This open access archive contains publications from University of Arizona faculty, researchers and staff, primarily open-access versions of formally published journal articles. The collection includes published articles and final accepted manuscripts submitted by UA faculty under the UA Open Access Policy. The collection also includes books, book chapters, book reviews, presentations, data, and other scholarly materials submitters have chosen to make available in the repository.


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Recent Submissions

  • From a crisis to an opportunity: Eight insights for doing science in the COVID‐19 era and beyond

    Chacón‐Labella, Julia; Boakye, Mickey; Enquist, Brian J.; Farfan‐Rios, William; Gya, Ragnhild; Halbritter, Aud H.; Middleton, Sara L.; von Oppen, Jonathan; Pastor‐Ploskonka, Samuel; Strydom, Tanya; et al. (WILEY, 2020-12-15)
    The COVID-19 crisis has forced researchers in Ecology to change the way we work almost overnight. Nonetheless, the pandemic has provided us with several novel components for a new way of conducting science. In this perspective piece, we summarize eight central insights that are helping us, as early career researchers, navigate the uncertainties, fears, and challenges of advancing science during the COVID-19 pandemic. We highlight how innovative, collaborative, and often Open Science-driven developments that have arisen from this crisis can form a blueprint for a community reinvention in academia. Our insights include personal approaches to managing our new reality, maintaining capacity to focus and resilience in our projects, and a variety of tools that facilitate remote collaboration. We also highlight how, at a community level, we can take advantage of online communication platforms for gaining accessibility to conferences and meetings, and for maintaining research networks and community engagement while promoting a more diverse and inclusive community. Overall, we are confident that these practices can support a more inclusive and kinder scientific culture for the longer term.
  • Design and development of innovative microparticulate/nanoparticulate inhalable dry powders of a novel synthetic trifluorinated chalcone derivative and Nrf2 agonist.

    Muralidharan, Priya; Jones, Brielle; Allaway, Graham; Biswal, Shyam S; Mansour, Heidi M; Univ Arizona, Coll Pharm; Univ Arizona, Coll Med; Univ Arizona, Coll Med, Dept Med, Div Translat & Regenerat Med; Univ Arizona, BIO5 Res Inst; Univ Arizona, Inst Environm; et al. (NATURE RESEARCH, 2020-11-13)
    Chalcone derivatives are shown to possess excellent anti-inflammatory and anti-oxidant properties which are of great interest in treating respiratory diseases such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF). This study successfully designed and developed dry powder inhaler (DPI) formulations of TMC (2-trifluoromethyl-2 ' -methoxychalone), a new synthetic trifluorinated chalcone and Nrf2 agonist, for targeted pulmonary inhalation aerosol drug delivery. An advanced co-spray drying particle engineering technique was used to design and produce microparticulate/nanoparticulate formulations of TMC with a suitable excipient (mannitol) as inhalable particles with tailored particle properties for inhalation. Raw TMC and co-spray dried TMC formulations were comprehensively characterized for the first time using scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) spectroscopy, thermal analysis, X-ray powder diffraction (XRPD), and molecular fingerprinting as dry powders by ATR-FTIR spectroscopy and Raman spectroscopy. Further, biocompatibility and suitability of formulations were tested with in vitro cellular transepithelial electrical resistance (TEER) in air-interface culture (AIC) using a human pulmonary airway cell line. The ability of these TMC formulations to perform as aerosolized dry powders was systematically evaluated by design of experiments (DOEs) using three different FDA-approved human inhaler devices followed by interaction parameter analyses. Multiple spray drying pump rates (25%, 75%, and 100%) successfully produced co-spray dried TMC:mannitol powders. Raw TMC exhibited a first-order phase transition temperature at 58.15 +/- 0.38 degrees C. Furthermore, the results demonstrate that these innovative TMC dry powder particles are suitable for targeted delivery to the airways by inhalation.
  • Anatomical and histological analyses reveal that tail repair is coupled with regrowth in wild-caught, juvenile American alligators (Alligator mississippiensis)

    Xu, Cindy; Palade, Joanna; Fisher, Rebecca E; Smith, Cameron I; Clark, Andrew R; Sampson, Samuel; Bourgeois, Russell; Rawls, Alan; Elsey, Ruth M; Wilson-Rawls, Jeanne; et al. (NATURE RESEARCH, 2020-11-18)
    Reptiles are the only amniotes that maintain the capacity to regenerate appendages. This study presents the first anatomical and histological evidence of tail repair with regrowth in an archosaur, the American alligator. The regrown alligator tails constituted approximately 6-18% of the total body length and were morphologically distinct from original tail segments. Gross dissection, radiographs, and magnetic resonance imaging revealed that caudal vertebrae were replaced by a ventrally-positioned, unsegmented endoskeleton. This contrasts with lepidosaurs, where the regenerated tail is radially organized around a central endoskeleton. Furthermore, the regrown alligator tail lacked skeletal muscle and instead consisted of fibrous connective tissue composed of type I and type III collagen fibers. The overproduction of connective tissue shares features with mammalian wound healing or fibrosis. The lack of skeletal muscle contrasts with lizards, but shares similarities with regenerated tails in the tuatara and regenerated limbs in Xenopus adult frogs, which have a cartilaginous endoskeleton surrounded by connective tissue, but lack skeletal muscle. Overall, this study of wild-caught, juvenile American alligator tails identifies a distinct pattern of wound repair in mammals while exhibiting features in common with regeneration in lepidosaurs and amphibia.
  • An Integrated Approach to Improve Maternal Mental Health and Well-Being During the COVID-19 Crisis

    Shidhaye, Rahul; Madhivanan, Purnima; Shidhaye, Pallavi; Krupp, Karl; Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Dept Hlth Promot Sci; Univ Arizona, Coll Med, Div Infect Dis; Univ Arizona, Coll Med, Dept Family & Community Med (FRONTIERS MEDIA SA, 2020-11-24)
    The ongoing COVID-19 pandemic has led to disruption of normal life across the globe, severely affecting the already vulnerable populations such as the pregnant women. Maternal mental health and well-being is a public health priority and the evidence about the impact of COVID-19 on mental health status of pregnant women is gradually emerging. The findings of the recently published studies suggest that increased risk perception about contracting COVID-19, reduced social support, increase in domestic violence, disruption of antenatal care, and economic consequences of COVID-19 mitigation strategies can lead to adverse mental health outcomes in antenatal period. There is a significant increase in antenatal depression and anxiety since the onset of COVID-19 and social determinants of health (e.g., younger age, lower education, lower income) are associated with these poor outcomes. In this paper, we propose an integrated approach to improve the mental health and well-being of pregnant women. Physical activity and/or mind-body interventions like yoga can be practiced as self-care interventions by pregnant women. Despite social distancing being the current norm, efforts should be made to strengthen social support. Evidence-based interventions for perinatal depression should be integrated within the health system and stepped, collaborative care using non-specialist health workers as key human resource be utilized to improve access to mental health services. Use of digital platforms and smartphone enabled delivery of services has huge potential to further improve the access to care. Most importantly, the COVID-19 related policy guidelines should categorically include maternal mental health and well-being as a priority area.
  • Gastric heterotopia with perforation mimicking neoplastic process in ileum

    Carlson, Quinlan; Golconda, Umamaheshwari; Sun, Belinda; Univ Arizona, Banner Univ Med Ctr, Coll Med, Dept Pathol (OXFORD UNIV PRESS, 2020-07-23)
    Gastric heterotopia (GH) is rare in ileum except in Meckel's diverticulum and rarely causes severe symptoms in adults. Here, we report a 31-year-old male patient with GH in ileum presented with bowel perforation and mass formation in the mesentery mimicking perforated small bowel tumor. Microscopic examination of the lesion showed completely differentiated gastric body-type mucosa with mucosal ulceration, fistula formation and bowel perforation. This case raises the awareness that GH may cause severe complications and should be included in the differential diagnosis for acute abdominal pain especially in patients with a mass lesion at an unusual location.
  • Hysteretic temperature sensitivity of wetland CH4 fluxes explained by substrate availability and microbial activity

    Chang, Kuang-Yu; Riley, William J.; Crill, Patrick M.; Grant, Robert F.; Saleska, Scott R.; Univ Arizona, Dept Ecol & Evolutionary Biol (COPERNICUS GESELLSCHAFT MBH, 2020-11-27)
    Methane (CH4) emissions from wetlands are likely increasing and important in global climate change assessments. However, contemporary terrestrial biogeochemical model predictions of CH4 emissions are very uncertain, at least in part due to prescribed temperature sensitivity of CH4 production and emission. While statistically consistent apparent CH4 emission temperature dependencies have been inferred from meta-analyses across microbial to ecosystem scales, year-round ecosystem-scale observations have contradicted that finding. Here, we show that apparent CH4 emission temperature dependencies inferred from year-round chamber measurements exhibit substantial intra-seasonal variability, suggesting that using static temperature relations to predict CH4 emissions is mechanistically flawed. Our model results indicate that such intra-seasonal variability is driven by substrate-mediated microbial and abiotic interactions: seasonal cycles in substrate availability favors CH4 production later in the season, leading to hysteretic temperature sensitivity of CH4 production and emission. Our findings demonstrate the uncertainty of inferring CH4 emission or production rates from temperature alone and highlight the need to represent microbial and abiotic interactions in wetland biogeochemical models.
  • Ensemble dimensionality reduction and feature gene extraction for single-cell RNA-seq data

    Sun, Xiaoxiao; Liu, Yiwen; An, Lingling; Univ Arizona, Dept Epidemiol & Biostat; Univ Arizona, Dept Biosyst Engn (NATURE RESEARCH, 2020-11-17)
    Single-cell RNA sequencing (scRNA-seq) technologies allow researchers to uncover the biological states of a single cell at high resolution. For computational efficiency and easy visualization, dimensionality reduction is necessary to capture gene expression patterns in low-dimensional space. Here we propose an ensemble method for simultaneous dimensionality reduction and feature gene extraction (EDGE) of scRNA-seq data. Different from existing dimensionality reduction techniques, the proposed method implements an ensemble learning scheme that utilizes massive weak learners for an accurate similarity search. Based on the similarity matrix constructed by those weak learners, the low-dimensional embedding of the data is estimated and optimized through spectral embedding and stochastic gradient descent. Comprehensive simulation and empirical studies show that EDGE is well suited for searching for meaningful organization of cells, detecting rare cell types, and identifying essential feature genes associated with certain cell types. Dimensionality reduction is used to make the analysis of single-cell RNA sequencing data more efficient. Here the authors propose a method, EDGE, which simultaneously carries out dimensionality reduction and feature gene extraction.
  • Point-of-care, multispectral, smartphone-based dermascopes for dermal lesion screening and erythema monitoring

    Uthoff, Ross; Song, Bofan; Maarouf, Melody; Shi, Vivian; Liang, Rongguang; Univ Arizona, James C Wyant Coll Opt Sci; Univ Arizona, Coll Med, Div Dermatol, Dept Med (SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS, 2020-06-23)
    Significance: The rates of melanoma and nonmelanoma skin cancer are rising across the globe. Due to a shortage of board-certified dermatologists, the burden of dermal lesion screening and erythema monitoring has fallen to primary care physicians (PCPs). An adjunctive device for lesion screening and erythema monitoring would be beneficial because PCPs are not typically extensively trained in dermatological care. Aim: We aim to examine the feasibility of using a smartphone-camera-based dermascope and a USB-camera-based dermascope utilizing polarized white-light imaging (PWLI) and polarized multispectral imaging (PMSI) to map dermal chromophores and erythema. Approach: Two dermascopes integrating LED-based PWLI and PMSI with both a smartphonebased camera and a USB-connected camera were developed to capture images of dermal lesions and erythema. Image processing algorithms were implemented to provide chromophore concentrations and redness measures. Results: PWLI images were successfully converted to an alternate colorspace for erythema measures, and the spectral bandwidth of the PMSI LED illumination was sufficient for mapping of deoxyhemoglobin, oxyhemoglobin, and melanin chromophores. Both types of dermascopes were able to achieve similar relative concentration results. Conclusion: Chromophore mapping and erythema monitoring are feasible with PWLI and PMSI using LED illumination and smartphone-based cameras. These systems can provide a simpler, more portable geometry and reduce device costs compared with interference-filter-based or spectrometer-based clinical-grade systems. Future research should include a rigorous clinical trial to collect longitudinal data and a large enough dataset to train and implement a machine learning-based image classifier.
  • Co-regulation of the transcription controlling ATF2 phosphoswitch by JNK and p38

    Kirsch, Klára; Zeke, András; Tőke, Orsolya; Sok, Péter; Sethi, Ashish; Sebő, Anna; Kumar, Ganesan Senthil; Egri, Péter; Póti, Ádám L; Gooley, Paul; et al. (NATURE RESEARCH, 2020-11-13)
    Transcription factor phosphorylation at specific sites often activates gene expression, but how environmental cues quantitatively control transcription is not well-understood. Activating protein 1 transcription factors are phosphorylated by mitogen-activated protein kinases (MAPK) in their transactivation domains (TAD) at so-called phosphoswitches, which are a hallmark in response to growth factors, cytokines or stress. We show that the ATF2 TAD is controlled by functionally distinct signaling pathways (JNK and p38) through structurally different MAPK binding sites. Moreover, JNK mediated phosphorylation at an evolutionarily more recent site diminishes p38 binding and made the phosphoswitch differently sensitive to JNK and p38 in vertebrates. Structures of MAPK-TAD complexes and mechanistic modeling of ATF2 TAD phosphorylation in cells suggest that kinase binding motifs and phosphorylation sites line up to maximize MAPK based co-regulation. This study shows how the activity of an ancient transcription controlling phosphoswitch became dependent on the relative flux of upstream signals. The ATF2 transcription factor is phosphorylated by different mitogen-activated protein (MAP) kinases. Here, the authors show that the functionally distinct MAP kinases JNK and p38 control ATF2 through different binding sites and differential phosphorylation, thereby modulating ATF2's sensitivity to the JNK and p38 pathways.
  • Creation of large temperature anisotropies in a laboratory plasma

    Beatty, C. B.; Steinberger, T. E.; Aguirre, E. M.; Beatty, R. A.; Klein, K. G.; McLaughlin, J. W.; Neal, L.; Scime, E. E.; Univ Arizona, Dept Planetary Sci (AMER INST PHYSICS, 2020-12-01)
    Ion temperature anisotropy in an expanding magnetized plasma is investigated using laser induced fluorescence. Parallel and perpendicular ion velocity distribution functions (IVDFs) were measured simultaneously with high spatial resolution in the expanding plasma. Large ion temperature anisotropies ( T perpendicular to i / T parallel to i similar to 10) are observed in a conical region at the periphery of the expanding plasma plume. A simple 2D Boris stepper model that incorporates the measured electric field structure is able to reproduce the gross features of the measured perpendicular IVDFs. A Nyquist stability analysis of the measured IVDFs suggests that multiple instabilities with k perpendicular to rho i similar to 1 and k | | rho i similar to 0.2 are likely to be excited in these plasmas.
  • Simple Global Ocean Biogeochemistry With Light, Iron, Nutrients and Gas Version 2 (BLINGv2): Model Description and Simulation Characteristics in GFDL's CM4.0

    Dunne, J. P.; Bociu, I.; Bronselaer, B.; Guo, H.; John, J. G.; Krasting, J. P.; Stock, C. A.; Winton, M.; Zadeh, N.; Univ Arizona, Dept Geosci (AMER GEOPHYSICAL UNION, 2020-08-18)
    Simulation of coupled carbon-climate requires representation of ocean carbon cycling, but the computational burden of simulating the dozens of prognostic tracers in state-of-the-art biogeochemistry ecosystem models can be prohibitive. We describe a six-tracer biogeochemistry module of steady-state phytoplankton and zooplankton dynamics in Biogeochemistry with Light, Iron, Nutrients and Gas (BLING version 2) with particular emphasis on enhancements relative to the previous version and evaluate its implementation in Geophysical Fluid Dynamics Laboratory's (GFDL) fourth-generation climate model (CM4.0) with 1/4 degrees ocean. Major geographical and vertical patterns in chlorophyll, phosphorus, alkalinity, inorganic and organic carbon, and oxygen are well represented. Major biases in BLINGv2 include overly intensified production in high-productivity regions at the expense of productivity in the oligotrophic oceans, overly zonal structure in tropical phosphorus, and intensified hypoxia in the eastern ocean basins as is typical in climate models. Overall, while BLINGv2 structural limitations prevent sophisticated application to plankton physiology, ecology, or biodiversity, its ability to represent major organic, inorganic, and solubility pumps makes it suitable for many coupled carbon-climate and biogeochemistry studies including eddy interactions in the ocean interior. We further overview the biogeochemistry and circulation mechanisms that shape carbon uptake over the historical period. As an initial analysis of model historical and idealized response, we show that CM4.0 takes up slightly more anthropogenic carbon than previous models in part due to enhanced ventilation in the absence of an eddy parameterization. The CM4.0 biogeochemistry response to CO2 doubling highlights a mix of large declines and moderate increases consistent with previous models.
  • Delta-doped electron-multiplying CCDs for FIREBall-2

    Kyne, Gillian; Hamden, Erika T.; Nikzad, Shouleh; Hoadley, Keri; Jewell, April; Jones, Todd; Hoenk, Michael; Cheng, Samuel; Martin, D. Christopher; Lingner, Nicole; et al. (SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS, 2020-03-12)
    We present the status of on-going detector development efforts for our joint NASA/Centre National d'Etudes Spatiales balloon-borne UV multiobject spectrograph, the Faint Intergalactic Redshifted Emission Balloon (FIREBall-2;1 13-2). FB-2 demonstrates a UV detector technology, the delta-doped electron-multiplying CCD (EMCCD), in a low-risk suborbital environment, to prove the performance of EMCCDs for future space missions and technology readiness level advancement. EMCCDs can be used in photon-counting mode to achieve extremely low readout noise (<1 electron). Our testing has focused on reducing clock-induced-charge (CIC) through wave shaping and well-depth optimization with a Nuvu V2 CCCP controller, measuring CIC at 0.001 e(-)/pixel/frame. This optimization also includes methods for reducing dark current, via cooling, and substrate voltage levels. We discuss the challenges of removing cosmic rays, which are also amplified by these detectors, as well as a data reduction pipeline designed for our noise measurement objectives. FB-2 flew in 2018, providing the first time an EMCCD, was used for UV observations in the stratosphere. FB-2 is currently being built up to fly again in 2020, and improvements are being made to the EMCCD to continue optimizing its performance for better noise control. (C) 2020 Society of Photo-Optical Instrumentation Engineers (SPIE)
  • Accelerated Greenland Ice Sheet Mass Loss Under High Greenhouse Gas Forcing as Simulated by the Coupled CESM2.1‐CISM2.1

    Muntjewerf, Laura; Sellevold, Raymond; Vizcaino, Miren; Ernani da Silva, Carolina; Petrini, Michele; Thayer‐Calder, Katherine; Scherrenberg, Meike D. W.; Bradley, Sarah L.; Katsman, Caroline A.; Fyke, Jeremy; et al. (AMER GEOPHYSICAL UNION, 2020-08-16)
    The Greenland ice sheet (GrIS) is now losing mass at a rate of 0.7 mm of sea level rise (SLR) per year. Here we explore future GrIS evolution and interactions with global and regional climate under high greenhouse gas forcing with the Community Earth System Model version 2.1 (CESM2.1), which includes an interactive ice sheet component (the Community Ice Sheet Model v2.1 [CISM2.1]) and an advanced energy balance-based calculation of surface melt. We run an idealized 350-year scenario in which atmospheric CO2 concentration increases by 1% annually until reaching four times pre-industrial values at year 140, after which it is held fixed. The global mean temperature increases by 5.2 and 8.5 K by years 131-150 and 331-350, respectively. The projected GrIS contribution to global mean SLR is 107 mm by year 150 and 1,140 mm by year 350. The rate of SLR increases from 2 mm yr(-1) at year 150 to almost 7 mm yr(-1) by year 350. The accelerated mass loss is caused by rapidly increasing surface melt as the ablation area expands, with associated albedo feedback and increased sensible and latent heat fluxes. This acceleration occurs for a global warming of approximately 4.2 K with respect to pre-industrial and is in part explained by the quasi-parabolic shape of the ice sheet, which favors rapid expansion of the ablation area as it approaches the interior "plateau."
  • Resection and Surgically Targeted Radiation Therapy for the Treatment of Larger Recurrent or Newly Diagnosed Brain Metastasis: Results From a Prospective Trial

    Nakaji, Peter; Smith, Kris; Youssef, Emad; Thomas, Theresa; Pinnaduwage, Dilini; Rogers, Leland; Wallstrom, Garrick; Brachman, David; Univ Arizona, Coll Med, Med Ctr Phoenix, Neurol Surg (CUREUS INC, 2020-11-19)
    Introduction Achieving durable local control (LC) for larger (e.g., >2-3 cm) brain metastasis whether newly diagnosed or recurrent remains problematic. Resection (R) alone is typically insufficient and adding radiation therapy (RT) still results in a 12-month recurrence rate of 20% or more in many series. Hypothesizing that R plus immediate radiation utilizing brachytherapy may improve outcomes for this cohort of patients, we designed and prospectively evaluated a permanently implanted surgically targeted radiation therapy (STaRT) device consisting of cesium-131 (Cs-131) seeds positioned within a collagen carrier (GammaTile, GT Medical Technologies, Tempe, AZ). The device was designed to prevent direct source-to-brain contact and maintain inter-source spacing after closure. Methods This was a subgroup analysis of a cohort of patients with either recurrent or previously untreated brain metastases enrolled in a prospective, multi-histology single-arm trial (ClinicalTrials.gov, NCT#03088579), conducted between February 2013 and February 2018, of resection and tumor bed brachytherapy with Cs-131 containing permanently implanted collagen tiles to deliver 60 Gray (Gy) at .5 cm depth. No additional local therapy was given without progression. Results A total of 16 metastases in 11 patients were treated; 12 tumors were recurrent and four were previously untreated. The median preoperative maximum diameter was 3.2 cm (range: 1.9-5.1 cm). Histology was seven breasts, six lungs, and three sarcomas. The median age was 60 years (range: 41-80 years); the Karnofsky Performance Status (KPS) was 70 (range: 70-90). The cohort consisted of seven females and four males. The mean time for implantation completion was five minutes. The median overall survival (OS) was 9.3 months. At a median radiographic follow-up of 9.5 months' treatment, site progression was found in 1/16 (6%) at 10.9 months, and the median treatment site time-to-progression (TTP) has not been reached [95% confidence interval (CI): >10.9 months]. At 12 months, the Kaplan-Meier (K-M) estimates for LC after R+STaRT for all tumors was 83%; for previously untreated tumors, LC at 12 months was 100% and for recurrent tumors, it was 80%. Two tumor beds (12.5%) experienced radiation brain changes: one had grade two and the other grade three. No surgical adverse events occurred. Conclusion In this single-arm precommercial study, R+STaRT demonstrated excellent safety and LC in this cohort. The device has recently received FDA clearance for use in newly diagnosed and recurrent brain metastasis, and randomized clinical trials vs. standard of care treatments in both settings are scheduled to open in 2020.
  • Role of secreted extracellular nicotinamide phosphoribosyltransferase (eNAMPT) in prostate cancer progression: Novel biomarker and therapeutic target

    Sun, Belinda L; Sun, Xiaoguang; Casanova, Nancy; Garcia, Alexander N; Oita, Radu; Algotar, Amit M; Camp, Sara M; Reyes Hernon, Vivian; Gregory, Taylor; Cress, Anne E; et al. (ELSEVIER, 2020-10-09)
    Background: There remains a serious need to prevent the progression of invasive prostate cancer (PCa). We previously showed that secreted extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is a multifunctional innate immunity regulator via TLR4 ligation which has been implicated in PCa progression. Here we investigate the role of eNAMPT as a diagnostic biomarker and therapeutic target in the progression of PCa. Methods: Tumor NAMPT expression and plasma eNAMPT level were evaluated in human subjects with various PCa tumor stages and high risk subjects followed-up clinically for PCa. The genetic regulation of NAMPT expression in PCa cells and the role of eNAMPT in PCa invasion were investigated utilizing in vitro and in vivo models. Findings: Marked NAMPT expression was detected in human extraprostatic-invasive PCa tissues compared to minimal expression of organ-confined PCa. Plasma eNAMPT levels were significantly elevated in PCa subjects compared to male controls, and significantly greater in subjects with extraprostatic-invasive PCa compared to subjects with organ-confined PCa. Plasma eNAMPT levels showed significant predictive value for diagnosing PCa. NAMPT expression and eNAMPT secretion were highly upregulated in human PCa cells in response to hypoxia-inducible factors and EGF. In vitro cell culture and in vivo preclinical mouse model studies confirmed eNAMPT-mediated enhancement of PCa invasiveness into muscle tissues and dramatic attenuation of PCa invasion by weekly treatment with an eNAMPT-neutralizing polyclonal antibody. Interpretation: This study suggests that eNAMPT is a potential biomarker for PCa, especially invasive PCa. Neutralization of eNAMPT may be an effective therapeutic approach to prevent PCa invasion and progression. (C) 2020 The Author(s). Published by Elsevier B.V.
  • A Parental Smoking Cessation Intervention in the Pediatric Emergency Setting: A Randomized Trial

    Mahabee-Gittens, E Melinda; Ammerman, Robert T; Khoury, Jane C; Tabangin, Meredith E; Ding, Lili; Merianos, Ashley L; Stone, Lara; Gordon, Judith S; Univ Arizona, Coll Nursing (MDPI, 2020-11-04)
    We examined the efficacy of a pediatric emergency visit-based screening, brief intervention, and referral to treatment (SBIRT) condition compared to a control condition (Healthy Habits Control, HHC) to help parental smokers quit smoking. We enrolled 750 parental smokers who presented to the pediatric emergency setting with their child into a two-group randomized controlled clinical trial. SBIRT participants received brief cessation coaching, quitting resources, and up to 12-weeks of nicotine replacement therapy (NRT). HHC participants received healthy lifestyle coaching and resources. The primary outcome was point-prevalence tobacco abstinence at six weeks (T1) and six months (T2). The mean (SD) age of parents was 31.8 (7.7) years, and 86.8% were female, 52.7% were Black, and 64.6% had an income of ≤$15,000. Overall abstinence rates were not statistically significant with 4.2% in both groups at T1 and 12.9% and 8.3% in the SBIRT and HHC groups, respectively, at T2. There were statistically significant differences in SBIRT versus HHC participants on the median (IQR) reduction of daily cigarettes smoked at T1 from baseline (-2 [-5, 0] versus 0 [-4, 0], p = 0.0008),at T2 from baseline (-4 [-9, -1] vs. -2 [-5, 0], p = 0.0006), and on the mean (SD) number of quit attempts at T2 from baseline (1.25 (6.5) vs. 0.02 (4.71), p = 0.02). Self-reported quitting rates were higher in SBIRT parents who received NRT (83.3% vs. 50.9%, p = 0.04). The novel use of the pediatric emergency visit to conduct cessation interventions helped parents quit smoking. The near equivalent abstinence rates in both the SBIRT and HHC groups may be due to underlying parental concern about their child's health. Cessation interventions in this setting may result in adult and pediatric public health benefits.
  • A Villin-Driven Fxr Transgene Modulates Enterohepatic Bile Acid Homeostasis and Response to an n-6-Enriched High-Fat Diet

    Wren, Spencer N; Donovan, Micah G; Selmin, Ornella I; Doetschman, Tom C; Romagnolo, Donato F; Univ Arizona, Dept Nutr Sci; Univ Arizona, Interdisciplinary Canc Biol Grad Program; Univ Arizona, Canc Ctr; Univ Arizona, Dept Cellular & Mol Med (MDPI, 2020-10-22)
    A diet high in n-6 polyunsaturated fatty acids (PUFAs) may contribute to inflammation and tissue damage associated with obesity and pathologies of the colon and liver. One contributing factor may be dysregulation by n-6 fatty acids of enterohepatic bile acid (BA) metabolism. The farnesoid X receptor (FXR) is a nuclear receptor that regulates BA homeostasis in the liver and intestine. This study aims to compare the effects on FXR regulation and BA metabolism of a palm oil-based diet providing 28% energy (28%E) from fat and low n-6 linoleic acid (LA, 2.5%E) (CNTL) with those of a soybean oil-based diet providing 50%E from fat and high (28%E) in LA (n-6HFD). Wild-type (WT) littermates and a transgenic mouse line overexpressing the Fxrα1 isoform under the control of the intestine-specific Villin promoter (Fxrα1TG) were fed the CNTL or n-6HFD starting at weaning through 16 weeks of age. Compared to the CNTL diet, the n-6HFD supports higher weight gain in both WT and FxrαTG littermates; increases the expression of Fxrα1/2, and peroxisome proliferator-activated receptor-γ1 (Pparγ1) in the small intestine, Fxrα1/2 in the colon, and cytochrome P4507A1 (Cyp7a1) and small heterodimer protein (Shp) in the liver; and augments the levels of total BA in the liver, and primary chenodeoxycholic (CDCA), cholic (CA), and β-muricholic (βMCA) acid in the cecum. Intestinal overexpression of the Fxra1TG augments expression of Shp and ileal bile acid-binding protein (Ibabp) in the small intestine and Ibabp in the proximal colon. Conversely, it antagonizes n-6HFD-dependent accumulation of intestinal and hepatic CDCA and CA; hepatic levels of Cyp7a1; and expression of Pparγ in the small intestine. We conclude that intestinal Fxrα1 overexpression represses hepatic de novo BA synthesis and protects against n-6HFD-induced accumulation of human-specific primary bile acids in the cecum.
  • Observable shape of black hole photon rings

    Gralla, Samuel E.; Lupsasca, Alexandru; Univ Arizona, Dept Phys (AMER PHYSICAL SOC, 2020-12-01)
    Motivated by the prospect of measuring a black hole photon ring, in previous work we explored the interferometric signature produced by a bright, narrow curve in the sky. interferometric observations of such a curve measure its "projected position function" r . (n) over cap, where r parametrizes the curve and (n) over cap denotes its unit normal vector. In this paper, we show by explicit construction that a curve can be fully reconstructed from its projected position, completing the argument that space interferometry can in principle determine the detailed photon ring shape. In practice, near-term observations may be limited to the visibility amplitude alone, which contains incomplete shape information: for convex curves, the amplitude only encodes the set of projected diameters (or "widths") of the shape. We explore the freedom in reconstructing a convex curve from its widths, giving insight into the shape information probed by technically plausible future astronomical measurements. Finally, we consider the Kerr "critical curve" in this framework and present some new results on its shape. We analytically show that the critical curve is an ellipse at small spin or inclination, while at extremal spin it becomes the convex hull of a Cartesian oval. We find a simple oval shape, the "phoval," which reproduces the critical curve with high fidelity over the whole parameter range.
  • Highly accurate long-read HiFi sequencing data for five complex genomes

    Hon, Ting; Mars, Kristin; Young, Greg; Tsai, Yu-Chih; Karalius, Joseph W; Landolin, Jane M; Maurer, Nicholas; Kudrna, David; Hardigan, Michael A; Steiner, Cynthia C; et al. (NATURE RESEARCH, 2020-11-17)
    The PacBio® HiFi sequencing method yields highly accurate long-read sequencing datasets with read lengths averaging 10-25 kb and accuracies greater than 99.5%. These accurate long reads can be used to improve results for complex applications such as single nucleotide and structural variant detection, genome assembly, assembly of difficult polyploid or highly repetitive genomes, and assembly of metagenomes. Currently, there is a need for sample data sets to both evaluate the benefits of these long accurate reads as well as for development of bioinformatic tools including genome assemblers, variant callers, and haplotyping algorithms. We present deep coverage HiFi datasets for five complex samples including the two inbred model genomes Mus musculus and Zea mays, as well as two complex genomes, octoploid Fragaria × ananassa and the diploid anuran Rana muscosa. Additionally, we release sequence data from a mock metagenome community. The datasets reported here can be used without restriction to develop new algorithms and explore complex genome structure and evolution. Data were generated on the PacBio Sequel II System.
  • The shape of the black hole photon ring: A precise test of strong-field general relativity

    Gralla, Samuel E.; Lupsasca, Alexandru; Marrone, Daniel P.; Univ Arizona, Dept Phys; Univ Arizona, Steward Observ (AMER INST PHYSICS, 2020-12-01)
    We propose a new test of strong-field general relativity (GR) based on the universal interferometric signature of the black hole photon ring. The photon ring is a narrow ring-shaped feature, predicted by GR but not yet observed, that appears on images of sources near a black hole. It is caused by extreme bending of light within a few Schwarzschild radii of the event horizon and provides a direct probe of the unstable bound photon orbits of the Kerr geometry. We show that the precise shape of the observable photon ring is remarkably insensitive to the astronomical source profile and can therefore be used as a stringent test of GR. We forecast that a tailored space-based interferometry experiment targeting M87* could test the Kerr nature of the source to the sub-subpercent level.

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