• A BERT-based One-Pass Multi-Task Model for Clinical Temporal Relation Extraction

      Lin, Chen; Miller, Timothy; Dligach, Dmitriy; Sadeque, Farig; Bethard, Steven; Savova, Guergana; Univ Arizona (ASSOC COMPUTATIONAL LINGUISTICS-ACL, 2020-07)
      Recently BERT has achieved a state-of-the-art performance in temporal relation extraction from clinical Electronic Medical Records text. However, the current approach is inefficient as it requires multiple passes through each input sequence. We extend a recently-proposed one-pass model for relation classification to a one-pass model for relation extraction. We augment this framework by introducing global embeddings to help with long-distance relation inference, and by multi-task learning to increase model performance and generalizability. Our proposed model produces results on par with the state-of-the-art in temporal relation extraction on the THYME corpus and is much "greener" in computational cost.
    • A Brighter Future: The Effect of Social Class on Responses to Future Debt

      Schmitt, Harrison J.; Keefer, Lucas A.; Sullivan, Daniel; Stewart, Sheridan; Young, Isaac F.; Univ Arizona, Dept Psychol (PSYCHOPEN, 2020-07)
      The present study serves as an exploratory investigation of the role of social class in responses to the threat of future debt. Previous work has shown that individuals of high and low subjective social class differ in the ways that they respond to a broad range of threats and uncertainties about the future. Across three studies, we found that lower social class individuals expect more future debt and suffer greater attendant stress than higher class individuals (Study 1). We found that experimental manipulations of debt salience increased stress for lower class and not for higher class individuals (Studies 2-3). Likewise, we found that higher class individuals experienced higher affect balance and perceptions of personal control when the possibility of future debt was made salient, specifically as a function of decreased fatalism about future debt (Study 3). These three studies reveal yet another situation in which individuals of lower and higher social class respond differently to threat, and serve as an important step toward understanding the psychological ramifications of rising debt in the United States.
    • A community-maintained standard library of population genetic models

      Adrion, Jeffrey R.; Cole, Christopher B.; Dukler, Noah; Galloway, Jared G.; Gladstein, Ariella L.; Gower, Graham; Kyriazis, Christopher C.; Ragsdale, Aaron P.; Tsambos, Georgia; Baumdicker, Franz; et al. (ELIFE SCIENCES PUBLICATIONS LTD, 2020-06)
      The explosion in population genomic data demands ever more complex modes of analysis, and increasingly, these analyses depend on sophisticated simulations. Recent advances in population genetic simulation have made it possible to simulate large and complex models, but specifying such models for a particular simulation engine remains a difficult and error-prone task. Computational genetics researchers currently re-implement simulation models independently, leading to inconsistency and duplication of effort. This situation presents a major barrier to empirical researchers seeking to use simulations for power analyses of upcoming studies or sanity checks on existing genomic data. Population genetics, as a field, also lacks standard benchmarks by which new tools for inference might be measured. Here, we describe a new resource, stdpopsim, that attempts to rectify this situation. Stdpopsim is a community-driven open source project, which provides easy access to a growing catalog of published simulation models from a range of organisms and supports multiple simulation engine backends. This resource is available as a well-documented python library with a simple command-line interface. We share some examples demonstrating how stdpopsim can be used to systematically compare demographic inference methods, and we encourage a broader community of developers to contribute to this growing resource.
    • A Comprehensive Analysis of Triggers and Risk Factors for Asthma Based on Machine Learning and Large Heterogeneous Data Sources

      Zhang, Wenli; Ram, Sudha; Univ Arizona, Eller Coll Management (SOC INFORM MANAGE-MIS RES CENT, 2020)
      Asthma is a common chronic health condition affecting millions of people in the United States. While asthma cannot be cured, it can be managed if we identify and understand triggers and risk factors that cause asthma exacerbations. However, this is challenging because these triggers and risk factors are complex and interconnected, and there are limitations to current mainstream approaches for identifying them. The recent availability of massive amounts of heterogeneous data has opened up new possibilities for asthma triggers and risk factors analyses. In this study, we introduce a data-driven framework, adapt and integrate multiple advanced machine learning techniques, and perform an empirical analysis to (1) derive characteristics of selfreported asthma patients from social media, (2) enable integration and repurposing of highly heterogeneous and commonly available datasets, and (3) uncover the sequential patterns of asthma triggers and risk factors, and their relative importance, both of which are difficult to achieve via retrospective cohort-based studies. Our methods and results can provide guidance for developing asthma management plans and interventions for specific subpopulations and, eventually, have the potential to reduce the societal burden of asthma.
    • A Diffuse Metal-poor Component of the Sagittarius Stream Revealed by the H3 Survey

      Johnson, Benjamin D.; Conroy, Charlie; Naidu, Rohan P.; Bonaca, Ana; Zaritsky, Dennis; Ting, Yuan-Sen; Cargile, Phillip A.; Han, Jiwon Jesse; Speagle, Joshua S.; Univ Arizona, Steward Observ (IOP PUBLISHING LTD, 2020-09)
      The tidal disruption of the Sagittarius dwarf galaxy has generated a spectacular stream of stars wrapping around the entire Galaxy. We use data from Gaia and the H3 Stellar Spectroscopic Survey to identify 823 high-quality Sagittarius members based on their angular momenta. The H3 Survey is largely unbiased in metallicity, and so our sample of Sagittarius members is similarly unbiased. Stream stars span a wide range in [Fe/H] from -0.2 to -3.0, with a mean overall metallicity of <[F/H]> = -0.99. We identify a strong metallicity dependence to the kinematics of the stream members. At [Fe/H] > -0.8 nearly all members belong to the well-known cold (sigma(v) < 20 km s(-1)) leading and trailing arms. At intermediate metallicities (-1.9 < [Fe/H] < -0.8) a significant population (24%) emerges of stars that are kinematically offset from the cold arms. These stars also appear to have hotter kinematics. At the lowest metallicities ([Fe/H] less than or similar to -2), the majority of stars (69%) belong to this kinematically offset diffuse population. Comparison to simulations suggests that the diffuse component was stripped from the Sagittarius progenitor at earlier epochs, and therefore resided at larger radius on average than the colder metal-rich component. We speculate that this kinematically diffuse, low-metallicity population is the stellar halo of the Sagittarius progenitor system.
    • A Meta-Analysis of the "Erasing Race" Effect in the United States and Some Theoretical Considerations

      Woodley Of Menie, Michael A.; Heeney, Michael D.; Penaherrera-Aguirre, Mateo; Sarraf, Matthew A.; Banner, Randy; Rindermann, Heiner; Univ Arizona, Dept Psychol (FRONTIERS MEDIA SA, 2020-08)
      The "erasing race" effect is the reduction of the salience of "race" as an alliance cue when recalling coalition membership, once more accurate information about coalition structure is presented. We conducted a random-effects model meta-analysis of this effect using five United States studies (containing nine independent effect sizes). The effect was found (rho = 0.137,K= 9, 95% CI = 0.085 to 0.188). However, no decline effect or moderation effects were found (a "decline effect" in this context would be a decrease in the effect size over time). Furthermore, we found little evidence of publication bias. Synthetically correcting the effect size for bias stemming from the use of an older method for calculating error base rates reduced the magnitude of the effect, but the it remained significant. Taken together, these findings indicate that the "erasing race" effect generalizes quite well across experimental contexts and would, therefore, appear to be quite robust. We reinterpret the theoretical basis for these effects in line with Brunswikian evolutionary-developmental theory and present a series of predictions to guide future research in this area.
    • A New Crater Near InSight: Implications for Seismic Impact Detectability on Mars

      Daubar, I. J.; Lognonne, P.; Teanby, N. A.; Collins, G. S.; Clinton, J.; Staehler, S.; Spiga, A.; Karakostas, F.; Ceylan, S.; Malin, M.; et al. (AMER GEOPHYSICAL UNION, 2020-08)
      A new 1.5 m diameter impact crater was discovered on Mars only similar to 40 km from the InSight lander. Context camera images constrained its formation between 21 February and 6 April 2019; follow-up High Resolution Imaging Science Experiment images resolved the crater. During this time period, three seismic events were identified in InSight data. We derive expected seismic signal characteristics and use them to evaluate each of the seismic events. However, none of them can definitively be associated with this source. Atmospheric perturbations are generally expected to be generated during impacts; however, in this case, no signal could be identified as related to the known impact. Using scaling relationships based on the terrestrial and lunar analogs and numerical modeling, we predict the amplitude, peak frequency, and duration of the seismic signal that would have emanated from this impact. The predicted amplitude falls near the lowest levels of the measured seismometer noise for the predicted frequency. Hence, it is not surprising this impact event was not positively identified in the seismic data. Finding this crater was a lucky event as its formation this close to InSight has a probability of only similar to 0.2, and the odds of capturing it in before and after images are extremely low. We revisit impact-seismic discriminators in light of real experience with a seismometer on the Martian surface. Using measured noise of the instrument, we revise our previous prediction of seismic impact detections downward, from similar to a few to tens, to just similar to 2 per Earth year, still with an order of magnitude uncertainty.
    • A Numerical Study of Metachronal Propulsion at Low to Intermediate Reynolds Numbers

      Granzier-Nakajima, Shawtaroh; Guy, Robert D.; Zhang-Molina, Calvin; Univ Arizona, Dept Math (MDPI, 2020-06)
      Inspired by the forward swimming of long-tailed crustaceans, we study an underwater propulsion mechanism for a swimming body with multiple rigid paddles attached underneath undergoing cycles of power and return strokes with a constant phase-difference between neighboring paddles, a phenomenon known as metachronal propulsion. To study how inter-paddle phase-difference affects flux production, we develop a computational fluid dynamics model and a numerical algorithm based on the immersed boundary method, which allows us to simulate metachronal propulsion at Reynolds numbers (RE) ranging from close to 0 to about 100. Our main finding is that the highest average flux is generated when nearest-neighbor paddles maintain an approximate 20%-25% phase-difference with the more posterior paddle leading the cycle; this result is independent of stroke frequency across the full range of RE considered here. We also find that the optimal paddle spacing and the number of paddles depend on RE; we see a qualitative transition in the dynamics of flow generated by metachronal propulsion as RE rises above 80. Roughly speaking, in terms of average flux generation, a tight paddle spacing is preferred when RE is less than 10, but a wider spacing becomes clearly favored when RE is close to or above 100. In terms of efficiency of flux generation, at RE 0.1 the maximum efficiency occurs at two paddles, and the efficiency decreases as the number of paddles increases. At RE 100 the efficiency increases as the number of paddles increases, and it appears to saturate by eight paddles, whereas using four paddles is a good tradeoff for both low and intermediate RE.
    • A Rainfall Intensity Data Rescue Initiative for Central Chile Utilizing a Pluviograph Strip Charts Reader (PSCR)

      Pizarro-Tapia, Roberto; Gonzalez-Leiva, Fernando; Valdes-Pineda, Rodrigo; Ingram, Ben; Sanguesa, Claudia; Vallejos, Carlos; Univ Arizona, Dept Hydrol & Atmospher Sci (MDPI, 2020-07)
      To develop intensity-duration-frequency (IDF) curves, it is necessary to calculate annual maximum rainfall intensities for different durations. Traditionally, these intensities have been calculated from the analysis of traces recorded by rain gauges on pluviograph strip charts (PSCs). For many years, these charts have been recorded and analyzed by the personnel who operate and maintain the pluviograph gauges, thus the reliability of the observational analysis depends exclusively on the professional experience of the person performing the analysis. Traditionally, the analyzed PSCs are physically stored in data repository centers. After storing rainfall data on aging paper for many years, the risk of losing rainfall records is very high. Therefore, the conversion of PSC records to digital format is crucial to preserve and improve the historical instrumental data base of these records. We conducted the first "Data Rescue Initiative" (DRI) for central Chile using a pluviograph strip charts reader (PSCR), a tool that uses a scanner-type device combined with digital image processing techniques to estimate maximum rainfall intensities for different durations for each paper band (>80,000 paper bands). On the paper bands, common irregularities associated with excess ink, annotations, or blemishes can affect the scanning process; this system was designed with a semi-automatic module that allows users to edit the detected trace to improve the recognition of the data from each PSC. The PSCR's semi-automatic characteristics were designed to read many PSCs in a short period of time. The tool also allows for the calculation of rainfall intensities in durations ranging between 15 min to 1 h. This capability improves the value of the data for water infrastructure design, since intense storms of shorter duration often have greater impacts than longer but less intense storms. In this study, the validation of the PSCR against records obtained from observational analysis showed no significant differences between maximum rainfall intensities for durations of 1 h, 6 h, and 24 h.
    • A Statistical Standard Siren Measurement of the Hubble Constant from the LIGO/Virgo Gravitational Wave Compact Object Merger GW190814 and Dark Energy Survey Galaxies

      Palmese, A.; deVicente, J.; Pereira, M. E. S.; Annis, J.; Hartley, W.; Herner, K.; Soares-Santos, M.; Crocce, M.; Huterer, D.; Magana Hernandez, I.; et al. (IOP PUBLISHING LTD, 2020-09)
      We present a measurement of the Hubble constant H-0 using the gravitational wave (GW) event GW190814, which resulted from the coalescence of a 23M(circle dot) black hole with a 2.6M(circle dot) compact object, as a standard siren. No compelling electromagnetic counterpart has been identified for this event; thus our analysis accounts for thousands of potential host galaxies within a statistical framework. The redshift information is obtained from the photometric redshift (photo-z) catalog from the Dark Energy Survey. The luminosity distance is provided by the LIGO/Virgo gravitational wave sky map. Since this GW event has the second-smallest localization volume after GW170817, GW190814 is likely to provide the best constraint on cosmology from a single standard siren without identifying an electromagnetic counterpart. Our analysis uses photo-z probability distribution functions and corrects for photoz biases. We also reanalyze the binary black hole GW170814 within this updated framework. We explore how our findings impact the H-0 constraints from GW170817, the only GW merger associated with a unique host galaxy. From a combination of GW190814, GW170814, and GW170817, our analysis yields H-0 = 72.0(-8.2)(+12) km s(-1) Mpc(-1) (68% highest-density interval, HDI) for a prior in H-0 uniform between [20and140] km s(-1)Mpc(-1). The addition of GW190814 and GW170814 to GW170817 improves the 68% HDI from GW170817 alone by similar to 18%, showing how well-localized mergers without counterparts can provide a significant contribution to standard siren measurements, provided that a complete galaxy catalog is available at the location of the event.
    • A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity

      O'Connor, Roberta M.; Nepveux, Felix J.; Abenoja, Jaypee; Bowden, Gregory; Reis, Patricia; Beaushaw, Josiah; Relat, Rachel M. Bone; Driskell, Iwona; Gimenez, Fernanda; Riggs, Michael W.; et al. (PUBLIC LIBRARY SCIENCE, 2020-05)
      Apicomplexan parasites cause severe disease in both humans and their domesticated animals. Since these parasites readily develop drug resistance, development of new, effective drugs to treat infection caused by these parasites is an ongoing challenge for the medical and veterinary communities. We hypothesized that invertebrate-bacterial symbioses might be a rich source of anti-apicomplexan compounds because invertebrates are susceptible to infections with gregarines, parasites that are ancestral to all apicomplexans. We chose to explore the therapeutic potential of shipworm symbiotic bacteria as they are bona fide symbionts, are easily grown in axenic culture and have genomes rich in secondary metabolite loci [1,2]. Two strains of the shipworm symbiotic bacterium, Teredinibacter turnerae, were screened for activity against Toxoplasma gondii and one strain, T7901, exhibited activity against intracellular stages of the parasite. Bioassay-guided fractionation identified tartrolon E (trtE) as the source of the activity. TrtE has an EC50 of 3 nM against T. gondii, acts directly on the parasite itself and kills the parasites after two hours of treatment. TrtE exhibits nanomolar to picomolar level activity against Cryptosporidium, Plasmodium, Babesia, Theileria, and Sarcocystis; parasites representing all branches of the apicomplexan phylogenetic tree. The compound also proved effective against Cryptosporidium parvum infection in neonatal mice, indicating that trtE may be a potential lead compound for preclinical development. Identification of a promising new compound after such limited screening strongly encourages further mining of invertebrate symbionts for new anti-parasitic therapeutics. Author summary Apicomplexans are intracellular protozoan parasites that cause significant disease in humans and the livestock we rely on for food. Because these parasites easily develop drug resistance, new drugs are always needed. To identify new anti-apicomplexan drugs, we investigated the compounds produced by symbiotic bacteria of shipworms, marine mollusks that burrow into and eat wood. We screened shipworm symbiotic bacteria for anti-parasitic activity and identified a compound, tartrolon E, with potent, rapid, highly selective and irreversible activity against parasites representing all branches of the apicomplexan tree. This compound was also highly effective in neonatal mice against infection with the intestinal apicomplexan parasite, Cryptosporidium. This study describes the first pan-anti-apicomplexan compound and unveils an unexplored source of anti-parasitic compounds.
    • A thirty-four billion solar mass black hole in SMSS J2157-3602, the most luminous known quasar

      Onken, Christopher A.; Bian, Fuyan; Fan, Xiaohui; Wang, Feige; Wolf, Christian; Yang, Jinyi; Univ Arizona, Steward Observ (OXFORD UNIV PRESS, 2020-08)
      From near-infrared spectroscopic measurements of the Mg II emission line doublet, we estimate the black hole (BH) mass of the quasar, SMSS J215728.21-360215.1, as being (3.4 +/- 0.6) x 10(10) M circle dot and refine the redshift of the quasar to be z = 4.692. SMSS J2157 is the most luminous known quasar, with a 3000 angstrom luminosity of (4.7 +/- 0.5) x 10(47) erg s(-1) and an estimated bolometric luminosity of 1.6 x 10(48) erg s(-1), yet its Eddington ratio is only similar to 0.4. Thus, the high luminosity of this quasar is a consequence of its extremely large BH - one of the most massive BHs at z > 4.
    • A Very Young Age for True Polar Wander on Europa From Related Fracturing

      Schenk, Paul; Matsuyama, Isamu; Nimmo, Francis; Univ Arizona, Lunar & Planetary Lab (AMER GEOPHYSICAL UNION, 2020-09)
      En echelon fissures 100-300 km long on Europa are found to be concentric and external to arcuate troughs previously attributed to true polar wander (TPW) of Europa's ice shell, strengthening the case for TPW. Fissures are composed of parallel faults distributed over 10-to-20-km-wide zones, with deformation focused in a main fissure 1-2 km wide and up to 200 m deep. Fissures crosscut all known terrains, including (apparently) ejecta of bright ray crater Manannan, establishing that fissures and by inference TPW are among the most recent geologic events on Europa. Very late similar to 70 degrees of TPW shell rotation requires that most observed structures on Europa are not in their original configuration with respect to other stress regimes, requiring complete reanalysis of Europa's strain history. If reorientation happened recently, we predict that any crater distribution asymmetries and shell thickness variations measured by Europa Clipper will be offset from expected equilibrium patterns. Plain Language Summary The large icy ocean world of Europa has a very young surface that has been highly deformed. Recent evidence for "polar wander," or reorientation of the floating outer ice shell away from its original orientation, has been confirmed by the recognition that long fissures are part of the polar wander tectonic pattern and arc among the youngest features on the planet. This means that polar wander occurred very recently and that older features are no longer in their original locations and will require a complete reassessment of Europa's tectonic history.
    • A Warm Jupiter Transiting an M Dwarf: A TESS Single-transit Event Confirmed with the Habitable-zone Planet Finder

      Canas, Caleb I.; Stefansson, Gudmundur; Kanodia, Shubham; Mahadevan, Suvrath; Cochran, William D.; Endl, Michael; Robertson, Paul; Bender, Chad F.; Ninan, Joe P.; Beard, Corey; et al. (IOP PUBLISHING LTD, 2020-09)
      We confirm the planetary nature of a warm Jupiter transiting the early M dwarf TOI-1899 using a combination of available TESS photometry; high-precision, near-infrared spectroscopy with the Habitable-zone Planet Finder; and speckle and adaptive optics imaging. The data reveal a transiting companion on an similar to 29 day orbit with a mass and radius of 0.66 +/- 0.07 M-J and 1.15(-0.05)(+0.04) R-J, respectively. The star, TOI-1899, is the lowest-mass star known to host a transiting warm Jupiter, and we discuss the follow-up opportunities afforded by a warm (T-eq similar to 362 K) gas giant orbiting an M0 star. Our observations reveal that TOI-1899.01 is a puffy warm Jupiter, and we suggest additional transit observations to both refine the orbit and constrain the true dilution observed in TESS.
    • A wind-albedo-wind feedback driven by landscape evolution

      Abell, Jordan T.; Pullen, Alex; Lebo, Zachary J.; Kapp, Paul; Gloege, Lucas; Metcalf, Andrew R.; Nie, Junsheng; Winckler, Gisela; Univ Arizona, Dept Geosci (NATURE PUBLISHING GROUP, 2020-01)
      The accurate characterization of near-surface winds is critical to our understanding of past and modern climate. Dust lofted by these winds has the potential to modify surface and atmospheric conditions as well as ocean biogeochemistry. Stony deserts, low dust emitting regions today, represent expansive areas where variations in surficial geology through time may drastically impact near-surface conditions. Here we use the Weather Research and Forecasting (WRF) model over the western Gobi Desert to demonstrate a previously undocumented process between wind-driven landscape evolution and boundary layer conditions. Our results show that altered surficial thermal properties through winnowing of fine-grained sediments and formation of low-albedo gravel-mantled surfaces leads to an increase in near-surface winds by up to 25%; paradoxically, wind erosion results in faster winds regionally. This wind-albedo-wind feedback also leads to an increase in the frequency of hours spent at higher wind speeds, which has implications for dust emission potential.
    • a-numbers of curves in Artin–Schreiercovers

      Booher, Jeremy; Cais, Bryden; Univ Arizona, Dept Math (MATHEMATICAL SCIENCE PUBL, 2020-06-01)
      Let pi : Y -> X be a branched Z/pZ-cover of smooth, projective, geometrically connected curves over a perfect field of characteristic p > 0. We investigate the relationship between the a-numbers of Y and X and the ramification of the map pi. This is analogous to the relationship between the genus (respectively p-rank) of Y and X given the Riemann-Hurwitz (respectively Deuring-Shafarevich) formula. Except in special situations, the a-number of Y is not determined by the a-number of X and the ramification of the cover, so we instead give bounds on the a-number of Y. We provide examples showing our bounds are sharp. The bounds come from a detailed analysis of the kernel of the Cartier operator.
    • The Abacus Cosmos: A Suite of Cosmological N-body Simulations

      Garrison, Lehman H.; Eisenstein, Daniel J.; Ferrer, Douglas; Tinker, Jeremy L.; Pinto, Philip A.; Weinberg, David H.; Univ Arizona, Steward Observ (IOP PUBLISHING LTD, 2018-06)
      We present a public data release of halo catalogs from a suite of 125 cosmological N-body simulations from the ABACUS project. The simulations span 40 wCDM cosmologies centered on the Planck 2015 cosmology at two mass resolutions, 4 x 10(10) h(-1) M-circle dot and 1 x 10(10) h(-1) M-circle dot, in 1.1 h(-1) Gpc and 720 h(-1) Mpc boxes, respectively. The boxes are phase-matched to suppress sample variance and isolate cosmology dependence. Additional volume is available via 16 boxes of fixed cosmology and varied phase; a few boxes of single-parameter excursions from Planck 2015 are also provided. Catalogs spanning z = 1.5 to 0.1 are available for friends-of-friends and ROCKSTAR halo finders and include particle subsamples. All data products are available at https://lgarrison.github.io/AbacusCosmos.
    • ABC Transporter Genes Show Upregulated Expression in Drug-Resistant Clinical Isolates of Candida auris: A Genome-Wide Characterization of ATP-Binding Cassette (ABC) Transporter Genes

      Wasi, Mohd; Khandelwal, Nitesh Kumar; Moorhouse, Alexander J.; Nair, Remya; Vishwakarma, Poonam; Bravo Ruiz, Gustavo; Ross, Zoe K.; Lorenz, Alexander; Rudramurthy, Shivaprakash M.; Chakrabarti, Arunaloke; et al. (FRONTIERS MEDIA SA, 2019-07-16)
      ATP-binding cassette (ABC) superfamily members have a key role as nutrient importers and exporters in bacteria. However, their role as drug exporters in eukaryotes brought this superfamily member to even greater prominence. The capacity of ABC transporters to efflux a broad spectrum of xenobiotics represents one of the major mechanisms of clinical multidrug resistance in pathogenic fungi including Candida species. Candida auris, a newly emerged multidrug-resistant fungal pathogen of humans, has been responsible for multiple outbreaks of drug-resistant infections in hospitals around the globe. Our study has analyzed the entire complement of ABC superfamily transporters to assess whether these play a major role in drug resistance mechanisms of C. auris. Our bioinformatics analyses identified 28 putative ABC proteins encoded in the genome of the C. auris type-strain CBS 10913T; 20 of which contain transmembrane domains (TMDs). Quantitative real-time PCR confirmed the expression of all 20 TMD transporters, underlining their potential in contributing to the C. auris drug-resistant phenotype. Changes in transcript levels after short-term exposure of drugs and in drug-resistant C. auris isolates suggested their importance in the drug resistance phenotype of this pathogen. CAUR_02725 orthologous to CDR1, a major multidrug exporter in other yeasts, showed consistently higher expression in multidrug-resistant strains of C. auris. Homologs of other ABC transporter genes, such as CDR4, CDR6, and SNQ2, also displayed raised expression in a sub-set of clinical isolates. Together, our analysis supports the involvement of these transporters in multidrug resistance in C. auris.
    • ABC transporter mis-splicing associated with resistance to Bt toxin Cry2Ab in laboratory- and field-selected pink bollworm

      Mathew, Lolita G.; Ponnuraj, Jeyakumar; Mallappa, Bheemanna; Chowdary, Lingutla R.; Zhang, Jianwei; Tay, Wee Tek; Walsh, Thomas K.; Gordon, Karl H. J.; Heckel, David G.; Downes, Sharon; et al. (NATURE PUBLISHING GROUP, 2018-09-10)
      Evolution of pest resistance threatens the benefits of genetically engineered crops that produce Bacillus thuringiensis (Bt) insecticidal proteins. Strategies intended to delay pest resistance are most effective when implemented proactively. Accordingly, researchers have selected for and analyzed resistance to Bt toxins in many laboratory strains of pests before resistance evolves in the field, but the utility of this approach depends on the largely untested assumption that laboratory-and field-selected resistance to Bt toxins are similar. Here we compared the genetic basis of resistance to Bt toxin Cry2Ab, which is widely deployed in transgenic crops, between laboratory-and field-selected populations of the pink bollworm (Pectinophora gossypiella), a global pest of cotton. We discovered that resistance to Cry2Ab is associated with mutations disrupting the same ATP-binding cassette transporter gene (PgABCA2) in a laboratory-selected strain from Arizona, USA, and in field-selected populations from India. The most common mutation, loss of exon 6 caused by alternative splicing, occurred in resistant larvae from both locations. Together with previous data, the results imply that mutations in the same gene confer Bt resistance in laboratory-and field-selected strains and suggest that focusing on ABCA2 genes may help to accelerate progress in monitoring and managing resistance to Cry2Ab.
    • ABCC2 is associated with Bacillus thuringiensis Cry1Ac toxin oligomerization and membrane insertion in diamondback moth

      Ocelotl, Josue; Sánchez, Jorge; Gómez, Isabel; Tabashnik, Bruce E.; Bravo, Alejandra; Soberón, Mario; Univ Arizona, Dept Entomol (NATURE PUBLISHING GROUP, 2017-05-24)
      Cry1A insecticidal toxins bind sequentially to different larval gut proteins facilitating oligomerization, membrane insertion and pore formation. Cry1Ac interaction with cadherin triggers oligomerization. However, a mutation in an ABC transporter gene (ABCC2) is linked to Cry1Ac resistance in Plutella xylostella. Cry1AcMod, engineered to lack helix alpha-1, was able to form oligomers without cadherinbinding and effectively countered Cry1Ac resistance linked to ABCC2. Here we analyzed Cry1Ac and Cry1AcMod binding and oligomerization by western blots using brush border membrane vesicles (BBMV) from a strain of P. xylostella susceptible to Cry1Ac (Geneva 88) and a strain with resistance to Cry1Ac (NO-QAGE) linked to an ABCC2 mutation. Resistance correlated with lack of specific binding and reduced oligomerization of Cry1Ac in BBMV from NO-QAGE. In contrast, Cry1AcMod bound specifically and still formed oligomers in BBMV from both strains. We compared association of pre-formed Cry1Ac oligomer, obtained by incubating Cry1Ac toxin with a Manduca sexta cadherin fragment, with BBMV from both strains. Our results show that pre-formed oligomers associate more efficiently with BBMV from Geneva 88 than with BBMV from NO-QAGE, indicating that the ABCC2 mutation also affects the association of Cry1Ac oligomer with the membrane. These data indicate, for the first time, that ABCC2 facilitates Cry1Ac oligomerization and oligomer membrane insertion in P. xylostella.