ASU Scholarship Showcase

Although the majority of late-onset Alzheimer's disease (AD) patients are labeled sporadic, multiple genetic risk variants have been identified, the most powerful and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene. Here, we generated human induced pluripotent stem cell (hiPSC) lines from the peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient [ASUi003-A] and a non-demented control (NDC) patient [ASUi004-A] homozygous for the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed pluripotency markers, exhibited a normal karyotype, and retained the ability to differentiate into cells representative of the three germ layers.

Specification of PM_2.5 transmission characteristics is important for pollution control and policymaking. We apply higher-order organization of complex networks to identify major potential PM_2.5 contributors and PM_2.5 transport pathways of a network of 189 cities in China. The network we create in this paper consists of major cities in China and contains information on meteorological conditions of wind speed and wind direction, data on geographic distance, mountains, and PM_2.5 concentrations. We aim to reveal PM_2.5 mobility between cities in China. Two major conclusions are revealed through motif analysis of complex networks. First, major potential PM_2.5 pollution contributors are identified for each cluster by one motif, which reflects movements from source to target. Second, transport pathways of PM_2.5 are revealed by another motif, which reflects transmission routes. To our knowledge, this is the first work to apply higher-order network analysis to study PM_2.5 transport.

To investigate dual-process persuasion theories in the context of group decision making, we studied low and high need-for-cognition (NFC) participants within a mock trial study. Participants considered plaintiff and defense expert scientific testimony that varied in argument strength. All participants heard a cross-examination of the experts focusing on peripheral information (e.g., credentials) about the expert, but half were randomly assigned to also hear central information highlighting flaws in the expert’s message (e.g., quality of the research presented by the expert). Participants rendered pre- and post-group-deliberation verdicts, which were considered “scientifically accurate” if the verdicts reflected the strong (versus weak) expert message, and “scientifically inaccurate” if they reflected the weak (versus strong) expert message. For individual participants, we replicated studies testing classic persuasion theories: Factors promoting reliance on central information (i.e., central cross-examination, high NFC) improved verdict accuracy because they sensitized individual participants to the quality discrepancy between the experts’ messages. Interestingly, however, at the group level, the more that scientifically accurate mock jurors discussed peripheral (versus central) information about the experts, the more likely their group was to reach the scientifically accurate verdict. When participants were arguing for the scientifically accurate verdict consistent with the strong expert message, peripheral comments increased their persuasiveness, which made the group more likely to reach the more scientifically accurate verdict.

Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs) demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages.

Aquatic vertebrates that emerge onto land to spawn, feed, or evade aquatic predators must return to the water to avoid dehydration or asphyxiation. How do such aquatic organisms determine their location on land? Do particular behaviors facilitate a safe return to the aquatic realm? In this study, we asked: will fully-aquatic mosquitofish (Gambusia affinis) stranded on a slope modulate locomotor behavior according to body position to facilitate movement back into the water? To address this question, mosquitofish (n = 53) were placed in four positions relative to an artificial slope (30° inclination) and their responses to stranding were recorded, categorized, and quantified.

We found that mosquitofish may remain immobile for up to three minutes after being stranded and then initiate either a “roll” or a “leap”. During a roll, mass is destabilized to trigger a downslope tumble; during a leap, the fish jumps up, above the substrate. When mosquitofish are oriented with the long axis of the body at 90° to the slope, they almost always (97%) initiate a roll. A roll is an energetically inexpensive way to move back into the water from a cross-slope body orientation because potential energy is converted back into kinetic energy. When placed with their heads toward the apex of the slope, most mosquitofish (>50%) produce a tail-flip jump to leap into ballistic flight. Because a tail-flip generates a caudually-oriented flight trajectory, this locomotor movement will effectively propel a fish downhill when the head is oriented up-slope. However, because the mass of the body is elevated against gravity, leaps require more mechanical work than rolls. We suggest that mosquitofish use the otolith-vestibular system to sense body position and generate a behavior that is “matched” to their orientation on a slope, thereby increasing the probability of a safe return to the water, relative to the energy expended.

Brucellosis is a bacterial disease caused by brucella; mainly spread by direct contact transmission through the brucella carriers, or indirect contact transmission by the environment containing large quantities of bacteria discharged by the infected individuals. At the beginning of 21st century, the epidemic among dairy cows in Zhejiang province, began to come back and has become a localized prevalent epidemic. Combining the pathology of brucellosis, the reported positive data characteristics, and the feeding method in Zhejiang province, this paper establishes an SEIV dynamic model to excavate the internal transmission dynamics, fit the real disease situation, predict brucellosis tendency and assess control measures in dairy cows. By careful analysis, we give some quantitative results as follows. (1) The external input of dairy cows from northern areas may lead to high fluctuation of the number of the infectious cows in Zhejiang province that can reach several hundreds. In this case, the disease cannot be controlled and the infection situation cannot easily be predicted. Thus, this paper encourages cows farms to insist on self-supplying production of the dairy cows. (2) The effect of transmission rate of brucella in environment to dairy cattle on brucellosis spreading is greater than transmission rate of the infectious dairy cattle to susceptible cattle. The prevalence of the epidemic is mainly aroused by environment transmission. (3) Under certain circumstances, the epidemic will become a periodic phenomenon. (4) For Zhejiang province, besides measures that have already been adopted, sterilization times of the infected regions is suggested as twice a week, and should be combined with management of the birth rate of dairy cows to control brucellosis spread.

Vitamin D receptor (VDR) is a substrate for modification with small ubiquitin-like modifier (SUMO). To further assess the role of reversible SUMOylation within the vitamin D hormonal response, we evaluated the effects of sentrin/SUMO-specific proteases (SENPs) that can function to remove small ubiquitin-like modifier (SUMO) from target proteins upon the activities of VDR and related receptors. We report that SENP1 and SENP2 strikingly potentiate ligand-mediated transactivation of VDR and also its heterodimeric partner, retinoid X receptor (RXRα) with depletion of cellular SENP1 significantly diminishing the hormonal responsiveness of the endogenous vitamin D target gene CYP24A1. We find that SENP-directed modulation of VDR activity is cell line-dependent, achieving potent modulatory effects in Caco-2 and HEK-293 cells, while in MCF-7 cells the vitamin D signal is unaffected by any tested SENP. In support of their function as novel modulators of the vitamin D hormonal pathway we demonstrate that both SENP1 and SENP2 can interact with VDR and reverse its modification with SUMO2. In a preliminary analysis we identify lysine 91, a residue known to be critical for formation and DNA binding of the VDR-RXR heterodimer, as a minor SUMO acceptor site within VDR. In combination, our results support a repressor function for SUMOylation of VDR and reveal SENPs as a novel class of VDR/RXR co-regulatory protein that significantly modulate the vitamin D response and which could also have important impact upon the functionality of both RXR-containing homo and heterodimers.

Through the mathematical study of two models we quantify some of the theories of co-development and co-existence of focused groups in the social sciences. This work attempts to develop the mathematical framework behind the social sciences of community formation. By using well developed theories and concepts from ecology and epidemiology we hope to extend the theoretical framework of organizing and self-organizing social groups and communities, including terrorist groups. The main goal of our work is to gain insight into the role of recruitment and retention in the formation and survival of social organizations. Understanding the underlining mechanisms of the spread of ideologies under competition is a fundamental component of this work. Here contacts between core and non-core individuals extend beyond its physical meaning to include indirect interaction and spread of ideas through phone conversations, emails, media sources and other similar mean.

This work focuses on the dynamics of formation of interest groups, either ideological, economical or ecological and thus we explore the questions such as, how do interest groups initiate and co-develop by interacting within a common environment and how do they sustain themselves? Our results show that building and maintaining the core group is essential for the existence and survival of an extreme ideology. Our research also indicates that in the absence of competitive ability (i.e., ability to take from the other core group or share prospective members) the social organization or group that is more committed to its group ideology and manages to strike the right balance between investment in recruitment and retention will prevail. Thus under no cross interaction between two social groups a single trade-off (of these efforts) can support only a single organization. The more efforts that an organization implements to recruit and retain its members the more effective it will be in transmitting the ideology to other vulnerable individuals and thus converting them to believers.

MALDI-TOF MS has been shown capable of rapidly and accurately characterizing bacteria. Highly reproducible spectra are required to ensure reliable characterization. Prior work has shown that spectra acquired manually can have higher reproducibility than those acquired automatically. For this reason, the objective of this study was to optimize automated data acquisition to yield spectra with reproducibility comparable to those acquired manually. Fractional factorial design was used to design experiments for robust optimization of settings, in which values of five parameters (peak selection mass range, signal to noise ratio (S:N), base peak intensity, minimum resolution and number of shots summed) commonly used to facilitate automated data acquisition were varied. Pseudomonas aeruginosa was used as a model bacterium in the designed experiments, and spectra were acquired using an intact cell sample preparation method. Optimum automated data acquisition settings (i.e., those settings yielding the highest reproducibility of replicate mass spectra) were obtained based on statistical analysis of spectra of P. aeruginosa. Finally, spectrum quality and reproducibility obtained from non-optimized and optimized automated data acquisition settings were compared for P. aeruginosa, as well as for two other bacteria, Klebsiella pneumoniae and Serratia marcescens. Results indicated that reproducibility increased from 90% to 97% (p-value [~ over =] 0.002) for P. aeruginosa when more shots were summed and, interestingly, decreased from 95% to 92% (p-value [~ over =] 0.013) with increased threshold minimum resolution. With regard to spectrum quality, highly reproducible spectra were more likely to have high spectrum quality as measured by several quality metrics, except for base peak resolution. Interaction plots suggest that, in cases of low threshold minimum resolution, high reproducibility can be achieved with fewer shots. Optimization yielded more reproducible spectra than non-optimized settings for all three bacteria.

Restoration projects can have varying goals, depending on the specific focus, rationale, and aims for restoration. When restoration projects use project-specific goals to define activities and gauge success without considering broader ecological context, determination of project implications and success can be confounding. We used case studies from the Middle Rio Grande (MRG), southwest USA, to demonstrate how restoration outcomes can rank inconsistently when narrowly-based goals are used. Resource managers have chosen MRG for restoration due to impacts to the natural flood regime, reduced native tree recruitment, and establishment of non-native plants. We show restoration “success” ranks differently based upon three goals: increasing biodiversity, increasing specific ecosystem functions, or restoring native communities. We monitored 12 restored and control sites for seven years. Treatments ranked higher in reducing exotic woody populations, and increasing proportions of native plants and groundwater salvage, but generally worse at removing fuels, and increasing species and habitat structural diversity. Managers cannot rely on the term “restoration” to sufficiently describe a project’s aim. Specific desired outcomes must be defined and monitored. Long-term planning should include flexibility to incorporate provisions for adaptive management to refine treatments to avoid unintended ecological consequences.