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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

  • Measurement of the splashback feature around SZ-selected Galaxy clusters with DES, SPT, and ACT

    Rozo, E; Gralla, M; Univ Arizona, Dept Phys; Univ Arizona, Dept Astron; Univ Arizona, Steward Observ (OXFORD UNIV PRESS, 2019-05-24)
    We present a detection of the splashback feature around galaxy clusters selected using the Sunyaev-Zel'dovich (SZ) signal. Recent measurements of the splashback feature around optically selected galaxy clusters have found that the splashback radius, rsp, is smaller than predicted by N-body simulations. Apossible explanation for this discrepancy is that rsp inferred from the observed radial distribution of galaxies is affected by selection effects related to the optical cluster-finding algorithms. We test this possibility by measuring the splashback feature in clusters selected via the SZ effect in data from the South Pole Telescope SZ survey and the Atacama Cosmology Telescope Polarimeter survey. The measurement is accomplished by correlating these cluster samples with galaxies detected in the Dark Energy Survey Year 3 data. The SZ observable used to select clusters in this analysis is expected to have a tighter correlation with halo mass and to be more immune to projection effects and aperture-induced biases, potentially ameliorating causes of systematic error for optically selected clusters. We find that the measured r(sp) for SZ-selected clusters is consistent with the expectations from simulations, although the small number of SZ-selected clusters makes a precise comparison difficult. In agreement with previous work, when using optically selected redMaPPer clusters with similar mass and redshift distributions, r(sp) is similar to 2 sigma smaller than in the simulations. These results motivate detailed investigations of selection biases in optically selected cluster catalogues and exploration of the splashback feature around larger samples of SZ-selected clusters. Additionally, we investigate trends in the galaxy profile and splashback feature as a function of galaxy colour, finding that blue galaxies have profiles close to a power law with no discernible splashback feature, which is consistent with them being on their first infall into the cluster.
  • Biophysics at the coffee shop: lessons learned working with George Oster

    Igoshin, Oleg A; Chen, Jing; Xing, Jianhua; Liu, Jian; Elston, Timothy C; Grabe, Michael; Kim, Kenneth S; Nirody, Jasmine A; Rangamani, Padmini; Sun, Sean X; et al. (AMER SOC CELL BIOLOGY, 2019-07-19)
    Over the past 50 years, the use of mathematical models, derived from physical reasoning, to describe molecular and cellular systems has evolved from an art of the few to a cornerstone of biological inquiry. George Oster stood out as a pioneer of this paradigm shift from descriptive to quantitative biology not only through his numerous research accomplishments, but also through the many students and postdocs he mentored over his long career. Those of us fortunate enough to have worked with George agree that his sharp intellect, physical intuition, and passion for scientific inquiry not only inspired us as scientists but also greatly influenced the way we conduct research. We would like to share a few important lessons we learned from George in honor of his memory and with the hope that they may inspire future generations of scientists.
  • MEMS Deformable Mirrors for Space-Based High-Contrast Imaging

    Morgan, Rachel E; Douglas, Ewan S; Allan, Gregory W; Bierden, Paul; Chakrabarti, Supriya; Cook, Timothy; Egan, Mark; Furesz, Gabor; Gubner, Jennifer N; Groff, Tyler D; et al. (MDPI, 2019-05-31)
    Micro-Electro-Mechanical Systems (MEMS) Deformable Mirrors (DMs) enable precise wavefront control for optical systems. This technology can be used to meet the extreme wavefront control requirements for high contrast imaging of exoplanets with coronagraph instruments. MEMS DM technology is being demonstrated and developed in preparation for future exoplanet high contrast imaging space telescopes, including the Wide Field Infrared Survey Telescope (WFIRST) mission which supported the development of a 2040 actuator MEMS DM. In this paper, we discuss ground testing results and several projects which demonstrate the operation of MEMS DMs in the space environment. The missions include the Planet Imaging Concept Testbed Using a Recoverable Experiment (PICTURE) sounding rocket (launched 2011), the Planet Imaging Coronagraphic Technology Using a Reconfigurable Experimental Base (PICTURE-B) sounding rocket (launched 2015), the Planetary Imaging Concept Testbed Using a Recoverable Experiment - Coronagraph (PICTURE-C) high altitude balloon (expected launch 2019), the High Contrast Imaging Balloon System (HiCIBaS) high altitude balloon (launched 2018), and the Deformable Mirror Demonstration Mission (DeMi) CubeSat mission (expected launch late 2019). We summarize results from the previously flown missions and objectives for the missions that are next on the pad. PICTURE had technical difficulties with the sounding rocket telemetry system. PICTURE-B demonstrated functionality at >100 km altitude after the payload experienced 12-g RMS (Vehicle Level 2) test and sounding rocket launch loads. The PICTURE-C balloon aims to demonstrate 10(-7) contrast using a vector vortex coronagraph, image plane wavefront sensor, and a 952 actuator MEMS DM. The HiClBaS flight experienced a DM cabling issue, but the 37-segment hexagonal piston-tip-tilt DM is operational post-flight. The DeMi mission aims to demonstrate wavefront control to a precision of less than 100 nm RMS in space with a 140 actuator MEMS DM.
  • T-BAS Version 2.1: Tree-Based Alignment Selector Toolkit for Evolutionary Placement of DNA Sequences and Viewing Alignments and Specimen Metadata on Curated and Custom Trees

    Carbone, Ignazio; White, James B; Miadlikowska, Jolanta; Arnold, A Elizabeth; Miller, Mark A; Magain, Nicolas; U'Ren, Jana M; Lutzoni, François; Univ Arizona, Dept Biosyst Engn; Univ Arizona, Sch Plant Sci; et al. (MICROBIOLOGY RESOURCE ANNOUNCEMENTS, 2019-07-18)
    The Tree-Based Alignment Selector (T-BAS) toolkit combines phylogenetic-based placement of DNA sequences with alignment and specimen metadata visualization tools in an integrative pipeline for analyzing microbial biodiversity. The release of T-BAS version 2.1 makes available reference phylogenies, supports multilocus sequence placements and permits uploading and downloading trees, alignments, and specimen metadata.
  • Complete Genome Sequence of Luteibacter pinisoli MAH-14

    Baltrus, David A; Clark, Meara; Inderbitzin, Patrik; Pignatta, Daniela; Knight-Connoni, Victoria; Arnold, A Elizabeth; Univ Arizona, Sch Plant Sci; Univ Arizona, Sch Anim & Comparat Biomed Sci; Univ Arizona, Dept Ecol & Evolutionary Biol (AMER SOC MICROBIOLOGY, 2019-07-18)
    Diverse strains of Luteibacter (Gammaproteobacteria) have been isolated from a variety of environments, most frequently in association with both plants and fungi. Motivated by the lack of genomic information for strains throughout the genus Luteibacter, we report here a complete genome sequence for Luteibacter pinisoli strain MAH-14.
  • Diverticulitis of isolated jejunal diverticulum complicated by small bowel obstruction secondary to de novo enterolith formation

    Aispuro, Ivan O; Yazzie, Nazhone P; Univ Arizona, Coll Med (OXFORD UNIV PRESS, 2019-05-01)
    Jejunoileal diverticula (JD) are an uncommon condition most prevalent in the sixth and seventh decade of life. Although mostly asymptomatic, JD can be complicated by perforation, diverticulitis, abscess, bleeding, fistula, and small bowel obstruction (SBO) secondary to enterolith formation. There are a limited number of cases describing JD complicated by SBO secondary to enterolith formation. Most of these cases are not associated with diverticulitis and multiple JD are present in all but one previously reported case. We present a case of diverticulitis of a large, isolated jejunal diverticulum complicated by de novo enterolith-induced SBO initially diagnosed as intussusception based on computerized tomography (CT) imaging. Our main objective is to increase awareness that isolated JD are not as readily evident on imaging as cases presenting with multiple JD, but nevertheless should be considered as possible etiology of acute abdomen.
  • No Clear, Direct Evidence for Multiple Protoplanets Orbiting LkCa 15: LkCa 15 bcd are Likely Inner Disk Signals

    Currie, Thayne; Marois, Christian; Cieza, Lucas; Mulders, Gijs D.; Lawson, Kellen; Caceres, Claudio; Rodriguez-Ruiz, Dary; Wisniewski, John; Guyon, Olivier; Brandt, Timothy D.; et al. (IOP PUBLISHING LTD, 2019-05-15)
    Two studies utilizing sparse aperture-masking (SAM) interferometry and H-alpha differential imaging have reported multiple Jovian companions around the young solar-mass star, LkCa 15 (LkCa 15 bcd): the first claimed direct detection of infant, newly formed planets ("protoplanets"). We present new near-infrared direct imaging/spectroscopy from the Subaru Coronagraphic Extreme Adaptive Optics (SCExAO) system coupled with Coronagraphic High Angular Resolution Imaging Spectrograph (CHARIS) integral field spectrograph and multi-epoch thermal infrared imaging from Keck/NIRC2 of LkCa 15 at high Strehl ratios. These data provide the first direct imaging look at the same wavelengths and in the same locations where previous studies identified the LkCa 15 protoplanets, and thus offer the first decisive test of their existence. The data do not reveal these planets. Instead, we resolve extended emission tracing a dust disk with a brightness and location comparable to that claimed for LkCa 15 bcd. Forward-models attributing this signal to orbiting planets are inconsistent with the combined SCExAO/CHARIS and Keck/NIRC2 data. An inner disk provides a more compelling explanation for the SAM detections and perhaps also the claimed H-alpha detection of LkCa 15 b. We conclude that there is currently no clear, direct evidence for multiple protoplanets orbiting LkCa 15, although the system likely contains at least one unseen Jovian companion. To identify Jovian companions around LkCa 15 from future observations, the inner disk should be detected and its effect modeled, removed, and shown to be distinguishable from planets. Protoplanet candidates identified from similar systems should likewise be clearly distinguished from disk emission through modeling.
  • The COS Absorption Survey of Baryon Harbors (CASBaH): Warm–Hot Circumgalactic Gas Reservoirs Traced by Ne VIII Absorption

    Burchett, Joseph N.; Tripp, Todd M.; Prochaska, J. Xavier; Werk, Jessica K.; Tumlinson, Jason; Howk, J. Christopher; Willmer, Christopher N. A.; Lehner, Nicolas; Meiring, Joseph D.; Bowen, David V.; et al. (IOP PUBLISHING LTD, 2019-05-24)
    We survey the highly ionized circumgalactic media (CGM) of 29 blindly selected galaxies at 0.49 < z(gal) < 1.44 based on high signal-to-noise ratio ultraviolet spectra of z greater than or similar to 1 quasi-stellar objects and the galaxy database from the COS Absorption Survey of Baryon Harbors (CASBaH). We detect the Ne VIII doublet in nine of the galaxies, and for gas with N(Ne VIII) > 10(13.3) cm(-2) (>10(13.5) cm(-2)), we derive a Ne VIII covering fraction f(c) = 75(-25)(+15)% (44(-20)(+22)%) within impact parameters rho <= 200 kpc of M-* =10(9.)(5-11.5)M(circle dot) galaxies and f(c) = 70(-22)(+16)% (f(c) = 42 (+20)(-17)%) within rho <= 1.5 virial radii. We estimate the mass in Ne VIII-traced gas to be M-gas (Ne VIII) >= 10(9.5)M(circle dot) (Z/Z(circle dot))(-1), or 6%-20% of the expected baryonic mass if the Ne VIII absorbers have solar metallicity. Ionizing Ne VII to Ne VIII requires 207 eV, and photons with this energy are scarce in the CGM. However, for the median halo mass and redshift of our sample, the virial temperature is close to the peak temperature for the Ne VIII ion, and the Ne VIII-bearing gas is plausibly collisionally ionized near this temperature. Moreover, we find that photoionized Ne VIII requires cool and low-density clouds that would be highly underpressured (by approximately two orders of magnitude) relative to the putative, ambient virialized medium, complicating scenarios where such clouds could survive. Thus, more complex (e.g., nonequilibrium) models may be required; this first statistical sample of Ne VIII absorber/galaxy systems will provide stringent constraints for future CGM studies.
  • Bayesian inference and predictive performance of soil respiration models in the presence of model discrepancy

    Elshall, Ahmed S.; Ye, Ming; Niu, Guo-Yue; Barron-Gafford, Greg A.; Univ Arizona, Biosphere 2; Univ Arizona, Dept Hydrol & Water Resources; Univ Arizona, Sch Geog & Dev (COPERNICUS GESELLSCHAFT MBH, 2019-05-23)
    Bayesian inference of microbial soil respiration models is often based on the assumptions that the residuals are independent (i.e., no temporal or spatial correlation), identically distributed (i.e., Gaussian noise), and have constant variance (i.e., homoscedastic). In the presence of model discrepancy, as no model is perfect, this study shows that these assumptions are generally invalid in soil respiration modeling such that residuals have high temporal correlation, an increasing variance with increasing magnitude of CO2 efflux, and non-Gaussian distribution. Relaxing these three assumptions stepwise results in eight data models. Data models are the basis of formulating likelihood functions of Bayesian inference. This study presents a systematic and comprehensive investigation of the impacts of data model selection on Bayesian inference and predictive performance. We use three mechanistic soil respiration models with different levels of model fidelity (i.e., model discrepancy) with respect to the number of carbon pools and the explicit representations of soil moisture controls on carbon degradation; therefore, we have different levels of model complexity with respect to the number of model parameters. The study shows that data models have substantial impacts on Bayesian inference and predictive performance of the soil respiration models such that the following points are true: (i) the level of complexity of the best model is generally justified by the cross-validation results for different data models; (ii) not accounting for heteroscedasticity and autocorrelation might not necessarily result in biased parameter estimates or predictions, but will definitely underestimate uncertainty; (iii) using a non-Gaussian data model improves the parameter estimates and the predictive performance; and (iv) accounting for autocorrelation only or joint inversion of correlation and heteroscedasticity can be problematic and requires special treatment. Although the conclusions of this study are empirical, the analysis may provide insights for selecting appropriate data models for soil respiration modeling.
  • Evaluating Knowledge to Support Climate Action: A Framework for Sustained Assessment. Report of an Independent Advisory Committee on Applied Climate Assessment

    Moss, R. H.; Avery, S.; Baja, K.; Burkett, M.; Chischilly, A. M.; Dell, J.; Fleming, P. A.; Geil, K.; Jacobs, K.; Jones, A.; et al. (AMER METEOROLOGICAL SOC, 2019-07)
    As states, cities, tribes, and private interests cope with climate damages and seek to increase preparedness and resilience, they will need to navigate myriad choices and options available to them. Making these choices in ways that identify pathways for climate action that support their development objectives will require constructive public dialogue, community participation, and flexible and ongoing access to science- and experience-based knowledge. In 2016, a Federal Advisory Committee (FAC) was convened to recommend how to conduct a sustained National Climate Assessment (NCA) to increase the relevance and usability of assessments for informing action. The FAC was disbanded in 2017, but members and additional experts reconvened to complete the report that is presented here. A key recommendation is establishing a new nonfederal "climate assessment consortium" to increase the role of state/local/tribal government and civil society in assessments. The expanded process would 1) focus on applied problems faced by practitioners, 2) organize sustained partnerships for collaborative learning across similar projects and case studies to identify effective tested practices, and 3) assess and improve knowledge-based methods for project implementation. Specific recommendations include evaluating climate models and data using user-defined metrics; improving benefit-cost assessment and supporting decision-making under uncertainty; and accelerating application of tools and methods such as citizen science, artificial intelligence, indicators, and geospatial analysis. The recommendations are the result of broad consultation and present an ambitious agenda for federal agencies, state/local/tribal jurisdictions, universities and the research sector, professional associations, nongovernmental and community-based organizations, and private-sector firms.
  • Chronic antibiotic use during adulthood and weight change in the Sister Study

    Furlong, Melissa; Deming-Halverson, Sandra; Sandler, Dale P; Univ Arizona, Dept Commun Environm & Policy (PUBLIC LIBRARY SCIENCE, 2019-05-16)
    Background/Objectives: Antibiotic use in early life has been associated with weight gain in several populations. However, associations between chronic antibiotic use and weight among adults in the general population are unknown. Subjects/Methods: The NIEHS Sister Study is a longitudinal cohort of sisters of women with breast cancer. We examined associations between chronic antibiotic use (>= 3 months) during the fourth decade of life (30-39 years) and subsequent obesity at enrollment (mean age = 55) via logistic regression. We also examined associations between chronic antibiotic use in the 5 years and 12 months prior to enrollment and weight gain after enrollment in linear mixed models. Models were adjusted for race/ethnicity, education, urban/rural status, age, and smoking. Results: In adjusted analyses (n = 50,237), chronic penicillin use during the 4 th decade of life was associated with obesity at enrollment (OR 2.00, 95% CI 1.40, 2.87), and use in the 5 years prior to enrollment was associated with increased BMI change after enrollment (beta 1.00 95% CI 0.01, 2.00). Use of bactericidals (OR 1.71, 95% CI 1.29, 2.26) during the 4 th decade of life was also associated with obesity at enrollment. Associations for penicillins and bactericidals were consistent across indications for use. Bacteriostatic use in the 5 years prior to enrollment was associated with a reduction in BMI after enrollment (beta -0.52, 95% CI -1.04, 0.00), and tetracycline use during the 4 th decade of life was associated with reduced odds of obesity at enrollment (OR 0.72, 95% CI 0.56, 0.92). However, these inverse associations were only present for those who reported taking antibiotics for skin purposes. Cephalosporins, macrolides, quinolones, and sulfonamides were not associated with BMI change over time. Conclusions: Chronic use of antibiotics during adulthood may have long-lasting impacts on BMI. Associations may differ by antibiotic class, and confounding by indication may be important for some antibiotic classes.
  • Carvedilol inhibits EGF-mediated JB6 P+ colony formation through a mechanism independent of adrenoceptors

    Cleveland, Kristan H; Liang, Sherry; Chang, Andy; Huang, Kevin M; Chen, Si; Guo, Lei; Huang, Ying; Andresen, Bradley T; Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol (PUBLIC LIBRARY SCIENCE, 2019-05-20)
    Carvedilol is reported to prevent cancers in humans and animal models. However, a molecular mechanism has yet to be established, and the extent to which other P-blockers are chemopreventive remains relatively unknown. A comparative pharmacological approach was utilized with the expectation that a mechanism of action could be devised. JB6 CI 41-5a (JB6 P+) murine epidermal cells were used to elucidate the chemopreventative properties of beta-blockers, as JB6 P+ cells recapitulate in vivo tumor promotion and chemoprevention. The initial hypothesis was that beta-blockers that are GRK/beta-arrestin biased agonists, like carvedilol, are chemopreventive. Sixteen beta-blockers of different classes, isoproterenol, and HEAT HCI were individually co-administered with epidermal growth factor (EGF) to JB6 P+ cells to examine the chemopreventative properties of each ligand. Cytotoxicity was examined to ensure that the anti-transformation effects of each ligand were not due to cellular growth inhibition. Many of the examined p-blockers suppressed EGF-induced JB6 P+ cell transformation in a non-cytotoxic and concentration-dependent manner. However, the IC50 values are high for the most potent inhibitors (243, 326, and 431 nM for carvedilol, labetalol, and alprenolol, respectively) and there is no correlation between pharmacological properties and inhibition of transformation. Therefore, the role of alpha 1- and beta 2-adrenergic receptors (AR) was examined by standard competition assays and shRNA targeting beta 2-ARs, the only beta-AR expressed in JB6 P+ cells. The results reveal that pharmacological inhibition of alpha 1- and beta 2-ARs and genetic knockdown of beta 2-ARs did not abrogate carvedilol-mediated inhibition of EGF-induced JB6 P+ cell transformation. Furthermore, topical administration of carvedilol protected mice from UV-induced skin damage, while genetic ablation of beta 2-ARs increased carvedilol-mediated effects. Therefore, the prevailing hypothesis that the chemopreventive property of carvedilol is mediated through P-ARs is not supported by this data.
  • Effectiveness and Tolerability of Vildagliptin and the Single Pill Combination of Vildagliptin and Metformin in "Real-World" Management of Type 2 Diabetes Mellitus: The G-FORCE Study

    Van Gaal, Luc; Hermans, Michel P; Daci, Evis; Denhaerynck, Kris; De Meester, Lut; MacDonald, Karen; Abraham, Ivo; Vancayzeele, Stefaan; Maris, Michael; Univ Arizona, Ctr Hlth Outcomes & Pharmacoecon Res; et al. (SPRINGER HEIDELBERG, 2019-06)
    Introduction: Randomized clinical trials showed that vildagliptin is well tolerated and leads to clinically meaningful decreases in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) both in monotherapy and as add-on therapy in inadequately controlled type 2 diabetes mellitus (T2DM) patients. Nevertheless, there is an increased interest for real-life studies to confirm the clinical trial findings in the setting of a daily clinical practice. The aim of this study was to evaluate the effectiveness and tolerability of vildagliptin in a real-life clinical setting and to explore factors determining drug adherence and T2DM management. Methods: G-FORCE was a prospective, observational, open-label, multi-center study in which T2DM patients were prescribed de novo vildagliptin. Clinical effectiveness was determined by changes in HbA1c and FPG and by the proportion of patients reaching glycemic goal. Data were collected at baseline, after 10515 days and after 18015 days. Results: A total of 1230 patients were included in this analysis. Mean age was 63.9 +/- 10.8years, and mean HbA1c and FPG levels were 8.2 +/- 1.3% and 171.0 +/- 53.3mg/dL, respectively. At 180days of treatment, HbA1c and FPG levels decreased to 7.2 +/- 1.0% and 141.1 +/- 44.0mg/dL, respectively, while the proportion of patients reaching HbA1c and FPG goals rose from 8.6 to 44.6% and from 14.2 to 42.8%, respectively. Conclusion: In this real-world study, vildagliptin was an effective and safe treatment for T2DM patients already treated with metformin, while the single pill combination of vildagliptin and metformin provides a convenient alternative while ensuring comparable effectiveness and tolerability. Funding: Novartis Pharma.
  • Tail Wags the Dog? Functional Gene Classes Driving Genome-Wide GC Content in Plasmodium spp

    Castillo, Andreina I; Nelson, Andrew D L; Lyons, Eric; Univ Arizona, Sch Plant Sci; Univ Arizona, Sch Plant Sci, BIO5 Inst (OXFORD UNIV PRESS, 2019-02)
    Plasmodium parasites are valuable models to understand how nucleotide composition affects mutation, diversification, and adaptation. No other observed eukaryotes have undergone such large changes in genomic Guanine-Cytosine (GC) content as seen in the genus Plasmodium (approximate to 30% within 35-40 Myr). Although mutational biases are known to influence GC content in the human-infective Plasmodium vivax and Plasmodium falciparum; no study has addressed how different gene functional classes contribute to genus-wide compositional changes, or if Plasmodium GC content variation is driven by natural selection. Here, we tested the hypothesis that certain gene processes and functions drive variation in global GC content between Plasmodium species. We performed a large-scale comparative genomic analysis using the genomes and predicted genes of 17 Plasmodium species encompassing a wide genomic GC content range. Genic GC content was sorted and divided into ten equally sized quantiles that were then assessed for functional enrichment classes. In agreement that selection on gene classes may drive genomic GC content, trans-membrane proteins were enriched within extreme GC content quantiles (Q1 and Q10). Specifically, variant surface antigens, which primarily interact with vertebrate immune systems, showed skewed GC content distributions compared with other trans-membrane proteins. Although a definitive causation linking GC content, expression, and positive selection within variant surface antigens from Plasmodium vivax, Plasmodium berghei, and Plasmodium falciparum could not be established, we found that regardless of genomic nucleotide composition, genic GC content and expression were positively correlated during trophozoite stages. Overall, these data suggest that, alongside mutational biases, functional protein classes drive Plasmodium GC content change.
  • Mitochondrial Dysfunction Is Inducible in Lymphoblastoid Cell Lines From Children With Autism and May Involve the TORC1 Pathway

    Bennuri, Sirish C.; Rose, Shannon; Frye, Richard E.; Univ Arizona, Coll Med Phoenix, Dept Child Hlth (FRONTIERS MEDIA SA, 2019-05-07)
    We previously developed a lymphoblastoid cell line (LCL) model of mitochondrial dysfunction in autism spectrum disorder (ASD); some individuals with ASD showed mitochondrial dysfunction (AD-A) while other individuals (AD-N) demonstrated mitochondrial respiration similar to controls (CNT). To test the hypothesis that mitochondrial dysfunction could be a consequence of environmental exposures through chronic elevations in reactive oxygen species (ROS), we exposed LCLs to prolonged ROS. We also examined expression of metabolic regulatory genes and the modulating effect of the mechanistic target of rapamycin (mTOR) pathway. Prolonged ROS exposure induced or worsened mitochondrial dysfunction in all LCL groups. Expression of genes associated with ROS protection was elevated in both AD-N and AD-A LCLs, but mitochondrial fission/fusion and mitoplasticity gene expression was only increased in AD-N LCLs. Partial least squares discriminant analysis showed that mTOR, UCP2 (uncoupling protein 2), SIRT1 (sirtuin 1), and MFN2 (mitofusin-2) gene expression differentiated LCL groups. Low-dose rapamycin (0.1 nM) normalized respiration with the magnitude of this normalization greater for AD-A LCLs, suggesting that the mammalian target of rapamycin complex 1 (mTORC1) pathway may have a different dynamic range for regulating mitochondrial activity in individuals with ASD with and without mitochondrial dysfunction, potentially related to S6K1 (S6 kinase beta-1) regulation. Understanding pathways that underlie mitochondrial dysfunction in ASD may lead to novel treatments.
  • Persistent cloaca and caudal duplication in a monovular twin, a rare case report

    Cohen, Naomi; Ahmed, Mohamed Nagy; Goldfischer, Rachelle; Zaghloul, Nahla; Univ Arizona, Coll Med; Univ Arizona, Div Neonatol; Univ Arizona, Steele Childrens Res Ctr; Univ Arizona, Diamond Childrens Med Ct (ELSEVIER SCI LTD, 2019-06)
    INTRODUCTION: A cloaca occurs when genitourinary tract and bowel converge into a common channel. We report a case of partial caudal duplication, persistent cloaca and vestigial appendage in a monovular female twin infant. PRESENTATION OF CASE: This is a monochorinonic-diamniotic twin born at 36 weeks with apgars of 9/9. She had a duplicated labia with two clitorises, and a partially formed accessory foot with 2 toes protruding from the right gluteal region. There was anal atresia and a punctate urethral opening in the right genitalia through which she voided spontaneously. X-ray of the accessory foot had rudimentary metatarsals and phalanges. There was left hydroureteronephrosis and a hydrocolpos causing severe mass effect. On the first day of life, she had exploratory laparotomy with a diverting colostomy and mucus fistula and drainage of hydrocolpos. At 6 months of age, she had removal of the accessory foot with flap closure of the perineal defect and vesicostomy. At 15 months of age she had laparotomy for repair of cloaca, excision of presacral pelvic mass and the duplicated vulva. DISCUSSION: Theories of etiology include failure of regression of Kovalevsky's canal (a communication that connects the amniotic and yolk sac), an incomplete form of twinning through iatrogenic damage to the zona pellucida or a failed triplet formation from a single embryo. CONCLUSION: Caudal duplication with persistent cloaca and vestigial appendage is a rare and complex malformation. Having a unified surgical and medical team to preserve quality of life and to treat complications is of key importance. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.
  • Optimized-Eight-State CV-QKD Protocol Outperforming Gaussian Modulation Based Protocols

    Djordjevic, Ivan B.; Univ Arizona, Dept Elect & Comp Engn (IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC, 2019-08)
    In this paper, an optimized-eight-state CV-QKD protocol is proposed significantly outperforming previously introduced discrete modulation (DM) protocols as well as the corresponding Gaussian modulation (GM)-based CV-QKD protocols for practical reconciliation efficiencies values in terms of both secret-key rate (SKR) and achievable distance. The proposed CV-QKD protocol also outperforms, in terms of SKR, the corresponding high-cost single-photon DV-QKD scheme, employing an array of multiplexed single-photon detectors, for several orders of magnitude. We also describe a generalized RF-assisted CV-QKD scheme with heterodyne detection applicable to arbitrary DM scheme, insensitive to the laser phase noise and frequency offset fluctuations.
  • Just the Two of Us? A Family of Pseudomonas Megaplasmids Offers a Rare Glimpse into the Evolution of Large Mobile Elements

    Smith, Brian A; Leligdon, Courtney; Baltrus, David A; Univ Arizona, Sch Plant Sci; Univ Arizona, Sch Anim & Comparat Biomed Sci (OXFORD UNIV PRESS, 2019-03-27)
    Pseudomonads are ubiquitous group of environmental proteobacteria, well known for their roles in biogeochemical cycling, in the breakdown of xenobiotic materials, as plant growth promoters, and as pathogens of a variety of host organisms. We have previously identified a large megaplasmid present within one isolate of the plant pathogen Pseudomonas syringae, and here we report that a second member of this megaplasmid family is found within an environmental Pseudomonad isolate most closely related to Pseudomonas putida. Many of the shared genes are involved in critical cellular processes like replication, transcription, translation, and DNA repair. We argue that presence of these shared pathways sheds new light on discussions about the types of genes that undergo horizontal gene transfer (i.e., the complexity hypothesis) as well as the evolution of pangenomes. Furthermore, although both megaplasmids display a high level of synteny, genes that are shared differ by over 50% on average at the amino acid level. This combination of conservation in gene order despite divergence in gene sequence suggests that this Pseudomonad megaplasmid family is relatively old, that gene order is under strong selection within this family, and that there are likely many more members of this megaplasmid family waiting to be found in nature.
  • Evolution of Hominin Polyunsaturated Fatty Acid Metabolism: From Africa to the New World

    Harris, Daniel N; Ruczinski, Ingo; Yanek, Lisa R; Becker, Lewis C; Becker, Diane M; Guio, Heinner; Cui, Tao; Chilton, Floyd H; Mathias, Rasika A; O'Connor, Timothy D; et al. (OXFORD UNIV PRESS, 2019-04-03)
    The metabolic conversion of dietary omega-3 and omega-6 18 carbon (18C) to long chain (>20 carbon) polyunsaturated fatty acids (LC-PUFAs) is vital for human life. The rate-limiting steps of this process are catalyzed by fatty acid desaturase (FADS) 1 and 2. Therefore, understanding the evolutionary history of the FADS genes is essential to our understanding of hominin evolution. The FADS genes have two haplogroups, ancestral and derived, with the derived haplogroup being associated with more efficient LC-PUFA biosynthesis than the ancestral haplogroup. In addition, there is a complex global distribution of these haplogroups that is suggestive of Neanderthal introgression. We confirm that Native American ancestry is nearly fixed for the ancestral haplogroup, and replicate a positive selection signal in Native Americans. This positive selection potentially continued after the founding of the Americas, although simulations suggest that the timing is dependent on the allele frequency of the ancestral Beringian population. We also find that the Neanderthal FADS haplotype is more closely related to the derived haplogroup and the Denisovan clusters closer to the ancestral haplogroup. Furthermore, the derived haplogroup has a time to the most recent common ancestor of 688,474years before present. These results support an ancient polymorphism, as opposed to Neanderthal introgression, forming in the FADS region during the Pleistocene with possibly differential selection pressures on both haplogroups. The near fixation of the ancestral haplogroup in Native American ancestry calls for future studies to explore the potential health risk of associated low LC-PUFA levels in these populations.
  • 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.

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