ASU Scholarship Showcase

Background: The green anole lizard, Anolis carolinensis, is a key species for both laboratory and field-based studies of evolutionary genetics, development, neurobiology, physiology, behavior, and ecology. As the first non-avian reptilian genome sequenced, A. carolinesis is also a prime reptilian model for comparison with other vertebrate genomes. The public databases of Ensembl and NCBI have provided a first generation gene annotation of the anole genome that relies primarily on sequence conservation with related species. A second generation annotation based on tissue-specific transcriptomes would provide a valuable resource for molecular studies.

Results: Here we provide an annotation of the A. carolinensis genome based on de novo assembly of deep transcriptomes of 14 adult and embryonic tissues. This revised annotation describes 59,373 transcripts, compared to 16,533 and 18,939 currently for Ensembl and NCBI, and 22,962 predicted protein-coding genes. A key improvement in this revised annotation is coverage of untranslated region (UTR) sequences, with 79% and 59% of transcripts containing 5’ and 3’ UTRs, respectively. Gaps in genome sequence from the current A. carolinensis build (Anocar2.0) are highlighted by our identification of 16,542 unmapped transcripts, representing 6,695 orthologues, with less than 70% genomic coverage.

Conclusions: Incorporation of tissue-specific transcriptome sequence into the A. carolinensis genome annotation has markedly improved its utility for comparative and functional studies. Increased UTR coverage allows for more accurate predicted protein sequence and regulatory analysis. This revised annotation also provides an atlas of gene expression specific to adult and embryonic tissues.

Background: Gene bodies are the most evolutionarily conserved targets of DNA methylation in eukaryotes. However, the regulatory functions of gene body DNA methylation remain largely unknown. DNA methylation in insects appears to be primarily confined to exons. Two recent studies in Apis mellifera (honeybee) and Nasonia vitripennis (jewel wasp) analyzed transcription and DNA methylation data for one gene in each species to demonstrate that exon-specific DNA methylation may be associated with alternative splicing events. In this study we investigated the relationship between DNA methylation, alternative splicing, and cross-species gene conservation on a genome-wide scale using genome-wide transcription and DNA methylation data.

Results: We generated RNA deep sequencing data (RNA-seq) to measure genome-wide mRNA expression at the exon- and gene-level. We produced a de novo transcriptome from this RNA-seq data and computationally predicted splice variants for the honeybee genome. We found that exons that are included in transcription are higher methylated than exons that are skipped during transcription. We detected enrichment for alternative splicing among methylated genes compared to unmethylated genes using fisher’s exact test. We performed a statistical analysis to reveal that the presence of DNA methylation or alternative splicing are both factors associated with a longer gene length and a greater number of exons in genes. In concordance with this observation, a conservation analysis using BLAST revealed that each of these factors is also associated with higher cross-species gene conservation.

Conclusions: This study constitutes the first genome-wide analysis exhibiting a positive relationship between exon-level DNA methylation and mRNA expression in the honeybee. Our finding that methylated genes are enriched for alternative splicing suggests that, in invertebrates, exon-level DNA methylation may play a role in the construction of splice variants by positively influencing exon inclusion during transcription. The results from our cross-species homology analysis suggest that DNA methylation and alternative splicing are genetic mechanisms whose utilization could contribute to a longer gene length and a slower rate of gene evolution.

Background: Brain regions that mediate learning of a conditioned place preference (CPP) undergo significant development in pre and periadolescence. Consuming a high fat (HF) diet during this developmental period and into adulthood can lead to learning impairments in rodents. The present study tested whether HF diet intake, consumed only in pre and periadolescence, would be sufficient to cause impairments using a CPP procedure.

Methods: Rats were randomly assigned to consume a HF or a low fat (LF) diet during postnatal days (PD) 21-40 and were then placed back on a standard lab chow diet. A 20-day CPP procedure, using HF Cheetos® as the unconditioned stimulus (US), began either the next day (PD 41) or 40 days later (PD 81). A separate group of adult rats were given the HF diet for 20 days beginning on PD 61, and then immediately underwent the 20-day CPP procedure beginning on PD 81.

Results: Pre and periadolescent exposure to a LF diet or adult exposure to a HF diet did not interfere with the development of a HF food-induced CPP, as these groups exhibited robust preferences for the HF Cheetos® food-paired compartment. However, pre and periadolescent exposure to the HF diet impaired the development of a HF food-induced CPP regardless of whether it was assessed immediately or 40 days after the exposure to the HF diet, and despite showing increased consumption of the HF Cheetos® in conditioning.

Conclusions: Intake of a HF diet, consumed only in pre and periadolescence, has long-lasting effects on learning that persist into adulthood.

Background: Worksites are important locations for interventions to promote health. However, occupational programs with documented efficacy often are not used, and those being implemented have not been studied. The research in this report was funded through the American Reinvestment and Recovery Act Challenge Topic 'Pathways for Translational Research,' to define and prioritize determinants that enable and hinder translation of evidenced-based health interventions in well-defined settings.

Methods: The IGNITE (investigation to guide new insights for translational effectiveness) trial is a prospective cohort study of a worksite wellness and injury reduction program from adoption to final outcomes among 12 fire departments. It will employ a mixed methods strategy to define a translational model. We will assess decision to adopt, installation, use, and outcomes (reach, individual outcomes, and economic effects) using onsite measurements, surveys, focus groups, and key informant interviews. Quantitative data will be used to define the model and conduct mediation analysis of each translational phase. Qualitative data will expand on, challenge, and confirm survey findings and allow a more thorough understanding and convergent validity by overcoming biases in qualitative and quantitative methods used alone.

Discussion: Findings will inform worksite wellness in fire departments. The resultant prioritized influences and model of effective translation can be validated and manipulated in these and other settings to more efficiently move science to service.

Background: Increasing our understanding of the factors affecting the severity of the 2009 A/H1N1 influenza pandemic in different regions of the world could lead to improved clinical practice and mitigation strategies for future influenza pandemics. Even though a number of studies have shed light into the risk factors associated with severe outcomes of 2009 A/H1N1 influenza infections in different populations (e.g., [1-5]), analyses of the determinants of mortality risk spanning multiple pandemic waves and geographic regions are scarce. Between-country differences in the mortality burden of the 2009 pandemic could be linked to differences in influenza case management, underlying population health, or intrinsic differences in disease transmission [6]. Additional studies elucidating the determinants of disease severity globally are warranted to guide prevention efforts in future influenza pandemics.

In Mexico, the 2009 A/H1N1 influenza pandemic was characterized by a three-wave pattern occurring in the spring, summer, and fall of 2009 with substantial geographical heterogeneity [7]. A recent study suggests that Mexico experienced high excess mortality burden during the 2009 A/H1N1 influenza pandemic relative to other countries [6]. However, an assessment of potential factors that contributed to the relatively high pandemic death toll in Mexico are lacking. Here, we fill this gap by analyzing a large series of laboratory-confirmed A/H1N1 influenza cases, hospitalizations, and deaths monitored by the Mexican Social Security medical system during April 1 through December 31, 2009 in Mexico. In particular, we quantify the association between disease severity, hospital admission delays, and neuraminidase inhibitor use by demographic characteristics, pandemic wave, and geographic regions of Mexico.

Methods: We analyzed a large series of laboratory-confirmed pandemic A/H1N1 influenza cases from a prospective surveillance system maintained by the Mexican Social Security system, April-December 2009. We considered a spectrum of disease severity encompassing outpatient visits, hospitalizations, and deaths, and recorded demographic and geographic information on individual patients. We assessed the impact of neuraminidase inhibitor treatment and hospital admission delay (≤ > 2 days after disease onset) on the risk of death by multivariate logistic regression.

Results: Approximately 50% of all A/H1N1-positive patients received antiviral medication during the Spring and Summer 2009 pandemic waves in Mexico while only 9% of A/H1N1 cases received antiviral medications during the fall wave (P < 0.0001). After adjustment for age, gender, and geography, antiviral treatment significantly reduced the risk of death (OR = 0.52 (95% CI: 0.30, 0.90)) while longer hospital admission delays increased the risk of death by 2.8-fold (95% CI: 2.25, 3.41).

Conclusions: Our findings underscore the potential impact of decreasing admission delays and increasing antiviral use to mitigate the mortality burden of future influenza pandemics.

This thirty-year case study uses surveys, semi-structured interviews, and content analysis to examine the adaptive capacity of Zanjera San Marcelino, an indigenous irrigation management system in the northern Philippines. This common pool resource (CPR) system exists within a turbulent social-ecological system (SES) characterized by episodic shocks such as large typhoons as well as novel surprises, such as national political regime change and the construction of large dams. The Zanjera nimbly responded to these challenges, although sometimes in ways that left its structure and function substantially altered. While a partial integration with the Philippine National Irrigation Agency was critical to the Zanjera’s success, this relationship required on-going improvisation and renegotiation. Over time, the Zanjera showed an increasing capacity to learn and adapt. A core contribution of this analysis is the integration of a CPR study within an SES framework to examine resilience, made possible the occurrence of a wide range of challenges to the Zanjera’s function and survival over the long period of study. Long-term analyses like this one, however rare, are particularly useful for understanding the adaptive and transformative dimensions of resilience.

The termites evolved eusociality and complex societies before the ants, but have been studied much less. The recent publication of the first two termite genomes provides a unique comparative opportunity, particularly because the sequenced termites represent opposite ends of the social complexity spectrum. Zootermopsis nevadensis has simple colonies with totipotent workers that can develop into all castes (dispersing reproductives, nest-inheriting replacement reproductives, and soldiers). In contrast, the fungus-growing termite Macrotermes natalensis belongs to the higher termites and has very large and complex societies with morphologically distinct castes that are life-time sterile. Here we compare key characteristics of genomic architecture, focusing on genes involved in communication, immune defenses, mating biology and symbiosis that were likely important in termite social evolution. We discuss these in relation to what is known about these genes in the ants and outline hypothesis for further testing.

The genus Apodrosus Marshall is newly recorded for, and revised for Cuba. Nine new species are recognized as follows: Apodrosus alberti (type locality, Granma, Parque Nacional Pico Turquino), A. alternatus (type locality, Guantánamo, El Yunque), A. franklyni (type locality, Cienfuegos, Parque Nacional Pico San Juan), A. griseus (type locality, Santiago de Cuba, Siboney-Jutici Ecological Reserve), A. mensurensis (type locality, Holguin, Parque Nacional La Mensura-Piloto), A. pseudoalternatus (type locality, Matanzas, Varahicacos), A. beckeli (type locality, Guantánamo, 8 km W. Imias), A. sandersoni (type locality, Guantánamo, Loma Lafarola), and A. zayasi (type locality, Cienfuegos, Parque Nacional Pico San Juan). A key for their identification, descriptions, summaries of natural history information and data on distributions are presented. A molecular phylogeny based on 11 species of Apodrosus from Cuba, Hispaniola and Puerto Rico is reconstructed. A sister group relationship between Polydrusus and Apodrosus is recovered with a limited sampling of the former genus. The monophyly of Apodrosus is recovered with strong support. Cuban Apodrosus are not monophyletic. Five of the six sampled Cuban species form a clade, sister to an undescribed Apodrosus species from the Dominican Republic; and, Apodrosus alternatus is sister to A. quisqueyanus Girón & Franz, 2010, a species from the Dominican Republic. Biogeographic implications for Cuban species are discussed in light of the phylogeny.

Tree-like structures are ubiquitous in nature. In particular, neuronal axons and dendrites have tree-like geometries that mediate electrical signaling within and between cells. Electrical activity in neuronal trees is typically modeled using coupled cable equations on multi-compartment representations, where each compartment represents a small segment of the neuronal membrane. The geometry of each compartment is usually defined as a cylinder or, at best, a surface of revolution based on a linear approximation of the radial change in the neurite. The resulting geometry of the model neuron is coarse, with non-smooth or even discontinuous jumps at the boundaries between compartments. We propose a hyperbolic approximation to model the geometry of neurite compartments, a branched, multi-compartment extension, and a simple graphical approach to calculate steady-state solutions of an associated system of coupled cable equations. A simple case of transient solutions is also briefly discussed.

Indigenous populations are generally reported to suffer greater active tuberculosis (TB) disease burden. The objective of this study was to examine ecological associations between cases of active adult and pediatric TB reported from 2002 to 2004 and community characteristics in indigenous communities of the Paraguayan Chaco. Adult and pediatric models were examined by negative binomial and Poisson GLM regression, respectively. Active TB prevalence in indigenous people was eight times higher than the nonindigenous population. Communities with a health post were more than twice as likely to report active adult TB (RR = 2.07, 95% confidence interval (CI) [1.14–3.83], and p < 0.05). Each additional average year of education in the community was associated with nearly 50% less likelihood of active pediatric TB (RR = 0.53, 95% CI [0.38–0.73], and p < 0.001). Although nonsignificant, the presence of nonindigenous community members had a strong protective association in both the adult (RR = 0.56, 95% CI [0.30–1.03], and p = 0.6) and pediatric models (RR = 0.64, 95% CI [0.34–1.14], and p = 0.14). These results reinforce the importance of increasing epidemiologic surveillance and investigating the social determinants of TB disease among vulnerable indigenous populations.