ASU Scholarship Showcase

Does school participatory budgeting (SPB) increase students’ political efficacy? SPB, which is implemented in thousands of schools around the world, is a democratic process of deliberation and decision-making in which students determine how to spend a portion of the school’s budget. We examined the impact of SPB on political efficacy in one middle school in Arizona. Our participants’ (n = 28) responses on survey items designed to measure self-perceived growth in political efficacy indicated a large effect size (Cohen’s d = 1.46), suggesting that SPB is an effective approach to civic pedagogy, with promising prospects for developing students’ political efficacy.

Plasmodium vivax is the most prevalent malarial species in South America and exerts a substantial burden on the populations it affects. The control and eventual elimination of P. vivax are global health priorities. Genomic research contributes to this objective by improving our understanding of the biology of P. vivax and through the development of new genetic markers that can be used to monitor efforts to reduce malaria transmission. Here we analyze whole-genome data from eight field samples from a region in Cordóba, Colombia where malaria is endemic. We find considerable genetic diversity within this population, a result that contrasts with earlier studies suggesting that P. vivax had limited diversity in the Americas. We also identify a selective sweep around a substitution known to confer resistance to sulphadoxine-pyrimethamine (SP). This is the first observation of a selective sweep for SP resistance in this species. These results indicate that P. vivax has been exposed to SP pressure even when the drug is not in use as a first line treatment for patients afflicted by this parasite. We identify multiple non-synonymous substitutions in three other genes known to be involved with drug resistance in Plasmodium species. Finally, we found extensive microsatellite polymorphisms. Using this information we developed 18 polymorphic and easy to score microsatellite loci that can be used in epidemiological investigations in South America.

Inbreeding in hermaphroditic plants can occur through two different mechanisms: biparental inbreeding, when a plant mates with a related individual, or self-fertilization, when a plant mates with itself. To avoid inbreeding, many hermaphroditic plants have evolved self-incompatibility (SI) systems which prevent or limit self-fertilization. One particular SI system—homomorphic SI—can also reduce biparental inbreeding. Homomorphic SI is found in many angiosperm species, and it is often assumed that the additional benefit of reduced biparental inbreeding may be a factor in the success of this SI system. To test this assumption, we developed a spatially-explicit, individual-based simulation of plant populations that displayed three different types of homomorphic SI. We measured the total level of inbreeding avoidance by comparing each population to a self-compatible population (NSI), and we measured biparental inbreeding avoidance by comparing to a population of self-incompatible plants that were free to mate with any other individual (PSI).

Because biparental inbreeding is more common when offspring dispersal is limited, we examined the levels of biparental inbreeding over a range of dispersal distances. We also tested whether the introduction of inbreeding depression affected the level of biparental inbreeding avoidance. We found that there was a statistically significant decrease in autozygosity in each of the homomorphic SI populations compared to the PSI population and, as expected, this was more pronounced when seed and pollen dispersal was limited. However, levels of homozygosity and inbreeding depression were not reduced. At low dispersal, homomorphic SI populations also suffered reduced female fecundity and had smaller census population sizes. Overall, our simulations showed that the homomorphic SI systems had little impact on the amount of biparental inbreeding in the population especially when compared to the overall reduction in inbreeding compared to the NSI population. With further study, this observation may have important consequences for research into the origin and evolution of homomorphic self-incompatibility systems.

Under models of isolation-by-distance, population structure is determined by the probability of identity-by-descent between pairs of genes according to the geographic distance between them. Well established analytical results indicate that the relationship between geographical and genetic distance depends mostly on the neighborhood size of the population which represents a standardized measure of gene flow. To test this prediction, we model local dispersal of haploid individuals on a two-dimensional landscape using seven dispersal kernels: Rayleigh, exponential, half-normal, triangular, gamma, Lomax and Pareto. When neighborhood size is held constant, the distributions produce similar patterns of isolation-by-distance, confirming predictions. Considering this, we propose that the triangular distribution is the appropriate null distribution for isolation-by-distance studies. Under the triangular distribution, dispersal is uniform over the neighborhood area which suggests that the common description of neighborhood size as a measure of an effective, local panmictic population is valid for popular families of dispersal distributions. We further show how to draw random variables from the triangular distribution efficiently and argue that it should be utilized in other studies in which computational efficiency is important.

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.

In this study, we present a novel methodology to infer indel parameters from multiple sequence alignments (MSAs) based on simulations. Our algorithm searches for the set of evolutionary parameters describing indel dynamics which best fits a given input MSA. In each step of the search, we use parametric bootstraps and the Mahalanobis distance to estimate how well a proposed set of parameters fits input data. Using simulations, we demonstrate that our methodology can accurately infer the indel parameters for a large variety of plausible settings. Moreover, using our methodology, we show that indel parameters substantially vary between three genomic data sets: Mammals, bacteria, and retroviruses. Finally, we demonstrate how our methodology can be used to simulate MSAs based on indel parameters inferred from real data sets.

Mathematical models of infectious diseases are a valuable tool in understanding the mechanisms and patterns of disease transmission. It is, however, a difficult subject to teach, requiring both mathematical expertise and extensive subject-matter knowledge of a variety of disease systems. In this article, we explore several uses of zombie epidemics to make mathematical modeling and infectious disease epidemiology more accessible to public health professionals, students, and the general public. We further introduce a web-based simulation, White Zed (http://cartwrig.ht/apps/whitezed/), that can be deployed in classrooms to allow students to explore models before implementing them. In our experience, zombie epidemics are familiar, approachable, flexible, and an ideal way to introduce basic concepts of infectious disease epidemiology.

Insulin-like growth factor 1 (IGF1) is an important biomarker for the management of growth hormone disorders. Recently there has been rising interest in deploying mass spectrometric (MS) methods of detection for measuring IGF1. However, widespread clinical adoption of any MS-based IGF1 assay will require increased throughput and speed to justify the costs of analyses, and robust industrial platforms that are reproducible across laboratories. Presented here is an MS-based quantitative IGF1 assay with performance rating of >1,000 samples/day, and a capability of quantifying IGF1 point mutations and posttranslational modifications. The throughput of the IGF1 mass spectrometric immunoassay (MSIA) benefited from a simplified sample preparation step, IGF1 immunocapture in a tip format, and high-throughput MALDI-TOF MS analysis. The Limit of Detection and Limit of Quantification of the resulting assay were 1.5 μg/L and 5 μg/L, respectively, with intra- and inter-assay precision CVs of less than 10%, and good linearity and recovery characteristics. The IGF1 MSIA was benchmarked against commercially available IGF1 ELISA via Bland-Altman method comparison test, resulting in a slight positive bias of 16%. The IGF1 MSIA was employed in an optimized parallel workflow utilizing two pipetting robots and MALDI-TOF-MS instruments synced into one-hour phases of sample preparation, extraction and MSIA pipette tip elution, MS data collection, and data processing. Using this workflow, high-throughput IGF1 quantification of 1,054 human samples was achieved in approximately 9 hours. This rate of assaying is a significant improvement over existing MS-based IGF1 assays, and is on par with that of the enzyme-based immunoassays. Furthermore, a mutation was detected in ∼1% of the samples (SNP: rs17884626, creating an A→T substitution at position 67 of the IGF1), demonstrating the capability of IGF1 MSIA to detect point mutations and posttranslational modifications.

Serum Amyloid A (SAA) is an acute phase protein complex consisting of several abundant isoforms. The N- terminus of SAA is critical to its function in amyloid formation. SAA is frequently truncated, either missing an arginine or an arginine-serine dipeptide, resulting in isoforms that may influence the capacity to form amyloid. However, the relative abundance of truncated SAA in diabetes and chronic kidney disease is not known.

Methods: Using mass spectrometric immunoassay, the abundance of SAA truncations relative to the native variants was examined in plasma of 91 participants with type 2 diabetes and chronic kidney disease and 69 participants without diabetes.

Results: The ratio of SAA 1.1 (missing N-terminal arginine) to native SAA 1.1 was lower in diabetics compared to non-diabetics (p = 0.004), and in males compared to females (p<0.001). This ratio was negatively correlated with glycated hemoglobin (r = −0.32, p<0.001) and triglyceride concentrations (r = −0.37, p<0.001), and positively correlated with HDL cholesterol concentrations (r = 0.32, p<0.001).

Conclusion: The relative abundance of the N-terminal arginine truncation of SAA1.1 is significantly decreased in diabetes and negatively correlates with measures of glycemic and lipid control.

Background: Blindness has evolved repeatedly in cave-dwelling organisms, and many hypotheses have been proposed to explain this observation, including both accumulation of neutral loss-of-function mutations and adaptation to darkness. Investigating the loss of sight in cave dwellers presents an opportunity to understand the operation of fundamental evolutionary processes, including drift, selection, mutation, and migration.

Results: Here we model the evolution of blindness in caves. This model captures the interaction of three forces: (1) selection favoring alleles causing blindness, (2) immigration of sightedness alleles from a surface population, and (3) mutations creating blindness alleles. We investigated the dynamics of this model and determined selection-strength thresholds that result in blindness evolving in caves despite immigration of sightedness alleles from the surface. We estimate that the selection coefficient for blindness would need to be at least 0.005 (and maybe as high as 0.5) for blindness to evolve in the model cave-organism, Astyanax mexicanus.

Conclusions: Our results indicate that strong selection is required for the evolution of blindness in cave-dwelling organisms, which is consistent with recent work suggesting a high metabolic cost of eye development.