ASU Scholarship Showcase

Background: Previous studies exploring sequence variation in the model legume, Medicago truncatula, relied on mapping short reads to a single reference. However, read-mapping approaches are inadequate to examine large, diverse gene families or to probe variation in repeat-rich or highly divergent genome regions. De novo sequencing and assembly of M. truncatula genomes enables near-comprehensive discovery of structural variants (SVs), analysis of rapidly evolving gene families, and ultimately, construction of a pan-genome.

Results: Genome-wide synteny based on 15 de novo M. truncatula assemblies effectively detected different types of SVs indicating that as much as 22% of the genome is involved in large structural changes, altogether affecting 28% of gene models. A total of 63 million base pairs (Mbp) of novel sequence was discovered, expanding the reference genome space for Medicago by 16%. Pan-genome analysis revealed that 42% (180 Mbp) of genomic sequences is missing in one or more accession, while examination of de novo annotated genes identified 67% (50,700) of all ortholog groups as dispensable – estimates comparable to recent studies in rice, maize and soybean. Rapidly evolving gene families typically associated with biotic interactions and stress response were found to be enriched in the accession-specific gene pool. The nucleotide-binding site leucine-rich repeat (NBS-LRR) family, in particular, harbors the highest level of nucleotide diversity, large effect single nucleotide change, protein diversity, and presence/absence variation. However, the leucine-rich repeat (LRR) and heat shock gene families are disproportionately affected by large effect single nucleotide changes and even higher levels of copy number variation.

Conclusions: Analysis of multiple M. truncatula genomes illustrates the value of de novo assemblies to discover and describe structural variation, something that is often under-estimated when using read-mapping approaches. Comparisons among the de novo assemblies also indicate that different large gene families differ in the architecture of their structural variation.

This survey of 206 forensic psychologists tested the “filtering” effects of preexisting expert attitudes in adversarial proceedings. Results confirmed the hypothesis that evaluator attitudes toward capital punishment influence willingness to accept capital case referrals from particular adversarial parties. Stronger death penalty opposition was associated with higher willingness to conduct evaluations for the defense and higher likelihood of rejecting referrals from all sources. Conversely, stronger support was associated with higher willingness to be involved in capital cases generally, regardless of referral source. The findings raise the specter of skewed evaluator involvement in capital evaluations, where evaluators willing to do capital casework may have stronger capital punishment support than evaluators who opt out, and evaluators with strong opposition may work selectively for the defense. The results may provide a partial explanation for the “allegiance effect” in adversarial legal settings such that preexisting attitudes may contribute to partisan participation through a self-selection process.

Multitrophic communities that maintain the functionality of the extreme Antarctic terrestrial ecosystems, while the simplest of any natural community, are still challenging our knowledge about the limits to life on earth. In this study, we describe and interpret the linkage between the diversity of different trophic level communities to the geological morphology and soil geochemistry in the remote Transantarctic Mountains (Darwin Mountains, 80°S). We examined the distribution and diversity of biota (bacteria, cyanobacteria, lichens, algae, invertebrates) with respect to elevation, age of glacial drift sheets, and soil physicochemistry. Results showed an abiotic spatial gradient with respect to the diversity of the organisms across different trophic levels. More complex communities, in terms of trophic level diversity, were related to the weakly developed younger drifts (Hatherton and Britannia) with higher soil C/N ratio and lower total soluble salts content (thus lower conductivity). Our results indicate that an increase of ion concentration from younger to older drift regions drives a succession of complex to more simple communities, in terms of number of trophic levels and diversity within each group of organisms analysed. This study revealed that integrating diversity across multi-trophic levels of biotic communities with abiotic spatial heterogeneity and geological history is fundamental to understand environmental constraints influencing biological distribution in Antarctic soil ecosystems.

More has changed in journal publishing in the past twenty years than the previous four centuries. Digital technologies have transformed the submission, review, production and distribution of scholarly materials, with the result that there has been exponential growth in the number of papers published in an expanding roster of journals—some are mainstream, some highly specialized, some are produced by publishers who have existed since printing began and others are produced by small groups with niche interests.

Although emerging evidence indicates that deep-sea water contains an untapped reservoir of high metabolic and genetic diversity, this realm has not been studied well compared with surface sea water. The study provided the first integrated meta-genomic and -transcriptomic analysis of the microbial communities in deep-sea water of North Pacific Ocean. DNA/RNA amplifications and simultaneous metagenomic and metatranscriptomic analyses were employed to discover information concerning deep-sea microbial communities from four different deep-sea sites ranging from the mesopelagic to pelagic ocean. Within the prokaryotic community, bacteria is absolutely dominant (~90%) over archaea in both metagenomic and metatranscriptomic data pools. The emergence of archaeal phyla Crenarchaeota, Euryarchaeota, Thaumarchaeota, bacterial phyla Actinobacteria, Firmicutes, sub-phyla Betaproteobacteria, Deltaproteobacteria, and Gammaproteobacteria, and the decrease of bacterial phyla Bacteroidetes and Alphaproteobacteria are the main composition changes of prokaryotic communities in the deep-sea water, when compared with the reference Global Ocean Sampling Expedition (GOS) surface water. Photosynthetic Cyanobacteria exist in all four metagenomic libraries and two metatranscriptomic libraries. In Eukaryota community, decreased abundance of fungi and algae in deep sea was observed. RNA/DNA ratio was employed as an index to show metabolic activity strength of microbes in deep sea. Functional analysis indicated that deep-sea microbes are leading a defensive lifestyle.

In order to determine the feasibility of utilizing novel rexinoids for chemotherapeutics and as potential treatments for neurological conditions, we undertook an assessment of the side effect profile of select rexinoid X receptor (RXR) analogs that we reported previously. We assessed pharmacokinetic profiles, lipid and thyroid-stimulating hormone (TSH) levels in rats, and cell culture activity of rexinoids in sterol regulatory element-binding protein (SREBP) induction and thyroid hormone inhibition assays. We also performed RNA sequencing of the brain tissues of rats that had been dosed with the compounds. We show here for the first time that potent rexinoid activity can be uncoupled from drastic lipid changes and thyroid axis variations, and we propose that rexinoids can be developed with improved side effect profiles than the parent compound, bexarotene (1).

Given species inventories of all sites in a planning area, integer programming or heuristic algorithms can prioritize sites in terms of the site's complementary value, that is, the ability of the site to complement (add unrepresented species to) other sites prioritized for conservation. The utility of these procedures is limited because distributions of species are typically available only as coarse atlases or range maps, whereas conservation planners need to prioritize relatively small sites. If such coarse-resolution information can be used to identify small sites that efficiently represent species (i.e., downscaled), then such data can be useful for conservation planning. We develop and test a new type of surrogate for biodiversity, which we call downscaled complementarity. In this approach, complementarity values from large cells are downscaled to small cells, using statistical methods or simple map overlays. We illustrate our approach for birds in Spain by building models at coarse scale (50 × 50 km atlas of European birds, and global range maps of birds interpreted at the same 50 × 50 km grid size), using this model to predict complementary value for 10 × 10 km cells in Spain, and testing how well-prioritized cells represented bird distributions in an independent bird atlas of those 10 × 10 km cells. Downscaled complementarity was about 63–77% as effective as having full knowledge of the 10-km atlas data in its ability to improve on random selection of sites. Downscaled complementarity has relatively low data acquisition cost and meets representation goals well compared with other surrogates currently in use. Our study justifies additional tests to determine whether downscaled complementarity is an effective surrogate for other regions and taxa, and at spatial resolution finer than 10 × 10 km cells. Until such tests have been completed, we caution against assuming that any surrogate can reliably prioritize sites for species representation.

Lack of biodiversity data is a major impediment to prioritizing sites for species representation. Because comprehensive species data are not available in any planning area, planners often use surrogates (such as vegetation communities, or mapped occurrences of a well-inventoried taxon) to prioritize sites. We propose and demonstrate the effectiveness of predicted rarity-weighted richness (PRWR) as a surrogate in situations where species inventories may be available for a portion of the planning area. Use of PRWR as a surrogate involves several steps. First, rarity-weighted richness (RWR) is calculated from species inventories for a q% subset of sites. Then random forest models are used to model RWR as a function of freely available environmental variables for that q% subset. This function is then used to calculate PRWR for all sites (including those for which no species inventories are available), and PRWR is used to prioritize all sites. We tested PRWR on plant and bird datasets, using the species accumulation index to measure efficiency of PRWR. Sites with the highest PRWR represented species with median efficiency of 56% (range 32%–77% across six datasets) when q = 20%, and with median efficiency of 39% (range 20%–63%) when q = 10%. An efficiency of 56% means that selecting sites in order of PRWR rank was 56% as effective as having full knowledge of species distributions in PRWR's ability to improve on the number of species represented in the same number of randomly selected sites. Our results suggest that PRWR may be able to help prioritize sites to represent species if a planner has species inventories for 10%–20% of the sites in the planning area.

Driven by an increasing number of studies demonstrating its relevance to a broad variety of disease states, the bioenergy production phenotype has been widely characterized at the bulk sample level. Its cell-to-cell variability, a key player associated with cancer cell survival and recurrence, however, remains poorly understood due to ensemble averaging of the current approaches. We present a technology platform for performing oxygen consumption and extracellular acidification measurements of several hundreds to 1,000 individual cells per assay, while offering simultaneous analysis of cellular communication effects on the energy production phenotype. The platform comprises two major components: a tandem optical sensor for combined oxygen and pH detection, and a microwell device for isolation and analysis of single and few cells in hermetically sealed sub-nanoliter chambers. Our approach revealed subpopulations of cells with aberrant energy production profiles and enables determination of cellular response variability to electron transfer chain inhibitors and ion uncouplers.

The histone deacetylase (HDAC) inhibitor vorinostat has received significant attention in recent years as an ‘epigenetic’ drug used to treat solid tumors. However, its mechanisms of action are not entirely understood, particularly with regard to its interaction with the aberrations in 3D nuclear structure that accompany neoplastic progression. We investigated the impact of vorinostat on human esophageal epithelial cell lines derived from normal, metaplastic (pre-cancerous), and malignant tissue. Using a combination of novel optical computed tomography (CT)-based quantitative 3D absorption microscopy and conventional confocal fluorescence microscopy, we show that subjecting malignant cells to vorinostat preferentially alters their 3D nuclear architecture relative to non-cancerous cells. Optical CT (cell CT) imaging of fixed single cells showed that drug-treated cancer cells exhibit significant alterations in nuclear morphometry. Confocal microscopy revealed that vorinostat caused changes in the distribution of H3K9ac-marked euchromatin and H3K9me3-marked constitutive heterochromatin. Additionally, 3D immuno-FISH showed that drug-induced expression of the DNA repair gene MGMT was accompanied by spatial relocation toward the center of the nucleus in the nuclei of metaplastic but not in non-neoplastic cells. Our data suggest that vorinostat’s differential modulation of 3D nuclear architecture in normal and abnormal cells could play a functional role in its anti-cancer action.