ASU Scholarship Showcase

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.

Recently fabricated two-dimensional phosphorene crystal structures have demonstrated great potential in applications of electronics. In this paper, strain effect on the electronic band structure of phosphorene was studied using first-principles methods including density functional theory (DFT) and hybrid functionals. It was found that phosphorene can withstand a tensile stress and strain up to 10 N/m and 30%, respectively. The band gap of phosphorene experiences a direct-indirect-direct transition when axial strain is applied. A moderate −2% compression in the zigzag direction can trigger this gap transition. With sufficient expansion (+11.3%) or compression (−10.2% strains), the gap can be tuned from indirect to direct again. Five strain zones with distinct electronic band structure were identified, and the critical strains for the zone boundaries were determined. Although the DFT method is known to underestimate band gap of semiconductors, it was proven to correctly predict the strain effect on the electronic properties with validation from a hybrid functional method in this work. The origin of the gap transition was revealed, and a general mechanism was developed to explain energy shifts with strain according to the bond nature of near-band-edge electronic orbitals. Effective masses of carriers in the armchair direction are an order of magnitude smaller than that of the zigzag axis, indicating that the armchair direction is favored for carrier transport. In addition, the effective masses can be dramatically tuned by strain, in which its sharp jump/drop occurs at the zone boundaries of the direct-indirect gap transition.

Vision and Change in Undergraduate Biology Education outlined five core concepts intended to guide undergraduate biology education: 1) evolution; 2) structure and function; 3) information flow, exchange, and storage; 4) pathways and transformations of energy and matter; and 5) systems. We have taken these general recommendations and created a Vision and Change BioCore Guide—a set of general principles and specific statements that expand upon the core concepts, creating a framework that biology departments can use to align with the goals of Vision and Change. We used a grassroots approach to generate the BioCore Guide, beginning with faculty ideas as the basis for an iterative process that incorporated feedback from more than 240 biologists and biology educators at a diverse range of academic institutions throughout the United States. The final validation step in this process demonstrated strong national consensus, with more than 90% of respondents agreeing with the importance and scientific accuracy of the statements. It is our hope that the BioCore Guide will serve as an agent of change for biology departments as we move toward transforming undergraduate biology education.

The role of ambiguity tolerance in career decision making was examined in a sample of college students (n = 275). Three hypotheses were proposed regarding the direct prediction of ambiguity tolerance on career indecision, the indirect prediction of ambiguity tolerance on career indecision through environmental and self explorations, and the moderation effect of ambiguity tolerance on the link of environmental and self explorations with career indecision. Results supported the significance of ambiguity tolerance with respect to career indecision, finding that it directly predicted general indecisiveness, dysfunctional beliefs, lack of information, and inconsistent information, and moderated the prediction of environmental exploration on inconsistent information. The implications of this study are discussed and suggestions for future research are provided.

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene output at the post-transcriptional level by targeting degenerate elements primarily in 3′untranslated regions (3′UTRs) of mRNAs. Individual miRNAs can regulate networks of hundreds of genes, yet for the majority of miRNAs few, if any, targets are known. Misexpression of miRNAs is also a major contributor to cancer progression, thus there is a critical need to validate miRNA targets in high-throughput to understand miRNAs' contribution to tumorigenesis. Here we introduce a novel high-throughput assay to detect miRNA targets in 3′UTRs, called Luminescent Identification of Functional Elements in 3′UTRs (3′LIFE). We demonstrate the feasibility of 3′LIFE using a data set of 275 human 3′UTRs and two cancer-relevant miRNAs, let-7c and miR-10b, and compare our results to alternative methods to detect miRNA targets throughout the genome. We identify a large number of novel gene targets for these miRNAs, with only 32% of hits being bioinformatically predicted and 27% directed by non-canonical interactions. Functional analysis of target genes reveals consistent roles for each miRNA as either a tumor suppressor (let-7c) or oncogenic miRNA (miR-10b), and preferentially target multiple genes within regulatory networks, suggesting 3′LIFE is a rapid and sensitive method to detect miRNA targets in high-throughput.

The U.S. scientific research community does not reflect America's diversity. Hispanics, African Americans, and Native Americans made up 31% of the general population in 2010, but they represented only 18 and 7% of science, technology, engineering, and mathematics (STEM) bachelor's and doctoral degrees, respectively, and 6% of STEM faculty members (National Science Foundation [NSF], 2013). Equity in the scientific research community is important for a variety of reasons; a diverse community of researchers can minimize the negative influence of bias in scientific reasoning, because people from different backgrounds approach a problem from different perspectives and can raise awareness regarding biases (Intemann, 2009). Additionally, by failing to be attentive to equity, we may exclude some of the best and brightest scientific minds and limit the pool of possible scientists (Intemann, 2009). Given this need for equity, how can our scientific research community become more inclusive?

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.

Women who start college in one of the natural or physical sciences leave in greater proportions than their male peers. The reasons for this difference are complex, and one possible contributing factor is the social environment women experience in the classroom. Using social network analysis, we explore how gender influences the confidence that college-level biology students have in each other’s mastery of biology. Results reveal that males are more likely than females to be named by peers as being knowledgeable about the course content. This effect increases as the term progresses, and persists even after controlling for class performance and outspokenness. The bias in nominations is specifically due to males over-nominating their male peers relative to their performance. The over-nomination of male peers is commensurate with an overestimation of male grades by 0.57 points on a 4 point grade scale, indicating a strong male bias among males when assessing their classmates. Females, in contrast, nominated equitably based on student performance rather than gender, suggesting they lacked gender biases in filling out these surveys. These trends persist across eleven surveys taken in three different iterations of the same Biology course. In every class, the most renowned students are always male. This favoring of males by peers could influence student self-confidence, and thus persistence in this STEM discipline.

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.

Background: Lizards are evolutionarily the most closely related vertebrates to humans that can lose and regrow an entire appendage. Regeneration in lizards involves differential expression of hundreds of genes that regulate wound healing, musculoskeletal development, hormonal response, and embryonic morphogenesis. While microRNAs are able to regulate large groups of genes, their role in lizard regeneration has not been investigated.

Results: MicroRNA sequencing of green anole lizard (Anolis carolinensis) regenerating tail and associated tissues revealed 350 putative novel and 196 known microRNA precursors. Eleven microRNAs were differentially expressed between the regenerating tail tip and base during maximum outgrowth (25 days post autotomy), including miR-133a, miR-133b, and miR-206, which have been reported to regulate regeneration and stem cell proliferation in other model systems. Three putative novel differentially expressed microRNAs were identified in the regenerating tail tip.

Conclusions: Differentially expressed microRNAs were identified in the regenerating lizard tail, including known regulators of stem cell proliferation. The identification of 3 putative novel microRNAs suggests that regulatory networks, either conserved in vertebrates and previously uncharacterized or specific to lizards, are involved in regeneration. These findings suggest that differential regulation of microRNAs may play a role in coordinating the timing and expression of hundreds of genes involved in regeneration.