental approach regarding the relationship between social roles and the performance of social-ecological systems. The computer-based irrigation experiment that was the basis of this study mimics the decisions faced by farmers in small-scale irrigation systems. In each of 20 rounds, which are analogous to growing seasons, participants face a two-stage commons dilemma. First they must decide how much to invest in the public infrastructure, e.g., canals and water diversion structures. Second, they must decide how much to extract from the water made available by that public infrastructure. Each round begins with a 60-second communication period before the players make their investment and extraction decisions. By analyzing the chat messages exchanged among participants during the communication stage of the experiment, we coded up to three roles per participant using the scheme of seven roles known to be important in the literature: leader, knowledge generator, connector, follower, moralist, enforcer, and observer. Our study supports the importance of certain social roles (e.g., connector) previously highlighted by several case study analyses. However, using qualitative comparative analysis we found that none of the individual roles was sufficient for groups to succeed, i.e., to reach a certain level of group production. Instead, we found that a combination of at least five roles was necessary for success. In addition, in the context of upstream-downstream asymmetry, we observed a pattern in which social roles assumed by participants tended to differ by their positions. Although our work generated some interesting insights, further research is needed to determine how robust our findings are to different action situations, such as biophysical context, social network, and resource uncertainty.

ContributorsPerez, Irene (Author) / Yu, David (Author) / Janssen, Marco (Author) / Anderies, John (Author) / ASU-SFI Center for Biosocial Complex Systems (Contributor)
Created2015