Science.gov

Sample records for additive gene action

  1. Heritability of heterozygosity offers a new way of understanding why dominant gene action contributes to additive genetic variance.

    PubMed

    Nietlisbach, Pirmin; Hadfield, Jarrod D

    2015-07-01

    Whenever allele frequencies are unequal, nonadditive gene action contributes to additive genetic variance and therefore the resemblance between parents and offspring. The reason for this has not been easy to understand. Here, we present a new single-locus decomposition of additive genetic variance that may give greater intuition about this important result. We show that the contribution of dominant gene action to parent-offspring resemblance only depends on the degree to which the heterozygosity of parents and offspring covary. Thus, dominant gene action only contributes to additive genetic variance when heterozygosity is heritable. Under most circumstances this is the case because individuals with rare alleles are more likely to be heterozygous, and because they pass rare alleles to their offspring they also tend to have heterozygous offspring. When segregating alleles are at equal frequency there are no rare alleles, the heterozygosities of parents and offspring are uncorrelated and dominant gene action does not contribute to additive genetic variance. PMID:26100570

  2. Transcriptional Regulation of Zein Gene Expression in Maize through the Additive and Synergistic Action of opaque2, Prolamine-Box Binding Factor, and O2 Heterodimerizing Proteins

    PubMed Central

    Zhang, Zhiyong; Yang, Jun; Wu, Yongrui

    2015-01-01

    Maize (Zea mays) zeins are some of the most abundant cereal seed storage proteins (SSPs). Their abundance influences kernel hardness but compromises its nutritional quality. Transcription factors regulating the expression of zein and other SSP genes in cereals are endosperm-specific and homologs of maize opaque2 (O2) and prolamine-box binding factor (PBF). This study demonstrates that the ubiquitously expressed transcription factors, O2 heterodimerizing proteins (OHPs), specifically regulate 27-kD γ-zein gene expression (through binding to an O2-like box in its promoter) and interact with PBF. The zein content of double mutants OhpRNAi;o2 and PbfRNAi;o2 and the triple mutant PbfRNAi;OhpRNAi;o2 is reduced by 83, 89, and 90%, respectively, compared with the wild type. The triple mutant developed the smallest zein protein bodies, which were merely one-tenth the wild type’s size. Total protein levels in these mutants were maintained in a relatively constant range through proteome rebalancing. These data show that OHPs, O2, and PBF are master regulators of zein storage protein synthesis, acting in an additive and synergistic mode. The differential expression patterns of OHP and O2 genes may cause the slight differences in the timing of 27-kD γ-zein and 22-kD α-zein accumulation during protein body formation. PMID:25901087

  3. 5 CFR 179.218 - Additional administrative collection action.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Additional administrative collection action. 179.218 Section 179.218 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CLAIMS COLLECTION STANDARDS Salary Offset § 179.218 Additional administrative collection...

  4. Additive Routes to Action Learning: Layering Experience Shapes Engagement of the Action Observation Network

    PubMed Central

    Kirsch, Louise P.; Cross, Emily S.

    2015-01-01

    The way in which we perceive others in action is biased by one's prior experience with an observed action. For example, we can have auditory, visual, or motor experience with actions we observe others perform. How action experience via 1, 2, or all 3 of these modalities shapes action perception remains unclear. Here, we combine pre- and post-training functional magnetic resonance imaging measures with a dance training manipulation to address how building experience (from auditory to audiovisual to audiovisual plus motor) with a complex action shapes subsequent action perception. Results indicate that layering experience across these 3 modalities activates a number of sensorimotor cortical regions associated with the action observation network (AON) in such a way that the more modalities through which one experiences an action, the greater the response is within these AON regions during action perception. Moreover, a correlation between left premotor activity and participants' scores for reproducing an action suggests that the better an observer can perform an observed action, the stronger the neural response is. The findings suggest that the number of modalities through which an observer experiences an action impacts AON activity additively, and that premotor cortical activity might serve as an index of embodiment during action observation. PMID:26209850

  5. 7 CFR 1403.12 - Additional administrative collection action.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Additional administrative collection action. 1403.12 Section 1403.12 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS AND POLICIES DEBT SETTLEMENT POLICIES...

  6. 12 CFR 1238.8 - Additional implementing action.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 10 2014-01-01 2014-01-01 false Additional implementing action. 1238.8 Section 1238.8 Banks and Banking FEDERAL HOUSING FINANCE AGENCY ENTITY REGULATIONS STRESS TESTING OF REGULATED..., require any regulated entity not subject to this part to conduct stress testing hereunder; and from...

  7. Genetic prerequisites for additive or synergistic actions of 5-fluorocytosine and fluconazole in baker's yeast.

    PubMed

    Paluszynski, John P; Klassen, Roland; Meinhardt, Friedhelm

    2008-10-01

    During applications of 5-fluorocytosine (5FC) and fluconazole (FLC), additive or synergistic action may even occur when primary resistance to 5FC is established. Here, we analysed conjoint drug action in Saccharomyces cerevisiae strains deficient in genes known to be essential for 5FC or FLC function. Despite clear primary resistance, residual 5FC activity and additive 5FC+FLC action in cells lacking cytosine permease (Fcy2p) or uracil phosphoribosyl transferase (Fur1p) were detected. In contrast, Deltafcy1 mutants, lacking cytosine deaminase, became entirely resistant to 5FC, concomitantly losing 5FC+FLC additivity. Disruption of the orotate phosphoribosyltransferase gene (URA5) in the wild-type led to low-level 5FC tolerance, while an alternative orotate phosphoribosyltransferase, encoded by URA10, contributed to 5FC toxicity only in the Deltaura5 background. Remarkably, combination of Deltaura5 and Deltafur1 resulted in complete 5FC resistance. Thus, yeast orotate phosphoribosyltransferases are involved in 5FC metabolism. Similarly, disruption of the ergosterol Delta(5,6)-desaturase-encoding gene ERG3 resulted only in partial resistance to FLC, and concomitantly a synergistic effect with 5FC became evident. Full resistance to FLC occurred in Deltaerg3 Deltaerg11 double mutants and, simultaneously, synergism or even an additive effect with FLC and 5FC was no longer discernible. Since the majority of spontaneously occurring resistant yeast clones displayed residual sensitivity to either 5FC or FLC and those strains responded to combined drug treatment in a predictable manner, careful resistance profiling based on the findings reported here may help to address yeast infections by combined application of antimycotic compounds.

  8. 41 CFR 60-2.17 - Additional required elements of affirmative action programs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... elements of affirmative action programs. 60-2.17 Section 60-2.17 Public Contracts and Property Management... Action Programs § 60-2.17 Additional required elements of affirmative action programs. In addition to the elements required by § 60-2.10 through § 60-2.16, an acceptable affirmative action program must include...

  9. 41 CFR 60-2.17 - Additional required elements of affirmative action programs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... elements of affirmative action programs. 60-2.17 Section 60-2.17 Public Contracts and Property Management... Action Programs § 60-2.17 Additional required elements of affirmative action programs. In addition to the elements required by § 60-2.10 through § 60-2.16, an acceptable affirmative action program must include...

  10. 41 CFR 60-2.17 - Additional required elements of affirmative action programs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... elements of affirmative action programs. 60-2.17 Section 60-2.17 Public Contracts and Property Management... Action Programs § 60-2.17 Additional required elements of affirmative action programs. In addition to the elements required by § 60-2.10 through § 60-2.16, an acceptable affirmative action program must include...

  11. Molecular mechanisms of curcumin action: gene expression.

    PubMed

    Shishodia, Shishir

    2013-01-01

    Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin.

  12. Molecular mechanisms of curcumin action: gene expression.

    PubMed

    Shishodia, Shishir

    2013-01-01

    Curcumin derived from the tropical plant Curcuma longa has a long history of use as a dietary agent, food preservative, and in traditional Asian medicine. It has been used for centuries to treat biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. The preventive and therapeutic properties of curcumin are associated with its antioxidant, anti-inflammatory, and anticancer properties. Extensive research over several decades has attempted to identify the molecular mechanisms of curcumin action. Curcumin modulates numerous molecular targets by altering their gene expression, signaling pathways, or through direct interaction. Curcumin regulates the expression of inflammatory cytokines (e.g., TNF, IL-1), growth factors (e.g., VEGF, EGF, FGF), growth factor receptors (e.g., EGFR, HER-2, AR), enzymes (e.g., COX-2, LOX, MMP9, MAPK, mTOR, Akt), adhesion molecules (e.g., ELAM-1, ICAM-1, VCAM-1), apoptosis related proteins (e.g., Bcl-2, caspases, DR, Fas), and cell cycle proteins (e.g., cyclin D1). Curcumin modulates the activity of several transcription factors (e.g., NF-κB, AP-1, STAT) and their signaling pathways. Based on its ability to affect multiple targets, curcumin has the potential for the prevention and treatment of various diseases including cancers, arthritis, allergies, atherosclerosis, aging, neurodegenerative disease, hepatic disorders, obesity, diabetes, psoriasis, and autoimmune diseases. This review summarizes the molecular mechanisms of modulation of gene expression by curcumin. PMID:22996381

  13. Gene products of corticosteroid action in hippocampus.

    PubMed

    Nichols, N R; Finch, C E

    1994-11-30

    We used two methods to examine altered patterns of gene expression in rat hippocampus in response to administered glucocorticoids: analysis of RNA in vitro translation products on 2-d gels and cloning of cDNAs from a rat hippocampal library by differential hybridization (+/- CORT). We determined that two of the CORT-responsive cDNA clones encoded the 35- and 50-kd RNA translation products and identified them as GPDH and GFAP, respectively, by sequence analysis. Cloned mRNAs that increased and decreased in response to CORT were determined to be under positive and negative regulation by glucocorticoids in intact rats. Despite their similarities in glucocorticoid response characteristics, we found three subsets of hippocampal mRNA responses to CORT and shaking stress which differ in temporal and level-dependent aspects of CORT regulation. In addition, GPDH gene expression represents a glucocorticoid-dependent stress response which is rapidly increased in a dose- and stressor-dependent manner. It is a candidate for a sensitive indicator of stress responsiveness in the brain as a function of neuroendocrine activity. Mechanisms of adaptation to stress in the brain are likely to involve responses that are both mediated by glucocorticoids and opposed by them. GFAP and TGF-beta 1 mRNA responses may be examples of the latter, since they are decreased in response to glucocorticoids, are under negative regulation by glucocorticoids in intact rats, and are increased in response to brain injury and disease and during aging. If these astrocytic and microglial responses are involved in cellular defense mechanisms in the brain, then their regulation by glucocorticoids would be important in maintaining and restoring cellular homeostasis in physiological and pathophysiological states. Future studies using these sensitive probes for glucocorticoid-regulated gene expression may identify new mechanisms by which the brain coordinates acute and chronic responses to stress and disease.

  14. 42 CFR 460.48 - Additional actions by CMS or the State.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) Sanctions, Enforcement Actions, and Termination § 460.48 Additional actions...

  15. 42 CFR 460.48 - Additional actions by CMS or the State.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) Sanctions, Enforcement Actions, and Termination § 460.48 Additional actions...

  16. 42 CFR 460.48 - Additional actions by CMS or the State.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) Sanctions, Enforcement Actions, and Termination § 460.48 Additional actions...

  17. 42 CFR 460.48 - Additional actions by CMS or the State.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) Sanctions, Enforcement Actions, and Termination § 460.48 Additional actions...

  18. 42 CFR 460.48 - Additional actions by CMS or the State.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) Sanctions, Enforcement Actions, and Termination § 460.48 Additional actions...

  19. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  20. Replacing and Additive Horizontal Gene Transfer in Streptococcus

    PubMed Central

    Choi, Sang Chul; Rasmussen, Matthew D.; Hubisz, Melissa J.; Gronau, Ilan; Stanhope, Michael J.; Siepel, Adam

    2012-01-01

    The prominent role of Horizontal Gene Transfer (HGT) in the evolution of bacteria is now well documented, but few studies have differentiated between evolutionary events that predominantly cause genes in one lineage to be replaced by homologs from another lineage (“replacing HGT”) and events that result in the addition of substantial new genomic material (“additive HGT”). Here in, we make use of the distinct phylogenetic signatures of replacing and additive HGTs in a genome-wide study of the important human pathogen Streptococcus pyogenes (SPY) and its close relatives S. dysgalactiae subspecies equisimilis (SDE) and S. dysgalactiae subspecies dysgalactiae (SDD). Using recently developed statistical models and computational methods, we find evidence for abundant gene flow of both kinds within each of the SPY and SDE clades and of reduced levels of exchange between SPY and SDD. In addition, our analysis strongly supports a pronounced asymmetry in SPY–SDE gene flow, favoring the SPY-to-SDE direction. This finding is of particular interest in light of the recent increase in virulence of pathogenic SDE. We find much stronger evidence for SPY–SDE gene flow among replacing than among additive transfers, suggesting a primary influence from homologous recombination between co-occurring SPY and SDE cells in human hosts. Putative virulence genes are correlated with transfer events, but this correlation is found to be driven by additive, not replacing, HGTs. The genes affected by additive HGTs are enriched for functions having to do with transposition, recombination, and DNA integration, consistent with previous findings, whereas replacing HGTs seen to influence a more diverse set of genes. Additive transfers are also found to be associated with evidence of positive selection. These findings shed new light on the manner in which HGT has shaped pathogenic bacterial genomes. PMID:22617954

  1. 40 CFR 26.1507 - Actions alternative or additional to disqualification.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Actions alternative or additional to disqualification. 26.1507 Section 26.1507 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL... judicial proceedings (civil or criminal) and any other appropriate regulatory action, in addition to or...

  2. 40 CFR 26.1507 - Actions alternative or additional to disqualification.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Actions alternative or additional to disqualification. 26.1507 Section 26.1507 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL... judicial proceedings (civil or criminal) and any other appropriate regulatory action, in addition to or...

  3. Gene dosage imbalances: action, reaction, and models.

    PubMed

    Veitia, Reiner A; Potier, Marie Claude

    2015-06-01

    Single-gene deletions, duplications, and misregulation, as well as aneuploidy, can lead to stoichiometric imbalances within macromolecular complexes and cellular networks, causing their malfunction. Such alterations can be responsible for inherited or somatic genetic disorders including Mendelian diseases, aneuploid syndromes, and cancer. We review the effects of gene dosage alterations at the transcriptomic and proteomic levels, and the various responses of the cell to counteract their effects. Furthermore, we explore several biochemical models and ideas that can provide the rationale for treatments modulating the effects of gene dosage imbalances.

  4. 41 CFR 60-2.17 - Additional required elements of affirmative action programs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 41 Public Contracts and Property Management 1 2014-07-01 2014-07-01 false Additional required elements of affirmative action programs. 60-2.17 Section 60-2.17 Public Contracts and Property Management... management to ensure the effective implementation of the affirmative action program. (b) Identification...

  5. 41 CFR 60-2.17 - Additional required elements of affirmative action programs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 41 Public Contracts and Property Management 1 2012-07-01 2009-07-01 true Additional required elements of affirmative action programs. 60-2.17 Section 60-2.17 Public Contracts and Property Management... management to ensure the effective implementation of the affirmative action program. (b) Identification...

  6. 21 CFR 58.215 - Alternative or additional actions to disqualification.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Alternative or additional actions to disqualification. 58.215 Section 58.215 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... proceedings or actions authorized by the act. The Food and Drug Administration may, at any time,...

  7. 21 CFR 58.215 - Alternative or additional actions to disqualification.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Alternative or additional actions to disqualification. 58.215 Section 58.215 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... proceedings or actions authorized by the act. The Food and Drug Administration may, at any time,...

  8. 21 CFR 58.215 - Alternative or additional actions to disqualification.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Alternative or additional actions to disqualification. 58.215 Section 58.215 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... proceedings or actions authorized by the act. The Food and Drug Administration may, at any time,...

  9. From gene action to reactive genomes

    PubMed Central

    Keller, Evelyn Fox

    2014-01-01

    Poised at a critical turning point in the history of genetics, recent work (e.g. in genomics, epigenetics, genomic plasticity) obliges us to critically reexamine many of our most basic concepts. For example, I argue that genomic research supports a radical transformation in our understanding of the genome – a shift from an earlier conception of that entity as an effectively static collection of active genes to that of a dynamic and reactive system dedicated to the context specific regulation of protein-coding sequences. PMID:24882822

  10. 26 CFR 301.6110-5 - Notice and time requirements; actions to restrain disclosure; actions to obtain additional...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the Internal Revenue Service determines that the request constitutes a request for disclosure of the... the Internal Revenue Service has determined that additional disclosure of information other than the... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Notice and time requirements; actions...

  11. Paralogous genes involved in juvenile hormone action in Drosophila melanogaster.

    PubMed

    Baumann, Aaron; Barry, Joshua; Wang, Shaoli; Fujiwara, Yoshihiro; Wilson, Thomas G

    2010-08-01

    Juvenile hormone (JH) is critical for multiple aspects of insect development and physiology. Although roles for the hormone have received considerable study, an understanding of the molecules necessary for JH action in insects has been frustratingly slow to evolve. Methoprene-tolerant (Met) in Drosophila melanogaster fulfills many of the requirements for a hormone receptor gene. A paralogous gene, germ-cell expressed (gce), possesses homology and is a candidate as a Met partner in JH action. Expression of gce was found to occur at multiple times and in multiple tissues during development, similar to that previously found for Met. To probe roles of this gene in JH action, we carried out in vivo gce over- and underexpression studies. We show by overexpression studies that gce can substitute in vivo for Met, alleviating preadult but not adult phenotypic characters. We also demonstrate that RNA interference-driven knockdown of gce expression in transgenic flies results in preadult lethality in the absence of MET. These results show that (1) unlike Met, gce is a vital gene and shows functional flexibility and (2) both gene products appear to promote JH action in preadult but not adult development.

  12. Additive functions in boolean models of gene regulatory network modules.

    PubMed

    Darabos, Christian; Di Cunto, Ferdinando; Tomassini, Marco; Moore, Jason H; Provero, Paolo; Giacobini, Mario

    2011-01-01

    Gene-on-gene regulations are key components of every living organism. Dynamical abstract models of genetic regulatory networks help explain the genome's evolvability and robustness. These properties can be attributed to the structural topology of the graph formed by genes, as vertices, and regulatory interactions, as edges. Moreover, the actual gene interaction of each gene is believed to play a key role in the stability of the structure. With advances in biology, some effort was deployed to develop update functions in boolean models that include recent knowledge. We combine real-life gene interaction networks with novel update functions in a boolean model. We use two sub-networks of biological organisms, the yeast cell-cycle and the mouse embryonic stem cell, as topological support for our system. On these structures, we substitute the original random update functions by a novel threshold-based dynamic function in which the promoting and repressing effect of each interaction is considered. We use a third real-life regulatory network, along with its inferred boolean update functions to validate the proposed update function. Results of this validation hint to increased biological plausibility of the threshold-based function. To investigate the dynamical behavior of this new model, we visualized the phase transition between order and chaos into the critical regime using Derrida plots. We complement the qualitative nature of Derrida plots with an alternative measure, the criticality distance, that also allows to discriminate between regimes in a quantitative way. Simulation on both real-life genetic regulatory networks show that there exists a set of parameters that allows the systems to operate in the critical region. This new model includes experimentally derived biological information and recent discoveries, which makes it potentially useful to guide experimental research. The update function confers additional realism to the model, while reducing the complexity

  13. Additive Functions in Boolean Models of Gene Regulatory Network Modules

    PubMed Central

    Darabos, Christian; Di Cunto, Ferdinando; Tomassini, Marco; Moore, Jason H.; Provero, Paolo; Giacobini, Mario

    2011-01-01

    Gene-on-gene regulations are key components of every living organism. Dynamical abstract models of genetic regulatory networks help explain the genome's evolvability and robustness. These properties can be attributed to the structural topology of the graph formed by genes, as vertices, and regulatory interactions, as edges. Moreover, the actual gene interaction of each gene is believed to play a key role in the stability of the structure. With advances in biology, some effort was deployed to develop update functions in Boolean models that include recent knowledge. We combine real-life gene interaction networks with novel update functions in a Boolean model. We use two sub-networks of biological organisms, the yeast cell-cycle and the mouse embryonic stem cell, as topological support for our system. On these structures, we substitute the original random update functions by a novel threshold-based dynamic function in which the promoting and repressing effect of each interaction is considered. We use a third real-life regulatory network, along with its inferred Boolean update functions to validate the proposed update function. Results of this validation hint to increased biological plausibility of the threshold-based function. To investigate the dynamical behavior of this new model, we visualized the phase transition between order and chaos into the critical regime using Derrida plots. We complement the qualitative nature of Derrida plots with an alternative measure, the criticality distance, that also allows to discriminate between regimes in a quantitative way. Simulation on both real-life genetic regulatory networks show that there exists a set of parameters that allows the systems to operate in the critical region. This new model includes experimentally derived biological information and recent discoveries, which makes it potentially useful to guide experimental research. The update function confers additional realism to the model, while reducing the complexity

  14. Circadian Variations in Liver Gene Expression: Relationships to Drug Actions

    PubMed Central

    Almon, Richard R.; Yang, Eric; Lai, William; Androulakis, Ioannis P.; DuBois, Debra C.; Jusko, William J.

    2008-01-01

    Chronopharmacology is an important but under-explored aspect of therapeutics. Rhythmic variations in biological processes can influence drug action, including pharmacodynamic responses, due to circadian variations in the availability or functioning of drug targets. We hypothesized that global gene expression analysis can be useful in the identification of circadian regulated genes involved in drug action. Circadian variations in gene expression in rat liver were explored using Affymetrix gene arrays. A rich time series involving animals analyzed at 18 time points within the 24 hour cycle was generated. Of the more than 15,000 probe sets on these arrays, 265 exhibited oscillations with a 24 hour frequency. Cluster analysis yielded 5 distinct circadian clusters, with approximately two-thirds of the transcripts reaching maximum expression during the animal’s dark/active period. Of the 265 probe sets, 107 of potential therapeutic importance were identified. The expression levels of clock genes were also investigated in this study. Five clock genes exhibited circadian variation in liver, and data suggest that these genes may also be regulated by corticosteroids. PMID:18562560

  15. 21 CFR 56.124 - Actions alternative or additional to disqualification.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Actions alternative or additional to disqualification. 56.124 Section 56.124 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... The Food and Drug Administration may, at any time, through the Department of Justice institute...

  16. 21 CFR 56.124 - Actions alternative or additional to disqualification.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Actions alternative or additional to disqualification. 56.124 Section 56.124 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... The Food and Drug Administration may, at any time, through the Department of Justice institute...

  17. 21 CFR 56.124 - Actions alternative or additional to disqualification.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Actions alternative or additional to disqualification. 56.124 Section 56.124 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... The Food and Drug Administration may, at any time, through the Department of Justice institute...

  18. Methods for detecting additional genes underlying Alzheimer disease

    SciTech Connect

    Locke, P.A.; Haines, J.L.; Ter-Minassian, M.

    1994-09-01

    Alzheimer`s disease (AD) is a complex inherited disorder with proven genetic heterogeneity. To date, genes on chromosome 21 (APP) and 14 (not yet identified) are associated with early-onset familial AD, while the APOE gene on chromosome 19 is associated with both late onset familial and sporadic AD and early onset sporadic AD. Although these genes likely account for the majority of AD, many familial cases cannot be traced to any of these genes. From a set of 127 late-onset multiplex families screened for APOE, 43 (34%) families have at least one affected individual with no APOE-4 allele, suggesting an alternative genetic etiology. Simulation studies indicated that additional loci could be identified through a genomic screen with a 10 cM sieve on a subset of 21 well documented, non-APOE-4 families. Given the uncertainties in the mode of inheritance, reliance on a single analytical method could result in a missed linkage. Therefore, we have developed a strategy of using multiple overlapping yet complementary methods to detect linkage. These include sib-pair analysis and affected-pedigree-member analysis, neither of which makes assumptions about mode of inheritance, and lod score analysis (using two predefined genetic models). In order for a marker to qualify for follow-up, it must fit at least two of three criteria. These are nominal P values of 0.05 or less for the non-parametric methods, and/or a lod score greater than 1.0. Adjacent markers each fulfilling a single criterion also warrant follow-up. To date, we have screened 61 markers on chromosomes 1, 2, 3, 18, 19, 21, and 22. One marker, D2S163, generated a lod score of 1.06 ({theta} = 0.15) and an APMT statistic of 3.68 (P < 0.001). This region is currently being investigated in more detail. Updated results of this region plus additional screening data will be presented.

  19. Explanation of non-additive effects in mixtures of similar mode of action chemicals.

    PubMed

    Kamo, Masashi; Yokomizo, Hiroyuki

    2015-09-01

    Many models have been developed to predict the combined effect of drugs and chemicals. Most models are classified into two additive models: independent action (IA) and concentration addition (CA). It is generally considered if the modes of action of chemicals are similar then the combined effect obeys CA; however, many empirical studies report nonlinear effects deviating from the predictions by CA. Such deviations are termed synergism and antagonism. Synergism, which leads to a stronger toxicity, requires more careful management, and hence it is important to understand how and which combinations of chemicals lead to synergism. In this paper, three types of chemical reactions are mathematically modeled and the cause of the nonlinear effects among chemicals with similar modes of action was investigated. Our results show that combined effects obey CA only when the modes of action are exactly the same. Contrary to existing knowledge, combined effects are generally nonlinear even if the modes of action of the chemicals are similar. Our results further show that the nonlinear effects vanish out when the chemical concentrations are low, suggesting that the current management procedure of assuming CA is rarely inappropriate because environmental concentrations of chemicals are generally low.

  20. Effect of Nitrogen Additives on Flame Retardant Action of Tributyl Phosphate: Phosphorus – Nitrogen Synergism

    SciTech Connect

    Gaan, Sabyasachi; Sun, Gang; Hutches, Katherine; Engelhard, Mark H.

    2008-01-01

    The effect of nitrogen additives like urea, guanidine carbonate and melamine formaldehyde on the flame retardant efficacy of tributyl phosphate (TBP) has been investigated. From the LOI tests on treated cotton it is clear that the nitrogen additives have synergistic action. Estimation of activation energy of decomposition of treated cotton indicated that nitrogen additives enhance the thermal stability during the burning process. SEM pictures of chars formed after LOI test showed the formation of protective polymeric coating on the surface. The surface of chars formed were evaluated using FTIR-ATR and XPS analysis which showed that the coating was composed of Phosphorus-Nitrogen-Oxygen containing species. Formation of this coating during the burning process could lead to the synergistic interaction of phosphorus and nitrogen. Based on the experimental data we have further proposed several reaction mechanisms which could contribute to synergistic action and formation of protective coating on the surface of char.

  1. Gene specific modifications unravel ethanol and acetaldehyde actions

    PubMed Central

    Israel, Yedy; Rivera-Meza, Mario; Karahanian, Eduardo; Quintanilla, María E.; Tampier, Lutske; Morales, Paola; Herrera-Marschitz, Mario

    2013-01-01

    Ethanol is metabolized into acetaldehyde mainly by the action of alcohol dehydrogenase in the liver, while mainly by the action of catalase in the brain. Aldehyde dehydrogenase-2 metabolizes acetaldehyde into acetate in both organs. Gene specific modifications reviewed here show that an increased liver generation of acetaldehyde (by transduction of a gene coding for a high-activity liver alcohol dehydrogenase ADH1*B2) leads to increased blood acetaldehyde levels and aversion to ethanol in animals. Similarly aversive is an increased acetaldehyde level resulting from the inhibition of liver aldehyde dehydrogenase-2 (ALDH2) synthesis (by an antisense coding gene against aldh2 mRNA). The situation is diametrically different when acetaldehyde is generated in the brain. When the brain ventral tegmental area (VTA) is endowed with an increased ability to generate acetaldehyde (by transfection of liver rADH) the reinforcing effects of ethanol are increased, while a highly specific inhibition of catalase synthesis (by transduction of a shRNA anti catalase mRNA) virtually abolishes the reinforcing effects of ethanol as seen by a complete abolition of ethanol intake in rats bred for generations as high ethanol drinkers. Data shows two divergent effects of increases in acetaldehyde generation: aversive in the periphery but reinforcing in the brain. PMID:23847486

  2. The effect of neutral nonadditive gene action on the quantitative index of population divergence.

    PubMed Central

    López-Fanjul, Carlos; Fernández, Almudena; Toro, Miguel A

    2003-01-01

    For neutral additive genes, the quantitative index of population divergence (Q(ST)) is equivalent to Wright's fixation index (F(ST)). Thus, divergent or convergent selection is usually invoked, respectively, as a cause of the observed increase (Q(ST) > F(ST)) or decrease (Q(ST) < F(ST)) of Q(ST) from its neutral expectation (Q(ST) = F(ST)). However, neutral nonadditive gene action can mimic the additive expectations under selection. We have studied theoretically the effect of consecutive population bottlenecks on the difference F(ST) - Q(ST) for two neutral biallelic epistatic loci, covering all types of marginal gene action. With simple dominance, Q(ST) < F(ST) for only low to moderate frequencies of the recessive alleles; otherwise, Q(ST) > F(ST). Additional epistasis extends the condition Q(ST) < F(ST) to a broader range of frequencies. Irrespective of the type of nonadditive action, Q(ST) < F(ST) generally implies an increase of both the within-line additive variance after bottlenecks over its ancestral value (V(A)) and the between-line variance over its additive expectation (2F(ST)V(A)). Thus, both the redistribution of the genetic variance after bottlenecks and the F(ST) - Q(ST) value are governed largely by the marginal properties of single loci. The results indicate that the use of the F(ST) - Q(ST) criterion to investigate the relative importance of drift and selection in population differentiation should be restricted to pure additive traits. PMID:12930766

  3. Additive effect of combined application of magnesium and MK-801 on analgesic action of morphine.

    PubMed

    Bujalska-Zadrożny, Magdalena; Duda, Kamila

    2014-01-01

    As previously reported, magnesium ions (Mg(2+)) administered in relatively low doses markedly potentiated opioid analgesia in neuropathic pain, in which the effectiveness of opioids is limited. Considering that Mg(2+) behaves like an N-methyl-D-aspartate receptor antagonist, the effect of this ion on the analgesic action of morphine was compared with that of MK-801. Acute pain was evoked by mechanical or thermal stimuli, whereas neuropathic hyperalgesia was induced by streptozotocin (STZ) administration. Magnesium sulphate (40 mg/kg i.p.) or MK-801 (0.05 mg/kg s.c.) administered alone did not modify the nociceptive threshold to acute stimuli or the streptozotocin hyperalgesia but significantly augmented the analgesic action of morphine (5 mg/kg i.p.). Furthermore, if these drugs (i.e. magnesium sulphate and MK-801) were applied concomitantly, a clear additive effect on the analgesic action of morphine occurred in both models of pain. Possible explanations of these observations are discussed. PMID:24577345

  4. Hairy and Groucho mediate the action of juvenile hormone receptor Methoprene-tolerant in gene repression.

    PubMed

    Saha, Tusar T; Shin, Sang Woon; Dou, Wei; Roy, Sourav; Zhao, Bo; Hou, Yuan; Wang, Xue-Li; Zou, Zhen; Girke, Thomas; Raikhel, Alexander S

    2016-02-01

    The arthropod-specific juvenile hormone (JH) controls numerous essential functions. Its involvement in gene activation is known to be mediated by the transcription factor Methoprene-tolerant (Met), which turns on JH-controlled genes by directly binding to E-box-like motifs in their regulatory regions. However, it remains unclear how JH represses genes. We used the Aedes aegypti female mosquito, in which JH is necessary for reproductive maturation, to show that a repressor, Hairy, is required for the gene-repressive action of JH and Met. The RNA interference (RNAi) screen for Met and Hairy in the Aedes female fat body revealed a large cohort of Met- and Hairy-corepressed genes. Analysis of selected genes from this cohort demonstrated that they are repressed by JH, but RNAi of either Met or Hairy renders JH ineffective in repressing these genes in an in vitro fat-body culture assay. Moreover, this JH action was prevented by the addition of the translational inhibitor cycloheximide (CHX) to the culture, indicating the existence of an indirect regulatory hierarchy. The lack of Hairy protein in the CHX-treated tissue was verified using immunoblot analysis, and the upstream regions of Met/Hairy-corepressed genes were shown to contain common binding motifs that interact with Hairy. Groucho (gro) RNAi silencing phenocopied the effect of Hairy RNAi knockdown, indicating that it is involved in the JH/Met/Hairy hierarchy. Finally, the requirement of Hairy and Gro for gene repression was confirmed in a cell transfection assay. Thus, our study has established that Hairy and its cofactor Gro mediate the repressive function of JH and Met. PMID:26744312

  5. Hairy and Groucho mediate the action of juvenile hormone receptor Methoprene-tolerant in gene repression

    PubMed Central

    Saha, Tusar T.; Shin, Sang Woon; Dou, Wei; Roy, Sourav; Zhao, Bo; Hou, Yuan; Wang, Xue-Li; Zou, Zhen; Girke, Thomas; Raikhel, Alexander S.

    2016-01-01

    The arthropod-specific juvenile hormone (JH) controls numerous essential functions. Its involvement in gene activation is known to be mediated by the transcription factor Methoprene-tolerant (Met), which turns on JH-controlled genes by directly binding to E-box–like motifs in their regulatory regions. However, it remains unclear how JH represses genes. We used the Aedes aegypti female mosquito, in which JH is necessary for reproductive maturation, to show that a repressor, Hairy, is required for the gene-repressive action of JH and Met. The RNA interference (RNAi) screen for Met and Hairy in the Aedes female fat body revealed a large cohort of Met- and Hairy-corepressed genes. Analysis of selected genes from this cohort demonstrated that they are repressed by JH, but RNAi of either Met or Hairy renders JH ineffective in repressing these genes in an in vitro fat-body culture assay. Moreover, this JH action was prevented by the addition of the translational inhibitor cycloheximide (CHX) to the culture, indicating the existence of an indirect regulatory hierarchy. The lack of Hairy protein in the CHX-treated tissue was verified using immunoblot analysis, and the upstream regions of Met/Hairy-corepressed genes were shown to contain common binding motifs that interact with Hairy. Groucho (gro) RNAi silencing phenocopied the effect of Hairy RNAi knockdown, indicating that it is involved in the JH/Met/Hairy hierarchy. Finally, the requirement of Hairy and Gro for gene repression was confirmed in a cell transfection assay. Thus, our study has established that Hairy and its cofactor Gro mediate the repressive function of JH and Met. PMID:26744312

  6. Lytic Action of the Truncated yncE Gene in Escherichia coli.

    PubMed

    Li, Jianhua; Xiong, Kun; Zou, Lingyun; Chen, Zhijin; Wang, Yiran; Hu, Xiaomei; Rao, Xiancai; Cong, Yanguang

    2016-04-01

    We recently found lytic action of the truncated yncE gene. When the truncated yncE gene of Salmonella enterica serovar Paratyphi A was expressed in Escherichia coli DH5α under the control of the Ara promoter, bacterial growth was markedly inhibited. In the present study, we characterized this lytic action. The N-terminal 103 aa of YncE, containing a signal peptide, was demonstrated to be essential for inhibition. Microscopic observation showed that the bacterial envelope of E. coli was damaged by the expression of truncated yncE, resulting in the release of cytoplasmic content and the formation of bacterial ghosts. The addition of MgSO4 or spermine, which is the stabilizer of bacterial membrane structure, dramatically reversed the cell lysis induced by the toxic truncated YncE. In contrast, the lytic action was significantly enhanced by the addition of SDS or EDTA. Our data indicated that the toxic truncated YncE could cause cell lysis by the disruption of the bacterial membrane. PMID:26687463

  7. Linking Genes to Cardiovascular Diseases: Gene Action and Gene-Environment Interactions.

    PubMed

    Pasipoularides, Ares

    2015-12-01

    A unique myocardial characteristic is its ability to grow/remodel in order to adapt; this is determined partly by genes and partly by the environment and the milieu intérieur. In the "post-genomic" era, a need is emerging to elucidate the physiologic functions of myocardial genes, as well as potential adaptive and maladaptive modulations induced by environmental/epigenetic factors. Genome sequencing and analysis advances have become exponential lately, with escalation of our knowledge concerning sometimes controversial genetic underpinnings of cardiovascular diseases. Current technologies can identify candidate genes variously involved in diverse normal/abnormal morphomechanical phenotypes, and offer insights into multiple genetic factors implicated in complex cardiovascular syndromes. The expression profiles of thousands of genes are regularly ascertained under diverse conditions. Global analyses of gene expression levels are useful for cataloging genes and correlated phenotypes, and for elucidating the role of genes in maladies. Comparative expression of gene networks coupled to complex disorders can contribute insights as to how "modifier genes" influence the expressed phenotypes. Increasingly, a more comprehensive and detailed systematic understanding of genetic abnormalities underlying, for example, various genetic cardiomyopathies is emerging. Implementing genomic findings in cardiology practice may well lead directly to better diagnosing and therapeutics. There is currently evolving a strong appreciation for the value of studying gene anomalies, and doing so in a non-disjointed, cohesive manner. However, it is challenging for many-practitioners and investigators-to comprehend, interpret, and utilize the clinically increasingly accessible and affordable cardiovascular genomics studies. This survey addresses the need for fundamental understanding in this vital area.

  8. Genes and Molecules of Lactobacilli Supporting Probiotic Action

    PubMed Central

    Lebeer, Sarah; Vanderleyden, Jos; De Keersmaecker, Sigrid C. J.

    2008-01-01

    Summary: Lactobacilli have been crucial for the production of fermented products for centuries. They are also members of the mutualistic microbiota present in the human gastrointestinal and urogenital tract. Recently, increasing attention has been given to their probiotic, health-promoting capacities. Many human intervention studies demonstrating health effects have been published. However, as not all studies resulted in positive outcomes, scientific interest arose regarding the precise mechanisms of action of probiotics. Many reported mechanistic studies have addressed mainly the host responses, with less attention being focused on the specificities of the bacterial partners, notwithstanding the completion of Lactobacillus genome sequencing projects, and increasing possibilities of genomics-based and dedicated mutant analyses. In this emerging and highly interdisciplinary field, microbiologists are facing the challenge of molecular characterization of probiotic traits. This review addresses the advances in the understanding of the probiotic-host interaction with a focus on the molecular microbiology of lactobacilli. Insight into the molecules and genes involved should contribute to a more judicious application of probiotic lactobacilli and to improved screening of novel potential probiotics. PMID:19052326

  9. Correlating chemical sensitivity and basal gene expression reveals mechanism of action | Office of Cancer Genomics

    Cancer.gov

    Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity across many cell lines to illuminate the actions of compounds whose MoA are unknown.

  10. Anticancer drug mithramycin interacts with core histones: An additional mode of action of the DNA groove binder

    PubMed Central

    Banerjee, Amrita; Sanyal, Sulagna; Kulkarni, Kirti K.; Jana, Kuladip; Roy, Siddhartha; Das, Chandrima; Dasgupta, Dipak

    2014-01-01

    Mithramycin (MTR) is a clinically approved DNA-binding antitumor antibiotic currently in Phase 2 clinical trials at National Institutes of Health for treatment of osteosarcoma. In view of the resurgence in the studies of this generic antibiotic as a human medicine, we have examined the binding properties of MTR with the integral component of chromatin – histone proteins – as a part of our broad objective to classify DNA-binding molecules in terms of their ability to bind chromosomal DNA alone (single binding mode) or both histones and chromosomal DNA (dual binding mode). The present report shows that besides DNA, MTR also binds to core histones present in chromatin and thus possesses the property of dual binding in the chromatin context. In contrast to the MTR–DNA interaction, association of MTR with histones does not require obligatory presence of bivalent metal ion like Mg2+. As a consequence of its ability to interact with core histones, MTR inhibits histone H3 acetylation at lysine 18, an important signature of active chromatin, in vitro and ex vivo. Reanalysis of microarray data of Ewing sarcoma cell lines shows that upon MTR treatment there is a significant down regulation of genes, possibly implicating a repression of H3K18Ac-enriched genes apart from DNA-binding transcription factors. Association of MTR with core histones and its ability to alter post-translational modification of histone H3 clearly indicates an additional mode of action of this anticancer drug that could be implicated in novel therapeutic strategies. PMID:25473595

  11. Additivity of Pyrethroid Actions on Sodium Influx in Cortical Neuronsin vitro

    EPA Science Inventory

    Background: Pyrethroid insecticides bind to voltage-gated sodium channels (VGSCs) and modify their gating kinetics, thereby disrupting neuronal function. While previous work has tested the additivity of pyrethroids in vivo, the additivity of these compounds at the major target si...

  12. Additivity of Pyrethroid Actions on Sodium Influx in Cortical Neurons in Cerebrocortical Neurons in Primary Culture

    EPA Science Inventory

    BACKGROUND: Pyrethroid insecticides bind to voltage-gated sodium channels and modify their gating kinetics, thereby disrupting neuronal function. Although previous work has tested the additivity of pyrethroids in vivo, this has not been assessed directly at the primary molecular ...

  13. Further Insights into the Mode of Action of the Lipoglycopeptide Telavancin through Global Gene Expression Studies

    PubMed Central

    Song, Yang; Lunde, Christopher S.; Benton, Bret M.

    2012-01-01

    Telavancin is a novel semisynthetic lipoglycopeptide derivative of vancomycin with a decylaminoethyl side chain that is active against Gram-positive bacteria, including Staphylococcus aureus strains resistant to methicillin or vancomycin. A dual mechanism of action has been proposed for telavancin involving inhibition of peptidoglycan biosynthesis and membrane depolarization. Here we report the results of genome-wide transcriptional profiling of the response of S. aureus to telavancin using microarrays. Short (15-min) challenge of S. aureus with telavancin revealed strong expression of the cell wall stress stimulon, a characteristic response to inhibition of cell wall biosynthesis. In the transcriptome obtained after 60-min telavancin challenge, in addition to induction of the cell wall stress stimulon, there was induction of various genes, including lrgA and lrgB, lysine biosynthesis operon (dap) genes, vraD and vraE, and hlgC, that have been reported to be induced by known membrane-depolarizing and active agents, including carbonyl cyanide m-chlorophenylhydrazone, daptomycin, bacitracin, and other antimicrobial peptides These genes were either not induced or only weakly induced by the parent molecule vancomycin. We suggest that expression of these genes is a response of the cell to mitigate and detoxify such molecules and is diagnostic of a membrane-depolarizing or membrane-active molecule. The results indicate that telavancin causes early and significant induction of the cell wall stress stimulon due to strong inhibition of peptidoglycan biosynthesis, with evidence in support of membrane depolarization and membrane activity that is expressed after a longer duration of drug treatment. PMID:22411615

  14. Nongenic transcription, gene regulation and action at a distance.

    PubMed

    Cook, Peter R

    2003-11-15

    In eukaryotes, motifs such as silencers, enhancers and locus control regions act over thousands of base pairs to regulate adjacent genes; insulators limit such effects, and barriers confine repressive heterochromatin to particular chromosomal segments. Recent results show that many of these motifs are nongenic transcription units, and two of them directly contact their targets lying further down the chromosome to loop the intervening DNA: the barriers (scs and scs') flanking the 87A7 heat-shock locus in the fly contact each other, and a locus control region touches the beta-globin gene in the mouse. I hypothesize that the act of transcription underlies the function of these regulators; active polymerizing complexes tend to cluster into 'factories' and this facilitates molecular contact between the transcribed regulator and its distant (and transcribed) target. PMID:14576342

  15. Novel action of FOXL2 as mediator of Col1a2 gene autoregulation.

    PubMed

    Marongiu, Mara; Deiana, Manila; Marcia, Loredana; Sbardellati, Andrea; Asunis, Isadora; Meloni, Alessandra; Angius, Andrea; Cusano, Roberto; Loi, Angela; Crobu, Francesca; Fotia, Giorgio; Cucca, Francesco; Schlessinger, David; Crisponi, Laura

    2016-08-01

    FOXL2 belongs to the evolutionarily conserved forkhead box (FOX) superfamily and is a master transcription factor in a spectrum of developmental pathways, including ovarian and eyelid development and bone, cartilage and uterine maturation. To analyse its action, we searched for proteins that interact with FOXL2. We found that FOXL2 interacts with specific C-terminal propeptides of several fibrillary collagens. Because these propeptides can participate in feedback regulation of collagen biosynthesis, we inferred that FOXL2 could thereby affect the transcription of the cognate collagen genes. Focusing on COL1A2, we found that FOXL2 indeed affects collagen synthesis, by binding to a DNA response element located about 65Kb upstream of this gene. According to our hypothesis we found that in Foxl2(-/-) mouse ovaries, Col1a2 was elevated from birth to adulthood. The extracellular matrix (ECM) compartmentalizes the ovary during folliculogenesis, (with type I, type III and type IV collagens as primary components), and ECM composition changes during the reproductive lifespan. In Foxl2(-/-) mouse ovaries, in addition to up-regulation of Col1a2, Col3a1, Col4a1 and fibronectin were also upregulated, while laminin expression was reduced. Thus, by regulating levels of extracellular matrix components, FOXL2 may contribute to both ovarian histogenesis and the fibrosis attendant on depletion of the follicle reserve during reproductive aging and menopause. PMID:27212026

  16. Antagonistic control of a dual-input mammalian gene switch by food additives.

    PubMed

    Xie, Mingqi; Ye, Haifeng; Hamri, Ghislaine Charpin-El; Fussenegger, Martin

    2014-08-01

    Synthetic biology has significantly advanced the design of mammalian trigger-inducible transgene-control devices that are able to programme complex cellular behaviour. Fruit-based benzoate derivatives licensed as food additives, such as flavours (e.g. vanillate) and preservatives (e.g. benzoate), are a particularly attractive class of trigger compounds for orthogonal mammalian transgene control devices because of their innocuousness, physiological compatibility and simple oral administration. Capitalizing on the genetic componentry of the soil bacterium Comamonas testosteroni, which has evolved to catabolize a variety of aromatic compounds, we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate. When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme. Additionally, the benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks providing expression dynamics reminiscent of a lap-timing stopwatch. Designer gene switches using licensed food additives as trigger compounds to achieve antagonistic dual-input expression profiles and provide novel control topologies and regulation dynamics may advance future gene- and cell-based therapies.

  17. Antagonistic control of a dual-input mammalian gene switch by food additives

    PubMed Central

    Xie, Mingqi; Ye, Haifeng; Hamri, Ghislaine Charpin-El; Fussenegger, Martin

    2014-01-01

    Synthetic biology has significantly advanced the design of mammalian trigger-inducible transgene-control devices that are able to programme complex cellular behaviour. Fruit-based benzoate derivatives licensed as food additives, such as flavours (e.g. vanillate) and preservatives (e.g. benzoate), are a particularly attractive class of trigger compounds for orthogonal mammalian transgene control devices because of their innocuousness, physiological compatibility and simple oral administration. Capitalizing on the genetic componentry of the soil bacterium Comamonas testosteroni, which has evolved to catabolize a variety of aromatic compounds, we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate. When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme. Additionally, the benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks providing expression dynamics reminiscent of a lap-timing stopwatch. Designer gene switches using licensed food additives as trigger compounds to achieve antagonistic dual-input expression profiles and provide novel control topologies and regulation dynamics may advance future gene- and cell-based therapies. PMID:25030908

  18. Action!

    ERIC Educational Resources Information Center

    Senese, Joseph

    1998-01-01

    A small group of teachers at one Illinois high school is helping to effect and promote change. Through the Action Research Laboratory (ARL), teams of teachers conduct collaborative action research to improve classroom practices. Data from the first two years of the ARL indicate that teachers are eager to participate in, and have thrived in, their…

  19. Expanding the bactericidal action of the food color additive phloxine B to gram-negative bacteria.

    PubMed

    Rasooly, Reuven

    2005-08-01

    Phloxine B (D&C red no. 28) is a color additive for food, drugs, and cosmetics. It has been previously shown to have anti-Staphylococcus aureus activities. In this work, the effect of Phloxine B on various gram-negative bacteria and other gram-positive bacteria including Bacillus cereus, Bacillus thuringiensis, Bacillus mycoides, Bacillus subtilis, Bacillus aureus, Salmonella, Escherichia coli and Shigella was studied, along with the mechanism of anti-microbial activity. In the presence of fluorescent light, the viable count for gram-positive bacteria, (Bacillus spp. and S. aureus) decreased in a dose and time dependent manner when incubated with Phloxine B. The viability of gram-positive bacteria was reduced by 99.99% in 40 min, while there was no effect on gram-negative bacteria (Salmonella choleraesuis, E. coli and Shigella flexneri). However, the use of ethylenediaminetetraacetic acid (EDTA) expands the spectrum of activity for Phloxine B to include gram-negative bacteria. EDTA increased membrane-permeability by releasing lipopolysaccharide. Overall, in an Agar diffusion test the light-dependent bactericidal activity of 1 microg of Phloxine B had a potency of 0.64 units of chloramphenicol and 0.5 units of tetracycline when tested on B. cereus, and had a potency of 0.7 units of chloramphenicol and 0.2 units of tetracycline when tested on S. aureus. The data suggest that the dye may have some potential anti-microbial applications.

  20. Global identification of target genes regulated by APETALA3 and PISTILLATA floral homeotic gene action.

    PubMed

    Zik, Moriyah; Irish, Vivian F

    2003-01-01

    Identifying the genes regulated by the floral homeotic genes APETALA3 (AP3) and PISTILLATA (PI) is crucial for understanding the molecular mechanisms that lead to petal and stamen formation. We have used microarray analysis to conduct a broad survey of genes whose expression is affected by AP3 and PI activity. DNA microarrays consisting of 9216 Arabidopsis ESTs were screened with probes corresponding to mRNAs from different mutant and transgenic lines that misexpress AP3 and/or PI. The microarray results were further confirmed by RNA gel blot analyses. Our results suggest that AP3 and PI regulate a relatively small number of genes, implying that many genes used in petal and stamen development are not tissue specific and likely have roles in other processes as well. We recovered genes similar to previously identified petal- and stamen-expressed genes as well as genes that were not implicated previously in petal and stamen development. A very low percentage of the genes recovered encoded transcription factors. This finding suggests that AP3 and PI act relatively directly to regulate the genes required for the basic cellular processes responsible for petal and stamen morphogenesis.

  1. Fine Mapping of Two Additive Effect Genes for Awn Development in Rice (Oryza sativa L.)

    PubMed Central

    Li, Jinjie; Yao, Guoxin; Pan, Huiqiao; Hu, Guanglong; Chen, Chao; Zhang, Hongliang; Li, Zichao

    2016-01-01

    Awns, important domestication and agronomic traits in rice (Oryza sativa L.), are conferred by polygenes and the environment. Near isogenic line (NIL) pairs BM33 and BM38 were constructed from crosses between awnless japonica cv Nipponbare as recurrent parent, and lines SLG or Funingxiaohongmang (awned japonica accessions), respectively, as donors. In order to study the genetic and molecular mechanism of awning, two unknown, independent genes with additive effects were identified in a cross between the NILs. To map and clone the two genes, a BC4F4 population of 8,103 individuals and a BC4F6 population of 11,206 individuals were constructed. Awn3-1 was fine mapped to a 101.13 kb genomic region between Indel marker In316 and SNP marker S9-1 on chromosome 3. Nine predicted genes in the interval were annotated in the Rice Annotation Project Database (RAP-DB), and Os03g0418600 was identified as the most likely candidate for Awn3-1 through sequence comparisons and RT-PCR assays. Awn4-2 was fine mapped to a 62.4 kb genomic region flanked by simple sequence repeat (SSR) marker M1126 and Indel maker In73 on chromosome 4L. This region contained the previously reported gene An-1 that regulates awn development. Thus, An-1 may be the candidate gene of Awn4-2. These results will facilitate cloning of the awn genes and thereby provide an understanding of the molecular basis of awn development. PMID:27494628

  2. Fine Mapping of Two Additive Effect Genes for Awn Development in Rice (Oryza sativa L.).

    PubMed

    Li, Ben; Zhang, Yanpei; Li, Jinjie; Yao, Guoxin; Pan, Huiqiao; Hu, Guanglong; Chen, Chao; Zhang, Hongliang; Li, Zichao

    2016-01-01

    Awns, important domestication and agronomic traits in rice (Oryza sativa L.), are conferred by polygenes and the environment. Near isogenic line (NIL) pairs BM33 and BM38 were constructed from crosses between awnless japonica cv Nipponbare as recurrent parent, and lines SLG or Funingxiaohongmang (awned japonica accessions), respectively, as donors. In order to study the genetic and molecular mechanism of awning, two unknown, independent genes with additive effects were identified in a cross between the NILs. To map and clone the two genes, a BC4F4 population of 8,103 individuals and a BC4F6 population of 11,206 individuals were constructed. Awn3-1 was fine mapped to a 101.13 kb genomic region between Indel marker In316 and SNP marker S9-1 on chromosome 3. Nine predicted genes in the interval were annotated in the Rice Annotation Project Database (RAP-DB), and Os03g0418600 was identified as the most likely candidate for Awn3-1 through sequence comparisons and RT-PCR assays. Awn4-2 was fine mapped to a 62.4 kb genomic region flanked by simple sequence repeat (SSR) marker M1126 and Indel maker In73 on chromosome 4L. This region contained the previously reported gene An-1 that regulates awn development. Thus, An-1 may be the candidate gene of Awn4-2. These results will facilitate cloning of the awn genes and thereby provide an understanding of the molecular basis of awn development. PMID:27494628

  3. THE mPER2 CLOCK GENE MODULATES COCAINE ACTIONS IN THE MOUSE CIRCADIAN SYSTEM

    PubMed Central

    Brager, Allison J.; Stowie, Adam C.; Prosser, Rebecca A.; Glass, J. David

    2014-01-01

    Cocaine is a potent disruptor of photic and non-photic pathways for circadian entrainment of the master circadian clock of the suprachiasmatic nucleus (SCN). These actions of cocaine likely involve its modulation of molecular (clock gene) components for SCN clock timekeeping. At present, however, the physiological basis of such an interaction is unclear. To address this question, we compared photic and non-photic phase-resetting responses between wild-type (WT) and Per2 mutant mice expressing nonfunctional PER2 protein to systemic and intra-SCN cocaine administrations. In the systemic trials, cocaine was administered i.p. (20 mg/kg) either at midday or prior to a light pulse in the early night to assess its non-photic and photic behavioral phase-resetting actions, respectively. In the intra-SCN trial, cocaine was administered by reverse microdialysis at midday to determine if the SCN is a direct target for its non-photic phase-resetting action. Non-photic phase-advancing responses to i.p. cocaine at midday were significantly (~3.5-fold) greater in Per2 mutants than WTs. However, the phase-advancing action of intra-SCN cocaine perfusion at midday did not differ between genotypes. In the light pulse trial, Per2 mutants exhibited larger photic phase-delays than did WTs, and the attenuating action of cocaine on this response was proportionately larger than in WTs. These data indicate that the Per2 clock gene is a potent modulator of cocaine’s actions in the circadian system. With regard to non-photic phase-resetting, the SCN is confirmed as a direct target of cocaine action; however, Per2 modulation of this effect likely occurs outside of the SCN. PMID:23333842

  4. Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases

    PubMed Central

    Moehle, Erica A.; Rock, Jeremy M.; Lee, Ya-Li; Jouvenot, Yann; DeKelver, Russell C.; Gregory, Philip D.; Urnov, Fyodor D.; Holmes, Michael C.

    2007-01-01

    Efficient incorporation of novel DNA sequences into a specific site in the genome of living human cells remains a challenge despite its potential utility to genetic medicine, biotechnology, and basic research. We find that a precisely placed double-strand break induced by engineered zinc finger nucleases (ZFNs) can stimulate integration of long DNA stretches into a predetermined genomic location, resulting in high-efficiency site-specific gene addition. Using an extrachromosomal DNA donor carrying a 12-bp tag, a 900-bp ORF, or a 1.5-kb promoter-transcription unit flanked by locus-specific homology arms, we find targeted integration frequencies of 15%, 6%, and 5%, respectively, within 72 h of treatment, and with no selection for the desired event. Importantly, we find that the integration event occurs in a homology-directed manner and leads to the accurate reconstruction of the donor-specified genotype at the endogenous chromosomal locus, and hence presumably results from synthesis-dependent strand annealing repair of the break using the donor DNA as a template. This site-specific gene addition occurs with no measurable increase in the rate of random integration. Remarkably, we also find that ZFNs can drive the addition of an 8-kb sequence carrying three distinct promoter-transcription units into an endogenous locus at a frequency of 6%, also in the absence of any selection. These data reveal the surprising versatility of the specialized polymerase machinery involved in double-strand break repair, illuminate a powerful approach to mammalian cell engineering, and open the possibility of ZFN-driven gene addition therapy for human genetic disease. PMID:17360608

  5. Genetic linkage analysis to identify a gene required for the addition of phosphoethanolamine to meningococcal lipopolysaccharide.

    PubMed

    Tang, Christoph M; Stroud, Dave; Mackinnon, Fiona; Makepeace, Katherine; Plested, Joyce; Moxon, E Richard; Chalmers, Ronald

    2002-02-01

    Lipopolysaccharide (LPS) is important for the virulence of Neisseria meningitidis, and is the target of immune responses. We took advantage of a monoclonal antibody (Mab B5) that recognises phosphoethanolamine (PEtn) attached to the inner core of meningococcal LPS to identify genes required for the addition of PEtn to LPS. Insertional mutants that lost Mab B5 reactivity were isolated and characterised, but failed to yield genes directly responsible for PEtn substitution. Subsequent genetic linkage analysis was used to define a region of DNA containing a single intact open reading frame which is sufficient to confer B5 reactivity to a B5 negative meningococcal isolate. The results provide an initial characterisation of the genetic basis of a key, immunodominant epitope of meningococcal LPS.

  6. [Gene therapy: nucleic acids as drugs. Action mechanisms and delivery into the cell].

    PubMed

    Cavagnari, Brian M

    2011-06-01

    Gene therapy involves the transference of new genetic material to the cell in order to obtain a therapeutic benefit, offering a new option for the treatment of various diseases. In this article, some of these nucleic acid-based drugs, such as plasmids, aptamers, oligonucleotides, ribozymes and small interfering ribonucleic acid, are presented. Their mechanism and level of action is commented and several delivery systems, such as liposomes, cationic polymers, direct nucleic acid transfer and viral vectors, are also discussed.

  7. Effect of ethylene action inhibitors upon wound-induced gene expression in tomato pericarp

    SciTech Connect

    Henstrand, J.M.; Handa, A.K. )

    1989-09-01

    The contribution of wound-ethylene to wound-induced gene expression was investigated in unripe tomato pericarp using inhibitors of ethylene action. Wounded unripe tomato pericarp was treated with 2,5-norbornadiene or silver thiosulfate to inhibit specifically the induction of ethylene-dependent mRNA species. Poly(A){sup +} RNAs isolated from these tissues after 12 hours of wounding were translated in vitro in a rabbit reticulocyte lysate system and ({sup 35}S)methionine-labeled polypeptides were compared to unwounded controls after separation by one and two-dimensional polyacrylamide gel electrophoresis. Results show that mechanical wounding induces a dramatic shift in gene expression (over 50 mRNA species) but expression of less than 15% of these genes is affected by the treatment with ethylene action inhibitors. A selective decrease in mRNAs coding for a 37 kilodalton doublet and 75 kilodalton polypeptides is observed in 2,5-norbornadiene and silver thiosulfate treated wounded pericarp. Levels of hydroxyproline-rich glycoprotein mRNAs induced in wounded tissue were not influenced by inhibitors of ethylene action.

  8. Five Additional Genes Are Involved in Clavulanic Acid Biosynthesis in Streptomyces clavuligerus

    PubMed Central

    Jensen, S. E.; Paradkar, A. S.; Mosher, R. H.; Anders, C.; Beatty, P. H.; Brumlik, M. J.; Griffin, A.; Barton, B.

    2004-01-01

    An approximately 12.5-kbp region of DNA sequence from beyond the end of the previously described clavulanic acid gene cluster was analyzed and found to encode nine possible open reading frames (ORFs). Involvement of these ORFs in clavulanic acid biosynthesis was assessed by creating mutants with defects in each of the ORFs. orf12 and orf14 had been previously reported to be involved in clavulanic acid biosynthesis. Now five additional ORFs are shown to play a role, since their mutation results in a significant decrease or total absence of clavulanic acid production. Most of these newly described ORFs encode proteins with little similarity to others in the databases, and so their roles in clavulanic acid biosynthesis are unclear. Mutation of two of the ORFs, orf15 and orf16, results in the accumulation of a new metabolite, N-acetylglycylclavaminic acid, in place of clavulanic acid. orf18 and orf19 encode apparent penicillin binding proteins, and while mutations in these genes have minimal effects on clavulanic acid production, their normal roles as cell wall biosynthetic enzymes and as targets for β-lactam antibiotics, together with their clustered location, suggest that they are part of the clavulanic acid gene cluster. PMID:14693539

  9. Gene expression signature-based approach identifies a pro-resolving mechanism of action for histone deacetylase inhibitors

    PubMed Central

    Montero-Melendez, T; Dalli, J; Perretti, M

    2013-01-01

    Despite several therapies being currently available to treat inflammatory diseases, new drugs to treat chronic conditions with less side effects and lower production costs are still needed. An innovative approach to drug discovery, the Connectivity Map (CMap), shows how integrating genome-wide gene expression data of drugs and diseases can accelerate this process. Comparison of genome-wide gene expression data generated with annexin A1 (AnxA1) with the CMap revealed significant alignment with gene profiles elicited by histone deacetylase inhibitors (HDACIs), what made us to hypothesize that AnxA1 might mediate the anti-inflammatory actions of HDACIs. Addition of HDACIs (valproic acid, sodium butyrate and thricostatin A) to mouse macrophages caused externalization of AnxA1 with concomitant inhibition of cytokine gene expression and release, events that occurred independently as this inhibition was retained in AnxA1 null macrophages. In contrast, novel AnxA1-mediated functions for HDACIs could be unveiled, including promotion of neutrophil apoptosis and macrophage phagocytosis, both steps crucial for effective resolution of inflammation. In a model of acute resolving inflammation, administration of valproic acid and sodium butyrate to mice at the peak of disease accelerated resolution processes in wild type, but much more modestly in AnxA1 null mice. Deeper analyses revealed a role for endogenous AnxA1 in the induction of neutrophil death in vivo by HDACIs. In summary, interrogation of the CMap revealed an unexpected association between HDACIs and AnxA1 that translated in mechanistic findings with particular impact on the processes that regulate the resolution of inflammation. We propose non-genomic modulation of AnxA1 in immune cells as a novel mechanism of action for HDACIs, which may underlie their reported efficacy in models of chronic inflammatory pathologies. PMID:23222458

  10. Defining the epigenetic actions of growth hormone: acute chromatin changes accompany GH-activated gene transcription.

    PubMed

    Chia, Dennis J; Rotwein, Peter

    2010-10-01

    Many of the long-term physiological effects of GH require hormone-mediated changes in gene expression. The transcription factor signal transducer and activator of transcription 5b (Stat5b) plays a critical role in the actions of GH on growth and metabolism by regulating a large number of GH-dependent genes by incompletely understood mechanisms. Here we have assessed the impact of GH-initiated and Stat5b-mediated signaling on the chromatin landscape of hormone-regulated genes in the liver of pituitary-deficient young adult male rats. In the absence of GH there was minimal ongoing transcription at the Socs2, Cish, Igfals, and Spi 2.1 promoters, minimal occupancy of Stat5b at proximal promoter sites, and relatively closed chromatin, as evidenced by low levels of core histone acetylation. In contrast, transcriptionally silent Igf1 promoter 1 appeared poised to be activated, based on binding of coactivators p300 and Med1/Trap220, high levels of histone acetylation, and the presence of RNA polymerase II. GH treatment led to a 8- to 20-fold rise in transcriptional activity of all five genes within 30-60 min and was accompanied by binding of Stat5b to the proximal Socs2, Cish, Igfals, and Spi 2.1 promoters and to seven distal Igf1 Stat5b elements, by enhanced histone acetylation at all five promoters, by recruitment of RNA polymerase II to the Socs2, Cish, Igfals, and Spi 2.1 promoters, and by loss of the transcriptional repressor Bcl6 from Socs2, Cish, and Igfals Stat5b sites, but not from two Igf1 Stat5b domains. We conclude that GH actions induce rapid and dramatic changes in hepatic chromatin at target promoters and propose that the chromatin signature of Igf1 differs from other GH-and Stat5b-dependent genes. PMID:20702579

  11. Inferring gene regulatory networks using a time-delayed mass action model.

    PubMed

    Zhao, Yaou; Jiang, Mingyan; Chen, Yuehui

    2016-08-01

    This paper demonstrates a new time-delayed mass action model which applies a set of delay differential equations (DDEs) to represent the dynamics of gene regulatory networks (GRNs). The mass action model is a classical model which is often used to describe the kinetics of biochemical processes, so it is fit for GRN modeling. The ability to incorporate time-delayed parameters in this model enables different time delays of interaction between genes. Moreover, an efficient learning method which employs population-based incremental learning (PBIL) algorithm and trigonometric differential evolution (TDE) algorithm TDE is proposed to automatically evolve the structure of the network and infer the optimal parameters from observed time-series gene expression data. Experiments on three well-known motifs of GRN and a real budding yeast cell cycle network show that the proposal can not only successfully infer the network structure and parameters but also has a strong anti-noise ability. Compared with other works, this method also has a great improvement in performances.

  12. Sparse Additive Ordinary Differential Equations for Dynamic Gene Regulatory Network Modeling

    PubMed Central

    Wu, Hulin; Lu, Tao; Xue, Hongqi; Liang, Hua

    2014-01-01

    Summary The gene regulation network (GRN) is a high-dimensional complex system, which can be represented by various mathematical or statistical models. The ordinary differential equation (ODE) model is one of the popular dynamic GRN models. High-dimensional linear ODE models have been proposed to identify GRNs, but with a limitation of the linear regulation effect assumption. In this article, we propose a sparse additive ODE (SA-ODE) model, coupled with ODE estimation methods and adaptive group LASSO techniques, to model dynamic GRNs that could flexibly deal with nonlinear regulation effects. The asymptotic properties of the proposed method are established and simulation studies are performed to validate the proposed approach. An application example for identifying the nonlinear dynamic GRN of T-cell activation is used to illustrate the usefulness of the proposed method. PMID:25061254

  13. Sparse Additive Ordinary Differential Equations for Dynamic Gene Regulatory Network Modeling.

    PubMed

    Wu, Hulin; Lu, Tao; Xue, Hongqi; Liang, Hua

    2014-04-01

    The gene regulation network (GRN) is a high-dimensional complex system, which can be represented by various mathematical or statistical models. The ordinary differential equation (ODE) model is one of the popular dynamic GRN models. High-dimensional linear ODE models have been proposed to identify GRNs, but with a limitation of the linear regulation effect assumption. In this article, we propose a sparse additive ODE (SA-ODE) model, coupled with ODE estimation methods and adaptive group LASSO techniques, to model dynamic GRNs that could flexibly deal with nonlinear regulation effects. The asymptotic properties of the proposed method are established and simulation studies are performed to validate the proposed approach. An application example for identifying the nonlinear dynamic GRN of T-cell activation is used to illustrate the usefulness of the proposed method. PMID:25061254

  14. Liver lipid molecules induce PEPCK-C gene transcription and attenuate insulin action

    SciTech Connect

    Chen Guoxun

    2007-09-28

    Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) plays key roles in gluconeogenesis, glyceroneogenesis, and cataplerosis. Experiments were designed to examine the effects of endogenous lipid molecules from rat livers on the expression of PEPCK-C gene in primary rat hepatocytes. The lipid extracts prepared from livers of Zucker fatty, lean, and Wistar rats induced the expression levels of PEPCK-C transcripts. Insulin-mediated reduction of PEPCK-C gene expression was attenuated by the same treatment. The lipid extracts induced the relative luciferase activity of reporter gene constructs that contain a 2.2-kb 5' promoter fragment of PEPCK-C gene, but not the construct that contains only the 3' untranslated region (UTR) of its mRNA. The estimated half life of PEPCK-C transcripts in the presence of the lipid extract is the same as that in the absence of it. My results demonstrate for the first time that endogenous lipid molecules induce PEPCK-C gene transcription and attenuate insulin action in liver.

  15. Developments in sclerostin biology: regulation of gene expression, mechanisms of action, and physiological functions.

    PubMed

    Weivoda, Megan M; Oursler, Merry Jo

    2014-03-01

    The SOST gene, which encodes the protein sclerostin, was identified through genetic linkage analysis of sclerosteosis and van Buchem's disease patients. Sclerostin is a secreted glycoprotein that binds to the low-density lipoprotein receptor-related proteins 4, 5, and 6 to inhibit Wnt signaling. Since the initial discovery of sclerostin, much understanding has been gained into the role of this protein in the regulation of skeletal biology. In this article, we discuss the latest findings in the regulation of SOST expression, sclerostin mechanisms of action, and the potential utility of targeting sclerostin in conditions of low bone mass.

  16. Gene-Environment Interactions in Stress Response Contribute Additively to a Genotype-Environment Interaction

    PubMed Central

    Matsui, Takeshi; Ehrenreich, Ian M.

    2016-01-01

    How combinations of gene-environment interactions collectively give rise to genotype-environment interactions is not fully understood. To shed light on this problem, we genetically dissected an environment-specific poor growth phenotype in a cross of two budding yeast strains. This phenotype is detectable when certain segregants are grown on ethanol at 37°C (‘E37’), a condition that differs from the standard culturing environment in both its carbon source (ethanol as opposed to glucose) and temperature (37°C as opposed to 30°C). Using recurrent backcrossing with phenotypic selection, we identified 16 contributing loci. To examine how these loci interact with each other and the environment, we focused on a subset of four loci that together can lead to poor growth in E37. We measured the growth of all 16 haploid combinations of alleles at these loci in all four possible combinations of carbon source (ethanol or glucose) and temperature (30 or 37°C) in a nearly isogenic population. This revealed that the four loci act in an almost entirely additive manner in E37. However, we also found that these loci have weaker effects when only carbon source or temperature is altered, suggesting that their effect magnitudes depend on the severity of environmental perturbation. Consistent with such a possibility, cloning of three causal genes identified factors that have unrelated functions in stress response. Thus, our results indicate that polymorphisms in stress response can show effects that are intensified by environmental stress, thereby resulting in major genotype-environment interactions when multiple of these variants co-occur. PMID:27437938

  17. Correlating chemical sensitivity and basal gene expression reveals mechanism of action.

    PubMed

    Rees, Matthew G; Seashore-Ludlow, Brinton; Cheah, Jaime H; Adams, Drew J; Price, Edmund V; Gill, Shubhroz; Javaid, Sarah; Coletti, Matthew E; Jones, Victor L; Bodycombe, Nicole E; Soule, Christian K; Alexander, Benjamin; Li, Ava; Montgomery, Philip; Kotz, Joanne D; Hon, C Suk-Yee; Munoz, Benito; Liefeld, Ted; Dančík, Vlado; Haber, Daniel A; Clish, Clary B; Bittker, Joshua A; Palmer, Michelle; Wagner, Bridget K; Clemons, Paul A; Shamji, Alykhan F; Schreiber, Stuart L

    2016-02-01

    Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity across many cell lines to illuminate the actions of compounds whose MoA are unknown. To test this idea, we correlated the sensitivity patterns of 481 compounds with ∼19,000 basal transcript levels across 823 different human cancer cell lines and identified selective outlier transcripts. This process yielded many novel mechanistic insights, including the identification of activation mechanisms, cellular transporters and direct protein targets. We found that ML239, originally identified in a phenotypic screen for selective cytotoxicity in breast cancer stem-like cells, most likely acts through activation of fatty acid desaturase 2 (FADS2). These data and analytical tools are available to the research community through the Cancer Therapeutics Response Portal.

  18. Correlating chemical sensitivity and basal gene expression reveals mechanism of action.

    PubMed

    Rees, Matthew G; Seashore-Ludlow, Brinton; Cheah, Jaime H; Adams, Drew J; Price, Edmund V; Gill, Shubhroz; Javaid, Sarah; Coletti, Matthew E; Jones, Victor L; Bodycombe, Nicole E; Soule, Christian K; Alexander, Benjamin; Li, Ava; Montgomery, Philip; Kotz, Joanne D; Hon, C Suk-Yee; Munoz, Benito; Liefeld, Ted; Dančík, Vlado; Haber, Daniel A; Clish, Clary B; Bittker, Joshua A; Palmer, Michelle; Wagner, Bridget K; Clemons, Paul A; Shamji, Alykhan F; Schreiber, Stuart L

    2016-02-01

    Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity across many cell lines to illuminate the actions of compounds whose MoA are unknown. To test this idea, we correlated the sensitivity patterns of 481 compounds with ∼19,000 basal transcript levels across 823 different human cancer cell lines and identified selective outlier transcripts. This process yielded many novel mechanistic insights, including the identification of activation mechanisms, cellular transporters and direct protein targets. We found that ML239, originally identified in a phenotypic screen for selective cytotoxicity in breast cancer stem-like cells, most likely acts through activation of fatty acid desaturase 2 (FADS2). These data and analytical tools are available to the research community through the Cancer Therapeutics Response Portal. PMID:26656090

  19. Correlating chemical sensitivity and basal gene expression reveals mechanism of action

    PubMed Central

    Rees, Matthew G.; Seashore-Ludlow, Brinton; Cheah, Jaime H.; Adams, Drew J.; Price, Edmund V.; Gill, Shubhroz; Javaid, Sarah; Coletti, Matthew E.; Jones, Victor L.; Bodycombe, Nicole E.; Soule, Christian K.; Alexander, Benjamin; Li, Ava; Montgomery, Philip; Kotz, Joanne D.; Hon, C. Suk-Yee; Munoz, Benito; Liefeld, Ted; Dančík, Vlado; Haber, Daniel A.; Clish, Clary B.; Bittker, Joshua A.; Palmer, Michelle; Wagner, Bridget K.; Clemons, Paul A.; Shamji, Alykhan F.; Schreiber, Stuart L.

    2015-01-01

    Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity across many cell lines to illuminate the actions of compounds whose MoA are unknown. To test this idea, we correlated the sensitivity patterns of 481 compounds with ~19,000 basal transcript levels across 823 different human cancer cell lines and identified selective outlier transcripts. This process yielded many novel mechanistic insights, including the identification of activation mechanisms, cellular transporters, and direct protein targets. We found that ML239, originally identified in a phenotypic screen for selective cytotoxicity in breast cancer stem-like cells, most likely acts through activation of fatty acid desaturase 2 (FADS2). These data and analytical tools are available to the research community through the Cancer Therapeutics Response Portal. PMID:26656090

  20. Additive insulinogenic action of Opuntia ficus-indica cladode and fruit skin extract and leucine after exercise in healthy males

    PubMed Central

    2013-01-01

    Background Oral intake of a specific extract of Opuntia ficus-indica cladode and fruit skin (OpunDia™) (OFI) has been shown to increase serum insulin concentration while reducing blood glucose level for a given amount of glucose ingestion after an endurance exercise bout in healthy young volunteers. However, it is unknown whether OFI-induced insulin stimulation after exercise is of the same magnitude than the stimulation by other insulinogenic agents like leucine as well as whether OFI can interact with those agents. Therefore, the aims of the present study were: 1) to compare the degree of insulin stimulation by OFI with the effect of leucine administration; 2) to determine whether OFI and leucine have an additive action on insulin stimulation post-exercise. Methods Eleven subjects participated in a randomized double-blind cross-over study involving four experimental sessions. In each session the subjects successively underwent a 2-h oral glucose tolerance test (OGTT) after a 30-min cycling bout at ~70% VO2max. At t0 and t60 during the OGTT, subjects ingested 75 g glucose and capsules containing either 1) a placebo; 2) 1000 mg OFI; 3) 3 g leucine; 4) 1000 mg OFI + 3 g leucine. Blood samples were collected before and at 30-min intervals during the OGTT for determination of blood glucose and serum insulin. Results Whereas no effect of leucine was measured, OFI reduced blood glucose at t90 by ~7% and the area under the glucose curve by ~15% and increased serum insulin concentration at t90 by ~35% compared to placebo (P<0.05). From t60 to the end of the OGTT, serum insulin concentration was higher in OFI+leucine than in placebo which resulted in a higher area under the insulin curve (+40%, P<0.05). Conclusion Carbohydrate-induced insulin stimulation post-exercise can be further increased by the combination of OFI with leucine. OFI and leucine could be interesting ingredients to include together in recovery drinks to resynthesize muscle glycogen faster post

  1. Localization of eight additional genes in the human major histocompatibility complex, including the gene encoding the casein kinase II {beta} subunit (CSNK2B)

    SciTech Connect

    Albertella, M.R.; Jones, H.; Thomson, W.

    1996-09-01

    A wide range of autoimmune and other diseases are known to be associated with the major histocompatibility complex. Many of these diseases are linked to the genes encoding the polymorphic histocompatibility complex. Many of these diseases are linked to the genes encoding the polymorphic histocompatibility antigens in the class I and class II regions, but some appear to be more strongly associated with genes in the central 1100-kb class III region, making it important to characterize this region fully for the presence of novel genes. An {approximately}220-kb segment of DNA in the class III region separating the Hsp70 (HSPA1L) and BAT1 (D6S8IE) genes, which was previously known to contain 14 genes. Genomic DNA fragments spanning the gaps between the known genes were used as probes to isolate cDNAs corresponding to five new genes within this region. Evidence from Northern blot analysis and exon trapping experiments that suggested the presence of at least two more new genes was also obtained. Partial cDNA and complete exonic genomic sequencing of one of the new genes has identified it as the casein kinase II{beta} subunit (CSNK2B). Two of the other novel genes lie within a region syntenic to that implicated in susceptibility to experimental allergic orchitis in the mouse, an autoimmune disease of the testis, and represent additional candidates for the Orch-1 locus associated with this disease. In addition, characterization of the 13-kb intergenic gap separating the RD (D6545) and G11 (D6S60E) genes has revealed the presence of a gene encoding a 1246-amino-acid polypeptide that shows significant sequence similarity to the yeast anti-viral Ski2p gene product. 49 refs., 8 figs.

  2. Toxicological safety assessment of genetically modified Bacillus thuringiensis with additional N-acyl homoserine lactonase gene.

    PubMed

    Peng, Donghai; Zhou, Chenfei; Chen, Shouwen; Ruan, Lifang; Yu, Ziniu; Sun, Ming

    2008-01-01

    The aim of the present study is to evaluate the toxicology safety to mammals of a genetically modified (GM) Bacillus thuringiensis with an additional N-acyl homoserine lactones gene (aiiA), which possesses insecticidal activity together with restraint of bacterial pathogenicity and is intended for use as a multifunctional biopesticide. Safety assessments included an acute oral toxicity test and 28-d animal feeding study in Wistar rats, primary eye and dermal irritation in Zealand White rabbits, and delayed contact hypersensitivity in guinea pigs. Tests were conducted using spray-dried powder preparation. This GM product showed toxicity neither in oral acute toxicity test nor in 28-d animal feeding test at a dose of 5,000 mg/kg body weight. During the animal feeding test, there were no significant differences in growth, food and water consumption, hematology, blood biochemical indices, organ weights, and histopathology finding between rats in controls and tested groups. Tested animals in primary eye and dermal irritation and delayed contact hypersensitivity test were also devoid of any toxicity compared to controls. All the above results demonstrated that the GM based multifunctional B. thuringiensis has low toxicity and low eye and dermal irritation and would not cause hypersensitivity to laboratory mammals and therefore could be regarded as safe for use as a pesticide.

  3. Additional Evidence of the Trypanocidal Action of (−)-Elatol on Amastigote Forms through the Involvement of Reactive Oxygen Species

    PubMed Central

    Desoti, Vânia Cristina; Lazarin-Bidóia, Danielle; Sudatti, Daniela Bueno; Pereira, Renato Crespo; Ueda-Nakamura, Tania; Nakamura, Celso Vataru; de Oliveira Silva, Sueli

    2014-01-01

    Chagas’ disease, a vector-transmitted infectious disease, is caused by the protozoa parasite Trypanosoma cruzi. Drugs that are currently available for the treatment of this disease are unsatisfactory, making the search for new chemotherapeutic agents a priority. We recently described the trypanocidal action of (−)-elatol, extracted from the macroalga Laurencia dendroidea. However, nothing has been described about the mechanism of action of this compound on amastigotes that are involved in the chronic phase of Chagas’ disease. The goal of the present study was to evaluate the effect of (−)-elatol on the formation of superoxide anions (O2•−), DNA fragmentation, and autophagy in amastigotes of T. cruzi to elucidate the possible mechanism of the trypanocidal action of (−)-elatol. Treatment of the amastigotes with (−)-elatol increased the formation of O2•− at all concentrations of (−)-elatol assayed compared with untreated parasites. Increased fluorescence was observed in parasites treated with (−)-elatol, indicating DNA fragmentation and the formation of autophagic compartments. The results suggest that the trypanocidal action of (−)-elatol might involve the induction of the autophagic and apoptotic death pathways triggered by an imbalance of the parasite’s redox metabolism. PMID:25257785

  4. Identification of additive, dominant, and epistatic variation conferred by key genes in cellulose biosynthesis pathway in Populus tomentosa†.

    PubMed

    Du, Qingzhang; Tian, Jiaxing; Yang, Xiaohui; Pan, Wei; Xu, Baohua; Li, Bailian; Ingvarsson, Pär K; Zhang, Deqiang

    2015-02-01

    Economically important traits in many species generally show polygenic, quantitative inheritance. The components of genetic variation (additive, dominant and epistatic effects) of these traits conferred by multiple genes in shared biological pathways remain to be defined. Here, we investigated 11 full-length genes in cellulose biosynthesis, on 10 growth and wood-property traits, within a population of 460 unrelated Populus tomentosa individuals, via multi-gene association. To validate positive associations, we conducted single-marker analysis in a linkage population of 1,200 individuals. We identified 118, 121, and 43 associations (P< 0.01) corresponding to additive, dominant, and epistatic effects, respectively, with low to moderate proportions of phenotypic variance (R(2)). Epistatic interaction models uncovered a combination of three non-synonymous sites from three unique genes, representing a significant epistasis for diameter at breast height and stem volume. Single-marker analysis validated 61 associations (false discovery rate, Q ≤ 0.10), representing 38 SNPs from nine genes, and its average effect (R(2) = 3.8%) nearly 2-fold higher than that identified with multi-gene association, suggesting that multi-gene association can capture smaller individual variants. Moreover, a structural gene-gene network based on tissue-specific transcript abundances provides a better understanding of the multi-gene pathway affecting tree growth and lignocellulose biosynthesis. Our study highlights the importance of pathway-based multiple gene associations to uncover the nature of genetic variance for quantitative traits and may drive novel progress in molecular breeding.

  5. Gene actions for yield and its attributes and their implications in the inheritance pattern over three generations in opium poppy (Papaver somniferum L.).

    PubMed

    Mishra, Brij K; Mishra, R; Jena, S N; Shukla, Sudhir

    2016-09-01

    The gene actions for yield and its attributes and their inheritance pattern based on five parameter model have been explored in four single crosses (NBIHT-5 × NBIHT-6, NBIHT-5 × NBMHT-1, NBMHT-1 × NBIHT-6 and NBMHT-2 × NBMHT-1) obtained using thebaine rich pure lines of opium poppy (Papaver somniferum L.) for three consecutive generations. All the traits showed nonallelic mode of interaction, however, dominance effect (h) was more pronounced for all the traits except thebaine and papaverine. The dominance × dominance (l) effects were predominant over additive × additive (i) for all traits in all the four crosses except for papaverine. The seed and opium yield, and its contributing traits inherited quantitatively. The fixable gene effects (d) and (i) were lower in magnitude than nonfixable (h) and (l) gene effects. The estimates of heterosis were also higher in comparison to the respective parents which suggested preponderance of dominance gene action for controlling most of the traits. The phenotypic coefficient of variation was marginally higher than those of genotypic coefficient of variation for all the traits. The traits thebaine, narcotine, morphine and opium yield had high heritability coupled with high genetic advance. The leaf number, branches per plant and stem diameter showed positive correlation with opium and seed yields. The selection of plants having large number of leaves, branches and capsules with bigger size would be advantageous to enhance the yield potential. PMID:27659342

  6. Gene actions for yield and its attributes and their implications in the inheritance pattern over three generations in opium poppy (Papaver somniferum L.).

    PubMed

    Mishra, Brij K; Mishra, R; Jena, S N; Shukla, Sudhir

    2016-09-01

    The gene actions for yield and its attributes and their inheritance pattern based on five parameter model have been explored in four single crosses (NBIHT-5 × NBIHT-6, NBIHT-5 × NBMHT-1, NBMHT-1 × NBIHT-6 and NBMHT-2 × NBMHT-1) obtained using thebaine rich pure lines of opium poppy (Papaver somniferum L.) for three consecutive generations. All the traits showed nonallelic mode of interaction, however, dominance effect (h) was more pronounced for all the traits except thebaine and papaverine. The dominance × dominance (l) effects were predominant over additive × additive (i) for all traits in all the four crosses except for papaverine. The seed and opium yield, and its contributing traits inherited quantitatively. The fixable gene effects (d) and (i) were lower in magnitude than nonfixable (h) and (l) gene effects. The estimates of heterosis were also higher in comparison to the respective parents which suggested preponderance of dominance gene action for controlling most of the traits. The phenotypic coefficient of variation was marginally higher than those of genotypic coefficient of variation for all the traits. The traits thebaine, narcotine, morphine and opium yield had high heritability coupled with high genetic advance. The leaf number, branches per plant and stem diameter showed positive correlation with opium and seed yields. The selection of plants having large number of leaves, branches and capsules with bigger size would be advantageous to enhance the yield potential.

  7. Cardiovascular actions of DOPA mediated by the gene product of ocular albinism 1.

    PubMed

    Goshima, Yoshio; Nakamura, Fumio; Masukawa, Daiki; Chen, Sandy; Koga, Motokazu

    2014-01-01

    l-3,4-Dihydroxyphenylalanine (DOPA) is the metabolic precursor of dopamine, and the single most effective agent in the treatment of Parkinson's disease. One problem with DOPA therapy for Parkinson's disease is its cardiovascular side effects including hypotension and syncope, the underlying mechanisms of which are largely unknown. We proposed that DOPA is a neurotransmitter in the central nervous system, but specific receptors for DOPA had not been identified. Recently, the gene product of ocular albinism 1 (OA1) was shown to possess DOPA-binding activity. It was unknown, however, whether or not OA1 is responsible for the actions of DOPA itself. Immunohistochemical examination revealed that OA1 was expressed in the nucleus tractus solitarii (NTS). OA1-positive cells adjacent to tyrosine hydroxylase-positive cell bodies and nerve fibers were detected in the depressor sites of the NTS. OA1 knockdown using oa1-specific shRNA-adenovirus vectors in the NTS reduced the expression levels of OA1 in the NTS. The prior injection of the shRNA against OA1 suppressed the depressor and bradycardic responses to DOPA but not to glutamate in the NTS of anesthetized rats. Thus OA-1 is a functional receptor of DOPA in the NTS, which warrants reexamination of the mechanisms for the therapeutic and untoward actions of DOPA. PMID:25185585

  8. Random transposon mutagenesis of the Saccharopolyspora erythraea genome reveals additional genes influencing erythromycin biosynthesis.

    PubMed

    Fedashchin, Andrij; Cernota, William H; Gonzalez, Melissa C; Leach, Benjamin I; Kwan, Noelle; Wesley, Roy K; Weber, J Mark

    2015-11-01

    A single cycle of strain improvement was performed in Saccharopolyspora erythraea mutB and 15 genotypes influencing erythromycin production were found. Genotypes generated by transposon mutagenesis appeared in the screen at a frequency of ~3%. Mutations affecting central metabolism and regulatory genes were found, as well as hydrolases, peptidases, glycosyl transferases and unknown genes. Only one mutant retained high erythromycin production when scaled-up from micro-agar plug fermentations to shake flasks. This mutant had a knockout of the cwh1 gene (SACE_1598), encoding a cell-wall-associated hydrolase. The cwh1 knockout produced visible growth and morphological defects on solid medium. This study demonstrated that random transposon mutagenesis uncovers strain improvement-related genes potentially useful for strain engineering. PMID:26468041

  9. Altered expression of genes involved in progesterone biosynthesis, metabolism and action in endometrial cancer.

    PubMed

    Sinreih, Maša; Hevir, Neli; Rižner, Tea Lanišnik

    2013-02-25

    Endometrial cancer (EC) is one of the most common gynecological malignancies worldwide. It is associated with prolonged exposure to estrogens that is unopposed by the protective effects of progesterone, which suggests that altered progesterone biosynthesis, metabolism and actions might be implicated in the development of EC. Our aim was to evaluate these processes through quantitative real-time PCR expression analysis in up to 47 pairs of EC tissue and adjacent control endometrium. First, we examined the expression of genes encoding proteins associated with progesterone biosynthesis: steroidogenic acute regulatory protein (STAR); a side chain cleavage enzyme (CYP11A1); and 3β-hydroxysteroid dehydrogenase/ketosteroid isomerase (HSD3B). There were 1.9- and 10.0-fold decreased expression of STAR and CYP11A1, respectively, in EC versus adjacent control endometrium, with no significant differences in the expression of HSD3B1 and HSD3B2. Next, we examined expression of genes encoding five progesterone metabolizing enzymes: the 3-keto and 20-ketosteroid reductases (AKR1C1-AKR1C3) and 5α-reductases (SRD5A1 and SRD5A2); and the opposing 20α-hydroxysteroid dehydrogenase (HSD17B2). These genes are expressed in EC and adjacent control endometrium. No statistically significant differences were seen in mRNA levels of AKR1C1, AKR1C2, AKR1C3 and SRD5A1. Expression of HSD17B2 was 3.0-fold increased, and expression of SRD5A2 was 3.7-fold decreased, in EC versus adjacent control endometrium. We also examined mRNA levels of progesterone receptors A and B (PGR), and separately the expression of progesterone receptor B (PR-B). Here we saw 1.8- and 2.0-fold lower mRNA levels of PGR and PR-B, respectively, in EC versus adjacent control endometrium. This down-regulation of STAR, CYP11A1 and PGR in endometrial cancer may lead to decreased progesterone biosynthesis and actions although the effects on progesterone levels should be further studied.

  10. Identification of a sugar beet BvM14-MADS box gene through differential gene expression analysis of monosomic addition line M14.

    PubMed

    Ma, Chunquan; Wang, Yuguang; Wang, Yuting; Wang, Lifa; Chen, Sixue; Li, Haiying

    2011-11-01

    Monosomic addition line M14 carrying an additional chromosome 9 from Beta corolliflora Zosimovic ex Buttler was obtained through hybridization between the wild species B. corolliflora and a cultivated species Beta vulgaris L. var Saccharifera Alef. The M14 line showed diplosporic reproduction and stress tolerance. To identify differentially expressed genes in M14, a subtractive cDNA library was prepared by suppression subtractive hybridization (SSH) between M14 (2n=18+1) and B. vulgaris (2n=18). A total of 190 unique sequences were identified in the library and their putative functions were analyzed using Gene Ontology (GO). One of the genes, designated as BvM14-MADS box, encodes a MADS box transcription factor. It was cloned from M14 and over-expressed in transgenic tobacco plants. Interestingly, this gene was located on chromosome 2 of B. vulgaris, not on the additional chromosome 9. Overexpression of BvM14-MADS box led to significant phenotypic changes in tobacco. The differential expression of BvM14-MADS box gene in M14 may be caused by the interaction between the additional chromosome 9 from B. corolliflora and the B. vulgaris chromosomes in M14.

  11. Identification of a sugar beet BvM14-MADS box gene through differential gene expression analysis of monosomic addition line M14.

    PubMed

    Ma, Chunquan; Wang, Yuguang; Wang, Yuting; Wang, Lifa; Chen, Sixue; Li, Haiying

    2011-11-01

    Monosomic addition line M14 carrying an additional chromosome 9 from Beta corolliflora Zosimovic ex Buttler was obtained through hybridization between the wild species B. corolliflora and a cultivated species Beta vulgaris L. var Saccharifera Alef. The M14 line showed diplosporic reproduction and stress tolerance. To identify differentially expressed genes in M14, a subtractive cDNA library was prepared by suppression subtractive hybridization (SSH) between M14 (2n=18+1) and B. vulgaris (2n=18). A total of 190 unique sequences were identified in the library and their putative functions were analyzed using Gene Ontology (GO). One of the genes, designated as BvM14-MADS box, encodes a MADS box transcription factor. It was cloned from M14 and over-expressed in transgenic tobacco plants. Interestingly, this gene was located on chromosome 2 of B. vulgaris, not on the additional chromosome 9. Overexpression of BvM14-MADS box led to significant phenotypic changes in tobacco. The differential expression of BvM14-MADS box gene in M14 may be caused by the interaction between the additional chromosome 9 from B. corolliflora and the B. vulgaris chromosomes in M14. PMID:21807438

  12. Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption

    PubMed Central

    Pirastu, Nicola; Kooyman, Maarten; Robino, Antonietta; van der Spek, Ashley; Navarini, Luciano; Amin, Najaf; Karssen, Lennart C.; Van Duijn, Cornelia M; Gasparini, Paolo

    2016-01-01

    Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption. PMID:27561104

  13. Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption.

    PubMed

    Pirastu, Nicola; Kooyman, Maarten; Robino, Antonietta; van der Spek, Ashley; Navarini, Luciano; Amin, Najaf; Karssen, Lennart C; Van Duijn, Cornelia M; Gasparini, Paolo

    2016-01-01

    Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption. PMID:27561104

  14. The identification of additional zebrafish DICP genes reveals haplotype variation and linkage to MHC class I genes.

    PubMed

    Rodriguez-Nunez, Ivan; Wcisel, Dustin J; Litman, Ronda T; Litman, Gary W; Yoder, Jeffrey A

    2016-04-01

    Bony fish encode multiple multi-gene families of membrane receptors that are comprised of immunoglobulin (Ig) domains and are predicted to function in innate immunity. One of these families, the diverse immunoglobulin (Ig) domain-containing protein (DICP) genes, maps to three chromosomal loci in zebrafish. Most DICPs possess one or two Ig ectodomains and include membrane-bound and secreted forms. Membrane-bound DICPs include putative inhibitory and activating receptors. Recombinant DICP Ig domains bind lipids with varying specificity, a characteristic shared with mammalian CD300 and TREM family members. Numerous DICP transcripts amplified from different lines of zebrafish did not match the zebrafish reference genome sequence suggesting polymorphic and haplotypic variation. The expression of DICPs in three different lines of zebrafish has been characterized employing PCR-based strategies. Certain DICPs exhibit restricted expression in adult tissues whereas others are expressed ubiquitously. Transcripts of a subset of DICPs can be detected during embryonic development suggesting roles in embryonic immunity or other developmental processes. Transcripts representing 11 previously uncharacterized DICP sequences were identified. The assignment of two of these sequences to an unplaced genomic scaffold resulted in the identification of an alternative DICP haplotype that is linked to a MHC class I Z lineage haplotype on zebrafish chromosome 3. The linkage of DICP and MHC class I genes also is observable in the genomes of the related grass carp (Ctenopharyngodon idellus) and common carp (Cyprinus carpio) suggesting that this is a shared character with the last common Cyprinidae ancestor.

  15. The identification of additional zebrafish DICP genes reveals haplotype variation and linkage to MHC class I genes.

    PubMed

    Rodriguez-Nunez, Ivan; Wcisel, Dustin J; Litman, Ronda T; Litman, Gary W; Yoder, Jeffrey A

    2016-04-01

    Bony fish encode multiple multi-gene families of membrane receptors that are comprised of immunoglobulin (Ig) domains and are predicted to function in innate immunity. One of these families, the diverse immunoglobulin (Ig) domain-containing protein (DICP) genes, maps to three chromosomal loci in zebrafish. Most DICPs possess one or two Ig ectodomains and include membrane-bound and secreted forms. Membrane-bound DICPs include putative inhibitory and activating receptors. Recombinant DICP Ig domains bind lipids with varying specificity, a characteristic shared with mammalian CD300 and TREM family members. Numerous DICP transcripts amplified from different lines of zebrafish did not match the zebrafish reference genome sequence suggesting polymorphic and haplotypic variation. The expression of DICPs in three different lines of zebrafish has been characterized employing PCR-based strategies. Certain DICPs exhibit restricted expression in adult tissues whereas others are expressed ubiquitously. Transcripts of a subset of DICPs can be detected during embryonic development suggesting roles in embryonic immunity or other developmental processes. Transcripts representing 11 previously uncharacterized DICP sequences were identified. The assignment of two of these sequences to an unplaced genomic scaffold resulted in the identification of an alternative DICP haplotype that is linked to a MHC class I Z lineage haplotype on zebrafish chromosome 3. The linkage of DICP and MHC class I genes also is observable in the genomes of the related grass carp (Ctenopharyngodon idellus) and common carp (Cyprinus carpio) suggesting that this is a shared character with the last common Cyprinidae ancestor. PMID:26801775

  16. Expression patterns and action analysis of genes associated with drug-induced liver diseases during rat liver regeneration

    PubMed Central

    Ning, Qian-Ji; Qin, Shao-Wei; Xu, Cun-Shuan

    2006-01-01

    AIM: To study the action of the genes associated with drug-induced liver diseases at the gene transcriptional level during liver regeneration (LR) in rats. METHODS: The genes associated with drug-induced liver diseases were obtained by collecting the data from databases and literature, and the gene expression changes in the regenerating liver were checked by the Rat Genome 230 2.0 array. RESULTS: The initial and total expression numbers of genes occurring in phases of 0.5-4 h after partial hepatectomy (PH), 4-6 h after PH (G0/G1 transition), 6-66 h after PH (cell proliferation), 66-168 h after PH (cell differentiation and structure-function reconstruction) were 21, 3, 9, 2 and 21, 9, 19, 18, respectively. It is illustrated that the associated genes were mainly triggered at the initial stage of LR and worked at different phases. According to their expression similarity, these genes were classified into 5 types: only up-regulated (12 genes), predominantly up-regulated (4 genes), only down-regulated (11 genes), predominantly down-regulated (3 genes), and approximately up-/down-regulated (2 genes). The total times of their up- and down-expression were 130 and 79, respectively, demonstrating that expression of most of the genes was increased during LR, while a few decreased. The cell physiological and biochemical activities during LR were staggered according to the time relevance and were diverse and complicated in gene expression patterns. CONCLUSION: Drug metabolic capacity in regenerating liver was enhanced. Thirty-two genes play important roles during liver regeneration in rats. PMID:17109518

  17. GENE EXPRESSION PROFILING IN TESTIS AND LIVER OF MICE TO IDENTIFY MODES OF ACTION OF CONAZOLE TOXICITIES

    EPA Science Inventory

    Gene Expression Profiling in Testis and Liver of Mice to Identify MODES OF ACTION OF Conazole TOXICITies

    Amber K. Goetz1, Wenjun Bao2, Judith E. Schmid2, Carmen Wood2, Hongzu Ren2, Deborah S. Best2, Rachel N. Murrell1, John C. Rockett2, Michael G. Narotsky2, Douglas C. Wol...

  18. Action dynamics in multitasking: the impact of additional task factors on the execution of the prioritized motor movement.

    PubMed

    Scherbaum, Stefan; Gottschalk, Caroline; Dshemuchadse, Maja; Fischer, Rico

    2015-01-01

    In multitasking, the execution of a prioritized task is in danger of crosstalk by the secondary task. Task shielding allows minimizing this crosstalk. However, the locus and temporal dynamics of crosstalk effects and further sources of influence on the execution of the prioritized task are to-date only vaguely understood. Here we combined a dual-task paradigm with an action dynamics approach and studied how and according to which temporal characteristics crosstalk, previously experienced interference and previously executed responses influenced participants' mouse movements in the prioritized task's execution. Investigating continuous mouse movements of the prioritized task, our results indicate a continuous crosstalk from secondary task processing until the endpoint of the movement was reached, although the secondary task could only be executed after finishing execution of the prioritized task. The motor movement in the prioritized task was further modulated by previously experienced interference between the prioritized and the secondary task. Furthermore, response biases from previous responses of the prioritized and the secondary task in movements indicate different sources of such biases. The bias by previous responses to the prioritized task follows a sustained temporal pattern typical for a contextual reactivation, while the bias by previous responses to the secondary task follows a decaying temporal pattern indicating residual activation of previously activated spatial codes.

  19. Communication as a predictor of willingness to donate one's organs: an addition to the Theory of Reasoned Action.

    PubMed

    Jeffres, Leo W; Carroll, Jeanine A; Rubenking, Bridget E; Amschlinger, Joe

    2008-12-01

    Fishbein and Ajzen's theory of reasoned action has been used by many researchers, particularly in regard to health communication, to predict behavioral intentions and behavior. According to that theory, one's intention is the best predictor that one will engage in a behavior, and attitudes and social norms predict behavioral intentions. Other researchers have added different variables to the postulates of attitudes and social norms that Fishbein and Ajzen maintain are the best predictors of behavioral intention. Here we draw on data from a 2006 telephone survey (N = 420) gauging the awareness of an organ donation campaign in Northeast Ohio to examine the impact of communication on people's intentions. The current study supports the hypothesis that those who communicate with others are more likely to express a greater willingness to become an organ donor, but it expands the range of communication contexts. With demographics and attitudes toward organ donation controlled for, this study shows that communication with others about organ donation increases the willingness of individuals to have favorable attitudes about being an organ donor.

  20. Action dynamics in multitasking: the impact of additional task factors on the execution of the prioritized motor movement.

    PubMed

    Scherbaum, Stefan; Gottschalk, Caroline; Dshemuchadse, Maja; Fischer, Rico

    2015-01-01

    In multitasking, the execution of a prioritized task is in danger of crosstalk by the secondary task. Task shielding allows minimizing this crosstalk. However, the locus and temporal dynamics of crosstalk effects and further sources of influence on the execution of the prioritized task are to-date only vaguely understood. Here we combined a dual-task paradigm with an action dynamics approach and studied how and according to which temporal characteristics crosstalk, previously experienced interference and previously executed responses influenced participants' mouse movements in the prioritized task's execution. Investigating continuous mouse movements of the prioritized task, our results indicate a continuous crosstalk from secondary task processing until the endpoint of the movement was reached, although the secondary task could only be executed after finishing execution of the prioritized task. The motor movement in the prioritized task was further modulated by previously experienced interference between the prioritized and the secondary task. Furthermore, response biases from previous responses of the prioritized and the secondary task in movements indicate different sources of such biases. The bias by previous responses to the prioritized task follows a sustained temporal pattern typical for a contextual reactivation, while the bias by previous responses to the secondary task follows a decaying temporal pattern indicating residual activation of previously activated spatial codes. PMID:26217267

  1. Action dynamics in multitasking: the impact of additional task factors on the execution of the prioritized motor movement

    PubMed Central

    Scherbaum, Stefan; Gottschalk, Caroline; Dshemuchadse, Maja; Fischer, Rico

    2015-01-01

    In multitasking, the execution of a prioritized task is in danger of crosstalk by the secondary task. Task shielding allows minimizing this crosstalk. However, the locus and temporal dynamics of crosstalk effects and further sources of influence on the execution of the prioritized task are to-date only vaguely understood. Here we combined a dual-task paradigm with an action dynamics approach and studied how and according to which temporal characteristics crosstalk, previously experienced interference and previously executed responses influenced participants' mouse movements in the prioritized task's execution. Investigating continuous mouse movements of the prioritized task, our results indicate a continuous crosstalk from secondary task processing until the endpoint of the movement was reached, although the secondary task could only be executed after finishing execution of the prioritized task. The motor movement in the prioritized task was further modulated by previously experienced interference between the prioritized and the secondary task. Furthermore, response biases from previous responses of the prioritized and the secondary task in movements indicate different sources of such biases. The bias by previous responses to the prioritized task follows a sustained temporal pattern typical for a contextual reactivation, while the bias by previous responses to the secondary task follows a decaying temporal pattern indicating residual activation of previously activated spatial codes. PMID:26217267

  2. Investigation of the peak action wavelength of light-activated gene transduction.

    PubMed

    Myakishev-Rempel, M; Kuper, J; Mintz, B; Hutchinson, S; Voris, J; Zavislan, K; Offley, S; Nardia, F B; Yaseen, Z; Yen, T; Zavislan, J M; Maloney, M D; Schwarz, E M

    2011-11-01

    Light-activated gene transduction (LAGT) is an approach to localize gene therapy via preactivation of cells with UV light, which facilitates transduction by recombinant adeno-associated virus vectors. Previous studies demonstrated that UVC induces LAGT secondary to pyrimidine dimer formation, whereas UVA induces LAGT secondary to reactive-oxygen species (ROS) generation. However, the empirical UVB boundary of these UV effects is unknown. Thus, we aimed to define the action spectra for UV-induced LAGT independent of DNA damage and determine an optimal wavelength to maximize safety and efficacy. UV at 288, 311 and 320 nm produced significant dose-dependent LAGT effects, of which the maximum (800-fold) was observed with 4 kJ m⁻² at 311 nm. Consistent with its robust cytotoxicity, 288 nm produced significantly high levels of DNA damage at all doses tested, whereas 311, 320 and 330 nm did not generate pyrimidine dimers and produced low levels of DNA damage detected by comet assay. Although 288 nm failed to induce ROS, the other wavelengths were effective, with the maximum (10-fold) effect observed with 30 kJ m⁻² at 311 nm. An in vivo pilot study assessing 311 nm-induced LAGT of rabbit articular chondrocytes demonstrated a significant 6.6-fold (P<0.05) increase in transduction with insignificant cytotoxicity. In conclusion, 311 nm was found to be the optimal wavelength for LAGT on the basis of its superior efficacy at the peak dose and its broad safety range that is remarkably wider than the other UV wavelengths tested.

  3. Investigation of the peak action wavelength of light-activated gene transduction (LAGT)

    PubMed Central

    Myakishev-Rempel, Max; Kuper, Jerry; Mintz, Benjamin; Hutchinson, Sara; Voris, Jay; Zavislan, Katrina; Offley, Sarah; Nardia, Frances Barg; Yaseen, Zaneb; Yen, Tony; Zavislan, James; Maloney, Michael D.; Schwarz, Edward M.

    2011-01-01

    Light-activated gene transduction (LAGT) is an approach to localize gene therapy via preactivation of cells with UV light, which facilitates transduction by recombinant adeno-associated virus vectors. Prior studies demonstrated that UVC induces LAGT secondary to pyrimidine dimer formation, while UVA induces LAGT secondary to reactive oxygen species (ROS) generation. However, the empirical UVB boundary of these UV effects is unknown. Thus, we aimed to define the action spectra for UV-induced LAGT independent of DNA damage, and determine an optimal wavelength to maximize safety and efficacy. Results: UV at 288, 311 and 320nm produced significant dose-dependent LAGT effects, of which the maximum (800-fold) was observed with 4kJ/m2 at 311nm. Consistent with its robust cytotoxicity, 288nm produced significantly high levels of DNA damage at all doses tested, while 311, 320 and 330nm did not generate pyrimidine dimers and produced low levels of DNA damage detected by comet assay. While 288nm failed to induce ROS, the other wavelengths were effective, with the maximum (10-fold) effect observed with 30 kJ/m2 at 311nm. An in vivo pilot study assessing 311nm-induced LAGT of rabbit articular chondrocytes demonstrated a significant 6.6-fold (p<0.05) increase in transduction with insignificant cytotoxicity. Conclusion: 311nm was found to be the optimal wavelength for LAGT based on its superior efficacy at the peak dose, and its broad safety range that is remarkably wider than the other UV wavelengths tested. PMID:21490685

  4. Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia.

    PubMed

    Pisciotta, Livia; Priore Oliva, Claudio; Cefalù, Angelo Baldassare; Noto, Davide; Bellocchio, Antonella; Fresa, Raffaele; Cantafora, Alfredo; Patel, Dilip; Averna, Maurizio; Tarugi, Patrizia; Calandra, Sebastiano; Bertolini, Stefano

    2006-06-01

    Patients homozygous or compound heterozygous for LDLR mutations or double heterozygous for LDLR and apo B R3500Q mutation have higher LDL-C levels, more extensive xanthomatosis and more severe premature coronary disease (pCAD) than simple heterozygotes for mutations in either these genes or for missense mutations in PCSK9 gene. It is not known whether combined mutations in LDLR and PKCS9 are associated with such a severe phenotype. We sequenced Apo B and PCSK9 genes in two patients with the clinical diagnosis of homozygous FH who were heterozygous for LDLR gene mutations. Proband Z.P. (LDL-C 13.39 mmol/L and pCAD) was heterozygous for an LDLR mutation (p.E228K) inherited from her father (LDL-C 8.07 mmol/L) and a PCSK9 mutation (p.R496W) from her mother (LDL-C 5.58 mmol/L). Proband L.R. and her sister (LDL-C 11.51 and 10.47 mmol/L, xanthomatosis and carotid atherosclerosis) were heterozygous for an LDLR mutation (p.Y419X) inherited from their mother (LDL-C 6.54 mmol/L) and a PCSK9 mutation (p.N425S) probably from their deceased father. The LDL-C levels in double heterozygotes of these two families were 56 and 44% higher than those found in simple heterozygotes for the two LDLR mutations, respectively. The two PCSK9 mutations are novel and were not found in 110 controls and 80 patients with co-dominant hypercholesterolemia. These observations indicate that rare missense mutations of PCSK9 may worsen the clinical phenotype of patients carrying LDLR mutations. PMID:16183066

  5. Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells

    SciTech Connect

    Heneweer, Marjoke . E-mail: M.Heneweer@iras.uu.nl; Muusse, Martine; Berg, Martin van den; Sanderson, J. Thomas

    2005-10-15

    In order to protect consumers from ultraviolet (UV) radiation and enhance light stability of the product, three to eight UV filters are usually added to consumer sunscreen products. High lipophilicity of the UV filters has been shown to cause bioaccumulation in fish and humans, leading to environmental levels of UV filters that are similar to those of PCBs and DDT. In this paper, estrogen-regulated pS2 gene transcription in the human mammary tumor cell line MCF-7 was used as a measure of estrogenicity of four individual UV filters. Since humans are exposed to more than one UV filter at a time, an equipotent binary mixture of 2-hydroxy-4-methoxy-benzophenone (BP-3) and its metabolite 2,4-dihydroxy benzophenone (BP-1), as well as an equipotent multi-component mixture of BP-1, BP-3, octyl methoxy cinnamate (OMC) and 3-(4-methylbenzylidene) camphor (4-MBC), were also evaluated for their ability to induce pS2 gene transcription in order to examine additivity. An estrogen receptor-mediated mechanism of action was expected for all UV filters. Therefore, our null-hypothesis was that combined estrogenic responses, measured as increased pS2 gene transcription in MCF-7 cells after exposure to mixtures of UV filters, are additive, according to a concentration-addition model. Not all UV filters produced a full concentration-response curve within the concentration range tested (100 nM-1 {mu}M). Therefore, instead of using EC{sub 50} values for comparison, the concentration at which each compound caused a 50% increase of basal pS2 gene transcription was defined as the C50 value for that compound and used to calculate relative potencies. For comparison, the EC{sub 50} value of a compound is the concentration at which the compound elicits an effect that is 50% of its maximal effect. Individual UV filters increased pS2 gene transcription concentration-dependently with C50 values of 0.12 {mu}M, 0.5 {mu}M, 1.9 {mu}M, and 1.0 {mu}M for BP-1, BP-3, 4-MBC and OMC, respectively. Estradiol

  6. Supplementing High-Density SNP Microarrays for Additional Coverage of Disease-Related Genes: Addiction as a Paradigm

    SciTech Connect

    SacconePhD, Scott F; Chesler, Elissa J; Bierut, Laura J; Kalivas, Peter J; Lerman, Caryn; Saccone, Nancy L; Uhl, George R; Li, Chuan-Yun; Philip, Vivek M; Edenberg, Howard; Sherry, Steven; Feolo, Michael; Moyzis, Robert K; Rutter, Joni L

    2009-01-01

    Commercial SNP microarrays now provide comprehensive and affordable coverage of the human genome. However, some diseases have biologically relevant genomic regions that may require additional coverage. Addiction, for example, is thought to be influenced by complex interactions among many relevant genes and pathways. We have assembled a list of 486 biologically relevant genes nominated by a panel of experts on addiction. We then added 424 genes that showed evidence of association with addiction phenotypes through mouse QTL mappings and gene co-expression analysis. We demonstrate that there are a substantial number of SNPs in these genes that are not well represented by commercial SNP platforms. We address this problem by introducing a publicly available SNP database for addiction. The database is annotated using numeric prioritization scores indicating the extent of biological relevance. The scores incorporate a number of factors such as SNP/gene functional properties (including synonymy and promoter regions), data from mouse systems genetics and measures of human/mouse evolutionary conservation. We then used HapMap genotyping data to determine if a SNP is tagged by a commercial microarray through linkage disequilibrium. This combination of biological prioritization scores and LD tagging annotation will enable addiction researchers to supplement commercial SNP microarrays to ensure comprehensive coverage of biologically relevant regions.

  7. Gene expression suggests conserved aspects of Hox gene regulation in arthropods and provides additional support for monophyletic Myriapoda.

    PubMed

    Janssen, Ralf; Budd, Graham E

    2010-01-01

    Antisense transcripts of Ultrabithorax (aUbx) in the millipede Glomeris and the centipede Lithobius are expressed in patterns complementary to that of the Ubx sense transcripts. A similar complementary expression pattern has been described for non-coding RNAs (ncRNAs) of the bithoraxoid (bxd) locus in Drosophila, in which the transcription of bxd ncRNAs represses Ubx via transcriptional interference. We discuss our findings in the context of possibly conserved mechanisms of Ubx regulation in myriapods and the fly.Bicistronic transcription of Ubx and Antennapedia (Antp) has been reported previously for a myriapod and a number of crustaceans. In this paper, we show that Ubx/Antp bicistronic transcripts also occur in Glomeris and an onychophoran, suggesting further conserved mechanisms of Hox gene regulation in arthropods.Myriapod monophyly is supported by the expression of aUbx in all investigated myriapods, whereas in other arthropod classes, including the Onychophora, aUbx is not expressed. Of the two splice variants of Ubx/Antp only one could be isolated from myriapods, representing a possible further synapomorphy of the Myriapoda. PMID:20849647

  8. Evaluation of genes involved in prostaglandin action in equine endometrium during estrous cycle and early pregnancy.

    PubMed

    Atli, Mehmet O; Kurar, Ercan; Kayis, Seyit A; Aslan, Selim; Semacan, Ahmet; Celik, Sefa; Guzeloglu, Aydin

    2010-10-01

    The aim was to evaluate expression of genes involved in the biosynthesis of prostaglandins (PTG), Prostaglandin H Synthase-1 (PTGS1) and PTGS2, PGF synthase (PTGFS), and PGE synthase (PTGES), PGF receptor (PTGFR), PGE receptors (PTGER2 and PTGER4), prostaglandin transporter (SLCO2A1) and hydroxyprostaglandin dehydrogenase-15 (HPGD). Endometrial biopsies were obtained from mares on day of ovulation (d0, n=4), late diestrus (LD, n=4), early luteolysis (EL, n=4) and after luteolysis (AL, n=4) during the cycle. Stages of the cycle were confirmed by plasma progesterone concentrations measured daily and ultrasound examinations. Biopsies were also taken on days 14 (P14; n=4), 15 (P15, n=4), 18 (P18, n=4) and 22 (P22; n=4) of pregnancy. Relative mRNA expressions were quantified using real-time RT-PCR. A mixed model was fitted on the normalized data and least significant difference test (α=0.05) was employed. Expression of PTGS1 mRNA was low throughout the estrous cycle and early days of pregnancy, but upregulated on P18 and P22. PTGS2 expression was increased on EL, but it was suppressed by pregnancy on P15, P18, and P22. PTGFS expression was upregulated in both cyclic and pregnant mares compared to d0 and its level was the highest on LD. PTGFR expression was transiently increased on LD and EL and was suppressed during early pregnancy. Both PTGES and PTGER2 expressions were increased on LD, EL, and early pregnancy, but were decreased after the luteolysis in cyclic mares as they remained high on P18 and P22. PTGER4 expression did not change throughout the cycle and early pregnancy. Levels of HPGD and SLCO2A1 were significantly increased only on P22. In conclusion, PTGS2 expression increases around the time of luteolysis and concurrent upregulation of PTGFS and PTGES indicates that equine endometrium has increased capability of PTG production around the time of luteolysis. However, pregnancy reduces PTGS2 expression, but maintains the high levels of PTGES during early

  9. Infection of mice by Salmonella enterica serovar Enteritidis involves additional genes that are absent in the genome of serovar Typhimurium.

    PubMed

    Silva, Cecilia A; Blondel, Carlos J; Quezada, Carolina P; Porwollik, Steffen; Andrews-Polymenis, Helene L; Toro, Cecilia S; Zaldívar, Mercedes; Contreras, Inés; McClelland, Michael; Santiviago, Carlos A

    2012-02-01

    Salmonella enterica serovar Enteritidis causes a systemic, typhoid-like infection in newly hatched poultry and mice. In the present study, a library of 54,000 transposon mutants of S. Enteritidis phage type 4 (PT4) strain P125109 was screened for mutants deficient in the in vivo colonization of the BALB/c mouse model using a microarray-based negative-selection screening. Mutants in genes known to contribute to systemic infection (e.g., Salmonella pathogenicity island 2 [SPI-2], aro, rfa, rfb, phoP, and phoQ) and enteric infection (e.g., SPI-1 and SPI-5) in this and other Salmonella serovars displayed colonization defects in our assay. In addition, a strong attenuation was observed for mutants in genes and genomic islands that are not present in S. Typhimurium or in most other Salmonella serovars. These genes include a type I restriction/modification system (SEN4290 to SEN4292), the peg fimbrial operon (SEN2144A to SEN2145B), a putative pathogenicity island (SEN1970 to SEN1999), and a type VI secretion system remnant SEN1001, encoding a hypothetical protein containing a lysin motif (LysM) domain associated with peptidoglycan binding. Proliferation defects for mutants in these individual genes and in exemplar genes for each of these clusters were confirmed in competitive infections with wild-type S. Enteritidis. A ΔSEN1001 mutant was defective for survival within RAW264.7 murine macrophages in vitro. Complementation assays directly linked the SEN1001 gene to phenotypes observed in vivo and in vitro. The genes identified here may perform novel virulence functions not characterized in previous Salmonella models.

  10. Computational investigations on polymerase actions in gene transcription and replication: Combining physical modeling and atomistic simulations

    NASA Astrophysics Data System (ADS)

    Jin, Yu

    2016-01-01

    Polymerases are protein enzymes that move along nucleic acid chains and catalyze template-based polymerization reactions during gene transcription and replication. The polymerases also substantially improve transcription or replication fidelity through the non-equilibrium enzymatic cycles. We briefly review computational efforts that have been made toward understanding mechano-chemical coupling and fidelity control mechanisms of the polymerase elongation. The polymerases are regarded as molecular information motors during the elongation process. It requires a full spectrum of computational approaches from multiple time and length scales to understand the full polymerase functional cycle. We stay away from quantum mechanics based approaches to the polymerase catalysis due to abundant former surveys, while addressing statistical physics modeling approaches along with all-atom molecular dynamics simulation studies. We organize this review around our own modeling and simulation practices on a single subunit T7 RNA polymerase, and summarize commensurate studies on structurally similar DNA polymerases as well. For multi-subunit RNA polymerases that have been actively studied in recent years, we leave systematical reviews of the simulation achievements to latest computational chemistry surveys, while covering only representative studies published very recently, including our own work modeling structure-based elongation kinetic of yeast RNA polymerase II. In the end, we briefly go through physical modeling on elongation pauses and backtracking activities of the multi-subunit RNAPs. We emphasize on the fluctuation and control mechanisms of the polymerase actions, highlight the non-equilibrium nature of the operation system, and try to build some perspectives toward understanding the polymerase impacts from the single molecule level to a genome-wide scale. Project supported by the National Natural Science Foundation (Grant No. 11275022).

  11. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo.

    PubMed

    Sinn, E; Muller, W; Pattengale, P; Tepler, I; Wallace, R; Leder, P

    1987-05-22

    We have derived and mated separate strains of transgenic mice that carry either the v-Ha-ras or the c-myc gene driven by the mouse mammary tumor virus (MMTV) promoter/enhancer. Mice carrying the MMTV/v-Ha-ras transgene manifest two distinct disturbances of cell growth. The first, a benign hyperplasia of the Harderian lacrimal gland, is diffuse, involves the entire gland, and likely requires only the abnormal action of the v-Ha-ras gene. The second involves the focal development of malignancies of mammary, salivary, and lymphoid tissue and likely requires additional somatic events. When the MMTV/v-Ha-ras and MMTV/c-myc strains are crossed to yield hybrid mice, their joint action results in a dramatic and synergistic acceleration of tumor formation. Since these tumors arise stochastically and are apparently monoclonal in origin, additional somatic events appear necessary for their full malignant progression, even in the presence of activated v-Ha-ras and c-myc transgenes.

  12. Action spectrum for expression of the high intensity light-inducible Lhc-like gene Lhl4 in the green alga Chlamydomonas reinhardtii.

    PubMed

    Teramoto, Haruhiko; Ishii, Asako; Kimura, Yukihiro; Hasegawa, Koji; Nakazawa, Shigeaki; Nakamura, Takanori; Higashi, Sho-ichi; Watanabe, Masakatsu; Ono, Taka-aki

    2006-03-01

    Lhl4 encodes a distant relative of light-harvesting Chl-a/b proteins in the green alga Chlamydomonas reinhardtii. Lhl4 mRNA markedly accumulated within 30 min after illumination and in proportion to the light intensity up to a fluence rate much higher than that required for photosynthesis. The high intensity light (HL)-induced accumulation of Lhl4 mRNA required continuous illumination, and the mRNA level rapidly decreased when the cells were placed in the dark. HL only slightly stabilized the mRNA, suggesting that the HL-induced expression of the Lhl4 gene is primarily regulated at the level of transcription. Blue light was more effective for inducing Lhl4 gene expression than green or red light, and far-red light had no effect. The action spectrum for Lhl4 gene expression was examined at wavelengths between 325 and 775 nm using the Okazaki Large Spectrograph. The obtained spectrum showed a distinct peak in the blue region (450 nm) and a shoulder in the UV-A region (375 nm). The curve in the spectrum rose steeply in the short wavelength UV region. In addition, we observed two minor peaks in the green (575 nm) and the red (675 nm) regions. The action spectrum suggests that a blue/UV-A light photoreceptor with a flavin-based chromophore participates in the HL response of Lhl4 gene expression. However, the hypersensitivity to near UV-B light suggests the involvement of an unidentified UV light perception system in the expression of the Lhl4 gene.

  13. Change in gene abundance in the nitrogen biogeochemical cycle with temperature and nitrogen addition in Antarctic soils.

    PubMed

    Jung, Jaejoon; Yeom, Jinki; Kim, Jisun; Han, Jiwon; Lim, Hyoun Soo; Park, Hyun; Hyun, Seunghun; Park, Woojun

    2011-12-01

    The microbial community (bacterial, archaeal, and fungi) and eight genes involved in the nitrogen biogeochemical cycle (nifH, nitrogen fixation; bacterial and archaeal amoA, ammonia oxidation; narG, nitrate reduction; nirS, nirK, nitrite reduction; norB, nitric oxide reduction; and nosZ, nitrous oxide reduction) were quantitatively assessed in this study, via real-time PCR with DNA extracted from three Antarctic soils. Interestingly, AOB amoA was found to be more abundant than AOA amoA in Antarctic soils. The results of microcosm studies revealed that the fungal and archaeal communities were diminished in response to warming temperatures (10 °C) and that the archaeal community was less sensitive to nitrogen addition, which suggests that those two communities are well-adapted to colder temperatures. AOA amoA and norB genes were reduced with warming temperatures. The abundance of only the nifH and nirK genes increased with both warming and the addition of nitrogen. NirS-type denitrifying bacteria outnumbered NirK-type denitrifiers regardless of the treatment used. Interestingly, dramatic increases in both NirS and NirK-types denitrifiers were observed with nitrogen addition. NirK types increase with warming, but NirS-type denitrifiers tend to be less sensitive to warming. Our findings indicated that the Antarctic microbial nitrogen cycle could be dramatically altered by temperature and nitrogen, and that warming may be detrimental to the ammonia-oxidizing archaeal community. To the best of our knowledge, this is the first report to investigate genes associated with each process of the nitrogen biogeochemical cycle in an Antarctic terrestrial soil environment.

  14. Genome-wide meta-analysis of maize heterosis reveals the potential role of additive gene expression at pericentromeric loci

    PubMed Central

    2014-01-01

    Background The identification of QTL involved in heterosis formation is one approach to unravel the not yet fully understood genetic basis of heterosis - the improved agronomic performance of hybrid F1 plants compared to their inbred parents. The identification of candidate genes underlying a QTL is important both for developing markers and determining the molecular genetic basis of a trait, but remains difficult owing to the large number of genes often contained within individual QTL. To address this problem in heterosis analysis, we applied a meta-analysis strategy for grain yield (GY) of Zea mays L. as example, incorporating QTL-, hybrid field-, and parental gene expression data. Results For the identification of genes underlying known heterotic QTL, we made use of tight associations between gene expression pattern and the trait of interest, identified by correlation analyses. Using this approach genes strongly associated with heterosis for GY were discovered to be clustered in pericentromeric regions of the complex maize genome. This suggests that expression differences of sequences in recombination-suppressed regions are important in the establishment of heterosis for GY in F1 hybrids and also in the conservation of heterosis for GY across genotypes. Importantly functional analysis of heterosis-associated genes from these genomic regions revealed over-representation of a number of functional classes, identifying key processes contributing to heterosis for GY. Based on the finding that the majority of the analyzed heterosis-associated genes were addtitively expressed, we propose a model referring to the influence of cis-regulatory variation on heterosis for GY by the compensation of fixed detrimental expression levels in parents. Conclusions The study highlights the utility of a meta-analysis approach that integrates phenotypic and multi-level molecular data to unravel complex traits in plants. It provides prospects for the identification of genes relevant for

  15. Gene expression patterns of wheat rust resistance gene Lr34/Yr18 indicate novel mode of action

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Lr34/Yr18 resistance gene provides durable, adult-plant, slow-rusting resistance to leaf rust and yellow rust of wheat. Patterns of gene expression were examined by microarray analysis in inoculated and mock-inoculated flag leaves of two pairs of near isogenic lines for Lr34/Yr18 (Thatcher/Thatc...

  16. Sequence Analysis of Insecticide Action and Detoxification-Related Genes in the Insect Pest Natural Enemy Pardosa pseudoannulata

    PubMed Central

    Bao, Haibo; Liu, Zewen

    2015-01-01

    The pond wolf spider Pardosa pseudoannulata, an important natural predatory enemy of rice planthoppers, is found widely distributed in paddy fields. However, data on the genes involved in insecticide action, detoxification, and response are very limited for P. pseudoannulata, which inhibits the development and appropriate use of selective insecticides to control insect pests on rice. We used transcriptome construction from adult spider cephalothoraxes to analyze and manually identify genes enconding metabolic enzymes and target receptors related to insecticide action and detoxification, including 90 cytochrome P450s, 14 glutathione S-transferases (GSTs), 17 acetylcholinesterases (AChEs), 17 nicotinic acetylcholine receptors (nAChRs), and 17 gamma-aminobutyric acid (GABA) receptors, as well as 12 glutamate-gated chloride channel (GluCl) unigenes. Sequence alignment and phylogenetic analysis revealed the different subclassifications of P450s and GSTs, some important sequence diversities in nAChRs and GABA receptors, polymorphism in AChEs, and high similarities in GluCls. For P450s in P. pseudoannulata, the number of unigenes belonging to the CYP2 clade was much higher than that in CYP3 and CYP4 clades. The results differed from insects in which most P450 genes were in CYP3 and CYP4 clades. For GSTs, most unigenes belonged to the delta and sigma classes, and no epsilon GST class gene was found, which differed from the findings for insects and acarina. Our results will be useful for studies on insecticide action, selectivity, and detoxification in the spider and other related animals, and the sequence differences in target genes between the spider and insects will provide important information for the design of selective insecticides. PMID:25923714

  17. Sequence Analysis of Insecticide Action and Detoxification-Related Genes in the Insect Pest Natural Enemy Pardosa pseudoannulata.

    PubMed

    Meng, Xiangkun; Zhang, Yixi; Bao, Haibo; Liu, Zewen

    2015-01-01

    The pond wolf spider Pardosa pseudoannulata, an important natural predatory enemy of rice planthoppers, is found widely distributed in paddy fields. However, data on the genes involved in insecticide action, detoxification, and response are very limited for P. pseudoannulata, which inhibits the development and appropriate use of selective insecticides to control insect pests on rice. We used transcriptome construction from adult spider cephalothoraxes to analyze and manually identify genes enconding metabolic enzymes and target receptors related to insecticide action and detoxification, including 90 cytochrome P450s, 14 glutathione S-transferases (GSTs), 17 acetylcholinesterases (AChEs), 17 nicotinic acetylcholine receptors (nAChRs), and 17 gamma-aminobutyric acid (GABA) receptors, as well as 12 glutamate-gated chloride channel (GluCl) unigenes. Sequence alignment and phylogenetic analysis revealed the different subclassifications of P450s and GSTs, some important sequence diversities in nAChRs and GABA receptors, polymorphism in AChEs, and high similarities in GluCls. For P450s in P. pseudoannulata, the number of unigenes belonging to the CYP2 clade was much higher than that in CYP3 and CYP4 clades. The results differed from insects in which most P450 genes were in CYP3 and CYP4 clades. For GSTs, most unigenes belonged to the delta and sigma classes, and no epsilon GST class gene was found, which differed from the findings for insects and acarina. Our results will be useful for studies on insecticide action, selectivity, and detoxification in the spider and other related animals, and the sequence differences in target genes between the spider and insects will provide important information for the design of selective insecticides.

  18. Additive gene-environment effects on hippocampal structure in healthy humans.

    PubMed

    Rabl, Ulrich; Meyer, Bernhard M; Diers, Kersten; Bartova, Lucie; Berger, Andreas; Mandorfer, Dominik; Popovic, Ana; Scharinger, Christian; Huemer, Julia; Kalcher, Klaudius; Pail, Gerald; Haslacher, Helmuth; Perkmann, Thomas; Windischberger, Christian; Brocke, Burkhard; Sitte, Harald H; Pollak, Daniela D; Dreher, Jean-Claude; Kasper, Siegfried; Praschak-Rieder, Nicole; Moser, Ewald; Esterbauer, Harald; Pezawas, Lukas

    2014-07-23

    Hippocampal volume loss has been related to chronic stress as well as genetic factors. Although genetic and environmental variables affecting hippocampal volume have extensively been studied and related to mental illness, limited evidence is available with respect to G × E interactions on hippocampal volume. The present MRI study investigated interaction effects on hippocampal volume between three well-studied functional genetic variants (COMT Val158Met, BDNF Val66Met, 5-HTTLPR) associated with hippocampal volume and a measure of environmental adversity (life events questionnaire) in a large sample of healthy humans (n = 153). All three variants showed significant interactions with environmental adversity with respect to hippocampal volume. Observed effects were additive by nature and driven by both recent as well as early life events. A consecutive analysis of hippocampal subfields revealed a spatially distinct profile for each genetic variant suggesting a specific role of 5-HTTLPR for the subiculum, BDNF Val66Met for CA4/dentate gyrus, and COMT Val158Met for CA2/3 volume changes. The present study underscores the importance of G × E interactions as determinants of hippocampal volume, which is crucial for the neurobiological understanding of stress-related conditions, such as mood disorders or post-traumatic stress disorder (PTSD). PMID:25057194

  19. Additive gene-environment effects on hippocampal structure in healthy humans.

    PubMed

    Rabl, Ulrich; Meyer, Bernhard M; Diers, Kersten; Bartova, Lucie; Berger, Andreas; Mandorfer, Dominik; Popovic, Ana; Scharinger, Christian; Huemer, Julia; Kalcher, Klaudius; Pail, Gerald; Haslacher, Helmuth; Perkmann, Thomas; Windischberger, Christian; Brocke, Burkhard; Sitte, Harald H; Pollak, Daniela D; Dreher, Jean-Claude; Kasper, Siegfried; Praschak-Rieder, Nicole; Moser, Ewald; Esterbauer, Harald; Pezawas, Lukas

    2014-07-23

    Hippocampal volume loss has been related to chronic stress as well as genetic factors. Although genetic and environmental variables affecting hippocampal volume have extensively been studied and related to mental illness, limited evidence is available with respect to G × E interactions on hippocampal volume. The present MRI study investigated interaction effects on hippocampal volume between three well-studied functional genetic variants (COMT Val158Met, BDNF Val66Met, 5-HTTLPR) associated with hippocampal volume and a measure of environmental adversity (life events questionnaire) in a large sample of healthy humans (n = 153). All three variants showed significant interactions with environmental adversity with respect to hippocampal volume. Observed effects were additive by nature and driven by both recent as well as early life events. A consecutive analysis of hippocampal subfields revealed a spatially distinct profile for each genetic variant suggesting a specific role of 5-HTTLPR for the subiculum, BDNF Val66Met for CA4/dentate gyrus, and COMT Val158Met for CA2/3 volume changes. The present study underscores the importance of G × E interactions as determinants of hippocampal volume, which is crucial for the neurobiological understanding of stress-related conditions, such as mood disorders or post-traumatic stress disorder (PTSD).

  20. A multi-gene phylogeny provides additional insight into the relationships between several Ascosphaera species.

    PubMed

    Klinger, E G; James, R R; Youssef, N N; Welker, D L

    2013-01-01

    Ascosphaera fungi are highly associated with social and solitary bees, with some species being pathogenic to bees (causing chalkbrood) while others are not, and proper identification within this genus is important. Unfortunately, morphological characterizations can be difficult, and molecular characterizations have only used one genetic region. We evaluated multiple phylogenies of the Ascosphaera using up to six loci: the Internal Transcribed Spacer (ITS) region, 18S rRNA, 28S rRNA, Elongation Factor-1α (EF-1α) the RNA polymerase II largest subunit (RPB1), and the second largest subunit (RPB2). The ITS sequence alone produced an inadequate phylogeny, and the addition of both the 18S and 28S rRNA loci to the ITS sequence produced a phylogeny similar to that based on all six genetic regions. For all phylogenies, Ascosphaera torchioi was in a separate clade that was the most basal, with a strong genetic similarity to Eremascus albus, introducing the possibility of paraphyly within Ascosphaera. Also, based on this new phylogeny, we now suggest that the Apis mellifera (honey bee) pathogens arose within a group of saprophytes, and the Megachile (leafcutting bees) pathogens arose separately. PMID:23147103

  1. [Site of fidget gene action and its interaction with the ocular retardation gene in cultured mouse embryo retinas].

    PubMed

    Koniukhov, B V; Ugol'kova, T S

    1978-01-01

    The eye rudiments of 10 and 11 days old mouse embryos of the genotypes +/+ +/+, fi/fi +/+, +/+ or/or, fi/fi or/or and 11 days old embryos of the genotype fi/+ or/+ were cultivated in vitro during 24, 48 and 72 hrs. The expression of the fi gene was shown in the cells of the cultivated fi/fi +/+ retina: its proliferative activity was inhibited. The fi gene was not active in the cells of the developing lens and the anomalies of the latter in homozygotes arose secondarily, due to the inhibition of growth of the retinal rudiment. The fi and or genes interacted synergically in the cultivated fi/fi or/or retina, thus resulting in the marked inhibition of its mitotic activity. This suggests that both the genes act in the retinal cells and, apparently, affect different links of the biochemical chain of events in the preparation of DNA replication.

  2. The Symbiotic Performance of Chickpea Rhizobia Can Be Improved by Additional Copies of the clpB Chaperone Gene.

    PubMed

    Paço, Ana; Brígido, Clarisse; Alexandre, Ana; Mateos, Pedro F; Oliveira, Solange

    2016-01-01

    The ClpB chaperone is known to be involved in bacterial stress response. Moreover, recent studies suggest that this protein has also a role in the chickpea-rhizobia symbiosis. In order to improve both stress tolerance and symbiotic performance of a chickpea microsymbiont, the Mesorhizobium mediterraneum UPM-Ca36T strain was genetically transformed with pPHU231 containing an extra-copy of the clpB gene. To investigate if the clpB-transformed strain displays an improved stress tolerance, bacterial growth was evaluated under heat and acid stress conditions. In addition, the effect of the extra-copies of the clpB gene in the symbiotic performance was evaluated using plant growth assays (hydroponic and pot trials). The clpB-transformed strain is more tolerant to heat shock than the strain transformed with pPHU231, supporting the involvement of ClpB in rhizobia heat shock tolerance. Both plant growth assays showed that ClpB has an important role in chickpea-rhizobia symbiosis. The nodulation kinetics analysis showed a higher rate of nodule appearance with the clpB-transformed strain. This strain also induced a greater number of nodules and, more notably, its symbiotic effectiveness increased ~60% at pH5 and 83% at pH7, compared to the wild-type strain. Furthermore, a higher frequency of root hair curling was also observed in plants inoculated with the clpB-transformed strain, compared to the wild-type strain. The superior root hair curling induction, nodulation ability and symbiotic effectiveness of the clpB-transformed strain may be explained by an increased expression of symbiosis genes. Indeed, higher transcript levels of the nodulation genes nodA and nodC (~3 folds) were detected in the clpB-transformed strain. The improvement of rhizobia by addition of extra-copies of the clpB gene may be a promising strategy to obtain strains with enhanced stress tolerance and symbiotic effectiveness, thus contributing to their success as crop inoculants, particularly under

  3. The Symbiotic Performance of Chickpea Rhizobia Can Be Improved by Additional Copies of the clpB Chaperone Gene

    PubMed Central

    Paço, Ana; Brígido, Clarisse; Alexandre, Ana; Mateos, Pedro F.; Oliveira, Solange

    2016-01-01

    The ClpB chaperone is known to be involved in bacterial stress response. Moreover, recent studies suggest that this protein has also a role in the chickpea-rhizobia symbiosis. In order to improve both stress tolerance and symbiotic performance of a chickpea microsymbiont, the Mesorhizobium mediterraneum UPM-Ca36T strain was genetically transformed with pPHU231 containing an extra-copy of the clpB gene. To investigate if the clpB-transformed strain displays an improved stress tolerance, bacterial growth was evaluated under heat and acid stress conditions. In addition, the effect of the extra-copies of the clpB gene in the symbiotic performance was evaluated using plant growth assays (hydroponic and pot trials). The clpB-transformed strain is more tolerant to heat shock than the strain transformed with pPHU231, supporting the involvement of ClpB in rhizobia heat shock tolerance. Both plant growth assays showed that ClpB has an important role in chickpea-rhizobia symbiosis. The nodulation kinetics analysis showed a higher rate of nodule appearance with the clpB-transformed strain. This strain also induced a greater number of nodules and, more notably, its symbiotic effectiveness increased ~60% at pH5 and 83% at pH7, compared to the wild-type strain. Furthermore, a higher frequency of root hair curling was also observed in plants inoculated with the clpB-transformed strain, compared to the wild-type strain. The superior root hair curling induction, nodulation ability and symbiotic effectiveness of the clpB-transformed strain may be explained by an increased expression of symbiosis genes. Indeed, higher transcript levels of the nodulation genes nodA and nodC (~3 folds) were detected in the clpB-transformed strain. The improvement of rhizobia by addition of extra-copies of the clpB gene may be a promising strategy to obtain strains with enhanced stress tolerance and symbiotic effectiveness, thus contributing to their success as crop inoculants, particularly under

  4. The Symbiotic Performance of Chickpea Rhizobia Can Be Improved by Additional Copies of the clpB Chaperone Gene.

    PubMed

    Paço, Ana; Brígido, Clarisse; Alexandre, Ana; Mateos, Pedro F; Oliveira, Solange

    2016-01-01

    The ClpB chaperone is known to be involved in bacterial stress response. Moreover, recent studies suggest that this protein has also a role in the chickpea-rhizobia symbiosis. In order to improve both stress tolerance and symbiotic performance of a chickpea microsymbiont, the Mesorhizobium mediterraneum UPM-Ca36T strain was genetically transformed with pPHU231 containing an extra-copy of the clpB gene. To investigate if the clpB-transformed strain displays an improved stress tolerance, bacterial growth was evaluated under heat and acid stress conditions. In addition, the effect of the extra-copies of the clpB gene in the symbiotic performance was evaluated using plant growth assays (hydroponic and pot trials). The clpB-transformed strain is more tolerant to heat shock than the strain transformed with pPHU231, supporting the involvement of ClpB in rhizobia heat shock tolerance. Both plant growth assays showed that ClpB has an important role in chickpea-rhizobia symbiosis. The nodulation kinetics analysis showed a higher rate of nodule appearance with the clpB-transformed strain. This strain also induced a greater number of nodules and, more notably, its symbiotic effectiveness increased ~60% at pH5 and 83% at pH7, compared to the wild-type strain. Furthermore, a higher frequency of root hair curling was also observed in plants inoculated with the clpB-transformed strain, compared to the wild-type strain. The superior root hair curling induction, nodulation ability and symbiotic effectiveness of the clpB-transformed strain may be explained by an increased expression of symbiosis genes. Indeed, higher transcript levels of the nodulation genes nodA and nodC (~3 folds) were detected in the clpB-transformed strain. The improvement of rhizobia by addition of extra-copies of the clpB gene may be a promising strategy to obtain strains with enhanced stress tolerance and symbiotic effectiveness, thus contributing to their success as crop inoculants, particularly under

  5. Improving nutrient management practices in agriculture: The role of risk-based beliefs in understanding farmers' attitudes toward taking additional action

    NASA Astrophysics Data System (ADS)

    Wilson, Robyn S.; Howard, Gregory; Burnett, Elizabeth A.

    2014-08-01

    A recent increase in the amount of dissolved reactive phosphorus (DRP) entering the western Lake Erie basin is likely due to increased spring storm events in combination with issues related to fertilizer application and timing. These factors in combination with warmer lake temperatures have amplified the spread of toxic algal blooms. We assessed the attitudes of farmers in northwest Ohio toward taking at least one additional action to reduce nutrient loss on their farm. Specifically, we (1) identified to what extent farm and farmer characteristics (e.g., age, gross farm sales) as well as risk-based beliefs (e.g., efficacy, risk perception) influenced attitudes, and (2) assessed how these characteristics and beliefs differ in their predictive ability based on unobservable latent classes of farmers. Risk perception, or a belief that negative impacts to profit and water quality from nutrient loss were likely, was the most consistent predictor of farmer attitudes. Response efficacy, or a belief that taking action on one's farm made a difference, was found to significantly influence attitudes, although this belief was particularly salient for the minority class of farmers who were older and more motivated by profit. Communication efforts should focus on the negative impacts of nutrient loss to both the farm (i.e., profit) and the natural environment (i.e., water quality) to raise individual perceived risk among the majority, while the minority need higher perceived efficacy or more specific information about the economic effectiveness of particular recommended practices.

  6. Expression patterns and action analysis of genes associated with inflammatory responses during rat liver regeneration

    PubMed Central

    Shao, Heng-Yi; Zhao, Li-Feng; Xu, Cun-Shuan

    2007-01-01

    AIM: To study the relationship between inflammatory response and liver regeneration (LR) at transcriptional level. METHODS: After partial hepatectomy (PH) of rats, the genes associated with inflammatory response were obtained according to the databases, and the gene expression changes during LR were checked by the Rat Genome 230 2.0 array. RESULTS: Two hundred and thirty-nine genes were associated with liver regeneration. The initial and total expressing gene numbers found in initiation phase (0.5-4 h after PH), G0/G1 transition (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and structure-function reconstruction (66-168 h after PH) of liver regeneration were 107, 34, 126, 6 and 107, 92, 233, 145 respectively, showing that the associated genes were mainly triggered at the beginning of liver regeneration, and worked at different phases. According to their expression similarity, these genes were classified into 5 groups: only up-regulated, predominantly up-, only down-, predominantly down-, up- and down-, involving 92, 25, 77, 14 and 31 genes, respectively. The total times of their up- and down-regulated expression were 975 and 494, respectively, demonstrating that the expressions of the majority of genes were increased, and that of a few genes were decreased. Their time relevance was classified into 13 groups, showing that the cellular physiological and biochemical activities were staggered during liver regeneration. According to gene expression patterns, they were classified into 33 types, suggesting that the activities were diverse and complex during liver regeneration. CONCLUSION: Inflammatory response is closely associated with liver regeneration, in which 239 LR-associated genes play an important role. PMID:17230604

  7. Connecting gene expression data from connectivity map and in silico target predictions for small molecule mechanism-of-action analysis.

    PubMed

    Ravindranath, Aakash Chavan; Perualila-Tan, Nolen; Kasim, Adetayo; Drakakis, Georgios; Liggi, Sonia; Brewerton, Suzanne C; Mason, Daniel; Bodkin, Michael J; Evans, David A; Bhagwat, Aditya; Talloen, Willem; Göhlmann, Hinrich W H; Shkedy, Ziv; Bender, Andreas

    2015-01-01

    Integrating gene expression profiles with certain proteins can improve our understanding of the fundamental mechanisms in protein-ligand binding. This paper spotlights the integration of gene expression data and target prediction scores, providing insight into mechanism of action (MoA). Compounds are clustered based upon the similarity of their predicted protein targets and each cluster is linked to gene sets using Linear Models for Microarray Data. MLP analysis is used to generate gene sets based upon their biological processes and a qualitative search is performed on the homogeneous target-based compound clusters to identify pathways. Genes and proteins were linked through pathways for 6 of the 8 MCF7 and 6 of the 11 PC3 clusters. Three compound clusters are studied; (i) the target-driven cluster involving HSP90 inhibitors, geldanamycin and tanespimycin induces differential expression for HSP90-related genes and overlap with pathway response to unfolded protein. Gene expression results are in agreement with target prediction and pathway annotations add information to enable understanding of MoA. (ii) The antipsychotic cluster shows differential expression for genes LDLR and INSIG-1 and is predicted to target CYP2D6. Pathway steroid metabolic process links the protein and respective genes, hypothesizing the MoA for antipsychotics. A sub-cluster (verepamil and dexverepamil), although sharing similar protein targets with the antipsychotic drug cluster, has a lower intensity of expression profile on related genes, indicating that this method distinguishes close sub-clusters and suggests differences in their MoA. Lastly, (iii) the thiazolidinediones drug cluster predicted peroxisome proliferator activated receptor (PPAR) PPAR-alpha, PPAR-gamma, acyl CoA desaturase and significant differential expression of genes ANGPTL4, FABP4 and PRKCD. The targets and genes are linked via PPAR signalling pathway and induction of apoptosis, generating a hypothesis for the MoA of

  8. Imaging brain gene expression profiles by antipsychotics: region-specific action of amisulpride on postsynaptic density transcripts compared to haloperidol.

    PubMed

    de Bartolomeis, Andrea; Marmo, Federica; Buonaguro, Elisabetta Filomena; Rossi, Rodolfo; Tomasetti, Carmine; Iasevoli, Felice

    2013-11-01

    Induction of motor disorders is considered the clinical landmark differentiating typical from atypical antipsychotics, and has been mainly correlated to dopamine D2 receptors blockade in striatum. This view is challenged by benzamides, such as amisulpride, which display low liability for motor side effects despite being D2/D3 receptors high-affinity blocking agents. These effects have been explained with the prominent presynaptic action of amisulpride or with the fast dissociation at D2 receptors, but there is scarce information on the effects of amisulpride on postsynaptic signaling. We carried out a molecular imaging study of gene expression after acute administration of haloperidol (0.8 mg/kg), amisulpride (10 or 35 mg/kg), or vehicle, focusing on postsynaptic genes that are key regulators of synaptic plasticity, such as Arc, c-fos, Zif-268, Norbin, Homer. The last one has been associated to schizophrenia both in clinical and preclinical studies, and is differentially induced by antipsychotics with different D2 receptors affinity. Topography of gene expression revealed that amisulpride, unlike haloperidol, triggers transcripts expression peak in medial striatal regions. Correlation analysis of gene expression revealed a prevalent correlated gene induction within motor corticostriatal regions by haloperidol and a more balanced gene induction within limbic and motor corticostriatal regions by amisulpride. Despite the selective dopaminergic profile of both compounds, our results demonstrated a differential modulation of postsynaptic molecules by amisulpride and haloperidol, the former impacting preferentially medial regions of striatum whereas the latter inducing strong gene expression in lateral regions. Thus, we provided a possible molecular profile of amisulpride, putatively explaining its "atypical atypicality".

  9. Novel glycol chitosan-based polymeric gene carrier synthesized by a Michael addition reaction with low molecular weight polyethylenimine.

    PubMed

    Lee, Young Hwa; Park, Hae In; Choi, Joon Sig

    2016-02-10

    A glycol chitosan-based polymer that spontaneously assembles with plasmid DNA into nanorods was evaluated as a non-viral vector for gene delivery. Glycol chitosan-methyl acrylate-polyethylenimine (GMP) was synthesized by grafting polyethylenimine onto glycol chitosan via amidation after Michael addition using methyl acrylate. Gel retardation and PicoGreen assay experiments showed complete complex formation with plasmid DNA. GMP/pDNA complexes were characterized using biophysical techniques and were found to be positively charged rod-shape structures with widths in the nanometer scale and lengths in the micrometer scale. Transfection efficiency and cytotoxicity of GMP polymer was evaluated in human epithelial ovary carcinoma (HeLa) cells, human embryonic kidney 293 (HEK293) cells, and human hepatocellular liver carcinoma (HepG2) cells, in comparison to high molecular weight polyethylenimine, a commonly used transfection reagent. Intracellular polymer uptake was compared and confirmed by confocal microscopy. The results demonstrate that GMP, a hybrid polymer of glycol chitosan grafted with branched polyethylenimine, may serve as a promising vehicle for efficient gene delivery.

  10. Coexpression of Nuclear Receptors and Histone Methylation Modifying Genes in the Testis: Implications for Endocrine Disruptor Modes of Action

    PubMed Central

    Anderson, Alison M.; Carter, Kim W.; Anderson, Denise; Wise, Michael J.

    2012-01-01

    Background Endocrine disruptor chemicals elicit adverse health effects by perturbing nuclear receptor signalling systems. It has been speculated that these compounds may also perturb epigenetic mechanisms and thus contribute to the early origin of adult onset disease. We hypothesised that histone methylation may be a component of the epigenome that is susceptible to perturbation. We used coexpression analysis of publicly available data to investigate the combinatorial actions of nuclear receptors and genes involved in histone methylation in normal testis and when faced with endocrine disruptor compounds. Methodology/Principal Findings The expression patterns of a set of genes were profiled across testis tissue in human, rat and mouse, plus control and exposed samples from four toxicity experiments in the rat. Our results indicate that histone methylation events are a more general component of nuclear receptor mediated transcriptional regulation in the testis than previously appreciated. Coexpression patterns support the role of a gatekeeper mechanism involving the histone methylation modifiers Kdm1, Prdm2, and Ehmt1 and indicate that this mechanism is a common determinant of transcriptional integrity for genes critical to diverse physiological endpoints relevant to endocrine disruption. Coexpression patterns following exposure to vinclozolin and dibutyl phthalate suggest that coactivity of the demethylase Kdm1 in particular warrants further investigation in relation to endocrine disruptor mode of action. Conclusions/Significance This study provides proof of concept that a bioinformatics approach that profiles genes related to a specific hypothesis across multiple biological settings can provide powerful insight into coregulatory activity that would be difficult to discern at an individual experiment level or by traditional differential expression analysis methods. PMID:22496781

  11. Classifying chemical mode of action using gene networks and machine learning: a case study with the herbicide linuron.

    PubMed

    Ornostay, Anna; Cowie, Andrew M; Hindle, Matthew; Baker, Christopher J O; Martyniuk, Christopher J

    2013-12-01

    The herbicide linuron (LIN) is an endocrine disruptor with an anti-androgenic mode of action. The objectives of this study were to (1) improve knowledge of androgen and anti-androgen signaling in the teleostean ovary and to (2) assess the ability of gene networks and machine learning to classify LIN as an anti-androgen using transcriptomic data. Ovarian explants from vitellogenic fathead minnows (FHMs) were exposed to three concentrations of either 5α-dihydrotestosterone (DHT), flutamide (FLUT), or LIN for 12h. Ovaries exposed to DHT showed a significant increase in 17β-estradiol (E2) production while FLUT and LIN had no effect on E2. To improve understanding of androgen receptor signaling in the ovary, a reciprocal gene expression network was constructed for DHT and FLUT using pathway analysis and these data suggested that steroid metabolism, translation, and DNA replication are processes regulated through AR signaling in the ovary. Sub-network enrichment analysis revealed that FLUT and LIN shared more regulated gene networks in common compared to DHT. Using transcriptomic datasets from different fish species, machine learning algorithms classified LIN successfully with other anti-androgens. This study advances knowledge regarding molecular signaling cascades in the ovary that are responsive to androgens and anti-androgens and provides proof of concept that gene network analysis and machine learning can classify priority chemicals using experimental transcriptomic data collected from different fish species.

  12. Elevational speciation in action? Restricted gene flow associated with adaptive divergence across an altitudinal gradient.

    PubMed

    Funk, W C; Murphy, M A; Hoke, K L; Muths, E; Amburgey, S M; Lemmon, E M; Lemmon, A R

    2016-02-01

    Evolutionary theory predicts that divergent selection pressures across elevational gradients could cause adaptive divergence and reproductive isolation in the process of ecological speciation. Although there is substantial evidence for adaptive divergence across elevation, there is less evidence that this restricts gene flow. Previous work in the boreal chorus frog (Pseudacris maculata) has demonstrated adaptive divergence in morphological, life history and physiological traits across an elevational gradient from approximately 1500-3000 m in the Colorado Front Range, USA. We tested whether this adaptive divergence is associated with restricted gene flow across elevation - as would be expected if incipient speciation were occurring - and, if so, whether behavioural isolation contributes to reproductive isolation. Our analysis of 12 microsatellite loci in 797 frogs from 53 populations revealed restricted gene flow across elevation, even after controlling for geographic distance and topography. Calls also varied significantly across elevation in dominant frequency, pulse number and pulse duration, which was partly, but not entirely, due to variation in body size and temperature across elevation. However, call variation did not result in strong behavioural isolation: in phonotaxis experiments, low-elevation females tended to prefer an average low-elevation call over a high-elevation call, and vice versa for high-elevation females, but this trend was not statistically significant. In summary, our results show that adaptive divergence across elevation restricts gene flow in P. maculata, but the mechanisms for this potential incipient speciation remain open. PMID:26363130

  13. Elevational speciation in action? Restricted gene flow associated with adaptive divergence across an altitudinal gradient

    USGS Publications Warehouse

    Funk, W. C.; Murphy, M.A.; Hoke, K. L.; Muths, Erin L.; Amburgey, Staci M.; Lemmon, Emily M.; Lemmon, A. R.

    2016-01-01

    Evolutionary theory predicts that divergent selection pressures across elevational gradients could cause adaptive divergence and reproductive isolation in the process of ecological speciation. Although there is substantial evidence for adaptive divergence across elevation, there is less evidence that this restricts gene flow. Previous work in the boreal chorus frog (Pseudacris maculata) has demonstrated adaptive divergence in morphological, life history and physiological traits across an elevational gradient from approximately 1500–3000 m in the Colorado Front Range, USA. We tested whether this adaptive divergence is associated with restricted gene flow across elevation – as would be expected if incipient speciation were occurring – and, if so, whether behavioural isolation contributes to reproductive isolation. Our analysis of 12 microsatellite loci in 797 frogs from 53 populations revealed restricted gene flow across elevation, even after controlling for geographic distance and topography. Calls also varied significantly across elevation in dominant frequency, pulse number and pulse duration, which was partly, but not entirely, due to variation in body size and temperature across elevation. However, call variation did not result in strong behavioural isolation: in phonotaxis experiments, low-elevation females tended to prefer an average low-elevation call over a high-elevation call, and vice versa for high-elevation females, but this trend was not statistically significant. In summary, our results show that adaptive divergence across elevation restricts gene flow in P. maculata, but the mechanisms for this potential incipient speciation remain open.

  14. The facilitating roles and uses of gene banks in addressing the global plan of action

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Contractions of livestock genetic resources are occurring as countries strive to meet increasing demand for livestock products. The Global Plan of Action’s (GPA) Strategic Priority Area 3 – Conservation, calls for governments to establish gene banks for ex-situ cryogenic conservation. Establishment ...

  15. Norepinephrine transporter knock-out alters expression of the genes connected with antidepressant drugs action.

    PubMed

    Solich, Joanna; Kolasa, Magdalena; Kusmider, Maciej; Faron-Gorecka, Agata; Pabian, Paulina; Zurawek, Dariusz; Szafran-Pilch, Kinga; Dziedzicka-Wasylewska, Marta

    2015-01-12

    Norepinephrine transporter knock-out mice (NET-KO) exhibit depression-resistant phenotypes. They manifest significantly shorter immobility times in both the forced swim test and the tail suspension test. Moreover, biochemical studies have revealed the up-regulation of other monoamine transporters (dopamine and serotonin) in the brains of NET-KO mice, similar to the phenomenon observed after the chronic pharmacological blockade of norepinephrine transporter by desipramine in wild-type (WT) animals. NET-KO mice are also resistant to stress, as we demonstrated previously by measuring plasma corticosterone concentration. In the present study, we used a microdissection technique to separate target brain regions and the TaqMan Low Density Array approach to test the expression of a group of genes in the NET-KO mice compared with WT animals. A group of genes with altered expression were identified in four brain structures (frontal and cingulate cortices, dentate gyrus of hippocampus and basal-lateral amygdala) of NET-KO mice compared with WT mice. These genes are known to be altered by antidepressant drugs administration. The most interesting gene is Crh-bp, which modulates the activity of corticotrophin--releasing hormone (CRH) and several CRH-family members. Generally, genetic disturbances within noradrenergic neurons result in biological changes, such as in signal transduction and intercellular communication, and may be linked to changes in noradrenaline levels in the brains of NET-KO mice.

  16. Control of developmentally primed erythroid genes by combinatorial co-repressor actions

    PubMed Central

    Stadhouders, Ralph; Cico, Alba; Stephen, Tharshana; Thongjuea, Supat; Kolovos, Petros; Baymaz, H. Irem; Yu, Xiao; Demmers, Jeroen; Bezstarosti, Karel; Maas, Alex; Barroca, Vilma; Kockx, Christel; Ozgur, Zeliha; van Ijcken, Wilfred; Arcangeli, Marie-Laure; Andrieu-Soler, Charlotte; Lenhard, Boris; Grosveld, Frank; Soler, Eric

    2015-01-01

    How transcription factors (TFs) cooperate within large protein complexes to allow rapid modulation of gene expression during development is still largely unknown. Here we show that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components that together maintain an erythroid-specific gene expression programme primed for rapid activation until differentiation is induced. A combination of proteomics, functional genomics and in vivo studies presented here identifies known and novel co-repressors, most notably the ETO2 and IRF2BP2 proteins, involved in maintaining this primed state. The ETO2–IRF2BP2 axis, interacting with the NCOR1/SMRT co-repressor complex, suppresses the expression of the vast majority of archetypical erythroid genes and pathways until its decommissioning at the onset of terminal erythroid differentiation. Our experiments demonstrate that multimeric regulatory complexes feature a dynamic interplay between activating and repressing components that determines lineage-specific gene expression and cellular differentiation. PMID:26593974

  17. Control of developmentally primed erythroid genes by combinatorial co-repressor actions.

    PubMed

    Stadhouders, Ralph; Cico, Alba; Stephen, Tharshana; Thongjuea, Supat; Kolovos, Petros; Baymaz, H Irem; Yu, Xiao; Demmers, Jeroen; Bezstarosti, Karel; Maas, Alex; Barroca, Vilma; Kockx, Christel; Ozgur, Zeliha; van Ijcken, Wilfred; Arcangeli, Marie-Laure; Andrieu-Soler, Charlotte; Lenhard, Boris; Grosveld, Frank; Soler, Eric

    2015-01-01

    How transcription factors (TFs) cooperate within large protein complexes to allow rapid modulation of gene expression during development is still largely unknown. Here we show that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components that together maintain an erythroid-specific gene expression programme primed for rapid activation until differentiation is induced. A combination of proteomics, functional genomics and in vivo studies presented here identifies known and novel co-repressors, most notably the ETO2 and IRF2BP2 proteins, involved in maintaining this primed state. The ETO2-IRF2BP2 axis, interacting with the NCOR1/SMRT co-repressor complex, suppresses the expression of the vast majority of archetypical erythroid genes and pathways until its decommissioning at the onset of terminal erythroid differentiation. Our experiments demonstrate that multimeric regulatory complexes feature a dynamic interplay between activating and repressing components that determines lineage-specific gene expression and cellular differentiation. PMID:26593974

  18. Next-generation sequencing identifies high frequency of mutations in potentially clinically actionable genes in sebaceous carcinoma.

    PubMed

    Tetzlaff, Michael T; Singh, Rajesh R; Seviour, Elena G; Curry, Jonathan L; Hudgens, Courtney W; Bell, Diana; Wimmer, Daniel A; Ning, Jing; Czerniak, Bogdan A; Zhang, Li; Davies, Michael A; Prieto, Victor G; Broaddus, Russell R; Ram, Prahlad; Luthra, Rajyalakshmi; Esmaeli, Bita

    2016-09-01

    Sebaceous carcinoma (SC) is a rare but aggressive malignancy with frequent recurrence and metastases. Surgery is the mainstay of therapy, but effective systemic therapies are lacking because the molecular alterations driving SC remain poorly understood. To identify these, we performed whole-exome next-generation sequencing of 409 cancer-associated genes on 27 SCs (18 primary/locally recurrent ocular, 5 paired metastatic ocular, and 4 primary extraocular) from 20 patients. In ocular SC, we identified 139 non-synonymous somatic mutations (median/lesion 3; range 0-23). Twenty-five of 139 mutations (18%) occurred in potentially clinically actionable genes in 6 of 16 patients. The most common mutations were mutations in TP53 (n = 9), RB1 (n = 6), PIK3CA (n = 2), PTEN (n = 2), ERBB2 (n = 2), and NF1 (n = 2). TP53 and RB1 mutations were restricted to ocular SC and correlated with aberrant TP53 and RB protein expression. Systematic pathway analyses demonstrated convergence of these mutations to activation of the PI3K signalling cascade, and PI3K pathway activation was confirmed in tumours with PTEN and/or PIK3CA mutations. Considerable inter-tumoural heterogeneity was observed between paired primary and metastatic ocular SCs. In primary extraocular SC, we identified 77 non-synonymous somatic mutations (median/lesion 22.5; range 3-29). This overall higher mutational load was attributed to a microsatellite instability phenotype in three of four patients and somatically acquired mutations in mismatch repair genes in two of four patients. Eighteen of 77 mutations (23%) were in potentially clinically actionable genes in three of four patients, including BTK, FGFR2, PDGFRB, HRAS, and NF1 mutations. Identification of potentially clinically actionable mutations in 9 of 20 SC patients (45%) underscores the importance of next-generation sequencing to expand the spectrum of genotype-matched targeted therapies. Frequent activation of PI3K signalling pathways provides a strong

  19. Mechanism of Action of 2-Aminobenzamide HDAC Inhibitors in Reversing Gene Silencing in Friedreich’s Ataxia

    PubMed Central

    Soragni, Elisabetta; Chou, C. James; Rusche, James R.; Gottesfeld, Joel M.

    2015-01-01

    The genetic defect in Friedreich’s ataxia (FRDA) is the hyperexpansion of a GAA•TTC triplet in the first intron of the FXN gene, encoding the essential mitochondrial protein frataxin. Histone post-translational modifications near the expanded repeats are consistent with heterochromatin formation and consequent FXN gene silencing. Using a newly developed human neuronal cell model, derived from patient-induced pluripotent stem cells, we find that 2-aminobenzamide histone deacetylase (HDAC) inhibitors increase FXN mRNA levels and frataxin protein in FRDA neuronal cells. However, only compounds targeting the class I HDACs 1 and 3 are active in increasing FXN mRNA in these cells. Structural analogs of the active HDAC inhibitors that selectively target either HDAC1 or HDAC3 do not show similar increases in FXN mRNA levels. To understand the mechanism of action of these compounds, we probed the kinetic properties of the active and inactive inhibitors, and found that only compounds that target HDACs 1 and 3 exhibited a slow-on/slow-off mechanism of action for the HDAC enzymes. HDAC1- and HDAC3-selective compounds did not show this activity. Using siRNA methods in the FRDA neuronal cells, we show increases in FXN mRNA upon silencing of either HDACs 1 or 3, suggesting the possibility that inhibition of each of these class I HDACs is necessary for activation of FXN mRNA synthesis, as there appears to be redundancy in the silencing mechanism caused by the GAA•TTC repeats. Moreover, inhibitors must have a long residence time on their target enzymes for this activity. By interrogating microarray data from neuronal cells treated with inhibitors of different specificity, we selected two genes encoding histone macroH2A (H2AFY2) and Polycomb group ring finger 2 (PCGF2) that were specifically down-regulated by the inhibitors targeting HDACs1 and 3 versus the more selective inhibitors for further investigation. Both genes are involved in transcriptional repression and we

  20. Global control of motor neuron topography mediated by the repressive actions of a single hox gene.

    PubMed

    Jung, Heekyung; Lacombe, Julie; Mazzoni, Esteban O; Liem, Karel F; Grinstein, Jonathan; Mahony, Shaun; Mukhopadhyay, Debnath; Gifford, David K; Young, Richard A; Anderson, Kathryn V; Wichterle, Hynek; Dasen, Jeremy S

    2010-09-01

    In the developing spinal cord, regional and combinatorial activities of Hox transcription factors are critical in controlling motor neuron fates along the rostrocaudal axis, exemplified by the precise pattern of limb innervation by more than fifty Hox-dependent motor pools. The mechanisms by which motor neuron diversity is constrained to limb levels are, however, not well understood. We show that a single Hox gene, Hoxc9, has an essential role in organizing the motor system through global repressive activities. Hoxc9 is required for the generation of thoracic motor columns, and in its absence, neurons acquire the fates of limb-innervating populations. Unexpectedly, multiple Hox genes are derepressed in Hoxc9 mutants, leading to motor pool disorganization and alterations in the connections by thoracic and forelimb-level subtypes. Genome-wide analysis of Hoxc9 binding suggests that this mode of repression is mediated by direct interactions with Hox regulatory elements, independent of chromatin marks typically associated with repressed Hox genes.

  1. Corn gluten hydrolysate and capsaicin have complimentary actions on body weight reduction and lipid-related genes in diet-induced obese rats.

    PubMed

    Mun, Joo-Mi; Ok, Hyang Mok; Kwon, Oran

    2014-05-01

    The aim of this study was to test the hypothesis that a combination of corn gluten hydrolysate (CGH) and capsaicin may have an additive or synergistic effect on body weight reduction. For 13 weeks, male Sprague-Dawley rats were provided a diet to induce obesity. Afterward, the rats were randomly divided into 5 dietary groups: the normal control (n = 5), the high-fat control (n = 8), the high-fat diet (HFD) containing 35% CGH (n = 7), the HFD containing 0.02% capsaicin (HF-P) (n = 8), and the HFD containing both CGH and capsaicin (HF-CP) (n = 7) for an additional 4 weeks. Administration of CGH plus capsaicin, along with a HFD, led to significant decreases in body weight, fat mass, lipids in the liver, and plasma leptin as well as increases in plasma adiponectin. The pattern of gene expression was different in each target organ. In the liver, up-regulation of peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1α, and acyl-coenzyme A oxidase was found in the HF-CP group. In contrast, down-regulation of peroxisome proliferator-activated receptor γ was found in both the HFD containing 35% CGH and HF-CP groups. In skeletal muscle, up-regulation of insulin receptor and uncoupling protein 3 was found in the HF-P group only, whereas up-regulation of the glucose transporter 4 gene was observed in both the HF-CP and HF-P groups. In adipose tissue, up-regulation of peroxisome proliferator-activated receptor γ and hormone-sensitive lipase was only found in the HF-CP group. In summary, this study suggests that CGH and capsaicin perform complementary actions on food intake, lipid metabolism, and insulin sensitivity by a coordinated control of energy metabolism in the liver, adipose tissue, and skeletal muscle, thus exerting an additive effect on body weight reduction.

  2. Branching in Pea (Action of Genes Rms3 and Rms4).

    PubMed Central

    Beveridge, C. A.; Ross, J. J.; Murfet, I. C.

    1996-01-01

    The nonallelic ramosus mutations rms3-2 and rms4 of pea (Pisum sativum L.) cause extensive release of vegetative axillary buds and lateral growth in comparison with wild-type (cv Torsdag) plants, in which axillary buds are not normally released under the conditions utilized. Grafting studies showed that the expression of the rms4 mutation in the shoot is independent of the genotype of the root-stock. In contrast, the length of the branches at certain nodes of rms3-2 plants was reduced by grafting to wild-type stocks, indicating that the wild-type Rms3 gene may control the level of a mobile substance produced in the root. This substance also appears to be produced in the shoot because Rms3 shoots did not branch when grafted to mutant rms3-2 rootstocks. However, the end product of the Rms3 gene appears to differ from that of the Rms2 gene (C.A. Beveridge, J.J. Ross, and I.C. Murfet [1994] Plant Physiol 104: 953-959) because reciprocal grafts between rms3-2 and rms2 seedlings produced mature shoots with apical dominance similar to that of rms3-2 and rms2 shoots grafted to wild-type stocks. Indole-3-acetic acid levels were not reduced in apical or nodal portions of rms4 plants and were actually elevated (up to 2-fold) in rms3-2 plants. It is suggested that further studies with these branching mutants may enable significant progress in understanding the normal control of apical dominance and the related communication between the root and shoot. PMID:12226224

  3. Global gene expression and Ingenuity biological functions analysis on PCBs 153 and 138 induced human PBMC in vitro reveals differential mode(s) of action in developing toxicities.

    PubMed

    Ghosh, Somiranjan; Zang, Shizhu; Mitra, Partha S; Ghimbovschi, Svetlana; Hoffman, Eric P; Dutta, Sisir K

    2011-07-01

    Several reports have indicated that low level of polychlorinated biphenyl (PCB) exposure can adversely affect a multitude of physiological disorders and diseases in in vitro, in vivo, and as reported in epidemiological studies. This investigation is focused on the possible contribution of two most prevalent PCB congeners in vitro in developing toxicities. We used PCBs 138 and 153 at the human equivalence level as model agents to test their specificity in developing toxicities. We chose a global approach using oligonucleotide microarray technology to investigate modulated gene expression for biological effects, upon exposure of PCBs, followed by Ingenuity Pathway Analysis (IPA), to understand the underlying consequence in developing disease and disorders. We performed in vitro studies with human peripheral blood mononuclear cells (PBMC), where PBMC cells were exposed to respective PCBs for 48 h. Overall, our observation on gene expression indicated that PCB produces a unique signature affecting different pathways, specific for each congener. While analyzing these data through IPA, the prominent and interesting disease and disorders were neurological disease, cancer, cardiovascular disease, respiratory disease, as well as endocrine system disorders, genetic disorders, and reproductive system disease. They showed strong resemblances with in vitro, in vivo, and in the epidemiological studies. A distinct difference was observed in renal and urological diseases, organisimal injury and abnormalities, dental disease, ophthalmic disease, and psychological disorders, which are only revealed by PCB 138 exposure, but not in PCB 153. The present study emphasizes the challenges of global gene expression in vitro and was correlated with the results of exposed human population. The microarray results give a molecular mechanistic insight and functional effects, following PCB exposure. The extent of changes in genes related to several possible mode(s) of action highlights the

  4. Maize Adh-1 promoter sequences control anaerobic regulation: addition of upstream promoter elements from constitutive genes is necessary for expression in tobacco

    PubMed Central

    Ellis, J.G.; Llewellyn, D.J.; Dennis, E.S.; Peacock, W.J.

    1987-01-01

    The promoter region of a maize alcohol dehydrogenase gene (Adh-1) was linked to a reporter gene encoding chloramphenicol acetyl transferase (CAT) and transformed stably into tobacco cells using T-DNA vectors. No CAT enzyme activity could be detected in transgenic tobacco plants unless upstream promoter elements from the octopine synthase gene or the cauliflower mosaic virus 35S promoter were supplied in addition to the maize promoter region. CAT enzyme activity and transcription of the chimaeric gene were then readily detected after anaerobic induction. The first 247 bp upstream of the translation initiation codon of the maize Adh-1 gene were sufficient to impose anaerobic regulation on the hybrid gene and S1 nuclease mapping confirmed mRNA initiation is from the normal maize Adh-1 transcription start point. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6. PMID:15981329

  5. Prediction of joint algal toxicity of nano-CeO2/nano-TiO2 and florfenicol: Independent action surpasses concentration addition.

    PubMed

    Wang, Zhuang; Wang, Se; Peijnenburg, Willie J G M

    2016-08-01

    Co-exposure of aquatic organisms to engineered nanoparticles (ENPs) and antibiotics is likely to take place in the environment. However, the impacts of co-exposure on aquatic organisms are virtually unknown and understanding the joint toxicity of ENPs and antibiotics is a topic of importance. The independent action (IA) model and the concentration addition (CA) model are two of the most common approaches to mixture toxicity assessment. In this study, the joint toxicity of two ENPs (nCeO2 and nTiO2) and one antibiotic (florfenicol, FLO) to Chlorella pyrenoidosa was determined to compare the applicability of the IA and the CA model. Concentration-response analyses were performed for single toxicants and for binary mixtures containing FLO and one of the ENPs at two suspended particle concentrations. The effect concentrations and the observed effects of the binary mixtures were compared to the predictions of the joint toxicity. The observed toxicity associated with the nCeO2 or nTiO2 exposure was enhanced by the concomitant FLO exposure. The joint toxicity of nCeO2 and FLO was significantly higher than that of nTiO2 and FLO. Predictions based on the IA and CA models tend to underestimate the overall toxicity (in terms of median effect concentration) of the binary mixtures, but IA performs better than CA, irrespective of the effect level under consideration and the types of mixtures studied. This result underpins the need to consider the effects of mixtures of ENPs and organic chemicals on aquatic organisms, and the practicability of the IA and CA methods in toxicity assessment of ENPs.

  6. Gas1 is a pleiotropic regulator of cellular functions: from embryonic development to molecular actions in cancer gene therapy.

    PubMed

    Segovia, José; Zarco, Natanael

    2014-01-01

    Cellular homeostasis is governed by a precise regulation of the molecular mechanisms of action of several proteins in a given time. There is a group of proteins that have a particular role depending on the cellular context in which they are present and are known as pleiotropic proteins. The Gas1 (Growth Arrest Specific 1) gene was isolated from a subtraction library from serum arrested versus growing NIH3T3 mouse fibroblast. Gas1 is a member of the alpha receptors (GFRα) for the family of GDNF ligands (GFL), we have previously shown that Gas1 acts as a negative modulator of the GDNF-induced intracellular signaling and induces cell arrest and apoptosis. This modulating activity is the cause of the capacity of Gas1 to act as a tumor suppressor. On the other hand, several studies have shown the interaction between Gas1 and Hh (Hedgehog) proteins to potentiate the positive regulation of this pathway, which is involved in the development of the nervous system, and in both the origin and progression of different tumors. This review summarizes our current understanding of the structure of Gas1 and the molecular mechanism of action in different cellular functions, both during embryonic development, in the adult and its effects inhibiting cell growth and inducing apoptosis of cancer cells.

  7. Somatostatin-28 inhibitory action on somatolactin-α and -β gene expression in goldfish.

    PubMed

    Jiang, Quan; Wong, Anderson O L

    2014-09-15

    Somatostain (SS) is known to inhibit growth hormone (GH) and prolactin (PRL) secretion. Somatolactin (SL) is a member of the GH/PRL family, but its regulation by goldfish brain somatostatin-28 (gbSS-28) has not been examined. To this end, the structural identity of goldfish SLα was established by 5'/3'-rapid amplification of cDNA ends. As revealed by in situ hybridization and immunohistochemical staining, the expression of SL isoforms was detected in pituitary cells located in the neurointermediate lobe (NIL). The transcripts of goldfish SS receptor 5a (Sst5a) but not Sst1b, Sst2, or Sst3a were detected in the goldfish NIL cells by RT-PCR. In goldfish pituitary cells, gbSS-28 not only had an inhibitory effect on basal SLα and SLβ mRNA levels but also could abolish insulin-like growth factor-stimulated SL gene expression. In primary cultures of goldfish NIL cells, gbSS-28 reduced forskolin-stimulated total cAMP production. With the use of a pharmacological approach, the adenylate cyclase (AC)/cAMP and phospholipase C (PLC)/inositol trisphosphate (IP3)/protein kinase C (PKC) cascades were shown to be involved in gbSS-28-inhibited SLα mRNA expression. Similar postreceptor signaling cascades were also observed for gbSS-28-reduced SLβ mRNA expression, except that PKC coupling to PLC was not involved. These results provide evidence that gbSS-28 can inhibit SLα and SLβ gene expression at the goldfish pituitary level via Sst5 through differential coupling of AC/cAMP and PLC/IP3/PKC cascades.

  8. Phytate addition to soil induces changes in the abundance and expression of Bacillus β-propeller phytase genes in the rhizosphere.

    PubMed

    Jorquera, Milko A; Saavedra, Nicolás; Maruyama, Fumito; Richardson, Alan E; Crowley, David E; del C Catrilaf, Rosa; Henriquez, Evelyn J; de la Luz Mora, María

    2013-02-01

    Phytate-mineralizing rhizobacteria (PMR) perform an essential function for the mineralization of organic phosphorus but little is known about their ecology in soils and rhizosphere. In this study, PCR-based methods were developed for detection and quantification of the Bacillus β-propeller phytase (BPP) gene. Experiments were conducted to monitor the presence and persistence of a phytate-mineralizing strain, Bacillus sp. MQH19, after inoculation of soil microcosms and within the rhizosphere. The occurrence of the BPP gene in natural pasture soils from Chilean Andisols was also examined. The results showed that the Bacillus BPP gene was readily detected in sterile and nonsterile microcosms, and that the quantitative PCR (qPCR) methods could be used to monitor changes in the abundance of the BPP gene over time. Our results also show that the addition of phytate to nonsterile soils induced the expression of the BPP gene in the rhizosphere of ryegrass and the BPP gene was detected in all pasture soils sampled. This study shows that phytate addition soils induced changes in the abundance and expression of Bacillus BPP to genes in the rhizosphere and demonstrates that Bacillus BPP gene is cosmopolitan in pasture soils from Chilean Andisols.

  9. Yeast-containing feed additive alters gene expression profiles associated with innate immunity in whole blood of a rodent model.

    PubMed

    Branson, Jennifer A; McLean, Derek J; Forsberg, Neil E; Bobe, Gerd

    2016-05-01

    Feeding a yeast-containing additive (YCA; OmniGen-AF) improves immune responses in ruminant livestock and reduces subsequent production losses. The objective was to identify molecular pathways by which dietary YCA may modify immune responses using a rodent model. Thirty-seven healthy, unchallenged CD rats received a diet containing 0 (control; n = 5, only 28 d), 0.5% (n = 15) or 1% (n = 17) YCA for 7 (n = 4/group), 14 (n = 3 or 4/group), 21 (n = 3 or 4/group) or 28 (n = 5/group) d. At the end of the feeding periods, whole blood was collected and the isolated RNA was analyzed for the expression of 84 genes involved in innate and cell-mediated adaptive immune responses. Three bacterial pattern recognition receptors TLR1 (0.5%: + 2.01; 1%: + 2.38), TLR6 (0.5%: + 2.11; 1%: + 2.34) and NOD2 (0.5%: + 2.32; 1%: + 2.23), two APC surface receptors CD1D1 (0.5%: + 1.75; 1%: + 2.33) and CD80 (0.5%: +2.45; 1%: +3.00), and the cell signaling molecule MAPK8 (0.5%: +1.87; 1%: +2.35) were significantly up-regulated by YCA at both inclusion rates. In conclusion, feeding YCA may potentially increase recognition and responses to bacterial pathogens and T-cell activation and differentiation and thereby maintain health and prevent production losses. PMID:27033362

  10. Physiological basis of tolerance to complete submergence in rice involves genetic factors in addition to the SUB1 gene.

    PubMed

    Singh, Sudhanshu; Mackill, David J; Ismail, Abdelbagi M

    2014-01-01

    Recurring floods in Asia cause poor crop establishment. Yields decline drastically when plants are completely submerged for a few days. Traditional rice cultivars predominate because they have acquired moderate tolerance to flooding but they carry the penalty of inherently lower grain yields. In contrast, modern high-yielding varieties are highly susceptible to flooding. Cultivars with tolerance to complete submergence were recently developed in the background of popular varieties by transferring the submergence tolerance gene SUBMERGENCE1 (SUB1) from the highly tolerant Indian landrace FR13A. The present study evaluated three pairs of Sub1 near-isogenic lines (NILs) together with FR13A and two of its submergence-tolerant derivatives under field conditions to assess the survival and growth processes occurring during submergence and recovery that are associated with SUB1. Under control conditions, the NILs showed similar growth and biomass accumulation, indicating that SUB1 had no apparent effects. Submergence substantially decreased biomass accumulation but with greater reduction in the genotypes lacking SUB1, particularly when submergence was prolonged for 17 days. When submerged, the lines lacking SUB1 showed greater elongation and lower or negative biomass accumulation. Sub1 lines maintained higher chlorophyll concentrations during submergence and lost less non-structural carbohydrates (NSC) after submergence. This indicates that the introgression of SUB1 resulted in better regulation of NSC during submergence and that high pre-submergence NSC is not essential for the submergence tolerance conferred by SUB1. During recovery, chlorophyll degradation was faster in genotypes lacking SUB1 and any surviving plants showed poorer and delayed emergence of tillers and leaves. Sub1 lines restored new leaf and tiller production faster. During submergence, FR13A showed not only slower leaf elongation but also accumulated extra biomass and was able to recover faster than Sub

  11. Modulation of chicken intestinal immune gene expression by small cationic peptides as feed additives during the first week posthatch.

    PubMed

    Kogut, Michael H; Genovese, Kenneth J; He, Haiqi; Swaggerty, Christina L; Jiang, Yiwei

    2013-09-01

    We have been investigating modulation strategies tailored around the selective stimulation of the host's immune system as an alternative to direct targeting of microbial pathogens by antibiotics. One such approach is the use of a group of small cationic peptides (BT) produced by a Gram-positive soil bacterium, Brevibacillus texasporus. These peptides have immune modulatory properties that enhance both leukocyte functional efficiency and leukocyte proinflammatory cytokine and chemokine mRNA transcription activities in vitro. In addition, when provided as a feed additive for just 4 days posthatch, BT peptides significantly induce a concentration-dependent protection against cecal and extraintestinal colonization by Salmonella enterica serovar Enteritidis. In the present studies, we assessed the effects of feeding BT peptides on transcriptional changes on proinflammatory cytokines, inflammatory chemokines, and Toll-like receptors (TLR) in the ceca of broiler chickens with and without S. Enteritidis infection. After feeding a BT peptide-supplemented diet for the first 4 days posthatch, chickens were then challenged with S. Enteritidis, and intestinal gene expression was measured at 1 or 7 days postinfection (p.i.) (5 or 11 days of age). Intestinal expression of innate immune mRNA transcripts was analyzed by quantitative real-time PCR (qRT-PCR). Analysis of relative mRNA expression showed that a BT peptide-supplemented diet did not directly induce the transcription of proinflammatory cytokine, inflammatory chemokine, type I/II interferon (IFN), or TLR mRNA in chicken cecum. However, feeding the BT peptide-supplemented diet primed cecal tissue for increased (P ≤ 0.05) transcription of TLR4, TLR15, and TLR21 upon infection with S. Enteritidis on days 1 and 7 p.i. Likewise, feeding the BT peptides primed the cecal tissue for increased transcription of proinflammatory cytokines (interleukin 1β [IL-1β], IL-6, IL-18, type I and II IFNs) and inflammatory chemokine (CxCLi2

  12. Dynamic Response of Pseudomonas putida S12 to Sudden Addition of Toluene and the Potential Role of the Solvent Tolerance Gene trgI

    PubMed Central

    Volkers, Rita J. M.; Snoek, L. Basten; Ruijssenaars, Harald J.; de Winde, Johannes H.

    2015-01-01

    Pseudomonas putida S12 is exceptionally tolerant to various organic solvents. To obtain further insight into this bacterium’s primary defence mechanisms towards these potentially harmful substances, we studied its genome wide transcriptional response to sudden addition of toluene. Global gene expression profiles were monitored for 30 minutes after toluene addition. During toluene exposure, high oxygen-affinity cytochrome c oxidase is specifically expressed to provide for an adequate proton gradient supporting solvent efflux mechanisms. Concomitantly, the glyoxylate bypass route was up-regulated, to repair an apparent toluene stress-induced redox imbalance. A knock-out mutant of trgI, a recently identified toluene-repressed gene, was investigated in order to identify TrgI function. Remarkably, upon addition of toluene the number of differentially expressed genes initially was much lower in the trgI-mutant than in the wild-type strain. This suggested that after deletion of trgI cells were better prepared for sudden organic solvent stress. Before, as well as after, addition of toluene many genes of highly diverse functions were differentially expressed in trgI-mutant cells as compared to wild-type cells. This led to the hypothesis that TrgI may not only be involved in the modulation of solvent-elicited responses but in addition may affect basal expression levels of large groups of genes. PMID:26181384

  13. Mitochondrial genome sequence and gene order of Sipunculus nudus give additional support for an inclusion of Sipuncula into Annelida

    PubMed Central

    Mwinyi, Adina; Meyer, Achim; Bleidorn, Christoph; Lieb, Bernhard; Bartolomaeus, Thomas; Podsiadlowski, Lars

    2009-01-01

    Background Mitochondrial genomes are a valuable source of data for analysing phylogenetic relationships. Besides sequence information, mitochondrial gene order may add phylogenetically useful information, too. Sipuncula are unsegmented marine worms, traditionally placed in their own phylum. Recent molecular and morphological findings suggest a close affinity to the segmented Annelida. Results The first complete mitochondrial genome of a member of Sipuncula, Sipunculus nudus, is presented. All 37 genes characteristic for metazoan mtDNA were detected and are encoded on the same strand. The mitochondrial gene order (protein-coding and ribosomal RNA genes) resembles that of annelids, but shows several derivations so far found only in Sipuncula. Sequence based phylogenetic analysis of mitochondrial protein-coding genes results in significant bootstrap support for Annelida sensu lato, combining Annelida together with Sipuncula, Echiura, Pogonophora and Myzostomida. Conclusion The mitochondrial sequence data support a close relationship of Annelida and Sipuncula. Also the most parsimonious explanation of changes in gene order favours a derivation from the annelid gene order. These results complement findings from recent phylogenetic analyses of nuclear encoded genes as well as a report of a segmental neural patterning in Sipuncula. PMID:19149868

  14. Epigenetic allelic states of a maize transcriptional regulatory locus exhibit overdominant gene action.

    PubMed Central

    Hollick, J B; Chandler, V L

    1998-01-01

    Using alleles of the maize purple plant locus (pl), which encodes a transcriptional regulator of anthocyanin pigment synthesis, we describe a case of single-locus heterosis, or overdominance, where the heterozygote displays a phenotype that is greater than either homozygote. The Pl-Rhoades (Pl-Rh) allele is subject to epigenetic changes in gene expression, resulting in quantitatively distinct expression states. Allelic states with low-expression levels, designated Pl'-mahogany (Pl'-mah), are dominant to the high-expression state of Pl-Rh. Pl'-mah states retain low-expression levels in subsequent generations when homozygous or heterozygous with Pl-Rh. However, Pl'-mah alleles frequently exhibit higher expression levels when heterozygous with other pl alleles; illustrating an overdominant allelic relationship. Higher expression levels are also observed when Pl'-mah is hemizygous. These results suggest that persistent allelic interactions between Pl'-mah and Pl-Rh are required to maintain the low-expression state and that other pl alleles are missing sequences required for this interaction. The Pl-Rh state can be sexually transmitted from Pl'-mah/pl heterozygotes, but not from Pl'-mah hemizygotes, suggesting that fixation of the high-expression state may involve synapsis. The existence of such allele-dependent regulatory mechanisms implicates a novel importance of allele polymorphisms in the genesis and maintenance of genetic variation. PMID:9755217

  15. A functional NPSR1 gene variant and environment shape personality and impulsive action: a longitudinal study.

    PubMed

    Laas, Kariina; Reif, Andreas; Kiive, Evelyn; Domschke, Katharina; Lesch, Klaus-Peter; Veidebaum, Toomas; Harro, Jaanus

    2014-03-01

    Neuropeptide S and its receptor NPSR1 are involved in the regulation of arousal, attention and anxiety. We examined whether the NPSR1 gene functional polymorphism Asn¹⁰⁷Ile (rs324981, A>T) influences personality, impulsivity, and attention-deficit/hyperactivity disorder (ADHD)-related symptoms in a population-representative sample, and whether any eventual associations depend on age, sex, family relations and stressful life events (SLE). We used self-reports or teachers' ratings for both the younger (n=593) and older (n=583) cohort of the longitudinal Estonian Children Personality, Behaviour and Health Study. Males with the TT genotype displayed more ADHD-related symptoms. Adaptive impulsivity and Extraversion increased the most from age 18 to 25. While highest increases were observed in AA men, TT women exhibited the largest decreases. For participants with the AA genotype, Warmth in family was inversely associated with Neuroticism, and positively associated with Extraversion and Adaptive impulsivity. High exposure to SLE increased impulsivity and ADHD scores in TT genotype subjects. We conclude that the NPSR1 A/T polymorphism is associated with impulsivity, ADHD symptoms and personality, mirroring the activity- and anxiety-mediating role of NPSR1. Heterozygous individuals were the least sensitive to environmental factors, whereas subjects with the AA genotype and TT genotype reacted to different types of environmental adversities.

  16. Microarray Analysis of Gene Expression in Saccharomyces cerevisiae kap108Δ Mutants upon Addition of Oxidative Stress.

    PubMed

    Belanger, Kenneth D; Larson, Nathaniel; Kahn, Jonathan; Tkachev, Dmitry; Ay, Ahmet

    2016-01-01

    Protein transport between the nucleus and cytoplasm of eukaryotic cells is tightly regulated, providing a mechanism for controlling intracellular localization of proteins, and regulating gene expression. In this study, we have investigated the importance of nucleocytoplasmic transport mediated by the karyopherin Kap108 in regulating cellular responses to oxidative stress in Saccharomyces cerevisiae We carried out microarray analyses on wild-type and kap108 mutant cells grown under normal conditions, shortly after introduction of oxidative stress, after 1 hr of oxidative stress, and 1 hr after oxidative stress was removed. We observe more than 500 genes that undergo a 40% or greater change in differential expression between wild-type and kap108Δ cells under at least one of these conditions. Genes undergoing changes in expression can be categorized in two general groups: 1) those that are differentially expressed between wild-type and kap108Δ cells, no matter the oxidative stress conditions; and 2) those that have patterns of response dependent upon both the absence of Kap108, and introduction or removal of oxidative stress. Gene ontology analysis reveals that, among the genes whose expression is reduced in the absence of Kap108 are those involved in stress response and intracellular transport, while those overexpressed are largely involved in mating and pheromone response. We also identified 25 clusters of genes that undergo similar patterns of change in gene expression when oxidative stresses are added and subsequently removed, including genes involved in stress response, oxidation-reduction processing, iron homeostasis, ascospore wall assembly, transmembrane transport, and cell fusion during mating. These data suggest that Kap108 is important for regulating expression of genes involved in a variety of specific cell functions.

  17. Identification of Gene Expression Signatures in the Chicken Intestinal Intraepithelial Lymphocytes in Response to Herb Additive Supplementations

    PubMed Central

    Won, Kyeong-Hye; Song, Ki-Duk; Park, Jong-Eun; Kim, Duk-Kyung; Na, Chong-Sam

    2016-01-01

    Anethole and garlic have an immune modulatory effects on avian coccidiosis, and these effects are correlated with gene expression changes in intestinal epithelial lymphocytes (IELs). In this study, we integrated gene expression datasets from two independent experiments and investigated gene expression profile changes by anethole and garlic respectively, and identified gene expression signatures, which are common targets of these herbs as they might be used for the evaluation of the effect of plant herbs on immunity toward avian coccidiosis. We identified 4,382 and 371 genes, which were differentially expressed in IELs of chickens supplemented with garlic and anethole respectively. The gene ontology (GO) term of differentially expressed genes (DEGs) from garlic treatment resulted in the biological processes (BPs) related to proteolysis, e.g., “modification-dependent protein catabolic process”, “proteolysis involved in cellular protein catabolic process”, “cellular protein catabolic process”, “protein catabolic process”, and “ubiquitin-dependent protein catabolic process”. In GO analysis, one BP term, “Proteolysis”, was obtained. Among DEGs, 300 genes were differentially regulated in response to both garlic and anethole, and 234 and 59 genes were either up- or down-regulated in supplementation with both herbs. Pathway analysis resulted in enrichment of the pathways related to digestion such as “Starch and sucrose metabolism” and “Insulin signaling pathway”. Taken together, the results obtained in the present study could contribute to the effective development of evaluation system of plant herbs based on molecular signatures related with their immunological functions in chicken IELs. PMID:26954117

  18. High frequency of additional gene mutations in acute myeloid leukemia with MLL partial tandem duplication: DNMT3A mutation is associated with poor prognosis.

    PubMed

    Kao, Hsiao-Wen; Liang, D Cherng; Kuo, Ming-Chung; Wu, Jin-Hou; Dunn, Po; Wang, Po-Nan; Lin, Tung-Liang; Shih, Yu-Shu; Liang, Sung-Tzu; Lin, Tung-Huei; Lai, Chen-Yu; Lin, Chun-Hui; Shih, Lee-Yung

    2015-10-20

    The mutational profiles of acute myeloid leukemia (AML) with partial tandem duplication of mixed-lineage leukemia gene (MLL-PTD) have not been comprehensively studied. We studied 19 gene mutations for 98 patients with MLL-PTD AML to determine the mutation frequency and clinical correlations. MLL-PTD was screened by reverse-transcriptase PCR and confirmed by real-time quantitative PCR. The mutational analyses were performed with PCR-based assays followed by direct sequencing. Gene mutations of signaling pathways occurred in 63.3% of patients, with FLT3-ITD (44.9%) and FLT3-TKD (13.3%) being the most frequent. 66% of patients had gene mutations involving epigenetic regulation, and DNMT3A (32.7%), IDH2 (18.4%), TET2 (18.4%), and IDH1 (10.2%) mutations were most common. Genes of transcription pathways and tumor suppressors accounted for 23.5% and 10.2% of patients. RUNX1 mutation occurred in 23.5% of patients, while none had NPM1 or double CEBPA mutation. 90.8% of MLL-PTD AML patients had at least one additional gene mutation. Of 55 MLL-PTD AML patients who received standard chemotherapy, age older than 50 years and DNMT3A mutation were associated with inferior outcome. In conclusion, gene mutations involving DNA methylation and activated signaling pathway were common co-existed gene mutations. DNMT3A mutation was a poor prognostic factor in MLL-PTD AML.

  19. Additive effect of polymorphisms in the β2 -adrenoceptor and NADPH oxidase p22 phox genes contributes to the loss of estimated glomerular filtration rate in Chinese.

    PubMed

    Wang, Tao; Zhang, Yan; Ma, JingTao; Feng, Zhen; Niu, Kai; Liu, Bing

    2014-09-01

    Because increased oxidative stress may mediate the detrimental actions of enhanced sympathetic nervous activity on renal function and vice versa, we investigated the effect of the polymorphic Arg16Gly in the β2 -adrenoceptor (ADRB2) gene, Trp64Arg in the β3 -adrenoceptor (ADRB3) gene and C242T in the NADPH oxidase p22phox (CYBA) gene on estimated glomerular filtration rate (eGFR) in a Chinese population. Initially recruited from different outpatient services of HeBei General Hospital in northern China, 668 individuals were finally included in the study, with complete demographic information. Laboratory tests were performed and estimated glomerular filtration rate (eGFR) was derived from the Modification of Diet in Renal Disease (MDRD) equation for the Chinese population. Plasma noradrenaline levels and genotype were determined by HPLC and the TaqMan method, respectively. Only across the Arg16Gly polymorphism did eGFR show significant difference: it was lower in individuals with the Gly16Gly variation, who also had the highest plasma noradrenaline levels. This polymorphism remained a significant determinant of eGFR after multivariate analysis. Of importance, the multifactor dimensionality reduction method further detected a significant synergism between the Arg16Gly and C242T polymorphisms in reducing eGFR. These observations clarify the effects of the studied polymorphisms on eGFR and exemplify gene-gene interactions influencing renal function.

  20. A Meta-Analytic Review of the Theories of Reasoned Action and Planned Behavior in Physical Activity: Predictive Validity and the Contribution of Additional Variables.

    ERIC Educational Resources Information Center

    Hagger, Martin S.; Chatzisarantis, Nikos L. D.; Biddle, Stuart J. H.

    2002-01-01

    Examined relations between behavior, intentions, attitudes, subjective norms, perceived behavioral control, self-efficacy, and past behaviors using the Theories of Reasoned Action (TRA) and Planned Behavior (TPB) in physical activity. This quantitative integration of the physical activity literature supported the major relationships of the…

  1. DOSE RESPONSE FROM HIGH THROUGHPUT GENE EXPRESSION STUDIES AND THE INFLUENCE OF TIME AND CELL LINE ON INFERRED MODE OF ACTION BY ONTOLOGIC ENRICHMENT (SOT)

    EPA Science Inventory

    Gene expression with ontologic enrichment and connectivity mapping tools is widely used to infer modes of action (MOA) for therapeutic drugs. Despite progress in high-throughput (HT) genomic systems, strategies suitable to identify industrial chemical MOA are needed. The L1000 is...

  2. Fire Usage and Ancient Hominin Detoxification Genes: Protective Ancestral Variants Dominate While Additional Derived Risk Variants Appear in Modern Humans

    PubMed Central

    Alink, Gerrit M.; Scherjon, Fulco; MacDonald, Katharine; Smith, Alison C.; Nijveen, Harm; Roebroeks, Wil

    2016-01-01

    Studies of the defence capacity of ancient hominins against toxic substances may contribute importantly to the reconstruction of their niche, including their diets and use of fire. Fire usage implies frequent exposure to hazardous compounds from smoke and heated food, known to affect general health and fertility, probably resulting in genetic selection for improved detoxification. To investigate whether such genetic selection occurred, we investigated the alleles in Neanderthals, Denisovans and modern humans at gene polymorphisms well-known to be relevant from modern human epidemiological studies of habitual tobacco smoke exposure and mechanistic evidence. We compared these with the alleles in chimpanzees and gorillas. Neanderthal and Denisovan hominins predominantly possess gene variants conferring increased resistance to these toxic compounds. Surprisingly, we observed the same in chimpanzees and gorillas, implying that less efficient variants are derived and mainly evolved in modern humans. Less efficient variants are observable from the first early Upper Palaeolithic hunter-gatherers onwards. While not clarifying the deep history of fire use, our results highlight the long-term stability of the genes under consideration despite major changes in the hominin dietary niche. Specifically for detoxification gene variants characterised as deleterious by epidemiological studies, our results confirm the predominantly recent appearance reported for deleterious human gene variants, suggesting substantial impact of recent human population history, including pre-Holocene expansions. PMID:27655273

  3. [Study on action mechanism and material base of compound Danshen dripping pills in treatment of carotid atherosclerosis based on techniques of gene expression profile and molecular fingerprint].

    PubMed

    Zhou, Wei; Song, Xiang-gang; Chen, Chao; Wang, Shu-mei; Liang, Sheng-wang

    2015-08-01

    Action mechanism and material base of compound Danshen dripping pills in treatment of carotid atherosclerosis were discussed based on gene expression profile and molecular fingerprint in this paper. First, gene expression profiles of atherosclerotic carotid artery tissues and histologically normal tissues in human body were collected, and were screened using significance analysis of microarray (SAM) to screen out differential gene expressions; then differential genes were analyzed by Gene Ontology (GO) analysis and KEGG pathway analysis; to avoid some genes with non-outstanding differential expression but biologically importance, Gene Set Enrichment Analysis (GSEA) were performed, and 7 chemical ingredients with higher negative enrichment score were obtained by Cmap method, implying that they could reversely regulate the gene expression profiles of pathological tissues; and last, based on the hypotheses that similar structures have similar activities, 336 ingredients of compound Danshen dripping pills were compared with 7 drug molecules in 2D molecular fingerprints method. The results showed that 147 differential genes including 60 up-regulated genes and 87 down regulated genes were screened out by SAM. And in GO analysis, Biological Process ( BP) is mainly concerned with biological adhesion, response to wounding and inflammatory response; Cellular Component (CC) is mainly concerned with extracellular region, extracellular space and plasma membrane; while Molecular Function (MF) is mainly concerned with antigen binding, metalloendopeptidase activity and peptide binding. KEGG pathway analysis is mainly concerned with JAK-STAT, RIG-I like receptor and PPAR signaling pathway. There were 10 compounds, such as hexadecane, with Tanimoto coefficients greater than 0.85, which implied that they may be the active ingredients (AIs) of compound Danshen dripping pills in treatment of carotid atherosclerosis (CAs). The present method can be applied to the research on material

  4. [Study on action mechanism and material base of compound Danshen dripping pills in treatment of carotid atherosclerosis based on techniques of gene expression profile and molecular fingerprint].

    PubMed

    Zhou, Wei; Song, Xiang-gang; Chen, Chao; Wang, Shu-mei; Liang, Sheng-wang

    2015-08-01

    Action mechanism and material base of compound Danshen dripping pills in treatment of carotid atherosclerosis were discussed based on gene expression profile and molecular fingerprint in this paper. First, gene expression profiles of atherosclerotic carotid artery tissues and histologically normal tissues in human body were collected, and were screened using significance analysis of microarray (SAM) to screen out differential gene expressions; then differential genes were analyzed by Gene Ontology (GO) analysis and KEGG pathway analysis; to avoid some genes with non-outstanding differential expression but biologically importance, Gene Set Enrichment Analysis (GSEA) were performed, and 7 chemical ingredients with higher negative enrichment score were obtained by Cmap method, implying that they could reversely regulate the gene expression profiles of pathological tissues; and last, based on the hypotheses that similar structures have similar activities, 336 ingredients of compound Danshen dripping pills were compared with 7 drug molecules in 2D molecular fingerprints method. The results showed that 147 differential genes including 60 up-regulated genes and 87 down regulated genes were screened out by SAM. And in GO analysis, Biological Process ( BP) is mainly concerned with biological adhesion, response to wounding and inflammatory response; Cellular Component (CC) is mainly concerned with extracellular region, extracellular space and plasma membrane; while Molecular Function (MF) is mainly concerned with antigen binding, metalloendopeptidase activity and peptide binding. KEGG pathway analysis is mainly concerned with JAK-STAT, RIG-I like receptor and PPAR signaling pathway. There were 10 compounds, such as hexadecane, with Tanimoto coefficients greater than 0.85, which implied that they may be the active ingredients (AIs) of compound Danshen dripping pills in treatment of carotid atherosclerosis (CAs). The present method can be applied to the research on material

  5. pdc1(0) mutants of Saccharomyces cerevisiae give evidence for an additional structural PDC gene: cloning of PDC5, a gene homologous to PDC1.

    PubMed Central

    Seeboth, P G; Bohnsack, K; Hollenberg, C P

    1990-01-01

    The PDC1 gene coding for a pyruvate decarboxylase (PDC; EC 4.1.1.1) was deleted from the Saccharomyces cerevisiae genome. The resulting pdc1(0) mutants were able to grow on glucose and still contained 60 to 70% of the wild-type PDC activity. Two DNA fragments with sequences homologous to that of the PDC1 gene were cloned from the yeast genome. One of the cloned genes (PDC5) was expressed at high rates predominantly in pdc1(0) strains and probably encodes the remaining PDC activity in these strains. Expression from the PDC1 promoter in PDC1 wild-type and pdc1(0) strains was examined by the use of two reporter genes. Deletion of PDC1 led to increased expression of the two reporter genes regardless of whether the fusions were integrated into the genome or present on autonomously replicating plasmids. The results suggested that this effect was due to feedback regulation of the PDC1 promoter-driven expression in S. cerevisiae pdc1(0) strains. The yeast PDC1 gene was expressed in Escherichia coli, leading to an active PDC. This result shows that the PDC1-encoded subunit alone can form an active tetramer without yeast-specific processing steps. Images FIG. 1 FIG. 4 FIG. 5 FIG. 6 PMID:2404950

  6. Tandem oleosin genes in a cluster acquired in Brassicaceae created tapetosomes and conferred additive benefit of pollen vigor

    PubMed Central

    Huang, Chien Yu; Chen, Pei-Ying; Huang, Ming-Der; Tsou, Chih-Hua; Jane, Wann-Neng; Huang, Anthony H. C.

    2013-01-01

    During evolution, genomes expanded via whole-genome, segmental, tandem, and individual-gene duplications, and the emerged redundant paralogs would be eliminated or retained owing to selective neutrality or adaptive benefit and further functional divergence. Here we show that tandem paralogs can contribute adaptive quantitative benefit and thus have been retained in a lineage-specific manner. In Brassicaceae, a tandem oleosin gene cluster of five to nine paralogs encodes ample tapetum-specific oleosins located in abundant organelles called tapetosomes in flower anthers. Tapetosomes coordinate the storage of lipids and flavonoids and their transport to the adjacent maturing pollen as the coat to serve various functions. Transfer-DNA and siRNA mutants of Arabidopsis thaliana with knockout and knockdown of different tandem oleosin paralogs had quantitative and correlated loss of organized structures of the tapetosomes, pollen-coat materials, and pollen tolerance to dehydration. Complementation with the knockout paralog restored the losses. Cleomaceae is the family closest to Brassicaceae. Cleome species did not contain the tandem oleosin gene cluster, tapetum oleosin transcripts, tapetosomes, or pollen tolerant to dehydration. Cleome hassleriana transformed with an Arabidopsis oleosin gene for tapetum expression possessed primitive tapetosomes and pollen tolerant to dehydration. We propose that during early evolution of Brassicaceae, a duplicate oleosin gene mutated from expression in seed to the tapetum. The tapetum oleosin generated primitive tapetosomes that organized stored lipids and flavonoids for their effective transfer to the pollen surface for greater pollen vitality. The resulting adaptive benefit led to retention of tandem-duplicated oleosin genes for production of more oleosin and modern tapetosomes. PMID:23940319

  7. DNA markers closely linked to nematode resistance genes in sugar beet (Beta vulgaris L.) mapped using chromosome additions and translocations originating from wild beets of the Procumbentes section.

    PubMed

    Jung, C; Koch, R; Fischer, F; Brandes, A; Wricke, G; Herrmann, R G

    1992-03-01

    Genes conferring resistance to the beet cyst nematode (Heterodera schachtii Schm.) have been transferred to sugar beet (Beta vulgaris L.) from three wild species of the Procumbentes section using monosomic addition and translocation lines, because no meiotic recombination occurs between chromosomes of cultured and wild species. In the course of a project to isolate the nematode resistance genes by strategies of reverse genetics, probes were cloned from DNA of a fragmented B. procumbens chromosome carrying a resistance gene, which had been isolated by pulsed-field gel electrophoresis. One probe (pRK643) hybridized with a short dispersed repetitive DNA element, which was found only in wild beets, and thus may be used as a molecular marker for nematode resistance to progeneis of monosomic addition lines segregating resistant and susceptible individuals. Additional probes for the resistance gene region were obtained with a polymerase chain reaction (PCR)-based strategy using repetitive primers to amplify DNA located between repetitive elements. One of these probes established the existence of at least six different chromosomes from wild beet species, each conferring resistance independently of the others. A strict correlation between the length of the wild beet chromatin introduced in fragment addition and translocation lines and the repeat copy number has been used physically to map the region conferring resistance to a chromosome segment of 0.5-3 Mb.

  8. Effect of red mud addition on tetracycline and copper resistance genes and microbial community during the full scale swine manure composting.

    PubMed

    Wang, Rui; Zhang, Junya; Sui, Qianwen; Wan, Hefeng; Tong, Juan; Chen, Meixue; Wei, Yuansong; Wei, Dongbin

    2016-09-01

    Swine manure has been considered as the reservoir of antibiotic resistance genes (ARGs). Composting is one of the most suitable technologies for treating livestock manures, and red mud was proved to have a positive effect on nitrogen conservation during composting. This study investigated the abundance of eight tetracycline and three copper resistance genes, the bacterial community during the full scale swine manure composting with or without addition of red mud. The results showed that ARGs in swine manure could be effectively removed through composting (reduced by 2.4log copies/g TS), especially during the thermophilic phase (reduced by 1.5log copies/g TS), which the main contributor might be temperature. Additionally, evolution of bacterial community could also have a great influence on ARGs. Although addition of red mud could enhance nitrogen conservation, it obviously hindered removal of ARGs (reduced by 1.7log copies/g TS) and affected shaping of bacterial community during composting.

  9. Progesterone Receptor-A and -B Have Opposite Effects on Proinflammatory Gene Expression in Human Myometrial Cells: Implications for Progesterone Actions in Human Pregnancy and Parturition

    PubMed Central

    Tan, Huiqing; Yi, Lijuan; Rote, Neal S.; Hurd, William W.

    2012-01-01

    Context: Progesterone promotes uterine relaxation during pregnancy and its withdrawal induces labor. Progesterone withdrawal in human parturition is mediated in part by changes in the relative levels of the nuclear progesterone receptor isoforms, PR-A and PR-B, in myometrial cells. Parturition also involves myometrial inflammation; however, the functional link between nuclear PR-mediated progesterone actions and inflammation in human myometrial cells is unclear. Objective: Our objective was to determine how PR-A and PR-B regulate progesterone action in human myometrial cells and specifically the expression of genes encoding contraction-associated proteins and proinflammatory mediators. Design: Effects of PR-A and PR-B on the capacity for progesterone to modulate gene expression was determined using an immortalized human myometrial cell line stably transfected with inducible PR-A and PR-B expression transgenes and conditioned to express various PR-A and PR-B levels. Gene expression was assessed by genome wide transcriptome analysis, quantitative RT-PCR and immunoblotting. Results: PR-A and PR-B were each transcriptionally active in response to progesterone and affected the expression of distinct gene cohorts. The capacity for progesterone to affect gene expression was dependent on the PR-A to PR-B ratio. This was especially apparent for the expression of proinflammatory genes. Progesterone decreased proinflammatory gene expression when the PR-A to PR-B ratio favored PR-B and increased proinflammatory gene expression when the ratio favored PR-A. Progesterone via PR-B increased expression of inhibitor-κBα, a repressor of the nuclear factor-κB transcription factor, and inhibited basal and lipopolysaccharide-induced proinflammatory gene expression. Both of those PR-B-mediated effects were inhibited by PR-A. Conclusions: Our data suggest that during most of human pregnancy, when myometrial cells are PR-B dominant, progesterone promotes myometrial quiescence through PR

  10. Addition of Escherichia coli K-12 growth observation and gene essentiality data to the EcoCyc database.

    PubMed

    Mackie, Amanda; Paley, Suzanne; Keseler, Ingrid M; Shearer, Alexander; Paulsen, Ian T; Karp, Peter D

    2014-03-01

    The sets of compounds that can support growth of an organism are defined by the presence of transporters and metabolic pathways that convert nutrient sources into cellular components and energy for growth. A collection of known nutrient sources can therefore serve both as an impetus for investigating new metabolic pathways and transporters and as a reference for computational modeling of known metabolic pathways. To establish such a collection for Escherichia coli K-12, we have integrated data on the growth or nongrowth of E. coli K-12 obtained from published observations using a variety of individual media and from high-throughput phenotype microarrays into the EcoCyc database. The assembled collection revealed a substantial number of discrepancies between the high-throughput data sets, which we investigated where possible using low-throughput growth assays on soft agar and in liquid culture. We also integrated six data sets describing 16,119 observations of the growth of single-gene knockout mutants of E. coli K-12 into EcoCyc, which are relevant to antimicrobial drug design, provide clues regarding the roles of genes of unknown function, and are useful for validating metabolic models. To make this information easily accessible to EcoCyc users, we developed software for capturing, querying, and visualizing cellular growth assays and gene essentiality data.

  11. Addition of Escherichia coli K-12 Growth Observation and Gene Essentiality Data to the EcoCyc Database

    PubMed Central

    Mackie, Amanda; Paley, Suzanne; Keseler, Ingrid M.; Shearer, Alexander; Paulsen, Ian T.

    2014-01-01

    The sets of compounds that can support growth of an organism are defined by the presence of transporters and metabolic pathways that convert nutrient sources into cellular components and energy for growth. A collection of known nutrient sources can therefore serve both as an impetus for investigating new metabolic pathways and transporters and as a reference for computational modeling of known metabolic pathways. To establish such a collection for Escherichia coli K-12, we have integrated data on the growth or nongrowth of E. coli K-12 obtained from published observations using a variety of individual media and from high-throughput phenotype microarrays into the EcoCyc database. The assembled collection revealed a substantial number of discrepancies between the high-throughput data sets, which we investigated where possible using low-throughput growth assays on soft agar and in liquid culture. We also integrated six data sets describing 16,119 observations of the growth of single-gene knockout mutants of E. coli K-12 into EcoCyc, which are relevant to antimicrobial drug design, provide clues regarding the roles of genes of unknown function, and are useful for validating metabolic models. To make this information easily accessible to EcoCyc users, we developed software for capturing, querying, and visualizing cellular growth assays and gene essentiality data. PMID:24363340

  12. Organization of the flaFG gene cluster and identification of two additional genes involved in flagellum biogenesis in Caulobacter crescentus.

    PubMed Central

    Schoenlein, P V; Gallman, L S; Ely, B

    1989-01-01

    In Caulobacter crescentus, mutations have been isolated in more than 30 flagellar genes (fla, flb, and flg) which are required in the cell cycle event of flagellum biogenesis. The flaF and flaG mutations and two newly identified mutations, flbT and flbA (P.V. Schoenlein and B. Ely, J. Bacteriol. 171:000-000, 1989), have been localized to the flaFG region. In this study, the genetic and physical organization of this region was analyzed, using the cloned 4.0-kilobase flaFG region in the recombinant plasmid pPLG727. Plasmid pPLG727 complemented flaF, flaG, flbA, and flbT mutations. Further complementation studies with pPLG727 derivatives indicated that flaF and flbT are unique but overlapping transcription units, whereas flbA and flaG constitute a single transcription unit. To determine the direction of transcription of the putative flbA-flaG operon, the promoterless chloramphenicol transacetylase gene was inserted into various positions in the flbA-flaG region, and merodiploid strains containing these transcriptional fusions were assayed for gene function and expression of chloramphenicol resistance. These studies showed that transcription proceeds from flbA to flaG. To confirm the complementation analysis, Southern analyses were performed on chromosomal DNAs isolated from strains containing insertion and deletion mutations. Taken together, these studies defined the relative gene order at one end of the flaYG flagellar gene cluser as flgL-flaF-flbT-flbA-flaG. PMID:2921244

  13. Reference Gene Selection for qPCR Analysis in Tomato-Bipartite Begomovirus Interaction and Validation in Additional Tomato-Virus Pathosystems

    PubMed Central

    Lacerda, Ana L. M.; Fonseca, Leonardo N.; Blawid, Rosana; Boiteux, Leonardo S.; Ribeiro, Simone G.; Brasileiro, Ana C. M.

    2015-01-01

    Quantitative Polymerase Chain Reaction (qPCR) is currently the most sensitive technique used for absolute and relative quantification of a target gene transcript, requiring the use of appropriated reference genes for data normalization. To accurately estimate the relative expression of target tomato (Solanum lycopersicum L.) genes responsive to several virus species in reverse transcription qPCR analysis, the identification of reliable reference genes is mandatory. In the present study, ten reference genes were analyzed across a set of eight samples: two tomato contrasting genotypes (‘Santa Clara’, susceptible, and its near-isogenic line ‘LAM 157’, resistant); subjected to two treatments (inoculation with Tomato chlorotic mottle virus (ToCMoV) and its mock-inoculated control) and in two distinct times after inoculation (early and late). Reference genes stability was estimated by three statistical programs (geNorm, NormFinder and BestKeeper). To validate the results over broader experimental conditions, a set of ten samples, corresponding to additional three tomato-virus pathosystems that included tospovirus, crinivirus and tymovirus + tobamovirus, was analyzed together with the tomato-ToCMoV pathosystem dataset, using the same algorithms. Taking into account the combined analyses of the ranking order outputs from the three algorithms, TIP41 and EF1 were identified as the most stable genes for tomato-ToCMoV pathosystem, and TIP41 and EXP for the four pathosystems together, and selected to be used as reference in the forthcoming expression qPCR analysis of target genes in experimental conditions involving the aforementioned tomato-virus pathosystems. PMID:26317870

  14. Glutathione S-transferase (GST) genes in the red flour beetle, Tribolium castaneum, and comparative analysis with five additional insects.

    PubMed

    Shi, Houxia; Pei, Lianghong; Gu, Shasha; Zhu, Shicheng; Wang, Yanyun; Zhang, Yi; Li, Bin

    2012-11-01

    Glutathione S-transferases are important detoxification enzymes involved in insecticide resistance. Sequencing the Tribolium castaneum genome provides an opportunity to investigate the structure, function, and evolution of GSTs on a genome-wide scale. Thirty-six putative cytosolic GSTs and 5 microsomal GSTs have been identified in T. castaneum. Furthermore, 40, 35, 13, 23, and 32 GSTs have been discovered the other insects, Drosophila, Anopheles, Apis, Bombyx, and Acyrthosiphon, respectively. Phylogenetic analyses reveal that insect-specific GSTs, Epsilon and Delta, are the largest species-specific expanded GSTs. In T. castaneum, most GSTs are tandemly arranged in three chromosomes. Particularly, Epsilon GSTs have an inverted long-fragment duplication in the genome. Other four widely distributed classes are highly conserved in all species. Given that GSTs specially expanded in Tribolium castaneum, these genes might help to resist poisonous chemical environments and produce resistance to kinds of different insecticides.

  15. Evolution of the CD4 family: teleost fish possess two divergent forms of CD4 in addition to lymphocyte activation gene-3

    USGS Publications Warehouse

    Laing, K.J.; Zou, J.J.; Purcell, M.K.; Phillips, R.; Secombes, C.J.; Hansen, J.D.

    2006-01-01

    The T cell coreceptor CD4 is a transmembrane glycoprotein belonging to the Ig superfamily and is essential for cell-mediated immunity. Two different genes were identified in rainbow trout that resemble mammalian CD4. One (trout CD4) encodes four extracellular Ig domains reminiscent off mammalian CD4, whereas the other (CD4REL) codes for two Ig domains. Structural motifs within the amino acid sequences suggest that the two Ig domains of CD4REL duplicated to generate the four-domain molecule of CD4 and the related gene, lymphocyte activation gene-3. Here we present evidence that both of these molecules in trout are homologous to mammalian CD4 and that teleosts encode an additional CD4 family member, lymphocyte activation gene-3, which is a marker for activated T cells. The syntenic relationships of similar genes in other teleost and non-fish genomes provide evidence for the likely evolution of CD4-related molecules in vertebrates, with CD4REL likely representing the primordial form in fish. Expression of both CD4 genes is highest in the thymus and spleen, and mRNA expression of these genes is limited to surface IgM- lymphocytes, consistent with a role for T cell functionality. Finally, the intracellular regions of both CD4 and CD4REL possess the canonical CXC motif involved in the interaction off CD4 with p56LCK, implying that similar mechanisms for CD4 + T cell activation are present in all vertebrates. Our results therefore raise new questions about T cell development and functionality in lower vertebrates that cannot be answered by current mammalian models and, thus, is of fundamental importance for understanding the evolution of cell-mediated immunity in gnathosomes. Copyright ?? 2006 by The American Association of Immunologists, Inc.

  16. The effect of nitrate addition on abundance of nirK, nirS and gln genes in acidified Norway spruce forest soil

    NASA Astrophysics Data System (ADS)

    Bárta, Jiří; Tahovská, Karolina; Kaåa, Jiří; Antrå¯Čková, Hana Å.

    2010-05-01

    The denitrification is the main biotic process leading to loses of fixed nitrogen as well as removal of excess of nitrate (NO3-) from the soil environment. The reduction of NO2- to nitric oxide (NO) distinguishes the 'true' denitrifiers from other nitrate-respiring bacteria. This reaction is catalyzed by two different types of nitrite reductases, either a cytochrome cd1 encoded by nirS gene (nirS denitrifiers) or a Cu-containing enzyme encoded by nirK gene (nirK denitrifiers). The nirS denitrifiers are located mostly in rhizosphere, while the nirK denitrifiers are more abundant in bulk soil. These two groups can be also classified as markers of denitrification. Glutamine synthetase is one of the main bacterial NH4+ assimilating enzymes; it is coded by glnI gene. Glutamine synthetase is mostly active when N is the limiting factor for bacterial growth. There is recent evidence that the activity may be affected by the presence of alternative N source (i.e. NO3-). However, in anaerobic condition NO3- can be used also by the denitrifying bacteria so there may be strong competition for this nutrient. The laboratory experiment was performed to evaluate the effect of nitrates (NO3-) on abundance of nirK, nirS and gln gene copy numbers. The amount of NO3- corresponded to the actual atmospheric depositions on experimental sites in the Bohemian Forest. Litter organic layer (0-5cm of soil) was used for laboratory incubation experiment. Four replicates of control (no addition of NO3-), and NO3-addition were incubated anaerobically for one month. After the incubation DNA was extracted and the number of nirK, nirS and gln gene copies was determined using qPCR (SYBRGreen methodology). Results showed that the addition of NO3- significantly increased the number of nirK and nirS denitrifiers from 5.9x106 to 1.1x107 and from not detectable amount to 1.4x106, respectively. The gln gene copy number was also higher after NO3-addition. However, the difference was not statistically

  17. Combined action of time-delay and colored cross-associated multiplicative and additive noises on stability and stochastic resonance for a stochastic metapopulation system

    NASA Astrophysics Data System (ADS)

    Wang, Kang-Kang; Zong, De-Cai; Wang, Ya-Jun; Li, Sheng-Hong

    2016-05-01

    In this paper, the transition between the stable state of a big density and the extinction state and stochastic resonance (SR) for a time-delayed metapopulation system disturbed by colored cross-correlated noises are investigated. By applying the fast descent method, the small time-delay approximation and McNamara and Wiesenfeld's SR theory, we investigate the impacts of time-delay, the multiplicative, additive noises and colored cross-correlated noise on the SNR and the shift between the two states of the system. Numerical results show that the multiplicative, additive noises and time-delay can all speed up the transition from the stable state to the extinction state, while the correlation noise and its correlation time can slow down the extinction process of the population system. With respect to SNR, the multiplicative noise always weakens the SR effect, while noise correlation time plays a dual role in motivating the SR phenomenon. Meanwhile, time-delay mainly plays a negative role in stimulating the SR phenomenon. Conversely, it could motivate the SR effect to increase the strength of the cross-correlation noise in the SNR-β plot, while the increase of additive noise intensity will firstly excite SR, and then suppress the SR effect.

  18. Action perception predicts action performance

    PubMed Central

    Bailey, Heather R.; Kurby, Christopher A.; Giovannetti, Tania; Zacks, Jeffrey M.

    2013-01-01

    Everyday action impairments often are observed in demented older adults, and they are common potential barriers to functional independence. We evaluated whether the ability to segment and efficiently encode activities is related to the ability to execute activities. Further, we evaluated whether brain regions important for segmentation also were important for action performance. Cognitively healthy older adults and those with very mild or mild dementia of the Alzheimer's type watched and segmented movies of everyday activities and then completed the Naturalistic Action Test. Structural MRI was used to measure volume in the dorsolateral prefrontal cortex (DLPFC), medial temporal lobes (MTL), posterior cortex, and anterior cingulate cortex (ACC). Dementia status and the ability to segment everyday activities strongly predicted naturalistic action performance, and MTL volume largely accounted for this relationship. In addition, the current results supported the Omission-Commission Model: Different cognitive and neurological mechanisms predicted different types of action error. Segmentation, dementia severity, and MTL volume predicted everyday omission errors, DLPFC volume predicted commission errors, and ACC volume predicted action additions. These findings suggest that event segmentation may be critical for effective action production, and that the segmentation and production of activities may recruit the same event representation system. PMID:23851113

  19. Action perception predicts action performance.

    PubMed

    Bailey, Heather R; Kurby, Christopher A; Giovannetti, Tania; Zacks, Jeffrey M

    2013-09-01

    Everyday action impairments often are observed in demented older adults, and they are common potential barriers to functional independence. We evaluated whether the ability to segment and efficiently encode activities is related to the ability to execute activities. Further, we evaluated whether brain regions important for segmentation also were important for action performance. Cognitively healthy older adults and those with very mild or mild dementia of the Alzheimer's type watched and segmented movies of everyday activities and then completed the Naturalistic Action Test. Structural MRI was used to measure volume in the dorsolateral prefrontal cortex (DLPFC), medial temporal lobes (MTL), posterior cortex, and anterior cingulate cortex (ACC). Dementia status and the ability to segment everyday activities strongly predicted naturalistic action performance, and MTL volume largely accounted for this relationship. In addition, the current results supported the Omission-Commission Model: Different cognitive and neurological mechanisms predicted different types of action error. Segmentation, dementia severity, and MTL volume predicted everyday omission errors, DLPFC volume predicted commission errors, and ACC volume predicted action additions. These findings suggest that event segmentation may be critical for effective action production, and that the segmentation and production of activities may recruit the same event representation system.

  20. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.

    PubMed

    Fan, Qiao; Verhoeven, Virginie J M; Wojciechowski, Robert; Barathi, Veluchamy A; Hysi, Pirro G; Guggenheim, Jeremy A; Höhn, René; Vitart, Veronique; Khawaja, Anthony P; Yamashiro, Kenji; Hosseini, S Mohsen; Lehtimäki, Terho; Lu, Yi; Haller, Toomas; Xie, Jing; Delcourt, Cécile; Pirastu, Mario; Wedenoja, Juho; Gharahkhani, Puya; Venturini, Cristina; Miyake, Masahiro; Hewitt, Alex W; Guo, Xiaobo; Mazur, Johanna; Huffman, Jenifer E; Williams, Katie M; Polasek, Ozren; Campbell, Harry; Rudan, Igor; Vatavuk, Zoran; Wilson, James F; Joshi, Peter K; McMahon, George; St Pourcain, Beate; Evans, David M; Simpson, Claire L; Schwantes-An, Tae-Hwi; Igo, Robert P; Mirshahi, Alireza; Cougnard-Gregoire, Audrey; Bellenguez, Céline; Blettner, Maria; Raitakari, Olli; Kähönen, Mika; Seppala, Ilkka; Zeller, Tanja; Meitinger, Thomas; Ried, Janina S; Gieger, Christian; Portas, Laura; van Leeuwen, Elisabeth M; Amin, Najaf; Uitterlinden, André G; Rivadeneira, Fernando; Hofman, Albert; Vingerling, Johannes R; Wang, Ya Xing; Wang, Xu; Tai-Hui Boh, Eileen; Ikram, M Kamran; Sabanayagam, Charumathi; Gupta, Preeti; Tan, Vincent; Zhou, Lei; Ho, Candice E H; Lim, Wan'e; Beuerman, Roger W; Siantar, Rosalynn; Tai, E-Shyong; Vithana, Eranga; Mihailov, Evelin; Khor, Chiea-Chuen; Hayward, Caroline; Luben, Robert N; Foster, Paul J; Klein, Barbara E K; Klein, Ronald; Wong, Hoi-Suen; Mitchell, Paul; Metspalu, Andres; Aung, Tin; Young, Terri L; He, Mingguang; Pärssinen, Olavi; van Duijn, Cornelia M; Jin Wang, Jie; Williams, Cathy; Jonas, Jost B; Teo, Yik-Ying; Mackey, David A; Oexle, Konrad; Yoshimura, Nagahisa; Paterson, Andrew D; Pfeiffer, Norbert; Wong, Tien-Yin; Baird, Paul N; Stambolian, Dwight; Wilson, Joan E Bailey; Cheng, Ching-Yu; Hammond, Christopher J; Klaver, Caroline C W; Saw, Seang-Mei; Rahi, Jugnoo S; Korobelnik, Jean-François; Kemp, John P; Timpson, Nicholas J; Smith, George Davey; Craig, Jamie E; Burdon, Kathryn P; Fogarty, Rhys D; Iyengar, Sudha K; Chew, Emily; Janmahasatian, Sarayut; Martin, Nicholas G; MacGregor, Stuart; Xu, Liang; Schache, Maria; Nangia, Vinay; Panda-Jonas, Songhomitra; Wright, Alan F; Fondran, Jeremy R; Lass, Jonathan H; Feng, Sheng; Zhao, Jing Hua; Khaw, Kay-Tee; Wareham, Nick J; Rantanen, Taina; Kaprio, Jaakko; Pang, Chi Pui; Chen, Li Jia; Tam, Pancy O; Jhanji, Vishal; Young, Alvin L; Döring, Angela; Raffel, Leslie J; Cotch, Mary-Frances; Li, Xiaohui; Yip, Shea Ping; Yap, Maurice K H; Biino, Ginevra; Vaccargiu, Simona; Fossarello, Maurizio; Fleck, Brian; Yazar, Seyhan; Tideman, Jan Willem L; Tedja, Milly; Deangelis, Margaret M; Morrison, Margaux; Farrer, Lindsay; Zhou, Xiangtian; Chen, Wei; Mizuki, Nobuhisa; Meguro, Akira; Mäkelä, Kari Matti

    2016-03-29

    Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

  1. Targeted gene addition in human CD34(+) hematopoietic cells for correction of X-linked chronic granulomatous disease.

    PubMed

    De Ravin, Suk See; Reik, Andreas; Liu, Pei-Qi; Li, Linhong; Wu, Xiaolin; Su, Ling; Raley, Castle; Theobald, Narda; Choi, Uimook; Song, Alexander H; Chan, Andy; Pearl, Jocelynn R; Paschon, David E; Lee, Janet; Newcombe, Hannah; Koontz, Sherry; Sweeney, Colin; Shivak, David A; Zarember, Kol A; Peshwa, Madhusudan V; Gregory, Philip D; Urnov, Fyodor D; Malech, Harry L

    2016-04-01

    Gene therapy with genetically modified human CD34(+) hematopoietic stem and progenitor cells (HSPCs) may be safer using targeted integration (TI) of transgenes into a genomic 'safe harbor' site rather than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno-associated virus (AAV) 6 delivery of donor constructs in human HSPCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus(+) HSPCs with 6-16% human cell marking were observed following engraftment into mice. In HSPCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 resulted in ∼15% gp91phox expression and increased NADPH oxidase activity in ex vivo-derived neutrophils. In mice transplanted with corrected HSPCs, 4-11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases.

  2. Targeted gene addition in human CD34(+) hematopoietic cells for correction of X-linked chronic granulomatous disease.

    PubMed

    De Ravin, Suk See; Reik, Andreas; Liu, Pei-Qi; Li, Linhong; Wu, Xiaolin; Su, Ling; Raley, Castle; Theobald, Narda; Choi, Uimook; Song, Alexander H; Chan, Andy; Pearl, Jocelynn R; Paschon, David E; Lee, Janet; Newcombe, Hannah; Koontz, Sherry; Sweeney, Colin; Shivak, David A; Zarember, Kol A; Peshwa, Madhusudan V; Gregory, Philip D; Urnov, Fyodor D; Malech, Harry L

    2016-04-01

    Gene therapy with genetically modified human CD34(+) hematopoietic stem and progenitor cells (HSPCs) may be safer using targeted integration (TI) of transgenes into a genomic 'safe harbor' site rather than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno-associated virus (AAV) 6 delivery of donor constructs in human HSPCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus(+) HSPCs with 6-16% human cell marking were observed following engraftment into mice. In HSPCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 resulted in ∼15% gp91phox expression and increased NADPH oxidase activity in ex vivo-derived neutrophils. In mice transplanted with corrected HSPCs, 4-11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases. PMID:26950749

  3. Gene expression suggests double-segmental and single-segmental patterning mechanisms during posterior segment addition in the beetle Tribolium castaneum.

    PubMed

    Janssen, Ralf

    2014-01-01

    In the model arthropod Drosophila, all segments are patterned simultaneously in the blastoderm. In most other arthropods, however, posterior segments are added sequentially from a posterior segment addition zone. Posterior addition of single segments likely represents the ancestral mode of arthropod segmentation, although in Drosophila, segments are patterned in pairs by the pair-rule genes. It has been shown that in the new model insect, the beetle Tribolium, a segmentation clock operates that apparently patterns all segments in pairs as well. Here, I report on the expression of the segment polarity gene H15/midline in Tribolium. In the anterior embryo, segmental stripes of H15 appear in pairs, but in the posterior of the embryo stripes appear in a single-segmental periodicity. This implies that either two completely different segmentation-mechanisms may act in the germ band of Tribolium, that the segmentation clock changes its periodicity during development, or that the speed in which posterior segments are patterned changes. In any case, the data suggest the presence of another (or modified), yet undiscovered, mechanism of posterior segment addition in one of the best-understood arthropod models. The finding of a hitherto unrecognized segmentation mechanism in Tribolium may have major implications for the understanding of the origin of segmentation mechanisms, including the origin of pair rule patterning. It also calls for (re)-investigation of posterior segment addition in Tribolium and other previously studied arthropod models.

  4. Action of multiple intra-QTL genes concerted around a co-localized transcription factor underpins a large effect QTL.

    PubMed

    Dixit, Shalabh; Kumar Biswal, Akshaya; Min, Aye; Henry, Amelia; Oane, Rowena H; Raorane, Manish L; Longkumer, Toshisangba; Pabuayon, Isaiah M; Mutte, Sumanth K; Vardarajan, Adithi R; Miro, Berta; Govindan, Ganesan; Albano-Enriquez, Blesilda; Pueffeld, Mandy; Sreenivasulu, Nese; Slamet-Loedin, Inez; Sundarvelpandian, Kalaipandian; Tsai, Yuan-Ching; Raghuvanshi, Saurabh; Hsing, Yue-Ie C; Kumar, Arvind; Kohli, Ajay

    2015-01-01

    Sub-QTLs and multiple intra-QTL genes are hypothesized to underpin large-effect QTLs. Known QTLs over gene families, biosynthetic pathways or certain traits represent functional gene-clusters of genes of the same gene ontology (GO). Gene-clusters containing genes of different GO have not been elaborated, except in silico as coexpressed genes within QTLs. Here we demonstrate the requirement of multiple intra-QTL genes for the full impact of QTL qDTY12.1 on rice yield under drought. Multiple evidences are presented for the need of the transcription factor 'no apical meristem' (OsNAM12.1) and its co-localized target genes of separate GO categories for qDTY12.1 function, raising a regulon-like model of genetic architecture. The molecular underpinnings of qDTY12.1 support its effectiveness in further improving a drought tolerant genotype and for its validity in multiple genotypes/ecosystems/environments. Resolving the combinatorial value of OsNAM12.1 with individual intra-QTL genes notwithstanding, identification and analyses of qDTY12.1has fast-tracked rice improvement towards food security. PMID:26507552

  5. Action of multiple intra-QTL genes concerted around a co-localized transcription factor underpins a large effect QTL

    PubMed Central

    Dixit, Shalabh; Kumar Biswal, Akshaya; Min, Aye; Henry, Amelia; Oane, Rowena H.; Raorane, Manish L.; Longkumer, Toshisangba; Pabuayon, Isaiah M.; Mutte, Sumanth K.; Vardarajan, Adithi R.; Miro, Berta; Govindan, Ganesan; Albano-Enriquez, Blesilda; Pueffeld, Mandy; Sreenivasulu, Nese; Slamet-Loedin, Inez; Sundarvelpandian, Kalaipandian; Tsai, Yuan-Ching; Raghuvanshi, Saurabh; Hsing, Yue-Ie C.; Kumar, Arvind; Kohli, Ajay

    2015-01-01

    Sub-QTLs and multiple intra-QTL genes are hypothesized to underpin large-effect QTLs. Known QTLs over gene families, biosynthetic pathways or certain traits represent functional gene-clusters of genes of the same gene ontology (GO). Gene-clusters containing genes of different GO have not been elaborated, except in silico as coexpressed genes within QTLs. Here we demonstrate the requirement of multiple intra-QTL genes for the full impact of QTL qDTY12.1 on rice yield under drought. Multiple evidences are presented for the need of the transcription factor ‘no apical meristem’ (OsNAM12.1) and its co-localized target genes of separate GO categories for qDTY12.1 function, raising a regulon-like model of genetic architecture. The molecular underpinnings of qDTY12.1 support its effectiveness in further improving a drought tolerant genotype and for its validity in multiple genotypes/ecosystems/environments. Resolving the combinatorial value of OsNAM12.1 with individual intra-QTL genes notwithstanding, identification and analyses of qDTY12.1has fast-tracked rice improvement towards food security. PMID:26507552

  6. Single Nucleotide Polymorphisms in Regulator-Encoding Genes Have an Additive Effect on Virulence Gene Expression in a Vibrio cholerae Clinical Isolate.

    PubMed

    Carignan, Bailey M; Brumfield, Kyle D; Son, Mike S

    2016-01-01

    Vibrio cholerae is the etiological agent of the infectious disease cholera, which is characterized by vomiting and severe watery diarrhea. Recently, V. cholerae clinical isolates have demonstrated increased virulence capabilities, causing more severe symptoms with a much higher rate of disease progression than previously observed. We have identified single nucleotide polymorphisms (SNPs) in four virulence-regulatory genes (hapR, hns, luxO, and vieA) of a hypervirulent V. cholerae clinical isolate, MQ1795. Herein, all SNPs and SNP combinations of interest were introduced into the prototypical El Tor reference strain N16961, and the effects on the production of numerous virulence-related factors, including cholera toxin (CT), the toxin-coregulated pilus (TCP), and ToxT, were analyzed. Our data show that triple-SNP (hapR hns luxO and hns luxO vieA) and quadruple-SNP combinations produced the greatest increases in CT, TCP, and ToxT production. The hns and hns luxO SNP combinations were sufficient for increased TCP and ToxT production. Notably, the hns luxO vieA triple-SNP combination strain produced TCP and ToxT levels similar to those of MQ1795. Certain SNP combinations (hapR and hapR vieA) had the opposite effect on CT, TCP, and ToxT expression. Interestingly, the hns vieA double-SNP combination strain increased TCP production while decreasing CT production. Our findings suggest that SNPs identified in the four regulatory genes, in various combinations, are associated with increased virulence capabilities observed in V. cholerae clinical isolates. These studies provide insight into the evolution of highly virulent strains. IMPORTANCE Cholera, an infectious disease of the small intestine caused by the aquatic bacterium Vibrio cholerae, often results in vomiting and acute watery diarrhea. If left untreated or if the response is too slow, the symptoms can quickly lead to extreme dehydration and ultimately death of the patient. Recent anecdotal evidence of cholera

  7. Single Nucleotide Polymorphisms in Regulator-Encoding Genes Have an Additive Effect on Virulence Gene Expression in a Vibrio cholerae Clinical Isolate

    PubMed Central

    Carignan, Bailey M.; Brumfield, Kyle D.

    2016-01-01

    ABSTRACT Vibrio cholerae is the etiological agent of the infectious disease cholera, which is characterized by vomiting and severe watery diarrhea. Recently, V. cholerae clinical isolates have demonstrated increased virulence capabilities, causing more severe symptoms with a much higher rate of disease progression than previously observed. We have identified single nucleotide polymorphisms (SNPs) in four virulence-regulatory genes (hapR, hns, luxO, and vieA) of a hypervirulent V. cholerae clinical isolate, MQ1795. Herein, all SNPs and SNP combinations of interest were introduced into the prototypical El Tor reference strain N16961, and the effects on the production of numerous virulence-related factors, including cholera toxin (CT), the toxin-coregulated pilus (TCP), and ToxT, were analyzed. Our data show that triple-SNP (hapR hns luxO and hns luxO vieA) and quadruple-SNP combinations produced the greatest increases in CT, TCP, and ToxT production. The hns and hns luxO SNP combinations were sufficient for increased TCP and ToxT production. Notably, the hns luxO vieA triple-SNP combination strain produced TCP and ToxT levels similar to those of MQ1795. Certain SNP combinations (hapR and hapR vieA) had the opposite effect on CT, TCP, and ToxT expression. Interestingly, the hns vieA double-SNP combination strain increased TCP production while decreasing CT production. Our findings suggest that SNPs identified in the four regulatory genes, in various combinations, are associated with increased virulence capabilities observed in V. cholerae clinical isolates. These studies provide insight into the evolution of highly virulent strains. IMPORTANCE Cholera, an infectious disease of the small intestine caused by the aquatic bacterium Vibrio cholerae, often results in vomiting and acute watery diarrhea. If left untreated or if the response is too slow, the symptoms can quickly lead to extreme dehydration and ultimately death of the patient. Recent anecdotal evidence of

  8. Single Nucleotide Polymorphisms in Regulator-Encoding Genes Have an Additive Effect on Virulence Gene Expression in a Vibrio cholerae Clinical Isolate

    PubMed Central

    Carignan, Bailey M.; Brumfield, Kyle D.

    2016-01-01

    ABSTRACT Vibrio cholerae is the etiological agent of the infectious disease cholera, which is characterized by vomiting and severe watery diarrhea. Recently, V. cholerae clinical isolates have demonstrated increased virulence capabilities, causing more severe symptoms with a much higher rate of disease progression than previously observed. We have identified single nucleotide polymorphisms (SNPs) in four virulence-regulatory genes (hapR, hns, luxO, and vieA) of a hypervirulent V. cholerae clinical isolate, MQ1795. Herein, all SNPs and SNP combinations of interest were introduced into the prototypical El Tor reference strain N16961, and the effects on the production of numerous virulence-related factors, including cholera toxin (CT), the toxin-coregulated pilus (TCP), and ToxT, were analyzed. Our data show that triple-SNP (hapR hns luxO and hns luxO vieA) and quadruple-SNP combinations produced the greatest increases in CT, TCP, and ToxT production. The hns and hns luxO SNP combinations were sufficient for increased TCP and ToxT production. Notably, the hns luxO vieA triple-SNP combination strain produced TCP and ToxT levels similar to those of MQ1795. Certain SNP combinations (hapR and hapR vieA) had the opposite effect on CT, TCP, and ToxT expression. Interestingly, the hns vieA double-SNP combination strain increased TCP production while decreasing CT production. Our findings suggest that SNPs identified in the four regulatory genes, in various combinations, are associated with increased virulence capabilities observed in V. cholerae clinical isolates. These studies provide insight into the evolution of highly virulent strains. IMPORTANCE Cholera, an infectious disease of the small intestine caused by the aquatic bacterium Vibrio cholerae, often results in vomiting and acute watery diarrhea. If left untreated or if the response is too slow, the symptoms can quickly lead to extreme dehydration and ultimately death of the patient. Recent anecdotal evidence of

  9. Array-Based Transcript Profiling and Limiting-Dilution Reverse Transcription-PCR Analysis Identify Additional Latent Genes in Kaposi's Sarcoma-Associated Herpesvirus▿ †

    PubMed Central

    Chandriani, Sanjay; Ganem, Don

    2010-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a B-lymphotropic herpesvirus strongly linked to both lymphoproliferative diseases and Kaposi's sarcoma. The viral latency program of KSHV is central to persistent infection and plays important roles in the pathogenesis of KSHV-related tumors. Up to six polypeptides and 18 microRNAs are known to be expressed in latency, but it is unclear if all major latency genes have been identified. Here, we have employed array-based transcript profiling and limiting-dilution reverse transcription-PCR (RT-PCR) methodologies to explore this issue in several KSHV-infected cell lines. Our results show that RNAs encoding the K1 protein are found at low levels in most latently infected cell lines. The gene encoding v-IL-6 is also expressed as a latent transcript in some contexts. Both genes encode powerful signaling molecules with particular relevance to B cell biology: K1 mimics signaling through the B cell receptor, and v-IL-6 promotes B cell survival. These data resolve earlier controversies about K1 and v-IL-6 expression and indicate that, in addition to core latency genes, some transcripts can be expressed in KSHV latency in a context-dependent manner. PMID:20219929

  10. Chromosomal locations and modes of action of genes of the retinoid (vitamin A) system support their involvement in the etiology of schizophrenia

    SciTech Connect

    Goodman, A.B.

    1995-08-14

    Vitamin A (retinoid), an essential nutrient for fetal and subsequent mammalian development, is involved in gene expression, cell differentiation, proliferation, migration, and death. Retinoic acid (RA) the morphogenic derivative of vitamin A is highly teratogenic. In humans retinoid excess or deficit can result in brain anomalies and psychosis. This review discusses chromosomal loci of genes that control the retinoid cascade in relation to some candidate genes in schizophrenia. The paper relates the knowledge about the transport, delivery, and action of retinoids to what is presently known about the pathology of schizophrenia, with particular reference to the dopamine hypothesis, neurotransmitters, the glutamate hypothesis, neurotransmitters, the glutamate hypothesis, retinitis pigmentosa, dermatologic disorders, and craniofacial anomalies. 201 refs., 1 tab.

  11. The UV filter benzophenone 3 (BP-3) activates hormonal genes mimicking the action of ecdysone and alters embryo development in the insect Chironomus riparius (Diptera).

    PubMed

    Ozáez, Irene; Martínez-Guitarte, José Luis; Morcillo, Gloria

    2014-09-01

    Numerous studies have evaluated the endocrine effects of UV filters in vertebrates, but little attention has been paid to their possible hormonal activity in invertebrates. We examined the effects of benzophenone-3 (BP-3), one of the most common sunscreen agents, in Chironomus riparius (Insecta), a reference organism in aquatic toxicology. Salivary glands from larvae were treated with either the hormone ecdysone or BP-3 to compare the response of endocrine genes. It was found that BP-3 elicits the same effects as the natural hormone activating the expression of a set of ecdysone responsive genes. BP-3 also activated the stress gene hsp70. Interestingly, similar effects have been confirmed in vivo in embryos. Moreover, BP-3 also altered embryogenesis delaying hatching. This is the first demonstration of hormonal activity of UV filters in invertebrates, showing a mode of action similar to ecdysteroid hormones. This finding highlights the potential endocrine disruptive effects of these emergent pollutants.

  12. The UV filter benzophenone 3 (BP-3) activates hormonal genes mimicking the action of ecdysone and alters embryo development in the insect Chironomus riparius (Diptera).

    PubMed

    Ozáez, Irene; Martínez-Guitarte, José Luis; Morcillo, Gloria

    2014-09-01

    Numerous studies have evaluated the endocrine effects of UV filters in vertebrates, but little attention has been paid to their possible hormonal activity in invertebrates. We examined the effects of benzophenone-3 (BP-3), one of the most common sunscreen agents, in Chironomus riparius (Insecta), a reference organism in aquatic toxicology. Salivary glands from larvae were treated with either the hormone ecdysone or BP-3 to compare the response of endocrine genes. It was found that BP-3 elicits the same effects as the natural hormone activating the expression of a set of ecdysone responsive genes. BP-3 also activated the stress gene hsp70. Interestingly, similar effects have been confirmed in vivo in embryos. Moreover, BP-3 also altered embryogenesis delaying hatching. This is the first demonstration of hormonal activity of UV filters in invertebrates, showing a mode of action similar to ecdysteroid hormones. This finding highlights the potential endocrine disruptive effects of these emergent pollutants. PMID:24878782

  13. Phylogenetic analysis of a gene cluster encoding an additional, rhizobial-like type III secretion system that is narrowly distributed among Pseudomonas syringae strains

    PubMed Central

    2012-01-01

    Background The central role of Type III secretion systems (T3SS) in bacteria-plant interactions is well established, yet unexpected findings are being uncovered through bacterial genome sequencing. Some Pseudomonas syringae strains possess an uncharacterized cluster of genes encoding putative components of a second T3SS (T3SS-2) in addition to the well characterized Hrc1 T3SS which is associated with disease lesions in host plants and with the triggering of hypersensitive response in non-host plants. The aim of this study is to perform an in silico analysis of T3SS-2, and to compare it with other known T3SSs. Results Based on phylogenetic analysis and gene organization comparisons, the T3SS-2 cluster of the P. syringae pv. phaseolicola strain is grouped with a second T3SS found in the pNGR234b plasmid of Rhizobium sp. These additional T3SS gene clusters define a subgroup within the Rhizobium T3SS family. Although, T3SS-2 is not distributed as widely as the Hrc1 T3SS in P. syringae strains, it was found to be constitutively expressed in P. syringae pv phaseolicola through RT-PCR experiments. Conclusions The relatedness of the P. syringae T3SS-2 to a second T3SS from the pNGR234b plasmid of Rhizobium sp., member of subgroup II of the rhizobial T3SS family, indicates common ancestry and/or possible horizontal transfer events between these species. Functional analysis and genome sequencing of more rhizobia and P. syringae pathovars may shed light into why these bacteria maintain a second T3SS gene cluster in their genome. PMID:22937899

  14. The Wnt and Delta-Notch signalling pathways interact to direct pair-rule gene expression via caudal during segment addition in the spider Parasteatoda tepidariorum.

    PubMed

    Schönauer, Anna; Paese, Christian L B; Hilbrant, Maarten; Leite, Daniel J; Schwager, Evelyn E; Feitosa, Natália Martins; Eibner, Cornelius; Damen, Wim G M; McGregor, Alistair P

    2016-07-01

    In short-germ arthropods, posterior segments are added sequentially from a segment addition zone (SAZ) during embryogenesis. Studies in spiders such as Parasteatoda tepidariorum have provided insights into the gene regulatory network (GRN) underlying segment addition, and revealed that Wnt8 is required for dynamic Delta (Dl) expression associated with the formation of new segments. However, it remains unclear how these pathways interact during SAZ formation and segment addition. Here, we show that Delta-Notch signalling is required for Wnt8 expression in posterior SAZ cells, but represses the expression of this Wnt gene in anterior SAZ cells. We also found that these two signalling pathways are required for the expression of the spider orthologues of even-skipped (eve) and runt-1 (run-1), at least in part via caudal (cad). Moreover, it appears that dynamic expression of eve in this spider does not require a feedback loop with run-1, as is found in the pair-rule circuit of the beetle Tribolium Taken together, our results suggest that the development of posterior segments in Parasteatoda is directed by dynamic interactions between Wnt8 and Delta-Notch signalling that are read out by cad, which is necessary but probably not sufficient to regulate the expression of eve and run-1 Our study therefore provides new insights towards better understanding the evolution and developmental regulation of segmentation in other arthropods, including insects. PMID:27287802

  15. The Wnt and Delta-Notch signalling pathways interact to direct pair-rule gene expression via caudal during segment addition in the spider Parasteatoda tepidariorum.

    PubMed

    Schönauer, Anna; Paese, Christian L B; Hilbrant, Maarten; Leite, Daniel J; Schwager, Evelyn E; Feitosa, Natália Martins; Eibner, Cornelius; Damen, Wim G M; McGregor, Alistair P

    2016-07-01

    In short-germ arthropods, posterior segments are added sequentially from a segment addition zone (SAZ) during embryogenesis. Studies in spiders such as Parasteatoda tepidariorum have provided insights into the gene regulatory network (GRN) underlying segment addition, and revealed that Wnt8 is required for dynamic Delta (Dl) expression associated with the formation of new segments. However, it remains unclear how these pathways interact during SAZ formation and segment addition. Here, we show that Delta-Notch signalling is required for Wnt8 expression in posterior SAZ cells, but represses the expression of this Wnt gene in anterior SAZ cells. We also found that these two signalling pathways are required for the expression of the spider orthologues of even-skipped (eve) and runt-1 (run-1), at least in part via caudal (cad). Moreover, it appears that dynamic expression of eve in this spider does not require a feedback loop with run-1, as is found in the pair-rule circuit of the beetle Tribolium Taken together, our results suggest that the development of posterior segments in Parasteatoda is directed by dynamic interactions between Wnt8 and Delta-Notch signalling that are read out by cad, which is necessary but probably not sufficient to regulate the expression of eve and run-1 Our study therefore provides new insights towards better understanding the evolution and developmental regulation of segmentation in other arthropods, including insects.

  16. Additive roles of PthAs in bacterial growth and pathogenicity associated with nucleotide polymorphisms in effector-binding elements of citrus canker susceptibility genes.

    PubMed

    Abe, Valeria Yukari; Benedetti, Celso Eduardo

    2016-10-01

    Citrus canker, caused by Xanthomonas citri, affects most commercial citrus varieties. All X. citri strains possess at least one transcription activator-like effector of the PthA family that activates host disease susceptibility (S) genes. The X. citri strain 306 encodes four PthA effectors; nevertheless, only PthA4 is known to elicit cankers on citrus. As none of the PthAs act as avirulence factors on citrus, we hypothesized that PthAs 1-3 might also contribute to pathogenicity on certain hosts. Here, we show that, although PthA4 is indispensable for canker formation in six Brazilian citrus varieties, PthAs 1 and 3 contribute to canker development in 'Pera' sweet orange, but not in 'Tahiti' lemon. Deletions in two or more pthA genes reduce bacterial growth in planta more pronouncedly than single deletions, suggesting an additive role of PthAs in pathogenicity and bacterial fitness. The contribution of PthAs 1 and 3 in canker formation in 'Pera' plants does not correlate with the activation of the canker S gene, LOB1 (LATERAL ORGAN BOUNDARIES 1), but with the induction of other PthA targets, including LOB2 and citrus dioxygenase (DIOX). LOB1, LOB2 and DIOX show differential PthA-dependent expression between 'Pera' and 'Tahiti' plants that appears to be associated with nucleotide polymorphisms found at or near PthA-binding sites. We also present evidence that LOB1 activation alone is not sufficient to elicit cankers on citrus, and that DIOX acts as a canker S gene in 'Pera', but not 'Tahiti', plants. Our results suggest that the activation of multiple S genes, such as LOB1 and DIOX, is necessary for full canker development.

  17. Fatty Acid Profiles and Stearoyl-CoA Desaturase Gene Expression in Longissimus dorsi Muscle of Growing Lambs Influenced by Addition of Tea Saponins and Soybean Oil

    PubMed Central

    Mao, H. L.; Wang, J. K.; Lin, J.; Liu, J. X.

    2012-01-01

    This study was conducted to determine the effects of dietary addition of tea saponins (TS) and soybean oil (SO) on fatty acid profile and gene expression of stearoyl-CoA desaturase (SCD) in longissimus dorsi (LD) muscle of growing lambs. Thirty-two Huzhou lambs were assigned to four dietary treatments in a 2×2 factorial arrangement with main effects of TS (0 or 3 g/d) and SO (0 or 30 g/kg of diet DM). The diet without additives was considered as NTNS (no TS or SO). After a feeding trial for 60 d, four lambs of each treatment were slaughtered to collect the samples of LD muscle. Percentage of trans-11 vaccenic acid was enhanced (p<0.05) in muscle of lambs fed TS and SO. The proportion of total conjugated linoleic acid (CLA) was increased (p<0.05) by SO, but decreased (p<0.05) by TS in LD muscle. The percentage of total saturated fatty acids in muscle was decreased (p<0.05) by addition of TS and SO, while addition of SO increased (p<0.05) the percentage of total polyunsaturated fatty acids. The ratio of cis-9, trans-11 CLA to tran-11 vaccenic acid was decreased (p<0.05) by TS, but increased (p<0.05) by SO. The same effects were observed in SCD mRNA expression. From these results it is indicated that including TS and SO in the diet of growing lambs affect the fatty acid profiles of LD muscle and that the proportion of cis-9, trans-11 CLA in the muscle influenced by TS and SO may be related to the SCD gene expression. PMID:25049609

  18. Induction of Olfaction and Cancer-Related Genes in Mice Fed a High-Fat Diet as Assessed through the Mode-of-Action by Network Identification Analysis

    PubMed Central

    Choi, Youngshim; Hur, Cheol-Goo; Park, Taesun

    2013-01-01

    The pathophysiological mechanisms underlying the development of obesity and metabolic diseases are not well understood. To gain more insight into the genetic mediators associated with the onset and progression of diet-induced obesity and metabolic diseases, we studied the molecular changes in response to a high-fat diet (HFD) by using a mode-of-action by network identification (MNI) analysis. Oligo DNA microarray analysis was performed on visceral and subcutaneous adipose tissues and muscles of male C57BL/6N mice fed a normal diet or HFD for 2, 4, 8, and 12 weeks. Each of these data was queried against the MNI algorithm, and the lists of top 5 highly ranked genes and gene ontology (GO)-annotated pathways that were significantly overrepresented among the 100 highest ranked genes at each time point in the 3 different tissues of mice fed the HFD were considered in the present study. The 40 highest ranked genes identified by MNI analysis at each time point in the different tissues of mice with diet-induced obesity were subjected to clustering based on their temporal patterns. On the basis of the above-mentioned results, we investigated the sequential induction of distinct olfactory receptors and the stimulation of cancer-related genes during the development of obesity in both adipose tissues and muscles. The top 5 genes recognized using the MNI analysis at each time point and gene cluster identified based on their temporal patterns in the peripheral tissues of mice provided novel and often surprising insights into the potential genetic mediators for obesity progression. PMID:23555558

  19. Induction of olfaction and cancer-related genes in mice fed a high-fat diet as assessed through the mode-of-action by network identification analysis.

    PubMed

    Choi, Youngshim; Hur, Cheol-Goo; Park, Taesun

    2013-01-01

    The pathophysiological mechanisms underlying the development of obesity and metabolic diseases are not well understood. To gain more insight into the genetic mediators associated with the onset and progression of diet-induced obesity and metabolic diseases, we studied the molecular changes in response to a high-fat diet (HFD) by using a mode-of-action by network identification (MNI) analysis. Oligo DNA microarray analysis was performed on visceral and subcutaneous adipose tissues and muscles of male C57BL/6N mice fed a normal diet or HFD for 2, 4, 8, and 12 weeks. Each of these data was queried against the MNI algorithm, and the lists of top 5 highly ranked genes and gene ontology (GO)-annotated pathways that were significantly overrepresented among the 100 highest ranked genes at each time point in the 3 different tissues of mice fed the HFD were considered in the present study. The 40 highest ranked genes identified by MNI analysis at each time point in the different tissues of mice with diet-induced obesity were subjected to clustering based on their temporal patterns. On the basis of the above-mentioned results, we investigated the sequential induction of distinct olfactory receptors and the stimulation of cancer-related genes during the development of obesity in both adipose tissues and muscles. The top 5 genes recognized using the MNI analysis at each time point and gene cluster identified based on their temporal patterns in the peripheral tissues of mice provided novel and often surprising insights into the potential genetic mediators for obesity progression.

  20. The action of a dietary retinoid on gene expression and cancer induction in electron-irradiated rat skin

    NASA Technical Reports Server (NTRS)

    Burns, Fredric J.; Chen, Shuaili; Xu, Guijuan; Wu, Feng; Tang, Moon-Shong

    2002-01-01

    Current models of radiation carcinogenesis generally assume that the DNA is damaged in a variety of ways by the radiation and that subsequent cell divisions contribute to the conversion of the damage to heritable mutations. Cancer may seem complex and intractable, but its complexity provides multiple opportunities for preventive interventions. Mitotic inhibitors are among the strongest cancer preventive agents, not only slowing the growth rate of preneoplasias but also increasing the fidelity of DNA repair processes. Ionizing radiation, including electrons, is a strong inducer of cancer in rat skin, and dietary retinoids have shown potent cancer preventive activity in the same system. A non-toxic dietary dose of retinyl acetate altered gene expression levels 24 hours after electron irradiation of rat skin. Of the 8740 genes on an Affymetrix rat expression array, the radiation significantly (5 fold or higher) altered 188, while the retinoid altered 231, including 16 radiation-altered genes that were reversely altered. While radiation strongly affected the expression of stress response, immune/inflammation and nucleic acid metabolism genes, the retinoid most strongly affected proliferation-related genes, including some significant reversals, such as, keratin 14, retinol binding protein, and calcium binding proteins. These results point to reversal of proliferation-relevant genes as a likely basis for the anti-radiogenic effects of dietary retinyl acetate.

  1. Combinatorial action of transcription factors orchestrates cell cycle-dependent expression of the ribosomal protein genes and ribosome biogenesis.

    PubMed

    Nosrati, Nagisa; Kapoor, Neetu R; Kumar, Vijay

    2014-05-01

    Nucleolar assembly begins at the early G1 phase of the cell cycle and is a hub of ribosomal DNA transcription and rRNA biosynthesis. The newly-formed rRNAs together with ribosomal proteins (RPs) constitute the building block of the ribosomal machinery. Although RPs play a major role in protein biosynthesis, their own regulation and expression is rather poorly understood. In the present study, we investigated the regulation of RP genes RPS27a, RPS24, RPS6, RPL9 and RPL4 in synchronized mammalian cell culture. Quantitative RT-PCR analysis indicated their expression during the mid to late G1 phase, whereas the rRNA genes were expressed during the early G1 phase of the cell cycle. The promoter reporter analysis of the RPS27a gene revealed that it could be synergistically stimulated by the transcription factors specificity protein 1 (Sp1) and cAMP response element-binding protein (CREB). However, E2F transcription factor 1 (E2F1) appeared to negatively regulate gene expression. Chromatin immunoprecipitation studies confirmed the promoter occupancy of Sp1, CREB and E2F1. Although Sp1 and CREB binding enhanced the promoter occupancy of histone acetyltransferases PCAF, p300 and CREB binding protein, E2F1 facilitated the recruitment of histone deacetylases. Both acetylation (histone H4 pan-acetyl, histone H3 acetyl Lys 14) and methylation (histone H3 trimethyl Lys 9) marks were observed in the RPS27a promoter region, suggesting their important regulatory role in gene expression. Because the promoter regions of most RP genes are well conserved, we propose that their orchestrated regulation and synthesis during the cell cycle facilitates ribosome biogenesis. PMID:24646001

  2. Gene Expression Profiles in Human and Mouse Primary Cells Provide New Insights into the Differential Actions of Vitamin D3 Metabolites

    PubMed Central

    Tuohimaa, Pentti; Wang, Jing-Huan; Khan, Sofia; Kuuslahti, Marianne; Qian, Kui; Manninen, Tommi; Auvinen, Petri; Vihinen, Mauno; Lou, Yan-Ru

    2013-01-01

    1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) had earlier been regarded as the only active hormone. The newly identified actions of 25-hydroxyvitamin D3 (25(OH)D3) and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) broadened the vitamin D3 endocrine system, however, the current data are fragmented and a systematic understanding is lacking. Here we performed the first systematic study of global gene expression to clarify their similarities and differences. Three metabolites at physiologically comparable levels were utilized to treat human and mouse fibroblasts prior to DNA microarray analyses. Human primary prostate stromal P29SN cells (hP29SN), which convert 25(OH)D3 into 1α,25(OH)2D3 by 1α-hydroxylase (encoded by the gene CYP27B1), displayed regulation of 164, 171, and 175 genes by treatment with 1α,25(OH)2D3, 25(OH)D3, and 24R,25(OH)2D3, respectively. Mouse primary Cyp27b1 knockout fibroblasts (mCyp27b1−/−), which lack 1α-hydroxylation, displayed regulation of 619, 469, and 66 genes using the same respective treatments. The number of shared genes regulated by two metabolites is much lower in hP29SN than in mCyp27b1−/−. By using DAVID Functional Annotation Bioinformatics Microarray Analysis tools and Ingenuity Pathways Analysis, we identified the agonistic regulation of calcium homeostasis and bone remodeling between 1α,25(OH)2D3 and 25(OH)D3 and unique non-classical actions of each metabolite in physiological and pathological processes, including cell cycle, keratinocyte differentiation, amyotrophic lateral sclerosis signaling, gene transcription, immunomodulation, epigenetics, cell differentiation, and membrane protein expression. In conclusion, there are three distinct vitamin D3 hormones with clearly different biological activities. This study presents a new conceptual insight into the vitamin D3 endocrine system, which may guide the strategic use of vitamin D3 in disease prevention and treatment. PMID:24116037

  3. Transcriptome analysis of genes related to resistance against powdery mildew in wheat-Thinopyrum alien addition disomic line germplasm SN6306.

    PubMed

    Li, Quanquan; Niu, Zubiao; Bao, Yinguang; Tian, Qiuju; Wang, Honggang; Kong, Lingrang; Feng, Deshun

    2016-09-15

    Wheat powdery mildew, which is mainly caused by Blumeria graminis f. sp. tritici (Bgt), seriously damages wheat production. The wheat-Thinopyrum intermedium alien addition disomic line germplasm SN6306, being one of the important sources of genes for wheat resistance, is highly resistant to Bgt E09 and to many other powdery mildew physiological races. However, knowledge on the resistance mechanism of SN6306 remains limited. Our study employed high-throughput RNA sequencing based on next-generation sequencing technology (Illumina) to obtain an overview of the transcriptome characteristics of SN6306 and its parent wheat Yannong 15 (YN15) during Bgt infection. The sequencing generated 104,773 unigenes, 9909 of which showed varied expression levels. Among the 9909 unigenes, 1678 unigenes showed 0 reads in YN15. The expression levels in Bgt-inoculated SN6306 and YN15 of exactly 39 unigenes that showed 0 or considerably low reads in YN15 were validated to identify the genes involved in Bgt resistance. Among the 39 unigenes, 12 unigenes were upregulated in SN6306 by 3-45 times. These unigenes mainly encoded kinase, synthase, proteases, and signal transduction proteins, which may play an important role in the resistance against Bgt. To confirm whether the unigenes that showed 0 reads in YN15 are really unique to SN6306, 8 unigenes were cloned and sequenced. Results showed that the selected unigenes are more similar to SN6306 and Th. intermedium than to the wheat cultivar YN15. The sequencing results further confirmed that the unigenes showing 0 reads in YN15 are unique to SN6306 and are most likely derived from Th. intermedium (Host) Nevski. Thus, the genes from Th. intermedium most probably conferred the resistance of SN6306 to Bgt. PMID:27265028

  4. The Rat Diabetes Susceptibility Locus Iddm4 And At Least One Additional Gene Are Required For Autoimmune Diabetes Induced By Viral Infection

    PubMed Central

    Blankenhorn, Elizabeth P.; Rodemich, Lucy; Martin-Fernandez, Cristina; Leif, Jean; Greiner, Dale L.; Mordes, John P.

    2008-01-01

    BBDR rats develop autoimmune diabetes mellitus only after challenge with environmental perturbants. These include polyinosinic:polycytidylic acid (poly I:C, a ligand of toll-like receptor 3), agents that deplete regulatory T cell populations (Tregs), and a non-beta-cell-cytopathic parvovirus (Kilham rat virus, KRV). The dominant diabetes susceptibility locus Iddm4 is required for diabetes induced by treatment with poly I:C plus Treg depletion. Iddm4 is penetrant in congenic heterozygote rats on the resistant WF background, and is 79% sensitive and 80% specific as a predictor of induced diabetes. Surprisingly, an analysis of 190 (BBDR × WF)F2 rats treated with KRV after brief exposure to poly I:C revealed that the BBDR origin allele of Iddm4 is necessary but not entirely sufficient for diabetes expression. A genome scan identified a locus on chromosome 17, designated Iddm20, that is also required for susceptibility to diabetes after exposure to KRV and poly I:C (LOD score 3.7). These data suggest that the expression of autoimmune diabetes is a complex process that requires both major histocompatibility complex (MHC) genes that confer susceptibility and additional genes like Iddm4 and Iddm20 that operate only in the context of specific environmental perturbants, amplifying the immune response and the rate of disease progression. PMID:15793267

  5. Analysis of genes negatively regulated by phytochrome action in Lemna gibba and identification of a promoter region required for phytochrome responsiveness.

    PubMed Central

    Okubara, P A; Williams, S A; Doxsee, R A; Tobin, E M

    1993-01-01

    As a step to understanding how the photoreceptor phytochrome acts to change the transcription of specific nuclear genes in Lemna gibba, we wish to compare promoter elements involved in negative regulation by phytochrome with those involved in positive regulation. We have isolated three genes negatively regulated by phytochrome, designated NR (negatively phytochrome regulated) genes (P.A. Okubara, E.M. Tobin [1991] Plant Physiol 96:1237-1245), and we have now sequenced two of these. The promoters of both contain some sequence motifs that are identical with motifs from other genes. We used a transient assay in L. gibba to demonstrate that approximately 1.7 kb pairs of the NPR1 promoter and 1.1 kb pairs of the NPR2 promoter could confer negative phytochrome regulation to a luciferase reporter gene. Deletion analysis of the NPR2 promoter showed that sequences between -208 and -82 from the transcription start were necessary for negative phytochrome regulation. However, this region was not sufficient to confer negative regulation by phytochrome to another promoter. Additionally, we noted that this region showed no similarity to a region identified as important for the negative regulation of the oat phyA promoter (W.B. Bruce, X.-W. Deng, P.H. Quail [1991] EMBO J 10:3015-3024), but it does contain a sequence element found in several other kinds of genes, including ones positively regulated by phytochrome. The deduced amino acid sequences of NPR1 and NPR2 were found to share similarities with many abscisic acid-induced or seed-abundant proteins. Thus, these genes, like other phytochrome-regulated genes, might respond to multiple regulatory signals. PMID:8310060

  6. Alcohol Regulates Genes that Are Associated with Response to Endocrine Therapy and Attenuates the Actions of Tamoxifen in Breast Cancer Cells

    PubMed Central

    Candelaria, Nicholes R.; Weldon, Ryan; Muthusamy, Selvaraj; Nguyen-Vu, Trang; Addanki, Sridevi; Yoffou, Paule-Helena; Karaboga, Husna; Blessing, Alicia M.; Bollu, Lakshmi Reddy; Miranda, Rajesh C.; Lin, Chin-Yo

    2015-01-01

    Hereditary, hormonal, and behavioral factors contribute to the development of breast cancer. Alcohol consumption is a modifiable behavior that is linked to increased breast cancer risks and is associated with the development of hormone-dependent breast cancers as well as disease progression and recurrence following endocrine treatment. In this study we examined the molecular mechanisms of action of alcohol by applying molecular, genetic, and genomic approaches in characterizing its effects on estrogen receptor (ER)-positive breast cancer cells. Treatments with alcohol promoted cell proliferation, increased growth factor signaling, and up-regulated the transcription of the ER target gene GREB1 but not the canonical target TFF1/pS2. Microarray analysis following alcohol treatment identified a large number of alcohol-responsive genes, including those which function in apoptotic and cell proliferation pathways. Furthermore, expression profiles of the responsive gene sets in tumors were strongly associated with clinical outcomes in patients who received endocrine therapy. Correspondingly, alcohol treatment attenuated the anti-proliferative effects of the endocrine therapeutic drug tamoxifen in ER-positive breast cancer cells. To determine the contribution and functions of responsive genes, their differential expression in tumors were assessed between outcome groups. The proto-oncogene BRAF was identified as a novel alcohol- and estrogen-induced gene that showed higher expression in patients with poor outcomes. Knock-down of BRAF, moreover, prevented the proliferation of breast cancer cells. These findings not only highlight the mechanistic basis of the effects of alcohol on breast cancer cells and increased risks for disease incidents and recurrence, but may facilitate the discovery and characterization of novel oncogenic pathways and markers in breast cancer research and therapeutics. PMID:26661278

  7. Alcohol Regulates Genes that Are Associated with Response to Endocrine Therapy and Attenuates the Actions of Tamoxifen in Breast Cancer Cells.

    PubMed

    Candelaria, Nicholes R; Weldon, Ryan; Muthusamy, Selvaraj; Nguyen-Vu, Trang; Addanki, Sridevi; Yoffou, Paule-Helena; Karaboga, Husna; Blessing, Alicia M; Bollu, Lakshmi Reddy; Miranda, Rajesh C; Lin, Chin-Yo

    2015-01-01

    Hereditary, hormonal, and behavioral factors contribute to the development of breast cancer. Alcohol consumption is a modifiable behavior that is linked to increased breast cancer risks and is associated with the development of hormone-dependent breast cancers as well as disease progression and recurrence following endocrine treatment. In this study we examined the molecular mechanisms of action of alcohol by applying molecular, genetic, and genomic approaches in characterizing its effects on estrogen receptor (ER)-positive breast cancer cells. Treatments with alcohol promoted cell proliferation, increased growth factor signaling, and up-regulated the transcription of the ER target gene GREB1 but not the canonical target TFF1/pS2. Microarray analysis following alcohol treatment identified a large number of alcohol-responsive genes, including those which function in apoptotic and cell proliferation pathways. Furthermore, expression profiles of the responsive gene sets in tumors were strongly associated with clinical outcomes in patients who received endocrine therapy. Correspondingly, alcohol treatment attenuated the anti-proliferative effects of the endocrine therapeutic drug tamoxifen in ER-positive breast cancer cells. To determine the contribution and functions of responsive genes, their differential expression in tumors were assessed between outcome groups. The proto-oncogene BRAF was identified as a novel alcohol- and estrogen-induced gene that showed higher expression in patients with poor outcomes. Knock-down of BRAF, moreover, prevented the proliferation of breast cancer cells. These findings not only highlight the mechanistic basis of the effects of alcohol on breast cancer cells and increased risks for disease incidents and recurrence, but may facilitate the discovery and characterization of novel oncogenic pathways and markers in breast cancer research and therapeutics.

  8. Gene cuisine or Frankenfood? The theory of reasoned action as an audience segmentation strategy for messages about genetically modified foods.

    PubMed

    Silk, Kami J; Weiner, Judith; Parrott, Roxanne L

    2005-12-01

    Genetically modified (GM) foods are currently a controversial topic about which the lay public in the United States knows little. Formative research has demonstrated that the lay public is uncertain and concerned about GM foods. This study (N = 858) extends focus group research by using the Theory of Reasoned Action (TRA) to examine attitudes and subjective norms related to GM foods as a theoretical strategy for audience segmentation. A hierarchical cluster analysis revealed four unique audiences based on their attitude and subjective norm toward GM foods (ambivalent-biotech, antibiotech, biotech-normer, and biotech individual). Results are discussed in terms of the theoretical and practical significance for audience segmentation.

  9. Generation and propagation of recombinant mumps viruses exhibiting an additional U residue in the homopolymeric U tract of the F gene-end signal.

    PubMed

    Sauder, Christian J; Ngo, Laurie; Simonyan, Vahan; Cong, Yu; Zhang, Cheryl; Link, Malen; Malik, Tahir; Rubin, Steven A

    2015-08-01

    As a member of the family paramyxoviridae, subfamily paramyxovirinae, the genome of mumps virus (MuV) is postulated to be polyhexameric in length in order to be able to replicate efficiently. While all natural MuV strains sequenced so far obey to this "rule of six," we describe here the isolation of recombinant MuVs that appeared to contain an additional U residue in the homopolymeric tract of the F gene-end signal, resulting in a genome length of 6n + 1. Sequencing of several plaque-purified viruses from these preparations did not reveal the existence of length-correcting mutations, suggesting that they are violators of the rule of six. Employing high-throughput sequencing technology, we provide evidence that the insertion of an additional U residue is mainly the result of the rescue system used that relies on T7 RNA polymerase. Limited in vitro and in vivo testing of the viruses did not reveal any significant impact of the longer genome on virus replication or virulence, suggesting that the rule of six is not a strict requirement for MuV replication.

  10. Gene expression profiles following exposure to a developmental neurotoxicant, Aroclor 1254: Pathway analysis for possible mode(s) of action

    SciTech Connect

    Royland, Joyce E.; Kodavanti, Prasada Rao S.

    2008-09-01

    Epidemiological studies indicate that low levels of polychlorinated biphenyl (PCB) exposure can adversely affect neurocognitive development. In animal models, perturbations in calcium signaling, neurotransmitters, and thyroid hormones have been postulated as potential mechanisms for PCB-induced developmental neurotoxicity. In order to understand the role of these proposed mechanisms and to identify other mechanisms in PCB-induced neurotoxicity, we have chosen a global approach utilizing oligonucleotide microarrays to examine gene expression profiles in the brain following developmental exposure to Aroclor 1254 (0 or 6 mg/kg/day from gestation day 6 through postnatal day (PND) 21) in Long-Evans rats. Gene expression levels in the cerebellum and hippocampus from PNDs 7 and 14 animals were determined on Affymetrix rat 230A{sub 2}.0 chips. In the cerebellum, 87 transcripts were altered at PND7 compared to 27 transcripts at PND14 by Aroclor 1254 exposure, with only one transcript affected at both ages. In hippocampus, 175 transcripts and 50 transcripts were altered at PND7 and PND14, respectively, by Aroclor 1254 exposure with five genes commonly affected. Functional analysis suggests that pathways related to calcium homeostasis (Gng3, Ryr2, Trdn, Cacna1a), intracellular signaling (Camk2d, Stk17b, Pacsin2, Ryr2, Trio, Fert2, Ptk2b), axonal guidance (Lum, Mxd3, Akap11, Gucy1b3), aryl hydrocarbon receptor signaling (Nfia, Col1a2), and transcripts involved in cell proliferation (Gspt2, Cdkn1c, Ptk2b) and differentiation (Ifitm31, Hpca, Zfp260, Igsf4a, Hes5) leading to the development of nervous system were significantly altered by Aroclor 1254 exposure. Of the two brain regions examined, Aroclor 1254-induced genomic changes were greater in the hippocampus than the cerebellum. The genomic data suggests that PCB-induced neurotoxic effects were due to disruption of normal ontogenetic pattern of nervous system growth and development by altering intracellular signaling pathways

  11. Addition of genes for cellobiase and pectinolytic activity in Escherichia coli for fuel ethanol production from pectin-rich lignocellulosic biomass.

    PubMed

    Edwards, Meredith C; Henriksen, Emily Decrescenzo; Yomano, Lorraine P; Gardner, Brian C; Sharma, Lekh N; Ingram, Lonnie O; Doran Peterson, Joy

    2011-08-01

    Ethanologenic Escherichia coli strain KO11 was sequentially engineered to contain the Klebsiella oxytoca cellobiose phosphotransferase genes (casAB) as well as a pectate lyase (pelE) from Erwinia chrysanthemi, yielding strains LY40A (casAB) and JP07 (casAB pelE), respectively. To obtain an effective secretion of PelE, the Sec-dependent pathway out genes from E. chrysanthemi were provided on a cosmid to strain JP07 to construct strain JP07C. Finally, oligogalacturonide lyase (ogl) from E. chrysanthemi was added to produce strain JP08C. E. coli strains LY40A, JP07, JP07C, and JP08C possessed significant cellobiase activity in cell lysates, while only strains JP07C and JP08C demonstrated extracellular pectate lyase activity. Fermentations conducted by using a mixture of pure sugars representative of the composition of sugar beet pulp (SBP) showed that strains LY40A, JP07, JP07C, and JP08C were able to ferment cellobiose, resulting in increased ethanol production from 15 to 45% in comparison to that of KO11. Fermentations with SBP at very low fungal enzyme loads during saccharification revealed significantly higher levels of ethanol production for LY40A, JP07C, and JP08C than for KO11. JP07C ethanol yields were not considerably higher than those of LY40A; however, oligogalacturonide polymerization studies showed an increased breakdown of biomass to small-chain (degree of polymerization, ≤6) oligogalacturonides. JP08C achieved a further breakdown of polygalacturonate to monomeric sugars, resulting in a 164% increase in ethanol yields compared to those of KO11. The addition of commercial pectin methylesterase (PME) further increased JP08C ethanol production compared to that of LY40A by demethylating the pectin for enzymatic attack by pectin-degrading enzymes.

  12. Addition of Genes for Cellobiase and Pectinolytic Activity in Escherichia coli for Fuel Ethanol Production from Pectin-Rich Lignocellulosic Biomass▿

    PubMed Central

    Edwards, Meredith C.; Henriksen, Emily DeCrescenzo; Yomano, Lorraine P.; Gardner, Brian C.; Sharma, Lekh N.; Ingram, Lonnie O.; Doran Peterson, Joy

    2011-01-01

    Ethanologenic Escherichia coli strain KO11 was sequentially engineered to contain the Klebsiella oxytoca cellobiose phosphotransferase genes (casAB) as well as a pectate lyase (pelE) from Erwinia chrysanthemi, yielding strains LY40A (casAB) and JP07 (casAB pelE), respectively. To obtain an effective secretion of PelE, the Sec-dependent pathway out genes from E. chrysanthemi were provided on a cosmid to strain JP07 to construct strain JP07C. Finally, oligogalacturonide lyase (ogl) from E. chrysanthemi was added to produce strain JP08C. E. coli strains LY40A, JP07, JP07C, and JP08C possessed significant cellobiase activity in cell lysates, while only strains JP07C and JP08C demonstrated extracellular pectate lyase activity. Fermentations conducted by using a mixture of pure sugars representative of the composition of sugar beet pulp (SBP) showed that strains LY40A, JP07, JP07C, and JP08C were able to ferment cellobiose, resulting in increased ethanol production from 15 to 45% in comparison to that of KO11. Fermentations with SBP at very low fungal enzyme loads during saccharification revealed significantly higher levels of ethanol production for LY40A, JP07C, and JP08C than for KO11. JP07C ethanol yields were not considerably higher than those of LY40A; however, oligogalacturonide polymerization studies showed an increased breakdown of biomass to small-chain (degree of polymerization, ≤6) oligogalacturonides. JP08C achieved a further breakdown of polygalacturonate to monomeric sugars, resulting in a 164% increase in ethanol yields compared to those of KO11. The addition of commercial pectin methylesterase (PME) further increased JP08C ethanol production compared to that of LY40A by demethylating the pectin for enzymatic attack by pectin-degrading enzymes. PMID:21666025

  13. STAT4 Associates with SLE Through Two Independent Effects that Correlate with Gene Expression and Act Additively with IRF5 to Increase Risk

    PubMed Central

    Abelson, Anna-Karin; Delgado-Vega, Angélica M.; Kozyrev, Sergey V.; Sánchez, Elena; Velázquez-Cruz, Rafael; Eriksson, Niclas; Wojcik, Jerome; Reddy, Prasad Linga; Lima, Guadalupe; D’Alfonso, Sandra; Migliaresi, Sergio; Baca, Vicente; Orozco, Lorena; Witte, Torsten; Ortego-Centeno, Norberto; Abderrahim, Hadi; Pons-Estel, Bernardo A.; Gutiérrez, Carmen; Suárez, Ana; González-Escribano, Maria Francisca; Martin, Javier; Alarcón-Riquelme, Marta E.

    2013-01-01

    Objectives To confirm and define the genetic association of STAT4 and systemic lupus erythematosus, investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5. Methods 30 tag SNPs were genotyped in an independent set of Spanish cases and controls. SNPs surviving correction for multiple tests were genotyped in 5 new sets of cases and controls for replication. STAT4 cDNA was analyzed by 5’-RACE PCR and sequencing. Expression levels were measured by quantitative PCR. Results In the fine-mapping, four SNPs were significant after correction for multiple testing, with rs3821236 and rs3024866 as the strongest signals, followed by the previously associated rs7574865, and by rs1467199. Association was replicated in all cohorts. After conditional regression analyses, two major independent signals represented by SNPs rs3821236 and rs7574865, remained significant across the sets. These SNPs belong to separate haplotype blocks. High levels of STAT4 expression correlated with SNPs rs3821236, rs3024866 (both in the same haplotype block) and rs7574865 but not with other SNPs. We also detected transcription of alternative tissue-specific exons 1, indicating presence of tissue-specific promoters of potential importance in the expression of STAT4. No interaction with associated SNPs of IRF5 was observed using regression analysis. Conclusions These data confirm STAT4 as a susceptibility gene for SLE and suggest the presence of at least two functional variants affecting levels of STAT4. Our results also indicate that both genes STAT4 and IRF5 act additively to increase risk for SLE. PMID:19019891

  14. Flavobacterium johnsoniae sprB Is Part of an Operon Spanning the Additional Gliding Motility Genes sprC, sprD, and sprF ▿ †

    PubMed Central

    Rhodes, Ryan G.; Nelson, Shawn S.; Pochiraju, Soumya; McBride, Mark J.

    2011-01-01

    Cells of Flavobacterium johnsoniae move rapidly over surfaces by a process known as gliding motility. Gld proteins are thought to comprise the gliding motor that propels cell surface adhesins, such as the 669-kDa SprB. A novel protein secretion apparatus called the Por secretion system (PorSS) is required for assembly of SprB on the cell surface. Genetic and molecular analyses revealed that sprB is part of a seven-gene operon spanning 29.3 kbp of DNA. In addition to sprB, three other genes of this operon (sprC, sprD, and sprF) are involved in gliding. Mutations in sprB, sprC, sprD, and sprF resulted in cells that failed to form spreading colonies on agar but that exhibited some motility on glass in wet mounts. SprF exhibits some similarity to Porphyromonas gingivalis PorP, which is required for secretion of gingipain protease virulence factors via the P. gingivalis PorSS. F. johnsoniae sprF mutants produced SprB protein but were defective in localization of SprB to the cell surface, suggesting a role for SprF in secretion of SprB. The F. johnsoniae PorSS is involved in secretion of extracellular chitinase in addition to its role in secretion of SprB. SprF was not needed for chitinase secretion and may be specifically required for SprB secretion by the PorSS. Cells with nonpolar mutations in sprC or sprD produced and secreted SprB and propelled it rapidly along the cell surface. Multiple paralogs of sprB, sprC, sprD, and sprF are present in the genome, which may explain why mutations in sprB, sprC, sprD, and sprF do not result in complete loss of motility and suggests the possibility that semiredundant SprB-like adhesins may allow movement of cells over different surfaces. PMID:21131497

  15. Cardiac-Specific Deletion of the Pdha1 Gene Sensitizes Heart to Toxicological Actions of Ischemic Stress.

    PubMed

    Sun, Wanqing; Quan, Nanhu; Wang, Lin; Yang, Hui; Chu, Dongyang; Liu, Quan; Zhao, Xuezhong; Leng, Jiyan; Li, Ji

    2016-05-01

    Pyruvate dehydrogenase (PDH) plays a key role in aerobic energy metabolism and occupies a central crossroad between glycolysis and the tricarboxylic acid cycle. We generated inducible cardiac-specific PDH E1α knockout (CreER(T2)-PDH(flox/flox)) mice that demonstrated a high mortality rate. It was hypothesized that PDH modulating cardiac glucose metabolism is crucial for heart functions under normal physiological and/or stress conditions. The myocardial infarction was conducted by a ligation of the left anterior descending coronary arteries. Cardiac PDH E1α deficiency caused large myocardial infarcts size and macrophage infiltration in the hearts (P < .01 vs wild-type [WT]). Wheat germ agglutinin and Masson trichrome staining revealed significantly increased hypertrophy and fibrosis in PDH E1α-deficient hearts (P < .05 vs WT). Measurements of heart substrate metabolism in an ex vivo working heart perfusion system demonstrated a significant impairment of glucose oxidation in PDH E1α-deficient hearts during ischemia/reperfusion (P < .05 vs WT). Dichloroacetate, a PDH activator, increased glucose oxidation in WT hearts during ischemia/reperfusion and reduced myocardial infarct size in WT, but not in PDH E1α-deficient hearts. Immunoblotting results demonstrated that cardiac PDH E1α deficiency leads to an impaired ischemic AMP-activated protein kinase activation through Sestrin2-liver kinase B1 interaction which is responsible for an increased susceptibility of PDH E1α-deficient heart to ischemic insults. Thus, cardiac PDH E1α deficiency impairs ischemic AMP-activated protein kinase signaling and sensitizes hearts to the toxicological actions of ischemic stress.

  16. Food additives

    PubMed Central

    Spencer, Michael

    1974-01-01

    Food additives are discussed from the food technology point of view. The reasons for their use are summarized: (1) to protect food from chemical and microbiological attack; (2) to even out seasonal supplies; (3) to improve their eating quality; (4) to improve their nutritional value. The various types of food additives are considered, e.g. colours, flavours, emulsifiers, bread and flour additives, preservatives, and nutritional additives. The paper concludes with consideration of those circumstances in which the use of additives is (a) justified and (b) unjustified. PMID:4467857

  17. Mechanism of action of a repressor of dioxin-dependent induction of Cyp1a1 gene transcription.

    PubMed Central

    Watson, A J; Weir-Brown, K I; Bannister, R M; Chu, F F; Reisz-Porszasz, S; Fujii-Kuriyama, Y; Sogawa, K; Hankinson, O

    1992-01-01

    A dominant mutant of Hepa-1 cells, c31, expresses a repressor that prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-dependent stimulation of Cyp1a1 transcription. The repressor acts via the xenobiotic-responsive elements (XREs), which are the DNA-binding sites for the aryl hydrocarbon (Ah) receptor-TCDD complex during transcriptional activation of the gene. High-salt nuclear extracts prepared from c31 cells grown with TCDD contained normal levels of the Ah receptor which bound the XRE with normal affinity, as judged by in vitro gel mobility shift assays. Furthermore, extracts prepared from these cells, grown either with or without TCDD, contained no novel XRE-binding proteins compared with extracts from wild-type Hepa-1 cells. However, in vivo genomic footprinting demonstrated that TCDD treatment leads to binding of the Ah receptor to the XREs in Hepa-1 but not mutant cells. This finding suggests that the repressor associates with the Ah receptor to prevent its binding to the XREs and that high-salt treatment either causes dissociation of the receptor/repressor complex or fails to extract the repressor from nuclei. The results underscore the importance of using both in vivo and in vitro assays for analyzing DNA-protein interactions. Images PMID:1314949

  18. Understanding affirmative action.

    PubMed

    Crosby, Faye J; Iyer, Aarti; Sincharoen, Sirinda

    2006-01-01

    Affirmative action is a controversial and often poorly understood policy. It is also a policy that has been widely studied by social scientists. In this review, we outline how affirmative action operates in employment and education settings and consider the major points of controversy. In addition, we detail the contributions of psychologists and other social scientists in helping to demonstrate why affirmative action is needed; how it can have unintended negative consequences; and how affirmative action programs can be most successful. We also review how psychologists have examined variations in people's attitudes toward affirmative action, in part as a means for testing different theories of social behavior. PMID:16318608

  19. ISR meets SAR outside: additive action of the endophyte Bacillus pumilus INR7 and the chemical inducer, benzothiadiazole, on induced resistance against bacterial spot in field-grown pepper

    PubMed Central

    Yi, Hwe-Su; Yang, Jung Wook; Ryu, Choong-Min

    2013-01-01

    Induced resistance has been recognized as an attractive tool for plant disease management in modern agriculture. During the last two decades, studies on chemically- and biologically elicited induced resistance have revealed previously unknown features of the plant defense response including defense priming. As a biological trigger for induced resistance, plant growth-promoting rhizobacteria (PGPR) are a group of root-associated bacteria that can reduce plant disease severity and incidence, and augment plant growth and yield under greenhouse and field conditions. We evaluated the potential of an endophytic PGPR, Bacillus pumilus INR7, to induce systemic resistance against bacterial spot caused by Xanthomonas axonopodis pv. vesicatoria in pepper. Trials in the greenhouse showed significantly less symptom development in pepper plants inoculated with strain INR7 compared to a water treatment. Furthermore, a single dipping treatment with INR7 before transplantation of pepper plants into the field elicited an induced systemic resistance response against bacterial spot caused by artificially infiltration of X. axonopodis pv. vesicatoria and even against naturally occurring bacterial spot disease. We identified an additive effect on induced resistance after administration of a combination treatment composed of strain INR7 with a chemical inducer, benzothiadiazole (BTH) in the field. The combination treatment stimulated expression of pepper defense marker genes CaPR1, CaTin1, and CaPR4 to a greater extent than did treatment with either agent alone. Similar experiments conducted with tobacco revealed no additive effects under field conditions. Interestingly, co-application of plants with INR7 lifted the growth repressing effect of BTH. Application of BTH onto pepper and tobacco did not affect rhizosphere colonization but supported a higher population density inside plant roots when compared to water-treated control plants. Our results indicate that PGPR can be used in

  20. ISR meets SAR outside: additive action of the endophyte Bacillus pumilus INR7 and the chemical inducer, benzothiadiazole, on induced resistance against bacterial spot in field-grown pepper.

    PubMed

    Yi, Hwe-Su; Yang, Jung Wook; Ryu, Choong-Min

    2013-01-01

    Induced resistance has been recognized as an attractive tool for plant disease management in modern agriculture. During the last two decades, studies on chemically- and biologically elicited induced resistance have revealed previously unknown features of the plant defense response including defense priming. As a biological trigger for induced resistance, plant growth-promoting rhizobacteria (PGPR) are a group of root-associated bacteria that can reduce plant disease severity and incidence, and augment plant growth and yield under greenhouse and field conditions. We evaluated the potential of an endophytic PGPR, Bacillus pumilus INR7, to induce systemic resistance against bacterial spot caused by Xanthomonas axonopodis pv. vesicatoria in pepper. Trials in the greenhouse showed significantly less symptom development in pepper plants inoculated with strain INR7 compared to a water treatment. Furthermore, a single dipping treatment with INR7 before transplantation of pepper plants into the field elicited an induced systemic resistance response against bacterial spot caused by artificially infiltration of X. axonopodis pv. vesicatoria and even against naturally occurring bacterial spot disease. We identified an additive effect on induced resistance after administration of a combination treatment composed of strain INR7 with a chemical inducer, benzothiadiazole (BTH) in the field. The combination treatment stimulated expression of pepper defense marker genes CaPR1, CaTin1, and CaPR4 to a greater extent than did treatment with either agent alone. Similar experiments conducted with tobacco revealed no additive effects under field conditions. Interestingly, co-application of plants with INR7 lifted the growth repressing effect of BTH. Application of BTH onto pepper and tobacco did not affect rhizosphere colonization but supported a higher population density inside plant roots when compared to water-treated control plants. Our results indicate that PGPR can be used in

  1. Cytotoxicity, genotoxicity and mechanism of action (via gene expression analysis) of the indole alkaloid aspidospermine (antiparasitic) extracted from Aspidosperma polyneuron in HepG2 cells.

    PubMed

    Coatti, Giuliana Castello; Marcarini, Juliana Cristina; Sartori, Daniele; Fidelis, Queli Cristina; Ferreira, Dalva Trevisan; Mantovani, Mário Sérgio

    2016-08-01

    Aspidospermine is an indole alkaloid with biological properties associated with combating parasites included in the genera Plasmodium, Leishmania and Trypanossoma. The present study evaluated the cytotoxicity (resazurin test), genotoxicity (comet assay) and mechanism of action (gene expression analysis via qRT-PCR) of this alkaloid in human HepG2 cells. The results demonstrated that treatment with aspidospermine was both cytotoxic (starting at 75 μM) and genotoxic (starting at 50 μM). There was no significant modulation of the expression of the following genes: GSTP1 and GPX1 (xenobiotic metabolism); CAT (oxidative stress); TP53 and CCNA2 (cell cycle); HSPA5, ERN1, EIF2AK3 and TRAF2 (endoplasmic reticulum stress); CASP8, CASP9, CASP3, CASP7, BCL-2, BCL-XL BAX and BAX (apoptosis); and PCBP4, ERCC4, OGG1, RAD21 and MLH1 (DNA repair). At a concentration of 50 μM (non-cytotoxic, but genotoxic), there was a significant increase in the expression of CYP1A1 (xenobiotic metabolism) and APC (cell cycle), and at a concentration of 100 μM, a significant increase in the expression of CYP1A1 (xenobiotic metabolism), GADD153 (endoplasmic reticulum stress) and SOD (oxidative stress) was detected, with repression of the expression of GR (xenobiotic metabolism and oxidative stress). The results of treatment with aspidospermine at a 100 μM concentration (the dose indicated in the literature to achieve 89 % reduction of the growth of L. amazonensis) suggest that increased oxidative stress and an unfolded protein response (UPR) occurred in HepG2 cells. For the therapeutic use of aspidospermine (antiparasitic), chemical alteration of the molecule to achieve a lower cytotoxicity/genotoxicity in host cells is recommended.

  2. Androgens and skeletal muscle: cellular and molecular action mechanisms underlying the anabolic actions.

    PubMed

    Dubois, Vanessa; Laurent, Michaël; Boonen, Steven; Vanderschueren, Dirk; Claessens, Frank

    2012-05-01

    Androgens increase both the size and strength of skeletal muscle via diverse mechanisms. The aim of this review is to discuss the different cellular targets of androgens in skeletal muscle as well as the respective androgen actions in these cells leading to changes in proliferation, myogenic differentiation, and protein metabolism. Androgens bind and activate a specific nuclear receptor which will directly affect the transcription of target genes. These genes encode muscle-specific transcription factors, enzymes, structural proteins, as well as microRNAs. In addition, anabolic action of androgens is partly established through crosstalk with other signaling molecules such as Akt, myostatin, IGF-I, and Notch. Finally, androgens may also exert non-genomic effects in muscle by increasing Ca(2+) uptake and modulating kinase activities. In conclusion, the anabolic effect of androgens on skeletal muscle is not only explained by activation of the myocyte androgen receptor but is also the combined result of many genomic and non-genomic actions.

  3. Choosing Actions

    PubMed Central

    Rosenbaum, David A.; Chapman, Kate M.; Coelho, Chase J.; Gong, Lanyun; Studenka, Breanna E.

    2013-01-01

    Actions that are chosen have properties that distinguish them from actions that are not. Of the nearly infinite possible actions that can achieve any given task, many of the unchosen actions are irrelevant, incorrect, or inappropriate. Others are relevant, correct, or appropriate but are disfavored for other reasons. Our research focuses on the question of what distinguishes actions that are chosen from actions that are possible but are not. We review studies that use simple preference methods to identify factors that contribute to action choices, especially for object-manipulation tasks. We can determine which factors are especially important through simple behavioral experiments. PMID:23761769

  4. Action semantics modulate action prediction.

    PubMed

    Springer, Anne; Prinz, Wolfgang

    2010-11-01

    Previous studies have demonstrated that action prediction involves an internal action simulation that runs time-locked to the real action. The present study replicates and extends these findings by indicating a real-time simulation process (Graf et al., 2007), which can be differentiated from a similarity-based evaluation of internal action representations. Moreover, results showed that action semantics modulate action prediction accuracy. The semantic effect was specified by the processing of action verbs and concrete nouns (Experiment 1) and, more specifically, by the dynamics described by action verbs (Experiment 2) and the speed described by the verbs (e.g., "to catch" vs. "to grasp" vs. "to stretch"; Experiment 3). These results propose a linkage between action simulation and action semantics as two yet unrelated domains, a view that coincides with a recent notion of a close link between motor processes and the understanding of action language.

  5. MtsR is a dual regulator that controls virulence genes and metabolic functions in addition to metal homeostasis in the group A streptococcus.

    PubMed

    Toukoki, Chadia; Gold, Kathryn M; McIver, Kevin S; Eichenbaum, Zehava

    2010-05-01

    MtsR is a metal-dependent regulator in the group A streptococcus (GAS) that directly represses the transcription of genes involved in haem and metal uptake. While MtsR has been implicated in GAS virulence, the DNA recognition and full regulatory scope exerted by the protein are unknown. In this study we identified the shr promoter (P(shr)) and mapped MtsR binding to a 69 bp segment in P(shr) that overlaps the core promoter elements. A global transcriptional analysis demonstrated that MtsR modulates the expression of 64 genes in GAS, 44 of which were upregulated and 20 were downregulated in the mtsR mutant. MtsR controls genes with diverse functions including metal homeostasis, nucleic acid and amino acid metabolism, and protein fate. Importantly, the MtsR regulon includes mga, emm49 and ska, which are central for GAS pathogenesis. MtsR binding to the promoter region of both negatively and positively regulated genes demonstrates that it functions as a dual regulator. MtsR footprints are large (47-130 bp) and vary between target promoters. A 16 bp motif that consists of an interrupted palindrome is implicated in the DNA recognition by the metalloregulator. In conclusion, we report here that MtsR is a global regulator in GAS that shapes the expression of vital virulence factors and genes involved in metabolic functions and metal transport, and we discuss the implications for the GAS disease process.

  6. Mechanism of action of nalidixic acid: Purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme

    PubMed Central

    Sugino, Akio; Peebles, Craig L.; Kreuzer, Kenneth N.; Cozzarelli, Nicholas R.

    1977-01-01

    A target protein for nalidixic and oxolinic acids in Escherichia coli, the nalA gene product (Pnal), was purified to homogeneity as judged by gel electrophoresis, using an in vitro complementation assay. It is a dimer of identical 110,000-dalton subunits. A polypeptide of this molecular weight is uniquely induced by a λ nalA transducing phage, thereby showing that the purified Pnal is a product of the nalA gene. Nalidixic and oxolinic acids inhibit DNA gyrase activity and induce formation of a relaxation complex analogue. Treatment of the complex with sodium dodecyl sulfate causes a doublestrand break in the DNA substrate and the resulting linear molecule seems covalently bound to protein. Complex formation, unlike the introduction of supertwists, does not require ATP or relaxed circular DNA and is insensitive to novobiocin. DNA gyrase from a strain with a nalA mutation conferring drug resistance (nalAr) is 1/100 as sensitive to oxolinic and nalidixic acids with respect to inhibition of supertwisting and induction of the pre-linearization complex. Addition of Pnal restores drug sensitivity and stimulates DNA gyrase activity. DNA gyrase preparations and Pnal catalyze a third reaction sensitive to nalidixic and oxolinic acids, the ATP-independent relaxation of supertwister DNA. Relaxation by gyrase from nalAr cells is drug resistant. The nicking-closing activity is distinct from E. coli ω protein in several properties, including the ability to relax positively supertwisted DNA. We postulate that the nalA gene product occurs in two molecular forms, as Pnal and as a gyrase component. Both forms catalyze nicking-closing, and inhibition of this activity by nalidixic and oxolinic acids may account for the inhibition of DNA synthesis by these drugs. Images PMID:200930

  7. Phosphazene additives

    DOEpatents

    Harrup, Mason K; Rollins, Harry W

    2013-11-26

    An additive comprising a phosphazene compound that has at least two reactive functional groups and at least one capping functional group bonded to phosphorus atoms of the phosphazene compound. One of the at least two reactive functional groups is configured to react with cellulose and the other of the at least two reactive functional groups is configured to react with a resin, such as an amine resin of a polycarboxylic acid resin. The at least one capping functional group is selected from the group consisting of a short chain ether group, an alkoxy group, or an aryloxy group. Also disclosed are an additive-resin admixture, a method of treating a wood product, and a wood product.

  8. Potlining Additives

    SciTech Connect

    Rudolf Keller

    2004-08-10

    In this project, a concept to improve the performance of aluminum production cells by introducing potlining additives was examined and tested. Boron oxide was added to cathode blocks, and titanium was dissolved in the metal pool; this resulted in the formation of titanium diboride and caused the molten aluminum to wet the carbonaceous cathode surface. Such wetting reportedly leads to operational improvements and extended cell life. In addition, boron oxide suppresses cyanide formation. This final report presents and discusses the results of this project. Substantial economic benefits for the practical implementation of the technology are projected, especially for modern cells with graphitized blocks. For example, with an energy savings of about 5% and an increase in pot life from 1500 to 2500 days, a cost savings of $ 0.023 per pound of aluminum produced is projected for a 200 kA pot.

  9. Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: The additive and subtractive effect of the three dopaminergic genes - DRD2, D{beta}H, and DAT1

    SciTech Connect

    Comings, D.E.; Wu, S.; Chiu, C.; Ring, R.H.; Gade, R.; Ahn, C.; Dietz, G.; Muhleman, D.

    1996-05-31

    Polymorphisms of three different dopaminergic genes, dopamine D{sub 2} receptor (DRD2), dopamine {beta}-hydroxylase (D{beta}H), and dopamine transporter (DAT1), were examined in Tourette syndrome (TS) probands, their relatives, and controls. Each gene individually showed a significant correlation with various behavioral variables in these subjects. The additive and subtractive effects of the three genes were examined by genotyping all three genes in the same set of subjects. For 9 of 20 TS associated comorbid behaviors there was a significant linear association between the degree of loading for markers of three genes and the mean behavior scores. The behavior variables showing the significant associations were, in order, attention deficit hyperactivity disorder (ADHD), stuttering, oppositional defiant, tics, conduct, obsessive-compulsive, mania, alcohol abuse, and general anxiety - behaviors that constitute the most overt clinical aspects of TS. For 16 of the 20 behavior scores there was a linear progressive decrease in the mean score with progressively lesser loading for the three gene markers. These results suggest that TS, ADHD, stuttering, oppositional defiant and conduct disorder, and other behaviors associated with TS, are polygenic, due in part to these three dopaminergic genes, and that the genetics of other polygenic psychiatric disorders may be deciphered using this technique. 144 refs., 2 figs., 13 tabs.

  10. Simvastatin and Dipentyl Phthalate Lower Ex vivo Testicular Testosterone Production and Exhibit Additive Effects on Testicular Testosterone and Gene Expression Via Distinct Mechanistic Pathways in the Fetal Rat

    EPA Science Inventory

    Sex differentiation of the male reproductive tract in mammals is driven, in part, by fetal androgen production. In utero, some phthalate esters (PEs) alter fetal Leydig cell differentiation, reducing the expression of several genes associated with steroid synthesis/transport, and...

  11. Association Between Single-Nucleotide Polymorphisms in Hormone Metabolism and DNA Repair Genes and Epithelial Ovarian Cancer: Results from Two Australian Studies and an Additional Validation Set

    PubMed Central

    Beesley, Jonathan; Jordan, Susan J.; Spurdle, Amanda B.; Song, Honglin; Ramus, Susan J.; Kjaer, Suzanne Kruger; Hogdall, Estrid; DiCioccio, Richard A.; McGuire, Valerie; Whittemore, Alice S.; Gayther, Simon A.; Pharoah, Paul D.P.; Webb, Penelope M.; Chenevix-Trench, Georgia

    2009-01-01

    Although some high-risk ovarian cancer genes have been identified, it is likely that common low penetrance alleles exist that confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP) in genes involved in steroid hormone synthesis (SRD5A2, CYP19A1, HSB17B1, and HSD17B4) and DNA repair (XRCC2, XRCC3, BRCA2, and RAD52) using two Australian ovarian cancer case-control studies, comprising a total of 1,466 cases and 1,821 controls of Caucasian origin. Genotype frequencies in cases and controls were compared using logistic regression. The only SNP we found to be associated with ovarian cancer risk in both of these two studies was SRD5A2 V89L (rs523349), which showed a significant trend of increasing risk per rare allele (P = 0.00002). We then genotyped another SNP in this gene (rs632148; r2 = 0.945 with V89L) in an attempt to validate this finding in an independent set of 1,479 cases and 2,452 controls from United Kingdom, United States, and Denmark. There was no association between rs632148 and ovarian cancer risk in the validation samples, and overall, there was no significant heterogeneity between the results of the five studies. Further analyses of SNPs in this gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition. PMID:18086758

  12. Characterization of Three mnp Genes of Fomitiporia mediterranea and Report of Additional Class II Peroxidases in the Order Hymenochaetales ▿ †

    PubMed Central

    Morgenstern, Ingo; Robertson, Deborah L.; Hibbett, David S.

    2010-01-01

    We report the sequence-based characterization and expression patterns of three manganese peroxidase genes from the white rot fungus and grape vine pathogen Fomitiporia mediterranea (Agaricomycotina, Hymenochaetales), termed Fmmnp1, Fmmnp2, and Fmmnp3. The predicted open reading frames (ORFs) are 1,516-, 1,351-, and 1,345-bp long and are interrupted by seven, four, and four introns, respectively. The deduced amino acid sequences encode manganese peroxidases (EC 1.11.1.13) containing 371, 369, and 371 residues, respectively, and are similar to the manganese peroxidases of the model white rot organism Phanerochaete chrysosporium. The expression of the genes is most likely differentially regulated, as revealed by real-time PCR analysis. Phylogenetic analysis reveals that other members of the order Hymenochaetales harbor mnp genes encoding proteins that are related only distantly to those of F. mediterranea. Furthermore, multiple partial lip- and mnp-like sequences obtained for Pycnoporus cinnabarinus (Agaricomycotina, Polyporales) suggest that lignin degradation by white rot taxa relies heavily on ligninolytic peroxidases and is not efficiently achieved by laccases only. PMID:20675443

  13. Action physics

    NASA Astrophysics Data System (ADS)

    McGinness, Lachlan P.; Savage, C. M.

    2016-09-01

    More than a decade ago, Edwin Taylor issued a "call to action" that presented the case for basing introductory university mechanics teaching around the principle of stationary action [E. F. Taylor, Am. J. Phys. 71, 423-425 (2003)]. We report on our response to that call in the form of an investigation of the teaching and learning of the stationary action formulation of physics in a first-year university course. Our action physics instruction proceeded from the many-paths approach to quantum physics to ray optics, classical mechanics, and relativity. Despite the challenges presented by action physics, students reported it to be accessible, interesting, motivational, and valuable.

  14. Direct comparison between genomic constitution and flavonoid contents in Allium multiple alien addition lines reveals chromosomal locations of genes related to biosynthesis from dihydrokaempferol to quercetin glucosides in scaly leaf of shallot (Allium cepa L.).

    PubMed

    Masuzaki, S; Shigyo, M; Yamauchi, N

    2006-02-01

    The extrachromosome 5A of shallot (Allium cepa L., genomes AA) has an important role in flavonoid biosynthesis in the scaly leaf of Allium fistulosum-shallot monosomic addition lines (FF+nA). This study deals with the production and biochemical characterisation of A. fistulosum-shallot multiple alien addition lines carrying at least 5A to determine the chromosomal locations of genes for quercetin formation. The multiple alien additions were selected from the crossing between allotriploid FFA (female symbol) and A. fistulosum (male symbol). The 113 plants obtained from this cross were analysed by a chromosome 5A-specific PGI isozyme marker of shallot. Thirty plants were preliminarily selected for an alien addition carrying 5A. The chromosome numbers of the 30 plants varied from 18 to 23. The other extrachromosomes in 19 plants were completely identified by using seven other chromosome markers of shallot. High-performance liquid chromatography analyses of the 19 multiple additions were conducted to identify the flavonoid compounds produced in the scaly leaves. Direct comparisons between the chromosomal constitution and the flavonoid contents of the multiple alien additions revealed that a flavonoid 3'-hydroxylase (F3'H) gene for the synthesis of quercetin from kaempferol was located on 7A and that an anonymous gene involved in the glucosidation of quercetin was on 3A or 4A. As a result of supplemental SCAR analyses by using genomic DNAs from two complete sets of A. fistulosum-shallot monosomic additions, we have assigned F3'H to 7A and flavonol synthase to 4A.

  15. Direct comparison between genomic constitution and flavonoid contents in Allium multiple alien addition lines reveals chromosomal locations of genes related to biosynthesis from dihydrokaempferol to quercetin glucosides in scaly leaf of shallot (Allium cepa L.).

    PubMed

    Masuzaki, S; Shigyo, M; Yamauchi, N

    2006-02-01

    The extrachromosome 5A of shallot (Allium cepa L., genomes AA) has an important role in flavonoid biosynthesis in the scaly leaf of Allium fistulosum-shallot monosomic addition lines (FF+nA). This study deals with the production and biochemical characterisation of A. fistulosum-shallot multiple alien addition lines carrying at least 5A to determine the chromosomal locations of genes for quercetin formation. The multiple alien additions were selected from the crossing between allotriploid FFA (female symbol) and A. fistulosum (male symbol). The 113 plants obtained from this cross were analysed by a chromosome 5A-specific PGI isozyme marker of shallot. Thirty plants were preliminarily selected for an alien addition carrying 5A. The chromosome numbers of the 30 plants varied from 18 to 23. The other extrachromosomes in 19 plants were completely identified by using seven other chromosome markers of shallot. High-performance liquid chromatography analyses of the 19 multiple additions were conducted to identify the flavonoid compounds produced in the scaly leaves. Direct comparisons between the chromosomal constitution and the flavonoid contents of the multiple alien additions revealed that a flavonoid 3'-hydroxylase (F3'H) gene for the synthesis of quercetin from kaempferol was located on 7A and that an anonymous gene involved in the glucosidation of quercetin was on 3A or 4A. As a result of supplemental SCAR analyses by using genomic DNAs from two complete sets of A. fistulosum-shallot monosomic additions, we have assigned F3'H to 7A and flavonol synthase to 4A. PMID:16411131

  16. Massively parallel sequencing of phyllodes tumours of the breast reveals actionable mutations, and TERT promoter hotspot mutations and TERT gene amplification as likely drivers of progression.

    PubMed

    Piscuoglio, Salvatore; Ng, Charlotte Ky; Murray, Melissa; Burke, Kathleen A; Edelweiss, Marcia; Geyer, Felipe C; Macedo, Gabriel S; Inagaki, Akiko; Papanastasiou, Anastasios D; Martelotto, Luciano G; Marchio, Caterina; Lim, Raymond S; Ioris, Rafael A; Nahar, Pooja K; Bruijn, Ino De; Smyth, Lillian; Akram, Muzaffar; Ross, Dara; Petrini, John H; Norton, Larry; Solit, David B; Baselga, Jose; Brogi, Edi; Ladanyi, Marc; Weigelt, Britta; Reis-Filho, Jorge S

    2016-03-01

    Phyllodes tumours (PTs) are breast fibroepithelial lesions that are graded based on histological criteria as benign, borderline or malignant. PTs may recur locally. Borderline PTs and malignant PTs may metastasize to distant sites. Breast fibroepithelial lesions, including PTs and fibroadenomas, are characterized by recurrent MED12 exon 2 somatic mutations. We sought to define the repertoire of somatic genetic alterations in PTs and whether these may assist in the differential diagnosis of these lesions. We collected 100 fibroadenomas, 40 benign PTs, 14 borderline PTs and 22 malignant PTs; six, six and 13 benign, borderline and malignant PTs, respectively, and their matched normal tissue, were subjected to targeted massively parallel sequencing (MPS) using the MSK-IMPACT sequencing assay. Recurrent MED12 mutations were found in 56% of PTs; in addition, mutations affecting cancer genes (eg TP53, RB1, SETD2 and EGFR) were exclusively detected in borderline and malignant PTs. We found a novel recurrent clonal hotspot mutation in the TERT promoter (-124 C>T) in 52% and TERT gene amplification in 4% of PTs. Laser capture microdissection revealed that these mutations were restricted to the mesenchymal component of PTs. Sequencing analysis of the entire cohort revealed that the frequency of TERT alterations increased from benign (18%) to borderline (57%) and to malignant PTs (68%; p < 0.01), and TERT alterations were associated with increased levels of TERT mRNA (p < 0.001). No TERT alterations were observed in fibroadenomas. An analysis of TERT promoter sequencing and gene amplification distinguished PTs from fibroadenomas with a sensitivity and a positive predictive value of 100% (CI 95.38-100%) and 100% (CI 85.86-100%), respectively, and a sensitivity and a negative predictive value of 39% (CI 28.65-51.36%) and 68% (CI 60.21-75.78%), respectively. Our results suggest that TERT alterations may drive the progression of PTs, and may assist in the differential diagnosis

  17. Massively parallel sequencing of phyllodes tumours of the breast reveals actionable mutations, and TERT promoter hotspot mutations and TERT gene amplification as likely drivers of progression.

    PubMed

    Piscuoglio, Salvatore; Ng, Charlotte Ky; Murray, Melissa; Burke, Kathleen A; Edelweiss, Marcia; Geyer, Felipe C; Macedo, Gabriel S; Inagaki, Akiko; Papanastasiou, Anastasios D; Martelotto, Luciano G; Marchio, Caterina; Lim, Raymond S; Ioris, Rafael A; Nahar, Pooja K; Bruijn, Ino De; Smyth, Lillian; Akram, Muzaffar; Ross, Dara; Petrini, John H; Norton, Larry; Solit, David B; Baselga, Jose; Brogi, Edi; Ladanyi, Marc; Weigelt, Britta; Reis-Filho, Jorge S

    2016-03-01

    Phyllodes tumours (PTs) are breast fibroepithelial lesions that are graded based on histological criteria as benign, borderline or malignant. PTs may recur locally. Borderline PTs and malignant PTs may metastasize to distant sites. Breast fibroepithelial lesions, including PTs and fibroadenomas, are characterized by recurrent MED12 exon 2 somatic mutations. We sought to define the repertoire of somatic genetic alterations in PTs and whether these may assist in the differential diagnosis of these lesions. We collected 100 fibroadenomas, 40 benign PTs, 14 borderline PTs and 22 malignant PTs; six, six and 13 benign, borderline and malignant PTs, respectively, and their matched normal tissue, were subjected to targeted massively parallel sequencing (MPS) using the MSK-IMPACT sequencing assay. Recurrent MED12 mutations were found in 56% of PTs; in addition, mutations affecting cancer genes (eg TP53, RB1, SETD2 and EGFR) were exclusively detected in borderline and malignant PTs. We found a novel recurrent clonal hotspot mutation in the TERT promoter (-124 C>T) in 52% and TERT gene amplification in 4% of PTs. Laser capture microdissection revealed that these mutations were restricted to the mesenchymal component of PTs. Sequencing analysis of the entire cohort revealed that the frequency of TERT alterations increased from benign (18%) to borderline (57%) and to malignant PTs (68%; p < 0.01), and TERT alterations were associated with increased levels of TERT mRNA (p < 0.001). No TERT alterations were observed in fibroadenomas. An analysis of TERT promoter sequencing and gene amplification distinguished PTs from fibroadenomas with a sensitivity and a positive predictive value of 100% (CI 95.38-100%) and 100% (CI 85.86-100%), respectively, and a sensitivity and a negative predictive value of 39% (CI 28.65-51.36%) and 68% (CI 60.21-75.78%), respectively. Our results suggest that TERT alterations may drive the progression of PTs, and may assist in the differential diagnosis

  18. Long-term nutrient addition differentially alters community composition and diversity of genes that control nitrous oxide flux from salt marsh sediments

    NASA Astrophysics Data System (ADS)

    Kearns, Patrick J.; Angell, John H.; Feinman, Sarah G.; Bowen, Jennifer L.

    2015-03-01

    Enrichment of natural waters, soils, and sediments by inorganic nutrients, including nitrogen, is occurring at an increasing rate and has fundamentally altered global biogeochemical cycles. Salt marshes are critical for the removal of land-derived nitrogen before it enters coastal waters. This is accomplished via multiple microbially mediated pathways, including denitrification. Many of these pathways, however, are also a source of the greenhouse gas nitrous oxide (N2O). We used clone libraries and quantative PCR (qPCR) to examine the effect of fertilization on the diversity and abundance of two functional genes associated with denitrification and N2O production (norB and nosZ) in experimental plots at the Great Sippewissett Salt Marsh (Falmouth, MA, USA) that have been enriched with nutrients for over 40 years. Our data showed distinct nosZ and norB community structures at different nitrogen loads, especially at the highest level of fertilization. Furthermore, calculations of the Shannon Diversity Index and Chao1 Richness Estimator indicated that nosZ gene diversity and richness increased with increased nitrogen supply, however no such relationship existed with regard to richness and diversity of the norB gene. Results from qPCR demonstrated that nosZ gene abundance was an order of magnitude lower in the extra-highly fertilized plots compared to the other plots, but the abundance of norB was not affected by fertilization. The majority of sequences obtained from the marsh plots had no close cultured relatives and they were divergent from previously sequenced norB and nosZ fragments. Despite their divergence from any cultured representatives, most of the norB and nosZ sequences appeared to be from members of the Alpha- and Betaproteobacteria, suggesting that these classes are particularly important in salt marsh nitrogen cycling. Our results suggest that both norB and nosZ containing microbes are affected by fertilization and that the Great Sippewissett Marsh may

  19. Development of a novel Sinapis arvensis disomic addition line in Brassica napus containing the restorer gene for Nsa CMS and improved resistance to Sclerotinia sclerotiorum and pod shattering.

    PubMed

    Wei, Wenhui; Li, Yunchang; Wang, Lijun; Liu, Shengyi; Yan, Xiaohong; Mei, Desheng; Li, Yinde; Xu, Yusong; Peng, Pengfei; Hu, Qiong

    2010-04-01

    An allo-cytoplasmic male sterile line, which was developed through somatic hybridization between Brassica napus and Sinapis arvensis (thus designated as Nsa CMS line), possesses high potential for hybrid production of rapeseed. In order to select for restorer lines, fertile plants derived from the same somatic hybridization combination were self-pollinated and testcrossed with the parental Nsa CMS line for six generations. A novel disomic alien addition line, B. napus-S. arvensis, has been successfully developed. GISH analysis showed that it contains one pair of chromosomes from S. arvensis and 19 pairs from B. napus, and retains stable and regular mitotic and meiotic processes. The addition line displays very strong restoration ability to Nsa CMS line, high resistance to Sclerotinia sclerotiorum and a low incidence of pod shattering. Because the addition line shares these very important agricultural characters, it is a valuable restorer to Nsa CMS line, and is named NR1 here (Nsa restorer no. 1).

  20. Generation of a recombinant rabies Flury LEP virus carrying an additional G gene creates an improved seed virus for inactivated vaccine production.

    PubMed

    Tao, Lihong; Ge, Jinying; Wang, Xijun; Wen, Zhiyuan; Zhai, Hongyue; Hua, Tao; Zhao, Bolin; Kong, Dongni; Yang, Chinglai; Bu, Zhigao

    2011-01-01

    The rabies Flury Low Egg Passage virus (LEP) has been widely used as a seed virus to generate inactive vaccine. Here, we established a reverse genetic system for LEP and generated a recombinant LEP virus (rLEP-G) that carries two identical G genes. This recombinant virus showed similar properties to those of LEP with respect to in vitro growth, neurotropism index, and virulence in mice. rLEP-G produced 4.3-fold more G protein than did LEP in BHK-21 cells. The inactivated vaccine generated from rLEP-G induced significantly higher virus neutralization titers in mice and dogs than those produced in response to LEP-derived vaccine. Our results suggest that rLEP-G is an improved seed virus candidate for inactivated rabies virus vaccine manufacture.

  1. hebp3, a novel member of the heme-binding protein gene family, is expressed in the medaka meninges with higher abundance in females due to a direct stimulating action of ovarian estrogens.

    PubMed

    Nakasone, Kiyoshi; Nagahama, Yoshitaka; Okubo, Kataaki

    2013-02-01

    The brains of teleost fish exhibit remarkable sexual plasticity throughout their life span. To dissect the molecular basis for the development and reversal of sex differences in the teleost brain, we screened for genes differentially expressed between sexes in the brain of medaka (Oryzias latipes). One of the genes identified in the screen as being preferentially expressed in females was found to be a new member of the heme-binding protein gene family that includes hebp1 and hebp2 and was designated here as hebp3. The medaka hebp3 is expressed in the meninges with higher abundance in females, whereas there is no expression within the brain parenchyma. This female-biased expression of hebp3 is not attributable to the direct action of sex chromosome genes but results from the transient and reversible action of estrogens derived from the ovary. Moreover, estrogens directly activate the transcription of hebp3 via a palindromic estrogen-responsive element in the hebp3 promoter. Taken together, our findings demonstrate that hebp3 is a novel transcriptional target of estrogens, with female-biased expression in the meninges. The definite but reversible sexual dimorphism of the meningeal hebp3 expression may contribute to the development and reversal of sex differences in the teleost brain.

  2. Effects of Addition of Linseed and Marine Algae to the Diet on Adipose Tissue Development, Fatty Acid Profile, Lipogenic Gene Expression, and Meat Quality in Lambs.

    PubMed

    Urrutia, Olaia; Mendizabal, José Antonio; Insausti, Kizkitza; Soret, Beatriz; Purroy, Antonio; Arana, Ana

    2016-01-01

    This study examined the effect of linseed and algae on growth and carcass parameters, adipocyte cellularity, fatty acid profile and meat quality and gene expression in subcutaneous and intramuscular adipose tissues (AT) in lambs. After weaning, 33 lambs were fed three diets up to 26.7 ± 0.3 kg: Control diet (barley and soybean); L diet (barley, soybean and 10% linseed) and L-A diet (barley, soybean, 5% linseed and 3.89% algae). Lambs fed L-A diet showed lower average daily gain and greater slaughter age compared to Control and L (P < 0.001). Carcass traits were not affected by L and L-A diets, but a trend towards greater adipocyte diameter was observed in L and L-A in the subcutaneous AT (P = 0.057). Adding either linseed or linseed and algae increased α-linolenic acid and eicosapentaenoic acid contents in both AT (P < 0.001); however, docosahexaenoic acid was increased by L-A (P < 0.001). The n-6/n-3 ratio decreased in L and L-A (P < 0.001). Algae had adverse effects on meat quality, with greater lipid oxidation and reduced ratings for odor and flavor. The expression of lipogenic genes was downregulated in the subcutaneous AT (P < 0.05): acetyl-CoA carboxylase 1 (ACACA) in L and L-A and lipoprotein lipase (LPL) and stearoyl-CoA desaturase (SCD) in L-A. Fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2) and fatty acid elongase 5 (ELOVL5) were unaffected. In the subcutaneous AT, supplementing either L or L-A increased peroxisome proliferator-activated receptor gamma (PPARG) and CAAT-enhancer binding protein alpha (CEBPA) (P < 0.05), although it had no effect on sterol regulatory element-binding factor 1 (SREBF1). In the intramuscular AT, expression of ACACA, SCD, FADS1 and FADS2 decreased in L and L-A (P < 0.001) and LPL in L (P < 0.01), but PPARG, CEBPA and SREBF1 were unaffected. PMID:27253325

  3. Effects of Addition of Linseed and Marine Algae to the Diet on Adipose Tissue Development, Fatty Acid Profile, Lipogenic Gene Expression, and Meat Quality in Lambs

    PubMed Central

    Urrutia, Olaia; Mendizabal, José Antonio; Insausti, Kizkitza; Soret, Beatriz; Purroy, Antonio; Arana, Ana

    2016-01-01

    This study examined the effect of linseed and algae on growth and carcass parameters, adipocyte cellularity, fatty acid profile and meat quality and gene expression in subcutaneous and intramuscular adipose tissues (AT) in lambs. After weaning, 33 lambs were fed three diets up to 26.7 ± 0.3 kg: Control diet (barley and soybean); L diet (barley, soybean and 10% linseed) and L-A diet (barley, soybean, 5% linseed and 3.89% algae). Lambs fed L-A diet showed lower average daily gain and greater slaughter age compared to Control and L (P < 0.001). Carcass traits were not affected by L and L-A diets, but a trend towards greater adipocyte diameter was observed in L and L-A in the subcutaneous AT (P = 0.057). Adding either linseed or linseed and algae increased α-linolenic acid and eicosapentaenoic acid contents in both AT (P < 0.001); however, docosahexaenoic acid was increased by L-A (P < 0.001). The n-6/n-3 ratio decreased in L and L-A (P < 0.001). Algae had adverse effects on meat quality, with greater lipid oxidation and reduced ratings for odor and flavor. The expression of lipogenic genes was downregulated in the subcutaneous AT (P < 0.05): acetyl-CoA carboxylase 1 (ACACA) in L and L-A and lipoprotein lipase (LPL) and stearoyl-CoA desaturase (SCD) in L-A. Fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2) and fatty acid elongase 5 (ELOVL5) were unaffected. In the subcutaneous AT, supplementing either L or L-A increased peroxisome proliferator-activated receptor gamma (PPARG) and CAAT-enhancer binding protein alpha (CEBPA) (P < 0.05), although it had no effect on sterol regulatory element-binding factor 1 (SREBF1). In the intramuscular AT, expression of ACACA, SCD, FADS1 and FADS2 decreased in L and L-A (P < 0.001) and LPL in L (P < 0.01), but PPARG, CEBPA and SREBF1 were unaffected. PMID:27253325

  4. Targeted Gene Addition to a Safe Harbor locus in human CD34+ Hematopoietic Stem Cells for Correction of X-linked Chronic Granulomatous Disease

    PubMed Central

    De Ravin, Suk See; Reik, Andreas; Liu, Pei-Qi; Li, Linhong; Wu, Xiaolin; Su, Ling; Raley, Castle; Theobald, Narda; Choi, Uimook; Song, Alexander H.; Chan, Andy; Pearl, Jocelynn R.; Paschon, David E.; Lee, Janet; Newcombe, Hannah; Koontz, Sherry; Sweeney, Colin; Shivak, David A.; Zarember, Kol A.; Peshwa, Madhusudan V.; Gregory, Philip D.; Urnov, Fyodor D.; Malech, Harry L.

    2016-01-01

    Gene therapy with genetically modified human CD34+ hematopoietic stem cells (HSCs) may be safer using targeted integration (TI) of transgenes into a genomic ‘safe harbor’ site than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno associated virus (AAV) 6 delivery of donor constructs in human HSCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus-positive HSCs with 6–16% human cell marking were observed following engraftment into mice. In HSCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 in resulted in ~15% gp91phox expression and increased NADPH oxidase activity in ex vivo–derived neutrophils. In mice transplanted with corrected HSCs, 4–11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases. PMID:26950749

  5. Replication of a gene-environment interaction Via Multimodel inference: additive-genetic variance in adolescents' general cognitive ability increases with family-of-origin socioeconomic status.

    PubMed

    Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

    2015-03-01

    The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES-an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research. PMID:25539975

  6. Replication of a Gene-Environment Interaction via Multimodel Inference: Additive-Genetic Variance in Adolescents’ General Cognitive Ability Increases with Family-of-Origin Socioeconomic Status

    PubMed Central

    Kirkpatrick, Robert M.; McGue, Matt; Iacono, William G.

    2015-01-01

    The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES—an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research. PMID:25539975

  7. Replication of a gene-environment interaction Via Multimodel inference: additive-genetic variance in adolescents' general cognitive ability increases with family-of-origin socioeconomic status.

    PubMed

    Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

    2015-03-01

    The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES-an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research.

  8. Action Learning.

    ERIC Educational Resources Information Center

    1996

    These four papers were presented at a symposium on action learning moderated by Lex Dilworth at the 1996 conference of the Academy of Human Resource Development. "Developing an Infrastructure for Individual and Organizational Change: Transfer of Learning from an Action Reflection Learning (ARL) Program" (ARL Inquiry) reports findings from a study…

  9. Non-additive hepatic gene expression elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) co-treatment in C57BL/6 mice

    SciTech Connect

    Kopec, Anna K.; D'Souza, Michelle L.; Mets, Bryan D.; Burgoon, Lyle D.; Reese, Sarah E.; Archer, Kellie J.; Potter, Dave; Tashiro, Colleen; Sharratt, Bonnie; Harkema, Jack R.; Zacharewski, Timothy R.

    2011-10-15

    Interactions between environmental contaminants can lead to non-additive effects that may affect the toxicity and risk assessment of a mixture. Comprehensive time course and dose-response studies with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), non-dioxin-like 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) and their mixture were performed in immature, ovariectomized C57BL/6 mice. Mice were gavaged once with 30 {mu}g/kg TCDD, 300 mg/kg PCB153, a mixture of 30 {mu}g/kg TCDD with 300 mg/kg PCB153 (MIX) or sesame oil vehicle for 4,12, 24,72 or 168 h. In the 24 h dose-response study, animals were gavaged with TCDD (0.3,1, 3, 6, 10, 15, 30, 45 {mu}g/kg), PCB153 (3,10, 30, 60, 100, 150, 300, 450 mg/kg), MIX (0.3 + 3, 1 + 10, 3 + 30, 6 + 60, 10 + 100, 15 + 150, 30 + 300, 45 {mu}g/kg TCDD + 450 mg/kg PCB153, respectively) or vehicle. All three treatments significantly increased relative liver weights (RLW), with MIX eliciting significantly greater increases compared to TCDD and PCB153 alone. Histologically, MIX induced hepatocellular hypertrophy, vacuolization, inflammation, hyperplasia and necrosis, a combination of TCDD and PCB153 responses. Complementary lipid analyses identified significant increases in hepatic triglycerides in MIX and TCDD samples, while PCB153 had no effect on lipids. Hepatic PCB153 levels were also significantly increased with TCDD co-treatment. Microarray analysis identified 167 TCDD, 185 PCB153 and 388 MIX unique differentially expressed genes. Statistical modeling of quantitative real-time PCR analysis of Pla2g12a, Serpinb6a, Nqo1, Srxn1, and Dysf verified non-additive expression following MIX treatment compared to TCDD and PCB153 alone. In summary, TCDD and PCB153 co-treatment elicited specific non-additive gene expression effects that are consistent with RLW increases, histopathology, and hepatic lipid accumulation. - Graphical abstract: Display Omitted Highlights: > MIX (TCDD:PCB153 at 1:10,000 ratio) exposure leads to non-additive gene expression

  10. Identification, mapping, cloning and characterization of a gene (sbmA) required for microcin B17 action on Escherichia coli K12.

    PubMed

    Laviña, M; Pugsley, A P; Moreno, F

    1986-06-01

    We have identified mutations in three different chromosomal genes of Escherichia coli K12 which reduce sensitivity to microcin B17. Mutations in ompF and ompR genes affected production of an outer membrane porin protein, OmpF, and resulted in reduced sensitivity to a number of other agents (colicins, bacteriophages) besides microcin B17. The third class of mutants were specifically and highly resistant to microcin B17. The mutations in these strains were mapped to a gene (sbmA), located at 8.7 min on the E. coli K12 chromosome, which is closely linked to phoA. The wild-type sbmA allele was cloned into multiple copy number plasmids, and its location within the cloned DNA fragment was further defined by mutagenesis with MiniMudII1681. These insertion mutations resulted in in-frame fusions between the sbmA and lacZ genes, thereby allowing us to determine the direction of sbmA gene transcription. Plasmids carrying these gene fusions produced low levels of beta-galactosidase, indicating that the sbmA gene is poorly expressed. We have been unable to identify the sbmA gene product, but indirect evidence indicates that it might be an envelope protein involved in microcin uptake.

  11. Gene delivery using calcium phosphate nanoparticles: Optimization of the transfection process and the effects of citrate and poly(l-lysine) as additives.

    PubMed

    Khan, Mohammed A; Wu, Victoria M; Ghosh, Shreya; Uskoković, Vuk

    2016-06-01

    Despite the long history of nanoparticulate calcium phosphate (CaP) as a non-viral transfection agent, there has been limited success in attempts to optimize its properties for transfection comparable in efficiency to that of viral vectors. Here we focus on the optimization of: (a) CaP nanoparticle precipitation conditions, predominantly supersaturation and Ca/P molar ratios; (b) transfection conditions, mainly the concentrations of the carrier and plasmid DNA; (c) the presence of surface additives, including citrate anion and cationic poly(l-lysine) (PLL). CaP nanoparticles significantly improved transfection with plasmid DNA encoding enhanced green fluorescent protein (eGFP) in pre-osteoblastic MC3T3-E1 cells compared to a commercial non-viral carrier. At the same time they elicited significantly lesser cytotoxicity than the commercial carrier. Plasmid DNA acted as a nucleation promoter, decreasing the nucleation lag time of metastable CaP solutions and leading to a higher rate of nucleation and a lower size of the precipitated particles. The degree of supersaturation (DS) of 15 was found to be more optimal for transfection than that of 12.5 or 17.5 and higher. Because CaP particles precipitated at DS 15 were spherical, while DS 17.5 and 21 yielded acicular particles, it was concluded that spherical particle morphologies were more conducive to transfection than the anisotropic ones. Even though the yield at DS 15 was 10 and 100 times lower than that at DS 17.5 and 21, respectively, transfection rates were higher using CaP nanoparticle colloids prepared at DS 15 than using those made at higher or lower DS, indicating that the right particle morphology can outweigh the difference in the amount of the carrier, even when this difference is close to 100×. In contrast to the commercial carrier, the concentration of CaP-pDNA delivered to the cells was directly proportional to the transfection rate. Osteosarcoma K7M2 cells were four times more easily transfectable with

  12. Genome‐scale analysis of the cotton KCS gene family revealed a binary mode of action for gibberellin A regulated fiber growth

    PubMed Central

    Xiao, Guang‐Hui; Wang, Kun; Huang, Gai

    2015-01-01

    Abstract Production of β‐ketoacyl‐CoA, which is catalyzed by 3‐ketoacyl‐CoA synthase (KCS), is the first step in very long chain fatty acid (VLCFA) biosynthesis. Here we identified 58 KCS genes from Gossypium hirsutum, 31 from G. arboreum and 33 from G. raimondii by searching the assembled cotton genomes. The gene family was divided into the plant‐specific FAE1‐type and the more general ELO‐type. KCS transcripts were widely expressed and 32 of them showed distinct subgenome‐specific expressions in one or more cotton tissues/organs studied. Six GhKCS genes rescued the lethality of elo2Δelo3Δ yeast double mutant, indicating that this gene family possesses diversified functions. Most KCS genes with GA‐responsive elements (GAREs) in the promoters were significantly upregulated by gibberellin A3 (GA). Exogenous GA3 not only promoted fiber length, but also increased the thickness of cell walls significantly. GAREs present also in the promoters of several cellulose synthase (CesA) genes required for cell wall biosynthesis and they were all induced significantly by GA3. Because GA treatment resulted in longer cotton fibers with thicker cell walls and higher dry weight per unit cell length, we suggest that it may regulate fiber elongation upstream of the VLCFA‐ethylene pathway and also in the downstream steps towards cell wall synthesis. PMID:26399709

  13. 77 FR 62220 - Procurement List; Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-12

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to the Procurement List. SUMMARY: This action adds products and services to the Procurement List that will be furnished by nonprofit...

  14. 77 FR 37659 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-22

    ... interested persons an opportunity to submit comments on the proposed actions. Revision On 5/25/2012 (77 FR... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions AGENCY: Committee for Purchase From People Who are Blind or Severely Disabled. ACTION: Proposed additions to the procurement...

  15. 76 FR 40341 - Procurement List; Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-08

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to the Procurement List. SUMMARY: This action adds products and services to the Procurement List that will be furnished by nonprofit...

  16. 78 FR 23542 - Procurement List Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-19

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to the Procurement List. SUMMARY: This action adds products and services to the Procurement List that will be furnished by nonprofit...

  17. 77 FR 77037 - Procurement List; Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-31

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to the Procurement List. SUMMARY: This action adds products and services to the Procurement List that will be furnished by nonprofit...

  18. Analysis of Five Gene Sets in Chimpanzees Suggests Decoupling between the Action of Selection on Protein-Coding and on Noncoding Elements

    PubMed Central

    Santpere, Gabriel; Carnero-Montoro, Elena; Petit, Natalia; Serra, François; Hvilsom, Christina; Rambla, Jordi; Heredia-Genestar, Jose Maria; Halligan, Daniel L.; Dopazo, Hernan; Navarro, Arcadi; Bosch, Elena

    2015-01-01

    We set out to investigate potential differences and similarities between the selective forces acting upon the coding and noncoding regions of five different sets of genes defined according to functional and evolutionary criteria: 1) two reference gene sets presenting accelerated and slow rates of protein evolution (the Complement and Actin pathways); 2) a set of genes with evidence of accelerated evolution in at least one of their introns; and 3) two gene sets related to neurological function (Parkinson’s and Alzheimer’s diseases). To that effect, we combine human–chimpanzee divergence patterns with polymorphism data obtained from target resequencing 20 central chimpanzees, our closest relatives with largest long-term effective population size. By using the distribution of fitness effect-alpha extension of the McDonald–Kreitman test, we reproduce inferences of rates of evolution previously based only on divergence data on both coding and intronic sequences and also obtain inferences for other classes of genomic elements (untranslated regions, promoters, and conserved noncoding sequences). Our results suggest that 1) the distribution of fitness effect-alpha method successfully helps distinguishing different scenarios of accelerated divergence (adaptation or relaxed selective constraints) and 2) the adaptive history of coding and noncoding sequences within the gene sets analyzed is decoupled. PMID:25977458

  19. Analysis of Five Gene Sets in Chimpanzees Suggests Decoupling between the Action of Selection on Protein-Coding and on Noncoding Elements.

    PubMed

    Santpere, Gabriel; Carnero-Montoro, Elena; Petit, Natalia; Serra, François; Hvilsom, Christina; Rambla, Jordi; Heredia-Genestar, Jose Maria; Halligan, Daniel L; Dopazo, Hernan; Navarro, Arcadi; Bosch, Elena

    2015-05-14

    We set out to investigate potential differences and similarities between the selective forces acting upon the coding and noncoding regions of five different sets of genes defined according to functional and evolutionary criteria: 1) two reference gene sets presenting accelerated and slow rates of protein evolution (the Complement and Actin pathways); 2) a set of genes with evidence of accelerated evolution in at least one of their introns; and 3) two gene sets related to neurological function (Parkinson's and Alzheimer's diseases). To that effect, we combine human-chimpanzee divergence patterns with polymorphism data obtained from target resequencing 20 central chimpanzees, our closest relatives with largest long-term effective population size. By using the distribution of fitness effect-alpha extension of the McDonald-Kreitman test, we reproduce inferences of rates of evolution previously based only on divergence data on both coding and intronic sequences and also obtain inferences for other classes of genomic elements (untranslated regions, promoters, and conserved noncoding sequences). Our results suggest that 1) the distribution of fitness effect-alpha method successfully helps distinguishing different scenarios of accelerated divergence (adaptation or relaxed selective constraints) and 2) the adaptive history of coding and noncoding sequences within the gene sets analyzed is decoupled.

  20. Action Research

    ERIC Educational Resources Information Center

    Milton-Brkich, Katie Lynn; Shumbera, Kristen; Beran, Becky

    2010-01-01

    Defined as "any systemic inquiry conducted by teachers... for the purpose of gathering information about how their particular schools operate, how they teach, and how their students learn" (Mertler, 2009), "action research" is empowering and professional research done by teachers to inform and improves their own practices. Although there are many…

  1. Evidence for an additional intracellular site of action of probucol in the prevention of oxidative modification of low density lipoprotein. Use of a new water-soluble probucol derivative.

    PubMed Central

    Parthasarathy, S

    1992-01-01

    Oxidative modification of low density lipoprotein (LDL) renders it more atherogenic. Probucol, a highly nonpolar antioxidant, is transported in lipoproteins, including LDL, and inhibits oxidative modification of LDL in vitro. The ability of probucol to inhibit atherogenesis in the LDL receptor-deficient rabbit has been attributed to its antioxidant effect. We report synthesis of a new water-soluble analogue of probucol that is very effective in preventing cell-induced LDL oxidation. The polar probucol derivative, diglutaryl probucol, is efficiently taken up by endothelial cells and macrophages in culture and is hydrolyzed to release the active antioxidant, probucol. The treated cells, after thorough washing, show a marked decrease in their capacity to oxidize LDL during a subsequent incubation. At high concentrations of the derivative, the cells also released free probucol into the medium. Thus, the effectiveness of probucol in vivo may be related both to its presence in LDL, acting as a nonspecific antioxidant, and to an additional ability to inhibit cell-mediated oxidation of LDL by virtue of its uptake into cells. PMID:1569200

  2. The Non-Genomic Actions of Vitamin D.

    PubMed

    Hii, Charles S; Ferrante, Antonio

    2016-03-01

    Since its discovery in 1920, a great deal of effort has gone into investigating the physiological actions of vitamin D and the impact its deficiency has on human health. Despite this intense interest, there is still disagreement on what constitutes the lower boundary of adequacy and on the Recommended Dietary Allowance. There has also been a major push to elucidate the biochemistry of vitamin D, its metabolic pathways and the mechanisms that mediate its action. Originally thought to act by altering the expression of target genes, it was realized in the mid-1980s that some of the actions of vitamin D were too rapid to be accounted for by changes at the genomic level. These rapid non-genomic actions have attracted as much interest as the genomic actions and they have spawned additional questions in an already busy field. This mini-review attempts to summarise the in vitro and in vivo work that has been conducted to characterise the rapid non-genomic actions, the mechanisms that give rise to these properties and the roles that these play in the overall action of vitamin D at the cellular level. Understanding the effects of vitamin D at the cellular level should enable the design of elegant human studies to extract the full potential of vitamin D to benefit human health. PMID:26950144

  3. The Non-Genomic Actions of Vitamin D

    PubMed Central

    Hii, Charles S; Ferrante, Antonio

    2016-01-01

    Since its discovery in 1920, a great deal of effort has gone into investigating the physiological actions of vitamin D and the impact its deficiency has on human health. Despite this intense interest, there is still disagreement on what constitutes the lower boundary of adequacy and on the Recommended Dietary Allowance. There has also been a major push to elucidate the biochemistry of vitamin D, its metabolic pathways and the mechanisms that mediate its action. Originally thought to act by altering the expression of target genes, it was realized in the mid-1980s that some of the actions of vitamin D were too rapid to be accounted for by changes at the genomic level. These rapid non-genomic actions have attracted as much interest as the genomic actions and they have spawned additional questions in an already busy field. This mini-review attempts to summarise the in vitro and in vivo work that has been conducted to characterise the rapid non-genomic actions, the mechanisms that give rise to these properties and the roles that these play in the overall action of vitamin D at the cellular level. Understanding the effects of vitamin D at the cellular level should enable the design of elegant human studies to extract the full potential of vitamin D to benefit human health. PMID:26950144

  4. Cardiac action potential imaging

    NASA Astrophysics Data System (ADS)

    Tian, Qinghai; Lipp, Peter; Kaestner, Lars

    2013-06-01

    Action potentials in cardiac myocytes have durations in the order of magnitude of 100 milliseconds. In biomedical investigations the documentation of the occurrence of action potentials is often not sufficient, but a recording of the shape of an action potential allows a functional estimation of several molecular players. Therefore a temporal resolution of around 500 images per second is compulsory. In the past such measurements have been performed with photometric approaches limiting the measurement to one cell at a time. In contrast, imaging allows reading out several cells at a time with additional spatial information. Recent developments in camera technologies allow the acquisition with the required speed and sensitivity. We performed action potential imaging on isolated adult cardiomyocytes of guinea pigs utilizing the fluorescent membrane potential sensor di-8-ANEPPS and latest electron-multiplication CCD as well as scientific CMOS cameras of several manufacturers. Furthermore, we characterized the signal to noise ratio of action potential signals of varying sets of cameras, dye concentrations and objective lenses. We ensured that di-8-ANEPPS itself did not alter action potentials by avoiding concentrations above 5 μM. Based on these results we can conclude that imaging is a reliable method to read out action potentials. Compared to conventional current-clamp experiments, this optical approach allows a much higher throughput and due to its contact free concept leaving the cell to a much higher degree undisturbed. Action potential imaging based on isolated adult cardiomyocytes can be utilized in pharmacological cardiac safety screens bearing numerous advantages over approaches based on heterologous expression of hERG channels in cell lines.

  5. Citizen's actions

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The role played by individual citizens as consumers of energy was examined, with emphasis on studying ways in which their action could result in energy conservation. It was shown that there are ways that energy can be conserved in this way, with citizens acting either individually or in groups. The potential savings are significant, but the actual savings may be quite small. The citizens need to be motivated to save and to believe in a conservation ethic; developing such an ethic is difficult, and perhaps not responsive to the shotgun approach now being attempted. The true course of action may be to synthesize new societal structures that provide the maximum evolution of culture within the limitation of scarce energy resources.

  6. Actionable Nuggets

    PubMed Central

    McColl, Mary Ann; Aiken, Alice; Smith, Karen; McColl, Alexander; Green, Michael; Godwin, Marshall; Birtwhistle, Richard; Norman, Kathleen; Brankston, Gabrielle; Schaub, Michael

    2015-01-01

    Abstract Objective To present the results of a pilot study of an innovative methodology for translating best evidence about spinal cord injury (SCI) for family practice. Design Review of Canadian and international peer-reviewed literature to develop SCI Actionable Nuggets, and a mixed qualitative-quantitative evaluation to determine Nuggets’ effect on physician knowledge of and attitudes toward patients with SCI, as well as practice accessibility. Setting Ontario, Newfoundland, and Australia. Participants Forty-nine primary care physicians. Methods Twenty Actionable Nuggets (pertaining to key health issues associated with long-term SCI) were developed. Nugget postcards were mailed weekly for 20 weeks to participating physicians. Prior knowledge of SCI was self-rated by participants; they also completed an online posttest to assess the information they gained from the Nugget postcards. Participants’ opinions about practice accessibility and accommodations for patients with SCI, as well as the acceptability and usefulness of Nuggets, were assessed in interviews. Main findings With Actionable Nuggets, participants’ knowledge of the health needs of patients with SCI improved, as knowledge increased from a self-rating of fair (58%) to very good (75%) based on posttest quiz results. The mean overall score for accessibility and accommodations in physicians’ practices was 72%. Participants’ awareness of the need for screening and disease prevention among this population also increased. The usefulness and acceptability of SCI Nugget postcards were rated as excellent. Conclusion Actionable Nuggets are a knowledge translation tool designed to provide family physicians with concise, practical information about the most prevalent and pressing primary care needs of patients with SCI. This evidence-based resource has been shown to be an excellent fit with information consumption processes in primary care. They were updated and adapted for distribution by the Canadian

  7. Conscious Action/Zombie Action

    PubMed Central

    Shepherd, Joshua

    2015-01-01

    Abstract I argue that the neural realizers of experiences of trying (that is, experiences of directing effort towards the satisfaction of an intention) are not distinct from the neural realizers of actual trying (that is, actual effort directed towards the satisfaction of an intention). I then ask how experiences of trying might relate to the perceptual experiences one has while acting. First, I assess recent zombie action arguments regarding conscious visual experience, and I argue that contrary to what some have claimed, conscious visual experience plays a causal role for action control in some circumstances. Second, I propose a multimodal account of the experience of acting. According to this account, the experience of acting is (at the very least) a temporally extended, co‐conscious collection of agentive and perceptual experiences, functionally integrated and structured both by multimodal perceptual processing as well as by what an agent is, at the time, trying to do. PMID:27667859

  8. Conscious Action/Zombie Action

    PubMed Central

    Shepherd, Joshua

    2015-01-01

    Abstract I argue that the neural realizers of experiences of trying (that is, experiences of directing effort towards the satisfaction of an intention) are not distinct from the neural realizers of actual trying (that is, actual effort directed towards the satisfaction of an intention). I then ask how experiences of trying might relate to the perceptual experiences one has while acting. First, I assess recent zombie action arguments regarding conscious visual experience, and I argue that contrary to what some have claimed, conscious visual experience plays a causal role for action control in some circumstances. Second, I propose a multimodal account of the experience of acting. According to this account, the experience of acting is (at the very least) a temporally extended, co‐conscious collection of agentive and perceptual experiences, functionally integrated and structured both by multimodal perceptual processing as well as by what an agent is, at the time, trying to do.

  9. Expression of AKR1B1, AKR1C3 and other genes of prostaglandin F2α biosynthesis and action in ovarian endometriosis tissue and in model cell lines.

    PubMed

    Sinreih, Maša; Anko, Maja; Kene, Neli Hevir; Kocbek, Vida; Rižner, Tea Lanišnik

    2015-06-01

    Endometriosis is a frequent benign gynecological disease characterized by endometrial tissue outside the uterine cavity. The estimated prevalence in the general population is 6-10%, but this reaches 30-50% in women with infertility and/or pain. As ectopic tissue within the pelvic cavity provokes inflammation, endometriosis is also considered a chronic inflammatory disease, and is characterized by increased peritoneal fluid levels of prostaglandin (PG)E2 and PGF2α. The AKR1B1 and AKR1C3 enzymes act as PG synthases and catalyze reduction of PGH2 to PGF2α, and PGD2 to 9α,11β-PGF2α, respectively. AKR1B1 and AKR1C3 may thus be associated with increased PGF2α production in endometriosis patients, as supported by our previous report of increased AKR1C1-AKR1C3 mRNA levels in endometriotic tissue, compared to control endometrium. Here, we initially evaluated PGF2α concentrations in peritoneal fluid from endometriosis patients and healthy women. We also examined expression of AKR1B1, AKR1C3 and other genes involved in PGF2α biosynthesis, metabolism, and action in ovarian endometriosis tissue versus healthy endometrium, and in peritoneal endometriosis and control endometrium model cell lines. Compared to controls, increased PGF2α concentrations in peritoneal fluid of patients were supported by endometriotic tissue showing increased AKR1B1 mRNA and protein levels, but unchanged AKR1C3 protein levels. Among genes involved in PGF2α biosynthesis, metabolism and action PLA2G2A, PTGS2/COX-2, ABCC4 and PTGFR were up-regulated, mRNA levels of SLCO2A, PTGDS and HPGDS were unchanged, and genes PLA2G4A and HPGD were down-regulated in diseased tissue. All of these PGF2α-associated genes were also expressed in control endometrial HIEEC epithelial and HIESC stromal cell lines, and in peritoneal endometriosis 12-Z epithelial and 22-B stromal cell lines. Higher expression of PLA2G2A, PTGS2, AKR1B1, AKR1C3 and ABCC4 was seen in 22-B endometriosis cells compared to HIESC control

  10. ES H action plan

    SciTech Connect

    Not Available

    1991-01-01

    This document contains planned actions to correct the deficiencies identified in the Pre-Tiger Team Self-Assessment (PTTSA), January 1991, of Sandia National Laboratories (SNL -- Albuquerque, New Mexico; Tonopah, Nevada; and Kauai, Hawaii). The Self-Assessment was conducted by a Self-Assessment Working Group consisting of 19 department managers, with support from Environment, Safety, and Health (ES H) professionals, from October through December 1990. Findings from other past audits, dating back to 1985, were reviewed and compared with the PTTSA findings to determine if additional findings, key findings, or root causes were warranted. The resulting ES H Action Plan and individual planned actions were prepared by the ES H Action Plan Project Group with assistance from the Program owners/authors during February and March 1991. The plan was reviewed by SNL Management in April 1991. This document serves as a planning instrument for the Laboratories to aid in the scoping and sizing of activities related to ES H compliance for the coming five years. It will be modified as required to ensure a workload/funding balance and to address the findings resulting from the Tiger Team assessment at SNL, Albuquerque. The process of producing this document has served well to prepare SNL, Albuquerque, for the coming task of producing the required post-Tiger Team action plan document. 8 tabs.

  11. Action Learning: Avoiding Conflict or Enabling Action

    ERIC Educational Resources Information Center

    Corley, Aileen; Thorne, Ann

    2006-01-01

    Action learning is based on the premise that action and learning are inextricably entwined and it is this potential, to enable action, which has contributed to the growth of action learning within education and management development programmes. However has this growth in action learning lead to an evolution or a dilution of Revan's classical…

  12. Expression patterns and potential action of the calcium transport genes Trpv5, Trpv6, Ncx1 and Pmca1b in the canine duodenum, kidney and uterus.

    PubMed

    Kim, Jeong-Ah; Yang, Hyun; Hwang, Inho; Jung, Eui-Man; Choi, Kyung-Chul; Jeung, Eui-Bae

    2011-01-01

    Four membrane calcium (Ca²⁺) channels are known to play an important role in calcium transport: transient receptor potential cation channel subfamily V members 5 and 6 (Trpv5/6), Na⁺/Ca²⁺ exchanger 1 (Ncx1) and plasma membrane Ca²⁺-transporting ATPase1 (Pmca1b). These channels have been shown to mediate the transport of Ca²⁺ between the cytosol and bloodstream in multiple tissues, including the duodenum, kidney, and uterus. Trpv5 and Trpv6 are known to selectively import Ca²⁺ into cells, while Ncx1 and Pmca1b function to extrude Ca²⁺. The present study examined and compared expression patterns of these genes in the canine duodenum, kidney and uterus. We confirmed expression of all four genes in this canine model. To collect tissues for analysis, two adult (2.5-year-old) female dogs were euthanized and tissue samples were collected from an abdominal incision. Expression of Trpv5/6, Ncx1 and Pmca1b was analyzed by reverse transcription polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemistry. Trpv5, Trpv6 and Ncx1 mRNA were highly expressed in the kidney, while Pmca1b mRNA was primarily detected in the uterus. Protein expression was verified by Western blot analysis and localized by immunohistochemistry. Protein expression showed patterns similar to those of mRNA expression. Taken together, these results indicate that transcriptional and transitional expression of Tprv5, Trpv6, Ncx1 and Pmca1b may play a critical role in calcium transport in the canine duodenum, kidney and uterus.

  13. Modes of Action of Acarbose Hydrolysis and Transglycosylation Catalyzed by a Thermostable Maltogenic Amylase, the Gene for Which Was Cloned from a Thermus Strain

    PubMed Central

    Kim, Tae-Jip; Kim, Myo-Jeong; Kim, Byung-Cheon; Kim, Jae-Cherl; Cheong, Tae-Kyou; Kim, Jung-Wan; Park, Kwan-Hwa

    1999-01-01

    A maltogenic amylase gene was cloned in Escherichia coli from a gram-negative thermophilic bacterium, Thermus strain IM6501. The gene encoded an enzyme (ThMA) with a molecular mass of 68 kDa which was expressed by the expression vector p6xHis119. The optimal temperature of ThMA was 60°C, which was higher than those of other maltogenic amylases reported so far. Thermal inactivation kinetic analysis of ThMA indicated that it was stabilized in the presence of 10 mM EDTA. ThMA harbored both hydrolysis and transglycosylation activities. It hydrolyzed β-cyclodextrin and starch mainly to maltose and pullulan to panose. ThMA not only hydrolyzed acarbose, an amylase inhibitor, to glucose and pseudotrisaccharide (PTS) but also transferred PTS to 17 sugar acceptors, including glucose, fructose, maltose, cellobiose, etc. Structural analysis of acarbose transfer products by using methylation, thin-layer chromatography, high-performance ion chromatography, and nuclear magnetic resonance indicated that PTS was transferred primarily to the C-6 of the acceptors and at lower degrees to the C-3 and/or C-4. The transglycosylation of sugar to methyl-α-d-glucopyranoside by forming an α-(1,3)-glycosidic linkage was demonstrated for the first time by using acarbose and ThMA. Kinetic analysis of the acarbose transfer products showed that the C-4 transfer product formed most rapidly but readily hydrolyzed, while the C-6 transfer product was stable and accumulated in the reaction mixture as the main product. PMID:10103262

  14. 77 FR 53180 - Procurement List; Additions

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  15. 76 FR 35415 - Procurement List; Addition

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  16. 78 FR 9386 - Procurement List; Addition

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  17. 77 FR 31335 - Procurement List; Additions

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  8. Activity of the upstream TATA-less promoter of the p21(Waf1/Cip1) gene depends on transcription factor IIA (TFIIA) in addition to TFIIA-reactive TBP-like protein.

    PubMed

    Suzuki, Hidefumi; Maeda, Ryo; Nakadai, Tomoyoshi; Tamura, Taka-aki

    2014-07-01

    TATA-binding protein-like protein (TLP) binds to transcription factor IIA (TFIIA) with high affinity, although the significance of this binding is poorly understood. In this study, we investigated the role of TFIIA in transcriptional regulation of the p21(Waf1/Cip1) (p21) gene. It has been shown that TLP is indispensable for p53-activated transcription from an upstream TATA-less promoter of the p21 gene. We found that mutant TLPs having decreased TFIIA-binding ability exhibited weakened transcriptional activation function for the upstream promoter. Activity of the upstream promoter was enhanced considerably by an increased amount of TFIIA in a p53-dependent manner, whereas activity of the TATA-containing downstream promoter was enhanced only slightly. TFIIA potentiated the upstream promoter additively with TLP. Although TFIIA is recruited to both promoters, activity of the upstream promoter was much more dependent on TFIIA. Recruitment of TFIIA and TLP to the upstream promoter was augmented in etoposide-treated cells, in which the amount of TFIIA-TLP complex is increased, and TFIIA-reactive TLP was required for the recruitment of both factors. It was confirmed that etoposide-stimulated transcription depends on TLP. We also found that TFIIA-reactive TLP acts to decrease cell growth rate, which can be explained by interaction of the p21 promoter with the transcription factors that we examined. The results of the present study suggest that the upstream TATA-less promoter of p21 needs TFIIA and TFIIA-reactive TLP for p53-dependent transcriptional enhancement.

  9. Additive lattice kirigami

    PubMed Central

    Castle, Toen; Sussman, Daniel M.; Tanis, Michael; Kamien, Randall D.

    2016-01-01

    Kirigami uses bending, folding, cutting, and pasting to create complex three-dimensional (3D) structures from a flat sheet. In the case of lattice kirigami, this cutting and rejoining introduces defects into an underlying 2D lattice in the form of points of nonzero Gaussian curvature. A set of simple rules was previously used to generate a wide variety of stepped structures; we now pare back these rules to their minimum. This allows us to describe a set of techniques that unify a wide variety of cut-and-paste actions under the rubric of lattice kirigami, including adding new material and rejoining material across arbitrary cuts in the sheet. We also explore the use of more complex lattices and the different structures that consequently arise. Regardless of the choice of lattice, creating complex structures may require multiple overlapping kirigami cuts, where subsequent cuts are not performed on a locally flat lattice. Our additive kirigami method describes such cuts, providing a simple methodology and a set of techniques to build a huge variety of complex 3D shapes. PMID:27679822

  10. Additive lattice kirigami

    PubMed Central

    Castle, Toen; Sussman, Daniel M.; Tanis, Michael; Kamien, Randall D.

    2016-01-01

    Kirigami uses bending, folding, cutting, and pasting to create complex three-dimensional (3D) structures from a flat sheet. In the case of lattice kirigami, this cutting and rejoining introduces defects into an underlying 2D lattice in the form of points of nonzero Gaussian curvature. A set of simple rules was previously used to generate a wide variety of stepped structures; we now pare back these rules to their minimum. This allows us to describe a set of techniques that unify a wide variety of cut-and-paste actions under the rubric of lattice kirigami, including adding new material and rejoining material across arbitrary cuts in the sheet. We also explore the use of more complex lattices and the different structures that consequently arise. Regardless of the choice of lattice, creating complex structures may require multiple overlapping kirigami cuts, where subsequent cuts are not performed on a locally flat lattice. Our additive kirigami method describes such cuts, providing a simple methodology and a set of techniques to build a huge variety of complex 3D shapes.

  11. The good-genes and compatible-genes benefits of mate choice.

    PubMed

    Puurtinen, Mikael; Ketola, Tarmo; Kotiaho, J S

    2009-11-01

    Genetic benefits from mate choice could be attained by choosing mates with high heritable quality ("good genes") and that are genetically compatible ("compatible genes"). We clarify the conceptual and empirical framework for estimating genetic benefits of mate choice, stressing that benefits must be measured from offspring fitness because there are no unequivocal surrogates for genetic quality of individuals or for compatibility of parents. We detail the relationship between genetic benefits and additive and nonadditive genetic variance in fitness, showing that the benefits have been overestimated in previous verbal treatments. We point out that additive benefits readily arise from nonadditive gene action and that the idea of "heritable nonadditive benefits" is a misconception. We review the empirical evidence of the magnitude of benefits of good genes and compatible genes in animal populations, and we outline the most promising future directions for empirical research on the genetic benefits of mate choice. PMID:19772439

  12. Action of calcitonin gene-related peptide upon bovine vascular endothelial and smooth muscle cells grown in isolation and co-culture.

    PubMed Central

    Crossman, D. C.; Dashwood, M. R.; Brain, S. D.; McEwan, J.; Pearson, J. D.

    1990-01-01

    1. Bovine aortic endothelial cells (BAE) and smooth muscle cells (BASM) were grown separately and in co-culture. 2. Calcitonin gene-related peptide (CGRP) caused dose-dependent activation of adenylate cyclase in each cell type when grown in isolation. The concentration of CGRP causing half-maximal activation in BAE and BASM was 200 nM and 310 nM, respectively. 3. In cells grown in co-culture exposure to bradykinin produced dose-dependent elevations in cyclic GMP content which were maximal 1 min after application of the agonist. 4. CGRP (1 nM-1 microM) did not stimulate a rise in cyclic GMP in co-cultures. 5. Displaceable CGRP binding was identified throughout the wall of the bovine aorta. 6. We conclude that CGRP receptors coupled to adenylate cyclase are present on BAE and BASM, but there is no coupling of these receptors to the release of any agent (such as endothelium-derived relaxing factor) that activates guanylate cyclase. Images Figure 1 Figure 2 PMID:2184911

  13. Deoxynivalenol impairs hepatic and intestinal gene expression of selected oxidative stress, tight junction and inflammation proteins in broiler chickens, but addition of an adsorbing agent shifts the effects to the distal parts of the small intestine.

    PubMed

    Osselaere, Ann; Santos, Regiane; Hautekiet, Veerle; De Backer, Patrick; Chiers, Koen; Ducatelle, Richard; Croubels, Siska

    2013-01-01

    Broiler chickens are rather resistant to deoxynivalenol and thus, clinical signs are rarely seen. However, effects of subclinical concentrations of deoxynivalenol on both the intestine and the liver are less frequently studied at the molecular level. During our study, we investigated the effects of three weeks of feeding deoxynivalenol on the gut wall morphology, intestinal barrier function and inflammation in broiler chickens. In addition, oxidative stress was evaluated in both the liver and intestine. Besides, the effect of a clay-based mycotoxin adsorbing agent on these different aspects was also studied. Our results show that feeding deoxynivalenol affects the gut wall morphology both in duodenum and jejenum of broiler chickens. A qRT-PCR analysis revealed that deoxynivalenol acts in a very specific way on the intestinal barrier, since only an up-regulation in mRNA expression of claudin 5 in jejunum was observed, while no effects were seen on claudin 1, zona occludens 1 and 2. Addition of an adsorbing agent resulted in an up-regulation of all the investigated genes coding for the intestinal barrier in the ileum. Up-regulation of Toll-like receptor 4 and two markers of oxidative stress (heme-oxigenase or HMOX and xanthine oxidoreductase or XOR) were mainly seen in the jejunum and to a lesser extent in the ileum in response to deoxynivalenol, while in combination with an adsorbing agent main effect was seen in the ileum. These results suggest that an adsorbing agent may lead to higher concentrations of deoxynivalenol in the more distal parts of the small intestine. In the liver, XOR was up-regulated due to DON exposure. HMOX and HIF-1α (hypoxia-inducible factor 1α) were down-regulated due to feeding DON but also due to feeding the adsorbing agent alone or in combination with DON.

  14. Complete elimination of established neuroblastoma by synergistic action of gamma-irradiation and DCs treated with rSeV expressing interferon-beta gene.

    PubMed

    Tatsuta, K; Tanaka, S; Tajiri, T; Shibata, S; Komaru, A; Ueda, Y; Inoue, M; Hasegawa, M; Suita, S; Sueishi, K; Taguchi, T; Yonemitsu, Y

    2009-02-01

    Dendritic cell (DC)-based immunotherapy has been investigated as a new therapeutic approach to intractable neuroblastomas; however, only limited clinical effect has been reported. To overcome the relatively low sensitivity of neuroblastomas against immunotherapy, we undertook a preclinical efficacy study to examine murine models to assess the combined effects of gamma-irradiation pretreatment and recombinant Sendai virus (ts-rSeV/dF)-mediated murine interferon-beta (mIFN-beta) gene transfer to DCs using established c1300 neuroblastomas. Similar to intractable neuroblastomas in the clinic, established c1300 tumors were highly resistant to monotherapy with either gamma-irradiation or DCs activated by ts-rSeV/dF without transgene (ts-rSeV/dF-null) that has been shown to be effective against other murine tumors, including B16F10 melanoma. In contrast, immunotherapy using DCs expressing mIFN-beta through ts-rSeV/dF (ts-rSeV/dF-mIFNbeta-DCs) effectively reduced tumor size, and its combination with gamma-irradiation pretreatment dramatically enhanced its antitumor effect, resulting frequently in the complete elimination of established c1300 tumors 7-9 mm in diameter, in a high survival rate among mice, and in the development of protective immunity in the mice against rechallenge by the tumor cells. These results indicate that the combination of ts-rSeV/dF-mIFNbeta-DCs with gamma-irradiation is a hopeful strategy for the treatment of intractable neuroblastomas, warranting further investigation in the clinical setting.

  15. Genome-wide Analysis of Body Proportion Classifies Height-Associated Variants by Mechanism of Action and Implicates Genes Important for Skeletal Development

    PubMed Central

    Chan, Yingleong; Salem, Rany M.; Hsu, Yu-Han H.; McMahon, George; Pers, Tune H.; Vedantam, Sailaja; Esko, Tonu; Guo, Michael H.; Lim, Elaine T.; Franke, Lude; Smith, George Davey; Strachan, David P.; Hirschhorn, Joel N.

    2015-01-01

    Human height is a composite measurement, reflecting the sum of leg, spine, and head lengths. Many common variants influence total height, but the effects of these or other variants on the components of height (body proportion) remain largely unknown. We studied sitting height ratio (SHR), the ratio of sitting height to total height, to identify such effects in 3,545 African Americans and 21,590 individuals of European ancestry. We found that SHR is heritable: 26% and 39% of the total variance of SHR can be explained by common variants in European and African Americans, respectively, and global European admixture is negatively correlated with SHR in African Americans (r2 ≈ 0.03). Six regions reached genome-wide significance (p < 5 × 10−8) for association with SHR and overlapped biological candidate genes, including TBX2 and IGFBP3. We found that 130 of 670 height-associated variants are nominally associated (p < 0.05) with SHR, more than expected by chance (p = 5 × 10−40). At these 130 loci, the height-increasing alleles are associated with either a decrease (71 loci) or increase (59 loci) in SHR, suggesting that different height loci disproportionally affect either leg length or spine/head length. Pathway analyses via DEPICT revealed that height loci affecting SHR, and especially those affecting leg length, show enrichment of different biological pathways (e.g., bone/cartilage/growth plate pathways) than do loci with no effect on SHR (e.g., embryonic development). These results highlight the value of using a pair of related but orthogonal phenotypes, in this case SHR with height, as a prism to dissect the biology underlying genetic associations in polygenic traits and diseases. PMID:25865494

  16. Social Action As An Objective of Social Studies Instruction.

    ERIC Educational Resources Information Center

    Curtis, Charles K.

    This paper presents a rationale for making social action a major goal of elementary and secondary school social studies education. In addition, it describes social action models, suggests social action approaches appropriate for students at various grade levels, and reviews literature on social action by public school students. Social action is…

  17. Enabling comparative gene expression studies of thyroid hormone action through the development of a flexible real-time quantitative PCR assay for use across multiple anuran indicator and sentinel species.

    PubMed

    Veldhoen, Nik; Propper, Catherine R; Helbing, Caren C

    2014-03-01

    Studies performed across diverse frog species have made substantial contributions to our understanding of basic vertebrate development and the natural or anthropogenic environmental factors impacting sensitive life stages. Because, anurans are developmental models, provide ecosystems services, and act as sentinels for the identification of environmental chemical contaminants that interfere with thyroid hormone (TH) action during postembryonic development, there is demand for flexible assessment techniques that can be applied to multiple species. As part of the "thyroid assays across indicator and sentinel species" (TAXISS) initiative, we have designed and validated a series of cross-species real time quantitative PCR (qPCR) primer sets that provide information on transcriptome components in evolutionarily distant anurans. Validation for fifteen gene transcripts involved a rigorous three-tiered quality control within tissue/development-specific contexts. Assay performance was confirmed on multiple tissues (tail fin, liver, brain, and intestine) of Rana catesbeiana and Xenopus laevis tadpoles enabling comparisons between tissues and generation of response profiles to exogenous TH. This revealed notable differences in TH-responsive gene transcripts including thra, thrb, thibz, klf9, col1a2, fn1, plp1, mmp2, timm50, otc, and dio2, suggesting differential regulation and susceptibility to contaminant effects. Evidence for the applicability of the TAXISS anuran qPCR assay across seven other species is also provided with five frog families represented and its utility in defining genome structure was demonstrated. This novel validated approach will enable meaningful comparative studies between frog species and aid in extending knowledge of developmental regulatory pathways and the impact of environmental factors on TH signaling in frog species for which little or no genetic information is currently available. PMID:24503578

  18. 77 FR 56813 - Procurement List, Proposed Additions

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  14. 78 FR 40727 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-08

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to the Procurement List. SUMMARY: The Committee is proposing to add products and a service to the Procurement List that will...

  15. 75 FR 69639 - Procurement List; Proposed Addition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Addition AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Addition to the Procurement List. SUMMARY: The Committee is proposing to add a service to the Procurement List that will be provided by...

  16. 78 FR 52512 - Procurement List Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-23

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed additions to the Procurement List. SUMMARY: The Committee is proposing to add products and a service to the Procurement List that will...

  17. 76 FR 75536 - Procurement List; Proposed Addition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-02

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Addition AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Addition to the Procurement List. SUMMARY: The Committee is proposing to add a service to the Procurement List that will be provided by...

  18. 75 FR 34701 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-18

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to the Procurement List. SUMMARY: The Committee is proposing to add products and services to the Procurement List that will...

  19. 78 FR 53734 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-30

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to the Procurement List. SUMMARY: The Committee is proposing to add products to the Procurement List that will be furnished by...

  20. 76 FR 26279 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-06

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed additions to the Procurement List. SUMMARY: The Committee is proposing to add services to the Procurement List that will be provided...

  1. 77 FR 69598 - Procurement List Proposed Addition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-20

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Proposed Addition AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed addition to the procurement list. SUMMARY: The Committee is proposing to add a service to the Procurement List that will be provided by...

  2. 76 FR 72908 - Procurement List Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed additions to the Procurement List. SUMMARY: The Committee is proposing to add products and a service to the Procurement List that will...

  3. 78 FR 34351 - Procurement List; Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-07

    ... (78 FR 21916), the Committee for Purchase from People Who are Blind or Severely Disabled published... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Additions AGENCY: Committee for Purchase from People Who are Blind or Severely Disabled. ACTION: Additions to the Procurement List. SUMMARY:...

  4. 75 FR 2510 - Procurement List: Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List: Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to Procurement List. SUMMARY: The Committee is proposing to add to the Procurement List services to be provided by...

  5. 78 FR 40727 - Procurement List Addition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-08

    ... (78 FR 25970-25971), the Committee for Purchase From People Who Are Blind or Severely Disabled... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Addition AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Addition to the Procurement List. SUMMARY: This...

  6. 75 FR 60739 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-01

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed additions to the procurement list. SUMMARY: The Committee is proposing to add services to the Procurement List that will be provided...

  7. 76 FR 14943 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-18

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to the Procurement List. SUMMARY: The Committee is proposing to add products to the Procurement List that will be furnished by...

  8. 75 FR 62370 - Procurement List Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-08

    ... PEOPLE WHO AREBLIND OR SEVERELY DISABLED Procurement List Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to the Procurement List. SUMMARY: The Committee is proposing to add products and services to the Procurement List that will...

  9. 78 FR 50040 - Procurement List, Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-16

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List, Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to the Procurement List. SUMMARY: The Committee is proposing to add services to the Procurement List that will be provided...

  10. 77 FR 41377 - Procurement List; Proposed Addition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Addition AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Addition to the Procurement List. SUMMARY: The Committee is proposing to add a service to the Procurement List that will be furnished by...

  11. 77 FR 67343 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-09

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to the Procurement List. SUMMARY: The Committee is proposing to add a product and services to the Procurement List that will...

  12. 78 FR 7412 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-01

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to the Procurement List. SUMMARY: The Committee is proposing to add products to the Procurement List that will be furnished by...

  13. 78 FR 32632 - Procurement List; Addition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-31

    ... 4/5/2013 (78 FR 20622-20623), the Committee for Purchase From People Who Are Blind or Severely... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Addition AGENCY: Committee for Purchase from People Who are Blind or Severely Disabled. ACTION: Addition to the Procurement List. SUMMARY: This...

  14. 76 FR 47565 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-05

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to the Procurement List. SUMMARY: The Committee is proposing to add services to the Procurement List that will be provided...

  15. 76 FR 32146 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-03

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed additions to the Procurement List. SUMMARY: The Committee is proposing to add products and a service to the Procurement List that will...

  16. 75 FR 14575 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-26

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed additions to the Procurement List. SUMMARY: The Committee is proposing to add to the Procurement List products and a service to be...

  17. 78 FR 22209 - Additional Synthetic Drug Testing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-15

    ... COMMISSION 10 CFR Part 26 Additional Synthetic Drug Testing AGENCY: Nuclear Regulatory Commission. ACTION... NRC amend its Fitness for Duty program regulations to amend drug testing requirements to test for additional synthetic drugs currently not included in the regulations. The NRC determined that the...

  18. Transcription of interferon-stimulated genes is induced by adenovirus particles but is suppressed by E1A gene products.

    PubMed Central

    Reich, N; Pine, R; Levy, D; Darnell, J E

    1988-01-01

    Interferon treatment of cell cultures results in the rapid transcriptional induction of a specific set of genes. In this paper we explore the effect of cellular infection by several adenoviruses, both wild type and mutant, on the expression of these genes. Infection with adenovirus induces the transcription of the interferon-stimulated genes in the absence of any protein synthesis. In fact, the inhibition of protein synthesis during a wild-type infection produces enhanced stimulation of transcription of these genes. Experiments with viral mutants indicate the ability to specifically suppress this transcription maps to the E1A gene. In addition, the E1A gene products are capable of suppressing the specific transcriptional induction of interferon-stimulated promoters during cotransfection experiments and therefore presumably during viral infection. The dual effect of adenovirus on the expression of interferon-stimulated genes may represent an example of action and evolutionary reaction between virus and host. Images PMID:2446013

  19. 48 CFR 22.406-3 - Additional classifications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... SOCIOECONOMIC PROGRAMS APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Labor Standards for Contracts... officer that additional time is necessary. (2) Upon receipt of the Department of Labor's action,...

  20. 48 CFR 22.406-3 - Additional classifications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SOCIOECONOMIC PROGRAMS APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Labor Standards for Contracts... officer that additional time is necessary. (2) Upon receipt of the Department of Labor's action,...

  1. The role of action prediction and inhibitory control for joint action coordination in toddlers.

    PubMed

    Meyer, M; Bekkering, H; Haartsen, R; Stapel, J C; Hunnius, S

    2015-11-01

    From early in life, young children eagerly engage in social interactions. Yet, they still have difficulties in performing well-coordinated joint actions with others. Adult literature suggests that two processes are important for smooth joint action coordination: action prediction and inhibitory control. The aim of the current study was to disentangle the potential role of these processes in the early development of joint action coordination. Using a simple turn-taking game, we assessed 2½-year-old toddlers' joint action coordination, focusing on timing variability and turn-taking accuracy. In two additional tasks, we examined their action prediction capabilities with an eye-tracking paradigm and examined their inhibitory control capabilities with a classic executive functioning task (gift delay task). We found that individual differences in action prediction and inhibitory action control were distinctly related to the two aspects of joint action coordination. Toddlers who showed more precision in their action predictions were less variable in their action timing during the joint play. Furthermore, toddlers who showed more inhibitory control in an individual context were more accurate in their turn-taking performance during the joint action. On the other hand, no relation between timing variability and inhibitory control or between turn-taking accuracy and action prediction was found. The current results highlight the distinct role of action prediction and inhibitory action control for the quality of joint action coordination in toddlers. Underlying neurocognitive mechanisms and implications for processes involved in joint action coordination in general are discussed. PMID:26150055

  2. The Take Action Project

    ERIC Educational Resources Information Center

    Boudreau, Sue

    2010-01-01

    The Take Action Project (TAP) was created to help middle school students take informed and effective action on science-related issues. The seven steps of TAP ask students to (1) choose a science-related problem of interest to them, (2) research their problem, (3) select an action to take on the problem, (4) plan that action, (5) take action, (6)…

  3. The +37 kb Cebpa Enhancer Is Critical for Cebpa Myeloid Gene Expression and Contains Functional Sites that Bind SCL, GATA2, C/EBPα, PU.1, and Additional Ets Factors.

    PubMed

    Cooper, Stacy; Guo, Hong; Friedman, Alan D

    2015-01-01

    The murine Cebpa gene contains an evolutionarily conserved 453 bp enhancer located at +37 kb that, together with its promoter, directs expression to myeloid progenitors and to long-term hematopoietic stem cells in transgenic mice. In human acute myeloid leukemia cases, the enhancer lacks point mutations but binds the RUNX1-ETO oncoprotein. The enhancer contains the H3K4me1 and H3K27Ac histone modifications, denoting an active enhancer, at progressively increasing levels as long-term hematopoietic stem cells transition to granulocyte-monocyte progenitors. We previously identified four enhancer sites that bind RUNX1 and demonstrated that their integrity is required for maximal enhancer activity in 32Dcl3 myeloid cells. The +37 kb Cebpa enhancer also contains C/EBP, Ets factor, Myb, GATA, and E-box consensus sites conserved in the human +42 kb CEBPA enhancer. Mutation of the two C/EBP, seven Ets, one Myb, two GATA, or two E-box sites reduces activity of an enhancer-promoter reporter in 32Dcl3 cells. In 293T gel shift assays, exogenous C/EBPα binds both C/EBP sites, c-Myb binds the Myb site, PU.1 binds the second Ets site, PU.1, Fli-1, ERG, and Ets1 bind the sixth Ets site, GATA2 binds both GATA sites, and SCL binds the second E-box. Endogenous hematopoietic RUNX1, PU.1, Fli-1, ERG, C/EBPα, GATA2, and SCL were previously shown to bind the enhancer, and we find that endogenous PU.1 binds the second Ets site in 32Dcl3 cells. Using CRISPR/Cas9, we developed 32Dcl3 lines in which the wild-type enhancer alleles are replaced with a variant mutant in the seven Ets sites. These lines have 20-fold reduced Cebpa mRNA when cultured in IL-3 or G-CSF, demonstrating a critical requirement for enhancer integrity for optimal Cebpa expression. In addition, these results indicate that the +37 kb Cebpa enhancer is the focus of multiple regulatory transcriptional pathways that impact its expression during normal hematopoiesis and potentially during myeloid transformation.

  4. The +37 kb Cebpa Enhancer Is Critical for Cebpa Myeloid Gene Expression and Contains Functional Sites that Bind SCL, GATA2, C/EBPα, PU.1, and Additional Ets Factors

    PubMed Central

    Cooper, Stacy; Guo, Hong; Friedman, Alan D.

    2015-01-01

    The murine Cebpa gene contains an evolutionarily conserved 453 bp enhancer located at +37 kb that, together with its promoter, directs expression to myeloid progenitors and to long-term hematopoietic stem cells in transgenic mice. In human acute myeloid leukemia cases, the enhancer lacks point mutations but binds the RUNX1-ETO oncoprotein. The enhancer contains the H3K4me1 and H3K27Ac histone modifications, denoting an active enhancer, at progressively increasing levels as long-term hematopoietic stem cells transition to granulocyte-monocyte progenitors. We previously identified four enhancer sites that bind RUNX1 and demonstrated that their integrity is required for maximal enhancer activity in 32Dcl3 myeloid cells. The +37 kb Cebpa enhancer also contains C/EBP, Ets factor, Myb, GATA, and E-box consensus sites conserved in the human +42 kb CEBPA enhancer. Mutation of the two C/EBP, seven Ets, one Myb, two GATA, or two E-box sites reduces activity of an enhancer-promoter reporter in 32Dcl3 cells. In 293T gel shift assays, exogenous C/EBPα binds both C/EBP sites, c-Myb binds the Myb site, PU.1 binds the second Ets site, PU.1, Fli-1, ERG, and Ets1 bind the sixth Ets site, GATA2 binds both GATA sites, and SCL binds the second E-box. Endogenous hematopoietic RUNX1, PU.1, Fli-1, ERG, C/EBPα, GATA2, and SCL were previously shown to bind the enhancer, and we find that endogenous PU.1 binds the second Ets site in 32Dcl3 cells. Using CRISPR/Cas9, we developed 32Dcl3 lines in which the wild-type enhancer alleles are replaced with a variant mutant in the seven Ets sites. These lines have 20-fold reduced Cebpa mRNA when cultured in IL-3 or G-CSF, demonstrating a critical requirement for enhancer integrity for optimal Cebpa expression. In addition, these results indicate that the +37 kb Cebpa enhancer is the focus of multiple regulatory transcriptional pathways that impact its expression during normal hematopoiesis and potentially during myeloid transformation. PMID:25938608

  5. Differential Gene Action in Neurospora crassa

    PubMed Central

    Bhagwat, A. S.; Mahadevan, P. R.

    1973-01-01

    Molecular hybridization experiments with pulse-labeled total ribonucleic acid (RNA) or isolated nonribosomal rapidly labeled RNA species and deoxyribonucleic acid from growth periods of 8, 16, and 24 hr of Neurospora crassa showed differential transcription. Hybridization competition experiments between RNA species isolated from 8, 16, and 24 hr of growth showed qualitative differences in the types of RNA synthesized during these periods. PMID:4266171

  6. Attention, biological motion, and action recognition.

    PubMed

    Thompson, James; Parasuraman, Raja

    2012-01-01

    Interacting with others in the environment requires that we perceive and recognize their movements and actions. Neuroimaging and neuropsychological studies have indicated that a number of brain regions, particularly the superior temporal sulcus, are involved in a number of processes essential for action recognition, including the processing of biological motion and processing the intentions of actions. We review the behavioral and neuroimaging evidence suggesting that while some aspects of action recognition might be rapid and effective, they are not necessarily automatic. Attention is particularly important when visual information about actions is degraded or ambiguous, or if competing information is present. We present evidence indicating that neural responses associated with the processing of biological motion are strongly modulated by attention. In addition, behavioral and neuroimaging evidence shows that drawing inferences from the actions of others is attentionally demanding. The role of attention in action observation has implications for everyday social interactions and workplace applications that depend on observing, understanding and interpreting actions. PMID:21640836

  7. ICDF Complex Remedial Action Report

    SciTech Connect

    W. M. Heileson

    2007-09-26

    This Idaho CERCLA Disposal Facility (ICDF) Remedial Action Report has been prepared in accordance with the requirements of Section 6.2 of the INEEL CERCLA Disposal Facility Remedial Action Work Plan. The agency prefinal inspection of the ICDF Staging, Storage, Sizing, and Treatment Facility (SSSTF) was completed in June of 2005. Accordingly, this report has been developed to describe the construction activities completed at the ICDF along with a description of any modifications to the design originally approved for the facility. In addition, this report provides a summary of the major documents prepared for the design and construction of the ICDF, a discussion of relevant requirements and remedial action objectives, the total costs associated with the development and operation of the facility to date, and identification of necessary changes to the Agency-approved INEEL CERCLA Disposal Facility Remedial Action Work Plan and the ICDF Complex Operations and Maintenance Plan.

  8. 75 FR 7451 - Procurement List Additions and Deletions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-19

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to the Procurement List. SUMMARY: This action adds to the Procurement List products and services to be furnished by nonprofit...

  9. [Food additives and healthiness].

    PubMed

    Heinonen, Marina

    2014-01-01

    Additives are used for improving food structure or preventing its spoilage, for example. Many substances used as additives are also naturally present in food. The safety of additives is evaluated according to commonly agreed principles. If high concentrations of an additive cause adverse health effects for humans, a limit of acceptable daily intake (ADI) is set for it. An additive is a risk only when ADI is exceeded. The healthiness of food is measured on the basis of nutrient density and scientifically proven effects.

  10. Action goals influence action-specific perception.

    PubMed

    Cañal-Bruland, Rouwen; van der Kamp, John

    2009-12-01

    We examined the processes that mediate the emergence of action-specific influences on perception that have recently been reported for baseball batting and golf putting (Witt, Linkenauger, Bakdash, & Proffitt, 2008; Witt & Proffitt, 2005). To this end, we used a Schokokusswurfmaschine: Children threw a ball at a target, which, if hit successfully, launched a ball that the children then had to catch. In two experiments, children performed either a throwing-and-catching task or a throwing-only task, in which no ball was launched. After each task, the size of the target or of the ball was estimated. Results indicate that action-specific influences on perceived size occur for objects that are related to the end goal of the action, but not for objects that are related to intermediate action goals. These results suggest that action-specific influences on perception are contingent upon the primary action goals to be achieved.

  11. Action Research: Rethinking Lewin.

    ERIC Educational Resources Information Center

    Dickens, Linda; Watkins, Karen

    1999-01-01

    Explores both historical and contemporary definitions of action research. Describes the process and goals of action research in the tradition of Lewin. Presents a case study of an action-research project involving two teams in a high-technology corporation that depicts the process in action. (Author/CCM)

  12. Action Learning at Work.

    ERIC Educational Resources Information Center

    Mumford, Alan, Ed.

    This book contains 34 papers examining the theory, process, and outcomes of action learning at work. The following papers are included: "An Introduction to the Text" (Alan Mumford); "The Learning Equation" (Reg Revans); "Action Learning as a Vehicle for Learning" (Alan Mumford); "Placing Action Learning and Action Research in Context" (Cliff…

  13. 12 CFR 1777.12 - Other supervisory action.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Other supervisory action. 1777.12 Section 1777... in § 1777.11, OFHEO may at any time undertake additional supervisory steps and actions in the form of..., 4632 and 4636). In addition, OFHEO may take any such steps or actions with respect to an...

  14. Heterologous expression of the Monilinia fructicola CYP51 (MfCYP51) gene in Pichia pastoris confirms the mode of action of the novel fungicide, SYP-Z048

    PubMed Central

    Chen, Fengping; Lin, Dong; Wang, Jingyuan; Li, Botao; Duan, Hongxia; Liu, Junli; Liu, Xili

    2015-01-01

    The novel agricultural fungicide 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl] pyridine (SYP-Z048) developed by China Shenyang Research Institute of Chemical Industry has been confirmed to be an ergosterol biosynthesis inhibitor (EBI). Previous studies have shown that EBIs target the proteins from a range of genes, including CYP51, ERG2 and/or ERG24, and ERG27, which are involved in the ergosterol biosynthesis pathway. In the current study the ERG2, ERG24, and ERG27 genes were cloned from wild type and resistant mutants of Monilinia fructicola in an attempt to clarify the target site of SYP-Z048. Comparative analysis of the deduced aa sequence of these genes, as well as CYP51, revealed several point mutations that resulted in amino acid variation among the sensitive and resistant isolates. However, sensitivity assays indicated that only one, the substitution of phenylalanine (F) for the tyrosine (Y) at 136 in CYP51, was correlated with reduced sensitivity to SYP-Z048. Heterologous expression of MfCYP51-136Y (MfCYP136Y) and MfCYP51-136F (MfCYP136F) in Pichia pastoris revealed that MfCYP136F significantly reduced sensitivity to SYP-Z048, increasing the average EC50 of the transformants 11-fold relative to those carrying MfCYP136Y. However, neither the additional copy of MfCYP136Y nor multiple copies of MfCYP136F were found to reduce sensitivity relative to the empty vector control or single copy transformants, respectively. Molecular docking experiments using SYP-Z048 with HsCYP145Y and the mutated version HsCYP145F as substitutes for MfCYP136Y and MfCYP136F, respectively, indicated that the reduced affinity of HsCYP145F for SYP-Z048 resulted from the loss of a hydrogen bond between the fungicide and the active site. Taken together these results indicate that MfCYP51 is the major target site of SYP-Z048 in M. fructicola, which has important implications for the resistance management of this fungicide in the field. PMID:26042103

  15. Genes and Gene Therapy

    MedlinePlus

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  16. 78 FR 41915 - Procurement List Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-12

    ... From the Federal Register Online via the Government Publishing Office COMMITTEE FOR PURCHASE FROM... Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed additions to the procurement list...: Comments must be received on or before: August 12, 2013. ADDRESSES: Committee for Purchase From People...

  17. 78 FR 73504 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-06

    ... From the Federal Register Online via the Government Publishing Office COMMITTEE FOR PURCHASE FROM... Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to the Procurement List... Received On or Before: 1/6/2014. ADDRESSES: Committee for Purchase From People Who Are Blind or...

  18. 75 FR 58366 - Procurement List Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ... INFORMATION: Additions On 6/11/2010 (75 FR 33270-33271) and 7/16/2010 (75 FR 41451), the Committee for... entities. The major factors considered for this certification were: 1. The action will not result in any.../Location: Transcription Service, US Army, US Army War College, Carlisle, PA (Offsite: 5590 Derry...

  19. 75 FR 68328 - Procurement List; Proposed Addition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-05

    ... From the Federal Register Online via the Government Publishing Office COMMITTEE FOR PURCHASE FROM... Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed addition to the Procurement List... Received on or Before: 12/6/2010. ADDRESSES: Committee for Purchase From People Who Are Blind or...

  20. 75 FR 8927 - Procurement List; Proposed Addition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-26

    ... From the Federal Register Online via the Government Publishing Office COMMITTEE FOR PURCHASE FROM... Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed addition to the Procurement List... before: March 29, 2010. ADDRESSES: Committee for Purchase From People Who Are Blind or Severely...

  1. 76 FR 7824 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-11

    ... From the Federal Register Online via the Government Publishing Office COMMITTEE FOR PURCHASE FROM... Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed additions to the Procurement List... Received On or Before: 3/14/2011. ADDRESSES: Committee for Purchase From People Who Are Blind or...

  2. Inferences about Action Engage Action Systems

    ERIC Educational Resources Information Center

    Taylor, Lawrence J.; Lev-Ari, Shiri; Zwaan, Rolf A.

    2008-01-01

    Verbal descriptions of actions activate compatible motor responses [Glenberg, A. M., & Kaschak, M. P. (2002). Grounding language in action. "Psychonomic Bulletin & Review, 9", 558-565]. Previous studies have found that the motor processes for manual rotation are engaged in a direction-specific manner when a verb disambiguates the direction of…

  3. The SU(2) action-angle variables

    NASA Technical Reports Server (NTRS)

    Ellinas, Demosthenes

    1993-01-01

    Operator angle-action variables are studied in the frame of the SU(2) algebra, and their eigenstates and coherent states are discussed. The quantum mechanical addition of action-angle variables is shown to lead to a noncommutative Hopf algebra. The group contraction is used to make the connection with the harmonic oscillator.

  4. Developmental perception of the self and action.

    PubMed

    Saegusa, Ryo; Metta, Giorgio; Sandini, Giulio; Natale, Lorenzo

    2014-01-01

    This paper describes a developmental framework for action-driven perception in anthropomorphic robots. The key idea of the framework is that action generation develops the agent's perception of its own body and actions. Action-driven development is critical for identifying changing body parts and understanding the effects of actions in unknown or nonstationary environments. We embedded minimal knowledge into the robot's cognitive system in the form of motor synergies and actions to allow motor exploration. The robot voluntarily generates actions and develops the ability to perceive its own body and the effect that it generates on the environment. The robot, in addition, can compose this kind of learned primitives to perform complex actions and characterize them in terms of their sensory effects. After learning, the robot can recognize manipulative human behaviors with cross-modal anticipation for recovery of unavailable sensory modality, and reproduce the recognized actions afterward. We evaluated the proposed framework in the experiments with a real robot. In the experiments, we achieved autonomous body identification, learning of fixation, reaching and grasping actions, and developmental recognition of human actions as well as their reproduction.

  5. Action plan for the Tiger Team assessment report

    SciTech Connect

    Not Available

    1990-08-30

    This document contains responses and planned actions that address the findings of the Tiger Team Assessment of Brookhaven National Laboratory, June 1990. In addition, the document contains descriptions of the management and organizational structure to be used in conducting planned actions, root causes for the problems identified in the findings, responses, planned actions, schedules and milestones for completing planned actions, and, where known, costs associated with planned actions.

  6. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Fletcher, James C. (Inventor); Pratt, J. Richard (Inventor); St.clair, Terry L. (Inventor); Stoakley, Diane M. (Inventor); Burks, Harold D. (Inventor)

    1992-01-01

    A process for preparing polyimides having enhanced melt flow properties is described. The process consists of heating a mixture of a high molecular weight poly-(amic acid) or polyimide with a low molecular weight amic acid or imide additive in the range of 0.05 to 15 percent by weight of additive. The polyimide powders so obtained show improved processability, as evidenced by lower melt viscosity by capillary rheometry. Likewise, films prepared from mixtures of polymers with additives show improved processability with earlier onset of stretching by TMA.

  7. Polyimide processing additives

    NASA Technical Reports Server (NTRS)

    Pratt, J. Richard (Inventor); St.clair, Terry L. (Inventor); Stoakley, Diane M. (Inventor); Burks, Harold D. (Inventor)

    1993-01-01

    A process for preparing polyimides having enhanced melt flow properties is described. The process consists of heating a mixture of a high molecular weight poly-(amic acid) or polyimide with a low molecular weight amic acid or imide additive in the range of 0.05 to 15 percent by weight of the additive. The polyimide powders so obtained show improved processability, as evidenced by lower melt viscosity by capillary rheometry. Likewise, films prepared from mixtures of polymers with additives show improved processability with earlier onset of stretching by TMA.

  8. Clinical actionability enhanced through deep targeted sequencing of solid tumors

    PubMed Central

    Chen, Ken; Meric-Bernstam, Funda; Zhao, Hao; Zhang, Qingxiu; Ezzeddine, Nader; Tang, Lin-ya; Qi, Yuan; Mao, Yong; Chen, Tenghui; Chong, Zechen; Zhou, Wanding; Zheng, Xiaofeng; Johnson, Amber; Aldape, Kenneth D.; Routbort, Mark J.; Luthra, Rajyalakshmi; Kopetz, Scott; Davies, Michael A.; de Groot, John; Moulder, Stacy; Vinod, Ravi; Farhangfar, Carol J.; Shaw, Kenna Mills; Mendelsohn, John; Mills, Gordon B.; Eterovic, Agda Karina

    2015-01-01

    Background Further advances of targeted cancer therapy require comprehensive in-depth profiling of somatic mutations that are present in subpopulations of tumor cells in a clinical tumor sample. However, it is unclear to what extent such intra-tumor heterogeneity is present and whether it may affect clinical decision making. To unravel this challenge, we established a deep targeted sequencing platform to identify potentially actionable DNA alterations in tumor samples. Methods We assayed 515 FFPE tumor samples and matched germline (475 patients) from 11 disease sites by capturing and sequencing all the exons in 201 cancer related genes. Mutations, indels and copy number data were reported. Results We obtained a 1000-fold average sequencing depth and identified 4794 non-synonymous mutations in the samples analyzed, which 15.2% were present at less than 10% allele frequency. Most of these low level mutations occurred at known oncogenic hotspots and are likely functional. Identifying low level mutations improved identification of mutations in actionable genes in 118 (24.84%) patients, among which 47 (9.8%) would otherwise be unactionable. In addition, acquiring ultra-high depth also ensured a low false discovery rate (less than 2.2%) from FFPE samples. Conclusion Our results were as accurate as a commercially available CLIA-compliant hotspot panel, but allowed the detection of a higher number of mutations in actionable genes. Our study revealed the critical importance of acquiring and utilizing high depth in profiling clinical tumor samples and presented a very useful platform for implementing routine sequencing in a cancer care institution. PMID:25626406

  9. Androgen actions and the ovary.

    PubMed

    Walters, K A; Allan, C M; Handelsman, D J

    2008-03-01

    Although androgens and the androgen receptor (AR) have defining roles in male reproductive development and function, previously no role in female reproductive physiology beyond testosterone (T) as the precursor in estradiol (E(2)) biosynthesis was firmly established. Understanding the role and specific mechanisms of androgen action via the AR in the ovary has been limited by confusion on how to interpret results from pharmacological studies, because many androgens can be metabolized in vivo and in vitro to steroids that can also exert actions via the estrogen receptor (ESR). Recent genetic studies using mouse models with specific disruption of the Ar gene have highlighted the role that AR-mediated actions play in maintaining female fertility through key roles in the regulation of follicle health, development, and ovulation. Furthermore, these genetic studies have revealed that AR-mediated effects influence age-related female fertility, possibly via mechanisms acting predominantly at the hypothalamic-pituitary axis in a dose-dependent manner. This review focuses on combining the findings from pharmacological studies and novel genetic mouse models to unravel the roles of ovarian androgen actions in relation to female fertility and ovarian aging, as well as creating new insights into the role of androgens in androgen-associated reproductive disorders such as polycystic ovarian syndrome.

  10. Additional Types of Neuropathy

    MedlinePlus

    ... A A Listen En Español Additional Types of Neuropathy Charcot's Joint Charcot's Joint, also called neuropathic arthropathy, ... can stop bone destruction and aid healing. Cranial Neuropathy Cranial neuropathy affects the 12 pairs of nerves ...

  11. Food Additives and Hyperkinesis

    ERIC Educational Resources Information Center

    Wender, Ester H.

    1977-01-01

    The hypothesis that food additives are causally associated with hyperkinesis and learning disabilities in children is reviewed, and available data are summarized. Available from: American Medical Association 535 North Dearborn Street Chicago, Illinois 60610. (JG)

  12. Smog control fuel additives

    SciTech Connect

    Lundby, W.

    1993-06-29

    A method is described of controlling, reducing or eliminating, ozone and related smog resulting from photochemical reactions between ozone and automotive or industrial gases comprising the addition of iodine or compounds of iodine to hydrocarbon-base fuels prior to or during combustion in an amount of about 1 part iodine per 240 to 10,000,000 parts fuel, by weight, to be accomplished by: (a) the addition of these inhibitors during or after the refining or manufacturing process of liquid fuels; (b) the production of these inhibitors for addition into fuel tanks, such as automotive or industrial tanks; or (c) the addition of these inhibitors into combustion chambers of equipment utilizing solid fuels for the purpose of reducing ozone.

  13. Gene Expression Levels Are Correlated with Synonymous Codon Usage, Amino Acid Composition, and Gene Architecture in the Red Flour Beetle, Tribolium castaneum

    PubMed Central

    Williford, Anna; Demuth, Jeffery P.

    2012-01-01

    Gene expression levels correlate with multiple aspects of gene sequence and gene structure in phylogenetically diverse taxa, suggesting an important role of gene expression levels in the evolution of protein-coding genes. Here we present results of a genome-wide study of the influence of gene expression on synonymous codon usage, amino acid composition, and gene structure in the red flour beetle, Tribolium castaneum. Consistent with the action of translational selection, we find that synonymous codon usage bias increases with gene expression. However, the correspondence between tRNA gene copy number and optimal codons is weak. At the amino acid level, translational selection is suggested by the positive correlation between tRNA gene numbers and amino acid usage, which is stronger for highly expressed genes. In addition, there is a clear trend for increased use of metabolically cheaper, less complex amino acids as gene expression increases. tRNA gene numbers also correlate negatively with amino acid size/complexity (S/C) score indicating the coupling between translational selection and selection to minimize the use of large/complex amino acids. Interestingly, the analysis of 10 additional genomes suggests that the correlation between tRNA gene numbers and amino acid S/C score is widespread and might be explained by selection against negative consequences of protein misfolding. At the level of gene structure, three major trends are detected: 1) complete coding region length increases across low and intermediate expression levels but decreases in highly expressed genes; 2) the average intron size shows the opposite trend, first decreasing with expression, followed by a slight increase in highly expressed genes; and 3) intron density remains nearly constant across all expression levels. These changes in gene architecture are only in partial agreement with selection favoring reduced cost of biosynthesis. PMID:22826459

  14. [Neuroprotective actions of lithium].

    PubMed

    Hashimoto, Ryota; Fujimaki, Koichiro; Jeong, Mi Ra; Senatorov, Vladimir V; Christ, Lori; Leeds, Peter; Chuang, De-Maw; Takeda, Masatoshi

    2003-01-01

    Lithium has long been one of the primary drugs used to treat bipolar mood disorder. However, neither the etiology of this disease nor the therapeutic mechanism(s) of this drug is well understood. Several lines of clinical evidence suggest that lithium has neurotrophic actions. For example chronic lithium treatment increases the volume of gray matter and the content of N-acetyl-aspartate, a cell survival marker, in bipolar mood disorder patients (Moore et al., 2000). Moreover, treatment with this mood-stabilizer suppresses the decrease in the volume of the subgenual pre-frontal cortex found in bipolar patients (Drevets, 2001). To elucidate molecular mechanisms underlying the neuroprotective and neurotrophic actions of lithium, we employed a preparation of cultured cortical neurons prepared form embryonic rats. We found that treatment with therapeutic doses (0.2-1.2 mM) of lithium robustly protects cortical neurons from multiple insults, notably glutamate-induced excitotoxicity. The neuroprotection against glutamate excitotoxicity is time-dependent, requiring treatment for 5-6 days for maximal effect, and is associated with a reduction in NMDA receptor-mediated Ca2+ influx. The latter is correlated with a decrease in Tyrosine 1472 phosphorylation levels in the NR2B subunit of NMDA receptors and a loss of Src kinase activity which is involved in NR2B tyrosine phosphorylation. Neither the activity of total tyrosine protein kinase nor that of tyrosine protein phosphatase is affected by this drug, indicating the selectivity of the modulation. Lithium neuroprotection against excitotoxicity is inhibited by a BDNF-neutralizing antibody and K252a, a Trk antagonist. Lithium treatment time-dependently increases the intracellular level of BDNF in cortical neurons and activates its receptor, TrkB. The neuroprotection can be completely blocked by either heterozygous or homozygous knockout of the BDNF gene. These results suggest a central role of BDNF and TrkB in mediating the

  15. Conservation Action Handbook.

    ERIC Educational Resources Information Center

    National Rifle Association, Washington, DC.

    Conservation problems are identified, with some suggestions for action. General areas covered are: Wildlife Conservation, Soil Conservation, Clean Water, Air Pollution Action, and Outdoor Recreation Action. Appendices list private organizations or agencies concerned with natural resource use and/or management, congressional committees considering…

  16. Action in Development

    ERIC Educational Resources Information Center

    von Hofsten, Claes

    2007-01-01

    It is argued that cognitive development has to be understood in the functional perspective provided by actions. Actions reflect all aspects of cognitive development including the motives of the child, the problems to be solved, and the constraints and possibilities of the child's body and sensorimotor system. Actions are directed into the future…

  17. Participatory Action Research.

    ERIC Educational Resources Information Center

    Walker, Martha Lentz

    1993-01-01

    Describes aspects of participatory action research and considers advantages of using participatory action research in research by disabilities and rehabilitation researchers. Notes that participatory action research can be built into any rehabilitation research design but that it rests upon the recognition of persons with disabilities as integral…

  18. Putting Action in Perspective

    ERIC Educational Resources Information Center

    Lozano, Sandra C.; Hard, Bridgette Martin; Tversky, Barbara

    2007-01-01

    Embodied approaches to cognition propose that our own actions influence our understanding of the world. Do other people's actions also have this influence? The present studies show that perceiving another person's actions changes the way people think about objects in a scene. In Study 1, participants viewed a photograph and answered a question…

  19. Planning as Action Research

    ERIC Educational Resources Information Center

    de Gonzalez, Carmen Beatriz; Hernandez, Teresa; Kusch, Jim; Ryan, Charly

    2004-01-01

    Planning contains so much more than the written plan. Early in 2000, an invitation came from the Collaborative Action Research Network (CARN), to people experienced in action research who might want to help plan and present an action research event for elementary school science teachers in Venezuela, South America, in Autumn 2000. This article…

  20. Additive Manufacturing Infrared Inspection

    NASA Technical Reports Server (NTRS)

    Gaddy, Darrell

    2014-01-01

    Additive manufacturing is a rapid prototyping technology that allows parts to be built in a series of thin layers from plastic, ceramics, and metallics. Metallic additive manufacturing is an emerging form of rapid prototyping that allows complex structures to be built using various metallic powders. Significant time and cost savings have also been observed using the metallic additive manufacturing compared with traditional techniques. Development of the metallic additive manufacturing technology has advanced significantly over the last decade, although many of the techniques to inspect parts made from these processes have not advanced significantly or have limitations. Several external geometry inspection techniques exist such as Coordinate Measurement Machines (CMM), Laser Scanners, Structured Light Scanning Systems, or even traditional calipers and gages. All of the aforementioned techniques are limited to external geometry and contours or must use a contact probe to inspect limited internal dimensions. This presentation will document the development of a process for real-time dimensional inspection technique and digital quality record of the additive manufacturing process using Infrared camera imaging and processing techniques.

  1. Phenylethynyl Containing Reactive Additives

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Smith, Joseph G., Jr. (Inventor); Hergenrother, Paul M. (Inventor)

    2002-01-01

    Phenylethynyl containing reactive additives were prepared from aromatic diamine, containing phenylethvnvl groups and various ratios of phthalic anhydride and 4-phenylethynviphthalic anhydride in glacial acetic acid to form the imide in one step or in N-methyl-2-pvrrolidinone to form the amide acid intermediate. The reactive additives were mixed in various amounts (10% to 90%) with oligomers containing either terminal or pendent phenylethynyl groups (or both) to reduce the melt viscosity and thereby enhance processability. Upon thermal cure, the additives react and become chemically incorporated into the matrix and effect an increase in crosslink density relative to that of the host resin. This resultant increase in crosslink density has advantageous consequences on the cured resin properties such as higher glass transition temperature and higher modulus as compared to that of the host resin.

  2. Identification of Medically Actionable Secondary Findings in the 1000 Genomes

    PubMed Central

    Olfson, Emily; Cottrell, Catherine E.; Davidson, Nicholas O.; Gurnett, Christina A.; Heusel, Jonathan W.; Stitziel, Nathan O.; Chen, Li-Shiun; Hartz, Sarah; Nagarajan, Rakesh; Saccone, Nancy L.; Bierut, Laura J.

    2015-01-01

    The American College of Medical Genetics and Genomics (ACMG) recommends that clinical sequencing laboratories return secondary findings in 56 genes associated with medically actionable conditions. Our goal was to apply a systematic, stringent approach consistent with clinical standards to estimate the prevalence of pathogenic variants associated with such conditions using a diverse sequencing reference sample. Candidate variants in the 56 ACMG genes were selected from Phase 1 of the 1000 Genomes dataset, which contains sequencing information on 1,092 unrelated individuals from across the world. These variants were filtered using the Human Gene Mutation Database (HGMD) Professional version and defined parameters, appraised through literature review, and examined by a clinical laboratory specialist and expert physician. Over 70,000 genetic variants were extracted from the 56 genes, and filtering identified 237 variants annotated as disease causing by HGMD Professional. Literature review and expert evaluation determined that 7 of these variants were pathogenic or likely pathogenic. Furthermore, 5 additional truncating variants not listed as disease causing in HGMD Professional were identified as likely pathogenic. These 12 secondary findings are associated with diseases that could inform medical follow-up, including cancer predisposition syndromes, cardiac conditions, and familial hypercholesterolemia. The majority of the identified medically actionable findings were in individuals from the European (5/379) and Americas (4/181) ancestry groups, with fewer findings in Asian (2/286) and African (1/246) ancestry groups. Our results suggest that medically relevant secondary findings can be identified in approximately 1% (12/1092) of individuals in a diverse reference sample. As clinical sequencing laboratories continue to implement the ACMG recommendations, our results highlight that at least a small number of potentially important secondary findings can be selected for

  3. Multifunctional fuel additives

    SciTech Connect

    Baillargeon, D.J.; Cardis, A.B.; Heck, D.B.

    1991-03-26

    This paper discusses a composition comprising a major amount of a liquid hydrocarbyl fuel and a minor low-temperature flow properties improving amount of an additive product of the reaction of a suitable diol and product of a benzophenone tetracarboxylic dianhydride and a long-chain hydrocarbyl aminoalcohol.

  4. Biobased lubricant additives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fully biobased lubricants are those formulated using all biobased ingredients, i.e. biobased base oils and biobased additives. Such formulations provide the maximum environmental, safety, and economic benefits expected from a biobased product. Currently, there are a number of biobased base oils that...

  5. Representation of action in Parkinson's disease: imagining, observing, and naming actions.

    PubMed

    Poliakoff, Ellen

    2013-09-01

    People with Parkinson's disease (PD) exhibit slowed movements and difficulty in initiating movements. This review addresses the issue of whether or not cognitive representations of actions in PD are affected, alongside these motor problems. In healthy people, the motor system can be involved in tasks such as observing a graspable object or another person's action, or imagining and naming actions, in the absence of overt movement. As described in this review, the fact that the slowed real movements exhibited by PD patients are coupled with slower motor imagery and verb processing provides additional evidence for the involvement of the motor system in these processes. On the other hand, PD patients can still engage in motor imagery and action observation to some extent, which is encouraging for the use of these processes in rehabilitation. Findings across the different domains of action-representation reveal several important factors. First, the nature of action is critical: patients' performance in observation and naming tasks is influenced by whether or not the action is in their repertoire and by the extent of motion required to execute the action. Second, people with PD may use alternative or compensatory mechanisms to represent actions, such as relying more on a third-person perspective or a visual strategy. Third, people with PD show a lack of specificity, responding as strongly to stimuli related and unrelated to actions. Investigating action-representation in PD has implications for our understanding of both the symptoms of PD and the cognitive representation of actions in the healthy system.

  6. Vinyl capped addition polyimides

    NASA Technical Reports Server (NTRS)

    Vannucci, Raymond D. (Inventor); Malarik, Diane C. (Inventor); Delvigs, Peter (Inventor)

    1991-01-01

    Polyimide resins (PMR) are generally useful where high strength and temperature capabilities are required (at temperatures up to about 700 F). Polyimide resins are particularly useful in applications such as jet engine compressor components, for example, blades, vanes, air seals, air splitters, and engine casing parts. Aromatic vinyl capped addition polyimides are obtained by reacting a diamine, an ester of tetracarboxylic acid, and an aromatic vinyl compound. Low void materials with improved oxidative stability when exposed to 700 F air may be fabricated as fiber reinforced high molecular weight capped polyimide composites. The aromatic vinyl capped polyimides are provided with a more aromatic nature and are more thermally stable than highly aliphatic, norbornenyl-type end-capped polyimides employed in PMR resins. The substitution of aromatic vinyl end-caps for norbornenyl end-caps in addition polyimides results in polymers with improved oxidative stability.

  7. Tackifier for addition polyimides

    NASA Technical Reports Server (NTRS)

    Butler, J. M.; St.clair, T. L.

    1980-01-01

    A modification to the addition polyimide, LaRC-160, was prepared to improve tack and drape and increase prepeg out-time. The essentially solventless, high viscosity laminating resin is synthesized from low cost liquid monomers. The modified version takes advantage of a reactive, liquid plasticizer which is used in place of solvent and helps solve a major problem of maintaining good prepeg tack and drape, or the ability of the prepeg to adhere to adjacent plies and conform to a desired shape during the lay up process. This alternate solventless approach allows both longer life of the polymer prepeg and the processing of low void laminates. This approach appears to be applicable to all addition polyimide systems.

  8. Electrophilic addition of astatine

    SciTech Connect

    Norseev, Yu.V.; Vasaros, L.; Nhan, D.D.; Huan, N.K.

    1988-03-01

    It has been shown for the first time that astatine is capable of undergoing addition reactions to unsaturated hydrocarbons. A new compound of astatine, viz., ethylene astatohydrin, has been obtained, and its retention numbers of squalane, Apiezon, and tricresyl phosphate have been found. The influence of various factors on the formation of ethylene astatohydrin has been studied. It has been concluded on the basis of the results obtained that the univalent cations of astatine in an acidic medium is protonated hypoastatous acid.

  9. Functional Generalized Additive Models.

    PubMed

    McLean, Mathew W; Hooker, Giles; Staicu, Ana-Maria; Scheipl, Fabian; Ruppert, David

    2014-01-01

    We introduce the functional generalized additive model (FGAM), a novel regression model for association studies between a scalar response and a functional predictor. We model the link-transformed mean response as the integral with respect to t of F{X(t), t} where F(·,·) is an unknown regression function and X(t) is a functional covariate. Rather than having an additive model in a finite number of principal components as in Müller and Yao (2008), our model incorporates the functional predictor directly and thus our model can be viewed as the natural functional extension of generalized additive models. We estimate F(·,·) using tensor-product B-splines with roughness penalties. A pointwise quantile transformation of the functional predictor is also considered to ensure each tensor-product B-spline has observed data on its support. The methods are evaluated using simulated data and their predictive performance is compared with other competing scalar-on-function regression alternatives. We illustrate the usefulness of our approach through an application to brain tractography, where X(t) is a signal from diffusion tensor imaging at position, t, along a tract in the brain. In one example, the response is disease-status (case or control) and in a second example, it is the score on a cognitive test. R code for performing the simulations and fitting the FGAM can be found in supplemental materials available online.

  10. Nonclassical Vitamin D Action

    PubMed Central

    Zittermann, Armin; Gummert, Jan F.

    2010-01-01

    It is becoming increasingly clear that vitamin D has a broad range of actions in the human body. Besides its well-known effects on calcium/phosphate homeostasis, vitamin D influences muscle function, cardiovascular homeostasis, nervous function, and the immune response. Vitamin D deficiency/insufficiency has been associated with muscle weakness and a high incidence of various chronic diseases such as cardiovascular disease, cancer, multiple sclerosis, and type 1 and 2 diabetes. Most importantly, low vitamin D status has been found to be an independent predictor of all-cause mortality. Several recent randomized controlled trials support the assumption that vitamin D can improve muscle strength, glucose homeostasis, and cardiovascular risk markers. In addition, vitamin D may reduce cancer incidence and elevated blood pressure. Since the prevalence of vitamin D deficiency/insufficiency is high throughout the world, there is a need to improve vitamin D status in the general adult population. However, the currently recommended daily vitamin D intake of 5-15 µg is too low to achieve an adequate vitamin D status in individuals with only modest skin synthesis. Thus, there is a need to recommend a vitamin D intake that is effective for achieving adequate circulating 25-hydroxyvitamin D concentrations (>75 nmol/L). PMID:22254030

  11. Defendants challenge class action certification.

    PubMed

    Dubin, C S; Wadleigh, J

    1995-04-01

    The National Hemophilia Foundation (NHF) and the manufacturers of Anti-Hemophilia Factor Concentrates (AHF) are being sued in a class action case for ignoring and downplaying risks of HIV infection from AHF in order to enhance their financial gain. The defendants in the case, however, have challenged the class action certification. Their Petition for a Writ of Mandamus argues that a class action lawsuit is not an appropriate legal vehicle for this type of case because, among other reasons, it will place an entire industry's survival in the hands of a single jury decision. The two primary challenges to certification by the petition are that 1) it would complicate hemophilia/AIDS litigation and not simplify it, and 2) there is no common definition of negligence throughout state law. With certification in question, it is conceivable, according to attorney David Shrager, "that hundreds or even thousands of additional claims will now be filed in state and Federal courts throughout the country." Essentially, the defense against the Writ argues that the defendants knew in the 1960s of the high risk from known and new viruses in the plasma pools, that they had a duty to reduce such risk, and that they not only failed to withdraw their products from the market, they downplayed the harm done to persons who used contaminated AHF by making misleading statements. The class action trial is scheduled to begin October 2, 1995. PMID:11362336

  12. The neural substrates of action identification

    PubMed Central

    Kozak, Megan N.; Wegner, Daniel M.; Reid, Marguerite E.; Yu, Henry H.; Blair, R. J. R.

    2010-01-01

    Mentalization is the process by which an observer views a target as possessing higher cognitive faculties such as goals, intentions and desires. Mentalization can be assessed using action identification paradigms, in which observers choose mentalistic (goals-focused) or mechanistic (action-focused) descriptions of targets’ actions. Neural structures that play key roles in inferring goals and intentions from others’ observed or imagined actions include temporo-parietal junction, ventral premotor cortex and extrastriate body area. We hypothesized that these regions play a role in action identification as well. Data collected using functional magnetic resonance imaging (fMRI) confirmed our predictions that activity in ventral premotor cortex and middle temporal gyrus near the extrastriate body area varies both as a function of the valence of the target and the extent to which actions are identified as goal-directed. In addition, the inferior parietal lobule is preferentially engaged when participants identify the actions of mentalized targets. Functional connectivity analyses suggest support from other regions, including the medial prefrontal cortex and amygdala, during mentalization. We found correlations between action identification and Autism Quotient scores, suggesting that understanding the neural correlates of action identification may enhance our understanding of the underpinnings of essential social cognitive processes. PMID:20150343

  13. Reversible Michael additions: covalent inhibitors and prodrugs.

    PubMed

    Johansson, Martin H

    2012-11-01

    Covalent inhibition is an efficient molecular mechanism for inhibiting enzymes or modulating the function of proteins and is found in the action of many drugs and biologically active natural products. However, it is has been less appreciated that the formation of covalent bonds can be reversible or irreversible. This review focuses on biologically active compounds that are Michael acceptors and how the reversible nature of the Michael addition reaction influences biological activity and how this can be exploited in designing prodrugs.

  14. Food Additives Permitted for Direct Addition to Food for Human Consumption; Folic Acid. Final rule.

    PubMed

    2016-04-15

    The Food and Drug Administration (FDA or we) is amending the food additive regulations to provide for the safe use of folic acid in corn masa flour. We are taking this action in response to a food additive petition filed jointly by Gruma Corporation, Spina Bifida Association, March of Dimes Foundation, American Academy of Pediatrics, Royal DSM N.V., and National Council of La Raza.

  15. Food Additives Permitted for Direct Addition to Food for Human Consumption; Folic Acid. Final rule.

    PubMed

    2016-04-15

    The Food and Drug Administration (FDA or we) is amending the food additive regulations to provide for the safe use of folic acid in corn masa flour. We are taking this action in response to a food additive petition filed jointly by Gruma Corporation, Spina Bifida Association, March of Dimes Foundation, American Academy of Pediatrics, Royal DSM N.V., and National Council of La Raza. PMID:27101640

  16. Molecular mechanisms of DAX1 action.

    PubMed

    Iyer, Anita K; McCabe, Edward R B

    2004-01-01

    DAX1 (dosage sensitive sex reversal (DSS), adrenal hypoplasia congenita (AHC) critical region on the X chromosome, gene 1) encoded by the gene NR0B1, is an unusual orphan nuclear receptor that when mutated causes AHC with associated hypogonadotropic hypogonadism (HH), and when duplicated causes DSS. DAX1 expression has been shown in all regions of the hypothalamic-pituitary-adrenal-gonadal (HPAG) axis during development and in adult tissues, suggesting a critical role for DAX1 in the normal development and function of this axis. Steroidogenic factor 1 (SF1, NR5A1) knockout mice show similar developmental defects as AHC and HH patients, but paradoxically, DAX1 is a negative coregulator of SF1 transactivation. The function of DAX1 as an antagonist of SF1 in gonadal development is consistent with the fact that in humans, duplication of the region of the X chromosome containing DAX1 causes a similar phenotype as mutations in SF1. However, how disruption of DAX1 leads to adrenal, hypothalamic, and pituitary developmental defects similar to SF1 disruption remains to be clarified. The exact mechanism of DAX1 action in each of these tissues during adulthood and critical stages of development are not fully understood. Recent evidence suggests a broader functional role for DAX1 as a negative coregulator of estrogen receptor (ER, NR3A1-2), liver receptor homologue-1 (LRH-1, NR5A2), androgen receptor (AR, NR3C4), and progesterone receptor (PR, NR3C3), each by distinct repression mechanisms. DAX1 may have pleiotropic roles in addition to its function as a negative regulator of steroidogenesis during the development and adult function of the HPAG axis.

  17. Stereoscopically Observing Manipulative Actions.

    PubMed

    Ferri, S; Pauwels, K; Rizzolatti, G; Orban, G A

    2016-08-01

    The purpose of this study was to investigate the contribution of stereopsis to the processing of observed manipulative actions. To this end, we first combined the factors "stimulus type" (action, static control, and dynamic control), "stereopsis" (present, absent) and "viewpoint" (frontal, lateral) into a single design. Four sites in premotor, retro-insular (2) and parietal cortex operated specifically when actions were viewed stereoscopically and frontally. A second experiment clarified that the stereo-action-specific regions were driven by actions moving out of the frontoparallel plane, an effect amplified by frontal viewing in premotor cortex. Analysis of single voxels and their discriminatory power showed that the representation of action in the stereo-action-specific areas was more accurate when stereopsis was active. Further analyses showed that the 4 stereo-action-specific sites form a closed network converging onto the premotor node, which connects to parietal and occipitotemporal regions outside the network. Several of the specific sites are known to process vestibular signals, suggesting that the network combines observed actions in peripersonal space with gravitational signals. These findings have wider implications for the function of premotor cortex and the role of stereopsis in human behavior. PMID:27252350

  18. Stereoscopically Observing Manipulative Actions

    PubMed Central

    Ferri, S.; Pauwels, K.; Rizzolatti, G.; Orban, G. A.

    2016-01-01

    The purpose of this study was to investigate the contribution of stereopsis to the processing of observed manipulative actions. To this end, we first combined the factors “stimulus type” (action, static control, and dynamic control), “stereopsis” (present, absent) and “viewpoint” (frontal, lateral) into a single design. Four sites in premotor, retro-insular (2) and parietal cortex operated specifically when actions were viewed stereoscopically and frontally. A second experiment clarified that the stereo-action-specific regions were driven by actions moving out of the frontoparallel plane, an effect amplified by frontal viewing in premotor cortex. Analysis of single voxels and their discriminatory power showed that the representation of action in the stereo-action-specific areas was more accurate when stereopsis was active. Further analyses showed that the 4 stereo-action-specific sites form a closed network converging onto the premotor node, which connects to parietal and occipitotemporal regions outside the network. Several of the specific sites are known to process vestibular signals, suggesting that the network combines observed actions in peripersonal space with gravitational signals. These findings have wider implications for the function of premotor cortex and the role of stereopsis in human behavior. PMID:27252350

  19. Decoding actions at different levels of abstraction.

    PubMed

    Wurm, Moritz F; Lingnau, Angelika

    2015-05-20

    Brain regions that mediate action understanding must contain representations that are action specific and at the same time tolerate a wide range of perceptual variance. Whereas progress has been made in understanding such generalization mechanisms in the object domain, the neural mechanisms to conceptualize actions remain unknown. In particular, there is ongoing dissent between motor-centric and cognitive accounts whether premotor cortex or brain regions in closer relation to perceptual systems, i.e., lateral occipitotemporal cortex, contain neural populations with such mapping properties. To date, it is unclear to which degree action-specific representations in these brain regions generalize from concrete action instantiations to abstract action concepts. However, such information would be crucial to differentiate between motor and cognitive theories. Using ROI-based and searchlight-based fMRI multivoxel pattern decoding, we sought brain regions in human cortex that manage the balancing act between specificity and generality. We investigated a concrete level that distinguishes actions based on perceptual features (e.g., opening vs closing a specific bottle), an intermediate level that generalizes across movement kinematics and specific objects involved in the action (e.g., opening different bottles with cork or screw cap), and an abstract level that additionally generalizes across object category (e.g., opening bottles or boxes). We demonstrate that the inferior parietal and occipitotemporal cortex code actions at abstract levels whereas the premotor cortex codes actions at the concrete level only. Hence, occipitotemporal, but not premotor, regions fulfill the necessary criteria for action understanding. This result is compatible with cognitive theories but strongly undermines motor theories of action understanding. PMID:25995462

  20. Performance Boosting Additive

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Mainstream Engineering Corporation was awarded Phase I and Phase II contracts from Goddard Space Flight Center's Small Business Innovation Research (SBIR) program in early 1990. With support from the SBIR program, Mainstream Engineering Corporation has developed a unique low cost additive, QwikBoost (TM), that increases the performance of air conditioners, heat pumps, refrigerators, and freezers. Because of the energy and environmental benefits of QwikBoost, Mainstream received the Tibbetts Award at a White House Ceremony on October 16, 1997. QwikBoost was introduced at the 1998 International Air Conditioning, Heating, and Refrigeration Exposition. QwikBoost is packaged in a handy 3-ounce can (pressurized with R-134a) and will be available for automotive air conditioning systems in summer 1998.

  1. Sewage sludge additive

    NASA Technical Reports Server (NTRS)

    Kalvinskas, J. J.; Mueller, W. A.; Ingham, J. D. (Inventor)

    1980-01-01

    The additive is for a raw sewage treatment process of the type where settling tanks are used for the purpose of permitting the suspended matter in the raw sewage to be settled as well as to permit adsorption of the dissolved contaminants in the water of the sewage. The sludge, which settles down to the bottom of the settling tank is extracted, pyrolyzed and activated to form activated carbon and ash which is mixed with the sewage prior to its introduction into the settling tank. The sludge does not provide all of the activated carbon and ash required for adequate treatment of the raw sewage. It is necessary to add carbon to the process and instead of expensive commercial carbon, coal is used to provide the carbon supplement.

  2. Perspectives on Additive Manufacturing

    NASA Astrophysics Data System (ADS)

    Bourell, David L.

    2016-07-01

    Additive manufacturing (AM) has skyrocketed in visibility commercially and in the public sector. This article describes the development of this field from early layered manufacturing approaches of photosculpture, topography, and material deposition. Certain precursors to modern AM processes are also briefly described. The growth of the field over the last 30 years is presented. Included is the standard delineation of AM technologies into seven broad categories. The economics of AM part generation is considered, and the impacts of the economics on application sectors are described. On the basis of current trends, the future outlook will include a convergence of AM fabricators, mass-produced AM fabricators, enabling of topology optimization designs, and specialization in the AM legal arena. Long-term developments with huge impact are organ printing and volume-based printing.

  3. Sarks as additional fermions

    NASA Astrophysics Data System (ADS)

    Agrawal, Jyoti; Frampton, Paul H.; Jack Ng, Y.; Nishino, Hitoshi; Yasuda, Osamu

    1991-03-01

    An extension of the standard model is proposed. The gauge group is SU(2) X ⊗ SU(3) C ⊗ SU(2) S ⊗ U(1) Q, where all gauge symmetries are unbroken. The colour and electric charge are combined with SU(2) S which becomes strongly coupled at approximately 500 GeV and binds preons to form fermionic and vector bound states. The usual quarks and leptons are singlets under SU(2) X but additional fermions, called sarks. transform under it and the electroweak group. The present model explains why no more than three light quark-lepton families can exist. Neutral sark baryons, called narks, are candidates for the cosmological dark matter having the characteristics designed for WIMPS. Further phenomenological implications of sarks are analyzed i including electron-positron annihilation. Z 0 decay, flavor-changing neutral currents. baryon-number non-conservation, sarkonium and the neutron electric dipole moment.

  4. Action video game experience affects oculomotor performance.

    PubMed

    West, Greg L; Al-Aidroos, Naseem; Pratt, Jay

    2013-01-01

    Action video games have been show to affect a variety of visual and cognitive processes. There is, however, little evidence of whether playing video games can also affect motor action. To investigate the potential link between experience playing action video games and changes in oculomotor action, we tested habitual action video game players (VGPs) and non-video game players (NVGPs) in a saccadic trajectory deviation task. We demonstrate that spatial curvature of a saccadic trajectory towards or away from distractor is profoundly different between VGPs and NVGPs. In addition, task performance accuracy improved over time only in VGPs. Results are discussed in the context of the competing interplay between stimulus-driven motor programming and top-down inhibition during oculomotor execution.

  5. Integrated gene set analysis for microRNA studies

    PubMed Central

    Garcia-Garcia, Francisco; Panadero, Joaquin; Dopazo, Joaquin; Montaner, David

    2016-01-01

    Motivation: Functional interpretation of miRNA expression data is currently done in a three step procedure: select differentially expressed miRNAs, find their target genes, and carry out gene set overrepresentation analysis. Nevertheless, major limitations of this approach have already been described at the gene level, while some newer arise in the miRNA scenario. Here, we propose an enhanced methodology that builds on the well-established gene set analysis paradigm. Evidence for differential expression at the miRNA level is transferred to a gene differential inhibition score which is easily interpretable in terms of gene sets or pathways. Such transferred indexes account for the additive effect of several miRNAs targeting the same gene, and also incorporate cancellation effects between cases and controls. Together, these two desirable characteristics allow for more accurate modeling of regulatory processes. Results: We analyze high-throughput sequencing data from 20 different cancer types and provide exhaustive reports of gene and Gene Ontology-term deregulation by miRNA action. Availability and Implementation: The proposed methodology was implemented in the Bioconductor library mdgsa. http://bioconductor.org/packages/mdgsa. For the purpose of reproducibility all of the scripts are available at https://github.com/dmontaner-papers/gsa4mirna Contact: david.montaner@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27324197

  6. Caffeine's Vascular Mechanisms of Action

    PubMed Central

    Echeverri, Darío; Montes, Félix R.; Cabrera, Mariana; Galán, Angélica; Prieto, Angélica

    2010-01-01

    Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial. PMID:21188209

  7. Acute alteration of cardiac ECG, action potential, I{sub Kr} and the human ether-a-go-go-related gene (hERG) K{sup +} channel by PCB 126 and PCB 77

    SciTech Connect

    Park, Mi-Hyeong; Park, Won Sun; Jo, Su-Hyun

    2012-07-01

    Polychlorinated biphenyls (PCBs) have been known as serious persistent organic pollutants (POPs), causing developmental delays and motor dysfunction. We have investigated the effects of two PCB congeners, 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) on ECG, action potential, and the rapidly activating delayed rectifier K{sup +} current (I{sub Kr}) of guinea pigs' hearts, and hERG K{sup +} current expressed in Xenopus oocytes. PCB 126 shortened the corrected QT interval (QTc) of ECG and decreased the action potential duration at 90% (APD{sub 90}), and 50% of repolarization (APD{sub 50}) (P < 0.05) without changing the action potential duration at 20% (APD{sub 20}). PCB 77 decreased APD{sub 20} (P < 0.05) without affecting QTc, APD{sub 90}, and APD{sub 50}. The PCB 126 increased the I{sub Kr} in guinea-pig ventricular myocytes held at 36 °C and hERG K{sup +} current amplitude at the end of the voltage steps in voltage-dependent mode (P < 0.05); however, PCB 77 did not change the hERG K{sup +} current amplitude. The PCB 77 increased the diastolic Ca{sup 2+} and decreased Ca{sup 2+} transient amplitude (P < 0.05), however PCB 126 did not change. The results suggest that PCB 126 shortened the QTc and decreased the APD{sub 90} possibly by increasing I{sub Kr}, while PCB 77 decreased the APD{sub 20} possibly by other modulation related with intracellular Ca{sup 2+}. The present data indicate that the environmental toxicants, PCBs, can acutely affect cardiac electrophysiology including ECG, action potential, intracellular Ca{sup 2+}, and channel activity, resulting in toxic effects on the cardiac function in view of the possible accumulation of the PCBs in human body. -- Highlights: ► PCBs are known as serious environmental pollutants and developmental disruptors. ► PCB 126 shortened QT interval of ECG and action potential duration. ► PCB 126 increased human ether-a-go-go-related K{sup +} current and I{sub Kr}. ► PCB

  8. Who Needs Affirmative Action.

    ERIC Educational Resources Information Center

    Ginger, Ann Fagan

    1979-01-01

    Affirmative action and reverse discrimination are discussed. Facts that were omitted from the court record on the Bakke case are examined. The need for encouraging minority students and women to continue to press for school admission and for lawyers to continue to press affirmative action suits is stressed. (MC)

  9. Community-Action Learning

    ERIC Educational Resources Information Center

    Bell, Sarah; Mattern, Mark; Telin, Mike

    2007-01-01

    This paper describes and analyzes an undergraduate course entitled Public Interest Research in which students learn research methods by conducting research on behalf of one or more community organizations. Students' work is conceived of as community action learning, a combination of participatory action research and service learning, emphasizing…

  10. Preferential Affirmative Action.

    ERIC Educational Resources Information Center

    Bell, Derrick A., Jr.

    1982-01-01

    Discusses the philosophical rationale for preferential affirmative action presented by Daniel C. Maguire in "A New American Justice." Maintains that self-interest bars present society's acceptance of Maguire's theories of justice, as demonstrated in negative reactions to the Harvard Law Review's affirmative action plan. (MJL)

  11. Action Learning in China

    ERIC Educational Resources Information Center

    Marquardt, Michael J.

    2015-01-01

    Action learning was introduced into China less than 20 years ago, but has rapidly become a valuable tool for organizations seeking to solve problems, develop their leaders, and become learning organizations. This article provides an historical overview of action learning in China, its cultural underpinnings, and five case studies. It concludes…

  12. Handbook for Ecology Action.

    ERIC Educational Resources Information Center

    Eber, Ronald

    This handbook has been compiled to aid concerned individuals and ecology groups more adequately define their goals, initiate good programs, and take effective action. It examines the ways a group of working individuals can become involved in action programs for ecological change. Part 1 deals with organization, preliminary organizing, structuring,…

  13. Renormalized action improvements

    SciTech Connect

    Zachos, C.

    1984-01-01

    Finite lattice spacing artifacts are suppressed on the renormalized actions. The renormalized action trajectories of SU(N) lattice gauge theories are considered from the standpoint of the Migdal-Kadanoff approximation. The minor renormalized trajectories which involve representations invariant under the center are discussed and quantified. 17 references.

  14. Action Research and Policy

    ERIC Educational Resources Information Center

    Foreman-Peck, Lorraine; Murray, Jane

    2008-01-01

    This article examines the relationship between action research and policy and the kind of confidence teachers, policy makers and other potential users may have in such research. Many published teacher action research accounts are criticised on the grounds that they do not fully meet the conventional standards for reporting social scientific…

  15. ACTION. Annual Report 1974.

    ERIC Educational Resources Information Center

    ACTION, Washington, DC.

    In this report are described projects and activities undertaken by ACTION's volunteer programs in 1974. After an introduction that notes accomplishments of the past year, a review of domestic operations discusses such programs as VISTA, University Year for ACTION, National Student Volunteer Program, Foster Grandparent Program, and others according…

  16. Reduced attentional capture in action video game players.

    PubMed

    Chisholm, Joseph D; Hickey, Clayton; Theeuwes, Jan; Kingstone, Alan

    2010-04-01

    Recent studies indicate that playing action video games improves performance on a number of attention-based tasks. However, it remains unclear whether action video game experience primarily affects endogenous or exogenous forms of spatial orienting. To examine this issue, action video game players and non-action video game players performed an attentional capture task. The results show that action video game players responded quicker than non-action video game players, both when a target appeared in isolation and when a salient, task-irrelevant distractor was present in the display. Action video game players additionally showed a smaller capture effect than did non-action video game players. When coupled with the findings of previous studies, the collective evidence indicates that extensive experience with action video games may enhance players' top-down attentional control, which, in turn, can modulate the negative effects of bottom-up attentional capture.

  17. Evidence for showing gene/protein name suggestions in bioscience literature search interfaces.

    PubMed

    Divoli, Anna; Hearst, Marti A; Wooldridge, Michael A

    2008-01-01

    This paper reports on the results of two questionnaires asking biologists about the incorporation of text-extracted entity information, specifically gene and protein names, into bioscience literature search user interfaces. Among the findings are that study participants want to see gene/protein metadata in combination with organism information; that a significant proportion would like to see gene names grouped by type (synonym, homolog, etc.), and that most participants want to see information that the system is confident about immediately, and see less certain information after taking additional action. These results inform future interface designs.

  18. Conscious Vision in Action.

    PubMed

    Briscoe, Robert; Schwenkler, John

    2015-09-01

    It is natural to assume that the fine-grained and highly accurate spatial information present in visual experience is often used to guide our bodily actions. Yet this assumption has been challenged by proponents of the Two Visual Systems Hypothesis (TVSH), according to which visuomotor programming is the responsibility of a "zombie" processing stream whose sources of bottom-up spatial information are entirely non-conscious (Clark, 2007, 2009; Goodale & Milner, 1992, 2004a; Milner & Goodale, 1995/2006, 2008). In many formulations of TVSH, the role of conscious vision in action is limited to "recognizing objects, selecting targets for action, and determining what kinds of action, broadly speaking, to perform" (Clark, 2007, p. 570). Our aim in this study is to show that the available evidence not only fails to support this dichotomous view but actually reveals a significant role for conscious vision in motor programming, especially for actions that require deliberate attention. PMID:25845648

  19. Points of regulation for auxin action.

    PubMed

    Zazimalova, E; Napier, R M

    2003-03-01

    There have been few examples of the application of our growing knowledge of hormone action to crop improvement. In this review we discuss what is known about the critical points regulating auxin action. We examine auxin metabolism, transport, perception and signalling and identify genes and proteins that might be keys to regulation, particularly the rate-limiting steps in various pathways. Certain mutants show that substrate flow in biosynthesis can be limiting. To date there is little information available on the genes and proteins of catabolism. There have been several auxin transport proteins and some elegant transport physiology described recently, and the potential for using transport proteins to manage free indole-3-acetic acid (IAA) concentrations is discussed. Free IAA is very mobile, and so while it may be more practical to control auxin action through managing the receptor and signalling pathways, the candidate genes and proteins through which this can be done remain largely unknown. From the available evidence, it is clear that the reason for so few commercial applications arising from the control of auxin action is that knowledge is still limited. PMID:12789411

  20. Following the Action in Action Learning: Towards Ethnomethodological Studies of (Critical) Action Learning

    ERIC Educational Resources Information Center

    Fox, Steve

    2009-01-01

    Action learning is a pedagogical practice that helps participants learn by talking about their workplace action with fellow participants ("comrades in adversity") in their action learning set. This paper raises questions about the action in action learning, such as: how do members of an action learning set learn from and through each other? How do…

  1. Corrective Action Investigation Plan for Corrective Action Unit 563: Septic Systems, Nevada Test Site, Nevada, with Errata Sheet, Revision 0

    SciTech Connect

    Alfred Wickline

    2007-01-01

    Corrective Action Unit 563, Septic Systems, is located in Areas 3 and 12 of the Nevada Test Site, which is 65 miles northwest of Las Vegas, Nevada. Corrective Action Unit 563 is comprised of the four corrective action sites (CASs) below: • 03-04-02, Area 3 Subdock Septic Tank • 03-59-05, Area 3 Subdock Cesspool • 12-59-01, Drilling/Welding Shop Septic Tanks • 12-60-01, Drilling/Welding Shop Outfalls These sites are being investigated because existing information on the nature and extent of potential contamination is insufficient to evaluate and recommend corrective action alternatives. Additional information will be obtained by conducting a corrective action investigation (CAI) before evaluating corrective action alternatives and selecting the appropriate corrective action for each CAS. The results of the field investigation will support a defensible evaluation of viable corrective action alternatives that will be presented in the Corrective Action Decision Document.

  2. Overview of herbicide mechanisms of action.

    PubMed Central

    Duke, S O

    1990-01-01

    Commercial herbicides exhibit many different mechanisms of action. Several enzymes involved in biosynthesis of amino acids are sites of action for herbicides. A large number of different herbicide classes inhibit photosynthesis by binding to the quinone-binding protein, D-1, to prevent photosynthetic electron transfer. Several different types of herbicides apparently cause accumulation of photodynamic porphyrins by inhibiting protoporphyrinogen oxidase. Bipyridyliums and heteropentalenes cause the production of superoxide radicals by energy diversion from photosystem I of photosynthesis. Lipid synthesis is the site of action of a broad array of herbicides used in controlling monocot weeds. Herbicides of several classes apparently act by inhibiting mitosis through direct interaction with tubulin. Several other molecular sites of herbicide action are known. Despite a growing body of knowledge, the exact molecular sites of action of many herbicides are unknown. Some herbicides are known to have more than one site of action. Virtually all knowledge of herbicide structure-activity relationships is semiempirical. In addition to site of action structure-activity relationships, herbicide structure and chemical properties also strongly influence absorption, translocation, bioactivation, and environmental stability. Considering how little is known about all the potential sites of herbicide action, it is unlikely that during the next decade more than a relatively small number of site-specific herbicide structure-activity relationships will be developed. PMID:1980104

  3. Binding space and time through action.

    PubMed

    Binetti, N; Hagura, N; Fadipe, C; Tomassini, A; Walsh, V; Bestmann, S

    2015-04-22

    Space and time are intimately coupled dimensions in the human brain. Several lines of evidence suggest that space and time are processed by a shared analogue magnitude system. It has been proposed that actions are instrumental in establishing this shared magnitude system. Here we provide evidence in support of this hypothesis, by showing that the interaction between space and time is enhanced when magnitude information is acquired through action. Participants observed increases or decreases in the height of a visual bar (spatial magnitude) while judging whether a simultaneously presented sequence of acoustic tones had accelerated or decelerated (temporal magnitude). In one condition (Action), participants directly controlled the changes in bar height with a hand grip device, whereas in the other (No Action), changes in bar height were externally controlled but matched the spatial/temporal profile of the Action condition. The sign of changes in bar height biased the perceived rate of the tone sequences, where increases in bar height produced apparent increases in tone rate. This effect was amplified when the visual bar was actively controlled in the Action condition, and the strength of the interaction was scaled by the magnitude of the action. Subsequent experiments ruled out that this was simply explained by attentional factors, and additionally showed that a monotonic mapping is also required between grip force and bar height in order to bias the perception of the tones. These data provide support for an instrumental role of action in interfacing spatial and temporal quantities in the brain.

  4. Action spectra again?

    PubMed

    Coohill, T P

    1991-11-01

    Action spectroscopy has a long history and is of central importance to photobiological studies. Action spectra were among the first assays to point to chlorophyll as the molecule most responsible for plant growth and to DNA as the genetic material. It is useful to construct action spectra early in the investigation of new areas of photobiological research in an attempt to determine the wavelength limits of the radiation region causing the studied response. But due to the severe absorption of ultraviolet (UV) radiation by biological samples, UV action spectra were first limited to small cells (bacteria and fungi). Advances in techniques (e.g. single cell culture) and analysis allowed accurate action spectra to be reported even for mammalian cells. But precise analytical action spectra are often difficult to obtain when large, pigmented, or groups of cells are investigated. Here some action spectra are limited in interpretation and merely supply a wavelength vs effect curve. When polychromatic sources are employed, the interpretation of action spectra is even more complex and formidable. But such polychromatic action spectra can be more directly related to ambient responses. Since precise action spectra usually require the completion of a relatively large number of careful experiments using somewhat sophisticated equipment over a range of at least six wavelengths, they are often not pursued. But they remain central to the elucidation of the effect being studied. The worldwide community has agreed that stratospheric ozone is depleting, with the possibility of a consequent rise in the amount of UV-B (290-320 nm) reaching the earth's surface. It is therefore essential that new action spectra be completed for UV-B effects on a large variety of responses of human, animal, and aquatic plant systems. Combining these action spectra with the known amounts of UV-B reaching the biosphere can give rise to solar UV effectiveness spectra that, in turn, can give rise to estimates

  5. Gene Overexpression Resources in Cereals for Functional Genomics and Discovery of Useful Genes

    PubMed Central

    Abe, Kiyomi; Ichikawa, Hiroaki

    2016-01-01

    Identification and elucidation of functions of plant genes is valuable for both basic and applied research. In addition to natural variation in model plants, numerous loss-of-function resources have been produced by mutagenesis with chemicals, irradiation, or insertions of transposable elements or T-DNA. However, we may be unable to observe loss-of-function phenotypes for genes with functionally redundant homologs and for those essential for growth and development. To offset such disadvantages, gain-of-function transgenic resources have been exploited. Activation-tagged lines have been generated using obligatory overexpression of endogenous genes by random insertion of an enhancer. Recent progress in DNA sequencing technology and bioinformatics has enabled the preparation of genomewide collections of full-length cDNAs (fl-cDNAs) in some model species. Using the fl-cDNA clones, a novel gain-of-function strategy, Fl-cDNA OvereXpressor gene (FOX)-hunting system, has been developed. A mutant phenotype in a FOX line can be directly attributed to the overexpressed fl-cDNA. Investigating a large population of FOX lines could reveal important genes conferring favorable phenotypes for crop breeding. Alternatively, a unique loss-of-function approach Chimeric REpressor gene Silencing Technology (CRES-T) has been developed. In CRES-T, overexpression of a chimeric repressor, composed of the coding sequence of a transcription factor (TF) and short peptide designated as the repression domain, could interfere with the action of endogenous TF in plants. Although plant TFs usually consist of gene families, CRES-T is effective, in principle, even for the TFs with functional redundancy. In this review, we focus on the current status of the gene-overexpression strategies and resources for identifying and elucidating novel functions of cereal genes. We discuss the potential of these research tools for identifying useful genes and phenotypes for application in crop breeding. PMID

  6. Histone deacetylase inhibitor (HDACI) mechanisms of action: emerging insights

    PubMed Central

    Bose, Prithviraj; Dai, Yun; Grant, Steven

    2014-01-01

    Initially regarded as “epigenetic modifiers” acting predominantly through chromatin remodeling via histone acetylation, HDACIs, alternatively referred to as lysine deacetylase or simply deacetylase inhibitors, have since been recognized to exert multiple cytotoxic actions in cancer cells, often through acetylation of non-histone proteins. Some well-recognized mechanisms of HDACI lethality include, in addition to relaxation of DNA and de-repression of gene transcription, interference with chaperone protein function, free radical generation, induction of DNA damage, up-regulation of endogenous inhibitors of cell cycle progression, e.g., p21, and promotion of apoptosis. Intriguingly, this class of agents is relatively selective for transformed cells, at least in pre-clinical studies. In recent years, additional mechanisms of action of these agents have been uncovered. For example, HDACIs interfere with multiple DNA repair processes, as well as disrupt cell cycle checkpoints, critical to the maintenance of genomic integrity in the face of diverse genotoxic insults. Despite their pre-clinical potential, the clinical use of HDACIs remains restricted to certain subsets of T-cell lymphoma. Currently, it appears likely that the ultimate role of these agents will lie in rational combinations, only a few of which have been pursued in the clinic to date. This review focuses on relatively recently identified mechanisms of action of HDACIs, with particular emphasis on those that relate to the DNA damage response (DDR), and discuss synergistic strategies combining HDACIs with several novel targeted agents that disrupt the DDR or antagonize anti-apoptotic proteins that could have implications for the future use of HDACIs in patients with cancer. PMID:24769080

  7. Microbial Functional Gene Diversity with a Shift of Subsurface Redox Conditions during In Situ Uranium Reduction

    PubMed Central

    Liang, Yuting; Van Nostrand, Joy D.; N′Guessan, Lucie A.; Peacock, Aaron D.; Deng, Ye; Long, Philip E.; Resch, C. Tom; Wu, Liyou; He, Zhili; Li, Guanghe; Hazen, Terry C.; Lovley, Derek R.

    2012-01-01

    To better understand the microbial functional diversity changes with subsurface redox conditions during in situ uranium bioremediation, key functional genes were studied with GeoChip, a comprehensive functional gene microarray, in field experiments at a uranium mill tailings remedial action (UMTRA) site (Rifle, CO). The results indicated that functional microbial communities altered with a shift in the dominant metabolic process, as documented by hierarchical cluster and ordination analyses of all detected functional genes. The abundance of dsrAB genes (dissimilatory sulfite reductase genes) and methane generation-related mcr genes (methyl coenzyme M reductase coding genes) increased when redox conditions shifted from Fe-reducing to sulfate-reducing conditions. The cytochrome genes detected were primarily from Geobacter sp. and decreased with lower subsurface redox conditions. Statistical analysis of environmental parameters and functional genes indicated that acetate, U(VI), and redox potential (Eh) were the most significant geochemical variables linked to microbial functional gene structures, and changes in microbial functional diversity were strongly related to the dominant terminal electron-accepting process following acetate addition. The study indicates that the microbial functional genes clearly reflect the in situ redox conditions and the dominant microbial processes, which in turn influence uranium bioreduction. Microbial functional genes thus could be very useful for tracking microbial community structure and dynamics during bioremediation. PMID:22327592

  8. Action-Based Planning

    NASA Technical Reports Server (NTRS)

    Lansky, Amy L.; Lum, Henry Jr. (Technical Monitor)

    1994-01-01

    This paper presents an approach to domain representation and planning that is fundamentally different from traditional methods; an approach based strictly on actions and their interrelationships, rather than on state-based goals and preconditions. In particular, we focus on the action-based planner COLLAGE, describe its methods for plan-construction, and contrast them with more traditional approaches to planning. Experiences with COLLAGE in realistic domains have shown that the action-based approach is not only more natural to use, but can also be more cost-efficient than traditional planning methods.

  9. Conscious Control over Action

    PubMed Central

    Shepherd, Joshua

    2015-01-01

    The extensive involvement of nonconscious processes in human behaviour has led some to suggest that consciousness is much less important for the control of action than we might think. In this article I push against this trend, developing an understanding of conscious control that is sensitive to our best models of overt (that is, bodily) action control. Further, I assess the cogency of various zombie challenges—challenges that seek to demote the importance of conscious control for human agency. I argue that though nonconscious contributions to action control are evidently robust, these challenges are overblown. PMID:26113753

  10. Political action committee for scientists

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    Spurred by budget proposals that could severely reduce science funding (Eos, March 24, March 3, February 10), seven scientists currently serving as Congressional Science or State Department Fellows recently founded a political action committee (PAC) for scientists. The Science and Technology Political Action Committee (SCITEC-PAC) aims to make scientists more politically aware and better informed about potential legislative actions that affect research. It will also serve to ‘establish a political presence’ with respect to science, said Donald Stein, SCITEC-PAC's chairman.The organization is not a lobbying group, explained Stein, professor of neurology and psychology at Clark University and the University of Massachusetts Medical Center. ‘Lobbyists seek to influence officials by presenting information to them,’ he said, ‘while a PAC tries to influence the outcome of elections through campaign contributions of money, time, and effort in behalf of candidates that share similar goals and aspirations.’ In other words, the PAC will be a vehicle for promoting candidates for federal office who advocate strong support for scientific research and training. In addition, the PAC will develop and study science policy and budget issues and will attempt to stimulate government and private sector interest in these issues.

  11. Immunization Action Coalition

    MedlinePlus

    ... IAC | Contact | A-Z Index | Donate | Shop | SUBSCRIBE Immunization Action Coalition Handouts for Patients & Staff A-Z ... Index Supplies Checklist Administering Vaccines Temperature Logs Adult Vaccination Topics of Interest Documenting Vaccination Translations Parent Handouts ...

  12. Postpartum Depression Action Plan

    MedlinePlus

    MENU Return to Web version Postpartum Depression | Postpartum Depression Action Plan Patient __________________________ Physician/NP/PA __________________ Clinic ____________________________ Phone Number ____________________ Choose one area and add other areas as you begin to ...

  13. The Action Lawyers

    ERIC Educational Resources Information Center

    Lubenow, Gerald C.

    1972-01-01

    A description of the Serrano vs. Priest class action suit in California, challenging the system of financing education through property taxes; author touches upon the possibilities for the courts becoming change agents in the struggle for social reform. (SP)

  14. Commitment to action. Population Action International.

    PubMed

    Squires, S

    1994-01-01

    The national chair of Population Action International (formerly the Population Crisis Committee), Robin Chandler Duke, is a crusader for women's reproductive rights. She was in Bangladesh in 1971 during its civil war. Soldiers would rape young Muslim women, and their families would reject them when they became pregnant. The head of the exiled government agreed to let physicians from IPPF perform abortions on these women, which allowed families to take them back. Opposition to the abortions arose, however. This experience in Bangladesh sparked Ms. Duke's interest in population control. Her years as the wife of a US diplomat granted her access to powerful people worldwide. Her predecessor, retired US Army General Bill Draper, called Ms. Duke from his death bed in 1974 to ask her to be national chair of PAI. She served as a delegate in various international meetings, e.g., the 1980 UNESCO meetings in Belgrade. Spain and Luxembourg honored her for her work of campaigning for women's reproductive rights. She believes that rapid population growth is the most significant problem in the world today. It exacerbates poverty, environmental destruction, and political instability. She believes that universal availability of high quality, voluntary family planning services, including safe abortion, is needed to save humanity from the vicious cycle. Since family planning, sex education, and abortion are the most personal and sensitive parts of people's lives, Population Action frames family planning in the context of basic health care. AIDS complicates the issue, because contraception is no longer limited to birth control. Even though the organization realizes that sexual abstinence is the best way to avoid AIDS, it tries to educate female teenagers not to let boys coerce them to have sex. If they do, have sex Population Action advocates condom use. Ms. Duke cites the family planning successes of Indonesia, Zimbabwe, and Thailand.

  15. Commitment to action. Population Action International.

    PubMed

    Squires, S

    1994-01-01

    The national chair of Population Action International (formerly the Population Crisis Committee), Robin Chandler Duke, is a crusader for women's reproductive rights. She was in Bangladesh in 1971 during its civil war. Soldiers would rape young Muslim women, and their families would reject them when they became pregnant. The head of the exiled government agreed to let physicians from IPPF perform abortions on these women, which allowed families to take them back. Opposition to the abortions arose, however. This experience in Bangladesh sparked Ms. Duke's interest in population control. Her years as the wife of a US diplomat granted her access to powerful people worldwide. Her predecessor, retired US Army General Bill Draper, called Ms. Duke from his death bed in 1974 to ask her to be national chair of PAI. She served as a delegate in various international meetings, e.g., the 1980 UNESCO meetings in Belgrade. Spain and Luxembourg honored her for her work of campaigning for women's reproductive rights. She believes that rapid population growth is the most significant problem in the world today. It exacerbates poverty, environmental destruction, and political instability. She believes that universal availability of high quality, voluntary family planning services, including safe abortion, is needed to save humanity from the vicious cycle. Since family planning, sex education, and abortion are the most personal and sensitive parts of people's lives, Population Action frames family planning in the context of basic health care. AIDS complicates the issue, because contraception is no longer limited to birth control. Even though the organization realizes that sexual abstinence is the best way to avoid AIDS, it tries to educate female teenagers not to let boys coerce them to have sex. If they do, have sex Population Action advocates condom use. Ms. Duke cites the family planning successes of Indonesia, Zimbabwe, and Thailand. PMID:12319083

  16. Action Learning as Invigoration

    ERIC Educational Resources Information Center

    Chivers, Terence S.

    2011-01-01

    The present account of action learning describes its adoption for pragmatic reasons by the University of the Third Age (U3A). The reason for the existence of this movement is the education of retired people. The account seeks to explain why the action learning method spread from one local U3A to another and across it to other local U3As. The case…

  17. Additional Continuing Appropriations Amendments, 2011

    THOMAS, 112th Congress

    Rep. Rogers, Harold [R-KY-5

    2011-03-11

    03/18/2011 Became Public Law No: 112-6. (TXT | PDF) (All Actions) Notes: Continuing appropriations through 4/8/2011. Tracker: This bill has the status Became LawHere are the steps for Status of Legislation:

  18. Action-based effects on music perception.

    PubMed

    Maes, Pieter-Jan; Leman, Marc; Palmer, Caroline; Wanderley, Marcelo M

    2014-01-01

    The classical, disembodied approach to music cognition conceptualizes action and perception as separate, peripheral processes. In contrast, embodied accounts of music cognition emphasize the central role of the close coupling of action and perception. It is a commonly established fact that perception spurs action tendencies. We present a theoretical framework that captures the ways in which the human motor system and its actions can reciprocally influence the perception of music. The cornerstone of this framework is the common coding theory, postulating a representational overlap in the brain between the planning, the execution, and the perception of movement. The integration of action and perception in so-called internal models is explained as a result of associative learning processes. Characteristic of internal models is that they allow intended or perceived sensory states to be transferred into corresponding motor commands (inverse modeling), and vice versa, to predict the sensory outcomes of planned actions (forward modeling). Embodied accounts typically refer to inverse modeling to explain action effects on music perception (Leman, 2007). We extend this account by pinpointing forward modeling as an alternative mechanism by which action can modulate perception. We provide an extensive overview of recent empirical evidence in support of this idea. Additionally, we demonstrate that motor dysfunctions can cause perceptual disabilities, supporting the main idea of the paper that the human motor system plays a functional role in auditory perception. The finding that music perception is shaped by the human motor system and its actions suggests that the musical mind is highly embodied. However, we advocate for a more radical approach to embodied (music) cognition in the sense that it needs to be considered as a dynamical process, in which aspects of action, perception, introspection, and social interaction are of crucial importance.

  19. Action-based effects on music perception

    PubMed Central

    Maes, Pieter-Jan; Leman, Marc; Palmer, Caroline; Wanderley, Marcelo M.

    2013-01-01

    The classical, disembodied approach to music cognition conceptualizes action and perception as separate, peripheral processes. In contrast, embodied accounts of music cognition emphasize the central role of the close coupling of action and perception. It is a commonly established fact that perception spurs action tendencies. We present a theoretical framework that captures the ways in which the human motor system and its actions can reciprocally influence the perception of music. The cornerstone of this framework is the common coding theory, postulating a representational overlap in the brain between the planning, the execution, and the perception of movement. The integration of action and perception in so-called internal models is explained as a result of associative learning processes. Characteristic of internal models is that they allow intended or perceived sensory states to be transferred into corresponding motor commands (inverse modeling), and vice versa, to predict the sensory outcomes of planned actions (forward modeling). Embodied accounts typically refer to inverse modeling to explain action effects on music perception (Leman, 2007). We extend this account by pinpointing forward modeling as an alternative mechanism by which action can modulate perception. We provide an extensive overview of recent empirical evidence in support of this idea. Additionally, we demonstrate that motor dysfunctions can cause perceptual disabilities, supporting the main idea of the paper that the human motor system plays a functional role in auditory perception. The finding that music perception is shaped by the human motor system and its actions suggests that the musical mind is highly embodied. However, we advocate for a more radical approach to embodied (music) cognition in the sense that it needs to be considered as a dynamical process, in which aspects of action, perception, introspection, and social interaction are of crucial importance. PMID:24454299

  20. Action, agency and responsibility.

    PubMed

    Frith, Chris D

    2014-03-01

    In a series of experiments Marc Jeannerod revealed that we have very little awareness of the details and causes of our actions. We are, however, vividly aware of being in control of our actions and this gives us a sense of responsibility. These feelings arise, first, from intentional binding which creates a perception of agency, linking an intentional action to its outcome and, second, from the counterfactual reasoning that we could have chosen some other action. These feelings of responsibility play a critical role in creating social cohesion since they allow people to be held to account for deliberate antisocial behaviour. Jeannerod's studies also showed that we are unaware of how little we know about our actions and so are happy to make up stories about the nature and causes of our behaviour. These stories often do not correspond with the underlying cognitive and neural processes, but they can be changed through instructions and through discussion with others. Our experience of responsibility for action emerges during our upbringing through exposure to our culture. This creates consensus about the causes of behaviour, but not necessarily accuracy. PMID:24036357

  1. 75 FR 18164 - Procurement List: Proposed Additions and Deletions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-09

    ...., Williamsport, PA Portfolio, Double Pocket NSN: 7510-01-411-7000 NPA: Susquehanna Association for the Blind and... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List: Proposed Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions To...

  2. 76 FR 66913 - Procurement List Proposed Additions and Deletions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Proposed Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to and... Procurement List that will be furnished by nonprofit agencies employing persons who are blind or have...

  3. 77 FR 53801 - Nexira; Filing of Food Additive Petition; Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-04

    ... Register on December 20, 2011 (76 FR 78866), FDA announced that a food additive petition (FAP 1A4784) had... HUMAN SERVICES Food and Drug Administration 21 CFR Part 172 Nexira; Filing of Food Additive Petition; Amendment AGENCY: Food and Drug Administration, HHS. ACTION: Notice of petition. SUMMARY: The Food and...

  4. 76 FR 78866 - Nexira; Filing of Food Additive Petition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-20

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 172 Nexira; Filing of Food Additive Petition AGENCY: Food and Drug Administration, HHS. ACTION: Notice of petition. SUMMARY: The Food and Drug Administration (FDA) is announcing that Nexira has filed a petition proposing that the food additive...

  5. 77 FR 40344 - Procurement List; Proposed Additions and Deletion

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-09

    ... Resource Center, Alexandria, VA (CONUS). Contracting Activity: Defense Human Resource Center, Alexandria... PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to...

  6. Sclerostin: therapeutic horizons based upon its actions.

    PubMed

    Costa, Aline G; Bilezikian, John P

    2012-03-01

    Inactivating mutations of the SOST gene cause a reduction in sclerostin levels and are associated with high bone mass. The clinical phenotypes, sclerosteosis and van Buchem's disease, were described in 1950s. Much later, it was learned that both diseases are due to loss-of-function mutations in the SOST gene. As a regulator of an important osteoanabolic pathway, Wnt, inactivation of SOST leads to a stimulation of the pathway it regulates. The high bone mass in patients with either sclerosteosis or van Buchem's disease is associated with unusual skeletal strength; they do not fracture. Knowledge of this molecule and its actions led rather quickly to the development of anti-sclerostin antibodies that lead to marked increases in bone mass in both animals and human subjects. Blocking sclerostin action with anti-sclerostin antibodies is a promising new therapeutic approach to osteoanabolic therapy of osteoporosis.

  7. Redox-Dependent Anti-Inflammatory Signaling Actions of Unsaturated Fatty Acids

    PubMed Central

    Delmastro-Greenwood, Meghan; Freeman, Bruce A.; Wendell, Stacy Gelhaus

    2014-01-01

    Unsaturated fatty acids are metabolized to reactive products that can act as pro- or anti-inflammatory signaling mediators. Electrophilic fatty acid species, including nitro- and oxo-containing fatty acids, display salutary anti-inflammatory and metabolic actions. Electrophilicity can be conferred by both enzymatic and oxidative reactions, via the homolytic addition of nitrogen dioxide to a double bond or via the formation of α,β-unsaturated carbonyl and epoxide substituents. The endogenous formation of electrophilic fatty acids is significant and influenced by diet, metabolic, and inflammatory reactions. Transcriptional regulatory proteins and enzymes can sense the redox status of the surrounding environment upon electrophilic fatty acid adduction of functionally significant, nucleophilic cysteines. Through this covalent and often reversible posttranslational modification, gene expression and metabolic responses are induced. At low concentrations, the pleiotropic signaling actions that are regulated by these protein targets suggest that some classes of electrophilic lipids may be useful for treating metabolic and inflammatory diseases. PMID:24161076

  8. Evaluation of growth hormone (GH) action in mice: discovery of GH receptor antagonists and clinical indications.

    PubMed

    Kopchick, John J; List, Edward O; Kelder, Bruce; Gosney, Elahu S; Berryman, Darlene E

    2014-04-01

    The discovery of a growth hormone receptor antagonist (GHA) was initially established via expression of mutated GH genes in transgenic mice. Following this discovery, development of the compound resulted in a drug termed pegvisomant, which has been approved for use in patients with acromegaly. Pegvisomant treatment in a dose dependent manner results in normalization of IGF-1 levels in most patients. Thus, it is a very efficacious and safe drug. Since the GH/IGF-1 axis has been implicated in the progression of several types of cancers, many have suggested the use of pegvisomant as an anti-cancer therapeutic. In this manuscript, we will review the use of mouse strains that possess elevated or depressed levels of GH action for unraveling many of GH actions. Additionally, we will describe experiments in which the GHA was discovered, review results of pegvisomant's preclinical and clinical trials, and provide data suggesting pegvisomant's therapeutic value in selected types of cancer. PMID:24035867

  9. National Security Technology Incubator Action Plan

    SciTech Connect

    2008-02-28

    This report documents the action plan for developing the National Security Technology Incubator (NSTI) program for southern New Mexico. The NSTI program is being developed as part of the National Security Preparedness Project (NSPP), funded by Department of Energy (DOE)/National Nuclear Security Administration (NNSA). This action plan serves as a tool in measuring progress in the development process and delivery of services for the NSTI program. Continuous review and evaluation of the action plan is necessary in the development process of the NSTI. The action plan includes detailed steps in developing the NSTI program based on recommended best practices in incubator development by the National Business Incubation Association (NBIA). Included are tasks required to implement the NSTI, developed within a work breakdown structure. In addition, a timeline is identified for each task.

  10. Inferring gene targets of drugs and chemical compounds from gene expression profiles

    PubMed Central

    Noh, Heeju; Gunawan, Rudiyanto

    2016-01-01

    Motivation: Finding genes which are directly perturbed or targeted by drugs is of great interest and importance in drug discovery. Several network filtering methods have been created to predict the gene targets of drugs from gene expression data based on an ordinary differential equation model of the gene regulatory network (GRN). A critical step in these methods involves inferring the GRN from the expression data, which is a very challenging problem on its own. In addition, existing network filtering methods require computationally intensive parameter tuning or expression data from experiments with known genetic perturbations or both. Results: We developed a method called DeltaNet for the identification of drug targets from gene expression data. Here, the gene target predictions were directly inferred from the data without a separate step of GRN inference. DeltaNet formulation led to solving an underdetermined linear regression problem, for which we employed least angle regression (DeltaNet-LAR) or LASSO regularization (DeltaNet-LASSO). The predictions using DeltaNet for expression data of Escherichia coli, yeast, fruit fly and human were significantly more accurate than those using network filtering methods, namely mode of action by network identification (MNI) and sparse simultaneous equation model (SSEM). Furthermore, DeltaNet using LAR did not require any parameter tuning and could provide computational speed-up over existing methods. Conclusion: DeltaNet is a robust and numerically efficient tool for identifying gene perturbations from gene expression data. Importantly, the method requires little to no expert supervision, while providing accurate gene target predictions. Availability and implementation: DeltaNet is available on http://www.cabsel.ethz.ch/tools/DeltaNet. Contact: rudi.gunawan@chem.ethz.ch Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153589

  11. Transport and transformation of genetic information in the critical zone: The case of antibiotic resistance genes

    NASA Astrophysics Data System (ADS)

    Zhu, Y. G.

    2015-12-01

    In addition to material and energy flows, the dynamics and functions of the Earth's critical zone are intensively mediated by biological actions performed by diverse organisms. These biological actions are modulated by the expression of functional genes and their translation into enzymes that catalyze geochemical reactions, such as nutrient turnover and pollutant biodegradation. Although geobiology, as an interdisciplinary research area, is playing and vital role in linking biological and geochemical processes at different temporal and spatial scales, the distribution and transport of functional genes have rarely been investigated from the Earth's critical zone perspectives. To illustrate the framework of studies on the transport and transformation of genetic information in the critical zone, antibiotic resistance is taken as an example. Antibiotic resistance genes are considered as a group of emerging contaminants, and their emergence and spread within the critical zone on one hand are induced by anthropogenic activities, and on other hand are threatening human health worldwide. The transport and transformation of antibiotic resistance genes are controlled by both horizontal gene transfer between bacterial cells and the movement of bacteria harboring antibiotic resistance genes. In this paper, the fate and behavior of antibiotic resistance genes will be discussed in the following aspects: 1) general overview of environmental antibiotic resistance; 2) high through quantification of the resistome in various environmental media; 3) pathways of resistance gene flow within the critical zone; and 4) potential strategies in mitigating antibiotic resistance, particularly from the critical zone perspectives.

  12. ANTIDEPRESSANT ACTIONS OF HDAC INHIBITORS

    PubMed Central

    Covington, Herbert E.; Maze, Ian; LaPlant, Quincey C.; Vialou, Vincent F.; Yoshinori, Ohnishi N.; Berton, Olivier; Fass, Dan M.; Renthal, William; Rush, Augustus J.; Wu, Emma Y.; Ghose, Subroto; Krishnan, Vaishnav; Russo, Scott J.; Tamminga, Carol; Haggarty, Stephen J.; Nestler, Eric J.

    2009-01-01

    Persistent symptoms of depression suggest the involvement of stable molecular adaptations in brain, which may be reflected at the level of chromatin remodeling. We find that chronic social defeat stress in mice causes a transient decrease, followed by a persistent increase, in levels of acetylated histone H3 in the nucleus accumbens, an important limbic brain region. This persistent increase in H3 acetylation is associated with decreased levels of histone deacetylase 2 (HDAC2) in the nucleus accumbens. Similar effects were observed in the nucleus accumbens of depressed humans studied postmortem. These changes in H3 acetylation and HDAC2 expression mediate long-lasting positive neuronal adaptations, since infusion of HDAC inhibitors into the nucleus accumbens, which increases histone acetylation, exerts robust antidepressant-like effects in the social defeat paradigm and other behavioral assays. HDAC inhibitor (MS-275) infusion also reverses the effects of chronic defeat stress on global patterns of gene expression in the nucleus accumbens, as determined by microarray analysis, with striking similarities to the effects of the standard antidepressant, fluoxetine. Stress-regulated genes whose expression is normalized selectively by MS-275 may provide promising targets for the future development of novel antidepressant treatments. Together, these findings provide new insight into the underlying molecular mechanisms of depression and antidepressant action, and support the antidepressant potential of HDAC inhibitors and perhaps other agents that act at the level of chromatin structure. PMID:19759294

  13. Prediction of gene-based drug indications using compendia of public gene expression data and PubMed abstracts.

    PubMed

    Qabaja, Ala; Jarada, Tamer; Elsheikh, Abdallah; Alhajj, Reda

    2014-06-01

    The tremendous research effort on diseases and drug discovery has produced a huge amount of important biomedical information which is mostly hidden in the web. In addition, many databases have been created for the purpose of storing enormous amounts of information and high-throughput experiments related to drugs and diseases' effects on genes. Thus, developing an algorithm to integrate biological data from different sources forms one of the greatest challenges in the field of computational biology. Based on our belief that data integration would result in better understanding for the drug mode of action or the disease pathophysiology, we have developed a novel paradigm to integrate data from three major sources in order to predict novel therapeutic drug indications. Microarray data, biomedical text mining data, and gene interaction data have been all integrated to predict ranked lists of genes based on their relevance to a particular drug or disease molecular action. These ranked lists of genes have finally been used as a raw material for building a disease-drug connectivity map based on the enrichment between the up/down tags of a particular disease signature and the ranked lists of drugs. Using this paradigm, we have reported 13% sensitivity improvement in comparison with using microarray or text mining data independently. In addition, our paradigm is able to predict many clinically validated disease-drug associations that could not be captured using microarray or text mining data independently.

  14. Genes and gene regulation

    SciTech Connect

    MacLean, N.

    1988-01-01

    Genetics has long been a central topic for biologists, and recent progress has captured the public imagination as well. This book addresses questions that are at the leading edge of this continually advancing discipline. In tune with the increasing emphasis on molecular biology and genetic engineering, this text emphasizes the molecular aspects of gene expression, and the evolution of gene sequence organization and control. It reviews the genetic material of viruses, bacteria, and of higher organisms. Cells and organisms are compared in terms of gene numbers, their arrangements within a cell, and the control mechanisms which regulate the activity of genes.

  15. Identifying the Cellular Targets of Drug Action in the Central Nervous System Following Corticosteroid Therapy

    PubMed Central

    2013-01-01

    Corticosteroid (CS) therapy is used widely in the treatment of a range of pathologies, but can delay production of myelin, the insulating sheath around central nervous system nerve fibers. The cellular targets of CS action are not fully understood, that is, “direct” action on cells involved in myelin genesis [oligodendrocytes and their progenitors the oligodendrocyte precursor cells (OPCs)] versus “indirect” action on other neural cells. We evaluated the effects of the widely used CS dexamethasone (DEX) on purified OPCs and oligodendrocytes, employing complementary histological and transcriptional analyses. Histological assessments showed no DEX effects on OPC proliferation or oligodendrocyte genesis/maturation (key processes underpinning myelin genesis). Immunostaining and RT-PCR analyses show that both cell types express glucocorticoid receptor (GR; the target for DEX action), ruling out receptor expression as a causal factor in the lack of DEX-responsiveness. GRs function as ligand-activated transcription factors, so we simultaneously analyzed DEX-induced transcriptional responses using microarray analyses; these substantiated the histological findings, with limited gene expression changes in DEX-treated OPCs and oligodendrocytes. With identical treatment, microglial cells showed profound and global changes post-DEX addition; an unexpected finding was the identification of the transcription factor Olig1, a master regulator of myelination, as a DEX responsive gene in microglia. Our data indicate that CS-induced myelination delays are unlikely to be due to direct drug action on OPCs or oligodendrocytes, and may occur secondary to alterations in other neural cells, such as the immune component. To the best of our knowledge, this is the first comparative molecular and cellular analysis of CS effects in glial cells, to investigate the targets of this major class of anti-inflammatory drugs as a basis for myelination deficits. PMID:24147833

  16. Daily differential expression of melatonin-related genes and clock genes in rat cumulus-oocyte complex: changes after pinealectomy.

    PubMed

    Coelho, L A; Peres, R; Amaral, F G; Reiter, R J; Cipolla-Neto, J

    2015-05-01

    This study investigated the maturational stage (immature and mature ovaries) differences of mRNA expression of melatonin-forming enzymes (Aanat and Asmt), melatonin membrane receptors (Mt1 and Mt2) and putative nuclear (Rorα) receptors, and clock genes (Clock, Bmal1, Per1, Per2, Cry1, Cry2) in cumulus-oocyte complexes (COC) from weaning Wistar rats. We also examined the effects of pinealectomy and of melatonin pharmacological replacement on the daily expression of these genes in COC. qRT-PCR analysis revealed that in oocytes, the mRNA expression of Asmt, Mt2, Clock, Bmal1, Per2, and Cry1 were higher (P < 0.05) in immature ovaries than in the mature ones. In cumulus cells, the same pattern of mRNA expression for Asmt, Aanat, Rorα, Clock, Per1, Cry1, and Cry2 genes was observed. In oocytes, pinealectomy altered the daily mRNA expression profiles of Asmt, Mt1, Mt2, Clock, Per1, Cry1, and Cry2 genes. In cumulus cells, removal of the pineal altered the mRNA expression profiles of Mt1, Mt2, Rorα, Aanat, Asmt, Clock, Bmal1, Per2, Cry1, and Cry2 genes. Melatonin treatment partially or completely re-established the daily mRNA expression profiles of most genes studied. The mRNA expression of melatonin-related genes and clock genes in rat COC varies with the maturational stage of the meiotic cellular cycle in addition to the hour of the day. This suggests that melatonin might act differentially in accordance with the maturational stage of cumulus/oocyte complex. In addition, it seems that circulating pineal melatonin is very important in the design of the daily profile of mRNA expression of COC clock genes and genes related to melatonin synthesis and action.

  17. Expression of bvg-repressed genes in Bordetella pertussis is controlled by RisA through a novel c-di-GMP signaling pathway

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The BvgAS two component system of Bordetella pertussis controls virulence factor expression. In addition, BvgAS controls expression of the bvg-repressed genes through the action of the repressor, BvgR. The transcription factor RisA is inhibited by BvgR, and when BvgR is not expressed RisA induces th...

  18. Bitumen fume-induced gene expression profile in rat lung

    SciTech Connect

    Gate, Laurent . E-mail: laurent.gate@inrs.fr; Langlais, Cristina; Micillino, Jean-Claude; Nunge, Herve; Bottin, Marie-Claire; Wrobel, Richard; Binet, Stephane

    2006-08-15

    Exposure to bitumen fumes during paving and roofing activities may represent an occupational health risk. To date, most of the studies performed on the biological effect of asphalt fumes have been done with regard to their content in carcinogenic polycyclic aromatic hydrocarbons (PAH). In order to gain an additional insight into the mechanisms of action of bitumen fumes, we studied their pulmonary effects in rodents following inhalation using the microarray technology. Fisher 344 rats were exposed for 5 days, 6 h/day to bitumen fumes generated at road paving temperature (170 {sup o}C) using a nose-only exposition device. With the intention of studying the early transcriptional events induced by asphalt fumes, lung tissues were collected immediately following exposure and gene expression profiles in control and exposed rats were determined by using oligonucleotide microarrays. Data analysis revealed that genes involved in lung inflammatory response as well as genes associated with PAH metabolization and detoxification were highly expressed in bitumen-exposed animals. In addition, the expression of genes related to elastase activity and its inhibition which are associated with emphysema was also modulated. More interestingly genes coding for monoamine oxidases A and B involved in the metabolism of neurotransmitters and xenobiotics were downregulated in exposed rats. Altogether, these data give additional information concerning the bitumen fumes biological effects and would allow to better review the health effects of occupational asphalt fumes exposure.

  19. Bitumen fume-induced gene expression profile in rat lung.

    PubMed

    Gate, Laurent; Langlais, Cristina; Micillino, Jean-Claude; Nunge, Hervé; Bottin, Marie-Claire; Wrobel, Richard; Binet, Stéphane

    2006-08-15

    Exposure to bitumen fumes during paving and roofing activities may represent an occupational health risk. To date, most of the studies performed on the biological effect of asphalt fumes have been done with regard to their content in carcinogenic polycyclic aromatic hydrocarbons (PAH). In order to gain an additional insight into the mechanisms of action of bitumen fumes, we studied their pulmonary effects in rodents following inhalation using the microarray technology. Fisher 344 rats were exposed for 5 days, 6 h/day to bitumen fumes generated at road paving temperature (170 degrees C) using a nose-only exposition device. With the intention of studying the early transcriptional events induced by asphalt fumes, lung tissues were collected immediately following exposure and gene expression profiles in control and exposed rats were determined by using oligonucleotide microarrays. Data analysis revealed that genes involved in lung inflammatory response as well as genes associated with PAH metabolization and detoxification were highly expressed in bitumen-exposed animals. In addition, the expression of genes related to elastase activity and its inhibition which are associated with emphysema was also modulated. More interestingly genes coding for monoamine oxidases A and B involved in the metabolism of neurotransmitters and xenobiotics were downregulated in exposed rats. Altogether, these data give additional information concerning the bitumen fumes biological effects and would allow to better review the health effects of occupational asphalt fumes exposure.

  20. Learning to take actions

    SciTech Connect

    Khardon, R.

    1996-12-31

    We formalize a model for supervised learning of action strategies in dynamic stochastic domains, and show that pac-learning results on Occam algorithms hold in this model as well. We then identify a particularly useful bias for action strategies based on production rule systems. We show that a subset of production rule systems, including rules in predicate calculus style, small hidden state, and unobserved support predicates, is properly learnable. The bias we introduce enables the learning algorithm to invent the recursive support predicates which are used in the action strategy, and to reconstruct the internal state of the strategy. It is also shown that hierarchical strategies are learnable if a helpful teacher is available, but that otherwise the problem is computationally hard.

  1. The shape of action.

    PubMed

    Hard, Bridgette Martin; Recchia, Gabriel; Tversky, Barbara

    2011-11-01

    How do people understand the everyday, yet intricate, behaviors that unfold around them? In the present research, we explored this by presenting viewers with self-paced slideshows of everyday activities and recording looking times, subjective segmentation (breakpoints) into action units, and slide-to-slide physical change. A detailed comparison of the joint time courses of these variables showed that looking time and physical change were locally maximal at breakpoints and greater for higher level action units than for lower level units. Even when slideshows were scrambled, breakpoints were regarded longer and were more physically different from ordinary moments, showing that breakpoints are distinct even out of context. Breakpoints are bridges: from one action to another, from one level to another, and from perception to conception.

  2. Action languages: Dimensions, effects

    NASA Technical Reports Server (NTRS)

    Hayes, Daniel G.; Streeter, Gordon

    1989-01-01

    Dimensions of action languages are discussed for communication between humans and machines, and the message handling capabilities of object oriented programming systems are examined. Design of action languages is seen to be very contextual. Economical and effective design will depend on features of situations, the tasks intended to be accomplished, and the nature of the devices themselves. Current object oriented systems turn out to have fairly simple and straightforward message handling facilities, which in themselves do little to buffer action or even in some cases to handle competing messages. Even so, it is possible to program a certain amount of discretion about how they react to messages. Such thoughtfulness and perhaps relative autonomy of program modules seems prerequisite to future systems to handle complex interactions in changing situations.

  3. Mitigation Action Plan

    SciTech Connect

    Not Available

    1994-02-01

    This Mitigation Action Plan (MAP) focuses on mitigation commitments stated in the Supplemental Environmental Impact Statement (SEIS) and the Record of Decision (ROD) for the Naval Petroleum Reserve No. 1 (NPR-1). Specific commitments and mitigation implementation actions are listed in Appendix A-Mitigation Actions, and form the central focus of this MAP. They will be updated as needed to allow for organizational, regulatory, or policy changes. It is the intent of DOE to comply with all applicable federal, state, and local environmental, safety, and health laws and regulations. Eighty-six specific commitments were identified in the SEIS and associated ROD which pertain to continued operation of NPR-1 with petroleum production at the Maximum Efficient Rate (MER). The mitigation measures proposed are expected to reduce impacts as much as feasible, however, as experience is gained in actual implementation of these measures, some changes may be warranted.

  4. 7 CFR 1794.33 - Agency action.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... (CONTINUED) ENVIRONMENTAL POLICIES AND PROCEDURES Procedure for Categorical Exclusions § 1794.33 Agency action. RUS may act on an application for financial assistance upon determining, based on the review of documents as set forth in § 1794.32 and such additional information as RUS deems necessary, that the...

  5. Chemotherapeutic Drugs Interfere with Gene Delivery Mediated by Chitosan-Graft-Poly(ethylenimine).

    PubMed

    Lai, Wing-Fu; Lin, Marie C

    2015-01-01

    Combined chemo-gene therapy is one of the treatment modalities that have attracted extensive research interests; however, there is little information regarding the influence of drug application on gene transfer. This study bridges this gap by examining how chemotherapeutic drugs (teniposide, cis-diamminedichloroplatinum(II) and temozolomide) interfere with polyplex formation and transfection of chitosan-graft-poly(ethylenimine). Our results indicate that the degree of drug interference varies with the mechanism of drug action, with the transgene expression being severely suppressed when the plasmid is co-delivered with cis-diamminedichloroplatinum(II) or teniposide but not temozolomide. In addition, the interference with transfection by drugs varies with different gene/drug co-formulations. This is the first study to evidence that, though combined chemo-gene therapy has therapeutic potential, some chemotherapeutic drugs may reduce the treatment efficiency of gene therapy. PMID:25961282

  6. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.

    PubMed

    Christakos, Sylvia; Dhawan, Puneet; Verstuyf, Annemieke; Verlinden, Lieve; Carmeliet, Geert

    2016-01-01

    1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease. PMID:26681795

  7. Investigations to the Antibacterial Mechanism of Action of Kendomycin

    PubMed Central

    A. Elnakady, Yasser; Chatterjee, Indranil; Bischoff, Markus; Rohde, Manfred; Josten, Michaele; Sahl, Hans-Georg; Herrmann, Mathias; Müller, Rolf

    2016-01-01

    Purpose The emergence of bacteria that are resistant to many currently used drugs emphasizes the need to discover and develop new antibiotics that are effective against such multi-resistant strains. Kendomycin is a novel polyketide that has a unique quinone methide ansa structure and various biological properties. This compound exhibits strong antibacterial activity against Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Despite the promise of kendomycinin in several therapeutic areas, its mode of action has yet to be identified. Methods In this study, we used a multidisciplinary approach to gain insight into the antibacterial mechanism of this compound. Results The antibacterial activity of kendomycin appears to be bacteriostatic rather than bactericidal. Kendomycin inhibited the growth of the MRSA strain COL at a low concentration (MIC of 5 μg/mL). Proteomic analysis and gene transcription profiling of kendomycin-treated cells indicated that this compound affected the regulation of numerous proteins and genes involved in central metabolic pathways, such as the tricarboxylic acid (TCA) cycle (SdhA) and gluconeogenesis (PckA and GapB), cell wall biosynthesis and cell division (FtsA, FtsZ, and MurAA), capsule production (Cap5A and Cap5C), bacterial programmed cell death (LrgA and CidA), the cellular stress response (ClpB, ClpC, ClpP, GroEL, DnaK, and GrpE), and oxidative stress (AhpC and KatA). Electron microscopy revealed that kendomycin strongly affected septum formation during cell division. Most kendomycin-treated cells displayed incomplete septa with abnormal morphology. Conclusions Kendomycin might directly or indirectly affect the cell division machinery, protein stability, and programmed cell death in S. aureus. Additional studies are still needed to obtain deeper insight into the mode of action of kendomycin. PMID:26795276

  8. Studying Genes

    MedlinePlus

    ... Area What are genes? Genes are sections of DNA that contain instructions for making the molecules—many ... material in an organism. This includes genes and DNA elements that control the activity of genes. Does ...

  9. Gastric cytoprotection beyond prostaglandins: cellular and molecular mechanisms of gastroprotective and ulcer healing actions of antacids.

    PubMed

    Tarnawski, Andrzej; Ahluwalia, Amrita; Jones, Michael K

    2013-01-01

    This article updates current views on gastric mucosal defense, injury, protection and ulcer healing with a focus on mucosal protective and ulcer healing actions of antacids. The gastric mucosa is continuously exposed to a variety of noxious factors, both endogenous such as: 0.1N hydrochloric acid, pepsin, bile acids, lysolecithin, H. pylori toxins and exogenous such as NSAIDs, ethanol and others. Gastric mucosal integrity is maintained by pre-epithelial, epithelial and post-epithelial defense mechanisms permitting the mucosa to withstand exposure to the above damaging factors. When mucosal defense is weakened or overwhelmed by injurious factors, injury develops in the form of erosions or ulcers. In the late 1970s Andre Robert and coworkers discovered that microgram amounts of a prostaglandin E2 analog protects the gastric mucosa against a variety of ulcerogenic and necrotizing agents - even such strong inducers of injury as 100% ethanol and boiling water. They proposed a new concept of cytoprotection. Subsequently, other compounds, such as sulfhydryls, sucralfate and epidermal growth factor were shown to exert protective action on gastric mucosa. Additionally, some antacids have been shown to exert a potent mucosal protective action against a variety of injurious factors and accelerate healing of erosions and gastric ulcers. These actions of antacids, especially hydrotalcite - the newest and the most extensively studied antacid - are due to activation of prostaglandin synthesis; binding to and inactivation of pepsin, bile acids and H. pylori toxins; induction of heat shock proteins; and, activation of genes encoding growth factors and their receptors.

  10. The Increase in Signaling by Kisspeptin Neurons in the Preoptic Area and Associated Changes in Clock Gene Expression That Trigger the LH Surge in Female Rats Are Dependent on the Facilitatory Action of a Noradrenaline Input.

    PubMed

    Kalil, Bruna; Ribeiro, Aline B; Leite, Cristiane M; Uchôa, Ernane T; Carolino, Ruither O; Cardoso, Thais S R; Elias, Lucila L K; Rodrigues, José A; Plant, Tony M; Poletini, Maristela O; Anselmo-Franci, Janete A

    2016-01-01

    In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) of the preoptic area are considered to provide a major stimulatory input to the GnRH neuronal network that is responsible for triggering the preovulatory LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release, and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an α1-adrenergic receptor antagonist. In control rats, the estradiol-induced LH surge at 17 hours was associated with a significant increase in GnRH and kisspeptin content in the median eminence with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3 hours prior to the predicted time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the median eminence. In the preoptic area, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in the expression of the clock genes, Per1 and Bmal1. Together these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of α1-adrenergic receptors prior to the initiation of the LH surge and indicate a potential role of α1-adrenergic signaling in the circadian-controlled pathway timing of the preovulatory LH surge. PMID:26556532

  11. The Increase in Signaling by Kisspeptin Neurons in the Preoptic Area and Associated Changes in Clock Gene Expression That Trigger the LH Surge in Female Rats Are Dependent on the Facilitatory Action of a Noradrenaline Input.

    PubMed

    Kalil, Bruna; Ribeiro, Aline B; Leite, Cristiane M; Uchôa, Ernane T; Carolino, Ruither O; Cardoso, Thais S R; Elias, Lucila L K; Rodrigues, José A; Plant, Tony M; Poletini, Maristela O; Anselmo-Franci, Janete A

    2016-01-01

    In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) of the preoptic area are considered to provide a major stimulatory input to the GnRH neuronal network that is responsible for triggering the preovulatory LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release, and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an α1-adrenergic receptor antagonist. In control rats, the estradiol-induced LH surge at 17 hours was associated with a significant increase in GnRH and kisspeptin content in the median eminence with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3 hours prior to the predicted time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the median eminence. In the preoptic area, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in the expression of the clock genes, Per1 and Bmal1. Together these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of α1-adrenergic receptors prior to the initiation of the LH surge and indicate a potential role of α1-adrenergic signaling in the circadian-controlled pathway timing of the preovulatory LH surge.

  12. Mechanisms of action of acetaldehyde in the up-regulation of the human α2(I) collagen gene in hepatic stellate cells: key roles of Ski, SMAD3, SMAD4, and SMAD7.

    PubMed

    Reyes-Gordillo, Karina; Shah, Ruchi; Arellanes-Robledo, Jaime; Hernández-Nazara, Zamira; Rincón-Sánchez, Ana Rosa; Inagaki, Yutaka; Rojkind, Marcos; Lakshman, M Raj

    2014-05-01

    Alcohol-induced liver fibrosis and eventually cirrhosis is a leading cause of death. Acetaldehyde, the first metabolite of ethanol, up-regulates expression of the human α2(I) collagen gene (COL1A2). Early acetaldehyde-mediated effects involve phosphorylation and nuclear translocation of SMAD3/4-containing complexes that bind to COL1A2 promoter to induce fibrogenesis. We used human and mouse hepatic stellate cells to elucidate the mechanisms whereby acetaldehyde up-regulates COL1A2 by modulating the role of Ski and the expression of SMADs 3, 4, and 7. Acetaldehyde induced up-regulation of COL1A2 by 3.5-fold, with concomitant increases in the mRNA (threefold) and protein (4.2- and 3.5-fold) levels of SMAD3 and SMAD4, respectively. It also caused a 60% decrease in SMAD7 expression. Ski, a member of the Ski/Sno oncogene family, is colocalized in the nucleus with SMAD4. Acetaldehyde induces translocation of Ski and SMAD4 to the cytoplasm, where Ski undergoes proteasomal degradation, as confirmed by the ability of the proteasomal inhibitor lactacystin to blunt up-regulation of acetaldehyde-dependent COL1A2, but not of the nonspecific fibronectin gene (FN1). We conclude that acetaldehyde up-regulates COL1A2 by enhancing expression of the transactivators SMAD3 and SMAD4 while inhibiting the repressor SMAD7, along with promoting Ski translocation from the nucleus to cytoplasm. We speculate that drugs that prevent proteasomal degradation of repressors targeting COL1A2 may have antifibrogenic properties.

  13. Loss of a 20S Proteasome Activator in Saccharomyces cerevisiae Downregulates Genes Important for Genomic Integrity, Increases DNA Damage, and Selectively Sensitizes Cells to Agents With Diverse Mechanisms of Action

    PubMed Central

    Doherty, Kevin M.; Pride, Leah D.; Lukose, James; Snydsman, Brian E.; Charles, Ronald; Pramanik, Ajay; Muller, Eric G.; Botstein, David; Moore, Carol Wood

    2012-01-01

    Cytoprotective functions of a 20S proteasome activator were investigated. Saccharomyces cerevisiae Blm10 and human 20S proteasome activator 200 (PA200) are homologs. Comparative genome-wide analyses of untreated diploid cells lacking Blm10 and growing at steady state at defined growth rates revealed downregulation of numerous genes required for accurate chromosome structure, assembly and repair, and upregulation of a specific subset of genes encoding protein-folding chaperones. Blm10 loss or truncation of the Ubp3/Blm3 deubiquitinating enzyme caused massive chromosomal damage and cell death in homozygous diploids after phleomycin treatments, indicating that Blm10 and Ubp3/Blm3 function to stabilize the genome and protect against cell death. Diploids lacking Blm10 also were sensitized to doxorubicin, hydroxyurea, 5-fluorouracil, rapamycin, hydrogen peroxide, methyl methanesulfonate, and calcofluor. Fluorescently tagged Blm10 localized in nuclei, with enhanced fluorescence after DNA replication. After DNA damage that caused a classic G2/M arrest, fluorescence remained diffuse, with evidence of nuclear fragmentation in some cells. Protective functions of Blm10 did not require the carboxyl-terminal region that makes close contact with 20S proteasomes, indicating that protection does not require this contact or the truncated Blm10 can interact with the proteasome apart from this region. Without its carboxyl-terminus, Blm10(−339aa) localized to nuclei in untreated, nonproliferating (G0) cells, but not during G1 S, G2, and M. The results indicate Blm10 functions in protective mechanisms that include the machinery that assures proper assembly of chromosomes. These essential guardian functions have implications for ubiquitin-independent targeting in anticancer therapy. Targeting Blm10/PA200 together with one or more of the upregulated chaperones or a conventional treatment could be efficacious. PMID:22908043

  14. Hope for Environmental Action

    ERIC Educational Resources Information Center

    Fleischer, Barbara J.; DeMoor, Emily

    2015-01-01

    Environmental consciousness-raising programs tend to emphasize the magnitude of imminent ecological disasters, if humans continue on their current trajectory. While these environmental literacy programs also call for action to avoid cataclysmic ecological changes, psychological research on "learned helplessness" suggests that information…

  15. Affirmative Action Plan.

    ERIC Educational Resources Information Center

    Triton Coll., River Grove, IL.

    In order to develop an affirmative action plan at Triton College, the college President appointed a committee made up of nine representatives from the various college constituencies, the majority of which were women and minorities, to determine the objectives to be achieved and how to implement them, and to establish appropriate review procedures.…

  16. Affirmative Action for Men?

    ERIC Educational Resources Information Center

    Malveaux, Julianne

    2005-01-01

    If colleges are willing to consider "social engineering" and affirmative action to ensure the inclusion of White men, are they willing to do so for African Americans and other people of color? Will the Center for Individual Rights ride to the rescue of the White women who may be unfairly nudged out of positions for which they are "qualified" in…

  17. Jump into Action

    ERIC Educational Resources Information Center

    Ball, Stephen; Cohen, Ann; Meyer, Margaret

    2012-01-01

    Jump Into Action (JIA) is a school-based team-taught program to help fifth-grade students make healthy food choices and be more active. The JIA team (physical education teacher, classroom teacher, school nurse, and parent) work together to provide a supportive environment as students set goals to improve food choices and increase activity.…

  18. From Awareness to Action

    ERIC Educational Resources Information Center

    Micklos, John, Jr.

    2012-01-01

    What inspires young people to become activists? Events such as wars or regime changes obviously raise high emotions. But some choose to get involved because they saw a need and felt compelled to take action. Young Americans have a long track record as activists. Among other things, they played a key role in the civil rights movement of the 1950s…

  19. Action for Children's Television.

    ERIC Educational Resources Information Center

    Ranly, Donald P.

    The origins, development, and effectiveness of Action for Children's Television (ACT) are examined in this pamphlet. The strategies used by ACT to obtain change at the congressional level and within television stations and networks include the following: a "tuneout" day when people are urged to turn off their television sets, a boycott of certain…

  20. Literacy Education Action.

    ERIC Educational Resources Information Center

    Clymer, Carol

    The Literacy Education Action (LEA) program was established in the fall of 1985 under the initiative of the president of the El Paso Community College (Texas). During 1985 and 1986, LEA concentrated on developing its own literacy tutoring program, including recruiting and training volunteers and community members with reading skills below the…

  1. Cognitive framing in action.

    PubMed

    Huhn, John M; Potts, Cory Adam; Rosenbaum, David A

    2016-06-01

    Cognitive framing effects have been widely reported in higher-level decision-making and have been ascribed to rules of thumb for quick thinking. No such demonstrations have been reported for physical action, as far as we know, but they would be expected if cognition for physical action is fundamentally similar to cognition for higher-level decision-making. To test for such effects, we asked participants to reach for a horizontally-oriented pipe to move it from one height to another while turning the pipe 180° to bring one end (the "business end") to a target on the left or right. From a physical perspective, participants could have always rotated the pipe in the same angular direction no matter which end was the business end; a given participant could have always turned the pipe clockwise or counter-clockwise. Instead, our participants turned the business end counter-clockwise for left targets and clockwise for right targets. Thus, the way the identical physical task was framed altered the way it was performed. This finding is consistent with the hypothesis that cognition for physical action is fundamentally similar to cognition for higher-level decision-making. A tantalizing possibility is that higher-level decision heuristics have roots in the control of physical action, a hypothesis that accords with embodied views of cognition. PMID:26970853

  2. Nutrition Action Pack.

    ERIC Educational Resources Information Center

    Sockut, Joanne; Stumpe, Stephanie

    One of five McDonald's Action Packs, these instructional materials integrate elementary school-level nutrition education into other disciplines--biology, sociology, physiology, mathematics, and art. Contents include four units consisting of twelve activities. Unit 1, Why You Need Food, is a self-examination of what is needed for growth, health,…

  3. Economics Action Pack.

    ERIC Educational Resources Information Center

    McDonald's Corp., Oak Brook, IL.

    One of five McDonald's Action Packs, this learning package introduces intermediate grade students to basic economic concepts. The fourteen activities include the topics of consumption (4 activities), production (5), the market system (3), a pretest, and a posttest. Specific titles under consumption include The Wonderful Treasure Tree (introduction…

  4. SYRACUSE ACTION FOR YOUTH.

    ERIC Educational Resources Information Center

    ADDINGTON, HAROLD E.; AND OTHERS

    A PROPOSAL WAS MADE TO PREVENT AND CONTROL JUVENILE DELINQUENCY BY OPENING OPPORTUNITIES AND DEVELOPING COMPETENCE AMONG DISADVANTAGED YOUTH. THE TOTAL COMMUNITY WAS MOBILIZED TO DEVELOP A PROGRAM TO ATTACK THE PROBLEM AT ALL LEVELS THEY WORKED FOR 18 MONTHS TO PLAN A SERIES OF CREATIVE ACTION PROGRAMS IN EDUCATION, EMPLOYMENT, AND COMMUNITY…

  5. From Intuition to Action

    ERIC Educational Resources Information Center

    Principal, 2012

    2012-01-01

    The vast majority of principals intuitively believe that the arts belong in schools and in every child's life. Now is the time to take action on your intuition--and become an instructional leader for the arts, just as you are for every core subject. Arts-engaged principals share strategies for becoming instructional leaders for the arts.

  6. Instructional Rounds in Action

    ERIC Educational Resources Information Center

    Roberts, John E.

    2012-01-01

    "Instructional Rounds in Action" is an invaluable guide for those involved in implementing instructional rounds as the foundation and framework for systemic improvement in schools. Over the past few years, districts across the United States, Canada, and Australia have begun implementing "instructional rounds," a set of ideas and practices for…

  7. Action Research in Practice

    ERIC Educational Resources Information Center

    Piggot-Irvine, Eileen

    2009-01-01

    Action research places a powerful tool for school improvement in the hands of teachers. By highlighting the outcomes that are possible and presenting clear steps in the research process, this book is one to encourage anyone who is seeking to implement evidence-based school improvement. Eileen Piggot-Irvine uses her Problem Resolving Action…

  8. The Shape of Action

    ERIC Educational Resources Information Center

    Hard, Bridgette Martin; Recchia, Gabriel; Tversky, Barbara

    2011-01-01

    How do people understand the everyday, yet intricate, behaviors that unfold around them? In the present research, we explored this by presenting viewers with self-paced slideshows of everyday activities and recording looking times, subjective segmentation (breakpoints) into action units, and slide-to-slide physical change. A detailed comparison of…

  9. School Reform in Action.

    ERIC Educational Resources Information Center

    Miller, A. Christine

    This study describes and analyzes the impact on student learning and the learning environment of 55 schools in Broward, Palm Beach, and Miami-Dade school districts as they implemented the schoolwide action-research framework for school improvement. Interviews, observations, document review during site visits, school framework reports, surveys,…

  10. Justifying Action Research

    ERIC Educational Resources Information Center

    Helskog, Guro Hansen

    2014-01-01

    In this paper I use a general philosophy of science perspective in looking at the problem of justifying action research. First I try to clarify the concept of justification, by contrasting it with the concept of validity, which seems to be used almost as a synonym in some parts of the literature. I discuss the need for taking a stand in relation…

  11. Promoting Environmental Action.

    ERIC Educational Resources Information Center

    Bowyer, John

    1994-01-01

    Outlines a lesson on the extinction process allowing students to better understand why and how species become endangered before they attempt to take action on this problem. Provides background information and describes several suggested methodologies, evaluation and enrichment ideas, six resources, and two references. (LZ)

  12. College Comedy and Action

    ERIC Educational Resources Information Center

    Moore, Rosanna

    1977-01-01

    A few materials such as yarn and scraps of paper and cloth can provide the media for recording limitless ideas from the imaginations of students. With a little encouragement and a few suggestions of actions, emotions, exaggerations and activities students will produce a vast array of amusing characters. (Author)

  13. 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…

  14. Literacy Portfolios in Action.

    ERIC Educational Resources Information Center

    Valencia, Sheila W.

    Intended for new and experienced teachers in grades K-8, this book takes readers through a process of thinking about how to put portfolios into action. The book models a process for making decisions about the type of portfolio, what to place in it, how to structure the interactions with it, and how to use it to evaluate student progress and report…

  15. Sustainability as Moral Action

    ERIC Educational Resources Information Center

    Dunn, Merrily S.; Hart-Steffes, Jeanne S.

    2012-01-01

    When one considers sustainability as a moral action, there are equally complex realities at hand--climate change, resource depletion, water and land rights. One author describes this broad sense of sustainability as "the connection of specific social and environmental problems to the functioning of human and ecological systems" (Jenkins, 2011).…

  16. Programs for Urban Action.

    ERIC Educational Resources Information Center

    National Board of Young Men's Christian Associations, New York, NY.

    This booklet contains descriptions of 150 urban action programs being conducted by Young Men's Christian Associations throughout the United States. Planning principles are included to assist those who wish to adapt the programs to local situations: involvement of people in planning; use of local indigenous leadership; planning in collaboration…

  17. Affirmative Action Fallout

    ERIC Educational Resources Information Center

    Roach, Ronald

    2005-01-01

    Race-conscious affirmative action in higher education survived a close challenge in 2003 when the U.S. Supreme Court ruled that race was a valid academic admission criteria in the "Grutter v. Bollinger" case. Two years later, a number of "pipeline" programs to help under-represented minorities gain admission to and complete graduate school have…

  18. Action Learning Issues.

    ERIC Educational Resources Information Center

    1998

    This document contains four papers from a symposium on adult learning issues and human resource development (HRD). "Creating a Systemic Framework for the Transfer of Learning from an Action Learning Experience" (Suzanne D. Butterfield, Kitty Gold, Verna J. Willis) discusses a study of the organizational elements that affect learning and transfer…

  19. Conjugate flow action functionals

    SciTech Connect

    Venturi, Daniele

    2013-11-15

    We present a new general framework to construct an action functional for a non-potential field theory. The key idea relies on representing the governing equations relative to a diffeomorphic flow of curvilinear coordinates which is assumed to be functionally dependent on the solution field. Such flow, which will be called the conjugate flow, evolves in space and time similarly to a physical fluid flow of classical mechanics and it can be selected in order to symmetrize the Gâteaux derivative of the field equations with respect to suitable local bilinear forms. This is equivalent to requiring that the governing equations of the field theory can be derived from a principle of stationary action on a Lie group manifold. By using a general operator framework, we obtain the determining equations of such manifold and the corresponding conjugate flow action functional. In particular, we study scalar and vector field theories governed by second-order nonlinear partial differential equations. The identification of transformation groups leaving the conjugate flow action functional invariant could lead to the discovery of new conservation laws in fluid dynamics and other disciplines.

  20. Angels in Action

    ERIC Educational Resources Information Center

    Stylianou, Xanthippi Cynthia

    2009-01-01

    In this article, the author discusses the importance of the placement of action lines to show the direction of movement. The author shows some visuals of angels and discusses in details the texture of the wings, the hair and the clothing.