ASU Scholarship Showcase

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.

Introduction: Apolipoprotein C-III (apoC-III) regulates triglyceride (TG) metabolism. In plasma, apoC-III exists in non-sialylated (apoC-III_0a without glycosylation and apoC-III[subscript 0b] with glycosylation), monosialylated (apoC-III₁) or disialylated (apoC-III₂) proteoforms. Our aim was to clarify the relationship between apoC-III sialylation proteoforms with fasting plasma TG concentrations.

Methods: In 204 non-diabetic adolescent participants, the relative abundance of apoC-III plasma proteoforms was measured using mass spectrometric immunoassay.

Results: Compared with the healthy weight subgroup (n = 16), the ratios of apoC-III_0a, apoC-III_0b, and apoC-III₁ to apoC-III₂ were significantly greater in overweight (n = 33) and obese participants (n = 155). These ratios were positively correlated with BMI z-scores and negatively correlated with measures of insulin sensitivity (S[subscript i]). The relationship of apoC-III₁ / apoC-III₂ with S_i persisted after adjusting for BMI (p = 0.02). Fasting TG was correlated with the ratio of apoC-III_0a / apoC-III₂ (r = 0.47, p<0.001), apoC-III_0b / apoC-III₂ (r = 0.41, p<0.001), apoC-III₁ / apoC-III₂ (r = 0.43, p<0.001). By examining apoC-III concentrations, the association of apoC-III proteoforms with TG was driven by apoC-III_0a (r = 0.57, p<0.001), apoC-III_0b (r = 0.56. p<0.001) and apoC-III₁ (r = 0.67, p<0.001), but not apoC-III₂ (r = 0.006, p = 0.9) concentrations, indicating that apoC-III relationship with plasma TG differed in apoC-III₂ compared with the other proteoforms.

Conclusion: We conclude that apoC-III_0a, apoC-III_0b, and apoC-III₁, but not apoC-III₂ appear to be under metabolic control and associate with fasting plasma TG. Measurement of apoC-III proteoforms can offer insights into the biology of TG metabolism in obesity.

Proteins can exist as multiple proteoforms in vivo, as a result of alternative splicing and single-nucleotide polymorphisms (SNPs), as well as posttranslational processing. To address their clinical significance in a context of diagnostic information, proteoforms require a more in-depth analysis. Mass spectrometric immunoassays (MSIA) have been devised for studying structural diversity in human proteins. MSIA enables protein profiling in a simple and high-throughput manner, by combining the selectivity of targeted immunoassays, with the specificity of mass spectrometric detection. MSIA has been used for qualitative and quantitative analysis of single and multiple proteoforms, distinguishing between normal fluctuations and changes related to clinical conditions. This mini review offers an overview of the development and application of mass spectrometric immunoassays for clinical and population proteomics studies. Provided are examples of some recent developments, and also discussed are the trends and challenges in mass spectrometry-based immunoassays for the next-phase of clinical applications.

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.

Extensive evidence has shown that long-range charge transport can occur along double helical DNA, but active control (switching) of single-DNA conductance with an external field has not yet been demonstrated. Here we demonstrate conductance switching in DNA by replacing a DNA base with a redox group. By applying an electrochemical (EC) gate voltage to the molecule, we switch the redox group between the oxidized and reduced states, leading to reversible switching of the DNA conductance between two discrete levels. We further show that monitoring the individual conductance switching allows the study of redox reaction kinetics and thermodynamics at single molecular level using DNA as a probe. Our theoretical calculations suggest that the switch is due to the change in the energy level alignment of the redox states relative to the Fermi level of the electrodes.

Human protein diversity arises as a result of alternative splicing, single nucleotide polymorphisms (SNPs) and posttranslational modifications. Because of these processes, each protein can exists as multiple variants in vivo. Tailored strategies are needed to study these protein variants and understand their role in health and disease. In this work we utilized quantitative mass spectrometric immunoassays to determine the protein variants concentration of beta-2-microglobulin, cystatin C, retinol binding protein, and transthyretin, in a population of 500 healthy individuals. Additionally, we determined the longitudinal concentration changes for the protein variants from four individuals over a 6 month period. Along with the native forms of the four proteins, 13 posttranslationally modified variants and 7 SNP-derived variants were detected and their concentration determined. Correlations of the variants concentration with geographical origin, gender, and age of the individuals were also examined. This work represents an important step toward building a catalog of protein variants concentrations and examining their longitudinal changes.