Sample records for background constitutive expression

  1. Constitutive interferon expression from retroviral vector.

    PubMed

    Knezic, Z; Nikcevic, G; Marjanovic, J; Glisin, V; Popovic, Z

    1993-10-01

    A genomic fragment with the human beta-interferon gene was cloned into a pL3-4, a defective Moloney murine leukemia virus (M-MuLV) vector. Here we show that clones selected after viral infection of mouse NIH 3T3 cells constitutively produced 128 IU/ml of human beta-interferon. Constitutive synthesis of retroviral RNA was confirmed by dot blot hybridization of RNA isolated from two of the selected clones. Poly(I) x poly(C) and cycloheximide induction resulted in an increased RNA level, but this was not reflected in an increased production of biologically active interferon. PMID:8279813

  2. Constitutional background to the Social Security Act of 1935.

    PubMed

    Lopez, E A

    1987-01-01

    In June 1937, the Senate Judiciary Committee reported unfavorably on Roosevelt's Court-packing plan and the bill was effectively killed. In the same month, Justice Van Devanter retired and gave Roosevelt his first opportunity to make an appointment to the Supreme Court. Over the following 6 years, Roosevelt made seven more appointments to the Court, and in the years that followed the Court continued in the direction boldly advanced in the spring of 1937. A residual effect of the taxing-spending construction of the old-age insurance provisions of the Social Security Act of 1935 has been the Court's continued adherence to the view that social security programs consist of separate taxing and spending provisions and are not, constitutionally speaking, social insurance programs. The issue has arisen in both a due process context and an equal protection context. But it is unlikely that the decisions reached in these contexts would have been different had the old-age insurance program been drafted as an earned-benefits program pursuant to the commerce power. Of course, the Court's decisions in the social security cases represented a significant constitutional development in establishing the breadth of Congress' powers to tax and spend for the general welfare. The decisions not only cleared the way for other general welfare programs, but more fundamentally provided the Federal Government with the substantive power and institutional flexibility to respond to the changing needs of the Nation. PMID:3547702

  3. Constitutive Expression of Metallothionein Genes in Mouse Brain

    Microsoft Academic Search

    S. Choudhuri; K. K. Kramer; N. E. J. Berman; T. P. Dalton; G. K. Andrews; C. D. Klaassen

    1995-01-01

    Metallothioneins (MTs) are ubiquitous low-molecular-weight proteins that are induced by a variety of inducers, including metals, lipopolysaccharides (LPS), cytokines, oxidative stress, etc., and are thought to play a protective role against various toxic insults. The constitutive level of metallothionein is an important determinant of a tissue?s susceptibility to toxic insults. In the present study, we report the constitutive expression of

  4. Sources of stochasticity in constitutive and autoregulated gene expression

    E-print Network

    Marathe, Rahul; Klumpp, Stefan

    2012-01-01

    Gene expression is inherently noisy as many steps in the read-out of the genetic information are stochastic. To disentangle the effect of different sources of stochasticity in such systems, we consider various models that describe some processes as stochastic and others as deterministic. We review earlier results for unregulated (constitutive) gene expression and present new results for a gene controlled by negative autoregulation with cell growth modeled by linear volume growth.

  5. Constitutive nitrate reductase expression and inhibition in winged bean

    SciTech Connect

    Wu, Shenchuan; Harper, J.E. (Univ. of Illinois, Urbana (USA))

    1990-05-01

    It was found that NO{sub 3}{sup {minus}} had no effect on winged bean nitrate reductase activity (NRA). Similar NRA was expressed in plants grown on NO{sub 3}{sup {minus}}, urea, NH{sub 4}{sup +}, and nil N. This indicated that the primary NR expressed in winged bean was constitutive, rather than substrate-inducible. Maximum NRA in winged bean was obtained in the light. KClO{sub 3} was capable of inhibiting NRA of leaves if added to the root growth medium or to the NR assay medium, indicating possible competition with NO{sub 3}{sup {minus}} at the reduction site. While it has previously been shown that either cycloheximide alone, or both cycloheximide and chloramphenicol impair the synthesis of NR protein, our data unexpectedly demonstrated that cycloheximide had little effect on NRA, whereas chloramphenicol greatly inhibited the expression of NRA in winged bean. One interpretation is that chloroplasts may influence the activity and/or synthesis of constitutive NR proteins.

  6. Constitutive and functional expression of YB-1 in microglial cells.

    PubMed

    Keilhoff, G; Titze, M; Esser, T; Langnaese, K; Ebmeyer, U

    2015-08-20

    Y-box-binding protein (YB-1) is a member of the cold-shock protein family and participates in a wide variety of DNA/RNA-dependent cellular processes including DNA repair, transcription, mRNA splicing, packaging, and translation. At the cellular level, YB-1 is involved in cell proliferation and differentiation, stress responses, and malignant cell transformation. A general role for YB-1 during inflammation has also been well described; however, there are minimal data concerning YB-1 expression in microglia, which are the immune cells of the brain. Therefore, we studied the expression of YB-1 in a clinically relevant global ischemia model for neurological injury following cardiac arrest. This model is characterized by massive neurodegeneration of the hippocampal CA1 region and the subsequent long-lasting activation of microglia. In addition, we studied YB-1 expression in BV-2 cells, which are an accepted microglia culture model. BV-2 cells were stressed by oxygen/glucose deprivation (OGD), OGD-relevant mediators, lipopolysaccharide (LPS), and phagocytosis-inducing cell debris and nanoparticles. Using quantitative polymerase chain reaction (PCR), we show constitutive expression of YB-1 transcripts in unstressed BV-2 cells. The functional upregulation of the YB-1 protein was demonstrated in microglia in vivo and in BV-2 cells in vitro. All stressors except for LPS were potent enhancers of the level of YB-1 protein, which appears to be regulated primarily by proteasomal degradation and, to a lesser extent, by the activation (phosphorylation) of the translation initiation factor eIF4E. The proteasome of BV-2 cells is impaired by OGD, which results in decreased protein degradation and therefore increased levels of YB-1 protein. LPS induces proteasome activity, which enables the level of YB-1 protein to remain at control levels despite enhanced protein ubiquitination. The proteasome inhibitor MG-132 was able to increase YB-1 protein levels in control and LPS-treated cultures. YB-1 upregulation was not accompanied by its translocation from the cytoplasm to the nucleus. YB-1 induction appeared to be related to microglial proliferation because it was partially co-regulated with Ki67. In addition, YB-1 protein levels correlated with microglia phagocytic activity because its upregulation could also be induced by inert NPs. PMID:26102006

  7. Expression and Maintenance of Embryogenic Potential Is Enhanced through Constitutive Expression of AGAMOUS-Like 151

    PubMed Central

    Harding, Ellen W.; Tang, Weining; Nichols, Karl W.; Fernandez, Donna E.; Perry, Sharyn E.

    2003-01-01

    The MADS domain protein AGL15 (AGAMOUS-Like 15) has been found to preferentially accumulate in angiosperm tissues derived from double fertilization (i.e. the embryo, suspensor, and endosperm) and in apomictic, somatic, and microspore embryos. Localization to the nuclei supports a role in gene regulation during this phase of the life cycle. To test whether AGL15 is involved in the promotion and maintenance of embryo identity, the embryogenic potential of transgenic plants that constitutively express AGL15 was assessed. Expression of AGL15 was found to enhance production of secondary embryos from cultured zygotic embryos, and constitutive expression led to long-term maintenance of development in this mode. Ectopic accumulation of AGL15 also promoted somatic embryo formation after germination from the shoot apical meristem of seedlings in culture. These results indicate that AGL15 is involved in support of development in an embryonic mode. PMID:14512519

  8. Constitution Constitution

    E-print Network

    Warkentin, Ian G.

    2009 Constitution #12;2009 Constitution #12;The Canadian Union of Public Employees is Canada Constitution came into existence at the Founding Convention in 1963 when the National Union of Public Employees of Public Employees. Changes to the Constitution can only be made by the delegates at the Union's Biennial

  9. Constitutive versus Responsive Gene Expression Strategies for Growth in Changing Environments

    PubMed Central

    Geisel, Nico

    2011-01-01

    Microbes respond to changing environments by adjusting gene expression levels to the demand for the corresponding proteins. Adjusting protein levels is slow, consequently cells may reach the optimal protein level only by a time when the demand changed again. It is therefore not a priori clear whether expression “on demand” is always the optimal strategy. Indeed, many genes are constitutively expressed at intermediate levels, which represents a permanent cost but provides an immediate benefit when the protein is needed. Which are the conditions that select for a responsive or a constitutive expression strategy, what determines the optimal constitutive expression level in a changing environment, and how is the fitness of the two strategies affected by gene expression noise? Based on an established model of the lac- and gal-operon expression dynamics, we study the fitness of a constitutive and a responsive expression strategy in time-varying environments. We find that the optimal constitutive expression level differs from the average demand for the gene product and from the average optimal expression level; depending on the shape of the growth rate function, the optimal expression level either provides intermediate fitness in all environments, or maximizes fitness in only one of them. We find that constitutive expression can provide higher fitness than responsive expression even when regulatory machinery comes at no cost, and we determine the minimal response rate necessary for “expression on demand” to confer a benefit. Environmental and inter-cellular noise favor the responsive strategy while reducing fitness of the constitutive one. Our results show the interplay between the demand-frequency for a gene product, the genetic response rate, and the fitness, and address important questions on the evolution of gene regulation. Some of our predictions agree with recent yeast high throughput data, for others we propose the experiments that are needed to verify them. PMID:22140435

  10. Constitutive expression of human angiostatin in Pichia pastoris by high-density cell culture.

    PubMed

    Zhang, A L; Zhang, T Y; Luo, J X; Chen, S C; Guan, W J; Fu, C Y; Peng, S Q; Li, H L

    2007-02-01

    A high-density cell culture method to produce human angiostatin has been successfully established by constitutive expression of the protein in Pichia pastoris. The fermentation was carried out in a 20 l bioreactor with a 10 l working volume, using a high-density cell culture method by continuously feeding with 50% glycerol-0.8% PTM4 to the growing culture for 60 h at 30 degrees C. Dissolved oxygen level was maintained at 25-30% and pH was controlled at 5 by the addition of 7 M NH4OH. Angiostatin was constitutively expressed during the fermentation by linking its expression to the P. pastoris constitutive GAP promoter (pGAP). But after 36 h of fermentation, the peak biomass growth was 305 as measured by absorption of 600 nm, while the peak angiostatin expression was 176 mg/l. Similar to the product expressed from inducible system [24], angiostatin produced from constitutive system also inhibited the angiogenesis on the CAM and suppressed the growth of B16 melanoma in C57BL/6J mouse. The above results suggest that GAP promoter is more efficient than AOX1 promoter for the expression of angiostatin in P. pastoris by shake flask culture or high-density cell fermentation and is likely to be an alternative to AOX1 promoter in large-scale expression of angiostatin and other heterologous proteins. PMID:16988811

  11. Constitutive expression of fibronectin binding in Streptococcus pyogenes as a result of anaerobic activation of rofA.

    PubMed Central

    Fogg, G C; Caparon, M G

    1997-01-01

    Protein F is a fibronectin-binding surface protein of Streptococcus pyogenes (group A streptococcus) that mediates adherence to host cells. A gene product encoded by rofA activates transcription of the gene that encodes protein F (prtF) and was identified in a strain of S. pyogenes that expressed high levels of protein F under all conditions tested. Insertional inactivation of rofA in this strain results in a phenotype similar to that of other strains where high-level transcription of prtF occurs only in response to increased oxygen tension. In this study, we have compared the regulation of prtF and rofA in O2-regulated and constitutive strains in order to gain further insight into the function of rofA. Comparison of the prtF and rofA transcripts by S1 nuclease and primer extension assays indicated that the same promoters for each transcript are used in both O2-regulated and constitutive strains. However, analyses of rofA-lacZ reporter alleles revealed that a key difference between strains involves regulation of rofA itself. In O2-regulated strains, expression of rofA was elevated following culture under conditions of reduced O2 tension. However, a much more robust activation of rofA expression was observed when constitutive strains were grown under similar conditions. Exchange of reporter and rofA alleles between strains demonstrated that host genetic background, and not the sequence of the respective rofA allele or regulatory region, dictates the expression phenotype. Activation of rofA required RofA, and RofA was shown to bind specifically to DNA containing the promoters for rofA and prtF. Finally, overexpression of either allele of rofA caused constitutive expression of prtF regardless of host background. These data suggest a model where anaerobic expression of prtF in constitutive hosts is controlled at the level of transcription of rofA and implicate additional factors in this regulatory pathway. PMID:9324268

  12. Lentiviral vector system for coordinated constitutive and drug controlled tetracycline-regulated gene co-expression.

    PubMed

    Stahlhut, Maike; Schwarzer, Adrian; Eder, Matthias; Yang, Min; Li, Zhixiong; Morgan, Michael; Schambach, Axel; Kustikova, Olga S

    2015-09-01

    Constitutive co-expression of cooperating transgenes using retroviral integrating vectors is frequently used for genetic modification of different cell types to establish therapeutic or cancer models. However, such approaches are unable to dissect the influence of dose, order and reversibility of transgene expression on the fate of newly developed therapeutic/malignant phenotypes. We present a modular lentiviral vector system, which provides expression of constitutive and inducible components. To demonstrate its functionality, we constitutively expressed the well-described transcription factor Meis1 followed by inducible co-expression of collaborating partner Hoxa9 under the control of tetracycline responsive promoters in murine fibroblasts and primary hematopoietic progenitor cells (HPCs). Fluorescent markers to track transgene co-expression revealed tightly controlled, efficiently inducible and reversible but cell type dependent gene transfer over time. We demonstrated dose-dependent blockade of myeloid differentiation when both Meis1/Hoxa9 were concomitantly overexpressed in primary HPCs in vitro, but the absence of the transformed phenotype in non-induced samples or when Hoxa9 expression was down-regulated. This system combines the advantages of lentiviral gene transfer and the opportunity for drug-controlled co-expression of multiple transgenes to dissect, among others, gene networks governing complex cell behavior, such as proto-oncogene dose-dependent leukemogenic pathways or collaborating mechanisms of genes enhancing competitive fitness of hematopoietic cells. PMID:26113075

  13. Adenovirus-Based Phospholamban Antisense Expression as a Novel Approach to Improve Cardiac Contractile Dysfunction Comparison of a Constitutive Viral Versus an Endothelin1Responsive Cardiac Promoter

    Microsoft Academic Search

    Karin Eizema; Henry Fechner; Karel Bezstarosti; Sonja Schneider-Rasp; Arnoud van der Laarse; Haili Wang; Heinz-Peter Schultheiss; Wolfgang C. Poller; Jos M. J. Lamers

    2010-01-01

    Background—A decrease in sarcoplasmic reticulum Ca 21 pump (SERCA2) activity is believed to play a role in the impairment of diastolic function of the failing heart. Because the expression ratio of phospholamban (PL) to SERCA2 may be a target to improve contractile dysfunction, a PL antisense RNA strategy was developed under the control of either a constitutive cytomegalovirus (CMV) or

  14. Constitutive homologous expression of phosphoglucomutase and transaldolase increases the metabolic flux of Fusarium oxysporum

    PubMed Central

    2014-01-01

    Background Fusarium oxysporum is among the few filamentous fungi that have been reported of being able to directly ferment biomass to ethanol in a consolidated bioprocess. Understanding its metabolic pathways and their limitations can provide some insights on the genetic modifications required to enhance its growth and subsequent fermentation capability. In this study, we investigated the hypothesis reported previously that phosphoglucomutase and transaldolase are metabolic bottlenecks in the glycolysis and pentose phosphate pathway of the F. oxysporum metabolism. Results Both enzymes were homologously overexpressed in F. oxysporum F3 using the gpdA promoter of Aspergillus nidulans for constitutive expression. Transformants were screened for their phosphoglucomutase and transaldolase genes expression levels with northern blot. The selected transformant exhibited high mRNA levels for both genes, as well as higher specific activities of the corresponding enzymes, compared to the wild type. It also displayed more than 20 and 15% higher specific growth rate upon aerobic growth on glucose and xylose, respectively, as carbon sources and 30% higher biomass to xylose yield. The determination of the relative intracellular amino and non-amino organic acid concentrations at the end of growth on glucose revealed higher abundance of most determined metabolites between 1.5- and 3-times in the recombinant strain compared to the wild type. Lower abundance of the determined metabolites of the Krebs cycle and an 68-fold more glutamate were observed at the end of the cultivation, when xylose was used as carbon source. Conclusions Homologous overexpression of phosphoglucomutase and transaldolase in F. oxysporum was shown to enhance the growth characteristics of the strain in both xylose and glucose in aerobic conditions. The intracellular metabolites profile indicated how the changes in the metabolome could have resulted in the observed growth characteristics. PMID:24649884

  15. Constitutive Expression of the CIRCADIAN CLOCK ASSOCIATED 1 ( CCA1) Gene Disrupts Circadian Rhythms and Suppresses Its Own Expression

    Microsoft Academic Search

    Zhi-Yong Wang; Elaine M. Tobin

    1998-01-01

    The CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) gene encodes a MYB-related transcription factor involved in the phytochrome induction of a light-harvesting chlorophyll a\\/b-protein (Lhcb) gene. Expression of the CCA1 gene is transiently induced by phytochrome and oscillates with a circadian rhythm. Constitutive expression of CCA1 protein in transgenic plants abolished the circadian rhythm of several genes with dramatically different phases. These

  16. Answers to the Urbino Questions support material WHAT CONSTITUTES THE OZONE (*) BACKGROUND OVER EUROPE?

    E-print Network

    levels compared to the background levels. However, close to sources of nitrogen oxide (NO), ozone includes ozone derived from stratospheric input, tropospheric formation from precursors (NOx and VOC) from biogenic sources, biomass burning emissions, methane oxidation and anthropogenic sources from various

  17. An efficient plasmid vector for constitutive high-level expression of foreign genes in Escherichia coli.

    PubMed

    Seo, Jeong-Woo; Hong, Won-kyung; Rairakhwada, Dina; Seo, Pil-Soo; Choi, Min Ho; Song, Ki-Bang; Rhee, Sang-Ki; Kim, Chul Ho

    2009-06-01

    The levansucrase gene (lsrA) from Rahnella aquatilis was strongly expressed in a constitutive manner in Escherichia coli when cloned into a pBluescript KS-based pRL1CP plasmid vector. The native promoter upstream of lsrA and the lacZ promoter cooperatively enhanced the expression of lsrA to a level that was comparable to that of the T7 promoter, which is used in commercial pET expression vector system. A putative rho-independent transcription termination signal downstream of lsrA was crucial for gene expression. This plasmid vector also proved to be applicable for efficient expression of other foreign genes in E. coli. PMID:19214389

  18. Neurons expressing trace amine-associated receptors project to discrete glomeruli and constitute an olfactory subsystem

    PubMed Central

    Johnson, Mark A.; Tsai, Lulu; Roy, Dheeraj S.; Valenzuela, David H.; Mosley, Colleen; Magklara, Angeliki; Lomvardas, Stavros; Liberles, Stephen D.; Barnea, Gilad

    2012-01-01

    Some chemoreceptors of the trace amine-associated receptor (TAAR) family detect innately aversive odors and are proposed to activate hardwired olfactory circuits. However, the wiring of TAAR neurons, the regulatory mechanisms of Taar gene choice, and the subcellular localization of TAAR proteins remain unknown. Here, we reveal similarities between neurons expressing TAARs and odorant receptors (ORs), but also unexpected differences. Like ORs, TAARs seem to be monoallelically expressed and localized both in cilia, the site of odor detection, and in axons, where they may participate in guidance. TAAR neurons project to discrete glomeruli predominantly localized to a confined bulb region. Taar expression involves different regulatory logic than OR expression, as neurons choosing a Taar5 knockout allele frequently express a second Taar without silencing the deleted allele. Moreover, the epigenetic signature of OR gene choice is absent from Taar genes. The unique molecular and anatomical features of the TAAR neurons suggest that they constitute a distinct olfactory subsystem. PMID:22837392

  19. A constitutive promoter directs expression of the nerve growth factor receptor gene.

    PubMed Central

    Sehgal, A; Patil, N; Chao, M

    1988-01-01

    Expression of nerve growth factor receptor is normally restricted to cells derived from the neural crest in a developmentally regulated manner. We analyzed promoter sequences for the human nerve growth factor receptor gene and found that the receptor promoter resembles others which are associated with constitutively expressed genes that have housekeeping and growth-related functions. Unlike these other genes, the initiation of transcription occurred at one major site rather than at multiple sites. The constitutive nature of the nerve growth factor receptor promoter may account for the ability of this gene to be transcribed in a diverse number of heterologous cells after gene transfer. The intron-exon structure of the receptor gene indicated that structural features are precisely divided into discrete domains. Images PMID:2850481

  20. Constitutive and functional expression of runt-related transcription factor-2 by microglial cells.

    PubMed

    Nakazato, Ryota; Takarada, Takeshi; Watanabe, Takumi; Nguyen, Binh Thanh; Ikeno, Shinsuke; Hinoi, Eiichi; Yoneda, Yukio

    2014-07-01

    Runt-related transcription factor-2 (Runx2) is the master regulator of osteoblastogenesis with an ability to promote differentiation of mesenchymal stem cells into the osteoblastic lineage. We have previously shown constitutive and functional expression of Runx2 by astroglial cells. In this study, we investigated the possible expression of Runx2 by both murine microglia and microglial cell line BV-2 cells. Runx2 expression was seen in cultured microglia and BV-2 cells, while sustained exposure to 1mM ATP led to a significant but transient increase in mRNA and corresponding protein expression of Runx2 within 24 h. The increase in Runx2 expression was invariably prevented by several chemicals with antagonistic properties for P2X7 purinergic receptor, calmodulin and calcineurin in BV-2 cells, with a P2X7 receptor agonist more than quadrupling Runx2 expression. A significant increase in Runx2 expression was seen in osteoclastic cells, but not in osteoblastic or chondrocytic cells, when exposed to a high concentration of ATP. In BV2-cells with control siRNA, a significant decrease was found in the number of cells with at least one process within 3 h after the exposure to 1mM ATP, followed by an increase up to 24 h. However, Runx2 siRNA significantly deteriorated the property to induce delayed process extension during 6-24 h after exposure to ATP along with drastically decreased Runx2 protein levels. These results suggest that Runx2 is constitutively and functionally expressed by microglial cells with responsiveness to ATP for upregulation in the murine brain. PMID:24768841

  1. Constitutive expression of transgenes encoding derivatives of the synthetic antimicrobial peptide BP100: impact on rice host plant fitness

    PubMed Central

    2012-01-01

    Background The Biopeptide BP100 is a synthetic and strongly cationic ?-helical undecapeptide with high, specific antibacterial activity against economically important plant-pathogenic bacteria, and very low toxicity. It was selected from a library of synthetic peptides, along with other peptides with activities against relevant bacterial and fungal species. Expression of the BP100 series of peptides in plants is of major interest to establish disease-resistant plants and facilitate molecular farming. Specific challenges were the small length, peptide degradation by plant proteases and toxicity to the host plant. Here we approached the expression of the BP100 peptide series in plants using BP100 as a proof-of-concept. Results Our design considered up to three tandemly arranged BP100 units and peptide accumulation in the endoplasmic reticulum (ER), analyzing five BP100 derivatives. The ER retention sequence did not reduce the antimicrobial activity of chemically synthesized BP100 derivatives, making this strategy possible. Transformation with sequences encoding BP100 derivatives (bp100der) was over ten-fold less efficient than that of the hygromycin phosphotransferase (hptII) transgene. The BP100 direct tandems did not show higher antimicrobial activity than BP100, and genetically modified (GM) plants constitutively expressing them were not viable. In contrast, inverted repeats of BP100, whether or not elongated with a portion of a natural antimicrobial peptide (AMP), had higher antimicrobial activity, and fertile GM rice lines constitutively expressing bp100der were produced. These GM lines had increased resistance to the pathogens Dickeya chrysanthemi and Fusarium verticillioides, and tolerance to oxidative stress, with agronomic performance comparable to untransformed lines. Conclusions Constitutive expression of transgenes encoding short cationic ?-helical synthetic peptides can have a strong negative impact on rice fitness. However, GM plants expressing, for example, BP100 based on inverted repeats, have adequate agronomic performance and resistant phenotypes as a result of a complex equilibrium between bp100der toxicity to plant cells, antimicrobial activity and transgene-derived plant stress response. It is likely that these results can be extended to other peptides with similar characteristics. PMID:22947243

  2. A new method to customize protein expression vectors for fast, efficient and background free parallel cloning

    PubMed Central

    2013-01-01

    Background Expression and purification of correctly folded proteins typically require screening of different parameters such as protein variants, solubility enhancing tags or expression hosts. Parallel vector series that cover all variations are available, but not without compromise. We have established a fast, efficient and absolutely background free cloning approach that can be applied to any selected vector. Results Here we describe a method to tailor selected expression vectors for parallel Sequence and Ligation Independent Cloning. SLIC cloning enables precise and sequence independent engineering and is based on joining vector and insert with 15–25 bp homologies on both DNA ends by homologous recombination. We modified expression vectors based on pET, pFastBac and pTT backbones for parallel PCR-based cloning and screening in E.coli, insect cells and HEK293E cells, respectively. We introduced the toxic ccdB gene under control of a strong constitutive promoter for counterselection of insert less vector. In contrast to DpnI treatment commonly used to reduce vector background, ccdB used in our vector series is 100% efficient in killing parental vector carrying cells and reduces vector background to zero. In addition, the 3’ end of ccdB functions as a primer binding site common to all vectors. The second shared primer binding site is provided by a HRV 3C protease cleavage site located downstream of purification and solubility enhancing tags for tag removal. We have so far generated more than 30 different parallel expression vectors, and successfully cloned and expressed more than 250 genes with this vector series. There is no size restriction for gene insertion, clone efficiency is > 95% with clone numbers up to 200. The procedure is simple, fast, efficient and cost-effective. All expression vectors showed efficient expression of eGFP and different target proteins requested to be produced and purified at our Core Facility services. Conclusion This new expression vector series allows efficient and cost-effective parallel cloning and thus screening of different protein constructs, tags and expression hosts. PMID:23410102

  3. Efficient production and evaluation of lignocellulolytic enzymes using a constitutive protein expression system in Penicillium oxalicum.

    PubMed

    Hu, Yibo; Xue, Haizhao; Liu, Guodong; Song, Xin; Qu, Yinbo

    2015-06-01

    Native lignocellulolytic enzyme systems secreted by filamentous fungi can be further optimized by protein engineering or supplementation of exogenous enzyme components. We developed a protein production and evaluation system in cellulase-producing fungus Penicillium oxalicum. First, by deleting the major amylase gene amy15A, a strain ?15A producing few extracellular proteins on starch was constructed. Then, three lignocellulolytic enzymes (BGL4, Xyn10B, and Cel12A) with originally low expression levels were successfully expressed with selected constitutive promoters in strain ?15A. BGL4 and Cel12A overexpression resulted in increased specific filter paper activity (FPA), while the overexpression of Xyn10B improved volumetric FPA but not specific FPA. By switching the culture medium, this platform is convenient to produce originally low-expressed lignocellulolytic enzymes in relatively high purities on starch and to evaluate the effect of their supplementation on the performance of a complex cellulase system on cellulose. PMID:25868624

  4. Constitutive expression of IRF-5 in HTLV-1-infected T cells.

    PubMed

    Ishikawa, Chie; Senba, Masachika; Barnes, Betsy J; Mori, Naoki

    2015-07-01

    Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL), an aggressive and fatal leukemia of T cells. Interferon regulatory factor (IRF)-5 plays a critical role in the induction of interferon genes in viral infected cells. We examined the specific mechanisms underlying the expression and regulation of IRF-5 in HTLV-1-infected T cells. IRF-5 was constitutively transcribed into three distinct alternatively spliced isoforms (V1, V3 and V4) in HTLV-1-infected T-cell lines but not in uninfected T-cell lines. IRF-5 was also upregulated in HTLV-1-infected T-cell lines at protein level. Nuclear IRF-5 expression was noted in ATL cells present in lymph nodes and skin lesions. IRF-5 mRNA expression was induced following infection of T cells with HTLV-1, and specifically by viral oncoprotein Tax. Tax also activated V3 promoter. Microarray analysis of IRF-5-expressing uninfected T cells demonstrated that IRF-5 induced the expression of tumor necrosis factor family cytokines. The results suggest that IRF-5 is a Tax-regulated gene, and its expression may be associated with the pathogenesis of ATL. PMID:26004104

  5. Conditional expression of constitutively active estrogen receptor {alpha} in chondrocytes impairs longitudinal bone growth in mice

    SciTech Connect

    Ikeda, Kazuhiro [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan)] [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Tsukui, Tohru [Experimental Animal Laboratory, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan)] [Experimental Animal Laboratory, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Imazawa, Yukiko; Horie-Inoue, Kuniko [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan)] [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Inoue, Satoshi, E-mail: INOUE-GER@h.u-tokyo.ac.jp [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan) [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Conditional transgenic mice expressing constitutively active estrogen receptor {alpha} (caER{alpha}) in chondrocytes were developed. Black-Right-Pointing-Pointer Expression of caER{alpha} in chondrocytes impaired longitudinal bone growth in mice. Black-Right-Pointing-Pointer caER{alpha} affects chondrocyte proliferation and differentiation. Black-Right-Pointing-Pointer This mouse model is useful for understanding the physiological role of ER{alpha}in vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caER{alpha}{sup ColII}, expressing constitutively active mutant estrogen receptor (ER) {alpha} in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caER{alpha}{sup ColII} mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caER{alpha}{sup ColII} mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caER{alpha}{sup ColII} mice. These results suggest that ER{alpha} is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

  6. Differential Expression of over 60 Chromosomal Genes in Escherichia coli by Constitutive Expression of MarA

    PubMed Central

    Barbosa, Teresa M.; Levy, Stuart B.

    2000-01-01

    In Escherichia coli, the MarA protein controls expression of multiple chromosomal genes affecting resistance to antibiotics and other environmental hazards. For a more-complete characterization of the mar regulon, duplicate macroarrays containing 4,290 open reading frames of the E. coli genome were hybridized to radiolabeled cDNA populations derived from mar-deleted and mar-expressing E. coli. Strains constitutively expressing MarA showed altered expression of more than 60 chromosomal genes: 76% showed increased expression and 24% showed decreased expression. Although some of the genes were already known to be MarA regulated, the majority were newly determined and belonged to a variety of functional groups. Some of the genes identified have been associated with iron transport and metabolism; other genes were previously known to be part of the soxRS regulon. Northern blot analysis of selected genes confirmed the results obtained with the macroarrays. The findings reveal that the mar locus mediates a global stress response involving one of the largest networks of genes described. PMID:10852879

  7. Resistance to simian immunodeficiency virus low dose rectal challenge is associated with higher constitutive TRIM5? expression in PBMC

    PubMed Central

    2014-01-01

    Background At least six host-encoded restriction factors (RFs), APOBEC3G, TRIM5?, tetherin, SAMHD1, schlafen 11, and Mx2 have now been shown to inhibit HIV and/or SIV replication in vitro. To determine their role in vivo in the resistance of macaques to mucosally-acquired SIV, we quantified both pre-exposure (basal) and post-exposure mRNA levels of these RFs, Mx1, and IFN? in PBMC, lymph nodes, and duodenum of rhesus macaques undergoing weekly low dose rectal exposures to the primary isolate, SIV/DeltaB670. Results Repetitive challenge divided the monkeys into two groups with respect to their susceptibility to infection: highly susceptible (2–3 challenges, 5 monkeys) and poorly susceptible (?6 challenges, 3 monkeys). Basal RF and Mx1 expression varied among the three tissues examined, with the lowest expression generally detected in duodenal tissues, and the highest observed in PBMC. The one exception was A3G whose basal expression was greatest in lymph nodes. Importantly, significantly higher basal expression of TRIM5? and Mx1 was observed in PBMC of animals more resistant to mucosal infection. Moreover, individual TRIM5? levels were stable throughout a year prior to infection. Post-exposure induction of these genes was also observed after virus appearance in plasma, with elevated levels in PBMC and duodenum transiently occurring 7–10 days post infection. They did not appear to have an effect on control of viremia. Interestingly, minimal to no induction was observed in the resistant animal that became an elite controller. Conclusions These results suggest that constitutively expressed TRIM5? appears to play a greater role in restricting mucosal transmission of SIV than that associated with type I interferon induction following virus entry. Surprisingly, this association was not observed with the other RFs. The higher basal expression of TRIM5? observed in PBMC than in duodenal tissues emphasizes the understated role of the second barrier to systemic infection involving the transport of virus from the mucosal compartment to the blood. Together, these observations provide a strong incentive for a more comprehensive examination of the intrinsic, variable control of constitutive expression of these genes in the sexual transmission of HIV. PMID:24884551

  8. Basic Equations and Constitutive Equations of Micropolar Magnetic Fluids with E-BAnalogy and the Abraham Expression of Electromagnetic Momentum

    Microsoft Academic Search

    Yasushi Ido

    2005-01-01

    A complete set of basic equations for magnetic fluids with internal rotation is proposed in this paper. The basic equations are derived from the conservation laws of mass, linear momentum, angular momentum and energy, while the constitutive equations are obtained by the thermodynamical method that is based on the free energy and the dissipation function. The concrete expression of constitutive

  9. Constitutive TL1A (TNFSF15) expression on lymphoid or myeloid cells leads to mild intestinal inflammation and fibrosis.

    PubMed

    Shih, David Q; Barrett, Robert; Zhang, Xiaolan; Yeager, Nicole; Koon, Hon Wai; Phaosawasdi, Piangwarin; Song, Yahui; Ko, Brian; Wong, Michelle H; Michelsen, Kathrin S; Martins, Gislaine; Pothoulakis, Charalabos; Targan, Stephan R

    2011-01-01

    TL1A is a member of the TNF superfamily and its expression is increased in the mucosa of inflammatory bowel disease patients. Moreover, a subset of Crohn's disease (CD) patients with the risk TL1A haplotype is associated with elevated TL1A expression and a more severe disease course. To investigate the in vivo role of elevated TL1A expression, we generated two transgenic (Tg) murine models with constitutive Tl1a expression in either lymphoid or myeloid cells. Compared to wildtype (WT) mice, constitutive expression of Tl1a in either lymphoid or myeloid cells showed mild patchy inflammation in the small intestine, which was more prominent in the ileum. In addition, mice with constitutive Tl1a expression exhibited enhanced intestinal and colonic fibrosis compared to WT littermates. The percentage of T cells expressing the gut homing chemokine receptors CCR9 and CCR10 was higher in the Tl1a Tg mice compared to WT littermates. Sustained expression of Tl1A in T cells also lead to increased Foxp3+ Treg cells. T cells or antigen presenting cells (APC) with constitutive expression of Tl1a were found to have a more activated phenotype and mucosal mononuclear cells exhibit enhanced Th1 cytokine activity. These results indicated an important role of TL1A in mucosal T cells and APC function and showed that up-regulation of TL1A expression can promote mucosal inflammation and gut fibrosis. PMID:21264313

  10. A Constitutive Expression System for Cellulase Secretion in Escherichia coli and Its Use in Bioethanol Production

    PubMed Central

    Munjal, Neha; Jawed, Kamran; Wajid, Saima; Yazdani, Syed Shams

    2015-01-01

    The production of biofuels from lignocellulosic biomass appears to be attractive and viable due to the abundance and availability of this biomass. The hydrolysis of this biomass, however, is challenging because of the complex lignocellulosic structure. The ability to produce hydrolytic cellulase enzymes in a cost-effective manner will certainly accelerate the process of making lignocellulosic ethanol production a commercial reality. These cellulases may need to be produced aerobically to generate large amounts of protein in a short time or anaerobically to produce biofuels from cellulose via consolidated bioprocessing. Therefore, it is important to identify a promoter that can constitutively drive the expression of cellulases under both aerobic and anaerobic conditions without the need for an inducer. Using lacZ as reporter gene, we analyzed the strength of the promoters of four genes, namely lacZ, gapA, ldhA and pflB, and found that the gapA promoter yielded the maximum expression of the ?-galactosidase enzyme under both aerobic and anaerobic conditions. We further cloned the genes for two cellulolytic enzymes, ?-1,4-endoglucanase and ?-1,4-glucosidase, under the control of the gapA promoter, and we expressed these genes in Escherichia coli, which secreted the products into the extracellular medium. An ethanologenic E. colistrain transformed with the secretory ?-glucosidase gene construct fermented cellobiose in both defined and complex medium. This recombinant strain also fermented wheat straw hydrolysate containing glucose, xylose and cellobiose into ethanol with an 85% efficiency of biotransformation. An ethanologenic strain that constitutively secretes a cellulolytic enzyme is a promising platform for producing lignocellulosic ethanol. PMID:25768292

  11. Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung

    PubMed Central

    1995-01-01

    Eotaxin is a member of the C-C family of chemokines and is related during antigen challenge in a guinea pig model of allergic airway inflammation (asthma). Consistent with its putative role in eosinophilic inflammation, eotaxin induces the selective infiltration of eosinophils when injected into the lung and skin. Using a guinea pig lung cDNA library, we have cloned full-length eotaxin cDNA. The cDNA encodes a protein of 96 amino acids, including a putative 23-amino acid hydrophobic leader sequence, followed by 73 amino acids composing the mature active eotaxin protein. The protein-coding region of this cDNA is 73, 71, 50, and 48% identical in nucleic acid sequence to those of human macrophage chemoattractant protein (MCP) 3, MCP-1, macrophage inflammatory protein (MIP) 1 alpha, and RANTES, respectively. Analysis of genomic DNA suggested that there is a single eotaxin gene in guinea pig which is apparently conserved in mice. High constitutive levels of eotaxin mRNA expression were observed in the lung, while the intestines, stomach, spleen, liver, heart, thymus, testes, and kidney expressed lower levels. To determine if eotaxin mRNA levels are elevated during allergen-induced eosinophilic airway inflammation, ovalbumin (OVA)-sensitized guinea pigs were challenged with aerosolized antigen. Compared with the lungs from saline-challenged animals, eotaxin mRNA levels increased sixfold within 3 h and returned to baseline by 6 h. Thus, eotaxin mRNA levels are increased in response to allergen challenge during the late phase response. The identification of constitutive eotaxin mRNA expression in multiple tissues suggests that in addition to regulating airway eosinophilia, eotaxin is likely to be involved in eosinophil recruitment into other tissues as well as in baseline tissue homing. PMID:7869037

  12. Constitutively expressed Protocadherin-? regulates the coalescence and elimination of homotypic olfactory axons through its cytoplasmic region

    PubMed Central

    Hasegawa, Sonoko; Hirabayashi, Takahiro; Kondo, Takahiko; Inoue, Ken; Esumi, Shigeyuki; Okayama, Atsushi; Hamada, Shun; Yagi, Takeshi

    2012-01-01

    Olfactory sensory neuron (OSN) axons coalesce into specific glomeruli in the olfactory bulb (OB) according to their odorant receptor (OR) expression. Several guidance molecules enhance the coalescence of homotypic OSN projections, in an OR-specific- and neural-activity-dependent manner. However, the mechanism by which homotypic OSN axons are organized into glomeruli is unsolved. We previously reported that the clustered protocadherin-? (Pcdh-?) family of diverse cadherin-related molecules plays roles in the coalescence and elimination of homotypic OSN axons throughout development. Here we showed that the elimination of small ectopic homotypic glomeruli required the constitutive expression of a Pcdh-? isoform and Pcdh-?'s cytoplasmic region, but not OR specificity or neural activity. These results suggest that Pcdh-? proteins provide a cytoplasmic signal to regulate repulsive activity for homotypic OSN axons independently of OR expression and neural activity. The counterbalancing effect of Pcdh-? proteins for the axonal coalescence mechanisms mediated by other olfactory guidance molecules indicate a possible mechanism for the organization of homotypic OSN axons into glomeruli during development. PMID:23087612

  13. Expression of Rhizobium galegae common nod clones in various backgrounds.

    PubMed

    Räsänen, L A; Heikkilä-Kallio, U; Suominen, L; Lipsanen, P; Lindström, K

    1991-01-01

    The cosmid clone pRg30, carrying common nodulation genes of Rhizobium galegae HAMBI 1174, and pRg33, a subclone of pRg30 that contains a 5.7-kb ClaI insert carrying nodDABC were conjugated into various Rhizobium nod- mutant strains and into a Ti plasmid-cured Agrobacterium tumefaciens. Complementation and expression of the nodABC genes of R. galegae were studied by following microscopically the infection process and the nodulation on different test plants. The nodABC genes of R. galegae complemented the nod- strains of other Rhizobium species. The presence of extra copies of common nod genes in the homologous R. galegae nodABC- strain induced an increased nodulation on Galega orientalis. However, the inserts of R. galegae in pRg30 and pRg33 do not carry sufficient genetic information for normal nodulation of test plants in an Agrobacterium background, because the Agrobacterium transconjugants induced root hair deformation on Galega plants, but no infection threads were detected and nodulelike structures developed only at low frequency. The Agrobacterium carrying the nodDABC of R. galegae did not cause the root hairs of Medigo sativa to deform. PMID:1804401

  14. Basic Equations and Constitutive Equations of Micropolar Magnetic Fluids with E-BAnalogy and the Abraham Expression of Electromagnetic Momentum

    NASA Astrophysics Data System (ADS)

    Ido, Yasushi

    A complete set of basic equations for magnetic fluids with internal rotation is proposed in this paper. The basic equations are derived from the conservation laws of mass, linear momentum, angular momentum and energy, while the constitutive equations are obtained by the thermodynamical method that is based on the free energy and the dissipation function. The concrete expression of constitutive equations are determined by the principle of material frame indifference and the principle of maximal dissipation rate. The Abraham expression of the electromagnetic momentum and E-Banalogy are adopted in this theory. It is shown that the difference in the basic equations in case of adopting the Abraham expression and the Minkowski expression, respectively. The constitutive equation of magnetization which includes the Shliomis relaxation equation (1972) is proposed.

  15. Enhancement of endothelial cell migration by constitutively active LPA{sub 1}-expressing tumor cells

    SciTech Connect

    Kitayoshi, Misaho; Kato, Kohei; Tanabe, Eriko; Yoshikawa, Kyohei; Fukui, Rie [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)] [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Fukushima, Nobuyuki [Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)] [Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Tsujiuchi, Toshifumi, E-mail: ttujiuch@life.kindai.ac.jp [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)] [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer Mutated LPA{sub 1} stimulates cell migration of endothelial cells. Black-Right-Pointing-Pointer VEGF expressions are increased by mutated LPA{sub 1}. Black-Right-Pointing-Pointer LPA signaling via mutated LPA{sub 1} is involved in angiogenesis. Black-Right-Pointing-Pointer Mutated LPA{sub 1} promotes cancer cell progression. -- Abstract: Lysophosphatidic acid (LPA) receptors belong to G protein-coupled transmembrane receptors (LPA receptors; LPA{sub 1} to LPA{sub 6}). They indicate a variety of cellular response by the interaction with LPA, including cell proliferation, migration and differentiation. Recently, we have reported that constitutive active mutated LPA{sub 1} induced the strong biological effects of rat neuroblastoma B103 cells. In the present study, we examined the effects of mutated LPA{sub 1} on the interaction between B103 cells and endothelial F-2 cells. Each LPA receptor expressing B103 cells were maintained in serum-free DMEM and cell motility assay was performed with a Cell Culture Insert. When F-2 cells were cultured with conditioned medium from Lpar1 and Lpar3-expressing cells, the cell motility of F-2 cells was significantly higher than control cells. Interestingly, the motile activity of F-2 cells was strongly induced by mutated LPA{sub 1} than other cells, correlating with the expression levels of vascular endothelial growth factor (Vegf)-A and Vegf-C. Pretreatment of LPA signaling inhibitors inhibited F-2 cell motility stimulated by mutated LPA{sub 1}. These results suggest that activation of LPA signaling via mutated LPA{sub 1} may play an important role in the promotion of angiogenesis in rat neuroblastoma cells.

  16. Constitutive expression of Thermobifida fusca thermostable Acetylxylan Esterase gene in Pichia pastoris.

    PubMed

    Yang, Chao-Hsun; Lin, Kun-I; Chen, Gen-Hung; Chen, Yu-Fen; Chen, Cheng-Yu; Chen, Wei-Lin; Huang, Yu-Chun

    2010-01-01

    A gene encoding the thermostable acetylxylan esterase (AXE) in Thermobifida fusca NTU22 was amplified by PCR, sequenced and cloned into the Pichia pastoris X-33 host strain using the vector pGAPZ?A, allowing constitutive expression and secretion of the protein. Recombinant expression resulted in high levels of extracellular AXE production, as high as 526 U/mL in the Hinton flask culture broth. The purified enzyme showed a single band at about 28 kDa by SDS-polyacrylamide gel electrophoresis after being treated with endo-?-N-acetylglycosaminidase H; this agrees with the predicted size based on the nucleotide sequence. About 70% of the original activity remained after heat treatment at 60 °C for three hours. The optimal pH and temperature of the purified enzyme were 8.0 and 60 °C, respectively. The properties of the purified AXE from the P. pastoris transformant are similar to those of the AXE from an E. coli transformant. PMID:21614198

  17. Blocking of Retroviral Infection at a Step Prior to Reverse Transcription in Cells Transformed to Constitutively Express Interferon beta

    Microsoft Academic Search

    Vincent Viellard; Evelyne Lauret; Veronique Rousseau; Edward de Maeyer

    1994-01-01

    We are developing methods for somatic-cell gene therapy directed against infection with human immunodeficiency virus, by enhancing antiviral resistance of target cells through the constitutive production of autocrine interferon (IFN). Using the human IFN-beta coding sequence under the constitutive low-expression control of a 0.6-kb murine H-2K^b promoter fragment, we have constructed a retroviral vector, HMB-K^bHuIFNbeta, and have transformed cells of

  18. Constitutive and modulated cytokine expression in two permanent human bone marrow stromal cell lines.

    PubMed

    Thalmeier, K; Meissner, P; Reisbach, G; Hültner, L; Mortensen, B T; Brechtel, A; Oostendorp, R A; Dörmer, P

    1996-01-01

    We present a detailed analysis of cytokine expression patterns of the two permanent human bone marrow stromal cell lines, L87/4 and L88/5. These cell lines, previously established in our laboratory, are highly radiotolerant without cell detachment and support long-term cultures of CD(34+)-enriched human cord blood cells. RT-PCR analysis of 22 different cytokines or cytokine receptor mRNAs showed an almost identical expression pattern in the two stromal cell lines compared to primary human Dexter-type stroma. Since stromal feeder lines employed in long-term cultures usually are irradiated and grown in media containing corticosteroids, we analyzed the impact of irradiation and dexamethasone on cytokine production in the two cell lines by RT-PCR, Northern blot analysis, bioassays, and RIAs. By RT-PCR analysis, constitutive mRNA expression of c-kit, G-CSF, GM-CSF, IL-1 beta, IL-6, IL-7, IL-8, IL-11, Kit ligand (KL), LIF, M-CSF, MIP-1 alpha, TGF-beta, and TNF-alpha was demonstrated in both cell lines, with L87/4 a more potent cytokine producer than L88/5. Northern blot data showed an increase in mRNA levels for GM-CSF, IL-1 beta, and LIF by irradiation and IL-1 alpha treatment in both cell lines. IL-1 alpha-induced GM-CSF, IL-1 beta, IL-6, IL-11, and LIF mRNA levels were reduced by the addition of dexamethasone, whereas dexamethasone had no influence on the amounts of IL-1 alpha-induced G-CSF mRNA. L87/4 and, to a lower extent, L88/5 cells showed dexamethasone-dependent increases in KL mRNA, while KL mRNA levels were not stimulated by IL-1 alpha. PMID:8536785

  19. Constitutive expression of a rhIL-2-HSA fusion protein in Pichia pastoris using glucose as carbon source.

    PubMed

    Guan, Bo; Chen, Fengxiang; Lei, Jianyong; Li, Yunhua; Duan, Zuoying; Zhu, Ruiyu; Chen, Yun; Li, Huazhong; Jin, Jian

    2013-12-01

    A constitutive expression vector for rhIL-2-HSA fusion protein production in yeast Pichia pastoris was constructed. The coding gene was placed in frame with the Saccharomyces cerevisiae ?-factor secretion signal sequence under the control of the GAP promoter. The recombinant plasmid pGAPZ?A-rhIL-2-HSA was integrated into the genome of the P. pastoris GS115. The effect of different carbon sources on rhIL-2-HSA fusion protein expression was evaluated in shaking flask cultures. We found that recombinant P. pastoris grew well and efficiently secreted rhIL-2-HSA fusion protein into the medium when using glucose as carbon source. To achieve higher production, the influence of initial pH and culture temperature was also evaluated. Fed-batch fermentation strategy using glucose as carbon source for constitutive expression of rhIL-2-HSA fusion protein was investigated in 5-L bioreactor and the expression level of rhIL-2-HSA could reach about 250 mg/L after 60-h fermentation. The rhIL-2-HSA fusion protein produced by this constitutive expression system was purified and exhibited a specific bioactivity of 1.040 × 10(6) IU/mg in vitro. This study described constitutive expression of rhIL-2-HSA fusion protein by P. pastoris and development of a simple high-cell density fermentation strategy for biologically active rhIL-2-HSA fusion protein using glucose as sole carbon source. PMID:23999737

  20. Constitutive expression of a grapevine polygalacturonase-inhibiting protein affects gene expression and cell wall properties in uninfected tobacco

    PubMed Central

    2011-01-01

    Background Polygalacturonase-inhibiting proteins (PGIPs) directly limit the effective ingress of fungal pathogens by inhibiting cell wall-degrading endopolygalacturonases (ePGs). Transgenic tobacco plants over-expressing grapevine (Vitis vinifera) Vvpgip1 have previously been shown to be resistant to Botrytis infection. In this study we characterized two of these PGIP over-expressing lines with known resistance phenotypes by gene expression and hormone profiling in the absence of pathogen infection. Results Global gene expression was performed by a cross-species microarray approach using a potato cDNA microarray. The degree of potential cross-hybridization between probes was modeled by a novel computational workflow designed in-house. Probe annotations were updated by predicting probe-to-transcript hybridizations and combining information derived from other plant species. Comparing uninfected Vvpgip1-overexpressing lines to wild-type (WT), 318 probes showed significant change in expression. Functional groups of genes involved in metabolism and associated to the cell wall were identified and consequent cell wall analysis revealed increased lignin-levels in the transgenic lines, but no major differences in cell wall-derived polysaccharides. GO enrichment analysis also identified genes responsive to auxin, which was supported by elevated indole-acetic acid (IAA) levels in the transgenic lines. Finally, a down-regulation of xyloglucan endotransglycosylase/hydrolases (XTHs), which are important in cell wall remodeling, was linked to a decrease in total XTH activity. Conclusions This evaluation of PGIP over-expressing plants performed under pathogen-free conditions to exclude the classical PGIP-ePG inhibition interaction indicates additional roles for PGIPs beyond the inhibition of ePGs. PMID:22078230

  1. The constitutive AHSB4 promoter--a novel component of the Arxula adeninivorans-based expression platform.

    PubMed

    Wartmann, T; Bellebna, C; Böer, E; Bartelsen, O; Gellissen, G; Kunze, G

    2003-10-01

    An Arxula adeninivorans-AHSB4 gene, encoding histone H4, was isolated and characterized. The gene includes a coding sequence of 363 bp disrupted by a 51-bp intron, similar to the situation in other fungal H4 genes. The identity of the gene was confirmed by the high degree of homology of the derived amino acid sequence with that of other H4 histones. The gene is strongly and constitutively expressed, maintaining this expression profile under salt-stress conditions. The AHSB4 promoter was tested for suitability in heterologous gene expression using genes encoding the intracellular green fluorescent protein and the secreted human serum albumin (HSA) for assessment. Plasmids incorporating respective expression cassettes were used to transform the host strain A. adeninivorans LS3, which forms budding cells at 30 degrees C, and strain 135, which forms mycelia under these conditions. Transformants of both types were found to harbor a single copy of the heterologous DNA. Strong constitutive expression was observed during culture in salt-containing and salt-free media, as expected from the expression profile of AHSB4. In 200-ml shake-flask cultures, maximal HSA levels of 20 mg l(-1) culture medium were achieved. This productivity could be increased to 50 mg l(-1 )in strains harboring two copies of the expression cassette. The AHSB4 promoter thus provides an attractive component for constitutive heterologous gene expression under salt-free and salt-stress conditions. PMID:12733004

  2. Constitutive Expression and Enzymatic Cleavage of ICAM-1 in the Spontaneously Hypertensive Rat

    PubMed Central

    Tong, Sheng; Neboori, Hanmanth J.; Tran, Edward D.; Schmid-Schönbein, Geert W.

    2011-01-01

    Background/Aims: Leukocyte adhesion to the endothelium is abnormal in hypertension. We have recently shown that spontaneously hypertensive rats (SHRs) have circulating leukocytes with enhanced CD18 receptor cleavage. In the current study, we investigate expression levels of its counter receptor, intercellular adhesion molecule (ICAM-1), and its possible proteolytic cleavage in the SHR and control Wistar rat. Methods ICAM-1 was labeled on tissue sections with two antibodies targeting its extracellular and intracellular domains and evaluated by light absorption measurements. The in situ cleavage of ICAM-1 was assessed by treating vessel sections with matrix metalloproteinase (MMP)-7, MMP-9 and elastase. Results SHRs showed a significant increase in ICAM-1 expression in liver and kidney compared with Wistar rats. The liver and kidney glomeruli exhibit a discrepancy in label density between intra- and extracellular antibodies, which suggests that enzymatic cleavage may be a factor determining ICAM-1 distribution. MMP-7 and MMP-9, which are elevated in SHR plasma, and elastase, which has elevated activity in SHR neutrophils, cleave the extracellular domain of ICAM-1 when applied to the tissue. Conclusion ICAM-1 expression in SHRs is upregulated in a tissue-specific manner. Proteolytic cleavage of the extracellular domain of ICAM-1 and accumulation in kidney glomeruli may play a role in the renal involvement of inflammation. PMID:21464573

  3. Mice expressing constitutively active Gsalpha exhibit stimulus encoding deficits similar to those observed in schizophrenia patients.

    PubMed

    Maxwell, C R; Liang, Y; Kelly, M P; Kanes, S J; Abel, T; Siegel, S J

    2006-09-01

    People with schizophrenia display sensory encoding deficits across a broad range of electrophysiological and behavioral measures, suggesting fundamental impairments in the ability to transduce the external environment into coherent neural representations. This inability to create basic components of complex stimuli interferes with a high fidelity representation of the world and likely contributes to cognitive deficits. The current study evaluates the effects of constitutive forebrain activation of the G(s)alpha G-protein subunit on auditory threshold and gain using acoustic brainstem responses and cortically generated N40 event-related potentials to assess the role of cyclic AMP signaling in sensory encoding. Additionally, we examine the ability of pharmacological treatments that mimic (amphetamine) or ameliorate (haloperidol) positive symptoms of schizophrenia to test the hypothesis that the encoding deficits observed in G(s)alpha transgenic mice can be normalized with treatment. We find that G(s)alpha transgenic mice have decreased amplitude of cortically generated N40 but normal acoustic brainstem response amplitude, consistent with forebrain transgene expression and a schizophrenia endophenotype. Transgenic mice also display decreased stimulus intensity response (gain) in both acoustic brainstem response and N40, indicating corticofugal influence on regions that lack transgene expression. N40 deficits in transgenic animals were ameliorated with low dose haloperidol and reversed with higher dose, suggesting dopamine D2 receptor-linked Gi activity contributes to the impairment. Consistent with this hypothesis, we recreated the G(s)alpha transgenic deficit in wild type animals using the indirect dopamine agonist amphetamine. This transgenic model of sensory encoding deficits provides a foundation for identifying biochemical contributions to sensory processing impairments associated with schizophrenia. PMID:16750890

  4. Estrogen upregulates endothelial constitutive nitric oxide synthase expression in human osteoblast-like cells.

    PubMed

    Armour, K E; Ralston, S H

    1998-02-01

    The protective effects of estrogen on the cardiovascular system are thought to be mediated, in part, by nitric oxide (NO). Estrogen also has protective effects on bone although the mechanisms of action have not been fully established. Since nitric oxide synthase (NOS) inhibitors have been found to abrogate the protective effect of estrogen on bone in ovariectomised rats, we studied the effects of 17beta-estradiol on NOS activity and NOS mRNA levels in cultured human osteoblast-like cells. 17beta-Estradiol stimulated NOS activity by approximately 2.0 fold and this effect was reversed by the calcium chelator, EGTA, and the NOS inhibitor, L-NMMA, implicating activation of a constitutive, calcium-dependent isoform. Further studies using RT/PCR indicated that only the endothelial nitric oxide synthase (ecNOS) isoform was expressed and RNase protection assays showed that 17beta-Estradiol treatment resulted in a 2.2 fold increase in ecNOS mRNA levels. These findings suggest that estrogen stimulates NOS activity in osteoblastic cells by activation of the ecNOS pathway, and taken together with previous data, is consistent with the possibility that NO may act as a mediator of estrogen actions on bone. PMID:9449657

  5. Constitutive mRNA Expression of Various Glutathione S-Transferase Isoforms in Different Tissues of Mice

    Microsoft Academic Search

    Tamara Raphael Knight; Supratim Choudhuri; Curtis D. Klaassen

    2007-01-01

    Glutathione S-transferase (Gst) enzymes are instrumental in protecting cellular macromolecules against electrophiles and products of oxidative stress. Of interest primarily to pharmacol- ogists and toxicologists is the ability of these enzymes to metabolize cancer chemotherapeutic drugs, insecticides, herbi- cides, and carcinogens. Thus, constitutive expression of Gsts might determine a tissue's ability to handle certain forms of chemical stress. In the

  6. CONSTITUTIVE AND STIMULATED MCP-1, GROA, B, AND Y EXPRESSION IN HUMAN A AIRWAY EPITHELIUM AND BRONCHOALVEOLAR MACROPHAGES

    EPA Science Inventory

    Constitutive expression of mRNAs for GROa, GROB, GROY, and MCP-1, belonging to the chemokine family of 8-10 kD cytokines with chemotactic properties for granulocytes and monocytes, has been identified in freshly isolated human nasal and bronchial epithelium, and in bronchoalveola...

  7. Paradata for 'ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-? and constitutively active receptor induced gene expression'

    NSDL National Science Digital Library

    This record contains paradata for the resource 'ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-? and constitutively active receptor induced gene expression'

  8. New Vectors for Chromosomal Integration Enable High-Level Constitutive or Inducible Magnetosome Expression of Fusion Proteins in Magnetospirillum gryphiswaldense

    PubMed Central

    Borg, Sarah; Hofmann, Julia; Pollithy, Anna; Lang, Claus

    2014-01-01

    The alphaproteobacterium Magnetospirillum gryphiswaldense biomineralizes magnetosomes, which consist of monocrystalline magnetite cores enveloped by a phospholipid bilayer containing specific proteins. Magnetosomes represent magnetic nanoparticles with unprecedented magnetic and physicochemical characteristics. These make them potentially useful in a number of biotechnological and biomedical applications. Further functionalization can be achieved by expression of foreign proteins via genetic fusion to magnetosome anchor peptides. However, the available genetic tool set for strong and controlled protein expression in magnetotactic bacteria is very limited. Here, we describe versatile vectors for either inducible or high-level constitutive expression of proteins in M. gryphiswaldense. The combination of an engineered native PmamDC promoter with a codon-optimized egfp gene (Mag-egfp) resulted in an 8-fold increase in constitutive expression and in brighter fluorescence. We further demonstrate that the widely used Ptet promoter is functional and tunable in M. gryphiswaldense. Stable and uniform expression of the EGFP and ?-glucuronidase (GusA) reporters was achieved by single-copy chromosomal insertion via Tn5-mediated transposition. In addition, gene duplication by Mag-EGFP–EGFP fusions to MamC resulted in further increased magnetosome expression and fluorescence. Between 80 and 210 (for single MamC–Mag-EGFP) and 200 and 520 (for MamC–Mag-EGFP–EGFP) GFP copies were estimated to be expressed per individual magnetosome particle. PMID:24532068

  9. Constitutive and Inducible Expression of Invasion-related Factors in PC-3 Prostate Cancer Cells

    PubMed Central

    Hwang, Young Sun; Lindholm, Paul F.

    2015-01-01

    Background: Tumor growth and invasion are interconnected with the tumor microenvironment. Overexpression of genes that regulate cancer cell invasion by growth factors, cytokines, and lipid factors can affect cancer aggressiveness. A comparative gene expression analysis between highly invasive and low invasive cells revealed that various genes are differentially expressed in association with invasive potential. In this study, we selected variant PC-3 prostate cancer cell sublines and discovered critical molecules that contributed to their invasive potential. Methods: The high invasive and low invasive variant PC-3 cell sublines were obtained by serial selection following Matrigel-coated Transwell invasion and were characterized by Transwell invasion, luciferase reporter assay, and Rhotekin pull-down assay. Lysophosphatidic acid (LPA) was added to the cultures to observe the response to this extracellular stimulus. The essential molecules related with cancer invasiveness were detected with Northern blotting, quantitative reverse transcription-polymerase chain reaction, and cDNA microarray. Results: Highly invasive PC-3 cells showed higher nuclear factor kappa B (NF-?B), activator protein 1 (AP-1) and RhoA activities than of low invasive PC-3 cells. LPA promoted cancer invasion through NF-?B, AP-1, and RhoA activities. Thrombospondin-1, interleukin-8, kallikrein 6, matrix metalloproteinase-1, and tissue factor were overexpressed in the highly invasive PC-3 variant cells and further upregulated by LPA stimulation. Conclusions: The results suggest that the target molecules are involved in invasiveness of prostate cancer. These molecules may have clinical value for anti-invasion therapy by serving as biomarkers for the prediction of aggressive cancers and the detection of pharmacological inhibitors.

  10. A dual cis-regulatory code links IRF8 to constitutive and inducible gene expression in macrophages.

    PubMed

    Mancino, Alessandra; Termanini, Alberto; Barozzi, Iros; Ghisletti, Serena; Ostuni, Renato; Prosperini, Elena; Ozato, Keiko; Natoli, Gioacchino

    2015-02-15

    The transcription factor (TF) interferon regulatory factor 8 (IRF8) controls both developmental and inflammatory stimulus-inducible genes in macrophages, but the mechanisms underlying these two different functions are largely unknown. One possibility is that these different roles are linked to the ability of IRF8 to bind alternative DNA sequences. We found that IRF8 is recruited to distinct sets of DNA consensus sequences before and after lipopolysaccharide (LPS) stimulation. In resting cells, IRF8 was mainly bound to composite sites together with the master regulator of myeloid development PU.1. Basal IRF8-PU.1 binding maintained the expression of a broad panel of genes essential for macrophage functions (such as microbial recognition and response to purines) and contributed to basal expression of many LPS-inducible genes. After LPS stimulation, increased expression of IRF8, other IRFs, and AP-1 family TFs enabled IRF8 binding to thousands of additional regions containing low-affinity multimerized IRF sites and composite IRF-AP-1 sites, which were not premarked by PU.1 and did not contribute to the basal IRF8 cistrome. While constitutively expressed IRF8-dependent genes contained only sites mediating basal IRF8/PU.1 recruitment, inducible IRF8-dependent genes contained variable combinations of constitutive and inducible sites. Overall, these data show at the genome scale how the same TF can be linked to constitutive and inducible gene regulation via distinct combinations of alternative DNA-binding sites. PMID:25637355

  11. BST2/Tetherin is constitutively expressed on human thymocytes with the phenotype and function of Treg cells.

    PubMed

    Epeldegui, Marta; Blom, Bianca; Uittenbogaart, Christel H

    2015-03-01

    In contrast to peripheral plasmacytoid DCs (pDCs), thymic pDCs constitutively express low levels of IFN-?. This leads to induction of interferon secondary genes (ISGs) in medullary thymocytes, raising the question whether IFN-? may play a role in T-cell development. When characterizing further differences between peripheral and thymic pDCs, we found that thymic pDCs have a phenotype consistent with an "activated signature" including expression of TNF-? and bone marrow stromal cell antigen 2 (BST2), but no expression of ILT7. Given that BST2 is induced by IFN-?, and IFN-? secretion is controlled by interaction between ILT7 and BST2, this regulatory pathway is apparently lost in thymic pDCs. Further, we also show that BST2 is constitutively expressed on a subset of medullary thymocytes at the mRNA and protein level reflecting a history of IFN-? transduced signals. The majority of BST2(+) thymocytes express CCR5 rendering them prevalent targets for R5-tropic HIV infection. Moreover, BST2(+) thymocytes express Foxp3 and CD25, consistent with the phenotype of natural Treg cells, and exert suppressive activity as they impair the proliferation of autologous CD3(+) thymocytes. Collectively, our results suggest that low levels of IFN-? secreted by thymic pDCs play an important role in the development of natural Treg cells. PMID:25408362

  12. Increased tolerance to Phytophthora citrophthora in transgenic orange plants constitutively expressing a tomato pathogenesis related protein PR5

    Microsoft Academic Search

    Carmen Fagoaga; Ismael Rodrigo; Vicente Conejero; Concha Hinarejos; Juan José Tuset; Joaquín Arnau; José Antonio Pina; Luis Navarro; Leandro Peńa

    2001-01-01

    Phytophthora citrophthora is the most widely spread oomycete plant pathogen over all the citrus growing areas and represents one of the major causes of crop losses. Constitutive over-expression of genes encoding proteins involved in plant defence mechanisms to disease is one of the strategies proposed to increase plant tolerance to oomycete and fungal pathogens. P23 (PR-5), a 23-kDa pathogenesis-related protein

  13. Revealing constitutively expressed resistance genes in Agrostis species using PCR-based motif-directed RNA fingerprinting.

    PubMed

    Budak, Hikmet; Su, Senem; Ergen, Neslihan

    2006-12-01

    Agrostis species are mainly used in athletic fields and golf courses. Their integrity is maintained by fungicides, which makes the development of disease-resistance varieties a high priority. However, there is a lack of knowledge about resistance (R) genes and their use for genetic improvement in Agrostis species. The objective of this study was to identify and clone constitutively expressed cDNAs encoding R gene-like (RGL) sequences from three Agrostis species (colonial bentgrass (A. capillaris L.), creeping bentgrass (A. stolonifera L.) and velvet bentgrass (A. canina L.)) by PCR-based motif-directed RNA fingerprinting towards relatively conserved nucleotide binding site (NBS) domains. Sixty-one constitutively expressed cDNA sequences were identified and characterized. Sequence analysis of ESTs and probable translation products revealed that RGLs are highly conserved among these three Agrostis species. Fifteen of them were shown to share conserved motifs found in other plant disease resistance genes such as MLA13, Xa1, YR6, YR23 and RPP5. The molecular evolutionary forces, analysed using the Ka/Ks ratio, reflected purifying selection both on NBS and leucine-rich repeat (LRR) intervening regions of discovered RGL sequences in these species. This study presents, for the first time, isolation and characterization of constitutively expressed RGL sequences from Agrostis species revealing the presence of TNL (TIR-NBS-LRR) type R genes in monocot plants. The characterized RGLs will further enhance knowledge on the molecular evolution of the R gene family in grasses. PMID:17371611

  14. Field tolerance to fungal pathogens of Brassica napus constitutively expressing a chimeric chitinase gene

    SciTech Connect

    Grison, R.; Grezes-Besset, B.; Lucante, N. [Rustica Prograin Genetique, Mondonville (France)] [and others] [Rustica Prograin Genetique, Mondonville (France); and others

    1996-05-01

    Constitutive overexpression of a protein involved in plant defense mechanisms to disease is one of the strategies proposed to increase plant tolerance to fungal pathogens. A hybrid endochitinase gene under a constitutive promoter was introduced by Agrobacterium-mediated transformation into a winter-type oilseed rape (Brassica napus var. oleifera) inbred line. Progeny from transformed plants was challenged using three different fungal pathogens (Cylindrosporium concentricum, Phoma lingam, Sclerotinia sclerotiorum) in field trials at two different geographical locations. These plants exhibited an increased tolerance to disease as compared with the nontransgenic parental plants. 31 refs., 1 fig., 2 tabs.

  15. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis

    Microsoft Academic Search

    Guilian Niu; Kenneth L Wright; Mei Huang; Lanxi Song; Eric Haura; James Turkson; Shumin Zhang; Tianhong Wang; Dominic Sinibaldi; Domenico Coppola; Richard Heller; Lee M Ellis; James Karras; Jacqueline Bromberg; Drew Pardoll; Richard Jove; Hua Yu; H Yu

    2002-01-01

    Non-receptor and receptor tyrosine kinases, such as Src and EGF receptor (EGFR), are major inducers of vascular endothelial growth factor (VEGF), one of the most potent mediators of angiogenesis. While tyrosine kinases signal through multiple pathways, signal transducer and activation of transcription 3 (Stat3) is a point of convergence for many of these and is constitutively activated with high frequency

  16. Multiple effects of genetic background on variegated transgene expression in mice.

    PubMed

    Opsahl, Margaret L; McClenaghan, Margaret; Springbett, Anthea; Reid, Sarah; Lathe, Richard; Colman, Alan; Whitelaw, C Bruce A

    2002-03-01

    BLG/7 transgenic mice express an ovine beta-lactoglobulin transgene during lactation. Unusually, transgene expression levels in milk differ between siblings. This variable expression is due to variegated transgene expression in the mammary gland and is reminiscent of position-effect variegation. The BLG/7 line was created and maintained on a mixed CBA x C57BL/6 background. We have investigated the effect on transgene expression of backcrossing for 13 generations into these backgrounds. Variable transgene expression was observed in all populations examined, confirming that it is an inherent property of the transgene array at its site of integration. There were also strain-specific effects on transgene expression that appear to be independent of the inherent variegation. The transgene, compared to endogenous milk protein genes, is specifically susceptible to inbreeding depression. Outcrossing restored transgene expression levels to that of the parental population; thus suppression was not inherited. Finally, no generation-dependent decrease in mean expression levels was observed in the parental population. Thus, although the BLG/7 transgene is expressed in a variegated manner, there was no generation-associated accumulated silencing of transgene expression. PMID:11901126

  17. Genomic Consequences of Background Effects on scalloped Mutant Expressivity in the Wing of Drosophila melanogaster

    PubMed Central

    Dworkin, Ian; Kennerly, Erin; Tack, David; Hutchinson, Jennifer; Brown, Julie; Mahaffey, James; Gibson, Greg

    2009-01-01

    Genetic background effects contribute to the phenotypic consequences of mutations and are pervasive across all domains of life that have been examined, yet little is known about how they modify genetic systems. In part this is due to the lack of tractable model systems that have been explicitly developed to study the genetic and evolutionary consequences of background effects. In this study we demonstrate that phenotypic expressivity of the scallopedE3 (sdE3) mutation of Drosophila melanogaster is background dependent and is the result of at least one major modifier segregating between two standard lab wild-type strains. We provide evidence that at least one of the modifiers is linked to the vestigial region and demonstrate that the background effects modify the spatial distribution of known sd target genes in a genotype-dependent manner. In addition, microarrays were used to examine the consequences of genetic background effects on the global transcriptome. Expression differences between wild-type strains were found to be as large as or larger than the effects of mutations with substantial phenotypic effects, and expression differences between wild type and mutant varied significantly between genetic backgrounds. Significantly, we demonstrate that the epistatic interaction between sdE3 and an optomotor blind mutation is background dependent. The results are discussed within the context of developing a complex but more realistic view of the consequences of genetic background effects with respect to mutational analysis and studies of epistasis and cryptic genetic variation segregating in natural populations. PMID:19064709

  18. Involvement of p300 in constitutive and HIV-1 Tat-activated expression of glial fibrillary acidic protein in astrocytes

    PubMed Central

    Zou, Wei; Wang, Zhenyuan; Liu, Ying; Fan, Yan; Zhou, Betty Y.; Yang, X. Frank; He, Johnny J.

    2010-01-01

    HIV-1 Tat protein is an important pathogenic factor in HIV-1-associated neurological diseases. One hallmark of HIV-1 infection of the central nervous system (CNS) is astrocytosis, which is characterized by elevated GFAP expression in astrocytes. We have shown that Tat activates GFAP expression in astrocytes (Zhou, et al., Mol. Cell. Neurosci. 27:296, 2004) and that GFAP is an important regulator of Tat neurotoxicity (Zou, et. al., Am. J. Pathol. 171:1293, 2007). However, the underlying mechanisms for Tat-mediated GFAP up-regulation are not understood. In the current study, we reported concurrent up-regulation of adenovirus E1a-associated 300 kDa protein p300 and GFAP in Tat-expressing human astroytoma cells and primary astrocytes. We showed that p300 was indeed induced by Tat expression and HIV-1 infection and that the induction occurred at the transcriptional level through the cis-acting elements of early growth response 1 (Egr-1) within its promoter. Using siRNA, we further showed that p300 regulated both constitutive and Tat-mediated GFAP expression. Moreover, we showed that ectopic expression of p300 potentiated Tat transactivation activity and increased proliferation of HIV-1-infected astrocytes, but had little effect on HIV-1 replication in these cells. Taken together, these results demonstrate for the first time that Tat is a positive regulator of p300 expression, which in turn regulates GFAP expression, and suggest that the Tat-Egr-1-p300-GFAP axis likely contributes to Tat neurotoxicity and predisposes astrocytes to be an HIV-1 sanctuary in the CNS. PMID:20578042

  19. Constitutive TL1A expression under colitogenic conditions modulates the severity and location of gut mucosal inflammation and induces fibrostenosis.

    PubMed

    Barrett, Robert; Zhang, Xiaolan; Koon, Hon Wai; Vu, Michelle; Chang, Jyh-Yau; Yeager, Nicole; Nguyen, Mary Ann; Michelsen, Kathrin S; Berel, Dror; Pothoulakis, Charalabos; Targan, Stephan R; Shih, David Q

    2012-02-01

    Intestinal fibrostenosis is a hallmark of severe Crohn's disease and can lead to multiple surgeries. Patients with certain TNFSF15 variants overexpress TL1A. The aim of this study was to determine the effect of TL1A overexpression on intestinal inflammation and the development of fibrostenosis. We assessed the in vivo consequences of constitutive TL1A expression on gut mucosal inflammation and fibrostenosis using two murine models of chronic colitis. In the dextran sodium sulfate (DSS) and adoptive T-cell transfer models, there was proximal migration of colonic inflammation, worsened patchy intestinal inflammation, and long gross intestinal strictures in Tl1a transgenic compared to wild-type littermates. In the DSS model, myeloid- and T-cell-expressing Tl1a transgenic mice had increased T-cell activation markers and interleukin-17 expression compared to wild-type mice. In the T-cell transfer model, Rag1(-/-) mice receiving Tl1a transgenic T cells had increased interferon-? expression but reduced T-helper 17 cells and IL-17 production. Narrowed ureters with hydronephrosis were found only in the Tl1a transgenic mice in all chronic colitis models. In human translational studies, Crohn's disease patients with higher peripheral TL1A expression also exhibited intestinal fibrostenosis and worsened ileocecal inflammation with relative sparing of rectosigmoid inflammation. These data show that TL1A is an important cytokine that not only modulates the location and severity of mucosal inflammation, but also induces fibrostenosis. PMID:22138299

  20. Constitutively expressed rat mRNA encoding a 70-kilodalton heat-shock-like protein.

    PubMed Central

    O'Malley, K; Mauron, A; Barchas, J D; Kedes, L

    1985-01-01

    A nearly full-length cDNA clone isolated from the rat pheochromocytoma cell line, PC12, revealed extensive nucleotide sequence similarity between the rat cDNA and the Drosophila melanogaster hsp70 gene. The rat recombinant clone encodes a 71,000-dalton protein that is 70% identical with the dipteran hsp70 protein. Remarkably, a truncated segment of this cDNA clone was originally isolated by immunoreactivity with antisera raised to catecholamine-synthesizing enzymes, suggesting that this heat shock protein and these catecholamine enzymes shared antigenic determinants. The rat hsp70-related mRNA is responsible for the production of a constitutive hsp70 protein, because it is present in abundant amounts in various tissues at normal growth temperatures and is only minimally induced by hyperthermia. The rat hsp70-related sequence is part of a multigene family that extends across species to mice and humans. Images PMID:3939319

  1. Antiviral specificity of the Solea senegalensis Mx protein constitutively expressed in CHSE-214 cells.

    PubMed

    Alvarez-Torres, Daniel; Garcia-Rosado, Esther; Fernandez-Trujillo, M Alejandra; Bejar, Julia; Alvarez, M Carmen; Borrego, Juan J; Alonso, M Carmen

    2013-04-01

    Interferons play a key role in fish resistance to viral infections by inducing the expression of antiviral proteins, such as Mx. The aim of the present study was to test the antiviral activity of the Senegalese sole Mx protein (SsMx) against RNA and DNA viruses pathogenic to fish, i.e. the infectious pancreatic necrosis virus (IPNV, dsRNA), the viral haemorrhagic septicaemia virus (VHSV, ssRNA), and the European sheatfish virus (ESV, dsDNA), using a CHSE-214 cell clone expressing this antiviral protein. A strong inhibition of IPNV and VHSV replication was recorded in SsMx-expressing cells, as has been shown by the virus yield reduction and the decrease in the synthesis of the viral RNA encoding the polyprotein (for IPNV) and the nucleoprotein (for VHSV). The titres of these viruses replicating on SsMx-expressing cells were 100 times lower than those recorded on non-transfected cells. In contrast, SsMx did not inhibit ESV replication since no significant differences were observed regarding the virus yield or the major capsid protein gene transcription in transfected and non-transfected cells. PMID:22886190

  2. Establishment of Sf9 transformants constitutively expressing PBAN receptor variants: application to functional evaluation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To facilitate further evaluation of pheromone biosynthesis activating neuropeptide receptor (PBANR) functionality and regulation, we generated cultured insect cell lines stably expressing a number of fluorescent Bombyx mori PBANR (BommoPBANR) and Pseudaletia separata PBANR (PsesePBANR) variants incl...

  3. GUS expression driven by constitutive and vascular specific promoters in citrus hybrid US-802

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transgenic solutions are being widely explored to develop huanglongbing (HLB) resistance in citrus, and a critical component of the transgenic construct is the promoter, which determines tissue specificity and level of target gene expression. This study compares the characteristics of five promoters...

  4. Constitutive nuclear expression of dentin matrix protein 1 fails to rescue the Dmp1-null phenotype.

    PubMed

    Lin, Shuxian; Zhang, Qi; Cao, Zhengguo; Lu, Yongbo; Zhang, Hua; Yan, Kevin; Liu, Ying; McKee, Marc D; Qin, Chunlin; Chen, Zhi; Feng, Jian Q

    2014-08-01

    Dentin matrix protein 1 (DMP1) plays multiple roles in bone, tooth, phosphate homeostasis, kidney, salivary gland, reproductive cycles, and the development of cancer. In vitro studies have indicated two different biological mechanisms: 1) as a matrix protein, DMP1 interacts with ?v?3 integrin and activates MAP kinase signaling; and 2) DMP1 serves as a transcription co-factor. In vivo studies have demonstrated its key role in osteocytes. This study attempted to determine whether DMP1 functions as a transcription co-factor and regulates osteoblast functions. For gene expression comparisons using adenovirus constructs, we targeted the expression of DMP1 either to the nucleus only by replacing the endogenous signal peptide with a nuclear localization signal (NLS) sequence (referred to as (NLS)DMP1) or to the extracellular matrix as the WT type (referred to as (SP)DMP1) in MC3T3 osteoblasts. High levels of DMP1 in either form greatly increased osteogenic gene expression in an identical manner. However, the targeted (NLS)DMP1 transgene driven by a 3.6-kb rat Col 1?1 promoter in the nucleus of osteoblasts and osteocytes failed to rescue the phenotyope of Dmp1-null mice, whereas the (SP)DMP1 transgene rescued the rickets defect. These studies support the notion that DMP1 functions as an extracellular matrix protein, rather than as a transcription co-factor in vivo. We also show that DMP1 continues its expression in osteoblasts during postnatal development and that the deletion of Dmp1 leads to an increase in osteoblast proliferation. However, poor mineralization in the metaphysis indicates a critical role for DMP1 in both osteoblasts and osteocytes. PMID:24917674

  5. Construction of a constitutively expressed homo-fermentative pathway in Lactobacillus brevis.

    PubMed

    Guo, Wei; He, Ronglin; Ma, Lijuan; Jia, Wendi; Li, Demao; Chen, Shulin

    2014-08-01

    Lactobacillus brevis is a promising lactic acid producing strain that simultaneously utilizes glucose and xylose from lignocellulosic hydrolysate without carbon catabolic repression and inhibition. The production of by-products acetic acid and ethanol has been the major drawback of this strain. Two genes, pfkA (fructose-6-phosphate kinase [PFK]) and fbaA (fructose-1,6-biphosphate aldolase [FBA]), that encode the key enzymes of the EMP/glycolytic pathway from Lactobacillus rhamnosus, were fused to the downstream of the strong promoter P32 and expressed in L. brevis s3f4 as a strategy to minimize the formation of by-products. By expressing the two enzymes, a homo-fermentative pathway for lactic acid production was constructed. The lactic acid yields achieved from glucose in the transformants were 1.12 and 1.16 mol/mol, which is higher than that of the native strain (0.74 mol/mol). However, the lactic acid yield from xylose in the transformants stayed the same as that of the native strain. Enzyme assay indicated that the activity of the foreign protein FBA in the transformants was much higher than that of the native strains, but was ten times lower than that in L. rhamnosus. This result was consistent with the metabolic flux analysis, which indicated that the conversion efficiency of the expressed PFK and FBA was somewhat low. Less than 20 % of the carbons accumulated in the form of fructose-6-phosphate were converted into glyceraldehyde-3-phosphate (GAP) by the expressed PFK and FBA. Metabolic flux analysis also indicated that the enzyme phosphoketolase (XPK) played an important role in splitting the carbon flow from the pentose phosphate pathway to the phosphoketolase pathway. This study suggested that the lactic acid yield of L. brevis could be improved by constructing a homo-fermentative pathway. PMID:24728715

  6. Selective lignin downregulation leads to constitutive defense response expression in alfalfa (Medicago sativa L.).

    PubMed

    Gallego-Giraldo, Lina; Jikumaru, Yusuke; Kamiya, Yuji; Tang, Yuhong; Dixon, Richard A

    2011-05-01

    • Downregulation of hydroxycinnamoyl CoA: shikimate hydroxycinnamoyl transferase (HCT) in alfalfa (Medicago sativa) reduces lignin levels and improves forage quality and saccharification efficiency for bioethanol production. However, the plants have reduced stature. It was previously reported that HCT-down-regulated Arabidopsis have impaired auxin transport, but this has recently been disproved. • To address the basis for the phenotypes of lignin-modified alfalfa, we measured auxin transport, profiled a range of metabolites including flavonoids and hormones, and performed in depth transcriptome analyses. • Auxin transport is unaffected in HCT antisense alfalfa despite increased flavonoid biosynthesis. The plants show increased cytokinin and reduced auxin levels, and gibberellin levels and sensitivity are both reduced. Levels of salicylic, jasmonic and abscisic acids are elevated, associated with massive upregulation of pathogenesis and abiotic stress-related genes and enhanced tolerance to fungal infection and drought. • We suggest that HCT downregulated alfalfa plants exhibit constitutive activation of defense responses, triggered by release of bioactive cell wall fragments and production of hydrogen peroxide as a result of impaired secondary cell wall integrity. PMID:21251001

  7. Mouse neutrophils express the decoy type 2 interleukin-1 receptor (IL-1R2) constitutively and in acute inflammatory conditions.

    PubMed

    Martin, Praxedis; Palmer, Gaby; Vigne, Solenne; Lamacchia, Céline; Rodriguez, Emiliana; Talabot-Ayer, Dominique; Rose-John, Stefan; Chalaris, Athena; Gabay, Cem

    2013-10-01

    The proinflammatory activities of IL-1 are tightly controlled at different levels. IL-1R2 acts as a decoy receptor and has been shown to regulate the biological effects of IL-1 in vitro and in vivo. However, little is known about its natural expression in the mouse in physiologic and pathologic conditions. In this study, we examined IL-1R2 mRNA and protein expression in isolated cells and tissues in response to different stimulatory conditions. Data obtained using ex vivo CD11b(+)Ly6G(+) peripheral blood cells and in vitro-differentiated CD11b(+)Ly6G(+) BMG indicated that neutrophils are the major source of constitutively expressed IL-1R2 in the mouse. The expression of IL-1R2 on BMG and ex vivo Ly6G(+) peripheral blood cells was highly up-regulated by HC. IL-1R2 pull-down experiments showed that mouse rIL-1? binds to BMG IL-1R2, whereas binding of IL-1Ra could not be detected. Furthermore, LPS treatment induced shedding of IL-1R2 from the neutrophil membrane in vitro and in vivo, executed mainly by ADAM17. Finally, in in vivo models of inflammation, including thioglycolate-induced acute peritonitis and acute lung injury, infiltrating Ly6G(+) neutrophils, expressed IL-1R2. Our data show that in the mouse, neutrophils mainly express the decoy receptor IL-1R2 under naďve and inflammatory conditions. These data suggest that neutrophils may contribute to the resolution of acute inflammation. PMID:23817563

  8. Constitutive gene expression profile segregates toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy

    PubMed Central

    Henríquez Hernández, Luis Alberto; Lara, Pedro Carlos; Pinar, Beatriz; Bordón, Elisa; Gallego, Carlos Rodríguez; Bilbao, Cristina; Pérez, Leandro Fernández; Morales, Amílcar Flores

    2009-01-01

    Breast cancer patients show a wide variation in normal tissue reactions after radiotherapy. The individual sensitivity to x-rays limits the efficiency of the therapy. Prediction of individual sensitivity to radiotherapy could help to select the radiation protocol and to improve treatment results. The aim of this study was to assess the relationship between gene expression profiles of ex vivo un-irradiated and irradiated lymphocytes and the development of toxicity due to high-dose hyperfractionated radiotherapy in patients with locally advanced breast cancer. Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database (GEO accession GSE15341). We obtained a small group of 81 genes significantly regulated by radiotherapy, lumped in 50 relevant pathways. Using ANOVA and t-test statistical tools we found 20 and 26 constitutive genes (0 Gy) that segregate patients with and without acute and late toxicity, respectively. Non-supervised hierarchical clustering was used for the visualization of results. Six and 9 pathways were significantly regulated respectively. Concerning to irradiated lymphocytes (2 Gy), we founded 29 genes that separate patients with acute toxicity and without it. Those genes were gathered in 4 significant pathways. We could not identify a set of genes that segregates patients with and without late toxicity. In conclusion, we have found an association between the constitutive gene expression profile of peripheral blood lymphocytes and the development of acute and late toxicity in consecutive, unselected patients. These observations suggest the possibility of predicting normal tissue response to irradiation in high-dose non-conventional radiation therapy regimens. Prospective studies with higher number of patients are needed to validate these preliminary results. PMID:19497124

  9. Identification of centrarchid hepcidins and evidence that 17beta-estradiol disrupts constitutive expression of hepcidin-1 and inducible expression of hepcidin-2 in largemouth bass (Micropterus salmoides).

    PubMed

    Robertson, Laura S; Iwanowicz, Luke R; Marranca, Jamie Marie

    2009-06-01

    Hepcidin is a highly conserved antimicrobial peptide and iron-regulatory hormone. Here, we identify two hepcidin genes (hep-1 and hep-2) in largemouth bass (Micropterus salmoides) and smallmouth bass (Micropterus dolomieu). Hepcidin-1 contains a putative ATCUN metal-binding site in the amino-terminus that is missing in hepcidin-2, suggesting that hepcidin-1 may function as an iron-regulatory hormone. Both hepcidins are predominately expressed in the liver of largemouth bass, similar to other fish and mammals. Experimental exposure of pond-raised largemouth bass to 17beta-estradiol and/or the bacteria Edwardsiella ictaluri led to distinct changes in expression of hep-1 and hep-2. Estradiol reduced the constitutive expression of hep-1 in the liver. Bacterial exposure induced expression of hep-2, suggesting that hepcidin-2 may have an antimicrobial function, and this induction was abolished by estradiol. To our knowledge, this is the first report of the regulation of hepcidin expression by estradiol in either fish or mammals. PMID:19376234

  10. Loss-of-Function of Constitutive Expresser of Pathogenesis Related Genes5 Affects Potassium Homeostasis in Arabidopsis thaliana

    PubMed Central

    Borghi, Monica; Rus, Ana; Salt, David E.

    2011-01-01

    Here, we demonstrate that the reduction in leaf K+ observed in a mutant previously identified in an ionomic screen of fast neutron mutagenized Arabidopsis thaliana is caused by a loss-of-function allele of CPR5, which we name cpr5-3. This observation establishes low leaf K+ as a new phenotype for loss-of-function alleles of CPR5. We investigate the factors affecting this low leaf K+ in cpr5 using double mutants defective in salicylic acid (SA) and jasmonic acid (JA) signalling, and by gene expression analysis of various channels and transporters. Reciprocal grafting between cpr5 and Col-0 was used to determine the relative importance of the shoot and root in causing the low leaf K+ phenotype of cpr5. Our data show that loss-of-function of CPR5 in shoots primarily determines the low leaf K+ phenotype of cpr5, though the roots also contribute to a lesser degree. The low leaf K+ phenotype of cpr5 is independent of the elevated SA and JA known to occur in cpr5. In cpr5 expression of genes encoding various Cyclic Nucleotide Gated Channels (CNGCs) are uniquely elevated in leaves. Further, expression of HAK5, encoding the high affinity K+ uptake transporter, is reduced in roots of cpr5 grown with high or low K+ supply. We suggest a model in which low leaf K+ in cpr5 is driven primarily by enhanced shoot-to-root K+ export caused by a constitutive activation of the expression of various CNGCs. This activation may enhance K+ efflux, either indirectly via enhanced cytosolic Ca2+ and/or directly by increased K+ transport activity. Enhanced shoot-to-root K+ export may also cause the reduced expression of HAK5 observed in roots of cpr5, leading to a reduction in uptake of K+. All ionomic data presented is publically available at www.ionomicshub.org. PMID:22046278

  11. Resistance to influenza virus infection of Mx transgenic mice expressing Mx protein under the control of two constitutive promoters.

    PubMed Central

    Kolb, E; Laine, E; Strehler, D; Staeheli, P

    1992-01-01

    Transgenic mice constitutively expressing in the brain the influenza virus resistance protein Mx1 controlled by the HMG (3-hydroxy-3-methylglutaryl coenzyme A reductase) promoter showed specific resistance against the neurotropic influenza A virus strain NWS. Control mice of the A2G strain express Mx1 protein in all organs, but only after induction by interferon type I upon or without viral infection. The extent of specific resistance in transgenic mice of the best-expressing line reached about two-thirds that of controls, most likely because of considerably less total-body Mx protein activity in the transgenic mice. Thus, the theoretical advantage in these mice of the continuous presence of Mx protein with early inhibitory potential to viral replication was apparently offset by restricted organ expression. Strong evidence that the Mx1 protein on its own is a specific anti-influenza A virus agent and that its efficiency in the experimental setting is independent of interferon actions could be derived from the treatment of experimental and control mice with anti-interferon antibodies at the time of virus tests. Whereas in A2G mice, Mx1 mRNA and Mx1 protein synthesis were abolished and viral resistance was markedly reduced or abolished, resistance in the transgenic mice persisted to almost the same degree. Transgenic mice generated with a mouse albumin/Mx1 cDNA construct showed liver-specific expression. However, in two expressing transgenic lines, Mx1 protein synthesis was suppressed after a few months. The mechanism of suppression could not be elucidated, but increasing methylation of the transgene's coding region was not the cause. It is possible that continuous Mx1 protein expression in the liver is less well tolerated than that in the brain. Whether this partial suppression and, with the HMG promoter, restricted organ expression are the organism's responses to interference of Mx1 with normal cellular activities such as nucleocytoplasmic transport of RNA and proteins cannot be determined until the molecular mechanisms of antiviral activity of Mx1 protein are understood. Images PMID:1371172

  12. Constitutive expression of the low-affinity neurotrophin receptor and changes during axotomy-induced death of sensory neurones in the neonatal rat dorsal root ganglion

    PubMed Central

    Murray, Simon S; Cheema, Surindar S

    2003-01-01

    Sensory neurones in the dorsal root ganglion (DRG) of the neonatal rat express the 75-kDa low-affinity neurotrophin receptor (p75NTR) and these neurones degenerate rapidly after axotomy. p75NTR belongs to the tumour necrosis factor superfamily, several members of which have a role in cell death and it is constitutively expressed within a subpopulation of DRG neurones. p75NTR has been implicated in mediating the degeneration of these neurones after axotomy. In this study, we characterize the expression of p75NTR in sensory neurones of the newborn rat DRG using immunohistochemistry. Furthermore, we investigate the change in constitutive expression pattern of p75NTR in these neurones following axotomy. In the C7 and C8 DRG of the newborn rat, p75NTR is expressed in approximately 70% of DRG neurones. Those expressing p75NTR can be classified into subpopulations with moderate or intense p75NTR expression, each present in approximately equal proportions. Whilst p75NTR expression is observed in neurones throughout the entire neuronal diameter range, a correlation exists between neuronal diameter and p75NTR expression intensity. We also found that the most vulnerable population following axotomy were those sensory neurones which constitutively express the highest levels of p75NTR, i.e. the large-diameter neurones. PMID:12647872

  13. Metformin represses drug-induced expression of CYP2B6 by modulating the constitutive androstane receptor signaling.

    PubMed

    Yang, Hui; Garzel, Brandy; Heyward, Scott; Moeller, Timothy; Shapiro, Paul; Wang, Hongbing

    2014-02-01

    Metformin is currently the most widely used drug for the treatment of type 2 diabetes. Mechanistically, metformin interacts with many protein kinases and transcription factors that alter the expression of numerous downstream target genes governing lipid metabolism, cell proliferation, and drug metabolism. The constitutive androstane receptor (CAR, NR1i3), a known xenobiotic sensor, has recently been recognized as a novel signaling molecule, in that its activation could be regulated by protein kinases in addition to the traditional ligand binding. We show that metformin could suppress drug-induced expression of CYP2B6 (a typical target gene of CAR) by modulating the phosphorylation status of CAR. In human hepatocytes, metformin robustly suppressed the expression of CYP2B6 induced by both indirect (phenobarbital) and direct CITCO [6-(4-chlorophenyl)imidazo[2,1-b]1,3thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime] activators of human CAR. Mechanistic investigation revealed that metformin specifically enhanced the phosphorylation of threonine-38 of CAR, which blocks CAR nuclear translocation and activation. Moreover, we showed that phosphorylation of CAR by metformin was primarily an AMP-activated protein kinase- and extracellular signal-regulated kinase 1/2-dependent event. Additional two-hybrid and coimmunoprecipitation assays demonstrated that metformin could also disrupt CITCO-mediated interaction between CAR and the steroid receptor coactivator 1 or the glucocorticoid receptor-interacting protein 1. Our results suggest that metformin is a potent repressor of drug-induced CYP2B6 expression through specific inhibition of human CAR activation. Thus, metformin may affect the metabolism and clearance of drugs that are CYP2B6 substrates. PMID:24252946

  14. Constitutive expression of B7 restores immunogenicity of tumor cells expressing truncated major histocompatibility complex class II molecules.

    PubMed Central

    Baskar, S; Ostrand-Rosenberg, S; Nabavi, N; Nadler, L M; Freeman, G J; Glimcher, L H

    1993-01-01

    The inability of the autologous host to reject resident tumor cells is frequently the result of inadequate generation of tumor-specific T cells. Specific activation of T cells occurs after delivery of two signals by the antigen-presenting cell. The first signal is antigen-specific and is the engagement of the T-cell antigen receptor by a specific major histocompatibility complex antigen-peptide complex. For some T cells, the second or costimulatory signal is the interaction of the T-cell CD28 receptor with the B7 activation molecule of the antigen-presenting cell. In the present study, we demonstrate that mouse sarcoma cells genetically engineered to provide both T-cell activation signals stimulate potent tumor-specific CD4+ T cells that cause rejection of both engineered and wild-type neoplastic cells. Two other recent studies have also demonstrated that costimulation via B7 can improve tumor immunity. However, our study differs from these reports by two important observations. (i) One of these studies utilized mouse tumor cells expressing xenogenic viral antigens, and hence, the results are not applicable to wild-type resident tumors. Our study, however, demonstrates that coexpression of B7 by major histocompatibility complex class II+ tumor cells induces immunity in the autologous host that is specific for naturally occurring tumor antigens of poorly immunogenic tumors. (ii) In both earlier studies, only CD8+ T cells were activated after coexpression of B7, whereas in the present report, tumor-specific CD4+ T cells are generated. This report therefore illustrates the role of B7 activation molecule in stimulating potent tumor-specific CD4+ T cells that mediate rejection of wild-type tumors and provides a theoretical basis for immunotherapy of established tumors. PMID:7685909

  15. Comparative Expression Profiling of Leishmania: Modulation in Gene Expression between Species and in Different Host Genetic Backgrounds

    PubMed Central

    Depledge, Daniel P.; Evans, Krystal J.; Ivens, Alasdair C.; Aziz, Naveed; Maroof, Asher; Kaye, Paul M.; Smith, Deborah F.

    2009-01-01

    Background Genome sequencing of Leishmania species that give rise to a range of disease phenotypes in the host has revealed highly conserved gene content and synteny across the genus. Only a small number of genes are differentially distributed between the three species sequenced to date, L. major, L. infantum and L. braziliensis. It is not yet known how many of these genes are expressed in the disease-promoting intracellular amastigotes of these species or whether genes conserved between the species are differentially expressed in the host. Methods/Principal Findings We have used customised oligonucleotide microarrays to confirm that all of the differentially distributed genes identified by genome comparisons are expressed in intracellular amastigotes, with only a few of these subject to regulation at the RNA level. In the first large-scale study of gene expression in L. braziliensis, we show that only ?9% of the genes analysed are regulated in their RNA expression during the L. braziliensis life cycle, a figure consistent with that observed in other Leishmania species. Comparing amastigote gene expression profiles between species confirms the proposal that Leishmania transcriptomes undergo little regulation but also identifies conserved genes that are regulated differently between species in the host. We have also investigated whether host immune competence influences parasite gene expression, by comparing RNA expression profiles in L. major amastigotes derived from either wild-type (BALB/c) or immunologically compromised (Rag2?/? ?c?/?) mice. While parasite dissemination from the site of infection is enhanced in the Rag2?/? ?c?/? genetic background, parasite RNA expression profiles are unperturbed. Conclusion/Significance These findings support the hypothesis that Leishmania amastigotes are pre-adapted for intracellular survival and undergo little dynamic modulation of gene expression at the RNA level. Species-specific parasite factors contributing to virulence and pathogenicity in the host may be limited to the products of a small number of differentially distributed genes or the differential regulation of conserved genes, either of which are subject to translational and/or post-translational controls. PMID:19582145

  16. Constitutive expression of prostaglandin endoperoxide G\\/H synthetase (PGHS)-2 but not PGHS-1 in hum an tracheal epithelial cells in vitro

    Microsoft Academic Search

    Ronald W. Walenga; Mark Kester; Emanuel Coroneos; Sarah Butcher; Rohit Dwivedi; Christopher Statt

    1996-01-01

    Primary cultures of human tracheal epithelial (HTE) cells cultured in vitro, in defined serum-free media, express prostaglandin endoperoxide G\\/H synthase (PGHS) activity and produce prostaglandin E2 (PGE2). In contrast to every other cell type studied to date, HTE cells appear to constitutively express PGHS-2, the ‘inducible’ form of the enzyme, while expressing little or no PGHS-1, the ‘housekeeping’ isoenzyme in

  17. The constitutive expression of Arabidopsis plasmodesmal-associated class 1 reversibly glycosylated polypeptide impairs plant development and virus spread

    PubMed Central

    Zavaliev, Raul; Sagi, Guy; Gera, Abed; Epel, Bernard L.

    2010-01-01

    Arabidopsis class 1 reversibly glycosylated polypeptides (C1RGPs) were shown to be plasmodesmal-associated proteins. Transgenic tobacco (Nicotiana tabacum) plants constitutively expressing GFP tagged AtRGP2 under the control of the CaMV 35S promoter are stunted, have a rosette-like growth pattern, and in source leaves exhibit strong chlorosis, increased photoassimilate retention and starch accumulation that results in elevated leaf specific fresh and dry weights. Basal callose levels around plasmodesmata (Pd) of leaf epidermal cells in transgenic plants are higher than in WT. Such a phenotype is characteristic of virus-infected plants and some transgenic plants expressing Pd-associated viral movement proteins (MP). The local spread of Tobacco mosaic virus (TMV) is inhibited in AtRGP2:GFP transgenics compared to WT. Taken together these observations suggest that overexpression of the AtRGP2:GFP leads to a reduction in Pd permeability to photoassimilate, thus lowering the normal rate of translocation from source leaves to sink organs. Such a reduction may also inhibit the local cell-to-cell spread of viruses in transgenic plants. The observed reduction in Pd permeability could be due to a partial Pd occlusion caused either by the accumulation of AtRGP2:GFP fusion in Pd, and/or by constriction of Pd by the excessive callose accumulation. PMID:19887501

  18. Human small intestinal epithelial cells constitutively express the key elements for antigen processing and the production of exosomes.

    PubMed

    Lin, X P; Almqvist, N; Telemo, E

    2005-01-01

    In humans, the small intestinal epithelial cells (IEC) have a high constitutive expression of MHC class II (MHC II), and contains lysosomes. The IEC also contains MHC II rich multivesicular compartments and has been shown to produce exosomes. This suggests a role for the IEC in antigen processing and presentation either directly or indirectly by the production of exosomes. However, the presence and localisation in the IEC of other key molecules involved in this process has not been studied previously. In the present work, we have investigated small intestinal biopsies from healthy adults and the HT29 IEC cell line with monoclonal antibodies against molecules involved in the antigen processing/presenting systems and molecules typically found on exosomes derived from professional APCs and IECs. Immunohistology was performed to study the expression and localisation of MHC II (HLA-DR), HLA-DM, MHC I (HLA-ABC), CD1d, Invariant chain, Lamp-1, CD68, CD63, B7.1, B7.2, ICAM-1, Cathepsin D/S/L and the IEC specific marker A33 in the IECs. We found that the IECs from the biopsies constitutively express MHC II, HLA-DM, MHC I, Invariant chain, Lamp-1, CD 68, CD63 and A33, and these markers were also found in the IFN-g treated HT-29 cells. All these molecules were found apically in the IECs of the biopsies, localised mainly in vesicular structures. Interestingly, in the baso-latereral area of the IEC, only MHC II, MHC I, Lamp 1, CD68, CD63 and A33 were found and also here with vesicular staining pattern which matches the molecules previously found on exosomes derived professional APCs and human IEC lines. CD1d, B7, ICAM-1, CD9 and cathepsin D and L were absent in the IEC compartment, but cathepsin S showed a relatively weak staining in the apical part of the IEC. The staining pattern and the morphological localisation of these markers suggest a prominent antigen processing/loading and trafficking compartment, and a possible baso-lateral release of exosomes in the normal human IEC. PMID:16027013

  19. Cloning of a heat stress transcription factor, CphsfB1, that is constitutively expressed in radicles and is heat-inducible in the leaves of Carica papaya

    Microsoft Academic Search

    Kazuhiko Tarora; Moritoshi Tamaki; Ayano Shudo; Naoya Urasaki; Hideo Matsumura; Shinichi Adaniya

    2010-01-01

    We used polymerase chain reaction (PCR) to clone the Carica papaya heat stress transcription factor gene, Cphsf. Phylogenetic analysis showed that Cphsf protein, named CphsfB1, is a homolog\\u000a of Lycopersicon peruvianum HsfB1. Northern blot analysis revealed that CphsfB1 is constitutively expressed in radicles and is heat-inducible in leaves.\\u000a The blast program embedded CphsfB1 in a gene cluster constituting four genes:

  20. The Host Environment Promotes the Constitutive Activation of Nuclear Factor-kB and Proinflammatory Cytokine Expression during Metastatic Tumor Progression of Murine Squamous Cell Carcinoma1

    Microsoft Academic Search

    Gang Dong; Zhong Chen; Taiji Kato; Carter Van Waes

    1999-01-01

    We reported previously that tumor cells isolated from metastases of the in vitro transformed squamous cell carcinoma line Pam 212 exhibit an elevation in constitutive production of proinflammatory cytokines inter- leukin (IL)-1a, IL-6, granulocyte-macrophage colony-stimulating factor, and KC (the murine homologue of chemokine Gro-a). The basis for constitutive expression of these cytokines after tumor progression in vivo is unknown. Regulation

  1. Constitutive migration and expression of three protease systems define in vitro the malignant phenotype of Ha-ras transformed rat liver epithelial cells.

    PubMed

    Zoller, J; Bauhofer, A; Crabb, J; Seebacher, T; Geimer, P; Schramke, H; Bade, E

    1996-02-01

    The analysis of migration and gene expression patterns of normal and Ha-ras transformed rat liver epithelial cells revealed differences of diagnostic relevance. The normal cells are induced to migrate by EGF/TGF alpha and to express a set of secreted proteins including fibronectin, EIP-1/PAI-1, and MEP cathepsin L, which the malignant, constitutively migratory cells express constitutively. Only the transformed cells produce proteins of Mr 58/60,000 identified by peptide sequencing as stromelysin-1. The constitutively migratory cells produce invasive tumors and, after intravenous injection, metastatic colonies in the lung ('experimental metastasis'). The results demonstrate specific differences between the migration/invasion of normal and malignant epithelial cells, with PAI-1 as a general biochemical marker for migration/invasion. Constitutive migration and the described gene expression pattern are proposed as in vitro indicators of an invasive phenotype. EGF inducibility of the transformed cells to maximal migration and to an increased expression of stromelysin indicates susceptibility to a paracrine stimulation of malignancy. PMID:21544365

  2. Ortho-aminoazotoluene activates mouse constitutive androstane receptor (mCAR) and increases expression of mCAR target genes

    SciTech Connect

    Smetanina, Mariya A., E-mail: maria.smetanina@gmail.com [Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030 (United States); Laboratory of Gene Expression Control, Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, prospekt Lavrentyeva 10, Novosibirsk 630090 (Russian Federation); Group of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences, prospekt Lavrentyeva 8, Novosibirsk 630090 (Russian Federation); Pakharukova, Mariya Y. [Laboratory of Gene Expression Control, Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, prospekt Lavrentyeva 10, Novosibirsk 630090 (Russian Federation); Kurinna, Svitlana M. [Department of Biochemistry and Molecular Biology, Unit 1000, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030 (United States); Dong, Bingning; Hernandez, Juan P.; Moore, David D. [Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030 (United States); Merkulova, Tatyana I. [Laboratory of Gene Expression Control, Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, prospekt Lavrentyeva 10, Novosibirsk 630090 (Russian Federation)

    2011-08-15

    2'-3-dimethyl-4-aminoazobenzene (ortho-aminoazotoluene, OAT) is an azo dye and a rodent carcinogen that has been evaluated by the International Agency for Research on Cancer (IARC) as a possible (class 2B) human carcinogen. Its mechanism of action remains unclear. We examined the role of the xenobiotic receptor Constitutive Androstane Receptor (CAR, NR1I3) as a mediator of the effects of OAT. We found that OAT increases mouse CAR (mCAR) transactivation in a dose-dependent manner. This effect is specific because another closely related azo dye, 3'-methyl-4-dimethyl-aminoazobenzene (3'MeDAB), did not activate mCAR. Real-time Q-PCR analysis in wild-type C57BL/6 mice revealed that OAT induces the hepatic mRNA expression of the following CAR target genes: Cyp2b10, Cyp2c29, Cyp3a11, Ugt1a1, Mrp4, Mrp2 and c-Myc. CAR-null (Car{sup -/-}) mice showed no increased expression of these genes following OAT treatment, demonstrating that CAR is required for their OAT dependent induction. The OAT-induced CAR-dependent increase of Cyp2b10 and c-Myc expression was confirmed by Western blotting. Immunohistochemistry analysis of wild-type and Car{sup -/-} livers showed that OAT did not acutely induce hepatocyte proliferation, but at much later time points showed an unexpected CAR-dependent proliferative response. These studies demonstrate that mCAR is an OAT xenosensor, and indicate that at least some of the biological effects of this compound are mediated by this nuclear receptor. - Highlights: > The azo dye and mouse carcinogen OAT is a very effective mCAR activator. > OAT increases mCAR transactivation in a dose-dependent manner. > OAT CAR-dependently increases the expression of a specific subset of CAR target genes. > OAT induces an unexpectedly deferred, but CAR-dependent hepatocyte proliferation.

  3. Female Mice Expressing Constitutively Active Mutants of FSH Receptor Present with a Phenotype of Premature Follicle Depletion and Estrogen Excess

    PubMed Central

    Peltoketo, Hellevi; Strauss, Leena; Karjalainen, Riikka; Zhang, Meilin; Stamp, Gordon W.; Segaloff, Deborah L.; Poutanen, Matti; Huhtaniemi, Ilpo T.

    2010-01-01

    Strong gain-of-function mutations have not been identified in humans in the FSH receptor (FSHR), whereas such mutations are common among many other G protein-coupled receptors. In order to predict consequences of such mutations on humans, we first identified constitutively activated mutants of the mouse (m) Fshr and then expressed them under the human anti-Müllerian hormone promoter in transgenic mice or created knock-in mutation into the mouse genome. We show here that mutations of Asp580 in the mFSHR significantly increase the basal receptor activity. D580H and D580Y mutations of mFSHR bind FSH, but the activity of the former is neither ligand-dependent nor promiscuous towards LH/human choriogonadotropin stimulation. Transgenic expression of mFshrD580H in granulosa cells leads to abnormal ovarian structure and function in the form of hemorrhagic cysts, accelerated loss of small follicles, augmented granulosa cell proliferation, increased estradiol biosynthesis, and occasional luteinized unruptured follicles or teratomas. The most affected mFshrD580H females are infertile with disturbed estrous cycle and decreased gonadotropin and increased prolactin levels. Increased estradiol and prolactin apparently underlie the enhanced development of the mammary glands, adenomatous pituitary growth, and lipofuscin accumulation in the adrenal gland. The influence of the mFSHRD580Y mutation is milder, mainly causing hemorrhagic cysts in transgenic mFSHRD580Y and mFSHRD580Y -knock-in mice. The results demonstrate that gain-of-function mutations of the FSHR in mice bring about distinct and clear changes in ovarian function, informative in the search of similar mutations in humans. PMID:20172968

  4. Evolution of Escherichia coli for maximum HOCl resistance through constitutive expression of the OxyR regulon.

    PubMed

    Gundlach, Jasmin; Winter, Jeannette

    2014-08-01

    Exposure of cells to stress impairs cellular functions and may cause killing or adaptation. Adaptation can be facilitated by stress-induced mutagenesis or epigenetic changes, i.e. phenotypic variation without mutations. Upon exposure to HOCl, which is produced by the innate immune system upon bacterial infection, bacteria trigger stress responses that enable increased survival against the stress. Here, we addressed the question whether bacteria can adapt to high HOCl doses and if so, how the acquired resistance is facilitated. We evolved Escherichia coli cells for maximum HOCl resistance by successively increasing the HOCl concentration in the cultivation medium. HOCl-resistant cells showed broad stress resistance but did not carry any chromosomal mutations as revealed by whole-genome sequencing. According to proteome analysis and analysis of transcript levels of stress-related genes, HOCl resistance was accompanied by altered levels of outer-membrane proteins A, C, F and W, and, most prominently, a constitutively expressed OxyR regulon. Induction of the OxyR regulon is facilitated by a partially oxidized OxyR leading to increased levels of antioxidant proteins such as Dps, AhpC/AhpF and KatG. These changes were maintained in evolved strains even when they were cultivated without stress for a prolonged time, indicating epigenetic changes contributed to stress resistance. This indicated that maximum HOCl resistance was conferred by the accumulated action of the OxyR stress response and other factors such as altered levels of outer-membrane proteins. PMID:24899627

  5. Functional ability of cytoskeletal ? - actin regulator to drive constitutive and ubiquitous expression of a fluorescent reporter throughout the life cycle of transgenic marine medaka Oryzias dancena

    Microsoft Academic Search

    Young Sun Cho; Sang Yoon Lee; Youn Kyoung Kim; Dong Soo Kim; Yoon Kwon Nam

    Marine medaka Oryzias dancena, a candidate model organism, represents many attractive merits as a material for experimental transgenesis and\\/or heterologous\\u000a expression assay particularly in the field of ecotoxicology and developmental biology. In this study, cytoskeletal ?-actin gene was characterized from O. dancena and the functional capability of its promoter to drive constitutive expression of foreign reporter protein was evaluated.\\u000a The

  6. Process optimization of constitutive human granulocyte–macrophage colony-stimulating factor (hGM-CSF) expression in Pichia pastoris fed-batch culture

    Microsoft Academic Search

    Yogender Pal; Amardeep Khushoo; K. J. Mukherjee

    2006-01-01

    Human granulocyte–macrophage colony-stimulating factor (hGM-CSF) is a therapeutically important cytokine that is poorly expressed\\u000a because of its toxic effects on the host cells. Extracellular expression of hGM-CSF was obtained by cloning its gene in Pichia pastoris under the constitutive glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter with an N-terminal ? peptide sequence for\\u000a its extracellular production. The clones obtained were screened for a

  7. Translocation of constitutively expressed heat shock protein Hsc70 to synapse-enriched areas of the cerebral cortex after hyperthermic stress

    Microsoft Academic Search

    Sheng Chen; Ian R. Brown

    2007-01-01

    Hsp70 is a multi-gene family composed of stress-induci- ble members (Hsp70) and other members that are consti- tutively expressed (Hsc70). The heat shock proteins Hsp70 and Hsc70 exhibit similar molecular structure and biochemical functions. Constitutively expressed Hsc70 is enriched in the mammalian nervous system compared with non-neural tissues and present at high levels in neu- ronal cell bodies. After thermal

  8. Transient Cardiac Expression of Constitutively Active Galpha q Leads to Hypertrophy and Dilated Cardiomyopathy by Calcineurin-Dependent and Independent Pathways

    Microsoft Academic Search

    U. Mende; A. Kagen; A. Cohen; J. Aramburu; F. J. Schoen; E. J. Neer

    1998-01-01

    Cardiac hypertrophy and dilatation can result from stimulation of signal transduction pathways mediated by heterotrimeric G proteins, especially Gq, whose alpha subunit activates phospholipase Cbeta (PLCbeta ). We now report that transient, modest expression of a hemagglutinin (HA) epitope-tagged, constitutively active mutant of the Gqalpha subunit (HAalpha q*) in hearts of transgenic mice is sufficient to induce cardiac hypertrophy and

  9. Constitutive Expression of Tert in Thymocytes Leads to Increased Incidence and Dissemination of T-Cell Lymphoma in Lck-Tert Mice

    PubMed Central

    Canela, Andrés; Martín-Caballero, Juan; Flores, Juana M.; Blasco, María A.

    2004-01-01

    Here we describe a new mouse model with constitutive expression of the catalytic subunit of telomerase (Tert) targeted to thymocytes and peripheral T cells (Lck-Tert mice). Two independent Lck-Tert mouse lines showed higher incidences of spontaneous T-cell lymphoma than the corresponding age-matched wild-type controls, indicating that constitutive expression of Tert promotes lymphoma. Interestingly, T-cell lymphomas in Lck-Tert mice were more disseminated than those in wild-type controls and affected both lymphoid and nonlymphoid tissues, while nonlymphoid tissues were never affected with lymphoma in age-matched wild-type controls. Importantly, these roles of Tert constitutive expression in promoting tumor progression and dissemination were independent of the role of telomerase in telomere length maintenance, since telomere length distributions on a single-cell basis were identical in Lck-Tert and wild-type thymocytes. Finally, Tert constitutive expression did not interfere with telomere capping in Lck-Tert primary thymocytes, although it resulted in greater chromosomal instability upon gamma irradiation in Lck-Tert primary lymphocytes than in controls, suggesting that Tert overexpression may interfere with the cellular response to DNA damage. PMID:15121848

  10. Genetic Background Modulates Gene Expression Profile Induced by Skin Irradiation in Ptch1 Mice

    SciTech Connect

    Galvan, Antonella; Noci, Sara [Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale Tumori, Milan (Italy); Mancuso, Mariateresa; Pazzaglia, Simonetta; Saran, Anna [ENEA Laboratories, Rome (Italy); Dragani, Tommaso A. [Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale Tumori, Milan (Italy)], E-mail: tommaso.dragani@istitutotumori.mi.it

    2008-12-01

    Purpose: Ptch1 germ-line mutations in mice predispose to radiation-induced basal cell carcinoma of the skin, with tumor incidence modulated by the genetic background. Here, we examined the possible mechanisms underlying skin response to radiation in F1 progeny of Ptch1{sup neo67/+} mice crossed with either skin tumor-susceptible (Car-S) or -resistant (Car-R) mice and X-irradiated (3 Gy) at 2 days of age or left untreated. Methods and Materials: We conducted a gene expression profile analysis in mRNA samples extracted from the skin of irradiated or control mice, using Affymetrix whole mouse genome expression array. Confirmation of the results was done using real-time reverse-transcriptase polymerase chain reaction. Results: Analysis of the gene expression profile of normal skin of F1 mice at 4 weeks of age revealed a similar basal profile in the nonirradiated mice, but alterations in levels of 71 transcripts in irradiated Ptch1{sup neo67/+} mice of the Car-R cross and modulation of only eight genes in irradiated Ptch1{sup neo67/+} mice of the Car-S cross. Conclusions: These results indicate that neonatal irradiation causes a persistent change in the gene expression profile of the skin. The tendency of mice genetically resistant to skin tumorigenesis to show a more complex pattern of transcriptional response to radiation than do genetically susceptible mice suggests a role for this response in genetic resistance to basal cell tumorigenesis.

  11. Impairments in cognition and neural precursor cell proliferation in mice expressing constitutively active glycogen synthase kinase-3

    PubMed Central

    Pardo, Marta; King, Margaret K.; Perez-Costas, Emma; Melendez-Ferro, Miguel; Martinez, Ana; Beurel, Eleonore; Jope, Richard S.

    2015-01-01

    Brain glycogen synthase kinase-3 (GSK3) is hyperactive in several neurological conditions that involve impairments in both cognition and neurogenesis. This raises the hypotheses that hyperactive GSK3 may directly contribute to impaired cognition, and that this may be related to deficiencies in neural precursor cells (NPC). To study the effects of hyperactive GSK3 in the absence of disease influences, we compared adult hippocampal NPC proliferation and performance in three cognitive tasks in male and female wild-type (WT) mice and GSK3 knockin mice, which express constitutively active GSK3. NPC proliferation was ~40% deficient in both male and female GSK3 knockin mice compared with WT mice. Environmental enrichment (EE) increased NPC proliferation in male, but not female, GSK3 knockin mice and WT mice. Male and female GSK3 knockin mice exhibited impairments in novel object recognition, temporal order memory, and coordinate spatial processing compared with gender-matched WT mice. EE restored impaired novel object recognition and temporal ordering in both sexes of GSK3 knockin mice, indicating that this repair was not dependent on NPC proliferation, which was not increased by EE in female GSK3 knockin mice. Acute 1 h pretreatment with the GSK3 inhibitor TDZD-8 also improved novel object recognition and temporal ordering in male and female GSK3 knockin mice. These findings demonstrate that hyperactive GSK3 is sufficient to impair adult hippocampal NPC proliferation and to impair performance in three cognitive tasks in both male and female mice, but these changes in NPC proliferation do not directly regulate novel object recognition and temporal ordering tasks. PMID:25788881

  12. Up-regulation of phosphoinositide metabolism in tobacco cells constitutively expressing the human type I inositol polyphosphate 5-phosphatase

    NASA Technical Reports Server (NTRS)

    Perera, Imara Y.; Love, John; Heilmann, Ingo; Thompson, William F.; Boss, Wendy F.; Brown, C. S. (Principal Investigator)

    2002-01-01

    To evaluate the impact of suppressing inositol 1,4,5-trisphosphate (InsP(3)) in plants, tobacco (Nicotiana tabacum) cells were transformed with the human type I inositol polyphosphate 5-phosphatase (InsP 5-ptase), an enzyme which specifically hydrolyzes InsP(3). The transgenic cell lines showed a 12- to 25-fold increase in InsP 5-ptase activity in vitro and a 60% to 80% reduction in basal InsP(3) compared with wild-type cells. Stimulation with Mas-7, a synthetic analog of the wasp venom peptide mastoparan, resulted in an approximately 2-fold increase in InsP(3) in both wild-type and transgenic cells. However, even with stimulation, InsP(3) levels in the transgenic cells did not reach wild-type basal values, suggesting that InsP(3) signaling is compromised. Analysis of whole-cell lipids indicated that phosphatidylinositol 4,5-bisphosphate (PtdInsP(2)), the lipid precursor of InsP(3), was greatly reduced in the transgenic cells. In vitro assays of enzymes involved in PtdInsP(2) metabolism showed that the activity of the PtdInsP(2)-hydrolyzing enzyme phospholipase C was not significantly altered in the transgenic cells. In contrast, the activity of the plasma membrane PtdInsP 5 kinase was increased by approximately 3-fold in the transgenic cells. In vivo labeling studies revealed a greater incorporation of (32)P into PtdInsP(2) in the transgenic cells compared with the wild type, indicating that the rate of PtdInsP(2) synthesis was increased. These studies show that the constitutive expression of the human type I InsP 5-ptase in tobacco cells leads to an up-regulation of the phosphoinositide pathway and highlight the importance of PtdInsP(2) synthesis as a regulatory step in this system.

  13. A Bacterial Biosensor for Oxidative Stress Using the Constitutively Expressed Redox-Sensitive Protein roGFP2

    PubMed Central

    Arias-Barreiro, Carlos R.; Okazaki, Keisuke; Koutsaftis, Apostolos; Inayat-Hussain, Salmaan H.; Tani, Akio; Katsuhara, Maki; Kimbara, Kazuhide; Mori, Izumi C.

    2010-01-01

    A highly specific, high throughput-amenable bacterial biosensor for chemically induced cellular oxidation was developed using constitutively expressed redox-sensitive green fluorescent protein roGFP2 in E. coli (E. coli-roGFP2). Disulfide formation between two key cysteine residues of roGFP2 was assessed using a double-wavelength ratiometric approach. This study demonstrates that only a few minutes were required to detect oxidation using E. coli-roGFP2, in contrast to conventional bacterial oxidative stress sensors. Cellular oxidation induced by hydrogen peroxide, menadione, sodium selenite, zinc pyrithione, triphenyltin and naphthalene became detectable after 10 seconds and reached the maxima between 80 to 210 seconds, contrary to Cd2+, Cu2+, Pb2+, Zn2+ and sodium arsenite, which induced the oxidation maximum immediately. The lowest observable effect concentrations (in ppm) were determined as 1.0 × 10?7 (arsenite), 1.0 × 10?4 (naphthalene), 1.0 × 10?4 (Cu2+), 3.8 × 10?4 (H2O2), 1.0 × 10?3 (Cd2+), 1.0 × 10?3 (Zn2+), 1.0 × 10?2 (menadione), 1.0 (triphenyltin), 1.56 (zinc pyrithione), 3.1 (selenite) and 6.3 (Pb2+), respectively. Heavy metal-induced oxidation showed unclear response patterns, whereas concentration-dependent sigmoid curves were observed for other compounds. In vivo GSH content and in vitro roGFP2 oxidation assays together with E. coli-roGFP2 results suggest that roGFP2 is sensitive to redox potential change and thiol modification induced by environmental stressors. Based on redox-sensitive technology, E. coli-roGFP2 provides a fast comprehensive detection system for toxicants that induce cellular oxidation. PMID:22163550

  14. Destabilizing Protein Polymorphisms in the Genetic Background Direct Phenotypic Expression of Mutant SOD1 Toxicity

    PubMed Central

    Gidalevitz, Tali; Krupinski, Thomas; Garcia, Susana; Morimoto, Richard I.

    2009-01-01

    Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease phenotype. Mutations in SOD1 in a subset of familial amyotrophic lateral sclerosis (ALS) cases confer dominant but clinically variable toxicity, thought to be mediated by misfolding and aggregation of mutant SOD1 protein. While the mechanism of toxicity remains unknown, both the nature of the SOD1 mutation and the genetic background in which it is expressed appear important. To address this, we established a Caenorhabditis elegans model to systematically examine the aggregation behavior and genetic interactions of mutant forms of SOD1. Expression of three structurally distinct SOD1 mutants in C. elegans muscle cells resulted in the appearance of heterogeneous populations of aggregates and was associated with only mild cellular dysfunction. However, introduction of destabilizing temperature-sensitive mutations into the genetic background strongly enhanced the toxicity of SOD1 mutants, resulting in exposure of several deleterious phenotypes at permissive conditions in a manner dependent on the specific SOD1 mutation. The nature of the observed phenotype was dependent on the temperature-sensitive mutation present, while its penetrance reflected the specific combination of temperature-sensitive and SOD1 mutations. Thus, the specific toxic phenotypes of conformational disease may not be simply due to misfolding/aggregation toxicity of the causative mutant proteins, but may be defined by their genetic interactions with cellular pathways harboring mildly destabilizing missense alleles. PMID:19266020

  15. Strain background influences neurotoxicity and behavioral abnormalities in mice expressing the tetracycline transactivator

    PubMed Central

    Han, Harry J.; Allen, Carolyn C.; Buchovecky, Christie M.; Yetman, Michael J.; Born, Heather A.; Marin, Miguel A.; Rodgers, Shaefali P.; Song, Bryan J.; Lu, Hui-Chen; Justice, Monica J.; Probst, Frank J.; Jankowsky, Joanna L.

    2012-01-01

    The tet-off system has been widely used to create transgenic models of neurological disorders including Alzheimer’s, Parkinson’s, Huntington’s, and prion disease. The utility of this system lies in the assumption that the tetracycline transactivator (TTA) acts as an inert control element and does not contribute to phenotypes under study. Here we report that neuronal expression of TTA can affect hippocampal cytoarchitecture and behavior in a strain-dependent manner. While studying neurodegeneration in two tet-off Alzheimer’s disease models, we unexpectedly discovered neuronal loss within the dentate gyrus of single transgenic TTA controls. Granule neurons appeared most sensitive to TTA exposure during postnatal development, and doxycycline treatment during this period was neuroprotective. TTA-induced degeneration could be rescued by moving the transgene onto a congenic C57BL/6J background, and recurred on re-introduction of either CBA or C3H/He backgrounds. Quantitative trait analysis of B6C3 F2 TTA mice identified a region on Chromosome 14 that contains a major modifier of the neurodegenerative phenotype. Although B6 mice were resistant to degeneration, they were not ideal for cognitive testing. F1 offspring of TTA C57BL/6J and 129X1/SvJ, FVB/NJ, or DBA/1J showed improved spatial learning, but TTA expression caused subtle differences in contextual fear conditioning on two of these backgrounds indicating that strain and genotype can interact independently under different behavioral settings. All model systems have limitations that should be recognized and mitigated where possible; our findings stress the importance of mapping the effects caused by TTA alone when working with tet-off models. PMID:22855807

  16. Constitutive expression of endothelin in bronchial epithelial cells of patients with symptomatic and asymptomatic asthma and modulation by histamine and interleukin-1

    Microsoft Academic Search

    Victoria Ackerman; Sandro Carpi; Alberto Bellini; Giovanni Vassalli; Maurizio Marini; Sabrina Mattoli

    1995-01-01

    Background: An upregulation of endothelin-1 expression occurs in bronchial epithelial cells of asthmatic patients. This peptide may mediate bronchoconstriction in asthma, but the mechanisms that modulate endothelin-1 synthesis and release are unknown. Objective: This study was done to compare the pattern of endothelin-1 expression in patients with symptomatic and asymptomatic asthma and evaluate the ability of inflammatory factors to upregulate

  17. Constitutively active erythropoietin receptor expression in breast cancer cells promotes cellular proliferation and migration through a MAP-kinase dependent pathway

    SciTech Connect

    Fu Ping; Jiang Xiaohong [Department of Medicine, Hematology-Medical Oncology, Duke University Medical Center, DUMC Box 3912, Durham, NC 27710 (United States); Arcasoy, Murat O. [Department of Medicine, Hematology-Medical Oncology, Duke University Medical Center, DUMC Box 3912, Durham, NC 27710 (United States)], E-mail: arcas001@mc.duke.edu

    2009-02-13

    The role of erythropoietin receptor (EpoR) expression in tumor cells and the potential of EpoR-mediated signaling to contribute to cellular proliferation and invasiveness require further characterization. To determine whether EpoR expression and activation in tumor cells modulates intracellular signal transduction to promote cellular proliferation and migration, we employed a novel experimental model using human breast cancer cells engineered to stably express a constitutively active EpoR-R129C variant. EpoR-R129C expression resulted in increased cellular proliferation and migration of breast cancer cells and these effects were associated with significantly increased Epo-induced phosphorylation of ERK1/2, AKT and c-Jun-NH2-kinase (SAPK/JNK) proteins. Expression of the constitutively active EpoR-R129C receptor promoted the proliferation and migration of breast cancer cells via activation of ERK- and SAPK/JNK-dependent signaling pathways, respectively. These findings suggest that EpoR over-expression and activation in breast cancer cells has the potential to contribute to tumor progression by promoting the proliferation and invasiveness of the neoplastic cells.

  18. Constitutive expression of Campylobacter jejuni truncated hemoglobin CtrHb improves the growth of Escherichia coli cell under aerobic and anaerobic conditions.

    PubMed

    Yang, Jiang-Ke; Xiong, Wei; Xu, Li; Li, Jia; Zhao, Xiu-Ju

    2015-01-01

    Bacteria hemoglobin could bind to the oxygen, transfer it from the intracellular microenvironment to the respiration process and sustain the energy for the metabolism and reproduction of cells. Heterologous expression of bacteria hemoglobin gene could improve the capacity of the host on oxygen-capturing and allow it to grow even under microaerophilic condition. To develop a system based on hemoglobin to help bacteria cells overcome the oxygen shortage in fermentation, in this study, Campylobacter jejuni truncated hemoglobin (CtrHb) gene was synthesized and expressed under the control of constitutive expression promoters P2 and PSPO1-II in Escherichia coli. As showed by the growth curves of the two recombinants P2-CtrHb and PSPO1-II-CtrHb, constitutive expression of CtrHb improved cell growth under aerobic shaking-flasks, anaerobic capped-bottles and bioreactor conditions. According to the NMR analysis, this improvement might come from the expression of hemoglobin which could boost the metabolism of cells by supplying more oxygen to the respiratory chain processes. Through semi-quantitative RT-PCR and CO differential spectrum assays, we further discussed the connection between the growth patterns of the recombinants, the expression level of CtrHb and oxygen binding capacity of CtrHb in cells. Based on the growth patterns of these recombinants in bioreactor, a possible choice on different type of recombinants under specific fermentation conditions was also suggested in this study. PMID:26047918

  19. Antisense Suppression of a (+)-?-Cadinene Synthase Gene in Cotton Prevents the Induction of This Defense Response Gene during Bacterial Blight Infection But Not Its Constitutive Expression1[w

    PubMed Central

    Townsend, Belinda J.; Poole, Andrew; Blake, Christopher J.; Llewellyn, Danny J.

    2005-01-01

    In cotton (Gossypium hirsutum) the enzyme (+)-?-cadinene synthase (CDNS) catalyzes the first committed step in the biosynthesis of cadinane-type sesquiterpenes, such as gossypol, that provide constitutive and inducible protection against pests and diseases. A cotton cDNA clone encoding CDNS (cdn1-C4) was isolated from developing embryos and functionally characterized. Southern analysis showed that CDNS genes belong to a large multigene family, of which five genomic clones were studied, including three pseudogenes and one gene that may represent another subfamily of CDNS. CDNS expression was shown to be induced in cotton infected with either the bacterial blight or verticillium wilt pathogens. Constructs for the constitutive or seed-specific antisense suppression of cdn1-C4 were introduced into cotton by Agrobacterium-mediated transformation. Gossypol levels were not reduced in the seeds of transformants with either construct, nor was the induction of CDNS expression affected in stems of the constitutive antisense plants infected with Verticillium dahliae Kleb. However, the induction of CDNS mRNA and protein in response to bacterial blight infection of cotyledons was completely blocked in the constitutive antisense plants. These results suggest that cdn1-C4 may be involved specifically in the bacterial blight response and that the CDNS multigene family comprises a complex set of genes differing in their temporal and spatial regulation and responsible for different branches of the cotton sesquiterpene pathway. PMID:15849309

  20. Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB\\/ATF proteins

    Microsoft Academic Search

    T. Herdegen; J. D. Leah

    1998-01-01

    This article reviews findings up to the end of 1997 about the inducible transcription factors (ITFs) c-Jun, JunB, JunD, c-Fos, FosB, Fra-1, Fra-2, Krox-20 (Egr-2) and Krox-24 (NGFI-A, Egr-1, Zif268); and the constitutive transcription factors (CTFs) CREB, CREM, ATF-2 and SRF as they pertain to gene expression in the mammalian nervous system. In the first part we consider basic facts

  1. Constitutive expression of a fungal glucose oxidase gene in transgenic tobacco confers chilling tolerance through the activation of antioxidative defence system

    Microsoft Academic Search

    Subbiyan Maruthasalam; Yi Lun Liu; Ching Mei Sun; Pei Ying Chen; Chih Wen Yu; Pei Fang Lee; Chin Ho Lin

    2010-01-01

    Scientific evidences in the literature have shown that plants treated exogenously with micromole concentration of hydrogen\\u000a peroxide (H2O2) acquire abiotic stress tolerance potential, without substantial disturbances in the endogenous H2O2 pool. In this study, we enhanced the endogenous H2O2 content of tobacco (Nicotiana tabaccum L. cv. SR1) plants by the constitutive expression of a glucose oxidase (GO; EC 1.1.3.4) gene

  2. Direct tensor expression by Eulerian approach for constitutive relations based on strain invariants in transversely isotropic green elasticity - finite extension and torsion 

    E-print Network

    Song, Min Jae

    2009-05-15

    DIRECT TENSOR EXPRESSION BY EULERIAN APPROACH FOR CONSTITUTIVE RELATIONS BASED ON STRAIN INVARIANTS IN TRANSVERSELY ISOTROPIC GREEN ELASTICITY: FINITE EXTENSION AND TORSION A Thesis by MIN JAE SONG Submitted to the Office of Graduate Studies... IN TRANSVERSELY ISOTROPIC GREEN ELASTICITY: FINITE EXTENSION AND TORSION A Thesis by MIN JAE SONG Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Approved by: Chair...

  3. Immunologic Self-Tolerance Maintained by CD25 1 CD4 1 Regulatory T Cells Constitutively Expressing Cytotoxic T Lymphocyte-associated Antigen 4

    Microsoft Academic Search

    Takeshi Takahashi; Tomoyuki Tagami; Sayuri Yamazaki; Toshimitsu Uede; Jun Shimizu; Noriko Sakaguchi; Tak W. Mak; Shimon Sakaguchi

    This report shows that cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a key role in T cell-mediated dominant immunologic self-tolerance. In vivo blockade of CTLA-4 for a limited period in normal mice leads to spontaneous development of chronic organ-specific au- toimmune diseases, which are immunopathologically similar to human counterparts. In normal naive mice, CTLA-4 is constitutively expressed on CD25 1

  4. Lytic susceptibility of target cells to cytotoxic T cells is determined by their constitutive major histocompatibility complex class I antigen expression and cytokine-induced activation status

    PubMed Central

    Ritter, M.; Huber, C.; Auböck, J.; Pohl-Markl, H.; Troppmair, I.; Herold, M.; Gächter, A.; Nussbaumer, W.; Böck, G.; Nachbaur, D.; Westhoff, U.; Eibl, B.; Schwaighofer, H.; Thaler, J.; Grosse-Wilde, H.; Niederwieser, D.

    1994-01-01

    Cytotoxic T-cell lines (TCL) were raised in vitro using stimulator cells with a defined major histocompatibility complex (MHC) mismatch and tested in a cytotoxic chromium-release assay against haemopoietic and non-haemopoietic target cells from the original stimulator. Monoclonal antibody (mAb)-blocking experiments and simultaneous determination of MHC class I, class II, lymphocyte function-associated antigen-1 (LFA-1) and intracellular adhesion molecule-1 (ICAM-1) density by quantitative radioimmunometric methods and flow cytometry on target cells demonstrated that lysis was restricted by MHC class I and dependent upon the constitutive MHC class I antigen expression. Measurements showed a high constitutive expression of class I MHC antigens on peripheral blood mononuclear cells (PBMC), but a low one on keratinocytes (K). Also, PBMC were more susceptible to lysis by TCL than K. Interferon-? (IFN-?) treatment of K resulted in increased MHC class I antigen expression and enhanced lytic susceptibility to TCL. IFN-? and tumour necrosis factor-? (TNF-?) treatment, which did not modulate MHC class I antigen expression on K, did not influence the amount of K lysis either. None of the cytokines tested in this analysis, however, increased the expression of MHC class I, class II, ICAM-1 and LFA-1 on PBMC. Only IFN? pretreatment showed a minimal, statistically significant increase in MHC class I antigen expression. In spite of the minimal effect of IFN-? and no effect of IFN-? on class I MHC expression, pretreatment of target cells with both cytokines considerably increased their lytic susceptibility. The mechanism of cytokine-induced enhanced lytic susceptibility to TCL was not explained by increased MHC class I, LFA-1 or ICAM-1 expression, since no correlation was found between surface expression of these molecules and lytic susceptibility to TCL. These data demonstrate that: (1) the constitutive density of MHC class I antigens determines the extent of TCL lysis; (2) IFN-?, and not IFN-? or TNF-?, controls the amount of K target cell lysis by increasing their MHC class I antigen expression; and (3) IFN-? and IFN-? control the amount of PBMC target cell lysis by a mechanism independent of MHC class I, ICAM-1 or LFA-1 expression. PMID:7913694

  5. Significance of p53 expression in background endometrium in endometrial carcinoma.

    PubMed

    Nguyen, Thuy Thi; Hachisuga, Toru; Urabe, Rie; Kurita, Tomoko; Kagami, Seiji; Kawagoe, Toshinori; Shimajiri, Shohei; Nabeshima, Kazuki

    2015-06-01

    The p53 signature (p53S) has been proposed to be a marker of the earliest phase of development of endometrial serous carcinoma. We examined the presence of p53S in the background endometrium in cases of endometrial carcinoma. From a series of 351 endometrial carcinomas, 225 (64.1 %) lesions, for which slides of the adjacent noncancerous endometrium were available for review, were included. Expression of estrogen receptor (ER)-alpha, Ki-67, and p53 in the adjacent endometrium was studied by immunohistochemistry. The p53S was defined as the presence of morphologically benign endometrial epithelial cells with moderate to strong intensity of p53 immunostaining. Of the 225 noncancerous endometrium samples, 34 consisted of hyperplastic and 191 of non-hyperplastic endometrium. A p53S was found in 22 cases (mean age 64.2 years), 2 in hyperplastic, and 20 in non-hyperplastic background endometrium. All p53S-positive cases also expressed ER-alpha; their median Ki-67 labeling index (LI) was 4.0 % (range 0.0 to 21.0 %). The two cases with hyperplastic p53S-positive background endometrium were in association with a grade 1 endometrioid tumor in a premenopausal woman with Lynch syndrome. Of the 152 cases of endometrioid adenocarcinomas with non-hyperplastic endometrium, 12 (8 %) were p53S positive, none of which associated with EIC. Of the 21 cases of serous carcinoma, five (24 %) were p53S positive, 4 of which (19 %) associated with EIC while in 5 others (24 %) EIC was found without p53S. Of three clear cell adenocarcinomas, none were p53S positive while two contained EIC without p53S. Of 15 carcinosarcomas, 3 (20 %) were p53S positive, all of which with EIC while 6 others (40 %) were associated with EIC but without p53S. Of the 8 non-endometrioid tumors with p53S, 7 (88 %) were associated with EIC. p53S is thought to be associated with precancerous lesions of non-endometrioid tumors, including carcinosarcomas. PMID:25788166

  6. Cell, Vol. 93, 12071217, June 26, 1998, Copyright 1998 by Cell Press Constitutive Expression of the CIRCADIAN CLOCK

    E-print Network

    Tobin, Elaine

    /b-protein (Lhcb) gene. Expression of the such as leaves and petals, stomata opening, stem elon- CCA1 gene and have a peakloop that is closely associated with the circadian clock level of expression in the morning

  7. Inducible but Not Constitutive Expression of PD-L1 in Human Melanoma Cells Is Dependent on Activation of NF-?B

    PubMed Central

    Gowrishankar, Kavitha; Gunatilake, Dilini; Gallagher, Stuart J.; Tiffen, Jessamy; Rizos, Helen; Hersey, Peter

    2015-01-01

    Monoclonal antibodies against immune checkpoint blockade have proven to be a major success in the treatment of melanoma. The programmed death receptor-1 ligand-1 (PD-L1) expression on melanoma cells is believed to have an inhibitory effect on T cell responses and to be an important escape mechanism from immune attack. Previous studies have shown that PD-L1 can be expressed constitutively or can be induced by IFN-? secreted by infiltrating lymphocytes. In the present study we have investigated the mechanism underlying these two modes of PD-L1 expression in melanoma cells including cells that had acquired resistance to the BRAF inhibitor vemurafenib. PD-L1 expression was examined by flow cytometry and immunoblotting. Specific inhibitors and siRNA knockdown approaches were used to examine the roles of the RAF/ MEK, PI3K, NF-?B, STAT3 and AP1/ c-Jun pathways. IFN-? inducible expression of PD-L1 was dependent on NF-?B as shown by inhibition with BMS-345541, an inhibitor of I?B and the BET protein inhibitor I-BET151, as well as by siRNA knockdown of NF-?B subunits. We were unable to implicate the BRAF/MEK pathway as major regulators in PD-L1 expression on vemurafenib resistant cells. Similarly the PI3K/AKT pathway and the transcription factors STAT3 and c-Jun had only minor roles in IFN-? induced expression of PD-L1. The mechanism underlying constitutive expression remains unresolved. We suggest these results have significance in selection of treatments that can be used in combination with monoclonal antibodies against PD1, to enhance their effectiveness and to reduce inhibitory effects melanoma cells have against cytotoxic T cell activity. PMID:25844720

  8. Uropathic Observations in Mice Expressing a Constitutively Active Point Mutation in the 5HT3A Receptor Subunit

    Microsoft Academic Search

    Anindya Bhattacharya; Hong Dang; Quan-Ming Zhu; Birthe Schnegelsberg; Nora Rozengurt; Gary Cain; Rachelle Prantil; David A. Vorp; Nicholas Guy; David Julius; Anthony P. D. W. Ford; Henry A. Lester; Debra A. Cockayne

    2004-01-01

    Mutant mice with a hypersensitive serotonin (5-HT)3A receptor were generated through targeted exon replacement. A valine to serine mutation (V13S) in the channel-lining M2 domain of the 5-HT3A receptor subunit rendered the 5-HT3 receptor70-fold more sensitive to serotonin and produced constitutive activity when combined with the 5-HT3B subunit. Mice homozygous for the mutant allele (5- HT3A vs\\/vs ) had decreased

  9. Constitutive knox1 gene expression in dandelion ( Taraxacum officinale , Web.) changes leaf morphology from simple to compound

    Microsoft Academic Search

    Kai J. Müller; Xinqiang He; Rainer Fischer; Dirk Prüfer

    2006-01-01

    Seed plants with compound leaves constitute a polyphyletic group, but studies of diverse taxa show that genes of the class 1 KNOTTED-LIKE HOMEOBOX (KNOX1) family are often involved in compound leaf development. This suggests that knox1 genes have been recruited on multiple occasions during angiosperm evolution (Bharathan et al. in Science 296:1858–1860, 2002). In agreement with this, we demonstrate that

  10. Constitutive Uncoupling of Pathways of Gene Expression That Control Growth and Differentiation in Myeloid Leukemia: A Model for the Origin and Progression of Malignancy

    NASA Astrophysics Data System (ADS)

    Sachs, Leo

    1980-10-01

    Chemical carcinogens and tumor promoters have pleiotropic effects. Tumor initiators can produce a variety of mutations and tumor promoters can regulate a variety of physiological molecules that control growth and differentiation. The appropriate mutation and the regulation of the appropriate molecules to induce cell growth can initiate and promote the sequence of changes required for transformation of normal cells into malignant cells. After this sequence of changes, some tumors can still be induced to revert with a high frequency from a malignant phenotype to a nonmalignant phenotype. Results obtained from analysis of regulation of growth and differentiation in normal and leukemic myeloid cells, the phenotypic reversion of malignancy by induction of normal differentiation in myeloid leukemia, and the blocks in differentiation-defective leukemic cell mutants have been used to propose a general model for the origin and progression of malignancy. The model states that malignancy originates by changing specific pathways of gene expression required for growth from inducible to constitutive in cells that can still be induced to differentiate normally by the physiological inducer of differentiation. The malignant cells, unlike the normal cells, then no longer require the physiological inducer for growth. This changes the requirements for growth and uncouples growth from differentiation. Constitutive expression of other specific pathways can uncouple other controls, which then causes blocks in differentiation and the further progression of malignancy. The existence of specific constitutive pathways of gene expression that uncouple controls in malignant cells can also explain the expression of fetal proteins, hormones, and some other specialized products of normal development in various types of tumors.

  11. Constitution Daily

    NSDL National Science Digital Library

    Everyone could use a bit of the Constitution added to their daily lives, and this website more than delivers on its promise to deliver "smart conversation about the Constitution". Constitution Daily is an experimental blog edited by the National Constitution Center (NCC) in Philadelphia, and commentary here can include conversations about student privacy rights, the Second Amendment, and the activities of Congress. Visitors can click on the "Issues" section to dive into topic areas that include civility and privacy. After looking at each topic area, visitors can look at an interactive timeline that arranges comments, posts, and discussion on the subject. The site also contains some nice polls, and information about upcoming events at the NCC.

  12. Development of Non-Antibiotic-Resistant, Chromosomally Based, Constitutive and Inducible Expression Systems for aroA-Attenuated Salmonella enterica Serovar Typhimurium ?

    PubMed Central

    Matic, Jake N.; Terry, Tamsin D.; Van Bockel, David; Maddocks, Tracy; Tinworth, David; Jennings, Michael P.; Djordjevic, Steven P.; Walker, Mark J.

    2009-01-01

    Live-vaccine delivery systems expressing two model antigens from Mycoplasma hyopneumoniae, F2P97 (Adh) and NrdF, were constructed using Salmonella enterica serovar Typhimurium aroA (STM-1), and immunogenicity in mice was evaluated. Recombinant plasmid-based expression (PBE) and chromosomally based expression (CBE) systems were constructed. The PBE system was formed by cloning both antigen genes into pJLA507 to create an operon downstream of temperature-inducible promoters. Constitutive CBE was achieved using a promoter-trapping technique whereby the promoterless operon was stably integrated into the chromosome of STM-1, and the expression of antigens was assessed. The chromosomal position of the operon was mapped in four clones. Inducible CBE was obtained by using the in vivo-induced sspA promoter and recombining the expression construct into aroD. Dual expression of the antigens was detected in all systems, with PBE producing much larger quantities of both antigens. The stability of antigen expression after in vivo passage was 100% for all CBE strains recovered. PBE and CBE strains were selected for comparison in a vaccination trial. The vaccine strains were delivered orally into mice, and significant systemic immunoglobulin M (IgM) and IgG responses against both antigens were detected among all CBE groups. No significant immune response was detected using PBE strains. Expression of recombinant antigens in S. enterica serovar Typhimurium aroA from chromosomally located strong promoters without the use of antibiotic resistance markers is a reliable and effective method of inducing a significant immune response. PMID:19223478

  13. Human eosinophils constitutively express multiple Th1, Th2, and immunoregulatory cytokines that are secreted rapidly and differentially

    PubMed Central

    Spencer, Lisa A.; Szela, Craig T.; Perez, Sandra A. C.; Kirchhoffer, Casey L.; Neves, Josiane S.; Radke, Amy L.; Weller, Peter F.

    2009-01-01

    Eosinophils are innate immune leukocytes implicated in the initiation and maintenance of type 2 immune responses, including asthma and allergy. The ability to store and rapidly secrete preformed cytokines distinguishes eosinophils from most lymphocytes, which must synthesize cytokine proteins prior to secretion and may be a factor in the apparent Th2 bias of eosinophils. Multiple studies confirm that human eosinophils from atopic or hypereosinophilic donors can secrete over 30 cytokines with a varying and often opposing immune-polarizing potential. However, it remains unclear whether all of these cytokines are constitutively preformed and available for rapid secretion from eosinophils in the circulation of healthy individuals or are restricted to eosinophils from atopic donors. Likewise, the relative concentrations of cytokines stored within eosinophils have not been studied. Here, we demonstrate that human blood eosinophils are not singularly outfitted with Th2-associated cytokines but rather, constitutively store a cache of cytokines with nominal Th1, Th2, and regulatory capacities, including IL-4, IL-13, IL-6, IL-10, IL-12, IFN-?, and TNF-?. We demonstrate further rapid and differential release of each cytokine in response to specific stimuli. As agonists, strong Th1 and inflammatory cytokines elicited release of Th2-promoting IL-4 but not Th1-inducing IL-12. Moreover, a large quantity of IFN-? was secreted in response to Th1, Th2, and inflammatory stimuli. Delineations of the multifarious nature of preformed eosinophil cytokines and the varied stimulus-dependent profiles of rapid cytokine secretion provide insights into the functions of human eosinophils in mediating inflammation and initiation of specific immunity. PMID:18840671

  14. Linkage and expression analysis to elucidate the genetic background of muscle structure and meat quality in the pig

    Microsoft Academic Search

    KLAUS WIMMERS; NGUYEN TRONG NGU; EDUARD MURANI; KARL SCHELLANDER; SIRILUCK PONSUKSILI

    2006-01-01

    Genome scans are the most general approaches to identify genomic regions exhibiting quantitative trait loci, QTL, without prior hypothesis of the physiology and genetic control of a trait. Function-oriented expression analyses are a complementary approach to derive hypotheses of the physiologic and genetic background of phenotypic variation. The proportion of muscle fibre types and their size affect body composition traits,

  15. The Constitution: Perspectives on Contemporary American Democracy.

    ERIC Educational Resources Information Center

    Close Up Foundation, Arlington, VA.

    Four articles expressing the views of nine prominent United States citizens about the Constitution provide a context for reflecting on the meaning of the Constitution in present-day America. In "Why Has the Constitution Endured So Long?" Don Edwards, chairman of the House Civil and Constitutional Rights Subcommittee, discusses why the Constitution

  16. Constitutive Smad signaling and Smad-dependent collagen gene expression in mouse embryonic fibroblasts lacking peroxisome proliferator-activated receptor-{gamma}

    SciTech Connect

    Ghosh, Asish K [Northwestern University Feinberg School of Medicine, Division of Rheumatology, 240 East Huron Street, Chicago, IL 60611 (United States)], E-mail: a-ghosh2@northwestern.edu; Wei, Jun; Wu, Minghua [Northwestern University Feinberg School of Medicine, Division of Rheumatology, 240 East Huron Street, Chicago, IL 60611 (United States); Varga, John [Northwestern University Feinberg School of Medicine, Division of Rheumatology, 240 East Huron Street, Chicago, IL 60611 (United States)], E-mail: j-varga@northwestern.edu

    2008-09-19

    Transforming growth factor-{beta} (TGF-{beta}), a potent inducer of collagen synthesis, is implicated in pathological fibrosis. Peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) is a nuclear hormone receptor that regulates adipogenesis and numerous other biological processes. Here, we demonstrate that collagen gene expression was markedly elevated in mouse embryonic fibroblasts (MEFs) lacking PPAR-{gamma} compared to heterozygous control MEFs. Treatment with the PPAR-{gamma} ligand 15d-PGJ{sub 2} failed to down-regulate collagen gene expression in PPAR-{gamma} null MEFs, whereas reconstitution of these cells with ectopic PPAR-{gamma} resulted in their normalization. Compared to control MEFs, PPAR-{gamma} null MEFs displayed elevated levels of the Type I TGF-{beta} receptor (T{beta}RI), and secreted more TGF-{beta}1 into the media. Furthermore, PPAR-{gamma} null MEFs showed constitutive phosphorylation of cellular Smad2 and Smad3, even in the absence of exogenous TGF-{beta}, which was abrogated by the ALK5 inhibitor SB431542. Constitutive Smad2/3 phosphorylation in PPAR-{gamma} null MEFs was associated with Smad3 binding to its cognate DNA recognition sequences, and interaction with coactivator p300 previously implicated in TGF-{beta} responses. Taken together, these results indicate that loss of PPAR-{gamma} in MEFs is associated with upregulation of collagen synthesis, and activation of intracellular Smad signal transduction, due, at least in part, to autocrine TGF-{beta} stimulation.

  17. Constitutive uncoupling of pathways of gene expression that control growth and differentiation in myeloid leukemia: a model for the origin and progression of malignancy.

    PubMed Central

    Sachs, L

    1980-01-01

    Chemical carcinogens and tumor promoters have pleiotropic effects. Tumor initiators can produce a variety of mutations and tumor promotres can regulate a variety of physiological molecles that control growth and differentiation. The appropriate mutation and the regulation of the appropriate molecules to induce cell growth can initiate and promote the sequence of changes required for transformation of normal cells into malignant cells. After this sequence of changes, some tumors can still be induced to revert with a high frequency from a malignant phenotype to a nonmalignant phenotype. Results obtained from analysis of regulation of growth and differentiation in normal and leukemic myeloid cells, the phenotypic reversion of malignancy by induction of normal differentiation in myeloid leukemia, and the blocks in differentiation-defective leukemic cell mutants have been used to propose a general model for the origin and progression of malignancy. The model states that malignancy originates by changing specific pathways of gene expresion required for growth from inducible to constitutive in cells that can still be induced to differentiate normally by the physiological inducer of differentiation. The malignant cells, unlike the normal cells, then no longer require the physiological inducer for growth. This changes the requirements for growth and uncouples growth from differentiation. Constitutive expression of other specific pathways can uncouple other controls, which then causes blocks in differentiation and the further progression of malignancy. The existence of specific constitutive pathways of gene expression that uncouple controls in malignant cells can also exlain the expresion of fetal proteins, hormones, and some other specialized products of normal development in various types of tumors. PMID:6934543

  18. Constitutive expression of HIF-? plays a major role in generation of clear-cell phenotype in human primary and metastatic renal carcinoma.

    PubMed

    Tóth, Károly; Chintala, Sreenivasulu; Rustum, Youcef M

    2014-10-01

    The extensive lipid accumulation occurring in clear-cell renal cell carcinoma (ccRCC) results in a clear-cell cytoplasm. Hypoxia-inducible factor ? (HIF-?) is constitutively expressed in many ccRCC and transcriptionally regulates >100 genes. In a recent breakthrough study, HIF-1? induced ccRCC in transgenic mice. On the basis of these findings, we developed a hypothesis that accounted for HIF-? generation of the clear-cell phenotype. The aim of the present study was to use immunohistochemical staining methods in tissue microarray to determine the extent to which the clear-cell phenotype coincided with HIF-? expression in primary and metastatic ccRCC. In addition, we studied whether the prolyl-hydroxylases (PHD2,3) play a role in promoting the elevated expression of HIF-? in tumor cells. The clear-cell phenotype was observed in all primary and metastatic cases of ccRCC examined. A total of 168 renal cell carcinomas were evaluated by immunohistochemical methods; 141 of the 168 (84%) tumors expressed HIF-? (HIF-1? and/or HIF-2?). In contrast, HIF-? was expressed in only 1 of the 23 (4%) non-ccRCCs. These data supported the hypothesis that in the majority of the tumors HIF-? expression overlapped with the clear-cell phenotype and was indicative of an HIF-?-mediated lipid accumulation. In a smaller percentage of ccRCC cases (16%), HIF-? was not detected in the tumor cells and suggested that lipid accumulation by HIF-?-lipid-independent process. PHD3 was undetectable in both primary and metastatic ccRCC cases. We concluded that the undetectable PHD3 could contribute to the higher HIF-? expression in ccRCC. PMID:25046225

  19. Ectopic expression of CsCTR1, a cucumber CTR-like gene, attenuates constitutive ethylene signaling in an Arabidopsis ctr1-1 mutant and expression pattern analysis of CsCTR1 in cucumber (Cucumis sativus).

    PubMed

    Bie, Beibei; Sun, Jin; Pan, Junsong; He, Huanle; Cai, Run

    2014-01-01

    The gaseous plant hormone ethylene regulates many aspects of plant growth, development and responses to the environment. Constitutive triple response 1 (CTR1) is a central regulator involved in the ethylene signal transduction pathway. To obtain a better understanding of this particular pathway in cucumber, the cDNA-encoding CTR1 (designated CsCTR1) was isolated from cucumber. A sequence alignment and phylogenetic analyses revealed that CsCTR1 has a high degree of homology with other plant CTR1 proteins. The ectopic expression of CsCTR1 in the Arabidopsis ctr1-1 mutant attenuates constitutive ethylene signaling of this mutant, suggesting that CsCTR1 indeed performs its function as negative regulator of the ethylene signaling pathway. CsCTR1 is constitutively expressed in all of the examined cucumber organs, including roots, stems, leaves, shoot apices, mature male and female flowers, as well as young fruits. CsCTR1 expression gradually declined during male flower development and increased during female flower development. Additionally, our results indicate that CsCTR1 can be induced in the roots, leaves and shoot apices by external ethylene. In conclusion, this study provides a basis for further studies on the role of CTR1 in the biological processes of cucumber and on the molecular mechanism of the cucumber ethylene signaling pathway. PMID:25226540

  20. Constitutive Expression of the Vi Polysaccharide Capsular Antigen in Attenuated Salmonella enterica Serovar Typhi Oral Vaccine Strain CVD 909

    Microsoft Academic Search

    JIN YUAN WANG; FERNANDO R. NORIEGA; JAMES E. GALEN; EILEEN BARRY; MYRON M. LEVINE

    2000-01-01

    Live oral Ty21a and parenteral Vi polysaccharide vaccines provide significant protection against typhoid fever, albeit by distinct immune mechanisms. Vi stimulates serum immunoglobulin G Vi antibodies, whereas Ty21a, which does not express Vi, elicits humoral and cell-mediated immune responses other than Vi anti- bodies. Protection may be enhanced if serum Vi antibody as well as cell-mediated and humoral responses can

  1. Constitution Annotated

    NSDL National Science Digital Library

    2013-06-26

    What exactly does the United States Constitution mean? It is subject, of course, to ongoing meditation, debate, argument, and interpretation. This useful site provides one lens of interpretation of the Constitution, based primarily on Supreme Court case law and legal analysis. Visitors can look over each section of the Constitution individually, including all of the articles and amendments. Additionally, the site contains a complete table of Supreme Court cases, along with those cases that have been overruled as well as proposed amendments that have not been ratified. Additionally, the site contains a gallery of significant primary source documents from American history. Interested users should not forget to download the helpful app that is also included here.

  2. Long noncoding RNA expression profiles in gut tissues constitute molecular signatures that reflect the types of microbes.

    PubMed

    Liang, Lunxi; Ai, Luoyan; Qian, Jin; Fang, Jing-Yuan; Xu, Jie

    2015-01-01

    The gut microbiota is commonly referred to as a hidden organ due to its pivotal effects on host physiology, metabolism, nutrition and immunity. The gut microbes may be shaped by environmental and host genetic factors, and previous studies have focused on the roles of protein-coding genes. Here we show a link between long non-coding RNA (lncRNA) expression and gut microbes. By repurposing exon microarrays and comparing the lncRNA expression profiles between germ-free, conventional and different gnotobiotic mice, we revealed subgroups of lncRNAs that were specifically enriched in each condition. A nearest shrunken centroid methodology was applied to obtain lncRNA-based signatures to identify mice in different conditions. The lncRNA-based prediction model successfully identified different gnotobiotic mice from conventional and germ-free mice, and also discriminated mice harboring transplanted microbes from fecal samples of mice or zebra fishes. To achieve optimal prediction accuracy, fewer lncRNAs were required in the prediction model than protein-coding genes. Taken together, our study demonstrated the effecacy of lncRNA expression profiles in discriminating the types of microbes in the gut. These results also provide a resource of gut microbe-associated lncRNAs for the development of lncRNA biomarkers and the identification of functional lncRNAs in host-microbes interactions. PMID:26123364

  3. Long noncoding RNA expression profiles in gut tissues constitute molecular signatures that reflect the types of microbes

    PubMed Central

    Liang, Lunxi; Ai, Luoyan; Qian, Jin; Fang, Jing-Yuan; Xu, Jie

    2015-01-01

    The gut microbiota is commonly referred to as a hidden organ due to its pivotal effects on host physiology, metabolism, nutrition and immunity. The gut microbes may be shaped by environmental and host genetic factors, and previous studies have focused on the roles of protein-coding genes. Here we show a link between long non-coding RNA (lncRNA) expression and gut microbes. By repurposing exon microarrays and comparing the lncRNA expression profiles between germ-free, conventional and different gnotobiotic mice, we revealed subgroups of lncRNAs that were specifically enriched in each condition. A nearest shrunken centroid methodology was applied to obtain lncRNA-based signatures to identify mice in different conditions. The lncRNA-based prediction model successfully identified different gnotobiotic mice from conventional and germ-free mice, and also discriminated mice harboring transplanted microbes from fecal samples of mice or zebra fishes. To achieve optimal prediction accuracy, fewer lncRNAs were required in the prediction model than protein-coding genes. Taken together, our study demonstrated the effecacy of lncRNA expression profiles in discriminating the types of microbes in the gut. These results also provide a resource of gut microbe-associated lncRNAs for the development of lncRNA biomarkers and the identification of functional lncRNAs in host-microbes interactions. PMID:26123364

  4. Expression of Constitutively Active CDK1 Stabilizes APC-Cdh1 Substrates and Potentiates Premature Spindle Assembly and Checkpoint Function in G1 Cells

    PubMed Central

    Wyatt, William R.; Pomerening, Joseph R.

    2012-01-01

    Mitotic progression in eukaryotic cells depends upon the activation of cyclin-dependent kinase 1 (CDK1), followed by its inactivation through the anaphase-promoting complex (APC)/cyclosome-mediated degradation of M-phase cyclins. Previous work revealed that expression of a constitutively active CDK1 (CDK1AF) in HeLa cells permitted their division, but yielded G1 daughter cells that underwent premature S-phase and early mitotic events. While CDK1AF was found to impede the sustained activity of APC-Cdh1, it was unknown if this defect improperly stabilized mitotic substrates and contributed to the occurrence of these premature M phases. Here, we show that CDK1AF expression in HeLa cells improperly stabilized APC-Cdh1 substrates in G1-phase daughter cells, including mitotic kinases and the APC adaptor, Cdc20. Division of CDK1AF-expressing cells produced G1 daughters with an accelerated S-phase onset, interrupted by the formation of premature bipolar spindles capable of spindle assembly checkpoint function. Further characterization of these phenotypes induced by CDK1AF expression revealed that this early spindle formation depended upon premature CDK1 and Aurora B activities, and their inhibition induced rapid spindle disassembly. Following its normal M-phase degradation, we found that the absence of Wee1 in these prematurely cycling daughter cells permitted the endogenous CDK1 to contribute to these premature mitotic events, since expression of a non-degradable Wee1 reduced the number of cells that exhibited premature cyclin B1oscillations. Lastly, we discovered that Cdh1-ablated cells could not be forced into a premature M phase, despite cyclin B1 overexpression and proteasome inhibition. Together, these results demonstrate that expression of constitutively active CDK1AF hampers the destruction of critical APC-Cdh1 targets, and that this type of condition could prevent newly divided cells from properly maintaining a prolonged interphase state. We propose that this more subtle type of defect in activity of the APC-driven negative-feedback loop may have implications for triggering genome instability and tumorigenesis. PMID:22479455

  5. Mitochondria of a human multidrug-resistant hepatocellular carcinoma cell line constitutively express inducible nitric oxide synthase in the inner membrane

    PubMed Central

    Fantappič, Ornella; Sassoli, Chiara; Tani, Alessia; Nosi, Daniele; Marchetti, Serena; Formigli, Lucia; Mazzanti, Roberto

    2015-01-01

    Mitochondria play a crucial role in pathways of stress conditions. They can be transported from one cell to another, bringing their features to the cell where they are transported. It has been shown in cancer cells overexpressing multidrug resistance (MDR) that mitochondria express proteins involved in drug resistance such as P-glycoprotein (P-gp), breast cancer resistant protein and multiple resistance protein-1. The MDR phenotype is associated with the constitutive expression of COX-2 and iNOS, whereas celecoxib, a specific inhibitor of COX-2 activity, reverses drug resistance of MDR cells by releasing cytochrome c from mitochondria. It is possible that COX-2 and iNOS are also expressed in mitochondria of cancer cells overexpressing the MDR phenotype. This study involved experiments using the human HCC PLC/PRF/5 cell line with and without MDR phenotype and melanoma A375 cells that do not express the MDR1 phenotype but they do iNOS. Western blot analysis, confocal immunofluorescence and immune electron microscopy showed that iNOS is localized in mitochondria of MDR1-positive cells, whereas COX-2 is not. Low and moderate concentrations of celecoxib modulate the expression of iNOS and P-gp in mitochondria of MDR cancer cells independently from inhibition of COX-2 activity. However, A375 cells that express iNOS also in mitochondria, were not MDR1 positive. In conclusion, iNOS can be localized in mitochondria of HCC cells overexpressing MDR1 phenotype, however this phenomenon appears independent from the MDR1 phenotype occurrence. The presence of iNOS in mitochondria of human HCC cells phenotype probably concurs to a more aggressive behaviour of cancer cells. PMID:25691007

  6. Mitochondria of a human multidrug-resistant hepatocellular carcinoma cell line constitutively express inducible nitric oxide synthase in the inner membrane.

    PubMed

    Fantappič, Ornella; Sassoli, Chiara; Tani, Alessia; Nosi, Daniele; Marchetti, Serena; Formigli, Lucia; Mazzanti, Roberto

    2015-06-01

    Mitochondria play a crucial role in pathways of stress conditions. They can be transported from one cell to another, bringing their features to the cell where they are transported. It has been shown in cancer cells overexpressing multidrug resistance (MDR) that mitochondria express proteins involved in drug resistance such as P-glycoprotein (P-gp), breast cancer resistant protein and multiple resistance protein-1. The MDR phenotype is associated with the constitutive expression of COX-2 and iNOS, whereas celecoxib, a specific inhibitor of COX-2 activity, reverses drug resistance of MDR cells by releasing cytochrome c from mitochondria. It is possible that COX-2 and iNOS are also expressed in mitochondria of cancer cells overexpressing the MDR phenotype. This study involved experiments using the human HCC PLC/PRF/5 cell line with and without MDR phenotype and melanoma A375 cells that do not express the MDR1 phenotype but they do iNOS. Western blot analysis, confocal immunofluorescence and immune electron microscopy showed that iNOS is localized in mitochondria of MDR1-positive cells, whereas COX-2 is not. Low and moderate concentrations of celecoxib modulate the expression of iNOS and P-gp in mitochondria of MDR cancer cells independently from inhibition of COX-2 activity. However, A375 cells that express iNOS also in mitochondria, were not MDR1 positive. In conclusion, iNOS can be localized in mitochondria of HCC cells overexpressing MDR1 phenotype, however this phenomenon appears independent from the MDR1 phenotype occurrence. The presence of iNOS in mitochondria of human HCC cells phenotype probably concurs to a more aggressive behaviour of cancer cells. PMID:25691007

  7. Constitutive expression of the cytochrome P450 EthABCD monooxygenase system enables degradation of synthetic dialkyl ethers in Aquincola tertiaricarbonis L108.

    PubMed

    Schuster, Judith; Purswani, Jessica; Breuer, Uta; Pozo, Clementina; Harms, Hauke; Müller, Roland H; Rohwerder, Thore

    2013-04-01

    In Rhodococcus ruber IFP 2001, Rhodococcus zopfii IFP 2005, and Gordonia sp. strain IFP 2009, the cytochrome P450 monooxygenase EthABCD catalyzes hydroxylation of methoxy and ethoxy residues in the fuel oxygenates methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME). The expression of the IS3-type transposase-flanked eth genes is ETBE dependent and controlled by the regulator EthR (C. Malandain et al., FEMS Microbiol. Ecol. 72:289-296, 2010). In contrast, we demonstrated by reverse transcription-quantitative PCR (RT-qPCR) that the betaproteobacterium Aquincola tertiaricarbonis L108, which possesses the ethABCD genes but lacks ethR, constitutively expresses the P450 system at high levels even when growing on nonether substrates, such as glucose. The mutant strain A. tertiaricarbonis L10, which is unable to degrade dialkyl ethers, resulted from a transposition event mediated by a rolling-circle IS91-type element flanking the eth gene cluster in the wild-type strain L108. The constitutive expression of Eth monooxygenase is likely initiated by the housekeeping sigma factor ?(70), as indicated by the presence in strain L108 of characteristic -10 and -35 binding sites upstream of ethA which are lacking in strain IFP 2001. This enables efficient degradation of diethyl ether, diisopropyl ether, MTBE, ETBE, TAME, and tert-amyl ethyl ether (TAEE) without any lag phase in strain L108. However, ethers with larger residues, n-hexyl methyl ether, tetrahydrofuran, and alkyl aryl ethers, were not attacked by the Eth system at significant rates in resting-cell experiments, indicating that the residue in the ether molecule which is not hydroxylated also contributes to the determination of substrate specificity. PMID:23354715

  8. Expression of a Constitutively Active Calcineurin Encoded by an Intron-Retaining mRNA in Follicular Keratinocytes

    PubMed Central

    Fujimura, Atsushi; Michiue, Hiroyuki; Nishiki, Tei-ichi; Ohmori, Iori; Wei, Fan-Yan; Matsui, Hideki; Tomizawa, Kazuhito

    2011-01-01

    Hair growth is a highly regulated cyclical process. Immunosuppressive immunophilin ligands such as cyclosporin A (CsA) and FK506 are known as potent hair growth modulatory agents in rodents and humans that induce active hair growth and inhibit hair follicle regression. The immunosuppressive effectiveness of these drugs has been generally attributed to inhibition of T cell activation through well-characterized pathways. Specifically, CsA and FK506 bind to intracellular proteins, principally cyclophilin A and FKBP12, respectively, and thereby inhibit the phosphatase calcineurin (Cn). The calcineurin (Cn)/NFAT pathway has an important, but poorly understood, role in the regulation of hair follicle development. Here we show that a novel-splicing variant of calcineurin Aß CnAß-FK, which is encoded by an intron-retaining mRNA and is deficient in the autoinhibitory domain, is predominantly expressed in mature follicular keratinocytes but not in the proliferating keratinocytes of rodents. CnAß-FK was weakly sensitive to Ca2+ and dephosphorylated NFATc2 under low Ca2+ levels in keratinocytes. Inhibition of Cn/NFAT induced hair growth in nude mice. Cyclin G2 was identified as a novel target of the Cn/NFATc2 pathway and its expression in follicular keratinocytes was reduced by inhibition of Cn/NFAT. Overexpression of cyclin G2 arrested the cell cycle in follicular keratinocytes in vitro and the Cn inhibitor, cyclosporin A, inhibited nuclear localization of NFATc2, resulting in decreased cyclin G2 expression in follicular keratinocytes of rats in vivo. We therefore suggest that the calcineurin/NFAT pathway has a unique regulatory role in hair follicle development. PMID:21423799

  9. Constitutional Conservatism

    ERIC Educational Resources Information Center

    Berkowitz, Peter

    2009-01-01

    After their dismal performance in election 2008, conservatives are taking stock. As they examine the causes that have driven them into the political wilderness and as they explore paths out, they should also take heart. After all, election 2008 shows that America's constitutional order is working as designed. Indeed, while sorting out their errors…

  10. Primary cultures of rat islet capillary endothelial cells. Constitutive and cytokine-inducible macrophagelike nitric oxide synthases are expressed and activities regulated by glucose concentration.

    PubMed Central

    Suschek, C.; Fehsel, K.; Kröncke, K. D.; Sommer, A.; Kolb-Bachofen, V.

    1994-01-01

    We have succeeded in obtaining cultures of pure rat islet capillary endothelial cells. These multiply in vitro and exhibit the same antigenic phenotype as expressed in situ: von Willebrand factorhigh, Ox43 (rat endothelial marker)weak, and Ox2 (thymocyte and brain endothelium marker)high. This phenotype differs from both exocrine endothelium stained in situ and rat aorta endothelial cells cultured in vitro under identical conditions. Islet and aorta endothelial cells were cultured in the presence of various glucose concentrations. Nitrite and citrulline concentrations in culture supernatants were measured as an indirect quantification of nitric oxide formation. In islet endothelia, both nitrite and citrulline levels were found to be strongly glucose-dependent, with high levels at high glucose concentrations and vice versa, in contrast to aorta endothelial cells, where no glucose effect was found. Shifting islet endothelial cultures from high to low glucose levels or the reverse led to a slow decrease or increase in nitrite and citrulline formation with several cell generations needed to reach steady levels. Adding a combination of the cytokines interleukin-1 beta, tumor necrosis factor-alpha, and interferon-gamma to both endothelial cell cultures led to a dramatic increase of nitric oxide formation. Again with islet but not with aorta endothelial cells a modulating effect by glucose concentrations was found. Reverse-transcription-polymerase chain reaction with specific primers demonstrated the presence of constitutively expressed nitric oxide synthase-RNA in the islet capillary endothelial cells and confirmed the glucose effect. In addition, we found that cytokines indeed induce the expression of inducible synthase messenger RNA in both endothelial cells, which was not found in the absence of cytokines. Electron paramagnetic resonance spectroscopy of islet endothelial cells confirmed intracellular synthesis of nitric oxide in the presence of cytokines. In conclusion, we here for the first time provide evidence that constitutive nitric oxide synthase is also expressed in capillary endothelium and that cytokine challenge leads to the expression of the inducible isoform in these cells. Images Figure 1 Figure 2 Figure 4 Figure 9 PMID:7521579

  11. The TLR4 D299G and T399I SNPs are constitutively active to up-regulate expression of Trif-dependent genes.

    PubMed

    Hold, Georgina L; Berry, Susan; Saunders, Karin A; Drew, Janice; Mayer, Claus; Brookes, Heather; Gay, Nick J; El-Omar, Emad M; Bryant, Clare E

    2014-01-01

    Dysregulated Toll-Like Receptor (TLR) signalling and genetic polymorphisms in these proteins are linked to many human diseases. We investigated TLR4 functional variants D299G and T399I to assess the impact on LPS-induced responsiveness in comparison to wild-type TLR4. The mechanism by which this occurs in unclear as these SNPs do not lie within the lipid A binding domain or dimerisation sites of the LPS-TLR4/MD2 receptor complexes. Transfection of TLR4D299G, TLR4T399I or TLR4D299G. T399I into HEK cells resulted in constitutive activation of an NF-?B reporter gene and a blunting of the LPS-induced reporter activation compared to WT-TLR4. Unstimulated human monocyte/macrophages, from patients with the D299G and T399I SNPs demonstrated a downregulation of many genes, particularly Tram/Trif signalling pathway constitutents compared to the TLR4 wild-type subjects supporting the concept of basal receptor activity. Monocyte/macrophages from carriers of the TLR4 D299G and T399I polymorphisms stimulated with LPS showed >6 fold lower levels of NF-?B and ?12 fold higher IFN-? gene expression levels compared to wild-type subjects (P<0.05; MWU test) and dramatically altered resultant cytokine profiles. We conclude that these TLR4 SNPs affect constitutive receptor activity which impacts on the hosts ability to respond to LPS challenge leading to a dysregulated sub-optimal immune response to infection. PMID:25365308

  12. The TLR4 D299G and T399I SNPs Are Constitutively Active to Up-Regulate Expression of Trif-Dependent Genes

    PubMed Central

    Hold, Georgina L.; Berry, Susan; Saunders, Karin A.; Drew, Janice; Mayer, Claus; Brookes, Heather; Gay, Nick J.; El-Omar, Emad M.; Bryant, Clare E.

    2014-01-01

    Dysregulated Toll-Like Receptor (TLR) signalling and genetic polymorphisms in these proteins are linked to many human diseases. We investigated TLR4 functional variants D299G and T399I to assess the impact on LPS-induced responsiveness in comparison to wild-type TLR4. The mechanism by which this occurs in unclear as these SNPs do not lie within the lipid A binding domain or dimerisation sites of the LPS-TLR4/MD2 receptor complexes. Transfection of TLR4D299G, TLR4T399I or TLR4D299G. T399I into HEK cells resulted in constitutive activation of an NF-?B reporter gene and a blunting of the LPS-induced reporter activation compared to WT-TLR4. Unstimulated human monocyte/macrophages, from patients with the D299G and T399I SNPs demonstrated a downregulation of many genes, particularly Tram/Trif signalling pathway constitutents compared to the TLR4 wild-type subjects supporting the concept of basal receptor activity. Monocyte/macrophages from carriers of the TLR4 D299G and T399I polymorphisms stimulated with LPS showed >6 fold lower levels of NF-?B and ?12 fold higher IFN-? gene expression levels compared to wild-type subjects (P<0.05; MWU test) and dramatically altered resultant cytokine profiles. We conclude that these TLR4 SNPs affect constitutive receptor activity which impacts on the hosts ability to respond to LPS challenge leading to a dysregulated sub-optimal immune response to infection. PMID:25365308

  13. Molecular cloning and characterization of PtrLAR3, a gene encoding leucoanthocyanidin reductase from Populus trichocarpa, and its constitutive expression enhances fungal resistance in transgenic plants

    PubMed Central

    Yuan, Li; Wang, Lijun; Han, Zujing; Jiang, Yuanzhong; Zhao, Lili; Liu, Hong; Yang, Li; Luo, Keming

    2012-01-01

    The flavonoid-derived proanthocyanidins (PAs) are one class of the major defence phenolics in poplar leaves. Transcriptional activation of PA biosynthetic genes, resulting in PA accumulation in leaves, was detected following infection by the fungal Marssonina brunnea f.sp. multigermtubi using digital gene expression analysis. In order to study PA biosynthesis and its induction by fungi, a putative leucoanthocyanidin reductase gene, PtrLAR3, was isolated from Populus trichocarpa. Sequence comparison of PtrLAR3 with other known leucoanthocyanidin reductase proteins revealed high amino acid sequence similarity. Semi-quantitative reverse-transcription (RT) PCR and quantitative real-time PCR analysis demonstrated that PtrLAR3 was expressed in various tissues and the highest level of expression was observed in roots. Overexpression of PtrLAR3 in Chinese white poplar (Populus tomentosa Carr.) led to a significant plant-wide increase in PA levels. In vitro assays showed that crude leaf extracts from 35S:PtrLAR3 transformants were able to inhibit significantly the hyphal growth of M. brunnea f.sp. multigermtubi compared to the extracts from control plants. The transgenic 35S:PtrLAR3 poplar plants displayed a significant (P < 0.05) reduction in their disease symptoms compared with the control. RT-PCR analysis showed that PtrLAR3 expression was up-regulated in all transformants. These results suggested that constitutive expression of endogenous PtrLAR3 could be exploited to improve resistance to fungal pathogens in poplar. PMID:22268151

  14. Multiple copies of the Mason–Pfizer monkey virus constitutive RNA transport element lead to enhanced HIV-1 Gag expression in a context-dependent manner

    PubMed Central

    Wodrich, Harald; Schambach, Axel; Kräusslich, Hans-Georg

    2000-01-01

    Retroviral gene expression requires nuclear export and translation of incompletely spliced RNA. In the case of human immunodeficiency virus (HIV), this is facilitated by the viral Rev protein binding to its cognate RNA response element (RRE), while other retroviruses contain constitutive transport elements (CTE) binding to cellular factors. These CTE can substitute for the HIV-1 Rev/RRE system, albeit with reduced efficiency. Here, we show that multimeric copies of the CTE restore HIV-1 protein expression to levels comparable to or higher than Rev/RRE in various cell lines from different species. We suggest that multimerization of export factors is important for CTE function, as reported for Rev. CTE function was not affected when the element was displaced from its natural position close to the poly(A) signal, while insertion of an intron into the 3?-untranslated region (3?-UTR) severely reduced CTE activity. In this case, cytoplasmic RNA degradation was observed, which may be mediated by nonsense-mediated RNA decay. In contrast, Rev-dependent gene expression was insensitive to an intron in the 3?-UTR. Finally, we show that the putative CTE-binding protein RNA helicase A is not specifically translocated into the cytoplasm upon overexpression of CTE-containing RNA. PMID:10648781

  15. Identification of centrarchid hepcidins and evidence that 17?-estradiol disrupts constitutive expression of hepcidin-1 and inducible expression of hepcidin-2 in largemouth bass ( Micropterus salmoides)

    Microsoft Academic Search

    Laura S. Robertson; Luke R. Iwanowicz; Jamie Marie Marranca

    2009-01-01

    Hepcidin is a highly conserved antimicrobial peptide and iron-regulatory hormone. Here, we identify two hepcidin genes (hep-1 and hep-2) in largemouth bass (Micropterus salmoides) and smallmouth bass (Micropterus dolomieu). Hepcidin-1 contains a putative ATCUN metal-binding site in the amino-terminus that is missing in hepcidin-2, suggesting that hepcidin-1 may function as an iron-regulatory hormone. Both hepcidins are predominately expressed in the

  16. A constitutively expressed Myc-like gene involved in anthocyanin biosynthesis from Perilla frutescens: molecular characterization, heterologous expression in transgenic plants and transactivation in yeast cells

    Microsoft Academic Search

    Zhi-Zhong Gong; Emiko Yamagishi; Mami Yamazaki; Kazuki Saito

    1999-01-01

    The coordinate expression of anthocyanin biosynthetic genes in leaves and stems of a red forma of Perilla frutescens is presumably controlled by regulatory gene(s). A Myc-like gene (Myc-rp) was isolated from a cDNA library prepared from the leaves of red P. frutescens, and its deduced amino acid sequence shows 64% identity with that of delila from snapdragon. The Myc-rp gene was

  17. Acetaminophen Modulates P-Glycoprotein Functional Expression at the Blood-Brain Barrier by a Constitutive Androstane Receptor–Dependent Mechanism

    PubMed Central

    Thompson, Brandon J.; Sanchez-Covarrubias, Lucy; Zhang, Yifeng; Laracuente, Mei-Li; Vanderah, Todd W.; Ronaldson, Patrick T.; Davis, Thomas P.

    2013-01-01

    Effective pharmacologic treatment of pain with opioids requires that these drugs attain efficacious concentrations in the central nervous system (CNS). A primary determinant of CNS drug permeation is P-glycoprotein (P-gp), an endogenous blood-brain barrier (BBB) efflux transporter that is involved in brain-to-blood transport of opioid analgesics (i.e., morphine). Recently, the nuclear receptor constitutive androstane receptor (CAR) has been identified as a regulator of P-gp functional expression at the BBB. This is critical to pharmacotherapy of pain/inflammation, as patients are often administered acetaminophen (APAP), a CAR-activating ligand, in conjunction with an opioid. Our objective was to investigate, in vivo, the role of CAR in regulation of P-gp at the BBB. Following APAP treatment, P-gp protein expression was increased up to 1.4–1.6-fold in a concentration-dependent manner. Additionally, APAP increased P-gp transport of BODIPY-verapamil in freshly isolated rat brain capillaries. This APAP-induced increase in P-gp expression and activity was attenuated in the presence of CAR pathway inhibitor okadaic acid or transcriptional inhibitor actinomycin D, suggesting P-gp regulation is CAR-dependent. Furthermore, morphine brain accumulation was enhanced by P-gp inhibitors in APAP-treated animals, suggesting P-gp–mediated transport. A warm-water (50°C) tail-flick assay revealed a significant decrease in morphine analgesia in animals treated with morphine 3 or 6 hours after APAP treatment, as compared with animals treated concurrently. Taken together, our data imply that inclusion of APAP in a pain treatment regimen activates CAR at the BBB and increases P-gp functional expression, a clinically significant drug-drug interaction that modulates opioid analgesic efficacy. PMID:24019224

  18. Many maize genes are expressed in an oat background carrying a specific maize chromosome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oat-maize addition (OMA) lines are derived from oat x maize sexual hybrids in which individual maize chromosomes have been retained in plants containing a full complement of oat chromosomes. Many of the OMA lines display specific phenotypes, which indicate that maize genes are likely expressed and c...

  19. Reduced expression of IL-12 p35 by SJL/J macrophages responding to Theiler's virus infection is associated with constitutive activation of IRF-3

    SciTech Connect

    Dahlberg, Angela [Department of Oral Biology and Nebraska Center for Virology, University of Nebraska Medical Center, 40th and Holdrege Sts., Lincoln, NE 68583-0740 (United States); Auble, Mark R. [Department of Oral Biology and Nebraska Center for Virology, University of Nebraska Medical Center, 40th and Holdrege Sts., Lincoln, NE 68583-0740 (United States); Petro, Thomas M. [Department of Oral Biology and Nebraska Center for Virology, University of Nebraska Medical Center, 40th and Holdrege Sts., Lincoln, NE 68583-0740 (United States)]. E-mail: tpetro@unmc.edu

    2006-09-30

    Macrophages responding to viral infections may contribute to autoimmune demyelinating diseases (ADD). Macrophages from ADD-susceptible SJL/J mice responding to Theiler's Virus (TMEV) infection, the TLR7 agonist loxoribine, or the TLR4 agonist-LPS expressed less IL-12 p35 but more IL-12/23 p40 and IFN-{beta} than macrophages from ADD-resistant B10.S mice. While expression of IRF-1 and -7 was similar between B10.S and SJL/J TMEV-infected macrophages, SJL/J but not B10.S macrophages exhibited constitutively active IRF-3. In contrast to overexpressed IRF-1, IRF-5, and IRF-7, which stimulated p35 promoter reporter activity, overexpressed IRF-3 repressed p35 promoter activity in response to TMEV infection, loxoribine, IFN-{gamma}/LPS, but not IFN-{gamma} alone. IRF-3 lessened but did not eliminate IRF-1-stimulated p35 promoter activity. Repression by IRF-3 required bp -172 to -122 of the p35 promoter. The data suggest that pre-activated IRF-3 is a major factor in the differences in IL-12 production between B10.S and SJL/J macrophages responding to TMEV.

  20. Construction and characterization of stable, constitutively expressed, chromosomal green and red fluorescent transcriptional fusions in the select agents, Bacillus anthracis, Yersinia pestis, Burkholderia mallei, and Burkholderia pseudomallei

    PubMed Central

    Su, Shengchang; Bangar, Hansraj; Saldanha, Roland; Pemberton, Adin; Aronow, Bruce; Dean, Gary E; Lamkin, Thomas J; Hassett, Daniel J

    2014-01-01

    Here, we constructed stable, chromosomal, constitutively expressed, green and red fluorescent protein (GFP and RFP) as reporters in the select agents, Bacillus anthracis, Yersinia pestis, Burkholderia mallei, and Burkholderia pseudomallei. Using bioinformatic approaches and other experimental analyses, we identified P0253 and P1 as potent promoters that drive the optimal expression of fluorescent reporters in single copy in B. anthracis and Burkholderia spp. as well as their surrogate strains, respectively. In comparison, Y. pestis and its surrogate strain need two chromosomal copies of cysZK promoter (P2cysZK) for optimal fluorescence. The P0253-, P2cysZK-, and P1-driven GFP and RFP fusions were first cloned into the vectors pRP1028, pUC18R6KT-mini-Tn7T-Km, pmini-Tn7-gat, or their derivatives. The resultant constructs were delivered into the respective surrogates and subsequently into the select agent strains. The chromosomal GFP- and RFP-tagged strains exhibited bright fluorescence at an exposure time of less than 200 msec and displayed the same virulence traits as their wild-type parental strains. The utility of the tagged strains was proven by the macrophage infection assays and lactate dehydrogenase release analysis. Such strains will be extremely useful in high-throughput screens for novel compounds that could either kill these organisms, or interfere with critical virulence processes in these important bioweapon agents and during infection of alveolar macrophages. PMID:25044501

  1. The Constitution Community

    NSDL National Science Digital Library

    A new addition to the National Archives and Records Administration (NARA) Digital Classroom site (see the November 18, 199 Scout Report for Social Sciences), the Constitution Community is a partnership between classroom teachers and education specialists from the NARA. Like other Digital Classroom projects, the Constitution Community offers sample lesson plans, correlated to the National History Standards, that make use of original documents and images from American history. In addition to the lesson plan, each also includes background information, a number of suggested teaching activities, and its connection to the US Constitution The lessons are grouped by eight historical eras, covering the American Revolution to the Great Depression to the Civil Rights Act. Highlights include The Growth of Regionalism, The Civil War as Photographed by Mathew Brady, FDR's First Inaugural Address: Declaring "War" on the Great Depression, and the Founding Documents of the Peace Corps.

  2. Salt-inducible isoform of plasma membrane H+ATPase gene in rice remains constitutively expressed in natural halophyte, Suaeda maritima.

    PubMed

    Sahu, Binod Bihari; Shaw, Birendra Prasad

    2009-07-01

    To look into a possible involvement of plasma membrane H+ATPase (PM-H+ATPase, EC 3.6.3.6) in mitigation of physiological disturbances imposed by salt stress, response of the enzyme was studied in two Oryza sativa Indica cultivars, salt-tolerant Lunishri and non-tolerant Badami, and a natural halophyte Suaeda maritima after challenge of the young plants with NaCl. Significant increase in activity of the enzyme was observed in response to NaCl in all the test plants with S. maritima showing maximum increase. Protein blot analysis, however, did not show any increase in the amount of the enzyme (protein). RNA blot analysis, on the other hand, revealed significant increase in transcript level of the enzyme upon NaCl treatment. In the rice cultivars, salt treatment also induced expression of a new isoform of PM-H+ATPase gene, not reported so far. The induced transcript showed maximum homology to OSA7 (O. sativa PM-H+ATPase isoform 7). Similar transcript message, however, remained constitutively present in S. maritima, along with the transcript of another isoform of PM-H+ATPase showing resemblance to OSA3 (O. sativa PM-H+ATPase isoform 3). The latter was the only PM-H+ATPase isoform expressed in both the rice cultivars not exposed to NaCl. In the salt-treated test plants, both rice and S. maritima, the salt-inducible PM-H+ATPase isoform resembling OSA7 was expressed in much greater amount than that resembling OSA3. Appearance of a new PM-H+ATPase transcript, besides increase in the enzyme activity, indicates the important role of the enzyme in maintaining ion-homeostasis in plants under salt stress, enabling them to survive under saline conditions. PMID:19167778

  3. Constitutive or Inducible Protective Mechanisms against UV-B Radiation in the Brown Alga Fucus vesiculosus? A Study of Gene Expression and Phlorotannin Content Responses

    PubMed Central

    Creis, Emeline; Delage, Ludovic; Charton, Sophie; Goulitquer, Sophie; Leblanc, Catherine; Potin, Philippe; Ar Gall, Erwan

    2015-01-01

    A role as UV sunscreens has been suggested for phlorotannins, the phenolic compounds that accumulate in brown algae in response to a number of external stimuli and take part in cell wall structure. After exposure of the intertidal brown alga Fucus vesiculosus to artificial UV-B radiation, we examined its physiological responses by following the transcript level of the pksIII gene encoding a phloroglucinol synthase, likely to be involved in the first step of phlorotannins biosynthesis. We also monitored the expression of three targeted genes, encoding a heat shock protein (hsp70), which is involved in global stress responses, an aryl sulfotransferase (ast), which could be involved in the sulfation of phlorotannins, and a vanadium bromoperoxidase (vbpo), which can potentially participate in the scavenging of Reactive Oxygen Species (ROS) and in the cross-linking and condensation of phlorotannins. We investigated whether transcriptional regulation of these genes is correlated with an induction of phlorotannin accumulation by establishing metabolite profiling of purified fractions of low molecular weight phlorotannins. Our findings demonstrated that a high dose of UV-B radiation induced a significant overexpression of hsp70 after 12 and 24 hours following the exposure to the UV-B treatment, compared to control treatment. The physiological performance of algae quantified by the photosynthetic efficiency (Fv/Fm) was slightly reduced. However UV-B treatment did not induce the accumulation of soluble phlorotannins in F. vesiculosus during the kinetics of four weeks, a result that may be related to the lack of induction of the pksIII gene expression. Taken together these results suggest a constitutive accumulation of phlorotannins occurring during the development of F.vesiculosus, rather than inducible processes. Gene expression studies and phlorotannin profiling provide here complementary approaches to global quantifications currently used in studies of phenolic compounds in brown algae. PMID:26030665

  4. Constitution, 15 August 1982.

    PubMed

    1987-01-01

    This document reprints major provisions of the 1982 Constitution of Equatorial Guinea. The Constitution calls for protection of the family as the basic building block of society. Foreigners are afforded the same civil rights as citizens and may seek asylum but may not exercise political rights. The Constitution guarantees equality before the law and prohibits discrimination based on ethnic background, race, sex, language, religion, filiation, political or other views, social origin, economic position, or birth. Women are afforded the same rights as men regardless of their marital status. The Constitution also guarantees citizens freedom to travel nationally and internationally and to choose a place of residence. Equatoguineans are also entitled to a standard of living that insures health, nutrition, education, clothing, housing, medical care, and necessary social services. The family policy contained in the Constitution protects all types of legal marriages equally and recognizes nonattachable and inalienable family patrimony. Children are protected from the time of conception, and all inhabitants are guaranteed a basic state education which is compulsory and free. Efforts are also being made to eradicate illiteracy. Women are insured training and promotion for their integration into the active life and development of the country, and farmers are guaranteed traditional ownership of the lands they possess, although the state retains the right of eminent domain. PMID:12346662

  5. Biochemical and Morphological Consequences of Human ?-Synuclein Expression in a Mouse ?-Synuclein Null Background

    PubMed Central

    Prasad, Kavita; Tarasewicz, Elizabeth; Strickland, Pamela A. Ohman; O’Neill, Michael; Mitchell, Stephen N.; Merchant, Kalpana; Tep, Samnang; Hilton, Kathryn; Datwani, Akash; Buttini, Manuel; Mueller-Steiner, Sarah; Richfield, Eric K.

    2011-01-01

    A consensus about the functions of human wild-type or mutated ?-synuclein (?SYN) is lacking. Both forms of ?SYN are implicated in Parkinson’s disease, whereas the wild-type form is implicated in substance abuse. Interactions with other cellular proteins and organelles may meditate its functions. We developed a series of congenic mouse lines containing various allele doses or combinations of the human wild type ?SYN (hw?SYN) or a doubly mutated (A30P*A53T) ?SYN (hm2?SYN) in a C57Bl/6J line spontaneously deleted in mouse ?SYN (C57BL/6JOla). Both transgenes had a functional role in the nigrostriatal system, demonstrated by significant elevations in striatal catecholamines, metabolites, and the enzyme tyrosine hydroxylase compared to null-mice without a transgene. Consequences occurred when the transgenes were expressed at a fraction of the endogenous level. Hemizygous congenic mice did not exhibit any change in the number or size of dopaminergic neurons in the ventral midbrain at nine months of age. Human ?SYN was predominantly located in neuronal cell bodies, neurites, synapses, and in intraneuronal/intraneuritic aggregates. The hm2?SYN transgene resulted in more aggregates and dystrophic neurites than did the hw5 transgene. The hw?SYN transgene resulted in higher expression of two striatal proteins, synaptogamin 7 and UCHL1, compared to the levels of the hm2?SYN transgene. These observations suggest that mutations in ?SYN may impair specific functional domains, leaving others intact. These lines may also be useful for exploring interactions between h?SYN and environmental or genetic risk factors in dopamine-related disorders using a mouse model. PMID:21272100

  6. Identification of the positive and negative cis-elements involved in modulating the constitutive expression of mouse thymosin beta4 gene.

    PubMed

    Hsiao, Hung-Liang; Su, Yeu

    2005-04-01

    We previously showed that the -278 to +410 region of mouse thymosin beta4 (mT,beta4) gene supports high levels of reporter gene expression in NIH3T3 cells. This region contains part of the 5'-flanking sequences (-278 to -1), the intact first exon (+1 to +133), and portion of the first intron (+134 to +410). However, the size of this exon is much longer than those of its rat and human counterparts. To resolve the question regarding this size discrepancy, transcription start site for the mTbeta4 gene was re-examined by primer extension and bioinformatics analyses. We found that the first exon of mTbeta4 gene spans 56 bp with its cap site situated in a putative initiator highly similar to the consensus mammalian sequence. In addition, a TATA box-like motif and two consecutive downstream promoter elements were also found. To delineate the cis-elements involved in modulating the constitutive expression of mTbeta4 gene, transient transfection assay was performed. Interestingly, expression level of the reporter gene driven by the -117 to +56 region of mTbeta4 gene was approximately 8-fold higher than that directed by the SV40 promoter and significant promoter activity was found to be associated with the smaller (-56 to +56) fragment. A nuclear protein-bound silencer was located in the region between the -167 and -118 and an enhancer whose effect did not seem to be dependent on protein binding was identified in the downstream (-117 to -88) region. However, neither of these cis-elements affected reporter expression driven by a SV40 promoter. Intriguingly, mTbeta4 promoter functioned well in human colorectal (SW480) and cervical (HeLa) carcinoma cells. Taken together, our findings not only provide crucial information for further elucidation of the transcriptional regulation of mTbeta4 gene but also raise the possibility of utilizing its promoter to produce large quantity of recombinant proteins in mammalian cells. PMID:16010974

  7. A set of fluorescent protein-based markers expressed from constitutive and arbuscular mycorrhiza-inducible promoters to label organelles, membranes and cytoskeletal elements in Medicago truncatula.

    PubMed

    Ivanov, Sergey; Harrison, Maria J

    2014-12-01

    Medicago truncatula is widely used for analyses of arbuscular mycorrhizal (AM) symbiosis and nodulation. To complement the genetic and genomic resources that exist for this species, we generated fluorescent protein fusions that label the nucleus, endoplasmic reticulum, Golgi apparatus, trans-Golgi network, plasma membrane, apoplast, late endosome/multivesicular bodies (MVB), transitory late endosome/ tonoplast, tonoplast, plastids, mitochondria, peroxisomes, autophagosomes, plasmodesmata, actin, microtubules, periarbuscular membrane (PAM) and periarbuscular apoplastic space (PAS) and expressed them from the constitutive AtUBQ10 promoter and the AM symbiosis-specific MtBCP1 promoter. All marker constructs showed the expected expression patterns and sub-cellular locations in M. truncatula root cells. As a demonstration of their utility, we used several markers to investigate AM symbiosis where root cells undergo major cellular alterations to accommodate their fungal endosymbiont. We demonstrate that changes in the position and size of the nuclei occur prior to hyphal entry into the cortical cells and do not require DELLA signaling. Changes in the cytoskeleton, tonoplast and plastids also occur in the colonized cells and in contrast to previous studies, we show that stromulated plastids are abundant in cells with developing and mature arbuscules, while lens-shaped plastids occur in cells with degenerating arbuscules. Arbuscule development and secretion of the PAM creates a periarbuscular apoplastic compartment which has been assumed to be continuous with apoplast of the cell. However, fluorescent markers secreted to the periarbuscular apoplast challenge this assumption. This marker resource will facilitate cell biology studies of AM symbiosis, as well as other aspects of legume biology. PMID:25329881

  8. What Is a Constitution?

    ERIC Educational Resources Information Center

    OAH Magazine of History, 1988

    1988-01-01

    Provides a lesson plan designed to help students better understand the concept of a constitution, distinguish constitutional law from statutory law, and recognize examples of constitutional government. (BSR)

  9. A constitutively expressed, truncated umuDC operon regulates the recA-dependent DNA damage induction of a gene in Acinetobacter baylyi strain ADP1.

    PubMed

    Hare, Janelle M; Perkins, Sara N; Gregg-Jolly, Leslie A

    2006-06-01

    In response to environmentally caused DNA damage, SOS genes are up-regulated due to RecA-mediated relief of LexA repression. In Escherichia coli, the SOS umuDC operon is required for DNA damage checkpoint functions and for replicating damaged DNA in the error-prone process called SOS mutagenesis. In the model soil bacterium Acinetobacter baylyi strain ADP1, however, the content, regulation, and function of the umuDC operon are unusual. The umuC gene is incomplete, and a remnant of an ISEhe3-like transposase has replaced the middle 57% of the umuC coding region. The umuD open reading frame is intact, but it is 1.5 times the size of other umuD genes and has an extra 5' region that lacks homology to known umuD genes. Analysis of a umuD::lacZ fusion showed that umuD was expressed at very high levels in both the absence and presence of mitomycin C and that this expression was not affected in a recA-deficient background. The umuD mutation did not affect the growth rate or survival after UV-induced DNA damage. However, the UmuD-like protein found in ADP1 (UmuDAb) was required for induction of an adjacent DNA damage-inducible gene, ddrR. The umuD mutation specifically reduced the DNA damage induction of the RecA-dependent DNA damage-inducible ddrR locus by 83% (from 12.9-fold to 2.3-fold induction), but it did not affect the 33.9-fold induction of benA, an unrelated benzoate degradation gene. These data suggest that the response of the ADP1 umuDC operon to DNA damage is unusual and that UmuDAb specifically regulates the expression of at least one DNA damage-inducible gene. PMID:16751513

  10. Constitution of the Union of Clare Draftsman's Note: Readers are advised to have regard to Constitution

    E-print Network

    Dixon, Peter

    Constitution of the Union of Clare Students Draftsman's Note: Readers are advised to have regard to Constitution 2004: The Constitution Explained in interpreting this document. 1. The UCS (1) The AMALGAMATED) In this Constitution, the expressions "Governing Body" and "Finance Committee" shall mean the Governing Body of Clare

  11. V Constitution / Universalis / 2007 (juin) CONSTITUTION

    E-print Network

    Paris-Sud XI, Université de

    Constitution / Universalis / 2007 (juin) 1 CONSTITUTION Encyclopédie Universalis Pierre Brunet « constitution » a longtemps évoqué des textes considérés comme sacrés et un peu lointains, dont on parlait avec on admettait volontiers que la constitution de l'État ne se trouvait certainement pas tout entičre enfermée

  12. Morphoproteomics identifies constitutive activation of the mTORC2/Akt and NF-?B pathways and expressions of IGF-1R, Sirt1, COX-2, and FASN in peripheral T-cell lymphomas: pathogenetic implications and therapeutic options

    PubMed Central

    Quesada, Andrés E; Nguyen, Nghia D; Rios, Adan; Brown, Robert E

    2014-01-01

    Background: Gaining a better understanding of the molecular circuitries and pathways implicated in the malignant growth and biological behavior of T cell lymphomas may identify potential cellular targets with clinical therapeutic potential. The immunohistochemical characterization of key cellular proteins participating in these pathways can provide surrogate markers of biological activity. The mammalian target of rapamycin complex (mTORC) signaling pathway has been implicated in T-cell lymphopoiesis. The mTORC2 pathway involves downstream activation of nuclear factor (NF)-?B and p-Akt (Ser 473). Fatty acid synthase (FASN) and insulin-like growth factor-1 receptor (IGF-1R) are expressed upstream of the mTORC and NF-?B signaling pathways. Cyclooxygenase (COX)-2 products influence these pathways. Our goal was to use morphoproteomics to characterize the expression patterns of the proteins in various peripheral T-cell lymphomas. Design: Ten cases of peripheral T-cell lymphoma (PTCL) were examined for expression of proteins along the mTORC, Akt and NF-?B pathways and affiliated tumorigenic molecules. These included two angioimmunoblastic PTCL, one natural killer/PTCL, one anaplastic large PTCL, and six PTCL not otherwise specified. Immunostaining for phosphorylated (p) mTOR (Ser 2448), p-Akt (Ser 473), p-NF-?Bp65 (Ser 536), IGF-1R (Tyr1165/1166), silent mating type information regulation 2 homolog 1 (Sirt1), COX-2 and FASN was performed on paraffin-embedded tissue for each case. Percent expression was scored using bright-field microscopy with high expression designated as more than 50% of the cells with positive stain in the appropriate subcellular compartment. Results: All ten cases demonstrated nuclear staining for p-mTOR (Ser 2448) corresponding to mTORC 2, and all cases showed strong, diffuse nuclear staining for p-NF-?Bp65 (Ser 536). All ten also showed nuclear and cytoplasmic staining for p-Akt (Ser 473) and cytoplasmic staining for IGF-1R. High expressions for nuclear Sirt1, and cytoplasmic COX-2 and FASN were detected in 7, 9, and 8 out of 10 cases, respectively. Six out of 10 cases demonstrated high expression of all the mentioned markers. Conclusion: The constitutive activation of mTORC2, NF-?B, p-Akt and the concomitant expression of IGF-1R suggests convergence of these molecular pathways in T-cell lymphoma. The results of this study also suggest that mTORC2 may be a common denominator among this heterogeneous group of lymphomas. Interference of key nodes of this pathway may carry a clinical therapeutic benefit. Agents that may be considered based on existing data include: bortezomib to inhibit NF-?B pathway activation; metformin to inhibit both NF-?B and mTORC2 and histone deacteylase inhibitors to inhibit mTORC2 pathway signaling. Furthermore, panobinostat inhibits Sirt1 pathway when present, and celecoxib inhibits NF-?B pathway activation independent of COX2. PMID:25674239

  13. The effect of Nrf2 knockout on the constitutive expression of drug metabolizing enzymes and transporters in C57Bl/6 mice livers.

    PubMed

    Anwar-Mohamed, Anwar; Degenhardt, Owen S; El Gendy, Mohamed A M; Seubert, John M; Kleeberger, Steven R; El-Kadi, Ayman O S

    2011-06-01

    Previous reports have proposed a cross-talk between the nuclear factor erythroid-2 p45-related factor-2 (Nrf2)/antioxidant response element (ARE) and the aryl hydrocarbon receptor (AhR)/xenobiotic response element (XRE) signaling pathways. Therefore, the aim of the current study was to examine the level of phase I, phase II drug metabolizing enzymes (DMEs), and phase III transporters and their related transcription factors in the Nrf2 knockout model. Our results showed that phase II DMEs that are under the control of Nrf2 typified by NAD(P)H: quinone oxidoreductase 1 (Nqo1), and glutathione S-transferase (Gst) were significantly lower at the mRNA, protein, and catalytic activity levels in the livers of Nrf2 knockout mice compared to wild type. Furthermore, phase I cytochrome P450s (CYPs), Cyp1, and Cyp2b10 at mRNA, protein, and catalytic activity levels were significantly lower in the livers of Nrf2 knockout mice. Interestingly, our results showed that the transcription factors AhR, constitutive androstane receptor (CAR), and pregnane X receptor (PXR) at mRNA, and protein expression levels were significantly lower in the livers of Nrf2 knockout mice compared to wild type. Importantly, phase III drug transporters mRNA levels of the multiple drug resistance associated proteins (Mrp2 and Mrp3), and solute carrier organic anion transporters (Slco1a6 and Slco2b1) were significantly lower in the liver of Nrf2 knockout mice. Co-activators, Ncoa1, Ncoa2, and Ncoa3 mRNA levels were not altered while co-repressors, Ncor1 and Ncor2 were significantly lower in the livers of Nrf2 knockout mice. In conclusion, knockout of Nrf2 causes disruption to the coordination of phase I, phase II drug DMEs, and phase III drug transporters through altering the transcription factors controlling them. PMID:21281708

  14. Relatedness of Streptococcus suis isolates of various serotypes and clinical backgrounds as evaluated by macrorestriction analysis and expression of potential virulence traits

    Microsoft Academic Search

    ACHIM ALLGAIER; RALPH GOETHE; HENK J. WISSELINK; HILDE E. SMITH; PETER VALENTIN-WEIGAND

    2001-01-01

    We evaluated the genetic diversity of Streptococcus suis isolates of different serotypes by macrorestriction analysis and elucidated possible relationships between the genetic background, expression of potential virulence traits, and source of isolation. Virulence traits included expression of serotype-specific polysaccharides, muramidase-released protein (MRP), extracellular protein factor (EF), hemolysin activity, and adherence to epithelial cells. Macrorestriction analysis of streptococcal DNA digested with

  15. SURVIVAL AND DEGRADATIVE CAPACITY OF PSEUDOMONAS PUTIDA INDUCED OR CONSTITUTIVELY EXPRESSING PLASMA-MEDIATED DEGRADATION OF 2,4-DICHLOROPHENOXYACETATE (TFD) IN SOIL

    EPA Science Inventory

    The survival of genetically altered Pseudomonas putida strains harboring an inducible plasmid, PRO101, or a constitutive plasmid, PRO103, was compared. hese plasmids encode for the degradation of 2,4-dichlorophenoxyacetate (TFD) to 2-chloromaleylacetate, and the maintenance of ei...

  16. SURVIVAL AND DEGRADATIVE CAPACITY OF PSEUDOMONAS PUTIDA INDUCED OR CONSTITUTIVELY EXPRESSING PLASMID-MEDIATED DEGRADATION OF 2,4-DICHLOROPHENOXYACETATE (TFD) IN SOIL

    EPA Science Inventory

    Survival of genetically altered Pseudonomas putida strains harboring an inducible plasmid, pRO101, or a constitutive plasmid, pRO103, was compared. hese plasmids encoded for the degradation of 2,4-dichlorophenoxyacetate (TFD) to 2-chloromaleylacetate, and the maintenance of eithe...

  17. Constitution Council on Student

    E-print Network

    Boonstra, Rudy

    Constitution of the Council on Student Services Revised April 2008 #12;Constitution by Governing Council #12;Constitution of the Council on Student Services (CSS) 3 [b] To review, in detail of services. [i] To review from timetotime and recommend revisions (if necessary) to this constitution

  18. Transcription regulatory networks in Caenorhabditis elegans inferred through reverse-engineering of gene expression profiles constitute biological hypotheses for metazoan development.

    PubMed

    Vermeirssen, Vanessa; Joshi, Anagha; Michoel, Tom; Bonnet, Eric; Casneuf, Tine; Van de Peer, Yves

    2009-12-01

    Differential gene expression governs the development, function and pathology of multicellular organisms. Transcription regulatory networks study differential gene expression at a systems level by mapping the interactions between regulatory proteins and target genes. While microarray transcription profiles are the most abundant data for gene expression, it remains challenging to correctly infer the underlying transcription regulatory networks. The reverse-engineering algorithm LeMoNe (learning module networks) uses gene expression profiles to extract ensemble transcription regulatory networks of coexpression modules and their prioritized regulators. Here we apply LeMoNe to a compendium of microarray studies of the worm Caenorhabditis elegans. We obtain 248 modules with a regulation program for 5020 genes and 426 regulators and a total of 24 012 predicted transcription regulatory interactions. Through GO enrichment analysis, comparison with the gene-gene association network WormNet and integration of other biological data, we show that LeMoNe identifies functionally coherent coexpression modules and prioritizes regulators that relate to similar biological processes as the module genes. Furthermore, we can predict new functional relationships for uncharacterized genes and regulators. Based on modules involved in molting, meiosis and oogenesis, ciliated sensory neurons and mitochondrial metabolism, we illustrate the value of LeMoNe as a biological hypothesis generator for differential gene expression in greater detail. In conclusion, through reverse-engineering of C. elegans expression data, we obtained transcription regulatory networks that can provide further insight into metazoan development. PMID:19763340

  19. Constitution of the Union of Clare Students Draftsman's Note: Readers are advised to have regard to Constitution 2004

    E-print Network

    Dixon, Peter

    - 1 - Constitution of the Union of Clare Students Draftsman's Note: Readers are advised to have regard to Constitution 2004: The Constitution Explained in interpreting this document. 1. The UCS (1. (2) In this Constitution, the expressions "Governing Body" and "Finance Committee" shall mean

  20. Efficient production of 1,3-propanediol from glycerol upon constitutive expression of the 1,3-propanediol oxidoreductase gene in engineered Klebsiella pneumoniae with elimination of by-product formation.

    PubMed

    Oh, Baek-Rock; Seo, Jeong-Woo; Heo, Sun-Yeon; Luo, Lian Hua; Hong, Won-Kyung; Park, Don-Hee; Kim, Chul-Ho

    2013-06-01

    In the present study, we developed an efficient method of 1,3-propanediol (1,3-PD) production from glycerol by genetic engineering of Klebsiella pneumoniae AK mutant strains. The proposed approach eliminated by-product formation and IPTG induction resulted in maximal production of 1,3-PD. A series of recombinant strains was designed to constitutively express the dhaB and/or dhaT genes, using the bacteriophage T5 P(DE20) promoter and the rho-independent transcription termination signal of the Rahnella aquatilis levansucrase gene. Among these strains, AK/pConT expressing dhaT alone gave the highest yield of 1,3-PD. Fed-batch fermentation resulted in efficient production of 1,3-PD from either pure or crude glycerol, without by-product formation. PMID:23361186

  1. COLLEGE OF ELECTORS CONSTITUTION

    E-print Network

    Boonstra, Rudy

    44755 COLLEGE OF ELECTORS CONSTITUTION I AUTHORITY Pursuant to the provisions of The University of the Governing Council and the Chancellor. II INTERPRETATION II.1. In this Constitution and in all other. In the event of conflict between any provision of this Constitution and the provisions of The University

  2. FACULTY SENATE CONSTITUTION AND

    E-print Network

    Gering, Jon C.

    FACULTY SENATE CONSTITUTION AND BYLAWS FOR TRUMAN STATE UNIVERSITY Preamble The members, do hereby establish this constitution as a pledge of faculty cooperation and support of Truman State to the Constitution and Bylaws shall be pro- posed to the electorate through a two-thirds vote of the vot- ing

  3. Thailand Draft Constitution

    NSDL National Science Digital Library

    1997-01-01

    On Saturday, October 11 The King of Thailand signed a new constitution, Thailand's 16th. The new constitution is not popular among many Thai politicians, but others see it as a route to greater democracy in the country. Nation Multimedia Group, publishers of the Thai newspaper The Nation, have posted the full text of the constitution on their site.

  4. Timpuyog Organization Constitution & Bylaws

    E-print Network

    Dong, Yingfei

    Timpuyog Organization Constitution & Bylaws Last Revised: 10/15/08 Timpuyog Organization Constitution and Bylaws Ilokano Language and Philippine Drama & Film Program Department of Indo Website: http://www2.hawaii.edu/~timpuyog CONSTITUTION Article I. Name Section 1. The name

  5. Hateful Expression and First Amendment Values: Toward a Theory of Constitutional Constraint on Hate Speech at Colleges and Universities after R.A.V. v. St. Paul.

    ERIC Educational Resources Information Center

    Hartman, Rhonda G.

    1993-01-01

    Discussion of hate speech on college campuses focuses on whether the concept of hate speech encompasses expression deserving full First Amendment protection and thus virtual immunity from college regulation. It is argued that the Supreme Court could sustain some form of hate-speech policy on campus based on precedent elsewhere. (MSE)

  6. Thrombopoietin receptor (c-Mpl) is constitutively expressed on platelets of patients with liver cirrhosis, and correlates with its disease progression

    Microsoft Academic Search

    Toru Ishikawa; Takafumi Ichida; Satoshi Sugahara; Satoshi Yamagiwa; Yasunobu Matsuda; Kazuhiro Uehara; Takashi Kato; Hiroshi Miyazaki; Hitoshi Asakura

    2002-01-01

    Thrombocytopenia is one of the major complications of liver cirrhosis. Except for hypersplenism associated with portal hypertension, it is not known which abnormalities of thrombopoiesis cause thrombocytopenia. To evaluate thrombopoiesis in liver cirrhosis, we analyzed thrombopoietin (TPO) and its receptor c-Mpl levels in cirrhotic patients. Expression of c-Mpl on platelets and the serum level of TPO were investigated from 38

  7. Transcriptome analysis of Hpa1Xoo transformed cotton revealed constitutive expression of genes in multiple signalling pathways related to disease resistance

    PubMed Central

    Miao, Weiguo; Song, Congfeng; Wang, Yu; Ren, Yonghong; Wang, Jinsheng

    2010-01-01

    The transcriptome profile in leaves and roots of the transgenic cotton line T-34 expressing hpa1Xoo from Xanthomonas oryzae pv. oryzae was analysed using a customized 12k cotton cDNA microarray. A total of 530 cDNA transcripts involved in 34 pathways were differentially expressed in the transgenic line T-34, in which 123 differentially expressed genes were related to the cotton defence responses including the hypersensitive reaction, defence responses associated with the recognition of pathogen-derived elicitors, and defence signalling pathways mediated by salicylic acid, jasmonic acid, ethylene, auxin, abscicic acid, and Ca2+. Furthermore, transcripts encoding various leucine-rich protein kinases and mitogen-activated protein kinases were up-regulated in the transgenic line T-34 and expression of transcripts related to the energy producing and consuming pathway was also increased, which suggested that the enhanced metabolism related to the host defence response in the transgenic line T-34 imposed an increased energy demand on the transgenic plant. PMID:20667962

  8. Transposon-Mediated Alteration of TaMATE1B Expression in Wheat Confers Constitutive Citrate Efflux from Root Apices[W

    PubMed Central

    Tovkach, Andriy; Ryan, Peter R.; Richardson, Alan E.; Lewis, David C.; Rathjen, Tina M.; Ramesh, Sunita; Tyerman, Stephen D.; Delhaize, Emmanuel

    2013-01-01

    The TaMATE1B gene (for multidrug and toxic compound extrusion) from wheat (Triticum aestivum) was isolated and shown to encode a citrate transporter that is located on the plasma membrane. TaMATE1B expression in roots was induced by iron deficiency but not by phosphorus deficiency or aluminum treatment. The coding region of TaMATE1B was identical in a genotype showing citrate efflux from root apices (cv Carazinho) to one that lacked citrate efflux (cv Egret). However, sequence upstream of the coding region differed between these two genotypes in two ways. The first difference was a single-nucleotide polymorphism located approximately 2 kb upstream from the start codon in cv Egret. The second difference was an 11.1-kb transposon-like element located 25 bp upstream of the start codon in cv Carazinho that was absent from cv Egret. The influence of these polymorphisms on TaMATE1B expression was investigated using fusions to green fluorescent protein expressed in transgenic lines of rice (Oryza sativa). Fluorescence measurements in roots of rice indicated that 1.5- and 2.3-kb regions upstream of TaMATE1B in cv Carazinho (which incorporated 3? regions of the transposon-like element) generated 20-fold greater expression in the apical 1 mm of root compared with the native promoter in cv Egret. By contrast, fluorescence in more mature tissues was similar in both cultivars. The presence of the single-nucleotide polymorphism alone consistently generated 2-fold greater fluorescence than the cv Egret promoter. We conclude that the transposon-like element in cv Carazinho extends TaMATE1B expression to the root apex, where it confers citrate efflux and enhanced aluminum tolerance. PMID:23204428

  9. Dynamic Alternations in Cellular and Molecular Components during Blossom-End Rot Development in Tomatoes Expressing sCAX1, a Constitutively Active Ca2+/H+ Antiporter from Arabidopsis1[W][OA

    PubMed Central

    Tonetto de Freitas, Sergio; Padda, Malkeet; Wu, Qingyu; Park, Sunghun; Mitcham, Elizabeth J.

    2011-01-01

    Although calcium (Ca) concentration in cellular compartments has been suggested to be tightly regulated, Ca deficiency disorders such as blossom-end rot (BER) in tomato (Solanum lycopersicum) fruit may be induced by abnormal regulation of Ca partitioning and distribution in the cell. The objectives of this work were to analyze the effects of high expression of the constitutively functional Arabidopsis (Arabidopsis thaliana) Ca2+/H+ exchanger (sCAX1) tonoplast protein in tomato fruit on cellular Ca partitioning and distribution, membrane integrity, and the transcriptional profile of genes potentially involved in BER development. Wild-type and sCAX1-expressing tomato plants were grown in a greenhouse. Wild-type plants did not develop BER, whereas sCAX1-expressing plants reached 100% BER incidence at 15 d after pollination. The sCAX1-expressing fruit pericarp had higher total tissue and water-soluble Ca concentrations, lower apoplastic and cytosolic Ca concentrations, higher membrane leakage, and Ca accumulation in the vacuole of sCAX1-expressing cells. Microarray analysis of healthy sCAX1-expressing fruit tissue indicated down-regulation of genes potentially involved in BER development, such as genes involved in membrane structure and repair and cytoskeleton metabolism, as well as up-regulation of genes that may have limited BER damage expansion, such as genes coding for heat shock proteins, glutathione S-transferases, and peroxidases. The results indicate that the high expression of the sCAX1 gene reduces cytosolic and apoplastic Ca concentrations, affecting plasma membrane structure and leading to BER symptom development in the fruit tissue. PMID:21464475

  10. Three second chromosome-linked clustered Cyp6 genes show differential constitutive and barbital-induced expression in DDT-resistant and susceptible strains of Drosophila melanogaster

    Microsoft Academic Search

    Sushmita Maitra; Susan M. Dombrowski; Larry C. Waters; Ranjan Ganguly

    1996-01-01

    The level of expression of the Cyp6a2 gene is much higher in the DDT-resistant 91-R strain than in the susceptible 91-C strain of Drosophila melanogaster (Waters et al. (1992b) Proc. Natl. Acad. Sci. USA, 89, 4855–4859). To understand the role of Cyp6a2 and related genes in insecticide resistance, we have isolated and characterized two new Cyp6 genes from the 91-R

  11. Constitutive expression of the Wilms' tumor gene (WT1) in the leukemic cell line U937 blocks parts of the differentiation program

    Microsoft Academic Search

    Helena Svedberg; Kristina Chylicki; Bo Baldetorp; Frank J Rauscher; Urban Gullberg

    1998-01-01

    The Wilms tumor gene, WT1, encodes a zinc-finger DNA binding protein which is thought to function as a tissue specific transcription factor, regulating cell growth and differentiation. High expression of WT1 has been detected in a range of acute leukemias. To elucidate a role for WT1 in leukemogenesis, we transfected the monoblastic cell line U937, which lacks detectable levels of

  12. Regulated expression of CXCR4 constitutive active mutants revealed the up-modulated chemotaxis and up-regulation of genes crucial for CXCR4 mediated homing and engraftment of hematopoietic stem/progenitor cells

    PubMed Central

    Sharma, M; Afrin, F; Tripathi, RP; Gangenahalli, G

    2013-01-01

    SDF-1/CXCR4 axis plays a principle role in the homing and engraftment of hematopoietic stem/progenitor cells (HSPCs), a process that defines cells ability to reach and seed recipient bone marrow niche following their intravenous infusion. However, the proper functioning of CXCR4 downstream signaling depends upon consistent optimal expression of both SDF-1 ligand and its receptor CXCR4, which in turn is variable and regulated by several factors. The constitutive active mutants of CXCR4 (N119A and N119S) being able to induce autonomous downstream signaling, overcome the limitation of ligand-receptor interaction for induction of CXCR4 signaling. Therefore, we intended to explore their potential in Chemotaxis; a key cellular process which crucially regulates cells homing to bone marrow. In present study, Tet-on inducible gene expression vector system was used for doxycycline inducible regulated transgene expression of CXCR4 active mutants in hematopoietic stem progenitor cell line K-562. Both of these mutants revealed significantly enhanced Chemotaxis to SDF-1 gradient as compared to wild type. Furthermore, gene expression profiling of these genetically engineered cells as assessed by microarray analysis revealed the up-regulation of group of genes that are known to play a crucial role in CXCR4 mediated cells homing and engraftment. Hence, this study suggest the potential prospects of CXCR4 active mutants in research and development aimed to improve the efficiency of cells in the mechanism of homing and engraftment process. PMID:24693205

  13. Comprehensive Genome-Wide Survey, Genomic Constitution and Expression Profiling of the NAC Transcription Factor Family in Foxtail Millet (Setaria italica L.)

    PubMed Central

    Puranik, Swati; Sahu, Pranav Pankaj; Mandal, Sambhu Nath; B., Venkata Suresh; Parida, Swarup Kumar; Prasad, Manoj

    2013-01-01

    The NAC proteins represent a major plant-specific transcription factor family that has established enormously diverse roles in various plant processes. Aided by the availability of complete genomes, several members of this family have been identified in Arabidopsis, rice, soybean and poplar. However, no comprehensive investigation has been presented for the recently sequenced, naturally stress tolerant crop, Setaria italica (foxtail millet) that is famed as a model crop for bioenergy research. In this study, we identified 147 putative NAC domain-encoding genes from foxtail millet by systematic sequence analysis and physically mapped them onto nine chromosomes. Genomic organization suggested that inter-chromosomal duplications may have been responsible for expansion of this gene family in foxtail millet. Phylogenetically, they were arranged into 11 distinct sub-families (I-XI), with duplicated genes fitting into one cluster and possessing conserved motif compositions. Comparative mapping with other grass species revealed some orthologous relationships and chromosomal rearrangements including duplication, inversion and deletion of genes. The evolutionary significance as duplication and divergence of NAC genes based on their amino acid substitution rates was understood. Expression profiling against various stresses and phytohormones provides novel insights into specific and/or overlapping expression patterns of SiNAC genes, which may be responsible for functional divergence among individual members in this crop. Further, we performed structure modeling and molecular simulation of a stress-responsive protein, SiNAC128, proffering an initial framework for understanding its molecular function. Taken together, this genome-wide identification and expression profiling unlocks new avenues for systematic functional analysis of novel NAC gene family candidates which may be applied for improvising stress adaption in plants. PMID:23691254

  14. A Continuous Bovine Kidney Cell Line Constitutively Expressing Bovine ?V?6 Integrin Has Increased Susceptibility to Foot-and-Mouth Disease Virus

    PubMed Central

    LaRocco, Michael; Kramer, Ed; Ahmed, Zaheer; Pacheco, Juan M.; Duque, Hernando; Baxt, Barry; Rodriguez, Luis L.

    2013-01-01

    Foot-and-mouth disease (FMD) is a worldwide problem limiting the trade of animals and their products from affected countries. The rapid isolation, serotyping, and vaccine matching of FMD virus from disease outbreaks is critical for enabling the implementation of effective vaccination programs and to stop the spread of infection during outbreaks. Some primary cells have been shown to be highly susceptible to most strains of FMD virus (FMDV) but are difficult and expensive to prepare and maintain. Since the ?V?6 integrin is a principal receptor for FMDV, we transduced a bovine kidney cell line to stably express both the ?V and ?6 bovine integrin subunits. This stable cell line (LFBK-?V?6) showed ?6 expression and enhanced susceptibility to FMDV infection for ?100 cell passages. LFBK-?V?6 cells were highly sensitive for detecting all serotypes of FMDV from experimentally infected animals, including the porcinophilic FMDV strain O/TAW/97. In comparison to other cell types that are currently used for virus isolation, LFBK-?V?6 cells were more effective at detecting FMDV in clinical samples, supporting their use as a more sensitive tool for virus isolation. PMID:23515553

  15. Constitutive or light-regulated expression of the rolC gene in transgenic potato plants has different effects on yield attributes and tuber carbohydrate composition.

    PubMed

    Fladung, M; Ballvora, A; Schmülling, T

    1993-11-01

    Tetraploid potato clones, transgenic for the rolC gene of Agrobacterium rhizogenes under control of the light-inducible ribulose bisphosphate carboxylase small subunit promoter (rbcS-rolC), were compared, with respect to yield attributes and tuber carbohydrates, with transformed and untransformed controls and with 35S-rolC transgenic potato plants. In rbcS-rolC plants, the expression of the rolC gene was located mainly in leaves, while in 35S-rolC plant transcripts were detected as well in shoots and roots. Phenotypically, rbcS-rolC transgenic plants were found to be slightly reduced in plant size with a few more tillers than control plants. Photosynthetic rate and chlorophyll content were significantly lower in all rolC transgenic plants irrespective of the type of construct used. Tuber yield was not significantly different between controls and rbcS-rolC transgenic plants, but was reduced in the 35S-rolC transformants. Sucrose level was unchanged in all rolC clones investigated, whereas fructose content was significantly enhanced in 35S-rolC transformants, but not in the plants expressing the rolC gene in aerial plant parts only. In both types of rolC transgenic plants, glucose content was lower than in controls, resulting in a significant reduction of reducing sugar in tubers. The results suggest a hormonal influence on the carbohydrate composition of potato tubers. PMID:8251628

  16. Constitutive expression and activation of stress response genes in cancer stem-like cells/tumour initiating cells: potent targets for cancer stem cell therapy.

    PubMed

    Torigoe, Toshihiko; Hirohashi, Yoshihiko; Yasuda, Kazuyo; Sato, Noriyuki

    2013-08-01

    Cancer stem-like cells (CSCs)/tumour-initiating cells (TICs) are defined as the small population of cancer cells that have stem cell-like phenotypes and high capacity for tumour initiation. These cells may have a huge impact in the field of cancer therapy since they are extremely resistant to standard chemoradiotherapy and thus are likely to be responsible for disease recurrence after therapy. Therefore, extensive efforts are being made to elucidate the pathological and molecular properties of CSCs/TICs and, with this information, to establish efficient anti-CSC/TIC targeting therapies. This review considers recent findings on stress response genes that are preferentially expressed in CSCs/TICs and their roles in tumour-promoting properties. Implications for a novel therapeutic strategy targeting CSCs/TICs are also discussed. PMID:23902339

  17. Constitutive expression of a miR319 gene alters plant development and enhances salt and drought tolerance in transgenic creeping bentgrass.

    PubMed

    Zhou, Man; Li, Dayong; Li, Zhigang; Hu, Qian; Yang, Chunhua; Zhu, Lihuang; Luo, Hong

    2013-03-01

    MicroRNA319 (miR319) is one of the first characterized and conserved microRNA families in plants and has been demonstrated to target TCP (for TEOSINTE BRANCHED/CYCLOIDEA/PROLIFERATING CELL FACTORS [PCF]) genes encoding plant-specific transcription factors. MiR319 expression is regulated by environmental stimuli, suggesting its involvement in plant stress response, although experimental evidence is lacking and the underlying mechanism remains elusive. This study investigates the role that miR319 plays in the plant response to abiotic stress using transgenic creeping bentgrass (Agrostis stolonifera) overexpressing a rice (Oryza sativa) miR319 gene, Osa-miR319a. We found that transgenic plants overexpressing Osa-miR319a displayed morphological changes and exhibited enhanced drought and salt tolerance associated with increased leaf wax content and water retention but reduced sodium uptake. Gene expression analysis indicated that at least four putative miR319 target genes, AsPCF5, AsPCF6, AsPCF8, and AsTCP14, and a homolog of the rice NAC domain gene AsNAC60 were down-regulated in transgenic plants. Our results demonstrate that miR319 controls plant responses to drought and salinity stress. The enhanced abiotic stress tolerance in transgenic plants is related to significant down-regulation of miR319 target genes, implying their potential for use in the development of novel molecular strategies to genetically engineer crop species for enhanced resistance to environmental stress. PMID:23292790

  18. Relatedness of Streptococcus suis isolates of various serotypes and clinical backgrounds as evaluated by macrorestriction analysis and expression of potential virulence traits.

    PubMed

    Allgaier, A; Goethe, R; Wisselink, H J; Smith, H E; Valentin-Weigand, P

    2001-02-01

    We evaluated the genetic diversity of Streptococcus suis isolates of different serotypes by macrorestriction analysis and elucidated possible relationships between the genetic background, expression of potential virulence traits, and source of isolation. Virulence traits included expression of serotype-specific polysaccharides, muramidase-released protein (MRP), extracellular protein factor (EF), hemolysin activity, and adherence to epithelial cells. Macrorestriction analysis of streptococcal DNA digested with restriction enzymes SmaI and ApaI allowed differentiation of single isolates that could be assigned to four major clusters, named A1, A2, B1, and B2. Comparison of the genotypic and phenotypic features of the isolates with their source of isolation showed that (i) the S. suis population examined, which originated mainly from German pigs, exhibited a genetic diversity and phenotypic patterns comparable to those found for isolates from other European countries; (ii) certain phenotypic features, such as the presence of capsular antigens of serotypes 2, 1, and 9, expression of MRP and EF, and hemolysin activity (and in particular, combinations of these features), were strongly associated with the clinical background of meningitis and septicemia; and (iii) isolates from pigs with meningitis and septicemia showed a significantly higher degree of genetic homogeneity compared to that for isolates from pigs with pneumonia and healthy pigs. Since the former isolates are considered highly virulent, this supports the theory of a clonal relationship among highly virulent strains. PMID:11158088

  19. Relatedness of Streptococcus suis Isolates of Various Serotypes and Clinical Backgrounds as Evaluated by Macrorestriction Analysis and Expression of Potential Virulence Traits

    PubMed Central

    Allgaier, Achim; Goethe, Ralph; Wisselink, Henk J.; Smith, Hilde E.; Valentin-Weigand, Peter

    2001-01-01

    We evaluated the genetic diversity of Streptococcus suis isolates of different serotypes by macrorestriction analysis and elucidated possible relationships between the genetic background, expression of potential virulence traits, and source of isolation. Virulence traits included expression of serotype-specific polysaccharides, muramidase-released protein (MRP), extracellular protein factor (EF), hemolysin activity, and adherence to epithelial cells. Macrorestriction analysis of streptococcal DNA digested with restriction enzymes SmaI and ApaI allowed differentiation of single isolates that could be assigned to four major clusters, named A1, A2, B1, and B2. Comparison of the genotypic and phenotypic features of the isolates with their source of isolation showed that (i) the S. suis population examined, which originated mainly from German pigs, exhibited a genetic diversity and phenotypic patterns comparable to those found for isolates from other European countries; (ii) certain phenotypic features, such as the presence of capsular antigens of serotypes 2, 1, and 9, expression of MRP and EF, and hemolysin activity (and in particular, combinations of these features), were strongly associated with the clinical background of meningitis and septicemia; and (iii) isolates from pigs with meningitis and septicemia showed a significantly higher degree of genetic homogeneity compared to that for isolates from pigs with pneumonia and healthy pigs. Since the former isolates are considered highly virulent, this supports the theory of a clonal relationship among highly virulent strains. PMID:11158088

  20. Transforming growth factor-?1b: a second TGF-?1 paralogue in the rainbow trout (Oncorhynchus mykiss) that has a lower constitutive expression but is more responsive to immune stimulation.

    PubMed

    Maehr, Tanja; Costa, Maria M; Vecino, Jose L González; Wadsworth, Simon; Martin, Samuel A M; Wang, Tiehui; Secombes, Christopher J

    2013-02-01

    The rainbow trout (Oncorhynchus mykiss) TGF-?1 sequence was one of the first fish cytokines described. Studies of its expression suggest it is constitutively expressed but displays refractory inducibility. Here we describe a second TGF-?1 (TGF-?1b) gene that is novel in several respects. TGF-?1b possesses typical TGF-? features, including a CXC motif and an integrin binding site, a tetrabasic cut site and a mature peptide of 112 amino acids (aa) containing nine conserved cysteine residues. The mature peptide is 83% identical to the first TGF-?1 sequence described in rainbow trout, that we designate TGF-?1a, and relative to TGF-?1a shows higher homology to Atlantic salmon TGF-?1b, zebrafish TGF-?1a, and sea bass and seabream TGF-?1. The gene organisation of salmonid TGF-?1b genes, as inferred from Atlantic salmon whole genome shotgun contigs, is a 6 exon/5 intron structure with exons 3 and 4 of salmonid TGF-?1a genes apparently fused together. The two trout TGF-?1 genes have a wide distribution in vivo, with highest expression found in immune tissues for both isoforms indicating that TGF-?1 has a predominant role in immunity of fish. Expression of both genes was also seen during the ontogeny of trout, with TGF-?1a relatively constant in expression level but TGF-?1b increasing over time. Immune responses in head kidney (HK) macrophages induced by pathogen associated molecular patterns (PAMPs), pro-inflammatory cytokines, mitogens and pathway activators highly elevated the expression level of TGF-?1b but not that of TGF-?1a. TGF-?1b expression was also increased by polyinosinic:polycytidylic acid (poly(I:C)) and/or lipopolysaccharide (LPS) stimulation in three different trout cell lines studied. Finally we show that TGF-?1b is potentially involved in defense against infection with viral haemorrhagic septicemia virus (VHSV), which had no effect on TGF-?1a expression. Thus, it is likely the TGF-?1b gene represents a copy which fulfils the major immune orchestrating functions of TGF-?1 as seen in other vertebrates. PMID:23178261

  1. Thermomechanical constitutive model of shape memory polymer

    Microsoft Academic Search

    Hisaaki Tobushi; Kayo Okumura; Shunichi Hayashi; Norimitsu Ito

    2001-01-01

    A nonlinear thermomechanical constitutive model of shape memory polymer (SMP) is developed by modifying a linear model. The coefficients in the model are expressed by the single exponential functions of temperature in order to describe the variation in mechanical properties of the material due to the glass transition. The proposed theory expresses well the thermomechanical properties of polyurethane-shape memory polymer,

  2. Constitutive over-expression of rice chymotrypsin protease inhibitor gene OCPI2 results in enhanced growth, salinity and osmotic stress tolerance of the transgenic Arabidopsis plants.

    PubMed

    Tiwari, Lalit Dev; Mittal, Dheeraj; Chandra Mishra, Ratnesh; Grover, Anil

    2015-07-01

    Protease inhibitors are involved primarily in defense against pathogens. In recent years, these proteins have also been widely implicated in response of plants to diverse abiotic stresses. Rice chymotrypsin protease inhibitor gene OCPI2 is highly induced under salt and osmotic stresses. The construct containing the complete coding sequence of OCPI2 cloned downstream to CaMV35S promoter was transformed in Arabidopsis and single copy, homozygous transgenic lines were produced. The transgenic plants exhibited significantly enhanced tolerance to NaCl, PEG and mannitol stress as compared to wild type plants. Importantly, the vegetative and reproductive growth of transgenic plants under unstressed, control conditions was also enhanced: transgenic plants were more vigorous than wild type, resulting into higher yield in terms of silique number. The RWC values and membrane stability index of transgenic in comparison to wild type plants was higher. Higher proline content was observed in the AtOCPI2 lines, which was associated with higher transcript expression of pyrroline-5-carboxylate synthase and lowered levels of proline dehydrogenase genes. The chymotrypsin protease activities were lower in the transgenic as against wild type plants, under both unstressed, control as well as stressed conditions. It thus appears that rice chymotrypsin protease inhibitor gene OCPI2 is a useful candidate gene for genetic improvement of plants against salt and osmotic stress. PMID:25910649

  3. Disabling the Constitution

    Microsoft Academic Search

    Miklós Bánkuti; Gábor Halmai

    2012-01-01

    Hungary’s 2010 election brought to power a Fidesz parliamentary supermajority led by Prime Minister Viktor Orban. In just two years, they have fundamentally changed the constitutional order of Hungary. The current government now has very few checks on its own power, but the new constitutional order permits the governing party to lodge its loyalists in crucial long-term positions with veto

  4. Constitution of the AFT.

    ERIC Educational Resources Information Center

    American Federation of Teachers, Washington, DC.

    This document contains the constitution and the bylaws of the American Federation of Teachers. The constitution is comprised of 12 articles which deal with the name and objectives of the organization, membership, chartering of state and local units, federation officers, the Executive Council, conventions, representation of state and local units at…

  5. Interpreting the Constitution.

    ERIC Educational Resources Information Center

    Brennan, William J., Jr.

    1987-01-01

    Discusses constitutional interpretations relating to capital punishment and protection of human dignity. Points out the document's effectiveness in creating a new society by adapting its principles to current problems and needs. Considers two views of the Constitution that lead to controversy over the legitimacy of judicial decisions. (PS)

  6. Constitutive Interoperability Amit K. Chopra

    E-print Network

    Constitutive Interoperability Amit K. Chopra Department of Computer Science North Carolina State of interoperability, constitutive and regulative. Constitutive interoperability takes into account solely the meaning, and data flow. We present a language for specifying agents constitutively and a decision procedure

  7. STELLENBOSCH UNIVERSITY STUDENT PARLIAMENT CONSTITUTION

    E-print Network

    Geldenhuys, Jaco

    0 STELLENBOSCH UNIVERSITY STUDENT PARLIAMENT CONSTITUTION 2013 Constitution This Constitution part of this constitution, or the Student Constitution, explicitly states a later date of application all of the terms and conditions come into effect on the date this Constitution is approved

  8. Purification from rat liver of a novel constitutively expressed member of the aldo-keto reductase 7 family that is widely distributed in extrahepatic tissues.

    PubMed Central

    Kelly, V P; Ireland, L S; Ellis, E M; Hayes, J D

    2000-01-01

    Antiserum raised against human aflatoxin B(1) aldehyde reductase 1 (hAFAR1) has been used to identify a previously unrecognized rat aldo-keto reductase (AKR). This novel enzyme is designated rat aflatoxin B(1) aldehyde reductase 2 (rAFAR2) and it characteristically migrates faster during SDS/PAGE than does the archetypal ethoxyquin-inducible rAFAR protein (now called rAFAR1). Significantly, rAFAR2 is essentially unreactive with polyclonal antibodies raised against rAFAR1. Besides its distinct electrophoretic and immunochemical properties, rAFAR2 appears to be regulated differently from rAFAR1 as it is expressed in most rat tissues and does not appear to be induced by ethoxyquin. Multiple forms of rAFAR2 have been identified. Anion-exchange chromatography on Q-Sepharose, followed by adsorption chromatography on columns of Matrex Orange A and Cibacron Blue, have been employed to purify rAFAR2 from rat liver cytosol. The Q-Sepharose chromatography step resulted in the resolution of rAFAR2 into three peaks of AKR activity, two of which were purified and shown to be capable of catalysing the reduction of 2-carboxybenzaldehyde, succinic semialdehyde, 4-nitrobenzaldehyde and 9,10-phenathrenequinone. The two most highly purified rAFAR2-containing preparations eluted from the Cibacron Blue column were 91 and 98% homogeneous. Analysis of these by SDS/PAGE indicated that the least anionic (peak CBA5) comprised a polypeptide of 37.0 kDa, whereas the most anionic (peak CBA6) contained two closely migrating polypeptides of 36.8 and 37.0 kDa; by contrast, in the present study, rAFAR1 was estimated by SDS/PAGE to be composed of 38.0 kDa subunits. Final purification of the 37 kDa polypeptide in CBA5 and CBA6 was accomplished by reversed-phase HPLC. Partial proteolysis of the two preparations of the 37 kDa polypeptide with Staphylococcus aureus V8 protease yielded fragments of identical size, suggesting that they represent the product of a single gene. Furthermore, the peptide maps from CBA5 and CBA6 differed substantially from that yielded by rAFAR1, indicating that they are genetically distinct from the inducible reductase. A peptide generated by CNBr digestion of the 37 kDa polypeptide from CBA6 was shown by Edman degradation to share 88% sequence identity with residues Tyr(168)-Leu(183) of rAFAR1. This provides evidence that the rat protein identified by its cross-reactivity with anti-hAFAR1 serum is an additional member of the AKR7 family. PMID:10816434

  9. Computational Analysis and Low-Scale Constitutive Expression of Laccases Synthetic Genes GlLCC1 from Ganoderma lucidum and POXA 1B from Pleurotus ostreatus in Pichia pastoris

    PubMed Central

    Reyes-Guzmán, Edwin Alfredo; Poutou-Pińales, Raúl A.; Reyes-Montańo, Edgar Antonio; Pedroza-Rodríguez, Aura Marina; Rodríguez-Vázquez, Refugio; Cardozo-Bernal, Ángela M.

    2015-01-01

    Lacasses are multicopper oxidases that can catalyze aromatic and non-aromatic compounds concomitantly with reduction of molecular oxygen to water. Fungal laccases have generated a growing interest due to their biotechnological potential applications, such as lignocellulosic material delignification, biopulping and biobleaching, wastewater treatment, and transformation of toxic organic pollutants. In this work we selected fungal genes encoding for laccase enzymes GlLCC1 in Ganoderma lucidum and POXA 1B in Pleurotus ostreatus. These genes were optimized for codon use, GC content, and regions generating secondary structures. Laccase proposed computational models, and their interaction with ABTS [2, 2?-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)] substrate was evaluated by molecular docking. Synthetic genes were cloned under the control of Pichia pastoris glyceraldehyde-3-phosphate dehydrogenase (GAP) constitutive promoter. P. pastoris X-33 was transformed with pGAPZ?A-LaccGluc-Stop and pGAPZ?A-LaccPost-Stop constructs. Optimization reduced GC content by 47 and 49% for LaccGluc-Stop and LaccPost-Stop genes, respectively. A codon adaptation index of 0.84 was obtained for both genes. 3D structure analysis using SuperPose revealed LaccGluc-Stop is similar to the laccase crystallographic structure 1GYC of Trametes versicolor. Interaction analysis of the 3D models validated through ABTS, demonstrated higher substrate affinity for LaccPost-Stop, in agreement with our experimental results with enzymatic activities of 451.08 ± 6.46 UL-1 compared to activities of 0.13 ± 0.028 UL-1 for LaccGluc-Stop. This study demonstrated that G. lucidum GlLCC1 and P. ostreatus POXA 1B gene optimization resulted in constitutive gene expression under GAP promoter and ?-factor leader in P. pastoris. These are important findings in light of recombinant enzyme expression system utility for environmentally friendly designed expression systems, because of the wide range of substrates that laccases can transform. This contributes to a great gamut of products in diverse settings: industry, clinical and chemical use, and environmental applications. PMID:25611746

  10. Nepal's Constitutional Process

    E-print Network

    International Crisis Group

    2007-02-26

    NEPAL’S CONSTITUTIONAL PROCESS Asia Report N°128 – 26 February 2007 TABLE OF CONTENTS EXECUTIVE SUMMARY AND RECOMMENDATIONS................................................. i I. INTRODUCTION... VIII. CONCLUSION ............................................................................................................. 31 APPENDICES A. MAP OF NEPAL...

  11. Kenya's New Constitution

    E-print Network

    Kramon, Eric

    On 4 August 2010, Kenyans voted to adopt a new constitution, culminating a process that began as part of a resolution to the violent conflict that followed the December 2007 elections. By reducing executive power, devolving ...

  12. Actions, Habits and Constitution 

    E-print Network

    Pollard, Bill

    2006-01-01

    In this paper I offer a critique of the view made popular by Davidson that rationalization is a species of causal explanation, and propose instead that in many cases the explanatory relation is constitutive. Given ...

  13. RESEARCH Open Access Dysregulated Tim-3 expression on natural killer

    E-print Network

    Paris-Sud XI, Université de

    RESEARCH Open Access Dysregulated Tim-3 expression on natural killer cells is associated,2 and Marylyn M Addo1* Abstract Background: Natural killer (NK) cells constitutively express high levels of Tim that incorporating components with the potential to harness the antiviral function of natural killer (NK) cells may

  14. Constitutive androstane receptor (CAR) as a potential sensing biomarker of persistent organic pollutants (POPs) in aquatic mammal: molecular characterization, expression level, and ligand profiling in Baikal seal (Pusa sibirica).

    PubMed

    Sakai, Hiroki; Iwata, Hisato; Kim, Eun-Young; Tsydenova, Oyuna; Miyazaki, Nobuyuki; Petrov, Evgeny A; Batoev, Valeriy B; Tanabe, Shinsuke

    2006-11-01

    To characterize the function of constitutive active/androstane receptor (CAR) in aquatic mammals, CAR complementary DNA (cDNA) was cloned from the liver of Baikal seal (Pusa sibirica) from Lake Baikal, Russia, and the messenger RNA (mRNA) expression levels in various tissues/organs of the wild population and the CAR ligand profiles were investigated. The seal CAR cDNA had an open reading frame of 1047 bp encoding 348 amino acids that revealed 74-84% amino acid identities with CARs from rodents and human. The mRNA expression profile of tissues/organs represented that Baikal seal CAR was predominantly expressed in the liver followed by heart and intestine. The expression analysis of hepatic CAR mRNA showed no correlation with expression of cytochrome P450 (CYP) 1A, 1B, 2B, 2C, and 3A-like proteins, indicating that the CAR expression level may not be the sole determinant of the regulation of these CYP expressions in the seal liver. There was no significant correlation between CAR expression and any of the persistent organic pollutants (POPs) levels. Furthermore, we performed an in vitro CAR transactivation assay using MCF-7 cells transfected with Baikal seal CAR expression plasmid and (NR1)(3)-luciferase reporter gene plasmid. In the transactivation analysis of Baikal seal CAR, neither repression by androstanol and androstenol, nor activation by estrone and estradiol, which are recognized as endogenous ligands for mouse and human CARs, was detected. On the other hand, bile acids such as chenodeoxycholic acid, deoxycholic acid, and lithocholic acid activated the seal CAR as well as mouse CAR. As for exogenous chemicals, the seal CAR was transactivated by a human CAR agonist, 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime), but not by a mouse CAR agonist, (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene). In addition, the seal CAR was also activated by polychlorinated biphenyls (PCBs) (Kanechlor-500, International Union of Pure and Applied Chemistry No. PCB153; 2,2',4,4',5,5'-hexachlorobiphenyl and PCB180; 2,2',3,4,4',5,5'-heptachlorobiphenyl), and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE). The seal CAR responded more sensitively to PCBs than the mouse CAR. Based on the results of CAR transactivation assay, the lowest observable effect levels of Kanechlor-500, PCB153, PCB180, p,p'-DDT, and p,p'-DDE in Baikal seal were estimated to be 10, 20, 20, 10, and 10 ppm on wet weight basis, respectively. These results suggest that CAR is conserved in diverse mammalian species including seals. Whereas the seal CAR-mediated gene transcription may potentially be a sensitive response to the exposure of certain POPs, the ligand profile of seal CAR may be different from those of other mammalian CARs. This study indicates that CAR-mediated responses may be useful information to assess the ecotoxicological risk of xenobiotics such as POPs in wildlife but the previous results derived from rodent and human CAR may not be applicable to the risk assessment in wild species. PMID:16929008

  15. Center Constitution 1/16/98 1 CONSTITUTION

    E-print Network

    Janssen, Michel

    Center Constitution 1/16/98 1 CONSTITUTION OF THE MINNESOTA CENTER FOR PHILOSOPHY OF SCIENCE NATURE, and any volumes thus generated will be submitted for publication in MSPS. #12;Center Constitution 1

  16. Human & Constitutional Rights

    NSDL National Science Digital Library

    The Arthur W. Diamond Law Library at Columbia Law School maintains this excellent resource for finding materials on human rights and constitutional rights. The metasite serves students, scholars, and practitioners as a portal to documents and Internet resources on international and domestic law related to human and constitutional rights. The information resources are divided into six sections: Country Reports, International Links, Regional Links, National Links, Documents, and Other Web Resources. Each section is clearly organized into neat lists or pop-up menus to ease navigation. Marylin Raisch -- the International, Comparative, and Foreign Law Librarian responsible for this metasite -- also provides a Hot Topics section, which posts information on current events related to human and constitutional rights.

  17. National Constitution Center

    NSDL National Science Digital Library

    On July 4, 2003, the new National Constitution Center will open in a brand new facility within Independence Historical Park in Philadelphia that will help it pursue its mission of "increasing public understanding of, and appreciation for, the Constitution, its history, and its contemporary relevance." Visitors will want to take the virtual tour available online, which moves through the building's Great Hall, the Kimmel Theatre (which will be used for museum orientation programs), the DeVos Exhibit Hall, and the rest of the building's different areas. As might be expected, the Web site has an online version of the complete Constitution (in English and Spanish), along with helpful educational resources such as lesson plans for grades K-12. The site is rounded out by information for visitors and a "Save the Bill of Rights!" educational game where students help recover the Bill of Rights by looking for clues in a series of graphic images depicting each right protected by this important document.

  18. Jefferson as constitutional theorist

    Microsoft Academic Search

    Merrill D. Peterson

    1986-01-01

    Thomas Jefferson, statesman, philosopher, architect, champion of freedom and enlightenment, was United States minister to France when the federal Constitutional Convention met in 1787. Long an advocate of a strengthened confederation, he applauded the convention and anxiously awaited the result of its deliberations. On seeing the roster of delegates, he exclaimed to his diplomatic colleague and friend John Adams, \\

  19. US CONSTITUTION 1

    NSDL National Science Digital Library

    dramsden

    2013-04-08

    Continue to study and review the uS Constitution. Welcome now get ready to study the document which has allowed our great nation to grow, provide our citizens to flourish, and ispired nations around the world. Answer each question in your spiral. Define the following. 1. admirality and maritime law 2.Bill of Rights 3. clear and ...

  20. Amending Higher Education's Constitution

    ERIC Educational Resources Information Center

    Trower, Cathy A.

    2008-01-01

    Beginning in 1934, representatives of the American Association of University Professors (AAUP) and the Association of American Colleges (AAC) met and drafted the definitive statement on academic freedom and tenure. Like the U.S. Constitution, the 1940 "Statement on Principles of Academic Freedom and Tenure" was a commendable, if deficient, product…

  1. The Constitution in Action

    ERIC Educational Resources Information Center

    Potter, Lee Ann

    2007-01-01

    In this article, the author describes the experiences middle school students on a field trip to the new Constitution in Action Learning Lab in the Boeing Learning Center at the National Archives can expect. There, middle school students take on the roles of archivists and researchers collecting and analyzing primary sources from the holdings of…

  2. AALTO UNIVERSITY FOUNDATION CONSTITUTION

    E-print Network

    Kaski, Samuel

    AALTO UNIVERSITY FOUNDATION CONSTITUTION Section 1. Name and domicile of the Foundation The Foundation shall be called Aalto-korkeakoulusäätiö (Swedish: Stiftelsen för Aaltohögskolan, English: Aalto University Foundation) and its domicile shall be the City of Helsinki. Section 2. Purpose of the Foundation

  3. Constituting children's bodily integrity.

    PubMed

    Hill, B Jessie

    2015-04-01

    Children have a constitutional right to bodily integrity. Courts do not hesitate to vindicate that right when children are abused by state actors. Moreover, in at least some cases, a child's right to bodily integrity applies within the family, giving the child the right to avoid unwanted physical intrusions regardless of the parents' wishes. Nonetheless, the scope of this right vis-ŕ-vis the parents is unclear; the extent to which it applies beyond the narrow context of abortion and contraception has been almost entirely unexplored and untheorized. This Article is the first in the legal literature to analyze the constitutional right of minors to bodily integrity within the family by spanning traditionally disparate doctrinal categories such as abortion rights; corporal punishment; medical decisionmaking; and nontherapeutic physical interventions such as tattooing, piercing, and circumcision. However, the constitutional right of minors to bodily integrity raises complex philosophical questions concerning the proper relationship between family and state, as well as difficult doctrinal and theoretical issues concerning the ever-murky idea of state action. This Article canvasses those issues with the ultimate goal of delineating a constitutional right of bodily security and autonomy for children. PMID:26016017

  4. Crushed Salt Constitutive Model

    SciTech Connect

    Callahan, G.D.

    1999-02-01

    The constitutive model used to describe the deformation of crushed salt is presented in this report. Two mechanisms -- dislocation creep and grain boundary diffusional pressure solution -- are combined to form the basis for the constitutive model governing the deformation of crushed salt. The constitutive model is generalized to represent three-dimensional states of stress. Upon complete consolidation, the crushed-salt model reproduces the Multimechanism Deformation (M-D) model typically used for the Waste Isolation Pilot Plant (WIPP) host geological formation salt. New shear consolidation tests are combined with an existing database that includes hydrostatic consolidation and shear consolidation tests conducted on WIPP and southeastern New Mexico salt. Nonlinear least-squares model fitting to the database produced two sets of material parameter values for the model -- one for the shear consolidation tests and one for a combination of the shear and hydrostatic consolidation tests. Using the parameter values determined from the fitted database, the constitutive model is validated against constant strain-rate tests. Shaft seal problems are analyzed to demonstrate model-predicted consolidation of the shaft seal crushed-salt component. Based on the fitting statistics, the ability of the model to predict the test data, and the ability of the model to predict load paths and test data outside of the fitted database, the model appears to capture the creep consolidation behavior of crushed salt reasonably well.

  5. ASBSU Constitution Revised Spring 2013 1 of 6 CONSTITUTION

    E-print Network

    Barrash, Warren

    ASBSU Constitution Revised Spring 2013 1 of 6 CONSTITUTION PREAMBLE We otherwise specified in this Constitution. They must also receive a 2.5 GPA or higher each semester in office Council Responsibilities #12;ASBSU Constitution Revised Spring 2013 2 of 6 1

  6. Student Events Board Constitution 1 Student Events Board Constitution

    E-print Network

    Student Events Board Constitution 1 Student Events Board Constitution Article I. Name Section 1 Relations Chair, and #12;Student Events Board Constitution 2 Communications Director. If the vote) of the Student Body Constitution of Siena College. 2. To be eligible for election to this position, candidates

  7. ASBSU Constitution Revised Spring 2012 1 of 6 CONSTITUTION

    E-print Network

    Barrash, Warren

    ASBSU Constitution Revised Spring 2012 1 of 6 CONSTITUTION PREAMBLE We the students of Boise in this Constitution. They must also receive a 2.5 GPA or higher each semester in office. Failure to do so would result Responsibilities #12;ASBSU Constitution Revised Spring 2012 2 of 6 1. The Executive Council will approve

  8. Explore the Constitution

    NSDL National Science Digital Library

    If you type the words â??U.S. Constitutionâ?ť into Google, the search engine returns about 31 million results. Thatâ??s a lot of talk about a document written by a handful of scholar-politicians in an upstart republic more than 227 years ago. Yet less than a quarter of Americans have actually read the document. This site, hosted by the National Constitution Center, includes the United States Constitution in its entirety, divided clearly by Article and Amendment, and annotated with notes by the Annenberg Classroom. Perhaps best of all, you can browse the site by Issue. For instance, click on Abortion and explore how the Roe v. Wade Supreme Court ruling was based on Ninth and 14th Amendment rights.

  9. Thomas Jefferson and the Constitution.

    ERIC Educational Resources Information Center

    Peterson, Merrill D.

    1987-01-01

    Examines Thomas Jefferson's role in the making and interpretation of the United States Constitution. Discusses the dominant features of Jefferson's constitutional theory; the character of Jefferson's presidency; and Jefferson's ongoing concern about constitutional preservation and change. Lists important dates in the history of the constitution.…

  10. Constitutive modeling and thermoviscoplasticity

    NASA Technical Reports Server (NTRS)

    Hetnarski, Richard B.; Ghoneim, Hany; Paul, Donald B.

    1988-01-01

    Development and solution of coupled thermomechanical equations at elevated temperature and/or high strain rates are discussed. Three main considerations are presented: development of the coupled thermomechanical equations by means of the rational theory of thermodynamics, development of a thermoviscoplastic constitutive equation which is congruous with the developed coupled equations, and the applicability of the developed equations to the treatment by the finite element method.

  11. Comparison of Efficacy of the Disease-Specific LOX1- and Constitutive Cytomegalovirus-Promoters in Expressing Interleukin 10 through Adeno-Associated Virus 2/8 Delivery in Atherosclerotic Mice

    PubMed Central

    Zhu, Hongqing; Cao, Maohua; Mirandola, Leonardo; Figueroa, Jose A.; Cobos, Everardo; Chiriva-Internati, Maurizio; Hermonat, Paul L.

    2014-01-01

    The development of gene therapy vectors for treating diseases of the cardiovascular system continues at a steady pace. Moreover, in the field of gene therapy the utility of “disease-specific promoters” has strong appeal. Many therapeutic genes, including transforming growth factor beta 1 or interleukin 10, are associated to adverse effects. The use of a disease-specific promoter might minimize toxicity. The lectin-like oxidized low density lipoprotein receptor 1 is a marker of cardiovascular disease and a potential therapeutic target. The lectin-like oxidized low density lipoprotein receptor 1 is known to be up-regulated early during disease onset in a number of cell types at the sites where the disease will be clinically evident. In this study an adeno-associated virus-2 DNA vector (AAV2) using the AAV8 capsid, and containing the full length The lectin-like oxidized low density lipoprotein receptor 1 promoter, was generated and assayed for its ability to express human interleukin 10 in low density lipoprotein receptor knockout mice on high cholesterol diet. The cytomegalovirus early promoter was used for comparison in a similarly structured vector. The two promoters were found to have equal efficacy in reducing atherogenesis as measured by aortic systolic blood velocity, aortic cross sectional area, and aortic wall thickness. This is the first head-to-head comparison of a constitutive with a disease-specific promoter in a therapeutic context. These data strongly suggest that the use of a disease-specific promoter is appropriate for therapeutic gene delivery. PMID:24736312

  12. Constitutive expression of abiotic stress-inducible hot pepper CaXTH3, which encodes a xyloglucan endotransglucosylase/hydrolase homolog, improves drought and salt tolerance in transgenic Arabidopsis plants.

    PubMed

    Cho, Seok Keun; Kim, Jee Eun; Park, Jong-A; Eom, Tae Jin; Kim, Woo Taek

    2006-05-29

    Xyloglucan endotransglucosylase/hydrolase (XTH) has been recognized as a cell wall-modifying enzyme, participating in the diverse physiological roles. From water-stressed hot pepper plants, we isolated three different cDNA clones (pCaXTH1, pCaXTH2, and pCaXTH3) that encode XTH homologs. RT-PCR analysis showed that three CaXTH mRNAs were concomitantly induced by a broad spectrum of abiotic stresses, including drought, high salinity and cold temperature, and in response to stress hormone ethylene, suggesting their role in the early events in the abiotic-related defense response. Transgenic Arabidopsis plants that constitutively expressed the CaXTH3 gene under the control of the CaMV 35S promoter exhibited abnormal leaf morphology; the transgenic leaves showed variable degrees of twisting and bending along the edges, resulting in a severely wrinkled leaf shape. Microscopic analysis showed that 35S-CaXTH3 leaves had increased numbers of small-sized cells, resulting in disordered, highly populated mesophyll cells in each dorsoventral layer, and appeared to contain a limited amount of starch. In addition, the 35S-CaXTH3 transgenic plants displayed markedly improved tolerance to severe water deficit, and to lesser extent to high salinity in comparison with the wild-type plants. These results indicate that CaXTH3 is functional in heterologous Arabidopsis cells, thereby effectively altering cell growth and also the response to abiotic stresses. Although the physiological function of CaXTHs is not yet clear, there are several possibilities for their involvement in a subset of physiological responses to counteract dehydration and high salinity stresses in transgenic Arabidopsis plants. PMID:16684525

  13. Extracting expression modules from perturbational gene expression compendia

    Microsoft Academic Search

    Steven Maere; Patrick Van Dijck; Martin Kuiper

    2008-01-01

    Background  Compendia of gene expression profiles under chemical and genetic perturbations constitute an invaluable resource from a systems\\u000a biology perspective. However, the perturbational nature of such data imposes specific challenges on the computational methods\\u000a used to analyze them. In particular, traditional clustering algorithms have difficulties in handling one of the prominent\\u000a features of perturbational compendia, namely partial coexpression relationships between genes.

  14. Conscience and the Constitution

    NSDL National Science Digital Library

    This companion site to the PBS national broadcast December 2000, of "Conscience and the Constitution" examines the historical and moral issues surrounding the decision of a handful of Japanese to refuse to be drafted from their location in an American concentration camp in 1944. The site also looks at the history of the Japanese American Citizens League (JACL), an organization of first generation Japanese-Americans that not only supported the efforts of the US military to apprehend and relocate Japanese citizens, but opposed all efforts of individual Japanese-Americans to challenge the constitutionality of the government's actions. In addition to the thoughtful narration of the history and the controversy it continues to generate, the Website provides access to original documents of the parties involved, including letters and statements from the draft resisters, who eventually served more than two years hard labor, the columns of the journalist who supported their civil disobedience, and public statements and correspondence of the JACL. Some video portions of the broadcast are also available here in RealPlayer.

  15. Ethics and constitutional government.

    PubMed

    Albright, James A

    2007-01-01

    The term ethics refers to a set of principles that govern acceptable, proper conduct. Attacks on the Constitution of the United States pose the most serious breach of ethics today. Our country was founded as a republic, not as a democracy. Our Founding Fathers' main concern was to protect citizens from the power of the federal government, so constitutionally, the central government has little or no authority over individual citizens except on federal property. One of the major problems today is the fact that we now have professional politicians. This is due in large part to the lure of financial gain from countless special interest groups. This would change under constitutional law because the federal budget would decrease drastically. Article 1 states that all legislative power is vested in Congress. Congress has only 18 enumerated powers, and almost half of these pertain to defense of the country. Many of our current problems are due to regulatory agencies that have become independent fiefdoms with unconstitutional legislative, as well as executive and judicial, powers. The regulatory agency most relevant to medicine, both clinical care and research, is the FDA. It is now obvious that its basic structure needs to be changed or abolished because its actions are identical to those inherent in authoritarian systems. Constructive change could come from Congress, but it would be most desirable if the Supreme Court would take the lead and reestablish the authority of the Constitution as the Supreme Law of the Land. The FDA's function could be limited to the determination of safety, but preferably its mission would be altered to that of product certification. Defenders of the current system claim that such a drastic change would be too dangerous and their prime example is thalidomide. But it is now known that the market has already solved that problem prior to the government-imposed sanctions. Realistically, market forces and their ramifications, including our legal system, provide the most effective methods of protecting the public from harmful drugs and devices. Fortunately, a model for miracles is available. It is New Zealand, which had become increasingly socialistic after WW II. As a result, they had become noncompetitive, and with the formation of the European Union, they lost their major market exports. In order to survive they made some astounding changes in the mid-1980s. They studied every agency that depended on government funding and transferred much of this work over to the private sector. They turned the remaining agencies into profit-making enterprises. These agencies had cost the government about $1 billion/year. Now, they produce about $1 billion in revenue and taxes. Without question, a return to constitutional government would be an invigorating stimulus to bioengineering research in the future. It would flourish. The eminence of this country did not develop from a strong central government. It is due to its absence, but we are rapidly reaching a point of no return. PMID:18298395

  16. Creep constitutive equations for damaged materials

    SciTech Connect

    Cocks, A.C.F.; Leckie, F.A. (Univ. of Illinois, Urbana, IL (United States))

    1987-01-01

    The object of the present paper is to combine knowledge of microscopic mechanisms with experimental observations to obtain constitutive equations for damaged materials. The initial focus is on the mechanisms of failure in creeping materials. A general structure for the constitutive equations is obtained which gives a framework for the development of constitute equations for particular materials. In the present paper this is attempted for copper and an aluminum alloy. A section of the paper is devoted to the application of the material models to structural problems. It is found that when the rate of increase of damage is mathematically separable in expressions for stress and damage that it is possible to obtain upper bounds for the life of a component. 35 refs., 17 figs.

  17. Guidelines for Teaching and Testing the Illinois Constitution.

    ERIC Educational Resources Information Center

    Illinois State Office of the Superintendent of Public Instruction, Springfield. Instructional Services Unit.

    This document sets forth guidelines for teaching and testing public school students on the principles of democratic government as expressed in the Constitution of the United States and the Constitution of the State of Illinois. Identification is made of ways of making the examination required by the state of Illinois not only an integral part of…

  18. DISROBED: THE CONSTITUTION OF MODESlY ANITA L. ALLEN

    E-print Network

    Sharp, Kim

    of the United States Constitution protects free- dom of speech and expression.l The Fourteenth Amendment pro2006] DISROBED: THE CONSTITUTION OF MODESlY ANITA L. ALLEN 1. INTRODUCTION THE First Amendment to Western Europe, topless sunbathing is rarely permitted in the United States. Even infant breast

  19. Sesquiterpene synthases from grand fir (Abies grandis). Comparison of constitutive and wound-induced activities, and cDNA isolation, characterization, and bacterial expression of delta-selinene synthase and gamma-humulene synthase.

    PubMed

    Steele, C L; Crock, J; Bohlmann, J; Croteau, R

    1998-01-23

    Grand fir (Abies grandis) has been developed as a model system for the study of oleoresin production in response to stem wounding and insect attack. The turpentine fraction of the oleoresin was shown to contain at least 38 sesquiterpenes that represent 12.5% of the turpentine, with the monoterpenes comprising the remainder. Assays of cell-free extracts from grand fir stem with farnesyl diphosphate as substrate indicated that the constitutive sesquiterpene synthases produced the same sesquiterpenes found in the oleoresin and that, in response to wounding, only two new products were synthesized, delta-cadinene and (E)-alpha-bisabolene. A similarity based cloning strategy yielded two new cDNA species from a stem cDNA library that, when expressed in Escherichia coli and the gene products subsequently assayed, yielded a remarkable number of sesquiterpene products. The encoded enzymes have been named delta-selinene synthase and gamma-humulene synthase based on the principal products formed; however, each enzyme synthesizes three major products and produces 34 and 52 total sesquiterpenes, respectively, thereby accounting for many of the sesquiterpenes of the oleoresin. The deduced amino acid sequence of the delta-selinene synthase cDNA open reading frame encodes a protein of 581 residues (at 67.6 kDa), whereas that of the gamma-humulene synthase cDNA encodes a protein of 593 residues (at 67.9 kDa). The two amino acid sequences are 83% similar and 65% identical to each other and range in similarity from 65 to 67% and in identity from 43 to 46% when compared with the known sequences of monoterpene and diterpene synthases from grand fir. Although the two sesquiterpene synthases from this gymnosperm do not very closely resemble terpene synthases from angiosperm species (52-56% similarity and 26-30% identity, there are clustered regions of significant apparent homology between the enzymes of these two plant classes. The multi-step, multi-product reactions catalyzed by the sesquiterpene synthases from grand fir are among the most complex of any terpenoid cyclase thus far described. PMID:9442047

  20. Polity.org: Constitutional Matters

    NSDL National Science Digital Library

    1996-01-01

    Full text of the new South African Constitution, adopted by the Constitutional Assembly on May 8, 1996, and the full text of President Nelson Mandela's address to the Constitutional Assembly upon its adoption, are available via the Web. The constitution is available as a single file, and as plain text, WordPerfect 5.1, 6.1 and Microsoft Word 6.0 .zip files.

  1. CONSTITUTIONAL LAW Political Science 320

    E-print Network

    Young, Paul Thomas

    1 CONSTITUTIONAL LAW Political Science 320 Maybank Room 111 T/TH 10:50-12:05 Spring 2013@cofc.edu ________________________________________________________________________ I. CONTENT & OBJECTIVES This course is an examination of the United States Constitution various theories of Constitutional interpretation, the influence of "extralegal" factors on judicial

  2. Constitution of the Student Council

    E-print Network

    Aronov, Boris

    1 Constitution of the Student Council Polytechnic Institute of New York University ­ Brooklyn of New York University." The Student Council is referred to in this constitution as the Student Council for itself additional duties and powers as prescribed by this constitution. Section 2. The Student Council

  3. Constitution1 ARTICLE I3

    E-print Network

    Indiana University

    Constitution1 2 ARTICLE I3 Section 1. NAME4 The name of this organization is the Indiana, establish this constitution.18 19 ARTICLE II20 Section 1. ACTIVE MEMBERS21 Every student officially constitute a quorum.67 3. All meetings of the Board shall be open.68 #12;Section 3. TERM69 The full term

  4. Constitution of the WELLCOME TRUST

    E-print Network

    Rambaut, Andrew

    1 Constitution of the WELLCOME TRUST (Charity registered in England and Wales no. 210183 Constitution 2 Name of the charity 4 3 Trustee 4 Objects 4 Objects of the Trust 4 5 Research in accordance Remuneration 9 Amendments 17 Amendment of Constitution 10 #12;3 18 Amendment of the Memorandum and 11 Articles

  5. Digital Media Design Students Constitution

    E-print Network

    Jones, Michelle

    Digital Media Design Students Constitution ARTICLE I: ORGANIZATION'S NAME AND PURPOSE Section 1 activities and design-related excursions for members. ARTICLE VIII: AMENDING CONSTITUTION A. A proposed amendment to this Constitution shall be emailed to the membership at least thirty (30) days prior to its

  6. CONSTITUTION AND STATUTES OF THE

    E-print Network

    Roy, Subrata

    CONSTITUTION AND STATUTES OF THE UNIVERSITY OF FLORIDA STUDENT BODY Student Body Statutes 2012 Submitted by: David M. Kerner, Chairman 2009-2010 Constitution Revision Commission On Behalf of the Full, 2011 #12;#12;TABLE OF CONTENTS 1. CONSTITUTION 2. STUDENT BODY STATUTES I. Administrative General

  7. Constitution1 ARTICLE I2

    E-print Network

    Indiana University

    Constitution1 ARTICLE I2 Section 1. NAME3 The name of this organization is the Indiana Memorial, establish this constitution.17 ARTICLE II18 Section 1. ACTIVE MEMBERS19 Every student officially enrolled.58 2. Two-thirds (2/3) of the voting directors shall constitute a quorum.59 3. All meetings

  8. Conversations on the Constitution

    NSDL National Science Digital Library

    Perhaps the United States might be a better place if at the dinner table one interested party might ask the question, "Hey Mom, can we talk about the establishment clause tonight?" Until such topics spontaneously arrive in a pre-prandial setting like the one just mentioned, there will still be great interest in this lovely website created by the American Bar Association. As its mission statement declares, "This project is designed to further dialogue in schools and in the workplace about American constitutional principles and values." Within the site, visitors can peruse a list of topics, such as war powers, the establishment of religion, and cruel and unusual punishment. Each area has a brief overview of each topic, and then three "starter" questions. These starter questions feature a list of specific queries, accompanied by brief illustrations (such as political cartoons and the like) that can be used at the dinner table, the boardroom table, or just about any table. Finally, interested parties can also take a few interactive tests on such areas as Supreme Court rulings and students' rights in the classroom.

  9. The Texas Constitutions Digitization Project

    NSDL National Science Digital Library

    Presented by the Tarlton Law Library at the University of Texas School of law, this site offers digital copies of the twelve constitutions of the State (and Republic) of Texas drafted between 1824 and 1876. Both transcriptions and digital images of the original documents are provided, along with a bibliography of printings, a supplemental bibliography, and a link to the relevant Handbook of Texas article. A Spanish version is also available for a few of the constitutions. An internal search engine, an annotated bibliography on the constitutions, a bibliography on Texas constitutional history, and a collection of related links are also provided.

  10. Differential gene expression mediated by 15-hydroxyeicosatetraenoic acid in LPS-stimulated RAW 264.7 cells

    Microsoft Academic Search

    Alexandra C Schrimpe; David W Wright

    2009-01-01

    BACKGROUND: Given the immuno-modulatory activity of native haemozoin (Hz), the effects of constitutive Hz components on immune response are of interest. Recently, gene expression changes mediated by HNE and the synthetic analogue of Hz, beta-haematin (BH), were identified and implicated a significant role for lipid peroxidation products in Hz's activity. The study presented herein examines gene expression changes in response

  11. Taking Constitutionalism Beyond the State

    Microsoft Academic Search

    Neil Walker

    2008-01-01

    In recent years, the idea that constitutional modes of government are exclusive to states has become the subject both of sustained challenge and of strong defence. This is due to the development at new regional and global sites of decision-making capacities of a scale and intensity often associated with the demand for constitutional governance at state level, to the supply

  12. Reordering American Constitutional Law Teaching.

    ERIC Educational Resources Information Center

    Gerber, Scott D.

    1994-01-01

    Maintains that constitutional law is the cornerstone of an undergraduate public law curriculum. Asserts that there is a welcome trend toward teaching the subject over a two-semester sequence, instead of only one. Describes course content and teaching strategies used in a college constitutional law course. (CFR)

  13. Constitutional Law and Liberal Education.

    ERIC Educational Resources Information Center

    Clor, Harry

    1985-01-01

    By studying constitutional law, students learn about the relationship between democratic theory and practice, one of the main concerns of liberal education. The mind is enlarged when it must apply ethical standards and political ideas to real human problems. How a political science professor teaches constitutional law is discussed. (RM)

  14. The Constitution and Its Critics

    ERIC Educational Resources Information Center

    Main, Thomas J.

    2011-01-01

    In planning a freshman undergraduate curriculum with colleagues recently, the question arose as to what type of understanding educators wanted to impart to their students about the Constitution. The alleged defects of the Constitution that these books point to are wide-ranging and can be classified into various categories. Some problems--such as…

  15. Constitution And Bylaws: 2004 Edition

    ERIC Educational Resources Information Center

    Distance Education and Training Council, 2004

    2004-01-01

    This document contains the constitution and bylaws of the Distance Education and Training Council. The constitution and bylaws include 13 articles. Sections include: Name; Mission and Goals; Administration of the Council; Membership; Meetings; The Commission; Terms of Office; Officers; Committees; Compensation; Dues and Assessments; Miscellaneous…

  16. Formal State Constitutional Change Processesi

    Microsoft Academic Search

    Gerald Benjamin

    Constitutional change in democracies occurs in two ways: by altering the meaning of the document through interpretation, or by altering the text of the document through amendment or revision. For the United States Constitution, change through interpretation predominates. Review of the extensive experience of the American states with \\

  17. Expression and Functional Roles of Angiopoietin-2 in Skeletal Muscles

    Microsoft Academic Search

    Mahroo Mofarrahi; Sabah N. A. Hussain

    2011-01-01

    BackgroundAngiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2) are angiogenesis factors that modulate endothelial cell differentiation, survival and stability. Recent studies have suggested that skeletal muscle precursor cells constitutively express ANGPT1 and adhere to recombinant ANGPT1 and ANGPT2 proteins. It remains unclear whether or not they also express ANGPT2, or if ANGPT2 regulates the myogenesis program of muscle precursors. In this study, ANGPT2

  18. 32 CFR 770.27 - Background.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...for Naval Installations in the State of Hawaii § 770.27 Background. (a) Naval installations in Hawaii constitute a significant element...industrial areas within naval installations in Hawaii wherein construction activities and...

  19. 32 CFR 770.27 - Background.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...for Naval Installations in the State of Hawaii § 770.27 Background. (a) Naval installations in Hawaii constitute a significant element...industrial areas within naval installations in Hawaii wherein construction activities and...

  20. 32 CFR 770.27 - Background.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...for Naval Installations in the State of Hawaii § 770.27 Background. (a) Naval installations in Hawaii constitute a significant element...industrial areas within naval installations in Hawaii wherein construction activities and...

  1. 32 CFR 770.27 - Background.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...for Naval Installations in the State of Hawaii § 770.27 Background. (a) Naval installations in Hawaii constitute a significant element...industrial areas within naval installations in Hawaii wherein construction activities and...

  2. 32 CFR 770.27 - Background.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...for Naval Installations in the State of Hawaii § 770.27 Background. (a) Naval installations in Hawaii constitute a significant element...industrial areas within naval installations in Hawaii wherein construction activities and...

  3. Commentary on the Kenya Constitution (consolidation of 15 articles in the East African Standard)

    E-print Network

    Sheridan, Jennifer

    Commentary on the Kenya Constitution (consolidation of 15 articles in the East African Standard) I The Background to the Referendum Origins of the review Kenyans have long struggled for constitutional reform the constitution and the rights of the people. The civil service and other executive organs lost independence

  4. Temporal and constitutive expression of homeobox-2 gene (Hu-2), human heat shock gene (hsp-70), and oncogenes C-sis and N-myc in early human trophoblast.

    PubMed

    Su, B C; Strand, D; McDonough, P G; McDonald, J F

    1988-11-01

    Recent studies of the genetic basis of animal development indicate that homeobox genes, protooncogenes, and some heat shock genes may play a role in early embryogenesis. To investigate the possibility that these genes function in early human embryonic development, we monitored the expression of a human homeobox gene (Hu-2), two human protooncogenes (C-sis and N-myc), and a human heat shock gene (hsp-70) in human trophoblasts at 7 to 13 weeks gestational age. All these genes were found to be expressed in the tissues analyzed. The hsp-70 gene was expressed at nearly constant levels throughout the development period surveyed, whereas N-myc, C-sis, and Hu-2 showed a coordinated pattern of regulated expression. These results are consistent with a functional role of these genes in the early course of human development. PMID:2461079

  5. Remarks on turbulent constitutive relations

    NASA Technical Reports Server (NTRS)

    Shih, Tsan-Hsing; Lumley, John L.

    1993-01-01

    The paper demonstrates that the concept of turbulent constitutive relations can be used to construct general models for various turbulent correlations. Some of the Generalized Cayley-Hamilton formulas for relating tensor products of higher extension to tensor products of lower extension are introduced. The combination of dimensional analysis and invariant theory can lead to 'turbulent constitutive relations' (or general turbulence models) for, in principle, any turbulent correlations. As examples, the constitutive relations for Reynolds stresses and scalar fluxes are derived. The results are consistent with ones from Renormalization Group (RNG) theory and two-scale Direct-Interaction Approximation (DIA) method, but with a more general form.

  6. UNIVERSITY OF FLORIDA 6C1-4.002 Student Affairs: Student Government Constitution.

    E-print Network

    Pilyugin, Sergei S.

    RULES OF UNIVERSITY OF FLORIDA 6C1-4.002 Student Affairs: Student Government Constitution. (1, and is entitled to vote in accordance with the Constitution of the Student Body of the University. The Student Body Constitution has been promulgated by the students and accepted by the University as expressing

  7. The Constitution's Prescription for Freedom.

    ERIC Educational Resources Information Center

    Peach, Lucinda

    1986-01-01

    Examines how the framers of the Constitution came to choose our system of government, how that system was designed to function, and how the separation of powers has served to maintain our democracy despite attempts to violate it. (JDH)

  8. Abnormal human sex chromosome constitutions

    SciTech Connect

    NONE

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  9. Constitutive modeling for isotropic materials

    NASA Technical Reports Server (NTRS)

    Ramaswamy, V. G.; Vanstone, R. H.; Dame, L. T.; Laflen, J. H.

    1984-01-01

    The unified constitutive theories for application to typical isotropic cast nickel base supperalloys used for air-cooled turbine blades were evaluated. The specific modeling aspects evaluated were: uniaxial, monotonic, cyclic, creep, relaxation, multiaxial, notch, and thermomechanical behavior. Further development of the constitutive theories to model thermal history effects, refinement of the material test procedures, evaluation of coating effects, and verification of the models in an alternate material will be accomplished in a follow-on for this base program.

  10. Different genetic backgrounds influence the secretory expression of the LKA1 -encoded Lipomyces kononenkoae ?-amylase in industrial strains of Saccharomyces cerevisiae

    Microsoft Academic Search

    S. B. Gundllapalli Moses; R. R. Cordero Otero; D. C. La Grange; P. van Rensburg; I. S. Pretorius

    2002-01-01

    A haploid laboratory strain and four industrial (baking, brewing, wine, ATCC) strains of Saccharomyces cerevisiae were transformed with the Lipomyces kononenkoae a-amylase-encoding gene (LKA1). These transformants displayed significant differences in terms of the level of secretory expression of LKA1 under control of the PGK1 promoter and terminator, as well as their ability to produce and secrete the LKA1-encoded rawstarch-degrading a-amylase

  11. Characterization of an rbcS gene from Nicotiana plumbaginifolia and expression of an rbc SCAT chimeric gene in homologous and heterologous nuclear background

    Microsoft Academic Search

    Carsten Poulsen; Robert Fluhr; John M. Kauffman; Marc Boutry; Nam-Hai Chua

    1986-01-01

    We have cloned a gene (rbcS-8B) encoding the small subunit of ribulose bisphosphate carboxylase from Nicotiana plumbaginifolia and analyzed it with respect to structure and expression. The nucleotide sequence of the rbcS-8B coding region is highly conserved when compared to rbcS sequences from N. tabacum and N. sylvestris. The first two of the three Nicotiana rbcS introns are also well

  12. Constitutive relations of ferroelectric ceramics

    NASA Astrophysics Data System (ADS)

    Su, Yu

    The objective of this thesis is to obtain a better understanding on the fundamental constitutive behavior of ferroelectric ceramics based on the physics of phase transition, micromechanics of heterogeneous materials, and principles of irreversible thermodynamics. Within this framework, a self-consistent model is developed to investigate the electromechanical responses of ferroelectric polycrystals under temperature change and electromechanical loading. Cooling of a paraelectric crystal below its curie temperature Tc would result in spontaneous polarization, whereas electromechanical loading on a poled crystal could lead to domain switch. Domain growth and reorientation inside ferroelectric crystals are studied in light of these phase transition and domain switch. In this process, the change of the effective elastic, dielectric and piezoelectric constants during the evolution of microstructures are examined. In addition, hysteresis loops for the electric displacement and other related phenomena are computed under cyclic electric load. On top of all methods implemented in this work, the kinetic equation derived from the irreversible thermodynamics is the key to study the domain evolution in ferroelectric crystals. The kinetic relation not only governs the growth of new domain in a ferroelectric crystal, but it also determines the onset of phase transition. This characteristic is used to study the effect of hydrostatic pressure on the shift of Curie temperature of a ferroelectric crystal. Based on the derived expressions, it is observed that the deriving force can increase or decrease upon applied hydrostatic mechanical loading, depending on the change of electromechanical moduli, eigenstrain and electro-polarization. Several typical cases are computed and it is found that the change of the electromechanical moduli during phase transformation plays the key role in the shift of Curie temperature. Since ferroelectric ceramics are in a polycrystal form, a self-consistent model is used to examine the issues involved. In this model, each grain is represented by a spherical inclusion embedded in an infinitely extended piezoelectric matrix, and the inclusion further possesses an eigenstrain and eigen polarization. Secant relations between the polycrystal-matrix and the embedded inclusion are established by extending Hill's [1] incremental relations. An iterative computational program is developed for this self-consistent model.

  13. 5a-Reductase Type 2 Is Constitutively Expressed in the Dermal Papilla and Connective Tissue Sheath of the Hair Follicle in Vivo But Not during Culture in Vitro

    Microsoft Academic Search

    YUJI ASADA; TADASHIGE SONODA; MAYUMI OJIRO; SOTARO KURATA; TOSHIHIRO SATO; TETSUO EZAKI; SUSUMU TAKAYASU

    Recent studies suggest that 5a-reductase type 2 (5aR2) rather than 5aR1 plays a key role in the pathogenesis of male-pattern baldness. To clarify the localization of the androgen receptor (AR), 5aR1, and 5aR2 in the hair follicle, we investigated the expression of the cor- responding genes by RT-PCR using microdissected hair follicles. AR and 5aR1 mRNAs were expressed in all

  14. [The changes in the biochemical indices of blood in cobalt intoxication on the background of the regulators of the expression of endothelial NO-synthase].

    PubMed

    Dzugkoev, S G; Mozhayeva, I V; Gigolaeva, L B; Tedtoeva, A I; Margieva, O I; Dzugkoeva, F S

    2014-01-01

    On the background of chronic cobalt intoxication in rats develops oxidative stress. This is accompanied by a decrease in the content of total metabolites of nitric oxide in the blood serum. The reasons for lower levels of the vasodilatation factor are the following: a deficiency of L-arginine and the increase in the content of the inhibitor of NOS-3. We found a decrease in the bioavailability of nitric oxide due to the increase in the content of oxidized low density lipids, total cholesterol and cholesterol-lowering lipids high density. PMID:25980229

  15. On the invariance of constitutive equations according to the kinetic theory of gases

    Microsoft Academic Search

    Charles G. Speziale

    1984-01-01

    Iterative techniques for solving the Boltzmann equation in the kinetic theory of gases yield expressions for the stress tensor and heat flux vector that are analogous to constitutive equations in continuum mechanics. However, these expressions are not generally invariant under the Euclidean group of transformations, whereas constitutive equations in continuum mechanics are usually required to be by the principle of

  16. 3 CFR 9019 - Proclamation 9019 of September 16, 2013. Constitution Day and Citizenship Day, Constitution Week...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...Proclamation 9019 of September 16, 2013. Constitution Day and Citizenship Day, Constitution Week, 2013 9019 Proclamation 9019...of September 16, 2013 Proc. 9019 Constitution Day and Citizenship Day,...

  17. 3 CFR 8714 - Proclamation 8714 of September 16, 2011. Constitution Day and Citizenship Day, Constitution Week...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...Proclamation 8714 of September 16, 2011. Constitution Day and Citizenship Day, Constitution Week, 2011 8714 Proclamation 8714...of September 16, 2011 Proc. 8714 Constitution Day and Citizenship Day,...

  18. 3 CFR 8418 - Proclamation 8418 of September 16, 2009. Constitution Day and Citizenship Day, Constitution Week...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...Proclamation 8418 of September 16, 2009. Constitution Day and Citizenship Day, Constitution Week, 2009 8418 Proclamation 8418...of September 16, 2009 Proc. 8418 Constitution Day and Citizenship Day,...

  19. 3 CFR 8562 - Proclamation 8562 of September 16, 2010. Constitution Day and Citizenship Day, Constitution Week...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...Proclamation 8562 of September 16, 2010. Constitution Day and Citizenship Day, Constitution Week, 2010 8562 Proclamation 8562...of September 16, 2010 Proc. 8562 Constitution Day and Citizenship Day,...

  20. 3 CFR 8862 - Proclamation 8862 of September 13, 2012. Constitution Day and Citizenship Day, Constitution Week...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...Proclamation 8862 of September 13, 2012. Constitution Day and Citizenship Day, Constitution Week, 2012 8862 Proclamation 8862...of September 13, 2012 Proc. 8862 Constitution Day and Citizenship Day,...

  1. Strain rate sensitive constitutive equations

    E-print Network

    Nelson, Charles Edward

    1971-01-01

    , the dynamic yield for steel was much larger than that in the static case, and for copper it was only slightly higher. Consequently, steel has more 11 strain rate sensitivity than copper. Drucker considered several classes of mathematical theories of... and strain rate was that presented by Iiohenemser and 31 Prager in 1932. It was their work which attempted to define a possible rate sensitive constitutive equation. They t? eorized that the form of a constitutive equation could be defined as 2nd . . = 20...

  2. 17 CFR 200.54 - Constitutional obligations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 2010-04-01 false Constitutional obligations. 200.54...of Ethics § 200.54 Constitutional obligations. The...must faithfully execute the laws which they are charged with...against any infringement of the constitutional rights, privileges,...

  3. Constitution AUSTRALIAN CONSORTIUM FOR `INCOUNTRY' INDONESIAN STUDIES

    E-print Network

    Constitution AUSTRALIAN CONSORTIUM FOR `INCOUNTRY' INDONESIAN STUDIES 1. INTRODUCTION 1 of understanding or agreements with Murdoch for the purpose of constituting and becoming members this Constitution to regulate the management and operation of ACICIS and their relationship with it. Provided

  4. President Mandela Address to Constitutional Assembly

    NSDL National Science Digital Library

    Mandela, Nelson, 1918-.

    1996-01-01

    Full text of the new South African Constitution, adopted by the Constitutional Assembly on May 8, 1996, and the full text of President Nelson Mandela's address to the Constitutional Assembly upon its adoption, are available via the Web.

  5. A high-throughput transient gene expression system for switchgrass (Panicum virgatum L.) seedlings

    Microsoft Academic Search

    Xinlu Chen; Raymie Equi; Holly Baxter; Kyle Berk; Jin Han; Sujata Agarwal; Janice Zale

    2010-01-01

    BACKGROUND: Grasses are relatively recalcitrant to genetic transformation in comparison to certain dicotyledons, yet they constitute some of the most important biofuel crops. Genetic transformation of switchgrass (Panicum virgatum L.) has previously been reported after cocultivation of explants with Agrobacterium and biolistics of embryogenic calli. Experiments to increase transient gene expression in planta may lead to stable transformation methods with

  6. Normalisation genes for expression analyses in the brown alga model Ectocarpus siliculosus

    Microsoft Academic Search

    Aude Le Bail; Simon M Dittami; Pierre-Olivier de Franco; Sylvie Rousvoal; Mark J Cock; Thierry Tonon; Bénédicte Charrier

    2008-01-01

    BACKGROUND: Brown algae are plant multi-cellular organisms occupying most of the world coasts and are essential actors in the constitution of ecological niches at the shoreline. Ectocarpus siliculosus is an emerging model for brown algal research. Its genome has been sequenced, and several tools are being developed to perform analyses at different levels of cell organization, including transcriptomic expression analyses.

  7. Historical background.

    PubMed Central

    Epstein, M A

    2001-01-01

    The persisting ancient view of cancer as a contagious disease ended with 19th century scientific investigations which seemed to show it was not. The resulting dogma against an infectious cause for cancer produced great prejudice in the scientific community against the first report of an oncogenic virus by Rous early in the 20th century and, even in the 1950s, against Gross's finding of a murine leukaemia virus and a murine virus causing solid tumours. The Lucké frog renal carcinoma virus was the first cancer-associated herpesvirus. Intriguingly, an environmental factor, ambient temperature, determines virus genome expression in the poikilothermic frog cells. Although an alpha-herpesvirus, Marek's disease virus of chickens shares some aspects of biological behaviour with Epstein-Barr virus (EBV) of man. Very significantly, its lymphomas are the first naturally occurring malignancy to be controlled by an antiviral vaccine, with implications for human virus-associated cancers. The circumstances and climate of opinion in which successive gamma-herpesviruses were discovered are described. The identification of EBV involved two unconventionalities: its finding in cultured Burkitt's lymphoma cells when no human lymphoid cell had ever been maintained in vitro, and its recognition in the absence of biological activity by the then new technique of electron microscopy. These factors engendered hostility to its acceptance as a new human tumour-associated virus. The EBV-like agents of Old World apes and monkeys and the T-lymphotropic gamma-herpesviruses of New World monkeys were found at about the same time, not long after the discovery of EBV. For many years these were thought to be the only gamma-herpesviruses of non-human primates; however, very recently B-lymphotropic EBV-like agents have been identified in New World species as well. Mouse herpesvirus 68 came to light by chance during a search for arboviruses and has become important as a laboratory model because of its close genetic relatedness to EBV and its comparable biological behaviour. The discovery of Kaposi's sarcoma-associated herpesvirus six years ago was made using unconventional new methods, but, unlike with EBV 30 years before, this did not hinder its acceptance. This contrast is discussed in the context of the great progress in human tumour virology which has been made in recent years. PMID:11313002

  8. CONSTITUTION Article I--NAME

    E-print Network

    CONSTITUTION Article I--NAME The Botany Club Article II--PURPOSE The Botany Club will foster--MEMBERSHIP Membership is open to all students, faculty, and staff that have an interest in Botany. Size is unlimited. We The Botany Club will elect a President, Vice President, and Treasurer once each year during the spring

  9. A Venture in Constitutional Law.

    ERIC Educational Resources Information Center

    Cole, W. Graham; Dillon, Dorothy H.

    1980-01-01

    Senior high girls and boys from two single-sex schools undertook a study of a Supreme Court case that provided insight not only into constitutional law and history but also into how men and women can work together and relate in other ways than dating. (DS)

  10. The Constitution: A Resource Guide.

    ERIC Educational Resources Information Center

    Social Studies Review, 1987

    1987-01-01

    Presents a 234-item annotated bibliography of a wide variety of resources for teaching about the Constitution at all grade levels. The materials include: books; computer software; inspirational literature; teaching aids such as letters, memoirs, and diaries; teacher's handbooks; portraits and pictures; music, songbooks, and recordings; and…

  11. Take Advantage of Constitution Day

    ERIC Educational Resources Information Center

    McCune, Bonnie F.

    2008-01-01

    The announcement of the mandate for Constitution and Citizenship Day shortly before September, 2005, probably led to groans of dismay. Not another "must-do" for teachers and schools already stressed by federal and state requirements for standardized tests, increasingly rigid curricula, and scrutiny from the public and officials. But the idea and…

  12. Constitution Harvard Law School Association

    E-print Network

    Chou, James

    Constitution of the Harvard Law School Association ~ADOPTED JUNE 3, 1947~ As amended April 29, 1949, the Harvard Law School Association ("HLSA") was founded in 1886 as an independent association, the first to advance the cause of legal education, to promote the interests and increase the usefulness of the Harvard

  13. Constitution Harvard Law School Association

    E-print Network

    Wolfe, Patrick J.

    - 1 - Constitution of the Harvard Law School Association ~ADOPTED JUNE 3, 1947~ As amended April 29, the Harvard Law School Association ("HLSA") was founded in 1886 as an independent association, the first to advance the cause of legal education, to promote the interests and increase the usefulness of the Harvard

  14. Everyday Constitutional Assessments and Their Relevance to Formal Assessments

    ERIC Educational Resources Information Center

    Varenne, Herve

    2014-01-01

    Background: In anthropology and related disciplines, the term "assessment" refers to the everyday activities of ordinary people as they figure out what to do next given what others have just done. The assessments, in turn, constitute what is happening, whether in encounters between policeman and person in the street, or classroom lesson,…

  15. Human rights and cultural identity in a constitutional framework

    Microsoft Academic Search

    Vincent Depaigne

    The purpose of the proposed paper is to address the potential contradiction between human rights and the expression of cultural values through a comparative approach. The focus will be on the constitutional law framework, how it deals with the assertion of cultural identities and how basic human rights standards, in particular non-discrimination, are reconciled with the protection of cultural rights.

  16. Constitution and By-laws Introduction

    E-print Network

    Stuart, Steven J.

    Constitution and By-laws Introduction The Constitution of an organization contains the fundamental a current copy of their constitution/by-laws on OrgSync@clemson each year as part of the re the year. Why Have a Constitution? By definition an organization is a "body of persons organized for some

  17. Indiana University School of Informatics, IUPUI Constitution

    E-print Network

    Zhou, Yaoqi

    1 Indiana University School of Informatics, IUPUI Constitution 3/4/05 Preamble The field imposed by the faculty constitution of the IUPUI campus, this Constitution confirms and establishes of Trustees, the laws of the state and other provisions of the Constitution. Section 3. Executive Associate

  18. CONSTITUTION OF THE MULTICULTURAL GREEK COUNCIL

    E-print Network

    Mohanty, Saraju P.

    CONSTITUTION OF THE MULTICULTURAL GREEK COUNCIL OF THE UNIVERSITY OF NORTH TEXAS PREAMBLE to the Constitution: This Constitution may be amended by a two-thirds (2/3) vote at any regular meeting. Notice of a vote to amend this Constitution must be given in writing at least one meeting prior to the vote

  19. STATUTES TO THE CONSTITUTION OF THE

    E-print Network

    Bordenstein, Seth

    STATUTES TO THE CONSTITUTION OF THE VANDERBILT STUDENT GOVERNMENT #12;Statutes to the Constitution of the Vanderbilt Student Government STATUTES TO THE CONSTITUTION OF THE VANDERBILT STUDENT GOVERNMENT TABLE BUDGET RULES AND REGULATIONS TITLE 8 STUDENT FINANCE COMMITTEE #12;Statutes to the Constitution

  20. The Constitution and Bylaws Board of Directors

    E-print Network

    Bogaerts, Steven

    The Constitution and Bylaws of the Board of Directors of Wittenberg College (Constitution, 2012) #12;THE CONSTITUTION ARTICLE I Name, Purpose, Property, and Relationship to the Evangelical Lutheran Church in America. #12;Page 2 - THE CONSTITUTION SECTION 4. SUPPORT BY LUTHERAN CHURCH BODIES

  1. What is a Twentieth-Century Constitution?

    Microsoft Academic Search

    Peter E. Quint

    2007-01-01

    At present, almost all of the constitutions in the world are twentieth-century constitutions; indeed, most of them were not adopted until the second half of the twentieth century. Accordingly, the eighteenth-century Constitution of the United States -- which includes the original constitution of 1787-89; the first ten amendments, adopted in 1791; and the Eleventh Amendment, adopted in 1798 -- antedates

  2. Judicial Illumination of the Constitutional \\

    Microsoft Academic Search

    Eamonn OHagan

    2003-01-01

    Police brutality is one of the most serious and enduring human rights violations in the United States today. One means by which victims may seek redress is under 42 U.S.C. 1983, which provides a civil cause of action against state actors who deprive individuals of their constitutional rights. This Note examines 1983 litigation brought by post-arrest, pretrial detainees alleging the

  3. Constitutive modeling for isotropic materials

    NASA Technical Reports Server (NTRS)

    Chan, K. S.; Lindholm, U. S.; Bodner, S. R.

    1988-01-01

    The third and fourth years of a 4-year research program, part of the NASA HOST Program, are described. The program goals were: (1) to develop and validate unified constitutive models for isotropic materials, and (2) to demonstrate their usefulness for structural analysis of hot section components of gas turbine engines. The unified models selected for development and evaluation were those of Bodner-Partom and of Walker. The unified approach for elastic-viscoplastic constitutive equations is a viable method for representing and predicting material response characteristics in the range where strain rate and temperature dependent inelastic deformations are experienced. This conclusion is reached by extensive comparison of model calculations against the experimental results of a test program of two high temperature Ni-base alloys, B1900+Hf and Mar-M247, over a wide temperature range for a variety of deformation and thermal histories including uniaxial, multiaxial, and thermomechanical loading paths. The applicability of the Bodner-Partom and the Walker models for structural applications has been demonstrated by implementing these models into the MARC finite element code and by performing a number of analyses including thermomechanical histories on components of hot sections of gas turbine engines and benchmark notch tensile specimens. The results of the 4-year program have been published in four annual reports. The results of the base program are summarized in this report. The tasks covered include: (1) development of material test procedures, (2) thermal history effects, and (3) verification of the constitutive model for an alternative material.

  4. Constitutive activity in gonadotropin receptors.

    PubMed

    Ulloa-Aguirre, Alfredo; Reiter, Eric; Bousfield, George; Dias, James A; Huhtaniemi, Ilpo

    2014-01-01

    Constitutively active mutants (CAMs) of gonadotropin receptors are, in general, rare conditions. Luteinizing hormone-choriogonadotropin receptor (LHCGR) CAMs provoke the dramatic phenotype of familial gonadotropin-independent isosexual male-limited precocious puberty, whereas in females, there is not yet any identified phenotype. Only one isolated follicle-stimulating hormone receptor (FSHR) CAM (Asp567Gly) has so far been detected in a single male patient, besides other FSHR weak CAMs linked to pregnancy-associated ovarian hyperstimulation syndrome or to impaired desensitization and internalization. Several animal models have been developed for studying enhanced gonadotropin action; in addition to unraveling valuable new information about the possible phenotypes of isolated FSHR and LHCGR CAMs in women, the information obtained from these mouse models has served multiple translational goals, including the development of new diagnostic and therapeutic targets as well as the prediction of phenotypes for mutations not yet identified in humans. Mutagenesis and computational studies have shed important information on the physiopathogenic mechanisms leading to constitutive activity of gonadotropin receptors; a common feature in these receptor CAMs is the release of stabilizing interhelical interactions between transmembrane domains (TMDs) 3 and 6 leading to an increase, with respect to the wild-type receptor, in the solvent accessibility at the cytosolic extension of TMDs 3, 5, and 6, which involves the highly conserved Glu/Asp-Arg-Tyr/Trp sequence. In this chapter, we summarize the structural features, functional consequences, and mechanisms that lead to constitutive activation of gonadotropin receptor CAMs and provide information on pharmacological approaches that might potentially modulate gonadotropin receptor CAM function. PMID:24931192

  5. Is the tobacco settlement constitutional?

    PubMed

    Rajkumar, Rahul; Gross, Cary P; Forman, Howard P

    2006-01-01

    In August 2005, the Competitive Enterprise Institute (CEI), a conservative advocacy organization, filed a lawsuit in Louisiana challenging the legality of the 1998 Master Settlement Agreement (MSA). The suit alleges that the MSA, under which the states receive monetary payments and the four major tobacco companies are insulated from price competition, violates the Compact Clause and other provisions of the U.S. Constitution. This lawsuit threatens to unravel of one of the most significant opportunities to improve public health in United States history. We consider the merits of the lawsuit, the problems with the MSA that it highlights, and the potential consequences of the suit for public health. PMID:17199817

  6. Constitutional Amendment A: Prohibit Property Taxes for School Funding. Issue Memorandum 98-13.

    ERIC Educational Resources Information Center

    Becker, David

    This issue memorandum describes Constitutional Amendment A, an initiative in South Dakota that, if approved, would prohibit taxation of real property for school purposes. The report provides background information on Constitutional Amendment A, which reads as follows: "The legislature shall make such provision by general taxation as with the…

  7. 75 FR 57835 - Constitution Day and Citizenship Day, Constitution Week, 2010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-22

    ...Day and Citizenship Day, Constitution Week, 2010 Proclamation 8563--National POW...Day and Citizenship Day, Constitution Week, 2010 By the President of the United States...Citizenship Day, and during Constitution Week, we commemorate the legacy passed...

  8. Constitutive stress--strain relations for the myocardium in diastole.

    PubMed

    Moskowitz, S E

    1985-01-01

    The importance of stress-strain myocardial constitutive relations is that they provide a criterion for behavior in vivo. Our purpose was to develop constitutive equations which are valid in diastole. The myocardium was assumed to be composed of a nonlinear viscoelastic, inhomogeneous, anisotropic (transversely isotropic) and incompressible material operating under adiabatic and isothermal conditions. The expressions contain five moduli. Two are fixed by the restriction of incompressibility, one is estimated, the remaining two refer to directions along and perpendicular to a fiber. Both possess a bimodal variation with intermodal switching occurring in late rapid filling and diastasis. They are functions of time and material constants. These constants can be observed. A dynamic test is suggested. Constitutive statements complete a set of equations sufficient for the solution of a class of boundary value problems. One type is formulated. They also permit the determination of stress from measured strain. Examples are given. PMID:3997902

  9. Constitutive Theories for Thermoelastic Solids in Lagrangian Description Using Gibbs Potential

    E-print Network

    Mendoza, Yusshy

    2012-08-31

    of the constitution of the matter, the second law of thermodynamics, i.e. entropy inequality, must form the basis for all constitutive theories of the deforming matter to ensure thermodynamic equilibrium during the evolution [1, 2]. The entropy inequality expressed...

  10. Constitutive modelling of abdominal organs.

    PubMed

    Miller, K

    2000-03-01

    Abdominal organs are very susceptible to trauma. In order to protect them properly against car crash and other impact consequences, we need to be able to simulate the abdominal organ deformation. Such simulation should account for proper stress-strain relation as well as stress dependence on strain rate. As the step in this direction, this paper presents three-dimensional, non-linear, viscoelastic constitutive models for liver and kidney tissue. The models have been constructed basing on in vivo experiments conducted in Highway Safety Research Institute and the Medical Centre of The University of Michigan (Melvin et al., 1973). The proposed models are valid for compressive nominal strains up to 35% and fast (impact) strain rates between 0.2 and 22.5 s(-1). Similar models can find applications in computer and robot assisted surgery, e.g. the realistic simulation of surgical procedures (including virtual reality) and non-rigid registration. PMID:10673121

  11. Antithetical Ethics: Kenneth Burke and the Constitution.

    ERIC Educational Resources Information Center

    Anderson, Virginia

    1995-01-01

    Shows how the textuality of the United States Constitution, the most venerable of classic democratic icons, might be exploited to nurture postmodern ethics. Shows how Kenneth Burke's reading of the Constitution accords with and augments the postmodern theories of J.-F. Lyotard and S. Jarratt. Discusses a postmodern Constitution and the…

  12. State Constitutional Law: Teaching and Scholarship.

    ERIC Educational Resources Information Center

    Williams, Robert F.

    1991-01-01

    State constitutional law is an emerging area for legal education, partly because of state supreme court decisions relying on state rather than federal constitutional law. Studying state constitutional law highlights similarities and diversity of legal and governmental systems. Interest in establishment of curricula and materials in state law is…

  13. 29 CFR 452.18 - Constitutional officers.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...position identified as an officer by the constitution and bylaws of the labor organization...elected where the labor organization's constitution identifies the holder of such a position...who are required to be elected by the constitution and bylaws of a labor...

  14. Florida Atlantic University Student Government Constitution

    E-print Network

    Fernandez, Eduardo

    Florida Atlantic University Student Government Constitution Preamble We the students of Florida the principles of the Constitution and laws of the United States and of the State of Florida, do ordain and establish this Constitution for the Florida Atlantic University Student Government. Article I. Establishment

  15. 29 CFR 452.18 - Constitutional officers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...position identified as an officer by the constitution and bylaws of the labor organization...elected where the labor organization's constitution identifies the holder of such a position...who are required to be elected by the constitution and bylaws of a labor...

  16. Constitutional Limits on Law Enforcement Spring, 2011

    E-print Network

    Gering, Jon C.

    Syllabus Constitutional Limits on Law Enforcement JUST 400 Spring, 2011 MWF 10:30 BT 2209 of the United States Constitution as it impacts criminal law and policing. It will provide you with an understanding of how constitutional law is developed from precedent (decisions in earlier cases) through

  17. 7 CFR 718.201 - Farm constitution.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...2011-01-01 2011-01-01 false Farm constitution. 718.201 Section 718.201...Quotas, and Bases § 718.201 Farm constitution. (a) In order to implement...paragraph (c) of this section. The constitution and identification of land as...

  18. 7 CFR 718.201 - Farm constitution.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 2014-01-01 false Farm constitution. 718.201 Section 718.201...Quotas, and Bases § 718.201 Farm constitution. (a) In order to implement...paragraph (c) of this section. The constitution and identification of land as...

  19. University of Florida Student Body Constitution

    E-print Network

    Roy, Subrata

    University of Florida Student Body Constitution Submitted by: David M. Kerner, Chairman 2009-2010 Constitution Revision Commission On Behalf of the Full Commission Adopted by the University of Florida Student Body on February 24th , 2010 CONSTITUTION OF THE STUDENT BODY OF THE UNIVERSITY OF FLORIDA #12;We

  20. Faculty Senate Constitution For Truman State University

    E-print Network

    Gering, Jon C.

    Faculty Senate Constitution For Truman State University Preamble The members of the faculty hereby establish this constitution as a pledge of faculty cooperation and support of Truman State for the Senate's transition under new amendments or bylaws. Article VII Amendments to the Constitution and Bylaws

  1. Boise State University Faculty Senate Constitution

    E-print Network

    Barrash, Warren

    Boise State University Faculty Senate Constitution Amended: May 2011 Effective Date: Upon Board subscribe to this constitution establishing principles of organization, authority, and responsibility of the Boise State University faculty. In adopting this constitution the president and faculty of Boise State

  2. 7 CFR 718.201 - Farm constitution.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 2010-01-01 false Farm constitution. 718.201 Section 718.201...Quotas, and Bases § 718.201 Farm constitution. (a) In order to implement...paragraph (c) of this section. The constitution and identification of land as...

  3. Supreme Constitution Clemson University Student Governments

    E-print Network

    Stuart, Steven J.

    Supreme Constitution of the Clemson University Student Governments Preamble The Undergraduate and Graduate Students of Clemson University do establish this Supreme Constitution for the preservation in the Constitution of the Clemson University Undergraduate Student Body. Section 2: Graduate Student Government A

  4. 29 CFR 452.18 - Constitutional officers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...position identified as an officer by the constitution and bylaws of the labor organization...elected where the labor organization's constitution identifies the holder of such a position...who are required to be elected by the constitution and bylaws of a labor...

  5. 7 CFR 718.201 - Farm constitution.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...2012-01-01 2012-01-01 false Farm constitution. 718.201 Section 718.201...Quotas, and Bases § 718.201 Farm constitution. (a) In order to implement...paragraph (c) of this section. The constitution and identification of land as...

  6. UWC Constitution and Bylaws Table of Contents

    E-print Network

    Guiltinan, Mark

    UWC Constitution and Bylaws Table of Contents Article I. Membership Section I. Membership. Meetings Section I. Frequency Section II. Governance Article V. Constitution and Bylaws Revisions Article VI. Dissolution of the Club #12;Constitution and Bylaws (Approved by Membership, Spring Business

  7. 29 CFR 452.18 - Constitutional officers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...position identified as an officer by the constitution and bylaws of the labor organization...elected where the labor organization's constitution identifies the holder of such a position...who are required to be elected by the constitution and bylaws of a labor...

  8. GSAUCSD Constitution ARTICLE I: NAME AND MEMBERSHIP

    E-print Network

    Gleeson, Joseph G.

    Page | 1 GSAUCSD Constitution ARTICLE I: NAME AND MEMBERSHIP Section I: Name The name to as the Council) is the duly constituted representative assembly of GSAUCSD. The Council's mandate is to act body of UCSD. The GSAUCSD is constituted as such according to the provisions of the United States

  9. Who, Where and When: The History & Constitution

    E-print Network

    Mottram, Nigel

    Who, Where and When: The History & Constitution of the University of Glasgow #12;#12;Compiled of Medicine 16 Trinity College 17 The Constitution 19 The Papal Bull 19 The Coat of Arms 22 Management 25 51 Science (1893-2000) 51 Social Sciences 52 Veterinary Medicine 53 #12;History and Constitution 6

  10. CONSTITUTION OF THE BRITISH COMBINATORIAL General Policy

    E-print Network

    Cameron, Peter

    CONSTITUTION OF THE BRITISH COMBINATORIAL COMMITTEE General Policy 1. The purpose of the Committee Meeting. #12;8. The constitution can be changed only by a two-thirds majority of those voting in the constitution. It shall also include the Committee's nomination for Chairman of the British Combinatorial Com

  11. 29 CFR 452.18 - Constitutional officers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...position identified as an officer by the constitution and bylaws of the labor organization...elected where the labor organization's constitution identifies the holder of such a position...who are required to be elected by the constitution and bylaws of a labor...

  12. 7 CFR 718.201 - Farm constitution.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 2013-01-01 false Farm constitution. 718.201 Section 718.201...Quotas, and Bases § 718.201 Farm constitution. (a) In order to implement...paragraph (c) of this section. The constitution and identification of land as...

  13. American Focus on World Constitutions. Teacher's Guide.

    ERIC Educational Resources Information Center

    Holmes, Stanley T., III

    This curriculum project was designed to familiarize high school students with their own constitutional roots while gaining a better understanding of governmental systems developed by other nations. The project uses the U.S. Constitution as a baseline for analyzing the constitutions of other nations, and is intended to supplement courses in such…

  14. Constitutive expression of the machinery for programmed cell death

    Microsoft Academic Search

    M. Weil; M. D. Jacobson; H. S. R. Coles; T. J. Davies; R. L. Gardner; K. D. Raft; M. C. Raft

    1996-01-01

    In the presence of cycloheximide (CHX) to inhibit protein synthesis, a high concentration of stau- rosporine (STS) induces almost all cells in explant cul- tures of 8\\/8 types of newborn mouse organs and 3\\/3 types of adult mouse organs to die with the characteris- tic features of apoptosis. Eggs and blastomeres also die in this way when treated with STS

  15. Constitutive model for porous materials

    SciTech Connect

    Weston, A.M.; Lee, E.L.

    1982-01-01

    A simple pressure versus porosity compaction model is developed to calculate the response of granular porous bed materials to shock impact. The model provides a scheme for calculating compaction behavior when relatively limited material data are available. While the model was developed to study porous explosives and propellants, it has been applied to a much wider range of materials. The early development of porous material models, such as that of Hermann, required empirical dynamic compaction data. Erkman and Edwards successfully applied the early theory to unreacted porous high explosives using a Gruneisen equation of state without yield behavior and without trapped gas in the pores. Butcher included viscoelastic rate dependance in pore collapse. The theoretical treatment of Carroll and Holt is centered on the collapse of a circular pore and includes radial inertia terms and a complex set of stress, strain and strain rate constitutive parameters. Unfortunately data required for these parameters are generally not available. The model described here is also centered on the collapse of a circular pore, but utilizes a simpler elastic-plastic static equilibrium pore collapse mechanism without strain rate dependence, or radial inertia terms. It does include trapped gas inside the pore, a solid material flow stress that creates both a yield point and a variation in solid material pressure with radius. The solid is described by a Mie-Gruneisen type EOS. Comparisons show that this model will accurately estimate major mechanical features which have been observed in compaction experiments.

  16. Internal Constitution of Neutron and Strange Stars

    E-print Network

    Norman K. Glendenning

    1997-06-24

    In the first of these two lectures I will discuss the rich constitution of neutron stars as a consequence of the Pauli principle which is engaged by the dominance of gravity over the nuclear force. Three especially interesting phenomena are discussed in this contect--(1) a mechanism for the formation of low-mass black holes distinct in their mass-range from the black holes formed in the prompt collapse of an entire star, (2) a multilayered crystalline structure consisting of confined hadronic matter embedded in a background of deconfined quark matter (or vice versa) which occupies a many kilometer thick inner region, and (3) a clean and pronounced signal of the formation of quark matter in the interior of neutron stars. In the second lecture I will discuss the strange matter hypothesis, its viability as well as its consequences for compact stars and a new family of white dwarfs with dense nuclear matter central regions some orders of magnuitude greater than in ordinary white dwarfs.

  17. University Assembly Constitution as approved 10.10.13 CONSTITUTION OF THE UNIVERSITY ASSEMBLY

    E-print Network

    Pantaleone, Jim

    University Assembly Constitution as approved 10.10.13 CONSTITUTION OF THE UNIVERSITY ASSEMBLY of the University of Alaska #12;University Assembly Constitution as approved 10.10.13 Anchorage by considering all by the Chancellor, in accordance with ARTICLE X of this Constitution. B. Delegated Authority The Assembly delegates

  18. 6. CONSTITUTIVE EQUATIONS 6.1 The need for constitutive equations

    E-print Network

    Cerveny, Vlastislav

    6. CONSTITUTIVE EQUATIONS 6.1 The need for constitutive equations Basic principles of continuum.2) D Dt = t .. d - div q + h . (6.3) In total, they constitute 5 independent equations (one for mass. The character of the material is brought into the formulation through the so-called constitutive equations

  19. EEGSA Constitution revised February 2008 page 1 of 4 CONSTITUTION OF THE

    E-print Network

    EEGSA Constitution revised February 2008 page 1 of 4 CONSTITUTION OF THE DEPARTMENT OF ELECTRICAL and establish this constitution to serve the needs, welfare, and interests of present and futures electrical engineering graduate students at UC Riverside, do ordain and establish this constitution and subscribe

  20. The Constitution of Highly Reliable Practices: Materializing Communication as Constitutive of Organizing

    E-print Network

    Spradley, Robert Tyler

    2012-10-19

    THE CONSTITUTION OF HIGHLY RELIABLE PRACTICES: MATERIALIZING COMMUNICATION AS CONSTITUTIVE OF ORGANIZING A Dissertation by ROBERT TYLER SPRADLEY Submitted to the Office of Graduate Studies of Texas A&M University in partial... fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY August 2012 Major Subject: Communication The Constitution of Highly Reliable Practices: Materializing Communication as Constitutive...

  1. Constitutive Activity of the Androgen Receptor

    PubMed Central

    Chan, Siu Chiu; Dehm, Scott M.

    2014-01-01

    Prostate cancer (PCa) is the most frequently diagnosed cancer in the United States. The androgen receptor (AR) signaling axis is central to all stages of PCa pathophysiology and serves as the main target for endocrine-based therapy. The most advanced stage of the disease, castration resistant prostate cancer (CRPC), is presently incurable and accounts for most PCa mortality. In this review, we highlight the mechanisms by which the AR signaling axis can bypass endocrine-targeted therapies and drive progression of CRPC. These mechanisms include alterations in growth factor, cytokine, and inflammatory signaling pathways, altered expression or activity of transcriptional co-regulators, AR point mutations, and AR gene amplification leading to AR protein overexpression. Additionally, we will discuss the mechanisms underlying the synthesis of constitutively active AR splice variants (AR-Vs) lacking the COOH-terminal ligand binding domain, as well as the role and regulation of AR-Vs in supporting therapeutic resistance in CRPC. Finally, we summarize the ongoing development of inhibitors targeting discrete AR functional domains as well as the status of new biomarkers for monitoring the AR signaling axis in patients. PMID:24931201

  2. The constitution of cometary nuclei

    NASA Technical Reports Server (NTRS)

    Whipple, F. L.

    1977-01-01

    The nongravitational term in the expression for the total force acting on a comet is calculated, and an upper limit is obtained for the product of the radial nongravitational term times the radius times the square root of the albedo. This condition is satisfied for ten periodic comets with q no greater than 1.5 AU, and the activity of these comets is consistent with control by H2O ice. Some of the comets must be spotty to account for their low albedo values. The effect of cosmic rays on comets, leading to frosting of their surface, is discussed.

  3. FindLaw Constitutional Law Center

    NSDL National Science Digital Library

    This offering from FindLaw (last discussed in the January 15, 1999 Scout Report) focuses on the US Constitution. The site is composed of two primary sections. The first offers an annotated Constitution, commentary on selected topics with links to key sections of the Constitution or The Federalist Papers, a history of the Constitution, and brief biographies of notable "Founding Fathers" and delegates to the Constitutional Convention. The second section highlights the Third Branch of government, with a history of the Supreme Court, landmark decisions regarding civil rights with the full opinions, a summary and analysis of the criminal law and procedure decisions of the October 1998 Supreme Court Term, and several links for current Supreme Court news and information. Both sections also feature a search engine. Additional resources at the site include a Town Hall section that explores Hot Topics (currently flag burning) and message boards on a wide variety of Constitutional issues.

  4. FindLaw Constitutional Law Center

    NSDL National Science Digital Library

    This latest offering from FindLaw (last discussed in the January 15, 1999 Scout Report) focuses on the US Constitution. The site is composed of two primary sections. The first offers an annotated Constitution, commentary on selected topics with links to key sections of the Constitution or The Federalist Papers, a history of the Constitution, and brief biographies of notable "Founding Fathers" and delegates to the Constitutional Convention. The second section highlights the Third Branch of government, with a history of the Supreme Court, landmark decisions regarding civil rights with the full opinions, a summary and analysis of the criminal law and procedure decisions of the October 1998 Supreme Court Term, and several links for current Supreme Court news and information. Both sections also feature a search engine. Additional resources at the site include a Town Hall section that explores Hot Topics (currently flag burning) and message boards on a wide variety of Constitutional issues.

  5. New constitutionalism, democratisation and global political economy

    Microsoft Academic Search

    Stephen Gill

    1998-01-01

    Constitutional revision is a feature of the 1990s. Specifically, this involves initiatives to politically ‘lock in’ neo?liberal reforms. These initiatives serve to secure investor freedoms and property rights for transnational enterprises. Yet students of international political economy have paid surprisingly little attention to the constitutional aspects of global restructuring. Thus this essay analyses the new constitutionalism of disciplinary neo?liberalism, understood

  6. Understanding the Federal Courts The Constitution and the Federal Judiciary

    E-print Network

    Shamos, Michael I.

    Understanding the Federal Courts The Constitution and the Federal Judiciary The Federal Courts The Constitution and the Federal Judiciary Article theConstitutionbecausetheir rulingsprotectrightsandlibertiesguaranteedbytheConstitution

  7. Ratification of European Union Constitution Hits a Roadblock

    NSDL National Science Digital Library

    This past week, the ratification of the European Union's constitution met with some resistance as voters in both the Netherlands and France both voted "no" to approving the document. Some analysts have suggested that this rejection of the constitution is indicative of the fact that there is an increasing unease about the process of unification more generally in various countries across the continent. Pundits and analysts also agreed that there was no one defining reason why voters rejected the constitution. In France, those voting "no" seemed to range from those on the far right to the far left, and interestingly enough, included a large proportion of young people. It is worth noting that a number of opponents (particularly those on the political left) of ratification continue to make the claim that the constitution promotes a type of unencumbered capitalism that is akin to the type of socioeconomic mode of governance practiced in the United Kingdom and the United States. It will be sometime before the full impact of this recent development is understood, but it is certainly a story that is worthy of a closer look. The first link will take users to coverage of the ongoing EU Constitution process offered by the Voice of America from this past Monday. The second link will take visitors to a fine news piece from the Guardian that provides some insight into the recent rejection of the EU Constitution by Dutch voters. The third link leads to an article from Deutsche Welle that discusses the implications of these latest developments in Europe. The fourth link leads to a very thorough set of analyses of the ratification process as reported by National Public Radio. From this main page, visitors can also learn about the history of the EU Constitution and read some essential background material about the document. The fifth link, offered by the BBC, provides a quick introduction to the Constitution, along with providing a link to the full text of the document. The final link leads to the homepage of the Historical Archives of the European Union, where visitors can review primary documents related to the EU's development and also learn about utilizing their various collections.

  8. Stress-inducible synthesis of proline in transgenic rice confers faster growth under stress conditions than that with constitutive synthesis

    Microsoft Academic Search

    Jin Su; Ray Wu

    2004-01-01

    Proline accumulation has been shown to correlate with tolerance to drought and salt stresses in plants. Our goal was to compare the growth rate of transgenic rice plants in which the expression of a mothbean ?1-pyrroline-5-carboxylate synthetase (p5cs) cDNA was driven separately with a constitutive and a stress-inducible promoter. We found that both constitutive expression and stress-inducible expression of the

  9. A macro-mechanical constitutive model of shape memory alloys

    NASA Astrophysics Data System (ADS)

    Zhou, Bo; Liu, Yanju; Leng, Jinsong; Zou, Guangping

    2009-09-01

    It is of practical interest to establish a precise constitutive model which includes the equations describing the phase transformation behaviors and thermo-mechanical processes of shape memory alloy (SMA). The microscopic mechanism of super elasticity and shape memory effect of SMA is explained based on the concept of shape memory factor defined by the author of this paper. The conventional super elasticity and shape memory effect of SMA are further unified as shape memory effect. Shape memory factor is redefined in order to make clear its physical meaning. A new shape memory evolution equation is developed to predict the phase transformation behaviors of SMA based on the differential relationship between martensitic volume fraction and phase transformation free energy and the results of DSC test. It overcomes the limitations that the previous shape memory evolution equations or phase transformation equations fail to express the influences of the phase transformation peak temperatures on the phase transformation behaviors and the transformation from twinned martensite to detwinned martensite occurring in SMA. A new macro-mechanical constitutive equation is established to predict the thermo-mechanical processes realizing the shape memory effect of SMA from the expression of Gibbs free energy. It is expanded from one-dimension to three-dimension with assuming SMA as isotropic material. All material constants in the new constitutive equation can be determined from macroscopic experiments, which makes it more easily used in practical applications.

  10. Documents from the Continental Congress and the Constitutional Convention

    NSDL National Science Digital Library

    The Library of Congress American Memory Project has been producing high-quality digital collections for a decade, and one of their first projects has recently been updated and is worthy of a second (or first) look. This particular collection brings together a number of documents, including dozens of broadsides related to the work of the Continental Congress, dating from 1774 to 1788. The majority of these items contain extracts of the journals of Congress, resolutions, proclamations, treaties, and other congressional proceedings. Other documents in the collection include early printed versions of the United States Constitution and the Declaration of Independence. Those persons who are seeking a bit more background information will want to take a look at two timelines that cover related events from the 1764 Sugar Act to the official ratification of the Constitution in 1788. Finally, the site also contains a nice essay titled â??To Form a More Perfect Union.â?ť.

  11. Constitutive equations for meeting elevated-temperature-design needs

    SciTech Connect

    Pugh, C.E.; Robinson, D.N.

    1981-01-01

    Constitutive equations for representing the inelastic behavior of structural alloys at temperatures in the creep regime are discussed from the viewpoint of advances made over the past decade. An emphasis is placed on the progress that has been made in meeting the needs of the program whose design process is based in part on a design-by-inelastic-analysis approach. In particular, the constitutive equations that have been put into place for current use in design analyses are discussed along with some material behavior background information. Equations representing short-term plastic and long-term creep behaviors are considered. Trends towards establishing improved equations for use in the future are also described. Progress relating to fundamentals of continuum mechanics, physical modeling, phenomenological modeling, and implementation is addressed.

  12. The Constitution in the Twentieth Century.

    ERIC Educational Resources Information Center

    Murphy, Paul L.

    1987-01-01

    Investigates the development of the United States Constitution in the twentieth century up to and including the Burger Court. Contends that interpreting the Constitution is an important issue of our times. Consequently argues that we should teach students about the development of this document. (RKM)

  13. Constitutive modeling of porous viscoelastic materials

    Microsoft Academic Search

    F. Xu; P. Sofronis; N. Aravas; S. Meyer

    2007-01-01

    The effect of porosity on the constitutive response of an isotropic linearly viscoelastic solid that obeys a constitutive law of the standard differential form is investigated under small strain deformation conditions. The correspondence principle of linear viscoelasticity is used to solve the viscoelastic boundary value problem at a unit cell containing a spherical void and loaded axisymmetrically by macroscopic stresses.

  14. An Internet Guide to Teaching the Constitution

    ERIC Educational Resources Information Center

    Risinger, C. Frederick

    2005-01-01

    In 2004, Congress passed and President Bush signed legislation designating every September 17 as Constitution Day and suggesting that all schools teach about the Constitution on that day. There are innumerable websites, countless lesson plans and a multitude of other teaching resources on the topic. Teachers were inundated with brochures,…

  15. Constitutive theory of anisotropic rigid heat conductors

    Microsoft Academic Search

    I-Shih Liu

    2009-01-01

    For rigid heat conductors, the constitutive equation of the heat flux is usually assumed to be independent of the deformation of the body, or equivalently by setting the deformation gradient as the identity tensor in the constitutive equations. However, the notion of material symmetry would have involved change in reference configurations, hence also change in deformation gradients. Consequently it would

  16. Outsourcing the Constitution and Administrative Law Norms

    Microsoft Academic Search

    David H. Rosenbloom; Suzanne J. Piotrowski

    2005-01-01

    In the United States, the constitutional constraints and administrative law requirements imposed on government agencies generally have no applicability to private entities performing outsourced public administrative activities. In this article, the authors broadly explore the issues associated with outsourcing constitutional and administrative law norms along with government work by imposing them on private contractors. The authors seek to help frame

  17. Stealths on Anisotropic Holographic Backgrounds

    E-print Network

    Eloy Ayón-Beato; Mokhtar Hassaďne; María Montserrat Juárez-Aubry

    2015-06-11

    In this paper, we are interested in exploring the existence of stealth configurations on anisotropic backgrounds playing a prominent role in the non-relativistic version of the gauge/gravity correspondence. By stealth configuration, we mean a nontrivial scalar field nonminimally coupled to gravity whose energy-momentum tensor evaluated on the anisotropic background vanishes identically. In the case of a Lifshitz spacetime with a nontrivial dynamical exponent z, we spotlight the role played by the anisotropy to establish the holographic character of the stealth configurations, i.e. the scalar field is shown to only depend on the radial holographic direction. This configuration which turns out to be massless and without integration constants is possible for a unique value of the nonminimal coupling parameter. Then, using a simple conformal argument, we map this configuration into a stealth solution defined on the so-called hyperscaling violation metric which is conformally related to the Lifshitz spacetime. This holographic configuration obtained through a conformal mapping constitutes only a particular class within the stealth solutions defined on the hyperscaling violation as it is shown by deriving the most general stealth configurations. The case of the Schrodinger background is also exhaustively analyzed and we establish that the presence of the null direction makes their stealth configurations not necessarily holographic in general and characterized by a self-interacting behavior. Finally, for completeness we also study the stealth configurations on the Schrodinger inspired hyperscaling violation spacetimes.

  18. 76 FR 58705 - Constitution Day and Citizenship Day, Constitution Week, 2011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-21

    ...Constitution Day and Citizenship Day, Constitution Week, 2011 Proclamation 8715--National Employer Support of the Guard and Reserve Week, 2011 Proclamation 8716--National Farm Safety and Health Week, 2011 Proclamation 8717--National...

  19. MEMORIAL UNIVERSITY OF NEWFOUNDLAND FACULTY ASSOCIATION CONSTITUTION (This copy of the Constitution contains amendments

    E-print Network

    Oyet, Alwell

    MEMORIAL UNIVERSITY OF NEWFOUNDLAND FACULTY ASSOCIATION CONSTITUTION (This copy of the Constitution (Name) Memorial University of Newfoundland Faculty Association (MUNFA). Article II (Purpose) The purpose teaching and research, and, within the Province of Newfoundland, to regulate relations between employers

  20. Constitutively active UVR8 photoreceptor variant in Arabidopsis

    PubMed Central

    Heijde, Marc; Binkert, Melanie; Yin, Ruohe; Ares-Orpel, Florence; Rizzini, Luca; Van De Slijke, Eveline; Persiau, Geert; Nolf, Jonah; Gevaert, Kris; De Jaeger, Geert; Ulm, Roman

    2013-01-01

    Arabidopsis thaliana UV RESISTANCE LOCUS 8 (UVR8) is a UV-B photoreceptor that initiates photomorphogenic responses underlying acclimation and UV-B tolerance in plants. UVR8 is a homodimer in its ground state, and UV-B exposure results in its instantaneous monomerization followed by interaction with CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1), a major factor in UV-B signaling. UV-B photoreception by UVR8 is based on intrinsic tryptophan aromatic amino acid residues, with tryptophan-285 as the main chromophore. We generated transgenic plants expressing UVR8 with a single amino acid change of tryptophan-285 to alanine. UVR8W285A appears monomeric and shows UV-B–independent interaction with COP1. Phenotypically, the plants expressing UVR8W285A exhibit constitutive photomorphogenesis associated with constitutive activation of target genes, elevated levels of anthocyanins, and enhanced, acclimation-independent UV-B tolerance. Moreover, we have identified COP1, REPRESSOR OF UV-B PHOTOMORPHOGENESIS 1 and 2 (RUP1 and RUP2), and the SUPPRESSOR OF PHYA-105 (SPA) family as proteins copurifying with UVR8W285A. Whereas COP1, RUP1, and RUP2 are known to directly interact with UVR8, we show that SPA1 interacts with UVR8 indirectly through COP1. We conclude that UVR8W285A is a constitutively active UVR8 photoreceptor variant in Arabidopsis, as is consistent with the crucial importance of monomer formation and COP1 binding for UVR8 activity. PMID:24277841

  1. Who wrote the Constitution and why was it written?

    NSDL National Science Digital Library

    Ms. Triola

    2009-10-13

    Researching the Constitution Use these approved websites to help prove your statement is correct. You do not have to look at all of them. These websites are here to help you research. Read carefully!:) Ben s guide to the Constitution Ben s guide to the Constitution # 2 Constitution Day Constitution for Kids Framers of the Constitution ...

  2. Closing in on the constitution of consciousness

    PubMed Central

    Miller, Steven M.

    2014-01-01

    The science of consciousness is a nascent and thriving field of research that is founded on identifying the minimally sufficient neural correlates of consciousness. However, I have argued that it is the neural constitution of consciousness that science seeks to understand and that there are no evident strategies for distinguishing the correlates and constitution of (phenomenal) consciousness. Here I review this correlation/constitution distinction problem and challenge the existing foundations of consciousness science. I present the main analyses from a longer paper in press on this issue, focusing on recording, inhibition, stimulation, and combined inhibition/stimulation strategies, including proposal of the Jenga analogy to illustrate why identifying the minimally sufficient neural correlates of consciousness should not be considered the ultimate target of consciousness science. Thereafter I suggest that while combined inhibition and stimulation strategies might identify some constitutive neural activities—indeed minimally sufficient constitutive neural activities—such strategies fail to identify the whole neural constitution of consciousness and thus the correlation/constitution distinction problem is not fully solved. Various clarifications, potential objections and related scientific and philosophical issues are also discussed and I conclude by proposing new foundational claims for consciousness science. PMID:25452738

  3. Closing in on the constitution of consciousness.

    PubMed

    Miller, Steven M

    2014-01-01

    The science of consciousness is a nascent and thriving field of research that is founded on identifying the minimally sufficient neural correlates of consciousness. However, I have argued that it is the neural constitution of consciousness that science seeks to understand and that there are no evident strategies for distinguishing the correlates and constitution of (phenomenal) consciousness. Here I review this correlation/constitution distinction problem and challenge the existing foundations of consciousness science. I present the main analyses from a longer paper in press on this issue, focusing on recording, inhibition, stimulation, and combined inhibition/stimulation strategies, including proposal of the Jenga analogy to illustrate why identifying the minimally sufficient neural correlates of consciousness should not be considered the ultimate target of consciousness science. Thereafter I suggest that while combined inhibition and stimulation strategies might identify some constitutive neural activities-indeed minimally sufficient constitutive neural activities-such strategies fail to identify the whole neural constitution of consciousness and thus the correlation/constitution distinction problem is not fully solved. Various clarifications, potential objections and related scientific and philosophical issues are also discussed and I conclude by proposing new foundational claims for consciousness science. PMID:25452738

  4. Dynamic functional modules in co-expressed protein interaction networks of dilated cardiomyopathy

    Microsoft Academic Search

    Chen-Ching Lin; Jen-Tsung Hsiang; Chia-Yi Wu; Yen-Jen Oyang; Hsueh-Fen Juan; Hsuan-Cheng Huang

    2010-01-01

    BACKGROUND: Molecular networks represent the backbone of molecular activity within cells and provide opportunities for understanding the mechanism of diseases. While protein-protein interaction data constitute static network maps, integration of condition-specific co-expression information provides clues to the dynamic features of these networks. Dilated cardiomyopathy is a leading cause of heart failure. Although previous studies have identified putative biomarkers or therapeutic

  5. Generalized constitutive relations for metamaterials based on the quasi-static Lorentz theory

    Microsoft Academic Search

    Akira Ishimaru; Seung-Woo Lee; Yasuo Kuga; Vikram Jandhyala

    2003-01-01

    This paper presents a method of calculating the elements of the generalized matrix representation of the macroscopic constitutive relations for a three-dimensional (3-D) array of non-magnetic inclusions with arbitrary shape. The derivation is based on the quasi-static Lorentz theory and the inclusions are represented by electric and magnetic dipole moments. The 6×6 constitutive relation matrix is expressed in terms of

  6. Building Background Knowledge

    ERIC Educational Resources Information Center

    Neuman, Susan B.; Kaefer, Tanya; Pinkham, Ashley

    2014-01-01

    This article make a case for the importance of background knowledge in children's comprehension. It suggests that differences in background knowledge may account for differences in understanding text for low- and middle-income children. It then describes strategies for building background knowledge in the age of common core standards.

  7. Background Subtraction Techniques

    Microsoft Academic Search

    Alan M. McIvor

    Background subtraction is a commonly used class of techniques for segmenting out objects of interest in a scene for applications such as surveillance. This paper surveys a repre- sentative sample of the published techiques for background subtraction, and analyses them with respect to three important attributes: foreground detection; background maintenance; and postprocessing.

  8. Constitutive theory of anisotropic rigid heat conductors

    NASA Astrophysics Data System (ADS)

    Liu, I.-Shih

    2009-08-01

    For rigid heat conductors, the constitutive equation of the heat flux is usually assumed to be independent of the deformation of the body, or equivalently by setting the deformation gradient as the identity tensor in the constitutive equations. However, the notion of material symmetry would have involved change in reference configurations, hence also change in deformation gradients. Consequently it would be impossible to consider anisotropic rigid heat conductors from such a formulation. In this paper, rigid heat conductors are treated with rigidity as internal constraint and a constitutive theory consistent with the principle of material frame indifference, material symmetry, and entropy principle is presented. Constitutive restrictions for a transversely isotropic rigid heat conductor are carefully analyzed.

  9. Toussaint’s Constitution (1801) With Introduction

    E-print Network

    Louverture, Toussaint; Freeman, Bryant C.

    1994-01-01

    KU ScholarWorks | http://kuscholarworks.ku.edu Toussaint’s Constitution (1801) With Introduction 1994 This work has been made available by the University of Kansas Libraries’ Office of Scholarly Communication and Copyright. Please share your....edu/~scholar/docs/license.shtml Introduction by Bryant C. Freeman Occasional Paper N° 2 Bryant C. Freeman, Ph.D. General Editor Toussaint's Constitution (1801) With Introduction re, s Institute of Haitian Studies University of Kansas 1994 University of Kansas Institute of Haitian...

  10. Medical intervention in a constitutionally tall child.

    PubMed

    Nasrat, Ghada H; Al-Alwan, Ibrahim

    2012-01-01

    Constitutionally tall stature (CTS) in children is a normal variant of growth within populations. Based mainly on psychological factors, sex steroids have been prescribed since the 1950s to induce puberty, as a mean to reduce final adult height. Controversy remains in the treatment of CTS, as well as lack of established criteria for initiating treatment. We report a constitutionally tall Saudi boy who was treated with sex steroids and was successful in reducing his final adult height. PMID:23076690

  11. Constitutional rights and hypnotically elicited testimony.

    PubMed

    Newman, A W; Thompson, J W

    1999-01-01

    Despite the former popularity of hypnosis as a way of "improving" eyewitness memory, many courts almost always regard the use of this testimony to be inadmissible, whereas others allow it only when strict procedural guidelines have been followed. Although the U.S. Supreme Court recognized a defendant's constitutional right to admit his own hypnotically elicited testimony, others have recognized a constitutional basis to exclude hypnotically elicited testimony in most other circumstances. PMID:10212035

  12. Constitutive model for cyclic deformation of perfluoroelastomers

    NASA Astrophysics Data System (ADS)

    Drozdov, A. D.

    2009-08-01

    Observations are reported in uniaxial cyclic tensile tests with a strain-controlled program on perfluoroelastomer Hyflon MFA. A constitutive model is developed for its viscoplastic response and damage at three-dimensional deformations with finite strains. Adjustable parameters in the stress-strain relations are found by fitting the experimental data. Numerical simulation demonstrates that the constitutive equations adequately describe the mechanical response of perfluoroelastomer in cyclic tests with complicated deformation programs.

  13. Constitutive model for cyclic deformation of perfluoroelastomers

    Microsoft Academic Search

    A. D. Drozdov

    2009-01-01

    Observations are reported in uniaxial cyclic tensile tests with a strain-controlled program on perfluoroelastomer Hyflon MFA. A constitutive model is developed for its viscoplastic response and damage at three-dimensional deformations with finite strains. Adjustable parameters in the stress-strain relations are found by fitting the experimental data. Numerical simulation demonstrates that the constitutive equations adequately describe the mechanical response of perfluoroelastomer

  14. Constitutive Androstane Receptor Ligands Modulate the Anti-Tumor Efficacy of Paclitaxel in Non-Small Cell Lung Cancer Cells

    PubMed Central

    Fukumasu, Heidge; Rochetti, Arina L.; Pires, Pedro R. L.; Silva, Edson R.; Mesquita, Ligia G.; Strefezzi, Ricardo F.; De Carvalho, Daniel D.; Dagli, Maria L.

    2014-01-01

    Background Lung tumors are the leading cause of cancer deaths worldwide and paclitaxel has proven to be useful for patients with lung cancer, however, acquired resistance is a major problem. To overcome this problem, one promising option is the use of Constitutive Androstane Receptor (CAR) ligands in combination with chemotherapeutics against cancer cells. Therefore, we wish to elucidate the effects of CAR ligands on the antineoplastic efficacy of paclitaxel in lung cancer cells. Methodology/Principal Findings Our results from cell viability assays exposing CAR agonist or inverse-agonist to mouse and human lung cancer cells modulated the antineoplastic effect of paclitaxel. The CAR agonists increased the effect of Paclitaxel in 6 of 7 lung cancer cell lines, whereas the inverse-agonist had no effect on paclitaxel cytotoxicity. Interestingly, the mCAR agonist TCPOBOP enhanced the expression of two tumor suppressor genes, namely WT1 and MGMT, which were additively enhanced in cells treated with CAR agonist in combination with paclitaxel. Also, in silico analysis showed that both paclitaxel and CAR agonist TCPOBOP docked into the mCAR structure but not the inverse agonist androstenol. Paclitaxel per se increases the expression of CAR in cancer cells. At last, we analyzed the expression of CAR in two public independent studies from The Cancer Genome Atlas (TCGA) of Non Small Cell Lung Cancer (NSCLC). CAR is expressed in variable levels in NSCLC samples and no association with overall survival was noted. Conclusions/Significance Taken together, our results demonstrated that CAR agonists modulate the antineoplastic efficacy of paclitaxel in mouse and human cancer cell lines. This effect was probably related by the enhanced expression of two tumor suppressor genes, viz. WT1 and MGMT. Most of NSCLC cases present CAR gene expression turning it possible to speculate the use of CAR modulation by ligands along with Paclitaxel in NSCLC therapy. PMID:24959746

  15. Constitutive overexpression of soybean plasma membrane intrinsic protein GmPIP1;6 confers salt tolerance

    PubMed Central

    2014-01-01

    Background Under saline conditions, plant growth is depressed via osmotic stress and salt can accumulate in leaves leading to further depression of growth due to reduced photosynthesis and gas exchange. Aquaporins are proposed to have a major role in growth of plants via their impact on root water uptake and leaf gas exchange. In this study, soybean plasma membrane intrinsic protein 1;6 (GmPIP1;6) was constitutively overexpressed to evaluate the function of GmPIP1;6 in growth regulation and salt tolerance in soybean. Results GmPIP1;6 is highly expressed in roots as well as reproductive tissues and the protein targeted to the plasma membrane in onion epidermis. Treatment with 100 mM NaCl resulted in reduced expression initially, then after 3 days the expression was increased in root and leaves. The effects of constitutive overexpression of GmPIP1;6 in soybean was examined under normal and salt stress conditions. Overexpression in 2 independent lines resulted in enhanced leaf gas exchange, but not growth under normal conditions compared to wild type (WT). With 100 mM NaCl, net assimilation was much higher in the GmPIP1;6-Oe and growth was enhanced relative to WT. GmPIP1;6-Oe plants did not have higher root hydraulic conductance (Lo) under normal conditions, but were able to maintain Lo under saline conditions compared to WT which decreased Lo. GmPIP1;6-Oe lines grown in the field had increased yield resulting mainly from increased seed size. Conclusions The general impact of overexpression of GmPIP1;6 suggests that it may be a multifunctional aquaporin involved in root water transport, photosynthesis and seed loading. GmPIP1;6 is a valuable gene for genetic engineering to improve soybean yield and salt tolerance. PMID:24998596

  16. A constitutive theory of reacting electrolyte mixtures

    NASA Astrophysics Data System (ADS)

    Costa Reis, Martina; Wang, Yongqi; Bono Maurizio Sacchi Bassi, Adalberto

    2013-11-01

    A constitutive theory of reacting electrolyte mixtures is formulated. The intermolecular interactions among the constituents of the mixture are accounted for through additional freedom degrees to each constituent of the mixture. Balance equations for polar reacting continuum mixtures are accordingly formulated and a proper set of constitutive equations is derived with basis in the Müller-Liu formulation of the second law of thermodynamics. Moreover, the non-equilibrium and equilibrium responses of the reacting mixture are investigated in detail by emphasizing the inner and reactive structures of the medium. From the balance laws and constitutive relations, the effects of molecular structure of constituents upon the fluid flow are studied. It is also demonstrated that the local thermodynamic equilibrium state can be reached without imposing that the set of independent constitutive variables is time independent, neither spatially homogeneous nor null. The resulting constitutive relations presented throughout this work are of relevance to many practical applications, such as swelling of clays, developing of bio and polymeric membranes, and use of electrorheological fluids in industrial processes. A constitutive theory of reacting electrolyte mixtures is formulated. The intermolecular interactions among the constituents of the mixture are accounted for through additional freedom degrees to each constituent of the mixture. Balance equations for polar reacting continuum mixtures are accordingly formulated and a proper set of constitutive equations is derived with basis in the Müller-Liu formulation of the second law of thermodynamics. Moreover, the non-equilibrium and equilibrium responses of the reacting mixture are investigated in detail by emphasizing the inner and reactive structures of the medium. From the balance laws and constitutive relations, the effects of molecular structure of constituents upon the fluid flow are studied. It is also demonstrated that the local thermodynamic equilibrium state can be reached without imposing that the set of independent constitutive variables is time independent, neither spatially homogeneous nor null. The resulting constitutive relations presented throughout this work are of relevance to many practical applications, such as swelling of clays, developing of bio and polymeric membranes, and use of electrorheological fluids in industrial processes. The first author acknowledges financial support from National Counsel of Technological and Scientific Development (CNPq) and German Academic Exchange Service (DAAD).

  17. Nonequilibrium electromagnetics: Local and macroscopic fields and constitutive relationships

    SciTech Connect

    Baker-Jarvis, James; Kabos, Pavel; Holloway, Christopher L. [NIST, Electromagnetics Divsion, MS 818-01, Boulder, Colorado 80305 (United States)

    2004-09-01

    We study the electrodynamics of materials using a Liouville-Hamiltonian-based statistical-mechanical theory. Our goal is to develop electrodynamics from an ensemble-average viewpoint that is valid for microscopic and nonequilibrium systems at molecular to submolecular scales. This approach is not based on a Taylor series expansion of the charge density to obtain the multipoles. Instead, expressions of the molecular multipoles are used in an inverse problem to obtain the averaging statistical-density function that is used to obtain the macroscopic fields. The advantages of this method are that the averaging function is constructed in a self-consistent manner and the molecules can either be treated as point multipoles or contain more microstructure. Expressions for the local and macroscopic fields are obtained, and evolution equations for the constitutive parameters are developed. We derive equations for the local field as functions of the applied, polarization, magnetization, strain density, and macroscopic fields.

  18. Expression of endoglucanases in Pichia pastoris under control of the GAP promoter

    PubMed Central

    2014-01-01

    Background Plant-derived biomass is a potential alternative to fossil feedstocks for a greener economy. Enzymatic saccharification of biomass has been studied extensively and endoglucanases have been found to be a prerequisite for quick initial liquefaction of biomass under industrial conditions. Pichia pastoris, widely used for heterologous protein expression, can be utilized for fungal endoglucanase production. The recently marketed PichiaPink™ expression system allows for rapid clone selection, and employs the methanol inducible AOX1 promoter to ensure high protein expression levels. However, methanol is toxic and poses a fire hazard, issues which become more significant at an industrial scale. It is possible to eliminate these risks and still maintain high productivity by switching to the constitutive GAP promoter. Results In the present study, a plasmid carrying the constitutive GAP promoter was created for PichiaPink™. We then studied expression of two endoglucanases, AfCel12A from Aspergillus fumigatus and TaCel5A from Thermoascus aurantiacus, regulated by either the AOX1 promoter or the GAP promoter. Initial experiments in tubes and small bioreactors showed that the levels of AfCel12A obtained with the constitutive promoter were similar or higher, compared to the AOX1 promoter, whereas the levels of TaCel5A were somewhat lower. After optimization of cultivation conditions using a 15-l bioreactor, the recombinant P. pastoris strains utilizing the GAP promoter produced ca. 3–5 g/l of total secreted protein, with CMCase activity equivalent to 1200 nkat/ml AfCel12A and 170 nkat/ml TaCel5A. Conclusions We present a strategy for constitutive recombinant protein expression in the novel PichiaPink™ system. Both AfCel12A and TaCel5A were successfully expressed constitutively in P. pastoris under the GAP promoter. Reasonable protein levels were reached after optimizing cultivation conditions. PMID:24742273

  19. Inducible and constitutive promoters for genetic systems in Sulfolobus acidocaldarius

    PubMed Central

    Berkner, Silvia; Wlodkowski, Alexander; Albers, Sonja-Verena

    2010-01-01

    Central to genetic work in any organism are the availability of a range of inducible and constitutive promoters. In this work we studied several promoters for use in the hyperthermophilic archaeon Sulfolobus acidocaldarius. The promoters were tested with the aid of an E. coli–Sulfolobus shuttle vector in reporter gene experiments. As the most suitable inducible promoter a maltose inducible promoter was identified. It comprises 266 bp of the sequence upstream of the gene coding for the maltose/maltotriose binding protein (mbp, Saci_1165). Induction is feasible with either maltose or dextrin at concentrations of 0.2–0.4%. The highest increase in expression (up to 17-fold) was observed in late exponential and stationary phase around 30–50 h after addition of dextrin. Whereas in the presence of glucose and xylose higher basal activity and reduced inducibility with maltose is observed, sucrose can be used in the growth medium additionally without affecting the basal activity or the inducibility. The minimal promoter region necessary could be narrowed down to 169 bp of the upstream sequence. The ABCE1 protein from S. solfataricus was successfully expressed under control of the inducible promoter with the shuttle vector pC and purified from the S. acidocaldarius culture with a yield of about 1 mg L?1 culture. In addition we also determined the promoter strength of several constitutive promoters. PMID:20221889

  20. Functional Validation of a Constitutive Autonomous Silencer Element

    PubMed Central

    Emery, David W.; Stamatoyannopoulos, George

    2015-01-01

    Sequences of the genome that are capable of silencing gene expression are thought to play a key role in gene regulation. However, very few silencer elements capable of functioning in mammalian cells have been described, and only a fraction of these have been tested for the ability to function in an autonomous fashion. We report here the characterization and functional validation of a constitutive autonomous silencer element from the human genome called T39, and the comparison of T39 to three other putative silencer elements previously described by others. Functional analysis included one assay for enhancer-blocking insulator activity and two independent assays for silencer activity, all based on stable transfection and comparison to a neutral spacer control. In erythroid K562 cells, T39 exhibited potent silencer activity, the previously described element PRE2-S5 exhibited modest silencer activity, and the two other previously described elements exhibited no silencer activity. T39 was further found to be capable of silencing three disparate promoters, of silencing gene expression in three disparate cell lines, and of functioning as a single copy in a topology-independent manner. Of the four elements analyzed, only T39 exhibits a constitutive pattern of DNase hypersensitivity and binding by CTCF. In its native location the T39 element also exhibits a unique interaction profile with a subset of distal putative regulatory elements. Taken together, these studies validate T39 as a constitutive autonomous silencer, identify T39 as a defined control for future studies of other regulatory elements such as insulators, and provide a basic chromatin profile for one highly potent silencer element. PMID:25910277

  1. Health care law versus constitutional law.

    PubMed

    Hall, Mark A

    2013-04-01

    National Federation of Independent Business v. Sebelius, the Supreme Court's ruling on the Patient Protection and Affordable Care Act, is a landmark decision - both for constitutional law and for health care law and policy. Others will study its implications for constitutional limits on a range of federal powers beyond health care. This article considers to what extent the decision is also about health care law, properly conceived. Under one view, health care law is the subdiscipline that inquires how courts and government actors take account of the special features of medicine that make legal or policy issues especially problematic - rather than regarding health care delivery and finance more generically, like most any other economic or social enterprise. Viewed this way, the opinions from the Court's conservative justices are mainly about general constitutional law principles. In contrast, Justice Ruth Bader Ginsburg's dissenting opinion for the four more liberal justices is just as much about health care law as it is about constitutional law. Her opinion gives detailed attention to the unique features of health care finance and delivery in order to inform her analysis of constitutional precedents and principles. Thus, the Court's multiple opinions give a vivid depiction of the compelling contrasts between communal versus individualistic conceptions of caring for those in need, and between health care and health insurance as ordinary commodities versus ones that merit special economic, social, and legal status. PMID:23262771

  2. The Cosmic Background Explorer.

    ERIC Educational Resources Information Center

    Gulkis, Samuel; And Others

    1990-01-01

    Outlines the Cosmic Background Explorer (COBE) mission to measure celestial radiation. Describes the instruments used and experiments involving differential microwave radiometers, and a far infrared absolute spectrophotometer. (YP)

  3. Application of symbolic computations to the constitutive modeling of structural materials

    NASA Technical Reports Server (NTRS)

    Arnold, Steven M.; Tan, H. Q.; Dong, X.

    1990-01-01

    In applications involving elevated temperatures, the derivation of mathematical expressions (constitutive equations) describing the material behavior can be quite time consuming, involved and error-prone. Therefore intelligent application of symbolic systems to faciliate this tedious process can be of significant benefit. Presented here is a problem oriented, self contained symbolic expert system, named SDICE, which is capable of efficiently deriving potential based constitutive models in analytical form. This package, running under DOE MACSYMA, has the following features: (1) potential differentiation (chain rule), (2) tensor computations (utilizing index notation) including both algebraic and calculus; (3) efficient solution of sparse systems of equations; (4) automatic expression substitution and simplification; (5) back substitution of invariant and tensorial relations; (6) the ability to form the Jacobian and Hessian matrix; and (7) a relational data base. Limited aspects of invariant theory were also incorporated into SDICE due to the utilization of potentials as a starting point and the desire for these potentials to be frame invariant (objective). The uniqueness of SDICE resides in its ability to manipulate expressions in a general yet pre-defined order and simplify expressions so as to limit expression growth. Results are displayed, when applicable, utilizing index notation. SDICE was designed to aid and complement the human constitutive model developer. A number of examples are utilized to illustrate the various features contained within SDICE. It is expected that this symbolic package can and will provide a significant incentive to the development of new constitutive theories.

  4. Thermoelastic constitutive equations for chemically hardening materials

    NASA Technical Reports Server (NTRS)

    Shaffer, B. W.; Levitsky, M.

    1974-01-01

    Thermoelastic constitutive equations are derived for a material undergoing solidification or hardening as the result of a chemical reaction. The derivation is based upon a two component model whose composition is determined by the degree of hardening, and makes use of strain-energy considerations. Constitutive equations take the form of stress rate-strain rate relations, in which the coefficients are time-dependent functions of the composition. Specific results are developed for the case of a material of constant bulk modulus which undergoes a transition from an initial liquidlike state into an isotropic elastic solid. Potential applications are discussed.

  5. The IBEX background monitor

    E-print Network

    Crew, Geoffrey B.

    The IBEX Background Monitor (IBaM) provides a small and lightweight method for independently measuring IBEX’s high-energy proton background by integrating the flux of >~14 keV protons over a ~7° conical FOV. The IBaM is ...

  6. The microwave background radiation

    Microsoft Academic Search

    Juan M. Uson; David T. Wilkinson

    1988-01-01

    Contents: 1. Introduction. 2. The spectrum of the microwave background: Heterodyne radiometer methods (lambda >= 3 mm). Bolometric measurements (lambda <= 3 mm). Measurements using interstellar molecules. Summary and future prospects. 3. Polarization of the microwave background. 4. Anisotropy searches. 5. The Sunyaev-Zel'dovich effect: Concept and cosmological consequences. Measurements. Cosmological applications.

  7. 43 CFR 1.5 - Signature to constitute certificate.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...2010-10-01 2010-10-01 false Signature to constitute certificate. 1.5...DEPARTMENT OF THE INTERIOR § 1.5 Signature to constitute certificate. When...in practice before the Department, his signature shall constitute his...

  8. 43 CFR 1.5 - Signature to constitute certificate.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...2011-10-01 2011-10-01 false Signature to constitute certificate. 1.5...DEPARTMENT OF THE INTERIOR § 1.5 Signature to constitute certificate. When...in practice before the Department, his signature shall constitute his...

  9. 43 CFR 1.5 - Signature to constitute certificate.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...2012-10-01 2011-10-01 true Signature to constitute certificate. 1.5...DEPARTMENT OF THE INTERIOR § 1.5 Signature to constitute certificate. When...in practice before the Department, his signature shall constitute his...

  10. 43 CFR 1.5 - Signature to constitute certificate.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...2014-10-01 2014-10-01 false Signature to constitute certificate. 1.5...DEPARTMENT OF THE INTERIOR § 1.5 Signature to constitute certificate. When...in practice before the Department, his signature shall constitute his...

  11. 43 CFR 1.5 - Signature to constitute certificate.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...2013-10-01 2013-10-01 false Signature to constitute certificate. 1.5...DEPARTMENT OF THE INTERIOR § 1.5 Signature to constitute certificate. When...in practice before the Department, his signature shall constitute his...

  12. 29 CFR 452.3 - Interpretations of constitution and bylaws.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... false Interpretations of constitution and bylaws. 452.3 Section...452.3 Interpretations of constitution and bylaws. The interpretation...consistently placed on a union's constitution by the responsible union...

  13. 29 CFR 402.1 - Labor organization constitution and bylaws.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2011-07-01 false Labor organization constitution and bylaws. 402.1 Section... § 402.1 Labor organization constitution and bylaws. Every labor organization shall adopt a constitution and bylaws consistent with...

  14. 29 CFR 402.1 - Labor organization constitution and bylaws.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2013-07-01 false Labor organization constitution and bylaws. 402.1 Section... § 402.1 Labor organization constitution and bylaws. Every labor organization shall adopt a constitution and bylaws consistent with...

  15. 29 CFR 452.3 - Interpretations of constitution and bylaws.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... false Interpretations of constitution and bylaws. 452.3 Section...452.3 Interpretations of constitution and bylaws. The interpretation...consistently placed on a union's constitution by the responsible union...

  16. 29 CFR 402.1 - Labor organization constitution and bylaws.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2012-07-01 false Labor organization constitution and bylaws. 402.1 Section... § 402.1 Labor organization constitution and bylaws. Every labor organization shall adopt a constitution and bylaws consistent with...

  17. 29 CFR 452.3 - Interpretations of constitution and bylaws.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... false Interpretations of constitution and bylaws. 452.3 Section...452.3 Interpretations of constitution and bylaws. The interpretation...consistently placed on a union's constitution by the responsible union...

  18. 29 CFR 402.1 - Labor organization constitution and bylaws.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2010-07-01 false Labor organization constitution and bylaws. 402.1 Section... § 402.1 Labor organization constitution and bylaws. Every labor organization shall adopt a constitution and bylaws consistent with...

  19. 29 CFR 402.1 - Labor organization constitution and bylaws.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2014-07-01 false Labor organization constitution and bylaws. 402.1 Section... § 402.1 Labor organization constitution and bylaws. Every labor organization shall adopt a constitution and bylaws consistent with...

  20. 29 CFR 452.3 - Interpretations of constitution and bylaws.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... false Interpretations of constitution and bylaws. 452.3 Section...452.3 Interpretations of constitution and bylaws. The interpretation...consistently placed on a union's constitution by the responsible union...

  1. 78 FR 39721 - Constitution Pipeline Company, LLC; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ...Nos. CP13-499-000; PF12-9-000] Constitution Pipeline Company, LLC; Notice of Application Take notice that on June 13, 2013, Constitution Pipeline Company, LLC (Constitution), having its principal place of...

  2. 29 CFR 452.3 - Interpretations of constitution and bylaws.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... false Interpretations of constitution and bylaws. 452.3 Section...452.3 Interpretations of constitution and bylaws. The interpretation...consistently placed on a union's constitution by the responsible union...

  3. Correlators in nontrivial backgrounds

    SciTech Connect

    Mello Koch, Robert de [National Institute for Theoretical Physics, Department of Physics and Centre for Theoretical Physics, University of the Witwatersrand, Wits, 2050 (South Africa); Stellenbosch Institute for Advanced Studies, Stellenbosch (South Africa); Ives, Norman; Stephanou, Michael [National Institute for Theoretical Physics, Department of Physics and Centre for Theoretical Physics, University of the Witwatersrand, Wits, 2050 (South Africa)

    2009-01-15

    Operators in N=4 super Yang-Mills theory with an R-charge of O(N{sup 2}) are dual to backgrounds which are asymtotically AdS{sub 5}xS{sup 5}. In this article we develop efficient techniques that allow the computation of correlation functions in these backgrounds. We find that (i) contractions between fields in the string words and fields in the operator creating the background are the field theory accounting of the new geometry, (ii) correlation functions of probes in these backgrounds are given by the free field theory contractions but with rescaled propagators and (iii) in these backgrounds there are no open string excitations with their special end point interactions; we have only closed string excitations.

  4. Cardiac Overexpression of Constitutively Active Galpha q Causes Angiotensin II Type1 Receptor Activation, Leading to Progressive Heart Failure and Ventricular Arrhythmias in Transgenic Mice

    PubMed Central

    Matsushita, Naoko; Kashihara, Toshihide; Shimojo, Hisashi; Suzuki, Satoshi; Nakada, Tsutomu; Takeishi, Yasuchika; Mende, Ulrike; Taira, Eiichi; Yamada, Mitsuhiko; Sanbe, Atsushi; Hirose, Masamichi

    2014-01-01

    Background Transgenic mice with transient cardiac expression of constitutively active Galpha q (G?q-TG) exhibt progressive heart failure and ventricular arrhythmias after the initiating stimulus of transfected constitutively active G?q becomes undetectable. However, the mechanisms are still unknown. We examined the effects of chronic administration of olmesartan on heart failure and ventricular arrhythmia in G?q-TG mice. Methodology/Principal Findings Olmesartan (1 mg/kg/day) or vehicle was chronically administered to G?q-TG from 6 to 32 weeks of age, and all experiments were performed in mice at the age of 32 weeks. Chronic olmesartan administration prevented the severe reduction of left ventricular fractional shortening, and inhibited ventricular interstitial fibrosis and ventricular myocyte hypertrophy in G?q-TG. Electrocardiogram demonstrated that premature ventricular contraction (PVC) was frequently (more than 20 beats/min) observed in 9 of 10 vehicle-treated G?q-TG but in none of 10 olmesartan-treated G?q-TG. The collected QT interval and monophasic action potential duration in the left ventricle were significantly shorter in olmesartan-treated G?q-TG than in vehicle-treated G?q-TG. CTGF, collagen type 1, ANP, BNP, and ?-MHC gene expression was increased and olmesartan significantly decreased the expression of these genes in G?q-TG mouse ventricles. The expression of canonical transient receptor potential (TRPC) 3 and 6 channel and angiotensin converting enzyme (ACE) proteins but not angiotensin II type 1 (AT1) receptor was increased in G?q-TG ventricles compared with NTG mouse ventricles. Olmesartan significantly decreased TRPC6 and tended to decrease ACE expressions in G?q-TG. Moreover, it increased AT1 receptor in G?q-TG. Conclusions/Significance These findings suggest that angiotensin II type 1 receptor activation plays an important role in the development of heart failure and ventricular arrhythmia in G?q-TG mouse model of heart failure. PMID:25171374

  5. 77 FR 57981 - Constitution Day and Citizenship Day, Constitution Week, 2012

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-18

    ...Day and Citizenship Day, Constitution Week, 2012 Presidential Documents Federal Register...Day and Citizenship Day, Constitution Week, 2012 By the President of the United States...contributions of all their members. This week, we reflect on the basic rights and...

  6. School Choice and State Constitutions' Religion Clauses

    ERIC Educational Resources Information Center

    Komer, Richard D.

    2009-01-01

    After the U.S. Supreme Court's decision in "Zelman v. Simmons-Harris," only state religion clauses represent a potential constitutional bar to the inclusion of religious options in properly designed school choice programs. The two most significant are compelled support clauses and Blaine Amendments. Both are frequently misinterpreted by state…

  7. A New Perspective on Teaching Constitutional Law

    ERIC Educational Resources Information Center

    Rosenblum, Robert

    1977-01-01

    The author suggests that a major failure of most law schools and traditional undergraduate constitutional law courses is that they omit an adequate analysis of the political nature of the judicial process. Political influences on a variety of court cases are discussed. (LBH)

  8. Globalization of Constitutional Law and Civil Rights.

    ERIC Educational Resources Information Center

    Weissbrodt, David

    1993-01-01

    Two issues are discussed: (1) reasons for raising global and international human rights issues in constitutional law, civil rights, and administrative law courses in United States law schools; and (2) barriers to globalization of courses and ways to overcome them. (MSE)

  9. A nonlinear viscoelastic constitutive model of solidpropellant

    Microsoft Academic Search

    Gyoo-Dong Jung; Sung-Kie Youn

    1999-01-01

    A nonlinear viscoelastic constitutive model for solid propellant is proposed. Theviscoelastic dewetting criteria is developed and the softening of the solid propellant due todamage is treated by the modulus decrease. In the calculation of the modulus decrease, themodulus of void, which is created by dewetting, is modeled with non zero constant values. Thevalues of adhesion energy between the binder and

  10. A constitutive model for partially saturated soils

    Microsoft Academic Search

    E. E. ALONSO; A. GENS; A. JOSA

    1990-01-01

    The Paper presents a constitutive model for describing the stress-strain behaviour of partially saturated soils. The model is formulated within the framework of hardening plasticity using two iode- pendent sets of stress variables: the excess of total stress over air pressure and the suction. The mode1 is able to represent, in a consistent and unified manner, many of the fundamental

  11. The Production and Reproduction of Constitutional Norms

    Microsoft Academic Search

    Judith Resnik

    2011-01-01

    Since 1973, Roe v.. Wade has served as shorthand in the United States for the proposition that women have a constitutionally protected right to abortion. Roe has also been used as a rallying cry for opponents of abortion rights who, in the words of Professors Reva Siegel and Robert Post, sparked\\

  12. College of Veterinary Medicine Alumni Association Constitution

    E-print Network

    Pawlowski, Wojtek

    College of Veterinary Medicine Alumni Association Constitution Article I - Name The Association shall be known as the "Alumni Association of the College of Veterinary Medicine at Cornell University University College of Veterinary Medicine and its alumni. It will aid in the preparation and development

  13. Social Work Students' Society Constitution November 2005

    E-print Network

    Argerami, Martin

    Social Work Students' Society Constitution ­ November 2005 Preamble The Social Work Students operating out of the University of Regina's Faculty of Social Work. Mission The SWSS exists as a venue for social work students to gather and pursue common goals and interests. The SWSS shall have as an over

  14. The Constitution and Administrative Ethics in America

    Microsoft Academic Search

    William D. Richardson; Lloyd G. Nigro

    1991-01-01

    This essay explores the contributions of founding thought to current issues regarding administrative ethics. It is argued that the founders understood public administration to be a political enterprise and, therefore, public administrators should not be excluded from their analysis of citizen character. The U.S. Constitution anticipates that self-interest will be the dominant motive of citizens and governors, including public administrators.

  15. Unified constitutive equations of foam materials

    Microsoft Academic Search

    Fu S. Chang; Y. Song; D. X. Lu; C. N. DeSilva

    1998-01-01

    Foam materials, because of their energy absorbing and recovery behavior during impact as well as lightweight and moldable characteristics, have found more and more applications in the automotive industry. A unified constitutive equation with the effect of compression strain rate, tension strain, and shear strain for foam materials with very low Poisson`s ratio has been developed. The mathematical derivation of

  16. Crushed-salt constitutive model update

    SciTech Connect

    Callahan, G.D.; Loken, M.C.; Mellegard, K.D. [RE/SPEC Inc., Rapid City, SD (United States); Hansen, F.D. [Sandia National Labs., Albuquerque, NM (United States)

    1998-01-01

    Modifications to the constitutive model used to describe the deformation of crushed salt are presented in this report. Two mechanisms--dislocation creep and grain boundary diffusional pressure solutioning--defined previously but used separately are combined to form the basis for the constitutive model governing the deformation of crushed salt. The constitutive model is generalized to represent three-dimensional states of stress. New creep consolidation tests are combined with an existing database that includes hydrostatic consolidation and shear consolidation tests conducted on Waste Isolation Pilot Plant and southeastern New Mexico salt to determine material parameters for the constitutive model. Nonlinear least-squares model fitting to data from the shear consolidation tests and a combination of the shear and hydrostatic consolidation tests produced two sets of material parameter values for the model. The change in material parameter values from test group to test group indicates the empirical nature of the model but demonstrates improvement over earlier work with the previous models. Key improvements are the ability to capture lateral strain reversal and better resolve parameter values. To demonstrate the predictive capability of the model, each parameter value set was used to predict each of the tests in the database. Based on the fitting statistics and the ability of the model to predict the test data, the model appears to capture the creep consolidation behavior of crushed salt quite well.

  17. Integration methods for complex plastic constitutive equations

    Microsoft Academic Search

    J. L. Chaboche; G. Cailletaud

    1996-01-01

    This paper shows new results concerning the Finite Element computations with complex plastic and viscoplastic constitutive equations. The integration procedure then needs special numerical treatments when a large number of internal variables are present, or for stiff non-linearities. Implicit and explicit integration methods are compared. The general solution proposed can be applied either in plasticity or in viscoplasticity, for isotropic

  18. The cosmic neutrino background

    NASA Technical Reports Server (NTRS)

    Dar, Arnon

    1991-01-01

    The cosmic neutrino background is expected to consist of relic neutrinos from the big bang, of neutrinos produced during nuclear burning in stars, of neutrinos released by gravitational stellar collapse, and of neutrinos produced by cosmic ray interactions with matter and radiation in the interstellar and intergalactic medium. Formation of baryonic dark matter in the early universe, matter-antimatter annihilation in a baryonic symmetric universe, and dark matter annihilation could have also contributed significantly to the cosmic neutrino background. The purpose of this paper is to review the properties of these cosmic neutrino backgrounds, the indirect evidence for their existence, and the prospects for their detection.

  19. The Cosmic Microwave Background

    Microsoft Academic Search

    Joseph Silk

    2003-01-01

    .  I review the discovery of the temperature fluctuations in the cosmic microwave background radiation. The underlying theory\\u000a and the implications for cosmology are described, and I summarize the prospects for future progress.

  20. Building Background Knowledge

    NSDL National Science Digital Library

    Donna Ross

    2010-01-01

    Too often, students enter our classrooms with insufficient knowledge of physical science. As a result, they have a difficult time understanding content in texts, lectures, and laboratory activities. This lack of background knowledge can have an impact on

  1. Background and Statistics

    MedlinePLUS

    Background & Statistics FAQ About Homeless Veterans Homeless Veterans Facts Demographics of Homeless Veterans Incarcerated Veterans Research Briefs Sources FAQ ... VETERANS In May 2007, the Bureau of Justice Statistics released a special report on incarcerated veterans. The ...

  2. Background Studies for EXIST

    NASA Technical Reports Server (NTRS)

    Wilson, Colleen A.; Pendleton, G. N.; Fishman, G. J.

    2004-01-01

    We present results from a study of the trapped proton and electron background for several orbital inclinations and altitudes. This study includes time dependent effects. In addition we describe a 3 component cosmic background model developed at the University of Southampton, UK. The three components are cosmic diffuse gamma rays, atmospheric albedo gamma rays, and cosmic ray protons. We present examples of how this model was applied to BATSE and discuss its application to EXIST.

  3. Modernising freedom of speech: the case of Article 100 of the Norwegian Constitution

    Microsoft Academic Search

    Asle Rolland

    2010-01-01

    In 2004, the Norwegian Parliament amended Article 100 of the Constitution, replacing freedom of print with freedom of expression. This article argues that the purpose of the amendment was not to expand freedom of speech, but to protect the state and political parties against the growing power of a non-partisan media system and of a new type of political party

  4. Constitutional promoter methylation and risk of familial melanoma

    PubMed Central

    Hyland, Paula L; Burke, Laura S; Pfeiffer, Ruth M; Rotunno, Melissa; Sun, David; Patil, Prasad; Wu, Xiaolin; Tucker, Margaret A; Goldstein, Alisa M; Yang, Xiaohong Rose

    2014-01-01

    Constitutional epigenetic changes detected in blood or non-disease involving tissues have been associated with disease susceptibility. We measured promoter methylation of CDKN2A (p16 and p14ARF) and 13 melanoma-related genes using bisulfite pyrosequencing of blood DNA from 114 cases and 122 controls in 64 melanoma-prone families (26 segregating CDKN2A germline mutations). We also obtained gene expression data for these genes using microarrays from the same blood samples. We observed that CDKN2A epimutation is rare in melanoma families, and therefore is unlikely to cause major susceptibility in families without CDKN2A mutations. Although methylation levels for most gene promoters were very low (<5%), we observed a significantly reduced promoter methylation (odds ratio = 0.63, 95% confidence interval = 0.50, 0.80, P < 0.001) and increased expression (fold change = 1.27, P = 0.048) for TNFRSF10C in melanoma cases. Future research in large prospective studies using both normal and melanoma tissues is required to assess the significance of TNFRSF10C methylation and expression changes in melanoma susceptibility. PMID:24762620

  5. Constitutive synthesis of tumor necrosis factor in the thymus.

    PubMed Central

    Giroir, B P; Brown, T; Beutler, B

    1992-01-01

    Although tumor necrosis factor (TNF) is a major mediator of endotoxic shock, the normal function of TNF that has preserved this protein throughout mammalian evolution remains unknown. If the protein serves a role in normal development or homeostasis, it must be produced under physiologic conditions. To determine whether TNF secretion occurs in normal animals, and to define the tissue sources of the protein, we prepared a reporter construct in which the TNF coding sequence and introns are replaced by the chloramphenicol acetyltransferase (CAT) coding sequence. This construct was inserted into the murine genome, yielding 13 transgenic founders. Macrophages harvested from 4 of the transgenic lines expressed CAT activity after stimulation with Escherichia coli lipopolysaccharide in vitro. Each of these 4 transgenic lines also constitutively expressed CAT activity in the thymus but in no other tissue examined. Cultured thymocytes secrete TNF, as demonstrated both by cytotoxicity assays and by immunoprecipitation of radiolabeled thymic culture medium. CAT activity was associated with the thymic lymphocyte population and not with thymic macrophages or dendritic cells. CAT activity was present in thymic lymphocytes irrespective of CD4 or CD8 expression; T cells from the spleen, however, had no detectable CAT activity. The biosynthesis of TNF in the thymus of normal animals implies a role for this protein in the development or regulation of the immune response. Images PMID:1594585

  6. Discovery of the Microwave Background Cosmic microwave background radiation

    E-print Network

    Barnes, Joshua Edward

    Discovery of the Microwave Background Cosmic microwave background radiation Signals from the early universe, or pigeon droppings? #12;Microwave Background Radiation The spectrum is a near- perfect match background. Fluctuations in the Cosmic Microwave Background MWMW 370 km/s #12;Microwave Background Features

  7. Sakhalin tender background detailed

    SciTech Connect

    Konoplyanik, A. (Russian Federation Ministry for Fuels and Energy (SU))

    1992-03-23

    This paper reports that on Jan. 27, 1992, the committee constituted by order of the Russian government of Dec. 23, 1991, and headed by V.I. Danilov-Danilyan, the Russian Federation's Minister for Ecology and Natural Resources, assessed the results of a tender announced in May 1991. The tender was for foreign companies to submit feasibility studies for exploration and development of oil and gas on the continental shelf off Sakhalin Island. The announced winner was the MMM group consisting of McDermott International Inc., Marathon Oil Co., and Mitsui and Co. Ltd. In its decision the governmental tender committee (GTC) begged to differ from V. Fedorov, governor of the Territory of Sakhalin, in whose opinion the U.S.-Japanese combine of Exxon Corp.-Sakhalin Oil Development Co. (Sodeco) should have been pronounced winner at the bidding's end. GTC's decision also ran counter to the verdict by a panel of experts constituted by decision of the Examining Council under the Chairman of the Russian Government on Dec. 3, 1991, and headed by F. Salmanov, first deputy Minister of Geology of the U.S.S.R.

  8. Constitutive Modeling of Crosslinked Nanotube Materials

    NASA Technical Reports Server (NTRS)

    Odegard, G. M.; Frankland, S. J. V.; Herzog, M. N.; Gates, T. S.; Fay, C. C.

    2004-01-01

    A non-linear, continuum-based constitutive model is developed for carbon nanotube materials in which bundles of aligned carbon nanotubes have varying amounts of crosslinks between the nanotubes. The model accounts for the non-linear elastic constitutive behavior of the material in terms of strain, and is developed using a thermodynamic energy approach. The model is used to examine the effect of the crosslinking on the overall mechanical properties of variations of the crosslinked carbon nanotube material with varying degrees of crosslinking. It is shown that the presence of the crosslinks has significant effects on the mechanical properties of the carbon nanotube materials. An increase in the transverse shear properties is observed when the nanotubes are crosslinked. However, this increase is accompanied by a decrease in axial mechanical properties of the nanotube material upon crosslinking.

  9. Constitutive modeling for single crystal superalloys

    NASA Technical Reports Server (NTRS)

    Stouffer, Donald C.; Dame, L. Thomas; Jayaraman, N.

    1985-01-01

    A crystallographic approach to constitutive modeling of single crystal superalloys is discussed. The approach is based on identifying the active slip planes and slip directions. The shear stresses are computed on each of the slip planes from applied stress components. The slip rate is then computed on each slip system and the microscopic inelastic strain rates are the sum of the slip in the individual slip systems. The constitutive model was implemented in a finite element code using twenty noted isoparametric solid elements. Constants were determined for octahedral and cube slip systems. These constants were then used to predict tension-compression asymmetry and fatigue loops. Other data was used to model the tensile and creep response.

  10. Biaxial constitutive equation development for single crystals

    NASA Technical Reports Server (NTRS)

    Jordan, E. H.

    1984-01-01

    Current gas turbine engines utilize large single crystal superalloy components in the hot section. Structural analysis of these components requires a valid stress strain temperature constitutive equation. The goal of the program described is to create one or more models and verify these models. A constitutive equation based on an assumed slip behavior of a single slip system was formulated, programmed, and debugged. Specifically, the basic theory for a model based on aggravating slip behavior on individual slip systems was formulated and programmed and some simulations were run using assumed values of constants. In addition, a formulation allowing strain controlled simulations was completed. An approach to structural analysis of the specimen was developed. This approach uses long tube consistancy conditions and finite elements specially formulated to take advantage of the symmetry of 100 oriented specimens.

  11. Mechanism of constitution liquid film migration

    SciTech Connect

    NONE

    1999-06-01

    Liquid film migration (LFM) in liquid phase sintering classically involves a large metastable liquid volume adjacent to solid, and migration occurs at an isolated solid-liquid (S-L) interface. Constitutional liquid film migration (CLFM), discovered in alloy 718, has major characteristics similar to those of LFM, except that the metastable liquid is from the constitutional liquation of precipitates on the grain boundary. The similarity between LFM and CLFM has led to the theory that coherency lattice strain responsible for LFM is also responsible for CLFM. The coherency strain hypothesis was tested in this study by evaluating whether the Hillert model of LFM would also apply for CLFM. Experimental results of CLFM in alloy 718 showed that migration velocity followed the trend predicted by the Hillert model. This indicates that the coherency strain hypothesis of LFM also applies for CLFM and that the coherency lattice strain responsible for LFM is also the driving force for CLFM.

  12. Rumex acetosa Y chromosomes: constitutive or facultative heterochromatin?

    PubMed

    Mosio?ek, Magdalena; Pasierbek, Pawe?; Malarz, Janusz; Mo?, Maria; Joachimiak, Andrzej J

    2005-01-01

    Condensed Y chromosomes in Rumex acetosa L. root-tip nuclei were studied using 5-azaC treatment and immunohistochemical detection of methylated histones. Although Y chromosomes were decondensed within root meristem in vivo, they became condensed and heteropycnotic in roots cultured in vitro. 5-azacytidine (5-azaC) treatment of cultured roots caused transitional dispersion of their Y chromosome bodies, but 7 days after removal of the drug from the culture medium, Y heterochromatin recondensed and again became visible. The response of Rumex sex chromatin to 5-azaC was compared with that of condensed segments of pericentromeric heterochromatin in Rhoeo spathacea (Sw.) Steam roots. It was shown that Rhoeo chromocentres, composed of AT-rich constitutive heterochromatin, did not undergo decondensation after 5-azaC treatment. The Y-bodies observed within male nuclei of R. acetosa were globally enriched with H3 histone, demethylated at lysine 4 and methylated at lysine 9. This is the first report of histone tail-modification in condensed sex chromatin in plants. Our results suggest that the interphase condensation of Y chromosomes in Rumex is facultative rather than constitutive. Furthermore, the observed response of Y-bodies to 5-azaC may result indirectly from demethylation and the subsequent altered expression of unknown genes controlling tissue-specific Y-inactivation as opposed to the global demethylation of Y-chromosome DNA. PMID:16201317

  13. Power: Constitutional Update. Bar/School Partnership Programs Series.

    ERIC Educational Resources Information Center

    American Bar Association, Chicago, IL. Special Committee on Youth Education for Citizenship.

    The fourth in a special series of handbooks dealing with constitutional themes, this document looks at power in the context of the U.S. Constitution. "The Constitution's Prescription for Freedom" (L. Peach) examines the separation of powers provided for in the Constitution. "The Concept of Power" (C. Roach) is a series of strategies, some using…

  14. Constitutionalism Through the Looking Glass of Latin America

    Microsoft Academic Search

    Miguel Schor

    2005-01-01

    This Article explores the following question: why did constitutionalism in Latin America take a different path than in the United States? Constitutions were adopted throughout the New World in the wake of independence movements in the late eighteenth and early nineteenth centuries to effectuate republican government. Yet constitutionalism in Latin America led to dictatorship whereas constitutionalism in the United States

  15. The United States Constitution as an Incomplete Text

    Microsoft Academic Search

    Donald S. Lutz

    1988-01-01

    Viewing the Constitution of the United States of America as a political text leads to the application of techniques of textual analysis when reading it. Textual analysis shows the Constitution to be incomplete, both as a constitution and as a founding instrument of the federal union. A complete text of a constitution for the United States requires inclusion of the

  16. Constitution of the Middle Common Room of The Queen's

    E-print Network

    Capdeboscq, Yves

    Constitution of the Middle Common Room of The Queen's College, Oxford Preamble: This Constitution repeals the existing constitution and shall come into force from the date it is passed. All acts validly undertaken under the previous constitution shall remain valid and cannot be called into question as being

  17. Constitution ARTICLE 1: Name, Purpose, and Non-Discrimination Policy

    E-print Network

    Jones, Michelle

    Constitution ARTICLE 1: Name, Purpose, and Non-Discrimination Policy Section 1: The Ohio State meeting. ARTICLE VIII: Amending the Constitution a. A proposed amendment to this Constitution shall to the consideration; c. This Constitution shall be amended only by the vote of two-thirds (2/3) of the members voting

  18. LE PAYSAGE EUROPEEN LE NON-LIEU DE LA CONSTITUTION

    E-print Network

    Boyer, Edmond

    LE PAYSAGE EUROPEEN OU LE NON-LIEU DE LA CONSTITUTION Le Traité établissant une Constitution pour l'Europe peut-il faire figure d'acte de constitution, compris comme principe organisateur, pour le paysage européen de nature institutionnelle ? Nous poserons comme postulat l'objet Constitution comme le lieu du

  19. Constitutive Norms in the Design of Normative Multiagent Systems

    E-print Network

    van der Torre, Leon

    Constitutive Norms in the Design of Normative Multiagent Systems Guido Boella1 and Leendert van der of normative multiagent systems composed of both constitutive and regulative norms. We analyze the properties of constitutive norms, in particular their lack of reflexivity, and the trade-off be- tween constitutive

  20. Updated May, 2002 Constitution Sample for Student Organizations

    E-print Network

    Liu, Taosheng

    Updated May, 2002 Constitution Sample for Student Organizations A Constitution contains the fundamental principles that govern an organization's operation. The development of a Constitution will serve-discriminatory. The constitution must state that the organization will not discriminate on the basis of age, color, gender, gender

  1. USUAA Constitution 1 Last Updated: MAY 2012 1

    E-print Network

    Pantaleone, Jim

    USUAA Constitution 1 Last Updated: MAY 2012 1 CONSTITUTION UNION OF STUDENTS UNIVERSITY OF ALASKA;USUAA Constitution 2 Last Updated: MAY 2012 2 Section One Process Section Two Proceedings ARTICLE; and to promote an understanding of the concept of self-governance, do affirm and establish this Constitution

  2. Genetic Approach to Elucidation of Sasang Constitutional Medicine

    Microsoft Academic Search

    Bu-Yeo Kim; Seongwon Cha; Hee-Jeong Jin; Sangkyun Jeong

    2009-01-01

    Sasang Constitutional Medicine (SCM) offers a medical principle that classifies humans into four constitution groups and guides their treatment with constitution-matched medical assis- tance. The principle of this traditional medicine, although requires significant scientific support, appears to suggest a genetic influence on constitution type. The relative frequency of constitu- tion types in a population, for instance, has remained relatively constant

  3. New cases of XXY constitution in cattle.

    PubMed

    Molteni, L; De Giovanni Macchi, A; Meggiolaro, D; Sironi, G; Enice, F; Popescu, P

    1999-03-19

    The present paper describes two cases of an XXY condition in Chianina cattle. Both young bulls were routinely investigated cytogenetically before entering progeny test stations. Every cell examined in the blood cell cultures showed an XXY constitution. The histological study of the gonads, performed on only one bull, showed degradation of the seminiferous tubules. Only Sertoli cells and hyperplastic interstitial cells were observed. PMID:10333067

  4. CONSTITUTION DIAGRAM OF In-Se ALLOYS

    Microsoft Academic Search

    G. K. Slavnova; N. P. Luzhnaya; Z. S. Medvedeva

    1963-01-01

    Thermal and x-ray phase analysis was used in developing an In- Se ; constitution diagram. Chemical compounds InSe, InâSeâ, and Inâ; Se were prepared and analyzed. The melting points were found for InSe, 660 450 ; deg C in a 10 un. Concent 85% ; InâSeâ, 900 450 deg C in a 10 un. ; Concent 85% ; and InâSe,

  5. An indifferent constitutive law in finite elasticity

    Microsoft Academic Search

    Ade Akinola

    2001-01-01

    The concepts of material frame-indifference and material symmetry group with respect to isotropic scalar functions, as represented\\u000a by energy functions, are discussed. An energy function for a structured heterogeneous (transversal isotropic) medium in large\\u000a elastic deformations, which is known to satisfy the Ponyting’s effect [1], is highlighted. It is shown that the constitutive\\u000a relation due to this energy function is

  6. Rapid implementation of advanced constitutive models

    NASA Astrophysics Data System (ADS)

    Starman, Bojan; Halilovi?, Miroslav; Vrh, Marko; Štok, Boris

    2013-12-01

    This paper presents a methodology based on the NICE integration scheme [1, 2] for simple and rapid numerical implementation of a class of plasticity constitutive models. In this regard, an algorithm is purposely developed for the implementation of newly developed advanced constitutive models into explicit finite element framework. The methodology follows the organization of the problem state variables into an extended form, which allows the constitutive models' equations to be organized in such a way, that the algorithm can be optionally extended with minimal effort to integrate also evolution equations related to a description of other specific phenomena, such as damage, distortional hardening, phase transitions, degradation etc. To confirm simplicity of the program implementation, computational robustness, effectiveness and improved accuracy of the implemented integration algorithm, a deep drawing simulation of the cylindrical cup is considered as the case study, performed in ABAQUS/Explicit. As a fairly complex considered model, the YLD2004-18p model [3, 4] is first implemented via external subroutine VUMAT. Further, to give additional proof of the simplicity of the proposed methodology, a combination of the YLD2004-18p model and Gurson-Tvergaard-Needleman model (GTN) is considered. As demonstrated, the implementation is really obtained in a very simple way.

  7. A constitutive theory for rigid polyurethane foam

    SciTech Connect

    Neilsen, M.K. [Sandia National Labs., Albuquerque, NM (United States); Krieg, R.D. [Tennessee Univ., Knoxville, TN (United States). Dept. of Engineering Science and Mechanics; Schreyer, H.L. [New Mexico Univ., Albuquerque, NM (United States). Dept. of Mechanical Engineering

    1992-12-31

    Rigid, closed-cell, polyurethane foam consists of interconnected polyurethane plates which form cells. When this foam is compressed, it exhibits an initial elastic regime which is followed by a plateau regime in which the load required to compress the foam remains nearly constant. In the plateau regime, cell walls are damaged and large permanent volume changes are generated. As additional load is applied, cell walls are compressed against neighboring cell walls, and the stiffness of the foam increases and approaches a value equal to that of solid polyurethane. When the foam is loaded in tension, the cell walls are damaged and the foam fractures. A constitutive theory for rigid polyurethane foam has been developed. This theory is based on a decomposition of the foam into two parts: a skeleton and a nonlinear elastic continuum in parallel. The skeleton accounts for the foam behavior in the elastic and plateau regimes and is described using a coupled plasticity with continuum damage theory. The nonlinear elastic continuum accounts for the lock-up of the foam due to internal gas pressure and cell wall interactions. This new constitutive theory has been implemented in both static and dynamic finite element codes. Numerical simulations performed using the new constitutive theory are presented.

  8. Energetically based phenomenological constitutive model for rubber

    NASA Astrophysics Data System (ADS)

    Popio, James Anthony

    This study is concerned with an energetically based phenomenological constitutive model for rubber under dynamic loading conditions. The dynamic rubber performance is explained using classical thermodynamics and linear viscoelasticity. The model is then applied to raw experimental and classical data. The raw experimental data is provided by the Goodyear Tire and Rubber Company at different temperatures and frequencies using dynamic forced vibration. The data is in the form of hysteresis loops that are shown to represent cycles similar to those in classical thermodynamics. The experimental data is implicitly fitted with the equation of an ellipse. This equation is shown to be a quadratic form containing stress and strain, and is shown to be equal to the rate of energy dissipation. Using principles associated with linear viscoelasticity, the model is shown to incorporate both fluid and solid aspects of material performance. The idea is that, no matter how explicit the constitutive model, it is inherently impossible to tell in advance how much the material behaves like a fluid and how much it behaves like a pure solid. It turns out that this behavior does not need to be quantified with this method; it naturally appears in the coefficients of the constitutive equation, which is a major contribution of this work. In addition, the other significant contribution of this work is a relationship between the coefficients of this model and the loss and storage moduli of the material, which allows the application of this method to classical experimental data.

  9. Constitutive models for impacted morsellised cortico-cancellous bone.

    PubMed

    Phillips, Andrew; Pankaj, Pankaj; May, Fraser; Taylor, Kenneth; Howie, Colin; Usmani, Asif

    2006-03-01

    Constitutive models are developed, based on the results of confined compression testing, to describe the visco-elastic, and non-linear elasto-plastic behaviour of morsellised cortico-cancellous bone (MCB). It is found that the elastic modulus, E of MCB can be expressed as a linear function of the applied pressure, p. E varied from 3 to 30N/mm(2) for pressures up to 1N/mm(2). The visco-elastic behaviour of MCB can be described using a fourth-order Prony series. The plastic behaviour of MCB can be described using a Drucker Prager Cap (DPC) yield criterion, in which consolidation behaviour is described using an exponential function. The developed relationships allow MCB to be included in a realistic manner in finite element models, for example of the acetabular construct, following revision hip arthroplasty, carried out using the Slooff-Ling impaction grafting technique. PMID:16309740

  10. The Cosmic Background Explorer

    NASA Technical Reports Server (NTRS)

    Gulkis, Samuel; Lubin, Philip M.; Meyer, Stephan S.; Silverberg, Robert F.

    1990-01-01

    The Cosmic Background Explorer (CBE), NASA's cosmological satellite which will observe a radiative relic of the big bang, is discussed. The major questions connected to the big bang theory which may be clarified using the CBE are reviewed. The satellite instruments and experiments are described, including the Differential Microwave Radiometer, which measures the difference between microwave radiation emitted from two points on the sky, the Far-Infrared Absolute Spectrophotometer, which compares the spectrum of radiation from the sky at wavelengths from 100 microns to one cm with that from an internal blackbody, and the Diffuse Infrared Background Experiment, which searches for the radiation from the earliest generation of stars.

  11. Cosmic Microwave Background

    NSDL National Science Digital Library

    2012-08-03

    In this lesson, students explore the cosmic microwave background to understand why it permeates the universe and why it peaks as microwave radiation. Students should be able to explain that the origin of the background radiation is the uniform thermal radiation of the big bang and that the radiation produced was evenly distributed around the small early universe, causing it to permeate today's universe. This activity is part of the Cosmic Times teachers guide and is intended to be used in conjunction with the 1965 Cosmic Times Poster.

  12. Matching Background Color

    NSDL National Science Digital Library

    David Ipsen

    2008-04-01

    This chapter introduces an especially important subject in the concealment of animals--countershading. One observes many animals with colors that match the general color of their usual backgrounds. Many leaf-eating insects appear green, for example, making them relatively inconspicuous against their normal background of leaves. The manner of coloration that will provide such a color match is not as obvious as one might imagine. It depends significantly on the nature of the lighting. The inquiry-based activities included in this section effectively illustrate this concept.

  13. The cosmic microwave background

    NASA Technical Reports Server (NTRS)

    Silk, Joseph

    1991-01-01

    Recent limits on spectral distortions and angular anisotropies in the cosmic microwave background are reviewed. The various backgrounds are described, and the theoretical implications are assessed. Constraints on inflationary cosmology dominated by cold dark matter (CDM) and on open cosmological models dominated by baryonic dark matter (BDM), with, respectively, primordial random phase scale-invariant curvature fluctuations or non-gaussian isocurvature fluctuations are described. More exotic theories are addressed, and I conclude with the 'bottom line': what theorists expect experimentalists to be measuring within the next two to three years without having to abandon their most cherished theories.

  14. Guidance for Environmental Background Analysis Volume III: Groundwater

    E-print Network

    the authors may have used some of these vendors and products in the past, mention in this report does not constitute the authors' recommendation for using these vendors or products. #12;iii EXECUTIVE SUMMARY This guidance document provides instructions for characterizing groundwater background conditions and comparing

  15. 2012 Constitutional Review: General Proposals The Students' Union's Constitution and Bye-Laws are reviewed each year by a

    E-print Network

    Oakley, Jeremy

    2012 Constitutional Review: General Proposals The Students' Union's Constitution and Bye-Laws are reviewed each year by a Constitutional Committee. The Committee consisted of Students' Union Officers Membership of the Trustee Board (Constitution and Bye-Law 5) To change the composition of the Trustee Board

  16. Constitution Sample for Student Organizations A Constitution contains the fundamental principles that govern an organization's operation. The development of a

    E-print Network

    Liu, Taosheng

    Constitution Sample for Student Organizations A Constitution contains the fundamental principles that govern an organization's operation. The development of a Constitution will serve to clarify your purpose, student groups wanting to be recognized by the University, must be non-discriminatory. The constitution

  17. CONSTITUTION OF THE UNIVERSITY The constitution of the University has evolved over a period of some five and a half

    E-print Network

    Brierley, Andrew

    CONSTITUTION OF THE UNIVERSITY The constitution of the University has evolved over a period of some also introduced another element into the constitution of the University in the form of (3) Ordinances Andrews Commissioners. The principal remaining element in the Constitution of the University is derived

  18. 1 The Constitution of the Stevens Honor System | Stevens Institute of Technology The Constitution of the Stevens Honor System

    E-print Network

    Yang, Eui-Hyeok

    1 The Constitution of the Stevens Honor System | Stevens Institute of Technology The Constitution, the governing body of the Honor System, are described in the following Constitution and By-laws. Article I. Name their association with the Institute. #12;2 The Constitution of the Stevens Honor System | Stevens Institute

  19. Draft Constitution, School of Informatics Page 1 12/6/2010 Constitution of the School of Informatics

    E-print Network

    Zhou, Yaoqi

    Draft Constitution, School of Informatics Page 1 12/6/2010 Constitution of the School in Bloomington and Indianapolis draws this constitution to provide the framework of governance and executive and consultative powers granted by the Indiana University Constitution and Academic Handbook, subject to law

  20. Constitution (as of Fall 2013) If you have any questions regarding the Constitution, please contact the GBB

    E-print Network

    Constitution (as of Fall 2013) If you have any questions regarding the Constitution, please contact this Constitution as the governing document intended to make clear the purposes, structures, and powers-Recognition Article X: Electing, Appointing and Removing GBB Members Article XI: Amendments to the Constitution

  1. ENHANCING CTR1-10 ETHYLENE RESPONSE2 is a novel allele involved in CONSTITUTIVE TRIPLE-RESPONSE1-mediated ethylene receptor signaling in Arabidopsis

    PubMed Central

    2014-01-01

    Background The signal output of ethylene receptor family members is mediated by unknown mechanisms to activate the Raf-like protein CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) in negatively regulating ethylene signaling. The physical interaction between the ethylene receptor histidine kinase (HK) domain and CTR1 N terminus is essential to the CTR1-mediated receptor signal output. To advance our knowledge of the involvement of CTR1-mediated ethylene receptor signaling, we performed a genetic screen for mutations that enhanced the constitutive ethylene response in the weak ctr1-10 allele. Results We isolated a loss-of-function allele of ENHANCING ctr1-10 ETHYLENE RESPONSE2 (ECR2) and found that ecr2-1 ctr1-10 and the strong allele ctr1-1 conferred a similar, typical constitutive ethylene response phenotype. Genetic analyses and transformation studies suggested that ECR2 acts downstream of the ethylene receptors and upstream of the transcription factors ETHYLENE INSENSITIVE3 (EIN3) and EIN3-LIKE1 (EIL1), which direct the expression of ethylene response genes. Signal output by the N terminus of the ethylene receptor ETHYLENE RESPONSE1 (ETR1) can be mediated by a pathway independent of CTR1. Expression of the N terminus of the ethylene-insensitive etr1-1 but not the full-length isoform rescued the ecr2-1 ctr1-10 phenotype, which indicates the involvement of ECR2 in CTR1-mediated but not -independent, ethylene receptor signaling. ECR2 was mapped to the centromere region on chromosome 2. With incomplete sequence and annotation information and rare chromosome recombination events in this region, the cloning of ECR2 is challenging and still in progress. Conclusions ECR2 is a novel allele involved in the ethylene receptor signaling that is mediated by CTR1. CTR1 activation by ethylene receptors may require ECR2 for suppressing the ethylene response. PMID:24529183

  2. David Smith Academic background

    E-print Network

    David Smith Academic background Ph.D. in Mathematics (Algebra), Université de Sherbrooke, Canada project program (I. Assem, F. Bergeron, C. Reutenauer, D. Smith) $132,000 ($44,000 per year for 3 years. Schiffler and D. Smith, Friezes, strings and cluster variables, to appear in Glasgow Mathematcal Journal. 2

  3. PANDEMIC INFLUENZA background briefing

    E-print Network

    Rambaut, Andrew

    PANDEMIC INFLUENZA background briefing Biomedicine Forum 5 November 2008 compiled by David Evans, Dave Carr, David Lynn and Phil Green Transmission electron micrograph of Influenza A virus (Wellcome influenza!' Page 2 #12;Consequences of an influenza pandemic THE PANDEMIC THREAT DEATH If the next pandemic

  4. Country background Forest history

    E-print Network

    Paris-Sud XI, Université de

    season prone to forest fires. Atlantic climate is wet with temperatures moderated by the ocean33 Country background Forest history During the Gallo-Roman period (1st­4th century AD), forests this proportion decreased dramatically to only 15­17 % of the land area. This residual forest was then severely

  5. Cosmic microwave background radiation

    Microsoft Academic Search

    Lyman Page; David Wilkinson

    1999-01-01

    The cosmic microwave background radiation (CMBR) is widely interpreted as the thermal afterglow of a hot big bang. Measurements of the CMBR intensity as a function of frequency constrain the history of cosmic energetics. Measurements of the anisotropy in the CMBR temperature provide a snapshot of the distribution of fluctuations in the gravitational potential at the earliest stages of cosmic

  6. Shark Species Profiles Background

    E-print Network

    Watson, Craig A.

    skeletons that are made of bone. Although all sharks have some similarities such as having gills and fins there are small spots long the sides of the shark and a black blotch near the pectoral fin Diet: Marine mammalsShark Species Profiles Background: Sharks have existed for about 400 million years, before

  7. A constitutive law for dense granular flows

    E-print Network

    Pierre Jop; Yoël Forterre; Olivier Pouliquen

    2006-12-05

    A continuum description of granular flows would be of considerable help in predicting natural geophysical hazards or in designing industrial processes. However, the constitutive equations for dry granular flows, which govern how the material moves under shear, are still a matter of debate. One difficulty is that grains can behave like a solid (in a sand pile), a liquid (when poured from a silo) or a gas (when strongly agitated). For the two extreme regimes, constitutive equations have been proposed based on kinetic theory for collisional rapid flows, and soil mechanics for slow plastic flows. However, the intermediate dense regime, where the granular material flows like a liquid, still lacks a unified view and has motivated many studies over the past decade. The main characteristics of granular liquids are: a yield criterion (a critical shear stress below which flow is not possible) and a complex dependence on shear rate when flowing. In this sense, granular matter shares similarities with classical visco-plastic fluids such as Bingham fluids. Here we propose a new constitutive relation for dense granular flows, inspired by this analogy and recent numerical and experimental work. We then test our three-dimensional (3D) model through experiments on granular flows on a pile between rough sidewalls, in which a complex 3D flow pattern develops. We show that, without any fitting parameter, the model gives quantitative predictions for the flow shape and velocity profiles. Our results support the idea that a simple visco-plastic approach can quantitatively capture granular flow properties, and could serve as a basic tool for modelling more complex flows in geophysical or industrial applications.

  8. Transcriptomic analysis of grain amaranth ( Amaranthus hypochondriacus ) using 454 pyrosequencing: comparison with A. tuberculatus , expression profiling in stems and in response to biotic and abiotic stress

    Microsoft Academic Search

    John P Délano-Frier; Hamlet Avilés-Arnaut; Kena Casarrubias-Castillo; Gabriela Casique-Arroyo; Paula A Castrillón-Arbeláez; Luis Herrera-Estrella; Julio Massange-Sánchez; Norma A Martínez-Gallardo; Fannie I Parra-Cota; Erandi Vargas-Ortiz; María G Estrada-Hernández

    2011-01-01

    Background  \\u000a Amaranthus hypochondriacus, a grain amaranth, is a C4 plant noted by its ability to tolerate stressful conditions and produce highly nutritious seeds.\\u000a These possess an optimal amino acid balance and constitute a rich source of health-promoting peptides. Although several recent\\u000a studies, mostly involving subtractive hybridization strategies, have contributed to increase the relatively low number of\\u000a grain amaranth expressed sequence

  9. NDE of historic structures: USS Constitution

    NASA Astrophysics Data System (ADS)

    Ross, Robert J.; McDonald, Kent A.; Soltis, Lawrence A.; Otton, Patrick

    1996-11-01

    The USS Constitution is the oldest flowing commissioned ship in the US Navy. Recently, the USDA Forest Service, Forest Products Laboratory, was involved in developing an inspection methodology for the use of Navy personnel responsible for maintaining the ship. Several NDE techniques were used to assess the condition of fasteners in the ship and the general condition of the wood comprising it. Radiography and ultrasonic techniques were used to assess the condition of the copper pins used as fasteners. Stress wave NDE techniques were used to locate areas of degradation in the wood. This paper describes the stress wave techniques employed and results obtained form their use.

  10. Constitutive modeling of glassy shape memory polymers

    NASA Astrophysics Data System (ADS)

    Khanolkar, Mahesh

    The aim of this research is to develop constitutive models for non-linear materials. Here, issues related for developing constitutive model for glassy shape memory polymers are addressed in detail. Shape memory polymers are novel material that can be easily formed into complex shapes, retaining memory of their original shape even after undergoing large deformations. The temporary shape is stable and return to the original shape is triggered by a suitable mechanism such heating the polymer above a transition temperature. Glassy shape memory polymers are called glassy because the temporary shape is fixed by the formation of a glassy solid, while return to the original shape is due to the melting of this glassy phase. The constitutive model has been developed to capture the thermo-mechanical behavior of glassy shape memory polymers using elements of nonlinear mechanics and polymer physics. The key feature of this framework is that a body can exist stress free in numerous natural configurations, the underlying natural configuration of the body changing during the process, with the response of the body being elastic from these evolving natural configurations. The aim of this research is to formulate a constitutive model for glassy shape memory polymers (GSMP) which takes in to account the fact that the stress-strain response depends on thermal expansion of polymers. The model developed is for the original amorphous phase, the temporary glassy phase and transition between these phases. The glass transition process has been modeled using a framework that was developed recently for studying crystallization in polymers and is based on the theory of multiple natural configurations. Using the same frame work, the melting of the glassy phase to capture the return of the polymer to its original shape is also modeled. The effect of nanoreinforcement on the response of shape memory polymers (GSMP) is studied and a model is developed. In addition to modeling and solving boundary value problems for GSMP's, problems of importance for CSMP, specifically a shape memory cycle (Torsion of a Cylinder) is solved using the developed crystallizable shape memory polymer model. To solve complex boundary value problems in realistic geometries a user material subroutine (UMAT) for GSMP model has been developed for use in conjunction with the commercial finite element software ABAQUS. The accuracy of the UMAT has been verified by testing it against problems for which the results are known.

  11. Numerically abnormal chromosome constitutions in humans

    SciTech Connect

    NONE

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  12. Native American Constitution and Law Digitization Project

    NSDL National Science Digital Library

    A cooperative effort from the University of Oklahoma Law Center, the National Indian Law Library (NILL), and Native American tribes, this site offers access to the full texts of selected legal documents. Among these are Constitutions, Tribal Codes, Charters, Indian Land Titles, and summaries of recent US Supreme Court cases that have involved or affected Native Americans. At present, the Project provides only about 30 documents total, but scholars and users with an interest in Native American legal issues will want to monitor the site.

  13. The cosmic microwave background

    NASA Technical Reports Server (NTRS)

    Silk, Joseph

    1989-01-01

    Recent observational and theoretical investigations of the cosmic microwave background radiation (CMBR) are reviewed. Particular attention is given to spectral distortions and CMBR temperature anisotropies at large, intermediate, and small angular scales. The implications of the observations for inflationary cosmological models with curvature fluctuation are explored, and it is shown that the limits determined for intermediate-scale CMBR anisotropy almost rule out a baryon-dominated cosmology.

  14. Quantum backgrounds and QFT

    E-print Network

    Jae-Suk Park; John Terilla; Thomas Tradler

    2009-09-21

    We introduce the concept of a quantum background and a functor QFT. In the case that the QFT moduli space is smooth formal, we construct a flat quantum superconnection on a bundle over QFT which defines algebraic structures relevant to correlation functions in quantum field theory. We go further and identify chain level generalizations of correlation functions which should be present in all quantum field theories.

  15. Cosmic Microwave Background Theory

    Microsoft Academic Search

    J. Richard Bond

    1998-01-01

    A long-standing goal of theorists has been to constrain cosmological parameters that define the structure formation theory from cosmic microwave background (CMB) anisotropy experiments and large-scale structure (LSS) observations. The status and future promise of this enterprise is described. Current band-powers in ell -space are consistent with a Delta T flat in frequency and broadly follow inflation-based expectations. That the

  16. Calprotectin Expression Inhibits Bacterial Binding to Mucosal Epithelial Cells

    Microsoft Academic Search

    KANOKWAN NISAPAKULTORN; KAREN F. ROSS; MARK C. HERZBERG

    2001-01-01

    Squamous mucosal epithelial cells constitutively express calprotectin in the cytoplasm. To study how this antimicrobial protein complex confers epithelial resistance to invading bacteria, an epithelial cell line was stably transfected to express the calprotectin complex. Cells expressing calprotectin resist invasion by Listeria monocytogenes and Salmonella enterica serovar Typhimurium. Calprotectin expression was accompanied by altered actin organization, increased a3 integrin expression,

  17. Constitutive Activity in an Ancestral Form of Abl Tyrosine Kinase

    PubMed Central

    Miller, W. Todd

    2015-01-01

    The c-abl proto-oncogene encodes a nonreceptor tyrosine kinase that is found in all metazoans, and is ubiquitously expressed in mammalian tissues. The Abl tyrosine kinase plays important roles in the regulation of mammalian cell physiology. Abl-like kinases have been identified in the genomes of unicellular choanoflagellates, the closest relatives to the Metazoa, and in related unicellular organisms. Here, we have carried out the first characterization of a premetazoan Abl kinase, MbAbl2, from the choanoflagellate Monosiga brevicollis. The enzyme possesses SH3, SH2, and kinase domains in a similar arrangement to its mammalian counterparts, and is an active tyrosine kinase. MbAbl2 lacks the N-terminal myristoylation and cap sequences that are critical regulators of mammalian Abl kinase activity, and we show that MbAbl2 is constitutively active. When expressed in mammalian cells, MbAbl2 strongly phosphorylates cellular proteins on tyrosine, and transforms cells much more potently than mammalian Abl kinase. Thus, MbAbl2 appears to lack the autoinhibitory mechanism that tightly constrains the activity of mammalian Abl kinases, suggesting that this regulatory apparatus arose more recently in metazoan evolution. PMID:26090675

  18. Structures of human constitutive nitric oxide synthases.

    PubMed

    Li, Huiying; Jamal, Joumana; Plaza, Carla; Pineda, Stephanie Hai; Chreifi, Georges; Jing, Qing; Cinelli, Maris A; Silverman, Richard B; Poulos, Thomas L

    2014-10-01

    Mammals produce three isoforms of nitric oxide synthase (NOS): neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The overproduction of NO by nNOS is associated with a number of neurodegenerative disorders; therefore, a desirable therapeutic goal is the design of drugs that target nNOS but not the other isoforms. Crystallography, coupled with computational approaches and medicinal chemistry, has played a critical role in developing highly selective nNOS inhibitors that exhibit exceptional neuroprotective properties. For historic reasons, crystallography has focused on rat nNOS and bovine eNOS because these were available in high quality; thus, their structures have been used in structure-activity-relationship studies. Although these constitutive NOSs share more than 90% sequence identity across mammalian species for each NOS isoform, inhibitor-binding studies revealed that subtle differences near the heme active site in the same NOS isoform across species still impact enzyme-inhibitor interactions. Therefore, structures of the human constitutive NOSs are indispensible. Here, the first structure of human neuronal NOS at 2.03?Ĺ resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73?Ĺ resolution. PMID:25286850

  19. Constitutive modeling for isotropic materials (HOST)

    NASA Technical Reports Server (NTRS)

    Lindholm, U. S.; Chan, K. S.; Bodner, S. R.; Weber, R. M.; Walker, K. P.; Cassenti, B. N.

    1985-01-01

    This report presents the results of the second year of work on a problem which is part of the NASA HOST Program. Its goals are: (1) to develop and validate unified constitutive models for isotropic materials, and (2) to demonstrate their usefulness for structural analyses of hot section components of gas turbine engines. The unified models selected for development and evaluation are that of Bodner-Partom and Walker. For model evaluation purposes, a large constitutive data base is generated for a B1900 + Hf alloy by performing uniaxial tensile, creep, cyclic, stress relation, and thermomechanical fatigue (TMF) tests as well as biaxial (tension/torsion) tests under proportional and nonproportional loading over a wide range of strain rates and temperatures. Systematic approaches for evaluating material constants from a small subset of the data base are developed. Correlations of the uniaxial and biaxial tests data with the theories of Bodner-Partom and Walker are performed to establish the accuracy, range of applicability, and integability of the models. Both models are implemented in the MARC finite element computer code and used for TMF analyses. Benchmark notch round experiments are conducted and the results compared with finite-element analyses using the MARC code and the Walker model.

  20. Critical Role of Interferon-? Constitutively Produced in Human Hepatocytes in Response to RNA Virus Infection

    PubMed Central

    Tsugawa, Yoji; Kato, Hiroki; Fujita, Takashi; Shimotohno, Kunitada; Hijikata, Makoto

    2014-01-01

    Several viruses are known to infect human liver and cause the hepatitis, but the interferon (IFN) response, a first-line defense against viral infection, of virus-infected hepatocytes is not clearly defined yet. We investigated innate immune system against RNA viral infection in immortalized human hepatocytes (HuS-E/2 cells), as the cells showed similar early innate immune responses to primary human hepatocytes (PHH). The low-level constitutive expression of IFN-?1 gene, but not IFN-? and IFN-?, was observed in both PHH and HuS-E/2 cells in the absence of viral infection, suggesting a particular subtype(s) of IFN-? is constitutively produced in human hepatocytes. To examine the functional role of such IFN-? in the antiviral response, the expression profiles of innate immune-related genes were studied in the cells with the treatment of neutralization against type I IFN receptor 2 (IFNAR2) or IFN-? itself to inhibit the constitutive IFN-? signaling before and after virus infection. As the results, a clear reduction of basal level expression of IFN-inducible genes was observed in uninfected cells. When the effect of the inhibition on the cells infected with hepatitis C virus (HCV) was examined, the significant decrease of IFN stimulated gene expression and the enhancement of initial HCV replication were observed, suggesting that the steady-state production of IFN-? plays a role in amplification of antiviral responses to control the spread of RNA viral infection in human hepatocytes. PMID:24587086

  1. A Comparative Analysis of Constitutive Promoters Located in Adeno-Associated Viral Vectors

    PubMed Central

    Ota, Akinobu; Hossain, Ekhtear; Konishi, Yuko; Hosokawa, Yoshitaka; Konishi, Hiroyuki

    2014-01-01

    The properties of constitutive promoters within adeno-associated viral (AAV) vectors have not yet been fully characterized. In this study, AAV vectors, in which enhanced GFP expression was directed by one of the six constitutive promoters (human ?-actin, human elongation factor-1?, chicken ?-actin combined with cytomegalovirus early enhancer, cytomegalovirus (CMV), simian virus 40, and herpes simplex virus thymidine kinase), were constructed and introduced into the HCT116, DLD-1, HT-1080, and MCF-10A cell lines. Quantification of GFP signals in infected cells demonstrated that the CMV promoter produced the highest GFP expression in the six promoters and maintained relatively high GFP expression for up to eight weeks after infection of HCT116, DLD-1, and HT-1080. Exogenous human CDKN2A gene expression was also introduced into DLD-1 and MCF-10A in a similar pattern by using AAV vectors bearing the human ?-actin and the CMV promoters. The six constitutive promoters were subsequently placed upstream of the neomycin resistance gene within AAV vectors, and HCT116, DLD-1, and HT-1080 were infected with the resulting vectors. Of the six promoters, the CMV promoter produced the largest number of G418-resistant colonies in all three cell lines. Because AAV vectors have been frequently used as a platform to construct targeting vectors that permit gene editing in human cell lines, we lastly infected the three cell lines with AAV-based targeting vectors against the human PIGA gene in which one of the six promoters regulate the neomycin resistance gene. This assay revealed that the CMV promoter led to the lowest PIGA gene targeting efficiency in the investigated promoters. These results provide a clue to the identification of constitutive promoters suitable to express exogenous genes with AAV vectors, as well as those helpful to conduct efficient gene targeting using AAV-based targeting vectors in human cell lines. PMID:25170953

  2. On the treatment of non-solvable implicit constitutive relations in solid mechanics

    NASA Astrophysics Data System (ADS)

    Sfyris, D.; Bustamante, R.

    2015-06-01

    We report results concerning the treatment of elastic bodies described by implicit constitutive relations which are not solvable, in the sense of expressing the stresses as functions of the strains or vice versa. Motivated by the theory of generalized hyperelastic materials, which applies also to polyatomic crystals, the field equations to be solved for a body described by a non-solvable implicit constitutive relation in the above sense are lied down. In addition to the momentum equation, auxiliary variables come into play. These variables are accompanied by an equation governing them. We specialize to the case of an isotropic constitutive relation and give some conditions in order for a broad subclass of an isotropic body to be a generalized material. Then, we lay down the field equations for such a body.

  3. Enhancing activity of N-glycosylation for constitutive proteins secretions in non-polarized cells

    SciTech Connect

    Akiyama, Nobutake, E-mail: nakiyama@jikei.ac.jp [Department of Molecular Immunology, Institute of DNA medicine, Jikei University, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan)] [Department of Molecular Immunology, Institute of DNA medicine, Jikei University, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan); Ohno, Yuji [Department of Pharmacology, Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan)] [Department of Pharmacology, Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan); Fukuda, Takahiro [Division of Neuropathology, Dept. of Neuroscience, Research Center of Medical Science, The Jikei Univ. Schl. Med., 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461 (Japan)] [Division of Neuropathology, Dept. of Neuroscience, Research Center of Medical Science, The Jikei Univ. Schl. Med., 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461 (Japan); Manome, Yosinobu [Department of Molecular Cell Biology, Institute of DNA medicine, Jikei University, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan)] [Department of Molecular Cell Biology, Institute of DNA medicine, Jikei University, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan); Saito, Saburo [Department of Molecular Immunology, Institute of DNA medicine, Jikei University, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan)] [Department of Molecular Immunology, Institute of DNA medicine, Jikei University, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan)

    2009-04-17

    Several fusion proteins of mouse Interleukins (mILs) and the enhanced green fluorescent protein (EGFP) were expressed in fibroblast and epithelial cells. Among these proteins, the mIL-31 derivative was the most efficiently secreted into the medium in a N-glycosylation-dependent manner. From the analysis of deletion mutants, the minimal structure for constitutive secretions consisted of a signal peptide and N-glycosylation. Introduction of the signal sequence from mIL-31 to human p53 protein failed to secrete the products, but further addition of the N-glycosylation site resulted in constitutive secretion of biologically active p53 protein into the medium in the N-glycosylated form. In this report, we showed the importance of N-glycosylation for constitutive protein secretions, especially using non-polarized cells.

  4. A continuum constitutive model for amorphous metallic materials

    E-print Network

    Su, Cheng, Ph. D. Massachusetts Institute of Technology

    2007-01-01

    A finite-deformation, Coulomb-Mohr type constitutive theory for the elastic-viscoplastic response of pressure-sensitive and plastically-dilatant isotropic materials has been developed. The constitutive model has been ...

  5. Close view of the Constitution Avenue elevation to show arched ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Close view of the Constitution Avenue elevation to show arched gateways and pedimented pavilion ("Commerce and Communication" sculpted pediment) - Interstate Commerce Commission, Constitution Avenue between Twelfth and Fourteenth streets, Washington, District of Columbia, DC

  6. Constitution of the Stevenson Student Council Ratified Article 1: Powers

    E-print Network

    California at Santa Cruz, University of

    Constitution of the Stevenson Student Council Ratified May 26th , 2009 Article 1: Powers Section 1, and the content of this constitution. Section 2: The Stevenson Student Council shall be responsible for answering

  7. Democracy in America: Labour Mobility, Ideology , and Constitutional Reform

    E-print Network

    Congleton, Roger D

    Constitutional democracy in the United States emerged very gradually through a long series of constitutional bargains in the course of three centuries. No revolutions or revolutionary threats were necessary or evident during most of the three...

  8. Beyond the future: Fortune telling as constituted in the media 

    E-print Network

    Lyon, Taryn

    This paper utilizes discourse analysis (DA) to research how fortune telling is constituted in the news media. As current paranormal belief research is largely inconclusive (Wiseman & Watt, 2006), this paper addresses the problem of constitution...

  9. The Environmental Estrogen, Nonylphenol, Activates the Constitutive Androstane Receptor

    PubMed Central

    Hernandez, Juan P.; Huang, Wendong; Chapman, Laura M.; Chua, Steven; Moore, David D.; Baldwin, William S.

    2007-01-01

    Nonylphenol (NP) and its parent compounds, the nonylphenol ethoxylates are some of the most prevalent chemicals found in U.S. waterways. NP is also resistant to biodegradation and is a known environmental estrogen, which makes NP a chemical of concern. Our data show that NP also activates the constitutive androstane receptor (CAR), an orphan nuclear receptor important in the induction of detoxification enzymes, including the P450s. Transactivation assays demonstrate that NP increases murine CAR (mCAR) transcriptional activity, and NP treatment can overcome the inhibitory effects of the inverse agonist, androstanol, on mCAR activation. Treatment of wild-type (CAR +/+) mice with NP at 50 or 75 mg/kg/day increases Cyp2b protein expression in a dose-dependent manner as demonstrated by Western blotting, and was confirmed by quantitative reverse transcription–PCR of Cyp2b10 transcript levels. CAR-null (CAR ?/?) mice show no increased expression of Cyp2b following NP treatment, indicating that CAR is required for NP-mediated Cyp2b induction. In addition, NP increases the translocation of CAR into the nucleus, which is the key step in the commencement of CAR's transcriptional activity. NP also induced CYP2B6 in primary human hepatocytes, and increased Cyp2b10 messenger RNA and protein expression in humanized CAR mice, indicating that NP is an activator of human CAR as well. In conclusion, NP is a CAR activator, and this was demonstrated in vitro with transactivation assays and in vivo with transgenic CAR mouse models. PMID:17483497

  10. Constitutive Models for Shape Memory Alloy Polycrystals

    NASA Technical Reports Server (NTRS)

    Comstock, R. J., Jr.; Somerday, M.; Wert, J. A.

    1996-01-01

    Shape memory alloys (SMA) exhibiting the superelastic or one-way effects can produce large recoverable strains upon application of a stress. In single crystals this stress and resulting strain are very orientation dependent. We show experimental stress/strain curves for a Ni-Al single crystal for various loading orientations. Also shown are model predictions; the open and closed circles indicate recoverable strains obtained at various stages in the transformation process. Because of the strong orientation dependence of shape memory properties, crystallographic texture can be expected to play an important role in the mechanical behavior of polycrystalline SMA. It is desirable to formulate a constitutive model to better understand and exploit the unique properties of SMA.

  11. Frame-invariance of turbulence constitutive relations

    NASA Astrophysics Data System (ADS)

    Thomas, T. G.; Takhar, H. S.

    1988-02-01

    The applicability of the principle of material frame-indifference to turbulence and its consequences for turbulence modeling are considered. By introducing a distinction between arbitrary time-dependent orthogonal transformations of (1) the fluid motion, and (2) the observer, we find that frame-invariant tensorial measures of the absolute angular velocity and acceleration can be defined. This follows from consideration of a four-dimensional formulation of classical mechanics which formally possesses the property of invariance under arbitrary changes of frame of the observer. These tensors allow the construction of constitutive equations which depend, for example, on the absolute angular velocity of the fluid, and which also satisfy the principle of material frame-indifference. The results of this analysis have application outside the field of turbulence modeling. The invariance properties of some previously published Reynolds stress transport turbulence models are examined and modifications are suggested.

  12. The Backgrounds Data Center

    NASA Technical Reports Server (NTRS)

    Snyder, W. A.; Gursky, H.; Heckathorn, H. M.; Lucke, R. L.; Berg, S. L.; Dombrowski, E. G.; Kessel, R. A.

    1993-01-01

    The Strategic Defense Initiative Organization has created data centers for midcourse, plumes, and backgrounds phenomenologies. The Backgrounds Data Center (BDC) has been designated as the prime archive for data collected by SDIO programs. The BDC maintains a Summary Catalog that contains 'metadata,' that is, information about data, such as when the data were obtained, what the spectral range of the data is, and what region of the Earth or sky was observed. Queries to this catalog result in a listing of all data sets (from all experiments in the Summary Catalog) that satisfy the specified criteria. Thus, the user can identify different experiments that made similar observations and order them from the BDC for analysis. On-site users can use the Science Analysis Facility (SAFE for this purpose. For some programs, the BDC maintains a Program Catalog, which can classify data in as many ways as desired (rather than just by position, time, and spectral range as in the Summary Catalog). For example, data sets could be tagged with such diverse parameters as solar illumination angle, signal level, or the value of a particular spectral ratio, as long as these quantities can be read from the digital record or calculated from it by the ingest program. All unclassified catalogs and unclassified data will be remotely accessible.

  13. Pinning down the Constitution: Interactively Teaching Congress's Power, Federalism, and Constitutional Interpretation

    ERIC Educational Resources Information Center

    Emenaker, Ryan

    2014-01-01

    "Pin-the-Tail-on-the-Constitution" is an engaged-learning activity that has been conducted in 26 classes over the past four years. The activity teaches multiple themes commonly included in a variety of courses on American politics such as federalism, congressional powers, the role of the federal courts, and the relevance of the commerce…

  14. Constitutional Provisions on the Press: A World View.

    ERIC Educational Resources Information Center

    Paraschos, Manny

    A study examined the legal treatment of the press in constitutions or other basic legal institutional documents from around the world. Sixty-three constitutions or basic documents from the Western World, the Communist Bloc, the Middle East, Africa, Southeast Asia, and Latin America were analyzed. Analysis revealed that most constitutions open with…

  15. Constitutional Commitment to Social Security and Welfare Policy

    Microsoft Academic Search

    Avi Ben-Bassat; Momi Dahan

    2006-01-01

    In this paper we explore whether the constitutional text has any practical meaning for welfare policy. To examine the empirical importance of the constitution, we first constructed for 68 countries an index of constitutional commitment to social security in five areas: Old Age, disability and survivors (OASDI), Unemployment, Sickness, Work Injury and Income Support. We find that the extent and

  16. A multi-dimensional constitutive model for shape memory alloys

    Microsoft Academic Search

    C. Liang; C. A. Rogers

    1992-01-01

    This paper presents a multi-dimensional thermomechanical constitutive model for shape memory alloys (SMAs). This constitutive relation is based upon a combination of both micromechanics and macromechanics. The martensite fraction is introduced as a variable in this model to reflect the martensitic transformation that determines the unique characteristics of shape memory alloys. This constitutive relation can be used to study the

  17. A constitutive model of cold drawing in polycarbonates

    E-print Network

    Masud, Arif

    A constitutive model of cold drawing in polycarbonates Arif Masud*, Alexander Chudnovsky Department-7023, USA Received in ®nal revised form 3 May 1999 Abstract This paper presents a set of constitutive preserving and spherical parts. Numerical constitutive integration algorithm is based on an operator

  18. CONSTITUTION OF THE ASSOCIATION OF BIOLOGISTS (Revised Fall 2010)

    E-print Network

    Rock, Chris

    1 CONSTITUTION OF THE ASSOCIATION OF BIOLOGISTS (Revised Fall 2010) ARTICLE I. NAME, PURPOSE actions against Members not considered in the Constitution shall be addressed by the Executive Council include a President, Vice President, Treasurer, and Secretary. These Elected Officers shall constitute

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