ASU Scholarship Showcase

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.

In Ritual and Religion in the Making of Humanity, Roy Rappaport misses an opportunity to more tightly theorize the synergistic relationship between concepts of the divine, the psyches of ritual participants, and the adaptive dynamics of religious sociality. This paper proposes such a theory by drawing on implicit features of Rappaport’s account, fulfilling his goal of a “cybernetics of the holy.” I argue that concepts of the divine, when made authoritative for participants through ritual, have three important effects: they invite intense and meaningful reconstructions of personal identity according to paradigmatic examples; they act as a form of encoded social memory by organizing human relationship according to a “spiritual map”; and they provide the cognitive framework that make religious community organization robust, adaptive, and reproductive. We can characterize divine concepts as “specified absences” that ground each of these effects and link them together in a mutually-reinforcing set.

The conscientious are morally conflicted when their moral dilemmas or incommensurabilities, real or apparent, have not been resolved. But such doublemindedness need not lead to ethical disintegration or moral insensitivity. For one may develop the moral virtue of doublemindedness, the settled power to deliberate and act well while morally conflicted. Such action will be accompanied by both moral loss (perhaps 'dirty hands') and ethical gain (salubrious agental stability). In explaining the virtue's moral psychology I show, among other things, its consistency with wholeheartedness and the unity of the virtues. To broaden its claim to recognition, I show the virtue's consistency with diverse models of practical reason. In conclusion, Michael Walzer's interpretation of Hamlet's attitude toward Gertrude exemplifies this virtue in a fragmentary but nonetheless praiseworthy form.

Rice is an essential crop in Ghana. Several aspects of rice have been studied to increase its production; however, the environmental aspects, including impact on climate change, have not been studied well. There is therefore a gap in knowledge, and hence the need for continuous research. By accessing academic portals, such as Springer Open, InTech Open, Elsevier, and the Kwame Nkrumah University of Science and Technology’s offline campus library, 61 academic publications including peer reviewed journals, books, working papers, reports, etc. were critically reviewed. It was found that there is a lack of data on how paddy rice production systems affect greenhouse gas (GHG) emissions, particularly emissions estimation, geographical location, and crops. Regarding GHG emission estimation, the review identified the use of emission factors calibrated using temperate conditions which do not suit tropical conditions. On location, most research on rice GHG emissions have been carried out in Asia with little input from Africa. In regard to crops, there is paucity of in-situ emissions data from paddy fields in Ghana. Drawing on the review, a conceptual framework is developed using Ghana as reference point to guide the discussion on fertilizer application, water management rice cultivars, and soil for future development of adaptation strategies for rice emission reduction.

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.

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.

Foodways have been a component of archaeological research for decades. However, cooking and food preparation, as specific acts that could reveal social information about life beyond the kitchen, only became a focus of archaeological inquiry more recently. A review of the literature on cooking and food preparation reveals a shift from previous studies on subsistence strategies, consumption, and feasting. The new research is different because of the social questions that are asked, the change in focus to preparation and production rather than consumption, and the interest in highlighting marginalized people and their daily experiences. The theoretical perspectives the literature addresses revolve around practice, agency, and gender. As a result, this new focus of archaeological research on cooking and preparing food is grounded in anthropology.

The oxidative modification of apolipoprotein A-I’s methionine148 (M148) is associated with defective HDL function in vitro. Multiple reaction monitoring (MRM) is a mass spectrometric technique that can be used to quantitate post-translational modifications. In this study, we developed an MRM assay to monitor the abundance ratio of the peptide containing oxidized M148 to the native peptide in ApoA-I. Measurement of the oxidized-to-unoxidized-M148 ratio was reproducible (CV < 5%). The extent of methionine M148 oxidation in the HDL of healthy controls, and type 2 diabetic participants with and without prior cardiovascular events (CVD) were then examined. The results suggest a significant increase in the relative ratio of the peptide containing oxidized M148 to the unmodified peptide in the HDL of participants with diabetes and CVD (p < 0.001), compared to participants without CVD. Monitoring the abundance ratio of the peptides containing oxidized and unoxidized M148 by MRM provides a means of examining the relationship between M148 oxidation and vascular complications in CVD.