ASU Scholarship Showcase

High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.

We present a microarray nonlinear calibration (MiNC) method for quantifying antibody binding to the surface of protein microarrays that significantly increases the linear dynamic range and reduces assay variation compared with traditional approaches. A serological analysis of guinea pig Mycobacterium tuberculosis models showed that a larger number of putative antigen targets were identified with MiNC, which is consistent with the improved assay performance of protein microarrays. MiNC has the potential to be employed in biomedical research using multiplex antibody assays that need quantitation, including the discovery of antibody biomarkers, clinical diagnostics with multi-antibody signatures, and construction of immune mathematical models.

Throughout the long history of virus-host co-evolution, viruses have developed delicate strategies to facilitate their invasion and replication of their genome, while silencing the host immune responses through various mechanisms. The systematic characterization of viral protein-host interactions would yield invaluable information in the understanding of viral invasion/evasion, diagnosis and therapeutic treatment of a viral infection, and mechanisms of host biology. With more than 2,000 viral genomes sequenced, only a small percent of them are well investigated. The access of these viral open reading frames (ORFs) in a flexible cloning format would greatly facilitate both in vitro and in vivo virus-host interaction studies. However, the overall progress of viral ORF cloning has been slow. To facilitate viral studies, we are releasing the initiation of our panviral proteome collection of 2,035 ORF clones from 830 viral genes in the Gateway® recombinational cloning system. Here, we demonstrate several uses of our viral collection including highly efficient production of viral proteins using human cell-free expression system in vitro, global identification of host targets for rubella virus using Nucleic Acid Programmable Protein Arrays (NAPPA) containing 10,000 unique human proteins, and detection of host serological responses using micro-fluidic multiplexed immunoassays. The studies presented here begin to elucidate host-viral protein interactions with our systemic utilization of viral ORFs, high-throughput cloning, and proteomic technologies. These valuable plasmid resources will be available to the research community to enable continued viral functional studies.

Rho GTPases are frequent targets of virulence factors as they are keystone signaling molecules. Herein, we demonstrate that AMPylation of Rho GTPases by VopS is a multifaceted virulence mechanism that counters several host immunity strategies. Activation of NFκB, Erk, and JNK kinase signaling pathways were inhibited in a VopS-dependent manner during infection with Vibrio parahaemolyticus. Phosphorylation and degradation of IKBα were inhibited in the presence of VopS as was nuclear translocation of the NFκB subunit p65. AMPylation also prevented the generation of superoxide by the phagocytic NADPH oxidase complex, potentially by inhibiting the interaction of Rac and p67. Furthermore, the interaction of GTPases with the E3 ubiquitin ligases cIAP1 and XIAP was hindered, leading to decreased degradation of Rac and RhoA during infection. Finally, we screened for novel Rac1 interactions using a nucleic acid programmable protein array and discovered that Rac1 binds to the protein C1QA, a protein known to promote immune signaling in the cytosol. Interestingly, this interaction was disrupted by AMPylation. We conclude that AMPylation of Rho Family GTPases by VopS results in diverse inhibitory consequences during infection beyond the most obvious phenotype, the collapse of the actin cytoskeleton.

Background: African American women are one of the least active demographic groups in the US, with only 36% meeting the national physical activity recommendations in comparison to 46% of White women. Physical activity begins to decline in African American women in adolescence and continues to decline into young adulthood. Yet, few interventions have been developed to promote physical activity in African American women during this critical period of life. The purpose of this article was to evaluate the acceptability and feasibility of a culturally-relevant Internet-enhanced physical activity pilot intervention for overweight/obese African American college females and to examine psychosocial and behavioral characteristics associated with intervention adherence and completion.

Methods: A 6-month single group pre-posttest design was used. Participants (n = 27) accessed a culturally-relevant Social Cognitive Theory-based physical activity promotion website while engaging in a minimum of four moderate-intensity physical activity sessions each week. Acceptability and feasibility of the intervention was assessed by participant retention and a consumer satisfaction survey completed by participants.

Results: Fifty-six percent of participants (n = 15) completed the intervention. Study completers were more physically active at baseline (P = 0.05) and had greater social support for exercise from family members (P = 0.04). Sixty percent of study completers (n = 9) reported the website as “enjoyable” or “very enjoyable” to use and 60% (n = 9) reported increased motivation from participation in the physical activity program. Moreover, 87% (n = 13) reported they would recommend the website to a friend.

Conclusions: Results provide some preliminary support for the acceptability and feasibility of an Internet-enhanced physical activity program for overweight/obese African American women, while highlighting important limitations of the approach. Successful promotion of physical activity in college aged African American women as they emerge into adulthood may result in the development of life-long healthy physical activity patterns which may ultimately reduce physical activity-related health disparities in this high risk underserved population. Future studies with larger samples are needed to further explore the use of Internet-based programs to promote physical activity in this population.

Lineage-committed cells of many tissues exhibit substantial plasticity in contexts such as wound healing and tumorigenesis, but the regulation of this process is not well understood. We identified the Hippo transducer WWTR1/TAZ in a screen of transcription factors that are able to prompt lineage switching of mammary epithelial cells. Forced expression of TAZ in luminal cells induces them to adopt basal characteristics, and depletion of TAZ in basal and/or myoepithelial cells leads to luminal differentiation. In human and mouse tissues, TAZ is active only in basal cells and is critical for basal cell maintenance during homeostasis. Accordingly, loss of TAZ affects mammary gland development, leading to an imbalance of luminal and basal populations as well as branching defects. Mechanistically, TAZ interacts with components of the SWI/SNF complex to modulate lineage-specific gene expression. Collectively, these findings uncover a new role for Hippo signaling in the determination of lineage identity through recruitment of chromatin-remodeling complexes.

Many drugs are effective in the early stage of treatment, but patients develop drug resistance after a certain period of treatment, causing failure of the therapy. An important example is Herceptin, a popular monoclonal antibody drug for breast cancer by specifically targeting human epidermal growth factor receptor 2 (Her2). Here we demonstrate a quantitative binding kinetics analysis of drug-target interactions to investigate the molecular scale origin of drug resistance. Using a surface plasmon resonance imaging, we measured the in situ Herceptin-Her2 binding kinetics in single intact cancer cells for the first time, and observed significantly weakened Herceptin-Her2 interactions in Herceptin-resistant cells, compared to those in Herceptin-sensitive cells. We further showed that the steric hindrance of Mucin-4, a membrane protein, was responsible for the altered drug-receptor binding. This effect of a third molecule on drug-receptor interactions cannot be studied using traditional purified protein methods, demonstrating the importance of the present intact cell-based binding kinetics analysis.

Objective: This cross sectional study aims to determine the effects of gender and parental perception of safety at school on children’s physical activity (PA) levels.

Materials and Methods: Parents of school aged Mexican children residing in Guadalajara, Mexico City, and Puerto Vallarta, completed surveys about their children’s PA measures. The physical activity indicators were evaluated using linear and logistical regression models.

Results: Analysis did not indicate that gender moderated the relationship between parental perception of safety and PA measures, but significant gender issues exist with girls participating less than boys in the three measures of PA in this study (p<0.001).

Conclusion: Results suggest the need for additional interventions promoting physical activity in girls in Mexico.

Changes in distribution policies have increased median MELD at transplant with recipients requiring increasing intensive care perioperatively. We aimed to evaluate association of preoperative variables with postoperative respiratory failure (PRF)/increased intensive care unit length of stay (ICU LOS)/short-term survival in a high MELD cohort undergoing liver transplant (LT). Retrospective analysis identified cases of PRF and increased ICU LOS with recipient, donor, and surgical variables examined. Variables were entered into regression with end points of PRF and ICU LOS > 3 days. 164 recipients were examined: 41 (25.0%) experienced PRF and 74 (45.1%) prolonged ICU LOS. Significant predictors of PRF with univariate analysis: BMI > 30, pretransplant MELD, preoperative respiratory failure, LVEF < 50%, FVC < 80%, intraoperative transfusion > 6 units, warm ischemic time > 4 minutes, and cold ischemic time > 240 minutes. On multivariate analysis, only pretransplant MELD predicted PRF (OR 1.14, 𝑝 = 0.01). Significant predictors of prolonged ICU LOS with univariate analysis are as follows: pretransplant MELD, FVC < 80%, FEV1 < 80%, deceased donor, and cold ischemic time > 240 minutes. On multivariate analysis, only pretransplant MELD predicted prolonged ICU LOS (OR 1.28, 𝑝 < 0.001). One-year survival among cohorts with PRF and increased ICU LOS was similar to subjects without. Pretransplant MELD is a robust predictor of PRF and ICU LOS. Higher MELDs at LT are expected to increase need for ICU utilization and modify expectations for recovery in the immediate postoperative period.

Objectives: To determine the off-shift sleep strategies of bi-ethnic night-shift nurses, the relationship between these sleep strategies and adaptation to shift work, and identify the participant-level characteristics associated with a given sleep strategy.

Methods: African-American and non-Hispanic White female, night-shift nurses from an academic hospital were recruited to complete a survey on sleep–wake patterns (n = 213). Participants completed the standard shiftwork index and the biological clocks questionnaire to determine sleep strategies and adaptation to night-shift work. In addition, chronotype was determined quantitatively with a modified version of the Munich ChronoType Questionnaire. Most participants worked ~3 consecutive 12-h night-shifts followed by several days off.

Results: Five sleep strategies used on days off were identified: (a) night stay, (b) nap proxy, (c) switch sleeper, (d) no sleep, and (e) incomplete switcher. Nap proxy and no sleep types were associated with poorer adaptation to night-shift work. The switch sleeper and incomplete switcher types were identified as more adaptive strategies that were associated with less sleep disturbance, a later chronotype, and less cardiovascular problems.

Conclusion: Behavioral sleep strategies are related to adaptation to a typical night-shift schedule among hospital nurses. Nurses are crucial to the safety and well-being of their patients. Therefore, adoption of more adaptive sleep strategies may reduce sleep/wake dysregulation in this population, and improve cardiovascular outcomes.