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  • Reproductive ecology of a parasitic plant differs by host species: vector interactions and the maintenance of host races

    Yule, Kelsey M.; Bronstein, Judith L.; Univ Arizona, Dept Ecol & Evolutionary Biol (SPRINGER, 2018-02)
    Parasitic plants often attack multiple host species with unique defenses, physiology, and ecology. Reproductive phenology and vectors of parasitic plant genes (pollinators and dispersers) can contribute to or erode reproductive isolation of populations infecting different host species. We asked whether desert mistletoe, Phoradendron californicum (Santalaceae tribe Visceae syn. Viscaceae), differs ecologically across its dominant leguminous hosts in ways affecting reproductive isolation. Parasite flowering phenology on one host species (velvet mesquite, Prosopis velutina) differed significantly from that on four others, and phenology was not predicted by host species phenology or host individual. Comparing mistletoe populations on mesquite and another common host species (catclaw acacia, Senegalia greggii) for which genetically distinct host races are known, we tested for differences in interactions with vectors by quantifying pollinator visitation, reward production, pollen receipt, and fruit consumption. Mistletoes on mesquite produced more pollinator rewards per flower (1.86 times the nectar and 1.92 times the pollen) and received similar to 2 more pollen grains per flower than those on acacia. Mistletoes on the two host species interacted with distinct but overlapping pollinator communities, and pollinator taxa differed in visitation according to host species. Yet, mistletoes of neither host showed uniformly greater reproductive success. Fruit set (0.70) did not differ by host, and the rates of fruit ripening and removal differed in contrasting ways. Altogether, we estimate strong but asymmetric pre-zygotic isolating barriers between mistletoes on the two hosts. These host-associated differences in reproduction have implications for interactions with mutualist vectors and population genetic structure.
  • Ethical issues in non-intervention trials for thyroid cancer

    Angelos, P.; Hartl, D.M.; Shah, J.P.; Nixon, I.J.; Owen, R.P.; Rinaldo, A.; Rodrigo, J.P.; Shaha, A.R.; Silver, C.E.; Suárez, C.; Ferlito, A.; Univ Arizona, Coll Med (ELSEVIER SCI LTD, 2018-03)
    In recent years, the increasing numbers of small, apparently indolent thyroid cancers diagnosed in the world have encouraged investigators to consider non-intervention as an alternative to surgical management. In the following pages, the prospect of a non-intervention trial for thyroid cancer is considered with attention to the ethical issues that such a trial might raise. Such a non-intervention trial is analyzed relative to 7 ethical considerations: the social or scientific value of the research, the scientific validity of the trial, the necessity of fair selection of participants, a favorable risk-benefit ratio for trial participants, independent review of the trial, informed consent, and allowing the study participants to withdraw from the trial. A non-intervention trial for thyroid cancer is also considered relative to the central concept of equipoise. (C) 2017 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
  • The effects of the alkaloid scopolamine on the performance and behavior of two caterpillar species

    Wilson, J. K.; Tseng, A. S.; Potter, K. A.; Davidowitz, G.; Hildebrand, J. G.; Univ Arizona, Dept Entomol; Univ Arizona, Dept Neurosci; Univ Arizona, Deparartment Ecol & Evolutionary Biol; Univ Arizona, Ctr Insect Sci (SPRINGER, 2018-02)
    Plants have evolved many defenses against insect herbivores, including numerous chemicals that can reduce herbivore growth, performance, and fitness. One group of chemicals, the tropane alkaloids, is commonly found in the nightshade family (Solanaceae) and has been thought to reduce performance and fitness in insects. We examined the effects of the tropane alkaloid scopolamine, an alkaloid constituent of Datura wrightii, which is the most frequent host plant for the abundant and widespread insect herbivore Manduca sexta in the southwestern United States. We exposed caterpillars of two different species to scopolamine: M. sexta, which has a shared evolutionary history with Datura and other solanaceous plants, and Galleria mellonella, which does not. We showed that the addition of ecologically realistic levels of scopolamine to both the diet and the hemolymph of these two caterpillar species (M. sexta and G. mellonella) had no effect on the growth of either species. We also showed that M. sexta has no behavioral preference for or against scopolamine incorporated into an artificial diet. These results are contrary to other work showing marked differences in performance for other insect species when exposed to scopolamine, and provide evidence that scopolamine might not provide the broad-spectrum herbivore resistance typically attributed to it. It also helps to clarify the coevolutionary relationship between M. sexta and one of its main host plants, as well as the physiological mechanism of resistance against scopolamine.
  • FERTILIZATION-INDEPENDENT SEED-Polycomb Repressive Complex 2 plays a dual role in regulating type I MADS-box genes in early endosperm development

    Zhang, Shanshan; Wang, Dongfang; Zhang, Huajian; Skaggs, Megan I.; Lloyd, Alan; Ran, Di; An, Lingling; Schumaker, Karen S.; Drews, Gary N.; Yadegari, Ramin; Univ Arizona, Sch Plant Sci; Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Div Epidemiol & Biostat; Univ Arizona, Dept Agr & Biosyst Engn (AMER SOC PLANT BIOLOGISTS, 2018-05)
    Early endosperm development presents a unique system in which to uncover epigenetic regulatory mechanisms because the contributing maternal and paternal genomes possess differential epigenetic modifications. In Arabidopsis (Arabidopsis thaliana), the initiation of endosperm coenocytic growth upon fertilization and the transition to endosperm cellularization are regulated by the FERTILIZATION-INDEPENDENT SEED (FIS)-Polycomb Repressive Complex 2 (PRC2), a putative H3K27 methyltransferase. Here, we address the possible role of the FIS-PRC2 complex in regulating the type I MADS-box gene family, which has been shown previously to regulate early endosperm development. We show that a subclass of type I MADS-box genes (C2 genes) was expressed in distinct domains of the coenocytic endosperm in wild-type seeds. Furthermore, the C2 genes were mostly up-regulated biallelically during the extended coenocytic phase of endosperm development in the FIS-PRC2 mutant background. Using allele-specific expression analysis, we also identified a small subset of C2 genes subjected to FIS-PRC2-dependent maternal or FIS-PRC2-independent paternal imprinting. Our data support a dual role for the FIS-PRC2 complex in the regulation of C2 type I MADS-box genes, as evidenced by a generalized role in the repression of gene expression at both alleles associated with endosperm cellularization and a specialized role in silencing the maternal allele of imprinted genes.
  • Ostomy telehealth for cancer survivors: Design of the Ostomy Self-management Training (OSMT) randomized trial

    Sun, Virginia; Ercolano, Elizabeth; McCorkle, Ruth; Grant, Marcia; Wendel, Christopher S.; Tallman, Nancy J.; Passero, Frank; Raza, Sabreen; Cidav, Zuleyha; Holcomb, Michael; Weinstein, Ronald S.; Hornbrook, Mark C.; Krouse, Robert S.; Univ Arizona (ELSEVIER SCIENCE INC, 2018-01)
    Purpose: An ostomy adversely affects health-related quality of life (HRQOL) in a diverse population of cancer survivors and their caregivers. Hit-or-miss ostomy care, nurse counseling, and community referral have been the primary modes of self-management education and support in the pert-operative setting. Few evidence-based, systematic ostomy self-management programs are available to ensure optimal post-operative care. This paper describes the study design of a telehealth-based Ostomy Self-management Training (OSMT) program for cancer survivors and their caregivers. Methods: The study is a three-year, randomized trial that tests the effectiveness of the OSMT program on survivor activation, self-efficacy, and HRQOL. The intervention integrates goal setting and problem-solving approaches to enhance survivor activation and self-efficacy to carry out ostomy care. The curriculum is delivered via four group sessions administered by trained ostomy certified nurses (WOCNs) and peer ostomates. An additional session is offered to caregivers to address their needs in relation to ostomy care. Telehealth approaches through videoconferencing are used to enhance program delivery to participants in three different geographic areas across two time zones. Participants join sessions via real-time videoconferencing from their homes. Conclusions: The OSMT program has high potential to make a positive impact on the unique physical, psychological, social, and spiritual needs of cancer survivors living with a permanent ostomy. The study design, process, and telehealth approach contributes to the success of future dissemination efforts of the intervention into diverse clinical and community settings.
  • Epigenetic modulation of Nrf2 and Ogg1 gene expression in testicular germ cells by methyl parathion exposure

    Hernandez-Cortes, D.; Alvarado-Cruz, I.; Solís-Heredia, M.J.; Quintanilla-Vega, B.; Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018-05)
    Methyl parathion (Me-Pa) is an oxidizing organophosphate (OP) pesticide that generates reactive oxygen species (ROS) through its biotransformation. Some studies have also suggested that OP pesticides have the capacity to alkylate biomolecules, including DNA. In general, DNA methylation in gene promoters represses transcription. NRF2 is a key transcription factor that regulates the expression of antioxidant, metabolic and detoxifying genes through the antioxidant response element (ARE) situated in promoters of regulated genes. Furthermore, DNA repair genes, including 8-oxoguanine DNA glycosidase (OGG1), have been proposed as NRF2 target genes. Me-Pa exposure produces poor semen quality, genetic and oxidative damage in sperm cells, and reduced fertility. However, the Me-Pa effects on the methylation status and the expression of antioxidant (Nrf2) or DNA repair (Ogg1) genes in male germ cells have not been investigated. Therefore, mice were exposed to Me-Pa to evaluate the global (%5-mC) and specific methylation of Nrf2 and 0:4:1 genes using pyrosequencing, gene expression, and total protein carbonylation in male germ cells. The results showed that Me-Pa significantly decreased the global DNA methylation pattern and significantly increased the methylation of two CpG sites within Ogg1 promoter and one CpG site within Nrf2 promoter, In addition, Ogg1 or Nrf2 expression did not change after Me-Pa exposure despite the oxidative damage produced. Altogether, our data suggest that Me-Pa toxicity alters Ogg1 and Nrf2 promoter methylation in male germ cells that may be modulating their gene expression.
  • TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD

    Chou, Ching-Chieh; Zhang, Yi; Umoh, Mfon E.; Vaughan, Spencer W.; Lorenzini, Ileana; Liu, Feilin; Sayegh, Melissa; Donlin-Asp, Paul G.; Chen, Yu Han; Duong, Duc M.; Seyfried, Nicholas T.; Powers, Maureen A.; Kukar, Thomas; Hales, Chadwick M.; Gearing, Marla; Cairns, Nigel J.; Boylan, Kevin B.; Dickson, Dennis W.; Rademakers, Rosa; Zhang, Yong-Jie; Petrucelli, Leonard; Sattler, Rita; Zarnescu, Daniela C.; Glass, Jonathan D.; Rossoll, Wilfried; Univ Arizona, Dept Mol & Cellular Biol (NATURE PUBLISHING GROUP, 2018-02)
    The cytoplasmic mislocalization and aggregation of TAR DNA-binding protein-43 (TDP-43) is a common histopathological hallmark of the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum (ALS/FTD). However, the composition of aggregates and their contribution to the disease process remain unknown. Here we used proximity-dependent biotin identification (BioID) to interrogate the interactome of detergent-insoluble TDP-43 aggregates and found them enriched for components of the nuclear pore complex and nucleocytoplasmic transport machinery. Aggregated and disease-linked mutant TDP-43 triggered the sequestration and/or mislocalization of nucleoporins and transport factors, and interfered with nuclear protein import and RNA export in mouse primary cortical neurons, human fibroblasts and induced pluripotent stem cell-derived neurons. Nuclear pore pathology is present in brain tissue in cases of sporadic ALS and those involving genetic mutations in TARDBP and C9orf72. Our data strongly implicate TDP-43-mediated nucleocytoplasmic transport defects as a common disease mechanism in ALS/FTD.
  • 16S rRNA gene sequencing on a benchtop sequencer: accuracy for identification of clinically important bacteria.

    Watts, G S; Youens-Clark, K; Slepian, M J; Wolk, D M; Oshiro, M M; Metzger, G S; Dhingra, D; Cranmer, L D; Hurwitz, B L; Univ Arizona, Ctr Canc; Univ Arizona, Dept Pharmacol; Univ Arizona, Dept Agr & Biosyst Engn; Univ Arizona, Dept Med; Univ Arizona, Dept Biomed Engn; Univ Arizona, Arizona Ctr Accelerated Biomed Innovat (WILEY, 2017-12-01)
    Test the choice of 16S rRNA gene amplicon and data analysis method on the accuracy of identification of clinically important bacteria utilizing a benchtop sequencer. Nine 16S rRNA amplicons were tested on an Ion Torrent PGM to identify 41 strains of clinical importance. The V1-V2 region identified 40 of 41 isolates to the species level. Three data analysis methods were tested, finding that the Ribosomal Database Project's SequenceMatch outperformed BLAST and the Ion Reporter Metagenomics analysis pipeline. Lastly, 16S rRNA gene sequencing mixtures of four species through a six log range of dilution showed species were identifiable even when present as 0·1% of the mixture. Sequencing the V1-V2 16S rRNA gene region, made possible by the increased read length Ion Torrent PGM sequencer's 400 base pair chemistry, may be a better choice over other commonly used regions for identifying clinically important bacteria. In addition, the SequenceMatch algorithm, freely available from the Ribosomal Database Project, is a good choice for matching filtered reads to organisms. Lastly, 16S rRNA gene sequencing's sensitivity to the presence of a bacterial species at 0·1% of a mixture suggests it has sufficient sensitivity for samples in which important bacteria may be rare. We have validated 16S rRNA gene sequencing on a benchtop sequencer including simple mixtures of organisms; however, our results highlight deficits for clinical application in place of current identification methods.
  • Search for new high-mass phenomena in the dilepton final state using 36 fb(-1) of proton-proton collision data at root s=13 TeV with the ATLAS detector

    Aaboud, M.; Cheu, E.; Delitzsch, C. M.; Johns, K. A.; Jones, S.; Lampl, W.; LeBlanc, M.; Lei, X.; Leone, R.; Loch, P.; Nayyar, R.; Rutherfoord, J. P.; Varnes, E. W.; Zhou, Y.; Univ Arizona, Dept Phys (SPRINGER, 2017-10-26)
    A search is conducted for new resonant and non-resonant high-mass phenomena in dielectron and dimuon fi nal states. The search uses 36 : 1 fb(-1) of proton-proton collision data, collected at root s = 13TeV by the ATLAS experiment at the LHC in 2015 and 2016. No signi fi cant deviation from the Standard Model prediction is observed. Upper limits at 95% credibility level are set on the cross-section times branching ratio for resonances decaying into dileptons, which are converted to lower limits on the resonance mass, up to 4.1 TeV for the E-6 -motivated Z(X)'. Lower limits on the qqll contact interaction scale are set between 2.4 TeV and 40 TeV, depending on the model.
  • Combination of inclusive and differential t(t)over-bar charge asymmetry measurements using ATLAS and CMS data at root S =7 and 8 TeV

    Aaboud, M.; Cheu, E.; Delitzsch, C. M.; Johns, K. A.; Jones, S.; Lampl, W.; LeBlanc, M.; Lei, X.; Leone, R.; Loch, P.; Nayyar, R.; Rutherfoord, J. P.; Varnes, E. W.; Zhou, Y.; Univ Arizona, Dept Phys (SPRINGER, 2018-04-09)
    This paper presents combinations of inclusive and differential measurements of the charge asymmetry (A(C)) in top quark pair (t(t)over-bar) events with a lepton+jets signature by the ATLAS and CMS Collaborations, using data from LHC proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. The data correspond to integrated luminosities of about 5 and 20 fb(-1) for each experiment, respectively. The resulting combined LHC measurements of the inclusive charge asymmetry are A(C)(LHC7) = 0.005 +/- 0.007 (stat) +/- 0.006 (syst) at 7 TeV and A(C)(LHC8) = 0.0055 +/- 0.0023 (stat) +/- 0.0025 (syst) at 8 TeV. These values, as well as the combination of A(C )measurements as a function of the invariant mass of the t(t)over-bar system at 8 TeV, are consistent with the respective standard model predictions.
  • Long non-coding RNA expression patterns in lung tissues of chronic cigarette smoke induced COPD mouse model

    Zhang, Haiyun; Sun, Dejun; Li, Defu; Zheng, Zeguang; Xu, Jingyi; Liang, Xue; Zhang, Chenting; Wang, Sheng; Wang, Jian; Lu, Wenju; Univ Arizona, Div Translat & Regenerat Med (NATURE PUBLISHING GROUP, 2018-05-15)
    Long non-coding RNAs (lncRNAs) have critical regulatory roles in protein-coding gene expression. Aberrant expression profiles of lncRNAs have been observed in various human diseases. In this study, we investigated transcriptome profiles in lung tissues of chronic cigarette smoke (CS)-induced COPD mouse model. We found that 109 lncRNAs and 260 mRNAs were significantly differential expressed in lungs of chronic CS-induced COPD mouse model compared with control animals. GO and KEGG analyses indicated that differentially expressed lncRNAs associated protein-coding genes were mainly involved in protein processing of endoplasmic reticulum pathway, and taurine and hypotaurine metabolism pathway. The combination of high throughput data analysis and the results of qRT-PCR validation in lungs of chronic CS-induced COPD mouse model, 16HBE cells with CSE treatment and PBMC from patients with COPD revealed that NR_102714 and its associated protein-coding gene UCHL1 might be involved in the development of COPD both in mouse and human. In conclusion, our study demonstrated that aberrant expression profiles of lncRNAs and mRNAs existed in lungs of chronic CS-induced COPD mouse model. From animal models perspective, these results might provide further clues to investigate biological functions of lncRNAs and their potential target protein-coding genes in the pathogenesis of COPD.
  • Linking cervicovaginal immune signatures, HPV and microbiota composition in cervical carcinogenesis in non-Hispanic and Hispanic women

    Łaniewski, Paweł; Barnes, Dominique; Goulder, Alison; Cui, Haiyan; Roe, Denise J.; Chase, Dana M.; Herbst-Kralovetz, Melissa M.; Univ Arizona, Coll Med Phoenix, Dept Basic Med Sci; Univ Arizona, Coll Med Phoenix, Dept Obstet & Gynecol; Univ Arizona, UA Canc Ctr (NATURE PUBLISHING GROUP, 2018-05-15)
    While high-risk human papillomavirus (HPV) infection is a well-established risk factor for cervical cancer, there are likely other factors within the local microenvironment that contribute to cervical carcinogenesis. Here we investigated relationships between HPV, vaginal pH, vaginal microbiota (VMB) composition, level of genital immune mediators and severity of cervical neoplasm. We enrolled women with low- and high-grade cervical dysplasia (LGD, HGD), invasive cervical carcinoma (ICC), and healthy controls. HPV16, HPV45, HPV58, and HPV31 were the most prevalent in our cohort with HPV16 and HPV31 genotypes more prevalent in Hispanics. Vaginal pH was associated with ethnicity and severity of cervical neoplasm. Lactobacillus dominance decreased with the severity of cervical neoplasm, which correlated with elevated vaginal pH. Hispanic ethnicity was also associated with decreased Lactobacillus dominance. Furthermore, Sneathia was enriched in all precancerous groups, ICC, abnormal pH and Hispanic origin. Patients with ICC, but not LGD and HGD, exhibited increased genital inflammatory scores and elevated specific immune mediators. Notably, IL-36 gamma was significantly associated with ICC. Our study revealed local, host immune and microbial signatures associated with cervical carcinogenesis and provides an initial step to understanding the complex interplay between mucosal inflammation, HPV persistence and the VMB.
  • Female combatants, forced recruitment, and civil conflict outcomes

    Braithwaite, Alex; Ruiz, Luna B.; Univ Arizona, Sch Govt & Publ Policy (SAGE PUBLICATIONS INC, 2018-05)
    Women participated as combatants in almost 40% of civil conflicts that occurred between 1979 and 2009. We offer a novel argument about the effect of female combatants upon the outcomes of the civil conflicts that they join. Groups that recruit female combatants are more likely to achieve victory in their conflicts than are groups that do not recruit female combatants. However, when rebel groups rely upon forced recruitment, they risk undermining the benefits associated with female combatants, lowering their likelihood of victory relative to that of the government. We test this conditional argument using multinomial logistic regression models on a sample of 194 rebel groups globally from 1979 to 2009. We find that female participation appears to decrease the likelihood of government victory in civil wars; this effect holds primarily in instances in which female participation could plausibly be thought of as voluntary. Forced female participation, by contrast, appears to increase the likelihood of a government victory.
  • Endothelial nitric oxide synthase genotype is associated with pulmonary hypertension severity in left heart failure patients

    Duarte, Julio D.; Kansal, Mayank; Desai, Ankit A.; Riden, Katherine; Arwood, Meghan J.; Yacob, Alex A.; Stamos, Thomas D.; Cavallari, Larisa H.; Zamanian, Roham T.; Shah, Sanjiv J.; Machado, Roberto F.; Univ Arizona, Coll Med, Dept Med; Univ Arizona, Coll Med, Sarver Heart Ctr (SAGE PUBLICATIONS INC, 2018-05-02)
    The biological mechanisms behind the development of pulmonary hypertension in the setting of left heart failure (HF-PH), including combined pre- and post-capillary pulmonary hypertension (Cpc-PH), remains unclear. This study aimed to use candidate polymorphisms in nitric oxide synthase (NOS) genes to explore the role of NOS in HF-PH. DNA samples from 118 patients with HF-PH were genotyped for the NOS3 rs1799983 and NOS2 rs3730017 polymorphisms. A multiple regression model was used to compare hemodynamic measurements between genotype groups. Patients with the T/T genotype at rs1799983 possessed a nearly 10 mmHg increased transpulmonary gradient (TPG) compared to those with other genotypes (P = 0.006). This finding was replicated in an independent cohort of 94 HF-PH patients (P = 0.005). However, when tested in a cohort of 162 pre-capillary pulmonary arterial hypertension patients, no association was observed. In a combined analysis of both HF-PH cohorts, mean pulmonary artery pressure (mPAP), diastolic pulmonary gradient (DPG), and CpcPH status were also associated with rs1799983 genotype (P = 0.005, P = 0.03, and P= 0.02, respectively). In patients with HF-PH, the NOS3 rs1799983 polymorphism is associated with TPG, and potentially mPAP and DPG as well. These findings suggest that endothelial NOS (encoded by NOS3) may be involved in the pulmonary vascular remodeling observed in Cpc-PH and warrants further study.
  • Host Pah1p phosphatidate phosphatase limits viral replication by regulating phospholipid synthesis.

    Zhang, Zhenlu; He, Guijuan; Han, Gil-Soo; Zhang, Jiantao; Catanzaro, Nicholas; Diaz, Arturo; Wu, Zujian; Carman, George M; Xie, Lianhui; Wang, Xiaofeng; Univ Arizona, Dept Pharmacol & Toxicol (PUBLIC LIBRARY SCIENCE, 2018-04)
    Replication of positive-strand RNA viruses [(+)RNA viruses] takes place in membrane-bound viral replication complexes (VRCs). Formation of VRCs requires virus-mediated manipulation of cellular lipid synthesis. Here, we report significantly enhanced brome mosaic virus (BMV) replication and much improved cell growth in yeast cells lacking PAH1 (pah1Δ), the sole yeast ortholog of human LIPIN genes. PAH1 encodes Pah1p (phosphatidic acid phosphohydrolase), which converts phosphatidate (PA) to diacylglycerol that is subsequently used for the synthesis of the storage lipid triacylglycerol. Inactivation of Pah1p leads to altered lipid composition, including high levels of PA, total phospholipids, ergosterol ester, and free fatty acids, as well as expansion of the nuclear membrane. In pah1Δ cells, BMV replication protein 1a and double-stranded RNA localized to the extended nuclear membrane, there was a significant increase in the number of VRCs formed, and BMV genomic replication increased by 2-fold compared to wild-type cells. In another yeast mutant that lacks both PAH1 and DGK1 (encodes diacylglycerol kinase converting diacylglycerol to PA), which has a normal nuclear membrane but maintains similar lipid compositional changes as in pah1Δ cells, BMV replicated as efficiently as in pah1Δ cells, suggesting that the altered lipid composition was responsible for the enhanced BMV replication. We further showed that increased levels of total phospholipids play an important role because the enhanced BMV replication required active synthesis of phosphatidylcholine, the major membrane phospholipid. Moreover, overexpression of a phosphatidylcholine synthesis gene (CHO2) promoted BMV replication. Conversely, overexpression of PAH1 or plant PAH1 orthologs inhibited BMV replication in yeast or Nicotiana benthamiana plants. Competing with its host for limited resources, BMV inhibited host growth, which was markedly alleviated in pah1Δ cells. Our work suggests that Pah1p promotes storage lipid synthesis and thus represses phospholipid synthesis, which in turn restricts both viral replication and cell growth during viral infection.
  • Summer dry-down modulates the isotopic composition of soil CO2 production in snow-dominated landscapes.

    Riveros-Iregui, Diego A; Lorenzo, Theresa M; Liang, Liyin L; Hu, Jia; Univ Arizona, Sch Nat Resources & Environm (PUBLIC LIBRARY SCIENCE, 2018-05-10)
    In mountainous landscapes, soil moisture is highly dynamic due to the effects of topography and the temporal variability imposed by seasonal precipitation, including rainfall and snow. Soil moisture is known to affect ecosystem carbon exchange both aboveground and belowground, as well as the stable isotopic composition of exchanged CO2. In this study we used an extensive suite of measurements to examine the effects of seasonal changes in soil moisture on the isotopic composition of soil CO2 production at the landscape level. We show that the seasonal decline in soil moisture (i.e., summer dry-down) appeared to impose a trend in the δ13C of soil CO2 production (δP) with more negative δP early in the growing season when soils were wet, and more positive δP as the growing season progressed and soils dried out. This seemingly generalizable pattern for a snow-dominated watershed is likely to represent the variability of recently assimilated C, tracked through the plant-soil system and imprinted in the respired CO2. Thus, our observations suggest that, at least for mountainous environments, seasonal changes in δP are largely mediated by soil moisture and their spatial variability is partially organized by topography.
  • Reflective all-sky thermal infrared cloud imager

    Redman, Brian J.; Shaw, Joseph A.; Nugent, Paul W.; Clark, R. Trevor; Piazzolla, Sabino; Univ Arizona, Ctr Opt Sci (OPTICAL SOC AMER, 2018-04-30)
    A reflective all-sky imaging system has been built using a long-wave infrared microbolometer camera and a reflective metal sphere. This compact system was developed for measuring spatial and temporal patterns of clouds and their optical depth in support of applications including Earth-space optical communications. The camera is mounted to the side of the reflective sphere to leave the zenith sky unobstructed. The resulting geometric distortion is removed through an angular map derived from a combination of checkerboard-target imaging, geometric ray tracing, and sun-location-based alignment. A tape of high-emissivity material on the side of the reflector acts as a reference that is used to estimate and remove thermal emission from the metal sphere. Once a bias that is under continuing study was removed, sky radiance measurements from the all-sky imager in the 8-14 mu m wave-length range agreed to within 0.91 W/(m(2) sr) of measurements from a previously calibrated, lens-based infrared cloud imager over its 110 degrees field of view. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.
  • Feature-based data assimilation in geophysics

    Morzfeld, Matthias; Adams, Jesse; Lunderman, Spencer; Orozco, Rafael; Univ Arizona, Dept Math (COPERNICUS GESELLSCHAFT MBH, 2018-05-03)
    Many applications in science require that computational models and data be combined. In a Bayesian framework, this is usually done by defining likelihoods based on the mismatch of model outputs and data. However, matching model outputs and data in this way can be unnecessary or impossible. For example, using large amounts of steady state data is unnecessary because these data are redundant. It is numerically difficult to assimilate data in chaotic systems. It is often impossible to assimilate data of a complex system into a low-dimensional model. As a specific example, consider a low-dimensional stochastic model for the dipole of the Earth's magnetic field, while other field components are ignored in the model. The above issues can be addressed by selecting features of the data, and defining likelihoods based on the features, rather than by the usual mismatch of model output and data. Our goal is to contribute to a fundamental understanding of such a feature-based approach that allows us to assimilate selected aspects of data into models. We also explain how the feature-based approach can be interpreted as a method for reducing an effective dimension and derive new noise models, based on perturbed observations, that lead to computationally efficient solutions. Numerical implementations of our ideas are illustrated in four examples.
  • Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection

    Song, Hongshuo; Giorgi, Elena E.; Ganusov, Vitaly V.; Cai, Fangping; Athreya, Gayathri; Yoon, Hyejin; Carja, Oana; Hora, Bhavna; Hraber, Peter; Romero-Severson, Ethan; Jiang, Chunlai; Li, Xiaojun; Wang, Shuyi; Li, Hui; Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Goonetilleke, Nilu; Keele, Brandon F.; Montefiori, David C.; Cohen, Myron S.; Shaw, George M.; Hahn, Beatrice H.; McMichael, Andrew J.; Haynes, Barton F.; Korber, Bette; Bhattacharya, Tanmoy; Gao, Feng; Univ Arizona, Off Res & Discovery (NATURE PUBLISHING GROUP, 2018-05-15)
    Recombination in HIV-1 is well documented, but its importance in the low-diversity setting of within-host diversification is less understood. Here we develop a novel computational tool (RAPR (Recombination Analysis PRogram)) to enable a detailed view of in vivo viral recombination during early infection, and we apply it to near-full-length HIV-1 genome sequences from longitudinal samples. Recombinant genomes rapidly replace transmitted/founder (T/F) lineages, with a median half-time of 27 days, increasing the genetic complexity of the viral population. We identify recombination hot and cold spots that differ from those observed in inter-subtype recombinants. Furthermore, RAPR analysis of longitudinal samples from an individual with well-characterized neutralizing antibody responses shows that recombination helps carry forward resistance-conferring mutations in the diversifying quasispecies. These findings provide insight into molecular mechanisms by which viral recombination contributes to HIV-1 persistence and immunopathogenesis and have implications for studies of HIV transmission and evolution in vivo.
  • Increased O-GlcNAcylation of SNAP29 Drives Arsenic-Induced Autophagic Dysfunction

    Dodson, Matthew; Liu, Pengfei; Jiang, Tao; Ambrose, Andrew J.; Luo, Gang; Rojo de la Vega, Montserrat; Cholanians, Aram B.; Wong, Pak Kin; Chapman, Eli; Zhang, Donna D.; Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol; Univ Arizona, Arizona Canc Ctr (AMER SOC MICROBIOLOGY, 2018-06)
    Environmental exposure to arsenic is linked to adverse health effects, including cancer and diabetes. Pleiotropic cellular effects are observed with arsenic exposure. Previously, we demonstrated that arsenic dysregulated the autophagy pathway at low, environmentally relevant concentrations. Here we show that arsenic blocks autophagy by preventing autophagosome-lysosome fusion. Specifically, arsenic disrupts formation of the STX17-SNAP29-VAMP8 SNARE complex, where SNAP29 mediates vesicle fusion through bridging STX17- containing autophagosomes to VAMP8-bearing lysosomes. Mechanistically, arsenic inhibits SNARE complex formation, at least in part, by enhancing O-GlcNAcylation of SNAP29. Transfection of O-GlcNAcylation-defective, but not wild-type, SNAP29 into clustered regularly interspaced short palindromic repeat (CRISPR)-mediated SNAP29 knockout cells abolishes arsenic-mediated autophagy inhibition. These findings reveal a mechanism by which low levels of arsenic perturb proteostasis through inhibition of SNARE complex formation, providing a possible therapeutic target for disease intervention in the more than 200 million people exposed to unsafe levels of arsenic.

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