ASU Scholarship Showcase

Investigation into the causes underlying the rapid, global amphibian decline provides critical insight into the effects of changing ecosystems. Hypothesized and confirmed links between amphibian declines, disease, and environmental changes are increasingly represented in published literature. However, there are few long-term amphibian studies that include data on population size, abnormality/injury rates, disease, and habitat variables to adequately assess changes through time. We cultured and identified microorganisms isolated from abnormal/injured and repressed tissue regeneration sites of the endangered Ozark Hellbender, Cryptobranchus alleganiensis bishopi, to discover potential causative agents responsible for their significant decline in health and population. This organism and our study site were chosen because the population and habitat of C. a. bishopi have been intensively studied from 1969–2009, and the abnormality/injury rate and apparent lack of regeneration were established.

Although many bacterial and fungal isolates recovered were common environmental organisms, several opportunistic pathogens were identified in association with only the injured tissues of C.a. bishopi. Bacterial isolates included Aeromonas hydrophila, a known amphibian pathogen, Granulicetella adiacens, Gordonai terrae, Stenotrophomonas maltophilia, Aerococcus viridans, Streptococcus pneumoniae and a variety of Pseudomonads, including Pseudomonas aeruginosa, P. stutzeri, and P. alcaligenes. Fungal isolates included species in the genera Penicillium, Acremonium, Cladosporium, Curvularia, Fusarium, Streptomycetes, and the Class Hyphomycetes. Many of the opportunistic pathogens identified are known to form biofilms. Lack of isolation of the same organism from all wounds suggests that the etiological agent responsible for the damage to C. a. bishopi may not be a single organism. To our knowledge, this is the first study to profile the external microbial consortia cultured from a Cryptobranchid salamander. The incidence of abnormalities/injury and retarded regeneration in C. a. bishopi may have many contributing factors including disease and habitat degradation. Results from this study may provide insight into other amphibian population declines.

This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans–induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance.

Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the low fluid-shear environment of microgravity is relevant to physical forces encountered by pathogens during the infection process, insights gained from this study could identify novel infectious disease mechanisms, with downstream benefits for the general public.

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a first-of-its-kind pilot study to assess spaceflight-related gene-expression changes in the whole blood of astronauts. Using an array comprised of 234 well-characterized stress-response genes, we profiled transcriptomic changes in six astronauts (four men and two women) from blood preserved before and immediately following the spaceflight. Differentially regulated transcripts included those important for DNA repair, oxidative stress, and protein folding/degradation, including HSP90AB1, HSP27, GPX1, XRCC1, BAG-1, HHR23A, FAP48, and C-FOS. No gender-specific differences or relationship to number of missions flown was observed. This study provides a first assessment of transcriptomic changes occurring in the whole blood of astronauts in response to spaceflight.

Salmonella enterica serovar Typhimurium strains belonging to sequence type ST313 are a major cause of fatal bacteremia among HIV-infected adults and children in sub-Saharan Africa. Unlike “classical” non-typhoidal Salmonella (NTS), gastroenteritis is often absent during ST313 infections and isolates are most commonly recovered from blood, rather than from stool. This is consistent with observations in animals, in which ST313 strains displayed lower levels of intestinal colonization and higher recovery from deeper tissues relative to classic NTS isolates. A better understanding of the key environmental factors regulating these systemic infections is urgently needed. Our previous studies using dynamic Rotating Wall Vessel (RWV) bioreactor technology demonstrated that physiological levels of fluid shear regulate virulence, gene expression, and stress response profiles of classic S. Typhimurium. Here we provide the first demonstration that fluid shear alters the virulence potential and pathogenesis-related stress responses of ST313 strain D23580 in a manner that differs from classic NTS.

Three-dimensional models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by two-dimensional monolayers and respond to Salmonella in key ways that reflect in vivo infections. To further enhance the physiological relevance of three-dimensional models to more closely approximate in vivo intestinal microenvironments encountered by Salmonella, we developed and validated a novel three-dimensional co-culture infection model of colonic epithelial cells and macrophages using the NASA Rotating Wall Vessel bioreactor. First, U937 cells were activated upon collagen-coated scaffolds. HT-29 epithelial cells were then added and the three-dimensional model was cultured in the bioreactor until optimal differentiation was reached, as assessed by immunohistochemical profiling and bead uptake assays. The new co-culture model exhibited in vivo-like structural and phenotypic characteristics, including three-dimensional architecture, apical-basolateral polarity, well-formed tight/adherens junctions, mucin, multiple epithelial cell types, and functional macrophages. Phagocytic activity of macrophages was confirmed by uptake of inert, bacteria-sized beads. Contribution of macrophages to infection was assessed by colonization studies of Salmonella pathovars with different host adaptations and disease phenotypes (Typhimurium ST19 strain SL1344 and ST313 strain D23580; Typhi Ty2). In addition, Salmonella were cultured aerobically or microaerobically, recapitulating environments encountered prior to and during intestinal infection, respectively. All Salmonella strains exhibited decreased colonization in co-culture (HT-29-U937) relative to epithelial (HT-29) models, indicating antimicrobial function of macrophages. Interestingly, D23580 exhibited enhanced replication/survival in both models following invasion. Pathovar-specific differences in colonization and intracellular co-localization patterns were observed. These findings emphasize the power of incorporating a series of related three-dimensional models within a study to identify microenvironmental factors important for regulating infection.

We study the so-called Descent, or [bar over Q], Equation for the null polygonal supersymmetric Wilson loop in the framework of the pentagon operator product expansion. To properly address this problem, one requires to restore the cyclicity of the loop broken by the choice of OPE channels. In the course of the study, we unravel a phenomenon of twist enhancement when passing to a cyclically shifted channel. Currently, we focus on the consistency of the all-order Descent Equation for the particular case relating the NMHV heptagon to MHV hexagon. We find that the equation establishes a relation between contributions of different twists and successfully verify it in perturbation theory making use of available bootstrap predictions for elementary pentagons.

We present a new approach to computing event shape distributions or, more precisely, charge flow correlations in a generic conformal field theory (CFT). These infrared finite observables are familiar from collider physics studies and describe the angular distribution of global charges in outgoing radiation created from the vacuum by some source. The charge flow correlations can be expressed in terms of Wightman correlation functions in a certain limit. We explain how to compute these quantities starting from their Euclidean analogues by means of a nontrivial analytic continuation which, in the framework of CFT, can be performed elegantly in Mellin space. The relation between the charge flow correlations and Euclidean correlation functions can be reformulated directly in configuration space, bypassing the Mellin representation, as a certain Lorentzian double discontinuity of the correlation function integrated along the cuts. We illustrate the general formalism in N = 4 SYM, making use of the well-known results on the four-point correlation function of half-BPS scalar operators. We compute the double scalar flow correlation in N = 4 SYM, at weak and strong coupling and show that it agrees with known results obtained by different techniques. One of the remarkable features of the N = 4 theory is that the scalar and energy flow correlations are proportional to each other. Imposing natural physical conditions on the energy flow correlations (finiteness, positivity and regularity), we formulate additional constraints on the four-point correlation functions in N = 4SYM that should be valid at any coupling and away from the planar limit.

We analyze the near-collinear limit of the null polygonal hexagon super Wilson loop in the planar N = 4 super-Yang–Mills theory. We focus on its Grassmann components which are dual to next-to-maximal helicity-violating (NMHV) scattering amplitudes. The kinematics in question is studied within a framework of the operator product expansion that encodes propagation of excitations on the background of the color flux tube stretched between the sides of Wilson loop contour. While their dispersion relation is known to all orders in 't Hooft coupling from previous studies, we find their form factor couplings to the Wilson loop. This is done making use of a particular tessellation of the loop where pentagon transitions play a fundamental role. Being interested in NMHV amplitudes, the corresponding building blocks carry a nontrivial charge under the SU(4) R-symmetry group. Restricting the current consideration to twist-two accuracy, we analyze two-particle contributions with a fermion as one of the constituents in the pair. We demonstrate that these nonsinglet pentagons obey bootstrap equations that possess consistent solutions for any value of the coupling constant. To confirm the correctness of these predictions, we calculate their contribution to the super Wilson loop demonstrating agreement with recent results to four-loop order in 't Hooft coupling.

We study event shapes in N = 4SYM describing the angular distribution of energy and R-charge in the final states created by the simplest half-BPS scalar operator. Applying the approach developed in the companion paper arXiv:1309.0769, we compute these observables using the correlation functions of certain components of the N = 4 stress-tensor supermultiplet: the half-BPS operator itself, the R-symmetry current and the stress tensor. We present master formulas for the all-order event shapes as convolutions of the Mellin amplitude defining the correlation function of the half-BPS operators, with a coupling-independent kernel determined by the choice of the observable. We find remarkably simple relations between various event shapes following from N = 4 superconformal symmetry. We perform thorough checks at leading order in the weak coupling expansion and show perfect agreement with the conventional calculations based on amplitude techniques. We extend our results to strong coupling using the correlation function of half-BPS operators obtained from the AdS/CFT correspondence.

Low fluid shear force, including that encountered in microgravity models, induces bacterial responses, but the range of bacteria capable of responding to this signal remains poorly characterized. We systematically analyzed a range of Gram negative Enterobacteriaceae for conservation of the low-shear modeled microgravity (LSMMG) response using phenotypic assays, qPCR, and targeted mutations. Our results indicate LSMMG response conservation across Enterobacteriacae with potential variance in up- or down-regulation of a given response depending on genus. Based on the data, we analyzed the role of the trp operon genes and the TrpR regulator in the LSMMG response using targeted mutations in these genes in S. Typhimurium and E. coli. We found no alteration of the LSMMG response compared to WT in these mutant strains under the conditions tested here. To our knowledge, this study is first-of-kind for Citrobacter, Enterobacter, and Serratia, presents novel data for Escherichia, and provides the first analysis of trp genes in LSMMG responses. This impacts our understanding of how LSMMG affects bacteria and our ability to modify bacteria with this condition in the future.