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Sample records for reveals regulated confinement

  1. Confinement and dynamical regulation in two-dimensional convective turbulence

    DEFF Research Database (Denmark)

    Bian, N.H.; Garcia, O.E.

    2003-01-01

    In this work the nature of confinement improvement implied by the self-consistent generation of mean flows in two-dimensional convective turbulence is studied. The confinement variations are linked to two distinct regulation mechanisms which are also shown to be at the origin of low......-frequency bursting in the fluctuation level and the convective heat flux integral, both resulting in a state of large-scale intermittency. The first one involves the control of convective transport by sheared mean flows. This regulation relies on the conservative transfer of kinetic energy from tilted fluctuations...

  2. Mechanical confinement regulates cartilage matrix formation by chondrocytes

    Science.gov (United States)

    Lee, Hong-Pyo; Gu, Luo; Mooney, David J.; Levenston, Marc E.; Chaudhuri, Ovijit

    2017-12-01

    Cartilage tissue equivalents formed from hydrogels containing chondrocytes could provide a solution for replacing damaged cartilage. Previous approaches have often utilized elastic hydrogels. However, elastic stresses may restrict cartilage matrix formation and alter the chondrocyte phenotype. Here we investigated the use of viscoelastic hydrogels, in which stresses are relaxed over time and which exhibit creep, for three-dimensional (3D) culture of chondrocytes. We found that faster relaxation promoted a striking increase in the volume of interconnected cartilage matrix formed by chondrocytes. In slower relaxing gels, restriction of cell volume expansion by elastic stresses led to increased secretion of IL-1β, which in turn drove strong up-regulation of genes associated with cartilage degradation and cell death. As no cell-adhesion ligands are presented by the hydrogels, these results reveal cell sensing of cell volume confinement as an adhesion-independent mechanism of mechanotransduction in 3D culture, and highlight stress relaxation as a key design parameter for cartilage tissue engineering.

  3. Control of 2D Flexible Structures by Confinement of Vibrations and Regulation of Their Energy Flow

    Directory of Open Access Journals (Sweden)

    Fakhreddine Landolsi

    2009-01-01

    Full Text Available In this paper, we investigate the control of 2D flexible structures by vibration confinement and the regulation of their energy flow along prespecified spatial paths. A discretized-model-based feedback strategy, aiming at confining and suppressing simultaneously the vibration, is proposed. It is assumed that the structure consists of parts that are sensitive to vibrations. The control design introduces a new pseudo-modal matrix derived from the computed eigenvectors of the discretized model. Simulations are presented to show the efficacy of the proposed control law. A parametric study is carried out to examine the effects of the different control parameters on the simultaneous confinement and suppression of vibrations. In addition, we conducted a set of simulations to investigate the flow control of vibrational energy during the confinement-suppression process. We found that the energy flow can be regulated via a set of control parameters for different confinement configurations.

  4. Regulation of the corticosteroid signalling system in rainbow trout HPI axis during confinement stress.

    Science.gov (United States)

    Kiilerich, Pia; Servili, Arianna; Péron, Sandrine; Valotaire, Claudiane; Goardon, Lionel; Leguen, Isabelle; Prunet, Patrick

    2018-03-01

    This study aims to shed light on corticosteroid regulation of stress in teleost fish with focus on the corticosteroid signalling system. The role of the mineralocorticoid-like hormone 11-deoxycorticosterone (DOC) in fish is still enigmatic, as is the function of the mineralocorticoid receptor, MR. Low plasma DOC levels and ubiquitous tissue distribution of MR question the physiological relevance of the mineralocorticoid-axis. Furthermore, the particular purpose of each of the three corticosteroid receptors in fish, the glucocorticoid receptors, GR1 and GR2, and the MR, is still largely unknown. Therefore we investigate the regulation of cortisol and DOC in plasma and mRNA levels of MR, GR1 and GR2 in the HPI-axis tissues (hypothalamus, pituitary and interrenal gland) during a detailed confinement stress time-course. Here we show a sustained up-regulation of plasma DOC levels during a confinement stress time-course. However, the low DOC levels compared to cortisol measured in the plasma do not favour an activity of DOC through MR receptors. Furthermore, we show differential contribution of the CRs in regulation and control of HPI axis activity following confinement stress. Judged by the variation of mRNA levels negative feedback regulation of cortisol release occurs on the level of the pituitary via MR and on the level of the interrenal gland via GR2. Finally, asa significant effect of confinement stress on CR expressions was observed in the pituitary gland, we completed this experiment by demonstrating that corticosteroid receptors (GR1, GR2 and MR) are co-expressed in the ACTH cells located in the adenohypophysis. Overall, these data suggest the involvement of these receptors in the regulation of the HPI axis activity by cortisol. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Regulation and Measurement of the Heat Generated by Automatic Tooth Preparation in a Confined Space.

    Science.gov (United States)

    Yuan, Fusong; Zheng, Jianqiao; Sun, Yuchun; Wang, Yong; Lyu, Peijun

    2017-06-01

    The aim of this study was to assess and regulate heat generation in the dental pulp cavity and circumambient temperature around a tooth during laser ablation with a femtosecond laser in a confined space. The automatic tooth preparing technique is one of the traditional oral clinical technology innovations. In this technique, a robot controlled an ultrashort pulse laser to automatically complete the three-dimensional teeth preparing in a confined space. The temperature control is the main measure for protecting the tooth nerve. Ten tooth specimens were irradiated with a femtosecond laser controlled by a robot in a confined space to generate 10 teeth preparation. During the process, four thermocouple sensors were used to record the pulp cavity and circumambient environment temperatures with or without air cooling. A statistical analysis of the temperatures was performed between the conditions with and without air cooling (p heat generated in the pulp cavity was lower than the threshold for dental pulp damage. These results indicate that femtosecond laser ablation with air cooling might be an appropriate method for automatic tooth preparing.

  6. Anisotropic carrier and exciton confinement in T-shaped quantum wires revealed by magneto-photoluminescence

    DEFF Research Database (Denmark)

    Langbein, Wolfgang Werner; Gislason, Hannes; Hvam, Jørn Märcher

    1998-01-01

    The realization of one-dimensional (1D) semiconductor nanostructures with large confinement energies is of importance for device applications. Different techniques such as growth on tilted substrates (Serpentine superlattices) or prepatterned substrates (V-groove quantum wires) and the cleaved...

  7. Single molecule tracking fluorescence microscopy in mitochondria reveals highly dynamic but confined movement of Tom40

    Science.gov (United States)

    Kuzmenko, Anton; Tankov, Stoyan; English, Brian P.; Tarassov, Ivan; Tenson, Tanel; Kamenski, Piotr; Elf, Johan; Hauryliuk, Vasili

    2011-12-01

    Tom40 is an integral protein of the mitochondrial outer membrane, which as the central component of the Translocase of the Outer Membrane (TOM) complex forms a channel for protein import. We characterize the diffusion properties of individual Tom40 molecules fused to the photoconvertable fluorescent protein Dendra2 with millisecond temporal resolution. By imaging individual Tom40 molecules in intact isolated yeast mitochondria using photoactivated localization microscopy with sub-diffraction limited spatial precision, we demonstrate that Tom40 movement in the outer mitochondrial membrane is highly dynamic but confined in nature, suggesting anchoring of the TOM complex as a whole.

  8. Artifact-free dynamic atomic force microscopy reveals monotonic dissipation for a simple confined liquid

    Science.gov (United States)

    Kaggwa, G. B.; Kilpatrick, J. I.; Sader, J. E.; Jarvis, S. P.

    2008-07-01

    We present definitive interaction measurements of a simple confined liquid (octamethylcyclotetrasiloxane) using artifact-free frequency modulation atomic force microscopy. We use existing theory to decouple the conservative and dissipative components of the interaction, for a known phase offset from resonance (90° phase shift), that has been deliberately introduced into the experiment. Further we show the qualitative influence on the conservative and dissipative components of the interaction of a phase error deliberately introduced into the measurement, highlighting that artifacts, such as oscillatory dissipation, can be readily observed when the phase error is not compensated for in the force analysis.

  9. Insulin regulates Glut4 confinement in plasma membrane clusters in adipose cells.

    Science.gov (United States)

    Lizunov, Vladimir A; Stenkula, Karin; Troy, Aaron; Cushman, Samuel W; Zimmerberg, Joshua

    2013-01-01

    Insulin-stimulated delivery of glucose transporter-4 (GLUT4) to the plasma membrane (PM) is the hallmark of glucose metabolism. In this study we examined insulin's effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchable fluorescent protein. In the basal state, after exocytotic delivery only a fraction of GLUT4 is dispersed into the PM as monomers, while most of the GLUT4 stays at the site of fusion and forms elongated clusters (60-240 nm). GLUT4 monomers outside clusters diffuse freely and do not aggregate with other monomers. In contrast, GLUT4 molecule collision with an existing cluster can lead to immediate confinement and association with that cluster. Insulin has three effects: it shifts the fraction of dispersed GLUT4 upon delivery, it augments the dissociation of GLUT4 monomers from clusters ∼3-fold and it decreases the rate of endocytic uptake. All together these three effects of insulin shift most of the PM GLUT4 from clustered to dispersed states. GLUT4 confinement in clusters represents a novel kinetic mechanism for insulin regulation of glucose homeostasis.

  10. Insulin regulates Glut4 confinement in plasma membrane clusters in adipose cells.

    Directory of Open Access Journals (Sweden)

    Vladimir A Lizunov

    Full Text Available Insulin-stimulated delivery of glucose transporter-4 (GLUT4 to the plasma membrane (PM is the hallmark of glucose metabolism. In this study we examined insulin's effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchable fluorescent protein. In the basal state, after exocytotic delivery only a fraction of GLUT4 is dispersed into the PM as monomers, while most of the GLUT4 stays at the site of fusion and forms elongated clusters (60-240 nm. GLUT4 monomers outside clusters diffuse freely and do not aggregate with other monomers. In contrast, GLUT4 molecule collision with an existing cluster can lead to immediate confinement and association with that cluster. Insulin has three effects: it shifts the fraction of dispersed GLUT4 upon delivery, it augments the dissociation of GLUT4 monomers from clusters ∼3-fold and it decreases the rate of endocytic uptake. All together these three effects of insulin shift most of the PM GLUT4 from clustered to dispersed states. GLUT4 confinement in clusters represents a novel kinetic mechanism for insulin regulation of glucose homeostasis.

  11. Electromagnetic device for confining a liquid metal and regulating the flow rate

    International Nuclear Information System (INIS)

    Garnier, Marcel; Moreau, R.J.

    1977-01-01

    The description is given of a device for confining a liquid metal jet, characterized in that it comprises in combination, at the jet outlet nozzle, (a) means for producing a high pressure in the jet composed of a coil around the nozzle and located on its outlet, in combination with facilities for passing a high frequency alternating current through the coil and (b) means for suppressing this high pressure. It is stated that this device has many uses, particularly for allowing the use of a relatively large diameter orifice, hence not subject to the risk of clogging, in order to produce a jet with a relatively small diameter. This invention particularly concerns the application of this device for regulating a flow of liquid metal at an outlet orifice located at the lower end of a receptacle containing this liquid metal [fr

  12. Subsurface imaging reveals a confined aquifer beneath an ice-sealed Antarctic lake

    DEFF Research Database (Denmark)

    Dugan, H. A.; Doran, P. T.; Tulaczyk, S.

    2015-01-01

    Liquid water oases are rare under extreme cold desert conditions found in the Antarctic McMurdo Dry Valleys. Here we report geophysical results that indicate that Lake Vida, one of the largest lakes in the region, is nearly frozen and underlain by widespread cryoconcentrated brine. A ground...... this zone to be a confined aquifer situated in sediments with a porosity of 23-42%. Discovery of this aquifer suggests that subsurface liquid water may be more pervasive in regions of continuous permafrost than previously thought and may represent an extensive habitat for microbial populations. Key Points...... Geophysical survey finds low resistivities beneath a lake in Antarctic Dry Valleys Liquid brine abundant beneath Antarctic lake Aquifer provides microbial refugium in cold desert environment...

  13. Exercise training during normobaric hypoxic confinement does not alter hormonal appetite regulation.

    Directory of Open Access Journals (Sweden)

    Tadej Debevec

    Full Text Available Both exposure to hypoxia and exercise training have the potential to modulate appetite and induce beneficial metabolic adaptations. The purpose of this study was to determine whether daily moderate exercise training performed during a 10-day exposure to normobaric hypoxia alters hormonal appetite regulation and augments metabolic health.Fourteen healthy, male participants underwent a 10-day hypoxic confinement at ∼ 4000 m simulated altitude (FIO2 = 0.139 ± 0.003% either combined with daily moderate intensity exercise (Exercise group; N = 8, Age = 25.8 ± 2.4 yrs, BMI = 22.9 ± 1.2 kg · m(-2 or without any exercise (Sedentary group; N = 6 Age = 24.8 ± 3.1 yrs, BMI = 22.3 ± 2.5 kg · m(-2. A meal tolerance test was performed before (Pre and after the confinement (Post to quantify fasting and postp randial concentrations of selected appetite-related hormones and metabolic risk markers. 13C-Glucose was dissolved in the test meal and 13CO2 determined in breath samples. Perceived appetite ratings were obtained throughout the meal tolerance tests.While body mass decreased in both groups (-1.4 kg; p = 0.01 following the confinement, whole body fat mass was only reduced in the Exercise group (-1.5 kg; p = 0.01. At Post, postprandial serum insulin was reduced in the Sedentary group (-49%; p = 0.01 and postprandial plasma glucose in the Exercise group (-19%; p = 0.03. Fasting serum total cholesterol levels were reduced (-12%; p = 0.01 at Post in the Exercise group only, secondary to low-density lipoprotein cholesterol reduction (-16%; p = 0.01. No differences between groups or testing periods were noted in fasting and/or postprandial concentrations of total ghrelin, peptide YY, and glucagon-like peptide-1, leptin, adiponectin, expired 13CO2 as well as perceived appetite ratings (p>0.05.These findings suggest that performing daily moderate intensity exercise training during continuous hypoxic exposure does not alter hormonal appetite regulation but

  14. Exercise training during normobaric hypoxic confinement does not alter hormonal appetite regulation.

    Science.gov (United States)

    Debevec, Tadej; Simpson, Elizabeth J; Macdonald, Ian A; Eiken, Ola; Mekjavic, Igor B

    2014-01-01

    Both exposure to hypoxia and exercise training have the potential to modulate appetite and induce beneficial metabolic adaptations. The purpose of this study was to determine whether daily moderate exercise training performed during a 10-day exposure to normobaric hypoxia alters hormonal appetite regulation and augments metabolic health. Fourteen healthy, male participants underwent a 10-day hypoxic confinement at ∼ 4000 m simulated altitude (FIO2 = 0.139 ± 0.003%) either combined with daily moderate intensity exercise (Exercise group; N = 8, Age = 25.8 ± 2.4 yrs, BMI = 22.9 ± 1.2 kg · m(-2)) or without any exercise (Sedentary group; N = 6 Age = 24.8 ± 3.1 yrs, BMI = 22.3 ± 2.5 kg · m(-2)). A meal tolerance test was performed before (Pre) and after the confinement (Post) to quantify fasting and postp randial concentrations of selected appetite-related hormones and metabolic risk markers. 13C-Glucose was dissolved in the test meal and 13CO2 determined in breath samples. Perceived appetite ratings were obtained throughout the meal tolerance tests. While body mass decreased in both groups (-1.4 kg; p = 0.01) following the confinement, whole body fat mass was only reduced in the Exercise group (-1.5 kg; p = 0.01). At Post, postprandial serum insulin was reduced in the Sedentary group (-49%; p = 0.01) and postprandial plasma glucose in the Exercise group (-19%; p = 0.03). Fasting serum total cholesterol levels were reduced (-12%; p = 0.01) at Post in the Exercise group only, secondary to low-density lipoprotein cholesterol reduction (-16%; p = 0.01). No differences between groups or testing periods were noted in fasting and/or postprandial concentrations of total ghrelin, peptide YY, and glucagon-like peptide-1, leptin, adiponectin, expired 13CO2 as well as perceived appetite ratings (p>0.05). These findings suggest that performing daily moderate intensity exercise training during continuous hypoxic exposure does not alter hormonal appetite regulation but can

  15. Extensive translational regulation during seed germination revealed by polysomal profiling

    NARCIS (Netherlands)

    Bai, Bing; Peviani, Alessia; Horst, van der Sjors; Gamm, Magdalena; Snel, Berend; Bentsink, Leónie; Hanson, Johannes

    2017-01-01

    This work investigates the extent of translational regulation during seed germination. The polysome occupancy of each gene is determined by genome-wide profiling of total mRNA and polysome-associated mRNA. This reveals extensive translational regulation during Arabidopsis thaliana seed

  16. Positive cell-free fetal DNA testing for trisomy 13 reveals confined placental mosaicism.

    Science.gov (United States)

    Hall, April L; Drendel, Holli M; Verbrugge, Jennifer L; Reese, Angela M; Schumacher, Katherine L; Griffith, Christopher B; Weaver, David D; Abernathy, Mary P; Litton, Christian G; Vance, Gail H

    2013-09-01

    We report on a case in which cell-free fetal DNA was positive for trisomy 13 most likely due to confined placental mosaicism. Cell-free fetal DNA testing analyzes DNA derived from placental trophoblast cells and can lead to incorrect results that are not representative of the fetus. We sought to confirm commercial cell-free fetal DNA testing results by chorionic villus sampling and amniocentesis. These results were followed up by postnatal chromosome analysis of cord blood and placental tissue. First-trimester cell-free fetal DNA test results were positive for trisomy 13. Cytogenetic analysis of chorionic villus sampling yielded a mosaic karyotype of 47,XY,+13[10]/46,XY[12]. G-banded analysis of amniotic fluid was normal, 46,XY. Postnatal cytogenetic analysis of cord blood was normal. Karyotyping of tissues from four quadrants of the placenta demonstrated mosaicism for trisomy 13 in two of the quadrants and a normal karyotype in the other two. Our case illustrates several important aspects of this new testing methodology: that cell-free fetal DNA may not be representative of the fetal karyotype; that follow-up with diagnostic testing of chorionic villus sampling and/or amniotic fluid for abnormal test results should be performed; and that pretest counseling regarding the full benefits, limitations, and possible testing outcomes of cell-free fetal DNA screening is important.

  17. Local regulation of interchange turbulence in a dipole-confined plasma torus using current-collection feedback

    International Nuclear Information System (INIS)

    Roberts, T. M.; Mauel, M. E.; Worstell, M. W.

    2015-01-01

    Turbulence in plasma confined by a magnetic dipole is dominated by interchange fluctuations with complex dynamics and short spatial coherence. We report the first use of local current-collection feedback to modify, amplify, and suppress these fluctuations. The spatial extent of turbulence regulation is limited to a correlation length near the collector. Changing the gain and phase of collection results in power either extracted from or injected into the turbulence. The measured plasma response shows some agreement with calculations of the linear response of global interchange-like MHD and entropy modes to current-collection feedback

  18. NeuCode Proteomics Reveals Bap1 Regulation of Metabolism

    Directory of Open Access Journals (Sweden)

    Joshua M. Baughman

    2016-07-01

    Full Text Available We introduce neutron-encoded (NeuCode amino acid labeling of mice as a strategy for multiplexed proteomic analysis in vivo. Using NeuCode, we characterize an inducible knockout mouse model of Bap1, a tumor suppressor and deubiquitinase whose in vivo roles outside of cancer are not well established. NeuCode proteomics revealed altered metabolic pathways following Bap1 deletion, including profound elevation of cholesterol biosynthetic machinery coincident with reduced expression of gluconeogenic and lipid homeostasis proteins in liver. Bap1 loss increased pancreatitis biomarkers and reduced expression of mitochondrial proteins. These alterations accompany a metabolic remodeling with hypoglycemia, hypercholesterolemia, hepatic lipid loss, and acinar cell degeneration. Liver-specific Bap1 null mice present with fully penetrant perinatal lethality, severe hypoglycemia, and hepatic lipid deficiency. This work reveals Bap1 as a metabolic regulator in liver and pancreas, and it establishes NeuCode as a reliable proteomic method for deciphering in vivo biology.

  19. Confined Diffusion Without Fences of a G-Protein-Coupled Receptor as Revealed by Single Particle Tracking

    Science.gov (United States)

    Daumas, Frédéric; Destainville, Nicolas; Millot, Claire; Lopez, André; Dean, David; Salomé, Laurence

    2003-01-01

    Single particle tracking is a powerful tool for probing the organization and dynamics of the plasma membrane constituents. We used this technique to study the μ-opioid receptor belonging to the large family of the G-protein-coupled receptors involved with other partners in a signal transduction pathway. The specific labeling of the receptor coupled to a T7-tag at its N-terminus, stably expressed in fibroblastic cells, was achieved by colloidal gold coupled to a monoclonal anti T7-tag antibody. The lateral movements of the particles were followed by nanovideomicroscopy at 40 ms time resolution during 2 min with a spatial precision of 15 nm. The receptors were found to have either a slow or directed diffusion mode (10%) or a walking confined diffusion mode (90%) composed of a long-term random diffusion and a short-term confined diffusion, and corresponding to a diffusion confined within a domain that itself diffuses. The results indicate that the confinement is due to an effective harmonic potential generated by long-range attraction between the membrane proteins. A simple model for interacting membrane proteins diffusion is proposed that explains the variations with the domain size of the short-term and long-term diffusion coefficients. PMID:12524289

  20. The Quantum Mechanics of Nano-Confined Water: New Cooperative Effects Revealed with Neutron and X-Ray Compton Scattering

    International Nuclear Information System (INIS)

    Reiter, G F; Deb, Aniruddha

    2014-01-01

    Neutron Compton scattering(NCS) measurements of the momentum distribution of light ions using the Vesuvio instrument at ISIS provide a sensitive local probe of the environment of those ions. NCS measurements of the proton momentum distribution in bulk water show only small deviations from the usual picture of water as a collection of molecules, with the protons covalently bonded to an oxygen and interacting weakly, primarily electrostatically, with nearby molecules. However, a series of measurements of the proton momentum distribution in carbon nanotubes, xerogel, and Nafion show that the proton delocalizes over distances of 0.2-0.3Å when water is confined on the scale of 20Å. This delocalization must be the result of changes in the Born-Oppenheimer surface for the protons, which would imply that there are large deviations in the electron distribution from that of a collection of weakly interacting molecules. This has been observed at Spring-8 using x-ray Compton scattering. The observed deviation in the valence electron momentum distribution from that of bulk water is more than an order of magnitude larger than the change observed in bulk water as the water is heated from just above melting to just below boiling. We conclude that the protons and electrons in nano-confined water are in a qualitatively different ground state from that of bulk water. Since the properties of this state persist at room temperature, and the confinement distance necessary to observe it is comparable to the distance between the elements of biological cells, this state presumably plays a role in the functioning of those cells

  1. Emotion frequency and emotion regulation under conditions of isolation and confinement

    Czech Academy of Sciences Publication Activity Database

    Poláčková Šolcová, Iva; Šolcová, Iva; Stuchlíková, I.; Mazehoová, Y.; Šerý, M.; Vinokhodova, A.

    2011-01-01

    Roč. 26, č. 2 (2011) ISSN 0887-0446. [European Health Psychology Conference: Engaging with Other Health Professions: Challenges and Perspectives /25./. 20.09.2011-24.09.2011, Hersonissos, Kréta] R&D Projects: GA ČR(CZ) GAP407/11/2226 Institutional research plan: CEZ:AV0Z70250504 Keywords : spaceflight * Mars500 * emotion regulation Subject RIV: AN - Psychology

  2. Conserved regulators of nucleolar size revealed by global phenotypic analyses.

    Science.gov (United States)

    Neumüller, Ralph A; Gross, Thomas; Samsonova, Anastasia A; Vinayagam, Arunachalam; Buckner, Michael; Founk, Karen; Hu, Yanhui; Sharifpoor, Sara; Rosebrock, Adam P; Andrews, Brenda; Winston, Fred; Perrimon, Norbert

    2013-08-20

    Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA) genes in the nucleolus. Rapidly growing cancer cells are characterized by increased Pol I-mediated transcription and, consequently, nucleolar hypertrophy. To map the genetic network underlying the regulation of nucleolar size and of Pol I-mediated transcription, we performed comparative, genome-wide loss-of-function analyses of nucleolar size in Saccharomyces cerevisiae and Drosophila melanogaster coupled with mass spectrometry-based analyses of the ribosomal DNA (rDNA) promoter. With this approach, we identified a set of conserved and nonconserved molecular complexes that control nucleolar size. Furthermore, we characterized a direct role of the histone information regulator (HIR) complex in repressing rRNA transcription in yeast. Our study provides a full-genome, cross-species analysis of a nuclear subcompartment and shows that this approach can identify conserved molecular modules.

  3. Conserved Regulators of Nucleolar Size Revealed by Global Phenotypic Analyses

    Science.gov (United States)

    Neumüller, Ralph A.; Gross, Thomas; Samsonova, Anastasia A.; Vinayagam, Arunachalam; Buckner, Michael; Founk, Karen; Hu, Yanhui; Sharifpoor, Sara; Rosebrock, Adam P.; Andrews, Brenda; Winston, Fred; Perrimon, Norbert

    2014-01-01

    Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA) genes in the nucleolus. Rapidly growing cancer cells are characterized by increased Pol I–mediated transcription and, consequently, nucleolar hypertrophy. To map the genetic network underlying the regulation of nucleolar size and of Pol I–mediated transcription, we performed comparative, genome-wide loss-of-function analyses of nucleolar size in Saccharomyces cerevisiae and Drosophila melanogaster coupled with mass spectrometry–based analyses of the ribosomal DNA (rDNA) promoter. With this approach, we identified a set of conserved and nonconserved molecular complexes that control nucleolar size. Furthermore, we characterized a direct role of the histone information regulator (HIR) complex in repressing rRNA transcription in yeast. Our study provides a full-genome, cross-species analysis of a nuclear subcompartment and shows that this approach can identify conserved molecular modules. PMID:23962978

  4. Bmp indicator mice reveal dynamic regulation of transcriptional response.

    Directory of Open Access Journals (Sweden)

    Anna L Javier

    Full Text Available Cellular responses to Bmp ligands are regulated at multiple levels, both extracellularly and intracellularly. Therefore, the presence of these growth factors is not an accurate indicator of Bmp signaling activity. While a common approach to detect Bmp signaling activity is to determine the presence of phosphorylated forms of Smad1, 5 and 8 by immunostaining, this approach is time consuming and not quantitative. In order to provide a simpler readout system to examine the presence of Bmp signaling in developing animals, we developed BRE-gal mouse embryonic stem cells and a transgenic mouse line that specifically respond to Bmp ligand stimulation. Our reporter identifies specific transcriptional responses that are mediated by Smad1 and Smad4 with the Schnurri transcription factor complex binding to a conserved Bmp-Responsive Element (BRE, originally identified among Drosophila, Xenopus and human Bmp targets. Our BRE-gal mES cells specifically respond to Bmp ligands at concentrations as low as 5 ng/ml; and BRE-gal reporter mice, derived from the BRE-gal mES cells, show dynamic activity in many cellular sites, including extraembryonic structures and mammary glands, thereby making this a useful scientific tool.

  5. Live Imaging of Influenza Infection of the Trachea Reveals Dynamic Regulation of CD8+ T Cell Motility by Antigen.

    Science.gov (United States)

    Lambert Emo, Kris; Hyun, Young-Min; Reilly, Emma; Barilla, Christopher; Gerber, Scott; Fowell, Deborah; Kim, Minsoo; Topham, David J

    2016-09-01

    During a primary influenza infection, cytotoxic CD8+ T cells need to infiltrate the infected airways and engage virus-infected epithelial cells. The factors that regulate T cell motility in the infected airway tissue are not well known. To more precisely study T cell infiltration of the airways, we developed an experimental model system using the trachea as a site where live imaging can be performed. CD8+ T cell motility was dynamic with marked changes in motility on different days of the infection. In particular, significant changes in average cell velocity and confinement were evident on days 8-10 during which the T cells abruptly but transiently increase velocity on day 9. Experiments to distinguish whether infection itself or antigen affect motility revealed that it is antigen, not active infection per se that likely affects these changes as blockade of peptide/MHC resulted in increased velocity. These observations demonstrate that influenza tracheitis provides a robust experimental foundation to study molecular regulation of T cell motility during acute virus infection.

  6. Live Imaging of Influenza Infection of the Trachea Reveals Dynamic Regulation of CD8+ T Cell Motility by Antigen.

    Directory of Open Access Journals (Sweden)

    Kris Lambert Emo

    2016-09-01

    Full Text Available During a primary influenza infection, cytotoxic CD8+ T cells need to infiltrate the infected airways and engage virus-infected epithelial cells. The factors that regulate T cell motility in the infected airway tissue are not well known. To more precisely study T cell infiltration of the airways, we developed an experimental model system using the trachea as a site where live imaging can be performed. CD8+ T cell motility was dynamic with marked changes in motility on different days of the infection. In particular, significant changes in average cell velocity and confinement were evident on days 8-10 during which the T cells abruptly but transiently increase velocity on day 9. Experiments to distinguish whether infection itself or antigen affect motility revealed that it is antigen, not active infection per se that likely affects these changes as blockade of peptide/MHC resulted in increased velocity. These observations demonstrate that influenza tracheitis provides a robust experimental foundation to study molecular regulation of T cell motility during acute virus infection.

  7. Quark confinement

    International Nuclear Information System (INIS)

    Joos, H.

    1976-07-01

    The main topics of these lectures are: phenomenological approach to quark confinement, standard Lagrangian of hadrondynamics, Lagrangian field theory and quark confinement, classical soliton solutions in a simple model, quantization of extended systems, colour charge screening and quantization on a lattice and remarks on applications. A survey of the scientific publications listed according to the topics until 26 March 1976 is supplemented. (BJ) [de

  8. Gluon confinement

    International Nuclear Information System (INIS)

    Novello, M.; Lorenci, V.A. de; Elbaz, E.

    1997-02-01

    In this paper we present a new model for a gauge field theory such that self-interacting spin-one particles can be confined in a compact domain. The necessary conditions to produce the confining potential appear already in the properties of the eikonal structure generated by the particular choice of the dynamics. (author)

  9. Plasma confinement

    CERN Document Server

    Hazeltine, R D

    2003-01-01

    Detailed and authoritative, this volume examines the essential physics underlying international research in magnetic confinement fusion. It offers readable, thorough accounts of the fundamental concepts behind methods of confining plasma at or near thermonuclear conditions. Designed for a one- or two-semester graduate-level course in plasma physics, it also represents a valuable reference for professional physicists in controlled fusion and related disciplines.

  10. Genome-Wide RNAi Ionomics Screen Reveals New Genes and Regulation of Human Trace Element Metabolism

    OpenAIRE

    Malinouski, Mikalai; Hasan, Nesrin M.; Zhang, Yan; Seravalli, Javier; Lin, Jie; Avanesov, Andrei; Lutsenko, Svetlana; Gladyshev, Vadim N.

    2017-01-01

    Trace elements are essential for human metabolism and dysregulation of their homeostasis is associated with numerous disorders. Here we characterize mechanisms that regulate trace elements in human cells by designing and performing a genome-wide high-throughput siRNA/ionomics screen, and examining top hits in cellular and biochemical assays. The screen reveals high stability of the ionomes, especially the zinc ionome, and yields known regulators and novel candidates. We further uncover fundam...

  11. Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling

    DEFF Research Database (Denmark)

    Batth, Tanveer S; Papetti, Moreno; Pfeiffer, Anamarija

    2018-01-01

    Despite its low cellular abundance, phosphotyrosine (pTyr) regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK)-initiated signaling networks upon activation by Pdgf-ββ, Fgf-2...... of Pdgfr pTyr signaling. Application of a recently introduced allosteric Shp-2 inhibitor revealed global regulation of the Pdgf-dependent tyrosine phosphoproteome, which significantly impaired cell migration. In addition, we present a list of hundreds of Shp-2-dependent targets and putative substrates...

  12. In vivo labelling of functional ribosomes reveals spatial regulation during starvation in Podospora anserina

    Directory of Open Access Journals (Sweden)

    Silar Philippe

    2000-11-01

    Full Text Available Abstract Background To date, in eukaryotes, ribosomal protein expression is known to be regulated at the transcriptional and/or translational levels. But other forms of regulation may be possible. Results Here, we report the successful tagging of functional ribosomal particles with a S7-GFP chimaeric protein, making it possible to observe in vivo ribosome dynamics in the filamentous fungus Podospora anserina. Microscopic observations revealed a novel kind of ribosomal protein regulation during the passage between cell growth and stationary phases, with a transient accumulation of ribosomal proteins and/or ribosome subunits in the nucleus, possibly the nucleolus, being observed at the beginning of stationary phase. Conclusion Nuclear sequestration can be another level of ribosomal protein regulation in eukaryotic cells.This may contribute to the regulation of cell growth and division.

  13. In vivo labelling of functional ribosomes reveals spatial regulation during starvation in Podospora anserina

    Science.gov (United States)

    Lalucque, Hervé; Silar, Philippe

    2000-01-01

    Background To date, in eukaryotes, ribosomal protein expression is known to be regulated at the transcriptional and/or translational levels. But other forms of regulation may be possible. Results Here, we report the successful tagging of functional ribosomal particles with a S7-GFP chimaeric protein, making it possible to observe in vivo ribosome dynamics in the filamentous fungus Podospora anserina. Microscopic observations revealed a novel kind of ribosomal protein regulation during the passage between cell growth and stationary phases, with a transient accumulation of ribosomal proteins and/or ribosome subunits in the nucleus, possibly the nucleolus, being observed at the beginning of stationary phase. Conclusion Nuclear sequestration can be another level of ribosomal protein regulation in eukaryotic cells.This may contribute to the regulation of cell growth and division. PMID:11112985

  14. Self-regulated shear flow turbulence in confined plasmas: Basic concepts and potential applications to the L → H transition

    International Nuclear Information System (INIS)

    Diamond, P.H.; Shapiro, V.; Schevchenko, V.; Kim, Y.B.; Rosenbluth, M.N.; Carreras, B.A.; Sidikman, K.; Lynch, V.E.; Garcia, L.; Terry, P.W.; Sagdeev, R.Z.

    1992-01-01

    This paper describes developments in the theory of edge plasma turbulence in a differentially rotating plasma. The thesis that such systems are dynamically self-regulating is presented. Results indicate that relevant fluctuations will generate a predominantly curved flow. Similar, curvature is shown to be the predominant flow profile effect on fluctuations. A system fixed point is identified, the eigenfrequencies for small oscillations around it are calculated, and an over-all stability criterion is determined

  15. Automated entry technologies for confined space work activities: A survey.

    Science.gov (United States)

    Botti, Lucia; Ferrari, Emilio; Mora, Cristina

    2017-04-01

    Work in confined spaces poses a significant risk to workers and rescuers involved in the emergency response when an accident occurs. Despite several standards and regulations define the safety requirements for such activities, injuries, and fatalities still occur. Furthermore, the on-site inspections after accidents often reveal that both employers and employees fail to implement safe entry procedures. Removing the risk is possible by avoiding the worker entry, but many activities require the presence of the operator inside the confined space to perform manual tasks. The following study investigates the available technologies for hazardous confined space work activities, e.g., cleaning, inspecting, and maintenance tasks. The aim is to provide a systematic review of the automated solutions for high-risk activities in confined spaces, considering the non-man entry as the most effective confined space safety strategy. Second, this survey aims to provide suggestions for future research addressing the design of new technologies. The survey consists of about 60 papers concerning innovative technologies for confined space work activities. The document review shows that several solutions have been developed and automation can replace the workers for a limited number of hazardous tasks. Several activities still require the manual intervention due to the complex characteristics of confined spaces, e.g., to remove the remains of the automatic cleaning process from the bottom of a tank. The results show that available technologies require more flexibility to adapt to such occupational environments and further research is needed.

  16. A multi-scale model of hepcidin promoter regulation reveals factors controlling systemic iron homeostasis.

    Directory of Open Access Journals (Sweden)

    Guillem Casanovas

    2014-01-01

    Full Text Available Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how BMP6 and IL6 control hepcidin expression. Transcription factor (TF phosphorylation and reporter gene expression were measured under co-stimulation conditions, and the promoter was perturbed by mutagenesis. Using mathematical modeling, we systematically analyzed potential mechanisms of cooperative and competitive promoter regulation by the transcription factors, and experimentally validated the model predictions. Our results reveal that hepcidin cross-regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signaling crosstalk is insignificant. We find that the presence of two BMP-responsive elements enhances the steepness of the promoter response towards the iron-sensing BMP signaling axis, which promotes iron homeostasis in vivo. IL6 co-stimulation reduces the promoter sensitivity towards the BMP signal, because the SMAD and STAT transcription factors compete for recruiting RNA polymerase to the transcription start site. This may explain why inflammatory signals disturb iron homeostasis in anemia of inflammation. Taken together, our results reveal why the iron homeostasis circuit is sensitive to perturbations implicated in disease.

  17. An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

    Science.gov (United States)

    Benitez, Cecil M.; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T.; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H. Efsun; Zhang, Jiajing; Dekker, Joseph D.; Tucker, Haley O.; Chang, Howard Y.; Kim, Seung K.

    2014-01-01

    The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

  18. An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

    Directory of Open Access Journals (Sweden)

    Cecil M Benitez

    2014-10-01

    Full Text Available The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

  19. Proteomic Analysis Reveals the Leaf Color Regulation Mechanism in Chimera Hosta "Gold Standard" Leaves.

    Science.gov (United States)

    Yu, Juanjuan; Zhang, Jinzheng; Zhao, Qi; Liu, Yuelu; Chen, Sixue; Guo, Hongliang; Shi, Lei; Dai, Shaojun

    2016-03-08

    Leaf color change of variegated leaves from chimera species is regulated by fine-tuned molecular mechanisms. Hosta "Gold Standard" is a typical chimera Hosta species with golden-green variegated leaves, which is an ideal material to investigate the molecular mechanisms of leaf variegation. In this study, the margin and center regions of young and mature leaves from Hosta "Gold Standard", as well as the leaves from plants after excess nitrogen fertilization were studied using physiological and comparative proteomic approaches. We identified 31 differentially expressed proteins in various regions and development stages of variegated leaves. Some of them may be related to the leaf color regulation in Hosta "Gold Standard". For example, cytosolic glutamine synthetase (GS1), heat shock protein 70 (Hsp70), and chloroplastic elongation factor G (cpEF-G) were involved in pigment-related nitrogen synthesis as well as protein synthesis and processing. By integrating the proteomics data with physiological results, we revealed the metabolic patterns of nitrogen metabolism, photosynthesis, energy supply, as well as chloroplast protein synthesis, import and processing in various leaf regions at different development stages. Additionally, chloroplast-localized proteoforms involved in nitrogen metabolism, photosynthesis and protein processing implied that post-translational modifications were crucial for leaf color regulation. These results provide new clues toward understanding the mechanisms of leaf color regulation in variegated leaves.

  20. In vivo RNAi screen reveals neddylation genes as novel regulators of Hedgehog signaling.

    Directory of Open Access Journals (Sweden)

    Juan Du

    Full Text Available Hedgehog (Hh signaling is highly conserved in all metazoan animals and plays critical roles in many developmental processes. Dysregulation of the Hh signaling cascade has been implicated in many diseases, including cancer. Although key components of the Hh pathway have been identified, significant gaps remain in our understanding of the regulation of individual Hh signaling molecules. Here, we report the identification of novel regulators of the Hh pathway, obtained from an in vivo RNA interference (RNAi screen in Drosophila. By selectively targeting critical genes functioning in post-translational modification systems utilizing ubiquitin (Ub and Ub-like proteins, we identify two novel genes (dUba3 and dUbc12 that negatively regulate Hh signaling activity. We provide in vivo and in vitro evidence illustrating that dUba3 and dUbc12 are essential components of the neddylation pathway; they function in an enzyme cascade to conjugate the ubiquitin-like NEDD8 modifier to Cullin proteins. Neddylation activates the Cullin-containing ubiquitin ligase complex, which in turn promotes the degradation of Cubitus interruptus (Ci, the downstream transcription factor of the Hh pathway. Our study reveals a conserved molecular mechanism of the neddylation pathway in Drosophila and sheds light on the complex post-translational regulations in Hh signaling.

  1. Spaceflight Alters Bacterial Gene Expression and Virulence and Reveals Role for Global Regulator Hfq

    Science.gov (United States)

    Wilson, J. W.; Ott, C. M.; zuBentrup, K. Honer; Ramamurthy R.; Quick, L.; Porwollik, S.; Cheng, P.; McClellan, M.; Tsaprailis, G.; Radabaugh, T.; hide

    2007-01-01

    A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the spaceflight environment has never been accomplished due to significant technological and logistical hurdles. Moreover, the effects of spaceflight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared to identical ground control cultures. Global microarray and proteomic analyses revealed 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground based microgravity culture model. Spaceflight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during spaceflight missions and provide novel therapeutic options on Earth.

  2. A functional genomics screen in planarians reveals regulators of whole-brain regeneration

    Science.gov (United States)

    Roberts-Galbraith, Rachel H; Brubacher, John L; Newmark, Phillip A

    2016-01-01

    Planarians regenerate all body parts after injury, including the central nervous system (CNS). We capitalized on this distinctive trait and completed a gene expression-guided functional screen to identify factors that regulate diverse aspects of neural regeneration in Schmidtea mediterranea. Our screen revealed molecules that influence neural cell fates, support the formation of a major connective hub, and promote reestablishment of chemosensory behavior. We also identified genes that encode signaling molecules with roles in head regeneration, including some that are produced in a previously uncharacterized parenchymal population of cells. Finally, we explored genes downregulated during planarian regeneration and characterized, for the first time, glial cells in the planarian CNS that respond to injury by repressing several transcripts. Collectively, our studies revealed diverse molecules and cell types that underlie an animal’s ability to regenerate its brain. DOI: http://dx.doi.org/10.7554/eLife.17002.001 PMID:27612384

  3. Physiological and Proteomics Analyses Reveal Low-Phosphorus Stress Affected the Regulation of Photosynthesis in Soybean.

    Science.gov (United States)

    Chu, Shanshan; Li, Hongyan; Zhang, Xiangqian; Yu, Kaiye; Chao, Maoni; Han, Suoyi; Zhang, Dan

    2018-06-06

    Previous studies have revealed a significant genetic relationship between phosphorus (P)-efficiency and photosynthesis-related traits in soybean. In this study, we used proteome profiling in combination with expression analysis, biochemical investigations, and leaf ultrastructural analysis to identify the underlying physiological and molecular responses. The expression analysis and ultrastructural analysis showed that the photosynthesis key genes were decreased at transcript levels and the leaf mesophyll and chloroplast were severely damaged after low-P stress. Approximately 55 protein spots showed changes under low-P condition by mass spectrometry, of which 17 were involved in various photosynthetic processes. Further analysis revealed the depression of photosynthesis caused by low-P stress mainly involves the regulation of leaf structure, adenosine triphosphate (ATP) synthesis, absorption and transportation of CO₂, photosynthetic electron transport, production of assimilatory power, and levels of enzymes related to the Calvin cycle. In summary, our findings indicated that the existence of a stringent relationship between P supply and the genomic control of photosynthesis in soybean. As an important strategy to protect soybean photosynthesis, P could maintain the stability of cell structure, up-regulate the enzymes’ activities, recover the process of photosystem II (PSII), and induce the expression of low-P responsive genes and proteins.

  4. Genome-Wide RNAi Ionomics Screen Reveals New Genes and Regulation of Human Trace Element Metabolism

    Science.gov (United States)

    Malinouski, Mikalai; Hasan, Nesrin M.; Zhang, Yan; Seravalli, Javier; Lin, Jie; Avanesov, Andrei; Lutsenko, Svetlana; Gladyshev, Vadim N.

    2017-01-01

    Trace elements are essential for human metabolism and dysregulation of their homeostasis is associated with numerous disorders. Here we characterize mechanisms that regulate trace elements in human cells by designing and performing a genome-wide high-throughput siRNA/ionomics screen, and examining top hits in cellular and biochemical assays. The screen reveals high stability of the ionomes, especially the zinc ionome, and yields known regulators and novel candidates. We further uncover fundamental differences in the regulation of different trace elements. Specifically, selenium levels are controlled through the selenocysteine machinery and expression of abundant selenoproteins; copper balance is affected by lipid metabolism and requires machinery involved in protein trafficking and posttranslational modifications; and the iron levels are influenced by iron import and expression of the iron/heme-containing enzymes. Our approach can be applied to a variety of disease models and/or nutritional conditions, and the generated dataset opens new directions for studies of human trace element metabolism. PMID:24522796

  5. Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.

    Science.gov (United States)

    Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Lorsch, Zachary S; Walker, Deena M; Wang, Junshi; Huang, Xiaojie; Schlüter, Oliver M; Maze, Ian; Peña, Catherine J; Heller, Elizabeth A; Issler, Orna; Wang, Minghui; Song, Won-Min; Stein, Jason L; Liu, Xiaochuan; Doyle, Marie A; Scobie, Kimberly N; Sun, Hao Sheng; Neve, Rachael L; Geschwind, Daniel; Dong, Yan; Shen, Li; Zhang, Bin; Nestler, Eric J

    2016-06-01

    Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Proteomic Analysis of Fetal Ovaries Reveals That Primordial Follicle Formation and Transition Are Differentially Regulated

    Directory of Open Access Journals (Sweden)

    Mengmeng Xu

    2017-01-01

    Full Text Available Primordial follicle formation represents a critical phase of the initiation of embryonic reproductive organ development, while the primordial follicle transition into primary follicle determines whether oestrus or ovulation will occur in female animals. To identify molecular mechanism of new proteins which are involved in ovarian development, we employed 2D-DIGE to compare the protein expression profiles of primordial follicles and primary follicles of fetal ovaries in pigs. Fetal ovaries were collected at distinct time-points of the gestation cycle (g55 and g90. The identified proteins at the g55 time-point are mainly involved in the development of anatomical structures [reticulocalbin-1 (RCN1, reticulocalbin-3 (RCN3], cell differentiation (actin, and stress response [heterogeneous nuclear ribonucleoprotein K (HNRNPK]. Meanwhile, at the g90 stage, the isolated proteins with altered expression levels were mainly associated with cell proliferation [major vault protein (MVP] and stress response [heat shock-related 70 kDa protein 2 (HSPA2]. In conclusion, our work revealed that primordial follicle formation is regulated by RCN1, RCN3, actin, and HNRNPK, while the primordial follicle transformation to primary follicle is regulated by MVP and HSPA2. Therefore, our results provide further information for the prospective understanding of the molecular mechanism(s involved in the regulation of the ovarian follicle development.

  7. Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential

    Science.gov (United States)

    Hurley, Jennifer M.; Dasgupta, Arko; Emerson, Jillian M.; Zhou, Xiaoying; Ringelberg, Carol S.; Knabe, Nicole; Lipzen, Anna M.; Lindquist, Erika A.; Daum, Christopher G.; Barry, Kerrie W.; Grigoriev, Igor V.; Smith, Kristina M.; Galagan, James E.; Bell-Pedersen, Deborah; Freitag, Michael; Cheng, Chao; Loros, Jennifer J.; Dunlap, Jay C.

    2014-01-01

    Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation–based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset of ccg promoters, including those of many transcription factors. High temporal resolution (2-h) sampling over 48 h using RNA sequencing (RNA-Seq) identified circadianly expressed genes in Neurospora, revealing that from ∼10% to as much 40% of the transcriptome can be expressed under circadian control. Functional classifications of these genes revealed strong enrichment in pathways involving metabolism, protein synthesis, and stress responses; in broad terms, daytime metabolic potential favors catabolism, energy production, and precursor assembly, whereas night activities favor biosynthesis of cellular components and growth. Discriminative regular expression motif elicitation (DREME) identified key promoter motifs highly correlated with the temporal regulation of ccgs. Correlations between ccg abundance from RNA-Seq, the degree of ccg-promoter activation as reported by ccg-promoter–luciferase fusions, and binding of WCC as measured by ChIP-Seq, are not strong. Therefore, although circadian activation is critical to ccg rhythmicity, posttranscriptional regulation plays a major role in determining rhythmicity at the mRNA level. PMID:25362047

  8. Association genetics and transcriptome analysis reveal a gibberellin-responsive pathway involved in regulating photosynthesis.

    Science.gov (United States)

    Xie, Jianbo; Tian, Jiaxing; Du, Qingzhang; Chen, Jinhui; Li, Ying; Yang, Xiaohui; Li, Bailian; Zhang, Deqiang

    2016-05-01

    Gibberellins (GAs) regulate a wide range of important processes in plant growth and development, including photosynthesis. However, the mechanism by which GAs regulate photosynthesis remains to be understood. Here, we used multi-gene association to investigate the effect of genes in the GA-responsive pathway, as constructed by RNA sequencing, on photosynthesis, growth, and wood property traits, in a population of 435 Populus tomentosa By analyzing changes in the transcriptome following GA treatment, we identified many key photosynthetic genes, in agreement with the observed increase in measurements of photosynthesis. Regulatory motif enrichment analysis revealed that 37 differentially expressed genes related to photosynthesis shared two essential GA-related cis-regulatory elements, the GA response element and the pyrimidine box. Thus, we constructed a GA-responsive pathway consisting of 47 genes involved in regulating photosynthesis, including GID1, RGA, GID2, MYBGa, and 37 photosynthetic differentially expressed genes. Single nucleotide polymorphism (SNP)-based association analysis showed that 142 SNPs, representing 40 candidate genes in this pathway, were significantly associated with photosynthesis, growth, and wood property traits. Epistasis analysis uncovered interactions between 310 SNP-SNP pairs from 37 genes in this pathway, revealing possible genetic interactions. Moreover, a structural gene-gene matrix based on a time-course of transcript abundances provided a better understanding of the multi-gene pathway affecting photosynthesis. The results imply a functional role for these genes in mediating photosynthesis, growth, and wood properties, demonstrating the potential of combining transcriptome-based regulatory pathway construction and genetic association approaches to detect the complex genetic networks underlying quantitative traits. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights

  9. Chromatin landscaping in algae reveals novel regulation pathway for biofuels production

    Energy Technology Data Exchange (ETDEWEB)

    Ngan, Chew Yee; Wong, Chee-Hong; Choi, Cindy; Pratap, Abhishek; Han, James; Wei, Chia-Lin

    2013-02-19

    The diminishing reserve of fossil fuels calls for the development of biofuels. Biofuels are produced from renewable resources, including photosynthetic organisms, generating clean energy. Microalgae is one of the potential feedstock for biofuels production. It grows easily even in waste water, and poses no competition to agricultural crops for arable land. However, little is known about the algae lipid biosynthetic regulatory mechanisms. Most studies relied on the homology to other plant model organisms, in particular Arabidopsis or through low coverage expression analysis to identify key enzymes. This limits the discovery of new components in the biosynthetic pathways, particularly the genetic regulators and effort to maximize the production efficiency of algal biofuels. Here we report an unprecedented and de novo approach to dissect the algal lipid pathways through disclosing the temporal regulations of chromatin states during lipid biosynthesis. We have generated genome wide chromatin maps in chlamydomonas genome using ChIP-seq targeting 7 histone modifications and RNA polymerase II in a time-series manner throughout conditions activating lipid biosynthesis. To our surprise, the combinatory profiles of histone codes uncovered new regulatory mechanism in gene expression in algae. Coupled with matched RNA-seq data, chromatin changes revealed potential novel regulators and candidate genes involved in the activation of lipid accumulations. Genetic perturbation on these candidate regulators further demonstrated the potential to manipulate the regulatory cascade for lipid synthesis efficiency. Exploring epigenetic landscape in microalgae shown here provides powerful tools needed in improving biofuel production and new technology platform for renewable energy generation, global carbon management, and environmental survey.

  10. A Systems-Level Analysis Reveals Circadian Regulation of Splicing in Colorectal Cancer.

    Science.gov (United States)

    El-Athman, Rukeia; Fuhr, Luise; Relógio, Angela

    2018-06-20

    Accumulating evidence points to a significant role of the circadian clock in the regulation of splicing in various organisms, including mammals. Both dysregulated circadian rhythms and aberrant pre-mRNA splicing are frequently implicated in human disease, in particular in cancer. To investigate the role of the circadian clock in the regulation of splicing in a cancer progression context at the systems-level, we conducted a genome-wide analysis and compared the rhythmic transcriptional profiles of colon carcinoma cell lines SW480 and SW620, derived from primary and metastatic sites of the same patient, respectively. We identified spliceosome components and splicing factors with cell-specific circadian expression patterns including SRSF1, HNRNPLL, ESRP1, and RBM 8A, as well as altered alternative splicing events and circadian alternative splicing patterns of output genes (e.g., VEGFA, NCAM1, FGFR2, CD44) in our cellular model. Our data reveals a remarkable interplay between the circadian clock and pre-mRNA splicing with putative consequences in tumor progression and metastasis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Magnetic confinement

    Energy Technology Data Exchange (ETDEWEB)

    Batistoni, Paola; De Marco, Francesco; Pieroni, Leonardo (ed.)

    2005-07-01

    The Frascati Tokamak Upgrade (FTU) is a compact, high-magnetic-field tokamak capable of operating at density and magnetic field values similar to, or even encompassing, those of International Thermonuclear Experimental Reactor (ITER) and therefore provides a unique opportunity to explore physics issues that are directly relevant to ITER. During 2004 the experimental activities were focussed on fully exploiting the lower hybrid system (for generating and controlling the plasma current) and the electron cyclotron heating system (joint experiment with the Institute of Plasma Physics of the National Research Council, Milan). With all four gyrotrons in operation, full electron cyclotron power was achieved up to a record level of 1.5 MW. By simultaneously injecting lower hybrid waves, to tailor the plasma current radial profile, and electron cyclotron waves, to heat the plasma centre, good confinement regimes with internal transport barriers were obtained at the highest plasma density values ever achieved for this operation regime (n {approx}1.5X10{sup 20}m{sup -3}). Specific studies were devoted to optimising the coupling of lower hybrid waves to the plasma (by real-time control of the plasma position) and to generating current by electron cyclotron current drive. The new scanning CO{sub 2} interferometer (developed by the Reversed Field Experiment Consortium) for high spatial and time resolution (1 cm/50 {mu}s) density profile measurements was extensively used. The Thomson scattering diagnostic was upgraded and enabled observation of scattered signals associated with the Confinement background plasma dynamics. As for theoretical studies on the dynamics of turbulence in plasmas, the transition from Bohm-like scaling to gyro-Bohm scaling of the local plasma diffusivity was demonstrated on the basis of a generalised four wave model (joint collaboration with Princeton Plasma Physics Laboratory and the University of California at Irvine). The transition from weak to strong

  12. Magnetic confinement

    International Nuclear Information System (INIS)

    Batistoni, Paola; De Marco, Francesco; Pieroni, Leonardo

    2005-01-01

    The Frascati Tokamak Upgrade (FTU) is a compact, high-magnetic-field tokamak capable of operating at density and magnetic field values similar to, or even encompassing, those of International Thermonuclear Experimental Reactor (ITER) and therefore provides a unique opportunity to explore physics issues that are directly relevant to ITER. During 2004 the experimental activities were focussed on fully exploiting the lower hybrid system (for generating and controlling the plasma current) and the electron cyclotron heating system (joint experiment with the Institute of Plasma Physics of the National Research Council, Milan). With all four gyrotrons in operation, full electron cyclotron power was achieved up to a record level of 1.5 MW. By simultaneously injecting lower hybrid waves, to tailor the plasma current radial profile, and electron cyclotron waves, to heat the plasma centre, good confinement regimes with internal transport barriers were obtained at the highest plasma density values ever achieved for this operation regime (n ∼1.5X10 20 m -3 ). Specific studies were devoted to optimising the coupling of lower hybrid waves to the plasma (by real-time control of the plasma position) and to generating current by electron cyclotron current drive. The new scanning CO 2 interferometer (developed by the Reversed Field Experiment Consortium) for high spatial and time resolution (1 cm/50 μs) density profile measurements was extensively used. The Thomson scattering diagnostic was upgraded and enabled observation of scattered signals associated with the Confinement background plasma dynamics. As for theoretical studies on the dynamics of turbulence in plasmas, the transition from Bohm-like scaling to gyro-Bohm scaling of the local plasma diffusivity was demonstrated on the basis of a generalised four wave model (joint collaboration with Princeton Plasma Physics Laboratory and the University of California at Irvine). The transition from weak to strong energetic particle

  13. Multiple oxygen tension environments reveal diverse patterns of transcriptional regulation in primary astrocytes.

    Directory of Open Access Journals (Sweden)

    Wayne Chadwick

    Full Text Available The central nervous system normally functions at O(2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O(2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O(2 tensions compared to the cell culture standard of 20% O(2, to investigate their ability to sense and translate this O(2 information to transcriptional activity. Variance of ambient O(2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O(2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O(2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O(2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional 'programs' may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity.

  14. Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates

    DEFF Research Database (Denmark)

    Hoffman, Nolan J; Parker, Benjamin L; Chaudhuri, Rima

    2015-01-01

    -intensity exercise bout, revealing 1,004 unique exercise-regulated phosphosites on 562 proteins. These included substrates of known exercise-regulated kinases (AMPK, PKA, CaMK, MAPK, mTOR), yet the majority of kinases and substrate phosphosites have not previously been implicated in exercise signaling. Given...

  15. Proteomics analysis of dendritic cell activation by contact allergens reveals possible biomarkers regulated by Nrf2

    Energy Technology Data Exchange (ETDEWEB)

    Mussotter, Franz, E-mail: franz.mussotter@bfr.bund.de [German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin (Germany); Tomm, Janina Melanie [Helmholtz Centre for Environmental Research (UFZ), Department of Molecular Systems Biology, Leipzig (Germany); El Ali, Zeina; Pallardy, Marc; Kerdine-Römer, Saadia [INSERM UMR 996, Univ Paris-Sud, Université Paris-Saclay, Chátenay-Malabry (France); Götz, Mario [German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin (Germany); Bergen, Martin von [Helmholtz Centre for Environmental Research (UFZ), Department of Molecular Systems Biology, Leipzig (Germany); University of Leipzig, Institute of Biochemistry, Leipzig (Germany); Aalborg University, Department of Chemistry and Bioscience, Aalborg (Denmark); Haase, Andrea; Luch, Andreas [German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin (Germany)

    2016-12-15

    Allergic contact dermatitis is a widespread disease with high clinical relevance affecting approximately 20% of the general population. Typically, contact allergens are low molecular weight electrophilic compounds which can activate the Keap1/Nrf2 pathway. We performed a proteomics study to reveal possible biomarkers for dendritic cell (DC) activation by contact allergens and to further elucidate the role of Keap1/Nrf2 signaling in this process. We used bone marrow derived dendritic cells (BMDCs) of wild-type (nrf2{sup +/+}) and Nrf2 knockout (nrf2{sup −/−}) mice and studied their response against the model contact sensitizers 2,4-dinitrochlorobenzene (DNCB), cinnamaldehyde (CA) and nickel(II) sulfate by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) in combination with electrospray ionization tandem mass spectrometry (ESI-MS/MS). Sodium dodecyl sulfate (SDS, 100 μM) served as irritant control. While treatment with nickel(II) sulfate and SDS had only little effects, CA and DNCB led to significant changes in protein expression. We found 18 and 30 protein spots up-regulated in wild-type cells treated with 50 and 100 μM CA, respectively. For 5 and 10 μM DNCB, 32 and 37 spots were up-regulated, respectively. Almost all of these proteins were not differentially expressed in nrf2{sup −/−} BMDCs, indicating an Nrf2-dependent regulation. Among them proteins were detected which are involved in oxidative stress and heat shock responses, as well as in signal transduction or basic cellular pathways. The applied approach allowed us to differentiate between Nrf2-dependent and Nrf2-independent cellular biomarkers differentially regulated upon allergen-induced DC activation. The data presented might contribute to the further development of suitable in vitro testing methods for chemical-mediated sensitization. - Highlights: • Contact allergens induce proteins involved in DC maturation Nrf2-dependently. • Induction of these proteins points to a functional

  16. Large-scale analysis of Arabidopsis transcription reveals a basal co-regulation network

    Directory of Open Access Journals (Sweden)

    Chamovitz Daniel A

    2009-09-01

    Full Text Available Abstract Background Analyses of gene expression data from microarray experiments has become a central tool for identifying co-regulated, functional gene modules. A crucial aspect of such analysis is the integration of data from different experiments and different laboratories. How to weigh the contribution of different experiments is an important point influencing the final outcomes. We have developed a novel method for this integration, and applied it to genome-wide data from multiple Arabidopsis microarray experiments performed under a variety of experimental conditions. The goal of this study is to identify functional globally co-regulated gene modules in the Arabidopsis genome. Results Following the analysis of 21,000 Arabidopsis genes in 43 datasets and about 2 × 108 gene pairs, we identified a globally co-expressed gene network. We found clusters of globally co-expressed Arabidopsis genes that are enriched for known Gene Ontology annotations. Two types of modules were identified in the regulatory network that differed in their sensitivity to the node-scoring parameter; we further showed these two pertain to general and specialized modules. Some of these modules were further investigated using the Genevestigator compendium of microarray experiments. Analyses of smaller subsets of data lead to the identification of condition-specific modules. Conclusion Our method for identification of gene clusters allows the integration of diverse microarray experiments from many sources. The analysis reveals that part of the Arabidopsis transcriptome is globally co-expressed, and can be further divided into known as well as novel functional gene modules. Our methodology is general enough to apply to any set of microarray experiments, using any scoring function.

  17. Patterns of hybrid loss of imprinting reveal tissue- and cluster-specific regulation.

    Directory of Open Access Journals (Sweden)

    Christopher D Wiley

    Full Text Available Crosses between natural populations of two species of deer mice, Peromyscus maniculatus (BW, and P. polionotus (PO, produce parent-of-origin effects on growth and development. BW females mated to PO males (bwxpo produce growth-retarded but otherwise healthy offspring. In contrast, PO females mated to BW males (POxBW produce overgrown and severely defective offspring. The hybrid phenotypes are pronounced in the placenta and include POxBW conceptuses which lack embryonic structures. Evidence to date links variation in control of genomic imprinting with the hybrid defects, particularly in the POxBW offspring. Establishment of genomic imprinting is typically mediated by gametic DNA methylation at sites known as gDMRs. However, imprinted gene clusters vary in their regulation by gDMR sequences.Here we further assess imprinted gene expression and DNA methylation at different cluster types in order to discern patterns. These data reveal POxBW misexpression at the Kcnq1ot1 and Peg3 clusters, both of which lose ICR methylation in placental tissues. In contrast, some embryonic transcripts (Peg10, Kcnq1ot1 reactivated the silenced allele with little or no loss of DNA methylation. Hybrid brains also display different patterns of imprinting perturbations. Several cluster pairs thought to use analogous regulatory mechanisms are differentially affected in the hybrids.These data reinforce the hypothesis that placental and somatic gene regulation differs significantly, as does that between imprinted gene clusters and between species. That such epigenetic regulatory variation exists in recently diverged species suggests a role in reproductive isolation, and that this variation is likely to be adaptive.

  18. The structure of Plasmodium falciparum serine hydroxymethyltransferase reveals a novel redox switch that regulates its activities

    Energy Technology Data Exchange (ETDEWEB)

    Chitnumsub, Penchit; Ittarat, Wanwipa; Jaruwat, Aritsara; Noytanom, Krittikar [National Center for Genetic Engineering and Biotechnology, 113 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumthani 12120 (Thailand); Amornwatcharapong, Watcharee [Mahidol University, Bangkok (Thailand); Pornthanakasem, Wichai [National Center for Genetic Engineering and Biotechnology, 113 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumthani 12120 (Thailand); Chaiyen, Pimchai [Mahidol University, Bangkok (Thailand); Yuthavong, Yongyuth; Leartsakulpanich, Ubolsree [National Center for Genetic Engineering and Biotechnology, 113 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumthani 12120 (Thailand)

    2014-06-01

    The crystal structure of P. falciparum SHMT revealed snapshots of an intriguing disulfide/sulfhydryl switch controlling the functional activity. Plasmodium falciparum serine hydroxymethyltransferase (PfSHMT), an enzyme in the dTMP synthesis cycle, is an antimalarial target because inhibition of its expression or function has been shown to be lethal to the parasite. As the wild-type enzyme could not be crystallized, protein engineering of residues on the surface was carried out. The surface-engineered mutant PfSHMT-F292E was successfully crystallized and its structure was determined at 3 Å resolution. The PfSHMT-F292E structure is a good representation of PfSHMT as this variant revealed biochemical properties similar to those of the wild type. Although the overall structure of PfSHMT is similar to those of other SHMTs, unique features including the presence of two loops and a distinctive cysteine pair formed by Cys125 and Cys364 in the tetrahydrofolate (THF) substrate binding pocket were identified. These structural characteristics have never been reported in other SHMTs. Biochemical characterization and mutation analysis of these two residues confirm that they act as a disulfide/sulfhydryl switch to regulate the THF-dependent catalytic function of the enzyme. This redox switch is not present in the human enzyme, in which the cysteine pair is absent. The data reported here can be further exploited as a new strategy to specifically disrupt the activity of the parasite enzyme without interfering with the function of the human enzyme.

  19. The structure of Plasmodium falciparum serine hydroxymethyltransferase reveals a novel redox switch that regulates its activities

    International Nuclear Information System (INIS)

    Chitnumsub, Penchit; Ittarat, Wanwipa; Jaruwat, Aritsara; Noytanom, Krittikar; Amornwatcharapong, Watcharee; Pornthanakasem, Wichai; Chaiyen, Pimchai; Yuthavong, Yongyuth; Leartsakulpanich, Ubolsree

    2014-01-01

    The crystal structure of P. falciparum SHMT revealed snapshots of an intriguing disulfide/sulfhydryl switch controlling the functional activity. Plasmodium falciparum serine hydroxymethyltransferase (PfSHMT), an enzyme in the dTMP synthesis cycle, is an antimalarial target because inhibition of its expression or function has been shown to be lethal to the parasite. As the wild-type enzyme could not be crystallized, protein engineering of residues on the surface was carried out. The surface-engineered mutant PfSHMT-F292E was successfully crystallized and its structure was determined at 3 Å resolution. The PfSHMT-F292E structure is a good representation of PfSHMT as this variant revealed biochemical properties similar to those of the wild type. Although the overall structure of PfSHMT is similar to those of other SHMTs, unique features including the presence of two loops and a distinctive cysteine pair formed by Cys125 and Cys364 in the tetrahydrofolate (THF) substrate binding pocket were identified. These structural characteristics have never been reported in other SHMTs. Biochemical characterization and mutation analysis of these two residues confirm that they act as a disulfide/sulfhydryl switch to regulate the THF-dependent catalytic function of the enzyme. This redox switch is not present in the human enzyme, in which the cysteine pair is absent. The data reported here can be further exploited as a new strategy to specifically disrupt the activity of the parasite enzyme without interfering with the function of the human enzyme

  20. Epigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation.

    Science.gov (United States)

    Yu, Bingfei; Zhang, Kai; Milner, J Justin; Toma, Clara; Chen, Runqiang; Scott-Browne, James P; Pereira, Renata M; Crotty, Shane; Chang, John T; Pipkin, Matthew E; Wang, Wei; Goldrath, Ananda W

    2017-05-01

    Dynamic changes in the expression of transcription factors (TFs) can influence the specification of distinct CD8 + T cell fates, but the observation of equivalent expression of TFs among differentially fated precursor cells suggests additional underlying mechanisms. Here we profiled the genome-wide histone modifications, open chromatin and gene expression of naive, terminal-effector, memory-precursor and memory CD8 + T cell populations induced during the in vivo response to bacterial infection. Integration of these data suggested that the expression and binding of TFs contributed to the establishment of subset-specific enhancers during differentiation. We developed a new bioinformatics method using the PageRank algorithm to reveal key TFs that influence the generation of effector and memory populations. The TFs YY1 and Nr3c1, both constitutively expressed during CD8 + T cell differentiation, regulated the formation of terminal-effector cell fates and memory-precursor cell fates, respectively. Our data define the epigenetic landscape of differentiation intermediates and facilitate the identification of TFs with previously unappreciated roles in CD8 + T cell differentiation.

  1. Epigenetic landscapes reveal transcription factors regulating CD8+ T cell differentiation

    Science.gov (United States)

    Yu, Bingfei; Zhang, Kai; Milner, J. Justin; Toma, Clara; Chen, Runqiang; Scott-Browne, James P.; Pereira, Renata M.; Crotty, Shane; Chang, John T.; Pipkin, Matthew E.; Wang, Wei; Goldrath, Ananda W.

    2017-01-01

    Dynamic changes in the expression of transcription factors (TFs) can influence specification of distinct CD8+ T cell fates, but the observation of equivalent expression of TF among differentially-fated precursor cells suggests additional underlying mechanisms. Here, we profiled genome-wide histone modifications, open chromatin and gene expression of naive, terminal-effector, memory-precursor and memory CD8+ T cell populations induced during the in vivo response to bacterial infection. Integration of these data suggested that TF expression and binding contributed to establishment of subset-specific enhancers during differentiation. We developed a new bioinformatics method using the PageRank algorithm to reveal novel TFs influencing the generation of effector and memory populations. The TFs YY1 and Nr3c1, both constitutively expressed during CD8+ T cell differentiation, regulated the formation of terminal-effector and memory-precursor cell-fates, respectively. Our data define the epigenetic landscape of differentiation intermediates, facilitating identification of TFs with previously unappreciated roles in CD8+ T cell differentiation. PMID:28288100

  2. The Brain–to–Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions

    Science.gov (United States)

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C.; Ali, Almas; Tamarina, Natalia; Philipson, Louis H.; Enquist, Lynn W.; Myers, Martin G.

    2016-01-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. PMID:27207534

  3. The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

    Science.gov (United States)

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

    2016-09-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. © 2016 by the American Diabetes Association.

  4. Comments on confinement criteria

    International Nuclear Information System (INIS)

    Kurak, V.; Schroer, B.; Swieca, J.A.

    1977-01-01

    For a QED 2 model with SU(n) flavour, the nature of the physical states space is more subtle than one expects on the basis of the loop criterion for confinement. One may have colour confinement without confinement of the fundamental flavour representation. Attempts to formulate confinement criteria in which the quark fields play a more fundamental role are discussed [pt

  5. Transcriptional regulation of rod photoreceptor homeostasis revealed by in vivo NRL targetome analysis.

    Directory of Open Access Journals (Sweden)

    Hong Hao

    Full Text Available A stringent control of homeostasis is critical for functional maintenance and survival of neurons. In the mammalian retina, the basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate and activates the expression of many rod-specific genes. Here, we report an integrated analysis of NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq data from Illumina and ABI platforms with global expression profiling and in vivo knockdown studies. We identified approximately 300 direct NRL target genes. Of these, 22 NRL targets are associated with human retinal dystrophies, whereas 95 mapped to regions of as yet uncloned retinal disease loci. In silico analysis of NRL ChIP-Seq peak sequences revealed an enrichment of distinct sets of transcription factor binding sites. Specifically, we discovered that genes involved in photoreceptor function include binding sites for both NRL and homeodomain protein CRX. Evaluation of 26 ChIP-Seq regions validated their enhancer functions in reporter assays. In vivo knockdown of 16 NRL target genes resulted in death or abnormal morphology of rod photoreceptors, suggesting their importance in maintaining retinal function. We also identified histone demethylase Kdm5b as a novel secondary node in NRL transcriptional hierarchy. Exon array analysis of flow-sorted photoreceptors in which Kdm5b was knocked down by shRNA indicated its role in regulating rod-expressed genes. Our studies identify candidate genes for retinal dystrophies, define cis-regulatory module(s for photoreceptor-expressed genes and provide a framework for decoding transcriptional regulatory networks that dictate rod homeostasis.

  6. Transcriptome Analysis Reveals Regulation of Gene Expression for Lipid Catabolism in Young Broilers by Butyrate Glycerides

    Science.gov (United States)

    Yin, Fugui; Yu, Hai; Lepp, Dion; Shi, Xuejiang; Yang, Xiaojian; Hu, Jielun; Leeson, Steve; Yang, Chengbo; Nie, Shaoping; Hou, Yongqing; Gong, Joshua

    2016-01-01

    indicated that dietary BG intervention induced 79 and 205 characterized DEGs in the jejunum and liver, respectively. In addition, 255 and 165 TSEGs were detected in the liver and jejunum of BG-fed group, while 162 and 211 TSEGs genes were observed in the liver and jejunum of BD-fed birds, respectively. Bioinformatic analysis with both IPA and DAVID-BR further revealed a significant enrichment of DEGs and TSEGs in the biological processes for reducing the synthesis, storage, transportation and secretion of lipids in the jejunum, while those in the liver were for enhancing the oxidation of ingested lipids and fatty acids. In particular, transcriptional regulators of THRSP and EGR-1 as well as several DEGs involved in the PPAR-α signaling pathway were significantly induced by dietary BG intervention for lipid catabolism. Conclusions Our results demonstrate that BG reduces body fat deposition via regulation of gene expression, which is involved in the biological events relating to the reduction of synthesis, storage, transportation and secretion, and improvement of oxidation of lipids and fatty acids. PMID:27508934

  7. Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

    Directory of Open Access Journals (Sweden)

    Stephanie Munk

    2017-10-01

    Full Text Available The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essential role for SUMOs (small ubiquitin-like modifiers has also been established. Here, we investigate the global interplay between phosphorylation and SUMOylation in response to replication stress. Using SUMO and phosphoproteomic technologies, we identify thousands of regulated modification sites. We find co-regulation of central DNA damage and replication stress responders, of which the ATR-activating factor TOPBP1 is the most highly regulated. Using pharmacological inhibition of the DNA damage response kinases ATR and ATM, we find that these factors regulate global protein SUMOylation in the protein networks that protect DNA upon replication stress and fork breakage, pointing to integration between phosphorylation and SUMOylation in the cellular systems that protect DNA integrity.

  8. Strigolactone-Regulated Proteins Revealed by iTRAQ-Based Quantitative Proteomics in Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhou [ORNL; Czarnecki, Olaf [ORNL; Chourey, Karuna [ORNL; Yang, Jun [ORNL; Tuskan, Gerald A [ORNL; Hurst, Gregory {Greg} B [ORNL; Pan, Chongle [ORNL; Chen, Jay [ORNL

    2014-01-01

    Strigolactones (SLs) are a new class of plant hormones. In addition to acting as a key inhibitor of shoot branching, SLs stimulate seed germination of root parasitic plants and promote hyphal branching and root colonization of symbiotic arbuscular mycorrhizal fungi. They also regulate many other aspects of plant growth and development. At the transcription level, SL-regulated genes have been reported. However, nothing is known about the proteome regulated by this new class of plant hormones. Here, a quantitative proteomics approach using an isobaric chemical labeling reagent, iTRAQ, to identify the proteome regulated by SLs in Arabidopsis seedlings is presented. It was found SLs regulate the expression of about three dozens of proteins that have not been previously assigned to SL pathways. These findings provide a new tool to investigate the molecular mechanism of action of SLs.

  9. Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

    DEFF Research Database (Denmark)

    Munk, Stephanie; Sigurðsson, Jón Otti; Xiao, Zhenyu

    2017-01-01

    The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM)-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essentia....... They analyze changes in the SUMO and phosphoproteome after MMC and hydroxyurea treatments and find that the DNA damage response kinases ATR and ATM globally regulate SUMOylation upon replication stress and fork breakage....

  10. Analysis of the Yeast Kinome Reveals a Network of Regulated Protein Localization during Filamentous Growth

    OpenAIRE

    Bharucha, Nikë; Ma, Jun; Dobry, Craig J.; Lawson, Sarah K.; Yang, Zhifen; Kumar, Anuj

    2008-01-01

    The subcellular distribution of kinases and other signaling proteins is regulated in response to cellular cues; however, the extent of this regulation has not been investigated for any gene set in any organism. Here, we present a systematic analysis of protein kinases in the budding yeast, screening for differential localization during filamentous growth. Filamentous growth is an important stress response involving mitogen-activated protein kinase and cAMP-dependent protein kinase signaling m...

  11. Chernobyl new safe confinement

    International Nuclear Information System (INIS)

    Dodd, L.

    2011-01-01

    The author presents the new safe confinement that will be commissioned at Unit 4 of the Chernobyl NPP in 2015. The confinement will ensure that Chernobyl Unit 4 will be placed in an environmentally safe condition for at least next 100 years. The article highlights the current work status, future perspectives and the feasibility of confinement concept [ru

  12. Confinement models for gluons

    International Nuclear Information System (INIS)

    Khadkikar, S.B.; Vinodkumar, P.C.

    1987-04-01

    Confinement model for gluons using a 'colour super current' is formulated. An attempt has been made to derive a suitable dielectric function corresponding to the current confinement model. A simple inhomogeneous dielectric confinement model for gluons is studied for comparison. The model Hamiltonians are second quantized and the glueball states are constructed. The spurious motion of the centre of confinement is accounted for. The results of the current confinement scheme are found to be in good agreement with the experimental candidates for glueballs. (author). 16 refs, 3 tabs

  13. Systems Analyses Reveal Shared and Diverse Attributes of Oct4 Regulation in Pluripotent Cells

    DEFF Research Database (Denmark)

    Ding, Li; Paszkowski-Rogacz, Maciej; Winzi, Maria

    2015-01-01

    We combine a genome-scale RNAi screen in mouse epiblast stem cells (EpiSCs) with genetic interaction, protein localization, and "protein-level dependency" studies-a systematic technique that uncovers post-transcriptional regulation-to delineate the network of factors that control the expression...... of Oct4, a key regulator of pluripotency. Our data signify that there are similarities, but also fundamental differences in Oct4 regulation in EpiSCs versus embryonic stem cells (ESCs). Through multiparametric data analyses, we predict that Tox4 is associating with the Paf1C complex, which maintains cell...... identity in both cell types, and validate that this protein-protein interaction exists in ESCs and EpiSCs. We also identify numerous knockdowns that increase Oct4 expression in EpiSCs, indicating that, in stark contrast to ESCs, Oct4 is under active repressive control in EpiSCs. These studies provide...

  14. Eco-Efficiency Assessments as a Tool for Revealing the Environmental Improvement Potential of New Regulations

    Directory of Open Access Journals (Sweden)

    Ottar Michelsen

    2010-01-01

    Full Text Available Public regulations can result in improved environmental performance of products. In this paper eco-efficiency is used to assess the most likely outcome of potential new regulations. The paper presents a case study of furniture production in Norway where different scenarios for improving the environmental performance of the products are presented. Four regulatory options for imposing environmental improvements are assessed; (1 an introduction of a tax on emissions, (2 an increase of the tax on landfills, (3 an introduction of a tax on raw material consumption, and (4 introduction of take-back legislation.

  15. Computational Approaches Reveal New Insights into Regulation and Function of Non; coding RNAs and their Targets

    KAUST Repository

    Alam, Tanvir

    2016-01-01

    Regulation and function of protein-coding genes are increasingly well-understood, but no comparable evidence exists for non-coding RNA (ncRNA) genes, which appear to be more numerous than protein-coding genes. We developed a novel machine

  16. Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism

    DEFF Research Database (Denmark)

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill

    2015-01-01

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular...

  17. Transcriptome analysis reveals the regulation of brassinosteroids on petal growth in Gerbera hybrida

    Directory of Open Access Journals (Sweden)

    Gan Huang

    2017-05-01

    Full Text Available Gerbera hybrida is a cut-flower crop of global importance, and an understanding of the mechanisms underlying petal development is vital for the continued commercial development of this plant species. Brassinosteroids (BRs, a class of phytohormones, are known to play a major role in cell expansion, but their effect on petal growth in G. hybrida is largely unexplored. In this study, we found that the brassinolide (BL, the most active BR, promotes petal growth by lengthening cells in the middle and basal regions of petals, and that this effect on petal growth was greater than that of gibberellin (GA. The RNA-seq (high-throughput cDNA sequencing technique was employed to investigate the regulatory mechanisms by which BRs control petal growth. A global transcriptome analysis of the response to BRs in petals was conducted and target genes regulated by BR were identified. These differentially expressed genes (DEGs include various transcription factors (TFs that were activated during the early stage (0.5 h of BL treatment, as well as cell wall proteins whose expression was regulated at a late stage (10 h. BR-responsive DEGs are involved in multiple plant hormone signal pathways, hormone biosynthesis and biotic and abiotic stress responses, showing that the regulation of petal growth by BRs is a complex network of processes. Thus, our study provides new insights at the transcriptional level into the molecular mechanisms of BR regulation of petal growth in G. hybrida.

  18. Bacterial competition reveals differential regulation of the pks genes by Bacillus subtilis.

    Science.gov (United States)

    Vargas-Bautista, Carol; Rahlwes, Kathryn; Straight, Paul

    2014-02-01

    Bacillus subtilis is adaptable to many environments in part due to its ability to produce a broad range of bioactive compounds. One such compound, bacillaene, is a linear polyketide/nonribosomal peptide. The pks genes encode the enzymatic megacomplex that synthesizes bacillaene. The majority of pks genes appear to be organized as a giant operon (>74 kb from pksC-pksR). In previous work (P. D. Straight, M. A. Fischbach, C. T. Walsh, D. Z. Rudner, and R. Kolter, Proc. Natl. Acad. Sci. U. S. A. 104:305-310, 2007, doi:10.1073/pnas.0609073103), a deletion of the pks operon in B. subtilis was found to induce prodiginine production by Streptomyces coelicolor. Here, colonies of wild-type B. subtilis formed a spreading population that induced prodiginine production from Streptomyces lividans, suggesting differential regulation of pks genes and, as a result, bacillaene. While the parent colony showed widespread induction of pks expression among cells in the population, we found the spreading cells uniformly and transiently repressed the expression of the pks genes. To identify regulators that control pks genes, we first determined the pattern of pks gene expression in liquid culture. We next identified mutations in regulatory genes that disrupted the wild-type pattern of pks gene expression. We found that expression of the pks genes requires the master regulator of development, Spo0A, through its repression of AbrB and the stationary-phase regulator, CodY. Deletions of degU, comA, and scoC had moderate effects, disrupting the timing and level of pks gene expression. The observed patterns of expression suggest that complex regulation of bacillaene and other antibiotics optimizes competitive fitness for B. subtilis.

  19. Bacterial Competition Reveals Differential Regulation of the pks Genes by Bacillus subtilis

    Science.gov (United States)

    Vargas-Bautista, Carol; Rahlwes, Kathryn

    2014-01-01

    Bacillus subtilis is adaptable to many environments in part due to its ability to produce a broad range of bioactive compounds. One such compound, bacillaene, is a linear polyketide/nonribosomal peptide. The pks genes encode the enzymatic megacomplex that synthesizes bacillaene. The majority of pks genes appear to be organized as a giant operon (>74 kb from pksC-pksR). In previous work (P. D. Straight, M. A. Fischbach, C. T. Walsh, D. Z. Rudner, and R. Kolter, Proc. Natl. Acad. Sci. U. S. A. 104:305–310, 2007, doi:10.1073/pnas.0609073103), a deletion of the pks operon in B. subtilis was found to induce prodiginine production by Streptomyces coelicolor. Here, colonies of wild-type B. subtilis formed a spreading population that induced prodiginine production from Streptomyces lividans, suggesting differential regulation of pks genes and, as a result, bacillaene. While the parent colony showed widespread induction of pks expression among cells in the population, we found the spreading cells uniformly and transiently repressed the expression of the pks genes. To identify regulators that control pks genes, we first determined the pattern of pks gene expression in liquid culture. We next identified mutations in regulatory genes that disrupted the wild-type pattern of pks gene expression. We found that expression of the pks genes requires the master regulator of development, Spo0A, through its repression of AbrB and the stationary-phase regulator, CodY. Deletions of degU, comA, and scoC had moderate effects, disrupting the timing and level of pks gene expression. The observed patterns of expression suggest that complex regulation of bacillaene and other antibiotics optimizes competitive fitness for B. subtilis. PMID:24187085

  20. Antidiabetic phospholipid-nuclear receptor complex reveals the mechanism for phospholipid-driven gene regulation

    Energy Technology Data Exchange (ETDEWEB)

    Musille, Paul M; Pathak, Manish C; Lauer, Janelle L; Hudson, William H; Griffin, Patrick R; Ortlund, Eric A [Emory-MED; (Scripps)

    2013-01-31

    The human nuclear receptor liver receptor homolog-1 (LRH-1) has an important role in controlling lipid and cholesterol homeostasis and is a potential target for the treatment of diabetes and hepatic diseases. LRH-1 is known to bind phospholipids, but the role of phospholipids in controlling LRH-1 activation remains highly debated. Here we describe the structure of both apo LRH-1 and LRH-1 in complex with the antidiabetic phospholipid dilauroylphosphatidylcholine (DLPC). Together with hydrogen-deuterium exchange MS and functional data, our studies show that DLPC binding is a dynamic process that alters co-regulator selectivity. We show that the lipid-free receptor undergoes previously unrecognized structural fluctuations, allowing it to interact with widely expressed co-repressors. These observations enhance our understanding of LRH-1 regulation and highlight its importance as a new therapeutic target for controlling diabetes.

  1. Cyt toxin expression reveals an inverse regulation of insect and plant virulence factors of Dickeya dadantii.

    Science.gov (United States)

    Costechareyre, Denis; Dridi, Bedis; Rahbé, Yvan; Condemine, Guy

    2010-12-01

    The plant pathogenic bacteria Dickeya dadantii is also a pathogen of the pea aphid Acyrthosiphon pisum. The genome of the bacteria contains four cyt genes, encoding homologues of Bacillus thuringiensis Cyt toxins, which are involved in its pathogenicity to insects. We show here that these genes are transcribed as an operon, and we determined the conditions necessary for their expression. Their expression is induced at high temperature and at an osmolarity equivalent to that found in the plant phloem sap. The regulators of cyt genes have also been identified: their expression is repressed by H-NS and VfmE and activated by PecS. These genes are already known to regulate plant virulence factors, but in an opposite way. When tested in a virulence assay by ingestion, the pecS mutant was almost non-pathogenic while hns and vfmE mutants behaved in the same way as the wild-type strain. Mutants of other regulators of plant virulence, GacA, OmpR and PhoP, that do not control Cyt toxin production, also showed reduced pathogenicity. In an assay by injection of bacteria, the gacA strain was less pathogenic but, surprisingly, the pecS mutant was slightly more virulent. These results show that Cyt toxins are not the only virulence factors required to kill aphids, and that these factors act at different stages of the infection. Moreover, their production is controlled by general virulence regulators known for their role in plant virulence. This integration could indicate that virulence towards insects is a normal mode of life for D. dadantii. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

  2. Coxiella burnetii transcriptional analysis reveals serendipity clusters of regulation in intracellular bacteria.

    Directory of Open Access Journals (Sweden)

    Quentin Leroy

    Full Text Available Coxiella burnetii, the causative agent of the zoonotic disease Q fever, is mainly transmitted to humans through an aerosol route. A spore-like form allows C. burnetii to resist different environmental conditions. Because of this, analysis of the survival strategies used by this bacterium to adapt to new environmental conditions is critical for our understanding of C. burnetii pathogenicity. Here, we report the early transcriptional response of C. burnetii under temperature stresses. Our data show that C. burnetii exhibited minor changes in gene regulation under short exposure to heat or cold shock. While small differences were observed, C. burnetii seemed to respond similarly to cold and heat shock. The expression profiles obtained using microarrays produced in-house were confirmed by quantitative RT-PCR. Under temperature stresses, 190 genes were differentially expressed in at least one condition, with a fold change of up to 4. Globally, the differentially expressed genes in C. burnetii were associated with bacterial division, (pppGpp synthesis, wall and membrane biogenesis and, especially, lipopolysaccharide and peptidoglycan synthesis. These findings could be associated with growth arrest and witnessed transformation of the bacteria to a spore-like form. Unexpectedly, clusters of neighboring genes were differentially expressed. These clusters do not belong to operons or genetic networks; they have no evident associated functions and are not under the control of the same promoters. We also found undescribed but comparable clusters of regulation in previously reported transcriptomic analyses of intracellular bacteria, including Rickettsia sp. and Listeria monocytogenes. The transcriptomic patterns of C. burnetii observed under temperature stresses permits the recognition of unpredicted clusters of regulation for which the trigger mechanism remains unidentified but which may be the result of a new mechanism of epigenetic regulation.

  3. Comparative genomics reveals candidate carotenoid pathway regulators of ripening watermelon fruit

    Science.gov (United States)

    2013-01-01

    Background Many fruits, including watermelon, are proficient in carotenoid accumulation during ripening. While most genes encoding steps in the carotenoid biosynthetic pathway have been cloned, few transcriptional regulators of these genes have been defined to date. Here we describe the identification of a set of putative carotenoid-related transcription factors resulting from fresh watermelon carotenoid and transcriptome analysis during fruit development and ripening. Our goal is to both clarify the expression profiles of carotenoid pathway genes and to identify candidate regulators and molecular targets for crop improvement. Results Total carotenoids progressively increased during fruit ripening up to ~55 μg g-1 fw in red-ripe fruits. Trans-lycopene was the carotenoid that contributed most to this increase. Many of the genes related to carotenoid metabolism displayed changing expression levels during fruit ripening generating a metabolic flux toward carotenoid synthesis. Constitutive low expression of lycopene cyclase genes resulted in lycopene accumulation. RNA-seq expression profiling of watermelon fruit development yielded a set of transcription factors whose expression was correlated with ripening and carotenoid accumulation. Nineteen putative transcription factor genes from watermelon and homologous to tomato carotenoid-associated genes were identified. Among these, six were differentially expressed in the flesh of both species during fruit development and ripening. Conclusions Taken together the data suggest that, while the regulation of a common set of metabolic genes likely influences carotenoid synthesis and accumulation in watermelon and tomato fruits during development and ripening, specific and limiting regulators may differ between climacteric and non-climacteric fruits, possibly related to their differential susceptibility to and use of ethylene during ripening. PMID:24219562

  4. Comparative vesicle proteomics reveals selective regulation of protein expression in chestnut blight fungus by a hypovirus.

    Science.gov (United States)

    Wang, Jinzi; Wang, Fangzhen; Feng, Youjun; Mi, Ke; Chen, Qi; Shang, Jinjie; Chen, Baoshan

    2013-01-14

    The chestnut blight fungus (Cryphonectria parasitica) and hypovirus constitute a model system to study fungal pathogenesis and mycovirus-host interaction. Knowledge in this field has been gained largely from investigations at gene transcription level so far. Here we report a systematic analysis of the vesicle proteins of the host fungus with/without hypovirus infection. Thirty-three differentially expressed protein spots were identified in the purified vesicle protein samples by two-dimensional electrophoresis and mass spectrometry. Down-regulated proteins were mostly cargo proteins involved in primary metabolism and energy generation and up-regulated proteins were mostly vesicle associated proteins and ABC transporter. A virus-encoded protein p48 was found to have four forms with different molecular mass in vesicles from the virus-infected strain. While a few of the randomly selected differentially expressed proteins were in accordance with their transcription profiles, majority were not in agreement with their mRNA accumulation patterns, suggesting that an extensive post-transcriptional regulation may have occurred in the host fungus upon a hypovirus infection. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Scaling properties reveal regulation of river flows in the Amazon through a forest reservoir

    Directory of Open Access Journals (Sweden)

    J. F. Salazar

    2018-03-01

    Full Text Available Many natural and social phenomena depend on river flow regimes that are being altered by global change. Understanding the mechanisms behind such alterations is crucial for predicting river flow regimes in a changing environment. Here we introduce a novel physical interpretation of the scaling properties of river flows and show that it leads to a parsimonious characterization of the flow regime of any river basin. This allows river basins to be classified as regulated or unregulated, and to identify a critical threshold between these states. We applied this framework to the Amazon river basin and found both states among its main tributaries. Then we introduce the forest reservoir hypothesis to describe the natural capacity of river basins to regulate river flows through land–atmosphere interactions (mainly precipitation recycling that depend strongly on the presence of forests. A critical implication is that forest loss can force the Amazonian river basins from regulated to unregulated states. Our results provide theoretical and applied foundations for predicting hydrological impacts of global change, including the detection of early-warning signals for critical transitions in river basins.

  6. A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation

    Science.gov (United States)

    McGarvey, Alison C.; Souilhol, Céline; Rice, Ritva; Hills, David; Rice, David; Tomlinson, Simon R.

    2017-01-01

    In the developing embryo, hematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region, but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA sequencing over these spatiotemporal transitions in the AGM region and supportive OP9 cell line. Screening several proteins through an ex vivo reaggregate culture system, we identify BMPER as a novel positive regulator of HSC development. We demonstrate that BMPER is associated with BMP signaling inhibition, but is transcriptionally induced by BMP4, suggesting that BMPER contributes to the precise control of BMP activity within the AGM region, enabling the maturation of HSCs within a BMP-negative environment. These findings and the availability of our transcriptional data through an accessible interface should provide insight into the maintenance and potential derivation of HSCs in culture. PMID:29093060

  7. Scaling properties reveal regulation of river flows in the Amazon through a forest reservoir

    Science.gov (United States)

    Salazar, Juan Fernando; Villegas, Juan Camilo; María Rendón, Angela; Rodríguez, Estiven; Hoyos, Isabel; Mercado-Bettín, Daniel; Poveda, Germán

    2018-03-01

    Many natural and social phenomena depend on river flow regimes that are being altered by global change. Understanding the mechanisms behind such alterations is crucial for predicting river flow regimes in a changing environment. Here we introduce a novel physical interpretation of the scaling properties of river flows and show that it leads to a parsimonious characterization of the flow regime of any river basin. This allows river basins to be classified as regulated or unregulated, and to identify a critical threshold between these states. We applied this framework to the Amazon river basin and found both states among its main tributaries. Then we introduce the forest reservoir hypothesis to describe the natural capacity of river basins to regulate river flows through land-atmosphere interactions (mainly precipitation recycling) that depend strongly on the presence of forests. A critical implication is that forest loss can force the Amazonian river basins from regulated to unregulated states. Our results provide theoretical and applied foundations for predicting hydrological impacts of global change, including the detection of early-warning signals for critical transitions in river basins.

  8. Dual activation of pathways regulated by steroid receptors and peptide growth factors in primary prostate cancer revealed by Factor Analysis of microarray data

    Directory of Open Access Journals (Sweden)

    Fernandez Pedro L

    2005-08-01

    Full Text Available Abstract Background We use an approach based on Factor Analysis to analyze datasets generated for transcriptional profiling. The method groups samples into biologically relevant categories, and enables the identification of genes and pathways most significantly associated to each phenotypic group, while allowing for the participation of a given gene in more than one cluster. Genes assigned to each cluster are used for the detection of pathways predominantly activated in that cluster by finding statistically significant associated GO terms. We tested the approach with a published dataset of microarray experiments in yeast. Upon validation with the yeast dataset, we applied the technique to a prostate cancer dataset. Results Two major pathways are shown to be activated in organ-confined, non-metastatic prostate cancer: those regulated by the androgen receptor and by receptor tyrosine kinases. A number of gene markers (HER3, IQGAP2 and POR1 highlighted by the software and related to the later pathway have been validated experimentally a posteriori on independent samples. Conclusion Using a new microarray analysis tool followed by a posteriori experimental validation of the results, we have confirmed several putative markers of malignancy associated with peptide growth factor signalling in prostate cancer and revealed others, most notably ERRB3 (HER3. Our study suggest that, in primary prostate cancer, HER3, together or not with HER4, rather than in receptor complexes involving HER2, could play an important role in the biology of these tumors. These results provide new evidence for the role of receptor tyrosine kinases in the establishment and progression of prostate cancer.

  9. Co-expression networks reveal the tissue-specific regulation of transcription and splicing.

    Science.gov (United States)

    Saha, Ashis; Kim, Yungil; Gewirtz, Ariel D H; Jo, Brian; Gao, Chuan; McDowell, Ian C; Engelhardt, Barbara E; Battle, Alexis

    2017-11-01

    Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. © 2017 Saha et al.; Published by Cold Spring Harbor Laboratory Press.

  10. RNAseq analysis of the parasitic nematode Strongyloides stercoralis reveals divergent regulation of canonical dauer pathways.

    Directory of Open Access Journals (Sweden)

    Jonathan D Stoltzfus

    Full Text Available The infectious form of many parasitic nematodes, which afflict over one billion people globally, is a developmentally arrested third-stage larva (L3i. The parasitic nematode Strongyloides stercoralis differs from other nematode species that infect humans, in that its life cycle includes both parasitic and free-living forms, which can be leveraged to investigate the mechanisms of L3i arrest and activation. The free-living nematode Caenorhabditis elegans has a similar developmentally arrested larval form, the dauer, whose formation is controlled by four pathways: cyclic GMP (cGMP signaling, insulin/IGF-1-like signaling (IIS, transforming growth factor β (TGFβ signaling, and biosynthesis of dafachronic acid (DA ligands that regulate a nuclear hormone receptor. We hypothesized that homologous pathways are present in S. stercoralis, have similar developmental regulation, and are involved in L3i arrest and activation. To test this, we undertook a deep-sequencing study of the polyadenylated transcriptome, generating over 2.3 billion paired-end reads from seven developmental stages. We constructed developmental expression profiles for S. stercoralis homologs of C. elegans dauer genes identified by BLAST searches of the S. stercoralis genome as well as de novo assembled transcripts. Intriguingly, genes encoding cGMP pathway components were coordinately up-regulated in L3i. In comparison to C. elegans, S. stercoralis has a paucity of genes encoding IIS ligands, several of which have abundance profiles suggesting involvement in L3i development. We also identified seven S. stercoralis genes encoding homologs of the single C. elegans dauer regulatory TGFβ ligand, three of which are only expressed in L3i. Putative DA biosynthetic genes did not appear to be coordinately regulated in L3i development. Our data suggest that while dauer pathway genes are present in S. stercoralis and may play a role in L3i development, there are significant differences between

  11. Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation

    DEFF Research Database (Denmark)

    Kieffer-Kwon, Kyong-Rim; Tang, Zhonghui; Mathe, Ewy

    2013-01-01

    IA-PET technologies to map the promoter-enhancer interactomes of pluripotent ES cells and differentiated B lymphocytes. We confirm that enhancer usage varies widely across tissues. Unexpectedly, we find that this feature extends to broadly transcribed genes, including Myc and Pim1 cell-cycle regulators, which...... associate with an entirely different set of enhancers in ES and B cells. By means of high-resolution CpG methylomes, genome editing, and digital footprinting, we show that these enhancers recruit lineage-determining factors. Furthermore, we demonstrate that the turning on and off of enhancers during...

  12. Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

    Science.gov (United States)

    Menet, Jerome S; Rodriguez, Joseph; Abruzzi, Katharine C; Rosbash, Michael

    2012-01-01

    A substantial fraction of the metazoan transcriptome undergoes circadian oscillations in many cells and tissues. Based on the transcription feedback loops important for circadian timekeeping, it is commonly assumed that this mRNA cycling reflects widespread transcriptional regulation. To address this issue, we directly measured the circadian dynamics of mouse liver transcription using Nascent-Seq (genome-wide sequencing of nascent RNA). Although many genes are rhythmically transcribed, many rhythmic mRNAs manifest poor transcriptional rhythms, indicating a prominent contribution of post-transcriptional regulation to circadian mRNA expression. This analysis of rhythmic transcription also showed that the rhythmic DNA binding profile of the transcription factors CLOCK and BMAL1 does not determine the transcriptional phase of most target genes. This likely reflects gene-specific collaborations of CLK:BMAL1 with other transcription factors. These insights from Nascent-Seq indicate that it should have broad applicability to many other gene expression regulatory issues. DOI: http://dx.doi.org/10.7554/eLife.00011.001 PMID:23150795

  13. Proteomic and functional analyses reveal MAPK1 regulates milk protein synthesis.

    Science.gov (United States)

    Lu, Li-Min; Li, Qing-Zhang; Huang, Jian-Guo; Gao, Xue-Jun

    2012-12-27

    L-Lysine (L-Lys) is an essential amino acid that plays fundamental roles in protein synthesis. Many nuclear phosphorylated proteins such as Stat5 and mTOR regulate milk protein synthesis. However, the details of milk protein synthesis control at the transcript and translational levels are not well known. In this current study, a two-dimensional gel electrophoresis (2-DE)/MS-based proteomic technology was used to identify phosphoproteins responsible for milk protein synthesis in dairy cow mammary epithelial cells (DCMECs). The effect of L-Lys on DCMECs was analyzed by CASY technology and reversed phase high performance liquid chromatography (RP-HPLC). The results showed that cell proliferation ability and β-casein expression were enhanced in DCMECs treated with L-Lys. By phosphoproteomics analysis, six proteins, including MAPK1, were identified up-expressed in DCMECs treated with 1.2 mM L-Lys for 24 h, and were verified by quantitative real-time PCR (qRT-PCR) and western blot. Overexpression and siRNA inhibition of MAPK1 experiments showed that MAPK1 upregulated milk protein synthesis through Stat5 and mTOR pathway. These findings that MAPK1 involves in regulation of milk synthesis shed new insights for understanding the mechanisms of milk protein synthesis.

  14. RNAi Reveals Phase-Specific Global Regulators of Human Somatic Cell Reprogramming

    Directory of Open Access Journals (Sweden)

    Cheng-Xu Delon Toh

    2016-06-01

    Full Text Available Incomplete knowledge of the mechanisms at work continues to hamper efforts to maximize reprogramming efficiency. Here, we present a systematic genome-wide RNAi screen to determine the global regulators during the early stages of human reprogramming. Our screen identifies functional repressors and effectors that act to impede or promote the reprogramming process. Repressors and effectors form close interacting networks in pathways, including RNA processing, G protein signaling, protein ubiquitination, and chromatin modification. Combinatorial knockdown of five repressors (SMAD3, ZMYM2, SFRS11, SAE1, and ESET synergistically resulted in ∼85% TRA-1-60-positive cells. Removal of the novel splicing factor SFRS11 during reprogramming is accompanied by rapid acquisition of pluripotency-specific spliced forms. Mechanistically, SFRS11 regulates exon skipping and mutually exclusive splicing of transcripts in genes involved in cell differentiation, mRNA splicing, and chromatin modification. Our study provides insights into the reprogramming process, which comprises comprehensive and multi-layered transcriptional, splicing, and epigenetic machineries.

  15. Exosome proteomics reveals transcriptional regulator proteins with potential to mediate downstream pathways.

    Science.gov (United States)

    Ung, Timothy H; Madsen, Helen J; Hellwinkel, Justin E; Lencioni, Alex M; Graner, Michael W

    2014-11-01

    Exosomes are virus-sized, membrane-enclosed vesicles with origins in the cellular endosomal system, but are released extracellularly. As a population, these tiny vesicles carry relatively enormous amounts of information in their protein, lipid and nucleic acid content, and the vesicles can have profound impacts on recipient cells. This review employs publically-available data combined with gene ontology applications to propose a novel concept, that exosomes transport transcriptional and translational machinery that may have direct impacts on gene expression in recipient cells. Here, we examine the previously published proteomic contents of medulloblastoma-derived exosomes, focusing on transcriptional regulators; we found that there are numerous proteins that may have potential roles in transcriptional and translational regulation with putative influence on downstream, cancer-related pathways. We expanded this search to all of the proteins in the Vesiclepedia database; using gene ontology approaches, we see that these regulatory factors are implicated in many of the processes involved in cancer initiation and progression. This information suggests that some of the effects of exosomes on recipient cells may be due to the delivery of protein factors that can directly and fundamentally change the transcriptional landscape of the cells. Within a tumor environment, this has potential to tilt the advantage towards the cancer. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  16. Tokamak confinement scaling laws

    International Nuclear Information System (INIS)

    Connor, J.

    1998-01-01

    The scaling of energy confinement with engineering parameters, such as plasma current and major radius, is important for establishing the size of an ignited fusion device. Tokamaks exhibit a variety of modes of operation with different confinement properties. At present there is no adequate first principles theory to predict tokamak energy confinement and the empirical scaling method is the preferred approach to designing next step tokamaks. This paper reviews a number of robust theoretical concepts, such as dimensional analysis and stability boundaries, which provide a framework for characterising and understanding tokamak confinement and, therefore, generate more confidence in using empirical laws for extrapolation to future devices. (author)

  17. Computational Approaches Reveal New Insights into Regulation and Function of Non; coding RNAs and their Targets

    KAUST Repository

    Alam, Tanvir

    2016-11-28

    Regulation and function of protein-coding genes are increasingly well-understood, but no comparable evidence exists for non-coding RNA (ncRNA) genes, which appear to be more numerous than protein-coding genes. We developed a novel machine-learning model to distinguish promoters of long ncRNA (lncRNA) genes from those of protein-coding genes. This represents the first attempt to make this distinction based on properties of the associated gene promoters. From our analyses, several transcription factors (TFs), which are known to be regulated by lncRNAs, also emerged as potential global regulators of lncRNAs, suggesting that lncRNAs and TFs may participate in bidirectional feedback regulatory network. Our results also raise the possibility that, due to the historical dependence on protein-coding gene in defining the chromatin states of active promoters, an adjustment of these chromatin signature profiles to incorporate lncRNAs is warranted in the future. Secondly, we developed a novel method to infer functions for lncRNA and microRNA (miRNA) transcripts based on their transcriptional regulatory networks in 119 tissues and 177 primary cells of human. This method for the first time combines information of cell/tissueVspecific expression of a transcript and the TFs and transcription coVfactors (TcoFs) that control activation of that transcript. Transcripts were annotated using statistically enriched GO terms, pathways and diseases across cells/tissues and associated knowledgebase (FARNA) is developed. FARNA, having the most comprehensive function annotation of considered ncRNAs across the widest spectrum of cells/tissues, has a potential to contribute to our understanding of ncRNA roles and their regulatory mechanisms in human. Thirdly, we developed a novel machine-learning model to identify LD motif (a protein interaction motif) of paxillin, a ncRNA target that is involved in cell motility and cancer metastasis. Our recognition model identified new proteins not

  18. High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcriptional regulation.

    Science.gov (United States)

    Anandapadamanaban, Madhanagopal; Andresen, Cecilia; Helander, Sara; Ohyama, Yoshifumi; Siponen, Marina I; Lundström, Patrik; Kokubo, Tetsuro; Ikura, Mitsuhiko; Moche, Martin; Sunnerhagen, Maria

    2013-08-01

    The general transcription factor TFIID provides a regulatory platform for transcription initiation. Here we present the crystal structure (1.97 Å) and NMR analysis of yeast TAF1 N-terminal domains TAND1 and TAND2 bound to yeast TBP, together with mutational data. We find that yeast TAF1-TAND1, which in itself acts as a transcriptional activator, binds TBP's concave DNA-binding surface by presenting similar anchor residues to TBP as does Mot1 but from a distinct structural scaffold. Furthermore, we show how TAF1-TAND2 uses an aromatic and acidic anchoring pattern to bind a conserved TBP surface groove traversing the basic helix region, and we find highly similar TBP-binding motifs also presented by the structurally distinct TFIIA, Mot1 and Brf1 proteins. Our identification of these anchoring patterns, which can be easily disrupted or enhanced, provides insight into the competitive multiprotein TBP interplay critical to transcriptional regulation.

  19. Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor-α-positive human cells

    International Nuclear Information System (INIS)

    Singleton, David W.; Feng, Yuxin; Yang, Jun; Puga, Alvaro; Lee, Adrian V.; Khan, Sohaib A.

    2006-01-01

    Bisphenol-A (BPA) shows proliferative actions in uterus and mammary glands and may influence the development of male and female reproductive tracts in utero or during early postnatal life. Because of its ability to function as an estrogen receptor (ER) agonist, BPA has the potential to disrupt normal endocrine signaling through regulation of ER target genes. Some genes are regulated by both estradiol (E2) and BPA, but those exclusive to either agent have not been described. Using a yeast strain incorporating a vitellogenin A2 ERE-LacZ reporter gene into the genome, we found that BPA induced expression of the reporter in colonies transformed with the ERα expression plasmid, illustrating BPA-mediated regulation within a chromatin context. Additionally, a reporter gene transiently transfected into the endometrial cancer (Ishikawa) cell line also showed BPA activity, although at 100-fold less potency than E2. To compare global gene expression in response to BPA and E2, we used a variant of the MCF-7 breast cancer cell line stably expressing HA-tagged ERα. Cultures were treated for 3 h with an ethanol vehicle, E2 (10 -8 M), or BPA (10 -6 M), followed by isolation of RNA and microarray analysis with the human U95A probe array (Affymetrix, Santa Clara, CA, USA). More than 300 genes were changed 2-fold or more by either or both agents, with roughly half being up-regulated and half down-regulated. A number of growth- and development-related genes, such as HOXC1 and C6, Wnt5A, Frizzled, TGFβ-2, and STAT inhibitor 2, were found to be affected exclusively by BPA. We used quantitative real-time PCR to verify regulation of the HOXC6 gene, which showed decreased expression of approximately 2.5-fold by BPA. These results reveal novel effects by BPA and E2, raising interesting possibilities regarding the role of endocrine disruptors in sexual development

  20. Genome-wide functional analysis of plasmodium protein phosphatases reveals key regulators of parasite development and differentiation

    KAUST Repository

    Guttery, David S.

    2014-07-09

    Reversible protein phosphorylation regulated by kinases and phosphatases controls many cellular processes. Although essential functions for the malaria parasite kinome have been reported, the roles of most protein phosphatases (PPs) during Plasmodium development are unknown. We report a functional analysis of the Plasmodium berghei protein phosphatome, which exhibits high conservation with the P. falciparum phosphatome and comprises 30 predicted PPs with differential and distinct expression patterns during various stages of the life cycle. Gene disruption analysis of P. berghei PPs reveals that half of the genes are likely essential for asexual blood stage development, whereas six are required for sexual development/sporogony in mosquitoes. Phenotypic screening coupled with transcriptome sequencing unveiled morphological changes and altered gene expression in deletion mutants of two N-myristoylated PPs. These findings provide systematic functional analyses of PPs in Plasmodium, identify how phosphatases regulate parasite development and differentiation, and can inform the identification of drug targets for malaria. © 2014 The Authors.

  1. Genome-wide functional analysis of plasmodium protein phosphatases reveals key regulators of parasite development and differentiation

    KAUST Repository

    Guttery, David  S.; Poulin, Benoit; Ramaprasad, Abhinay; Wall, Richard  J.; Ferguson, David  J.P.; Brady, Declan; Patzewitz, Eva-Maria; Whipple, Sarah; Straschil, Ursula; Wright, Megan  H.; Mohamed, Alyaa  M.A.H.; Radhakrishnan, Anand; Arold, Stefan T.; Tate, Edward  W.; Holder, Anthony  A.; Wickstead, Bill; Pain, Arnab; Tewari, Rita

    2014-01-01

    Reversible protein phosphorylation regulated by kinases and phosphatases controls many cellular processes. Although essential functions for the malaria parasite kinome have been reported, the roles of most protein phosphatases (PPs) during Plasmodium development are unknown. We report a functional analysis of the Plasmodium berghei protein phosphatome, which exhibits high conservation with the P. falciparum phosphatome and comprises 30 predicted PPs with differential and distinct expression patterns during various stages of the life cycle. Gene disruption analysis of P. berghei PPs reveals that half of the genes are likely essential for asexual blood stage development, whereas six are required for sexual development/sporogony in mosquitoes. Phenotypic screening coupled with transcriptome sequencing unveiled morphological changes and altered gene expression in deletion mutants of two N-myristoylated PPs. These findings provide systematic functional analyses of PPs in Plasmodium, identify how phosphatases regulate parasite development and differentiation, and can inform the identification of drug targets for malaria. © 2014 The Authors.

  2. Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes

    Energy Technology Data Exchange (ETDEWEB)

    Lowden, Michael J.; Skorupski, Karen; Pellegrini, Maria; Chiorazzo, Michael G.; Taylor, Ronald K.; Kull, F. Jon (Dartmouth)

    2010-03-04

    Cholera is an acute intestinal infection caused by the bacterium Vibrio cholerae. In order for V. cholerae to cause disease, it must produce two virulence factors, the toxin-coregulated pilus (TCP) and cholera toxin (CT), whose expression is controlled by a transcriptional cascade culminating with the expression of the AraC-family regulator, ToxT. We have solved the 1.9 {angstrom} resolution crystal structure of ToxT, which reveals folds in the N- and C-terminal domains that share a number of features in common with AraC, MarA, and Rob as well as the unexpected presence of a buried 16-carbon fatty acid, cis-palmitoleate. The finding that cis-palmitoleic acid reduces TCP and CT expression in V. cholerae and prevents ToxT from binding to DNA in vitro provides a direct link between the host environment of V. cholerae and regulation of virulence gene expression.

  3. Construction of an miRNA-Regulated Pathway Network Reveals Candidate Biomarkers for Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    Min Shao

    2017-01-01

    Full Text Available We aimed to identify risk pathways for postmenopausal osteoporosis (PMOP via establishing an microRNAs- (miRNA- regulated pathway network (MRPN. Firstly, we identified differential pathways through calculating gene- and pathway-level statistics based on the accumulated normal samples using the individual pathway aberrance score (iPAS. Significant pathways based on differentially expressed genes (DEGs using DAVID were extracted, followed by identifying the common pathways between iPAS and DAVID methods. Next, miRNAs prediction was implemented via calculating TargetScore values with precomputed input (log fold change (FC, TargetScan context score (TSCS, and probabilities of conserved targeting (PCT. An MRPN construction was constructed using the common genes in the common pathways and the predicted miRNAs. Using false discovery rate (FDR < 0.05, 279 differential pathways were identified. Using the criteria of FDR < 0.05 and log⁡FC≥2, 39 DEGs were retrieved, and these DEGs were enriched in 64 significant pathways identified by DAVID. Overall, 27 pathways were the common ones between two methods. Importantly, MAPK signaling pathway and PI3K-Akt signaling pathway were the first and second significantly enriched ones, respectively. These 27 common pathways separated PMOP from controls with the accuracy of 0.912. MAPK signaling pathway and PI3K/Akt signaling pathway might play crucial roles in PMOP.

  4. Identification of TOEFAZ1-interacting proteins reveals key regulators of Trypanosoma brucei cytokinesis.

    Science.gov (United States)

    Hilton, Nicholas A; Sladewski, Thomas E; Perry, Jenna A; Pataki, Zemplen; Sinclair-Davis, Amy N; Muniz, Richard S; Tran, Holly L; Wurster, Jenna I; Seo, Jiwon; de Graffenried, Christopher L

    2018-05-21

    The protist parasite Trypanosoma brucei is an obligate extracellular pathogen that retains its highly-polarized morphology during cell division and has evolved a novel cytokinetic process independent of non-muscle myosin II. The polo-like kinase homolog TbPLK is essential for transmission of cell polarity during division and for cytokinesis. We previously identified a putative TbPLK substrate named Tip of the Extending FAZ 1 (TOEFAZ1) as an essential kinetoplastid-specific component of the T. brucei cytokinetic machinery. We performed a proximity-dependent biotinylation (BioID) screen using TOEFAZ1 as a means to identify additional proteins that are involved in cytokinesis. Using quantitative proteomic methods, we identified nearly 500 TOEFAZ1-proximal proteins and characterized 59 in further detail. Among the candidates, we identified an essential putative phosphatase that regulates the expression level and localization of both TOEFAZ1 and TbPLK, a previously uncharacterized protein that is necessary for the assembly of a new cell posterior, and a microtubule plus-end directed orphan kinesin that is required for completing cleavage furrow ingression. The identification of these proteins provides new insight into T. brucei cytokinesis and establishes TOEFAZ1 as a key component of this essential and uniquely-configured process in kinetoplastids. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.

  5. Dynamics in geometrical confinement

    CERN Document Server

    Kremer, Friedrich

    2014-01-01

    This book describes the dynamics of low molecular weight and polymeric molecules when they are constrained under conditions of geometrical confinement. It covers geometrical confinement in different dimensionalities: (i) in nanometer thin layers or self supporting films (1-dimensional confinement) (ii) in pores or tubes with nanometric diameters (2-dimensional confinement) (iii) as micelles embedded in matrices (3-dimensional) or as nanodroplets.The dynamics under such conditions have been a much discussed and central topic in the focus of intense worldwide research activities within the last two decades. The present book discusses how the resulting molecular mobility is influenced by the subtle counterbalance between surface effects (typically slowing down molecular dynamics through attractive guest/host interactions) and confinement effects (typically increasing the mobility). It also explains how these influences can be modified and tuned, e.g. through appropriate surface coatings, film thicknesses or pore...

  6. Systems genomics study reveals expression quantitative trait loci, regulator genes and pathways associated with boar taint in pigs

    DEFF Research Database (Denmark)

    Drag, Markus; Hansen, Mathias B.; Kadarmideen, Haja N.

    2018-01-01

    Boar taint is an offensive odour and/or taste from a proportion of non-castrated male pigs caused by skatole and androstenone accumulation during sexual maturity. Castration is widely used to avoid boar taint but is currently under debate because of animal welfare concerns. This study aimed...... to identify expression quantitative trait loci (eQTLs) with potential effects on boar taint compounds to improve breeding possibilities for reduced boar taint. Danish Landrace male boars with low, medium and high genetic merit for skatole and human nose score (HNS) were slaughtered at similar to 100 kg. Gene...... and SSC14. Functional characterisation of eQTLs revealed functions within regulation of androgen and the intracellular steroid hormone receptor signalling pathway and of xenobiotic metabolism by cytochrome P450 system and cellular response to oestradiol. A QTL enrichment test revealed 89 QTL traits...

  7. Comparative transcriptome analysis reveals distinct ethylene-independent regulation of ripening in response to low temperature in kiwifruit.

    Science.gov (United States)

    Asiche, William O; Mitalo, Oscar W; Kasahara, Yuka; Tosa, Yasuaki; Mworia, Eric G; Owino, Willis O; Ushijima, Koichiro; Nakano, Ryohei; Yano, Kentaro; Kubo, Yasutaka

    2018-03-21

    Kiwifruit are classified as climacteric since exogenous ethylene (or its analogue propylene) induces rapid ripening accompanied by ethylene production under positive feedback regulation. However, most of the ripening-associated changes (Phase 1 ripening) in kiwifruit during storage and on-vine occur largely in the absence of any detectable ethylene. This ripening behavior is often attributed to basal levels of system I ethylene, although it is suggested to be modulated by low temperature. To elucidate the mechanisms regulating Phase 1 ripening in kiwifruit, a comparative transcriptome analysis using fruit continuously exposed to propylene (at 20 °C), and during storage at 5 °C and 20 °C was conducted. Propylene exposure induced kiwifruit softening, reduction of titratable acidity (TA), increase in soluble solids content (SSC) and ethylene production within 5 days. During storage, softening and reduction of TA occurred faster in fruit at 5 °C compared to 20 °C although no endogenous ethylene production was detected. Transcriptome analysis revealed 3761 ripening-related differentially expressed genes (DEGs), of which 2742 were up-regulated by propylene while 1058 were up-regulated by low temperature. Propylene exclusively up-regulated 2112 DEGs including those associated with ethylene biosynthesis and ripening such as AcACS1, AcACO2, AcPL1, AcXET1, Acβ-GAL, AcAAT, AcERF6 and AcNAC7. Similarly, low temperature exclusively up-regulated 467 DEGS including AcACO3, AcPL2, AcPMEi, AcADH, Acβ-AMY2, AcGA2ox2, AcNAC5 and AcbZIP2 among others. A considerable number of DEGs such as AcPG, AcEXP1, AcXET2, Acβ-AMY1, AcGA2ox1, AcNAC6, AcMADS1 and AcbZIP1 were up-regulated by either propylene or low temperature. Frequent 1-MCP treatments failed to inhibit the accelerated ripening and up-regulation of associated DEGs by low temperature indicating that the changes were independent of ethylene. On-vine kiwifruit ripening proceeded in the absence of any detectable

  8. Characterization of the sebocyte lipid droplet proteome reveals novel potential regulators of sebaceous lipogenesis.

    Science.gov (United States)

    Dahlhoff, Maik; Fröhlich, Thomas; Arnold, Georg J; Müller, Udo; Leonhardt, Heinrich; Zouboulis, Christos C; Schneider, Marlon R

    2015-03-01

    Lipid metabolism depends on lipid droplets (LD), cytoplasmic structures surrounded by a protein-rich phospholipid monolayer. Although lipid synthesis is the hallmark of sebaceous gland cell differentiation, the LD-associated proteins of sebocytes have not been evaluated systematically. The LD fraction of SZ95 sebocytes was collected by density gradient centrifugation and associated proteins were analyzed by nanoliquid chromatography/tandem mass spectrometry. 54 proteins were significantly enriched in LD fractions, and 6 of them have not been detected previously in LDs. LD fractions contained high levels of typical LD-associated proteins as PLIN2/PLIN3, and most proteins belonged to functional categories characteristic for LD-associated proteins, indicating a reliable dataset. After confirming expression of transcripts encoding the six previously unidentified proteins by qRT-PCR in SZ95 sebocytes and in another sebocyte line (SebE6E7), we focused on two of these proteins, ALDH1A3 and EPHX4. While EPHX4 was localized almost exclusively on the surface of LDs, ALDH1A3 showed a more widespread localization that included additional cytoplasmic structures. siRNA-mediated downregulation revealed that depletion of EPHX4 increases LD size and sebaceous lipogenesis. Further studies on the roles of these proteins in sebocyte physiology and sebaceous lipogenesis may indicate novel strategies for the therapy of sebaceous gland-associated diseases such as acne. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions

    International Nuclear Information System (INIS)

    Eibl, Clarissa; Hessenberger, Manuel; Wenger, Julia; Brandstetter, Hans

    2014-01-01

    Pyrin domains (PYDs) recruit downstream effector molecules in NLR signalling. A specific charge-relay system suggests a the formation of a signalling complex involving a PYD dimer. The cytosolic tripartite NLR receptors serve as important signalling platforms in innate immunity. While the C-terminal domains act as sensor and activation modules, the N-terminal death-like domain, e.g. the CARD or pyrin domain, is thought to recruit downstream effector molecules by homotypic interactions. Such homotypic complexes have been determined for all members of the death-domain superfamily except for pyrin domains. Here, crystal structures of human NLRP14 pyrin-domain variants are reported. The wild-type protein as well as the clinical D86V mutant reveal an unexpected rearrangement of the C-terminal helix α6, resulting in an extended α5/6 stem-helix. This reordering mediates a novel symmetric pyrin-domain dimerization mode. The conformational switching is controlled by a charge-relay system with a drastic impact on protein stability. How the identified charge relay allows classification of NLRP receptors with respect to distinct recruitment mechanisms is discussed

  10. Suicide Gene-Engineered Stromal Cells Reveal a Dynamic Regulation of Cancer Metastasis

    Science.gov (United States)

    Shen, Keyue; Luk, Samantha; Elman, Jessica; Murray, Ryan; Mukundan, Shilpaa; Parekkadan, Biju

    2016-02-01

    Cancer-associated fibroblasts (CAFs) are a major cancer-promoting component in the tumor microenvironment (TME). The dynamic role of human CAFs in cancer progression has been ill-defined because human CAFs lack a unique marker needed for a cell-specific, promoter-driven knockout model. Here, we developed an engineered human CAF cell line with an inducible suicide gene to enable selective in vivo elimination of human CAFs at different stages of xenograft tumor development, effectively circumventing the challenge of targeting a cell-specific marker. Suicide-engineered CAFs were highly sensitive to apoptosis induction in vitro and in vivo by the addition of a simple small molecule inducer. Selection of timepoints for targeted CAF apoptosis in vivo during the progression of a human breast cancer xenograft model was guided by a bi-phasic host cytokine response that peaked at early timepoints after tumor implantation. Remarkably, we observed that the selective apoptosis of CAFs at these early timepoints did not affect primary tumor growth, but instead increased the presence of tumor-associated macrophages and the metastatic spread of breast cancer cells to the lung and bone. The study revealed a dynamic relationship between CAFs and cancer metastasis that has counter-intuitive ramifications for CAF-targeted therapy.

  11. Quantitative cell signalling analysis reveals down-regulation of MAPK pathway activation in colorectal cancer.

    LENUS (Irish Health Repository)

    Gulmann, Christian

    2009-08-01

    Mitogen-activated protein kinases (MAPK) are considered to play significant roles in colonic carcinogenesis and kinase inhibitor therapy has been proposed as a potential tool in the treatment of this disease. Reverse-phase microarray assays using phospho-specific antibodies can directly measure levels of phosphorylated protein isoforms. In the current study, samples from 35 cases of untreated colorectal cancer colectomies were laser capture-microdissected to isolate epithelium and stroma from cancer as well as normal (i.e. uninvolved) mucosa. Lysates generated from these four tissue types were spotted onto reverse-phase protein microarrays and probed with a panel of antibodies to ERK, p-ERK, p38, p-p38, p-JNK, MEK and p-MEK. Whereas total protein levels were unchanged, or slightly elevated (p38, p = 0.0025) in cancers, activated isoforms, including p-ERK, p-p38 and p-JNK, were decreased two- to four-fold in cancers compared with uninvolved mucosa (p < 0.0023 in all cases except for p-JNK in epithelium, where decrement was non-significant). This was backed up by western blotting. Dukes\\' stage B and C cancers displayed lower p-ERK and p-p38 expression than Dukes\\' stage A cancers, although this was not statistically significant. It is concluded that MAPK activity may be down-regulated in colorectal cancer and that further exploration of inhibitory therapy in this system should be carefully evaluated if this finding is confirmed in larger series.

  12. Substrate specificity changes for human reticulocyte and epithelial 15-lipoxygenases reveal allosteric product regulation.

    Science.gov (United States)

    Wecksler, Aaron T; Kenyon, Victor; Deschamps, Joshua D; Holman, Theodore R

    2008-07-15

    Human reticulocyte 15-lipoxygenase (15-hLO-1) and epithelial 15-lipoxygenase (15-hLO-2) have been implicated in a number of human diseases, with differences in their substrate specificity potentially playing a central role. In this paper, we present a novel method for accurately measuring the substrate specificity of the two 15-hLO isozymes and demonstrate that both cholate and specific LO products affect substrate specificity. The linoleic acid (LA) product, 13-hydroperoxyoctadienoic acid (13-HPODE), changes the ( k cat/ K m) (AA)/( k cat/ K m) (LA) ratio more than 5-fold for 15-hLO-1 and 3-fold for 15-hLO-2, while the arachidonic acid (AA) product, 12-( S)-hydroperoxyeicosatetraenoic acid (12-HPETE), affects only the ratio of 15-hLO-1 (more than 5-fold). In addition, the reduced products, 13-( S)-hydroxyoctadecadienoic acid (13-HODE) and 12-( S)-hydroxyeicosatetraenoic acid (12-HETE), also affect substrate specificity, indicating that iron oxidation is not responsible for the change in the ( k cat/ K m) (AA)/( k cat/ K m) (LA) ratio. These results, coupled with the dependence of the 15-hLO-1 k cat/ K m kinetic isotope effect ( (D) k cat/ K m) on the presence of 12-HPETE and 12-HETE, indicate that the allosteric site, previously identified in 15-hLO-1 [Mogul, R., Johansen, E., and Holman, T. R. (1999) Biochemistry 39, 4801-4807], is responsible for the change in substrate specificity. The ability of LO products to regulate substrate specificity may be relevant with respect to cancer progression and warrants further investigation into the role of this product-feedback loop in the cell.

  13. Characterization of the biocontrol activity of pseudomonas fluorescens strain X reveals novel genes regulated by glucose.

    Directory of Open Access Journals (Sweden)

    Gerasimos F Kremmydas

    Full Text Available Pseudomonas fluorescens strain X, a bacterial isolate from the rhizosphere of bean seedlings, has the ability to suppress damping-off caused by the oomycete Pythium ultimum. To determine the genes controlling the biocontrol activity of strain X, transposon mutagenesis, sequencing and complementation was performed. Results indicate that, biocontrol ability of this isolate is attributed to gcd gene encoding glucose dehydrogenase, genes encoding its co-enzyme pyrroloquinoline quinone (PQQ, and two genes (sup5 and sup6 which seem to be organized in a putative operon. This operon (named supX consists of five genes, one of which encodes a non-ribosomal peptide synthase. A unique binding site for a GntR-type transcriptional factor is localized upstream of the supX putative operon. Synteny comparison of the genes in supX revealed that they are common in the genus Pseudomonas, but with a low degree of similarity. supX shows high similarity only to the mangotoxin operon of Ps. syringae pv. syringae UMAF0158. Quantitative real-time PCR analysis indicated that transcription of supX is strongly reduced in the gcd and PQQ-minus mutants of Ps. fluorescens strain X. On the contrary, transcription of supX in the wild type is enhanced by glucose and transcription levels that appear to be higher during the stationary phase. Gcd, which uses PQQ as a cofactor, catalyses the oxidation of glucose to gluconic acid, which controls the activity of the GntR family of transcriptional factors. The genes in the supX putative operon have not been implicated before in the biocontrol of plant pathogens by pseudomonads. They are involved in the biosynthesis of an antimicrobial compound by Ps. fluorescens strain X and their transcription is controlled by glucose, possibly through the activity of a GntR-type transcriptional factor binding upstream of this putative operon.

  14. DIVERSITY in binding, regulation, and evolution revealed from high-throughput ChIP.

    Science.gov (United States)

    Mitra, Sneha; Biswas, Anushua; Narlikar, Leelavati

    2018-04-23

    Genome-wide in vivo protein-DNA interactions are routinely mapped using high-throughput chromatin immunoprecipitation (ChIP). ChIP-reported regions are typically investigated for enriched sequence-motifs, which are likely to model the DNA-binding specificity of the profiled protein and/or of co-occurring proteins. However, simple enrichment analyses can miss insights into the binding-activity of the protein. Note that ChIP reports regions making direct contact with the protein as well as those binding through intermediaries. For example, consider a ChIP experiment targeting protein X, which binds DNA at its cognate sites, but simultaneously interacts with four other proteins. Each of these proteins also binds to its own specific cognate sites along distant parts of the genome, a scenario consistent with the current view of transcriptional hubs and chromatin loops. Since ChIP will pull down all X-associated regions, the final reported data will be a union of five distinct sets of regions, each containing binding sites of one of the five proteins, respectively. Characterizing all five different motifs and the corresponding sets is important to interpret the ChIP experiment and ultimately, the role of X in regulation. We present diversity which attempts exactly this: it partitions the data so that each partition can be characterized with its own de novo motif. Diversity uses a Bayesian approach to identify the optimal number of motifs and the associated partitions, which together explain the entire dataset. This is in contrast to standard motif finders, which report motifs individually enriched in the data, but do not necessarily explain all reported regions. We show that the different motifs and associated regions identified by diversity give insights into the various complexes that may be forming along the chromatin, something that has so far not been attempted from ChIP data. Webserver at http://diversity.ncl.res.in/; standalone (Mac OS X/Linux) from https

  15. Quantitative transcription dynamic analysis reveals candidate genes and key regulators for ethanol tolerance in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Ma Menggen

    2010-06-01

    and enhanced expressions of ethanol-tolerance genes associated with heat shock proteins, trehalose-glycolysis-pentose phosphate pathways and PDR gene family are accountable for the tolerant yeast to withstand the ethanol stress, maintain active metabolisms, and complete ethanol fermentation under the ethanol stress. Transcription factor Msn4p appeared to be a key regulator of gene interactions for ethanol-tolerance in the tolerant yeast Y-50316.

  16. Identification of colonic fibroblast secretomes reveals secretory factors regulating colon cancer cell proliferation.

    Science.gov (United States)

    Chen, Sun-Xia; Xu, Xiao-En; Wang, Xiao-Qing; Cui, Shu-Jian; Xu, Lei-Lei; Jiang, Ying-Hua; Zhang, Yang; Yan, Hai-Bo; Zhang, Qian; Qiao, Jie; Yang, Peng-Yuan; Liu, Feng

    2014-10-14

    Stromal microenvironment influences tumor cell proliferation and migration. Fibroblasts represent the most abundant stromal constituents. Here, we established two pairs of normal fibroblast (NF) and cancer-associated fibroblast (CAF) cultures from colorectal adenocarcinoma tissues and the normal counterparts. The NFs and CAFs were stained positive for typical fibroblast markers and inhibited colon cancer (CC) cell proliferation in in vitro cocultures and in xenograft mouse models. The fibroblast conditioned media were analyzed using LC-MS and 227 proteins were identified at a false discovery rate of 1.3%, including 131 putative secretory and 20 plasma membrane proteins. These proteins were enriched for functional categories of extracellular matrix, adhesion, cell motion, inflammatory response, redox homeostasis and peptidase inhibitor. Secreted protein acidic and rich in cysteine, transgelin, follistatin-related protein 1 (FSTL1) and decorin was abundant in the fibroblast secretome as confirmed by Western blot. Silencing of FSTL1 and transgelin in colonic fibroblast cell line CCD-18Co induced an accelerated proliferation of CC cells in cocultures. Exogenous FSTL1 attenuates CC cell proliferation in a negative fashion. FSTL1 was upregulated in CC patient plasma and cancerous tissues but had no implication in prognosis. Our results provided novel insights into the molecular signatures and modulatory role of CC associated fibroblasts. In this study, a label-free LC-MS was performed to analyze the secretomes of two paired primary fibroblasts, which were isolated from fresh surgical specimen of colorectal adenocarcinoma and adjacent normal colonic tissues and exhibited negative modulatory activity for colon cancer cell growth in in vitro cocultures and in vivo xenograph mouse models. Follistatin-related protein 1 was further revealed to be one of the stroma-derived factors of potential suppression role for colon cancer cell proliferation. Our results provide novel

  17. Differential co-expression and regulation analyses reveal different mechanisms underlying major depressive disorder and subsyndromal symptomatic depression.

    Science.gov (United States)

    Xu, Fan; Yang, Jing; Chen, Jin; Wu, Qingyuan; Gong, Wei; Zhang, Jianguo; Shao, Weihua; Mu, Jun; Yang, Deyu; Yang, Yongtao; Li, Zhiwei; Xie, Peng

    2015-04-03

    Recent depression research has revealed a growing awareness of how to best classify depression into depressive subtypes. Appropriately subtyping depression can lead to identification of subtypes that are more responsive to current pharmacological treatment and aid in separating out depressed patients in which current antidepressants are not particularly effective. Differential co-expression analysis (DCEA) and differential regulation analysis (DRA) were applied to compare the transcriptomic profiles of peripheral blood lymphocytes from patients with two depressive subtypes: major depressive disorder (MDD) and subsyndromal symptomatic depression (SSD). Six differentially regulated genes (DRGs) (FOSL1, SRF, JUN, TFAP4, SOX9, and HLF) and 16 transcription factor-to-target differentially co-expressed gene links or pairs (TF2target DCLs) appear to be the key differential factors in MDD; in contrast, one DRG (PATZ1) and eight TF2target DCLs appear to be the key differential factors in SSD. There was no overlap between the MDD target genes and SSD target genes. Venlafaxine (Efexor™, Effexor™) appears to have a significant effect on the gene expression profile of MDD patients but no significant effect on the gene expression profile of SSD patients. DCEA and DRA revealed no apparent similarities between the differential regulatory processes underlying MDD and SSD. This bioinformatic analysis may provide novel insights that can support future antidepressant R&D efforts.

  18. A whole-body model for glycogen regulation reveals a critical role for substrate cycling in maintaining blood glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Ke Xu

    2011-12-01

    Full Text Available Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into "whole-body" contextual models that mimic in vivo conditions.

  19. Metabolic regulation of trisporic acid on Blakeslea trispora revealed by a GC-MS-based metabolomic approach.

    Directory of Open Access Journals (Sweden)

    Jie Sun

    Full Text Available The zygomycete Blakeslea trispora is used commercially as natural source of â-carotene. Trisporic acid (TA is secreted from the mycelium of B. trispora during mating between heterothallic strains and is considered as a mediator of the regulation of mating processes and an enhancer of carotene biosynthesis. Gas chromatography-mass spectrometry and multivariate analysis were employed to investigate TA-associated intracellular biochemical changes in B. trispora. By principal component analysis, the differential metabolites discriminating the control groups from the TA-treated groups were found, which were also confirmed by the subsequent hierarchical cluster analysis. The results indicate that TA is a global regulator and its main effects at the metabolic level are reflected on the content changes in several fatty acids, carbohydrates, and amino acids. The carbon metabolism and fatty acids synthesis are sensitive to TA addition. Glycerol, glutamine, and ã-aminobutyrate might play important roles in the regulation of TA. Complemented by two-dimensional electrophoresis, the results indicate that the actions of TA at the metabolic level involve multiple metabolic processes, such as glycolysis and the bypass of the classical tricarboxylic acid cycle. These results reveal that the metabolomics strategy is a powerful tool to gain insight into the mechanism of a microorganism's cellular response to signal inducers at the metabolic level.

  20. Characterization of a null allelic mutant of the rice NAL1 gene reveals its role in regulating cell division.

    Directory of Open Access Journals (Sweden)

    Dan Jiang

    Full Text Available Leaf morphology is closely associated with cell division. In rice, mutations in Narrow leaf 1 (NAL1 show narrow leaf phenotypes. Previous studies have shown that NAL1 plays a role in regulating vein patterning and increasing grain yield in indica cultivars, but its role in leaf growth and development remains unknown. In this report, we characterized two allelic mutants of NARROW LEAF1 (NAL1, nal1-2 and nal1-3, both of which showed a 50% reduction in leaf width and length, as well as a dwarf culm. Longitudinal and transverse histological analyses of leaves and internodes revealed that cell division was suppressed in the anticlinal orientation but enhanced in the periclinal orientation in the mutants, while cell size remained unaltered. In addition to defects in cell proliferation, the mutants showed abnormal midrib in leaves. Map-based cloning revealed that nal1-2 is a null allelic mutant of NAL1 since both the whole promoter and a 404-bp fragment in the first exon of NAL1 were deleted, and that a 6-bp fragment was deleted in the mutant nal1-3. We demonstrated that NAL1 functions in the regulation of cell division as early as during leaf primordia initiation. The altered transcript level of G1- and S-phase-specific genes suggested that NAL1 affects cell cycle regulation. Heterogeneous expression of NAL1 in fission yeast (Schizosaccharomyces pombe further supported that NAL1 affects cell division. These results suggest that NAL1 controls leaf width and plant height through its effects on cell division.

  1. The confinement problem

    International Nuclear Information System (INIS)

    Seiler, E.

    1985-01-01

    Confinement of quarks is sometimes taken as some kind of dogma in the contemporary theory of strong interactions - quantum chromo-dynamics (QCD). Scientists should not be content with that. What is meant by ''permanent confinement'' should be formulated more precisely to see whether the theory has this property or not. The author looks at some possible interpretations of ''confinement'' and their shortcomings and then turns to the most widely used rather pragmatic definition based on the somewhat unphysical notion of infinitely heavy external sources. He describes what is known about the problem and tries to bring into focus some aspects that are insufficiently understood in his opinion

  2. Temporal gene expression profiling reveals CEBPD as a candidate regulator of brain disease in prosaposin deficient mice

    Directory of Open Access Journals (Sweden)

    Ran Huimin

    2008-08-01

    Full Text Available Abstract Background Prosaposin encodes, in tandem, four small acidic activator proteins (saposins with specificities for glycosphingolipid (GSL hydrolases in lysosomes. Extensive GSL storage occurs in various central nervous system regions in mammalian prosaposin deficiencies. Results Our hypomorphic prosaposin deficient mouse, PS-NA, exhibited 45% WT levels of brain saposins and showed neuropathology that included neuronal GSL storage and Purkinje cell loss. Impairment of neuronal function was observed as early as 6 wks as demonstrated by the narrow bridges tests. Temporal transcriptome microarray analyses of brain tissues were conducted with mRNA from three prosaposin deficient mouse models: PS-NA, prosaposin null (PS-/- and a V394L/V394L glucocerebrosidase mutation combined with PS-NA (4L/PS-NA. Gene expression alterations in cerebrum and cerebellum were detectable at birth preceding the neuronal deficits. Differentially expressed genes encompassed a broad spectrum of cellular functions. The number of down-regulated genes was constant, but up-regulated gene numbers increased with age. CCAAT/enhancer-binding protein delta (CEBPD was the only up-regulated transcription factor in these two brain regions of all three models. Network analyses revealed that CEBPD has functional relationships with genes in transcription, pro-inflammation, cell death, binding, myelin and transport. Conclusion These results show that: 1 Regionally specific gene expression abnormalities precede the brain histological and neuronal function changes, 2 Temporal gene expression profiles provide insights into the molecular mechanism during the GSL storage disease course, and 3 CEBPD is a candidate regulator of brain disease in prosaposin deficiency to participate in modulating disease acceleration or progression.

  3. The confining trailing string

    CERN Document Server

    Kiritsis, E; Nitti, F

    2014-01-01

    We extend the holographic trailing string picture of a heavy quark to the case of a bulk geometry dual to a confining gauge theory. We compute the classical trailing confining string solution for a static as well as a uniformly moving quark. The trailing string is infinitely extended and approaches a confining horizon, situated at a critical value of the radial coordinate, along one of the space-time directions, breaking boundary rotational invariance. We compute the equations for the fluctuations around the classical solutions, which are used to obtain boundary force correlators controlling the Langevin dynamics of the quark. The imaginary part of the correlators has a non-trivial low-frequency limit, which gives rise to a viscous friction coefficient induced by the confining vacuum. The vacuum correlators are used to define finite-temperature dressed Langevin correlators with an appropriate high-frequency behavior.

  4. Solitons and confinement

    International Nuclear Information System (INIS)

    Swieca, J.A.

    1976-01-01

    Some aspects of two recent developments in quantum field theory are discussed. First, related with 'extended particles' such as soliton, kink and the 't Hooft monopole. Second, with confinement of particles which are realized in the Schwinger model [pt

  5. Confinement and the Pomeron

    International Nuclear Information System (INIS)

    White, A.R.

    1989-01-01

    The importance of confinement for obtaining a unitary high-energy limit for QCD is discussed. ''Minijets'' are argued to build up non-unitary behavior endash when k T > Λ is imposed. For minijets to mix with low k T Pomeron Field Theory describing confinement, and give consistent asymptotic behavior, new ''quarks'' must enter the theory above the minijet transverse momentum scale. The Critical Pomeron is the resulting high-energy limit. 22 refs

  6. Fusion, magnetic confinement

    International Nuclear Information System (INIS)

    Berk, H.L.

    1992-01-01

    An overview is presented of the principles of magnetic confinement of plasmas for the purpose of achieving controlled fusion conditions. Sec. 1 discusses the different nuclear fusion reactions which can be exploited in prospective fusion reactors and explains why special technologies need to be developed for the supply of tritium or 3 He, the probable fuels. In Sec. 2 the Lawson condition, a criterion that is a measure of the quality of confinement relative to achieving fusion conditions, is explained. In Sec. 3 fluid equations are used to describe plasma confinement. Specific confinement configurations are considered. In Sec. 4 the orbits of particle sin magneti and electric fields are discussed. In Sec. 5 stability considerations are discussed. It is noted that confinement systems usually need to satisfy stability constraints imposed by ideal magnetohydrodynamic (MHD) theory. The paper culminates with a summary of experimental progress in magnetic confinement. Present experiments in tokamaks have reached the point that the conditions necessary to achieve fusion are being satisfied

  7. The L1TD1 Protein Interactome Reveals the Importance of Post-transcriptional Regulation in Human Pluripotency

    Directory of Open Access Journals (Sweden)

    Maheswara Reddy Emani

    2015-03-01

    Full Text Available The RNA-binding protein L1TD1 is one of the most specific and abundant proteins in pluripotent stem cells and is essential for the maintenance of pluripotency in human cells. Here, we identify the protein interaction network of L1TD1 in human embryonic stem cells (hESCs and provide insights into the interactome network constructed in human pluripotent cells. Our data reveal that L1TD1 has an important role in RNA splicing, translation, protein traffic, and degradation. L1TD1 interacts with multiple stem-cell-specific proteins, many of which are still uncharacterized in the context of development. Further, we show that L1TD1 is a part of the pluripotency interactome network of OCT4, SOX2, and NANOG, bridging nuclear and cytoplasmic regulation and highlighting the importance of RNA biology in pluripotency.

  8. Deep RNA sequencing reveals dynamic regulation of myocardial noncoding RNAs in failing human heart and remodeling with mechanical circulatory support.

    Science.gov (United States)

    Yang, Kai-Chien; Yamada, Kathryn A; Patel, Akshar Y; Topkara, Veli K; George, Isaac; Cheema, Faisal H; Ewald, Gregory A; Mann, Douglas L; Nerbonne, Jeanne M

    2014-03-04

    Microarrays have been used extensively to profile transcriptome remodeling in failing human heart, although the genomic coverage provided is limited and fails to provide a detailed picture of the myocardial transcriptome landscape. Here, we describe sequencing-based transcriptome profiling, providing comprehensive analysis of myocardial mRNA, microRNA (miRNA), and long noncoding RNA (lncRNA) expression in failing human heart before and after mechanical support with a left ventricular (LV) assist device (LVAD). Deep sequencing of RNA isolated from paired nonischemic (NICM; n=8) and ischemic (ICM; n=8) human failing LV samples collected before and after LVAD and from nonfailing human LV (n=8) was conducted. These analyses revealed high abundance of mRNA (37%) and lncRNA (71%) of mitochondrial origin. miRNASeq revealed 160 and 147 differentially expressed miRNAs in ICM and NICM, respectively, compared with nonfailing LV. Among these, only 2 (ICM) and 5 (NICM) miRNAs are normalized with LVAD. RNASeq detected 18 480, including 113 novel, lncRNAs in human LV. Among the 679 (ICM) and 570 (NICM) lncRNAs differentially expressed with heart failure, ≈10% are improved or normalized with LVAD. In addition, the expression signature of lncRNAs, but not miRNAs or mRNAs, distinguishes ICM from NICM. Further analysis suggests that cis-gene regulation represents a major mechanism of action of human cardiac lncRNAs. The myocardial transcriptome is dynamically regulated in advanced heart failure and after LVAD support. The expression profiles of lncRNAs, but not mRNAs or miRNAs, can discriminate failing hearts of different pathologies and are markedly altered in response to LVAD support. These results suggest an important role for lncRNAs in the pathogenesis of heart failure and in reverse remodeling observed with mechanical support.

  9. Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Trey K Sato

    2016-10-01

    Full Text Available The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically. We report that rapid xylose conversion by engineered and evolved S. cerevisiae strains depends upon epistatic interactions among genes encoding a xylose reductase (GRE3, a component of MAP Kinase (MAPK signaling (HOG1, a regulator of Protein Kinase A (PKA signaling (IRA2, and a scaffolding protein for mitochondrial iron-sulfur (Fe-S cluster biogenesis (ISU1. Interestingly, the mutation in IRA2 only impacted anaerobic xylose consumption and required the loss of ISU1 function, indicating a previously unknown connection between PKA signaling, Fe-S cluster biogenesis, and anaerobiosis. Proteomic and metabolomic comparisons revealed that the xylose-metabolizing mutant strains exhibit altered metabolic pathways relative to the parental strain when grown in xylose. Further analyses revealed that interacting mutations in HOG1 and ISU1 unexpectedly elevated mitochondrial respiratory proteins and enabled rapid aerobic respiration of xylose and other non-fermentable carbon substrates. Our findings suggest a surprising connection between Fe-S cluster biogenesis and signaling that facilitates aerobic respiration and anaerobic fermentation of xylose, underscoring how much remains unknown about the eukaryotic signaling systems that regulate carbon metabolism.

  10. Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae.

    Science.gov (United States)

    Sato, Trey K; Tremaine, Mary; Parreiras, Lucas S; Hebert, Alexander S; Myers, Kevin S; Higbee, Alan J; Sardi, Maria; McIlwain, Sean J; Ong, Irene M; Breuer, Rebecca J; Avanasi Narasimhan, Ragothaman; McGee, Mick A; Dickinson, Quinn; La Reau, Alex; Xie, Dan; Tian, Mingyuan; Reed, Jennifer L; Zhang, Yaoping; Coon, Joshua J; Hittinger, Chris Todd; Gasch, Audrey P; Landick, Robert

    2016-10-01

    The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically. We report that rapid xylose conversion by engineered and evolved S. cerevisiae strains depends upon epistatic interactions among genes encoding a xylose reductase (GRE3), a component of MAP Kinase (MAPK) signaling (HOG1), a regulator of Protein Kinase A (PKA) signaling (IRA2), and a scaffolding protein for mitochondrial iron-sulfur (Fe-S) cluster biogenesis (ISU1). Interestingly, the mutation in IRA2 only impacted anaerobic xylose consumption and required the loss of ISU1 function, indicating a previously unknown connection between PKA signaling, Fe-S cluster biogenesis, and anaerobiosis. Proteomic and metabolomic comparisons revealed that the xylose-metabolizing mutant strains exhibit altered metabolic pathways relative to the parental strain when grown in xylose. Further analyses revealed that interacting mutations in HOG1 and ISU1 unexpectedly elevated mitochondrial respiratory proteins and enabled rapid aerobic respiration of xylose and other non-fermentable carbon substrates. Our findings suggest a surprising connection between Fe-S cluster biogenesis and signaling that facilitates aerobic respiration and anaerobic fermentation of xylose, underscoring how much remains unknown about the eukaryotic signaling systems that regulate carbon metabolism.

  11. A Knockout Screen of ApiAP2 Genes Reveals Networks of Interacting Transcriptional Regulators Controlling the Plasmodium Life Cycle.

    Science.gov (United States)

    Modrzynska, Katarzyna; Pfander, Claudia; Chappell, Lia; Yu, Lu; Suarez, Catherine; Dundas, Kirsten; Gomes, Ana Rita; Goulding, David; Rayner, Julian C; Choudhary, Jyoti; Billker, Oliver

    2017-01-11

    A family of apicomplexa-specific proteins containing AP2 DNA-binding domains (ApiAP2s) was identified in malaria parasites. This family includes sequence-specific transcription factors that are key regulators of development. However, functions for the majority of ApiAP2 genes remain unknown. Here, a systematic knockout screen in Plasmodium berghei identified ten ApiAP2 genes that were essential for mosquito transmission: four were critical for the formation of infectious ookinetes, and three were required for sporogony. We describe non-essential functions for AP2-O and AP2-SP proteins in blood stages, and identify AP2-G2 as a repressor active in both asexual and sexual stages. Comparative transcriptomics across mutants and developmental stages revealed clusters of co-regulated genes with shared cis promoter elements, whose expression can be controlled positively or negatively by different ApiAP2 factors. We propose that stage-specific interactions between ApiAP2 proteins on partly overlapping sets of target genes generate the complex transcriptional network that controls the Plasmodium life cycle. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes.

    Science.gov (United States)

    Abu-Remaileh, Monther; Wyant, Gregory A; Kim, Choah; Laqtom, Nouf N; Abbasi, Maria; Chan, Sze Ham; Freinkman, Elizaveta; Sabatini, David M

    2017-11-10

    The lysosome degrades and recycles macromolecules, signals to the cytosol and nucleus, and is implicated in many diseases. Here, we describe a method for the rapid isolation of mammalian lysosomes and use it to quantitatively profile lysosomal metabolites under various cell states. Under nutrient-replete conditions, many lysosomal amino acids are in rapid exchange with those in the cytosol. Loss of lysosomal acidification through inhibition of the vacuolar H + -adenosine triphosphatase (V-ATPase) increased the luminal concentrations of most metabolites but had no effect on those of the majority of essential amino acids. Instead, nutrient starvation regulates the lysosomal concentrations of these amino acids, an effect we traced to regulation of the mechanistic target of rapamycin (mTOR) pathway. Inhibition of mTOR strongly reduced the lysosomal efflux of most essential amino acids, converting the lysosome into a cellular depot for them. These results reveal the dynamic nature of lysosomal metabolites and that V-ATPase- and mTOR-dependent mechanisms exist for controlling lysosomal amino acid efflux. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  13. Proteomic analysis reveals APC-dependent post-translational modifications and identifies a novel regulator of β-catenin.

    Science.gov (United States)

    Blundon, Malachi A; Schlesinger, Danielle R; Parthasarathy, Amritha; Smith, Samantha L; Kolev, Hannah M; Vinson, David A; Kunttas-Tatli, Ezgi; McCartney, Brooke M; Minden, Jonathan S

    2016-07-15

    Wnt signaling generates patterns in all embryos, from flies to humans, and controls cell fate, proliferation and metabolic homeostasis. Inappropriate Wnt pathway activation results in diseases, including colorectal cancer. The adenomatous polyposis coli (APC) tumor suppressor gene encodes a multifunctional protein that is an essential regulator of Wnt signaling and cytoskeletal organization. Although progress has been made in defining the role of APC in a normal cellular context, there are still significant gaps in our understanding of APC-dependent cellular function and dysfunction. We expanded the APC-associated protein network using a combination of genetics and a proteomic technique called two-dimensional difference gel electrophoresis (2D-DIGE). We show that loss of Drosophila Apc2 causes protein isoform changes reflecting misregulation of post-translational modifications (PTMs), which are not dependent on β-catenin transcriptional activity. Mass spectrometry revealed that proteins involved in metabolic and biosynthetic pathways, protein synthesis and degradation, and cell signaling are affected by Apc2 loss. We demonstrate that changes in phosphorylation partially account for the altered PTMs in APC mutants, suggesting that APC mutants affect other types of PTM. Finally, through this approach Aminopeptidase P was identified as a new regulator of β-catenin abundance in Drosophila embryos. This study provides new perspectives on the cellular effects of APC that might lead to a deeper understanding of its role in development. © 2016. Published by The Company of Biologists Ltd.

  14. Mass Spectrometry Reveals Changes in MHC I Antigen Presentation After Lentivector Expression of a Gene Regulation System

    Directory of Open Access Journals (Sweden)

    Roland Vogel

    2013-01-01

    Full Text Available The rapamycin-inducible gene regulation system was designed to minimize immune reactions in man and may thus be suited for gene therapy. We assessed whether this system indeed induces no immune responses. The protein components of the regulation system were produced in the human cell lines HEK 293T, D407, and HER 911 following lentiviral transfer of the corresponding genes. Stable cell lines were established, and the peptides presented by major histocompatibility complex class I (MHC I molecules on transduced and wild-type (wt cells were compared by differential mass spectrometry. In all cell lines examined, expression of the transgenes resulted in prominent changes in the repertoire of MHC I-presented self-peptides. No MHC I ligands originating from the transgenic proteins were detected. In vitro analysis of immunogenicity revealed that transduced D407 cells displayed slightly higher capacity than wt controls to promote proliferation of cytotoxic T cells. These results indicate that therapeutic manipulations within the genome of target cells may affect pathways involved in the processing of peptide antigens and their presentation by MHC I. This makes the genomic modifications visible to the immune system which may recognize these events and respond. Ultimately, the findings call attention to a possible immune risk.

  15. Experimental and observational evidence reveals that predators in natural environments do not regulate their prey: They are passengers, not drivers

    Science.gov (United States)

    White, T. C. R.

    2013-11-01

    Among both ecologists and the wider community there is a tacit assumption that predators regulate populations of their prey. But there is evidence from a wide taxonomic and geographic range of studies that predators that are adapted to co-evolved prey generally do not regulate their prey. This is because predators either cannot reproduce as fast as their prey and/or are inefficient hunters unable to catch enough prey to sustain maximum reproduction. The greater capacity of herbivores to breed successfully is, however, normally restricted by a lack of enough food of sufficient quality to support reproduction. But whenever this shortage is alleviated by a large pulse of food, herbivores increase their numbers to outbreak levels. Their predators are unable to contain this increase, but their numbers, too, surge in response to this increase in food. Eventually both their populations will crash once the food supply runs out, first for the herbivores and then for the predators. Then an “over-run” of predators will further depress the already declining prey population, appearing to be controlling its abundance. This latter phenomenon has led many ecologists to conclude that predators are regulating the numbers of their prey. However, it is the same process that is revealed during outbreaks that limits populations of both predator and prey in “normal” times, although this is usually not readily apparent. Nevertheless, as all the diverse cases discussed here attest, the abundance of predators and their co-evolved prey are both limited by their food: the predators are passengers, not drivers.

  16. Crystal structures of the transcriptional repressor RolR reveals a novel recognition mechanism between inducer and regulator.

    Directory of Open Access Journals (Sweden)

    De-Feng Li

    Full Text Available Many members of the TetR family control the transcription of genes involved in multidrug resistance and pathogenicity. RolR (ResorcinolRegulator, the recently reported TetR-type regulator for aromatic catabolism from Corynebacterium glutamicum, distinguishes itself by low sequence similarities and different regulation from the previously known members of the TetR family. Here we report the crystal structures of RolR in its effector-bound (with resorcinol and aop- forms at 2.5 Å and 3.6 Å, respectively. The structure of resorcinol-RolR complex reveal that the hydrogen-bonded network mediated by the four-residue motif (Asp94- Arg145- Arg148- Asp149 with two water molecules and the hydrophobic interaction via five residues (Phe107, Leu111, Leu114, Leu142, and Phe172 are the key factors for the recognition and binding between the resorcinol and RolR molecules. The center-to-center separation of the recognition helices h3-h3' is decreased upon effector-binding from 34.9 Å to 30.4 Å. This structural change results in that RolR was unsuitable for DNA binding. Those observations are distinct from that in other TetR members. Structure-based mutagenesis on RolR was carried out and the results confirmed the critical roles of the above mentioned residues for effector-binding specificity and affinity. Similar sequence searches and sequence alignments identified 29 RolR homologues from GenBank, and all the above mentioned residues are highly conserved in the homologues. Based on these structural and other functional investigations, it is proposed that RolR may represent a new subfamily of TetR proteins that are invovled in aromatic degradation and sharing common recognition mode as for RolR.

  17. The MTP1 promoters from Arabidopsis halleri reveal cis-regulating elements for the evolution of metal tolerance.

    Science.gov (United States)

    Fasani, Elisa; DalCorso, Giovanni; Varotto, Claudio; Li, Mingai; Visioli, Giovanna; Mattarozzi, Monica; Furini, Antonella

    2017-06-01

    In the hyperaccumulator Arabidopsis halleri, the zinc (Zn) vacuolar transporter MTP1 is a key component of hypertolerance. Because protein sequences and functions are highly conserved between A. halleri and Arabidopsis thaliana, Zn tolerance in A. halleri may reflect the constitutively higher MTP1 expression compared with A. thaliana, based on copy number expansion and different cis regulation. Three MTP1 promoters were characterized in A. halleri ecotype I16. The comparison with the A. thaliana MTP1 promoter revealed different expression profiles correlated with specific cis-acting regulatory elements. The MTP1 5' untranslated region, highly conserved among A. thaliana, Arabidopsis lyrata and A. halleri, contains a dimer of MYB-binding motifs in the A. halleri promoters absent in the A. thaliana and A. lyrata sequences. Site-directed mutagenesis of these motifs revealed their role for expression in trichomes. A. thaliana mtp1 transgenic lines expressing AtMTP1 controlled by the native A. halleri promoter were more Zn-tolerant than lines carrying mutations on MYB-binding motifs. Differences in Zn tolerance were associated with different distribution of Zn among plant organs and in trichomes. The different cis-acting elements in the MTP1 promoters of A. halleri, particularly the MYB-binding sites, are probably involved in the evolution of Zn tolerance. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  18. Topology of polymer chains under nanoscale confinement.

    Science.gov (United States)

    Satarifard, Vahid; Heidari, Maziar; Mashaghi, Samaneh; Tans, Sander J; Ejtehadi, Mohammad Reza; Mashaghi, Alireza

    2017-08-24

    Spatial confinement limits the conformational space accessible to biomolecules but the implications for bimolecular topology are not yet known. Folded linear biopolymers can be seen as molecular circuits formed by intramolecular contacts. The pairwise arrangement of intra-chain contacts can be categorized as parallel, series or cross, and has been identified as a topological property. Using molecular dynamics simulations, we determine the contact order distributions and topological circuits of short semi-flexible linear and ring polymer chains with a persistence length of l p under a spherical confinement of radius R c . At low values of l p /R c , the entropy of the linear chain leads to the formation of independent contacts along the chain and accordingly, increases the fraction of series topology with respect to other topologies. However, at high l p /R c , the fraction of cross and parallel topologies are enhanced in the chain topological circuits with cross becoming predominant. At an intermediate confining regime, we identify a critical value of l p /R c , at which all topological states have equal probability. Confinement thus equalizes the probability of more complex cross and parallel topologies to the level of the more simple, non-cooperative series topology. Moreover, our topology analysis reveals distinct behaviours for ring- and linear polymers under weak confinement; however, we find no difference between ring- and linear polymers under strong confinement. Under weak confinement, ring polymers adopt parallel and series topologies with equal likelihood, while linear polymers show a higher tendency for series arrangement. The radial distribution analysis of the topology reveals a non-uniform effect of confinement on the topology of polymer chains, thereby imposing more pronounced effects on the core region than on the confinement surface. Additionally, our results reveal that over a wide range of confining radii, loops arranged in parallel and cross

  19. Exceptional confinement in G(2) gauge theory

    International Nuclear Information System (INIS)

    Holland, K.; Minkowski, P.; Pepe, M.; Wiese, U.-J.

    2003-01-01

    We study theories with the exceptional gauge group G(2). The 14 adjoint 'gluons' of a G(2) gauge theory transform as {3}, {3-bar} and {8} under the subgroup SU(3), and hence have the color quantum numbers of ordinary quarks, anti-quarks and gluons in QCD. Since G(2) has a trivial center, a 'quark' in the {7} representation of G(2) can be screened by 'gluons'. As a result, in G(2) Yang-Mills theory the string between a pair of static 'quarks' can break. In G(2) QCD there is a hybrid consisting of one 'quark' and three 'gluons'. In supersymmetric G(2) Yang-Mills theory with a {14} Majorana 'gluino' the chiral symmetry is Z(4) χ . Chiral symmetry breaking gives rise to distinct confined phases separated by confined-confined domain walls. A scalar Higgs field in the {7} representation breaks G(2) to SU(3) and allows us to interpolate between theories with exceptional and ordinary confinement. We also present strong coupling lattice calculations that reveal basic features of G(2) confinement. Just as in QCD, where dynamical quarks break the Z(3) symmetry explicitly, G(2) gauge theories confine even without a center. However, there is not necessarily a deconfinement phase transition at finite temperature

  20. ATR confinement leakage determination

    International Nuclear Information System (INIS)

    Kuan, P.; Buescher, B.J.

    1998-01-01

    The air leakage rate from the Advanced Test Reactor (ATR) confinement is an important parameter in estimating hypothesized accidental releases of radiation to the environment. The leakage rate must be determined periodically to assure that the confinement has not degraded with time and such determination is one of the technical safety requirements of ATR operation. This paper reviews the methods of confinement leakage determination and presents an analysis of leakage determination under windy conditions, which can complicate the interpretation of the determined leakage rates. The paper also presents results of analyses of building air exchange under windy conditions. High wind can enhance air exchange and this could increase the release rates of radioisotopes following an accident

  1. Confinement of quarks

    International Nuclear Information System (INIS)

    Nambu, J.

    1978-01-01

    Three quark models of hadron structure, which suggest an explanation of quarks confinement mechanism in hadrons are considered. Quark classifications, quark flawors and colours, symmetry model of hadron structure based on the colour theory of strong interaction are discussed. Diagrams of colour combinations of quarks and antiquarks, exchange of gluons, binding quarks in hadron. Quark confinement models based on the field theory, string model rotating and bag model are discussed. Diagrams of the colour charge distribution explaining the phenomena of infrared ''slavery'' and ultraviolet ''freedom'' are given. The models considered explain but some quark properties, creating prerequisites for the development of the consequent theory of hadron structure

  2. Revealing localization and regulation of GTPase PmRab7 in lymphoid cells of Penaeus monodon after WSSV infection

    Directory of Open Access Journals (Sweden)

    Amrendra Kumar

    2016-10-01

    Full Text Available Objective: To identify white spot syndrome virus (WSSV entry into the host-cells of the cultured shrimp Penaeus monodon, we have attempted to localize PmRab7 (Ras-related in brain which is playing a vital role in the WSSV internalization. Methods: In this study, we have cloned PmRab7 and expressed in Escherichia coli, further purified rPmRab7 was used for antibody production, isolation of lysosomal sub-cellular fractions and western blot against lysosomal protein. Moreover, high fold-change in PmRab7 regulation with increasing copy number of WSSV has been studied by using real-time PCR. Results: 651 bp amplicon size gene was successfully amplified, ligated amplicon with pTZ T-tail vector confirmed by colony PCR and retriction enzyme digestion on agarose gel. Subcloned (pRSET-B 651 bp gene transformed successfully in Rosetta and after 6 h of induction expressed rPmRab7 was on SDS page, furthermore soluble fraction of rPmRab7 (26 kDa was purified by ni-NTA column. AntiPmRab7 antibody was received by Merk Pvt. Ltd., and western blot analysis revealed that PmRab7 is present in the lysosomal sub-cellular fraction. Copy number of WSSV was increased 5 fold in 24 h and 20 fold in 72 h of infection and subsequently transcrtipt of PmRab7 was Ct = 1.0 to Ct = 8.5. Conclusions: Presence of PmRab7 on lysosome clearly indicating PmRab7 participating in lysosomal maturation, other hand WSSV may follow the same route of entry. WSSV internalization has directly linked with regulation of PmRab7.

  3. Kisspeptin Antagonists Reveal Kisspeptin 1 and Kisspeptin 2 Differential Regulation of Reproduction in the Teleost, Morone saxatilis.

    Science.gov (United States)

    Zmora, Nilli; Stubblefield, John David; Wong, Ten-Tsao; Levavi-Sivan, Berta; Millar, Robert Peter; Zohar, Yonathan

    2015-09-01

    The importance of kisspeptin in regulating vertebrate reproduction has been well established, but the exact mechanism continues to unfold. Unlike mammals, many lower vertebrates possess a dual kisspeptin system, Kiss1 and Kiss2. To decipher the roles of the kisspeptins in fish, we identified two potential kisspeptin antagonists, pep 234 and pep 359, by screening analogs for their ability to inactivate striped bass Kiss1 and Kiss2 receptors expressed in COS7 cells. Pep 234 (a mammalian KISS1 antagonist) antagonizes Kiss1r signaling activated by Kiss1 and Kiss2, and pep 359 (a novel analog) antagonizes Kiss2 activation of both receptors. In vitro studies using brain slices demonstrated that only Kiss2 can upregulate the expression of the hypophysiotropic gnrh1, which was subsequently diminished by pep 234 and pep 359. In primary pituitary cell cultures, the two antagonists revealed a complex network of putative endogenous and exogenous regulation by kisspeptin. While both kisspeptins stimulate Fsh expression and secretion, Kiss2 predominately induces Lh secretion. Pep 234 and 359 treatment of spawning males hindered sperm production. This effect was accompanied with decreased brain gnrh1 and gnrh2 mRNA levels and peptide content in the pituitary, and increased levels of pituitary Lh, probably due to attenuation of Lh release. Strikingly, the mRNA levels of arginine-vasotocin, the neurons of which in the preoptic area coexpress kiss2r, were dramatically reduced by the antagonists. Our results demonstrate differential actions of Kiss1 and Kiss2 systems along the hypothalamic-pituitary axis and interactions with other neuropeptides, and further reinforce the importance of kisspeptin in the execution of spawning. © 2015 by the Society for the Study of Reproduction, Inc.

  4. Hydrogen-Deuterium Exchange Mass Spectrometry Reveals Calcium Binding Properties and Allosteric Regulation of Downstream Regulatory Element Antagonist Modulator (DREAM).

    Science.gov (United States)

    Zhang, Jun; Li, Jing; Craig, Theodore A; Kumar, Rajiv; Gross, Michael L

    2017-07-18

    Downstream regulatory element antagonist modulator (DREAM) is an EF-hand Ca 2+ -binding protein that also binds to a specific DNA sequence, downstream regulatory elements (DRE), and thereby regulates transcription in a calcium-dependent fashion. DREAM binds to DRE in the absence of Ca 2+ but detaches from DRE under Ca 2+ stimulation, allowing gene expression. The Ca 2+ binding properties of DREAM and the consequences of the binding on protein structure are key to understanding the function of DREAM. Here we describe the application of hydrogen-deuterium exchange mass spectrometry (HDX-MS) and site-directed mutagenesis to investigate the Ca 2+ binding properties and the subsequent conformational changes of full-length DREAM. We demonstrate that all EF-hands undergo large conformation changes upon calcium binding even though the EF-1 hand is not capable of binding to Ca 2+ . Moreover, EF-2 is a lower-affinity site compared to EF-3 and -4 hands. Comparison of HDX profiles between wild-type DREAM and two EF-1 mutated constructs illustrates that the conformational changes in the EF-1 hand are induced by long-range structural interactions. HDX analyses also reveal a conformational change in an N-terminal leucine-charged residue-rich domain (LCD) remote from Ca 2+ -binding EF-hands. This LCD domain is responsible for the direct interaction between DREAM and cAMP response element-binding protein (CREB) and regulates the recruitment of the co-activator, CREB-binding protein. These long-range interactions strongly suggest how conformational changes transmit the Ca 2+ signal to CREB-mediated gene transcription.

  5. Comparative Transcriptome Analysis Reveal Candidate Genes Potentially Involved in Regulation of Primocane Apex Rooting in Raspberry (Rubus spp.).

    Science.gov (United States)

    Liu, Jianfeng; Ming, Yuetong; Cheng, Yunqing; Zhang, Yuchu; Xing, Jiyang; Sun, Yuqi

    2017-01-01

    Raspberries ( Rubus spp.) exhibit a unique rooting process that is initiated from the stem apex of primocane, conferring an unusual asexual mode of reproduction to this plant. However, the full complement of genes involved in this process has not been identified. To this end, the present study analyzed the transcriptomes of the Rubus primocane and floricane stem apex at three developmental stages by Digital Gene Expression profiling to identify genes that regulate rooting. Sequencing and de novo assembly yielded 26.82 Gb of nucleotides and 59,173 unigenes; 498, 7,346, 4,110, 7,900, 9,397, and 4,776 differently expressed genes were identified in paired comparisons of SAF1 (floricane at developmental stage 1) vs. SAP1 (primocane at developmental stage 1), SAF2 vs. SAP2, SAF3 vs. SAP3, SAP1 vs. SAP2, SAP1 vs. SAP3, and SAP2 vs. SAP3, respectively. SAP1 maintains an extension growth pattern; SAP2 then exhibits growth arrest and vertical (downward) gravitropic deflection; and finally, short roots begin to form on the apex of SAP3. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis of SAP1 vs. SAP2 revealed 12 pathways that were activated in response to shoot growth arrest and root differentiation, including circadian rhythm-plant (ko04712) and plant hormone signal transduction (ko04075). Our results indicate that genes related to circadian rhythm, ethylene and auxin signaling, shoot growth, and root development are potentially involved in the regulation of primocane apex rooting in Rubus . These findings provide a basis for elucidating the molecular mechanisms of primocane apex rooting in this economically valuable crop.

  6. Transcriptome Analysis Reveals that Red and Blue Light Regulate Growth and Phytohormone Metabolism in Norway Spruce [Picea abies (L. Karst].

    Directory of Open Access Journals (Sweden)

    Fangqun OuYang

    Full Text Available The mechanisms by which different light spectra regulate plant shoot elongation vary, and phytohormones respond differently to such spectrum-associated regulatory effects. Light supplementation can effectively control seedling growth in Norway spruce. However, knowledge of the effective spectrum for promoting growth and phytohormone metabolism in this species is lacking. In this study, 3-year-old Norway spruce clones were illuminated for 12 h after sunset under blue or red light-emitting diode (LED light for 90 d, and stem increments and other growth traits were determined. Endogenous hormone levels and transcriptome differences in the current needles were assessed to identify genes related to the red and blue light regulatory responses. The results showed that the stem increment and gibberellin (GA levels of the seedlings illuminated by red light were 8.6% and 29.0% higher, respectively, than those of the seedlings illuminated by blue light. The indoleacetic acid (IAA level of the seedlings illuminated by red light was 54.6% lower than that of the seedlings illuminated by blue light, and there were no significant differences in abscisic acid (ABA or zeatin riboside [ZR] between the two groups of seedlings. The transcriptome results revealed 58,736,166 and 60,555,192 clean reads for the blue-light- and red-light-illuminated samples, respectively. Illumina sequencing revealed 21,923 unigenes, and 2744 (approximately 93.8% out of 2926 differentially expressed genes (DEGs were found to be upregulated under blue light. The main KEGG classifications of the DEGs were metabolic pathway (29%, biosynthesis of secondary metabolites (20.49% and hormone signal transduction (8.39%. With regard to hormone signal transduction, AUXIN-RESISTANT1 (AUX1, AUX/IAA genes, auxin-inducible genes, and early auxin-responsive genes [(auxin response factor (ARF and small auxin-up RNA (SAUR] were all upregulated under blue light compared with red light, which might have

  7. Integration of lncRNA–miRNA–mRNA reveals novel insights into oviposition regulation in honey bees

    Directory of Open Access Journals (Sweden)

    Xiao Chen

    2017-10-01

    Full Text Available Background The honey bee (Apis mellifera is a highly diverse species commonly used for honey production and pollination services. The oviposition of the honey bee queen affects the development and overall performance of the colony. To investigate the ovary activation and oviposition processes on a molecular level, a genome-wide analysis of lncRNAs, miRNAs and mRNA expression in the ovaries of the queens was performed to screen for differentially expressed coding and noncoding RNAs. Further analysis identified relevant candidate genes or RNAs. Results The analysis of the RNA profiles in different oviposition phase of the queens revealed that 740 lncRNAs, 81 miRNAs and 5,481 mRNAs were differently expressed during the ovary activation; 88 lncRNAs, 13 miRNAs and 338 mRNAs were differently expressed during the oviposition inhibition process; and finally, 100 lncRNAs, four miRNAs and 497 mRNAs were differently expressed during the oviposition recovery process. In addition, functional annotation of differentially expressed RNAs revealed several pathways that are closely related to oviposition, including hippo, MAPK, notch, Wnt, mTOR, TGF-beta and FoxO signaling pathways. Furthermore, in the QTL region for ovary size, 73 differentially expressed genes and 14 differentially expressed lncRNAs were located, which are considered as candidate genes affecting ovary size and oviposition. Moreover, a core set of genes served as bridges among different miRNAs were identified through the integrated analysis of lncRNA-miRNA-mRNA network. Conclusion The observed dramatic expression changes of coding and noncoding RNAs suggest that they may play a critical role in honey bee queens’ oviposition. The identified candidate genes for oviposition activation and regulation could serve as a resource for further studies of genetic markers of oviposition in honey bees.

  8. Confinement for More Space

    DEFF Research Database (Denmark)

    Kipnusu, Wycliffe K.; Elsayed, Mohamed; Kossack, Wilhelm

    2015-01-01

    Broadband dielectric spectroscopy and positron annihilation lifetime spectroscopy are employed to study the molecular dynamics and effective free volume of 2-ethyl-1-hexanol (2E1H) in the bulk state and when confined in unidirectional nanopores with average diameters of 4, 6, and 8 nm. Enhanced α...

  9. Disorder parameter of confinement

    International Nuclear Information System (INIS)

    Nakamura, N.; Ejiri, S.; Matsubara, Y.; Suzuki, T.

    1996-01-01

    The disorder parameter of confinement-deconfinement phase transition based on the monopole action determined previously in SU(2) QCD are investigated. We construct an operator which corresponds to the order parameter defined in the abelian Higgs model. The operator shows proper behaviors as the disorder parameter in the numerical simulations of finite temperature QCD. (orig.)

  10. On confinement and duality

    Energy Technology Data Exchange (ETDEWEB)

    Strassler, M J [University of Pennsylvania, Philadelphia, PA (United States)

    2002-05-15

    Confinement in four-dimensional gauge theories is considered from several points of view. General features are discussed, and the mechanism of confinement is investigated. Dualities between field theories, and duality between field theory and string theory, are both put to use. In these lectures I have given an overview of some of the key ideas underlying confinement as a property of field theory, and now, of string theory as well. This is a tiny fraction of what field theory (and now string theory) is capable of, and we are still uncovering new features on a monthly basis. In fact, most field theories do not have confinement, for reasons entirely different from those of QCD. Many become nontrivial conformal field theories at low energy. Others become composite, weakly-coupled gauge theories. Dualities of many stripes are found everywhere. Ordinary dimensional analysis in string theory is totally wrong in the regime where it looks like weakly-coupled field theory, and ordinary dimensional analysis in field theory is totally wrong in the regime where it looks like weakly-coupled supergravity.

  11. Expression Profiling Reveals Genes Involved in the Regulation of Wool Follicle Bulb Regression and Regeneration in Sheep

    Directory of Open Access Journals (Sweden)

    Guangbin Liu

    2015-04-01

    Full Text Available Wool is an important material in textile manufacturing. In order to investigate the intrinsic factors that regulate wool follicle cycling and wool fiber properties, Illumina sequencing was performed on wool follicle bulb samples from the middle anagen, catagen and late telogen/early anagen phases. In total, 13,898 genes were identified. KRTs and KRTAPs are the most highly expressed gene families in wool follicle bulb. In addition, 438 and 203 genes were identified to be differentially expressed in wool follicle bulb samples from the middle anagen phase compared to the catagen phase and the samples from the catagen phase compared to the late telogen/early anagen phase, respectively. Finally, our data revealed that two groups of genes presenting distinct expression patterns during the phase transformation may have important roles for wool follicle bulb regression and regeneration. In conclusion, our results demonstrated the gene expression patterns in the wool follicle bulb and add new data towards an understanding of the mechanisms involved in wool fiber growth in sheep.

  12. Genetic regulation of salt stress tolerance revealed by RNA-Seq in cotton diploid wild species, Gossypium davidsonii.

    Science.gov (United States)

    Zhang, Feng; Zhu, Guozhong; Du, Lei; Shang, Xiaoguang; Cheng, Chaoze; Yang, Bing; Hu, Yan; Cai, Caiping; Guo, Wangzhen

    2016-02-03

    Cotton is an economically important crop throughout the world, and is a pioneer crop in salt stress tolerance research. Investigation of the genetic regulation of salinity tolerance will provide information for salt stress-resistant breeding. Here, we employed next-generation RNA-Seq technology to elucidate the salt-tolerant mechanisms in cotton using the diploid cotton species Gossypium davidsonii which has superior stress tolerance. A total of 4744 and 5337 differentially expressed genes (DEGs) were found to be involved in salt stress tolerance in roots and leaves, respectively. Gene function annotation elucidated salt overly sensitive (SOS) and reactive oxygen species (ROS) signaling pathways. Furthermore, we found that photosynthesis pathways and metabolism play important roles in ion homeostasis and oxidation balance. Moreover, our studies revealed that alternative splicing also contributes to salt-stress responses at the posttranscriptional level, implying its functional role in response to salinity stress. This study not only provides a valuable resource for understanding the genetic control of salt stress in cotton, but also lays a substantial foundation for the genetic improvement of crop resistance to salt stress.

  13. Genetic analysis of Chinese families reveals a novel truncation allele of the retinitis pigmentosa GTPase regulator gene

    Directory of Open Access Journals (Sweden)

    Fang Hu

    2014-10-01

    Full Text Available AIM: To make comprehensive molecular diagnosis for retinitis pigmentosa (RP patients in a consanguineous Han Chinese family using next generation sequencing based Capture-NGS screen technology. METHODS: A five-generation Han Chinese family diagnosed as non-syndromic X-linked recessive RP (XLRP was recruited, including four affected males, four obligate female carriers and eleven unaffected family members. Capture-NGS was performed using a custom designed capture panel covers 163 known retinal disease genes including 47 RP genes, followed by the validation of detected mutation using Sanger sequencing in all recruited family members. RESULTS: Capture-NGS in one affected 47-year-old male reveals a novel mutation, c.2417_2418insG:p.E806fs, in exon ORF15 of RP GTPase regulator (RPGR gene results in a frameshift change that results in a premature stop codon and a truncated protein product. The mutation was further validated in three of four affected males and two of four female carriers but not in the other unaffected family members. CONCLUSION: We have identified a novel mutation, c.2417_2418insG:p.E806fs, in a Han Chinese family with XLRP. Our findings expand the mutation spectrum of RPGR and the phenotypic spectrum of XLRP in Han Chinese families, and confirms Capture-NGS could be an effective and economic approach for the comprehensive molecular diagnosis of RP.

  14. Exoproteome Analysis of the Seaweed Pathogen Nautella italica R11 Reveals Temperature-Dependent Regulation of RTX-Like Proteins

    Directory of Open Access Journals (Sweden)

    Melissa Gardiner

    2017-06-01

    Full Text Available Climate fluctuations have been linked to an increased prevalence of disease in seaweeds, including the red alga Delisea pulchra, which is susceptible to a bleaching disease caused by the bacterium Nautella italica R11 under elevated seawater temperatures. To further investigate the role of temperature in the induction of disease by N. italica R11, we assessed the effect of temperature on the expression of the extracellular proteome (exoproteome in this bacterium. Label-free quantitative mass spectrometry was used to identify 207 proteins secreted into supernatant fraction, which is equivalent to 5% of the protein coding genes in the N. italica R11 genome. Comparative analysis demonstrated that expression of over 30% of the N. italica R11 exoproteome is affected by temperature. The temperature-dependent proteins include traits that could facilitate the ATP-dependent transport of amino acid and carbohydrate, as well as several uncharacterized proteins. Further, potential virulence determinants, including two RTX-like proteins, exhibited significantly higher expression in the exoproteome at the disease inducing temperature of 24°C relative to non-inducing temperature (16°C. This is the first study to demonstrate that temperature has an influence exoproteome expression in a macroalgal pathogen. The results have revealed several temperature regulated candidate virulence factors that may have a role in macroalgal colonization and invasion at elevated sea-surface temperatures, including novel RTX-like proteins.

  15. Super-resolution microscopy reveals the insulin-resistance-regulated reorganization of GLUT4 on plasma membranes.

    Science.gov (United States)

    Gao, Lan; Chen, Junling; Gao, Jing; Wang, Hongda; Xiong, Wenyong

    2017-01-15

    GLUT4 (also known as SLC2A4) is essential for glucose uptake in skeletal muscles and adipocytes, which play central roles in whole-body glucose metabolism. Here, using direct stochastic optical reconstruction microscopy (dSTORM) to investigate the characteristics of plasma-membrane-fused GLUT4 at the single-molecule level, we have demonstrated that insulin and insulin resistance regulate the spatial organization of GLUT4 in adipocytes. Stimulation with insulin shifted the balance of GLUT4 on the plasma membrane toward a more dispersed configuration. In contrast, insulin resistance induced a more clustered distribution of GLUT4 and increased the mean number of molecules per cluster. Furthermore, our data demonstrate that the F 5 QQI motif and lipid rafts mediate the maintenance of GLUT4 clusters on the plasma membrane. Mutation of F 5 QQI (F 5 QQA-GLUT4) induced a more clustered distribution of GLUT4; moreover, destruction of lipid rafts in adipocytes expressing F 5 QQA-GLUT4 dramatically decreased the percentage of large clusters and the mean number of molecules per cluster. In conclusion, our data clarify the effects of insulin stimulation or insulin resistance on GLUT4 reorganization on the plasma membrane and reveal new pathogenic mechanisms of insulin resistance. © 2017. Published by The Company of Biologists Ltd.

  16. Holographic repulsion and confinement in gauge theory

    Science.gov (United States)

    Husain, Viqar; Kothawala, Dawood

    2013-02-01

    We show that for asymptotically anti-de Sitter (AdS) backgrounds with negative energy, such as the AdS soliton and regulated negative-mass AdS-Schwarzshild metrics, the Wilson loop expectation value in the AdS/CFT conjecture exhibits a Coulomb to confinement transition. We also show that the quark-antiquark (q \\bar{q}) potential can be interpreted as affine time along null geodesics on the minimal string worldsheet and that its intrinsic curvature provides a signature of transition to confinement phase. Our results suggest a generic (holographic) relationship between confinement in gauge theory and repulsive gravity, which in turn is connected with singularity avoidance in quantum gravity. Communicated by P R L V Moniz

  17. Chlamydia trachomatis In Vivo to In Vitro Transition Reveals Mechanisms of Phase Variation and Down-Regulation of Virulence Factors.

    Directory of Open Access Journals (Sweden)

    Vítor Borges

    Full Text Available Research on the obligate intracellular bacterium Chlamydia trachomatis demands culture in cell-lines, but the adaptive process behind the in vivo to in vitro transition is not understood. We assessed the genomic and transcriptomic dynamics underlying C. trachomatis in vitro adaptation of strains representing the three disease groups (ocular, epithelial-genital and lymphogranuloma venereum propagated in epithelial cells over multiple passages. We found genetic features potentially underlying phase variation mechanisms mediating the regulation of a lipid A biosynthesis enzyme (CT533/LpxC, and the functionality of the cytotoxin (CT166 through an ON/OFF mechanism. We detected inactivating mutations in CT713/porB, a scenario suggesting metabolic adaptation to the available carbon source. CT135 was inactivated in a tropism-specific manner, with CT135-negative clones emerging for all epithelial-genital populations (but not for LGV and ocular populations and rapidly increasing in frequency (~23% mutants per 10 passages. RNA-sequencing analyses revealed that a deletion event involving CT135 impacted the expression of multiple virulence factors, namely effectors known to play a role in the C. trachomatis host-cell invasion or subversion (e.g., CT456/Tarp, CT694, CT875/TepP and CT868/ChlaDub1. This reflects a scenario of attenuation of C. trachomatis virulence in vitro, which may take place independently or in a cumulative fashion with the also observed down-regulation of plasmid-related virulence factors. This issue may be relevant on behalf of the recent advances in Chlamydia mutagenesis and transformation where culture propagation for selecting mutants/transformants is mandatory. Finally, there was an increase in the growth rate for all strains, reflecting gradual fitness enhancement over time. In general, these data shed light on the adaptive process underlying the C. trachomatis in vivo to in vitro transition, and indicates that it would be prudent to

  18. High performance mass spectrometry based proteomics reveals enzyme and signaling pathway regulation in neutrophils during the early stage of surgical trauma

    DEFF Research Database (Denmark)

    Arshid, Samina; Tahir, Muhammad; Fontes, Belchor

    2017-01-01

    and surgical trauma rats in this study. Extracted proteins were analyzed using nano liquid chromatography coupled to tandem mass spectrometry. A total of 2924 rat neutrophil proteins were identified in our analysis, of which 393 were found differentially regulated between control and trauma groups. By using...... functional pathways analysis of the 190 proteins up-regulated in surgical trauma we found proteins related to transcription initiation and protein biosynthesis. On the other hand, among the 203 proteins down-regulated in surgical trauma we found enrichment for proteins of the immune response, proteasome...... degradation and actin cytoskeleton. Overall, enzyme prediction analysis revealed that regulated enzymes are directly involved in neutrophil apoptosis, directional migration and chemotaxis. Our observations were then confirmed by in silico protein-protein interaction analysis. Collectively, our results reveal...

  19. Systems genomics study reveals expression quantitative trait loci, regulator genes and pathways associated with boar taint in pigs.

    Directory of Open Access Journals (Sweden)

    Markus Drag

    Full Text Available Boar taint is an offensive odour and/or taste from a proportion of non-castrated male pigs caused by skatole and androstenone accumulation during sexual maturity. Castration is widely used to avoid boar taint but is currently under debate because of animal welfare concerns. This study aimed to identify expression quantitative trait loci (eQTLs with potential effects on boar taint compounds to improve breeding possibilities for reduced boar taint. Danish Landrace male boars with low, medium and high genetic merit for skatole and human nose score (HNS were slaughtered at ~100 kg. Gene expression profiles were obtained by RNA-Seq, and genotype data were obtained by an Illumina 60K Porcine SNP chip. Following quality control and filtering, 10,545 and 12,731 genes from liver and testis were included in the eQTL analysis, together with 20,827 SNP variants. A total of 205 and 109 single-tissue eQTLs associated with 102 and 58 unique genes were identified in liver and testis, respectively. By employing a multivariate Bayesian hierarchical model, 26 eQTLs were identified as significant multi-tissue eQTLs. The highest densities of eQTLs were found on pig chromosomes SSC12, SSC1, SSC13, SSC9 and SSC14. Functional characterisation of eQTLs revealed functions within regulation of androgen and the intracellular steroid hormone receptor signalling pathway and of xenobiotic metabolism by cytochrome P450 system and cellular response to oestradiol. A QTL enrichment test revealed 89 QTL traits curated by the Animal Genome PigQTL database to be significantly overlapped by the genomic coordinates of cis-acting eQTLs. Finally, a subset of 35 cis-acting eQTLs overlapped with known boar taint QTL traits. These eQTLs could be useful in the development of a DNA test for boar taint but careful monitoring of other overlapping QTL traits should be performed to avoid any negative consequences of selection.

  20. Phase transitions and quark confinement

    International Nuclear Information System (INIS)

    Polyakov, A.M.; Gava, E.

    1978-02-01

    The publication collects six lectures on the following themes: quantum field theory and classical statistical mechanics, continuous symmetries, lattice gauge theories, the nature of confinement, a criterion for confinement and non-abelian Yang-Mills theories

  1. Transcriptomic analysis reveals ethylene as stimulator and auxin as regulator of adventitious root formation in petunia cuttings

    Science.gov (United States)

    Druege, Uwe; Franken, Philipp; Lischewski, Sandra; Ahkami, Amir H.; Zerche, Siegfried; Hause, Bettina; Hajirezaei, Mohammad R.

    2014-01-01

    Adventitious root (AR) formation in the stem base (SB) of cuttings is the basis for propagation of many plant species and petunia is used as model to study this developmental process. Following AR formation from 2 to 192 hours post-excision (hpe) of cuttings, transcriptome analysis by microarray revealed a change of the character of the rooting zone from SB to root identity. The greatest shift in the number of differentially expressed genes was observed between 24 and 72 hpe, when the categories storage, mineral nutrient acquisition, anti-oxidative and secondary metabolism, and biotic stimuli showed a notable high number of induced genes. Analyses of phytohormone-related genes disclosed multifaceted changes of the auxin transport system, auxin conjugation and the auxin signal perception machinery indicating a reduction in auxin sensitivity and phase-specific responses of particular auxin-regulated genes. Genes involved in ethylene biosynthesis and action showed a more uniform pattern as a high number of respective genes were generally induced during the whole process of AR formation. The important role of ethylene for stimulating AR formation was demonstrated by the application of inhibitors of ethylene biosynthesis and perception as well as of the precursor aminocyclopropane-1-carboxylic acid, all changing the number and length of AR. A model is proposed showing the putative role of polar auxin transport and resulting auxin accumulation in initiation of subsequent changes in auxin homeostasis and signal perception with a particular role of Aux/IAA expression. These changes might in turn guide the entrance into the different phases of AR formation. Ethylene biosynthesis, which is stimulated by wounding and does probably also respond to other stresses and auxin, acts as important stimulator of AR formation probably via the expression of ethylene responsive transcription factor genes, whereas the timing of different phases seems to be controlled by auxin. PMID

  2. Structure-guided investigation of lipopolysaccharide O-antigen chain length regulators reveals regions critical for modal length control.

    Science.gov (United States)

    Kalynych, Sergei; Ruan, Xiang; Valvano, Miguel A; Cygler, Miroslaw

    2011-08-01

    The O-antigen component of the lipopolysaccharide (LPS) represents a population of polysaccharide molecules with nonrandom (modal) chain length distribution. The number of the repeat O units in each individual O-antigen polymer depends on the Wzz chain length regulator, an inner membrane protein belonging to the polysaccharide copolymerase (PCP) family. Different Wzz proteins confer vastly different ranges of modal lengths (4 to >100 repeat units), despite having remarkably conserved structural folds. The molecular mechanism responsible for the selective preference for a certain number of O units is unknown. Guided by the three-dimensional structures of PCPs, we constructed a panel of chimeric molecules containing parts of two closely related Wzz proteins from Salmonella enterica and Shigella flexneri which confer different O-antigen chain length distributions. Analysis of the O-antigen length distribution imparted by each chimera revealed the region spanning amino acids 67 to 95 (region 67 to 95), region 200 to 255, and region 269 to 274 as primarily affecting the length distribution. We also showed that there is no synergy between these regions. In particular, region 269 to 274 also influenced chain length distribution mediated by two distantly related PCPs, WzzB and FepE. Furthermore, from the 3 regions uncovered in this study, region 269 to 274 appeared to be critical for the stability of the oligomeric form of Wzz, as determined by cross-linking experiments. Together, our data suggest that chain length determination depends on regions that likely contribute to stabilize a supramolecular complex.

  3. Transcriptomic analysis reveals ethylene as stimulator and auxin as regulator of adventitious root formation in petunia cuttings.

    Science.gov (United States)

    Druege, Uwe; Franken, Philipp; Lischewski, Sandra; Ahkami, Amir H; Zerche, Siegfried; Hause, Bettina; Hajirezaei, Mohammad R

    2014-01-01

    Adventitious root (AR) formation in the stem base (SB) of cuttings is the basis for propagation of many plant species and petunia is used as model to study this developmental process. Following AR formation from 2 to 192 hours post-excision (hpe) of cuttings, transcriptome analysis by microarray revealed a change of the character of the rooting zone from SB to root identity. The greatest shift in the number of differentially expressed genes was observed between 24 and 72 hpe, when the categories storage, mineral nutrient acquisition, anti-oxidative and secondary metabolism, and biotic stimuli showed a notable high number of induced genes. Analyses of phytohormone-related genes disclosed multifaceted changes of the auxin transport system, auxin conjugation and the auxin signal perception machinery indicating a reduction in auxin sensitivity and phase-specific responses of particular auxin-regulated genes. Genes involved in ethylene biosynthesis and action showed a more uniform pattern as a high number of respective genes were generally induced during the whole process of AR formation. The important role of ethylene for stimulating AR formation was demonstrated by the application of inhibitors of ethylene biosynthesis and perception as well as of the precursor aminocyclopropane-1-carboxylic acid, all changing the number and length of AR. A model is proposed showing the putative role of polar auxin transport and resulting auxin accumulation in initiation of subsequent changes in auxin homeostasis and signal perception with a particular role of Aux/IAA expression. These changes might in turn guide the entrance into the different phases of AR formation. Ethylene biosynthesis, which is stimulated by wounding and does probably also respond to other stresses and auxin, acts as important stimulator of AR formation probably via the expression of ethylene responsive transcription factor genes, whereas the timing of different phases seems to be controlled by auxin.

  4. Transcriptomic analysis reveals ethylene as stimulator and auxin as regulator of adventitious root formation in petunia cuttings

    Directory of Open Access Journals (Sweden)

    Uwe eDruege

    2014-09-01

    Full Text Available Adventitious root (AR formation in the stem base of cuttings is the basis for propagation of many plant species and petunia is used as model to study this developmental process. Following AR formation from 2 to 192 hours after excision (hpe of cuttings, transcriptome analysis by microarray revealed a change of the character of the rooting zone from stem base to root identity. The greatest shift in the number of differentially expressed genes was observed between 24 and 72 hpe, when the categories storage, mineral nutrient acquisition, anti-oxidative and secondary metabolism, and biotic stimuli showed a notable high number of induced genes. Analyses of phytohormone-related genes disclosed multifaceted changes of the auxin transport system, auxin conjugation and the auxin signal perception machinery indicating a reduction in auxin sensitivity and phase-specific responses of particular auxin-regulated genes. Genes involved in ethylene biosynthesis and action showed a more uniform pattern as a high number of respective genes were generally induced during the whole process of AR formation. The important role of ethylene for stimulating AR formation was demonstrated by the application of inhibitors of ethylene biosynthesis and perception as well as of the precursor aminocyclopropane-1-carboxylic acid, all changing the number and length of AR. A model is proposed showing the putative role of polar auxin transport and resulting auxin accumulation in initiation of subsequent changes in auxin homeostasis and signal perception with a particular role of Aux/IAA expression. These changes might in turn guide the entrance into the different phases of AR formation. Ethylene biosynthesis, which is stimulated by wounding and does probably also respond to other stresses and auxin, acts as important stimulator of AR formation probably via the expression of ethylene responsive transcription factor genes, whereas the timing of different phases seems to be controlled

  5. Qualitative quark confinement

    International Nuclear Information System (INIS)

    Jackson, T.L.

    1976-01-01

    The infrared limit in asymptotically free non-abelian gauge theories using recently developed non-perturbative methods which allow derivation of zero momentum theorems for Green's functions and vertices is described. These low-energy theorems are compared to the infrared behavior predicted from the renormalization group equation when the existence of an infrared fixed point is assumed. A set of objects is exhibited whose low energy theorems violate the scaling behavior predicted by the renormalization group. This shows that the assumed fixed point cannot exist and that in the Landau gauge the effective charge becomes infinite in the infrared. Qualitatively this implies that as an attempt is made to separate elementary quanta the interaction between the quanta becomes arbitrarily strong. This indicates at least that the theories studied are capable of color confinement. Results are true only for theories with large numbers of quarks. This opens the possibility that large numbers of quarks are actually necessary for confinement

  6. Topological confinement and superconductivity

    Energy Technology Data Exchange (ETDEWEB)

    Al-hassanieh, Dhaled A [Los Alamos National Laboratory; Batista, Cristian D [Los Alamos National Laboratory

    2008-01-01

    We derive a Kondo Lattice model with a correlated conduction band from a two-band Hubbard Hamiltonian. This mapping allows us to describe the emergence of a robust pairing mechanism in a model that only contains repulsive interactions. The mechanism is due to topological confinement and results from the interplay between antiferromagnetism and delocalization. By using Density-Matrix-Renormalization-Group (DMRG) we demonstrate that this mechanism leads to dominant superconducting correlations in aID-system.

  7. Innovative confinement concepts workshop

    International Nuclear Information System (INIS)

    Kirkpatrick, R.C.

    1998-01-01

    The Innovative Confinement Concepts Workshop occurred in California during the week preceding the Second Symposium on Current Trends in International Fusion Research. An informal report was made to the Second Symposium. A summary of the Workshop concluded that some very promising ideas were presented, that innovative concept development is a central element of the restructured US DOE. Fusion Energy Sciences program, and that the Workshop should promote real scientific progress in fusion

  8. Confined exciton spectroscopy

    International Nuclear Information System (INIS)

    Torres, Clivia M.S.

    1998-01-01

    Full text: In this work, the exciton is considered as a sensor of the electronic and optical properties of materials such as semiconductors, which have size compared to the exciton De Broglie wavelength, approximately 20 nm, depending on the semiconductor. Examples of electron-phonon, electron-electron, photon-electron, exciton-polariton, phonon-plasmon, are presented, under different confinement conditions such as quantum wells, superlattices

  9. Helical Confinement Concepts

    Energy Technology Data Exchange (ETDEWEB)

    Beidler, C; Brakel, R; Burhenn, R; Dinklage, A; Erckmann, V; Feng, Y; Geiger, J; Hartmann, D; Hirsch, M; Jaenicke, R; Koenig, R; Laqua, H P; Maassberg, H; Wagner, F; Weller, A; Wobig, H [Max-Planck Institut fuer Plasmaphysik, EURATOM Association, Greifswald (Germany)

    2012-09-15

    Stellarators, conceived 1951 by Lyman Spitzer in Princeton, are toroidal devices that confine a plasma in a magnetic field which originates from currents in coils outside the plasma. A plasma current driven by external means, for example by an ohmic transformer, is not required for confinement. Supplying the desired poloidal field component by external coils leads to a helically structured plasma topology. Thus stellarators - or helical confinement devices - are fully three-dimensional in contrast to the toroidal (rotational) symmetry of tokamaks. As stellarators can be free of an inductive current, whose radial distribution depends on the plasma parameters, their equilibrium must not be established via the evolving plasma itself, but to a first order already given by the vacuum magnetic field. They do not need an active control (like positional feedback) and therefore cannot suffer from its failure. The outstanding conceptual advantage of stellarators is the potential of steady state plasma operation without current drive. As there is no need for current drive, the recirculating power is expected to be smaller than in equivalent tokamaks. The lack of a net current avoids current driven instabilities; specifically, no disruptions, no resistive wall modes and no conventional or neoclassical tearing modes appear. Second order pressure-driven currents (Pfirsch-Schlueter, bootstrap) exist but they can be modified and even minimized by the magnetic design. The magnetic configuration of helical devices naturally possesses a separatrix, which allows the implementation of a helically structured divertor for exhaust and impurity control. (author)

  10. Pattern replication by confined dewetting

    NARCIS (Netherlands)

    Harkema, S.; Schäffer, E.; Morariu, M.D.; Steiner, U

    2003-01-01

    The dewetting of a polymer film in a confined geometry was employed in a pattern-replication process. The instability of dewetting films is pinned by a structured confining surface, thereby replicating its topographic pattern. Depending on the surface energy of the confining surface, two different

  11. Differential RNA-seq, Multi-Network Analysis and Metabolic Regulation Analysis of Kluyveromyces marxianus Reveals a Compartmentalised Response to Xylose.

    Directory of Open Access Journals (Sweden)

    Du Toit W P Schabort

    Full Text Available We investigated the transcriptomic response of a new strain of the yeast Kluyveromyces marxianus, in glucose and xylose media using RNA-seq. The data were explored in a number of innovative ways using a variety of networks types, pathway maps, enrichment statistics, reporter metabolites and a flux simulation model, revealing different aspects of the genome-scale response in an integrative systems biology manner. The importance of the subcellular localisation in the transcriptomic response is emphasised here, revealing new insights. As was previously reported by others using a rich medium, we show that peroxisomal fatty acid catabolism was dramatically up-regulated in a defined xylose mineral medium without fatty acids, along with mechanisms to activate fatty acids and transfer products of β-oxidation to the mitochondria. Notably, we observed a strong up-regulation of the 2-methylcitrate pathway, supporting capacity for odd-chain fatty acid catabolism. Next we asked which pathways would respond to the additional requirement for NADPH for xylose utilisation, and rationalised the unexpected results using simulations with Flux Balance Analysis. On a fundamental level, we investigated the contribution of the hierarchical and metabolic regulation levels to the regulation of metabolic fluxes. Metabolic regulation analysis suggested that genetic level regulation plays a major role in regulating metabolic fluxes in adaptation to xylose, even for the high capacity reactions, which is unexpected. In addition, isozyme switching may play an important role in re-routing of metabolic fluxes in subcellular compartments in K. marxianus.

  12. Characterization of VuMATE1 expression in response to iron nutrition and aluminum stress reveals adaptation of rice bean (Vigna umbellata to acid soils through cis regulation

    Directory of Open Access Journals (Sweden)

    Meiya eLiu

    2016-04-01

    Full Text Available Rice bean (Vigna umbellata VuMATE1 appears to be constitutively expressed at vascular system but root apex, and Al stress extends its expression to root apex. Whether VuMATE1 participates in both Al tolerance and Fe nutrition, and how VuMATE1 expression is regulated is of great interest. In this study, the role of VuMATE1 in Fe nutrition was characterized through in planta complementation assays. The transcriptional regulation of VuMATE1 was investigated through promoter analysis and promoter-GUS reporter assays. The results showed that the expression of VuMATE1 was regulated by Al stress but not Fe status. Complementation of frd3-1 with VuMATE1 under VuMATE1 promoter could not restore phenotype, but restored with 35SCaMV promoter. Immunostaining of VuMATE1 revealed abnormal localization of VuMATE1 in vasculature. In planta GUS reporter assay identified Al-responsive cis-acting elements resided between -1228 and -574 bp. Promoter analysis revealed several cis-acting elements, but transcription is not simply regulated by one of these elements. We demonstrated that cis regulation of VuMATE1 expression is involved in Al tolerance mechanism, while not involved in Fe nutrition. These results reveal the evolution of VuMATE1 expression for better adaptation of rice bean to acidic soils where Al stress imposed but Fe deficiency pressure released.

  13. Transcriptome analysis of temporal regulation of carbon metabolism by CcpA in Bacillus subtilis reveals additional target genes

    NARCIS (Netherlands)

    Lulko, Andrzej T.; Buist, Girbe; Kok, Jan; Kuipers, Oscar P.

    2007-01-01

    The pleiotropic regulator of carbon metabolism in Grampositive bacteria, CcpA, regulates gene expression by binding to so-called cre elements, which are located either upstream or in promoter regions, or in open-reading frames. In this study we compared the transcriptomes of Bacillus subtilis 168

  14. Mechanistic studies of anticancer aptamer AS1411 reveal a novel role for nucleolin in regulating Rac1 activation.

    Science.gov (United States)

    Reyes-Reyes, E Merit; Šalipur, Francesca R; Shams, Mitra; Forsthoefel, Matthew K; Bates, Paula J

    2015-08-01

    AS1411 is a G-rich quadruplex-forming oligodeoxynucleotide that binds specifically to nucleolin, a protein found on the surface and in the cytoplasm of most malignant cells but absent from the surface/cytoplasm of most normal cells. AS1411 has shown promising clinical activity and is being widely used as a tumor-targeting agent, but its mechanism of action is not fully understood. Previously, we showed that AS1411 is taken up in cancer cells by macropinocytosis (fluid phase endocytosis) and subsequently stimulates further macropinocytosis by a nucleolin-dependent mechanism. In the current study, we have investigated the significance and molecular mechanisms of AS1411-induced macropinocytosis. Our results indicate that the antiproliferative activity of AS1411 in various cell lines correlated with its capacity to stimulate macropinocytosis. In DU145 prostate cancer cells, AS1411 induced activation of EGFR, Akt, p38, and Rac1. Activation of Akt and p38 were not critical for AS1411 activity because Akt activation was not observed in all AS1411-responsive cell lines and knockdown of p38 had no effect on AS1411's ability to inhibit proliferation. On the other hand, activation of EGFR and Rac1 appeared to play a role in AS1411 activity in all cancer cell lines examined (DU145, MDA-MB-468, A549, LNCaP) and their inhibition significantly reduced AS1411-mediated macropinocytosis and AS1411 antiproliferative activity. Interestingly, downregulation of nucleolin expression by siRNA also produced a substantial increase in activated Rac1, revealing a previously unknown role for nucleolin as a negative regulator of Rac1 activation. Our results are consistent with a model whereby AS1411 binding to nucleolin leads to sustained activation of Rac1 and causes methuosis, a novel type of nonapoptotic cell death characterized by hyperstimulation of macropinocytosis. We speculate that methuosis is a tumor/metastasis suppressor mechanism that opposes the malignant functions of Rac1 and that

  15. Inertial confinement fusion (ICF)

    International Nuclear Information System (INIS)

    Nuckolls, J.

    1977-01-01

    The principal goal of the inertial confinement fusion program is the development of a practical fusion power plant in this century. Rapid progress has been made in the four major areas of ICF--targets, drivers, fusion experiments, and reactors. High gain targets have been designed. Laser, electron beam, and heavy ion accelerator drivers appear to be feasible. Record-breaking thermonuclear conditions have been experimentally achieved. Detailed diagnostics of laser implosions have confirmed predictions of the LASNEX computer program. Experimental facilities are being planned and constructed capable of igniting high gain fusion microexplosions in the mid 1980's. A low cost long lifetime reactor design has been developed

  16. Confinement and 4-manifolds

    CERN Multimedia

    CERN. Geneva

    2014-01-01

    In this talk I will survey a connection between two very challenging problems, one in physics and one in math. The physics problem involves quantitative understanding of confinement in a system with least amount of supersymmetry that has been studied so far and that has a wide range of applications, from semi-realistic string models to qualitatively new examples of gauge-gravity duality. Surprisingly, the rich physics of this system translates into incredibly rich mathematics of the only remaining unsolved case of the Poincare conjecture.

  17. Hadrosynthesis and Quark Confinement

    Directory of Open Access Journals (Sweden)

    Satz Helmut

    2014-04-01

    Full Text Available Multihadron production in high energy collisions, from e+e− annihilation to heavy ion interactions, shows remarkable thermal behaviour, specified by a universal “Hagedorn” temperature. We argue that this hadronic radiation is formed by tunnelling through the event horizon of colour confinement, i.e., that it is the QCD counterpart of Hawking-Unruh radiation from black holes. It is shown to be emitted at a universal temperature TH ≃ (σ/2π1/2, where σ denotes the string tension. Since the event horizon does not allow information transfer, the radiation is thermal “at birth”.

  18. Minimal quantization and confinement

    International Nuclear Information System (INIS)

    Ilieva, N.P.; Kalinowskij, Yu.L.; Nguyen Suan Han; Pervushin, V.N.

    1987-01-01

    A ''minimal'' version of the Hamiltonian quantization based on the explicit solution of the Gauss equation and on the gauge-invariance principle is considered. By the example of the one-particle Green function we show that the requirement for gauge invariance leads to relativistic covariance of the theory and to more proper definition of the Faddeev - Popov integral that does not depend on the gauge choice. The ''minimal'' quantization is applied to consider the gauge-ambiguity problem and a new topological mechanism of confinement

  19. Small RNA-Seq analysis reveals microRNA-regulation of the Imd pathway during Escherichia coli infection in Drosophila.

    Science.gov (United States)

    Li, Shengjie; Shen, Li; Sun, Lianjie; Xu, Jiao; Jin, Ping; Chen, Liming; Ma, Fei

    2017-05-01

    Drosophila have served as a model for research on innate immunity for decades. However, knowledge of the post-transcriptional regulation of immune gene expression by microRNAs (miRNAs) remains rudimentary. In the present study, using small RNA-seq and bioinformatics analysis, we identified 67 differentially expressed miRNAs in Drosophila infected with Escherichia coli compared to injured flies at three time-points. Furthermore, we found that 21 of these miRNAs were potentially involved in the regulation of Imd pathway-related genes. Strikingly, based on UAS-miRNAs line screening and Dual-luciferase assay, we identified that miR-9a and miR-981 could both negatively regulate Drosophila antibacterial defenses and decrease the level of the antibacterial peptide, Diptericin. Taken together, these data support the involvement of miRNAs in the regulation of the Drosophila Imd pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Greater-confinement disposal

    International Nuclear Information System (INIS)

    Trevorrow, L.E.; Schubert, J.P.

    1989-01-01

    Greater-confinement disposal (GCD) is a general term for low-level waste (LLW) disposal technologies that employ natural and/or engineered barriers and provide a degree of confinement greater than that of shallow-land burial (SLB) but possibly less than that of a geologic repository. Thus GCD is associated with lower risk/hazard ratios than SLB. Although any number of disposal technologies might satisfy the definition of GCD, eight have been selected for consideration in this discussion. These technologies include: (1) earth-covered tumuli, (2) concrete structures, both above and below grade, (3) deep trenches, (4) augered shafts, (5) rock cavities, (6) abandoned mines, (7) high-integrity containers, and (8) hydrofracture. Each of these technologies employ several operations that are mature,however, some are at more advanced stages of development and demonstration than others. Each is defined and further described by information on design, advantages and disadvantages, special equipment requirements, and characteristic operations such as construction, waste emplacement, and closure

  1. A combination of genomic approaches reveals the role of FOXO1a in regulating an oxidative stress response pathway.

    Directory of Open Access Journals (Sweden)

    Paola de Candia

    2008-02-01

    Full Text Available While many of the phenotypic differences between human and chimpanzee may result from changes in gene regulation, only a handful of functionally important regulatory differences are currently known. As a first step towards identifying transcriptional pathways that have been remodeled in the human lineage, we focused on a transcription factor, FOXO1a, which we had previously found to be up-regulated in the human liver compared to that of three other primate species. We concentrated on this gene because of its known role in the regulation of metabolism and in longevity.Using a combination of expression profiling following siRNA knockdown and chromatin immunoprecipitation in a human liver cell line, we identified eight novel direct transcriptional targets of FOXO1a. This set includes the gene for thioredoxin-interacting protein (TXNIP, the expression of which is directly repressed by FOXO1a. The thioredoxin-interacting protein is known to inhibit the reducing activity of thioredoxin (TRX, thereby hindering the cellular response to oxidative stress and affecting life span.Our results provide an explanation for the repeated observations that differences in the regulation of FOXO transcription factors affect longevity. Moreover, we found that TXNIP is down-regulated in human compared to chimpanzee, consistent with the up-regulation of its direct repressor FOXO1a in humans, and with differences in longevity between the two species.

  2. Iron homeostasis in Arabidopsis thaliana: transcriptomic analyses reveal novel FIT-regulated genes, iron deficiency marker genes and functional gene networks.

    Science.gov (United States)

    Mai, Hans-Jörg; Pateyron, Stéphanie; Bauer, Petra

    2016-10-03

    FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes. 448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT-regulated in root and seedling samples and included 13 novel FIT-dependent genes. Three hundred thirty-one genes showed differential regulation in response to the presence and absence of FIT only in the root samples, while this was the case for 83 genes in the seedling samples. We assembled a virtual dataset of iron-regulated genes based on a total of 14 transcriptomic analyses of iron-deficient and iron-sufficient wild-type plants to pinpoint the best marker genes for iron deficiency and analyzed this dataset in depth. Co-expression analysis of this dataset revealed 13 distinct regulons part of which predominantly contained functionally related genes. We could enlarge the list of FIT-dependent genes and discriminate between genes that are robustly FIT-regulated in roots and seedlings or only in one of those. FIT-regulated genes were mostly induced, few of them were repressed by FIT. With the analysis of a virtual dataset we could filter out and pinpoint new candidates among the most reliable marker genes for iron deficiency. Moreover, co-expression and functional analysis of this virtual dataset revealed iron deficiency-induced and functionally distinct regulons.

  3. Transcriptomic analysis reveals the roles of gibberellin-regulated genes and transcription factors in regulating bolting in lettuce (Lactuca sativa L.).

    Science.gov (United States)

    Liu, Xueying; Lv, Shanshan; Liu, Ran; Fan, Shuangxi; Liu, Chaojie; Liu, Renyi; Han, Yingyan

    2018-01-01

    A cool temperature is preferred for lettuce cultivation, as high temperatures cause premature bolting. Accordingly, exploring the mechanism of bolting and preventing premature bolting is important for agriculture. To explore this relationship in depth, morphological, physiological, and transcriptomic analyses of the bolting-sensitive line S39 at the five-leaf stage grown at 37°C were performed in the present study. Based on paraffin section results, we observed that S39 began bolting on the seventh day at 37°C. During bolting in the heat-treated plants, GA3 and GA4 levels in leaves and the indoleacetic acid (IAA) level in the stem reached a maximum on the sixth day, and these high contents were maintained. Additionally, bolting begins in the fifth day after GA3 treatment in S39 plants, GA3 and GA4 increased and then decreased, reaching a maximum on the fourth day in leaves. Similarly, IAA contents reached a maximum in the stem on the fifth day. No bolting was observed in the control group grown at 25°C, and significant changes were not observed in GA3 and GA4 levels in the controls during the observation period. RNA-sequencing data implicated transcription factors (TFs) in regulating bolting in lettuce, suggesting that the high GA contents in the leaves and IAA in the stem promote bolting. TFs possibly modulate the expression of related genes, such as those encoding hormones, potentially regulating bolting in lettuce. Compared to the control group, 258 TFs were identified in the stem of the treatment group, among which 98 and 156 were differentially up- and down-regulated, respectively; in leaves, 202 and 115 TFs were differentially up- and down-regulated, respectively. Significant changes in the treated group were observed for C2H2 zinc finger, AP2-EREBP, and WRKY families, indicating that these TFs may play important roles in regulating bolting.

  4. miRNA and mRNA Expression Profiles Reveal Insight into Chitosan-Mediated Regulation of Plant Growth.

    Science.gov (United States)

    Zhang, Xiaoqian; Li, Kecheng; Xing, Ronge; Liu, Song; Chen, Xiaolin; Yang, Haoyue; Li, Pengcheng

    2018-04-18

    Chitosan has been numerously studied as a plant growth regulator and stress tolerance inducer. To investigate the roles of chitosan as bioregulator on plant and unravel its possible metabolic responses mechanisms, we simultaneously investigated mRNAs and microRNAs (miRNAs) expression profiles of wheat seedlings in response to chitosan heptamer. We found 400 chitosan-responsive differentially expressed genes, including 268 up-regulated and 132 down-regulated mRNAs, many of which were related to photosynthesis, primary carbon and nitrogen metabolism, defense responses, and transcription factors. Moreover, miRNAs also participate in chitosan-mediated regulation on plant growth. We identified 87 known and 21 novel miRNAs, among which 56 miRNAs were induced or repressed by chitosan heptamer, such as miRNA156, miRNA159a, miRNA164, miRNA171a, miRNA319, and miRNA1127. The integrative analysis of miRNA and mRNA expression profiles in this case provides fundamental information for further investigation of regulation mechanisms of chitosan on plant growth and will facilitate its application in agriculture.

  5. Mesoscale simulations of confined Nafion thin films

    Science.gov (United States)

    Vanya, P.; Sharman, J.; Elliott, J. A.

    2017-12-01

    The morphology and transport properties of thin films of the ionomer Nafion, with thicknesses on the order of the bulk cluster size, have been investigated as a model system to explain the anomalous behaviour of catalyst/electrode-polymer interfaces in membrane electrode assemblies. We have employed dissipative particle dynamics (DPD) to investigate the interaction of water and fluorocarbon chains, with carbon and quartz as confining materials, for a wide range of operational water contents and film thicknesses. We found confinement-induced clustering of water perpendicular to the thin film. Hydrophobic carbon forms a water depletion zone near the film interface, whereas hydrophilic quartz results in a zone with excess water. There are, on average, oscillating water-rich and fluorocarbon-rich regions, in agreement with experimental results from neutron reflectometry. Water diffusivity shows increasing directional anisotropy of up to 30% with decreasing film thickness, depending on the hydrophilicity of the confining material. A percolation analysis revealed significant differences in water clustering and connectivity with the confining material. These findings indicate the fundamentally different nature of ionomer thin films, compared to membranes, and suggest explanations for increased ionic resistances observed in the catalyst layer.

  6. Adenovirus Protein E4-ORF1 activation of PI3 kinase reveals differential regulation of downstream effector pathways in adipocytes

    OpenAIRE

    Chaudhary, Natasha; Gonzalez, Eva; Chang, Sung-Hee; Geng, Fuqiang; Rafii, Shahin; Altorki, Nasser K.; McGraw, Timothy E.

    2016-01-01

    Insulin activation of phosphatidylinositol 3-kinase (PI3K) regulates metabolism, including the translocation of the Glut4 glucose transporter to the plasma membrane and inactivation of the FoxO1 transcription factor. Adenoviral protein E4-ORF1 stimulates cellular glucose metabolism by mimicking growth-factor activation of PI3K. We have used E4-ORF1 as a tool to dissect PI3K-mediated signaling in adipocytes. E4-ORF1 activation of PI3K in adipocytes recapitulates insulin regulation of FoxO1 but...

  7. Inertial confinement fusion target

    International Nuclear Information System (INIS)

    Bourdier, A.

    2001-12-01

    A simple, zero-dimensional model describing the temporal behaviour of an imploding-shell, magnetized fuel inertial confinement fusion target is formulated. The addition of a magnetic field to the fuel reduces thermal conduction losses. As a consequence, it might lead to high gains and reduce the driver requirements. This beneficial effect of the magnetic field on thermonuclear gains is confirmed qualitatively by the zero-dimensional model results. Still, the extent of the initial-condition space for which significant gains can occur is not, by far, as large as previously reported. One-dimensional CEA code simulations which confirm this results are also presented. Finally, we suggest to study the approach proposed by Hasegawa. In this scheme, the laser target is not imploded, and the life-time of the plasma can be very much increased. (author)

  8. Femtochemistry of confined water

    Science.gov (United States)

    Douhal, A.; Carranza, M. A.; Sanz, M.; Organero, J. A.; Santos, L.

    In this contribution, we applied ultrafast spectroscopy to study the H-bond network of water confined in nanostructures (Cyclodextrins and Micelles). We examine the effect of caging on ultrafast reaction dynamics and discuss the related processes under different experimental conditions. The results show an ultrafast dynamic giving birth to intermediates of the probe, which show femtosecond and picosecond dynamics leading to the final structure at the excited state. The results show the high sensitivity of the used technique in detecting small of water. This work was supported by the Ministry of Science and Technology (MCYT, Spain) and ``Conserjería de Ciencia y Tecnologia de la JCCM, Spain'' through projects MAT2002-01829 and PAI-02-004.

  9. Section 1. Confinement systems

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    Major experimental and theoretical results achieved by the Controlled Thermonuclear Research (CTR) program at Lawrence Livermore Laboratory during FY 1975 gave the greatest encouragement to date that the ultimate goal of a deuterium-tritium-fueled mirror reactor can be reached. In the experimental program, the year was characterized by unusually important physics results from the 2XIIB experiment and by significant steps in the plan to change the Baseball II mode of operation. The stabilization of ion-cyclotron instabilities in the 2XIIB experiment by the introduction of an auxiliary warm plasma permitted the buildup of a high-temperature, high-density plasma with an n tau parameter an order of magnitude larger than the 2XII experiment.I In the Baseball II experiment, preliminary tests and computer predictions indicated that a dense, transient, target plasma can be created by laser irradiation of a pellet in midflight through the center of the Baseball confinement zone

  10. Genome-Scale Analysis Reveals Sst2 as the Principal Regulator of Mating Pheromone Signaling in the Yeast Saccharomyces cerevisiae†

    Science.gov (United States)

    Chasse, Scott A.; Flanary, Paul; Parnell, Stephen C.; Hao, Nan; Cha, Jiyoung Y.; Siderovski, David P.; Dohlman, Henrik G.

    2006-01-01

    A common property of G protein-coupled receptors is that they become less responsive with prolonged stimulation. Regulators of G protein signaling (RGS proteins) are well known to accelerate G protein GTPase activity and do so by stabilizing the transition state conformation of the G protein α subunit. In the yeast Saccharomyces cerevisiae there are four RGS-homologous proteins (Sst2, Rgs2, Rax1, and Mdm1) and two Gα proteins (Gpa1 and Gpa2). We show that Sst2 is the only RGS protein that binds selectively to the transition state conformation of Gpa1. The other RGS proteins also bind Gpa1 and modulate pheromone signaling, but to a lesser extent and in a manner clearly distinct from Sst2. To identify other candidate pathway regulators, we compared pheromone responses in 4,349 gene deletion mutants representing nearly all nonessential genes in yeast. A number of mutants produced an increase (sst2, bar1, asc1, and ygl024w) or decrease (cla4) in pheromone sensitivity or resulted in pheromone-independent signaling (sst2, pbs2, gas1, and ygl024w). These findings suggest that Sst2 is the principal regulator of Gpa1-mediated signaling in vivo but that other proteins also contribute in distinct ways to pathway regulation. PMID:16467474

  11. A dynamic network model of mTOR signaling reveals TSC-independent mTORC2 regulation

    NARCIS (Netherlands)

    Dalle Pezze, Piero; Sonntag, Annika G; Thien, Antje; Prentzell, Mirja T; Gödel, Markus; Fischer, Sven; Neumann-Haefelin, Elke; Huber, Tobias B; Baumeister, Ralf; Shanley, Daryl P; Thedieck, Kathrin

    2012-01-01

    The kinase mammalian target of rapamycin (mTOR) exists in two multiprotein complexes (mTORC1 and mTORC2) and is a central regulator of growth and metabolism. Insulin activation of mTORC1, mediated by phosphoinositide 3-kinase (PI3K), Akt, and the inhibitory tuberous sclerosis complex 1/2

  12. Comparative proteomics of a tor inducible Aspergillus fumigatus mutant reveals involvement of the Tor kinase in iron regulation.

    Science.gov (United States)

    Baldin, Clara; Valiante, Vito; Krüger, Thomas; Schafferer, Lukas; Haas, Hubertus; Kniemeyer, Olaf; Brakhage, Axel A

    2015-07-01

    The Tor (target of rapamycin) kinase is one of the major regulatory nodes in eukaryotes. Here, we analyzed the Tor kinase in Aspergillus fumigatus, which is the most important airborne fungal pathogen of humans. Because deletion of the single tor gene was apparently lethal, we generated a conditional lethal tor mutant by replacing the endogenous tor gene by the inducible xylp-tor gene cassette. By both 2DE and gel-free LC-MS/MS, we found that Tor controls a variety of proteins involved in nutrient sensing, stress response, cell cycle progression, protein biosynthesis and degradation, but also processes in mitochondria, such as respiration and ornithine metabolism, which is required for siderophore formation. qRT-PCR analyses indicated that mRNA levels of ornithine biosynthesis genes were increased under iron limitation. When tor was repressed, iron regulation was lost. In a deletion mutant of the iron regulator HapX also carrying the xylp-tor cassette, the regulation upon iron deprivation was similar to that of the single tor inducible mutant strain. In line, hapX expression was significantly reduced when tor was repressed. Thus, Tor acts either upstream of HapX or independently of HapX as a repressor of the ornithine biosynthesis genes and thereby regulates the production of siderophores. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator

    DEFF Research Database (Denmark)

    Usaite, Renata; Jewett, Michael Christopher; Soberano de Oliveira, Ana Paula

    2009-01-01

    Highly conserved among eukaryotic cells, the AMP-activated kinase (AMPK) is a central regulator of carbon metabolism. To map the complete network of interactions around AMPK in yeast (Snf1) and to evaluate the role of its regulatory subunit Snf4, we measured global mRNA, protein and metabolite...

  14. Site-Specific Phosphorylation of PSD-95 PDZ Domains Reveals Fine-Tuned Regulation of Protein-Protein Interactions

    DEFF Research Database (Denmark)

    Pedersen, Søren W; Albertsen, Louise; Moran, Griffin E

    2017-01-01

    The postsynaptic density protein of 95 kDa (PSD-95) is a key scaffolding protein that controls signaling at synapses in the brain through interactions of its PDZ domains with the C-termini of receptors, ion channels, and enzymes. PSD-95 is highly regulated by phosphorylation. To explore the effec...

  15. Adenovirus Protein E4-ORF1 Activation of PI3 Kinase Reveals Differential Regulation of Downstream Effector Pathways in Adipocytes.

    Science.gov (United States)

    Chaudhary, Natasha; Gonzalez, Eva; Chang, Sung-Hee; Geng, Fuqiang; Rafii, Shahin; Altorki, Nasser K; McGraw, Timothy E

    2016-12-20

    Insulin activation of phosphatidylinositol 3-kinase (PI3K) regulates metabolism, including the translocation of the Glut4 glucose transporter to the plasma membrane and inactivation of the FoxO1 transcription factor. Adenoviral protein E4-ORF1 stimulates cellular glucose metabolism by mimicking growth-factor activation of PI3K. We have used E4-ORF1 as a tool to dissect PI3K-mediated signaling in adipocytes. E4-ORF1 activation of PI3K in adipocytes recapitulates insulin regulation of FoxO1 but not regulation of Glut4. This uncoupling of PI3K effects occurs despite E4-ORF1 activating PI3K and downstream signaling to levels achieved by insulin. Although E4-ORF1 does not fully recapitulate insulin's effects on Glut4, it enhances insulin-stimulated insertion of Glut4-containing vesicles to the plasma membrane independent of Rab10, a key regulator of Glut4 trafficking. E4-ORF1 also stimulates plasma membrane translocation of ubiquitously expressed Glut1 glucose transporter, an effect that is likely essential for E4-ORF1 to promote an anabolic metabolism in a broad range of cell types. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Adenovirus Protein E4-ORF1 Activation of PI3 Kinase Reveals Differential Regulation of Downstream Effector Pathways in Adipocytes

    Directory of Open Access Journals (Sweden)

    Natasha Chaudhary

    2016-12-01

    Full Text Available Insulin activation of phosphatidylinositol 3-kinase (PI3K regulates metabolism, including the translocation of the Glut4 glucose transporter to the plasma membrane and inactivation of the FoxO1 transcription factor. Adenoviral protein E4-ORF1 stimulates cellular glucose metabolism by mimicking growth-factor activation of PI3K. We have used E4-ORF1 as a tool to dissect PI3K-mediated signaling in adipocytes. E4-ORF1 activation of PI3K in adipocytes recapitulates insulin regulation of FoxO1 but not regulation of Glut4. This uncoupling of PI3K effects occurs despite E4-ORF1 activating PI3K and downstream signaling to levels achieved by insulin. Although E4-ORF1 does not fully recapitulate insulin’s effects on Glut4, it enhances insulin-stimulated insertion of Glut4-containing vesicles to the plasma membrane independent of Rab10, a key regulator of Glut4 trafficking. E4-ORF1 also stimulates plasma membrane translocation of ubiquitously expressed Glut1 glucose transporter, an effect that is likely essential for E4-ORF1 to promote an anabolic metabolism in a broad range of cell types.

  17. Comparative proteomic analyses reveal that the regulators of G-protein signaling proteins regulate amino acid metabolism of the rice blast fungus Magnaporthe oryzae.

    Science.gov (United States)

    Zhang, Haifeng; Ma, Hongyu; Xie, Xin; Ji, Jun; Dong, Yanhan; Du, Yan; Tang, Wei; Zheng, Xiaobo; Wang, Ping; Zhang, Zhengguang

    2014-11-01

    The rice blast fungus Magnaporthe oryzae encodes eight regulators of G-protein (GTP-binding protein) signaling (RGS) proteins MoRgs1-MoRgs8 that orchestrate the growth, asexual/sexual production, appressorium differentiation, and pathogenicity. To address the mechanisms by which MoRgs proteins function, we conducted a 2DE proteome study and identified 82 differentially expressed proteins by comparing five ∆Morgs mutants with wild-type Guy11 strain. We found that the abundances of eight amino acid (AA) biosynthesis or degradation associated proteins were markedly altered in five ∆Morgs mutants, indicating one of the main collective roles for the MoRgs proteins is to influence AA metabolism. We showed that MoRgs proteins have distinct roles in AA metabolism and nutrient responses from growth assays. In addition, we characterized MoLys20 (Lys is lysine), a homocitrate synthase, whose abundance was significantly decreased in the ∆Morgs mutants. The ∆Molys20 mutant is auxotrophic for lys and exogenous lys could partially rescue its auxotrophic defects. Deletion of MoLYS20 resulted in defects in conidiation and infection, as well as pathogenicity on rice. Overall, our results indicate that one of the critical roles for MoRgs proteins is to regulate AA metabolism, and that MoLys20 may be directly or indirectly regulated by MoRgs and participated in lys biosynthesis, thereby affecting fungal development and pathogenicity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. A functional microRNA library screen reveals miR-410 as a novel anti-apoptotic regulator of cholangiocarcinoma

    International Nuclear Information System (INIS)

    Palumbo, Tiziana; Poultsides, George A.; Kouraklis, Grigorios; Liakakos, Theodore; Drakaki, Alexandra; Peros, George; Hatziapostolou, Maria; Iliopoulos, Dimitrios

    2016-01-01

    Cholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo. A functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors. The screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas. Taken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma. The online version of this article (doi:10.1186/s12885-016-2384-0) contains supplementary material, which is available to authorized users

  19. Analysis of the meiotic transcriptome reveals the genes related to the regulation of pollen abortion in cytoplasmic male-sterile pepper (Capsicum annuum L.).

    Science.gov (United States)

    Qiu, Yilan; Liao, Lijuan; Jin, Xiaorui; Mao, Dandan; Liu, Rushi

    2018-01-30

    CMS, which refers to the inability to generate functional pollen grains while still producing a normal gynoecium, has been widely used for pepper hybrid seed production. Pepper line 8214A is an excellent CMS line exhibiting 100% male sterility and superior economic characteristics. A TUNEL assay revealed the nuclear DNA is damaged in 8214A PMCs during meiosis. TEM images indicated that the 8214A PMCs exhibited asynchronous meiosis after prophase I, and some PMCs degraded prematurely with morphological features typical of PCD. Additionally, at the end of meiosis, the 8214A PMCs formed abnormal non-tetrahedral tetrads that degraded in situ. To identify the genes involved in the pollen abortion of line 8214A, the transcriptional profiles of the 8214A and the 8214B anthers (i.e., from the fertile maintainer line) during meiosis were analyzed using an RNA-seq approach. A total of 1355 genes were determined to be differentially expressed, including 424 and 931 up- and down- regulated genes, respectively, in the 8214A anthers during meiosis relative to the expression levels in the 8214B. The expression levels of ubiquitin ligase and cell cycle-related genes were apparently down-regulated, while the expression of methyltransferase genes was up-regulated in the 8214A anthers during meiosis, which likely contributed to the PCD of these PMCs during meiosis. Thus, our results may be useful for revealing the molecular mechanism regulating the pollen abortion of CMS pepper. Copyright © 2017. Published by Elsevier B.V.

  20. Transcriptomic and proteomic approach to identify differentially expressed genes and proteins in Arabidopsis thaliana mutants lacking chloroplastic 1 and cytosolic FBPases reveals several levels of metabolic regulation.

    Science.gov (United States)

    Soto-Suárez, Mauricio; Serrato, Antonio J; Rojas-González, José A; Bautista, Rocío; Sahrawy, Mariam

    2016-12-01

    During the photosynthesis, two isoforms of the fructose-1,6-bisphosphatase (FBPase), the chloroplastidial (cFBP1) and the cytosolic (cyFBP), catalyse the first irreversible step during the conversion of triose phosphates (TP) to starch or sucrose, respectively. Deficiency in cyFBP and cFBP1 isoforms provokes an imbalance of the starch/sucrose ratio, causing a dramatic effect on plant development when the plastidial enzyme is lacking. We study the correlation between the transcriptome and proteome profile in rosettes and roots when cFBP1 or cyFBP genes are disrupted in Arabidopsis thaliana knock-out mutants. By using a 70-mer oligonucleotide microarray representing the genome of Arabidopsis we were able to identify 1067 and 1243 genes whose expressions are altered in the rosettes and roots of the cfbp1 mutant respectively; whilst in rosettes and roots of cyfbp mutant 1068 and 1079 genes are being up- or down-regulated respectively. Quantitative real-time PCR validated 100% of a set of 14 selected genes differentially expressed according to our microarray analysis. Two-dimensional (2-D) gel electrophoresis-based proteomic analysis revealed quantitative differences in 36 and 26 proteins regulated in rosettes and roots of cfbp1, respectively, whereas the 18 and 48 others were regulated in rosettes and roots of cyfbp mutant, respectively. The genes differentially expressed and the proteins more or less abundant revealed changes in protein metabolism, RNA regulation, cell signalling and organization, carbon metabolism, redox regulation, and transport together with biotic and abiotic stress. Notably, a significant set (25%) of the proteins identified were also found to be regulated at a transcriptional level. This transcriptomic and proteomic analysis is the first comprehensive and comparative study of the gene/protein re-adjustment that occurs in photosynthetic and non-photosynthetic organs of Arabidopsis mutants lacking FBPase isoforms.

  1. Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos

    Directory of Open Access Journals (Sweden)

    Rachel E. Jennings

    2017-11-01

    Full Text Available To interrogate the alternative fates of pancreas and liver in the earliest stages of human organogenesis, we developed laser capture, RNA amplification, and computational analysis of deep sequencing. Pancreas-enriched gene expression was less conserved between human and mouse than for liver. The dorsal pancreatic bud was enriched for components of Notch, Wnt, BMP, and FGF signaling, almost all genes known to cause pancreatic agenesis or hypoplasia, and over 30 unexplored transcription factors. SOX9 and RORA were imputed as key regulators in pancreas compared with EP300, HNF4A, and FOXA family members in liver. Analyses implied that current in vitro human stem cell differentiation follows a dorsal rather than a ventral pancreatic program and pointed to additional factors for hepatic differentiation. In summary, we provide the transcriptional codes regulating the start of human liver and pancreas development to facilitate stem cell research and clinical interpretation without inter-species extrapolation.

  2. The Global Acetylome of the Human Pathogen Vibrio cholerae V52 Reveals Lysine Acetylation of Major Transcriptional Regulators

    DEFF Research Database (Denmark)

    Jers, Carsten; Ravikumar, Vaishnavi; Lezyk, Mateusz Jakub

    2018-01-01

    Protein lysine acetylation is recognized as an important reversible post translational modification in all domains of life. While its primary roles appear to reside in metabolic processes, lysine acetylation has also been implicated in regulating pathogenesis in bacteria. Several global lysine...... acetylome analyses have been carried out in various bacteria, but thus far there have been no reports of lysine acetylation taking place in the important human pathogen Vibrio cholerae. In this study, we analyzed the lysine acetylproteome of the human pathogen V. cholerae V52. By applying a combination...... in direct regulation of virulence in V. cholerae were acetylated. In conclusion, this is the first global protein lysine acetylome analysis of V. cholerae and should constitute a valuable resource for in-depth studies of the impact of lysine acetylation in pathogenesis and other cellular processes....

  3. Exposure to Glycolytic Carbon Sources Reveals a Novel Layer of Regulation for the MalT Regulon

    Directory of Open Access Journals (Sweden)

    Sylvia A. Reimann

    2011-01-01

    Full Text Available Bacteria adapt to changing environments by means of tightly coordinated regulatory circuits. The use of synthetic lethality, a genetic phenomenon in which the combination of two nonlethal mutations causes cell death, facilitates identification and study of such circuitry. In this study, we show that the E. coli ompR malTcon double mutant exhibits a synthetic lethal phenotype that is environmentally conditional. MalTcon, the constitutively active form of the maltose system regulator MalT, causes elevated expression of the outer membrane porin LamB, which leads to death in the absence of the osmoregulator OmpR. However, the presence and metabolism of glycolytic carbon sources, such as sorbitol, promotes viability and unveils a novel layer of regulation within the complex circuitry that controls maltose transport and metabolism.

  4. Promoter Analysis Reveals Globally Differential Regulation of Human Long Non-Coding RNA and Protein-Coding Genes

    KAUST Repository

    Alam, Tanvir

    2014-10-02

    Transcriptional regulation of protein-coding genes is increasingly well-understood on a global scale, yet no comparable information exists for long non-coding RNA (lncRNA) genes, which were recently recognized to be as numerous as protein-coding genes in mammalian genomes. We performed a genome-wide comparative analysis of the promoters of human lncRNA and protein-coding genes, finding global differences in specific genetic and epigenetic features relevant to transcriptional regulation. These two groups of genes are hence subject to separate transcriptional regulatory programs, including distinct transcription factor (TF) proteins that significantly favor lncRNA, rather than coding-gene, promoters. We report a specific signature of promoter-proximal transcriptional regulation of lncRNA genes, including several distinct transcription factor binding sites (TFBS). Experimental DNase I hypersensitive site profiles are consistent with active configurations of these lncRNA TFBS sets in diverse human cell types. TFBS ChIP-seq datasets confirm the binding events that we predicted using computational approaches for a subset of factors. For several TFs known to be directly regulated by lncRNAs, we find that their putative TFBSs are enriched at lncRNA promoters, suggesting that the TFs and the lncRNAs may participate in a bidirectional feedback loop regulatory network. Accordingly, cells may be able to modulate lncRNA expression levels independently of mRNA levels via distinct regulatory pathways. Our results also raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed lncRNA genes is warranted in the future.

  5. Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator

    Science.gov (United States)

    Usaite, Renata; Jewett, Michael C; Oliveira, Ana Paula; Yates, John R; Olsson, Lisbeth; Nielsen, Jens

    2009-01-01

    Highly conserved among eukaryotic cells, the AMP-activated kinase (AMPK) is a central regulator of carbon metabolism. To map the complete network of interactions around AMPK in yeast (Snf1) and to evaluate the role of its regulatory subunit Snf4, we measured global mRNA, protein and metabolite levels in wild type, Δsnf1, Δsnf4, and Δsnf1Δsnf4 knockout strains. Using four newly developed computational tools, including novel DOGMA sub-network analysis, we showed the benefits of three-level ome-data integration to uncover the global Snf1 kinase role in yeast. We for the first time identified Snf1's global regulation on gene and protein expression levels, and showed that yeast Snf1 has a far more extensive function in controlling energy metabolism than reported earlier. Additionally, we identified complementary roles of Snf1 and Snf4. Similar to the function of AMPK in humans, our findings showed that Snf1 is a low-energy checkpoint and that yeast can be used more extensively as a model system for studying the molecular mechanisms underlying the global regulation of AMPK in mammals, failure of which leads to metabolic diseases. PMID:19888214

  6. Listeria monocytogenes differential transcriptome analysis reveals temperature-dependent Agr regulation and suggests overlaps with other regulons.

    Science.gov (United States)

    Garmyn, Dominique; Augagneur, Yoann; Gal, Laurent; Vivant, Anne-Laure; Piveteau, Pascal

    2012-01-01

    Listeria monocytogenes is a ubiquitous, opportunistic pathogenic organism. Environmental adaptation requires constant regulation of gene expression. Among transcriptional regulators, AgrA is part of an auto-induction system. Temperature is an environmental cue critical for in vivo adaptation. In order to investigate how temperature may affect AgrA-dependent transcription, we compared the transcriptomes of the parental strain L. monocytogenes EGD-e and its ΔagrA mutant at the saprophytic temperature of 25°C and in vivo temperature of 37°C. Variations of transcriptome were higher at 37°C than at 25°C. Results suggested that AgrA may be involved in the regulation of nitrogen transport, amino acids, purine and pyrimidine biosynthetic pathways and phage-related functions. Deregulations resulted in a growth advantage at 37°C, but affected salt tolerance. Finally, our results suggest overlaps with PrfA, σB, σH and CodY regulons. These overlaps may suggest that through AgrA, Listeria monocytogenes integrates information on its biotic environment.

  7. Analysis of experience-regulated transcriptome and imprintome during critical periods of mouse visual system development reveals spatiotemporal dynamics.

    Science.gov (United States)

    Hsu, Chi-Lin; Chou, Chih-Hsuan; Huang, Shih-Chuan; Lin, Chia-Yi; Lin, Meng-Ying; Tung, Chun-Che; Lin, Chun-Yen; Lai, Ivan Pochou; Zou, Yan-Fang; Youngson, Neil A; Lin, Shau-Ping; Yang, Chang-Hao; Chen, Shih-Kuo; Gau, Susan Shur-Fen; Huang, Hsien-Sung

    2018-03-15

    Visual system development is light-experience dependent, which strongly implicates epigenetic mechanisms in light-regulated maturation. Among many epigenetic processes, genomic imprinting is an epigenetic mechanism through which monoallelic gene expression occurs in a parent-of-origin-specific manner. It is unknown if genomic imprinting contributes to visual system development. We profiled the transcriptome and imprintome during critical periods of mouse visual system development under normal- and dark-rearing conditions using B6/CAST F1 hybrid mice. We identified experience-regulated, isoform-specific and brain-region-specific imprinted genes. We also found imprinted microRNAs were predominantly clustered into the Dlk1-Dio3 imprinted locus with light experience affecting some imprinted miRNA expression. Our findings provide the first comprehensive analysis of light-experience regulation of the transcriptome and imprintome during critical periods of visual system development. Our results may contribute to therapeutic strategies for visual impairments and circadian rhythm disorders resulting from a dysfunctional imprintome.

  8. Comparative metabolomics reveals endogenous ligands of DAF-12, a nuclear hormone receptor regulating C. elegans development and lifespan

    Science.gov (United States)

    Mahanti, Parag; Bose, Neelanjan; Bethke, Axel; Judkins, Joshua C.; Wollam, Joshua; Dumas, Kathleen J.; Zimmerman, Anna M.; Campbell, Sydney L.; Hu, Patrick J.; Antebi, Adam; Schroeder, Frank C.

    2014-01-01

    SUMMARY Small-molecule ligands of nuclear hormone receptors (NHRs) govern the transcriptional regulation of metazoan development, cell differentiation, and metabolism. However, the physiological ligands of many NHRs remain poorly characterized primarily due to lack of robust analytical techniques. Using comparative metabolomics, we identified endogenous steroids that act as ligands of the C. elegans NHR, DAF-12, a vitamin-D and liver-X receptor homolog regulating larval development, fat metabolism, and lifespan. The identified molecules feature unexpected chemical modifications and include only one of two DAF-12 ligands reported earlier, necessitating a revision of previously proposed ligand biosynthetic pathways. We further show that ligand profiles are regulated by a complex enzymatic network including the Rieske oxygenase DAF-36, the short-chain dehydrogenase DHS-16, and the hydroxysteroid dehydrogenase, HSD-1. Our results demonstrate the advantages of comparative metabolomics over traditional candidate-based approaches and provide a blueprint for the identification of ligands for other C. elegans and mammalian NHRs. PMID:24411940

  9. Confinement at large-N

    International Nuclear Information System (INIS)

    Klinkhamer, F.R.

    1985-06-01

    Recent numerical results indicate that QCD in the limit of an infinite number (N) of colors also has confinement and moreover that it looks rather similar to normal QCD with N = 3 colors. This imposes severe restrictions on what the mechanism of confinement can be

  10. Arabidopsis mutant sk156 reveals complex regulation of SPL15 in a miR156-controlled gene network.

    Science.gov (United States)

    Wei, Shu; Gruber, Margaret Y; Yu, Bianyun; Gao, Ming-Jun; Khachatourians, George G; Hegedus, Dwayne D; Parkin, Isobel A P; Hannoufa, Abdelali

    2012-09-18

    The Arabidopsis microRNA156 (miR156) regulates 11 members of the SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) family by base pairing to complementary target mRNAs. Each SPL gene further regulates a set of other genes; thus, miR156 controls numerous genes through a complex gene regulation network. Increased axillary branching occurs in transgenic Arabidopsis overexpressing miR156b, similar to that observed in loss-of-function max3 and max4 mutants with lesions in carotenoid cleavage dioxygenases. Arabidopsis miR156b was found to enhance carotenoid levels and reproductive shoot branching when expressed in Brassica napus, suggesting a link between miR156b expression and carotenoid metabolism. However, details of the miR156 regulatory network of SPL genes related to carotenoid metabolism are not known. In this study, an Arabidopsis T-DNA enhancer mutant, sk156, was identified due to its altered branching and trichome morphology and increased seed carotenoid levels compared to wild type (WT) ecovar Columbia. Enhanced miR156b expression due to the 35S enhancers present on the T-DNA insert was responsible for these phenotypes. Constitutive and leaf primodium-specific expression of a miR156-insensitive (mutated) SPL15 (SPL15m) largely restored WT seed carotenoid levels and plant morphology when expressed in sk156. The Arabidopsis native miR156-sensitive SPL15 (SPL15n) and SPL15m driven by a native SPL15 promoter did not restore the WT phenotype in sk156. Our findings suggest that SPL15 function is somewhat redundant with other SPL family members, which collectively affect plant phenotypes. Moreover, substantially decreased miR156b transcript levels in sk156 expressing SPL15m, together with the presence of multiple repeats of SPL-binding GTAC core sequence close to the miR156b transcription start site, suggested feedback regulation of miR156b expression by SPL15. This was supported by the demonstration of specific in vitro interaction between DNA-binding SBP domain of SPL15

  11. Arabidopsis mutant sk156 reveals complex regulation of SPL15 in a miR156-controlled gene network

    Directory of Open Access Journals (Sweden)

    Wei Shu

    2012-09-01

    Full Text Available Abstract Background The Arabidopsis microRNA156 (miR156 regulates 11 members of the SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL family by base pairing to complementary target mRNAs. Each SPL gene further regulates a set of other genes; thus, miR156 controls numerous genes through a complex gene regulation network. Increased axillary branching occurs in transgenic Arabidopsis overexpressing miR156b, similar to that observed in loss-of-function max3 and max4 mutants with lesions in carotenoid cleavage dioxygenases. Arabidopsis miR156b was found to enhance carotenoid levels and reproductive shoot branching when expressed in Brassica napus, suggesting a link between miR156b expression and carotenoid metabolism. However, details of the miR156 regulatory network of SPL genes related to carotenoid metabolism are not known. Results In this study, an Arabidopsis T-DNA enhancer mutant, sk156, was identified due to its altered branching and trichome morphology and increased seed carotenoid levels compared to wild type (WT ecovar Columbia. Enhanced miR156b expression due to the 35S enhancers present on the T-DNA insert was responsible for these phenotypes. Constitutive and leaf primodium-specific expression of a miR156-insensitive (mutated SPL15 (SPL15m largely restored WT seed carotenoid levels and plant morphology when expressed in sk156. The Arabidopsis native miR156-sensitive SPL15 (SPL15n and SPL15m driven by a native SPL15 promoter did not restore the WT phenotype in sk156. Our findings suggest that SPL15 function is somewhat redundant with other SPL family members, which collectively affect plant phenotypes. Moreover, substantially decreased miR156b transcript levels in sk156 expressing SPL15m, together with the presence of multiple repeats of SPL-binding GTAC core sequence close to the miR156b transcription start site, suggested feedback regulation of miR156b expression by SPL15. This was supported by the demonstration of specific in vitro

  12. Integrating genome-wide genetic variations and monocyte expression data reveals trans-regulated gene modules in humans.

    Directory of Open Access Journals (Sweden)

    Maxime Rotival

    2011-12-01

    Full Text Available One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. So far, few cis expression quantitative trait loci (eQTLs have been reliably related to disease susceptibility. Trans-regulating mechanisms may play a more prominent role in disease susceptibility. We analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 European unrelated subjects. We applied a method of extraction of expression patterns-independent component analysis-to identify sets of co-regulated genes. These patterns were then related to 675,350 SNPs to identify major trans-acting regulators. We detected three genomic regions significantly associated with co-regulated gene modules. Association of these loci with multiple expression traits was replicated in Cardiogenics, an independent study in which expression profiles of monocytes were available in 758 subjects. The locus 12q13 (lead SNP rs11171739, previously identified as a type 1 diabetes locus, was associated with a pattern including two cis eQTLs, RPS26 and SUOX, and 5 trans eQTLs, one of which (MADCAM1 is a potential candidate for mediating T1D susceptibility. The locus 12q24 (lead SNP rs653178, which has demonstrated extensive disease pleiotropy, including type 1 diabetes, hypertension, and celiac disease, was associated to a pattern strongly correlating to blood pressure level. The strongest trans eQTL in this pattern was CRIP1, a known marker of cellular proliferation in cancer. The locus 12q15 (lead SNP rs11177644 was associated with a pattern driven by two cis eQTLs, LYZ and YEATS4, and including 34 trans eQTLs, several of them tumor-related genes. This study shows that a method exploiting the structure of co-expressions among genes can help identify genomic regions involved in trans regulation of sets of genes and can provide clues for understanding the

  13. Loss of PTB or negative regulation of Notch mRNA reveals distinct zones of Notch and actin protein accumulation in Drosophila embryo.

    Directory of Open Access Journals (Sweden)

    Cedric S Wesley

    Full Text Available Polypyrimidine Tract Binding (PTB protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1 the Notch mRNA is a potential target of PTB, (2 PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3 the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions.

  14. Loss of PTB or Negative Regulation of Notch mRNA Reveals Distinct Zones of Notch and Actin Protein Accumulation in Drosophila Embryo

    Science.gov (United States)

    Wesley, Cedric S.; Guo, Heng; Chaudhry, Kanita A.; Thali, Markus J.; Yin, Jerry C.; Clason, Todd; Wesley, Umadevi V.

    2011-01-01

    Polypyrimidine Tract Binding (PTB) protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1) the Notch mRNA is a potential target of PTB, (2) PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3) the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions. PMID:21750738

  15. Transcriptomic analysis reveals ethylene as stimulator and auxin as regulator of adventitious root formation in petunia cuttings

    OpenAIRE

    Druege, Uwe; Franken, Philipp; Lischewski, Sandra; Ahkami, Amir H.; Zerche, Siegfried; Hause, Bettina; Hajirezaei, Mohammad R.

    2014-01-01

    Adventitious root (AR) formation in the stem base of cuttings is the basis for propagation of many plant species and petunia is used as model to study this developmental process. Following AR formation from 2 to 192 hours after excision (hpe) of cuttings, transcriptome analysis by microarray revealed a change of the character of the rooting zone from stem base to root identity. The greatest shift in the number of differentially expressed genes was observed between 24 and 72 hpe, when the cate...

  16. Gravitationally confined relativistic neutrinos

    Science.gov (United States)

    Vayenas, C. G.; Fokas, A. S.; Grigoriou, D.

    2017-09-01

    Combining special relativity, the equivalence principle, and Newton’s universal gravitational law with gravitational rather than rest masses, one finds that gravitational interactions between relativistic neutrinos with kinetic energies above 50 MeV are very strong and can lead to the formation of gravitationally confined composite structures with the mass and other properties of hadrons. One may model such structures by considering three neutrinos moving symmetrically on a circular orbit under the influence of their gravitational attraction, and by assuming quantization of their angular momentum, as in the Bohr model of the H atom. The model contains no adjustable parameters and its solution, using a neutrino rest mass of 0.05 eV/c2, leads to composite state radii close to 1 fm and composite state masses close to 1 GeV/c2. Similar models of relativistic rotating electron - neutrino pairs give a mass of 81 GeV/c2, close to that of W bosons. This novel mechanism of generating mass suggests that the Higgs mass generation mechanism can be modeled as a latent gravitational field which gets activated by relativistic neutrinos.

  17. Inertial confinement fusion

    International Nuclear Information System (INIS)

    Nuckolls, J.H.; Wood, L.L.

    1988-01-01

    Edward Teller has been a strong proponent of harnessing nuclear explosions for peaceful purposes. There are two approaches: Plowshare, which utilizes macro- explosions, and inertial confinement fusion, which utilizes microexplosions. The development of practical fusion power plants is a principal goal of the inertial program. It is remarkable that Teller's original thermonuclear problem, how to make super high yield nuclear explosions, and the opposite problem, how to make ultra low yield nuclear explosions, may both be solved by Teller's radiation implosion scheme. This paper reports on the essential physics of these two thermonuclear domains, which are separated by nine orders of magnitude in yield, provided by Teller's similarity theorem and its exceptions. Higher density makes possible thermonuclear burn of smaller masses of fuel. The leverage is high: the scale of the explosion diminishes with the square of the increase in density. The extraordinary compressibility of matter, first noticed by Teller during the Los Alamos atomic bomb program, provides an almost incredible opportunity to harness fusion. The energy density of thermonuclear fuels isentropically compressed to super high-- -densities---even to ten thousand times solid density---is small compared to the energy density at thermonuclear ignition temperatures. In small masses of fuel imploded to these super high matter densities, the energy required to achieve ignition may be greatly reduced by exploiting thermonuclear propagation from a relatively small hot spot

  18. Thermostating highly confined fluids.

    Science.gov (United States)

    Bernardi, Stefano; Todd, B D; Searles, Debra J

    2010-06-28

    In this work we show how different use of thermostating devices and modeling of walls influence the mechanical and dynamical properties of confined nanofluids. We consider a two dimensional fluid undergoing Couette flow using nonequilibrium molecular dynamics simulations. Because the system is highly inhomogeneous, the density shows strong fluctuations across the channel. We compare the dynamics produced by applying a thermostating device directly to the fluid with that obtained when the wall is thermostated, considering also the effects of using rigid walls. This comparison involves an analysis of the chaoticity of the fluid and evaluation of mechanical properties across the channel. We look at two thermostating devices with either rigid or vibrating atomic walls and compare them with a system only thermostated by conduction through vibrating atomic walls. Sensitive changes are observed in the xy component of the pressure tensor, streaming velocity, and density across the pore and the Lyapunov localization of the fluid. We also find that the fluid slip can be significantly reduced by rigid walls. Our results suggest caution in interpreting the results of systems in which fluid atoms are thermostated and/or wall atoms are constrained to be rigid, such as, for example, water inside carbon nanotubes.

  19. Transcriptional profiles of hybrid Eucalyptus genotypes with contrasting lignin content reveal that monolignol biosynthesis-related genes regulate wood composition

    Directory of Open Access Journals (Sweden)

    Tomotaka eShinya

    2016-04-01

    Full Text Available Eucalyptus species constitutes the most widely planted hardwood trees in temperate and subtropical regions. In this study, we compared the transcript levels of genes involved in lignocellulose formation such as cellulose, hemicellulose and lignin biosynthesis in two selected three-year old hybrid Eucalyptus (Eucalyptus urophylla x E. grandis genotypes (AM063 and AM380 that have different lignin content. AM063 and AM380 had 20.2 and 35.5% of Klason lignin content and 59.0% and 48.2%, -cellulose contents, respectively. We investigated the correlation between wood properties and transcript levels of wood formation-related genes using RNA-seq with total RNAs extracted from developing xylem tissues at a breast height. Transcript levels of cell wall construction genes such as cellulose synthase (CesA and sucrose synthase (SUSY were almost the same in both genotypes. However, AM063 exhibited higher transcript levels of UDP-glucose pyrophosphorylase (UGP and xyloglucan endotransglucoxylase (XTH than those in AM380. Most monolignol biosynthesis- related isozyme genes showed higher transcript levels in AM380. These results indicate monolignol biosynthesis-related genes may regulate wood composition in Eucalyptus. Flavonoids contents were also observed at much higher levels in AM380 as a result of the elevated transcript levels of common phenylpropanoid pathway genes, phenylalanine ammonium lyase (PAL, cinnamate-4-hydroxylase (C4H and 4-coumarate-CoA ligase (4CL. Secondary plant cell wall formation is regulated by many transcription factors. We analyzed genes encoding NAC, WRKY, AP2/ERF and KNOX transcription factors and found higher transcript levels of these genes in AM380. We also observed increased transcription of some MYB and LIM domain transcription factors in AM380 compared to AM063. All these results show that genes related to monolignol biosynthesis may regulate the wood composition and help maintain the ratio of cellulose and lignin contents

  20. Proteomic Analysis Reveals Coordinated Regulation of Anthocyanin Biosynthesis through Signal Transduction and Sugar Metabolism in Black Rice Leaf.

    Science.gov (United States)

    Chen, Linghua; Huang, Yining; Xu, Ming; Cheng, Zuxin; Zheng, Jingui

    2017-12-15

    Black rice ( Oryza sativa L.) is considered to be a healthy food due to its high content of anthocyanins in the pericarp. The synthetic pathway of anthocyanins in black rice grains has been identified, however, the proteomic profile of leaves during grain development is still unclear. Here, isobaric Tags Relative and Absolute Quantification (iTRAQ) MS/MS was carried out to identify statistically significant changes of leaf proteome in the black rice during grain development. Throughout three sequential developmental stages, a total of 3562 proteins were detected and 24 functional proteins were differentially expressed 3-10 days after flowering (DAF). The detected proteins are known to be involved in various biological processes and most of these proteins were related to gene expression regulatory (33.3%), signal transduction (16.7%) and developmental regulation and hormone-like proteins (12.5%). The coordinated changes were consistent with changes in regulatory proteins playing a leading role in leaves during black rice grain development. This indicated that signal transduction between leaves and grains may have an important role in anthocyanin biosynthesis and accumulation during grain development of black rice. In addition, four identified up-regulated proteins associated with starch metabolism suggested that the remobilization of nutrients for starch synthesis plays a potential role in anthocyanin biosynthesis of grain. The mRNA transcription for eight selected proteins was validated with quantitative real-time PCR. Our results explored the proteomics of the coordination between leaf and grain in anthocyanins biosynthesis of grain, which might be regulated by signal transduction and sugar metabolism in black rice leaf.

  1. Proteomic Analysis Reveals Coordinated Regulation of Anthocyanin Biosynthesis through Signal Transduction and Sugar Metabolism in Black Rice Leaf

    Directory of Open Access Journals (Sweden)

    Linghua Chen

    2017-12-01

    Full Text Available Black rice (Oryza sativa L. is considered to be a healthy food due to its high content of anthocyanins in the pericarp. The synthetic pathway of anthocyanins in black rice grains has been identified, however, the proteomic profile of leaves during grain development is still unclear. Here, isobaric Tags Relative and Absolute Quantification (iTRAQ MS/MS was carried out to identify statistically significant changes of leaf proteome in the black rice during grain development. Throughout three sequential developmental stages, a total of 3562 proteins were detected and 24 functional proteins were differentially expressed 3–10 days after flowering (DAF. The detected proteins are known to be involved in various biological processes and most of these proteins were related to gene expression regulatory (33.3%, signal transduction (16.7% and developmental regulation and hormone-like proteins (12.5%. The coordinated changes were consistent with changes in regulatory proteins playing a leading role in leaves during black rice grain development. This indicated that signal transduction between leaves and grains may have an important role in anthocyanin biosynthesis and accumulation during grain development of black rice. In addition, four identified up-regulated proteins associated with starch metabolism suggested that the remobilization of nutrients for starch synthesis plays a potential role in anthocyanin biosynthesis of grain. The mRNA transcription for eight selected proteins was validated with quantitative real-time PCR. Our results explored the proteomics of the coordination between leaf and grain in anthocyanins biosynthesis of grain, which might be regulated by signal transduction and sugar metabolism in black rice leaf.

  2. Protein expression profiling of the drosophila fragile X mutant brain reveals up-regulation of monoamine synthesis.

    Science.gov (United States)

    Zhang, Yong Q; Friedman, David B; Wang, Zhe; Woodruff, Elvin; Pan, Luyuan; O'donnell, Janis; Broadie, Kendal

    2005-03-01

    Fragile X syndrome is the most common form of inherited mental retardation, associated with both cognitive and behavioral anomalies. The disease is caused by silencing of the fragile X mental retardation 1 (fmr1) gene, which encodes the mRNA-binding, translational regulator FMRP. Previously we established a disease model through mutation of Drosophila fmr1 (dfmr1) and showed that loss of dFMRP causes defects in neuronal structure, function, and behavioral output similar to the human disease state. To uncover molecular targets of dFMRP in the brain, we use here a proteomic approach involving two-dimensional difference gel electrophoresis analyses followed by mass spectrometry identification of proteins with significantly altered expression in dfmr1 null mutants. We then focus on two misregulated enzymes, phenylalanine hydroxylase (Henna) and GTP cyclohydrolase (Punch), both of which mediate in concert the synthetic pathways of two key monoamine neuromodulators, dopamine and serotonin. Brain enzymatic assays show a nearly 2-fold elevation of Punch activity in dfmr1 null mutants. Consistently brain neurochemical assays show that both dopamine and serotonin are significantly increased in dfmr1 null mutants. At a cellular level, dfmr1 null mutant neurons display a highly significant elevation of the dense core vesicles that package these monoamine neuromodulators for secretion. Taken together, these data indicate that dFMRP normally down-regulates the monoamine pathway, which is consequently up-regulated in the mutant condition. Elevated brain levels of dopamine and serotonin provide a plausible mechanistic explanation for aspects of cognitive and behavioral deficits in human patients.

  3. Phosphoproteomic Analysis Reveals a Novel Mechanism of CaMKIIα Regulation Inversely Induced by Cocaine Memory Extinction versus Reconsolidation

    Science.gov (United States)

    Rich, Matthew T.; Abbott, Thomas B.; Chung, Lisa; Gulcicek, Erol E.; Stone, Kathryn L.; Colangelo, Christopher M.; Lam, TuKiet T.; Nairn, Angus C.; Taylor, Jane R.

    2016-01-01

    Successful addiction treatment depends on maintaining long-term abstinence, making relapse prevention an essential therapeutic goal. However, exposure to environmental cues associated with drug use often thwarts abstinence efforts by triggering drug using memories that drive craving and relapse. We sought to develop a dual approach for weakening cocaine memories through phosphoproteomic identification of targets regulated in opposite directions by memory extinction compared with reconsolidation in male Sprague-Dawley rats that had been trained to self-administer cocaine paired with an audiovisual cue. We discovered a novel, inversely regulated, memory-dependent phosphorylation event on calcium-calmodulin-dependent kinase II α (CaMKIIα) at serine (S)331. Correspondingly, extinction-associated S331 phosphorylation inhibited CaMKIIα activity. Intra-basolateral amygdala inhibition of CaMKII promoted memory extinction and disrupted reconsolidation, leading to a reduction in subsequent cue-induced reinstatement. CaMKII inhibition had no effect if the memory was neither retrieved nor extinguished. Therefore, inhibition of CaMKII represents a novel mechanism for memory-based addiction treatment that leverages both extinction enhancement and reconsolidation disruption to reduce relapse-like behavior. SIGNIFICANCE STATEMENT Preventing relapse to drug use is an important goal for the successful treatment of addictive disorders. Relapse-prevention therapies attempt to interfere with drug-associated memories, but are often hindered by unintentional memory strengthening. In this study, we identify phosphorylation events that are bidirectionally regulated by the reconsolidation versus extinction of a cocaine-associated memory, including a novel site on CaMKIIα. Additionally, using a rodent model of addiction, we show that CaMKII inhibition in the amygdala can reduce relapse-like behavior. Together, our data supports the existence of mechanisms that can be used to enhance

  4. Transcriptional similarity in couples reveals the impact of shared environment and lifestyle on gene regulation through modified cytosines

    Directory of Open Access Journals (Sweden)

    Ke Tang

    2016-06-01

    Full Text Available Gene expression is a complex and quantitative trait that is influenced by both genetic and non-genetic regulators including environmental factors. Evaluating the contribution of environment to gene expression regulation and identifying which genes are more likely to be influenced by environmental factors are important for understanding human complex traits. We hypothesize that by living together as couples, there can be commonly co-regulated genes that may reflect the shared living environment (e.g., diet, indoor air pollutants, behavioral lifestyle. The lymphoblastoid cell lines (LCLs derived from unrelated couples of African ancestry (YRI, Yoruba people from Ibadan, Nigeria from the International HapMap Project provided a unique model for us to characterize gene expression pattern in couples by comparing gene expression levels between husbands and wives. Strikingly, 778 genes were found to show much smaller variances in couples than random pairs of individuals at a false discovery rate (FDR of 5%. Since genetic variation between unrelated family members in a general population is expected to be the same assuming a random-mating society, non-genetic factors (e.g., epigenetic systems are more likely to be the mediators for the observed transcriptional similarity in couples. We thus evaluated the contribution of modified cytosines to those genes showing transcriptional similarity in couples as well as the relationships these CpG sites with other gene regulatory elements, such as transcription factor binding sites (TFBS. Our findings suggested that transcriptional similarity in couples likely reflected shared common environment partially mediated through cytosine modifications.

  5. Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

    Directory of Open Access Journals (Sweden)

    Monica S Guzman

    2011-11-01

    Full Text Available Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.

  6. Combining abundance and performance data reveals how temperature regulates coastal occurrences and activity of a roaming apex predator.

    Science.gov (United States)

    Payne, Nicholas L; Meyer, Carl G; Smith, James A; Houghton, Jonathan D R; Barnett, Adam; Holmes, Bonnie J; Nakamura, Itsumi; Papastamatiou, Yannis P; Royer, Mark A; Coffey, Daniel M; Anderson, James M; Hutchinson, Melanie R; Sato, Katsufumi; Halsey, Lewis G

    2018-05-01

    The redistribution of species has emerged as one of the most pervasive impacts of anthropogenic climate warming, and presents many societal challenges. Understanding how temperature regulates species distributions is particularly important for mobile marine fauna such as sharks given their seemingly rapid responses to warming, and the socio-political implications of human encounters with some dangerous species. The predictability of species distributions can potentially be improved by accounting for temperature's influence on performance, an elusive relationship for most large animals. We combined multi-decadal catch data and bio-logging to show that coastal abundance and swimming performance of tiger sharks Galeocerdo cuvier are both highest at ~22°C, suggesting thermal constraints on performance may regulate this species' distribution. Tiger sharks are responsible for a large proportion of shark bites on humans, and a focus of controversial control measures in several countries. The combination of distribution and performance data moves towards a mechanistic understanding of tiger shark's thermal niche, and delivers a simple yet powerful indicator for predicting the location and timing of their occurrences throughout coastlines. For example, tiger sharks are mostly caught at Australia's popular New South Wales beaches (i.e. near Sydney) in the warmest months, but our data suggest similar abundances will occur in winter and summer if annual sea surface temperatures increase by a further 1-2°C. © 2018 John Wiley & Sons Ltd.

  7. Identification of Human P2X1 Receptor-interacting Proteins Reveals a Role of the Cytoskeleton in Receptor Regulation*

    Science.gov (United States)

    Lalo, Ulyana; Roberts, Jonathan A.; Evans, Richard J.

    2011-01-01

    P2X1 receptors are ATP-gated ion channels expressed by smooth muscle and blood cells. Carboxyl-terminally His-FLAG-tagged human P2X1 receptors were stably expressed in HEK293 cells and co-purified with cytoskeletal proteins including actin. Disruption of the actin cytoskeleton with cytochalasin D inhibited P2X1 receptor currents with no effect on the time course of the response or surface expression of the receptor. Stabilization of the cytoskeleton with jasplakinolide had no effect on P2X1 receptor currents but decreased receptor mobility. P2X2 receptor currents were unaffected by cytochalasin, and P2X1/2 receptor chimeras were used to identify the molecular basis of actin sensitivity. These studies showed that the intracellular amino terminus accounts for the inhibitory effects of cytoskeletal disruption similar to that shown for lipid raft/cholesterol sensitivity. Stabilization of the cytoskeleton with jasplakinolide abolished the inhibitory effects of cholesterol depletion on P2X1 receptor currents, suggesting that lipid rafts may regulate the receptor through stabilization of the cytoskeleton. These studies show that the cytoskeleton plays an important role in P2X1 receptor regulation. PMID:21757694

  8. Patterns of subnet usage reveal distinct scales of regulation in the transcriptional regulatory network of Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Carsten Marr

    Full Text Available The set of regulatory interactions between genes, mediated by transcription factors, forms a species' transcriptional regulatory network (TRN. By comparing this network with measured gene expression data, one can identify functional properties of the TRN and gain general insight into transcriptional control. We define the subnet of a node as the subgraph consisting of all nodes topologically downstream of the node, including itself. Using a large set of microarray expression data of the bacterium Escherichia coli, we find that the gene expression in different subnets exhibits a structured pattern in response to environmental changes and genotypic mutation. Subnets with fewer changes in their expression pattern have a higher fraction of feed-forward loop motifs and a lower fraction of small RNA targets within them. Our study implies that the TRN consists of several scales of regulatory organization: (1 subnets with more varying gene expression controlled by both transcription factors and post-transcriptional RNA regulation and (2 subnets with less varying gene expression having more feed-forward loops and less post-transcriptional RNA regulation.

  9. Transcriptomic and Functional Analyses Reveal That PpGLK1 Regulates Chloroplast Development in Peach (Prunus persica

    Directory of Open Access Journals (Sweden)

    Min Chen

    2018-01-01

    Full Text Available Peach is an ideal species for fruit tree research because of its small, fully sequenced genome. Chloroplast development is dependent on the tight cooperation between the nuclear and plastid genomes, and is regulated by GLK transcription factors. In this work, the pigment content was monitored and the chloroplast-to-chromoplast conversion during the fruit ripening was visualized by transmission electron microscopy. Localization and expression analyses showed that PpGLK1 was located in the nucleus and expressed mainly in the leaves and fruit skin. A transcriptome analysis showed that PpGLK1 and its target genes were significantly differentially expressed in ripening peach fruit skin. PpGLK1 silencing affected chlorophyll accumulation in peach leaves and fruits. Overexpression of PpGLK1 rescued the phenotypes of the Arabidopsis Atglk1Atglk2 double mutant and the tomato uniform ripening mutant. The results of a yeast two-hybrid analysis showed that PpGLK1 is autoactivated and that PpGLK1 (301-542 a.a. interacted with PpARF5. Together, our results indicate that PpGLK1 regulates chloroplast development in green tissues in peach. Therefore, it may be a promising target gene for improving the production and quality of peach by genetic engineering and breeding approaches.

  10. ChIP-seq and in vivo transcriptome analyses of the Aspergillus fumigatus SREBP SrbA reveals a new regulator of the fungal hypoxia response and virulence.

    Directory of Open Access Journals (Sweden)

    Dawoon Chung

    2014-11-01

    Full Text Available The Aspergillus fumigatus sterol regulatory element binding protein (SREBP SrbA belongs to the basic Helix-Loop-Helix (bHLH family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete loss of virulence in murine models of invasive pulmonary aspergillosis (IPA. How fungal SREBPs mediate fungal virulence is unknown, though it has been suggested that lack of growth in hypoxic conditions accounts for the attenuated virulence. To further understand the role of SrbA in fungal infection site pathobiology, chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq was used to identify genes under direct SrbA transcriptional regulation in hypoxia. These results confirmed the direct regulation of ergosterol biosynthesis and iron uptake by SrbA in hypoxia and revealed new roles for SrbA in nitrate assimilation and heme biosynthesis. Moreover, functional characterization of an SrbA target gene with sequence similarity to SrbA identified a new transcriptional regulator of the fungal hypoxia response and virulence, SrbB. SrbB co-regulates genes involved in heme biosynthesis and demethylation of C4-sterols with SrbA in hypoxic conditions. However, SrbB also has regulatory functions independent of SrbA including regulation of carbohydrate metabolism. Loss of SrbB markedly attenuates A. fumigatus virulence, and loss of both SREBPs further reduces in vivo fungal growth. These data suggest that both A. fumigatus SREBPs are critical for hypoxia adaptation and virulence and reveal new insights into SREBPs' complex role in infection site adaptation and fungal virulence.

  11. High-throughput sequencing of small RNA transcriptome reveals salt stress regulated microRNAs in sugarcane.

    Directory of Open Access Journals (Sweden)

    Mariana Carnavale Bottino

    Full Text Available Salt stress is a primary cause of crop losses worldwide, and it has been the subject of intense investigation to unravel the complex mechanisms responsible for salinity tolerance. MicroRNA is implicated in many developmental processes and in responses to various abiotic stresses, playing pivotal roles in plant adaptation. Deep sequencing technology was chosen to determine the small RNA transcriptome of Saccharum sp cultivars grown on saline conditions. We constructed four small RNAs libraries prepared from plants grown on hydroponic culture submitted to 170 mM NaCl and harvested after 1 h, 6 hs and 24 hs. Each library was sequenced individually and together generated more than 50 million short reads. Ninety-eight conserved miRNAs and 33 miRNAs* were identified by bioinformatics. Several of the microRNA showed considerable differences of expression in the four libraries. To confirm the results of the bioinformatics-based analysis, we studied the expression of the 10 most abundant miRNAs and 1 miRNA* in plants treated with 170 mM NaCl and in plants with a severe treatment of 340 mM NaCl. The results showed that 11 selected miRNAs had higher expression in samples treated with severe salt treatment compared to the mild one. We also investigated the regulation of the same miRNAs in shoots of four cultivars grown on soil treated with 170 mM NaCl. Cultivars could be grouped according to miRNAs expression in response to salt stress. Furthermore, the majority of the predicted target genes had an inverse regulation with their correspondent microRNAs. The targets encode a wide range of proteins, including transcription factors, metabolic enzymes and genes involved in hormone signaling, probably assisting the plants to develop tolerance to salinity. Our work provides insights into the regulatory functions of miRNAs, thereby expanding our knowledge on potential salt-stressed regulated genes.

  12. Analysis of the highly diverse gene borders in Ebola virus reveals a distinct mechanism of transcriptional regulation.

    Science.gov (United States)

    Brauburger, Kristina; Boehmann, Yannik; Tsuda, Yoshimi; Hoenen, Thomas; Olejnik, Judith; Schümann, Michael; Ebihara, Hideki; Mühlberger, Elke

    2014-11-01

    Ebola virus (EBOV) belongs to the group of nonsegmented negative-sense RNA viruses. The seven EBOV genes are separated by variable gene borders, including short (4- or 5-nucleotide) intergenic regions (IRs), a single long (144-nucleotide) IR, and gene overlaps, where the neighboring gene end and start signals share five conserved nucleotides. The unique structure of the gene overlaps and the presence of a single long IR are conserved among all filoviruses. Here, we sought to determine the impact of the EBOV gene borders during viral transcription. We show that readthrough mRNA synthesis occurs in EBOV-infected cells irrespective of the structure of the gene border, indicating that the gene overlaps do not promote recognition of the gene end signal. However, two consecutive gene end signals at the VP24 gene might improve termination at the VP24-L gene border, ensuring efficient L gene expression. We further demonstrate that the long IR is not essential for but regulates transcription reinitiation in a length-dependent but sequence-independent manner. Mutational analysis of bicistronic minigenomes and recombinant EBOVs showed no direct correlation between IR length and reinitiation rates but demonstrated that specific IR lengths not found naturally in filoviruses profoundly inhibit downstream gene expression. Intriguingly, although truncation of the 144-nucleotide-long IR to 5 nucleotides did not substantially affect EBOV transcription, it led to a significant reduction of viral growth. Our current understanding of EBOV transcription regulation is limited due to the requirement for high-containment conditions to study this highly pathogenic virus. EBOV is thought to share many mechanistic features with well-analyzed prototype nonsegmented negative-sense RNA viruses. A single polymerase entry site at the 3' end of the genome determines that transcription of the genes is mainly controlled by gene order and cis-acting signals found at the gene borders. Here, we examined

  13. Transcriptomic Profiling Reveals Complex Molecular Regulation in Cotton Genic Male Sterile Mutant Yu98-8A.

    Directory of Open Access Journals (Sweden)

    Weiping Fang

    Full Text Available Although cotton genic male sterility (GMS plays an important role in the utilization of hybrid vigor, its precise molecular mechanism remains unclear. To characterize the molecular events of pollen abortion, transcriptome analysis, combined with histological observations, was conducted in the cotton GMS line, Yu98-8A. A total of 2,412 genes were identified as significant differentially expressed genes (DEGs before and during the critical pollen abortion stages. Bioinformatics and biochemical analysis showed that the DEGs mainly associated with sugars and starch metabolism, oxidative phosphorylation, and plant endogenous hormones play a critical and complicated role in pollen abortion. These findings extend a better understanding of the molecular events involved in the regulation of pollen abortion in genic male sterile cotton, which may provide a foundation for further research studies on cotton heterosis breeding.

  14. Taxon-specific metagenomics of Trichoderma reveals a narrow community of opportunistic species that regulate each other’s development

    Science.gov (United States)

    Friedl, Martina A.

    2012-01-01

    In this paper, we report on the in situ diversity of the mycotrophic fungus Trichoderma (teleomorph Hypocrea, Ascomycota, Dikarya) revealed by a taxon-specific metagenomic approach. We designed a set of genus-specific internal transcribed spacer (ITS)1 and ITS2 rRNA primers and constructed a clone library containing 411 molecular operational taxonomic units (MOTUs). The overall species composition in the soil of the two distinct ecosystems in the Danube floodplain consisted of 15 known species and two potentially novel taxa. The latter taxa accounted for only 1.5 % of all MOTUs, suggesting that almost no hidden or uncultivable Hypocrea/Trichoderma species are present at least in these temperate forest soils. The species were unevenly distributed in vertical soil profiles although no universal factors controlling the distribution of all of them (chemical soil properties, vegetation type and affinity to rhizosphere) were revealed. In vitro experiments simulating infrageneric interactions between the pairs of species that were detected in the same soil horizon showed a broad spectrum of reactions from very strong competition over neutral coexistence to the pronounced synergism. Our data suggest that only a relatively small portion of Hypocrea/Trichoderma species is adapted to soil as a habitat and that the interaction between these species should be considered in a screening for Hypocrea/Trichoderma as an agent(s) of biological control of pests. PMID:22075025

  15. Genomic and transcriptomic analyses reveal differential regulation of diverse terpenoid and polyketides secondary metabolites in Hericium erinaceus.

    Science.gov (United States)

    Chen, Juan; Zeng, Xu; Yang, Yan Long; Xing, Yong Mei; Zhang, Qi; Li, Jia Mei; Ma, Ke; Liu, Hong Wei; Guo, Shun Xing

    2017-08-31

    The lion's mane mushroom Hericium erinaceus is a famous traditional medicinal fungus credited with anti-dementia activity and a producer of cyathane diterpenoid natural products (erinacines) useful against nervous system diseases. To date, few studies have explored the biosynthesis of these compounds, although their chemical synthesis is known. Here, we report the first genome and tanscriptome sequence of the medicinal fungus H. erinaceus. The size of the genome is 39.35 Mb, containing 9895 gene models. The genome of H. erinaceus reveals diverse enzymes and a large family of cytochrome P450 (CYP) proteins involved in the biosynthesis of terpenoid backbones, diterpenoids, sesquiterpenes and polyketides. Three gene clusters related to terpene biosynthesis and one gene cluster for polyketides biosynthesis (PKS) were predicted. Genes involved in terpenoid biosynthesis were generally upregulated in mycelia, while the PKS gene was upregulated in the fruiting body. Comparative genome analysis of 42 fungal species of Basidiomycota revealed that most edible and medicinal mushroom show many more gene clusters involved in terpenoid and polyketide biosynthesis compared to the pathogenic fungi. None of the gene clusters for terpenoid or polyketide biosynthesis were predicted in the poisonous mushroom Amanita muscaria. Our findings may facilitate future discovery and biosynthesis of bioactive secondary metabolites from H. erinaceus and provide fundamental information for exploring the secondary metabolites in other Basidiomycetes.

  16. Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3

    KAUST Repository

    Schmidt, Angelika

    2018-04-27

    BackgroundRegulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood.ResultsTo gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by a targeted shRNA screen confirming a functional role in FOXP3 induction, discriminant analyses classifying iTregs accordingly, and comparable expression in an independent novel iTreg RNA-Seq dataset.ConclusionThe data generated by this novel approach facilitates understanding of the molecular mechanisms underlying iTreg generation as well as of the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune, and inflammatory diseases.

  17. The integrative omics of white-rot fungus Pycnoporus coccineus reveals co-regulated CAZymes for orchestrated lignocellulose breakdown.

    Directory of Open Access Journals (Sweden)

    Shingo Miyauchi

    Full Text Available Innovative green technologies are of importance for converting plant wastes into renewable sources for materials, chemicals and energy. However, recycling agricultural and forestry wastes is a challenge. A solution may be found in the forest. Saprotrophic white-rot fungi are able to convert dead plants into consumable carbon sources. Specialized fungal enzymes can be utilized for breaking down hard plant biopolymers. Thus, understanding the enzymatic machineries of such fungi gives us hints for the efficient decomposition of plant materials. Using the saprotrophic white-rot fungus Pycnoporus coccineus as a fungal model, we examined the dynamics of transcriptomic and secretomic responses to different types of lignocellulosic substrates at two time points. Our integrative omics pipeline (SHIN+GO enabled us to compress layers of biological information into simple heatmaps, allowing for visual inspection of the data. We identified co-regulated genes with corresponding co-secreted enzymes, and the biological roles were extrapolated with the enriched Carbohydrate-Active Enzyme (CAZymes and functional annotations. We observed the fungal early responses for the degradation of lignocellulosic substrates including; 1 simultaneous expression of CAZy genes and secretion of the enzymes acting on diverse glycosidic bonds in cellulose, hemicelluloses and their side chains or lignin (i.e. hydrolases, esterases and oxido-reductases; 2 the key role of lytic polysaccharide monooxygenases (LPMO; 3 the early transcriptional regulation of lignin active peroxidases; 4 the induction of detoxification processes dealing with biomass-derived compounds; and 5 the frequent attachments of the carbohydrate binding module 1 (CBM1 to enzymes from the lignocellulose-responsive genes. Our omics combining methods and related biological findings may contribute to the knowledge of fungal systems biology and facilitate the optimization of fungal enzyme cocktails for various

  18. Regulation of apoptotic mediators reveals dynamic responses to thermal stress in the reef building coral Acropora millepora.

    Science.gov (United States)

    Pernice, Mathieu; Dunn, Simon R; Miard, Thomas; Dufour, Sylvie; Dove, Sophie; Hoegh-Guldberg, Ove

    2011-01-24

    Mass coral bleaching is increasing in scale and frequency across the world's coral reefs and is being driven primarily by increased levels of thermal stress arising from global warming. In order to understand the impacts of projected climate change upon corals reefs, it is important to elucidate the underlying cellular mechanisms that operate during coral bleaching and subsequent mortality. In this respect, increased apoptotic cell death activity is an important cellular process that is associated with the breakdown of the mutualistic symbiosis between the cnidarian host and their dinoflagellate symbionts. The PRESENT study reports the impacts of different stressors (colchicine and heat stress) on three phases of apoptosis: (i) the potential initiation by differential expression of Bcl-2 members, (ii) the execution of apoptotic events by activation of caspase 3-like proteases and (iii) and finally, the cell disposal indicated by DNA fragmentation in the reef building coral Acropora millepora. In corals incubated with colchicine, an increase in caspase 3-like activity and DNA fragmentation was associated with a relative down-regulation of Bcl-2, suggesting that the initiation of apoptosis may be mediated by the suppression of an anti-apoptotic mechanism. In contrast, in the early steps of heat stress, the induction of caspase-dependent apoptosis was related to a relative up-regulation of Bcl-2 consecutively followed by a delayed decrease in apoptosis activity. In the light of these results, we propose a model of heat stress in coral hosts whereby increasing temperatures engage activation of caspase 3-dependent apoptosis in cells designated for termination, but also the onset of a delayed protective response involving overexpression of Bcl-2 in surviving cells. This mitigating response to thermal stress could conceivably be an important regulatory mechanism for cell survival in corals exposed to sudden environmental changes.

  19. Regulation of apoptotic mediators reveals dynamic responses to thermal stress in the reef building coral Acropora millepora.

    Directory of Open Access Journals (Sweden)

    Mathieu Pernice

    2011-01-01

    Full Text Available Mass coral bleaching is increasing in scale and frequency across the world's coral reefs and is being driven primarily by increased levels of thermal stress arising from global warming. In order to understand the impacts of projected climate change upon corals reefs, it is important to elucidate the underlying cellular mechanisms that operate during coral bleaching and subsequent mortality. In this respect, increased apoptotic cell death activity is an important cellular process that is associated with the breakdown of the mutualistic symbiosis between the cnidarian host and their dinoflagellate symbionts.The PRESENT study reports the impacts of different stressors (colchicine and heat stress on three phases of apoptosis: (i the potential initiation by differential expression of Bcl-2 members, (ii the execution of apoptotic events by activation of caspase 3-like proteases and (iii and finally, the cell disposal indicated by DNA fragmentation in the reef building coral Acropora millepora. In corals incubated with colchicine, an increase in caspase 3-like activity and DNA fragmentation was associated with a relative down-regulation of Bcl-2, suggesting that the initiation of apoptosis may be mediated by the suppression of an anti-apoptotic mechanism. In contrast, in the early steps of heat stress, the induction of caspase-dependent apoptosis was related to a relative up-regulation of Bcl-2 consecutively followed by a delayed decrease in apoptosis activity.In the light of these results, we propose a model of heat stress in coral hosts whereby increasing temperatures engage activation of caspase 3-dependent apoptosis in cells designated for termination, but also the onset of a delayed protective response involving overexpression of Bcl-2 in surviving cells. This mitigating response to thermal stress could conceivably be an important regulatory mechanism for cell survival in corals exposed to sudden environmental changes.

  20. Modeling the effector - regulatory T cell cross-regulation reveals the intrinsic character of relapses in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Torrealdea Javier

    2011-07-01

    Full Text Available Abstract Background The relapsing-remitting dynamics is a hallmark of autoimmune diseases such as Multiple Sclerosis (MS. Although current understanding of both cellular and molecular mechanisms involved in the pathogenesis of autoimmune diseases is significant, how their activity generates this prototypical dynamics is not understood yet. In order to gain insight about the mechanisms that drive these relapsing-remitting dynamics, we developed a computational model using such biological knowledge. We hypothesized that the relapsing dynamics in autoimmunity can arise through the failure in the mechanisms controlling cross-regulation between regulatory and effector T cells with the interplay of stochastic events (e.g. failure in central tolerance, activation by pathogens that are able to trigger the immune system. Results The model represents five concepts: central tolerance (T-cell generation by the thymus, T-cell activation, T-cell memory, cross-regulation (negative feedback between regulatory and effector T-cells and tissue damage. We enriched the model with reversible and irreversible tissue damage, which aims to provide a comprehensible link between autoimmune activity and clinical relapses and active lesions in the magnetic resonances studies in patients with Multiple Sclerosis. Our analysis shows that the weakness in this negative feedback between effector and regulatory T-cells, allows the immune system to generate the characteristic relapsing-remitting dynamics of autoimmune diseases, without the need of additional environmental triggers. The simulations show that the timing at which relapses appear is highly unpredictable. We also introduced targeted perturbations into the model that mimicked immunotherapies that modulate effector and regulatory populations. The effects of such therapies happened to be highly dependent on the timing and/or dose, and on the underlying dynamic of the immune system. Conclusion The relapsing dynamic in MS

  1. BY FRUSTUM CONFINING VESSEL

    Directory of Open Access Journals (Sweden)

    Javad Khazaei

    2016-09-01

    Full Text Available Helical piles are environmentally friendly and economical deep foundations that, due to environmental considerations, are excellent additions to a variety of deep foundation alternatives available to the practitioner. Helical piles performance depends on soil properties, the pile geometry and soil-pile interaction. Helical piles can be a proper alternative in sensitive environmental sites if their bearing capacity is sufficient to support applied loads. The failure capacity of helical piles in this study was measured via an experimental research program that was carried out by Frustum Confining Vessel (FCV. FCV is a frustum chamber by approximately linear increase in vertical and lateral stresses along depth from top to bottom. Due to special geometry and applied bottom pressure, this apparatus is a proper choice to test small model piles which can simulate field stress conditions. Small scale helical piles are made with either single helix or more helixes and installed in fine grained sand with three various densities. Axial loading tests including compression and tension tests were performed to achieve pile ultimate capacity. The results indicate the helical piles behavior depends essentially on pile geometric characteristics, i.e. helix configuration and soil properties. According to the achievements, axial uplift capacity of helical model piles is about equal to usual steel model piles that have the helixes diameter. Helical pile compression bearing capacity is too sufficient to act as a medium pile, thus it can be substituted other piles in special geoenvironmental conditions. The bearing capacity also depends on spacing ratio, S/D, and helixes diameter.

  2. Characterization of the polyphenol oxidase gene family reveals a novel microRNA involved in posttranscriptional regulation of PPOs in Salvia miltiorrhiza.

    Science.gov (United States)

    Li, Caili; Li, Dongqiao; Li, Jiang; Shao, Fenjuan; Lu, Shanfa

    2017-03-17

    Salvia miltiorrhiza is a well-known material of traditional Chinese medicine. Understanding the regulatory mechanisms of phenolic acid biosynthesis and metabolism are important for S. miltiorrhiza quality improvement. We report here that S. miltiorrhiza contains 19 polyphenol oxidases (PPOs), forming the largest PPO gene family in plant species to our knowledge. Analysis of gene structures and sequence features revealed the conservation and divergence of SmPPOs. SmPPOs were differentially expressed in plant tissues and eight of them were predominantly expressed in phloem and xylem, indicating that some SmPPOs are functionally redundant, whereas the others are associated with different physiological processes. Expression patterns of eighteen SmPPOs were significantly altered under MeJA treatment, and twelve were yeast extract and Ag + -responsive, suggesting the majority of SmPPOs are stress-responsive. Analysis of high-throughput small RNA sequences and degradome data showed that miR1444-mediated regulation of PPOs existing in P. trichocarpa is absent from S. miltiorrhiza. Instead, a subset of SmPPOs was posttranscriptionally regulated by a novel miRNA, termed Smi-miR12112. It indicates the specificity and significance of miRNA-mediated regulation of PPOs. The results shed light on the regulation of SmPPO expression and suggest the complexity of SmPPO-associated phenolic acid biosynthesis and metabolism.

  3. Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism

    Directory of Open Access Journals (Sweden)

    Roze Ludmila V

    2010-08-01

    Full Text Available Abstract Background Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. Results Volatile compounds were examined using solid phase microextraction - gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine; we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. Conclusions 1 Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2 VeA coordinates the

  4. Transgenic Analysis of the Leishmania MAP Kinase MPK10 Reveals an Auto-inhibitory Mechanism Crucial for Stage-Regulated Activity and Parasite Viability

    DEFF Research Database (Denmark)

    Cayla, M.; Rachidi, N.; Leclercq, O.

    2014-01-01

    Protozoan pathogens of the genus Leishmania have evolved unique signaling mechanisms that can sense changes in the host environment and trigger adaptive stage differentiation essential for host cell infection. The signaling mechanisms underlying parasite development remain largely elusive even...... though Leishmania mitogen-activated protein kinases (MAPKs) have been linked previously to environmentally induced differentiation and virulence. Here, we unravel highly unusual regulatory mechanisms for Leishmania MAP kinase 10 (MPK10). Using a transgenic approach, we demonstrate that MPK10 is stage...... at position 395 that could be implicated in kinase regulation. Finally, we uncovered a feedback loop that limits MPK10 activity through dephosphorylation of the tyrosine residue of the TxY motif. Together our data reveal novel aspects of protein kinase regulation in Leishmania, and propose MPK10...

  5. Expression profile analysis of aorta-gonad-mesonephros region-derived stromal cells reveals genes that regulate hematopoiesis

    International Nuclear Information System (INIS)

    Nagao, Kenji; Ohta, Takayuki; Hinohara, Atsushi; Tahara, Tomoyuki; Hagiwara, Tetsuya; Maeda, Yoshitake; Yoneya, Takashi; Sohma, Yoshiaki; Heike, Toshio; Nakahata, Tatsutoshi; Inagaki, Yoshimasa; Nishikawa, Mitsuo

    2008-01-01

    The aorta-gonad-mesonephros (AGM) region is involved in the generation and maintenance of the first definitive hematopoietic stem cells (HSCs). A mouse AGM-derived cell line, AGM-S3, was shown to support the development of HSCs. To elucidate the molecular mechanisms regulating early hematopoiesis, we obtained subclones from AGM-S3, one of which was hematopoiesis supportive (S3-A9) and the other one of which was non-supportive (S3-A7), and we analyzed their gene expression profiles by gene chip analysis. In the present study, we found that Glypican-1 (GPC1) was highly expressed in the supportive subclone AGM-S3-A9. Over-expression of GPC1 in non-supportive cells led to the proliferation of progenitor cells in human cord blood when cocultured with the transfected-stromal cells. Thus, GPC1 may have an important role in the establishment of a microenvironment that supports early events in hematopoiesis

  6. A survey of Type III restriction-modification systems reveals numerous, novel epigenetic regulators controlling phase-variable regulons; phasevarions

    Science.gov (United States)

    Atack, John M; Yang, Yuedong; Jennings, Michael P

    2018-01-01

    Abstract Many bacteria utilize simple DNA sequence repeats as a mechanism to randomly switch genes on and off. This process is called phase variation. Several phase-variable N6-adenine DNA-methyltransferases from Type III restriction-modification systems have been reported in bacterial pathogens. Random switching of DNA methyltransferases changes the global DNA methylation pattern, leading to changes in gene expression. These epigenetic regulatory systems are called phasevarions — phase-variable regulons. The extent of these phase-variable genes in the bacterial kingdom is unknown. Here, we interrogated a database of restriction-modification systems, REBASE, by searching for all simple DNA sequence repeats in mod genes that encode Type III N6-adenine DNA-methyltransferases. We report that 17.4% of Type III mod genes (662/3805) contain simple sequence repeats. Of these, only one-fifth have been previously identified. The newly discovered examples are widely distributed and include many examples in opportunistic pathogens as well as in environmental species. In many cases, multiple phasevarions exist in one genome, with examples of up to 4 independent phasevarions in some species. We found several new types of phase-variable mod genes, including the first example of a phase-variable methyltransferase in pathogenic Escherichia coli. Phasevarions are a common epigenetic regulation contingency strategy used by both pathogenic and non-pathogenic bacteria. PMID:29554328

  7. A Stochastic Model of the Yeast Cell Cycle Reveals Roles for Feedback Regulation in Limiting Cellular Variability.

    Science.gov (United States)

    Barik, Debashis; Ball, David A; Peccoud, Jean; Tyson, John J

    2016-12-01

    The cell division cycle of eukaryotes is governed by a complex network of cyclin-dependent protein kinases (CDKs) and auxiliary proteins that govern CDK activities. The control system must function reliably in the context of molecular noise that is inevitable in tiny yeast cells, because mistakes in sequencing cell cycle events are detrimental or fatal to the cell or its progeny. To assess the effects of noise on cell cycle progression requires not only extensive, quantitative, experimental measurements of cellular heterogeneity but also comprehensive, accurate, mathematical models of stochastic fluctuations in the CDK control system. In this paper we provide a stochastic model of the budding yeast cell cycle that accurately accounts for the variable phenotypes of wild-type cells and more than 20 mutant yeast strains simulated in different growth conditions. We specifically tested the role of feedback regulations mediated by G1- and SG2M-phase cyclins to minimize the noise in cell cycle progression. Details of the model are informed and tested by quantitative measurements (by fluorescence in situ hybridization) of the joint distributions of mRNA populations in yeast cells. We use the model to predict the phenotypes of ~30 mutant yeast strains that have not yet been characterized experimentally.

  8. A Stochastic Model of the Yeast Cell Cycle Reveals Roles for Feedback Regulation in Limiting Cellular Variability.

    Directory of Open Access Journals (Sweden)

    Debashis Barik

    2016-12-01

    Full Text Available The cell division cycle of eukaryotes is governed by a complex network of cyclin-dependent protein kinases (CDKs and auxiliary proteins that govern CDK activities. The control system must function reliably in the context of molecular noise that is inevitable in tiny yeast cells, because mistakes in sequencing cell cycle events are detrimental or fatal to the cell or its progeny. To assess the effects of noise on cell cycle progression requires not only extensive, quantitative, experimental measurements of cellular heterogeneity but also comprehensive, accurate, mathematical models of stochastic fluctuations in the CDK control system. In this paper we provide a stochastic model of the budding yeast cell cycle that accurately accounts for the variable phenotypes of wild-type cells and more than 20 mutant yeast strains simulated in different growth conditions. We specifically tested the role of feedback regulations mediated by G1- and SG2M-phase cyclins to minimize the noise in cell cycle progression. Details of the model are informed and tested by quantitative measurements (by fluorescence in situ hybridization of the joint distributions of mRNA populations in yeast cells. We use the model to predict the phenotypes of ~30 mutant yeast strains that have not yet been characterized experimentally.

  9. A genome-wide RNAi screen reveals MAP kinase phosphatases as key ERK pathway regulators during embryonic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Shen-Hsi Yang

    Full Text Available Embryonic stem cells and induced pluripotent stem cells represent potentially important therapeutic agents in regenerative medicine. Complex interlinked transcriptional and signaling networks control the fate of these cells towards maintenance of pluripotency or differentiation. In this study we have focused on how mouse embryonic stem cells begin to differentiate and lose pluripotency and, in particular, the role that the ERK MAP kinase and GSK3 signaling pathways play in this process. Through a genome-wide siRNA screen we have identified more than 400 genes involved in loss of pluripotency and promoting the onset of differentiation. These genes were functionally associated with the ERK and/or GSK3 pathways, providing an important resource for studying the roles of these pathways in controlling escape from the pluripotent ground state. More detailed analysis identified MAP kinase phosphatases as a focal point of regulation and demonstrated an important role for these enzymes in controlling ERK activation kinetics and subsequently determining early embryonic stem cell fate decisions.

  10. A Global Analysis of Kinase Function in Candida albicans Hyphal Morphogenesis Reveals a Role for the Endocytosis Regulator Akl1

    Directory of Open Access Journals (Sweden)

    Hagit Bar-Yosef

    2018-02-01

    Full Text Available The human pathogenic fungus Candida albicans can switch between yeast and hyphal morphologies as a function of environmental conditions and cellular physiology. The yeast-to-hyphae morphogenetic switch is activated by well-established, kinase-based signal transduction pathways that are induced by extracellular stimuli. In order to identify possible inhibitory pathways of the yeast-to-hyphae transition, we interrogated a collection of C. albicans protein kinases and phosphatases ectopically expressed under the regulation of the TETon promoter. Proportionately more phosphatases than kinases were identified that inhibited hyphal morphogenesis, consistent with the known role of protein phosphorylation in hyphal induction. Among the kinases, we identified AKL1 as a gene that significantly suppressed hyphal morphogenesis in serum. Akl1 specifically affected hyphal elongation rather than initiation: overexpression of AKL1 repressed hyphal growth, and deletion of AKL1 resulted in acceleration of the rate of hyphal elongation. Akl1 suppressed fluid-phase endocytosis, probably via Pan1, a putative clathrin-mediated endocytosis scaffolding protein. In the absence of Akl1, the Pan1 patches were delocalized from the sub-apical region, and fluid-phase endocytosis was intensified. These results underscore the requirement of an active endocytic pathway for hyphal morphogenesis. Furthermore, these results suggest that under standard conditions, endocytosis is rate-limiting for hyphal elongation.

  11. A Global Analysis of Kinase Function in Candida albicans Hyphal Morphogenesis Reveals a Role for the Endocytosis Regulator Akl1.

    Science.gov (United States)

    Bar-Yosef, Hagit; Gildor, Tsvia; Ramírez-Zavala, Bernardo; Schmauch, Christian; Weissman, Ziva; Pinsky, Mariel; Naddaf, Rawi; Morschhäuser, Joachim; Arkowitz, Robert A; Kornitzer, Daniel

    2018-01-01

    The human pathogenic fungus Candida albicans can switch between yeast and hyphal morphologies as a function of environmental conditions and cellular physiology. The yeast-to-hyphae morphogenetic switch is activated by well-established, kinase-based signal transduction pathways that are induced by extracellular stimuli. In order to identify possible inhibitory pathways of the yeast-to-hyphae transition, we interrogated a collection of C. albicans protein kinases and phosphatases ectopically expressed under the regulation of the TETon promoter. Proportionately more phosphatases than kinases were identified that inhibited hyphal morphogenesis, consistent with the known role of protein phosphorylation in hyphal induction. Among the kinases, we identified AKL1 as a gene that significantly suppressed hyphal morphogenesis in serum. Akl1 specifically affected hyphal elongation rather than initiation: overexpression of AKL1 repressed hyphal growth, and deletion of AKL1 resulted in acceleration of the rate of hyphal elongation. Akl1 suppressed fluid-phase endocytosis, probably via Pan1, a putative clathrin-mediated endocytosis scaffolding protein. In the absence of Akl1, the Pan1 patches were delocalized from the sub-apical region, and fluid-phase endocytosis was intensified. These results underscore the requirement of an active endocytic pathway for hyphal morphogenesis. Furthermore, these results suggest that under standard conditions, endocytosis is rate-limiting for hyphal elongation.

  12. Crystal Structure of the CTP1L Endolysin Reveals How Its Activity Is Regulated by a Secondary Translation Product.

    Science.gov (United States)

    Dunne, Matthew; Leicht, Stefan; Krichel, Boris; Mertens, Haydyn D T; Thompson, Andrew; Krijgsveld, Jeroen; Svergun, Dmitri I; Gómez-Torres, Natalia; Garde, Sonia; Uetrecht, Charlotte; Narbad, Arjan; Mayer, Melinda J; Meijers, Rob

    2016-03-04

    Bacteriophages produce endolysins, which lyse the bacterial host cell to release newly produced virions. The timing of lysis is regulated and is thought to involve the activation of a molecular switch. We present a crystal structure of the activated endolysin CTP1L that targets Clostridium tyrobutyricum, consisting of a complex between the full-length protein and an N-terminally truncated C-terminal cell wall binding domain (CBD). The truncated CBD is produced through an internal translation start site within the endolysin gene. Mutants affecting the internal translation site change the oligomeric state of the endolysin and reduce lytic activity. The activity can be modulated by reconstitution of the full-length endolysin-CBD complex with free CBD. The same oligomerization mechanism applies to the CD27L endolysin that targets Clostridium difficile and the CS74L endolysin that targets Clostridium sporogenes. When the CTP1L endolysin gene is introduced into the commensal bacterium Lactococcus lactis, the truncated CBD is also produced, showing that the alternative start codon can be used in other bacterial species. The identification of a translational switch affecting oligomerization presented here has implications for the design of effective endolysins for the treatment of bacterial infections. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Tandem mirror plasma confinement apparatus

    International Nuclear Information System (INIS)

    Fowler, T.K.

    1978-01-01

    Apparatus and method are described for confining a plasma in a center mirror cell by use of two end mirror cells as positively charged end stoppers to minimize leakage of positive particles from the ends of the center mirror cell

  14. Tandem mirror plasma confinement apparatus

    Science.gov (United States)

    Fowler, T. Kenneth

    1978-11-14

    Apparatus and method for confining a plasma in a center mirror cell by use of two end mirror cells as positively charged end stoppers to minimize leakage of positive particles from the ends of the center mirror cell.

  15. Alternate fusion -- continuous inertial confinement

    International Nuclear Information System (INIS)

    Barnes, D.C.; Turner, L.; Nebel, R.A.

    1993-01-01

    The authors argue that alternate approaches to large tokamak confinement are appropriate for fusion applications if: (1) They do not require magnetic confinement of a much higher quality than demonstrated in tokamaks; (2) Their physics basis may be succinctly stated and experimentally tested; (3) They offer near-term applications to important technical problems; and (4) Their cost to proof-of-principle is low enough to be consistent with current budget realities. An approach satisfying all of these criteria is presented. Fusion systems based on continuous inertial confinement are described. In these approaches, the inertia of a nonequilibrium plasma is used to produce local concentrations of plasma density in space and/or time. One implementation (inertial electrostatic confinement) which has been investigated both experimentally and theoretically uses a system of electrostatic grids to accelerate plasma ions toward a spherical focus. This system produced a steady 2 x 10 10 D-T neutrons/second with an overall fusion gain of 10 -5 in a sphere of about 9 cm radius. Recent theoretical developments show how to raise the fusion gain to order unity or greater by replacing the internal grids by a combination of applied magnetic and electrostatic fields. In these approaches, useful thermonuclear conditions may be produced in a system as small as a few mm radius. Confinement is that of a nonneutralized plasma. A pure electron plasma with a radial beam velocity distribution is absolutely confined by an applied Penning trap field. Spherical convergence of the confined electrons forms a deep virtual cathode near r = 0, in which thermonuclear ions are absolutely confined at useful densities. The authors have examined the equilibrium, stability, and classical relaxation of such systems, and obtained many positive physics results. Equilibria exist for both pure electron and partially charge-neutralized systems with arbitrarily high core-plasma densities

  16. Physics of inertial confinement pellets

    International Nuclear Information System (INIS)

    Mead, W.C.

    1979-01-01

    An overview of inertial confinement fusion pellet physics is given. A discussion is presented of current estimated ICF driver requirements and a couple of pellet examples. The physics of driver/plasma coupling for two drivers which are being considered, namely a laser driver and a heavy ion accelerator driver, is described. Progress towards inertial confinement fusion that has been made using laser drivers in target experiments to date is discussed

  17. Infrared slavery and quark confinement

    CERN Document Server

    Alabiso, C

    1976-01-01

    The question is considered of whether the so-called infrared slavery mechanism as, e.g., being manifest in non-Abelian gauge theories, necessarily confines quarks. Making a specific ansatz for the long- range forces, the Schwinger-Dyson equation is solved for the quark Green function. Besides having a confining solution, it appears that quarks may by-pass the long-range forces and be produced. (20 refs).

  18. Infrared slavery and quark confinement

    International Nuclear Information System (INIS)

    Alabiso, C.; Schierholz, G.

    1976-01-01

    The question of whether the so-called infrared slavery mechanism as, e.g., being manifest in non-Abelian gauge theories, necessarily confines quarks is posed. Making a specific ansatz for the long-range forces, the Schwinger-Dyson equation is solved for the quark Green function. Besides having a confining solution, it appears that quarks may by-pass the long-range forces and be produced. (Auth.)

  19. Magnetic well for plasma confinement

    International Nuclear Information System (INIS)

    Valfells, A.; Chiu, Y.C.

    1977-01-01

    A multipole magnetic well for plasma confinement includes a plurality of current-carrying coils placed on planes corresponding to the facets of a regular polyhedron that can be symmetrically circumscribed about a sphere. The direction of current in the coils is such as to minimize the flux density at the center of the polyhedron, thereby providing a confinement well with three-dimensional symmetry having an increasing flux density in all directions from the center. 16 claims, 18 figures

  20. Neutron spectroscopy for confinement studies

    International Nuclear Information System (INIS)

    Zorn, R.

    2010-01-01

    Neutron spectroscopy is an important method for the study of microscopic dynamics because it captures the spatial as well as the temporal aspects of the atomic or molecular motion. In this article techniques will be presented which are of special importance for the study of confined systems. Many of these are based on the fact that neutron scattering is isotope-dependent. Possible sources of systematic errors in measurements of confined systems will be pointed out. (author)

  1. Autophagy regulation revealed by SapM-induced block of autophagosome-lysosome fusion via binding RAB7

    International Nuclear Information System (INIS)

    Hu, Dong; Wu, Jing; Wang, Wan; Mu, Min; Zhao, Runpeng; Xu, Xuewei; Chen, Zhaoquan; Xiao, Jian; Hu, Fengyu; Yang, Yabo; Zhang, Rongbo

    2015-01-01

    The mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. Our previous study shows LpqH, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. It is well known that SapM, another virulence factor, plays an important role in blocking phagosome-endosome fusion. However, the mechanism that SapM interferes with autophagy remains poorly defined. In this study, we report that SapM suppresses the autophagy flux by blocking autophagosome fusion with lysosome. Exposure to SapM results in accumulations of autophagosomes and decreased co-localization of autophagosome with lysosome. Molecularly, Rab7, a small GTPase, is blocked by SapM through its CT domain and is prevented from involvement of autophagosome-lysosome fusion. In conclusion, our study reveals that SapM takes Rab7 as a previously unknown target to govern a distinct molecular mechanism underlying autophagosome-lysosome fusion, which may bring light to a new thought about developing potential drugs or vaccines against tuberculosis. - Highlights: • A mechanism for disrupting autophagosome-lysosome fusion induced by SapM. • Rab7 is involved in SapM-inhibited autophagy. • SapM interacts with Rab7 by CT-domain. • CT-domain is indispensable to SapM-inhibited autophagy

  2. Autophagy regulation revealed by SapM-induced block of autophagosome-lysosome fusion via binding RAB7

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Dong, E-mail: austhudong@126.com [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China); Wu, Jing, E-mail: wujing8008@126.com [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China); Wang, Wan; Mu, Min; Zhao, Runpeng; Xu, Xuewei; Chen, Zhaoquan [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China); Xiao, Jian [School of Pharmacy, Wenzhou Medical College, Wenzhou (China); Hu, Fengyu; Yang, Yabo [Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou (China); Zhang, Rongbo, E-mail: lory456@126.com [Institute of Infection and Immunology, Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan (China)

    2015-05-29

    The mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. Our previous study shows LpqH, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. It is well known that SapM, another virulence factor, plays an important role in blocking phagosome-endosome fusion. However, the mechanism that SapM interferes with autophagy remains poorly defined. In this study, we report that SapM suppresses the autophagy flux by blocking autophagosome fusion with lysosome. Exposure to SapM results in accumulations of autophagosomes and decreased co-localization of autophagosome with lysosome. Molecularly, Rab7, a small GTPase, is blocked by SapM through its CT domain and is prevented from involvement of autophagosome-lysosome fusion. In conclusion, our study reveals that SapM takes Rab7 as a previously unknown target to govern a distinct molecular mechanism underlying autophagosome-lysosome fusion, which may bring light to a new thought about developing potential drugs or vaccines against tuberculosis. - Highlights: • A mechanism for disrupting autophagosome-lysosome fusion induced by SapM. • Rab7 is involved in SapM-inhibited autophagy. • SapM interacts with Rab7 by CT-domain. • CT-domain is indispensable to SapM-inhibited autophagy.

  3. A Nonlinear Dynamic Approach Reveals a Long-Term Stroke Effect on Cerebral Blood Flow Regulation at Multiple Time Scales

    Science.gov (United States)

    Hu, Kun; Lo, Men-Tzung; Peng, Chung-Kang; Liu, Yanhui; Novak, Vera

    2012-01-01

    Cerebral autoregulation (CA) is an important vascular control mechanism responsible for relatively stable cerebral blood flow despite changes of systemic blood pressure (BP). Impaired CA may leave brain tissue unprotected against potentially harmful effects of BP fluctuations. It is generally accepted that CA is less effective or even inactive at frequencies >∼0.1 Hz. Without any physiological foundation, this concept is based on studies that quantified the coupling between BP and cerebral blood flow velocity (BFV) using transfer function analysis. This traditional analysis assumes stationary oscillations with constant amplitude and period, and may be unreliable or even invalid for analysis of nonstationary BP and BFV signals. In this study we propose a novel computational tool for CA assessment that is based on nonlinear dynamic theory without the assumption of stationary signals. Using this method, we studied BP and BFV recordings collected from 39 patients with chronic ischemic infarctions and 40 age-matched non-stroke subjects during baseline resting conditions. The active CA function in non-stroke subjects was associated with an advanced phase in BFV oscillations compared to BP oscillations at frequencies from ∼0.02 to 0.38 Hz. The phase shift was reduced in stroke patients even at > = 6 months after stroke, and the reduction was consistent at all tested frequencies and in both stroke and non-stroke hemispheres. These results provide strong evidence that CA may be active in a much wider frequency region than previously believed and that the altered multiscale CA in different vascular territories following stroke may have important clinical implications for post-stroke recovery. Moreover, the stroke effects on multiscale cerebral blood flow regulation could not be detected by transfer function analysis, suggesting that nonlinear approaches without the assumption of stationarity are more sensitive for the assessment of the coupling of nonstationary

  4. Genome-wide mRNA processing in methanogenic archaea reveals post-transcriptional regulation of ribosomal protein synthesis.

    Science.gov (United States)

    Qi, Lei; Yue, Lei; Feng, Deqin; Qi, Fengxia; Li, Jie; Dong, Xiuzhu

    2017-07-07

    Unlike stable RNAs that require processing for maturation, prokaryotic cellular mRNAs generally follow an 'all-or-none' pattern. Herein, we used a 5΄ monophosphate transcript sequencing (5΄P-seq) that specifically captured the 5΄-end of processed transcripts and mapped the genome-wide RNA processing sites (PSSs) in a methanogenic archaeon. Following statistical analysis and stringent filtration, we identified 1429 PSSs, among which 23.5% and 5.4% were located in 5΄ untranslated region (uPSS) and intergenic region (iPSS), respectively. A predominant uridine downstream PSSs served as a processing signature. Remarkably, 5΄P-seq detected overrepresented uPSS and iPSS in the polycistronic operons encoding ribosomal proteins, and the majority upstream and proximal ribosome binding sites, suggesting a regulatory role of processing on translation initiation. The processed transcripts showed increased stability and translation efficiency. Particularly, processing within the tricistronic transcript of rplA-rplJ-rplL enhanced the translation of rplL, which can provide a driving force for the 1:4 stoichiometry of L10 to L12 in the ribosome. Growth-associated mRNA processing intensities were also correlated with the cellular ribosomal protein levels, thereby suggesting that mRNA processing is involved in tuning growth-dependent ribosome synthesis. In conclusion, our findings suggest that mRNA processing-mediated post-transcriptional regulation is a potential mechanism of ribosomal protein synthesis and stoichiometry. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Structure of the cystic fibrosis transmembrane conductance regulator in the inward-facing conformation revealed by single particle electron microscopy

    Directory of Open Access Journals (Sweden)

    Ateeq Al-Zahrani

    2015-05-01

    Full Text Available The most common inherited disease in European populations is cystic fibrosis. Mutations in the gene lead to loss of function of the cystic fibrosis transmembrane conductance regulator protein (CFTR. CFTR is a member of the ATP-binding cassette family of membrane proteins that mostly act as active transporters using ATP to move substances across membranes. These proteins undergo large conformational changes during the transport cycle, consistent with an inward-facing to outward-facing translocation mechanism that was originally proposed by Jardetzky. CFTR is the only member of this family of proteins that functions as an ion channel, and in this case ATP and phosphorylation of a regulatory domain controls the opening of the channel. In this article we describe the inward-facing conformation of the protein and show it can be modulated by the presence of a purified recombinant NHERF1-PDZ1 domain that binds with high affinity to the CFTR C-terminal PDZ motif (-QDTRL. ATP hydrolysis activity of CFTR can also be modulated by glutathione, which we postulate may bind to the inward-facing conformation of the protein. A homology model for CFTR, based on a mitochondrial ABC transporter of glutathione in the inward-facing configuration has been generated. The map and the model are discussed with respect to the biology of the channel and the specific relationship between glutathione levels in the cell and CFTR. Finally, disease-causing mutations are mapped within the model and discussed in terms of their likely physiological effects.

  6. Transcriptome Analysis of Ullrich Congenital Muscular Dystrophy Fibroblasts Reveals a Disease Extracellular Matrix Signature and Key Molecular Regulators.

    Directory of Open Access Journals (Sweden)

    Sonia Paco

    Full Text Available Collagen VI related myopathies encompass a range of phenotypes with involvement of skeletal muscle, skin and other connective tissues. They represent a severe and relatively common form of congenital disease for which there is no treatment. Collagen VI in skeletal muscle and skin is produced by fibroblasts.In order to gain insight into the consequences of collagen VI mutations and identify key disease pathways we performed global gene expression analysis of dermal fibroblasts from patients with Ullrich Congenital Muscular Dystrophy with and without vitamin C treatment. The expression data were integrated using a range of systems biology tools. Results were validated by real-time PCR, western blotting and functional assays.We found significant changes in the expression levels of almost 600 genes between collagen VI deficient and control fibroblasts. Highly regulated genes included extracellular matrix components and surface receptors, including integrins, indicating a shift in the interaction between the cell and its environment. This was accompanied by a significant increase in fibroblasts adhesion to laminin. The observed changes in gene expression profiling may be under the control of two miRNAs, miR-30c and miR-181a, which we found elevated in tissue and serum from patients and which could represent novel biomarkers for muscular dystrophy. Finally, the response to vitamin C of collagen VI mutated fibroblasts significantly differed from healthy fibroblasts. Vitamin C treatment was able to revert the expression of some key genes to levels found in control cells raising the possibility of a beneficial effect of vitamin C as a modulator of some of the pathological aspects of collagen VI related diseases.

  7. High throughput analysis reveals dissociable gene expression profiles in two independent neural systems involved in the regulation of social behavior

    Directory of Open Access Journals (Sweden)

    Stevenson Tyler J

    2012-10-01

    Full Text Available Abstract Background Production of contextually appropriate social behaviors involves integrated activity across many brain regions. Many songbird species produce complex vocalizations called ‘songs’ that serve to attract potential mates, defend territories, and/or maintain flock cohesion. There are a series of discrete interconnect brain regions that are essential for the successful production of song. The probability and intensity of singing behavior is influenced by the reproductive state. The objectives of this study were to examine the broad changes in gene expression in brain regions that control song production with a brain region that governs the reproductive state. Results We show using microarray cDNA analysis that two discrete brain systems that are both involved in governing singing behavior show markedly different gene expression profiles. We found that cortical and basal ganglia-like brain regions that control the socio-motor production of song in birds exhibit a categorical switch in gene expression that was dependent on their reproductive state. This pattern is in stark contrast to the pattern of expression observed in a hypothalamic brain region that governs the neuroendocrine control of reproduction. Subsequent gene ontology analysis revealed marked variation in the functional categories of active genes dependent on reproductive state and anatomical localization. HVC, one cortical-like structure, displayed significant gene expression changes associated with microtubule and neurofilament cytoskeleton organization, MAP kinase activity, and steroid hormone receptor complex activity. The transitions observed in the preoptic area, a nucleus that governs the motivation to engage in singing, exhibited variation in functional categories that included thyroid hormone receptor activity, epigenetic and angiogenetic processes. Conclusions These findings highlight the importance of considering the temporal patterns of gene expression

  8. Shifts in river-floodplain relationship reveal the impacts of river regulation: A case study of Dongting Lake in China

    Science.gov (United States)

    Lu, Cai; Jia, Yifei; Jing, Lei; Zeng, Qing; Lei, Jialin; Zhang, Shuanghu; Lei, Guangchun; Wen, Li

    2018-04-01

    Better understanding of the dynamics of hydrological connectivity between river and floodplain is essential for the ecological integrity of river systems. In this study, we proposed a regime-switch modelling (RSM) framework, which integrates change point analysis with dynamic linear regression, to detect and date change points in linear regression, and to quantify the relative importance of natural variations and anthropogenic disturbances. The approach was applied to the long-term hydrological time series to investigate the evolution of river-floodplain relation in Dongting Lake in the last five decades, during which the Yangtze River system experienced unprecedented anthropogenic manipulations. Our results suggested that 1) there were five distinct regimes during which the influence of inflows and local climate on lake water level changed significantly. The detected change points were well corresponding to the major events occurred upon the Yangtze; 2) although the importance of inflows from the Yangtze was greater than that of the tributaries flows over the five regimes, the relative contribution gradually decreased from regime 1 to regime 5. The weakening of hydrological forcing from the Yangtze was mainly attributed to the reduction in channel capacity resulting from sedimentation in the outfalls and water level dropping caused by river bed scour in the mainstream; 3) the effects of local climate was much smaller than these of inflows; and 4) since the operation of The Three Gorges Dam in 2006, the river-floodplain relationship entered a new equilibrium in that all investigated variables changed synchronously in terms of direction and magnitude. The results from this study reveal the mechanisms underlying the alternated inundation regime in Dongting Lake. The identified change points, some of which have not been previously reported, will allow a reappraisal of the current dam and reservoir operation strategies not only for flood/drought risk management but

  9. Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer.

    Directory of Open Access Journals (Sweden)

    Dogus Murat Altintas

    Full Text Available BACKGROUND: Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa among androgen-regulated genes (ARG and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely give rise to cancer. METHODS: ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1. RESULTS AND DISCUSSION: By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91 and DLX1 (0.94. CONCLUSIONS: We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could

  10. Structural variations in nanosized confined gallium

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Min Kai [Department of Physics, National Cheng Kung University, Tainan 70101, Taiwan (China); Tien Cheng [Department of Physics, National Cheng Kung University, Tainan 70101, Taiwan (China)] [Center for Micro/Nano Science of Technology, National Cheng Kung University, Tainan 70101, Taiwan, ROC (China); Charnaya, E.V., E-mail: charnaya@live.co [Department of Physics, National Cheng Kung University, Tainan 70101, Taiwan (China)] [Institute of Physics, St. Petersburg State University, St. Petersburg, Petrodvorets 198504 (Russian Federation); Sheu, Hwo-Shuenn [National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan (China); Kumzerov, Yu.A. [A.F. Ioffe Physico-Technical Institute RAS, St. Petersburg, 194021 (Russian Federation)

    2010-03-29

    The complex crystalline structure of gallium under nanoconfinement was revealed by synchrotron radiation x-ray powder diffraction. Nanoconfinement was shown to stabilize delta-Ga which is metastable in bulk. Two new gallium phases named iota- and kappa-Ga were found upon cooling below room temperature. These crystalline modifications were stable and coexisted with known gallium phases. Correlations between confined gallium particle shapes and emergence of particular crystalline phases were observed. Melting and freezing temperatures for different gallium phases were obtained. Remarkable supercooling of liquid gallium was seen in 3.5 nm pores.

  11. A Review of Quantum Confinement

    Science.gov (United States)

    Connerade, Jean-Patrick

    2009-12-01

    A succinct history of the Confined Atom problem is presented. The hydrogen atom confined to the centre of an impenetrable sphere counts amongst the exactly soluble problems of physics, alongside much more noted exact solutions such as Black Body Radiation and the free Hydrogen atom in absence of any radiation field. It shares with them the disadvantage of being an idealisation, while at the same time encapsulating in a simple way particular aspects of physical reality. The problem was first formulated by Sommerfeld and Welker [1]—henceforth cited as SW—in connection with the behaviour of atoms at very high pressures, and the solution was published on the occasion of Pauli's 60th birthday celebration. At the time, it seemed that there was not much other connection with physical reality beyond a few simple aspects connected to the properties of atoms in solids, for which more appropriate models were soon developed. Thus, confined atoms attracted little attention until the advent of the metallofullerene, which provided the first example of a confined atom with properties quite closely related to those originally considered by SW. Since then, the problem has received much more attention, and many more new features of quantum confinement, quantum compression, the quantum Faraday cage, electronic reorganisation, cavity resonances, etc have been described, which are relevant to real systems. Also, a number of other situations have been uncovered experimentally to which quantum confinement is relevant. Thus, studies of the confined atom are now more numerous, and have been extended both in terms of the models used and the systems to which they can be applied. Connections to thermodynamics are explored through the properties of a confined two-level atom adapted from Einstein's celebrated model, and issues of dynamical screening of electromagnetic radiation by the confining shell are discussed in connection with the Faraday cage produced by a confining conducting shell

  12. A Review of Quantum Confinement

    International Nuclear Information System (INIS)

    Connerade, Jean-Patrick

    2009-01-01

    A succinct history of the Confined Atom problem is presented. The hydrogen atom confined to the centre of an impenetrable sphere counts amongst the exactly soluble problems of physics, alongside much more noted exact solutions such as Black Body Radiation and the free Hydrogen atom in absence of any radiation field. It shares with them the disadvantage of being an idealisation, while at the same time encapsulating in a simple way particular aspects of physical reality. The problem was first formulated by Sommerfeld and Welker - henceforth cited as SW - in connection with the behaviour of atoms at very high pressures, and the solution was published on the occasion of Pauli's 60th birthday celebration. At the time, it seemed that there was not much other connection with physical reality beyond a few simple aspects connected to the properties of atoms in solids, for which more appropriate models were soon developed. Thus, confined atoms attracted little attention until the advent of the metallofullerene, which provided the first example of a confined atom with properties quite closely related to those originally considered by SW. Since then, the problem has received much more attention, and many more new features of quantum confinement, quantum compression, the quantum Faraday cage, electronic reorganisation, cavity resonances, etc have been described, which are relevant to real systems. Also, a number of other situations have been uncovered experimentally to which quantum confinement is relevant. Thus, studies of the confined atom are now more numerous, and have been extended both in terms of the models used and the systems to which they can be applied. Connections to thermodynamics are explored through the properties of a confined two-level atom adapted from Einstein's celebrated model, and issues of dynamical screening of electromagnetic radiation by the confining shell are discussed in connection with the Faraday cage produced by a confining conducting shell. The

  13. The structure of the first representative of Pfam family PF09836 reveals a two-domain organization and suggests involvement in transcriptional regulation

    International Nuclear Information System (INIS)

    Das, Debanu; Grishin, Nick V.; Kumar, Abhinav; Carlton, Dennis; Bakolitsa, Constantina; Miller, Mitchell D.; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Burra, Prasad; Chen, Connie; Chiu, Hsiu-Ju; Chiu, Michelle; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Ellrott, Kyle; Ernst, Dustin; Farr, Carol L.; Feuerhelm, Julie; Grzechnik, Anna; Grzechnik, Slawomir K.; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Johnson, Hope A.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Oommachen, Silvya; Paulsen, Jessica; Puckett, Christina; Reyes, Ron; Rife, Christopher L.; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; Bedem, Henry van den; Weekes, Dana; Wooten, Tiffany; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2009-01-01

    The crystal structure of the NGO1945 gene product from N. gonorrhoeae (UniProt Q5F5IO) reveals that the N-terminal domain assigned as a domain of unknown function (DUF2063) is likely to bind DNA and that the protein may be involved in transcriptional regulation. Proteins with the DUF2063 domain constitute a new Pfam family, PF09836. The crystal structure of a member of this family, NGO1945 from Neisseria gonorrhoeae, has been determined and reveals that the N-terminal DUF2063 domain is likely to be a DNA-binding domain. In conjunction with the rest of the protein, NGO1945 is likely to be involved in transcriptional regulation, which is consistent with genomic neighborhood analysis. Of the 216 currently known proteins that contain a DUF2063 domain, the most significant sequence homologs of NGO1945 (∼40–99% sequence identity) are from various Neisseria and Haemophilus species. As these are important human pathogens, NGO1945 represents an interesting candidate for further exploration via biochemical studies and possible therapeutic intervention

  14. The regulation mechanisms of soluble starch and glycerol for production of azaphilone pigments in Monascus purpureus FAFU618 as revealed by comparative proteomic and transcriptional analyses.

    Science.gov (United States)

    Huang, Zi-Rui; Zhou, Wen-Bin; Yang, Xue-Ling; Tong, Ai-Jun; Hong, Jia-Li; Guo, Wei-Ling; Li, Tian-Tian; Jia, Rui-Bo; Pan, Yu-Yang; Lin, Jun; Lv, Xu-Cong; Liu, Bin

    2018-04-01

    Monascus spp. have been used for thousands of years as a traditional food additive in China. This mold can produce many different types of commercially valuable secondary metabolites of biological activity. Soluble starch and glycerol are the two principal carbon sources universally utilized by Monascus for the production of beneficial metabolites. In this study, the effects and regulation mechanisms of soluble starch and glycerol for M. purpureus FAFU618 on Monascus azaphilone pigments (MonAzPs) were investigated through ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS/MS), comparative proteomics and quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR). The production of intracellular and extracellular pigments was significantly different between the soluble starch group (SSG) and glycerol group (GCG). Additionally, the components of intracellular pigments revealed by UPLC-QTOF-MS/MS showed that Monascin and Ankaflavin increased significantly in the GCG, while Rubropunctatin and Monascorubrin increased in the SSG. Differentially expressed proteins of mycelia between SSG and GCG were analyzed by two-dimensional gel electrophoresis (2-DE) and MALDI-TOF/TOF MS. We identified 27 proteins with statistically altered expression, of which 18 proteins associated with the EMP (glycolytic pathway), translation, energy generation, proteolysis, etc. were up-regulated, and 9 proteins, including ribosomal proteins, heat shock proteins (HSPs) and others, were down-regulated in GCG. Meanwhile, the expression levels of MonAzP biosynthetic genes were also analyzed by RT-qPCR, and the results showed that mppA, mppC, mppR1 and mppR2 were down-regulated, whereas genes MpPKS5, MpFasA2, MpFasB2, mppB, mppD and mppE were up-regulated. Collectively, these findings illustrate that the regulation of MonAzPs is not only closely related to the expression levels of certain proteins in the polyketide synthesis pathway

  15. Monopoles, vortices, and confinement

    International Nuclear Information System (INIS)

    Mack, G.; Pietarinen, E.

    1981-10-01

    An exact relation is established between an SO(3) lattice gauge theory model without monopoles, and a corresponding SU(2) model. Elimination of the monopoles (and their strings) leads to a substantial lowering of the entropy of thin vortices and a corresponding decrease of the string tension for low γ. This is revealed by approximate calculations of the vortex free energy and is confirmed by Monte Carlo data. The value of the physical transition temperature to 'hot gluon soup' is also lowered considerably. (orig.)

  16. Transcriptome analysis reveals differences in mechanisms regulating cessation of luteal function in pregnant and non-pregnant dogs.

    Science.gov (United States)

    Zatta, Sophie; Rehrauer, Hubert; Gram, Aykut; Boos, Alois; Kowalewski, Mariusz Pawel

    2017-09-27

    In the domestic dog, corpora lutea (CL) are the only source of progesterone (P4), both in pregnant and non-pregnant cycles because there is no placental steroidogenesis. The absence of an endogenous luteolysin in absence of pregnancy results in long-lasting physiological pseudopregnancy, strongly contrasting with the acute luteolysis observed prepartum. The underlying biological mechanisms and the involvement of P4 signalling remain, however, not fully understood. Therefore, here, next-generation sequencing (RNA-Seq) was performed on CL from the late luteal phase and compared with normally luteolyzing CL collected at the prepartum P4 decrease. The contrast "luteal regression over luteolysis" yielded 1595 differentially expressed genes (DEG). The CL in late luteal regression were predominantly associated with functional terms linked to extracellular matrix (p = 5.52e-05). Other terms related to transcriptional activity (p = 2.45e-04), and steroid hormone signalling (p = 2.29e-04), which were more highly represented in late regression than during luteolysis. The prepartum luteolysis was associated with immune inflammatory responses (p = 2.87e-14), including acute-phase reaction (p = 4.10e-06). Immune system-related events were also more highly represented in CL derived from normal luteolysis (p = 7.02e-04), compared with those from dogs in which luteolysis was induced with an antigestagen (1480 DEG in total). Additionally, the withdrawal of P4 at mid-gestation resulted in 92 DEG; over-represented terms enriched in antigestagen-treated dogs were related to the inflammatory response (p = 0.005) or response to IL1 (p = 7.29e-05). Terms related to proliferation, e.g., centrosome organization (p = 0.002) and steroid metabolic processes (p = 0.001), prevailed at mid-gestation. Thereby, our results revealed the nature of luteotropic effects of P4 within canine CL. It appears that, even though they result in diminished steroidogenic output, the effect of

  17. Peptide microarray analysis of substrate specificity of the transmembrane Ser/Thr kinase KPI-2 reveals reactivity with cystic fibrosis transmembrane conductance regulator and phosphorylase.

    Science.gov (United States)

    Wang, Hong; Brautigan, David L

    2006-11-01

    Human lemur (Lmr) kinases are predicted to be Tyr kinases based on sequences and are related to neurotrophin receptor Trk kinases. This study used homogeneous recombinant KPI-2 (Lmr2, LMTK2, Cprk, brain-enriched protein kinase) kinase domain and a library of 1,154 peptides on a microarray to analyze substrate specificity. We found that KPI-2 is strictly a Ser/Thr kinase that reacts with Ser either preceded by or followed by Pro residues but unlike other Pro-directed kinases does not strictly require an adjacent Pro residue. The most reactive peptide in the library corresponds to Ser-737 of cystic fibrosis transmembrane conductance regulator, and the recombinant R domain of cystic fibrosis transmembrane conductance regulator was a preferred substrate. Furthermore the KPI-2 kinase phosphorylated peptides corresponding to the single site in phosphorylase and purified phosphorylase b, making this only the second known phosphorylase b kinase. Phosphorylase was used as a specific substrate to show that KPI-2 is inhibited in living cells by addition of nerve growth factor or serum. The results demonstrate the utility of the peptide library to probe specificity and discover kinase substrates and offer a specific assay that reveals hormonal regulation of the activity of this unusual transmembrane kinase.

  18. A systems biology approach reveals that tissue tropism to West Nile virus is regulated by antiviral genes and innate immune cellular processes.

    Directory of Open Access Journals (Sweden)

    Mehul S Suthar

    2013-02-01

    Full Text Available The actions of the RIG-I like receptor (RLR and type I interferon (IFN signaling pathways are essential for a protective innate immune response against the emerging flavivirus West Nile virus (WNV. In mice lacking RLR or IFN signaling pathways, WNV exhibits enhanced tissue tropism, indicating that specific host factors of innate immune defense restrict WNV infection and dissemination in peripheral tissues. However, the immune mechanisms by which the RLR and IFN pathways coordinate and function to impart restriction of WNV infection are not well defined. Using a systems biology approach, we defined the host innate immune response signature and actions that restrict WNV tissue tropism. Transcriptional profiling and pathway modeling to compare WNV-infected permissive (spleen and nonpermissive (liver tissues showed high enrichment for inflammatory responses, including pattern recognition receptors and IFN signaling pathways, that define restriction of WNV replication in the liver. Assessment of infected livers from Mavs(-/- × Ifnar(-/- mice revealed the loss of expression of several key components within the natural killer (NK cell signaling pathway, including genes associated with NK cell activation, inflammatory cytokine production, and NK cell receptor signaling. In vivo analysis of hepatic immune cell infiltrates from WT mice demonstrated that WNV infection leads to an increase in NK cell numbers with enhanced proliferation, maturation, and effector action. In contrast, livers from Mavs(-/- × Ifnar(-/- infected mice displayed reduced immune cell infiltration, including a significant reduction in NK cell numbers. Analysis of cocultures of dendritic and NK cells revealed both cell-intrinsic and -extrinsic roles for the RLR and IFN signaling pathways to regulate NK cell effector activity. Taken together, these observations reveal a complex innate immune signaling network, regulated by the RLR and IFN signaling pathways, that drives tissue

  19. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  20. Probing Leader Cells in Endothelial Collective Migration by Plasma Lithography Geometric Confinement.

    Science.gov (United States)

    Yang, Yongliang; Jamilpour, Nima; Yao, Baoyin; Dean, Zachary S; Riahi, Reza; Wong, Pak Kin

    2016-03-03

    When blood vessels are injured, leader cells emerge in the endothelium to heal the wound and restore the vasculature integrity. The characteristics of leader cells during endothelial collective migration under diverse physiological conditions, however, are poorly understood. Here we investigate the regulation and function of endothelial leader cells by plasma lithography geometric confinement generated. Endothelial leader cells display an aggressive phenotype, connect to follower cells via peripheral actin cables and discontinuous adherens junctions, and lead migrating clusters near the leading edge. Time-lapse microscopy, immunostaining, and particle image velocimetry reveal that the density of leader cells and the speed of migrating clusters are tightly regulated in a wide range of geometric patterns. By challenging the cells with converging, diverging and competing patterns, we show that the density of leader cells correlates with the size and coherence of the migrating clusters. Collectively, our data provide evidence that leader cells control endothelial collective migration by regualting the migrating clusters.

  1. 8 CFR 236.2 - Confined aliens, incompetents, and minors.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Confined aliens, incompetents, and minors. 236.2 Section 236.2 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS APPREHENSION AND DETENTION OF INADMISSIBLE AND DEPORTABLE ALIENS; REMOVAL OF ALIENS ORDERED REMOVED Detention...

  2. 8 CFR 1236.2 - Confined aliens, incompetents, and minors.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Confined aliens, incompetents, and minors. 1236.2 Section 1236.2 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE IMMIGRATION REGULATIONS APPREHENSION AND DETENTION OF INADMISSIBLE AND DEPORTABLE ALIENS; REMOVAL...

  3. Momentum confinement at low torque

    Energy Technology Data Exchange (ETDEWEB)

    Solomon, W M [Princeton Plasma Physics Laboratory, Princeton University, Princeton, NJ 08543 (United States); Burrell, K H [General Atomics, PO Box 85608, San Diego, CA 92186-5608 (United States); De Grassie, J S [General Atomics, PO Box 85608, San Diego, CA 92186-5608 (United States); Budny, R [Princeton Plasma Physics Laboratory, Princeton University, Princeton, NJ 08543 (United States); Groebner, R J [General Atomics, PO Box 85608, San Diego, CA 92186-5608 (United States); Kinsey, J E [General Atomics, PO Box 85608, San Diego, CA 92186-5608 (United States); Kramer, G J [Princeton Plasma Physics Laboratory, Princeton University, Princeton, NJ 08543 (United States); Luce, T C [General Atomics, PO Box 85608, San Diego, CA 92186-5608 (United States); Makowski, M A [Lawrence Livermore National Laboratory, Livermore, CA 94550 (United States); Mikkelsen, D [Princeton Plasma Physics Laboratory, Princeton University, Princeton, NJ 08543 (United States); Nazikian, R [Princeton Plasma Physics Laboratory, Princeton University, Princeton, NJ 08543 (United States); Petty, C C [General Atomics, PO Box 85608, San Diego, CA 92186-5608 (United States); Politzer, P A [General Atomics, PO Box 85608, San Diego, CA 92186-5608 (United States); Scott, S D [Princeton Plasma Physics Laboratory, Princeton University, Princeton, NJ 08543 (United States); Zeeland, M A Van [General Atomics, PO Box 85608, San Diego, CA 92186-5608 (United States); Zarnstorff, M C [Princeton Plasma Physics Laboratory, Princeton University, Princeton, NJ 08543 (United States)

    2007-12-15

    Momentum confinement was investigated on DIII-D as a function of applied neutral beam torque at constant normalized beta {beta}{sub N}, by varying the mix of co (parallel to the plasma current) and counter neutral beams. Under balanced neutral beam injection (i.e. zero total torque to the plasma), the plasma maintains a significant rotation in the co-direction. This 'intrinsic' rotation can be modeled as being due to an offset in the applied torque (i.e. an 'anomalous torque'). This anomalous torque appears to have a magnitude comparable to one co neutral beam source. The presence of such an anomalous torque source must be taken into account to obtain meaningful quantities describing momentum transport, such as the global momentum confinement time and local diffusivities. Studies of the mechanical angular momentum in ELMing H-mode plasmas with elevated q{sub min} show that the momentum confinement time improves as the torque is reduced. In hybrid plasmas, the opposite effect is observed, namely that momentum confinement improves at high torque/rotation. GLF23 modeling suggests that the role of E x B shearing is quite different between the two plasmas, which may help to explain the different dependence of the momentum confinement on torque.

  4. Phenomenology and theory of confinement

    International Nuclear Information System (INIS)

    Pervushin, V.N.

    1987-01-01

    Phenomenological and theoretical arguments of the separation of the hadronization dynamics from confinement and the idea of the ''kinematic'' confinement are discussed. The recent theory contains results which point out that the Wilson criterion and the confinement potentials are not sufficient for explaining the phenomenological confinement in the sense of zero color amplitudes or Green functions. However, these potentials well explain the hadron spectrum and spontaneous breaking of chiral symmetry, i.e., the hadronization dynamics. The ''kinematic'' confinement can be explained by the topological degeneration of all color-particle physical states in QCD. This degeneration arises if the theory is quantized by explicitly solving the gauge and dynamic constraints: all color states are defined up to gauge(phase) factors describing the map of the three-dimensional space onto SU(3) c -group (π 3 (SU(3) c =Z). The total probability of the color particle generation is equal to zero due to the destructive interference of these phase factors. As a result, in QCD there remains only a hadron sector used in the phenomenology

  5. Revealing Rembrandt

    Directory of Open Access Journals (Sweden)

    Andrew J Parker

    2014-04-01

    Full Text Available The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI. Our results emphasised the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt’s portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings.

  6. Fluctuations and confinement in ATF

    International Nuclear Information System (INIS)

    Isler, R.C.; Harris, J.H.; Murakami, M.

    1993-01-01

    In the period immediately prior to the suspension of ATF operation in November, 1991, a great deal of emphasis was palced on investigations of the fundamental mechanisms controlling confinement in this device. At that time, measurements of the density fluctuations throughout the plasma volume indicated the existence of theoretically predicted dissipative trapped electron and resistive interchange instabilities. These identifications were supported by results of dynamic configuration scans of the magnetic fields during which the extent of the magnetic well, shear, and fraction of confined trapped particles were changed continuously. Interpretation of the data from these experiments has been an ongoing exercise. Most recently, analysis of discharges employing strong gas puffing to change density gradients and fluctuation levels have strengthened the view that dissipative trapped electron modes may be present but do not play a significant direct role in energy transport. The present paper summarizes the current understanding concerning the identification of instabilities and their relationship to confinement in ATF

  7. Correlations In Confined Quantum Plasmas

    International Nuclear Information System (INIS)

    Dufty, J.W.

    2012-01-01

    This is the final report for the project 'Correlations in Confined Quantum Plasmas', NSF-DOE Partnership Grant DE FG02 07ER54946, 8/1/2007 - 7/30/2010. The research was performed in collaboration with a group at Christian Albrechts University (CAU), Kiel, Germany. That collaboration, almost 15 years old, was formalized during the past four years under this NSF-DOE Partnership Grant to support graduate students at the two institutions and to facilitate frequent exchange visits. The research was focused on exploring the frontiers of charged particle physics evolving from new experimental access to unusual states associated with confinement. Particular attention was paid to combined effects of quantum mechanics and confinement. A suite of analytical and numerical tools tailored to the specific inquiry has been developed and employed

  8. Finite temperature approach to confinement

    International Nuclear Information System (INIS)

    Gave, E.; Jengo, R.; Omero, C.

    1980-06-01

    The finite temperature treatment of gauge theories, formulated in terms of a gauge invariant variable as in a Polyakov method, is used as a device for obtaining an effective theory where the confinement test takes the form of a correlation function. The formalism is discussed for the abelian CPsup(n-1) model in various dimensionalities and for the pure Yang-Mills theory in the limit of zero temperature. In the latter case a class of vortex like configurations of the effective theory which induce confinement correspond in particular to the instanton solutions. (author)

  9. Some aspects of geometrical confinement

    Energy Technology Data Exchange (ETDEWEB)

    Novello, M.; De Lorenci, V.A. [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil); Elbaz, E. [Lyon-1 Univ., 69 - Villeurbanne (France)

    1998-04-01

    In this paper we present a toy model for the dynamics of a gauge field theory in such way that spin-one particles can be confined in a compact domain. We show that the property of confinement can be associated to the formation of a null surface identified to a horizon. This is due to the presence of an effective geometry generated by the self-interaction of the gauge field that guides the wave propagation of the field. This phenomenon has a striking analogy to the gravitational black hole in Einstein general theory of relativity, separating two domains of spacetime that can be trespassed only into one direction. (author) 4 refs.

  10. Hermitian relativity, chromodynamics and confinement

    International Nuclear Information System (INIS)

    Treder, H.J.

    1983-01-01

    The extension of the Riemann metrics of General Relativity to the complex domain (substitution of the symmetry conditions for the fundamental tensor, the affinity and the Ricci curvature by the conditions of hermicity) leads to a 'Generalized Theory of Gravity' (Einstein) describing the Newton-Einstein gravodynamics combined with the chromodynamics of quarks. The interaction of gravodynamics and chromodynamics implied by the Einstein-Schroedinger field equations of the hermitian relativity theory enforces the 'confinement'. The 'confinement' prevents the gravitational potential from divergence which would result in the lack of a Riemann space-time metric

  11. Pellet injection and toroidal confinement

    International Nuclear Information System (INIS)

    1989-12-01

    The proceedings of a technical committee meeting on pellet injection and toroidal confinement, held in Gut Ising, Federal Republic of Germany, 24-26 October, 1988, are given in this report. Most of the major fusion experiments are using pellet injectors; these were reported at this meeting. Studies of confinement, which is favorably affected, impurity transport, radiative energy losses, and affects on the ion temperature gradient instability were given. Studies of pellet ablation and effects on plasma profiles were presented. Finally, several papers described present and proposed injection guns. Refs, figs and tabs

  12. CONFINEMENT OF HIGH TEMPERATURE PLASMA

    Science.gov (United States)

    Koenig, H.R.

    1963-05-01

    The confinement of a high temperature plasma in a stellarator in which the magnetic confinement has tended to shift the plasma from the center of the curved, U-shaped end loops is described. Magnetic means are provided for counteracting this tendency of the plasma to be shifted away from the center of the end loops, and in one embodiment this magnetic means is a longitudinally extending magnetic field such as is provided by two sets of parallel conductors bent to follow the U-shaped curvature of the end loops and energized oppositely on the inside and outside of this curvature. (AEC)

  13. Building solids inside nano-space: from confined amorphous through confined solvate to confined 'metastable' polymorph.

    Science.gov (United States)

    Nartowski, K P; Tedder, J; Braun, D E; Fábián, L; Khimyak, Y Z

    2015-10-14

    The nanocrystallisation of complex molecules inside mesoporous hosts and control over the resulting structure is a significant challenge. To date the largest organic molecule crystallised inside the nano-pores is a known pharmaceutical intermediate - ROY (259.3 g mol(-1)). In this work we demonstrate smart manipulation of the phase of a larger confined pharmaceutical - indomethacin (IMC, 357.8 g mol(-1)), a substance with known conformational flexibility and complex polymorphic behaviour. We show the detailed structural analysis and the control of solid state transformations of encapsulated molecules inside the pores of mesoscopic cellular foam (MCF, pore size ca. 29 nm) and controlled pore glass (CPG, pore size ca. 55 nm). Starting from confined amorphous IMC we drive crystallisation into a confined methanol solvate, which upon vacuum drying leads to the stabilised rare form V of IMC inside the MCF host. In contrast to the pure form, encapsulated form V does not transform into a more stable polymorph upon heating. The size of the constraining pores and the drug concentration within the pores determine whether the amorphous state of the drug is stabilised or it recrystallises into confined nanocrystals. The work presents, in a critical manner, an application of complementary techniques (DSC, PXRD, solid-state NMR, N2 adsorption) to confirm unambiguously the phase transitions under confinement and offers a comprehensive strategy towards the formation and control of nano-crystalline encapsulated organic solids.

  14. Genome-wide identification and expression profiling reveal tissue-specific expression and differentially-regulated genes involved in gibberellin metabolism between Williams banana and its dwarf mutant.

    Science.gov (United States)

    Chen, Jingjing; Xie, Jianghui; Duan, Yajie; Hu, Huigang; Hu, Yulin; Li, Weiming

    2016-05-27

    Dwarfism is one of the most valuable traits in banana breeding because semi-dwarf cultivars show good resistance to damage by wind and rain. Moreover, these cultivars present advantages of convenient cultivation, management, and so on. We obtained a dwarf mutant '8818-1' through EMS (ethyl methane sulphonate) mutagenesis of Williams banana 8818 (Musa spp. AAA group). Our research have shown that gibberellins (GAs) content in 8818-1 false stems was significantly lower than that in its parent 8818 and the dwarf type of 8818-1 could be restored by application of exogenous GA3. Although GA exerts important impacts on the 8818-1 dwarf type, our understanding of the regulation of GA metabolism during banana dwarf mutant development remains limited. Genome-wide screening revealed 36 candidate GA metabolism genes were systematically identified for the first time; these genes included 3 MaCPS, 2 MaKS, 1 MaKO, 2 MaKAO, 10 MaGA20ox, 4 MaGA3ox, and 14 MaGA2ox genes. Phylogenetic tree and conserved protein domain analyses showed sequence conservation and divergence. GA metabolism genes exhibited tissue-specific expression patterns. Early GA biosynthesis genes were constitutively expressed but presented differential regulation in different tissues in Williams banana. GA oxidase family genes were mainly transcribed in young fruits, thus suggesting that young fruits were the most active tissue involved in GA metabolism, followed by leaves, bracts, and finally approximately mature fruits. Expression patterns between 8818 and 8818-1 revealed that MaGA20ox4, MaGA20ox5, and MaGA20ox7 of the MaGA20ox gene family and MaGA2ox7, MaGA2ox12, and MaGA2ox14 of the MaGA2ox gene family exhibited significant differential expression and high-expression levels in false stems. These genes are likely to be responsible for the regulation of GAs content in 8818-1 false stems. Overall, phylogenetic evolution, tissue specificity and differential expression analyses of GA metabolism genes can provide a

  15. Transcriptome analysis by GeneTrail revealed regulation of functional categories in response to alterations of iron homeostasis in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Lenhof Hans-Peter

    2011-05-01

    Full Text Available Abstract Background High-throughput technologies have opened new avenues to study biological processes and pathways. The interpretation of the immense amount of data sets generated nowadays needs to be facilitated in order to enable biologists to identify complex gene networks and functional pathways. To cope with this task multiple computer-based programs have been developed. GeneTrail is a freely available online tool that screens comparative transcriptomic data for differentially regulated functional categories and biological pathways extracted from common data bases like KEGG, Gene Ontology (GO, TRANSPATH and TRANSFAC. Additionally, GeneTrail offers a feature that allows screening of individually defined biological categories that are relevant for the respective research topic. Results We have set up GeneTrail for the use of Arabidopsis thaliana. To test the functionality of this tool for plant analysis, we generated transcriptome data of root and leaf responses to Fe deficiency and the Arabidopsis metal homeostasis mutant nas4x-1. We performed Gene Set Enrichment Analysis (GSEA with eight meaningful pairwise comparisons of transcriptome data sets. We were able to uncover several functional pathways including metal homeostasis that were affected in our experimental situations. Representation of the differentially regulated functional categories in Venn diagrams uncovered regulatory networks at the level of whole functional pathways. Over-Representation Analysis (ORA of differentially regulated genes identified in pairwise comparisons revealed specific functional plant physiological categories as major targets upon Fe deficiency and in nas4x-1. Conclusion Here, we obtained supporting evidence, that the nas4x-1 mutant was defective in metal homeostasis. It was confirmed that nas4x-1 showed Fe deficiency in roots and signs of Fe deficiency and Fe sufficiency in leaves. Besides metal homeostasis, biotic stress, root carbohydrate, leaf

  16. Deciphering of the Human Interferon-Regulated Proteome by Mass Spectrometry-Based Quantitative Analysis Reveals Extent and Dynamics of Protein Induction and Repression.

    Science.gov (United States)

    Megger, Dominik A; Philipp, Jos; Le-Trilling, Vu Thuy Khanh; Sitek, Barbara; Trilling, Mirko

    2017-01-01

    Interferons (IFNs) are pleotropic cytokines secreted upon encounter of pathogens and tumors. Applying their antipathogenic, antiproliferative, and immune stimulatory capacities, recombinant IFNs are frequently prescribed as drugs to treat different diseases. IFNs act by changing the gene expression profile of cells. Due to characteristics such as rapid gene induction and signaling, IFNs also represent prototypical model systems for various aspects of biomedical research (e.g., signal transduction). In regard to the signaling and activated promoters, IFNs can be subdivided into two groups. Here, alterations of the cellular proteome of human cells treated with IFNα and IFNγ were elucidated in a time-resolved manner by quantitative proteome analysis. The majority of protein regulations were strongly IFN type and time dependent. In addition to the expected upregulation of IFN-responsive proteins, an astonishing number of proteins became profoundly repressed especially by IFNγ. Thus, our comprehensive analysis revealed important insights into the human IFN-regulated proteome and its dynamics of protein induction and repression. Interestingly, the new class of IFN-repressed genes comprises known host factors for highly relevant pathogens such as HIV, dengue virus, and hepatitis C virus.

  17. Deciphering of the Human Interferon-Regulated Proteome by Mass Spectrometry-Based Quantitative Analysis Reveals Extent and Dynamics of Protein Induction and Repression

    Directory of Open Access Journals (Sweden)

    Dominik A. Megger

    2017-09-01

    Full Text Available Interferons (IFNs are pleotropic cytokines secreted upon encounter of pathogens and tumors. Applying their antipathogenic, antiproliferative, and immune stimulatory capacities, recombinant IFNs are frequently prescribed as drugs to treat different diseases. IFNs act by changing the gene expression profile of cells. Due to characteristics such as rapid gene induction and signaling, IFNs also represent prototypical model systems for various aspects of biomedical research (e.g., signal transduction. In regard to the signaling and activated promoters, IFNs can be subdivided into two groups. Here, alterations of the cellular proteome of human cells treated with IFNα and IFNγ were elucidated in a time-resolved manner by quantitative proteome analysis. The majority of protein regulations were strongly IFN type and time dependent. In addition to the expected upregulation of IFN-responsive proteins, an astonishing number of proteins became profoundly repressed especially by IFNγ. Thus, our comprehensive analysis revealed important insights into the human IFN-regulated proteome and its dynamics of protein induction and repression. Interestingly, the new class of IFN-repressed genes comprises known host factors for highly relevant pathogens such as HIV, dengue virus, and hepatitis C virus.

  18. Quantum statistics of ideal gases in confined space

    OpenAIRE

    Dai, Wu-Sheng; Xie, Mi

    2002-01-01

    In this paper, the effects of boundary and connectivity on ideal gases in two-dimensional confined space and three-dimensional tubes are discussed in detail based on the analytical result. The implication of such effects on the mesoscopic system is also revealed.

  19. Quantum statistics of ideal gases in confined space

    International Nuclear Information System (INIS)

    Dai Wusheng; Xie Mi

    2003-01-01

    In this Letter, the effects of boundary and connectivity on ideal gases in two-dimensional confined space and three-dimensional tubes are discussed in detail based on the analytical result. The implication of such effects on the mesoscopic system is also revealed

  20. Enhancement of confinement in tokamaks

    International Nuclear Information System (INIS)

    Furth, H.P.

    1986-05-01

    A plausible interpretation of the experimental evidence is that energy confinement in tokamaks is governed by two separate considerations: (1) the need for resistive MHD kink-stability, which limits the permissible range of current profiles - and therefore normally also the range of temperature profiles; and (2) the presence of strongly anomalous microscopic energy transport near the plasma edge, which calibrates the amplitude of the global temperature profile, thus determining the energy confinement time tau/sub E/. Correspondingly, there are two main paths towards the enhancement of tokamak confinement: (1) Configurational optimization, to increase the MHD-stable energy content of the plasma core, can evidently be pursued by varying the cross-sectional shape of the plasma and/or finding stable radial profiles with central q-values substantially below unity - but crossing from ''first'' to ''second'' stability within the peak-pressure region would have the greatest ultimate potential. (2) Suppression of edge turbulence, so as to improve the heat insulation in the outer plasma shell, can be pursued by various local stabilizing techniques, such as use of a poloidal divertor. The present confinement model and initial TFTR pellet-injection results suggest that the introduction of a super-high-density region within the plasma core should be particularly valuable for enhancing ntau/subE/. In D-T operation, a centrally peaked plasma pressure profile could possibly lend itself to alpha-particle-driven entry into the second-stability regime

  1. Frictional properties of confined polymers

    DEFF Research Database (Denmark)

    Sivebæk, Ion Marius; Samoilov, Vladimir N; Persson, Bo N J

    2008-01-01

    We present molecular dynamics friction calculations for confined hydrocarbon solids with molecular lengths from 20 to 1400 carbon atoms. Two cases are considered: a) polymer sliding against a hard substrate, and b) polymer sliding on polymer. In the first setup the shear stresses are relatively i...

  2. String theory and quark confinement

    International Nuclear Information System (INIS)

    Polyakov, A.M.

    1998-01-01

    This article is based on a talk given at the ''Strings '97'' conference. It discusses the search for the universality class of confining strings. The key ingredients include the loop equations, the zigzag symmetry, the non-linear renormalization group. Some new tests for the equivalence between gauge fields and strings are proposed. (orig.)

  3. Mirror Confinement Systems: project summaries

    International Nuclear Information System (INIS)

    1980-07-01

    This report contains descriptions of the projects supported by the Mirror Confinement Systems (MCS) Division of the Office of Fusion Energy. The individual project summaries were prepared by the principal investigators, in collaboration with MCS staff office, and include objectives and milestones for each project. In addition to project summaries, statements of Division objectives and budget summaries are also provided

  4. Effective viscosity of confined hydrocarbons

    DEFF Research Database (Denmark)

    Sivebæk, Ion Marius; Samoilov, V.N.; Persson, B.N.J.

    2012-01-01

    We present molecular dynamics friction calculations for confined hydrocarbon films with molecular lengths from 20 to 1400 carbon atoms. We find that the logarithm of the effective viscosity ηeff for nanometer-thin films depends linearly on the logarithm of the shear rate: log ηeff=C-nlog γ̇, where...

  5. Is confinement the ultimate truth

    International Nuclear Information System (INIS)

    Thirrring, W.

    1980-01-01

    This seminar discusses a field theory which leads to a r-potential and therefore to a confinement. By comparison to the instability due to a resonance phenomenon, the author concentrates on the theory's ghost problem and concludes that for some couplings this does not occur and the theory behaves reasonably

  6. Confined flow of polymer blends

    NARCIS (Netherlands)

    Tufano, C.; Peters, G.W.M.; Meijer, H.E.H.

    2008-01-01

    The influence of confinement on the steady-state morphology of two different emulsions is investigated. The blends, made from polybutene (PB) in polydimethylsiloxane (PDMS) and polybutadiene (PBD) in PDMS, are sheared between two parallel plates, mostly with a standard gap spacing of 40 m, in the

  7. Two flavor QCD and Confinement

    DEFF Research Database (Denmark)

    D'Elia, M.; Di Giacomo, A.; Pica, Claudio

    2005-01-01

    We argue that the order of the chiral transition for N_f=2 is a sensitive probe of the QCD vacuum, in particular of the mechanism of color confinement. A strategy is developed to investigate the order of the transition by use of finite size scaling analysis. An in-depth numerical investigation is...

  8. Turbulent jet in confined counterflow

    Indian Academy of Sciences (India)

    The mean flowfield of a turbulent jet issuing into a confined, uniform counterflow was investigated computationally. Based on dimensional analysis, the jet penetration length was shown to scale with jet-to-counterflow momentum flux ratio. This scaling and the computational results reproduce the well-known correct limit of ...

  9. Momentum Confinement at Low Torque

    International Nuclear Information System (INIS)

    Solomon, W.M.; Burrell, K.H.; deGrassie, J.S.; Budny, R.; Groebner, R.J.; Heidbrink, W.W.; Kinsey, J.E.; Kramer, G.J.; Makowski, M.A.; Mikkelsen, D.; Nazikian, R.; Petty, C.C.; Politzer, P.A.; Scott, S.D.; Van Zeeland, M.A.; Zarnstorff, M.C.

    2007-01-01

    Momentum confinement was investigated on DIII-D as a function of applied neutral beam torque at constant normalized β N , by varying the mix of co (parallel to the plasma current) and counter neutral beams. Under balanced neutral beam injection (i.e. zero total torque to the plasma), the plasma maintains a significant rotation in the co-direction. This 'intrinsic' rotation can be modeled as being due to an offset in the applied torque (i.e. an 'anomalous torque'). This anomalous torque appears to have a magnitude comparable to one co-neutral beam source. The presence of such an anomalous torque source must be taken into account to obtain meaningful quantities describing momentum transport, such as the global momentum confinement time and local diffusivities. Studies of the mechanical angular momentum in ELMing H-mode plasmas with elevated q min show that the momentum confinement time improves as the torque is reduced. In hybrid plasmas, the opposite effect is observed, namely that momentum confinement improves at high torque/rotation. The relative importance of E x B shearing between the two is modeled using GLF23 and may suggest a possible explanation.

  10. On the implications of confinement

    International Nuclear Information System (INIS)

    Roberts, C.D.

    1992-01-01

    In this paper, the authors consider some implications of confinement starting from the basic observation that cross-sections for the production of colored asymptotic states, such as free quarks and gluons, from color singlet initial states must be zero if QCD is to be confining. The authors discuss two pictures of confinement: the failure of the cluster decomposition property and the absence of a pole at timelike momenta in the propagator of a confined particle. The authors use QCD-based models as a framework to relate the failure of the cluster decomposition property to other ideas, such as the role of a nonzero gluon condensate. The authors' primary interest is to address the question of the absence of a mass pole through a study of model Schwinger-Dyson equations. These equations contain some of the dynamical information that is present in the study of the cluster decomposition property. The authors discuss the problems within this idea and its study using the Schwinger-Dyson equations

  11. Baryon observables and color confinement

    International Nuclear Information System (INIS)

    Jackson, A.D.

    1987-01-01

    Calculations of baryon observables within the framework of the chiral bag model are reviewed. The results of such calculations are found to be remarkably insensitive to the radius of color confinement and indicate the difficulty of finding unambiguous evidence for quarks in nuclei. 13 refs.; 5 figs

  12. Tissue and cell-specific transcriptomes in cotton reveal the subtleties of gene regulation underlying the diversity of plant secondary cell walls.

    Science.gov (United States)

    MacMillan, Colleen P; Birke, Hannah; Chuah, Aaron; Brill, Elizabeth; Tsuji, Yukiko; Ralph, John; Dennis, Elizabeth S; Llewellyn, Danny; Pettolino, Filomena A

    2017-07-18

    Knowledge of plant secondary cell wall (SCW) regulation and deposition is mainly based on the Arabidopsis model of a 'typical' lignocellulosic SCW. However, SCWs in other plants can vary from this. The SCW of mature cotton seed fibres is highly cellulosic and lacks lignification whereas xylem SCWs are lignocellulosic. We used cotton as a model to study different SCWs and the expression of the genes involved in their formation via RNA deep sequencing and chemical analysis of stem and seed fibre. Transcriptome comparisons from cotton xylem and pith as well as from a developmental series of seed fibres revealed tissue-specific and developmentally regulated expression of several NAC transcription factors some of which are likely to be important as top tier regulators of SCW formation in xylem and/or seed fibre. A so far undescribed hierarchy was identified between the top tier NAC transcription factors SND1-like and NST1/2 in cotton. Key SCW MYB transcription factors, homologs of Arabidopsis MYB46/83, were practically absent in cotton stem xylem. Lack of expression of other lignin-specific MYBs in seed fibre relative to xylem could account for the lack of lignin deposition in seed fibre. Expression of a MYB103 homolog correlated with temporal expression of SCW CesAs and cellulose synthesis in seed fibres. FLAs were highly expressed and may be important structural components of seed fibre SCWs. Finally, we made the unexpected observation that cell walls in the pith of cotton stems contained lignin and had a higher S:G ratio than in xylem, despite that tissue's lacking many of the gene transcripts normally associated with lignin biosynthesis. Our study in cotton confirmed some features of the currently accepted gene regulatory cascade for 'typical' plant SCWs, but also revealed substantial differences, especially with key downstream NACs and MYBs. The lignocellulosic SCW of cotton xylem appears to be achieved differently from that in Arabidopsis. Pith cell walls in

  13. Comparative proteomic analyses reveal that FlbA down-regulates gliT expression and SOD activity in Aspergillus fumigatus.

    Science.gov (United States)

    Shin, Kwang-Soo; Park, Hee-Soo; Kim, Young-Hwan; Yu, Jae-Hyuk

    2013-07-11

    FlbA is a regulator of G-protein signaling protein that plays a central role in attenuating heterotrimeric G-protein mediated vegetative growth signaling in Aspergillus. The deletion of flbA (∆flbA) in the opportunistic human pathogen Aspergillus fumigatus results in accelerated cell death and autolysis in submerged culture. To further investigate the effects of ∆flbA on intracellular protein levels we carried out 2-D proteome analyses of 2-day old submerged cultures of ∆flbA and wild type (WT) strains and observed 160 differentially expressed proteins. Via nano-LC-ESI-MS/MS analyses, we revealed the identity of 10 and 2 proteins exhibiting high and low level accumulation, respectively, in ∆flbA strain. Notably, the GliT protein is accumulated at about 1800-fold higher levels in ∆flbA than WT. Moreover, GliT is secreted at high levels from ∆flbA strain, whereas Sod1 (superoxide dismutase) is secreted at a higher level in WT. Northern blot analyses reveal that ∆flbA results in elevated accumulation of gliT mRNA. Consequently, ∆flbA strain exhibits enhanced tolerance to gliotoxin toxicity. Finally, ∆flbA strain displayed enhanced SOD activity and elevated resistance to menadione and paraquat. In summary, FlbA-mediated signaling control negatively affects cellular responses associated with detoxification of reactive oxygen species and of exogenous gliotoxin in A. fumigatus. Regulator of G protein Signaling (RGS) proteins play crucial roles in fundamental biological processes in filamentous fungi. FlbA is the first studied filamentous fungal RGS protein, yet much remains to be understood about its roles in the opportunistic human pathogen Aspergillus fumigatus. In the present study, we examined the effects of the deletion of flbA using comprehensive analyses of the intra- and extracellular proteomes of A. fumigatus wild type and the flbA deletion mutant. Via MS analyses, we identified 10 proteins exhibiting high level accumulation in the flbA deletion

  14. Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway

    International Nuclear Information System (INIS)

    Drakaki, Alexandra; Hatziapostolou, Maria; Polytarchou, Christos; Vorvis, Christina; Poultsides, George A.; Souglakos, John; Georgoulias, Vassilis; Iliopoulos, Dimitrios

    2015-01-01

    Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths, reflecting the aggressiveness of this type of cancer and the absence of effective therapeutic regimens. MicroRNAs have been involved in the pathogenesis of different types of cancers, including liver cancer. Our aim was to identify microRNAs that have both functional and clinical relevance in HCC and examine their downstream signaling effectors. MicroRNA and gene expression levels were measured by quantitative real-time PCR in HCC tumors and controls. A TargetScan algorithm was used to identify miR-9 downstream direct targets. A high-throughput screen of the human microRNAome revealed 28 microRNAs as regulators of liver cancer cell invasiveness. MiR-9, miR-21 and miR-224 were the top inducers of HCC invasiveness and also their expression was increased in HCC relative to control liver tissues. Integration of the microRNA screen and expression data revealed miR-9 as the top microRNA, having both functional and clinical significance. MiR-9 levels correlated with HCC tumor stage and miR-9 overexpression induced SNU-449 and HepG2 cell growth, invasiveness and their ability to form colonies in soft agar. Bioinformatics and 3′UTR luciferase analyses identified E-cadherin (CDH1) and peroxisome proliferator-activated receptor alpha (PPARA) as direct downstream effectors of miR-9 activity. Inhibition of PPARA suppressed CDH1 mRNA levels, suggesting that miR-9 regulates CDH1 expression directly through binding in its 3′UTR and indirectly through PPARA. On the other hand, miR-9 inhibition of overexpression suppressed HCC tumorigenicity and invasiveness. PPARA and CDH1 mRNA levels were decreased in HCC relative to controls and were inversely correlated with miR-9 levels. Taken together, this study revealed the involvement of the miR-9/PPARA/CDH1 signaling pathway in HCC oncogenesis. The online version of this article (doi:10.1186/s12885-015-1562-9) contains supplementary material, which is

  15. Surface motion and confinement potential for a microwave confined corona

    International Nuclear Information System (INIS)

    Ensley, D.L.

    1979-07-01

    Approximate time dependent solutions for surface velocities and potentials are given for a plane polarized microwave field confining a hot, over-dense plasma corona. Steady state solutions to Poissons' equation can be applied to the time dependent case, provided transit time effects are included. The product of ion pressure and potential wave (surface) velocity gives an average heating rate approx. 7/32 NKT 0 V/sub theta/ directly to the ions

  16. Study of quantum confinement effects in ZnO nanostructures

    Science.gov (United States)

    Movlarooy, Tayebeh

    2018-03-01

    Motivation to fact that zinc oxide nanowires and nanotubes with successful synthesis and the mechanism of formation, stability and electronic properties have been investigated; in this study the structural, electronic properties and quantum confinement effects of zinc oxide nanotubes and nanowires with different diameters are discussed. The calculations within density functional theory and the pseudo potential approximation are done. The electronic structure and energy gap for Armchair and zigzag ZnO nanotubes with a diameter of about 4 to 55 Angstrom and ZnO nanowires with a diameter range of 4 to 23 Å is calculated. The results revealed that due to the quantum confinement effects, by reducing the diameter of nanowires and nanotubes, the energy gap increases. Zinc oxide semiconductor nanostructures since having direct band gap with size-dependent and quantum confinement effect are recommended as an appropriate candidate for making nanoscale optoelectronic devices.

  17. Lack of quantum confinement in Ga2O3 nanolayers

    Science.gov (United States)

    Peelaers, Hartwin; Van de Walle, Chris G.

    2017-08-01

    β -Ga2Ox3 is a wide-band-gap semiconductor with promising applications in transparent electronics and in power devices. β -Ga2O3 has monoclinic crystal symmetry and does not display a layered structured characteristic of 2D materials in the bulk; nevertheless, monolayer-thin Ga2O3 layers can be created. We used first-principles techniques to investigate the structural and electronic properties of these nanolayers. Surprisingly, freestanding films do not exhibit any signs of quantum confinement and exhibit the same electronic structure as bulk material. A detailed examination reveals that this can be attributed to the presence of states that are strongly confined near the surface. When the Ga2O3 layers are embedded in a wider band-gap material such as Al2O3 , the expected effects of quantum confinement can be observed. The effective mass of electrons in all the nanolayers is small, indicating promising device applications.

  18. Spatial confinement governs orientational order in patchy particles

    Science.gov (United States)

    Iwashita, Yasutaka; Kimura, Yasuyuki

    2016-06-01

    Orientational order in condensed matter plays a key role in determining material properties such as ferromagnetism, viscoelasticity or birefringence. We studied purely orientational ordering in closely-packed one-patch colloidal particles confined between flat substrates, where the particles can only rotate and are ordered via the sticky interaction between the patches. For the first time, we experimentally realized a rich variety of mesoscopic patterns through orientational ordering of colloids by controlling patch size and confinement thickness. The combination of experiment and numerical simulation reveals the decisive role of confinement: An ordered state(s) is selected from the (meta)stable options in bulk when it is commensurate with the system geometry and boundary conditions; otherwise, frustration induces a unique order. Our study offers a new means of systematic control over mesoscopic structures via orientational ordering in patchy particles. The system would also possess unique functionalities through the rotational response of the particles to external stimuli.

  19. Transcriptional regulation of the outer membrane porin gene ompW reveals its physiological role during the transition from the aerobic to the anaerobic lifestyle of Escherichia coli

    Directory of Open Access Journals (Sweden)

    Minfeng eXiao

    2016-05-01

    Full Text Available Understanding bacterial physiology relies on elucidating the regulatory mechanisms and cellular functions of those differentially expressed genes in response to environmental changes. A widespread Gram-negative bacterial outer membrane protein OmpW has been implicated in the adaptation to stresses in various species. It is recently found to be present in the regulon of the global anaerobic transcription factor FNR and ArcA in E. coli. However, little is known about the physiological implications of this regulatory disposition. In this study, we demonstrate that transcription of ompW is indeed mediated by a series of global regulators involved in the anaerobiosis of E. coli. We show that FNR can both activate and repress the expression of ompW through its direct binding to two distinctive sites, -81.5 and -126.5 bp respectively, on ompW promoter. ArcA also participates in repression of ompW under anaerobic condition, but in an FNR dependent manner. Additionally, ompW is also subject to the regulation by CRP and NarL which senses the availability and types of carbon sources and respiration electron acceptors in the environment respectively, implying a role of OmpW in the carbon and energy metabolism of E. coli during its anaerobic adaptation. Molecular docking reveals that OmpW can bind fumarate, an alternative electron acceptor in anaerobic respiration, with sufficient affinity. Moreover, supplement of fumarate or succinate which belongs to the C4-dicarboxylates family of metabolite, to E. coli culture rescues OmpW-mediated colicin S4 killing. Taken together, we propose that OmpW is involved in anaerobic carbon and energy metabolism to mediate the transition from aerobic to anaerobic lifestyle in E. coli.

  20. Diguanylate cyclase null mutant reveals that C-Di-GMP pathway regulates the motility and adherence of the extremophile bacterium Acidithiobacillus caldus.

    Directory of Open Access Journals (Sweden)

    Matías Castro

    Full Text Available An understanding of biofilm formation is relevant to the design of biological strategies to improve the efficiency of the bioleaching process and to prevent environmental damages caused by acid mine/rock drainage. For this reason, our laboratory is focused on the characterization of the molecular mechanisms involved in biofilm formation in different biomining bacteria. In many bacteria, the intracellular levels of c-di-GMP molecules regulate the transition from the motile planktonic state to sessile community-based behaviors, such as biofilm development, through different kinds of effectors. Thus, we recently started a study of the c-di-GMP pathway in several biomining bacteria including Acidithiobacillus caldus. C-di-GMP molecules are synthesized by diguanylate cyclases (DGCs and degraded by phosphodiesterases (PDEs. We previously reported the existence of intermediates involved in c-di-GMP pathway from different Acidithiobacillus species. Here, we report our work related to At. caldus ATCC 51756. We identified several putative-ORFs encoding DGC and PDE and effector proteins. By using total RNA extracted from At. caldus cells and RT-PCR, we demonstrated that these genes are expressed. We also demonstrated the presence of c-di-GMP by mass spectrometry and showed that genes for several of the DGC enzymes were functional by heterologous genetic complementation in Salmonella enterica serovar Typhimurium mutants. Moreover, we developed a DGC defective mutant strain (Δc1319 that strongly indicated that the c-di-GMP pathway regulates the swarming motility and adherence to sulfur surfaces by At. caldus. Together, our results revealed that At. caldus possesses a functional c-di-GMP pathway which could be significant for ores colonization during the bioleaching process.

  1. Genome-wide mapping of Sox6 binding sites in skeletal muscle reveals both direct and indirect regulation of muscle terminal differentiation by Sox6

    Directory of Open Access Journals (Sweden)

    An Chung-Il

    2011-10-01

    Full Text Available Abstract Background Sox6 is a multi-faceted transcription factor involved in the terminal differentiation of many different cell types in vertebrates. It has been suggested that in mice as well as in zebrafish Sox6 plays a role in the terminal differentiation of skeletal muscle by suppressing transcription of slow fiber specific genes. In order to understand how Sox6 coordinately regulates the transcription of multiple fiber type specific genes during muscle development, we have performed ChIP-seq analyses to identify Sox6 target genes in mouse fetal myotubes and generated muscle-specific Sox6 knockout (KO mice to determine the Sox6 null muscle phenotype in adult mice. Results We have identified 1,066 Sox6 binding sites using mouse fetal myotubes. The Sox6 binding sites were found to be associated with slow fiber-specific, cardiac, and embryonic isoform genes that are expressed in the sarcomere as well as transcription factor genes known to play roles in muscle development. The concurrently performed RNA polymerase II (Pol II ChIP-seq analysis revealed that 84% of the Sox6 peak-associated genes exhibited little to no binding of Pol II, suggesting that the majority of the Sox6 target genes are transcriptionally inactive. These results indicate that Sox6 directly regulates terminal differentiation of muscle by affecting the expression of sarcomere protein genes as well as indirectly through influencing the expression of transcription factors relevant to muscle development. Gene expression profiling of Sox6 KO skeletal and cardiac muscle revealed a significant increase in the expression of the genes associated with Sox6 binding. In the absence of the Sox6 gene, there was dramatic upregulation of slow fiber-specific, cardiac, and embryonic isoform gene expression in Sox6 KO skeletal muscle and fetal isoform gene expression in Sox6 KO cardiac muscle, thus confirming the role Sox6 plays as a transcriptional suppressor in muscle development

  2. Inertial Electrostatic Confinement (IEC) devices

    International Nuclear Information System (INIS)

    Nebel, R.A.; Turner, L.; Tiouririne, T.N.; Barnes, D.C.; Nystrom, W.D.; Bussard, R.W.; Miley, G.H.; Javedani, J.; Yamamoto, Y.

    1994-01-01

    Inertial Electrostatic Confinement (IEC) is one of the earliest plasma confinement concepts, having first been suggested by P. T. Farnsworth in the 1950s. The concept involves a simple apparatus of concentric spherical electrostatic grids or a combination of grids and magnetic fields. An electrostatic structure is formed from the confluence of electron or ion beams. Gridded IEC systems have demonstrated neutron yields as high as 2 * 10 10 neutrons/sec. These systems have considerable potential as small, inexpensive, portable neutron sources for assaying applications. Neutron tomography is also a potential application. Atomic physics effects strongly influence the performance of all of these systems. Important atomic effects include elastic scattering, ionization, excitation, and charge exchange. This paper discusses how an IEC system is influenced by these effects and how to design around them. Theoretical modeling and experimental results are presented

  3. Extra dimensions and color confinement

    Energy Technology Data Exchange (ETDEWEB)

    Pleitez, V

    1995-04-01

    An extension of the ordinary four dimensional Minkowski space by introducing additional dimensions which have their own Lorentz transformation is considered. Particles can transform in a different way under each Lorentz group. It is shown that only quark interactions are slightly modified and that color confinement automatic since these degrees of freedom run only in the extra dimensions. No compactification of the extra dimensions is needed. (author). 4 refs.

  4. Confinement facilities for handling plutonium

    International Nuclear Information System (INIS)

    Maraman, W.J.; McNeese, W.D.; Stafford, R.G.

    1975-01-01

    Plutonium handling on a multigram scale began in 1944. Early criteria, equipment, and techniques for confining contamination have been superseded by more stringent criteria and vastly improved equipment and techniques for in-process contamination control, effluent air cleaning and treatment of liquid wastes. This paper describes the evolution of equipment and practices to minimize exposure of workers and escape of contamination into work areas and into the environment. Early and current contamination controls are compared. (author)

  5. Inertial-confinement-fusion targets

    International Nuclear Information System (INIS)

    Hendricks, C.D.

    1981-01-01

    Inertial confinement fusion (ICF) targets are made as simple flat discs, as hollow shells or as complicated multilayer structures. Many techniques have been devised for producing the targets. Glass and metal shells are made by using drop and bubble techniques. Solid hydrogen shells are also produced by adapting old methods to the solution of modern problems. Some of these techniques, problems and solutions are discussed. In addition, the applications of many of the techniques to fabrication of ICF targets is presented

  6. Confinement and diffusion in tokamaks

    International Nuclear Information System (INIS)

    McWilliams, R.

    1988-01-01

    The effect of electric field fluctuations on confinement and diffusion in tokamak is discussed. Based on the experimentally determined cross-field turbolent diffusion coefficient, D∼3.7*cT e /eB(δn i /n i ) rms which is also derived by a simple theory, the cross-field diffusion time, tp=a 2 /D, is calculated and compared to experimental results from 51 tokamak for standard Ohmic operation

  7. Enhancement of confinement in tokamaks

    International Nuclear Information System (INIS)

    Furth, H.P.

    1986-01-01

    The analysis begins by identifying a hypothetical model of tokamak confinement that is designed to take into account the conflict between Tsub(e)(r)-profile shapes arising from microscopic transport and J(r)-profile shapes required for gross stability. On the basis of this model, a number of hypothetical lines of advance are developed. Some TFTR experiments that may point the way to a particularly attractive type of tokamak reactor regime are discussed. (author)

  8. Capillary Condensation in Confined Media

    OpenAIRE

    Charlaix, Elisabeth; Ciccotti, Matteo

    2009-01-01

    28 pages - To appear in 2010 in the Handbook of Nanophysics - Vol 1 - Edited by Klaus Sattler - CRC Press; We review here the physics of capillary condensation of liquids in confined media, with a special regard to the application in nanotechnologies. The thermodynamics of capillary condensation and thin film adsorption are first exposed along with all the relevant notions. The focus is then shifted to the modelling of capillary forces, to their measurements techniques (including SFA, AFM and...

  9. Metastability in Magnetically Confined Plasmas

    International Nuclear Information System (INIS)

    Fong, B.H.; Cowley, S.C.; Hurricane, O.A.

    1999-01-01

    The parameter space of magnetically confined plasmas near marginal instability for interchange-type modes is divided into three regions according to qualitative stability properties. Region I is linearly stable though nonlinearly unstable to large excitations. Region II is linearly unstable, nonlinearly stable to small excitations, and nonlinearly unstable to large excitations. Region III is linearly and nonlinearly unstable. For an equilibrium evolving through marginal stability, region III and therefore explosive instability are inevitably encountered. copyright 1999 The American Physical Society

  10. Confinement and strings in MQCD

    International Nuclear Information System (INIS)

    Hanany, A.; Strassler, M.J.; Zaffaroni, A.

    1998-01-01

    We study aspects of confinement in the M-theory fivebrane version of QCD (MQCD). We show heavy quarks are confined in hadrons (which take the form of membrane-fivebrane bound states) for N=1 and softly broken N=2 SU(N) MQCD. We explore and clarify the transition from the exotic physics of the latter to the standard physics of the former. In particular, the many strings and quark-antiquark mesons found in N=2 field theory by Douglas and Shenker are reproduced. It is seen that in the N=1 limit all but one such meson disappears while all of the strings survive. The strings of softly broken N=2, N=1, and even non-supersymmetric SU(N) MQCD have a common ratio for their tensions as a function of the amount of flux they carry. We also comment on the almost BPS properties of the Douglas-Shenker strings and discuss the brane picture for monopole confinement on N=2 QCD Higgs branches. (orig.)

  11. Comprehensive analysis of miRNAs expression profiles revealed potential key miRNA/mRNAs regulating colorectal cancer stem cell self-renewal.

    Science.gov (United States)

    Xu, Peng; Wang, Junhua; Sun, Bo; Xiao, Zhongdang

    2018-05-20

    Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood. Recently, miRNAs are reported to be relevant to the self-renewal ability of cancer stem cells. In this study, we first isolated colorectal cancer stem cell from colorectal cancer cell line HCT-116 by 1% low serum culture. Then we conducted a comprehensive analysis based on the miRNAs profiles data of both colorectal cancer stem cells and normal cultured colorectal cancer cells. Pathway analysis revealed multiple pathways including Jak-STAT, TGF-beta, PI3K-Akt and MAPK signaling pathway that are correlated to colorectal cancer. Further, we constructed a miRNA-mRNA network, based on which, several miRNA/mRNA pairs were ranked according to their impact index to the self-renewal of colorectal cancer stem cells. Further biological experiment showed that up-regulation of miR-92a-3p led to cell cycle arrest and reduced colony formation. This work provides clues to find the new potential biomarkers for colorectal cancer stem cell diagnosis and select effective miRNAs for targeted therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity.

    Directory of Open Access Journals (Sweden)

    Judit Remenyi

    Full Text Available miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity.

  13. MicroRNAs in Amoebozoa: deep sequencing of the small RNA population in the social amoeba Dictyostelium discoideum reveals developmentally regulated microRNAs.

    Science.gov (United States)

    Avesson, Lotta; Reimegård, Johan; Wagner, E Gerhart H; Söderbom, Fredrik

    2012-10-01

    The RNA interference machinery has served as a guardian of eukaryotic genomes since the divergence from prokaryotes. Although the basic components have a shared origin, silencing pathways directed by small RNAs have evolved in diverse directions in different eukaryotic lineages. Micro (mi)RNAs regulate protein-coding genes and play vital roles in plants and animals, but less is known about their functions in other organisms. Here, we report, for the first time, deep sequencing of small RNAs from the social amoeba Dictyostelium discoideum. RNA from growing single-cell amoebae as well as from two multicellular developmental stages was sequenced. Computational analyses combined with experimental data reveal the expression of miRNAs, several of them exhibiting distinct expression patterns during development. To our knowledge, this is the first report of miRNAs in the Amoebozoa supergroup. We also show that overexpressed miRNA precursors generate miRNAs and, in most cases, miRNA* sequences, whose biogenesis is dependent on the Dicer-like protein DrnB, further supporting the presence of miRNAs in D. discoideum. In addition, we find miRNAs processed from hairpin structures originating from an intron as well as from a class of repetitive elements. We believe that these repetitive elements are sources for newly evolved miRNAs.

  14. Crystal Structure of Human Dual-Specificity Tyrosine-Regulated Kinase 3 Reveals New Structural Features and Insights into its Auto-phosphorylation.

    Science.gov (United States)

    Kim, Kuglae; Cha, Jeong Seok; Cho, Yong-Soon; Kim, Hoyoung; Chang, Nienping; Kim, Hye-Jung; Cho, Hyun-Soo

    2018-04-07

    Dual-specificity tyrosine-regulated kinases (DYRKs) auto-phosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues. The auto-phosphorylation occurs intramolecularly and is a one-off event. DYRK3 is selectively expressed at a high level in hematopoietic cells and attenuates erythroblast development, leading to anemia. In the present study, we determined the crystal structure of the mature form of human DYRK3 in complex with harmine, an ATP competitive inhibitor. The crystal structure revealed a phosphorylation site, residue S350, whose phosphorylation increases the stability of DYRK3 and enhances its kinase activity. In addition, our structural and biochemical assays suggest that the N-terminal auto-phosphorylation accessory domain stabilizes the DYRK3 protein, followed by auto-phosphorylation of the tyrosine of the activation loop, which is important for kinase activity. Finally, our docking analysis provides information for the design of novel and potent therapeutics to treat anemia. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Proteomics of red and white corolla limbs in petunia reveals a novel function of the anthocyanin regulator ANTHOCYANIN1 in determining flower longevity.

    Science.gov (United States)

    Prinsi, Bhakti; Negri, Alfredo S; Quattrocchio, Francesca M; Koes, Ronald E; Espen, Luca

    2016-01-10

    The Petunia hybrida ANTHOCYANIN1 (AN1) gene encodes a transcription factor that regulates both the expression of genes involved in anthocyanin synthesis and the acidification of the vacuolar lumen in corolla epidermal cells. In this work, the comparison between the red flowers of the R27 line with the white flowers of the isogenic an1 mutant line W225 showed that the AN1 gene has further pleiotropic effects on flavonoid biosynthesis as well as on distant physiological traits. The proteomic profiling showed that the an1 mutation was associated to changes in accumulation of several proteins, affecting both anthocyanin synthesis and primary metabolism. The flavonoid composition study confirmed that the an1 mutation provoked a broad attenuation of the entire flavonoid pathway, probably by indirect biochemical events. Moreover, proteomic changes and variation of biochemical parameters revealed that the an1 mutation induced a delay in the onset of flower senescence in W225, as supported by the enhanced longevity of the W225 flowers in planta and the loss of sensitivity of cut flowers to sugar. This study suggests that AN1 is possibly involved in the perception and/or transduction of ethylene signal during flower senescence. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation.

    Science.gov (United States)

    Grandy, Rodrigo A; Whitfield, Troy W; Wu, Hai; Fitzgerald, Mark P; VanOudenhove, Jennifer J; Zaidi, Sayyed K; Montecino, Martin A; Lian, Jane B; van Wijnen, André J; Stein, Janet L; Stein, Gary S

    2016-02-15

    Stem cell phenotypes are reflected by posttranslational histone modifications, and this chromatin-related memory must be mitotically inherited to maintain cell identity through proliferative expansion. In human embryonic stem cells (hESCs), bivalent genes with both activating (H3K4me3) and repressive (H3K27me3) histone modifications are essential to sustain pluripotency. Yet, the molecular mechanisms by which this epigenetic landscape is transferred to progeny cells remain to be established. By mapping genomic enrichment of H3K4me3/H3K27me3 in pure populations of hESCs in G2, mitotic, and G1 phases of the cell cycle, we found striking variations in the levels of H3K4me3 through the G2-M-G1 transition. Analysis of a representative set of bivalent genes revealed that chromatin modifiers involved in H3K4 methylation/demethylation are recruited to bivalent gene promoters in a cell cycle-dependent fashion. Interestingly, bivalent genes enriched with H3K4me3 exclusively during mitosis undergo the strongest upregulation after induction of differentiation. Furthermore, the histone modification signature of genes that remain bivalent in differentiated cells resolves into a cell cycle-independent pattern after lineage commitment. These results establish a new dimension of chromatin regulation important in the maintenance of pluripotency. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  17. Conserved Lipid and Small-Molecule Modulation of COQ8 Reveals Regulation of the Ancient Kinase-like UbiB Family.

    Science.gov (United States)

    Reidenbach, Andrew G; Kemmerer, Zachary A; Aydin, Deniz; Jochem, Adam; McDevitt, Molly T; Hutchins, Paul D; Stark, Jaime L; Stefely, Jonathan A; Reddy, Thiru; Hebert, Alex S; Wilkerson, Emily M; Johnson, Isabel E; Bingman, Craig A; Markley, John L; Coon, Joshua J; Dal Peraro, Matteo; Pagliarini, David J

    2018-02-15

    Human COQ8A (ADCK3) and Saccharomyces cerevisiae Coq8p (collectively COQ8) are UbiB family proteins essential for mitochondrial coenzyme Q (CoQ) biosynthesis. However, the biochemical activity of COQ8 and its direct role in CoQ production remain unclear, in part due to lack of known endogenous regulators of COQ8 function and of effective small molecules for probing its activity in vivo. Here, we demonstrate that COQ8 possesses evolutionarily conserved ATPase activity that is activated by binding to membranes containing cardiolipin and by phenolic compounds that resemble CoQ pathway intermediates. We further create an analog-sensitive version of Coq8p and reveal that acute chemical inhibition of its endogenous activity in yeast is sufficient to cause respiratory deficiency concomitant with CoQ depletion. Collectively, this work defines lipid and small-molecule modulators of an ancient family of atypical kinase-like proteins and establishes a chemical genetic system for further exploring the mechanistic role of COQ8 in CoQ biosynthesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Confinement Sensing and Signal Optimization via Piezo1/PKA and Myosin II Pathways

    Directory of Open Access Journals (Sweden)

    Wei-Chien Hung

    2016-05-01

    Full Text Available Summary: Cells adopt distinct signaling pathways to optimize cell locomotion in different physical microenvironments. However, the underlying mechanism that enables cells to sense and respond to physical confinement is unknown. Using microfabricated devices and substrate-printing methods along with FRET-based biosensors, we report that, as cells transition from unconfined to confined spaces, intracellular Ca2+ level is increased, leading to phosphodiesterase 1 (PDE1-dependent suppression of PKA activity. This Ca2+ elevation requires Piezo1, a stretch-activated cation channel. Moreover, differential regulation of PKA and cell stiffness in unconfined versus confined cells is abrogated by dual, but not individual, inhibition of Piezo1 and myosin II, indicating that these proteins can independently mediate confinement sensing. Signals activated by Piezo1 and myosin II in response to confinement both feed into a signaling circuit that optimizes cell motility. This study provides a mechanism by which confinement-induced signaling enables cells to sense and adapt to different physical microenvironments. : Hung et al. demonstrate that a Piezo1-dependent intracellular calcium increase negatively regulates protein kinase A (PKA as cells transit from unconfined to confined spaces. The Piezo1/PKA and myosin II signaling modules constitute two confinement-sensing mechanisms. This study provides a paradigm by which signaling enables cells to sense and adapt to different microenvironments.

  19. Confinement dynamics in the reversed field pinch

    International Nuclear Information System (INIS)

    Schoenberg, K.F.

    1988-01-01

    The study of basic transport and confinement dynamics is central to the development of the reversed field pinch (RFP) as a confinement concept. Thus, the goal of RFP research is to understand the connection between processes that sustain the RFP configuration and related transport/confinement properties. Recently, new insights into confinement have emerged from a detailed investigation of RFP electron and ion physics. These insights derive from the recognition that both magnetohydrodynamic (MHD) and electron kinetic effects play an important and strongly coupled role in RFP sustainment and confinement dynamics. In this paper, we summarize the results of these studies on the ZT-40M experiment. 8 refs

  20. Global confinement characteristics of Jet limiter plasmas

    International Nuclear Information System (INIS)

    Campbell, D.J.; Christiansen, J.P.; Cordey, J.G.; Thomas, P.R.; Thomsen, K.

    1989-01-01

    Data from a wide variety of plasma pulses on JET (aux. heating, current, field, minority species, plasma shape, etc) are analysed in order to assess the characteristics of global confinement. The scaling of confinement in ohmically and auxiliary heated discharges is examined. The ohmic confinement in the present new JET configuration (Belt Limiter) is essentially the same as previously. Confinement in auxiliary heated discharges shows presently a slight improvement since 1986. Both ohmic and non-ohmic data is used in a set of confinement time regression analyses and certain constraints derived from theory are imposed

  1. Coding-Sequence Identification and Transcriptional Profiling of Nine AMTs and Four NRTs From Tobacco Revealed Their Differential Regulation by Developmental Stages, Nitrogen Nutrition, and Photoperiod

    Directory of Open Access Journals (Sweden)

    Lai-Hua Liu

    2018-03-01

    Full Text Available Although many members encoding different ammonium- and nitrate-transporters (AMTs, NRTs were identified and functionally characterized from several plant species, little is known about molecular components for NH4+- and NO3- acquisition/transport in tobacco, which is often used as a plant model for biological studies besides its agricultural and industrial interest. We reported here the first molecular identification in tobacco (Nicotiana tabacum of nine AMTs and four NRTs, which are respectively divided into four (AMT1/2/3/4 and two (NRT1/2 clusters and whose functionalities were preliminarily evidenced by heterologous functional-complementation in yeast or Arabidopsis. Tissue-specific transcriptional profiling by qPCR revealed that NtAMT1.1/NRT1.1 mRNA occurred widely in leaves, flower organs and roots; only NtAMT1.1/1.3/2.1NRT1.2/2.2 were strongly transcribed in the aged leaves, implying their dominant roles in N-remobilization from source/senescent tissues. N-dependent expression analysis showed a marked upregulation of NtAMT1.1 in the roots by N-starvation and resupply with N including NH4+, suggesting a predominant action of NtAMT1.1 in NH4+ uptake/transport whenever required. The obvious leaf-expression of other NtAMTs e.g., AMT1.2 responsive to N indicates a major place, where they may play transport roles associated with plant N-status and (NH4+-N movement within aerial-parts. The preferentially root-specific transcription of NtNRT1.1/1.2/2.1 responsive to N argues their importance for root NO3- uptake and even sensing in root systems. Moreover, of all NtAMTs/NRTs, only NtAMT1.1/NRT1.1/1.2 showed their root-expression alteration in a typical diurnal-oscillation pattern, reflecting likely their significant roles in root N-acquisition regulated by internal N-demand influenced by diurnal-dependent assimilation and translocation of carbohydrates from shoots. This suggestion could be supported at least in part by sucrose- and MSX

  2. Coding-Sequence Identification and Transcriptional Profiling of Nine AMTs and Four NRTs From Tobacco Revealed Their Differential Regulation by Developmental Stages, Nitrogen Nutrition, and Photoperiod

    Science.gov (United States)

    Liu, Lai-Hua; Fan, Teng-Fei; Shi, Dong-Xue; Li, Chang-Jun; He, Ming-Jie; Chen, Yi-Yin; Zhang, Lei; Yang, Chao; Cheng, Xiao-Yuan; Chen, Xu; Li, Di-Qin; Sun, Yi-Chen

    2018-01-01

    Although many members encoding different ammonium- and nitrate-transporters (AMTs, NRTs) were identified and functionally characterized from several plant species, little is known about molecular components for NH4+- and NO3- acquisition/transport in tobacco, which is often used as a plant model for biological studies besides its agricultural and industrial interest. We reported here the first molecular identification in tobacco (Nicotiana tabacum) of nine AMTs and four NRTs, which are respectively divided into four (AMT1/2/3/4) and two (NRT1/2) clusters and whose functionalities were preliminarily evidenced by heterologous functional-complementation in yeast or Arabidopsis. Tissue-specific transcriptional profiling by qPCR revealed that NtAMT1.1/NRT1.1 mRNA occurred widely in leaves, flower organs and roots; only NtAMT1.1/1.3/2.1NRT1.2/2.2 were strongly transcribed in the aged leaves, implying their dominant roles in N-remobilization from source/senescent tissues. N-dependent expression analysis showed a marked upregulation of NtAMT1.1 in the roots by N-starvation and resupply with N including NH4+, suggesting a predominant action of NtAMT1.1 in NH4+ uptake/transport whenever required. The obvious leaf-expression of other NtAMTs e.g., AMT1.2 responsive to N indicates a major place, where they may play transport roles associated with plant N-status and (NH4+-)N movement within aerial-parts. The preferentially root-specific transcription of NtNRT1.1/1.2/2.1 responsive to N argues their importance for root NO3- uptake and even sensing in root systems. Moreover, of all NtAMTs/NRTs, only NtAMT1.1/NRT1.1/1.2 showed their root-expression alteration in a typical diurnal-oscillation pattern, reflecting likely their significant roles in root N-acquisition regulated by internal N-demand influenced by diurnal-dependent assimilation and translocation of carbohydrates from shoots. This suggestion could be supported at least in part by sucrose- and MSX-affected transcriptional-regulation

  3. {sup 1}H NMR-based metabolomics reveals sub-lethal toxicity of a mixture of diabetic and lipid-regulating pharmaceuticals on amphibian larvae

    Energy Technology Data Exchange (ETDEWEB)

    Melvin, Steven D., E-mail: s.melvin@griffith.edu.au [Australian Rivers Institute, Griffith University, Southport, QLD 4222 (Australia); Habener, Leesa J. [Griffith School of Environment, Griffith University, Southport, QLD 4222 (Australia); Leusch, Frederic D.L. [Australian Rivers Institute, Griffith University, Southport, QLD 4222 (Australia); Griffith School of Environment, Griffith University, Southport, QLD 4222 (Australia); Carroll, Anthony R. [Griffith School of Environment, Griffith University, Southport, QLD 4222 (Australia)

    2017-03-15

    Highlights: • Pharmaceutical pollutants are a concern for eliciting adverse effects in wildlife. • Diabetes and lipid regulating drugs are widely used and poorly removed from sewage. • We explored the toxicity of a mixture of metformin, atorvastatin and bezafibrate on tadpoles. • Exposure caused increased growth and development but no effects on lipids or cholesterol. • {sup 1}H NMR-based metabolomics reveal increased lactic acid and BCAAs in exposed animals. - Abstract: Pharmaceuticals are widely used for the treatment of various physical and psychological ailments. Due to incomplete removal during sewage treatment many pharmaceuticals are frequently detected in aquatic waterways at trace concentrations. The diversity of pharmaceutical contaminants and potential for complex mixtures to occur makes it very difficult to predict the toxicity of these compounds on wildlife, and robust methods are therefore needed to explore sub-lethal effects. Metabolic syndrome is one of the most widespread health concerns currently facing the human population, and various drugs, including anti-diabetic medications and lipid- and cholesterol-lowering fibrates and statins, are widely prescribed as treatment. In this study, we exposed striped marsh frog (Limnodynastes peronii) tadpoles to a mixture of the drugs metformin, atorvastatin and bezafibrate at 0.5, 5, 50 and 500 μg/L to explore possible effects on growth and development, energy reserves (triglycerides and cholesterol), and profiles of small polar metabolites extracted from hepatic tissues. It was hypothesised that exposure would result in a general reduction in energy reserves, and that this would subsequently correspond with reduced growth and development. Responses differed from expected outcomes based on the known mechanisms of these compounds in humans, with no changes to hepatic triglycerides or cholesterol and a general increase in mass and condition with increasing exposure concentration. Deviation from the

  4. "1H NMR-based metabolomics reveals sub-lethal toxicity of a mixture of diabetic and lipid-regulating pharmaceuticals on amphibian larvae

    International Nuclear Information System (INIS)

    Melvin, Steven D.; Habener, Leesa J.; Leusch, Frederic D.L.; Carroll, Anthony R.

    2017-01-01

    Highlights: • Pharmaceutical pollutants are a concern for eliciting adverse effects in wildlife. • Diabetes and lipid regulating drugs are widely used and poorly removed from sewage. • We explored the toxicity of a mixture of metformin, atorvastatin and bezafibrate on tadpoles. • Exposure caused increased growth and development but no effects on lipids or cholesterol. • "1H NMR-based metabolomics reveal increased lactic acid and BCAAs in exposed animals. - Abstract: Pharmaceuticals are widely used for the treatment of various physical and psychological ailments. Due to incomplete removal during sewage treatment many pharmaceuticals are frequently detected in aquatic waterways at trace concentrations. The diversity of pharmaceutical contaminants and potential for complex mixtures to occur makes it very difficult to predict the toxicity of these compounds on wildlife, and robust methods are therefore needed to explore sub-lethal effects. Metabolic syndrome is one of the most widespread health concerns currently facing the human population, and various drugs, including anti-diabetic medications and lipid- and cholesterol-lowering fibrates and statins, are widely prescribed as treatment. In this study, we exposed striped marsh frog (Limnodynastes peronii) tadpoles to a mixture of the drugs metformin, atorvastatin and bezafibrate at 0.5, 5, 50 and 500 μg/L to explore possible effects on growth and development, energy reserves (triglycerides and cholesterol), and profiles of small polar metabolites extracted from hepatic tissues. It was hypothesised that exposure would result in a general reduction in energy reserves, and that this would subsequently correspond with reduced growth and development. Responses differed from expected outcomes based on the known mechanisms of these compounds in humans, with no changes to hepatic triglycerides or cholesterol and a general increase in mass and condition with increasing exposure concentration. Deviation from the

  5. Inertial confinement fusion at NRL

    International Nuclear Information System (INIS)

    Bodner, S.E.; Boris, J.P.; Cooperstein, G.

    1979-01-01

    The NRL Inertial Confinement Fusion Program's emphasis has moved toward pellet concepts which use longer (approximately 10ns) lower intensity driver pulses than previously assumed. For laser drivers, this change was motivated by recent experiments at NRL with enhanced stimulated Brillouin backscatter. For ion drivers, the motivation is the possibility that substantial energy at 10-ns pulse lengths may soon be available. To accept these 10-ns pulses, it may be necessary to consider pellets of larger radius and thinner shell. The computational studies of Rayleigh-Taylor instability at NRL indicate the possibility of a dynamic stabilization of these thinner shells. (author)

  6. Confinement through tensor gauge fields

    International Nuclear Information System (INIS)

    Salam, A.; Strathdee, J.

    1977-12-01

    Using the 0(3,2)-symmetric de Sitter solution of Einstein's equation describing a strongly interacting tensor field it is shown that hadronic bags confining quarks can be represented as de Sitter ''micro-universes'' with radii given 1/R 2 =lambdak 2 /6. Here k 2 and lambda are the strong coupling and the ''cosmological'' constant which apear in the Einstein equation used. Surprisingly the energy spectrum for the two-body hadronic states is the same as that for a harmonic oscillator potential, though the wave functions are completely different. The Einstein equation can be extended to include colour for the tensor fields

  7. Compact inertial confinement multireactor concepts

    International Nuclear Information System (INIS)

    Pendergrass, J.H.

    1985-01-01

    Inertial confinement fusion (ICF) commercial-applications plant-optimum driver pulse repetition rates may exceed reactor pulse-repetition-rate capabilities. Thus, more than one reactor may be required for low-cost production of electric power, process heat, fissionable fuels, etc., in ICF plants. Substantial savings in expensive reactor containment cells and blankets can be realized by placing more than one reactor in a cell and by surrounding more than one reactor cavity with a single blanket system. There are also some potential disadvantages associated with close coupling in compact multicavity blankets and multireactor cells. Tradeoffs associated with several scenarios have been studied

  8. Deciphering the Cryptic Genome: Genome-wide Analyses of the Rice Pathogen Fusarium fujikuroi Reveal Complex Regulation of Secondary Metabolism and Novel Metabolites

    Science.gov (United States)

    Studt, Lena; Niehaus, Eva-Maria; Espino, Jose J.; Huß, Kathleen; Michielse, Caroline B.; Albermann, Sabine; Wagner, Dominik; Bergner, Sonja V.; Connolly, Lanelle R.; Fischer, Andreas; Reuter, Gunter; Kleigrewe, Karin; Bald, Till; Wingfield, Brenda D.; Ophir, Ron; Freeman, Stanley; Hippler, Michael; Smith, Kristina M.; Brown, Daren W.; Proctor, Robert H.; Münsterkötter, Martin; Freitag, Michael; Humpf, Hans-Ulrich; Güldener, Ulrich; Tudzynski, Bettina

    2013-01-01

    The fungus Fusarium fujikuroi causes “bakanae” disease of rice due to its ability to produce gibberellins (GAs), but it is also known for producing harmful mycotoxins. However, the genetic capacity for the whole arsenal of natural compounds and their role in the fungus' interaction with rice remained unknown. Here, we present a high-quality genome sequence of F. fujikuroi that was assembled into 12 scaffolds corresponding to the 12 chromosomes described for the fungus. We used the genome sequence along with ChIP-seq, transcriptome, proteome, and HPLC-FTMS-based metabolome analyses to identify the potential secondary metabolite biosynthetic gene clusters and to examine their regulation in response to nitrogen availability and plant signals. The results indicate that expression of most but not all gene clusters correlate with proteome and ChIP-seq data. Comparison of the F. fujikuroi genome to those of six other fusaria revealed that only a small number of gene clusters are conserved among these species, thus providing new insights into the divergence of secondary metabolism in the genus Fusarium. Noteworthy, GA biosynthetic genes are present in some related species, but GA biosynthesis is limited to F. fujikuroi, suggesting that this provides a selective advantage during infection of the preferred host plant rice. Among the genome sequences analyzed, one cluster that includes a polyketide synthase gene (PKS19) and another that includes a non-ribosomal peptide synthetase gene (NRPS31) are unique to F. fujikuroi. The metabolites derived from these clusters were identified by HPLC-FTMS-based analyses of engineered F. fujikuroi strains overexpressing cluster genes. In planta expression studies suggest a specific role for the PKS19-derived product during rice infection. Thus, our results indicate that combined comparative genomics and genome-wide experimental analyses identified novel genes and secondary metabolites that contribute to the evolutionary success of F

  9. Comparison of 454-ESTs from Huperzia serrata and Phlegmariurus carinatus reveals putative genes involved in lycopodium alkaloid biosynthesis and developmental regulation

    Directory of Open Access Journals (Sweden)

    Steinmetz André

    2010-09-01

    Full Text Available Abstract Background Plants of the Huperziaceae family, which comprise the two genera Huperzia and Phlegmariurus, produce various types of lycopodium alkaloids that are used to treat a number of human ailments, such as contusions, swellings and strains. Huperzine A, which belongs to the lycodine type of lycopodium alkaloids, has been used as an anti-Alzheimer's disease drug candidate. Despite their medical importance, little genomic or transcriptomic data are available for the members of this family. We used massive parallel pyrosequencing on the Roche 454-GS FLX Titanium platform to generate a substantial EST dataset for Huperzia serrata (H. serrata and Phlegmariurus carinatus (P. carinatus as representative members of the Huperzia and Phlegmariurus genera, respectively. H. serrata and P. carinatus are important plants for research on the biosynthesis of lycopodium alkaloids. We focused on gene discovery in the areas of bioactive compound biosynthesis and transcriptional regulation as well as genetic marker detection in these species. Results For H. serrata, 36,763 unique putative transcripts were generated from 140,930 reads totaling over 57,028,559 base pairs; for P. carinatus, 31,812 unique putative transcripts were generated from 79,920 reads totaling over 30,498,684 base pairs. Using BLASTX searches of public databases, 16,274 (44.3% unique putative transcripts from H. serrata and 14,070 (44.2% from P. carinatus were assigned to at least one protein. Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG orthology annotations revealed that the functions of the unique putative transcripts from these two species cover a similarly broad set of molecular functions, biological processes and biochemical pathways. In particular, a total of 20 H. serrata candidate cytochrome P450 genes, which are more abundant in leaves than in roots and might be involved in lycopodium alkaloid biosynthesis, were found based on the comparison of H

  10. A Tragedy of Democracy: Japanese Confinement in North America

    Directory of Open Access Journals (Sweden)

    Greg Robinson

    2010-03-01

    Full Text Available

    The confinement of some 120,000 Japanese Americans during World War II, often called the Japanese American internment, has been described as the worst official civil rights violation of modern U. S. history. Greg Robinson not only offers a bold new understanding of these events but also studies them within a larger time frame and from a transnational perspective. Drawing on newly discovered material, Robinson provides a backstory of confinement that reveals for the first time the extent of the American government's surveillance of Japanese communities in the years leading up to war and the construction of what officials termed "concentration camps" for enemy aliens. He also considers the aftermath of confinement, including the place of Japanese Americans in postwar civil rights struggles, the long movement by former camp inmates for redress, and the continuing role of the camps as touchstones for nationwide commemoration and debate. Most remarkably, A Tragedy of Democracy is the first book to analyze official policy toward West Coast Japanese Americans within a North American context. Robinson studies confinement on the mainland alongside events in wartime Hawaii, where fears of Japanese Americans justified Army dictatorship, suspension of the Constitution, and the imposition of military tribunals. He similarly reads the treatment of Japanese Americans against Canada's confinement of 22,000 citizens and residents of Japanese ancestry from British Columbia. A Tragedy of Democracy recounts the expulsion of almost 5,000 Japanese from Mexico's Pacific Coast and the poignant story of the Japanese Latin Americans who were kidnapped from their homes and interned in the United States. Approaching Japanese confinement as a continental and international phenomenon, Robinson offers a truly kaleidoscopic understanding of its genesis and outcomes.

  11. A Tragedy of Democracy: Japanese Confinement in North America

    Directory of Open Access Journals (Sweden)

    Greg Robinson

    2010-03-01

    Full Text Available The confinement of some 120,000 Japanese Americans during World War II, often called the Japanese American internment, has been described as the worst official civil rights violation of modern U. S. history. Greg Robinson not only offers a bold new understanding of these events but also studies them within a larger time frame and from a transnational perspective. Drawing on newly discovered material, Robinson provides a backstory of confinement that reveals for the first time the extent of the American government's surveillance of Japanese communities in the years leading up to war and the construction of what officials termed "concentration camps" for enemy aliens. He also considers the aftermath of confinement, including the place of Japanese Americans in postwar civil rights struggles, the long movement by former camp inmates for redress, and the continuing role of the camps as touchstones for nationwide commemoration and debate. Most remarkably, A Tragedy of Democracy is the first book to analyze official policy toward West Coast Japanese Americans within a North American context. Robinson studies confinement on the mainland alongside events in wartime Hawaii, where fears of Japanese Americans justified Army dictatorship, suspension of the Constitution, and the imposition of military tribunals. He similarly reads the treatment of Japanese Americans against Canada's confinement of 22,000 citizens and residents of Japanese ancestry from British Columbia. A Tragedy of Democracy recounts the expulsion of almost 5,000 Japanese from Mexico's Pacific Coast and the poignant story of the Japanese Latin Americans who were kidnapped from their homes and interned in the United States. Approaching Japanese confinement as a continental and international phenomenon, Robinson offers a truly kaleidoscopic understanding of its genesis and outcomes.

  12. Holographic collisions in confining theories

    International Nuclear Information System (INIS)

    Cardoso, Vitor; Emparan, Roberto; Mateos, David; Pani, Paolo; Rocha, Jorge V.

    2014-01-01

    We study the gravitational dual of a high-energy collision in a confining gauge theory. We consider a linearized approach in which two point particles traveling in an AdS-soliton background suddenly collide to form an object at rest (presumably a black hole for large enough center-of-mass energies). The resulting radiation exhibits the features expected in a theory with a mass gap: late-time power law tails of the form t −3/2 , the failure of Huygens’ principle and distortion of the wave pattern as it propagates. The energy spectrum is exponentially suppressed for frequencies smaller than the gauge theory mass gap. Consequently, we observe no memory effect in the gravitational waveforms. At larger frequencies the spectrum has an upward-stairway structure, which corresponds to the excitation of the tower of massive states in the confining gauge theory. We discuss the importance of phenomenological cutoffs to regularize the divergent spectrum, and the aspects of the full non-linear collision that are expected to be captured by our approach

  13. Magnetic confinement fusion energy research

    International Nuclear Information System (INIS)

    Grad, H.

    1977-03-01

    Controlled Thermonuclear Fusion offers probably the only relatively clean energy solution with completely inexhaustible fuel and unlimited power capacity. The scientific and technological problem consists in magnetically confining a hot, dense plasma (pressure several to hundreds of atmospheres, temperature 10 8 degrees or more) for an appreciable fraction of a second. The scientific and mathematical problem is to describe the behavior, such as confinement, stability, flow, compression, heating, energy transfer and diffusion of this medium in the presence of electromagnetic fields just as we now can for air or steam. Some of the extant theory consists of applications, routine or ingenious, of known mathematical structures in the theory of differential equations and in traditional analysis. Other applications of known mathematical structures offer surprises and new insights: the coordination between sub-supersonic and elliptic-hyperbolic is fractured; supersonic propagation goes upstream; etc. Other completely nonstandard mathematical structures with significant theory are being rapidly uncovered (and somewhat less rapidly understood) such as non-elliptic variational equations and new types of weak solutions. It is these new mathematical structures which one should expect to supply the foundation for the next generation's pure mathematics, if history is a guide. Despite the substantial effort over a period of some twenty years, there are still basic and important scintific and mathematical discoveries to be made, lying just beneath the surface

  14. Quark cluster model and confinement

    International Nuclear Information System (INIS)

    Koike, Yuji; Yazaki, Koichi

    2000-01-01

    How confinement of quarks is implemented for multi-hadron systems in the quark cluster model is reviewed. In order to learn the nature of the confining interaction for fermions we first study 1+1 dimensional QED and QCD, in which the gauge field can be eliminated exactly and generates linear interaction of fermions. Then, we compare the two-body potential model, the flip-flop model and the Born-Oppenheimer approach in the strong coupling lattice QCD for the meson-meson system. Having shown how the long-range attraction between hadrons, van der Waals interaction, shows up in the two-body potential model, we discuss two distinct attempts beyond the two-body potential model: one is a many-body potential model, the flip-flop model, and the other is the Born-Oppenheimer approach in the strong coupling lattice QCD. We explain how the emergence of the long-range attraction is avoided in these attempts. Finally, we present the results of the application of the flip-flop model to the baryon-baryon scattering in the quark cluster model. (author)

  15. Multiple-mirror plasma confinement

    International Nuclear Information System (INIS)

    Lichtenberg, A.J.; Lieberman, M.A.; Logan, B.G.

    1975-01-01

    A large enhancement of the confinement time can be achieved in a straight system of multiple mirrors over an equal length uniform magnetic field. The scaling is diffusive rather than that of flow, thereby scaling the square of the system length rather than linear with system length. Probably the most economic mode of operation for a reactor occurs when lambda/M is approximately l/sub c/, where lambda is the mean free path, M the mirror ratio, and l/sub c/ the length between mirrors; but where the scale length of the mirror field l/sub m/ is much less than lambda. The axial confinement time has been calculated theoretically and numerically for all important parameter regimes, and confirmed experimentally. A typical reactor calculation gives Q/sub E/ = 2 for a 400 meter system with 3000 MW(e) output. The main concern of a multiple-mirror system is stability. Linked quadrupoles can achieve average minimum-B stabilization of flute modes, and experiments have demonstrated this stabilization. Localized instabilities at finite β and enhanced diffusion resulting from the distorted flux surfaces and possibly from turbulent higher order modes still remain to be investigated

  16. Generating random walks and polygons with stiffness in confinement

    International Nuclear Information System (INIS)

    Diao, Y; Ernst, C; Saarinen, S; Ziegler, U

    2015-01-01

    The purpose of this paper is to explore ways to generate random walks and polygons in confinement with a bias toward stiffness. Here the stiffness refers to the curvature angle between two consecutive edges along the random walk or polygon. The stiffer the walk (polygon), the smaller this angle on average. Thus random walks and polygons with an elevated stiffness have lower than expected curvatures. The authors introduced and studied several generation algorithms with a stiffness parameter s>0 that regulates the expected curvature angle at a given vertex in which the random walks and polygons are generated one edge at a time using conditional probability density functions. Our generating algorithms also allow the generation of unconfined random walks and polygons with any desired mean curvature angle. In the case of random walks and polygons confined in a sphere of fixed radius, we observe that, as expected, stiff random walks or polygons are more likely to be close to the confinement boundary. The methods developed here require that the random walks and random polygons be rooted at the center of the confinement sphere. (paper)

  17. Transient heat transfer into superfluid helium under confined conditions

    International Nuclear Information System (INIS)

    Filippov, Yu.P.; Miklyaev, V.M.; Sergeev, I.A.

    1988-01-01

    Transient thermal processes at solid-HeII interface at input of step pulse of heat load was investigated. Particular attention is given to the study of influence of geometry of experimental specimen upon the heat transfer dynamics. Abrupt breakdown of highly efficient transfer modes caused by the developmet of superfluid turbulence under confined condition is revealed, and accompanying temperature shift is registered. Some characteristic parameters are selected, their dependence on experimental conditions is established

  18. Elmo bumpy square plasma confinement device

    Science.gov (United States)

    Owen, L.W.

    1985-01-01

    The invention is an Elmo bumpy type plasma confinement device having a polygonal configuration of closed magnet field lines for improved plasma confinement. In the preferred embodiment, the device is of a square configuration which is referred to as an Elmo bumpy square (EBS). The EBS is formed by four linear magnetic mirror sections each comprising a plurality of axisymmetric assemblies connected in series and linked by 90/sup 0/ sections of a high magnetic field toroidal solenoid type field generating coils. These coils provide corner confinement with a minimum of radial dispersion of the confined plasma to minimize the detrimental effects of the toroidal curvature of the magnetic field. Each corner is formed by a plurality of circular or elliptical coils aligned about the corner radius to provide maximum continuity in the closing of the magnetic field lines about the square configuration confining the plasma within a vacuum vessel located within the various coils forming the square configuration confinement geometry.

  19. Single-Molecule Sensing with Nanopore Confinement: from Chemical Reactions to Biological Interactions.

    Science.gov (United States)

    Lin, Yao; Ying, Yi-Lun; Gao, Rui; Long, Yi-Tao

    2018-03-25

    The nanopore can generate an electrochemical confinement for single-molecule sensing which help understand the fundamental chemical principle in nanoscale dimensions. By observing the generated ionic current, individual bond-making and bond-breaking steps, single biomolecule dynamic conformational changes and electron transfer processes that occur within pore can be monitored with high temporal and current resolution. These single-molecule studies in nanopore confinement are revealing information about the fundamental chemical and biological processes that cannot be extracted from ensemble measurements. In this concept, we introduce and discuss the electrochemical confinement effects on single-molecule covalent reactions, conformational dynamics of individual molecules and host-guest interactions in protein nanopores. Then, we extend the concept of nanopore confinement effects to confine electrochemical redox reactions in solid-state nanopores for developing new sensing mechanisms. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Quark confinement in a constituent quark model

    International Nuclear Information System (INIS)

    Langfeld, K.; Rho, M.

    1995-01-01

    On the level of an effective quark theory, we define confinement by the absence of quark anti-quark thresholds in correlation function. We then propose a confining Nambu-Jona-Lasinio-type model. The confinement is implemented in analogy to Anderson localization in condensed matter systems. We study the model's phase structure as well as its behavior under extreme conditions, i.e. high temperature and/or high density

  1. Combined confinement system applied to tokamaks

    International Nuclear Information System (INIS)

    Ohkawa, Tihiro

    1986-01-01

    From particle orbit point of view, a tokamak is a combined confinement configuration where a closed toroidal volume is surrounded by an open confinement system like a magnetic mirror. By eliminating a cold halo plasma, the energy loss from the plasma becomes convective. The H-mode in diverted tokamaks is an example. Because of the favorable scaling of the energy confinement time with temperature, the performance of the tokamak may be significantly improved by taking advantage of this effect. (author)

  2. Functional analysis of the conserved transcriptional regulator CfWor1 in Cladosporium fulvum reveals diverse roles in the virulence of plant pathogenic fungi

    NARCIS (Netherlands)

    Ökmen, B.; Collemare, J.; Griffiths, S.A.; Burgt, van der A.; Cox, R.; Wit, de P.J.G.M.

    2014-01-01

    Fungal Wor1-like proteins are conserved transcriptional regulators that are reported to regulate the virulence of several plant pathogenic fungi by affecting the expression of virulence genes. Here, we report the functional analysis of CfWor1, the homologue of Wor1 in Cladosporium fulvum. ¿cfwor1

  3. Confinement studies of ohmically heated plasmas in TFTR

    International Nuclear Information System (INIS)

    Efthimion, P.C.; Bretz, N.L.; Bell, M.G.

    1985-03-01

    Systematic scans of density in large deuterium plasmas (a = 0.83 m) at several values of plasma current and toroidal magnetic field strength indicate that the total energy confinement time, tau/sub E/, is proportional to the line-average density anti n/sub e/ and the limiter q. Confinement times of approx. 0.3 s have been observed for anti n/sub e/ = 2.8 x 10 19 m -3 . Plasma size scaling experiments with plasmas of minor radii a = 0.83, 0.69, 0.55, and 0.41 m at constant limiter q reveal a confinement dependence on minor radius. The major-radius dependence of tau/sub E/, based on a comparison between TFTR and PLT results, is consistent with R 2 scaling. From the power balance, the thermal diffusivity chi/sub e/ is found to be significantly less than the INTOR value. In the a = 0.41 m plasmas, saturation of confinement is due to neoclassical ion conduction (chi/sub i/ neoclassical >> chi/sub e/)

  4. SOLAR MULTIPLE ERUPTIONS FROM A CONFINED MAGNETIC STRUCTURE

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeongwoo; Chae, Jongchul [Department of Physics and Astronomy, Seoul National University, Seoul 08826 (Korea, Republic of); Liu, Chang; Jing, Ju [Space Weather Research Laboratory, New Jersey Institute of Technology, Newark, NJ 07102 (United States)

    2016-09-20

    How eruption can recur from a confined magnetic structure is discussed based on the Solar Dynamics Observatory observations of the NOAA active region 11444, which produced three eruptions within 1.5 hr on 2012 March 27. The active region (AR) had the positive-polarity magnetic fields in the center surrounded by the negative-polarity fields around. Since such a distribution of magnetic polarity tends to form a dome-like magnetic fan structure confined over the AR, the multiple eruptions were puzzling. Our investigation reveals that this event exhibits several properties distinct from other eruptions associated with magnetic fan structures: (i) a long filament encircling the AR was present before the eruptions; (ii) expansion of the open–closed boundary (OCB) of the field lines after each eruption was suggestive of the growing fan-dome structure, and (iii) the ribbons inside the closed magnetic polarity inversion line evolved in response to the expanding OCB. It thus appears that in spite of multiple eruptions the fan-dome structure remained undamaged, and the closing back field lines after each eruption rather reinforced the fan-dome structure. We argue that the multiple eruptions could occur in this AR in spite of its confined magnetic structure because the filament encircling the AR was adequate for slipping through the magnetic separatrix to minimize the damage to its overlying fan-dome structure. The result of this study provides a new insight into the productivity of eruptions from a confined magnetic structure.

  5. SOLAR MULTIPLE ERUPTIONS FROM A CONFINED MAGNETIC STRUCTURE

    International Nuclear Information System (INIS)

    Lee, Jeongwoo; Chae, Jongchul; Liu, Chang; Jing, Ju

    2016-01-01

    How eruption can recur from a confined magnetic structure is discussed based on the Solar Dynamics Observatory observations of the NOAA active region 11444, which produced three eruptions within 1.5 hr on 2012 March 27. The active region (AR) had the positive-polarity magnetic fields in the center surrounded by the negative-polarity fields around. Since such a distribution of magnetic polarity tends to form a dome-like magnetic fan structure confined over the AR, the multiple eruptions were puzzling. Our investigation reveals that this event exhibits several properties distinct from other eruptions associated with magnetic fan structures: (i) a long filament encircling the AR was present before the eruptions; (ii) expansion of the open–closed boundary (OCB) of the field lines after each eruption was suggestive of the growing fan-dome structure, and (iii) the ribbons inside the closed magnetic polarity inversion line evolved in response to the expanding OCB. It thus appears that in spite of multiple eruptions the fan-dome structure remained undamaged, and the closing back field lines after each eruption rather reinforced the fan-dome structure. We argue that the multiple eruptions could occur in this AR in spite of its confined magnetic structure because the filament encircling the AR was adequate for slipping through the magnetic separatrix to minimize the damage to its overlying fan-dome structure. The result of this study provides a new insight into the productivity of eruptions from a confined magnetic structure.

  6. Global analysis of estrogen receptor beta binding to breast cancer cell genome reveals an extensive interplay with estrogen receptor alpha for target gene regulation

    Directory of Open Access Journals (Sweden)

    Papa Maria

    2011-01-01

    Full Text Available Abstract Background Estrogen receptors alpha (ERα and beta (ERβ are transcription factors (TFs that mediate estrogen signaling and define the hormone-responsive phenotype of breast cancer (BC. The two receptors can be found co-expressed and play specific, often opposite, roles, with ERβ being able to modulate the effects of ERα on gene transcription and cell proliferation. ERβ is frequently lost in BC, where its presence generally correlates with a better prognosis of the disease. The identification of the genomic targets of ERβ in hormone-responsive BC cells is thus a critical step to elucidate the roles of this receptor in estrogen signaling and tumor cell biology. Results Expression of full-length ERβ in hormone-responsive, ERα-positive MCF-7 cells resulted in a marked reduction in cell proliferation in response to estrogen and marked effects on the cell transcriptome. By ChIP-Seq we identified 9702 ERβ and 6024 ERα binding sites in estrogen-stimulated cells, comprising sites occupied by either ERβ, ERα or both ER subtypes. A search for TF binding matrices revealed that the majority of the binding sites identified comprise one or more Estrogen Response Element and the remaining show binding matrixes for other TFs known to mediate ER interaction with chromatin by tethering, including AP2, E2F and SP1. Of 921 genes differentially regulated by estrogen in ERβ+ vs ERβ- cells, 424 showed one or more ERβ site within 10 kb. These putative primary ERβ target genes control cell proliferation, death, differentiation, motility and adhesion, signal transduction and transcription, key cellular processes that might explain the biological and clinical phenotype of tumors expressing this ER subtype. ERβ binding in close proximity of several miRNA genes and in the mitochondrial genome, suggests the possible involvement of this receptor in small non-coding RNA biogenesis and mitochondrial genome functions. Conclusions Results indicate that the

  7. Sialotranscriptomics of Rhipicephalus zambeziensis reveals intricate expression profiles of secretory proteins and suggests tight temporal transcriptional regulation during blood-feeding.

    Science.gov (United States)

    de Castro, Minique Hilda; de Klerk, Daniel; Pienaar, Ronel; Rees, D Jasper G; Mans, Ben J

    2017-08-10

    Ticks secrete a diverse mixture of secretory proteins into the host to evade its immune response and facilitate blood-feeding, making secretory proteins attractive targets for the production of recombinant anti-tick vaccines. The largely neglected tick species, Rhipicephalus zambeziensis, is an efficient vector of Theileria parva in southern Africa but its available sequence information is limited. Next generation sequencing has advanced sequence availability for ticks in recent years and has assisted the characterisation of secretory proteins. This study focused on the de novo assembly and annotation of the salivary gland transcriptome of R. zambeziensis and the temporal expression of secretory protein transcripts in female and male ticks, before the onset of feeding and during early and late feeding. The sialotranscriptome of R. zambeziensis yielded 23,631 transcripts from which 13,584 non-redundant proteins were predicted. Eighty-six percent of these contained a predicted start and stop codon and were estimated to be putatively full-length proteins. A fifth (2569) of the predicted proteins were annotated as putative secretory proteins and explained 52% of the expression in the transcriptome. Expression analyses revealed that 2832 transcripts were differentially expressed among feeding time points and 1209 between the tick sexes. The expression analyses further indicated that 57% of the annotated secretory protein transcripts were differentially expressed. Dynamic expression profiles of secretory protein transcripts were observed during feeding of female ticks. Whereby a number of transcripts were upregulated during early feeding, presumably for feeding site establishment and then during late feeding, 52% of these were downregulated, indicating that transcripts were required at specific feeding stages. This suggested that secretory proteins are under stringent transcriptional regulation that fine-tunes their expression in salivary glands during feeding. No open

  8. Dynamics and reactivity of confined water

    International Nuclear Information System (INIS)

    Musat, R.

    2008-01-01

    In the context of new sustainable energy sources quest, the nuclear energy remains a key solution. However, with the development of nuclear technology, problems relating to nuclear waste disposal arise; thus, the radiolysis of water in confined media is extremely important with respect to matters related to long time storage of nuclear waste. Studies in model porous media would allow the projection of a confined water radiolysis simulator. A first step in this direction was made by studying the radiolysis of water confined in Vycor and CPG glasses; this study continues the trend set and investigates the effects of confinement in metal materials upon the water radiolysis allowing the understanding of metal - water radiation induced corrosion. A further/complete understanding of the radiolytic process under confinement requires knowledge of the effect of confinement upon the dynamics of confined molecules and on the evolution of the species produced upon ionizing radiation. In this respect, we have used the OH vibrator as a probe of the hydrogen bond network properties and thus investigated the dynamics of confined water using IR time resolved spectroscopy. The evolution of the hydrated electron under confinement was studied on a nano and picosecond time scale using UV pump - visible probe technique and single shot spectroscopy. (author) [fr

  9. Summary on inertial confinement fusion

    International Nuclear Information System (INIS)

    Meyer-Ter-Vehn, J.

    1995-01-01

    Highlights on inertial confinement during the fifteenth international conference on plasma physics and controlled nuclear fusion are briefly summarized. Specifically the following topics are discussed: the US National Ignition Facility presently planned by the US Department of Energy; demonstration of diagnostics for hot spot formation; declassification of Hohlraum target design; fusion targets, in particular, the Hohlraum target design for the National Ignition Facility (NIF), Hohlraum experiments, direct drive implosions, ablative Rayleigh-Taylor instabilities, laser imprinting (of perturbations by the laser on the laser target surface), hot spot formation and mixing, hot spot implosion experiments at Lawrence Livermore National Laboratory, Livermore, USA, time resolving hot spot dynamics at the Institute of Laser Engineering (ILE), Osaka, Japan, laser-plasma interaction

  10. Confined subdiffusion in three dimensions

    International Nuclear Information System (INIS)

    Qin Shan-Lin; He Yong

    2014-01-01

    Three-dimensional (3D) Fick's diffusion equation and fractional diffusion equation are solved for different reflecting boundaries. We use the continuous time random walk model (CTRW) to investigate the time-averaged mean square displacement (MSD) of a 3D single particle trajectory. Theoretical results show that the ensemble average of the time-averaged MSD can be expressed analytically by a Mittag—Leffler function. Our new expression is in agreement with previous formulas in two limiting cases: <δ 2 -bar> ∼ Δ in short lag time and <δ 2 -bar> ∼ Δ 1-α in long lag time. We also simulate the experimental data of mRNA diffusion in living E. coli using a 3D CTRW model under confined and crowded conditions. The simulation results are well consistent with experimental results. The calculations of power spectral density (PSD) further indicate the subdiffsive behavior of an individual trajectory. (general)

  11. Colour screening and quark confinement

    International Nuclear Information System (INIS)

    Mack, G.

    1978-03-01

    It is proposed that in Quantum Chromodynamics the colour charge of gluons and of anything with zero triality is screened by a dynamical Higgs mechanism with Higgs scalars made out of gluons. The center Z 3 of the gauge group SU(3) is left unbroken in this way, and single quarks, which have nonzero triality, cannot be screened. Long range forces between them persist therefore. Given that the Higgs mechanism produces a mass gap, the most favorable configuration of field lines between e.g. quark and antiquark will be in strings analogous to magnetic field lines in a superconductor. The strings confine the quarks. The screening mechanism, on the other hand, produces not only the mass gap (which leads to string formation) but is also responsible for saturation of forces, i.e. absence of bound states of six quarks etc. (orig.) [de

  12. Colour screening and quark confinement

    International Nuclear Information System (INIS)

    Mack, G.

    1978-01-01

    It is proposed that in quantum chromodynamics the colour charge of gluons and of anything with zero triality is screened by a dynamic Higgs mechanism with Higgs scalars made out of gluons, but the center Z 3 of the gauge group SU(3) is left unbroken, and single quarks, which have nonzero triality, are not screened. Long range forces between them persist therefore. Given that the Higgs mechanism produces a mass gap, the most favourable configuration of field lines between e.g., quark and antiquark will be in strings analogous to magnetic field lines in a superconductor. The string confine the quarks. The screening mechanism, on the other hand, produces not only the mass gap (which leads to string formation) but is also responsible for saturation of forces, i.e. absence of bound states of six quarks, etc. (Auth.)

  13. Tormac confinement, theory, and experiment

    International Nuclear Information System (INIS)

    Berk, H.L.; Brown, I.G.; Feinberg, B.

    1978-01-01

    Tormac is a stuffed toroidal line cusp: the magnetic field is divided into two distinct regions, i.e., an outside ''sheath'' layer where the plasma is mirror-confined on open field lines and an internal high-β region of closed nested flux surfaces. The sheath is arranged with the appropriate curvature to ensure absolute MHD stability everywhere. The bulk of the plasma is maintained on closed flux surfaces as in a typical toroidal configuration, but with enhanced MHD stability due to the external field shaping. Experimental results on a toroidal ''bicusp'' (Tormac IV) will be reported. This device has a boro-silicate glass chamber and holds a plasma with an aspect ratio of 4 and a major diameter of 35 cm

  14. Planning for greater confinement disposal

    International Nuclear Information System (INIS)

    Gilbert, T.L.; Luner, C.; Meshkov, N.K.; Trevorrow, L.E.; Yu, C.

    1985-01-01

    A report that provides guidance for planning for greater-confinement disposal (GCD) of low-level radioactive waste is being prepared. The report addresses procedures for selecting a GCD technology and provides information for implementing these procedures. The focus is on GCD; planning aspects common to GCD and shallow-land burial are covered by reference. Planning procedure topics covered include regulatory requirements, waste characterization, benefit-cost-risk assessment and pathway analysis methodologies, determination of need, waste-acceptance criteria, performance objectives, and comparative assessment of attributes that support these objectives. The major technologies covered include augered shafts, deep trenches, engineered structures, hydrofracture, improved waste forms, and high-integrity containers. Descriptive information is provided, and attributes that are relevant for risk assessment and operational requirements are given. 10 refs., 3 figs., 2 tabs

  15. Numerical modeling of the transition from low to high confinement in magnetically confined plasma

    DEFF Research Database (Denmark)

    Rasmussen, Jens Juul; Nielsen, Anders Henry; Madsen, Jens

    2016-01-01

    The transition dynamics from low (L) to high (H) mode confinement in magnetically confined plasmas is investigated using a four-field drift fluid model—HESEL (Hot Edge-Sol-Electrostatic). The model includes profile evolution and is solved in a 2D domain at the out-board mid-plane of a tokamak......–I–H transition with an intermediate I-phase displaying limit-cycle oscillations (LCO). The model recovers the power threshold for the L–H transition, the scaling of the threshold with the density and with the loss-rate in the SOL, indicating a decrease in power threshold when switching from single to double null...... including both open and closed field lines. The results reveal different types of L–H-like transitions in response to ramping up the input power by increasing the ion temperature in the edge region. For a fast rising input power we obtain an abrupt transition, and for a slow rising power we obtain a L...

  16. Numerical modeling of the transition from low to high confinement in magnetically confined plasma

    International Nuclear Information System (INIS)

    Rasmussen, J Juul; Nielsen, A H; Madsen, J; Naulin, V; Xu, G S

    2016-01-01

    The transition dynamics from low (L) to high (H) mode confinement in magnetically confined plasmas is investigated using a four-field drift fluid model—HESEL (Hot Edge-Sol-Electrostatic). The model includes profile evolution and is solved in a 2D domain at the out-board mid-plane of a tokamak including both open and closed field lines. The results reveal different types of L–H-like transitions in response to ramping up the input power by increasing the ion temperature in the edge region. For a fast rising input power we obtain an abrupt transition, and for a slow rising power we obtain a L–I–H transition with an intermediate I-phase displaying limit-cycle oscillations (LCO). The model recovers the power threshold for the L–H transition, the scaling of the threshold with the density and with the loss-rate in the SOL, indicating a decrease in power threshold when switching from single to double null configuration. The results hold promises for developing full predictive modeling of the L–H transition, which is an essential step in understanding and optimizing fusion devices. (paper)

  17. 2XIIB plasma confinement experiments

    International Nuclear Information System (INIS)

    Coensgen, F.H.; Clauser, J.F.; Correll, D.L.

    1976-01-01

    This paper reports results of 2XIIB neutral-beam injection experiments with plasma-stream stabilization. The plasma stream is provided either by a pulsed plasma generator located on the field lines outside the plasma region or by ionization of neutral gas introduced at the mirror throat. In the latter case, the gas is ionized by the normal particle flux through the magnetic mirror. A method of plasma startup and sustenance in a steady-state magnetic field is reported in which the plasma stream from the pulsed plasma generator serves as the initial target for the neutral beams. After an energetic plasma of sufficient density is established, the plasma generator stream is replaced by the gas-fed stream. Lifetimes of the stabilized plasma increase with plasma temperature in agreement with the plasma stabilization of the drift-cyclotron loss-cone mode. The following plasma parameters are attained using the pulsed plasma generator for stabilization: n approximately 5 x 10 13 cm -3 , anti W/sub i/ approximately 13 keV, T/sub e/ = 140 eV, and ntau/sub p/ approximately 7 x 10 10 cm -3 .s. With the gas feed, the mean deuterium ion energy is 9 keV and the peak density n approximately 10 14 cm -3 . In the latter case, the energy confinement parameter reaches ntau/sub E/ = 7 x 10 10 cm -3 .s, and the particle confinement parameter reaches ntau/sub p/ = 1 x 10 11 cm -3 .s

  18. Confinement and electron correlation effects in photoionization of atoms in endohedral anions: Ne-Cz-60

    International Nuclear Information System (INIS)

    Dolmatov, V K; Craven, G T; Keating, D

    2010-01-01

    Trends in resonances, termed confinement resonances, in photoionization of atoms A in endohedral fullerene anions A-C z- 60 are theoretically studied and exemplified by the photoionization of Ne in Ne-C z- 60 . Remarkably, above a particular nl ionization threshold of Ne in neutral Ne-C 60 (I z=0 nl ), confinement resonances in corresponding partial photoionization cross sections σ nl of Ne in any charged Ne-C z- 60 are not affected by a variation in the charge z of the carbon cage, as a general phenomenon. At lower photon energies, ω z=0 nl , the corresponding photoionization cross sections of charged Ne-C z- 60 (i.e., those with z ≠ 0) develop additional, strong, z-dependent resonances, termed Coulomb confinement resonances, as a general occurrence. Furthermore, near the innermost 1s ionization threshold, the 2p photoionization cross section σ 2p of the outermost 2p subshell of thus confined Ne is found to inherit the confinement resonance structure of the 1s photoionization spectrum, via interchannel coupling. As a result, new confinement resonances emerge in the 2p photoionization cross section of the confined Ne atom at photoelectron energies which exceed the 2p threshold by about a thousand eV, i.e., far above where conventional wisdom said they would exist. Thus, the general possibility for confinement resonances to resurrect in photoionization spectra of encapsulated atoms far above thresholds is revealed, as an interesting novel general phenomenon.

  19. Generating equilateral random polygons in confinement III

    International Nuclear Information System (INIS)

    Diao, Y; Ernst, C; Montemayor, A; Ziegler, U

    2012-01-01

    In this paper we continue our earlier studies (Diao et al 2011 J. Phys. A: Math. Theor. 44 405202, Diao et al J. Phys. A: Math. Theor. 45 275203) on the generation methods of random equilateral polygons confined in a sphere. The first half of this paper is concerned with the generation of confined equilateral random walks. We show that if the selection of a vertex is uniform subject to the position of its previous vertex and the confining condition, then the distributions of the vertices are not uniform, although there exists a distribution such that if the initial vertex is selected following this distribution, then all vertices of the random walk follow this same distribution. Thus in order to generate a confined equilateral random walk, the selection of a vertex cannot be uniform subject to the position of its previous vertex and the confining condition. We provide a simple algorithm capable of generating confined equilateral random walks whose vertex distribution is almost uniform in the confinement sphere. In the second half of this paper we show that any process generating confined equilateral random walks can be turned into a process generating confined equilateral random polygons with the property that the vertex distribution of the polygons approaches the vertex distribution of the walks as the polygons get longer and longer. In our earlier studies, the starting point of the confined polygon is fixed at the center of the sphere. The new approach here allows us to move the starting point of the confined polygon off the center of the sphere. (paper)

  20. An optimized method for measuring hypocretin-1 peptide in the mouse brain reveals differential circadian regulation of hypocretin-1 levels rostral and caudal to the hypothalamus

    DEFF Research Database (Denmark)

    Justinussen, J L; Holm, A; Kornum, B R

    2015-01-01

    an optimized peptide quantification method for hypocretin-1 extracted from different mouse brain areas and use this method for investigating circadian fluctuations of hypocretin-1 levels in these areas. The results show that hypocretin-1 peptide can be extracted from small pieces of intact tissue...... as does prepro-hypocretin mRNA in the hypothalamus. However, in midbrain and brainstem tissue caudal to the hypothalamus, there was less circadian fluctuation and a tendency for higher levels during the light phase. These data suggest that regulation of the hypocretin system differs between brain areas.......The hypocretin/orexin system regulates, among other things, sleep and energy homeostasis. The system is likely regulated by both homeostatic and circadian mechanisms. Little is known about local differences in the regulation of hypocretin activity. The aim of this study was to establish...

  1. Near-membrane dynamics and capture of TRPM8 channels within transient confinement domains.

    Directory of Open Access Journals (Sweden)

    Luis A Veliz

    Full Text Available BACKGROUND: The cold and menthol receptor, TRPM8, is a non-selective cation channel expressed in a subset of peripheral neurons that is responsible for neuronal detection of environmental cold stimuli. It was previously shown that members of the transient receptor potential (TRP family of ion channels are translocated toward the plasma membrane (PM in response to agonist stimulation. Because the spatial and temporal dynamics of cold receptor cell-surface residence may determine neuronal activity, we hypothesized that the movement of TRPM8 to and from the PM might be a regulated process. Single particle tracking (SPT is a useful tool for probing the organization and dynamics of protein constituents in the plasma membrane. METHODOLOGY/PRINCIPAL FINDINGS: We used SPT to study the receptor dynamics and describe membrane/near-membrane behavior of particles containing TRPM8-EGFP in transfected HEK-293T and F-11 cells. Cells were imaged using total internal reflection fluorescence (TIRF microscopy and the 2D and 3D trajectories of TRPM8 molecules were calculated by analyzing mean-square particle displacement against time. Four characteristic types of motion were observed: stationary mode, simple Brownian diffusion, directed motion, and confined diffusion. In the absence of cold or menthol to activate the channel, most TRPM8 particles move in network covering the PM, periodically lingering for 2-8 s in confined microdomains of about 800 nm radius. Removing cholesterol with methyl-beta-cyclodextrin (MβCD stabilizes TRPM8 motion in the PM and is correlated with larger TRPM8 current amplitude that results from an increase in the number of available channels without a change in open probability. CONCLUSIONS/SIGNIFICANCE: These results reveal a novel mechanism for regulating TRPM8 channel activity, and suggest that PM dynamics may play an important role in controlling electrical activity in cold-sensitive neurons.

  2. Climate conditions in bedded confinement buildings

    Science.gov (United States)

    Confinement buildings are utilized for finishing cattle to allow more efficient collection of animal waste and to buffer animals against adverse climatic conditions. Environmental data were obtained from a 29 m wide x 318 m long bedded confinement building with the long axis oriented east to west. T...

  3. Characterization of cleavage events in the multifunctional cilium adhesin Mhp684 (P146) reveals a mechanism by which Mycoplasma hyopneumoniae regulates surface topography.

    Science.gov (United States)

    Bogema, Daniel R; Deutscher, Ania T; Woolley, Lauren K; Seymour, Lisa M; Raymond, Benjamin B A; Tacchi, Jessica L; Padula, Matthew P; Dixon, Nicholas E; Minion, F Chris; Jenkins, Cheryl; Walker, Mark J; Djordjevic, Steven P

    2012-01-01

    Mycoplasma hyopneumoniae causes enormous economic losses to swine production worldwide by colonizing the ciliated epithelium in the porcine respiratory tract, resulting in widespread damage to the mucociliary escalator, prolonged inflammation, reduced weight gain, and secondary infections. Protein Mhp684 (P146) comprises 1,317 amino acids, and while the N-terminal 400 residues display significant sequence identity to the archetype cilium adhesin P97, the remainder of the molecule is novel and displays unusual motifs. Proteome analysis shows that P146 preprotein is endogenously cleaved into three major fragments identified here as P50(P146), P40(P146), and P85(P146) that reside on the cell surface. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) identified a semitryptic peptide that delineated a major cleavage site in Mhp684. Cleavage occurred at the phenylalanine residue within sequence (672)ATEF↓QQ(677), consistent with a cleavage motif resembling S/T-X-F↓X-D/E recently identified in Mhp683 and other P97/P102 family members. Biotinylated surface proteins recovered by avidin chromatography and separated by two-dimensional gel electrophoresis (2-D GE) showed that more-extensive endoproteolytic cleavage of P146 occurs. Recombinant fragments F1(P146)-F3(P146) that mimic P50(P146), P40(P146), and P85(P146) were constructed and shown to bind porcine epithelial cilia and biotinylated heparin with physiologically relevant affinity. Recombinant versions of F3(P146) generated from M. hyopneumoniae strain J and 232 sequences strongly bind porcine plasminogen, and the removal of their respective C-terminal lysine and arginine residues significantly reduces this interaction. These data reveal that P146 is an extensively processed, multifunctional adhesin of M. hyopneumoniae. Extensive cleavage coupled with variable cleavage efficiency provides a mechanism by which M. hyopneumoniae regulates protein topography. Vaccines used to control Mycoplasma

  4. Counterion effects on nano-confined metal–drug–DNA complexes

    Directory of Open Access Journals (Sweden)

    Nupur Biswas

    2016-01-01

    Full Text Available We have explored morphology of DNA molecules bound with Cu complexes of piroxicam (a non-steroidal anti-inflammatory drug molecules under one-dimensional confinement of thin films and have studied the effect of counterions present in a buffer. X-ray reflectivity at and away from the Cu K absorption edge and atomic force microscopy studies reveal that confinement segregates the drug molecules preferentially in a top layer of the DNA film, and counterions enhance this segregation.

  5. Comparison of confinement characters between porous silicon and silicon nanowires

    International Nuclear Information System (INIS)

    Tit, Nacir; Yamani, Zain H.; Pizzi, Giovanni; Virgilio, Michele

    2011-01-01

    Confinement character and its effects on photoluminescence (PL) properties are theoretically investigated and compared between porous silicon (p-Si) and silicon nanowires (Si-NWs). The method is based on the application of the tight-binding technique using the minimal sp 3 -basis set, including the second-nearest-neighbor interactions. The results show that the quantum confinement (QC) is not entirely controlled by the porosity, rather it is mainly affected by the average distance between pores (d). The p-Si is found to exhibit weaker confinement character than Si-NWs. The confinement energy of charge carriers decays against d exponentially for p-Si and via a power-law for Si-NWs. This latter type of QC is much stronger and is somewhat similar to the case of a single particle in a quantum box. The excellent fit to the PL data demonstrates that the experimental samples of p-Si do exhibit strong QC character and thus reveals the possibility of silicon clustering into nano-crystals and/or nanowires. Furthermore, the results show that the passivation of the surface dangling bonds by the hydrogen atoms plays an essential role in preventing the appearance of gap states and consequently enhances the optical qualities of the produced structures. The oscillator strength (OS) is found to increase exponentially with energy in Si-NWs confirming the strong confinement character of carriers. Our theoretical findings suggest the existence of Si nanocrystals (Si-NCs) of sizes 1-3 nm and/or Si-NWs of cross-sectional sizes in the 1-3 nm range inside the experimental p-Si samples. The experimentally-observed strong photoluminescence from p-Si should be in favor of an exhibition of 3D-confinement character. The favorable comparison of our theoretical results with the experimental data consolidates our above claims. -- Highlights: → Tight-binding is used to study quantum-confinement (QC) effects in p-Si and Si-NWs. → QC is not entirely controlled by the porosity but also by the d

  6. An introduction to the confinement problem

    International Nuclear Information System (INIS)

    Greensite, Jeff

    2011-01-01

    This book addresses the confinement problem, which quite generally deals with the behavior of non-abelian gauge theories, and the force which is mediated by gauge fields, at large distances.The word ''confinement'' in the context of hadronic physics originally referred to the fact that quarks and gluons appear to be trapped inside mesons and baryons, from which they cannot escape. There are other, and possibly deeper meanings that can be attached to the term, and these will be explored in this book. Although the confinement problem is far from solved, much is now known about the general features of the confining force, and there are a number of very well motivated theories of confinement which are under active investigation. This volume gives a both pedagogical and concise introduction and overview of the main ideas in this field, their attractive features, and, as appropriate, their shortcomings. (orig.)

  7. Global energy confinement in TORE SUPRA

    International Nuclear Information System (INIS)

    Hoang, G.T.; Bizarro, J.P.; Genile, B. de; Hutter, Th.; Laurent, L.; Litaudon, X.; Moreau, D.; Peysson, Y.; Tonon, G.; Houtte, D. van

    1992-01-01

    The global energy confinement behaviour of mixed Ohmic/Lower Hybrid driven Tore Supra plasmas has been analysed at various densities. In contradiction with L-mode ITER scaling law, this analysis indicates that the global energy confinement time depends strongly on the plasma density and the isotopic dependence seems not to be observed. The thermal electron energy content of steady-state discharges is in good agreement with the offset linear Rebut-Lallia scaling law. During current ramp experiments, the global energy confinement time was found to depend on the internal self-inductance (li). Improved confinement has been obtained for a steady-state 0.8 MA plasma where the plasma current profile is peaked by LH waves (li ∼1.8). In this case, the global confinement time is found to be about 40% higher than the value predicted by the Rebut-Lallia scaling law. (author) 3 refs., 6 figs

  8. Confinement-induced resonances in anharmonic waveguides

    Energy Technology Data Exchange (ETDEWEB)

    Peng Shiguo [Department of Physics, Tsinghua University, Beijing 100084 (China); Centre for Atom Optics and Ultrafast Spectroscopy, Swinburne University of Technology, Melbourne 3122 (Australia); Hu Hui; Liu Xiaji; Drummond, Peter D. [Centre for Atom Optics and Ultrafast Spectroscopy, Swinburne University of Technology, Melbourne 3122 (Australia)

    2011-10-15

    We develop the theory of anharmonic confinement-induced resonances (ACIRs). These are caused by anharmonic excitation of the transverse motion of the center of mass (c.m.) of two bound atoms in a waveguide. As the transverse confinement becomes anisotropic, we find that the c.m. resonant solutions split for a quasi-one-dimensional (1D) system, in agreement with recent experiments. This is not found in harmonic confinement theories. A new resonance appears for repulsive couplings (a{sub 3D}>0) for a quasi-two-dimensional (2D) system, which is also not seen with harmonic confinement. After inclusion of anharmonic energy corrections within perturbation theory, we find that these ACIRs agree extremely well with anomalous 1D and 2D confinement-induced resonance positions observed in recent experiments. Multiple even- and odd-order transverse ACIRs are identified in experimental data, including up to N=4 transverse c.m. quantum numbers.

  9. Forms of cohesion in confinement institutions

    Directory of Open Access Journals (Sweden)

    Ekaterina D. Slobodenyuk

    2015-12-01

    Full Text Available Objective to identify the diversity of cohesion forms in confinement institutions. Methods qualitative analyses based on indepth semistructured interviews. Results the study included adaptation of Western methodologies of the cohesion phenomenon analysis to the Russian reality and operationalization of the moral bases of group cohesion. This served as the bases for designing a guide for indepth semistructured interviews 10 interviews were conducted with people recently released from general and strict regime colonies. Content analysis of the interviews revealed a number of structural sections that demonstrate the diversity of cohesion forms alongside with one that is most meaningful to the prisoners and therefore the most well perceived and articulated by respondents. Analysis of the latter allowed to identify a set of groups showing different degree and nature of cohesion. By the degree of cohesion one can identify the poorly cohesive groups quotloutsquot moderately cohesive quotredsquot quotthievesquot and highly cohesive quotfightersquot. By the nature of cohesion in the prisonersrsquo community there are both groups united on the basis of social morality quotredsquot quotthievesquot and groups demonstrating a high degree of cohesion based on the social justice morality quotfightersquot. A detailed analysis of the latter group also showed that the cohesion can have both traits of morality social justice and features of social order moral. Scientific novelty using the sociopsychological theory of the moral motives in determining the bases of cohesion. Practical significance the research results can be applied for the development of sociopsychological techniques for the penal system reform.

  10. Transcriptome analyses reveal the involvement of both C and N termini of cryptochrome 1 in its regulation of phytohormone-responsive gene expression in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Wenxiu eWang

    2016-03-01

    Full Text Available Cryptochromes (CRY are blue-light photoreceptors that mediate various light responses in plants and animals. It has long been demonstrated that Arabidopsis CRY (CRY1 and CRY2 C termini (CCT1 and CCT2 mediate light signaling through direct interaction with COP1. Most recently, CRY1 N terminus (CNT1 has been found to be involved in CRY1 signaling independent of CCT1, and implicated in the inhibition of gibberellin acids (GA/brassinosteroids (BR/auxin-responsive gene expression. Here, we performed RNA-Seq assay using transgenic plants expressing CCT1 fused to β-glucuronidase (GUS-CCT1, abbreviated as CCT1, which exhibit a constitutively photomorphogenic phenotype, and compared the results with those obtained previously from cry1cry2 mutant and the transgenic plants expressing CNT1 fused to nuclear localization signal sequence (NLS-tagged YFP (CNT1-NLS-YFP, abbreviated as CNT1, which display enhanced responsiveness to blue light. We found that 2,903 (67.85% of the CRY-regulated genes are regulated by CCT1 and that 1,095 of these CCT1-regulated genes are also regulated by CNT1. After annotating the gene functions, we found that CCT1 is involved in mediating CRY1 regulation of phytohormone-responsive genes, like CNT1, and that about half of the up-regulated genes by GA/BR/auxin are down-regulated by CCT1 and CNT1, consistent with the antagonistic role for CRY1 and these phytohormones in regulating hypocotyl elongation. Physiological studies showed that both CCT1 and CNT1 are likely involved in mediating CRY1 reduction of seedlings sensitivity to GA under blue light. Furthermore, protein expression studies demonstrate that the inhibition of GA promotion of HY5 degradation by CRY1 is likely mediated by CCT1, but not by CNT1. These results give genome-wide transcriptome information concerning the signaling mechanism of CRY1, unraveling possible involvement of its C and N termini in its regulation of response of GA and likely other phytohormones.

  11. Whole blood transcriptional profiling reveals significant down-regulation of human leukocyte antigen class I and II genes in essential thrombocythemia, polycythemia vera and myelofibrosis

    DEFF Research Database (Denmark)

    Skov, Vibe; Riley, Caroline Hasselbalch; Thomassen, Mads

    2013-01-01

    Gene expression profiling studies in the Philadelphia-negative chronic myeloproliferative neoplasms have revealed significant deregulation of several immune and inflammation genes that might be of importance for clonal evolution due to defective tumor immune surveillance. Other mechanisms might b...

  12. The nature of confined states

    International Nuclear Information System (INIS)

    Woo, C.H.

    1979-01-01

    We show that in spite of charge confinement in the Schwinger model and its nonconfinement in (QED) 4 , the charged states in the two theories have many features in common. A convenient infrared regularization procedure is introduced to facilitate the study of large-distance behaviors in the Schwinger model, particularly those properties that are relevant ot the question of when a charged state is physical. One difference that emerges between the two theories is that when a charged state in the Schwinger model is made physical while its energy is kept bounded, the charge goes off to infinity. Thr end-product could be considered neutral if the charge is defined as the limit of local measurements. On the other hadn, if one attempts to change a local charged state in the Schwinger model into a physical state by transportin the localization region to asymptotic distances, the state may end up in either a THETA-sector or the corresponding (THETA + π)-sector, depending on the direction of transport. A possible generalization of this THETA-mixing property to quark-like states in QCD is commented upon. (orig.)

  13. Extremely confined gap surface-plasmon modes excited by electrons

    DEFF Research Database (Denmark)

    Raza, Søren; Stenger, Nicolas; Pors, Anders Lambertus

    2014-01-01

    High-spatial and energy resolution electron energy-loss spectroscopy (EELS) can be used for detailed characterization of localized and propagating surface-plasmon excitations in metal nanostructures, giving insight into fundamental physical phenomena and various plasmonic effects. Here, applying...... EELS to ultra-sharp convex grooves in gold, we directly probe extremely confined gap surface-plasmon (GSP) modes excited by swift electrons in nanometre-wide gaps. We reveal the resonance behaviour associated with the excitation of the antisymmetric GSP mode for extremely small gap widths, down to ~5...... mode exploited in plasmonic waveguides with extreme light confinement is a very important factor that should be taken into account in the design of nanoplasmonic circuits and devices....

  14. Genetic and systems level analysis of Drosophila sticky/citron kinase and dFmr1 mutants reveals common regulation of genetic networks

    Directory of Open Access Journals (Sweden)

    Zarnescu Daniela C

    2008-11-01

    Full Text Available Abstract Background In Drosophila, the genes sticky and dFmr1 have both been shown to regulate cytoskeletal dynamics and chromatin structure. These genes also genetically interact with Argonaute family microRNA regulators. Furthermore, in mammalian systems, both genes have been implicated in neuronal development. Given these genetic and functional similarities, we tested Drosophila sticky and dFmr1 for a genetic interaction and measured whole genome expression in both mutants to assess similarities in gene regulation. Results We found that sticky mutations can dominantly suppress a dFmr1 gain-of-function phenotype in the developing eye, while phenotypes produced by RNAi knock-down of sticky were enhanced by dFmr1 RNAi and a dFmr1 loss-of-function mutation. We also identified a large number of transcripts that were misexpressed in both mutants suggesting that sticky and dFmr1 gene products similarly regulate gene expression. By integrating gene expression data with a protein-protein interaction network, we found that mutations in sticky and dFmr1 resulted in misexpression of common gene networks, and consequently predicted additional specific phenotypes previously not known to be associated with either gene. Further phenotypic analyses validated these predictions. Conclusion These findings establish a functional link between two previously unrelated genes. Microarray analysis indicates that sticky and dFmr1 are both required for regulation of many developmental genes in a variety of cell types. The diversity of transcripts regulated by these two genes suggests a clear cause of the pleiotropy that sticky and dFmr1 mutants display and provides many novel, testable hypotheses about the functions of these genes. As both of these genes are implicated in the development and function of the mammalian brain, these results have relevance to human health as well as to understanding more general biological processes.

  15. Transcriptome-wide analysis of jasmonate-treated BY-2 cells reveals new transcriptional regulators associated with alkaloid formation in tobacco.

    Science.gov (United States)

    Yang, Yuping; Yan, Pengcheng; Yi, Che; Li, Wenzheng; Chai, Yuhui; Fei, Lingling; Gao, Ping; Zhao, Heping; Wang, Yingdian; Timko, Michael P; Wang, Bingwu; Han, Shengcheng

    2017-08-01

    Jasmonates (JAs) are well-known regulators of stress, defence, and secondary metabolism in plants, with JA perception triggering extensive transcriptional reprogramming, including both activation and/or repression of entire metabolic pathways. We performed RNA sequencing based transcriptomic profiling of tobacco BY-2 cells before and after treatment with methyl jasmonate (MeJA) to identify novel transcriptional regulators associated with alkaloid formation. A total of 107,140 unigenes were obtained through de novo assembly, and at least 33,213 transcripts (31%) encode proteins, in which 3419 transcription factors (TFs) were identified, representing 72 gene families, as well as 840 transcriptional regulators (TRs) distributed among 19 gene families. After MeJA treatment BY-2 cells, 7260 differentially expressed transcripts were characterised, which include 4443 MeJA-upregulated and 2817 MeJA-downregulated genes. Of these, 227 TFs/TRs in 36 families were specifically upregulated, and 102 TFs/TRs in 38 families were downregulated in MeJA-treated BY-2 cells. We further showed that the expression of 12 ethylene response factors and four basic helix-loop-helix factors increased at the transcriptional level after MeJA treatment in BY-2 cells and displayed specific expression patterns in nic mutants with or without MeJA treatments. Our data provide a catalogue of transcripts of tobacco BY-2 cells and benefit future study of JA-modulated regulation of secondary metabolism in tobacco. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. A genome-wide scan reveals important roles of DNA methylation in human longevity by regulating age-related disease genes.

    Directory of Open Access Journals (Sweden)

    Fu-Hui Xiao

    Full Text Available It is recognized that genetic factors contribute to human longevity. Besides the hypothesis of existence of longevity genes, another suggests that a lower frequency of risk alleles decreases the incidence of age-related diseases in the long-lived people. However, the latter finds no support from recent genetic studies. Considering the crucial role of epigenetic modification in gene regulation, we then hypothesize that suppressing disease-related genes in longevity individuals is likely achieved by epigenetic modification, e.g. DNA methylation. To test this hypothesis, we investigated the genome-wide methylation profile in 4 Chinese female centenarians and 4 middle-aged controls using methyl-DNA immunoprecipitation sequencing. 626 differentially methylated regions (DMRs were observed between both groups. Interestingly, genes with these DMRs were enriched in age-related diseases, including type-2 diabetes, cardiovascular disease, stroke and Alzheimer's disease. This pattern remains rather stable after including methylomes of two white individuals. Further analyses suggest that the observed DMRs likely have functional roles in regulating disease-associated gene expressions, with some genes [e.g. caspase 3 (CASP3] being down-regulated whereas the others [i.e. interleukin 1 receptor, type 2 (IL1R2] up-regulated. Therefore, our study suggests that suppressing the disease-related genes via epigenetic modification is an important contributor to human longevity.

  17. An optimized method for measuring hypocretin-1 peptide in the mouse brain reveals differential circadian regulation of hypocretin-1 levels rostral and caudal to the hypothalamus.

    Science.gov (United States)

    Justinussen, J L; Holm, A; Kornum, B R

    2015-12-03

    The hypocretin/orexin system regulates, among other things, sleep and energy homeostasis. The system is likely regulated by both homeostatic and circadian mechanisms. Little is known about local differences in the regulation of hypocretin activity. The aim of this study was to establish an optimized peptide quantification method for hypocretin-1 extracted from different mouse brain areas and use this method for investigating circadian fluctuations of hypocretin-1 levels in these areas. The results show that hypocretin-1 peptide can be extracted from small pieces of intact tissue, with sufficient yield for measurements in a standard radioimmunoassay. Utilizing the optimized method, it was found that prepro-hypocretin mRNA and peptide show circadian fluctuations in the mouse brain. This study further demonstrates that the hypocretin-1 peptide level in the frontal brain peaks during dark as does prepro-hypocretin mRNA in the hypothalamus. However, in midbrain and brainstem tissue caudal to the hypothalamus, there was less circadian fluctuation and a tendency for higher levels during the light phase. These data suggest that regulation of the hypocretin system differs between brain areas. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation

    DEFF Research Database (Denmark)

    Milani, Lili; Lundmark, Anders; Nordlund, Jessica

    2008-01-01

    To identify genes that are regulated by cis-acting functional elements in acute lymphoblastic leukemia (ALL) we determined the allele-specific expression (ASE) levels of 2, 529 genes by genotyping a genome-wide panel of single nucleotide polymorphisms in RNA and DNA from bone marrow and blood...

  19. Proteomics of red and white corolla limbs in petunia reveals a novel function of the anthocyanin regulator ANTHOCYANIN1 in determining flower longevity

    NARCIS (Netherlands)

    Prinsi, B.; Negri, A.S.; Quattrocchio, F.; Koes, R.E.; Espen, L.

    2016-01-01

    The Petunia hybrida ANTHOCYANIN1 (AN1) gene encodes a transcription factor that regulates both the expression of genes involved in anthocyanin synthesis and the acidification of the vacuolar lumen in corolla epidermal cells. In this work, the comparison between the red flowers of the R27 line with

  20. Metabolic Genetic Screens Reveal Multidimensional Regulation of Virulence Gene Expression in Listeria monocytogenes and an Aminopeptidase That Is Critical for PrfA Protein Activation.

    Science.gov (United States)

    Friedman, Sivan; Linsky, Marika; Lobel, Lior; Rabinovich, Lev; Sigal, Nadejda; Herskovits, Anat A

    2017-06-01

    Listeria monocytogenes is an environmental saprophyte and intracellular bacterial pathogen. Upon invading mammalian cells, the bacterium senses abrupt changes in its metabolic environment, which are rapidly transduced to regulation of virulence gene expression. To explore the relationship between L. monocytogenes metabolism and virulence, we monitored virulence gene expression dynamics across a library of genetic mutants grown under two metabolic conditions known to activate the virulent state: charcoal-treated rich medium containing glucose-1-phosphate and minimal defined medium containing limiting concentrations of branched-chain amino acids (BCAAs). We identified over 100 distinct mutants that exhibit aberrant virulence gene expression profiles, the majority of which mapped to nonessential metabolic genes. Mutants displayed enhanced, decreased, and early and late virulence gene expression profiles, as well as persistent levels, demonstrating a high plasticity in virulence gene regulation. Among the mutants, one was noteworthy for its particularly low virulence gene expression level and mapped to an X-prolyl aminopeptidase (PepP). We show that this peptidase plays a role in posttranslational activation of the major virulence regulator, PrfA. Specifically, PepP mediates recruitment of PrfA to the cytoplasmic membrane, a step identified as critical for PrfA protein activation. This study establishes a novel step in the complex mechanism of PrfA activation and further highlights the cross regulation of metabolism and virulence. Copyright © 2017 American Society for Microbiology.

  1. Comparative Analysis of Muscle Hypertrophy Models Reveals Divergent Gene Transcription Profiles and Points to Translational Regulation of Muscle Growth through Increased mTOR Signaling

    Directory of Open Access Journals (Sweden)

    Marcelo G. Pereira

    2017-12-01

    Full Text Available Skeletal muscle mass is a result of the balance between protein breakdown and protein synthesis. It has been shown that multiple conditions of muscle atrophy are characterized by the common regulation of a specific set of genes, termed atrogenes. It is not known whether various models of muscle hypertrophy are similarly regulated by a common transcriptional program. Here, we characterized gene expression changes in three different conditions of muscle growth, examining each condition during acute and chronic phases. Specifically, we compared the transcriptome of Extensor Digitorum Longus (EDL muscles collected (1 during the rapid phase of postnatal growth at 2 and 4 weeks of age, (2 24 h or 3 weeks after constitutive activation of AKT, and (3 24 h or 3 weeks after overload hypertrophy caused by tenotomy of the Tibialis Anterior muscle. We observed an important overlap between significantly regulated genes when comparing each single condition at the two different timepoints. Furthermore, examining the transcriptional changes occurring 24 h after a hypertrophic stimulus, we identify an important role for genes linked to a stress response, despite the absence of muscle damage in the AKT model. However, when we compared all different growth conditions, we did not find a common transcriptional fingerprint. On the other hand, all conditions showed a marked increase in mTORC1 signaling and increased ribosome biogenesis, suggesting that muscle growth is characterized more by translational, than transcriptional regulation.

  2. Generating equilateral random polygons in confinement

    International Nuclear Information System (INIS)

    Diao, Y; Ernst, C; Montemayor, A; Ziegler, U

    2011-01-01

    One challenging problem in biology is to understand the mechanism of DNA packing in a confined volume such as a cell. It is known that confined circular DNA is often knotted and hence the topology of the extracted (and relaxed) circular DNA can be used as a probe of the DNA packing mechanism. However, in order to properly estimate the topological properties of the confined circular DNA structures using mathematical models, it is necessary to generate large ensembles of simulated closed chains (i.e. polygons) of equal edge lengths that are confined in a volume such as a sphere of certain fixed radius. Finding efficient algorithms that properly sample the space of such confined equilateral random polygons is a difficult problem. In this paper, we propose a method that generates confined equilateral random polygons based on their probability distribution. This method requires the creation of a large database initially. However, once the database has been created, a confined equilateral random polygon of length n can be generated in linear time in terms of n. The errors introduced by the method can be controlled and reduced by the refinement of the database. Furthermore, our numerical simulations indicate that these errors are unbiased and tend to cancel each other in a long polygon. (paper)

  3. Mechanical collapse of confined fluid membrane vesicles.

    Science.gov (United States)

    Rim, Jee E; Purohit, Prashant K; Klug, William S

    2014-11-01

    Compact cylindrical and spherical invaginations are common structural motifs found in cellular and developmental biology. To understand the basic physical mechanisms that produce and maintain such structures, we present here a simple model of vesicles in confinement, in which mechanical equilibrium configurations are computed by energy minimization, balancing the effects of curvature elasticity, contact of the membrane with itself and the confining geometry, and adhesion. For cylindrical confinement, the shape equations are solved both analytically and numerically by finite element analysis. For spherical confinement, axisymmetric configurations are obtained numerically. We find that the geometry of invaginations is controlled by a dimensionless ratio of the adhesion strength to the bending energy of an equal area spherical vesicle. Larger adhesion produces more concentrated curvatures, which are mainly localized to the "neck" region where the invagination breaks away from its confining container. Under spherical confinement, axisymmetric invaginations are approximately spherical. For extreme confinement, multiple invaginations may form, bifurcating along multiple equilibrium branches. The results of the model are useful for understanding the physical mechanisms controlling the structure of lipid membranes of cells and their organelles, and developing tissue membranes.

  4. Overexpression of FurA in Anabaena sp. PCC 7120 reveals new targets for this regulator involved in photosynthesis, iron uptake and cellular morphology.

    Science.gov (United States)

    González, Andrés; Bes, M Teresa; Barja, François; Peleato, M Luisa; Fillat, María F

    2010-11-01

    Previous genomic analyses of the filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120 have identified three ferric uptake regulator (Fur) homologs with low sequence identities and probably different functions in the cell. FurA is a constitutive protein that shares the highest homology with Fur from heterotrophic bacteria and appears to be essential for in vitro growth. In this study, we have analysed the effects of FurA overexpression on the Anabaena sp. phenotype and investigated which of the observed alterations were directly operated by FurA. Overexpression of the regulator led to changes in cellular morphology, resulting in shorter filaments with rounded cells of different sizes. The furA-overexpressing strain showed a slower photoautotrophic growth and a marked decrease in the oxygen evolution rate. Overexpression of the regulator also decreased both catalase and superoxide dismutase activities, but did not lead to an increase in the levels of intracellular reactive oxygen species. By combining phenotypic studies, reverse transcription-PCR analyses and electrophoretic mobility shift assays, we identified three novel direct targets of FurA, including genes encoding a siderophore outer membrane transporter (schT), bacterial actins (mreBCD) and the PSII reaction center protein D1 (psbA). The affinity of FurA for these novel targets was markedly affected by the absence of divalent metal ions, confirming previous evidence of a critical role for the metal co-repressor in the function of the regulator in vivo. The results unravel new cellular processes modulated by FurA, supporting its role as a global transcriptional regulator in Anabaena sp. PCC 7120.

  5. Circular RNA profiling reveals that circCOL3A1-859267 regulate type I collagen expression in photoaged human dermal fibroblasts

    International Nuclear Information System (INIS)

    Peng, Yating; Song, Xiaojing; Zheng, Yue; Wang, Xinyi; Lai, Wei

    2017-01-01

    Production of type I collagen declines is a main characteristic during photoaging, but the mechanism is still not fully understood. Circular RNAs (circRNAs) are a class of newly identified non-coding RNAs with regulatory potency by sequestering miRNAs like a sponge. It's more stable than linear RNAs, and would be a useful tool for regulation of gene expression. However, the role of circRNAs in collagen expression during photoaging is still unclear. Here we performed deep sequencing of RNA generated from UVA irradiated and no irradiated human dermal fibroblasts (HDFs) and identified 29 significantly differentially expressed circRNAs (fold change ≥ 1.5, P < 0.05), 12 circRNAs were up-regulated and 17 circRNAs were down-regulated.3 most differentially expressed circRNAs were verified by qRT-PCR and the down-regulated circCOL3A1-859267 exhibited the most significantly altered in photoaged HDFs. Overexpression of circCOL3A1-859267 inhibited UVA-induced decrease of type I collagen expression and silencing of it reduced type I collagen intensity. Via a bioinformatic method, 44 miRNAs were predicted to binding with circCOL3A1-859267, 5 of them have been confirmed or predicted to interact with type I collagen. This study show that circCOL3A1-859267 regulate type I collagen expression in photoaged HDFs, suggesting it may be a novel target for interfering photoaging.

  6. Aerofractures in Confined Granular Media

    Science.gov (United States)

    Eriksen, Fredrik K.; Turkaya, Semih; Toussaint, Renaud; Måløy, Knut J.; Flekkøy, Eirik G.

    2015-04-01

    We will present the optical analysis of experimental aerofractures in confined granular media. The study of this generic process may have applications in industries involving hydraulic fracturing of tight rocks, safe construction of dams, tunnels and mines, and in earth science where phenomena such as mud volcanoes and sand injectites are results of subsurface sediment displacements driven by fluid overpressure. It is also interesting to increase the understanding the flow instability itself, and how the fluid flow impacts the solid surrounding fractures and in the rest of the sample. Such processes where previously studied numerically [Niebling 2012a, Niebling 2012b] or in circular geometries. We will here explore experimentally linear geometries. We study the fracturing patterns that form when air flows into a dense, non-cohesive porous medium confined in a Hele-Shaw cell - i.e. into a packing of dry 80 micron beads placed between two glass plates separated by ~1mm. The cell is rectangular and fitted with a semi-permeable boundary to the atmosphere - blocking beads but not air - on one short edge, while the other three edges are impermeable. The porous medium is packed inside the cell between the semi-permeable boundary and an empty volume at the sealed side where the air pressure can be set and kept at a constant overpressure (1-2bar). Thus, for the air trapped inside the cell to release the overpressure it has to move through the solid. At high enough overpressures the air flow deforms the solid and increase permeability in some regions along the air-solid interface, which results in unstable flow and aerofracturing. Aerofractures are thought to be an analogue to hydrofractures, and an advantage of performing aerofracturing experiments in a Hele-Shaw cell is that the fracturing process can easily be observed in the lab. Our experiments are recorded with a high speed camera with a framerate of 1000 frames per second. In the analysis, by using various image

  7. Review of Inertial Confinement Fusion

    Science.gov (United States)

    Haines, M. G.

    The physics of inertial confinement fusion is reviewed. The trend to short-wavelength lasers is argued, and the distinction between direct and indirect (soft X-ray) drive is made. Key present issues include the non-linear growth of Rayleigh-Taylor (R-T) instabilities, the seeding of this instability by the initial laser imprint, the relevance of self-generated magnetic fields, and the importance of parametric instabilities (stimulated Brillouin and Raman scattering) in gas-filled hohlraums. Experiments are reviewed which explore the R-T instability in both planar and converging geometry. The employment of various optical smoothing techniques is contrasted with the overcoating of the capsule by gold coated plastic foams to reduce considerably the imprint problem. The role of spontaneously generated magnetic fields in non-symmetric plasmas is discussed. Recent hohlraum compression results are presented together with gas bag targets which replicate the long-scale-length low density plasmas expected in NIF gas filled hohlraums. The onset of first Brillouin and then Raman scattering is observed. The fast ignitor scheme is a proposal to use an intense short pulse laser to drill a hole through the coronal plasma and then, with laser excited fast electrons, create a propagating thermonuclear spark in a dense, relatively cold laser-compressed target. Some preliminary results of laser hole drilling and 2-D and 3-D PIC simulations of this and the > 10^8 Gauss self-generated magnetic fields are presented. The proposed National Ignition Facility (NIF) is described.

  8. Percolating cluster of center vortices and confinement

    International Nuclear Information System (INIS)

    Gliozzi, Ferdinando; Panero, Marco; Provero, Paolo

    2003-01-01

    We study the role of percolating clusters of center vortices in configurations of an Ising gauge theory in 3D. It is known that low energy features of gauge theories can be described in terms of an 'effective string picture', and that confinement properties are associated with topologically non-trivial configurations. We focus our attention upon percolating clusters of center vortices, and present numerical evidence for the fact that these objects play a preminent role in confinement phenomenon, since their removal sweeps off confinement altogether. Moreover, numerical simulations show that the string fluctuations, and in particular the Mischer term, are completely encoded in the percolating cluster

  9. FRP confined smart concrete/mortar

    Science.gov (United States)

    Xiao, Y.; Zhu, P. S.; Choi, K. G.; Wu, Y. T.; Huang, Z. Y.; Shan, B.

    2006-03-01

    In this study, fiber reinforced polymer (FRP) confined smart concrete/mortar sensors were invented and validated for significantly improved measurement range. Several trial mixes were made using cement mortar and micron-phase graphite powders at different mix proportions. Compressive loading tests were conducted on smart mortar cylinder specimens with or without FRP confinement. Two-probe method was used to detect the electrical resistance of the smart cement mortar specimens. Strong correlation was recognized between the stress and electric resistance of the smart mortar. The test results indicated that the FRP wrapping could significantly enlarge the range of such self-sensing property as a consequence of confinement.

  10. Confinement and quark structure of light hadrons

    International Nuclear Information System (INIS)

    Efimov, G.V.; Ivanov, M.A.

    1988-01-01

    We present a quark confinement model (QCM) for the description of the low-energy physics of light hadrons (mesons and baryons). The model is based on two hypotheses. First, the quark confinement is realized as averaging over vacuum gluon fields which are believed to provide the confinement of any colour objects. Second, hadrons are treated as collective colourless excitations of quark-gluon interactions. The description of strong, electromagnetic and weak interactions of mesons and baryons at the low energy is given from a unique point of view

  11. Plasma confinement in the TMX tandem mirror

    International Nuclear Information System (INIS)

    Hooper, E.B. Jr.; Allen, S.L.; Casper, T.A.

    1981-01-01

    Plasma confinement in the Tandem Mirror Experiment (TMX) is described. Axially confining potentials are shown to exist throughout the central 20-cm core of TMX. Axial electron-confinement time is up to 100 times that of single-cell mirror machines. Radial transport of ions is smaller than axial transport near the axis. It has two parts at large radii: nonambipolar, in rough agreement with predictions from resonant-neoclassical transport theory, and ambipolar, observed near the plasma edge under certain conditions, accompanied by a low-frequency, m = 1 instability or strong turbulence

  12. Plasma confinement in a magnetic dipole

    International Nuclear Information System (INIS)

    Kesner, J.; Bromberg, L.; Garnier, D.; Mauel, M.

    1999-01-01

    A dipole fusion confinement device is stable to MHD interchange and ballooning modes when the pressure profile is sufficiently gentle. The plasma can be confined at high beta, is steady state and disruption free. Theory indicates that when the pressure gradient is sufficiently gentle to satisfy MHD requirements drift waves will also be stable. The dipole approach is particularly applicable for advanced fuels. A new experimental facility is presently being built to test the stability and transport properties of a dipole-confined plasma. (author)

  13. Plasma confinement in a magnetic dipole

    International Nuclear Information System (INIS)

    Kesner, J.; Bromberg, L.; Garnier, D.; Mauel, M.

    2001-01-01

    A dipole fusion confinement device is stable to MHD interchange and ballooning modes when the pressure profile is sufficiently gentle. The plasma can be confined at high beta, is steady state and disruption free. Theory indicates that when the pressure gradient is sufficiently gentle to satisfy MHD requirements drift waves will also be stable. The dipole approach is particularly applicable for advanced fuels. A new experimental facility is presently being built to test the stability and transport properties of a dipole-confined plasma. (author)

  14. Monitoring airborne biotic contaminants in the indoor environment of pig and poultry confinement buildings.

    Science.gov (United States)

    Hong, Pei-Ying; Li, Xiangzhen; Yang, Xufei; Shinkai, Takumi; Zhang, Yuanhui; Wang, Xinlei; Mackie, Roderick I

    2012-06-01

    Given the growing concerns over human and animal health issues related to confined animal feeding operations, an in-depth examination is required to monitor for airborne bacteria and associated antibiotic resistance genes. Our 16S rRNA-based pyrosequencing revealed that the airborne microbial community skewed towards a higher abundance of Firmicutes (> 59.2%) and Bacteroidetes (4.2-31.4%) within the confinement buildings, while the office environment was predominated by Proteobacteria (55.2%). Furthermore, bioaerosols in the confinement buildings were sporadically associated with genera of potential pathogens, and these genera were more frequently observed in the bioaerosols of pig and layer hen confinement than the turkey confinement buildings and office environment. High abundances of tetracycline resistance genes (9.55 × 10(2) to 1.69 × 10(6) copies ng(-1) DNA) were also detected in the bioaerosols sampled from confinement buildings. Bacterial lineages present in the poultry bioaerosols clustered apart from those present in the pig bioaerosols and among the different phases of pig production, suggesting that different livestock as well as production phase were associated with a distinct airborne microbial community. By understanding the diversity of biotic contaminants associated with the different confinement buildings, this study facilitates the implementation of better management strategies to minimize potential health impacts on both livestock and humans working in this environment. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

  15. Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1

    NARCIS (Netherlands)

    Glubb, Dylan M.; Maranian, Mel J.; Michailidou, Kyriaki; Pooley, Karen A.; Meyer, Kerstin B.; Kar, Siddhartha; Carlebur, Saskia; O'Reilly, Martin; Betts, Joshua A.; Hillman, Kristine M.; Kaufmann, Susanne; Beesley, Jonathan; Canisius, Sander; Hopper, John L.; Southey, Melissa C.; Tsimiklis, Helen; Apicella, Carmel; Schmidt, Marjanka K.; Broeks, Annegien; Hogervorst, Frans B.; van der Schoot, C. Ellen; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Ruebner, Matthias; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Pharoah, Paul D. P.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Burwinkel, Barbara; Marme, Frederik; Yang, Rongxi; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; González-Neira, Anna; Benitez, Javier; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Anton-Culver, Hoda; Neuhausen, Susan L.; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Ko, Yon-Dschun; Brüning, Thomas; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tanaka, Hideo; Dörk, Thilo; Bogdanova, Natalia V.; Helbig, Sonja; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Wu, Anna H.; Tseng, Chiu-Chen; van den Berg, David; Stram, Daniel O.; Lambrechts, Diether; Zhao, Hui; Weltens, Caroline; van Limbergen, Erik; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Seibold, Petra; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Capra, Fabio; Couch, Fergus J.; Olson, Janet E.; Hallberg, Emily; Vachon, Celine; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; teo, Soo Hwang; Yip, Cheng Har; See, Mee-Hoong; Cornes, Belinda; Cheng, Ching-Yu; Ikram, M. Kamran; Kristensen, Vessela; Zheng, Wei; Halverson, Sandra L.; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A. E. M.; Seynaeve, Caroline; van Asperen, Christi J.; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J.; Lissowska, Jolanta; Czene, Kamila; Klevebring, Daniel; Darabi, Hatef; Eriksson, Mikael; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W. M.; Collée, J. Margriet; Hall, Per; Li, Jingmei; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Shah, Mitul; Ghoussaini, Maya; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Tang, Anthony; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Olswold, Curtis; Slager, Susan; Toland, Amanda E.; Yannoukakos, Drakoulis; Shen, Chen-Yang; Wu, Pei-Ei; Yu, Jyh-Cherng; Hou, Ming-Feng; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Pita, Guillermo; Alonso, M. Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S.; Brown, Melissa A.; Ponder, Bruce A. J.; Chenevix-Trench, Georgia; Thompson, Deborah J.; Edwards, Stacey L.; Easton, Douglas F.; Dunning, Alison M.; French, Juliet D.

    2015-01-01

    Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and

  16. Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1

    NARCIS (Netherlands)

    D.M. Glubb (Dylan); M. Maranian (Melanie); K. Michailidou (Kyriaki); K.A. Pooley (Karen); K.B. Meyer (Kerstin); S. Kar (Siddhartha); A.F.C. Carlebur; M. O'Reilly (Marian); J.A. Betts (Joshua); K.M. Hillman (Kristine); S. Kaufmann (Susanne); J. Beesley (Jonathan); S. Canisius (Sander); J.L. Hopper (John); M.C. Southey (Melissa); H. Tsimiklis (Helen); C. Apicella (Carmel); M.K. Schmidt (Marjanka); A. Broeks (Annegien); F.B.L. Hogervorst (Frans); C.E. van der Schoot (Ellen); K.R. Muir (K.); A. Lophatananon (Artitaya); S. Stewart-Brown (Sarah); P. Siriwanarangsan (Pornthep); P.A. Fasching (Peter); M. Ruebner (Matthias); A.B. Ekici (Arif); M.W. Beckmann (Matthias); J. Peto (Julian); I. dos Santos Silva (Isabel); O. Fletcher (Olivia); N. Johnson (Nichola); P.D.P. Pharoah (Paul D.P.); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); B. Burwinkel (Barbara); F. Marme (Federick); R. Yang (Rongxi); H. Surowy (Harald); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); M. Sanchez (Marie); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); A. González-Neira (Anna); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Meindl (Alfons); R.K. Schmutzler (Rita); H. Brauch (Hiltrud); Y.-D. Ko (Yon-Dschun); T. Brüning (Thomas); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); K. Matsuo (Keitaro); H. Ito (Hidemi); H. Iwata (Hisato); H. Tanaka (Hideo); T. Dörk (Thilo); N.V. Bogdanova (Natalia); S. Helbig (Sonja); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); A.H. Wu (Anna H.); C.-C. Tseng (Chiu-Chen); D. Van Den Berg (David); D.O. Stram (Daniel O.); D. Lambrechts (Diether); H. Zhao (Hui); C. Weltens (Caroline); E. van Limbergen (Erik); J. Chang-Claude (Jenny); D. Flesch-Janys (Dieter); A. Rudolph (Anja); P. Seibold (Petra); P. Radice (Paolo); P. Peterlongo (Paolo); M. Barile (Monica); F. Capra (Fabio); F.J. Couch (Fergus); J.E. Olson (Janet); B. Hallberg (Boubou); C. Vachon (Celine); G.G. Giles (Graham); R.L. Milne (Roger); C.A. McLean (Catriona Ann); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Simard (Jacques); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); S.-H. Teo (Soo-Hwang); C.H. Yip (Cheng Har); M.-H. See (Mee-Hoong); B.K. Cornes (Belinda); C-Y. Cheng (Ching-Yu); M.K. Ikram (Kamran); V. Kristensen (Vessela); W. Zheng (Wei); S.L. Halverson (Sandra L.); M. Shrubsole (Martha); J. Long (Jirong); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); S. Kauppila (Saila); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); S. Tchatchou (Sandrine); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); M. García-Closas (Montserrat); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); J. Lissowska (Jolanta); K. Czene (Kamila); D. Klevebring (Daniel); H. Darabi (Hatef); M. Eriksson (Mikael); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); J.W.M. Martens (John W. M.); J.M. Collée (Margriet); P. Hall (Per); J. Li (Jingmei); K. Humphreys (Keith); X.-O. Shu (Xiao-Ou); W. Lu (Wei); Y.-T. Gao (Yu-Tang); H. Cai (Hui); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); W.J. Blot (William); L.B. Signorello (Lisa B.); Q. Cai (Qiuyin); M. Shah (Mitul); M. Ghoussaini (Maya); D. Kang (Daehee); J.-Y. Choi (J.); S.K. Park (Sue); D-Y. Noh (Dong-Young); M. Hartman (Mikael); X. Miao; W.-Y. Lim (Wei-Yen); A. Tang (Anthony); U. Hamann (Ute); D. Torres (Diana); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); K. Durda (Katarzyna); S. Sangrajrang (Suleeporn); V. Gaborieau (Valerie); P. Brennan (Paul); J.D. McKay (James); C. Olswold (Curtis); S. Slager (Susan); A.E. Toland (Amanda); D. Yannoukakos (Drakoulis); C-Y. Shen (Chen-Yang); P.-E. Wu (Pei-Ei); J-C. Yu (Jyh-Cherng); M.-F. Hou (Ming-Feng); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Jones (Michael); G. Pita (Guillermo); M.R. Alonso (Rosario); N. Álvarez (Nuria); D. Herrero (Daniel); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); S. Healey (Sue); M. Brown (Melissa); B.A.J. Ponder (Bruce A.J.); G. Chenevix-Trench (Georgia); D. Thompson (Deborah); S.L. Edwards (Stacey); D.F. Easton (Douglas); A.M. Dunning (Alison); J.D. French (Juliet)

    2015-01-01

    textabstractGenome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer

  17. Differential microRNA Analysis of Glandular Trichomes and Young Leaves in Xanthium strumarium L. Reveals Their Putative Roles in Regulating Terpenoid Biosynthesis

    OpenAIRE

    Fan, Rongyan; Li, Yuanjun; Li, Changfu; Zhang, Yansheng

    2015-01-01

    The medicinal plant Xanthium strumarium L. (X. strumarium) is covered with glandular trichomes, which are the sites for synthesizing pharmacologically active terpenoids such as xanthatin. MicroRNAs (miRNAs) are a class of 21-24 nucleotide (nt) non-coding RNAs, most of which are identified as regulators of plant growth development. Identification of miRNAs involved in the biosynthesis of plant secondary metabolites remains limited. In this study, high-throughput Illumina sequencing, combined w...

  18. Systems-level approaches reveal conservation of trans-regulated genes in the rat and genetic determinants of blood pressure in humans

    Czech Academy of Sciences Publication Activity Database

    Langley, S. R.; Bottolo, L.; Kuneš, Jaroslav; Zicha, Josef; Zídek, Václav; Hubner, N.; Cook, S.A.; Pravenec, Michal; Aitman, T. J.; Petretto, E.

    2013-01-01

    Roč. 97, č. 4 (2013), s. 653-665 ISSN 0008-6363 R&D Projects: GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MŠk(CZ) 7E10067 Institutional support: RVO:67985823 Keywords : integrative genomics * expression QTLs * time series analysis * trans-acting regulation * genome-wide association studies Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.808, year: 2013

  19. Organotypic culture of normal, dysplastic and squamous cell carcinoma-derived oral cell lines reveals loss of spatial regulation of CD44 and p75 NTR in malignancy.

    Science.gov (United States)

    Dalley, Andrew J; AbdulMajeed, Ahmad A; Upton, Zee; Farah, Camile S

    2013-01-01

    Oral squamous cell carcinomas (OSCC) often arise from dysplastic lesions. The role of cancer stem cells in tumour initiation is widely accepted, yet the potential existence of pre-cancerous stem cells in dysplastic tissue has received little attention. Cell lines from oral diseases ranging in severity from dysplasia to malignancy provide opportunity to investigate the involvement of stem cells in malignant progression from dysplasia. Stem cells are functionally defined by their ability to generate hierarchical tissue structures in consortium with spatial regulation. Organotypic cultures readily display tissue hierarchy in vitro; hence, in this study, we compared hierarchical expression of stem cell-associated markers in dermis-based organotypic cultures of oral epithelial cells from normal tissue (OKF6-TERT2), mild dysplasia (DOK), severe dysplasia (POE-9n) and OSCC (PE/CA P J15). Expression of CD44, p75(NTR), CD24 and ALDH was studied in monolayers by flow cytometry and in organotypic cultures by immunohistochemistry. Spatial regulation of CD44 and p75(NTR) was evident for organotypic cultures of normal (OKF6-TERT2) and dysplasia (DOK and POE-9n) but was lacking for OSCC (PE/CA PJ15)-derived cells. Spatial regulation of CD24 was not evident. All monolayer cultures exhibited CD44, p75(NTR), CD24 antigens and ALDH activity (ALDEFLUOR(®) assay), with a trend towards loss of population heterogeneity that mirrored disease severity. In monolayer, increased FOXA1 and decreased FOXA2 expression correlated with disease severity, but OCT3/4, Sox2 and NANOG did not. We conclude that dermis-based organotypic cultures give opportunity to investigate the mechanisms that underlie loss of spatial regulation of stem cell markers seen with OSCC-derived cells. © 2012 John Wiley & Sons A/S.

  20. Transcriptome Profiling Reveals the Negative Regulation of Multiple Plant Hormone Signaling Pathways Elicited by Overexpression of C-Repeat Binding Factors

    Directory of Open Access Journals (Sweden)

    Aixin Li

    2017-09-01

    Full Text Available C-repeat binding factors (CBF are a subfamily of AP2 transcription factors that play critical roles in the regulation of plant cold tolerance and growth in low temperature. In the present work, we sought to perform a detailed investigation into global transcriptional regulation of plant hormone signaling associated genes in transgenic plants engineered with CBF genes. RNA samples from Arabidopsis thaliana plants overexpressing two CBF genes, CBF2 and CBF3, were subjected to Illumina HiSeq 2000 RNA sequencing (RNA-Seq. Our results showed that more than half of the hormone associated genes that were differentially expressed in CBF2 or CBF3 transgenic plants were related to auxin signal transduction and metabolism. Most of these alterations in gene expression could lead to repression of auxin signaling. Accordingly, the IAA content was significantly decreased in young tissues of plants overexpressing CBF2 and CBF3 compared with wild type. In addition, genes associated with the biosynthesis of Jasmonate (JA and Salicylic acid (SA, as well as the signal sensing of Brassinolide (BR and SA, were down-regulated, while genes associated with Gibberellin (GA deactivation were up-regulated. In general, overexpression of CBF2 and CBF3 negatively affects multiple plant hormone signaling pathways in Arabidopsis. The transcriptome analysis using CBF2 and CBF3 transgenic plants provides novel and integrated insights into the interaction between CBFs and plant hormones, particularly the modulation of auxin signaling, which may contribute to the improvement of crop yields under abiotic stress via molecular engineering using CBF genes.

  1. Assessment of global stellarator confinement: Status of the international stellarator confinement scaling data base

    International Nuclear Information System (INIS)

    Dinklage, A.; Beidler, C.D.; Dose, V.; Geiger, J.; Kus, A.; Preuss, R.; Ascasibar, E.; Tribaldos, V.; Harris, J.H.; Murakami, S.; Sano, F.; Okamura, S.; Suzuki, Y.; Watanabe, K.Y.; Yamada, H.; Yokoyama, M.; Stroth, U.; Talmadge, J.

    2005-01-01

    Different stellarator/heliotron devices along with their respective flexibility cover a large magnetic configuration space. Since the ultimate goal of stellarator research aims at an alternative fusion reactor concept, the exploration of the most promising configurations requires a comparative assessment of the plasma performance and how different aspects of a 3D configuration influence it. Therefore, the International Stellarator Confinement Database (ISCDB) has been re- initiated in 2004 and the ISS95 database has been extended to roughly 3000 discharges from eight different devices. Further data-sets are continuously added. A revision of a data set restricted to comparable scenarios lead to the ISS04 scaling law which confirmed ISS95 but also revealed clearly the necessity to incorporate configuration descriptive parameters. In other words, an extension beyond the set of regression parameters used for ISS95/ISS04 appears to be necessary and candidates, such as the elongation are investigated. Since grouping of data is a key-issue for deriving ISS04, basic assumptions are revised, e.g. the dependence on the heating scheme. Moreover, an assessment of statistical approaches is investigated with respect to their impact on the scaling. A crucial issue is the weighting of data groups which is discussed in terms of error-in-variable techniques and Bayesian model comparison. The latter is employed for testing scaling ansatzes depending on scaling invariance principles hence allowing the assessment of applicability of theory-based scaling laws on stellarator confinement. 1. ISCDB resources are jointly hosted by NIFS and IPP, see http://iscdb.nifs.ac.jp and http://www.ipp.mpg.de/ISS. (author)

  2. Promoter Engineering Reveals the Importance of Heptameric Direct Repeats for DNA Binding by Streptomyces Antibiotic Regulatory Protein-Large ATP-Binding Regulator of the LuxR Family (SARP-LAL) Regulators in Streptomyces natalensis.

    Science.gov (United States)

    Barreales, Eva G; Vicente, Cláudia M; de Pedro, Antonio; Santos-Aberturas, Javier; Aparicio, Jesús F

    2018-05-15

    The biosynthesis of small-size polyene macrolides is ultimately controlled by a couple of transcriptional regulators that act in a hierarchical way. A Streptomyces antibiotic regulatory protein-large ATP-binding regulator of the LuxR family (SARP-LAL) regulator binds the promoter of a PAS-LuxR regulator-encoding gene and activates its transcription, and in turn, the gene product of the latter activates transcription from various promoters of the polyene gene cluster directly. The primary operator of PimR, the archetype of SARP-LAL regulators, contains three heptameric direct repeats separated by four-nucleotide spacers, but the regulator can also bind a secondary operator with only two direct repeats separated by a 3-nucleotide spacer, both located in the promoter region of its unique target gene, pimM A similar arrangement of operators has been identified for PimR counterparts encoded by gene clusters for different antifungal secondary metabolites, including not only polyene macrolides but peptidyl nucleosides, phoslactomycins, or cycloheximide. Here, we used promoter engineering and quantitative transcriptional analyses to determine the contributions of the different heptameric repeats to transcriptional activation and final polyene production. Optimized promoters have thus been developed. Deletion studies and electrophoretic mobility assays were used for the definition of DNA-binding boxes formed by 22-nucleotide sequences comprising two conserved heptameric direct repeats separated by four-nucleotide less conserved spacers. The cooperative binding of PimR SARP appears to be the mechanism involved in the binding of regulator monomers to operators, and at least two protein monomers are required for efficient binding. IMPORTANCE Here, we have shown that a modulation of the production of the antifungal pimaricin in Streptomyces natalensis can be accomplished via promoter engineering of the PAS-LuxR transcriptional activator pimM The expression of this gene is

  3. Brain-to-brain synchrony in parent-child dyads and the relationship with emotion regulation revealed by fNIRS-based hyperscanning.

    Science.gov (United States)

    Reindl, Vanessa; Gerloff, Christian; Scharke, Wolfgang; Konrad, Kerstin

    2018-05-25

    Parent-child synchrony, the coupling of behavioral and biological signals during social contact, may fine-tune the child's brain circuitries associated with emotional bond formation and the child's development of emotion regulation. Here, we examined the neurobiological underpinnings of these processes by measuring parent's and child's prefrontal neural activity concurrently with functional near-infrared spectroscopy hyperscanning. Each child played both a cooperative and a competitive game with the parent, mostly the mother, as well as an adult stranger. During cooperation, parent's and child's brain activities synchronized in the dorsolateral prefrontal and frontopolar cortex (FPC), which was predictive for their cooperative performance in subsequent trials. No significant brain-to-brain synchrony was observed in the conditions parent-child competition, stranger-child cooperation and stranger-child competition. Furthermore, parent-child compared to stranger-child brain-to-brain synchrony during cooperation in the FPC mediated the association between the parent's and the child's emotion regulation, as assessed by questionnaires. Thus, we conclude that brain-to-brain synchrony may represent an underlying neural mechanism of the emotional connection between parent and child, which is linked to the child's development of adaptive emotion regulation. Future studies may uncover whether brain-to-brain synchrony can serve as a neurobiological marker of the dyad's socio-emotional interaction, which is sensitive to risk conditions, and can be modified by interventions. Copyright © 2018. Published by Elsevier Inc.

  4. Integrative RNA- and miRNA-Profile Analysis Reveals a Likely Role of BR and Auxin Signaling in Branch Angle Regulation of B. napus

    Directory of Open Access Journals (Sweden)

    Hongtao Cheng

    2017-05-01

    Full Text Available Oilseed rape (Brassica napus L. is the second largest oilseed crop worldwide and one of the most important oil crops in China. As a component of plant architecture, branch angle plays an important role in yield performance, especially under high-density planting conditions. However, the mechanisms underlying the regulation of branch angle are still largely not understood. Two oilseed rape lines with significantly different branch angles were used to conduct RNA- and miRNA-profiling at two developmental stages, identifying differential expression of a large number of genes involved in auxin- and brassinosteroid (BR-related pathways. Many auxin response genes, including AUX1, IAA, GH3, and ARF, were enriched in the compact line. However, a number of genes involved in BR signaling transduction and biosynthesis were down-regulated. Differentially expressed miRNAs included those involved in auxin signaling transduction. Expression patterns of most target genes were fine-tuned by related miRNAs, such as miR156, miR172, and miR319. Some miRNAs were found to be differentially expressed at both developmental stages, including three miR827 members. Our results provide insight that auxin- and BR-signaling may play a pivotal role in branch angle regulation.

  5. Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses.

    Science.gov (United States)

    Baril, Martin; Es-Saad, Salwa; Chatel-Chaix, Laurent; Fink, Karin; Pham, Tram; Raymond, Valérie-Ann; Audette, Karine; Guenier, Anne-Sophie; Duchaine, Jean; Servant, Marc; Bilodeau, Marc; Cohen, Eric; Grandvaux, Nathalie; Lamarre, Daniel

    2013-01-01

    To identify new regulators of antiviral innate immunity, we completed the first genome-wide gene silencing screen assessing the transcriptional response at the interferon-β (IFNB1) promoter following Sendai virus (SeV) infection. We now report a novel link between WNT signaling pathway and the modulation of retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)-dependent innate immune responses. Here we show that secretion of WNT2B and WNT9B and stabilization of β-catenin (CTNNB1) upon virus infection negatively regulate expression of representative inducible genes IFNB1, IFIT1 and TNF in a CTNNB1-dependent effector mechanism. The antiviral response is drastically reduced by glycogen synthase kinase 3 (GSK3) inhibitors but restored in CTNNB1 knockdown cells. The findings confirm a novel regulation of antiviral innate immunity by a canonical-like WNT/CTNNB1 signaling pathway. The study identifies novel avenues for broad-spectrum antiviral targets and preventing immune-mediated diseases upon viral infection.

  6. Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses.

    Directory of Open Access Journals (Sweden)

    Martin Baril

    Full Text Available To identify new regulators of antiviral innate immunity, we completed the first genome-wide gene silencing screen assessing the transcriptional response at the interferon-β (IFNB1 promoter following Sendai virus (SeV infection. We now report a novel link between WNT signaling pathway and the modulation of retinoic acid-inducible gene I (RIG-I-like receptor (RLR-dependent innate immune responses. Here we show that secretion of WNT2B and WNT9B and stabilization of β-catenin (CTNNB1 upon virus infection negatively regulate expression of representative inducible genes IFNB1, IFIT1 and TNF in a CTNNB1-dependent effector mechanism. The antiviral response is drastically reduced by glycogen synthase kinase 3 (GSK3 inhibitors but restored in CTNNB1 knockdown cells. The findings confirm a novel regulation of antiviral innate immunity by a canonical-like WNT/CTNNB1 signaling pathway. The study identifies novel avenues for broad-spectrum antiviral targets and preventing immune-mediated diseases upon viral infection.

  7. Network-based characterization of the synaptic proteome reveals that removal of epigenetic regulator Prmt8 restricts proteins associated with synaptic maturation.

    Science.gov (United States)

    Lee, Patrick Kia Ming; Goh, Wilson Wen Bin; Sng, Judy Chia Ghee

    2017-02-01

    The brain adapts to dynamic environmental conditions by altering its epigenetic state, thereby influencing neuronal transcriptional programs. An example of an epigenetic modification is protein methylation, catalyzed by protein arginine methyltransferases (PRMT). One member, Prmt8, is selectively expressed in the central nervous system during a crucial phase of early development, but little else is known regarding its function. We hypothesize Prmt8 plays a role in synaptic maturation during development. To evaluate this, we used a proteome-wide approach to characterize the synaptic proteome of Prmt8 knockout versus wild-type mice. Through comparative network-based analyses, proteins and functional clusters related to neurite development were identified to be differentially regulated between the two genotypes. One interesting protein that was differentially regulated was tenascin-R (TNR). Chromatin immunoprecipitation demonstrated binding of PRMT8 to the tenascin-r (Tnr) promoter. TNR, a component of perineuronal nets, preserves structural integrity of synaptic connections within neuronal networks during the development of visual-somatosensory cortices. On closer inspection, Prmt8 removal increased net formation and decreased inhibitory parvalbumin-positive (PV+) puncta on pyramidal neurons, thereby hindering the maturation of circuits. Consequently, visual acuity of the knockout mice was reduced. Our results demonstrated Prmt8's involvement in synaptic maturation and its prospect as an epigenetic modulator of developmental neuroplasticity by regulating structural elements such as the perineuronal nets. © 2016 International Society for Neurochemistry.

  8. Transcriptomic Analysis Reveals Wound Healing of Morus alba Root Extract by Up-Regulating Keratin Filament and CXCL12/CXCR4 Signaling.

    Science.gov (United States)

    Kim, Kang-Hoon; Chung, Won-Seok; Kim, Yoomi; Kim, Ki-Suk; Lee, In-Seung; Park, Ji Young; Jeong, Hyeon-Soo; Na, Yun-Cheol; Lee, Chang-Hun; Jang, Hyeung-Jin

    2015-08-01

    Facilitation of the wound healing process is important because a prolonged wound site increases pain and the risk of infection. In oriental medicine, an extract of Morus alba root (MA) has usually been prescribed as traditional treatment for accelerating wound healing, and it has been proven to be safe for centuries. To study the molecular mechanism of MA-mediated skin wound healing, we performed a primary cell culture and a skin explant culture and observed significant difference between the groups with and without MA extract. In the cellular system, a real-time cell analysis and real-time quantitative PCR were performed. It was found that MA extract enhanced proliferation in a dose-dependent manner on Kera-308 cell line, and up-regulated keratin expression including wound-induced Krt6a. In skin explant culture, the mRNA level derived from cell outgrowth displayed a tendency toward more up-regulated mRNA associated keratin filaments and toward a more up-regulated mRNA level of C-X-C motif chemokine 12 (CXCL12) and a chemokine receptor 4 (CXCR4) axis signaling pathway downstream. In this process, we concluded that MA extract had a scientific possibility of wound repair by increasing intracellular and extracellular supports and by inducing a CXCL12/CXCR4 signaling pathway. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury.

    Directory of Open Access Journals (Sweden)

    Mannion James W

    2002-10-01

    Full Text Available Abstract Background Rat oligonucleotide microarrays were used to detect changes in gene expression in the dorsal root ganglion (DRG 3 days following sciatic nerve transection (axotomy. Two comparisons were made using two sets of triplicate microarrays, naïve versus naïve and naïve versus axotomy. Results Microarray variability was assessed using the naïve versus naïve comparison. These results support use of a P 1.5-fold expression change and P 1.5-fold and P in situ hybridization verified the expression of 24 transcripts. These data showed an 83% concordance rate with the arrays; most mismatches represent genes with low expression levels reflecting limits of array sensitivity. A significant correlation was found between actual mRNA differences and relative changes between microarrays (r2 = 0.8567. Temporal patterns of individual genes regulation varied. Conclusions We identify parameters for microarray analysis which reduce error while identifying many putatively regulated genes. Functional classification of these genes suggest reorganization of cell structural components, activation of genes expressed by immune and inflammatory cells and down-regulation of genes involved in neurotransmission.

  10. A Bioinformatics Analysis Reveals a Group of MocR Bacterial Transcriptional Regulators Linked to a Family of Genes Coding for Membrane Proteins

    Directory of Open Access Journals (Sweden)

    Teresa Milano

    2016-01-01

    Full Text Available The MocR bacterial transcriptional regulators are characterized by an N-terminal domain, 60 residues long on average, possessing the winged-helix-turn-helix (wHTH architecture responsible for DNA recognition and binding, linked to a large C-terminal domain (350 residues on average that is homologous to fold type-I pyridoxal 5′-phosphate (PLP dependent enzymes like aspartate aminotransferase (AAT. These regulators are involved in the expression of genes taking part in several metabolic pathways directly or indirectly connected to PLP chemistry, many of which are still uncharacterized. A bioinformatics analysis is here reported that studied the features of a distinct group of MocR regulators predicted to be functionally linked to a family of homologous genes coding for integral membrane proteins of unknown function. This group occurs mainly in the Actinobacteria and Gammaproteobacteria phyla. An analysis of the multiple sequence alignments of their wHTH and AAT domains suggested the presence of specificity-determining positions (SDPs. Mapping of SDPs onto a homology model of the AAT domain hinted at possible structural/functional roles in effector recognition. Likewise, SDPs in wHTH domain suggested the basis of specificity of Transcription Factor Binding Site recognition. The results reported represent a framework for rational design of experiments and for bioinformatics analysis of other MocR subgroups.

  11. Energy Confinement of both Ohmic and LHW Plasma on EAST

    International Nuclear Information System (INIS)

    Yang Yao; Gao Xiang

    2011-01-01

    Study on the characters of energy confinement in both Ohmic and lower hybrid wave (LHW) discharges on EAST is conducted and the linear Ohmic confinement (LOC), saturated ohmic confinement (SOC) and improved Ohmic confinement (IOC) regimes are investigated in this paper. It is observed that an improved confinement mode characterized by both a drop of D α line intensity and an increase in line average density can be triggered by a gas puffing pulse. (magnetically confined plasma)

  12. Global gene expression in muscle from fasted/refed trout reveals up-regulation of genes promoting myofibre hypertrophy but not myofibre production.

    Science.gov (United States)

    Rescan, Pierre-Yves; Le Cam, Aurelie; Rallière, Cécile; Montfort, Jérôme

    2017-06-07

    Compensatory growth is a phase of rapid growth, greater than the growth rate of control animals, that occurs after a period of growth-stunting conditions. Fish show a capacity for compensatory growth after alleviation of dietary restriction, but the underlying cellular mechanisms are unknown. To learn more about the contribution of genes regulating hypertrophy (an increase in muscle fibre size) and hyperplasia (the generation of new muscle fibres) in the compensatory muscle growth response in fish, we used high-density microarray analysis to investigate the global gene expression in muscle of trout during a fasting-refeeding schedule and in muscle of control-fed trout displaying normal growth. The compensatory muscle growth signature, as defined by genes up-regulated in muscles of refed trout compared with control-fed trout, showed enrichment in functional categories related to protein biosynthesis and maturation, such as RNA processing, ribonucleoprotein complex biogenesis, ribosome biogenesis, translation and protein folding. This signature was also enriched in chromatin-remodelling factors of the protein arginine N-methyl transferase family. Unexpectedly, functional categories related to cell division and DNA replication were not inferred from the molecular signature of compensatory muscle growth, and this signature contained virtually none of the genes previously reported to be up-regulated in hyperplastic growth zones of the late trout embryo myotome and to potentially be involved in production of new myofibres, notably genes encoding myogenic regulatory factors, transmembrane receptors essential for myoblast fusion or myofibrillar proteins predominant in nascent myofibres. Genes promoting myofibre growth, but not myofibre formation, were up-regulated in muscles of refed trout compared with continually fed trout. This suggests that a compensatory muscle growth response, resulting from the stimulation of hypertrophy but not the stimulation of hyperplasia

  13. A Study of Confined Helium Atom

    International Nuclear Information System (INIS)

    Xie Wenfang

    2007-01-01

    The helium atom confined by a spherical parabolic potential well is studied employing the adiabatic hyperspherical approach method. Total energies of the ground and three low-excited states are obtained as a function of the confined potential radii. We find that the energies of a spherical parabolic potential well are in good agreement with those of an impenetrable spherical box for the larger confined potential radius. We find also that the confinement may cause accidental degeneracies between levels with different low-excited states and the inversion of the energy values. The results for the three-dimensional spherical potential well and the two-dimensional disc-like potential well are compared with each other. We find that the energy difference between states in a two-dimensional parabolic potential is also obviously larger than the corresponding levels for a spherical parabolic potential.

  14. The Physics Basis of ITER Confinement

    International Nuclear Information System (INIS)

    Wagner, F.

    2009-01-01

    ITER will be the first fusion reactor and the 50 year old dream of fusion scientists will become reality. The quality of magnetic confinement will decide about the success of ITER, directly in the form of the confinement time and indirectly because it decides about the plasma parameters and the fluxes, which cross the separatrix and have to be handled externally by technical means. This lecture portrays some of the basic principles which govern plasma confinement, uses dimensionless scaling to set the limits for the predictions for ITER, an approach which also shows the limitations of the predictions, and describes briefly the major characteristics and physics behind the H-mode--the preferred confinement regime of ITER.

  15. Nucleon in confining models with glueballs

    International Nuclear Information System (INIS)

    Broniowski, W.

    1987-07-01

    Solutions to non-chiral and chiral color dielectric models are discussed. The coupling of glueballs produces absolute quark confinement and generates selfconsistently a bag. 9 refs., 2 figs., 1 tab. (author)

  16. Random walks and polygons in tight confinement

    International Nuclear Information System (INIS)

    Diao, Y; Ernst, C; Ziegler, U

    2014-01-01

    We discuss the effect of confinement on the topology and geometry of tightly confined random walks and polygons. Here the walks and polygons are confined in a sphere of radius R ≥ 1/2 and the polygons are equilateral with n edges of unit length. We illustrate numerically that for a fixed length of random polygons the knotting probability increases to one as the radius decreases to 1/2. We also demonstrate that for random polygons (walks) the curvature increases to πn (π(n – 1)) as the radius approaches 1/2 and that the torsion decreases to ≈ πn/3 (≈ π(n – 1)/3). In addition we show the effect of length and confinement on the average crossing number of a random polygon

  17. Plasma confinement system and methods for use

    Science.gov (United States)

    Jarboe, Thomas R.; Sutherland, Derek

    2017-09-05

    A plasma confinement system is provided that includes a confinement chamber that includes one or more enclosures of respective helicity injectors. The one or more enclosures are coupled to ports at an outer radius of the confinement chamber. The system further includes one or more conductive coils aligned substantially parallel to the one or more enclosures and a further set of one or more conductive coils respectively surrounding portions of the one or more enclosures. Currents may be provided to the sets of conductive coils to energize a gas within the confinement chamber into a plasma. Further, a heat-exchange system is provided that includes an inner wall, an intermediate wall, an outer wall, and pipe sections configured to carry coolant through cavities formed by the walls.

  18. Monte Carlo simulations of confined polymer systems

    NARCIS (Netherlands)

    Vliet, Johannes Henricus van

    1991-01-01

    This thesis considers confined polymer systems. These systems are of considerable interest, e.g., thin polymer films, chromotography of polymer solutions, drag reduction, enhanced oil recovery, stabilization of colloidal dispersions, lubrication and biolubrication. The method used to study these

  19. Capillary condensation and orientational ordering of confined polar fluids.

    Science.gov (United States)

    Gramzow, Matthias; Klapp, Sabine H L

    2007-01-01

    The phase behavior and the orientational structure of polar model fluids confined to slit pores is investigated by means of density functional theory in a modified mean-field approximation. We focus on fluid states and further assume a uniform number density throughout the pore. Our results for spherical dipolar particles with additional van der Waals-like interactions (Stockmayer fluids) reveal complex fluid-fluid phase behavior involving condensation and first- and second-order isotropic-to-ferroelectric phase transitions, where the ferroelectric ordering occurs parallel to the confining walls. The relative importance of these phase transitions depends on two "tuning" parameters, that is the strength of the dipolar interactions (relative to the isotropic attractive ones) between fluid particles, and on the pore width. In particular, in narrow pores the condensation transition seen in bulk Stockmayer fluids is entirely suppressed. For dipolar hard spheres, on the other hand, the impact of confinement consists in a decrease of the isotropic-to-ferroelectric transition temperatures. We also demonstrate that the local orientational structure is inhomogeneous and anisotropic even in globally isotropic systems, in agreement with computer simulation results.

  20. Predictions of a theory of quark confinement

    International Nuclear Information System (INIS)

    Mack, G.

    1980-03-01

    We propose a theory of quark confinement which uses only the simplest of approximations. It explains persistence of quark confinement in Yang Mills theories with gauge group SU(2) or SU(3) as a consequence of asymptotic freedom in perturbation theory and of the known phase structure of Z(2) resp. Z(3) lattice gauge theory. Predictions are derived which can in principle be tested by computer simulation. Some are already tested by results of Creutz. They are in good agreement. (orig.)

  1. Confined catalysis under two-dimensional materials

    OpenAIRE

    Li, Haobo; Xiao, Jianping; Fu, Qiang; Bao, Xinhe

    2017-01-01

    Small spaces in nanoreactors may have big implications in chemistry, because the chemical nature of molecules and reactions within the nanospaces can be changed significantly due to the nanoconfinement effect. Two-dimensional (2D) nanoreactor formed under 2D materials can provide a well-defined model system to explore the confined catalysis. We demonstrate a general tendency for weakened surface adsorption under the confinement of graphene overlayer, illustrating the feasible modulation of su...

  2. Magnetic confinement in plasmas in nuclear devices

    International Nuclear Information System (INIS)

    Tull, C.G.

    1979-01-01

    The main emphasis of the magnetic fusion energy research program today lies in the development of two types of confinement schemes: magnetic mirrors and tokamaks. Experimental programs for both of these confinement schemes have shown steady progress toward achieving fusion power breakeven. The scaling of the current machines to a reactor operating regime and newly developed methods for plasma heating will very likely produce power breakeven within the next decade. Predictions are that the efficiency in a fusion power plant should exceed 32%

  3. Predictions of a theory of quark confinement

    International Nuclear Information System (INIS)

    Mack, G.

    1980-01-01

    A theory of quark confinement is proposed which uses only the simplest of approximations. It explains persistence of quark confinement in Yang-Mills theories with gauge group SU(2) or SU(3) as a consequence of asymptotic freedom in perturbation theory and of the known phase structure of Z(2) and Z(3) lattice gauge theory. Predictions are derived which can in principle be tested by computer simulation. Some are are already tested by results of Creutz. They are in good agreement

  4. Isotope effect on confinement in DT plasmas

    International Nuclear Information System (INIS)

    Fukuyama, A.; Itoh, K.; Itoh, S.; Yagi, M.; Azumi, M.

    1994-03-01

    Isotope effect on the energy confinement time is discussed for the DT plasma. The transport theory which is based on the ballooning mode turbulence is applied. When the DT plasma is produced under the condition of β p >1, the energy confinement time of DT plasma (50% mixture) is expected to be about 1.2 times better than the D plasma with the same operation condition. (author)

  5. Fluorescence Microscopy of Nanochannel-Confined DNA.

    Science.gov (United States)

    Westerlund, Fredrik; Persson, Fredrik; Fritzsche, Joachim; Beech, Jason P; Tegenfeldt, Jonas O

    2018-01-01

    Stretching of DNA in nanoscale confinement allows for several important studies. The genetic contents of the DNA can be visualized on the single DNA molecule level and both the polymer physics of confined DNA and also DNA/protein and other DNA/DNA-binding molecule interactions can be explored. This chapter describes the basic steps to fabricate the nanostructures, perform the experiments and analyze the data.

  6. Extended BRS algebra and color confinement criteria

    International Nuclear Information System (INIS)

    Shintani, Meiun.

    1983-09-01

    We examine the color-confinement criteria proposed by Kugo and Ojima. With the use of the extended BRS symmetry and the Nakanishi's theorem, we look for the representations of the BRS algebra compatible with the first condition of their criteria (the K-O condition) and then ask whether or not they are physically acceptable. As a result, the quartet mechanism does not work, and the K-O condition is not regarded as a confinement condition. (author)

  7. Stellarator approach to toroidal plasma confinement

    International Nuclear Information System (INIS)

    Johnson, J.L.

    1981-12-01

    An overview is presented of the development and current status of the stellarator approach to controlled thermonuclear confinement. Recent experimental, theoretical, and systems developments have made this concept a viable option for the evolution of the toroidal confinement program. Some experimental study of specific problems associated with departure from two-dimensional symmetry must be undertaken before the full advantages and opportunities of steady-state, net-current-free operation can be realized

  8. Confinement in W7-AS and the role of radial electric field and magnetic shear

    International Nuclear Information System (INIS)

    Brakel, R.; Anton, M.; Baldzuhn, J.; Burhenn, R.; Erckmann, V.; Fiedler, S.; Geiger, J.; Hartfuss, H.J.; Heinrich, O.; Hirsch, M.; Jaenicke, R.; Kick, M.; Kuehner, G.; Maassberg, H.; Stroth, U.; Wagner, F.; Weller, A.

    1997-01-01

    Improved neoclassical electron confinement in the centre of low-density ECRH plasmas has been observed in the presence of a strong positive radial electric field, which resembles the electron root solution of the neoclassical ambipolarity condition but is obviously driven by the loss of ECRH-generated suprathermal electrons. At higher densities and with NBI heating, a high confinement regime substantially above the ISS95-scaling and different from the H-mode is established with a strongly sheared negative radial electric field at the boundary. The application of plasma-current induced magnetic shear reveals that confinement in W7-AS is essentially determined by perturbations at high-order rational surfaces. For optimum confinement, these resonances have either to be avoided in the boundary region or magnetic shear must be sufficiently large. Independent of its sign, magnetic shear can reduce electron energy transport which is enhanced in the presence of such resonances to the neoclassical level. (author)

  9. Characterization of the polyphenol oxidase gene family reveals a novel microRNA involved in posttranscriptional regulation of PPOs in Salvia miltiorrhiza

    OpenAIRE

    Li, Caili; Li, Dongqiao; Li, Jiang; Shao, Fenjuan; Lu, Shanfa

    2017-01-01

    Salvia miltiorrhiza is a well-known material of traditional Chinese medicine. Understanding the regulatory mechanisms of phenolic acid biosynthesis and metabolism are important for S. miltiorrhiza quality improvement. We report here that S. miltiorrhiza contains 19 polyphenol oxidases (PPOs), forming the largest PPO gene family in plant species to our knowledge. Analysis of gene structures and sequence features revealed the conservation and divergence of SmPPOs. SmPPOs were differentially exp...

  10. Bifurcated equilibria in centrifugally confined plasma

    International Nuclear Information System (INIS)

    Shamim, I.; Teodorescu, C.; Guzdar, P. N.; Hassam, A. B.; Clary, R.; Ellis, R.; Lunsford, R.

    2008-01-01

    A bifurcation theory and associated computational model are developed to account for abrupt transitions observed recently on the Maryland Centrifugal eXperiment (MCX) [R. F. Ellis et al. Phys. Plasmas 8, 2057 (2001)], a supersonically rotating magnetized plasma that relies on centrifugal forces to prevent thermal expansion of plasma along the magnetic field. The observed transitions are from a well-confined, high-rotation state (HR-mode) to a lower-rotation, lesser-confined state (O-mode). A two-dimensional time-dependent magnetohydrodynamics code is used to simulate the dynamical equilibrium states of the MCX configuration. In addition to the expected viscous drag on the core plasma rotation, a momentum loss term is added that models the friction of plasma on the enhanced level of neutrals expected in the vicinity of the insulators at the throats of the magnetic mirror geometry. At small values of the external rotation drive, the plasma is not well-centrifugally confined and hence experiences the drag from near the insulators. Beyond a critical value of the external drive, the system makes an abrupt transition to a well-centrifugally confined state in which the plasma has pulled away from the end insulator plates; more effective centrifugal confinement lowers the plasma mass near the insulators allowing runaway increases in the rotation speed. The well-confined steady state is reached when the external drive is balanced by only the viscosity of the core plasma. A clear hysteresis phenomenon is shown.

  11. Confined Space Evaluation Student Manual, #19613

    Energy Technology Data Exchange (ETDEWEB)

    Wilmot, David Ezekiel [Los Alamos National Laboratory

    2016-08-29

    Many workplaces contain spaces that are considered to be “confined” because their configuration hinders the activities of employees who must enter into, work in, and exit from them. In general, the permit-required confined spaces (PRCSs) Occupational Safety and Health Administration (OSHA) standard requires that Los Alamos National Laboratory (LANL) evaluate the workplace to determine if any spaces are PRCSs. The standard specifies strict procedures for the evaluation and atmospheric testing of a space before and during an entry by workers. The OSHA PRCS standard provides for alternative (less stringent than full-permit) entry procedures in cases where the only hazard in a space is atmospheric and the hazard can be controlled by forced air. At LANL, all confined spaces or potential confined spaces on LANL-owned or -operated property must be identified and evaluated by a confined space evaluator accompanied by a knowledgeable person. This course provides the information needed by confined space evaluators to make judgements about whether a space is a confined space, and if so, whether the space will require a permit for entry.

  12. Proteomic investigation of Vibrio alginolyticus challenged Caenorhabditis elegans revealed regulation of cellular homeostasis proteins and their role in supporting innate immune system.

    Science.gov (United States)

    Durai, Sellegounder; Singh, Nirpendra; Kundu, Suman; Balamurugan, Krishnaswamy

    2014-08-01

    Caenorhabditis elegans has been the preferred model system for many investigators to study pathogenesis. In the present investigation, regulation of C. elegans proteome was explored against V. alginolyticus infection using quantitative proteomics approach. Proteins were separated using 2D-DIGE and the differentially regulated proteins were identified using PMF and MALDI TOF/TOF analysis. The results thus obtained were validated using Western blotting for candidate proteins. The corresponding transcriptional regulation was quantified subsequently using real-time PCR. Interaction network for candidate proteins was predicted using search tool for the retrieval of interacting genes/proteins (STRING) and functional validation was performed using respective mutant strains. Out of the 25 proteins identified, 21 proteins appeared to be upregulated while four were downregulated. Upregulated proteins included those involved in stress-response (PDI-2, HSP-6), immune-response (protein kinase -18, GST-8) and energy-production (ATP-2) while proteins involved in structural maintenance (IFB-2) and lipid metabolism (SODH-1) were downregulated. The roles of these players in the host system during Vibrio infection was analyzed in vivo using wild type and mutant C. elegans. Survival assays using mutants lacking pdi-2, ire-1, and xbp-1 displayed enhanced susceptibility to V. alginolyticus. Cellular stress generated by V. alginolyticus was determined using ROS assay. This is the first report of proteome changes in C. elegans against V. alginolyticus challenge and highlights the significance of unfolded protein response (UPR) pathway during bacterial infection. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Complex and extensive post-transcriptional regulation revealed by integrative proteomic and transcriptomic analysis of metabolite stress response in Clostridium acetobutylicum.

    Science.gov (United States)

    Venkataramanan, Keerthi P; Min, Lie; Hou, Shuyu; Jones, Shawn W; Ralston, Matthew T; Lee, Kelvin H; Papoutsakis, E Terry

    2015-01-01

    Clostridium acetobutylicum is a model organism for both clostridial biology and solvent production. The organism is exposed to its own toxic metabolites butyrate and butanol, which trigger an adaptive stress response. Integrative analysis of proteomic and RNAseq data may provide novel insights into post-transcriptional regulation. The identified iTRAQ-based quantitative stress proteome is made up of 616 proteins with a 15 % genome coverage. The differentially expressed proteome correlated poorly with the corresponding differential RNAseq transcriptome. Up to 31 % of the differentially expressed proteins under stress displayed patterns opposite to those of the transcriptome, thus suggesting significant post-transcriptional regulation. The differential proteome of the translation machinery suggests that cells employ a different subset of ribosomal proteins under stress. Several highly upregulated proteins but with low mRNA levels possessed mRNAs with long 5'UTRs and strong RBS scores, thus supporting the argument that regulatory elements on the long 5'UTRs control their translation. For example, the oxidative stress response rubrerythrin was upregulated only at the protein level up to 40-fold without significant mRNA changes. We also identified many leaderless transcripts, several displaying different transcriptional start sites, thus suggesting mRNA-trimming mechanisms under stress. Downregulation of Rho and partner proteins pointed to changes in transcriptional elongation and termination under stress. The integrative proteomic-transcriptomic analysis demonstrated complex expression patterns of a large fraction of the proteome. Such patterns could not have been detected with one or the other omic analyses. Our analysis proposes the involvement of specific molecular mechanisms of post-transcriptional regulation to explain the observed complex stress response.

  14. Differential microRNA Analysis of Glandular Trichomes and Young Leaves in Xanthium strumarium L. Reveals Their Putative Roles in Regulating Terpenoid Biosynthesis.

    Science.gov (United States)

    Fan, Rongyan; Li, Yuanjun; Li, Changfu; Zhang, Yansheng

    2015-01-01

    The medicinal plant Xanthium strumarium L. (X. strumarium) is covered with glandular trichomes, which are the sites for synthesizing pharmacologically active terpenoids such as xanthatin. MicroRNAs (miRNAs) are a class of 21-24 nucleotide (nt) non-coding RNAs, most of which are identified as regulators of plant growth development. Identification of miRNAs involved in the biosynthesis of plant secondary metabolites remains limited. In this study, high-throughput Illumina sequencing, combined with target gene prediction, was performed to discover novel and conserved miRNAs with potential roles in regulating terpenoid biosynthesis in X. strumarium glandular trichomes. Two small RNA libraries from leaves and glandular trichomes of X. strumarium were established. In total, 1,185 conserved miRNAs and 37 novel miRNAs were identified, with 494 conserved miRNAs and 18 novel miRNAs being differentially expressed between the two tissue sources. Based on the X. strumarium transcriptome data that we recently constructed, 3,307 annotated mRNA transcripts were identified as putative targets of the differentially expressed miRNAs. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis suggested that some of the differentially expressed miRNAs, including miR6435, miR5021 and miR1134, might be involved in terpenoid biosynthesis in the X. strumarium glandular trichomes. This study provides the first comprehensive analysis of miRNAs in X. strumarium, which forms the basis for further understanding of miRNA-based regulation on terpenoid biosynthesis.

  15. Differential microRNA Analysis of Glandular Trichomes and Young Leaves in Xanthium strumarium L. Reveals Their Putative Roles in Regulating Terpenoid Biosynthesis.

    Directory of Open Access Journals (Sweden)

    Rongyan Fan

    Full Text Available The medicinal plant Xanthium strumarium L. (X. strumarium is covered with glandular trichomes, which are the sites for synthesizing pharmacologically active terpenoids such as xanthatin. MicroRNAs (miRNAs are a class of 21-24 nucleotide (nt non-coding RNAs, most of which are identified as regulators of plant growth development. Identification of miRNAs involved in the biosynthesis of plant secondary metabolites remains limited. In this study, high-throughput Illumina sequencing, combined with target gene prediction, was performed to discover novel and conserved miRNAs with potential roles in regulating terpenoid biosynthesis in X. strumarium glandular trichomes. Two small RNA libraries from leaves and glandular trichomes of X. strumarium were established. In total, 1,185 conserved miRNAs and 37 novel miRNAs were identified, with 494 conserved miRNAs and 18 novel miRNAs being differentially expressed between the two tissue sources. Based on the X. strumarium transcriptome data that we recently constructed, 3,307 annotated mRNA transcripts were identified as putative targets of the differentially expressed miRNAs. KEGG (Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that some of the differentially expressed miRNAs, including miR6435, miR5021 and miR1134, might be involved in terpenoid biosynthesis in the X. strumarium glandular trichomes. This study provides the first comprehensive analysis of miRNAs in X. strumarium, which forms the basis for further understanding of miRNA-based regulation on terpenoid biosynthesis.

  16. Reexamination of the Physiological Role of PykA in Escherichia coli Revealed that It Negatively Regulates the Intracellular ATP Levels under Anaerobic Conditions.

    Science.gov (United States)

    Zhao, Chunhua; Lin, Zhao; Dong, Hongjun; Zhang, Yanping; Li, Yin

    2017-06-01

    Pyruvate kinase is one of the three rate-limiting glycolytic enzymes that catalyze the last step of glycolysis, conversion of phosphoenolpyruvate (PEP) into pyruvate, which is associated with ATP generation. Two isozymes of pyruvate kinase, PykF and PykA, are identified in Escherichia coli PykF is considered important, whereas PykA has a less-defined role. Prior studies inactivated the pykA gene to increase the level of its substrate, PEP, and thereby increased the yield of end products derived from PEP. We were surprised when we found a pykA ::Tn 5 mutant in a screen for increased yield of an end product derived from pyruvate ( n -butanol), suggesting that the role of PykA needs to be reexamined. We show that the pykA mutant exhibited elevated intracellular ATP levels, biomass concentrations, glucose consumption, and n -butanol production. We also discovered that the pykA mutant expresses higher levels of a presumed pyruvate transporter, YhjX, permitting the mutant to recapture and metabolize excreted pyruvate. Furthermore, we demonstrated that the nucleotide diphosphate kinase activity of PykA leads to negative regulation of the intracellular ATP levels. Taking the data together, we propose that inactivation of pykA can be considered a general strategy to enhance the production of pyruvate-derived metabolites under anaerobic conditions. IMPORTANCE This study showed that knocking out pykA significantly increased the intracellular ATP level and thus significantly increased the levels of glucose consumption, biomass formation, and pyruvate-derived product formation under anaerobic conditions. pykA was considered to be encoding a dispensable pyruvate kinase; here we show that pykA negatively regulates the anaerobic glycolysis rate through regulating the energy distribution. Thus, knocking out pykA can be used as a general strategy to increase the level of pyruvate-derived fermentative products. Copyright © 2017 American Society for Microbiology.

  17. Conference summary: Experiments in confinement and plasma-wall interaction and innovative confinement concept

    International Nuclear Information System (INIS)

    Ninomiya, H.

    2005-01-01

    This paper summarizes the results presented at the 20th IAEA Fusion Energy Conference 2004 in the sessions of confinement, plasma-wall interaction and innovative confinement concept. The highlights of the presentations are as follows. Long pulse operation with high beta and high bootstrap fraction much longer than the current diffusion time has been achieved. The discharge scenario optimization and its extrapolation towards ITER have progressed remarkably. Significant progress has been made in understanding of global confinement and transport physics. (author)

  18. Multiple patterns of diblock copolymer confined in irregular geometries with soft surface

    Science.gov (United States)

    Li, Ying; Sun, Min-Na; Zhang, Jin-Jun; Pan, Jun-Xing; Guo, Yu-Qi; Wang, Bao-Feng; Wu, Hai-Shun

    2015-12-01

    The different confinement shapes can induce the formation of various interesting and novel morphologies, which might inspire potential applications of materials. In this paper, we study the directed self-assembly of diblock copolymer confined in irregular geometries with a soft surface by using self-consistent field theory. Two types of confinement geometries are considered, namely, one is the concave pore with one groove and the other is the concave pore with two grooves. We obtain more novel and different structures which could not be produced in other two-dimensional (2D) confinements. Comparing these new structures with those obtained in regular square confinement, we find that the range of ordered lamellae is enlarged and the range of disordered structure is narrowed down under the concave pore confinement. We also compare the different structures obtained under the two types of confinement geometries, the results show that the effect of confinement would increase, which might induce the diblock copolymer to form novel structures. We construct the phase diagram as a function of the fraction of B block and the ratio of h/L of the groove. The simulation reveals that the wetting effect of brushes and the shape of confinement geometries play important roles in determining the morphologies of the system. Our results improve the applications in the directed self-assembly of diblock copolymer for fabricating the irregular structures. Project supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20121404110004), the Research Foundation for Excellent Talents of Shanxi Provincial Department of Human Resources and Social Security, China, and the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi Province, China.

  19. Impact of production systems on swine confinement buildings bioaerosols.

    Science.gov (United States)

    Létourneau, Valérie; Nehmé, Benjamin; Mériaux, Anne; Massé, Daniel; Duchaine, Caroline

    2010-02-01

    Hog production has been substantially intensified in Eastern Canada. Hogs are now fattened in swine confinement buildings with controlled ventilation systems and high animal densities. Newly designed buildings are equipped with conventional manure handling and management systems, shallow or deep litter systems, or source separation systems to manage the large volumes of waste. However, the impacts of those alternative production systems on bioaerosol concentrations within the barns have never been evaluated. Bioaerosols were characterized in 18 modern swine confinement buildings, and the differences in bioaerosol composition in the three different production systems were evaluated. Total dust, endotoxins, culturable actinomycetes, fungi, and bacteria were collected with various apparatuses. The total DNA of the air samples was extracted, and quantitative polymerase chain reaction (PCR) was used to assess the total number of bacterial genomes, as a total (culturable and nonculturable) bacterial assessment. The measured total dust and endotoxin concentrations were not statistically different in the three studied production systems. In buildings with sawdust beds, actinomycetes and molds were found in higher concentrations than in the conventional barns. Aspergillus, Cladosporium, Penicillium, and Scopulariopsis species were identified in all the studied swine confinement buildings. A. flavus, A. terreus, and A. versicolor were abundantly present in the facilities with sawdust beds. Thermotolerant A. fumigatus and Mucor were usually found in all the buildings. The culturable bacteria concentrations were higher in the barns with litters than in the conventional buildings, while real-time PCR revealed nonstatistically different concentrations of total bacteria in all the studied swine confinement buildings. In terms of workers' respiratory health, barns equipped with a solid/liquid separation system may offer better air quality than conventional buildings or barns with

  20. The Knot Spectrum of Confined Random Equilateral Polygons

    Directory of Open Access Journals (Sweden)

    Diao Y.

    2014-01-01

    Full Text Available It is well known that genomic materials (long DNA chains of living organisms are often packed compactly under extreme confining conditions using macromolecular self-assembly processes but the general DNA packing mechanism remains an unsolved problem. It has been proposed that the topology of the packed DNA may be used to study the DNA packing mechanism. For example, in the case of (mutant bacteriophage P4, DNA molecules packed inside the bacteriophage head are considered to be circular since the two sticky ends of the DNA are close to each other. The DNAs extracted from the capsid without separating the two ends can thus preserve the topology of the (circular DNAs. It turns out that the circular DNAs extracted from bacteriophage P4 are non-trivially knotted with very high probability and with a bias toward chiral knots. In order to study this problem using a systematic approach based on mathematical modeling, one needs to introduce a DNA packing model under extreme volume confinement condition and test whether such a model can produce the kind of knot spectrum observed in the experiments. In this paper we introduce and study a model of equilateral random polygons con_ned in a sphere. This model is not meant to generate polygons that model DNA packed in a virus head directly. Instead, the average topological characteristics of this model may serve as benchmark data for totally randomly packed circular DNAs. The difference between the biologically observed topological characteristics and our benchmark data might reveal the bias of DNA packed in the viral capsids and possibly lead to a better understanding of the DNA packing mechanism, at least for the bacteriophage DNA. The purpose of this paper is to provide information about the knot spectrum of equilateral random polygons under such a spherical confinement with length and confinement ratios in a range comparable to circular DNAs packed inside bacteriophage heads.

  1. In-surface confinement of topological insulator nanowire surface states

    International Nuclear Information System (INIS)

    Chen, Fan W.; Jauregui, Luis A.; Tan, Yaohua; Manfra, Michael; Klimeck, Gerhard; Chen, Yong P.; Kubis, Tillmann

    2015-01-01

    The bandstructures of [110] and [001] Bi 2 Te 3 nanowires are solved with the atomistic 20 band tight binding functionality of NEMO5. The theoretical results reveal: The popular assumption that all topological insulator (TI) wire surfaces are equivalent is inappropriate. The Fermi velocity of chemically distinct wire surfaces differs significantly which creates an effective in-surface confinement potential. As a result, topological insulator surface states prefer specific surfaces. Therefore, experiments have to be designed carefully not to probe surfaces unfavorable to the surface states (low density of states) and thereby be insensitive to the TI-effects

  2. In-surface confinement of topological insulator nanowire surface states

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Fan W., E-mail: fanchen@purdue.edu [Department of Physics and Astronomy, Purdue, West Lafayette, Indiana 47907 (United States); Network for Computational Nanotechnology, Purdue, West Lafayette, Indiana 47907 (United States); Jauregui, Luis A. [School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907 (United States); Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana 47907 (United States); Tan, Yaohua [Network for Computational Nanotechnology, Purdue, West Lafayette, Indiana 47907 (United States); School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907 (United States); Manfra, Michael [Department of Physics and Astronomy, Purdue, West Lafayette, Indiana 47907 (United States); School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907 (United States); Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana 47907 (United States); School of Materials Engineering, Purdue University, West Lafayette, Indiana 47907 (United States); Klimeck, Gerhard [Network for Computational Nanotechnology, Purdue, West Lafayette, Indiana 47907 (United States); School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907 (United States); Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana 47907 (United States); Chen, Yong P. [Department of Physics and Astronomy, Purdue, West Lafayette, Indiana 47907 (United States); School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907 (United States); Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana 47907 (United States); Kubis, Tillmann [Network for Computational Nanotechnology, Purdue, West Lafayette, Indiana 47907 (United States)

    2015-09-21

    The bandstructures of [110] and [001] Bi{sub 2}Te{sub 3} nanowires are solved with the atomistic 20 band tight binding functionality of NEMO5. The theoretical results reveal: The popular assumption that all topological insulator (TI) wire surfaces are equivalent is inappropriate. The Fermi velocity of chemically distinct wire surfaces differs significantly which creates an effective in-surface confinement potential. As a result, topological insulator surface states prefer specific surfaces. Therefore, experiments have to be designed carefully not to probe surfaces unfavorable to the surface states (low density of states) and thereby be insensitive to the TI-effects.

  3. In-surface confinement of topological insulator nanowire surface states

    Science.gov (United States)

    Chen, Fan W.; Jauregui, Luis A.; Tan, Yaohua; Manfra, Michael; Klimeck, Gerhard; Chen, Yong P.; Kubis, Tillmann

    2015-09-01

    The bandstructures of [110] and [001] Bi2Te3 nanowires are solved with the atomistic 20 band tight binding functionality of NEMO5. The theoretical results reveal: The popular assumption that all topological insulator (TI) wire surfaces are equivalent is inappropriate. The Fermi velocity of chemically distinct wire surfaces differs significantly which creates an effective in-surface confinement potential. As a result, topological insulator surface states prefer specific surfaces. Therefore, experiments have to be designed carefully not to probe surfaces unfavorable to the surface states (low density of states) and thereby be insensitive to the TI-effects.

  4. Overexpression of the PAP1 transcription factor reveals a complex regulation of flavonoid and phenylpropanoid metabolism in Nicotiana tabacum plants attacked by Spodoptera litura.

    Science.gov (United States)

    Mitsunami, Tomoko; Nishihara, Masahiro; Galis, Ivan; Alamgir, Kabir Md; Hojo, Yuko; Fujita, Kohei; Sasaki, Nobuhiro; Nemoto, Keichiro; Sawasaki, Tatsuya; Arimura, Gen-ichiro

    2014-01-01

    Anthocyanin pigments and associated flavonoids have demonstrated antioxidant properties and benefits for human health. Consequently, current plant bioengineers have focused on how to modify flavonoid metabolism in plants. Most of that research, however, does not consider the role of natural biotic stresses (e.g., herbivore attack). To understand the influence of herbivore attack on the metabolic engineering of flavonoids, we examined tobacco plants overexpressing the Arabidopsis PAP1 gene (encoding an MYB transcription factor), which accumulated anthocyanin pigments and other flavonoids/phenylpropanoids. In comparison to wild-type and control plants, transgenic plants exhibited greater resistance to Spodoptera litura. Moreover, herbivory suppressed the PAP1-induced increase of transcripts of flavonoid/phenylpropanoid biosynthetic genes (e.g., F3H) and the subsequent accumulation of these genes' metabolites, despite the unaltered PAP1 mRNA levels after herbivory. The instances of down-regulation were independent of the signaling pathways mediated by defense-related jasmonates but were relevant to the levels of PAP1-induced and herbivory-suppressed transcription factors, An1a and An1b. Although initially F3H transcripts were suppressed by herbivory, after the S. litura feeding was interrupted, F3H transcripts increased. We hypothesize that in transgenic plants responding to herbivory, there is a complex mechanism regulating enriched flavonoid/phenylpropanoid compounds, via biotic stress signals.

  5. Overexpression of the PAP1 transcription factor reveals a complex regulation of flavonoid and phenylpropanoid metabolism in Nicotiana tabacum plants attacked by Spodoptera litura.

    Directory of Open Access Journals (Sweden)

    Tomoko Mitsunami

    Full Text Available Anthocyanin pigments and associated flavonoids have demonstrated antioxidant properties and benefits for human health. Consequently, current plant bioengineers have focused on how to modify flavonoid metabolism in plants. Most of that research, however, does not consider the role of natural biotic stresses (e.g., herbivore attack. To understand the influence of herbivore attack on the metabolic engineering of flavonoids, we examined tobacco plants overexpressing the Arabidopsis PAP1 gene (encoding an MYB transcription factor, which accumulated anthocyanin pigments and other flavonoids/phenylpropanoids. In comparison to wild-type and control plants, transgenic plants exhibited greater resistance to Spodoptera litura. Moreover, herbivory suppressed the PAP1-induced increase of transcripts of flavonoid/phenylpropanoid biosynthetic genes (e.g., F3H and the subsequent accumulation of these genes' metabolites, despite the unaltered PAP1 mRNA levels after herbivory. The instances of down-regulation were independent of the signaling pathways mediated by defense-related jasmonates but were relevant to the levels of PAP1-induced and herbivory-suppressed transcription factors, An1a and An1b. Although initially F3H transcripts were suppressed by herbivory, after the S. litura feeding was interrupted, F3H transcripts increased. We hypothesize that in transgenic plants responding to herbivory, there is a complex mechanism regulating enriched flavonoid/phenylpropanoid compounds, via biotic stress signals.

  6. Overexpression of the PAP1 Transcription Factor Reveals a Complex Regulation of Flavonoid and Phenylpropanoid Metabolism in Nicotiana tabacum Plants Attacked by Spodoptera litura

    Science.gov (United States)

    Mitsunami, Tomoko; Nishihara, Masahiro; Galis, Ivan; Alamgir, Kabir Md; Hojo, Yuko; Fujita, Kohei; Sasaki, Nobuhiro; Nemoto, Keichiro; Sawasaki, Tatsuya; Arimura, Gen-ichiro

    2014-01-01

    Anthocyanin pigments and associated flavonoids have demonstrated antioxidant properties and benefits for human health. Consequently, current plant bioengineers have focused on how to modify flavonoid metabolism in plants. Most of that research, however, does not consider the role of natural biotic stresses (e.g., herbivore attack). To understand the influence of herbivore attack on the metabolic engineering of flavonoids, we examined tobacco plants overexpressing the Arabidopsis PAP1 gene (encoding an MYB transcription factor), which accumulated anthocyanin pigments and other flavonoids/phenylpropanoids. In comparison to wild-type and control plants, transgenic plants exhibited greater resistance to Spodoptera litura. Moreover, herbivory suppressed the PAP1-induced increase of transcripts of flavonoid/phenylpropanoid biosynthetic genes (e.g., F3H) and the subsequent accumulation of these genes' metabolites, despite the unaltered PAP1 mRNA levels after herbivory. The instances of down-regulation were independent of the signaling pathways mediated by defense-related jasmonates but were relevant to the levels of PAP1-induced and herbivory-suppressed transcription factors, An1a and An1b. Although initially F3H transcripts were suppressed by herbivory, after the S. litura feeding was interrupted, F3H transcripts increased. We hypothesize that in transgenic plants responding to herbivory, there is a complex mechanism regulating enriched flavonoid/phenylpropanoid compounds, via biotic stress signals. PMID:25268129

  7. Quantitative Phosphoproteomic Study Reveals that Protein Kinase A Regulates Neural Stem Cell Differentiation Through Phosphorylation of Catenin Beta-1 and Glycogen Synthase Kinase 3β.

    Science.gov (United States)

    Wang, Shuxin; Li, Zheyi; Shen, Hongyan; Zhang, Zhong; Yin, Yuxin; Wang, Qingsong; Zhao, Xuyang; Ji, Jianguo

    2016-08-01

    Protein phosphorylation is central to the understanding of multiple cellular signaling pathways responsible for regulating the self-renewal and differentiation of neural stem cells (NSCs). Here we performed a large-scale phosphoproteomic analysis of rat fetal NSCs using strong cation exchange chromatography prefractionation and citric acid-assisted two-step enrichment with TiO2 strategy followed by nanoLC-MS/MS analysis. Totally we identified 32,546 phosphosites on 5,091 phosphoproteins, among which 23,945 were class I phosphosites, and quantified 16,000 sites during NSC differentiation. More than 65% of class I phosphosites were novel when compared with PhosphoSitePlus database. Quantification results showed that the early and late stage of NSC differentiation differ greatly. We mapped 69 changed phosphosites on 20 proteins involved in Wnt signaling pathway, including S552 on catenin beta-1 (Ctnnb1) and S9 on glycogen synthase kinase 3β (Gsk3β). Western blotting and real-time PCR results proved that Wnt signaling pathway plays critical roles in NSC fate determination. Furthermore, inhibition and activation of PKA dramatically affected the phosphorylation state of Ctnnb1 and Gsk3β, which regulates the differentiation of NSCs. Our data provides a valuable resource for studying the self-renewal and differentiation of NSCs. Stem Cells 2016;34:2090-2101. © 2016 AlphaMed Press.

  8. Resveratrol treatment reveals a novel role for HMGB1 in regulation of the type 1 interferon response in dengue virus infection.

    Science.gov (United States)

    Zainal, Nurhafiza; Chang, Chih-Peng; Cheng, Yi-Lin; Wu, Yan-Wei; Anderson, Robert; Wan, Shu-Wen; Chen, Chia-Ling; Ho, Tzong-Shiann; AbuBakar, Sazaly; Lin, Yee-Shin

    2017-02-20

    Dengue is one of the most significant mosquito-borne virus diseases worldwide, particularly in tropical and subtropical regions. This study sought to examine the antiviral activity of resveratrol (RESV), a phytoalexin secreted naturally by plants, against dengue virus (DENV) infection. Our data showed that RESV inhibits the translocation of high mobility group box 1 (HMGB1), a DNA binding protein that normally resides in the nucleus, into the cytoplasm and extracellular milieu. HMGB1 migrates out of the nucleus during DENV infection. This migration is inhibited by RESV treatment and is mediated by induction of Sirt1 which leads to the retention of HMGB1 in the nucleus and consequently helps in the increased production of interferon-stimulated genes (ISGs). Nuclear HMGB1 was found to bind to the promoter region of the ISG and positively regulated the expression of ISG. The enhanced transcription of ISGs by nuclear HMGB1 thus contributes to the antiviral activity of RESV against DENV. To the best of our knowledge, this is the first report to demonstrate that RESV antagonizes DENV replication and that nuclear HMGB1 plays a role in regulating ISG production.

  9. Search for KPNA7 cargo proteins in human cells reveals MVP and ZNF414 as novel regulators of cancer cell growth.

    Science.gov (United States)

    Vuorinen, Elisa M; Rajala, Nina K; Rauhala, Hanna E; Nurminen, Anssi T; Hytönen, Vesa P; Kallioniemi, Anne

    2017-01-01

    Karyopherin alpha 7 (KPNA7) belongs to a family of nuclear import proteins that recognize and bind nuclear localization signals (NLSs) in proteins to be transported to the nucleus. Previously we found that KPNA7 is overexpressed in a subset of pancreatic cancer cell lines and acts as a critical regulator of growth in these cells. This characteristic of KPNA7 is likely to be mediated by its cargo proteins that are still mainly unknown. Here, we used protein affinity chromatography in Hs700T and MIA PaCa-2 pancreatic cancer cell lines and identified 377 putative KPNA7 cargo proteins, most of which were known or predicted to localize to the nucleus. The interaction was confirmed for two of the candidates, MVP and ZNF414, using co-immunoprecipitation, and their transport to the nucleus was hindered by siRNA based KPNA7 silencing. Most importantly, silencing of MVP and ZNF414 resulted in marked reduction in Hs700T cell growth. In conclusion, these data uncover two previously unknown human KPNA7 cargo proteins with distinct roles as novel regulators of pancreatic cancer cell growth, thus deepening our understanding on the contribution of nuclear transport in cancer pathogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Global Kinetic Analysis of Mammalian E3 Reveals pH-dependent NAD+/NADH Regulation, Physiological Kinetic Reversibility, and Catalytic Optimum*

    Science.gov (United States)

    Moxley, Michael A.; Beard, Daniel A.; Bazil, Jason N.

    2016-01-01

    Mammalian E3 is an essential mitochondrial enzyme responsible for catalyzing the terminal reaction in the oxidative catabolism of several metabolites. E3 is a key regulator of metabolic fuel selection as a component of the pyruvate dehydrogenase complex (PDHc). E3 regulates PDHc activity by altering the affinity of pyruvate dehydrogenase kinase, an inhibitor of the enzyme complex, through changes in reduction and acetylation state of lipoamide moieties set by the NAD+/NADH ratio. Thus, an accurate kinetic model of E3 is needed to predict overall mammalian PDHc activity. Here, we have combined numerous literature data sets and new equilibrium spectroscopic experiments with a multitude of independently collected forward and reverse steady-state kinetic assays using pig heart E3. The latter kinetic assays demonstrate a pH-dependent transition of NAD+ activation to inhibition, shown here, to our knowledge, for the first time in a single consistent data set. Experimental data were analyzed to yield a thermodynamically constrained four-redox-state model of E3 that simulates pH-dependent activation/inhibition and active site redox states for various conditions. The developed model was used to determine substrate/product conditions that give maximal E3 rates and show that, due to non-Michaelis-Menten behavior, the maximal flux is different compared with the classically defined kcat. PMID:26644471

  11. Crucial role of dynamic linker histone binding and divalent ions for DNA accessibility and gene regulation revealed by mesoscale modeling of oligonucleosomes

    Science.gov (United States)

    Collepardo-Guevara, Rosana; Schlick, Tamar

    2012-01-01

    Monte Carlo simulations of a mesoscale model of oligonucleosomes are analyzed to examine the role of dynamic-linker histone (LH) binding/unbinding in high monovalent salt with divalent ions, and to further interpret noted chromatin fiber softening by dynamic LH in monovalent salt conditions. We find that divalent ions produce a fiber stiffening effect that competes with, but does not overshadow, the dramatic softening triggered by dynamic-LH behavior. Indeed, we find that in typical in vivo conditions, dynamic-LH binding/unbinding reduces fiber stiffening dramatically (by a factor of almost 5, as measured by the elasticity modulus) compared with rigidly fixed LH, and also the force needed to initiate chromatin unfolding, making it consistent with those of molecular motors. Our data also show that, during unfolding, divalent ions together with LHs induce linker-DNA bending and DNA–DNA repulsion screening, which guarantee formation of heteromorphic superbeads-on-a-string structures that combine regions of loose and compact fiber independently of the characteristics of the LH–core bond. These structures might be important for gene regulation as they expose regions of the DNA selectively. Dynamic control of LH binding/unbinding, either globally or locally, in the presence of divalent ions, might constitute a mechanism for regulation of gene expression. PMID:22790986

  12. Proteomic analysis of a model unicellular green alga, Chlamydomonas reinhardtii, during short-term exposure to irradiance stress reveals significant down regulation of several heat-shock proteins.

    Science.gov (United States)

    Mahong, Bancha; Roytrakul, Suttiruk; Phaonaklop, Narumon; Wongratana, Janewit; Yokthongwattana, Kittisak

    2012-03-01

    Oxygenic photosynthetic organisms often suffer from excessive irradiance, which cause harmful effects to the chloroplast proteins and lipids. Photoprotection and the photosystem II repair processes are the mechanisms that plants deploy to counteract the drastic effects from irradiance stress. Although the protective and repair mechanisms seemed to be similar in most plants, many species do confer different level of tolerance toward high light. Such diversity may originate from differences at the molecular level, i.e., perception of the light stress, signal transduction and expression of stress responsive genes. Comprehensive analysis of overall changes in the total pool of proteins in an organism can be performed using a proteomic approach. In this study, we employed 2-DE/LC-MS/MS-based comparative proteomic approach to analyze total proteins of the light sensitive model unicellular green alga Chlamydomonas reinhardtii in response to excessive irradiance. Results showed that among all the differentially expressed proteins, several heat-shock proteins and molecular chaperones were surprisingly down-regulated after 3-6 h of high light exposure. Discussions were made on the possible involvement of such down regulation and the light sensitive nature of this model alga.

  13. Expression profiling and functional analysis reveals that TOR is a key player in regulating photosynthesis and phytohormone signaling pathways in Arabidopsis.

    Science.gov (United States)

    Dong, Pan; Xiong, Fangjie; Que, Yumei; Wang, Kai; Yu, Lihua; Li, Zhengguo; Ren, Maozhi

    2015-01-01

    Target of rapamycin (TOR) acts as a master regulator to control cell growth by integrating nutrient, energy, and growth factors in all eukaryotic species. TOR plays an evolutionarily conserved role in regulating the transcription of genes associated with anabolic and catabolic processes in Arabidopsis, but little is known about the functions of TOR in photosynthesis and phytohormone signaling, which are unique features of plants. In this study, AZD8055 (AZD) was screened as the strongest active-site TOR inhibitor (asTORi) in Arabidopsis compared with TORIN1 and KU63794 (KU). Gene expression profiles were evaluated using RNA-seq after treating Arabidopsis seedlings with AZD. More than three-fold differentially expressed genes (DEGs) were identified in AZD-treated plants relative to rapamycin-treated plants in previous studies. Most of the DEGs and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in cell wall elongation, ribosome biogenesis, and cell autophagy were common to both AZD- and rapamycin-treated samples, but AZD displayed much broader and more efficient inhibition of TOR compared with rapamycin. Importantly, the suppression of TOR by AZD resulted in remodeling of the expression profile of the genes associated with photosynthesis and various phytohormones, indicating that TOR plays a crucial role in modulating photosynthesis and phytohormone signaling in Arabidopsis. These newly identified DEGs expand the understanding of TOR signaling in plants. This study elucidates the novel functions of TOR in photosynthesis and phytohormone signaling and provides a platform to study the downstream targets of TOR in Arabidopsis.

  14. A Key Role of Xanthophylls That Are Not Embedded in Proteins in Regulation of the Photosynthetic Antenna Function in Plants, Revealed by Monomolecular Layer Studies.

    Science.gov (United States)

    Welc, Renata; Luchowski, Rafal; Grudzinski, Wojciech; Puzio, Michal; Sowinski, Karol; Gruszecki, Wieslaw I

    2016-12-29

    The main physiological function of LHCII (light-harvesting pigment-protein complex of photosystem II), the largest photosynthetic antenna complex of plants, is absorption of light quanta and transfer of excitation energy toward the reaction centers, to drive photosynthesis. However, under strong illumination, the photosynthetic apparatus faces the danger of photodegradation and therefore excitations in LHCII have to be down-regulated, e.g., via thermal energy dissipation. One of the elements of the regulatory system, operating in the photosynthetic apparatus under light stress conditions, is a conversion of violaxanthin, the xanthophyll present under low light, to zeaxanthin, accumulated under strong light. In the present study, an effect of violaxanthin and zeaxanthin on the molecular organization and the photophysical properties of LHCII was studied in a monomolecular layer system with application of molecular imaging (atomic force microscopy, fluorescence lifetime imaging microscopy) and spectroscopy (UV-Vis absorption, FTIR, fluorescence spectroscopy) techniques. The results of the experiments show that violaxanthin promotes the formation of supramolecular LHCII structures preventing dissipative excitation quenching while zeaxanthin is involved in the formation of excitonic energy states able to quench chlorophyll excitations in both the higher (B states) and lower (Q states) energy levels. The results point to a strategic role of xanthophylls that are not embedded in a protein environment, in regulation of the photosynthetic light harvesting activity in plants.

  15. Genome-wide miRNA screening reveals miR-310 family members negatively regulate the immune response in Drosophila melanogaster via co-targeting Drosomycin.

    Science.gov (United States)

    Li, Yao; Li, Shengjie; Li, Ruimin; Xu, Jiao; Jin, Ping; Chen, Liming; Ma, Fei

    2017-03-01

    Although innate immunity mediated by Toll signaling has been extensively studied in Drosophila melanogaster, the role of miRNAs in regulating the Toll-mediated immune response remains largely unknown. In this study, following Gram-positive bacterial challenge, we identified 93 differentially expressed miRNAs via genome-wide miRNA screening. These miRNAs were regarded as immune response related (IRR). Eight miRNAs were confirmed to be involved in the Toll-mediated immune response upon Gram-positive bacterial infection through genetic screening of 41 UAS-miRNA lines covering 60 miRNAs of the 93 IRR miRNAs. Interestingly, four out of these eight miRNAs, miR-310, miR-311, miR-312 and miR-313, are clustered miRNAs and belong to the miR-310 family. These miR-310 family members were shown to target and regulate the expression of Drosomycin, an antimicrobial peptide produced by Toll signaling. Taken together, our study implies important regulatory roles of miRNAs in the Toll-mediated innate immune response of Drosophila upon Gram-positive bacterial infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Ductility of reinforced concrete columns confined with stapled strips

    International Nuclear Information System (INIS)

    Tahir, M.F.; Khan, Q.U.Z.; Shabbir, F.; Sharif, M.B.; Ijaz, N.

    2015-01-01

    Response of three 150x150x450mm short reinforced concrete (RC) columns confined with different types of confining steel was investigated. Standard stirrups, strips and stapled strips, each having same cross-sectional area, were employed as confining steel around four comer column bars. Experimental work was aimed at probing into the affect of stapled strip confinement on post elastic behavior and ductility level under cyclic axial load. Ductility ratios, strength enhancement factor and core concrete strengths were compared to study the affect of confinement. Results indicate that strength enhancement in RC columns due to strip and stapled strip confinement was not remarkable as compared to stirrup confined column. It was found that as compared to stirrup confined column, stapled strip confinement enhanced the ductility of RC column by 183% and observed axial capacity of stapled strip confined columns was 41 % higher than the strip confined columns. (author)

  17. Transcriptome analysis of Sulfolobus solfataricus infected with two related fuselloviruses reveals novel insights into the regulation of CRISPR-Cas system

    DEFF Research Database (Denmark)

    Fusco, Salvatore; Liguori, Rossana; Limauro, Danila

    2015-01-01

    in a double-infected strain to explore both virus-host and virus-virus interactions. Whereas SSV1 did not induce major changes of the host gene expression, SSV2 elicited a strong host response, which includes the transcriptional activation of CRISPR loci and cas genes. As a consequence, a significant decrease...... of the SSV2 copy number has been observed, which in turn led to provirus-capture into the host chromosome. Results of this study have revealed novel aspects of the host-viral interaction in the frame of the CRISPR-response....

  18. Transcriptome analyses of a salt-tolerant cytokinin-deficient mutant reveal differential regulation of salt stress response by cytokinin deficiency.

    Directory of Open Access Journals (Sweden)

    Rie Nishiyama

    Full Text Available Soil destruction by abiotic environmental conditions, such as high salinity, has resulted in dramatic losses of arable land, giving rise to the need of studying mechanisms of plant adaptation to salt stress aimed at creating salt-tolerant plants. Recently, it has been reported that cytokinins (CKs regulate plant environmental stress responses through two-component systems. A decrease in endogenous CK levels could enhance salt and drought stress tolerance. Here, we have investigated the global transcriptional change caused by a reduction in endogenous CK content under both normal and salt stress conditions. Ten-day-old Arabidopsis thaliana wild-type (WT and CK-deficient ipt1,3,5,7 plants were transferred to agar plates containing either 0 mM (control or 200 mM NaCl and maintained at normal growth conditions for 24 h. Our experimental design allowed us to compare transcriptome changes under four conditions: WT-200 mM vs. WT-0 mM, ipt1,3,5,7-0 mM vs. WT-0 mM, ipt1,3,5,7-200 mM vs. ipt1,3,5,7-0 mM and ipt1,3,5,7-200 mM vs. WT-200 mM NaCl. Our results indicated that the expression of more than 10% of all of the annotated Arabidopsis genes was altered by CK deficiency under either normal or salt stress conditions when compared to WT. We found that upregulated expression of many genes encoding either regulatory proteins, such as NAC, DREB and ZFHD transcription factors and the calcium sensor SOS3, or functional proteins, such as late embryogenesis-abundant proteins, xyloglucan endo-transglycosylases, glycosyltransferases, glycoside hydrolases, defensins and glyoxalase I family proteins, may contribute to improved salt tolerance of CK-deficient plants. We also demonstrated that the downregulation of photosynthesis-related genes and the upregulation of several NAC genes may cause the altered morphological phenotype of CK-deficient plants. This study highlights the impact of CK regulation on the well-known stress-responsive signaling pathways, which

  19. Optogenetic Manipulation of Cyclic Di-GMP (c-di-GMP) Levels Reveals the Role of c-di-GMP in Regulating Aerotaxis Receptor Activity in Azospirillum brasilense.

    Science.gov (United States)

    O'Neal, Lindsey; Ryu, Min-Hyung; Gomelsky, Mark; Alexandre, Gladys

    2017-09-15

    Bacterial chemotaxis receptors provide the sensory inputs that inform the direction of navigation in changing environments. Recently, we described the bacterial second messenger cyclic di-GMP (c-di-GMP) as a novel regulator of a subclass of chemotaxis receptors. In Azospirillum brasilense , c-di-GMP binds to a chemotaxis receptor, Tlp1, and modulates its signaling function during aerotaxis. Here, we further characterize the role of c-di-GMP in aerotaxis using a novel dichromatic optogenetic system engineered for manipulating intracellular c-di-GMP levels in real time. This system comprises a red/near-infrared-light-regulated diguanylate cyclase and a blue-light-regulated c-di-GMP phosphodiesterase. It allows the generation of transient changes in intracellular c-di-GMP concentrations within seconds of irradiation with appropriate light, which is compatible with the time scale of chemotaxis signaling. We provide experimental evidence that binding of c-di-GMP to the Tlp1 receptor activates its signaling function during aerotaxis, which supports the role of transient changes in c-di-GMP levels as a means of adjusting the response of A. brasilense to oxygen gradients. We also show that intracellular c-di-GMP levels in A. brasilense change with carbon metabolism. Our data support a model whereby c-di-GMP functions to imprint chemotaxis receptors with a record of recent metabolic experience, to adjust their contribution to the signaling output, thus allowing the cells to continually fine-tune chemotaxis sensory perception to their metabolic state. IMPORTANCE Motile bacteria use chemotaxis to change swimming direction in response to changes in environmental conditions. Chemotaxis receptors sense environmental signals and relay sensory information to the chemotaxis machinery, which ultimately controls the swimming pattern of cells. In bacteria studied to date, differential methylation has been known as a mechanism to control the activity of chemotaxis receptors and

  20. The odyssey of a young gene: structure-function studies in human glutamate dehydrogenases reveal evolutionary-acquired complex allosteric regulation mechanisms.

    Science.gov (United States)

    Zaganas, Ioannis V; Kanavouras, Konstantinos; Borompokas, Nikolas; Arianoglou, Giovanna; Dimovasili, Christina; Latsoudis, Helen; Vlassi, Metaxia; Mastorodemos, Vasileios

    2014-01-01

    Mammalian glutamate dehydrogenase (GDH) catalyzes the reversible inter-conversion of glutamate to α-ketoglutarate and ammonia, interconnecting carbon skeleton and nitrogen metabolism. In addition, it functions as an energy switch by its ability to fuel the Krebs cycle depending on the energy status of the cell. As GDH lies at the intersection of several metabolic pathways, its activity is tightly regulated by several allosteric compounds that are metabolic intermediates. In contrast to other mammals that have a single GDH-encoding gene, humans and great apes possess two isoforms of GDH (hGDH1 and hGDH2, encoded by the GLUD1 and GLUD2 genes, respectively) with distinct regulation pattern, but remarkable sequence similarity (they differ, in their mature form, in only 15 of their 505 amino-acids). The GLUD2 gene is considered a very young gene, emerging from the GLUD1 gene through retro-position only recently (<23 million years ago). The new hGDH2 iso-enzyme, through random mutations and natural selection, is thought to have conferred an evolutionary advantage that helped its persistence through primate evolution. The properties of the two highly homologous human GDHs have been studied using purified recombinant hGDH1 and hGDH2 proteins obtained by expression of the corresponding cDNAs in Sf21 cells. According to these studies, in contrast to hGDH1 that maintains basal activity at 35-40 % of its maximal, hGDH2 displays low basal activity that is highly responsive to activation by rising levels of ADP and/or L-leucine which can also act synergistically. While hGDH1 is inhibited potently by GTP, hGDH2 shows remarkable GTP resistance. Furthermore, the two iso-enzymes are differentially inhibited by estrogens, polyamines and neuroleptics, and also differ in heat-lability. To elucidate the molecular mechanisms that underlie these different regulation patterns of the two iso-enzymes (and consequently the evolutionary adaptation of hGDH2 to a new functional role), we have

  1. Greater confinement disposal of high activity and special case wastes at the Nevada Test Site: A unified migration assessment approach

    International Nuclear Information System (INIS)

    Davis, P.A.; Olague, N.E.; Johnson, V.L.; Dickman, P.T.; O'Neill, L.J.

    1993-01-01

    The Department of Energy's Nevada Field Office has disposed of a small quantity of high activity and special case wastes using Greater Confinement Disposal facilities in Area 5 of the Nevada Test Site. Because some of these wastes are transuranic radioactive wastes, the Environmental Protection Agency standards for their disposal under 40 CFR Part 191 which requires a compliance assessment. In conducting the 40 CFR Part 191 compliance assessment, review of the Greater Confinement Disposal inventory revealed potentially land disposal restricted hazardous wastes. The regulatory options for disposing of land disposal restricted wastes consist of (1) treatment and monitoring, or (2) developing a no-migration petition. Given that the waste is already buried without treatment, a no-migration petition becomes the primary option. Based on a desire to minimize costs associated with site characterization and performance assessment, a single approach has been developed for assessing compliance with 40 CFR Part 191, DOE Order 5820.2A (which regulates low-level radioactive wastes contained in Greater Confinement Disposal facilities) and developing a no-migration petition. The approach consists of common points of compliance, common time frame for analysis, and common treatment of uncertainty. The procedure calls for conservative bias of modeling assumptions, including model input parameter distributions and adverse processes and events that can occur over the regulatory time frame, coupled with a quantitative treatment of data and parameter uncertainty. This approach provides a basis for a defensible regulatory decision. In addition, the process is iterative between modeling and site characterization activities, where the need for site characterization activities is based on a quantitative definition of the most important and uncertain parameters or assumptions

  2. New features on the environmental regulation of metabolism revealed by modeling the cellular proteomic adaptations induced by light, carbon and inorganic nitrogen in Chlamydomonas reinhardtii

    Directory of Open Access Journals (Sweden)

    Stéphanie Gérin

    2016-08-01

    Full Text Available Microalgae are currently emerging to be very promising organisms for the production of biofuels and high-added value compounds. Understanding the influence of environmental alterations on their metabolism is a crucial issue. Light, carbon and nitrogen availability have been reported to induce important metabolic adaptations. So far, the influence of these variables has essentially been studied while varying only one or two environmental factors at the same time. The goal of the present work was to model the cellular proteomic adaptations of the green microalga Chlamydomonas reinhardtii upon the simultaneous changes of light intensity, carbon concentrations (CO2 and acetate and inorganic nitrogen concentrations (nitrate and ammonium in the culture medium. Statistical design of experiments (DOE enabled to define 32 culture conditions to be tested experimentally. Relative protein abundance was quantified by two dimensional differential in-gel electrophoresis (2D-DIGE. Additional assays for respiration, photosynthesis, and lipid and pigment concentrations were also carried out. A hierarchical clustering survey enabled to partition biological variables (proteins + assays into eight co-regulated clusters. In most cases, the biological variables partitioned in the same cluster had already been reported to participate to common biological functions (acetate assimilation, bioenergetic processes, light harvesting, Calvin cycle and protein metabolism. The environmental regulation within each cluster was further characterized by a series of multivariate methods including principal component analysis and multiple linear regressions. This metadata analysis enabled to highlight the existence of a clear regulatory pattern for every cluster and to mathematically simulate the effects of light, carbon and nitrogen. The influence of these environmental variables on cellular metabolism is described in details and thoroughly discussed. This work provides an overview

  3. Transcriptional profiling of sugarcane leaves and roots under progressive osmotic stress reveals a regulated coordination of gene expression in a spatiotemporal manner.

    Directory of Open Access Journals (Sweden)

    Alejandro Pereira-Santana

    Full Text Available Sugarcane is one of the most important crops worldwide and is a key plant for the global production of sucrose. Sugarcane cultivation is severely affected by drought stress and it is considered as the major limiting factor for their productivity. In recent years, this plant has been subjected to intensive research focused on improving its resilience against water scarcity; particularly the molecular mechanisms in response to drought stress have become an underlying issue for its improvement. To better understand water stress and the molecular mechanisms we performed a de novo transcriptomic assembly of sugarcane (var. Mex 69-290. A total of 16 libraries were sequenced in a 2x100 bp configuration on a HiSeq-Illumina platform. A total of 536 and 750 genes were differentially up-regulated along with the stress treatments for leave and root tissues respectively, while 1093 and 531 genes were differentially down-regulated in leaves and roots respectively. Gene Ontology functional analysis showed that genes related to response of water deprivation, heat, abscisic acid, and flavonoid biosynthesis were enriched during stress treatment in our study. The reliability of the observed expression patterns was confirmed by RT-qPCR. Additionally, several physiological parameters of sugarcane were significantly affected due to stress imposition. The results of this study may help identify useful target genes and provide tissue-specific data set of genes that are differentially expressed in response to osmotic stress, as well as a complete analysis of the main groups is significantly enriched under this condition. This study provides a useful benchmark for improving drought tolerance in sugarcane and other economically important grass species.

  4. Chilling-Mediated DNA Methylation Changes during Dormancy and Its Release Reveal the Importance of Epigenetic Regulation during Winter Dormancy in Apple (Malus x domestica Borkh..

    Directory of Open Access Journals (Sweden)

    Gulshan Kumar

    Full Text Available Winter dormancy is a well known mechanism adopted by temperate plants, to mitigate the chilling temperature of winters. However, acquisition of sufficient chilling during winter dormancy ensures the normal phenological traits in subsequent growing period. Thus, low temperature appears to play crucial roles in growth and development of temperate plants. Apple, being an important temperate fruit crop, also requires sufficient chilling to release winter dormancy and normal phenological traits, which are often associated with yield and quality of fruits. DNA cytosine methylation is one of the important epigenetic modifications which remarkably affect the gene expression during various developmental and adaptive processes. In present study, methylation sensitive amplified polymorphism was employed to assess the changes in cytosine methylation during dormancy, active growth and fruit set in apple, under differential chilling conditions. Under high chill conditions, total methylation was decreased from 27.2% in dormant bud to 21.0% in fruit set stage, while no significant reduction was found under low chill conditions. Moreover, the demethylation was found to be decreased, while methylation increased from dormant bud to fruit set stage under low chill as compared to high chill conditions. In addition, RNA-Seq analysis showed high expression of DNA methyltransferases and histone methyltransferases during dormancy and fruit set, and low expression of DNA glcosylases during active growth under low chill conditions, which was in accordance with changes in methylation patterns. The RNA-Seq data of 47 genes associated with MSAP fragments involved in cellular metabolism, stress response, antioxidant system and transcriptional regulation showed correlation between methylation and their expression. Similarly, bisulfite sequencing and qRT-PCR analysis of selected genes also showed correlation between gene body methylation and gene expression. Moreover

  5. A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.

    Directory of Open Access Journals (Sweden)

    Eleonora Porcu

    Full Text Available Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3 and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2. Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2 show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.

  6. Chilling-Mediated DNA Methylation Changes during Dormancy and Its Release Reveal the Importance of Epigenetic Regulation during Winter Dormancy in Apple (Malus x domestica Borkh.).

    Science.gov (United States)

    Kumar, Gulshan; Rattan, Usha Kumari; Singh, Anil Kumar

    2016-01-01

    Winter dormancy is a well known mechanism adopted by temperate plants, to mitigate the chilling temperature of winters. However, acquisition of sufficient chilling during winter dormancy ensures the normal phenological traits in subsequent growing period. Thus, low temperature appears to play crucial roles in growth and development of temperate plants. Apple, being an important temperate fruit crop, also requires sufficient chilling to release winter dormancy and normal phenological traits, which are often associated with yield and quality of fruits. DNA cytosine methylation is one of the important epigenetic modifications which remarkably affect the gene expression during various developmental and adaptive processes. In present study, methylation sensitive amplified polymorphism was employed to assess the changes in cytosine methylation during dormancy, active growth and fruit set in apple, under differential chilling conditions. Under high chill conditions, total methylation was decreased from 27.2% in dormant bud to 21.0% in fruit set stage, while no significant reduction was found under low chill conditions. Moreover, the demethylation was found to be decreased, while methylation increased from dormant bud to fruit set stage under low chill as compared to high chill conditions. In addition, RNA-Seq analysis showed high expression of DNA methyltransferases and histone methyltransferases during dormancy and fruit set, and low expression of DNA glcosylases during active growth under low chill conditions, which was in accordance with changes in methylation patterns. The RNA-Seq data of 47 genes associated with MSAP fragments involved in cellular metabolism, stress response, antioxidant system and transcriptional regulation showed correlation between methylation and their expression. Similarly, bisulfite sequencing and qRT-PCR analysis of selected genes also showed correlation between gene body methylation and gene expression. Moreover, significant association

  7. Crystal structure of a minimal eIF4E–Cup complex reveals a general mechanism of eIF4E regulation in translational repression

    Science.gov (United States)

    Kinkelin, Kerstin; Veith, Katharina; Grünwald, Marlene; Bono, Fulvia

    2012-01-01

    Cup is an eIF4E-binding protein (4E-BP) that plays a central role in translational regulation of localized mRNAs during early Drosophila development. In particular, Cup is required for repressing translation of the maternally contributed oskar, nanos, and gurken mRNAs, all of which are essential for embryonic body axis determination. Here, we present the 2.8 Å resolution crystal structure of a minimal eIF4E–Cup assembly, consisting of the interacting regions of the two proteins. In the structure, two separate segments of Cup contact two orthogonal faces of eIF4E. The eIF4E-binding consensus motif of Cup (YXXXXLΦ) binds the convex side of eIF4E similarly to the consensus of other eIF4E-binding proteins, such as 4E-BPs and eIF4G. The second, noncanonical, eIF4E-binding site of Cup binds laterally and perpendicularly to the eIF4E β-sheet. Mutations of Cup at this binding site were shown to reduce binding to eIF4E and to promote the destabilization of the associated mRNA. Comparison with the binding mode of eIF4G to eIF4E suggests that Cup and eIF4G binding would be mutually exclusive at both binding sites. This shows how a common molecular surface of eIF4E might recognize different proteins acting at different times in the same pathway. The structure provides insight into the mechanism by which Cup disrupts eIF4E–eIF4G interaction and has broader implications for understanding the role of 4E-BPs in translational regulation. PMID:22832024

  8. A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and Gender-Specific Differences in the Regulation of Thyroid Function

    Science.gov (United States)

    Volpato, Claudia B.; Wilson, Scott G.; Cappola, Anne R.; Bos, Steffan D.; Deelen, Joris; den Heijer, Martin; Freathy, Rachel M.; Lahti, Jari; Liu, Chunyu; Lopez, Lorna M.; Nolte, Ilja M.; O'Connell, Jeffrey R.; Tanaka, Toshiko; Trompet, Stella; Arnold, Alice; Bandinelli, Stefania; Beekman, Marian; Böhringer, Stefan; Brown, Suzanne J.; Buckley, Brendan M.; Camaschella, Clara; de Craen, Anton J. M.; Davies, Gail; de Visser, Marieke C. H.; Ford, Ian; Forsen, Tom; Frayling, Timothy M.; Fugazzola, Laura; Gögele, Martin; Hattersley, Andrew T.; Hermus, Ad R.; Hofman, Albert; Houwing-Duistermaat, Jeanine J.; Jensen, Richard A.; Kajantie, Eero; Kloppenburg, Margreet; Lim, Ee M.; Masciullo, Corrado; Mariotti, Stefano; Minelli, Cosetta; Mitchell, Braxton D.; Nagaraja, Ramaiah; Netea-Maier, Romana T.; Palotie, Aarno; Persani, Luca; Piras, Maria G.; Psaty, Bruce M.; Räikkönen, Katri; Richards, J. Brent; Rivadeneira, Fernando; Sala, Cinzia; Sabra, Mona M.; Sattar, Naveed; Shields, Beverley M.; Soranzo, Nicole; Starr, John M.; Stott, David J.; Sweep, Fred C. G. J.; Usala, Gianluca; van der Klauw, Melanie M.; van Heemst, Diana; van Mullem, Alies; H.Vermeulen, Sita; Visser, W. Edward; Walsh, John P.; Westendorp, Rudi G. J.; Widen, Elisabeth; Zhai, Guangju; Cucca, Francesco; Deary, Ian J.; Eriksson, Johan G.; Ferrucci, Luigi; Fox, Caroline S.; Jukema, J. Wouter; Kiemeney, Lambertus A.; Pramstaller, Peter P.; Schlessinger, David; Shuldiner, Alan R.; Slagboom, Eline P.; Uitterlinden, André G.; Vaidya, Bijay; Visser, Theo J.; Wolffenbuttel, Bruce H. R.; Meulenbelt, Ingrid; Rotter, Jerome I.; Spector, Tim D.; Hicks, Andrew A.; Toniolo, Daniela; Sanna, Serena; Peeters, Robin P.; Naitza, Silvia

    2013-01-01

    Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism. PMID:23408906

  9. Down-regulation of Connexin43 expression reveals the involvement of caveolin-1 containing lipid rafts in human U251 glioblastoma cell invasion.

    Science.gov (United States)

    Strale, Pierre-Olivier; Clarhaut, Jonathan; Lamiche, Coralie; Cronier, Laurent; Mesnil, Marc; Defamie, Norah

    2012-11-01

    Glioblastoma cells are characterized by high proliferation and invasive capacities. Tumor development has been associated with a decrease of gap-junctional intercellular communication, but the concrete involvement of gap junction proteins, connexins, remains elusive since they are also suspected to promote cell invasion. In order to better understand how connexins control the glioma cell phenotype, we studied the consequences of inhibiting the intrinsic expression of the major astrocytic connexin, Connexin43, in human U251 glioblastoma cells by the shRNA strategy. The induced down-regulation of Cx43 expression has various effects on the U251 cells such as increased clonogenicity, angiogenesis and decreased adhesion on specific extracellular matrix proteins. We demonstrate that the invasion capacity measured in vitro and ex vivo correlates with Cx43 expression level. For the first time in a cancer cell context, our work demonstrates that Cx43 cofractionates, colocalizes and coimmunoprecipitates with a lipid raft marker, caveolin-1 and that this interaction is inversely correlated to the level of Cx43. This localization of Cx43 in these lipid raft microdomains regulates both homo- and heterocellular gap junctional communication