ASU Scholarship Showcase

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.

Background: Elucidating the role of the underlying risk factors for severe outcomes of the 2009 A/H1N1 influenza pandemic could be crucial to define priority risk groups in resource-limited settings in future pandemics.

Methods: We use individual-level clinical data on a large series of ARI (acute respiratory infection) hospitalizations from a prospective surveillance system of the Mexican Social Security medical system to analyze clinical features at presentation, admission delays, selected comorbidities and receipt of seasonal vaccine on the risk of A/H1N1-related death. We considered ARI hospitalizations and inpatient-deaths, and recorded demographic, geographic, and medical information on individual patients during August-December, 2009.

Results: Seasonal influenza vaccination was associated with a reduced risk of death among A/H1N1 inpatients (OR = 0.43 (95% CI: 0.25, 0.74)) after adjustment for age, gender, geography, antiviral treatment, admission delays, comorbidities and medical conditions. However, this result should be interpreted with caution as it could have been affected by factors not directly measured in our study. Moreover, the effect of antiviral treatment against A/H1N1 inpatient death did not reach statistical significance (OR = 0.56 (95% CI: 0.29, 1.10)) probably because only 8.9% of A/H1N1 inpatients received antiviral treatment. Moreover, diabetes (OR = 1.6) and immune suppression (OR = 2.3) were statistically significant risk factors for death whereas asthmatic persons (OR = 0.3) or pregnant women (OR = 0.4) experienced a reduced fatality rate among A/H1N1 inpatients. We also observed an increased risk of death among A/H1N1 inpatients with admission delays >2 days after symptom onset (OR = 2.7). Similar associations were also observed for A/H1N1-negative inpatients.

Conclusions: Geographical variation in identified medical risk factors including prevalence of diabetes and immune suppression may in part explain between-country differences in pandemic mortality burden. Furthermore, access to care including hospitalization without delay and antiviral treatment and are also important factors, as well as vaccination coverage with the 2008–09 trivalent inactivated influenza vaccine.

Background: Healthy individuals on the lower end of the insulin sensitivity spectrum also have a reduced gene expression response to exercise for specific genes. The goal of this study was to determine the relationship between insulin sensitivity and exercise-induced gene expression in an unbiased, global manner.

Methods and Findings: Euglycemic clamps were used to measure insulin sensitivity and muscle biopsies were done at rest and 30 minutes after a single acute exercise bout in 14 healthy participants. Changes in mRNA expression were assessed using microarrays, and miRNA analysis was performed in a subset of 6 of the participants using sequencing techniques. Following exercise, 215 mRNAs were changed at the probe level (Bonferroni-corrected P<0.00000115). Pathway and Gene Ontology analysis showed enrichment in MAP kinase signaling, transcriptional regulation and DNA binding. Changes in several transcription factor mRNAs were correlated with insulin sensitivity, including MYC, r=0.71; SNF1LK, r=0.69; and ATF3, r= 0.61 (5 corrected for false discovery rate). Enrichment in the 5’-UTRs of exercise-responsive genes suggested regulation by common transcription factors, especially EGR1. miRNA species of interest that changed after exercise included miR-378, which is located in an intron of the PPARGC1B gene.

Conclusions: These results indicate that transcription factor gene expression responses to exercise depend highly on insulin sensitivity in healthy people. The overall pattern suggests a coordinated cycle by which exercise and insulin sensitivity regulate gene expression in muscle.

Background: The impact of socio-demographic factors and baseline health on the mortality burden of seasonal and pandemic influenza remains debated. Here we analyzed the spatial-temporal mortality patterns of the 1918 influenza pandemic in Spain, one of the countries of Europe that experienced the highest mortality burden.

Methods: We analyzed monthly death rates from respiratory diseases and all-causes across 49 provinces of Spain, including the Canary and Balearic Islands, during the period January-1915 to June-1919. We estimated the influenza-related excess death rates and risk of death relative to baseline mortality by pandemic wave and province. We then explored the association between pandemic excess mortality rates and health and socio-demographic factors, which included population size and age structure, population density, infant mortality rates, baseline death rates, and urbanization.

Results: Our analysis revealed high geographic heterogeneity in pandemic mortality impact. We identified 3 pandemic waves of varying timing and intensity covering the period from Jan-1918 to Jun-1919, with the highest pandemic-related excess mortality rates occurring during the months of October-November 1918 across all Spanish provinces. Cumulative excess mortality rates followed a south–north gradient after controlling for demographic factors, with the North experiencing highest excess mortality rates. A model that included latitude, population density, and the proportion of children living in provinces explained about 40% of the geographic variability in cumulative excess death rates during 1918–19, but different factors explained mortality variation in each wave.

Conclusions: A substantial fraction of the variability in excess mortality rates across Spanish provinces remained unexplained, which suggests that other unidentified factors such as comorbidities, climate and background immunity may have affected the 1918-19 pandemic mortality rates. Further archeo-epidemiological research should concentrate on identifying settings with combined availability of local historical mortality records and information on the prevalence of underlying risk factors, or patient-level clinical data, to further clarify the drivers of 1918 pandemic influenza mortality.

Background: On 31 March 2013, the first human infections with the novel influenza A/H7N9 virus were reported in Eastern China. The outbreak expanded rapidly in geographic scope and size, with a total of 132 laboratory-confirmed cases reported by 3 June 2013, in 10 Chinese provinces and Taiwan. The incidence of A/H7N9 cases has stalled in recent weeks, presumably as a consequence of live bird market closures in the most heavily affected areas. Here we compare the transmission potential of influenza A/H7N9 with that of other emerging pathogens and evaluate the impact of intervention measures in an effort to guide pandemic preparedness.

Methods: We used a Bayesian approach combined with a SEIR (Susceptible-Exposed-Infectious-Removed) transmission model fitted to daily case data to assess the reproduction number (R) of A/H7N9 by province and to evaluate the impact of live bird market closures in April and May 2013. Simulation studies helped quantify the performance of our approach in the context of an emerging pathogen, where human-to-human transmission is limited and most cases arise from spillover events. We also used alternative approaches to estimate R based on individual-level information on prior exposure and compared the transmission potential of influenza A/H7N9 with that of other recent zoonoses.

Results: Estimates of R for the A/H7N9 outbreak were below the epidemic threshold required for sustained human-to-human transmission and remained near 0.1 throughout the study period, with broad 95% credible intervals by the Bayesian method (0.01 to 0.49). The Bayesian estimation approach was dominated by the prior distribution, however, due to relatively little information contained in the case data. We observe a statistically significant deceleration in growth rate after 6 April 2013, which is consistent with a reduction in A/H7N9 transmission associated with the preemptive closure of live bird markets. Although confidence intervals are broad, the estimated transmission potential of A/H7N9 appears lower than that of recent zoonotic threats, including avian influenza A/H5N1, swine influenza H3N2sw and Nipah virus.

Conclusion: Although uncertainty remains high in R estimates for H7N9 due to limited epidemiological information, all available evidence points to a low transmission potential. Continued monitoring of the transmission potential of A/H7N9 is critical in the coming months as intervention measures may be relaxed and seasonal factors could promote disease transmission in colder months.

A novel portable wireless volatile organic compound (VOC) monitoring device with disposable sensors is presented. The device is miniaturized, light, easy-to-use, and cost-effective. Different field tests have been carried out to identify the operational, analytical, and functional performance of the device and its sensors. The device was compared to a commercial photo-ionization detector, gas chromatography-mass spectrometry, and carbon monoxide detector. In addition, environmental operational conditions, such as barometric change, temperature change and wind conditions were also tested to evaluate the device performance. The multiple comparisons and tests indicate that the proposed VOC device is adequate to characterize personal exposure in many real-world scenarios and is applicable for personal daily use.

Quantifying the interactions of bacteria with external ligands is fundamental to the understanding of pathogenesis, antibiotic resistance, immune evasion, and mechanism of antimicrobial action. Due to inherent cell-to-cell heterogeneity in a microbial population, each bacterium interacts differently with its environment. This large variability is washed out in bulk assays, and there is a need of techniques that can quantify interactions of bacteria with ligands at the single bacterium level. In this work, we present a label-free and real-time plasmonic imaging technique to measure the binding kinetics of ligand interactions with single bacteria, and perform statistical analysis of the heterogeneity. Using the technique, we have studied interactions of antibodies with single Escherichia coli O157:H7 cells and demonstrated a capability of determining the binding kinetic constants of single live bacteria with ligands, and quantify heterogeneity in a microbial population.

The coastal environments of South Africa’s Cape Floristic Region (CFR) provide some of the earliest and most abundant evidence for the emergence of cognitively modern humans. In particular, the south coast of the CFR provided a uniquely diverse resource base for hunter-gatherers, which included marine shellfish, game, and carbohydrate-bearing plants, especially those with Underground Storage Organs (USOs). It has been hypothesized that these resources underpinned the continuity of human occupation in the region since the Middle Pleistocene. Very little research has been conducted on the foraging potential of carbohydrate resources in the CFR. This study focuses on the seasonal availability of plants with edible carbohydrates at six-weekly intervals over a two-year period in four vegetation types on South Africa’s Cape south coast. Different plant species were considered available to foragers if the edible carbohydrate was directly (i.e. above-ground edible portions) or indirectly (above-ground indications to below-ground edible portions) visible to an expert botanist familiar with this landscape. A total of 52 edible plant species were recorded across all vegetation types. Of these, 33 species were geophytes with edible USOs and 21 species had aboveground edible carbohydrates. Limestone Fynbos had the richest flora, followed by Strandveld, Renosterveld and lastly, Sand Fynbos. The availability of plant species differed across vegetation types and between survey years. The number of available USO species was highest for a six-month period from winter to early summer (Jul–Dec) across all vegetation types. Months of lowest species’ availability were in mid-summer to early autumn (Jan–Apr); the early winter (May–Jun) values were variable, being highest in Limestone Fynbos. However, even during the late summer carbohydrate “crunch,” 25 carbohydrate bearing species were visible across the four vegetation types. To establish a robust resource landscape will require additional spatial mapping of plant species abundances. Nonetheless, our results demonstrate that plant-based carbohydrate resources available to Stone Age foragers of the Cape south coast, especially USOs belonging to the Iridaceae family, are likely to have comprised a reliable and nutritious source of calories over most of the year.

Piezoresistivity is a fundamental property of materials that has found many device applications. Here we report piezoresistivity in double helical DNA molecules. By studying the dependence of molecular conductance and piezoresistivity of single DNA molecules with different sequences and lengths, and performing molecular orbital calculations, we show that the piezoresistivity of DNA is caused by force-induced changes in the π–π electronic coupling between neighbouring bases, and in the activation energy of hole hopping. We describe the results in terms of thermal activated hopping model together with the ladder-based mechanical model for DNA proposed by de Gennes.

Studying the thermoelectric effect in DNA is important for unravelling charge transport mechanisms and for developing relevant applications of DNA molecules. Here we report a study of the thermoelectric effect in single DNA molecules. By varying the molecular length and sequence, we tune the charge transport in DNA to either a hopping- or tunnelling-dominated regimes. The thermoelectric effect is small and insensitive to the molecular length in the hopping regime. In contrast, the thermoelectric effect is large and sensitive to the length in the tunnelling regime. These findings indicate that one may control the thermoelectric effect in DNA by varying its sequence and length. We describe the experimental results in terms of hopping and tunnelling charge transport models.