• HSP60/10 chaperonin systems are inhibited by a variety of approved drugs, natural products, and known bioactive molecules

      Stevens, Mckayla; Abdeen, Sanofar; Salim, Nilshad; Ray, Anne-Marie; Washburn, Alex; Chitre, Siddhi; Sivinski, Jared; Park, Yangshin; Hoang, Quyen Q; Chapman, Eli; Johnson, Steven M; Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol (PERGAMON-ELSEVIER SCIENCE LTD, 2019-05-01)
      All living organisms contain a unique class of molecular chaperones called 60 kDa heat shock proteins (HSP60 - also known as GroEL in bacteria). While some organisms contain more than one HSP60 or GroEL isoform, at least one isoform has always proven to be essential. Because of this, we have been investigating targeting HSP60 and GroEL chaperonin systems as an antibiotic strategy. Our initial studies focused on applying this antibiotic strategy for treating African sleeping sickness (caused by Trypanosoma brucei parasites) and drug-resistant bacterial infections (in particular Methicillin-resistant Staphylococcus aureus - MRSA). Intriguingly, during our studies we found that three known antibiotics - suramin, closantel, and rafoxanide - were potent inhibitors of bacterial GroEL and human HSP60 chaperonin systems. These findings prompted us to explore what other approved drugs, natural products, and known bioactive molecules might also inhibit HSP60 and GroEL chaperonin systems. Initial high-throughput screening of 3680 approved drugs, natural products, and known bioactives identified 161 hit inhibitors of the Escherichia coli GroEL chaperonin system (4.3% hit rate). From a purchased subset of 60 hits, 29 compounds (48%) re-confirmed as selective GroEL inhibitors in our assays, all of which were nearly equipotent against human HSP60. These findings illuminate the notion that targeting chaperonin systems might be a more common occurrence than we previously appreciated. Future studies are needed to determine if the in vivo modes of action of these approved drugs, natural products, and known bioactive molecules are related to GroEL and HSP60 inhibition.
    • Diagnosing Abnormal Electrocardiogram (ECG) via Deep Learning

      Gao, Xin; Univ Arizona, Dept Elect & Comp Engn (INTECHOPEN, 2019-04-03)
      In this chapter, we investigate the most recent automatic detecting algorithms on abnormal electrocardiogram (ECG) in a variety of cardiac arrhythmias. We present typical examples of a medical case study and technical applications related to diagnosing ECG, which include (i) a recently patented data classifier on the basis of deep learning model, (ii) a deep neural network scheme to diagnose variable types of arrhythmia through wearable ECG monitoring devices, and (iii) implementation of the health cloud platform, which consists of automatic detection, data mining, and classifying via the Android terminal module. Our work establishes a cross-area study, which relates artificial intelligence (AI), deep learning, cloud computing on huge amount of data to minishape ECG monitoring devices, and portable interaction platforms. Experimental results display the technical advantages such as saving cost, better reliability, and higher accuracy of deep learning-based models in contrast to conventional schemes on cardiac diagnosis.
    • Transition to practice experiences of first- and second-career nurses: A mixed-methods study

      Rainbow, Jessica G; Steege, Linsey M; Univ Arizona, Coll Nursing (WILEY, 2019-04-01)
      To explore the transition to nursing practice experiences of first- and second-career nursing students. To address the nursing shortage, alternative educational programmes have been increasingly developed and implemented with to help individuals with prior career experiences transition into a career in nursing (second-career nurses). However, we know little about the transition to practice experiences of second-career nurses. This mixed-methods study utilised qualitative interviews with nurses who had completed a year of practice and a longitudinal survey of nurses' perceptions of stress, coping and burnout throughout their first year of nursing practice. Qualitative data (n = 15) were analysed using latent thematic analysis and following COREQ guidelines. Descriptive and effect size analysis of quantitative data (n = 122) was conducted in order to assess for significant differences across time points.
    • Prevalence and Associated Risk Factors of Diabetes in the African Immigrant Population of Sacramento County, California

      Kindarara, Désiré M; Silva, Graciela E; Univ Arizona, Coll Nursing; Univ Arizona, Coll Publ Hlth (SAGE PUBLICATIONS INC, 2019-04-01)
      The purpose of this study was to determine the prevalence and associated risk factors of diabetes in the African immigrant population in Sacramento County, California. A cross-sectional study was conducted in Sacramento County, California, from June to August 2018. The convenience sample included 126 African immigrants aged 21 years and older. Sociodemographic and clinical characteristics were collected. Hemoglobin A1C (A1C) level, blood pressure, height, and weight were measured per standard methods. Data were analyzed using descriptive statistics and χ Of 126 adult individuals included in this study, 32 (25.4%) had diabetes, of whom 25 (19.8%) were previously diagnosed and 7 (5.6%) represented new cases of diabetes. Also, 36 (28.6%) had prediabetes, of whom 24 (19.1%) had previously been told they had prediabetes and 12 (9.5%) represented new cases of prediabetes. Diabetes and prediabetes were significantly higher among participants in the age group of 36 to 60 years, married, employed full-time, and those with hypertension, high blood cholesterol, and participating in 0 to 2 days per week of moderate physical activities. Only one-fifth of all participants with previously known diabetes or previously on treatment had a good glycemic control status. The present study found a high prevalence of prediabetes, diabetes, and multiple risk factors of diabetes in the African immigrant population, as well as a poor glycemic control among those with diabetes, calling for urgent attention. Strategies aimed to improving a healthy lifestyle in the African immigrant population are necessary to reduce the burden of diabetes.
    • The reality of "food porn": Larger brain responses to food-related cues than to erotic images predict cue-induced eating

      Versace, Francesco; Frank, David W; Stevens, Elise M; Deweese, Menton M; Guindani, Michele; Schembre, Susan M; Univ Arizona, Dept Family & Community Med, Coll Med Tucson (WILEY, 2019-04-01)
      While some individuals can defy the lure of temptation, many others find appetizing food irresistible. The goal of this study was to investigate the neuropsychological mechanisms that increase individuals' vulnerability to cue-induced eating. Using ERPs, a direct measure of brain activity, we showed that individuals with larger late positive potentials in response to food-related cues than to erotic images are more susceptible to cue-induced eating and, in the presence of a palatable food option, eat more than twice as much as individuals with the opposite brain reactivity profile. By highlighting the presence of individual brain reactivity profiles associated with susceptibility to cue-induced eating, these findings contribute to the understanding of the neurobiological basis of vulnerability to obesity.
    • Orbifolds of lattice vertex operator algebras at d = 48 and d = 72

      Gemünden, Thomas; Keller, Christoph A.; Univ Arizona, Dept Math (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2019-04-01)
      Motivated by the notion of extremal vertex operator algebras, we investigate cyclic orbifolds of vertex operator algebras coming from extremal even self-dual lattices in d = 48 and d = 72. In this way we construct about one hundred new examples of holomorphic VOAs with a small number of low weight states. (C) 2019 Elsevier Inc. All rights reserved.
    • Broadband extended source imaging Mueller-matrix polarimeter

      López-Téllez, Juan Manuel; Chipman, Russell A.; Li, Lisa W.; McEldowney, Scott C.; Smith, Matthew H.; Univ Arizona, Coll Opt Sci (OPTICAL SOC AMER, 2019-04-01)
      An imaging Mueller matrix polarimeter, named the red–green–blue (RGB)950, takes images of medium-sized (tens of centimeters) objects by using a very bright source, large polarization state generator, and high-quality camera. Its broadband extended light source switches between red, green, blue, and near-infrared light to allow taking polarimetric images for comparison with RGB camera images. The large diffuse source makes shadow transitions gradual and spreads out the specular reflected spot into a larger less conspicuous area.
    • Industry Familiarity and Trading: Evidence from the Personal Portfolios of Industry Insiders

      Ben-David, Itzhak; Birru, Justin; Rossi, Andrea; Univ Arizona, Eller Coll Management (ELSEVIER SCIENCE SA, 2019-04)
      We study whether industry familiarity is an advantage in stock trading by exploring the trading patterns of industry insiders in their own personal portfolios. To do so, we identify accounts of industry insiders in a large data set provided by a retail discount broker. We find that insiders trade firms from their own industry more frequently. Furthermore, they earn abnormal returns exclusively when trading own-industry stocks, especially obscure stocks (small, low analyst coverage, high volatility). In a battery of tests, we find no evidence of the use of private information. The results are most consistent with the interpretation that industry familiarity is an advantage in stock trading. (C) 2018 Elsevier B.V. All rights reserved.
    • Genetic diversity and metapopulation structure of the brown swimming crab (Callinectes bellicosus) along the coast of Sonora, Mexico: Implications for fisheries management

      Cisneros-Mata, Miguel Ángel; Munguía-Vega, Adrián; Rodríguez-Félix, Demetrio; Aragón-Noriega, Eugenio Alberto; Grijalva-Chon, José Manuel; Arreola-Lizárraga, José Alfredo; Hurtado, Luis A.; Univ Arizona, Sch Nat Resources & Environm (ELSEVIER SCIENCE BV, 2019-04)
      Management of commercial fisheries resources is commonly done assuming that populations are spatially homogeneous throughout their geographic range. However, uneven gene flow can result in gradients of genetic diversity that can affect population dynamics and management reference points and may contribute to over-fishing. We examined whether the brown swimming crab, Callinectes bellicosus, fished along 1200 km on the coast of Sonora (Mexico) is a homogeneous population. Based on previous empirical evidence of differences in phenology, we hypothesized that C. bellicosus has a metapopulation structure which needs to be included in management tools. We conducted a genetic study of C. bellicosus taken at seven sites along the coast of Sonora and obtained their microsatellite genotypes. Recent gene flow, as well as the role of each site as source or sink, were investigated. We found a latitudinal gradient in genetic diversity and identified sites along the coast acting as sources or sinks of migrants. Central sites act as sources, while northern sites are sinks; the main source of migrants was the southern-most site. A predominantly asymmetric metapopulation structure composed of local populations with moderate connectivity may be explained by larval dispersal in the northward oceanic current during the spawning period. Including migration rates between sites in a metapopulation dynamics model of C. bellicosus and considering that fishing and management decisions in source populations will impact neighboring populations located downstream can improve current management of this important commercial fishery.
    • Visible and Near-infrared Laboratory Demonstration of a Simplified Pyramid Wavefront Sensor

      Lozi, Julien; Jovanovic, Nemanja; Guyon, Olivier; Chun, Mark; Jacobson, Shane; Goebel, Sean; Martinache, Frantz; Univ Arizona, Coll Opt Sci (IOP PUBLISHING LTD, 2019-04)
      Wavefront sensing and control are important for enabling one of the key advantages of using large apertures, namely higher angular resolution. Pyramid wavefront sensors are becoming commonplace in new instrument designs owing to their superior sensitivity. However, one remaining roadblock to their widespread use is the fabrication of the pyramidal optic. This complex optic is challenging to fabricate due to the pyramid tip, where four planes need to intersect at a single point. Thus far, only a handful of these have been produced due to the low yields and long lead times. To address this, we present an alternative implementation of the pyramid wavefront sensor which relies instead on two roof prisms. Such prisms are easy and inexpensive to source. We demonstrate the successful operation of the roof prism pyramid wavefront sensor on an 8 m class telescope, at visible and near-infrared wavelengths, for the first time using a SAPHIRA HgCdTe detector without modulation for a laboratory demonstration, and elucidate how this sensor can be used more widely on wavefront control test benches and instruments.
    • Conceptual profile of chemistry: a framework for enriching thinking and action in chemistry education

      Freire, Melquesedeque; Talanquer, Vicente; Amaral, Edenia; Univ Arizona, Dept Chem & Biochem (ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD, 2019-03-24)
      Understanding the nature of chemical thinking and action, as well as their application and impact on our world should be central goals of chemistry education at all educational levels. However, traditional school chemistry is still mostly focused on having students learn the body of declarative knowledge built over the years in the discipline. Achieving changes in curriculum and teaching practices in this context remains a challenging task. Studies in the history and philosophy of the discipline suggest that chemistry has unique characteristics that need to be recognised and considered in chemistry education. Many of these studies point to a pluralism in the discipline, and in the understanding of and about chemistry, that should be characterised and incorporated into our educational models. In this essay, we have attempted to build such a characterisation using conceptual profiles theory to propose a framework that can be used to enrich and support the thinking and action of chemistry teachers at all educational levels.
    • Data Science Support at the Academic Library

      Oliver, Jeffrey C.; Kollen, Christine; Hickson, Benjamin; Rios, Fernando; Office of Digital Innovation and Stewardship, University Libraries, University of Arizona (Taylor & Francis Group, 2019-03-20)
      Data science is a rapidly growing field with applications across all scientific domains. The demand for support in data science literacy is outpacing available resources at college campuses. The academic library is uniquely positioned to provide training and guidance in a number of areas relevant to data science. The University of Arizona Libraries has built a successful data science support program, focusing on computational literacy, geographic information systems, and reproducible science. Success of the program has largely been due to the strength of library personnel and strategic partnerships with units outside of the library. Academic libraries can support campus data science needs through professional development of current staff and recruitment of new personnel with expertise in data-intensive domains.
    • Understanding the relationship between vegetation greenness and productivity across dryland ecosystems through the integration of PhenoCam, satellite, and eddy covariance data

      Yan, D.; Scott, R.L.; Moore, D.J.P.; Biederman, J.A.; Smith, W.K.; Univ Arizona, Sch Nat Resources & Environm (ELSEVIER SCIENCE INC, 2019-03-15)
      Drylands account for approximately 40% of the global land surface and play a dominant role in the trend and variability of terrestrial carbon uptake and storage. Gross ecosystem photosynthesis termed gross primary productivity (GPP) is a critical driver of terrestrial carbon uptake and remains challenging to be observed directly. Currently, vegetation indices that largely capture changes in greenness are the most commonly used datasets in satellite-based GPP modeling. However, there remains significant uncertainty in the spatiotemporal relationship between greenness indices and GPP, especially for relatively heterogeneous dryland ecosystems. In this paper, we compared vegetation greenness indices from PhenoCam and satellite (Landsat and MODIS) observations against GPP estimates from the eddy covariance technique, across three representative ecosystem types of the southwestern United States. We systematically evaluated the changes in the relationship between vegetation greenness indices and GPP: i) across spatial scales of canopy-level, 30-meter, and 500-meter resolution; and ii) across temporal scale of daily, 8-day, 16-day, and monthly resolution. We found that greenness-GPP relationships were independent of spatial scales as long as land cover type and composition remained relatively constant. We also found that the greenness-GPP relationships became stronger as the time interval increased, with the strongest relationships observed at the monthly resolution. We posit that the greenness-GPP relationship breaks down at short timescales because greenness changes more slowly than plant physiological function, which responds rapidly to changes in key biophysical drivers. These findings provide insights into the potential for and limitations of modeling GPP using remotely sensed greenness indices across dryland ecosystem types.
    • Bloch oscillations of multidimensional dark soliton wave packets and light bullets

      Driben, Rodislav; Ma, Xuekai; Schumacher, Stefan; Meier, Torsten; Univ Arizona, Coll Opt Sci (OPTICAL SOC AMER, 2019-03-15)
      The robust propagation of dark solitonic waves featuring Bloch oscillations (BOs) in media with a Kerr nonlinearity is demonstrated. The models considered have a discrete refractive index gradient in one dimension and are continuous in the orthogonal direction or directions. Such systems can be realized in photonic settings, where temporal dispersion of a normal type is able to support dark solitons. The demonstrated effects may also appear in the dynamics of Bose-Einstein condensates (BECs), where dark solitons appear due to the joint action of diffraction and a self-defocusing nonlinearity. Furthermore, our analysis shows that a periodic variation of the refractive index gradient in the propagation direction allows us to realize the spatial analog of dynamical localization. In addition, we demonstrate that dark solitons serve as excellent supporters for light bullets of a peculiar dark-bright type that can also feature robust BOs.
    • Social context-dependent singing alters molecular markers of dopaminergic and glutamatergic signaling in finch basal ganglia Area X

      So, Lisa Y; Munger, Stephanie J; Miller, Julie E; Univ Arizona, Program Neurosci; Univ Arizona, Dept Neurosci; Univ Arizona, Dept Speech Language & Hearing Sci (ELSEVIER SCIENCE BV, 2019-03-15)
      Dopamine (DA) is an important neuromodulator of motor control across species. In zebra finches, DA levels vary in song nucleus Area X depending upon social context. DA levels are high and song output is less variable when a male finch sings to a female (female directed, FD) compared to when he is singing by himself (undirected, UD). DA modulates glutamatergic input onto cortico-striatal synapses in Area X via N-methyl-d-aspartate (NMDA) and DA receptor mechanisms, but the relationship to UD vs. FD song output is unclear. Here, we investigate the expression of molecular markers of dopaminergic and glutamatergic synaptic transmission (tyrosine hydroxylase - TH, alpha-synuclein - α-syn) and plasticity (NMDA 2B receptor - GRIN2B) following singing (UD vs. FD) and non-singing states to understand the molecular mechanisms driving differences in song output. We identified relationships between protein levels for these biomarkers in Area X based on singing state and the amount of song, measured as the number of motifs and time spent singing. UD song amount drove increases in TH, α-syn, and NMDA 2B receptor protein levels. By contrast, the amount of FD song did not alter TH and NMDA 2B receptor expression. Levels of α-syn showed differential expression patterns based on UD vs. FD song, consistent with its role in modulating synaptic transmission. We propose a molecular pathway model to explain how social context and amount of song are important drivers of molecular changes required for synaptic transmission and plasticity.
    • Evidence for hidden order in a nonlinear model elastic system

      Deymier, P A; Runge, K; Univ Arizona, Dept Mat Sci & Engn (IOP PUBLISHING LTD, 2019-03-13)
      Hidden order may arise in strongly correlated systems even if there is an apparent lack of long-range order as measured by local order parameters. This phenomenon has been essentially associated with topological order in quantum systems. Here, we demonstrate the emergence of hidden order in a 1D non-linear classical mechanical system that supports rotational degrees of freedom. The potential energy of the model system creates a bistable system for which hidden order emerges with the introduction of a biquadratic term. To our surprise, we discover that varying the strength of the biquadratic term leads to four distinct phases quantified by the behaviors of the Néel and string order parameters. Three of these phases are locally disordered. Hidden order is identified by a string order parameter that shows correlations with significantly longer range than the Néel order parameter. The hidden order correlation length diverges as the kinetic energy of the system is lowered with a critical exponent ~0.5. The observation of hidden order in a mechanical system reveals that instability and non-linearity may play critical roles in the generation of nonlocal long-range correlations in apparently locally disordered systems.
    • Linking Duplication of a Calcium Sensor to Salt Tolerance in Eutrema salsugineum

      Monihan, Shea M; Ryu, Choong-Hwan; Magness, Courtney A; Schumaker, Karen S; Univ Arizona, Sch Plant Sci (AMER SOC PLANT BIOLOGISTS, 2019-03-01)
      The SALT-OVERLY-SENSITIVE (SOS) pathway in Arabidopsis (Arabidopsis thaliana) functions to prevent the toxic accumulation of sodium in the cytosol when plants are grown in salt-affected soils. In this pathway, the CALCINEURIN B-LIKE10 (AtCBL10) calcium sensor interacts with the AtSOS2 kinase to activate the AtSOS1 plasma membrane sodium/proton exchanger. CBL10 has been duplicated in Eutrema (Eutrema salsugineum), a salt-tolerant relative of Arabidopsis. Because Eutrema maintains growth in salt-affected soils that kill most crop plants, the duplication of CBL10 provides a unique opportunity to functionally test the outcome of gene duplication and its link to plant salt tolerance. In Eutrema, individual down-regulation of the duplicated CBL10 genes (EsCBL10a and EsCBL10b) decreased growth in the presence of salt and, in combination, led to an even greater decrease, suggesting that both genes function in response to salt and have distinct functions. Cross-species complementation assays demonstrated that EsCBL10b has an enhanced ability to activate the SOS pathway while EsCBL10a has a function not performed by AtCBL10 or EsCBL10b. Chimeric EsCBL10a/EsCBL10b proteins revealed that the specific functions of the EsCBL10 proteins resulted from changes in the amino terminus. The duplication of CBL10 increased calcium-mediated signaling capacity in Eutrema and conferred increased salt tolerance to salt-sensitive Arabidopsis.
    • Quantal Risk Assessment Database: A Database for Exploring Patterns in Quantal Dose-Response Data in Risk Assessment and its Application to Develop Priors for Bayesian Dose-Response Analysis

      Wheeler, Matthew W; Piegorsch, Walter W; Bailer, Albert John; Univ Arizona, Interdisciplinary Program Stat (WILEY, 2019-03-01)
      Quantitative risk assessments for physical, chemical, biological, occupational, or environmental agents rely on scientific studies to support their conclusions. These studies often include relatively few observations, and, as a result, models used to characterize the risk may include large amounts of uncertainty. The motivation, development, and assessment of new methods for risk assessment is facilitated by the availability of a set of experimental studies that span a range of dose-response patterns that are observed in practice. We describe construction of such a historical database focusing on quantal data in chemical risk assessment, and we employ this database to develop priors in Bayesian analyses. The database is assembled from a variety of existing toxicological data sources and contains 733 separate quantal dose-response data sets. As an illustration of the database's use, prior distributions for individual model parameters in Bayesian dose-response analysis are constructed. Results indicate that including prior information based on curated historical data in quantitative risk assessments may help stabilize eventual point estimates, producing dose-response functions that are more stable and precisely estimated. These in turn produce potency estimates that share the same benefit. We are confident that quantitative risk analysts will find many other applications and issues to explore using this database.
    • Endonuclease Activity Inhibition of the NS1 Protein of Parvovirus B19 as a Novel Target for Antiviral Drug Development

      Xu, Peng; Ganaie, Safder S; Wang, Xiaomei; Wang, Zekun; Kleiboeker, Steve; Horton, Nancy C; Heier, Richard F; Meyers, Marvin J; Tavis, John E; Qiu, Jianming; Univ Arizona, Dept Mol & Cellular Biol (AMER SOC MICROBIOLOGY, 2019-03-01)
      Human parvovirus B19 (B19V), a member of the genus
    • The Need for Speed: Run-On Oligomer Filament Formation Provides Maximum Speed with Maximum Sequestration of Activity

      Barahona, Claudia J; Basantes, L Emilia; Tompkins, Kassidy J; Heitman, Desirae M; Chukwu, Barbara I; Sanchez, Juan; Sanchez, Jonathan L; Ghadirian, Niloofar; Park, Chad K; Horton, N C; Univ Arizona, Dept Mol & Cellular Biol (AMER SOC MICROBIOLOGY, 2019-03-01)
      Here, we investigate an unusual antiviral mechanism developed in the bacterium Streptomyces griseus. SgrAI is a type II restriction endonuclease that forms run-on oligomer filaments when activated and possesses both accelerated DNA cleavage activity and expanded DNA sequence specificity. Mutations disrupting the run-on oligomer filament eliminate the robust antiphage activity of wild-type SgrAI, and the observation that even relatively modest disruptions completely abolish this anti-viral activity shows that the greater speed imparted by the run-on oligomer filament mechanism is critical to its biological function. Simulations of DNA cleavage by SgrAI uncover the origins of the kinetic advantage of this newly described mechanism of enzyme regulation over more conventional mechanisms, as well as the origin of the sequestering effect responsible for the protection of the host genome against damaging DNA cleavage activity of activated SgrAI. IMPORTANCE This work is motivated by an interest in understanding the characteristics and advantages of a relatively newly discovered enzyme mechanism involving filament formation. SgrAI is an enzyme responsible for protecting against viral infections in its host bacterium and was one of the first such enzymes shown to utilize such a mechanism. In this work, filament formation by SgrAI is disrupted, and the effects on the speed of the purified enzyme as well as its function in cells are measured. It was found that even small disruptions, which weaken but do not destroy filament formation, eliminate the ability of SgrAI to protect cells from viral infection, its normal biological function. Simulations of enzyme activity were also performed and show how filament formation can greatly speed up an enzyme's activation compared to that of other known mechanisms, as well as to better localize its action to molecules of interest, such as invading phage DNA.