ASU Scholarship Showcase

Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing normalization methods, including NODES, SAMstrt, SCnorm, scran, DESeq and TMM. Linnorm shows advantages in speed, technical noise removal and preservation of cell heterogeneity, which can improve existing methods in the discovery of novel subtypes, pseudo-temporal ordering of cells, clustering analysis, etc. Linnorm also performs better than existing DEG analysis methods, including BASiCS, NODES, SAMstrt, Seurat and DESeq2, in false positive rate control and accuracy.

This article develops a welfare theoretic framework for interpreting evidence on the impacts of public programs on housing markets. We extend Rosen's hedonic model to explain how housing prices capitalize exogenous shocks to public goods and externalities. The model predicts that trading between heterogeneous buyers and sellers will drive a wedge between these “capitalization effects” and welfare changes. We test this hypothesis in the context of changes in measures of school quality in five metropolitan areas. Results from boundary discontinuity designs suggest that capitalization effects understate parents’ willingness to pay for public school improvements by as much as 75%.

Increasing levels of financial inequality prompt questions about the relationship between income and well-being. Using a twins sample from the Survey of Midlife Development in the U. S. and controlling for personality as core self-evaluations (CSE), we found that men, but not women, had higher subjective financial well-being (SFWB) when they had higher incomes. This relationship was due to ‘unshared environmental’ factors rather than genes, suggesting that the effect of income on SFWB is driven by unique experiences among men. Further, for women and men, we found that CSE influenced income and SFWB, and that both genetic and environmental factors explained this relationship. Given the relatively small and male-specific relationship between income and SFWB, and the determination of both income and SFWB by personality, we propose that policy makers focus on malleable factors beyond merely income in order to increase SFWB, including financial education and building self-regulatory capacity.

The debate about representation in the brain and the nature of the cognitive system has been going on for decades now. This paper examines the neurophysiological evidence, primarily from single cell recordings, to get a better perspective on both the issues. After an initial review of some basic concepts, the paper reviews the data from single cell recordings – in cortical columns and of category-selective and multisensory neurons. In neuroscience, columns in the neocortex (cortical columns) are understood to be a basic functional/computational unit. The paper reviews the fundamental discoveries about the columnar organization and finds that it reveals a massively parallel search mechanism. This columnar organization could be the most extensive neurophysiological evidence for the widespread use of localist representation in the brain. The paper also reviews studies of category-selective cells. The evidence for category-selective cells reveals that localist representation is also used to encode complex abstract concepts at the highest levels of processing in the brain. A third major issue is the nature of the cognitive system in the brain and whether there is a form that is purely abstract and encoded by single cells. To provide evidence for a single-cell based purely abstract cognitive system, the paper reviews some of the findings related to multisensory cells. It appears that there is widespread usage of multisensory cells in the brain in the same areas where sensory processing takes place. Plus there is evidence for abstract modality invariant cells at higher levels of cortical processing. Overall, that reveals the existence of a purely abstract cognitive system in the brain. The paper also argues that since there is no evidence for dense distributed representation and since sparse representation is actually used to encode memories, there is actually no evidence for distributed representation in the brain. Overall, it appears that, at an abstract level, the brain is a massively parallel, distributed computing system that is symbolic. The paper also explains how grounded cognition and other theories of the brain are fully compatible with localist representation and a purely abstract cognitive system.

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C^low and Ly6C^hi) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E₂ is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6C^low Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signaling and subsequently inhibits Ly6C^low Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE₂/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6C^low Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.

Modeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple TFs, is still challenging. In this study, we introduced an integrative method, LogicTRN, to decode TF–TF interactions that form TF logics in regulating target genes. By combining cis-regulatory logics and transcriptional kinetics into one single model framework, LogicTRN can naturally integrate dynamic gene expression data and TF-DNA-binding signals in order to identify the TF logics and to reconstruct the underlying TRNs. We evaluated the newly developed methodology using simulation, comparison and application studies, and the results not only show their consistence with existing knowledge, but also demonstrate its ability to accurately reconstruct TRNs in biological complex systems.

Although perceptions of physically, socially, and morally stigmatized occupations – ‘dirty work’ – are socially constructed, very little attention has been paid to how the context shapes those constructions. We explore the impact of historical trends (when), macro and micro cultures (where), and demographic characteristics (who) on the social construction of dirty work. Historically, the rise of hygiene, along with economic and technological development, resulted in greater societal distancing from dirty work, while the rise of liberalism has resulted in greater social acceptance of some morally stigmatized occupations. Culturally, masculinity tends to be preferred over femininity as an ideological discourse for dirty work, unless the occupation is female-dominated; members of collectivist cultures are generally better able than members of individualist cultures to combat the collective-level threat that stigma inherently represents; and members of high power-distance cultures tend to view dirty work more negatively than members of low power-distance cultures. Demographically, marginalized work tends to devolve to marginalized socioeconomic, gender, and racioethnic categories, creating a pernicious and entrapping recursive loop between ‘dirty work’ and being labeled as ‘dirty people.’

Accumulating data from genome-wide association studies (GWAS) have provided a collection of novel candidate genes associated with complex diseases, such as atherosclerosis. We identified an atherosclerosis-associated single-nucleotide polymorphism (SNP) located in the intron of the long noncoding RNA (lncRNA) LINC00305 by searching the GWAS database. Although the function of LINC00305 is unknown, we found that LINC00305 expression is enriched in atherosclerotic plaques and monocytes. Overexpression of LINC00305 promoted the expression of inflammation-associated genes in THP-1 cells and reduced the expression of contractile markers in co-cultured human aortic smooth muscle cells (HASMCs). We showed that overexpression of LINC00305 activated nuclear factor-kappa beta (NF-κB) and that inhibition of NF-κB abolished LINC00305-mediated activation of cytokine expression. Mechanistically, LINC00305 interacted with lipocalin-1 interacting membrane receptor (LIMR), enhanced the interaction of LIMR and aryl-hydrocarbon receptor repressor (AHRR), and promoted protein expression as well as nuclear localization of AHRR. Moreover, LINC00305 activated NF-κB exclusively in the presence of LIMR and AHRR. In light of these findings, we propose that LINC00305 promotes monocyte inflammation by facilitating LIMR and AHRR cooperation and the AHRR activation, which eventually activates NF-κB, thereby inducing HASMC phenotype switching.

National and state organizations have developed policies calling upon afterschool programs (ASPs, 3–6 pm) to serve a fruit or vegetable (FV) each day for snack, while eliminating foods and beverages high in added-sugars, and to ensure children accumulate a minimum of 30 min/d of moderate-to-vigorous physical activity (MVPA). Few efficacious and cost-effective strategies exist to assist ASP providers in achieving these important public health goals. This paper reports on the design and conceptual framework of Making Healthy Eating and Physical Activity (HEPA) Policy Practice in ASPs, a 3-year group randomized controlled trial testing the effectiveness of strategies designed to improve snacks served and increase MVPA in children attending community-based ASPs. Twenty ASPs, serving over 1800 children (6–12 years) will be enrolled and match-paired based on enrollment size, average daily min/d MVPA, and days/week FV served, with ASPs randomized after baseline data collection to immediate intervention or a 1-year delayed group. The framework employed, STEPs (Strategies To Enhance Practice), focuses on intentional programming of HEPA in each ASPs' daily schedule, and includes a grocery store partnership to reduce price barriers to purchasing FV, professional development training to promote physical activity to develop core physical activity competencies, as well as ongoing technical support/assistance. Primary outcome measures include children's accelerometry-derived MVPA and time spend sedentary while attending an ASP, direct observation of staff HEPA promoting and inhibiting behaviors, types of snacks served, and child consumption of snacks, as well as, cost of snacks via receipts and detailed accounting of intervention delivery costs to estimate cost-effectiveness.

Background: GoGirlGo! (GGG) is designed to increase girls’ physical activity (PA) using a health behavior and PA-based curriculum and is widely available for free to afterschool programs across the nation. However, GGG has not been formally evaluated. The purpose of this pilot study was to evaluate the effectiveness of the GGG curricula to improve PA, and self-efficacy for and enjoyment of PA in elementary aged girls (i.e., 5-13 years).

Methods: Nine afterschool programs were recruited to participate in the pilot (within subjects repeated measures design). GGG is a 12-week program, with a once a week, one-hour lesson with 30 minutes of education and 30 minutes of PA). Data collection occurred at baseline, mid (twice), post, and at follow-up (3-months after the intervention ended). PA was assessed via accelerometry at each time point. Self-efficacy for and enjoyment of PA was measured using the Self-Efficacy Scale and the Short-PA enjoyment scale and was assessed at baseline, post, and follow-up. Fidelity was assessed at midpoint.

Results: Across all age groups there was a statistically significant increase in PA. Overall, on days GGG was offered girls accumulated an average of 11 minutes of moderate-to-vigorous PA compared to 8 minutes during non-GGG days. There was a statistically significant difference in girls’ self-efficacy for PA reported between baseline and post, which was maintained at follow-up. An improvement in enjoyment of PA for girls was found between baseline and follow-up. According to fidelity assessment, 89% of the activities within the curriculum were completed each lesson. Girls appeared to respond well to the curriculum but girls 5-7 years had difficulties paying attention and understanding discussion questions.

Conclusions: Even though there were statistically significant differences in self-efficacy for PA and enjoyment of PA, minimal increases in girls’ PA were observed. GGG curricula improvements are warranted. Future GGG programming should explore offering GGG every day, modifying activities so that they are moderate-to-vigorous in intensity, and providing additional trainings that allow staff to better implement PA and improve behavior management techniques. With modifications, GGG could provide a promising no-cost curriculum that afterschool programs may implement to help girls achieve recommendations for PA.