Science.gov

Sample records for calb2 promoter acts

  1. Act To Promote Adult Education.

    ERIC Educational Resources Information Center

    1970

    An act of the German Lower Saxony Parliament to promote adult education is presented. It has 24 general provisions relating to the following: purpose of adult education, principle for promotion, conditions for promotions of establishments, independence of adult education, prerequisites and form of acknowledgement of entitlement to promotion,…

  2. Identification of cis- and trans-acting elements regulating calretinin expression in mesothelioma cells

    PubMed Central

    Kresoja-Rakic, Jelena; Kapaklikaya, Esra; Ziltener, Gabriela; Dalcher, Damian; Santoro, Raffaella; Christensen, Brock C.; Johnson, Kevin C.; Schwaller, Beat; Weder, Walter; Stahel, Rolf A.; Felley-Bosco, Emanuela

    2016-01-01

    Calretinin (CALB2) is a diagnostic marker for epithelioid mesothelioma. It is also a prognostic marker since patients with tumors expressing high calretinin levels have better overall survival. Silencing of calretinin decreases viability of epithelioid mesothelioma cells. Our aim was to elucidate mechanisms regulating calretinin expression in mesothelioma. Analysis of calretinin transcript and protein suggested a control at the mRNA level. Treatment with 5-aza-2′-deoxycytidine and analysis of TCGA data indicated that promoter methylation is not likely to be involved. Therefore, we investigated CALB2 promoter by analyzing ~1kb of genomic sequence surrounding the transcription start site (TSS) + 1 using promoter reporter assay. Deletion analysis of CALB2 proximal promoter showed that sequence spanning the −161/+80bp region sustained transcriptional activity. Site-directed analysis identified important cis-regulatory elements within this −161/+80bp CALB2 promoter. EMSA and ChIP assays confirmed binding of NRF-1 and E2F2 to the CALB2 promoter and siRNA knockdown of NRF-1 led to decreased expression of calretinin. Cell synchronization experiment showed that calretinin expression was cell cycle regulated with a peak of expression at G1/S phase. This study provides the first insight in the regulation of CALB2 expression in mesothelioma cells. PMID:26848772

  3. Antibodies Act Jointly to Promote Inflammation in Rheumatoid Arthritis

    MedlinePlus

    ... 1999 Spotlight on Research 2014 September 2014 (historical) Antibodies Act Jointly to Promote Inflammation in Rheumatoid Arthritis Two types of antibody molecules act in concert to stimulate inflammation in ...

  4. Mutations of the Act Promoter in Myxococcus xanthus▿ †

    PubMed Central

    Gronewold, Thomas M. A.; Kaiser, Dale

    2007-01-01

    Mutations within the −12 and −24 elements provide evidence that the act promoter is recognized by sigma-54 RNA polymerase. Deletion of the −20 base pair, which lies between the two conserved elements of sigma-54 promoters, decreased expression by 90%. In addition, mutation of a potential enhancer sequence, around −120, led to an 80% reduction in act gene expression. actB, the second gene in the act operon, encodes a sigma-54 activator protein that is proposed to be an enhancer-binding protein for the act operon. All act genes, actA to actE, are expressed together and constitute an operon, because an in-frame deletion of actB decreased expression of actA and actE to the same extent. After an initially slow phase of act operon expression, which depends on FruA, there is a rapid phase. The rapid phase is shown to be due to the activation of the operon expression by ActB, which completes a positive feedback loop. That loop appears to be nested within a larger positive loop in which ActB is activated by the C signal via ActA, and the act operon activates transcription of the csgA gene. We propose that, as cells engage in more C signaling, positive feedback raises the number of C-signal molecules per cell and drives the process of fruiting body development forward. PMID:17189369

  5. Characterization of cis-acting elements residing in the chitinase promoter of Bacillus pumilus SG2.

    PubMed

    Heravi, K Morabbi; Shali, A; Naghibzadeh, N; Ahmadian, G

    2014-05-01

    Bacillus pumilus SG2 is a chitinolytic bacterium that produces two chitinases, namely ChiS and ChiL. The chiS and chiL genes are consecutively expressed under a common promoter. Regulation of the chiS and chiL genes is under the control of carbon catabolite repression (CCR) in B. pumilus. This study aimed to investigate the cis-acting elements of the chitinase promoter. For this purpose, we transferred the chiS gene along with its specific promoter to Bacillus subtilis as a host. Primer extension analysis revealed two transcription start sites located 287 and 65 bp upstream of the chiS start codon. The distal promoter was highly compatible with the consensus sequence of the σ(A)-type promoters in B. subtilis, whereas the proximal promoter sequence showed less similarity to the σ(A)-type consensus sequence. A catabolite responsive element (cre), which is required for CCR in Bacillus species, was found to be 136 to 123 bp upstream of the chiS start codon. Interestingly, this cre site was located upstream of the -35 of the proximal promoter and downstream of the distal promoter. Deletion of this cre site sequence rendered the chiS expression constitutive. PMID:24293243

  6. Isolation of mutations that act in trans to alter expression from a yeast hsp70 promoter.

    PubMed Central

    Findly, R C; Alavi, H; Platt, T

    1988-01-01

    Transcription of SSA1 (formerly YG100), a member of the hsp70 gene family in Saccharomyces cerevisiae, increases dramatically upon heat shock. An expression vector in which the promoter of SSA1 is fused to the Escherichia coli galactokinase gene (galK) was constructed and transformed into a galactokinase-deficient yeast strain. The transformants grew on galactose at 23 degrees C, but increased expression of the SSA1-galK fusion gene inhibited growth of cells on galactose at 37 degrees C. Selection for survivors under nonpermissive conditions yielded a class of mutants, termed HSR (for heat shock regulation), which showed reduced levels of expression of the hsp70-galK gene fusion as determined by measurement of galactokinase activity. Similar effects on beta-galactosidase activity were obtained when an SSA1-lacZ fusion vector was introduced into the mutants, suggesting action in trans through the SSA1 promoter. Analysis of Northern (RNA) blots demonstrated that the reduction in expression was a result of decreased mRNA levels for the fusion gene. In addition, mRNA levels of the endogenous SSA1 gene are reduced in an HSR mutant. Genetic analysis has shown that these mutations act in trans and affect both transcription from the SSA1 promoter and turnover of the fusion transcript. These are the first trans-acting mutations known to affect directly the transcriptional regulation and transcript stability of heat shock genes in eucaryotes. Images PMID:3145411

  7. Implementing the Affordable Care Act: Promoting Competition in the Individual Marketplaces.

    PubMed

    Cusano, David; Lucia, Kevin

    2016-02-01

    A main goal of the Affordable Care Act is to provide Americans with access to affordable coverage in the individual market, achieved in part by pro­moting competition among insurers on premium price and value. One primary mechanism for meeting that goal is the establishment of new individual health insurance marketplaces where consumers can shop for, compare, and purchase plans, with subsidies if they are eligible. In this issue brief, we explore how the Affordable Care Act is influencing competition in the individual marketplaces in four states--Kansas, Nevada, Rhode Island, and Washington. Strategies include: educating consumers and providing coverage information in one place to ease decision-making; promoting competition among insurers; and ensuring a level playing field for premium rate development through the rate review process. PMID:26910926

  8. National workplace health promotion surveys: the Affordable Care Act and future surveys.

    PubMed

    DeJoy, David M; Dyal, Mari-Amanda; Padilla, Heather M; Wilson, Mark G

    2014-01-01

    This commentary reviews findings from the four previous national surveys of workplace health promotion activities (1985, 1992, 1999, and 2004, respectively) and offers recommendations for future surveys mandated under the Affordable Care Act of 2010. Future surveys should place greater emphasis on assessing program quality, reach, and effectiveness. Both employer and employee input should be sought. In addition, sampling plans should differentiate worksites from employers, and results should include public as well as private sector organizations. Ideas are offered for addressing these limitations and for creating a sustainable survey process and multifunctional database of results. PMID:24380423

  9. The Pain Relief Promotion Act of 1999: a serious threat to palliative care.

    PubMed

    Orentlicher, D; Caplan, A

    2000-01-12

    Recent educational efforts in the US medical community have begun to address the critical issue of palliative care for terminally ill patients. However, a newly introduced bill in Congress, the Pain Relief Promotion Act of 1999 (PRPA), could dramatically hinder these efforts if enacted. The act criminally punishes the use of controlled substances to cause-or assist in causing-a patient's death. The primary purposes of PRPA are to override the physician-assisted suicide law currently in effect in Oregon and prohibit other states from enacting similar laws. The act also includes valuable provisions for better research and education in palliative care, but the benefits of those provisions are outweighed by the punitive sections of the act. Under PRPA, the quality of palliative care in the United States could be compromised when physicians, fearing criminal prosecution, err on the side of caution rather than risk their patients' deaths by using highly aggressive pain treatments. Furthermore, PRPA would put Drug Enforcement Administration officials, who have no medical expertise, in the position of regulating medical decisions. The act also would interfere with individual states' long-standing authority over medical practice. Finally, PRPA would discourage physicians from engaging in experimentation and innovation in palliative care, again out of concern for crossing the line between relief of suffering and physician-assisted suicide. Other bills have been introduced that go much further than PRPA to encourage palliative care, without its problematic provisions. Regardless of the controversy surrounding physician-assisted suicide in the United States, the need for quality end-of-life care will be far better served if Congress enacts one of these bills rather than PRPA. PMID:10634344

  10. Perfluorooctanoic acid (PFOA) acts as a tumor promoter on Syrian hamster embryo (SHE) cells.

    PubMed

    Jacquet, N; Maire, M A; Rast, C; Bonnard, M; Vasseur, P

    2011-08-01

    Perfluorooctane sulfonate (PFOS) (C(8)F(17)SO(3)) and perfluorooctanoic acid (PFOA) (C(8)HF(15)O(2)) are synthetic chemicals widely used in industrial applications for their hydrophobic and oleophobic properties. They are persistent, bioaccumulative, and toxic to mammalian species. Their widespread distribution on earth and contamination of human serum raised concerns about long-term side effects. They are suspected to be carcinogenic through a nongenotoxic mode of action, a mechanism supported by recent findings that PFOS induced cell transformation but no genotoxicity in Syrian hamster embryo (SHE) cells. In the present study, we evaluated carcinogenic potential of PFOA using the cell transformation assay on SHE cells. The chemical was applied alone or in combination with a nontransformant concentration of benzo[a]pyrene (BaP, 0.4 μM) in order to detect PFOA ability to act as tumor initiator or tumor promoter. The results showed that PFOA tested alone in the range 3.7 × 10(-5) to 300 μM did not induce SHE cell transformation frequency in a 7-day treatment. On the other side, the combination BaP/PFOA induced cell transformation at all PFOA concentrations tested, which revealed synergistic effects. No genotoxicity of PFOA on SHE cells was detected using the comet assay after 5 and 24 h of exposure. No significant increase in DNA breakage was found in BaP-initiated cells exposed to PFOA in a 7-day treatment. The whole results showed that PFOA acts as a tumor promoter and a nongenotoxic carcinogen. Cell transformation in initiated cells was observed at concentrations equivalent to the ones found in human serum of nonoccupationally and occupationally exposed populations. An involvement of PFOA in increased incidence of cancer recorded in occupationally exposed population cannot be ruled out. PMID:22828883

  11. A Cis-Acting Locus That Promotes Crossing over between X Chromosomes in Caenorhabditis Elegans

    PubMed Central

    Villeneuve, A. M.

    1994-01-01

    This study reports the characterization of a cis-acting locus on the Caenorhabditis elegans X chromosome that is crucial for promoting normal levels of crossing over specifically between the X homologs and for ensuring their proper disjunction at meiosis I. The function of this locus is disrupted by the mutation me8, which maps to the extreme left end of the X chromosome within the region previously implicated by studies of X;A translocations and X duplications to contain a meiotic pairing site. Hermaphrodites homozygous for a deletion of the locus (Df/Df) or heterozygous for a deletion and the me8 mutation (me8/Df) exhibit extremely high levels of X chromosome nondisjunction at the reductional division; this is correlated with a sharp decrease in crossing over between the X homologs as evidenced both by reductions in genetic map distances and by the presence of achiasmate chromosomes in cytological preparations of oocyte nuclei. Duplications of the wild-type region that are unlinked to the X chromosome cannot complement the recombination and disjunction defects in trans, indicating that this region must be present in cis to the X chromosome to ensure normal levels of crossing over and proper homolog disjunction. me8 homozygotes exhibit an altered distribution of crossovers along the X chromosome that suggests a defect in processivity along the X chromosome of an event that initiates at the chromosome end. Models are discussed in which the cis-acting locus deleted by the Dfs functions as a meiotic pairing center that recruits trans-acting factors onto the chromosomes to nucleate assembly of a crossover-competent complex between the X homologs. This pairing center might function in the process of homolog recognition, or in the initiation of homologous synapsis. PMID:8005443

  12. Health promotion research and practice require sound policy analysis models: the case of Quebec's Tobacco Act.

    PubMed

    Breton, Eric; Richard, Lucie; Gagnon, France; Jacques, Marie; Bergeron, Pierre

    2008-12-01

    In this paper we illustrate how policy analysis models can deepen our understanding of the challenges facing health promoters advocating for policy change. Specifically we describe the factors underpinning the adoption of Québec's Tobacco Act (1998) and the role played by actors from governmental public health agencies (GPHAs). Data were collected through interviews (n=39), newspapers articles (n=569) and documents (n > 200) from GPHAs, NGOs, the Québec National Assembly, and opponents to the legislative measures. Data collection and analysis were based on Sabatier and Jenkins-Smith's Advocacy Coalition Framework (1999) and Lemieux's theorization of coalition structuring (1998). We explain the adoption of the Act by: (1) the broad recognition within the policy elite of the main parameters of tobacco use (i.e. lethality, addictive properties, and legitimacy of governmental intervention), (2) the impacts of a series of events (e.g. cigarette contraband crisis) that enabled tobacco control advocates to influence public debates, and the governmental agenda, (3) the critical contribution of a coalition of GPHAs pooling resources to address both the sanitary and economic aspects of the legislation while countering the opposition's strategy, and (4) the failure of the opponents to present an unified voice on the definition of the tobacco policy. This study illustrates the merits of applying a policy-change model to grasp the complexity of the process. Our findings call for the development of permanent policy analysis capabilities within public health agencies and for a broader scrutiny of the non-health-related dimensions of policy debates. PMID:18829147

  13. A Dominantly Acting Murine Allele of Mcm4 Causes Chromosomal Abnormalities and Promotes Tumorigenesis

    PubMed Central

    Bagley, Bruce N.; Keane, Thomas M.; Maklakova, Vilena I.; Marshall, Jonathon G.; Lester, Rachael A.; Cancel, Michelle M.; Paulsen, Alex R.; Bendzick, Laura E.; Been, Raha A.; Kogan, Scott C.; Cormier, Robert T.; Kendziorski, Christina; Adams, David J.; Collier, Lara S.

    2012-01-01

    Here we report the isolation of a murine model for heritable T cell lymphoblastic leukemia/lymphoma (T-ALL) called Spontaneous dominant leukemia (Sdl). Sdl heterozygous mice develop disease with a short latency and high penetrance, while mice homozygous for the mutation die early during embryonic development. Sdl mice exhibit an increase in the frequency of micronucleated reticulocytes, and T-ALLs from Sdl mice harbor small amplifications and deletions, including activating deletions at the Notch1 locus. Using exome sequencing it was determined that Sdl mice harbor a spontaneously acquired mutation in Mcm4 (Mcm4D573H). MCM4 is part of the heterohexameric complex of MCM2–7 that is important for licensing of DNA origins prior to S phase and also serves as the core of the replicative helicase that unwinds DNA at replication forks. Previous studies in murine models have discovered that genetic reductions of MCM complex levels promote tumor formation by causing genomic instability. However, Sdl mice possess normal levels of Mcms, and there is no evidence for loss-of-heterozygosity at the Mcm4 locus in Sdl leukemias. Studies in Saccharomyces cerevisiae indicate that the Sdl mutation produces a biologically inactive helicase. Together, these data support a model in which chromosomal abnormalities in Sdl mice result from the ability of MCM4D573H to incorporate into MCM complexes and render them inactive. Our studies indicate that dominantly acting alleles of MCMs can be compatible with viability but have dramatic oncogenic consequences by causing chromosomal abnormalities. PMID:23133403

  14. Identification of two candidate collecting duct cell-specific cis-acting elements in the Hoxb-7 promoter region.

    PubMed

    Plaisier, Emmanuelle; Ribes, David; Ronco, Pierre; Rossert, Jérome

    2005-02-14

    HOX genes encode highly conserved transcription factors responsible for developmental patterning and postnatal tissue homeostasis. Previous studies have shown that a 1.4-kb segment of the Hoxb-7 proximal promoter drives renal expression of reporter genes specifically in the ureteric bud and collecting ducts. In this study using stably transfected renal tubule cell lines, we have identified three short cis-acting sequences within this promoter segment that cooperate to induce high-level expression specifically in collecting duct cells. In addition to an inverted CCAAT box (-71/-67) that acts as an ubiquitous enhancer and binds the transcription factor CBF/NF-Y, two different cis-acting sequences, named CDSE-1 and CDSE-2 (for Collecting Duct Specific Element 1 and 2), allow collecting duct cell-specific promoter activation. CDSE-1 (-56/-34) is composed of two E-boxes separated by a 9-bp GC-rich sequence. Only the latter sequence enhances reporter gene expression specifically in collecting duct cells. CDSE-2 (-34/-13) contains sequence bears high homology with a segment of the Pax-2 promoter. CDSE-2 also conveys cell specificity but has no enhancer activity by itself. PMID:15716052

  15. Hospital and Health Plan Partnerships: The Affordable Care Act's Impact on Promoting Health and Wellness

    PubMed Central

    Vu, Michelle; White, Annesha; Kelley, Virginia P.; Hopper, Jennifer Kuca; Liu, Cathy

    2016-01-01

    Background The Affordable Care Act (ACA) healthcare reforms, centered on achieving the Centers for Medicare & Medicaid Services (CMS) Triple Aim goals of improving patient care quality and satisfaction, improving population health, and reducing costs, have led to increasing partnerships between hospitals and insurance companies and the implementation of employee wellness programs. Hospitals and insurance companies have opted to partner to distribute the risk and resources and increase coordination of care. Objective To examine the ACA's impact on the health and wellness programs that have resulted from the joint ventures of hospitals and health plans based on the published literature. Method We conducted a review of the literature to identify successful mergers and best practices of health and wellness programs. Articles published between January 2007 and January 2015 were compiled from various search engines, using the search terms “corporate,” “health and wellness program,” “health plan,” “insurance plan,” “hospital,” “joint venture,” and “vertical merger.” Publications that described consolidations or wellness programs not tied to health insurance plans were excluded. Noteworthy characteristics of these programs were summarized and tabulated. Results A total of 44 eligible articles were included in the analysis. The findings showed that despite rising healthcare costs, joint ventures prevent hospitals from trading-off quality and services for cost reductions. Administrators believed that partnering would allow the companies to meet ACA standards for improving clinical outcomes at reduced costs. Before the implementation of the ACA, some employers had wellness programs, but these were not standardized and did not need to produce measurable results. The ACA encouraged improvement of employee wellness programs by providing funding for expanded health services and by mandating quality care. Successful workplace health and wellness

  16. [The Act of Promotion of Personal Autonomy and Long-Term Care. Reflections and recommendations for better development].

    PubMed

    López Casasnovas, Guillem

    2011-12-01

    The present article provides a critical analysis of the state of affairs of the care of dependent individuals and proposals for reform of social protection systems for dependency - especially the Act of Promotion of Personal Autonomy and Long-Term Care. The existing form of public coverage is linked to the theory of public finance. Against this background, a series of recommendations are made to achieve the goals of this important component of the welfare state. PMID:22047621

  17. Early growth response protein 1 acts as an activator of SOX18 promoter

    PubMed Central

    Petrovic, Isidora; Kovacevic-Grujicic, Natasa

    2010-01-01

    Sex-determining region Y box 18 (Sox18/SOX18) gene is an important regulator of vascular development playing a role in endothelial cell specification or differentiation, angiogenesis and atherogenesis. The aim of this study was to perform comprehensive functional characterization of the human SOX18 promoter, including determination of transcription start point (tsp) and identification of control elements involved in the regulation of SOX18 gene expression, with an emphasis on angiogenesis-related transcription factors. Analyses were performed in HeLa cells, representing a tumor cell line, and in EA.hy926 cells used as an endothelial model system. We have determined unique tsp of SOX18 gene, located 172 nucleotides upstream from ATG codon. Further, we have shown that SOX18 promoter region, -726 to -89 bp relative to tsp, contains positive cis-regulatory element(s) that stimulates SOX18 promoter activity, while region -89 to + 166 represents the minimal promoter. Within this region we have recognized the presence of essential element(s), positioned from -89 to +29, which harbors cluster of three putative early growth response 1 (EGR1) binding sites. By in vitro binding assays and functional analyses we have shown that these three putative binding sites are functionally relevant and sufficient for EGR1-induced SOX18 transcription. Mutations of these binding sites significantly impaired activity of the SOX18 promoter, particularly in EA.hy926 cells, indicating the importance of these regulatory elements for SOX18 promoter activity in endothelial setting. By data presented in this study, we have established SOX18 as a novel target gene regulated by EGR1 transcription factor, thus providing the first functional link between two transcription factors previously shown to be involved in the control of angiogenesis. PMID:20054233

  18. Promoting Innovation and Controversy in Adult Basic Education: Section 309 of the Adult Education Act.

    ERIC Educational Resources Information Center

    Radwin, Eugene

    Section 309 of the Adult Education Act of 1966 provided discretionary grants for special projects and teacher training in adult basic education (ABE). The 309 program played an important role in innovations, recruitment, instructional materials, and teaching strategies, and it demonstrated how active Federal officials could boost state and local…

  19. Reward Excellence and Promote Innovation. Reauthorizing the Elementary and Secondary Education Act

    ERIC Educational Resources Information Center

    US Department of Education, 2010

    2010-01-01

    To achieve President Obama's stated goal of providing a world-class education to every child in America, the administration has designed a blueprint for a reenvisioned federal role in education through the reauthorization of the "Elementary and Secondary Education Act" ("ESEA"). The new "ESEA" will raise the bar for and reward excellence in…

  20. "Act Healthy": Promoting Health Behaviors and Self-Efficacy in the Workplace

    ERIC Educational Resources Information Center

    Schopp, Laura H.; Bike, Denise H.; Clark, Mary J.; Minor, Marian A.

    2015-01-01

    Chronic health conditions and multiple health risk factors afflict Americans and burden employers, but effective, affordable, workplace-based health promotion interventions have not been widely implemented. This is the first study to adapt the empirically validated Chronic Disease Self-Management Program for a general employee population in a…

  1. Promotion

    PubMed Central

    Alam, Hasan B.

    2013-01-01

    This article gives an overview of the promotion process in an academic medical center. A description of different promotional tracks, tenure and endowed chairs, and the process of submitting an application is provided. Finally, some practical advice about developing skills and attributes that can help with academic growth and promotion is dispensed. PMID:24436683

  2. Chicken ovalbumin upstream promoter transcription factors act as auxiliary cofactors for hepatocyte nuclear factor 4 and enhance hepatic gene expression.

    PubMed Central

    Ktistaki, E; Talianidis, I

    1997-01-01

    Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) strongly inhibit transcriptional activation mediated by nuclear hormone receptors, including hepatocyte nuclear factor 4 (HNF-4). COUP-TFs repress HNF-4-dependent gene expression by competition with HNF-4 for common binding sites found in several regulatory regions. Here we show that promoters, such as the HNF-1 promoter, which are recognized by HNF-4 but not by COUP-TFs are activated by COUP-TFI and COUP-TFII in conjunction with HNF-4 more than 100-fold above basal levels, as opposed to about 8-fold activation by HNF-4 alone. This enhancement was strictly dependent on an intact HNF-4 E domain. In vitro and in vivo evidence suggests that COUP-TFs enhance HNF-4 activity by a mechanism that involves their physical interaction with the amino acid 227 to 271 region of HNF-4. Our results indicate that in certain promoters, COUP-TFs act as auxiliary cofactors for HNF-4, orienting the HNF-4 activation domain in a more efficient configuration to achieve enhanced transcriptional activity. These findings provide new insights into the regulatory functions of COUP-TFs, suggesting their involvement in the initial activation and subsequent high-level expression of hepatic regulators, as well as in the positive and negative modulation of downstream target genes. PMID:9111350

  3. Chicken ovalbumin upstream promoter transcription factors act as auxiliary cofactors for hepatocyte nuclear factor 4 and enhance hepatic gene expression.

    PubMed

    Ktistaki, E; Talianidis, I

    1997-05-01

    Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) strongly inhibit transcriptional activation mediated by nuclear hormone receptors, including hepatocyte nuclear factor 4 (HNF-4). COUP-TFs repress HNF-4-dependent gene expression by competition with HNF-4 for common binding sites found in several regulatory regions. Here we show that promoters, such as the HNF-1 promoter, which are recognized by HNF-4 but not by COUP-TFs are activated by COUP-TFI and COUP-TFII in conjunction with HNF-4 more than 100-fold above basal levels, as opposed to about 8-fold activation by HNF-4 alone. This enhancement was strictly dependent on an intact HNF-4 E domain. In vitro and in vivo evidence suggests that COUP-TFs enhance HNF-4 activity by a mechanism that involves their physical interaction with the amino acid 227 to 271 region of HNF-4. Our results indicate that in certain promoters, COUP-TFs act as auxiliary cofactors for HNF-4, orienting the HNF-4 activation domain in a more efficient configuration to achieve enhanced transcriptional activity. These findings provide new insights into the regulatory functions of COUP-TFs, suggesting their involvement in the initial activation and subsequent high-level expression of hepatic regulators, as well as in the positive and negative modulation of downstream target genes. PMID:9111350

  4. AP-1 family members act with Sox9 to promote chondrocyte hypertrophy.

    PubMed

    He, Xinjun; Ohba, Shinsuke; Hojo, Hironori; McMahon, Andrew P

    2016-08-15

    An analysis of Sox9 binding profiles in developing chondrocytes identified marked enrichment of an AP-1-like motif. Here, we have explored the functional interplay between Sox9 and AP-1 in mammalian chondrocyte development. Among AP-1 family members, Jun and Fosl2 were highly expressed within prehypertrophic and early hypertrophic chondrocytes. Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) showed a striking overlap in Jun- and Sox9-bound regions throughout the chondrocyte genome, reflecting direct binding of each factor to the same enhancers and a potential for protein-protein interactions within AP-1- and Sox9-containing complexes. In vitro reporter analysis indicated that direct co-binding of Sox9 and AP-1 at target motifs promoted gene activity. By contrast, where only one factor can engage its DNA target, the presence of the other factor suppresses target activation consistent with protein-protein interactions attenuating transcription. Analysis of prehypertrophic chondrocyte removal of Sox9 confirmed the requirement of Sox9 for hypertrophic chondrocyte development, and in vitro and ex vivo analyses showed that AP-1 promotes chondrocyte hypertrophy. Sox9 and Jun co-bound and co-activated a Col10a1 enhancer in Sox9 and AP-1 motif-dependent manners consistent with their combined action promoting hypertrophic gene expression. Together, the data support a model in which AP-1 family members contribute to Sox9 action in the transition of chondrocytes to the hypertrophic program. PMID:27471255

  5. Will the No Child Left Behind Act Promote Direct Instruction of Science?

    NASA Astrophysics Data System (ADS)

    Hake, Richard

    2005-03-01

    Education research in physics at the high school and undergraduate level strongly suggests that interactive engagement enhances students' conceptual understanding much more than traditional Direct Science Instruction (DSI). Similar conclusions can be drawn from K-8 science-education research. Nevertheless, DSI predominates in CA because of the DSI- orientation of the CA State Board of Education and Curriculum Commission [1]. Likewise the U.S. Dept. of Education's (USDE's): (a) DSI-orientation as demonstrated by its recent national-education summit showcasing of the research of Klahr and Nigam [2]; and (b) science achievement testing starting in 2007; threatens to promote DSI nationwide. It might be hoped that NRC's expert science education committees will steer the USDE away from promoting DSI, the antithesis of the NRC's own recommendations for inquiry methods. [1] R.R. Hake. ``Direct Science Instruction Suffers a Setback in California - Or Does It?" (2004), <ł http://www.physics.indiana.edu/˜hake/DirInstSetback-041104f.pdf>. [2] Klahr, D. & M. Nigam. 2004. ``The equivalence of learning paths in early science instruction: effects of direct instruction and discovery learning" (2004), .

  6. Cbx8 acts non-canonically with Wdr5 to promote mammary tumorigenesis

    PubMed Central

    Chung, Chi-Yeh; Sun, Zhen; Mullokandov, Gavriel; Bosch, Almudena; Qadeer, Zulekha A.; Cihan, Esma; Rapp, Zachary; Parsons, Ramon; Aguirre-Ghiso, Julio A.; Farias, Eduardo F.; Brown, Brian D.; Gaspar-Maia, Alexandre; Bernstein, Emily

    2016-01-01

    SUMMARY Chromatin-mediated processes influence the development and progression of breast cancer. Using murine mammary carcinoma-derived tumorspheres as a functional readout for an aggressive breast cancer phenotype, we performed a loss-of-function screen targeting sixty epigenetic regulators. We identified the Polycomb protein Cbx8 as a key regulator of mammary carcinoma both in vitro and in vivo. Accordingly, Cbx8 is overexpressed in human breast cancer and correlates with poor survival. Our genomic analyses revealed that Cbx8 positively regulates Notch signaling by maintaining H3K4me3 levels on Notch-network gene promoters. Ectopic expression of Notch receptors partially rescues tumorsphere formation in Cbx8-depleted cells. We find that Cbx8 associates with non-PRC1 complexes containing the H3K4 methyltransferase complex component WDR5, which together regulate Notch gene expression. Thus, our study implicates a key non-canonical role for Cbx8 in promoting breast tumorigenesis. PMID:27346354

  7. Cbx8 Acts Non-canonically with Wdr5 to Promote Mammary Tumorigenesis.

    PubMed

    Chung, Chi-Yeh; Sun, Zhen; Mullokandov, Gavriel; Bosch, Almudena; Qadeer, Zulekha A; Cihan, Esma; Rapp, Zachary; Parsons, Ramon; Aguirre-Ghiso, Julio A; Farias, Eduardo F; Brown, Brian D; Gaspar-Maia, Alexandre; Bernstein, Emily

    2016-07-12

    Chromatin-mediated processes influence the development and progression of breast cancer. Using murine mammary carcinoma-derived tumorspheres as a functional readout for an aggressive breast cancer phenotype, we performed a loss-of-function screen targeting 60 epigenetic regulators. We identified the Polycomb protein Cbx8 as a key regulator of mammary carcinoma both in vitro and in vivo. Accordingly, Cbx8 is overexpressed in human breast cancer and correlates with poor survival. Our genomic analyses revealed that Cbx8 positively regulates Notch signaling by maintaining H3K4me3 levels on Notch-network gene promoters. Ectopic expression of Notch1 partially rescues tumorsphere formation in Cbx8-depleted cells. We find that Cbx8 associates with non-PRC1 complexes containing the H3K4 methyltransferase complex component WDR5, which together regulate Notch gene expression. Thus, our study implicates a key non-canonical role for Cbx8 in promoting breast tumorigenesis. PMID:27346354

  8. SDN-1/Syndecan Acts in Parallel to the Transmembrane Molecule MIG-13 to Promote Anterior Neuroblast Migration

    PubMed Central

    Sundararajan, Lakshmi; Norris, Megan L.; Lundquist, Erik A.

    2015-01-01

    The Q neuroblasts in Caenorhabditis elegans display left-right asymmetry in their migration, with QR and descendants on the right migrating anteriorly, and QL and descendants on the left migrating posteriorly. Initial QR and QL migration is controlled by the transmembrane receptors UNC-40/DCC, PTP-3/LAR, and the Fat-like cadherin CDH-4. After initial migration, QL responds to an EGL-20/Wnt signal that drives continued posterior migration by activating MAB-5/Hox activity in QL but not QR. QR expresses the transmembrane protein MIG-13, which is repressed by MAB-5 in QL and which drives anterior migration of QR descendants. A screen for new Q descendant AQR and PQR migration mutations identified mig-13 as well as hse-5, the gene encoding the glucuronyl C5-epimerase enzyme, which catalyzes epimerization of glucuronic acid to iduronic acid in the heparan sulfate side chains of heparan sulfate proteoglycans (HSPGs). Of five C. elegans HSPGs, we found that only SDN-1/Syndecan affected Q migrations. sdn-1 mutants showed QR descendant AQR anterior migration defects, and weaker QL descendant PQR migration defects. hse-5 affected initial Q migration, whereas sdn-1 did not. sdn-1 and hse-5 acted redundantly in AQR and PQR migration, but not initial Q migration, suggesting the involvement of other HSPGs in Q migration. Cell-specific expression studies indicated that SDN-1 can act in QR to promote anterior migration. Genetic interactions between sdn-1, mig-13, and mab-5 suggest that MIG-13 and SDN-1 act in parallel to promote anterior AQR migration and that SDN-1 also controls posterior migration. Together, our results indicate previously unappreciated complexity in the role of multiple signaling pathways and inherent left-right asymmetry in the control of Q neuroblast descendant migration. PMID:26022293

  9. Bicycle Helmet Promotion Act. Report of the Senate Committee on Commerce, Science, and Transportation on S. 3096. 102d Congress, 2d Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Committee on Commerce, Science, and Transportation.

    Senate Bill 3096 (S. 3096), the Bicycle Helmet Promotion Act, provides incentive grants to state and local governments that seek to promote the use of bicycle helmets by children under the age of 16. Between 1984 and 1988, a total of 4,815 Americans died and 2,830,475 suffered injuries requiring hospitalization as a result of accidents that…

  10. Effect of the act on promotion of personal autonomy and care for dependent persons on their family caregivers

    PubMed Central

    2012-01-01

    Background The need of home care services is becoming an increasingly common scenario. These cares are mainly provided by the dependents’ relatives specifically, by the women part of the family. This situation might take years, decreasing the physical and psychological health of the caregiver. In Spain, the Act of Promotion of Personal Autonomy and Care for dependent persons, guarantees those dependent persons and their caregivers to have access to social services or to financial grants. The aim of this study is to Know the possible effects of the benefits provided by this Act in regards to the mental health, the quality of life and use of health services by the family caregivers assisting their relatives in situation of dependency. Methods and design A longitudinal descriptive study following-up a cohort of patients and caregivers. The study shall be carried out in Andalusia. It shall include the baseline assessment of the variables in those caregivers free from the exposure factor (reception of assistance pursuant to the Act). Following, once the benefits have been received, this cohort shall be followed-up. The study shall take three years, and the starting date for its development as well as its funding is January 2011. Discussion The longitudinal assessment of the rate of change of the variables studied shall allow us to know the implications which might be potentially generated as well as the natural evolution of those. PMID:23244337

  11. SIRT6 promotes COX-2 expression and acts as an oncogene in skin cancer

    PubMed Central

    Ming, Mei; Han, Weinong; Zhao, Baozhong; Sundaresan, Nagalingam R.; Deng, Chu-Xia; Gupta, Mahesh; He, Yu-Ying

    2014-01-01

    SIRT6 is a SIR2 family member that regulates multiple molecular pathways involved in metabolism, genomic stability and aging. It has been proposed previously that SIRT6 is a tumor suppressor in cancer. Here we challenge this concept by presenting evidence that skin-specific deletion of SIRT6 in the mouse inhibits skin tumorigenesis. SIRT6 promoted expression of COX-2 by repressing AMPK signaling, thereby increasing cell proliferation and survival and in the skin epidermis. SIRT6 expression in skin keratinocytes was increased by exposure to UVB light through activation of the AKT pathway. Clinically, we found that SIRT6 was upregulated in human skin squamous cell carcinoma. Taken together, our results provide evidence that SIRT6 functions an oncogene in the epidermis and suggest greater complexity to its role in epithelial carcinogenesis. PMID:25320180

  12. Selfish third parties act as peacemakers by transforming conflicts and promoting cooperation.

    PubMed

    Halevy, Nir; Halali, Eliran

    2015-06-01

    The tremendous costs of conflict have made humans resourceful not only at warfare but also at peacemaking. Although third parties have acted as peacemakers since the dawn of history, little is known about voluntary, informal third-party intervention in conflict. Here we introduce the Peacemaker Game, a novel experimental paradigm, to model and study the interdependence between disputants and third parties in conflict. In the game, two disputants choose whether to cooperate or compete and a third party chooses whether or not to intervene in the conflict. Intervention introduces side payments that transform the game disputants are playing; it also introduces risk for the third party by making it vulnerable to disputants' choices. Six experiments revealed three robust effects: (i) The mere possibility of third-party intervention significantly increases cooperation in interpersonal and intergroup conflicts; (ii) reducing the risk to third parties dramatically increases intervention rates, to everyone's benefit; and (iii) disputants' cooperation rates are consistently higher than third parties' intervention rates. These findings explain why, how, and when self-interested third parties facilitate peaceful conflict resolution. PMID:26038546

  13. Selfish third parties act as peacemakers by transforming conflicts and promoting cooperation

    PubMed Central

    Halevy, Nir; Halali, Eliran

    2015-01-01

    The tremendous costs of conflict have made humans resourceful not only at warfare but also at peacemaking. Although third parties have acted as peacemakers since the dawn of history, little is known about voluntary, informal third-party intervention in conflict. Here we introduce the Peacemaker Game, a novel experimental paradigm, to model and study the interdependence between disputants and third parties in conflict. In the game, two disputants choose whether to cooperate or compete and a third party chooses whether or not to intervene in the conflict. Intervention introduces side payments that transform the game disputants are playing; it also introduces risk for the third party by making it vulnerable to disputants’ choices. Six experiments revealed three robust effects: (i) The mere possibility of third-party intervention significantly increases cooperation in interpersonal and intergroup conflicts; (ii) reducing the risk to third parties dramatically increases intervention rates, to everyone’s benefit; and (iii) disputants’ cooperation rates are consistently higher than third parties’ intervention rates. These findings explain why, how, and when self-interested third parties facilitate peaceful conflict resolution. PMID:26038546

  14. LTPB2 acts as a prognostic factor and promotes progression of cervical adenocarcinoma

    PubMed Central

    Ren, Yuan; Lu, Huan; Zhao, Danmei; Ou, Yangjun; Yu, Kang; Gu, Jiandong; Wang, Li; Jiang, Shuheng; Chen, Mo; Wang, Jinghao; Zhang, Rong; Xu, Congjian

    2015-01-01

    Latent transforming growth factor-beta-1 binding protein-2 (LTBP-2) is a member of the fibrillin/LTBP super family of extracellular matrix proteins, found to be overexpressed in certain malignant tumors. However, the clinical significance and biological role of LTBP-2 in cervical adenocarcinoma has remains unclear. We found that the expression of LTBP2 was higher in cervical adenocarcinoma than in normal cervical epithelial tissue as assessed by immunohistochemistry. Expression of LTBP2 is related to clinical stage, cervical tumor size, depth of cervical stromal invasion and lymph node metastasis. Knockdown of LTBP2 expression can inhibit the proliferation and migration of HeLa cells. Moreover, LTBP2 knockdown affected multiple tumor-related pathway genes including: the MAPK signaling pathway, the PI3K-AKT signaling pathway, receptor tyrosine kinase signaling and the P53 pathway. Taken together, this work suggests that LTBP2 may promote the development of cervical adenocarcinoma and serve as a prognostic factor in the clinical evaluation of patients with cervical adenocarcinoma. Our findings provide a new strategy for the diagnosis and treatment of cervical adenocarcinoma. PMID:26279753

  15. Human cytomegalovirus-encoded US28 may act as a tumor promoter in colorectal cancer

    PubMed Central

    Cai, Zhen-Zhai; Xu, Jian-Gang; Zhou, Yu-Hui; Zheng, Ji-Hang; Lin, Ke-Zhi; Zheng, Shu-Zhi; Ye, Meng-Si; He, Yun; Liu, Chang-Bao; Xue, Zhan-Xiong

    2016-01-01

    AIM: To assess human cytomegalovirus-encoded US28 gene function in colorectal cancer (CRC) pathogenesis. METHODS: Immunohistochemical analysis was performed to determine US28 expression in 103 CRC patient samples and 98 corresponding adjacent noncancerous samples. Patient data were compared by age, sex, tumor location, histological grade, Dukes’ stage, and overall mean survival time. In addition, the US28 gene was transiently transfected into the CRC LOVO cell line, and cell proliferation was assessed using a cell counting kit-8 assay. Cell cycle analysis by flow cytometry and a cell invasion transwell assay were also carried out. RESULTS: US28 levels were clearly higher in CRC tissues (38.8%) than in adjacent noncancerous samples (7.1%) (P = 0.000). Interestingly, elevated US28 amounts in CRC tissues were significantly associated with histological grade, metastasis, Dukes’ stage, and overall survival (all P < 0.05); meanwhile, US28 expression was not significantly correlated with age, sex or tumor location. In addition, multivariate Cox regression data revealed US28 level as an independent CRC prognostic marker (P = 0.000). LOVO cells successfully transfected with the US28 gene exhibited higher viability, greater chemotherapy resistance, accelerated cell cycle progression, and increased invasion ability. CONCLUSION: US28 expression is predictive of poor prognosis and may promote CRC. PMID:26973417

  16. Cathepsin D acts as an essential mediator to promote malignancy of benign prostatic epithelium

    PubMed Central

    Pruitt, Freddie L.; He, Yue; Franco, Omar E.; Jiang, Ming; Cates, Justin M.; Hayward, Simon W.

    2012-01-01

    BACKGROUND Stromal-epithelial interactions are important in both development and prostate cancer. Stromal changes have been shown to be powerful prognostic indicators of prostate cancer progression and of patient death helping to define lethal versus indolent phenotypes. The specific molecular underpinnings of these interactions are incompletely understood. We investigated whether stromal cathepsin D (CathD) overexpression affects prostate tumorigenesis through a paracrine mechanism. METHODS Normal prostate fibroblasts (NPF) were retrovirally transduced to overexpress cyclin D1 (CD1) cells were designated NPFCD1. Cathepsin D expression was knocked down using shRNA in cancer associated fibroblasts (CAF) and NPFCD1. We analyzed these stromal cell lines using immunohistochemistry, Western blot, and tissue recombination. RESULTS An examination of human prostate tissue revealed significantly increased stromal staining of CathD in malignant prostate tissue. Overexpression of CD1 in normal prostate fibroblasts (NPFCD1) produced a phenotype similar to, but more moderate than, CAF in a tissue recombination model. Knockdown studies revealed that CathD is required for NPFCD1 motility and invasive growth in vitro. BPH-1 cell proliferation was found to be induced when cultured with NPFCD1 conditioned medium, this effect was inhibited when CathD was knocked down in NPFCD1 cells. Overexpression of CathD in prostate stromal cells induced malignancy in adjacent epithelium, and this transformation was inhibited when stromal CathD expression was knocked down in CAF. CONCLUSIONS The study presented here demonstrates increased CathD expression is seen in human CAF. The upregulation of CD1 results in concomitant increases in CathD expression. Elevated CathD expression in the stroma contributes to tumor promotion. PMID:22996917

  17. Valve Interstitial Cells Act in a Pericyte Manner Promoting Angiogensis and Invasion by Valve Endothelial Cells.

    PubMed

    Arevalos, C Alexander; Berg, Jonathan M; Nguyen, Jacqueline M V; Godfrey, Elizabeth L; Iriondo, Claudia; Grande-Allen, K Jane

    2016-09-01

    Neovascularization is an understudied aspect of calcific aortic valve disease (CAVD). Within diseased valves, cells along the neovessels' periphery stain for pericyte markers, but it is unclear whether valvular interstitial cells (VICs) can demonstrate a pericyte-like phenotype. This investigation examined the perivascular potential of VICs to regulate valve endothelial cell (VEC) organization and explored the role of Angiopoeitin1-Tie2 signaling in this process. Porcine VECs and VICs were fluorescently tracked and co-cultured in Matrigel over 7 days. VICs regulated early VEC network organization in a ROCK-dependent manner, then guided later VEC network contraction through chemoattraction. Unlike vascular control cells, the valve cell cultures ultimately formed invasive spheroids with 3D angiogenic-like sprouts. VECs co-cultured with VICs displayed significantly more invasion than VECs alone; with VICs generally leading and wrapping around VEC invasive sprouts. Lastly, Angiopoietin1-Tie2 signaling was found to regulate valve cell organization during VEC/VIC spheroid formation and invasion. VICs demonstrated pericyte-like behaviors toward VECs throughout sustained co-culture. The change from a vasculogenic network to an invasive sprouting spheroid suggests that both cell types undergo phenotypic changes during long-term culture in the model angiogenic environment. Valve cells organizing into spheroids and undergoing 3D invasion of Matrigel demonstrated several typical angiogenic-like phenotypes dependent on basal levels of Angiopoeitin1-Tie2 signaling and ROCK activation. These results suggest that the ectopic sustained angiogenic environment during the early stages of valve disease promotes organized activity by both VECs and VICs, contributing to neovessel formation and the progression of CAVD. PMID:26905695

  18. 4-Hydroxyisoleucine improves insulin resistance by promoting mitochondrial biogenesis and act through AMPK and Akt dependent pathway.

    PubMed

    Rawat, Arun Kumar; Korthikunta, Venkateswarlu; Gautam, Sudeep; Pal, Savita; Tadigoppula, Narender; Tamrakar, Akhilesh Kumar; Srivastava, Arvind Kumar

    2014-12-01

    4-Hydroxyisoleucine (4-HIL) is an unusual amino acid isolated from fenugreek seeds (Trigonella foenum graecum L). Various studies have shown that it acts as an antidiabetic agent yet its mechanism of action is not clear. We therefore investigated the effect 4-HIL on the high fructose diet fed streptozotocin induced diabetic rats and L6 myotubes. 4-HIL (50 mg/kg) has improved blood lipid profile, glucose tolerance and insulin sensitivity in a diabetic rat model. It has increased the glucose uptake in L6 myotubes in AMPK-dependent manner and upregulated the expression of genes (PGC-1α, PGC-1β, CPT 1 and CPT 2), which have role in mitochondrial biogenesis and energy metabolism in the liver, skeletal muscles as well as in L6 myotubes. Interestingly, it also increased the AMPK and Akt expression along with their phosphorylated forms in the liver and muscle tissues of treated animals. Altogether we concluded that 4-HIL acts to improve insulin resistance by promoting mitochondrial biogenesis in high fructose diet fed STZ induced diabetic rats. PMID:25454462

  19. LGR4 acts as a key receptor for R-spondin 2 to promote osteogenesis through Wnt signaling pathway.

    PubMed

    Zhu, Chao; Zheng, Xin-Feng; Yang, Yue-Hua; Li, Bo; Wang, Yu-Ren; Jiang, Sheng-Dan; Jiang, Lei-Sheng

    2016-08-01

    R-spondin proteins are identified as secreted agonists of the canonical Wnt/β-catenin signaling pathway, and leucine-rich repeat-containing G-protein-coupled receptors (LGR) are recognized as R-spondin receptors. The potential role of R-spondin 2 (Rspo2) and LGR4 in mediating osteogenesis remains poorly understood. In our in vitro experiments, we found that Rspo2 could promote osteogenesis through activating the Wnt signaling pathway in MC3T3-E1 cells. However, this effect of Rsop2 disappeared in the cells with functional disruption of LGR4. Meanwhile, Rspo2 significantly inhibited osteoclastogenesis and this effect of Rspo2 was dependent on the presence of osteoblasts with normal function of LGR4. In our in vivo experiments, we found that application of exogenous Rspo2 rescued the bone loss and improved the microarchitecture of bone in OVX mice. Rspo2 could be a positive regulator of bone metabolism through activating the canonical Wnt/β-catenin signaling, and LGR4 acted as a key receptor for Rspo2 to promote osteogenesis. PMID:27140682

  20. Role of cis-Acting Sites in Stimulation of the Phage λ PRM Promoter by CI-Mediated Looping

    PubMed Central

    Michalowski, Christine B.

    2013-01-01

    The lysogenic state of phage λ is maintained by the CI repressor. CI binds to three operators each in the right operator (OR) and left operator (OL) regions, which lie 2.4 kb apart. At moderate CI levels, the predominant binding pattern is two dimers of CI bound cooperatively at each regulatory region. The resulting tetramers can then interact, forming an octamer and a loop of the intervening DNA. CI is expressed from the PRM promoter, which lies in the OR region and is subjected to multiple regulatory controls. Of these, the most recently discovered is stimulation by loop formation. In this work, we have investigated the mechanism by which looping stimulates PRM. We find that two cis-acting sites lying in the OL region are involved. One site, an UP element, is required for stimulation. Based on the behavior of other promoters with UP elements located upstream of the −35 region, we suggest that a subunit of RNA polymerase (RNAP) bound at PRM binds to the UP element located in the OL region. In addition, adjacent to the UP element lies a binding site for integration host factor (IHF); this site plays a less critical role but is required for stimulation of the weak prm240 allele. A loop with CI at the OL2 and OL3 operators does not stimulate PRM, while one with CI only at OL2 provides some stimulation. We discuss possible mechanisms for stimulation. PMID:23708136

  1. "America COMPETES Reauthorization Act of 2010" or the "America Creating Opportunities to Meaningfully Promote Excellence in Technology, Education, and Science Reauthorization Act of 2010." House of Representatives, One Hundred Eleventh Congress, Second Session. H.R. 5116

    ERIC Educational Resources Information Center

    US House of Representatives, 2010

    2010-01-01

    The America COMPETES (Creating Opportunities to Meaningfully Promote Excellence in Technology, Education, and Science) Reauthorization Act of 2010 documented here is divided into the following titles: (1) Office of Science and Technology Policy (Coordination of Federal STEM [science, technology, engineering, and mathematics] education;…

  2. State, District, and School Implementation of Reforms Promoted under the Recovery Act: 2009-10 through 2011-12. The Final Report from Charting the Progress of Education Reform: An Evaluation of the Recovery Act's Role. NCEE 2015-4016

    ERIC Educational Resources Information Center

    Troppe, Patricia; Milanowski, Anthony; Garrison-Mogren, Roberta; Webber, Ann; Gutmann, Babette; Reisner, Elizabeth; Goertz, Margaret

    2015-01-01

    This report, based on surveys completed by all 50 State Education Agencies (SEAs) and the District of Columbia (DC) and nationally representative samples of districts and schools during spring 2011 and 2012, examines implementation of the key education reform strategies promoted by the Recovery Act in 2011-12, the extent to which implementation…

  3. Promoting New Manufacturing Act

    THOMAS, 113th Congress

    Rep. Scalise, Steve [R-LA-1

    2014-05-30

    12/01/2014 Received in the Senate and Read twice and referred to the Committee on Environment and Public Works. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  4. Export Promotion Reform Act

    THOMAS, 112th Congress

    Rep. Berman, Howard L. [D-CA-28

    2012-02-15

    06/04/2012 Received in the Senate and Read twice and referred to the Committee on Banking, Housing, and Urban Affairs. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  5. American Savings Promotion Act

    THOMAS, 113th Congress

    Sen. Moran, Jerry [R-KS

    2013-10-29

    10/29/2013 Read twice and referred to the Committee on Banking, Housing, and Urban Affairs. (All Actions) Notes: For further action, see H.R.3374, which became Public Law 113-251 on 12/18/2014. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  6. Msc1 acts through histone H2A.Z to promote chromosome stability in Schizosaccharomyces pombe.

    PubMed

    Ahmed, Shakil; Dul, Barbara; Qiu, Xinxing; Walworth, Nancy C

    2007-11-01

    As a central component of the DNA damage checkpoint pathway, the conserved protein kinase Chk1 mediates cell cycle progression when DNA damage is generated. Msc1 was identified as a multicopy suppressor capable of facilitating survival in response to DNA damage of cells mutant for chk1. We demonstrate that loss of msc1 function results in an increased rate of chromosome loss and that an msc1 null allele exhibits genetic interactions with mutants in key kinetochore components. Multicopy expression of msc1 robustly suppresses a temperature-sensitive mutant (cnp1-1) in the centromere-specific histone H3 variant CENP-A, and localization of CENP-A to the centromere is compromised in msc1 null cells. We present several lines of evidence to suggest that Msc1 carries out its function through the histone H2A variant H2A.Z, encoded by pht1 in fission yeast. Like an msc1 mutant, a pht1 mutant also exhibits chromosome instability and genetic interactions with kinetochore mutants. Suppression of cnp1-1 by multicopy msc1 requires pht1. Likewise, suppression of the DNA damage sensitivity of a chk1 mutant by multicopy msc1 also requires pht1. We present the first genetic evidence that histone H2A.Z may participate in centromere function in fission yeast and propose that Msc1 acts through H2A.Z to promote chromosome stability and cell survival following DNA damage. PMID:17947424

  7. Binding of transcription factors to Presenilin 1 and 2 promoter cis-acting elements varies during the development of mouse cerebral cortex.

    PubMed

    Kumar, Ashish; Thakur, M K

    2016-08-15

    Previously, we reported differential expression of Presenilin (PS)1 and 2 and epigenetic modifications of their gene promoter in the cerebral cortex of mice during development. We identified the crucial role of DNA methylation and H3K9/14 acetylation in stage specific PS expression during brain development. Interestingly, we noted differential DNA methylation in putative binding sites of transcription factors considered pivotal for brain development. This prompted us to study the binding of transcription factors to cis-acting elements of PS1 and PS2 promoter in the cerebral cortex of mice during development. In-silico analysis revealed various cis-acting elements of PS1 and PS2 promoter and their putative transcription factors. We selected those cis-acting elements that were proven by wet lab experiments to interact with the transcription factors crucial for brain development. Electrophoretic mobility shift assay revealed that the binding of nuclear proteins to PS1 promoter cis-acting elements like HSF-1, Cdx1, Ets-1 and Sp1 significantly increased at embryonic day (E) 12.5, postnatal day (P) 45 and 20 weeks (w) as compared to P0. The binding pattern of these factors correlated well with the PS1 expression profile, indicating their cumulative influence on PS1 gene transcription. For PS2 promoter, the binding of Nkx2.2 and HFH-2 was high at prenatal stages (E12.5 and E18.5) while that of Cdx1 and NF-κB was maximum at postnatal stages (P45 and 20w). Taken together, our study shows that the binding of HSF-1, Cdx1, Ets-1 and Sp1 to PS1 promoter and that of Nkx2.2, HFH-2, Cdx1 and NF-κB to PS2 promoter regulate their differential expression during brain development. PMID:27177724

  8. HRS1 Acts as a Negative Regulator of Abscisic Acid Signaling to Promote Timely Germination of Arabidopsis Seeds

    PubMed Central

    Wang, Ran; Liu, Hong; Yang, Huixia; Rodriguez, Pedro L.; Qin, Huanju; Liu, Xin; Wang, Daowen

    2012-01-01

    In this work, we conducted functional analysis of Arabidopsis HRS1 gene in order to provide new insights into the mechanisms governing seed germination. Compared with wild type (WT) control, HRS1 knockout mutant (hrs1-1) exhibited significant germination delays on either normal medium or those supplemented with abscisic acid (ABA) or sodium chloride (NaCl), with the magnitude of the delay being substantially larger on the latter media. The hypersensitivity of hrs1-1 germination to ABA and NaCl required ABI3, ABI4 and ABI5, and was aggravated in the double mutant hrs1-1abi1-2 and triple mutant hrs1-1hab1-1abi1-2, indicating that HRS1 acts as a negative regulator of ABA signaling during seed germination. Consistent with this notion, HRS1 expression was found in the embryo axis, and was regulated both temporally and spatially, during seed germination. Further analysis showed that the delay of hrs1-1 germination under normal conditions was associated with reduction in the elongation of the cells located in the lower hypocotyl (LH) and transition zone (TZ) of embryo axis. Interestingly, the germination rate of hrs1-1 was more severely reduced by the inhibitor of cell elongation, and more significantly decreased by the suppressors of plasmalemma H+-ATPase activity, than that of WT control. The plasmalemma H+-ATPase activity in the germinating seeds of hrs1-1 was substantially lower than that exhibited by WT control, and fusicoccin, an activator of this pump, corrected the transient germination delay of hrs1-1. Together, our data suggest that HRS1 may be needed for suppressing ABA signaling in germinating embryo axis, which promotes the timely germination of Arabidopsis seeds probably by facilitating the proper function of plasmalemma H+-ATPase and the efficient elongation of LH and TZ cells. PMID:22545134

  9. Caenorhabditis elegans PIG-1/MELK acts in a conserved PAR-4/LKB1 polarity pathway to promote asymmetric neuroblast divisions.

    PubMed

    Chien, Shih-Chieh; Brinkmann, Eva-Maria; Teuliere, Jerome; Garriga, Gian

    2013-03-01

    Asymmetric cell divisions produce daughter cells with distinct sizes and fates, a process important for generating cell diversity during development. Many Caenorhabditis elegans neuroblasts, including the posterior daughter of the Q cell (Q.p), divide to produce a larger neuron or neuronal precursor and a smaller cell that dies. These size and fate asymmetries require the gene pig-1, which encodes a protein orthologous to vertebrate MELK and belongs to the AMPK-related family of kinases. Members of this family can be phosphorylated and activated by the tumor suppressor kinase LKB1, a conserved polarity regulator of epithelial cells and neurons. In this study, we present evidence that the C. elegans orthologs of LKB1 (PAR-4) and its partners STRAD (STRD-1) and MO25 (MOP-25.2) regulate the asymmetry of the Q.p neuroblast division. We show that PAR-4 and STRD-1 act in the Q lineage and function genetically in the same pathway as PIG-1. A conserved threonine residue (T169) in the PIG-1 activation loop is essential for PIG-1 activity, consistent with the model that PAR-4 (or another PAR-4-regulated kinase) phosphorylates and activates PIG-1. We also demonstrate that PIG-1 localizes to centrosomes during cell divisions of the Q lineage, but this localization does not depend on T169 or PAR-4. We propose that a PAR-4-STRD-1 complex stimulates PIG-1 kinase activity to promote asymmetric neuroblast divisions and the generation of daughter cells with distinct fates. Changes in cell fate may underlie many of the abnormal behaviors exhibited by cells after loss of PAR-4 or LKB1. PMID:23267054

  10. Stimulation of in vitro transcription from the SV40 early promoter by the enhancer involves a specific trans-acting factor.

    PubMed Central

    Wildeman, A G; Sassone-Corsi, P; Grundström, T; Zenke, M; Chambon, P

    1984-01-01

    A nuclear extract prepared from HeLa cells has been used to study in vitro the transcription of the SV40 early promoter. The deletion of the enhancer results in a strong decrease of transcription, with spermidine and MgCl2 being critical variables in the transcription reactions. Furthermore a competition assay indicates that the stimulation by the enhancer is due to a specific trans-acting factor(s) which acts on it. This factor appears not to interact with SV40 or adenovirus-2 major late upstream (distal) promoter sequences, and its ability to bind to the enhancer is diminished by mutations known to decrease enhancer function in vivo and in vitro. Images Fig. 2. Fig. 3. Fig. 4. PMID:6098465

  11. Tissue-specific regulation of BiP genes: a cis-acting regulatory domain is required for BiP promoter activity in plant meristems.

    PubMed

    Buzeli, Reginaldo A A; Cascardo, Júlio C M; Rodrigues, Leonardo A Z; Andrade, Maxuel O; Almeida, Raul S; Loureiro, Marcelo E; Otoni, Wagner C; Fontes, Elizabeth P B

    2002-11-01

    The binding protein BiP is an endoplasmic reticulum (ER)-resident member of the HSP70 stress-related protein family, which is essential for the constitutive function of the ER. In addition to responding to a variety of environmental stimuli, plant BiP exhibits a tissue-specific regulation. We have isolated two soybean BiP genomic clones, designated gsBiP6 and gsBiP9, and different extensions of their 5' flanking sequences were fused to beta-glucuronidase (GUS) reporter gene and introduced into Nicotiana tabacum by Agrobacterium tumefaciens-mediated transformation. Transgenic plants displayed prominent GUS activity in the vascular bundles of roots and shoots as well as in regions of intense cell division, such as procambial region and apical meristems. Promoter deletion analyses identified two cis-regulatory functional domains that are important for the spatially-regulated activation of BiP expression under normal plant development. While an AT-rich enhancer-like sequence, designated cis-acting regulatory domain 1, CRD1 (-358 to -211, on gsBiP6), activated expression of the BiP minimal promoter in all organs analyzed, BiP promoter activity in meristematic tissues and phloem cells required the presence of a second activating domain, CRD2 (-211 to -80). Apparently, the CRD2 sequence also harbors negative cis-acting elements, because removal of this region caused activation of gsBiP6 promoter in parenchymatic xylem rays. These results suggest that the tissue-specific control of BiP gene expression requires a complex integration of multiple cis-acting regulatory elements on the promoter. PMID:12374306

  12. cis-Acting elements within the Candida albicans ERG11 promoter mediate the azole response through transcription factor Upc2p.

    PubMed

    Oliver, Brian G; Song, Jia L; Choiniere, Jake H; White, Theodore C

    2007-12-01

    The azole antifungal drugs are used to treat infections caused by Candida albicans and other fungi. These drugs interfere with the biosynthesis of ergosterol, the major sterol in fungal cells, by inhibiting an ergosterol biosynthetic enzyme, lanosterol 14 alpha-demethylase, encoded by the ERG11 gene. In vitro, these drugs as well as other ergosterol biosynthesis inhibitors increase ERG11 mRNA expression by activation of the ERG11 promoter. The signal for this activation most likely is the depletion of ergosterol, the end product of the pathway. To identify cis-acting regulatory elements that mediate this activation, ERG11 promoter fragments have been fused to the luciferase reporter gene from Renilla reniformis. Promoter deletions and linker scan mutations localized the region important for azole induction to a segment from bp -224 to -251 upstream of the start codon, specifically two 7-bp sequences separated by 13 bp. These sequences form an imperfect inverted repeat. The region is recognized by the transcription factor Upc2p and functions as an enhancer of transcription, as it can be placed upstream of a heterologous promoter in either direction, resulting in the azole induction of that promoter. The promoter constructs are not azole inducible in the upc2/upc2 homozygous deletion, demonstrating that Upc2p controls the azole induction of ERG11. These results identify an azole-responsive enhancer element (ARE) in the ERG11 promoter that is controlled by the Upc2p transcription factor. No other ARE is present in the promoter. Thus, this ARE and Upc2p are necessary and sufficient for azole induction of ERG11. PMID:17951521

  13. Distal apolipoprotein C-III regulatory elements F to J act as a general modular enhancer for proximal promoters that contain hormone response elements. Synergism between hepatic nuclear factor-4 molecules bound to the proximal promoter and distal enhancer sites.

    PubMed

    Kardassis, D; Tzameli, I; Hadzopoulou-Cladaras, M; Talianidis, I; Zannis, V

    1997-01-01

    Transient transfection assays have shown that the distal apoC-III promoter segments that contain the regulatory elements F to J enhance the strength of the tandemly linked proximal apoA-I promoter 5- to 13-fold in hepatic (HepG2) cells. Activation in intestinal (CaCo-2) cells to levels comparable to those obtained in HepG2 cells requires a larger apoA-I promoter sequence that extends to nucleotide -1500 as well as the presence of hepatic nuclear factor-4 (HNF-4). The distal apoC-III regulatory elements can also enhance 4- to 8-fold the strength of the heterologous apoB promoter in HepG2 and CaCo-2 cells. Finally, these elements in the presence of HNF-4 enhance 14.5- to 18.5-fold the strength of the minimal adenovirus major late promoter linked to two copies of the hormone response element (HRE) AID of apoA-I in both HepG2 and CaCo-2 cells. In vitro mutagenesis of the promoter/enhancer cluster established that the enhancer activity is lost by a mutation in the HRE present in the 3' end of the regulatory element I (-736 to -714) and is reduced significantly by point mutations or deletions in one or more of the regulatory elements F to J of the apoC-III enhancer. The enhancer activity also requires the HREs of the proximal apoA-I promoter. The apoC-III enhancer can also restore the activity of the proximal apoA-I and apoB promoters that have been inactivated by mutations in CCAAT/enhancers binding protein binding sites, indicating that C/EBP may not participate in the synergistic activation of the promoter/enhancer cluster. The findings suggest that the regulatory elements F to J of the apoC-III promoter act as a general modular enhancer that can potentiate the strength of proximal promoters that contain HREs. Such potentiation in the HepG2 cells can be accounted for by synergistic interactions between HNF-4 or other nuclear hormone receptors bound to the proximal and distal HREs and SP1 or other factors bound to the apoC-III enhancer. Additional factors may be

  14. The CovR response regulator of group A streptococcus (GAS) acts directly to repress its own promoter.

    PubMed

    Gusa, Asiya A; Scott, June R

    2005-06-01

    The CovR/S (CsrR/S) two component system is a global regulator of virulence gene expression in the group A streptococcus (GAS, Streptococcus pyogenes). The response regulator, CovR, regulates about 15% of the genes of GAS, including its own operon. Using in vitro DNA binding assays with purified CovR protein, we found that CovR binds a DNA fragment including the covR promoter (Pcov). DNaseI footprint analyses showed that phosphorylation of CovR enhanced and extended the protected regions. The proposed CovR consensus binding sequence (ATTARA) was present at most, but not all protected regions. The effect of replacing the two thymine residues in the consensus binding sequence (CB) with guanine residues was evaluated both in vitro and in vivo. Most, but not all, CB mutations reduced binding of CovR in vitro. Using a transcriptional reporter introduced in single copy into the GAS chromosome, we found that mutations at each CB completely or partially relieved CovR-mediated repression in vivo. This suggests that CovR regulation of Pcov is direct. Further support for this conclusion comes from use of an in vitro GAS transcription system in which CovR was sufficient to mediate repression of Pcov. This repression was enhanced by phosphorylation of the protein. In addition, we found that the CovR binding region overlapping the promoter was essential for wild type repression of Pcov both in vitro and in vivo, suggesting that promoter occlusion is a primary mechanism of Pcov repression by CovR. PMID:15882414

  15. Promoting Mentalizing in Pupils by Acting on Teachers: Preliminary Italian Evidence of the “Thought in Mind” Project

    PubMed Central

    Valle, Annalisa; Massaro, Davide; Castelli, Ilaria; Sangiuliano Intra, Francesca; Lombardi, Elisabetta; Bracaglia, Edoardo; Marchetti, Antonella

    2016-01-01

    Mentalization research focuses on different aspects of this topic, highlighting individual differences in mentalizing and proposing programs of intervention for children and adults to increase this ability. The “Thought in Mind Project” (TiM Project) provides training targeted to adults—teachers or parents—to increase their mentalization and, consequently, to obtain mentalization improvement in children. The present research aimed to explore for the first time ever the potential of training for teachers based on the TiM Project, regarding the enhancement of mentalizing of an adult who would have interacted as a teacher with children. For this reason, two teachers – similar for meta-cognitive and meta-emotional skills - and their classes (N = 46) were randomly assigned to the training or control condition. In the first case, the teacher participated in training on the implementation of promotion of mentalizing in everyday school teaching strategies; in the second case the teacher participated in a control activity, similar to training for scheduling and methods, but without promoting the implementation of mentalization (in both conditions two meetings lasting about 3 h at the beginning of the school year and two supervisions during the school year were conducted). The children were tested by tasks assessing several aspects of mentalization (second and third-order false belief understanding, Strange Stories, Reading the mind in the Eyes, Mentalizing Task) both before and after the teacher participate in the TiM or control training (i.e., at the beginning and at the end of the school year). The results showed that, although some measured components of mentalization progressed over time, only the TiM Project training group significantly improved in third order false belief understanding and changed - in a greater way compared to the control group – in two of the three components of the Mentalizing Task. These evidences are promising about the idea that the

  16. The value of advocacy in promoting social change: implementing the new Domestic Violence Act in South Africa.

    PubMed

    Usdin, S; Christofides, N; Malepe, L; Maker, A

    2000-11-01

    South Africa's first democratic government passed the Domestic Violence Act (DVA) into law in 1998 as part of local and international commitments to protecting the human rights of women. Although the Act was welcomed as groundbreaking legislation, delays in implementing it led to increasing frustration. This paper describes an advocacy campaign conducted by the Soul City Institute for Health and Development Communication in partnership with the National Network on Violence against Women, to ensure the effective implementation of the DVA. Lessons from the campaign stress the importance of coalition building to draw on diverse strengths, and the use of a combination of advocacy tools, including lobbying, media advocacy and social mobilisation to achieve campaign goals. Given the critical role NGOs dealing with victims/survivors of domestic violence and the justice system played in lobbying for change and drafting the new law, their exclusion from the implementation process was ironic. While many advocacy efforts focus on the development of policy and legislation, ongoing efforts are needed to ensure effective implementation, the commitment of adequate resources and monitoring to identify gaps and propose new solutions. Our experience highlights the important role of policy advocates in connecting the multiple streams at play in the policy and legislative arena. PMID:11424250

  17. Polymorphic tandem repeats within gene promoters act as modifiers of gene expression and DNA methylation in humans

    PubMed Central

    Quilez, Javier; Guilmatre, Audrey; Garg, Paras; Highnam, Gareth; Gymrek, Melissa; Erlich, Yaniv; Joshi, Ricky S.; Mittelman, David; Sharp, Andrew J.

    2016-01-01

    Despite representing an important source of genetic variation, tandem repeats (TRs) remain poorly studied due to technical difficulties. We hypothesized that TRs can operate as expression (eQTLs) and methylation (mQTLs) quantitative trait loci. To test this we analyzed the effect of variation at 4849 promoter-associated TRs, genotyped in 120 individuals, on neighboring gene expression and DNA methylation. Polymorphic promoter TRs were associated with increased variance in local gene expression and DNA methylation, suggesting functional consequences related to TR variation. We identified >100 TRs associated with expression/methylation levels of adjacent genes. These potential eQTL/mQTL TRs were enriched for overlaps with transcription factor binding and DNaseI hypersensitivity sites, providing a rationale for their effects. Moreover, we showed that most TR variants are poorly tagged by nearby single nucleotide polymorphisms (SNPs) markers, indicating that many functional TR variants are not effectively assayed by SNP-based approaches. Our study assigns biological significance to TR variations in the human genome, and suggests that a significant fraction of TR variations exert functional effects via alterations of local gene expression or epigenetics. We conclude that targeted studies that focus on genotyping TR variants are required to fully ascertain functional variation in the genome. PMID:27060133

  18. Polymorphic tandem repeats within gene promoters act as modifiers of gene expression and DNA methylation in humans.

    PubMed

    Quilez, Javier; Guilmatre, Audrey; Garg, Paras; Highnam, Gareth; Gymrek, Melissa; Erlich, Yaniv; Joshi, Ricky S; Mittelman, David; Sharp, Andrew J

    2016-05-01

    Despite representing an important source of genetic variation, tandem repeats (TRs) remain poorly studied due to technical difficulties. We hypothesized that TRs can operate as expression (eQTLs) and methylation (mQTLs) quantitative trait loci. To test this we analyzed the effect of variation at 4849 promoter-associated TRs, genotyped in 120 individuals, on neighboring gene expression and DNA methylation. Polymorphic promoter TRs were associated with increased variance in local gene expression and DNA methylation, suggesting functional consequences related to TR variation. We identified >100 TRs associated with expression/methylation levels of adjacent genes. These potential eQTL/mQTL TRs were enriched for overlaps with transcription factor binding and DNaseI hypersensitivity sites, providing a rationale for their effects. Moreover, we showed that most TR variants are poorly tagged by nearby single nucleotide polymorphisms (SNPs) markers, indicating that many functional TR variants are not effectively assayed by SNP-based approaches. Our study assigns biological significance to TR variations in the human genome, and suggests that a significant fraction of TR variations exert functional effects via alterations of local gene expression or epigenetics. We conclude that targeted studies that focus on genotyping TR variants are required to fully ascertain functional variation in the genome. PMID:27060133

  19. IL-18 acts in synergy with IL-7 to promote ex vivo expansion of T lymphoid progenitor cells

    PubMed Central

    Gandhapudi, Siva K.; Tan, Chibing; Marino, Julie H.; Taylor, Ashlee A.; Pack, Christopher C.; Gaikwad, Joel; Van De Wiele, C. Justin; Wren, Jonathan D.; Teague, T. Kent

    2015-01-01

    Although IL-18 has not previously been shown to promote T lymphopoiesis, results obtained via a novel data mining algorithm (GAMMA), led us to explore a predicted role for this cytokine in T cell development. IL-18 is a member of the IL-1 cytokine family that has been extensively characterized as a mediator of inflammatory immune responses. To assess a potential role for IL-18 in T cell development, we sort-purified mouse bone marrow derived common lymphoid progenitor cells (CLP), early thymic progenitors (ETP) and DN2 thymocytes and cultured these populations on OP9-DL4 stromal layers in the presence or absence of IL-18 and/or IL-7. After one week of culture, IL-18 promoted proliferation and accelerated differentiation of ETPs to the DN3 stage, similar in efficiency to IL-7. IL-18 showed synergy with IL-7 and enhanced proliferation of both the thymus derived progenitor cells and the bone marrow derived common lymphoid progenitor cells. The synergistic effect on the ETP population was further characterized and found to correlate with increased surface expression of c-Kit and IL-7 receptors on the IL-18-treated cells. In summary, we successfully validated the GAMMA prediction that IL-18 affects T lymphopoiesis and demonstrated that IL-18 can positively impact bone marrow lymphopoiesis and T cell development, presumably via interaction with the c-Kit and IL-7 signaling axis. PMID:25780034

  20. Vascular Endothelial Growth Factor Acts Primarily via Platelet-Derived Growth Factor Receptor α to Promote Proliferative Vitreoretinopathy

    PubMed Central

    Pennock, Steven; Haddock, Luis J.; Mukai, Shizuo; Kazlauskas, Andrius

    2015-01-01

    Proliferative vitreoretinopathy (PVR) is a nonneovascular blinding disease and the leading cause for failure in surgical repair of rhegmatogenous retinal detachments. Once formed, PVR is difficult to treat. Hence, there is an acute interest in developing approaches to prevent PVR. Of the many growth factors and cytokines that accumulate in vitreous as PVR develops, neutralizing vascular endothelial growth factor (VEGF) A has recently been found to prevent PVR in at least one animal model. The goal of this study was to test if Food and Drug Administration–approved agents could protect the eye from PVR in multiple animal models and to further investigate the underlying mechanisms. Neutralizing VEGF with aflibercept (VEGF Trap-Eye) safely and effectively protected rabbits from PVR in multiple models of disease. Furthermore, aflibercept reduced the bioactivity of both experimental and clinical PVR vitreous. Finally, although VEGF could promote some PVR-associated cellular responses via VEGF receptors expressed on the retinal pigment epithelial cells that drive this disease, VEGF's major contribution to vitreal bioactivity occurred via platelet-derived growth factor receptor α. Thus, VEGF promotes PVR by a noncanonical ability to engage platelet-derived growth factor receptor α. These findings indicate that VEGF contributes to nonangiogenic diseases and that anti–VEGF-based therapies may be effective on a wider spectrum of diseases than previously appreciated. PMID:25261788

  1. The ribonucleotidyl transferase USIP-1 acts with SART3 to promote U6 snRNA recycling

    PubMed Central

    Rüegger, Stefan; Miki, Takashi S.; Hess, Daniel; Großhans, Helge

    2015-01-01

    The spliceosome is a large molecular machine that serves to remove the intervening sequences that are present in most eukaryotic pre-mRNAs. At its core are five small nuclear ribonucleoprotein complexes, the U1, U2, U4, U5 and U6 snRNPs, which undergo dynamic rearrangements during splicing. Their reutilization for subsequent rounds of splicing requires reversion to their original configurations, but little is known about this process. Here, we show that ZK863.4/USIP-1 (U Six snRNA-Interacting Protein-1) is a ribonucleotidyl transferase that promotes accumulation of the Caenorhabditis elegans U6 snRNA. Endogenous USIP-1–U6 snRNA complexes lack the Lsm proteins that constitute the protein core of the U6 snRNP, but contain the U6 snRNP recycling factor SART3/B0035.12. Furthermore, co-immunoprecipitation experiments suggest that SART3 but not USIP-1 occurs also in a separate complex containing both the U4 and U6 snRNPs. Based on this evidence, genetic interaction between usip-1 and sart-3, and the apparent dissociation of Lsm proteins from the U6 snRNA during spliceosome activation, we propose that USIP-1 functions upstream of SART3 to promote U6 snRNA recycling. PMID:25753661

  2. C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation

    PubMed Central

    Bulla, Roberta; Tripodo, Claudio; Rami, Damiano; Ling, Guang Sheng; Agostinis, Chiara; Guarnotta, Carla; Zorzet, Sonia; Durigutto, Paolo; Botto, Marina; Tedesco, Francesco

    2016-01-01

    Complement C1q is the activator of the classical pathway. However, it is now recognized that C1q can exert functions unrelated to complement activation. Here we show that C1q, but not C4, is expressed in the stroma and vascular endothelium of several human malignant tumours. Compared with wild-type (WT) or C3- or C5-deficient mice, C1q-deficient (C1qa−/−) mice bearing a syngeneic B16 melanoma exhibit a slower tumour growth and prolonged survival. This effect is not attributable to differences in the tumour-infiltrating immune cells. Tumours developing in WT mice display early deposition of C1q, higher vascular density and an increase in the number of lung metastases compared with C1qa−/− mice. Bone marrow (BM) chimeras between C1qa−/− and WT mice identify non-BM-derived cells as the main local source of C1q that can promote cancer cell adhesion, migration and proliferation. Together these findings support a role for locally synthesized C1q in promoting tumour growth. PMID:26831747

  3. Meta-Analysis of Arabidopsis KANADI1 Direct Target Genes Identifies a Basic Growth-Promoting Module Acting Upstream of Hormonal Signaling Pathways.

    PubMed

    Xie, Yakun; Straub, Daniel; Eguen, Tenai; Brandt, Ronny; Stahl, Mark; Martínez-García, Jaime F; Wenkel, Stephan

    2015-10-01

    An intricate network of antagonistically acting transcription factors mediates the formation of a flat leaf lamina of Arabidopsis (Arabidopsis thaliana) plants. In this context, members of the class III homeodomain leucine zipper (HD-ZIPIII) transcription factor family specify the adaxial domain (future upper side) of the leaf, while antagonistically acting KANADI transcription factors determine the abaxial domain (future lower side). Here, we used a messenger RNA sequencing approach to identify genes regulated by KANADI1 (KAN1) and subsequently performed a meta-analysis combining our data sets with published genome-wide data sets. Our analysis revealed that KAN1 acts upstream of several genes encoding auxin biosynthetic enzymes. When exposed to shade, we found three YUCCA genes, YUC2, YUC5, and YUC8, to be transcriptionally up-regulated, which correlates with an increase in the levels of free auxin. When ectopically expressed, KAN1 is able to transcriptionally repress these three YUC genes and thereby block shade-induced auxin biosynthesis. Consequently, KAN1 is able to strongly suppress shade-avoidance responses. Taken together, we hypothesize that HD-ZIPIII/KAN form the basis of a basic growth-promoting module. Hypocotyl extension in the shade and outgrowth of new leaves both involve auxin synthesis and signaling, which are under the direct control of HD-ZIPIII/KAN. PMID:26246448

  4. Meta-Analysis of Arabidopsis KANADI1 Direct Target Genes Identifies a Basic Growth-Promoting Module Acting Upstream of Hormonal Signaling Pathways1[OPEN

    PubMed Central

    Xie, Yakun; Straub, Daniel; Eguen, Tenai; Brandt, Ronny; Stahl, Mark; Martínez-García, Jaime F.; Wenkel, Stephan

    2015-01-01

    An intricate network of antagonistically acting transcription factors mediates the formation of a flat leaf lamina of Arabidopsis (Arabidopsis thaliana) plants. In this context, members of the class III homeodomain leucine zipper (HD-ZIPIII) transcription factor family specify the adaxial domain (future upper side) of the leaf, while antagonistically acting KANADI transcription factors determine the abaxial domain (future lower side). Here, we used a messenger RNA sequencing approach to identify genes regulated by KANADI1 (KAN1) and subsequently performed a meta-analysis combining our data sets with published genome-wide data sets. Our analysis revealed that KAN1 acts upstream of several genes encoding auxin biosynthetic enzymes. When exposed to shade, we found three YUCCA genes, YUC2, YUC5, and YUC8, to be transcriptionally up-regulated, which correlates with an increase in the levels of free auxin. When ectopically expressed, KAN1 is able to transcriptionally repress these three YUC genes and thereby block shade-induced auxin biosynthesis. Consequently, KAN1 is able to strongly suppress shade-avoidance responses. Taken together, we hypothesize that HD-ZIPIII/KAN form the basis of a basic growth-promoting module. Hypocotyl extension in the shade and outgrowth of new leaves both involve auxin synthesis and signaling, which are under the direct control of HD-ZIPIII/KAN. PMID:26246448

  5. Clobetasol and Halcinonide Act as Smoothened Agonists to Promote Myelin Gene Expression and RxRγ Receptor Activation

    PubMed Central

    De Nardis, Velia; Di Giandomenico, Daniele; Lucisano, Giuseppe; Scardapane, Marco; Poma, Anna; Ragnini-Wilson, Antonella

    2015-01-01

    One of the causes of permanent disability in chronic multiple sclerosis patients is the inability of oligodendrocyte progenitor cells (OPCs) to terminate their maturation program at lesions. To identify key regulators of myelin gene expression acting at the last stages of OPC maturation we developed a drug repositioning strategy based on the mouse immortalized oligodendrocyte (OL) cell line Oli-neu brought to the premyelination stage by stably expressing a key factor regulating the last stages of OL maturation. The Prestwick Chemical Library® of 1,200 FDA-approved compound(s) was repositioned at three dosages based on the induction of Myelin Basic Protein (MBP) expression. Drug hits were further validated using dosage-dependent reproducibility tests and biochemical assays. The glucocorticoid class of compounds was the most highly represented and we found that they can be divided in three groups according to their efficacy on MBP up-regulation. Since target identification is crucial before bringing compounds to the clinic, we searched for common targets of the primary screen hits based on their known chemical-target interactomes, and the pathways predicted by top ranking compounds were validated using specific inhibitors. Two of the top ranking compounds, Halcinonide and Clobetasol, act as Smoothened (Smo) agonists to up-regulate myelin gene expression in the Oli-neuM cell line. Further, RxRγ activation is required for MBP expression upon Halcinonide and Clobetasol treatment. These data indicate Clobetasol and Halcinonide as potential promyelinating drugs and also provide a mechanistic understanding of their mode of action in the pathway leading to myelination in OPCs. Furthermore, our classification of glucocorticoids with respect to MBP expression provides important novel insights into their effects in the CNS and a rational criteria for their choice in combinatorial therapies in de-myelinating diseases. PMID:26658258

  6. MicroRNA-135b Promotes Cancer Progression by Acting as a Downstream Effector of Oncogenic Pathways in Colon Cancer

    PubMed Central

    Valeri, Nicola; Braconi, Chiara; Gasparini, Pierluigi; Murgia, Claudio; Lampis, Andrea; Paulus-Hock, Viola; Hart, Jonathan R.; Ueno, Lynn; Grivennikov, Sergei I.; Lovat, Francesca; Paone, Alessio; Cascione, Luciano; Sumani, Khlea M.; Veronese, Angelo; Fabbri, Muller; Carasi, Stefania; Alder, Hansjuerg; Lanza, Giovanni; Gafa’, Roberta; Moyer, Mary P.; Ridgway, Rachel A.; Cordero, Julia; Nuovo, Gerard J.; Frankel, Wendy L.; Rugge, Massimo; Fassan, Matteo; Groden, Joanna; Vogt, Peter K.; Karin, Michael; Sansom, Owen J.; Croce, Carlo M.

    2014-01-01

    Summary MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment. PMID:24735923

  7. MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer.

    PubMed

    Valeri, Nicola; Braconi, Chiara; Gasparini, Pierluigi; Murgia, Claudio; Lampis, Andrea; Paulus-Hock, Viola; Hart, Jonathan R; Ueno, Lynn; Grivennikov, Sergei I; Lovat, Francesca; Paone, Alessio; Cascione, Luciano; Sumani, Khlea M; Veronese, Angelo; Fabbri, Muller; Carasi, Stefania; Alder, Hansjuerg; Lanza, Giovanni; Gafa', Roberta; Moyer, Mary P; Ridgway, Rachel A; Cordero, Julia; Nuovo, Gerard J; Frankel, Wendy L; Rugge, Massimo; Fassan, Matteo; Groden, Joanna; Vogt, Peter K; Karin, Michael; Sansom, Owen J; Croce, Carlo M

    2014-04-14

    MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment. PMID:24735923

  8. IL-18 acts in synergy with IL-7 to promote ex vivo expansion of T lymphoid progenitor cells.

    PubMed

    Gandhapudi, Siva K; Tan, Chibing; Marino, Julie H; Taylor, Ashlee A; Pack, Christopher C; Gaikwad, Joel; Van De Wiele, C Justin; Wren, Jonathan D; Teague, T Kent

    2015-04-15

    Although IL-18 has not previously been shown to promote T lymphopoiesis, results obtained via a novel data mining algorithm (global microarray meta-analysis) led us to explore a predicted role for this cytokine in T cell development. IL-18 is a member of the IL-1 cytokine family that has been extensively characterized as a mediator of inflammatory immune responses. To assess a potential role for IL-18 in T cell development, we sort-purified mouse bone marrow-derived common lymphoid progenitor cells, early thymic progenitors (ETPs), and double-negative 2 thymocytes and cultured these populations on OP9-Delta-like 4 stromal layers in the presence or absence of IL-18 and/or IL-7. After 1 wk of culture, IL-18 promoted proliferation and accelerated differentiation of ETPs to the double-negative 3 stage, similar in efficiency to IL-7. IL-18 showed synergy with IL-7 and enhanced proliferation of both the thymus-derived progenitor cells and the bone marrow-derived common lymphoid progenitor cells. The synergistic effect on the ETP population was further characterized and found to correlate with increased surface expression of c-Kit and IL-7 receptors on the IL-18-treated cells. In summary, we successfully validated the global microarray meta-analysis prediction that IL-18 affects T lymphopoiesis and demonstrated that IL-18 can positively impact bone marrow lymphopoiesis and T cell development, presumably via interaction with the c-Kit and IL-7 signaling axis. PMID:25780034

  9. Id4, a new candidate gene for senile osteoporosis, acts as a molecular switch promoting osteoblast differentiation.

    PubMed

    Tokuzawa, Yoshimi; Yagi, Ken; Yamashita, Yzumi; Nakachi, Yutaka; Nikaido, Itoshi; Bono, Hidemasa; Ninomiya, Yuichi; Kanesaki-Yatsuka, Yukiko; Akita, Masumi; Motegi, Hiromi; Wakana, Shigeharu; Noda, Tetsuo; Sablitzky, Fred; Arai, Shigeki; Kurokawa, Riki; Fukuda, Toru; Katagiri, Takenobu; Schönbach, Christian; Suda, Tatsuo; Mizuno, Yosuke; Okazaki, Yasushi

    2010-07-01

    Excessive accumulation of bone marrow adipocytes observed in senile osteoporosis or age-related osteopenia is caused by the unbalanced differentiation of MSCs into bone marrow adipocytes or osteoblasts. Several transcription factors are known to regulate the balance between adipocyte and osteoblast differentiation. However, the molecular mechanisms that regulate the balance between adipocyte and osteoblast differentiation in the bone marrow have yet to be elucidated. To identify candidate genes associated with senile osteoporosis, we performed genome-wide expression analyses of differentiating osteoblasts and adipocytes. Among transcription factors that were enriched in the early phase of differentiation, Id4 was identified as a key molecule affecting the differentiation of both cell types. Experiments using bone marrow-derived stromal cell line ST2 and Id4-deficient mice showed that lack of Id4 drastically reduces osteoblast differentiation and drives differentiation toward adipocytes. On the other hand knockdown of Id4 in adipogenic-induced ST2 cells increased the expression of Ppargamma2, a master regulator of adipocyte differentiation. Similar results were observed in bone marrow cells of femur and tibia of Id4-deficient mice. However the effect of Id4 on Ppargamma2 and adipocyte differentiation is unlikely to be of direct nature. The mechanism of Id4 promoting osteoblast differentiation is associated with the Id4-mediated release of Hes1 from Hes1-Hey2 complexes. Hes1 increases the stability and transcriptional activity of Runx2, a key molecule of osteoblast differentiation, which results in an enhanced osteoblast-specific gene expression. The new role of Id4 in promoting osteoblast differentiation renders it a target for preventing the onset of senile osteoporosis. PMID:20628571

  10. The Arabidopsis CORI3 promoter contains two cis-acting regulatory regions required for transcriptional activity in companion cells.

    PubMed

    Tsuwamoto, Ryo; Harada, Takeo

    2011-09-01

    Companion cells are metabolically active and functionally specialized cells that behave as terminals for the transport of materials between phloem and the surrounding tissue. Although previous research has clarified the distinct function of companion cells, it is still largely unknown how plants establish and maintain the special identity of these cells. To shed further light on this issue, we carried out expressed sequence tag (EST) analysis. To minimize the difficulty of dissociating and gathering intact companion cells, vascular strings with an abundant content of companion cells were excised from the petioles of Brassica napus. By random sequencing with a string-specific cDNA library derived by suppression subtractive hybridization between the string itself and the petiole from which it had been removed, we identified 377 ESTs and assembled them into 247 EST groups. The most frequent EST was ExBdl-102 (15 of 377 ESTs), which showed the highest sequence similarity to the Arabidopsis CORI3 (CORONATINE INDUCED 3) gene. The CORI3 promoter:GUS showed predominant expression in the vascular tissue of Arabidopsis. Through transient expression assay using Brassica vasculature and gene-gun-mediated transient assay, we found two integrated cis-regulatory regions of the CORI3 promoter. This work has provided not only string-specific EST information and shown that two novel cis-regulatory regions sustain transcriptional activity in companion cells, but also a series of procedures for efficiently examining the transcriptional framework of companion cells by exploiting the histochemical advantage of B. napus as an experimental material. PMID:21559970

  11. Sea Changes - ACT : Artists and Scientists collaborating to promote ocean activism and conservation. (www.seachanges.org)

    NASA Astrophysics Data System (ADS)

    Lueker, T.

    2012-12-01

    We are a group of ocean scientists, artists, and educators working to publicize the urgent environmental problems facing our ocean environs, including overfishing, climate change and ocean acidification, and environmental degradation due to plastic and other forms of pollution. Our team leader, Kira Carrillo Corser, is an artist and educator known nationally for affecting policy and social change. Our collaboration results from the DNA of Creativity Project - the brainchild of Patricia Frischer, co-ordinator for the San Diego Visual Arts Network (http://dnaofc.weebly.com). The DNA of Creativity funded teams composed of artists and scientists with the goal of fusing the creative energies of both into projects that will enhance the public's perception of creativity, and make the complexities of art and science collaborations accessible to a new and larger audience. Sea Changes - ACT was funded initially by the DNA of Creativity Project. Our project goals are : 1) To entice people to participate in the joys of discovery of art AND science and 2) To motivate the public to work for real, committed and innovative change to protect our oceans. Part of our strategy for achieving our goals is to create a traveling art installation to illustrate the beauty of the oceans and to instill in our viewers the joys of discovery and creativity that we as scientists and artists pursue. And following this, to make the destructive changes occurring in the ocean and the future consequences more visible and understandable. We will develop lesson plans to integrate our ideas into the educational system and we are documenting our collaborative and creative process to inform future art-science collaborations. Finally, after emotionally connecting with our viewers to provide a means to ACT to make real and positive CHANGES for the future. Our project aims to build commitment and action for environmental conservation and stewardship as we combine scientific research with ways to take action

  12. Flow-induced protein kinase A–CREB pathway acts via BMP signaling to promote HSC emergence

    PubMed Central

    Kim, Peter Geon; Nakano, Haruko; Das, Partha P.; Chen, Michael J.; Rowe, R. Grant; Chou, Stephanie S.; Ross, Samantha J.; Sakamoto, Kathleen M.; Zon, Leonard I.; Schlaeger, Thorsten M.; Orkin, Stuart H.; Nakano, Atsushi

    2015-01-01

    Fluid shear stress promotes the emergence of hematopoietic stem cells (HSCs) in the aorta–gonad–mesonephros (AGM) of the developing mouse embryo. We determined that the AGM is enriched for expression of targets of protein kinase A (PKA)–cAMP response element-binding protein (CREB), a pathway activated by fluid shear stress. By analyzing CREB genomic occupancy from chromatin-immunoprecipitation sequencing (ChIP-seq) data, we identified the bone morphogenetic protein (BMP) pathway as a potential regulator of CREB. By chemical modulation of the PKA–CREB and BMP pathways in isolated AGM VE-cadherin+ cells from mid-gestation embryos, we demonstrate that PKA–CREB regulates hematopoietic engraftment and clonogenicity of hematopoietic progenitors, and is dependent on secreted BMP ligands through the type I BMP receptor. Finally, we observed blunting of this signaling axis using Ncx1-null embryos, which lack a heartbeat and intravascular flow. Collectively, we have identified a novel PKA–CREB–BMP signaling pathway downstream of shear stress that regulates HSC emergence in the AGM via the endothelial-to-hematopoietic transition. PMID:25870201

  13. Non-centrosomal epidermal microtubules act in parallel to LET-502/ROCK to promote C. elegans elongation.

    PubMed

    Quintin, Sophie; Wang, Shahoe; Pontabry, Julien; Bender, Ambre; Robin, François; Hyenne, Vincent; Landmann, Frédéric; Gally, Christelle; Oegema, Karen; Labouesse, Michel

    2016-01-01

    C. elegans embryonic elongation is a morphogenetic event driven by actomyosin contractility and muscle-induced tension transmitted through hemidesmosomes. A role for the microtubule cytoskeleton has also been proposed, but its contribution remains poorly characterized. Here, we investigate the organization of the non-centrosomal microtubule arrays present in the epidermis and assess their function in elongation. We show that the microtubule regulators γ-tubulin and NOCA-1 are recruited to hemidesmosomes and adherens junctions early in elongation. Several parallel approaches suggest that microtubule nucleation occurs from these sites. Disrupting the epidermal microtubule array by overexpressing the microtubule-severing protein Spastin or by inhibiting the C. elegans ninein homolog NOCA-1 in the epidermis mildly affected elongation. However, microtubules were essential for elongation when hemidesmosomes or the activity of the Rho kinase LET-502/ROCK were partially compromised. Imaging of junctional components and genetic analyses suggest that epidermal microtubules function together with Rho kinase to promote the transport of E-cadherin to adherens junctions and myotactin to hemidesmosomes. Our results indicate that the role of LET-502 in junctional remodeling is likely to be independent of its established function as a myosin II activator, but requires a microtubule-dependent pathway involving the syntaxin SYX-5. Hence, we propose that non-centrosomal microtubules organized by epidermal junctions contribute to elongation by transporting junction remodeling factors, rather than having a mechanical role. PMID:26586219

  14. Flow-induced protein kinase A-CREB pathway acts via BMP signaling to promote HSC emergence.

    PubMed

    Kim, Peter Geon; Nakano, Haruko; Das, Partha P; Chen, Michael J; Rowe, R Grant; Chou, Stephanie S; Ross, Samantha J; Sakamoto, Kathleen M; Zon, Leonard I; Schlaeger, Thorsten M; Orkin, Stuart H; Nakano, Atsushi; Daley, George Q

    2015-05-01

    Fluid shear stress promotes the emergence of hematopoietic stem cells (HSCs) in the aorta-gonad-mesonephros (AGM) of the developing mouse embryo. We determined that the AGM is enriched for expression of targets of protein kinase A (PKA)-cAMP response element-binding protein (CREB), a pathway activated by fluid shear stress. By analyzing CREB genomic occupancy from chromatin-immunoprecipitation sequencing (ChIP-seq) data, we identified the bone morphogenetic protein (BMP) pathway as a potential regulator of CREB. By chemical modulation of the PKA-CREB and BMP pathways in isolated AGM VE-cadherin(+) cells from mid-gestation embryos, we demonstrate that PKA-CREB regulates hematopoietic engraftment and clonogenicity of hematopoietic progenitors, and is dependent on secreted BMP ligands through the type I BMP receptor. Finally, we observed blunting of this signaling axis using Ncx1-null embryos, which lack a heartbeat and intravascular flow. Collectively, we have identified a novel PKA-CREB-BMP signaling pathway downstream of shear stress that regulates HSC emergence in the AGM via the endothelial-to-hematopoietic transition. PMID:25870201

  15. Cancer Stem-like Cells Act via Distinct Signaling Pathways in Promoting Late Stages of Malignant Progression.

    PubMed

    da Silva-Diz, Victoria; Simón-Extremera, Pilar; Bernat-Peguera, Adrià; de Sostoa, Jana; Urpí, Maria; Penín, Rosa M; Sidelnikova, Diana Pérez; Bermejo, Oriol; Viñals, Joan Maria; Rodolosse, Annie; González-Suárez, Eva; Moruno, Antonio Gómez; Pujana, Miguel Ángel; Esteller, Manel; Villanueva, Alberto; Viñals, Francesc; Muñoz, Purificación

    2016-03-01

    Cancer stem-like cells (CSC) play key roles in long-term tumor propagation and metastasis, but their dynamics during disease progression are not understood. Tumor relapse in patients with initially excised skin squamous cell carcinomas (SCC) is characterized by increased metastatic potential, and SCC progression is associated with an expansion of CSC. Here, we used genetically and chemically-induced mouse models of skin SCC to investigate the signaling pathways contributing to CSC function during disease progression. We found that CSC regulatory mechanisms change in advanced SCC, correlating with aggressive tumor growth and enhanced metastasis. β-Catenin and EGFR signaling, induced in early SCC CSC, were downregulated in advanced SCC. Instead, autocrine FGFR1 and PDGFRα signaling, which have not been previously associated with skin SCC CSC, were upregulated in late CSC and promoted tumor growth and metastasis, respectively. Finally, high-grade and recurrent human skin SCC recapitulated the signaling changes observed in advanced mouse SCC. Collectively, our findings suggest a stage-specific switch in CSC regulation during disease progression that could be therapeutically exploited by targeting the PDGFR and FGFR1 pathways to block relapse and metastasis of advanced human skin SCC. PMID:26719534

  16. The Nuclear DNA Sensor IFI16 Acts as a Restriction Factor for Human Papillomavirus Replication through Epigenetic Modifications of the Viral Promoters

    PubMed Central

    Lo Cigno, Irene; De Andrea, Marco; Borgogna, Cinzia; Albertini, Silvia; Landini, Manuela M.; Peretti, Alberto; Johnson, Karen E.; Chandran, Bala; Landolfo, Santo

    2015-01-01

    ABSTRACT The human interferon-inducible IFI16 protein, an innate immune sensor of intracellular DNA, was recently demonstrated to act as a restriction factor for human cytomegalovirus (HCMV) and herpes simplex virus 1 (HSV-1) infection by inhibiting both viral-DNA replication and transcription. Through the use of two distinct cellular models, this study provides strong evidence in support of the notion that IFI16 can also restrict human papillomavirus 18 (HPV18) replication. In the first model, an immortalized keratinocyte cell line (NIKS) was used, in which the IFI16 protein was knocked down through the use of small interfering RNA (siRNA) technology and overexpressed following transduction with the adenovirus IFI16 (AdVIFI16) vector. The second model consisted of U2OS cells transfected by electroporation with HPV18 minicircles. In differentiated IFI16-silenced NIKS-HPV18 cells, viral-load values were significantly increased compared with differentiated control cells. Consistent with this, IFI16 overexpression severely impaired HPV18 replication in both NIKS and U2OS cells, thus confirming its antiviral restriction activity. In addition to the inhibition of viral replication, IFI16 was also able to reduce viral transcription, as demonstrated by viral-gene expression analysis in U2OS cells carrying episomal HPV18 minicircles and HeLa cells. We also provide evidence that IFI16 promotes the addition of heterochromatin marks and the reduction of euchromatin marks on viral chromatin at both early and late promoters, thus reducing both viral replication and transcription. Altogether, these results argue that IFI16 restricts chromatinized HPV DNA through epigenetic modifications and plays a broad surveillance role against viral DNA in the nucleus that is not restricted to herpesviruses. IMPORTANCE Intrinsic immunity is mediated by cellular restriction factors that are constitutively expressed and active even before a pathogen enters the cell. The host nuclear factor IFI

  17. 7 CFR 1216.1 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.1 Act. Act means...

  18. 7 CFR 1216.1 - Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.1 Act. Act means...

  19. 7 CFR 1216.1 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.1 Act. Act means...

  20. 7 CFR 1216.1 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.1 Act. Act means...

  1. 7 CFR 1216.1 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PEANUT PROMOTION, RESEARCH, AND INFORMATION ORDER Peanut Promotion, Research, and Information Order Definitions § 1216.1 Act. Act means...

  2. 7 CFR 1221.1 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.1 Act. Act means...

  3. 7 CFR 1221.1 - Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.1 Act. Act means...

  4. 7 CFR 1221.1 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.1 Act. Act means...

  5. 7 CFR 1221.1 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.1 Act. Act means...

  6. 7 CFR 1206.1 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.1 Act. Act means the...

  7. 7 CFR 1206.1 - Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.1 Act. Act means the...

  8. 7 CFR 1206.1 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.1 Act. Act means the...

  9. 7 CFR 1206.1 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.1 Act. Act means the...

  10. 7 CFR 1206.1 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MANGO PROMOTION, RESEARCH, AND INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.1 Act. Act means the...

  11. 7 CFR 1221.1 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SORGHUM PROMOTION, RESEARCH, AND INFORMATION ORDER Sorghum Promotion, Research, and Information Order Definitions § 1221.1 Act. Act means...

  12. 7 CFR 1207.302 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Definitions § 1207.302 Act. Act means the Potato Research...

  13. 7 CFR 1207.302 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Definitions § 1207.302 Act. Act means the Potato Research...

  14. 7 CFR 1207.302 - Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Definitions § 1207.302 Act. Act means the Potato Research...

  15. 7 CFR 1207.302 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Definitions § 1207.302 Act. Act means the Potato Research...

  16. 7 CFR 1207.302 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan Definitions § 1207.302 Act. Act means the Potato Research...

  17. 7 CFR 1218.1 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.1 Act. Act means...

  18. 7 CFR 1218.1 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.1 Act. Act means...

  19. 7 CFR 1218.1 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.1 Act. Act means...

  20. 7 CFR 1218.1 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.1 Act. Act means...

  1. 7 CFR 1218.1 - Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.1 Act. Act means...

  2. The catecholamine biosynthetic enzyme dopamine β-hydroxylase (DBH): first genome-wide search positions trait-determining variants acting additively in the proximal promoter

    PubMed Central

    Mustapic, Maja; Maihofer, Adam X.; Mahata, Manjula; Chen, Yuqing; Baker, Dewleen G.; O'Connor, Daniel T.; Nievergelt, Caroline M.

    2014-01-01

    Dopamine beta-hydroxylase (DBH) is the biosynthetic enzyme catalyzing formation of norepinephrine. Changes in DBH expression or activity have been implicated in the pathogenesis of cardiovascular and neuropsychiatric disorders. Genetic determination of DBH enzymatic activity and its secretion are only incompletely understood. We began with a genome-wide association search for loci contributing to DBH activity in human plasma. Initially, in a population sample of European ancestry, we identified the proximal DBH promoter as a region harboring three common trait-determining variants (top hit rs1611115, P = 7.2 × 10−51). We confirmed their effects on transcription and showed that the three variants each acted additively on gene expression. Results were replicated in a population sample of Native American descent (top hit rs1611115, P = 4.1 × 10−15). Jointly, DBH variants accounted for 57% of DBH trait variation. We further identified a genome-wide significant SNP at the LOC338797 locus on chromosome 12 as trans-quantitative trait locus (QTL) (rs4255618, P = 4.62 × 10−8). Conditional analyses on DBH identified a third genomic region contributing to DBH variation: a likely cis-QTL adjacent to DBH in SARDH (rs7040170, P = 1.31 × 10−14) on chromosome 9q. We conclude that three common SNPs in the DBH promoter act additively to control phenotypic variation in DBH levels, and that two additional novel loci (SARDH and LOC338797) may also contribute to the expression of this catecholamine biosynthetic trait. Identification of DBH variants with strong effects makes it possible to take advantage of Mendelian randomization approaches to test causal effects of this intermediate trait on disease. PMID:24986918

  3. Polo-like kinase 2 acting as a promoter in human tumor cells with an abundance of TAp73

    PubMed Central

    Hu, ZhengBo; Xu, ZunYing; Liao, XiaoHong; Yang, Xiao; Dong, Cao; Luk, KuaDi; Jin, AnMin; Lu, Hai

    2015-01-01

    suppresses TAp73 functions. PLK2 promotes the survival of human tumor cells, a novel insight into the workings of malignant tumors characterized by TAp73 overexpression, and one that could speed the development of therapies. PMID:26640387

  4. Nitrogen transporter and assimilation genes exhibit developmental stage-selective expression in maize (Zea mays L.) associated with distinct cis-acting promoter motifs

    PubMed Central

    Liseron-Monfils, Christophe; Bi, Yong-Mei; Downs, Gregory S; Wu, Wenqing; Signorelli, Tara; Lu, Guangwen; Chen, Xi; Bondo, Eddie; Zhu, Tong; Lukens, Lewis N; Colasanti, Joseph; Rothstein, Steven J; Raizada, Manish N

    2013-01-01

    Nitrogen is considered the most limiting nutrient for maize (Zea mays L.), but there is limited understanding of the regulation of nitrogen-related genes during maize development. An Affymetrix 82K maize array was used to analyze the expression of ≤ 46 unique nitrogen uptake and assimilation probes in 50 maize tissues from seedling emergence to 31 d after pollination. Four nitrogen-related expression clusters were identified in roots and shoots corresponding to, or overlapping, juvenile, adult, and reproductive phases of development. Quantitative real time PCR data was consistent with the existence of these distinct expression clusters. Promoters corresponding to each cluster were screened for over-represented cis-acting elements. The 8-bp distal motif of the Arabidopsis 43-bp nitrogen response element (NRE) was over-represented in nitrogen-related maize gene promoters. This conserved motif, referred to here as NRE43-d8, was previously shown to be critical for nitrate-activated transcription of nitrate reductase (NIA1) and nitrite reductase (NIR1) by the NIN-LIKE PROTEIN 6 (NLP6) in Arabidopsis. Here, NRE43-d8 was over-represented in the promoters of maize nitrate and ammonium transporter genes, specifically those that showed peak expression during early-stage vegetative development. This result predicts an expansion of the NRE-NLP6 regulon and suggests that it may have a developmental component in maize. We also report leaf expression of putative orthologs of nitrite transporters (NiTR1), a transporter not previously reported in maize. We conclude by discussing how each of the four transcriptional modules may be responsible for the different nitrogen uptake and assimilation requirements of leaves and roots at different stages of maize development. PMID:24270626

  5. Role of cis-acting sites in stimulation of the phage λ P(RM) promoter by CI-mediated looping.

    PubMed

    Michalowski, Christine B; Little, John W

    2013-08-01

    The lysogenic state of phage λ is maintained by the CI repressor. CI binds to three operators each in the right operator (O(R)) and left operator (O(L)) regions, which lie 2.4 kb apart. At moderate CI levels, the predominant binding pattern is two dimers of CI bound cooperatively at each regulatory region. The resulting tetramers can then interact, forming an octamer and a loop of the intervening DNA. CI is expressed from the P(RM) promoter, which lies in the O(R) region and is subjected to multiple regulatory controls. Of these, the most recently discovered is stimulation by loop formation. In this work, we have investigated the mechanism by which looping stimulates P(RM). We find that two cis-acting sites lying in the O(L) region are involved. One site, an UP element, is required for stimulation. Based on the behavior of other promoters with UP elements located upstream of the -35 region, we suggest that a subunit of RNA polymerase (RNAP) bound at P(RM) binds to the UP element located in the O(L) region. In addition, adjacent to the UP element lies a binding site for integration host factor (IHF); this site plays a less critical role but is required for stimulation of the weak prm240 allele. A loop with CI at the O(L)2 and O(L)3 operators does not stimulate P(RM), while one with CI only at O(L)2 provides some stimulation. We discuss possible mechanisms for stimulation. PMID:23708136

  6. Collinsville Renewable Energy Promotion Act

    THOMAS, 112th Congress

    Rep. Murphy, Christopher S. [D-CT-5

    2012-05-08

    06/27/2012 Received in the Senate and Read twice and referred to the Committee on Energy and Natural Resources. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  7. Collinsville Renewable Energy Promotion Act

    THOMAS, 112th Congress

    Sen. Lieberman, Joseph I. [ID-CT

    2011-04-04

    06/23/2011 Committee on Energy and Natural Resources Subcommittee on Water and Power. Hearings held. With printed Hearing: S.Hrg. 112-129. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  8. U-box E3 ubiquitin ligase PUB17 acts in the nucleus to promote specific immune pathways triggered by Phytophthora infestans.

    PubMed

    He, Qin; McLellan, Hazel; Boevink, Petra C; Sadanandom, Ari; Xie, Conghua; Birch, Paul R J; Tian, Zhendong

    2015-06-01

    Ubiquitination regulates many processes in plants, including immunity. The E3 ubiquitin ligase PUB17 is a positive regulator of programmed cell death (PCD) triggered by resistance proteins CF4/9 in tomato. Its role in immunity to the potato late blight pathogen, Phytophthora infestans, was investigated here. Silencing StPUB17 in potato by RNAi and NbPUB17 in Nicotiana benthamiana by virus-induced gene silencing (VIGS) each enhanced P. infestans leaf colonization. PAMP-triggered immunity (PTI) transcriptional responses activated by flg22, and CF4/Avr4-mediated PCD were attenuated by silencing PUB17. However, silencing PUB17 did not compromise PCD triggered by P. infestans PAMP INF1, or co-expression of R3a/AVR3a, demonstrating that not all PTI- and PCD-associated responses require PUB17. PUB17 localizes to the plant nucleus and especially in the nucleolus. Transient over-expression of a dominant-negative StPUB17(V314I,V316I) mutant, which retained nucleolar localization, suppressed CF4-mediated cell death and enhanced P. infestans colonization. Exclusion of the StPUB17(V314I,V316I) mutant from the nucleus abolished its dominant-negative activity, demonstrating that StPUB17 functions in the nucleus. PUB17 is a positive regulator of immunity to late blight that acts in the nucleus to promote specific PTI and PCD pathways. PMID:25873665

  9. Juvenile Hormone-Receptor Complex Acts on Mcm4 and Mcm7 to Promote Polyploidy and Vitellogenesis in the Migratory Locust

    PubMed Central

    Song, Jiasheng; Jiang, Feng; Wang, Zhiming; Deng, Shun; Walker, Virginia K.; Zhou, Shutang

    2014-01-01

    Juvenile hormone (JH), a sesquiterpenoid produced by the corpora allata, coordinates insect growth, metamorphosis, and reproduction. While JH action for the repression of larval metamorphosis has been well studied, the molecular basis of JH in promoting adult reproduction has not been fully elucidated. Methoprene-tolerant (Met), the JH receptor, has been recently shown to mediate JH action during metamorphosis as well as in vitellogenesis, but again, the precise mechanism underlying the latter has been lacking. We have now demonstrated using Met RNAi to phenocopy a JH-deprived condition in migratory locusts, that JH stimulates DNA replication and increases ploidy in preparation for vitellogenesis. Mcm4 and Mcm7, two genes in the DNA replication pathway were expressed in the presence of JH and Met. Depletion of Mcm4 or Mcm7 inhibited de novo DNA synthesis and polyploidization, and resulted in the substantial reduction of vitellogenin mRNA levels as well as severely impaired oocyte maturation and ovarian growth. By using luciferase reporter and electrophoretic mobility shift assays, we have shown that Met directly regulates the transcription of Mcm4 and Mcm7 by binding to upstream consensus sequences with E-box or E-box-like motifs. Our work suggests that the JH-receptor complex acts on Mcm4 and Mcm7 to regulate DNA replication and polyploidy for vitellogenesis and oocyte maturation. PMID:25340846

  10. Juvenile hormone-receptor complex acts on mcm4 and mcm7 to promote polyploidy and vitellogenesis in the migratory locust.

    PubMed

    Guo, Wei; Wu, Zhongxia; Song, Jiasheng; Jiang, Feng; Wang, Zhiming; Deng, Shun; Walker, Virginia K; Zhou, Shutang

    2014-10-01

    Juvenile hormone (JH), a sesquiterpenoid produced by the corpora allata, coordinates insect growth, metamorphosis, and reproduction. While JH action for the repression of larval metamorphosis has been well studied, the molecular basis of JH in promoting adult reproduction has not been fully elucidated. Methoprene-tolerant (Met), the JH receptor, has been recently shown to mediate JH action during metamorphosis as well as in vitellogenesis, but again, the precise mechanism underlying the latter has been lacking. We have now demonstrated using Met RNAi to phenocopy a JH-deprived condition in migratory locusts, that JH stimulates DNA replication and increases ploidy in preparation for vitellogenesis. Mcm4 and Mcm7, two genes in the DNA replication pathway were expressed in the presence of JH and Met. Depletion of Mcm4 or Mcm7 inhibited de novo DNA synthesis and polyploidization, and resulted in the substantial reduction of vitellogenin mRNA levels as well as severely impaired oocyte maturation and ovarian growth. By using luciferase reporter and electrophoretic mobility shift assays, we have shown that Met directly regulates the transcription of Mcm4 and Mcm7 by binding to upstream consensus sequences with E-box or E-box-like motifs. Our work suggests that the JH-receptor complex acts on Mcm4 and Mcm7 to regulate DNA replication and polyploidy for vitellogenesis and oocyte maturation. PMID:25340846

  11. 7 CFR 1150.101 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Orders; Milk), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research Order Definitions § 1150.101 Act. Act means Title I, Subtitle B, of the Dairy and Tobacco Adjustment Act of...

  12. 7 CFR 1150.101 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ORDERS; MILK), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research Order Definitions § 1150.101 Act. Act means Title I, Subtitle B, of the Dairy and Tobacco Adjustment Act of...

  13. 7 CFR 1150.101 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Orders; Milk), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research Order Definitions § 1150.101 Act. Act means Title I, Subtitle B, of the Dairy and Tobacco Adjustment Act of...

  14. 7 CFR 1150.101 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ORDERS; MILK), DEPARTMENT OF AGRICULTURE DAIRY PROMOTION PROGRAM Dairy Promotion and Research Order Definitions § 1150.101 Act. Act means Title I, Subtitle B, of the Dairy and Tobacco Adjustment Act of...

  15. The Indian Health Promotion and Disease Prevention Act of 1985. Hearing before the Select Committee on Indian Affairs. United States Senate, Ninety-Ninth Congress, First Session on S. 400. (Gallup, NM, June 1, 1985).

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Select Committee on Indian Affairs.

    The document contains transcripts of a Congressional hearing on providing health promotion and disease prevention services to American Indians. The bill under consideration would add the following programs to the Indian Health Care Improvement Act (25, U.S.C. 1603): reduction of drug, alcohol, and tobacco use; improvement of nutrition and physical…

  16. State Implementation of Reforms Promoted under the Recovery Act. A Report from Charting the Progress of Education Reform: An Evaluation of the Recovery Act's Role. NCEE 2014-4011

    ERIC Educational Resources Information Center

    Webber, Ann; Troppe, Patricia; Milanowski, Anthony; Gutmann, Babette; Reisner, Elizabeth; Goertz, Margaret

    2014-01-01

    The American Recovery and Reinvestment Act (ARRA or the Recovery Act) of 2009 provided an unprecedented level of funding for K-12 education. The program created a "historic opportunity to save hundreds of thousands of jobs, support states and school districts, and advance reforms and improvements that will create long-lasting results for our…

  17. Calreticulin acts as an adjuvant to promote dendritic cell maturation and enhances antigen-specific cytotoxic T lymphocyte responses against non-small cell lung cancer cells.

    PubMed

    Liu, Xinli; Li, Jijia; Liu, Yu; Ding, Jianqiao; Tong, Zhuang; Liu, Yang; Zhou, Yang; Liu, Yongyu

    2016-02-01

    Dendritic cell (DC)-based immunotherapy has promising for treatment of non-small cell lung cancer (NSCLC). Melanoma-associated antigen 3 (MAGE-A3) is a tumor-specific antigen and expressed in approximately 35-40% of NSCLC tissues. Calreticulin (CALR) is a protein chaperone and can enhance DC maturation and antigen presentation. In this study, we evaluated the adjuvant activity of CALR in human DC maturation and their capacity to induce MAGE-A3-specific CD8+ cytotoxic T lymphocyte (CTL) responses to NSCLC in vitro. Infection with recombinant Ad-CALR and/or Ad-MAGE-A3, but not with control Ads, induced CALR and/or MAGE-A3 expression in DCs. Infection with Ad-CALR significantly increased the percentages of CD80+, CD83+, CD86+ and HLA-DR+ DCs and IL-12 secretion, but reduced IL-10 production in DCs. Co-culture of autologous lymphocytes with DC-Ad-CALR or DC-Ad-CM significantly increased the numbers of induced CD8+ CTLs. The percentages of IFNγ-secreting CTLs responding to SK-LU-1 and NCI-H522 NSCLC, but not to non-tumor NL-20 cells in Ad-C-CTL, Ad-M-CTL and Ad-CM-CTL were significantly higher than that of DC-CTL and Ad-null-CTL. Ad-C-CTL, Ad-M-CTL and Ad-CM-CTL, but not control DC-CTL and Ad-null-CTL, induced higher frequency of MAGE-A3+HLA-A2+ NCI-H-522 cell apoptosis, but did not affect the survival of MAGE-A3+HLA-A2- SK-LU-1 and non-tumor NL20 cells in vitro. Treatment with anti-HLA-I antibody, but not with anti-HLA-II, dramatically diminished the cytotoxicity of Ad-CM-CTLs against NCI-H522 cells. Our data indicated that CALR acted as an adjuvant to promote DC maturation, which induced CTL development and enhanced MAGE-A3-specific CTL cytotoxicity against NSCLC. PMID:26702740

  18. 7 CFR 1220.600 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.600 Act. Act means the...

  19. 7 CFR 1220.600 - Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.600 Act. Act means the...

  20. 7 CFR 1220.600 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.600 Act. Act means the...

  1. 7 CFR 1220.600 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.600 Act. Act means the...

  2. 7 CFR 1220.600 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Procedures To Request a Referendum Definitions § 1220.600 Act. Act means the...

  3. 7 CFR 1214.1 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE CHRISTMAS TREE PROMOTION, RESEARCH, AND INFORMATION ORDER Christmas Tree Promotion, Research, and Information Order Definitions § 1214.1 Act....

  4. 7 CFR 1214.1 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE CHRISTMAS TREE PROMOTION, RESEARCH, AND INFORMATION ORDER Christmas Tree Promotion, Research, and Information Order Definitions § 1214.1 Act....

  5. 7 CFR 1214.1 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE CHRISTMAS TREE PROMOTION, RESEARCH, AND INFORMATION ORDER Christmas Tree Promotion, Research, and Information Order Definitions § 1214.1 Act....

  6. 7 CFR 1260.630 - Paperwork Reduction Act assigned number.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... BEEF PROMOTION AND RESEARCH Beef Promotion and Research: Certification and Nomination Procedures for the Cattlemen's Beef Promotion and Research Board § 1260.630 Paperwork Reduction Act assigned...

  7. 7 CFR 1260.630 - Paperwork Reduction Act assigned number.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... BEEF PROMOTION AND RESEARCH Beef Promotion and Research: Certification and Nomination Procedures for the Cattlemen's Beef Promotion and Research Board § 1260.630 Paperwork Reduction Act assigned...

  8. The heptanucleotide motif GAGACGC is a key component of a cis-acting promoter element that is critical for SnSAG1 expression in Sarcocystis neurona.

    PubMed

    Gaji, Rajshekhar Y; Howe, Daniel K

    2009-07-01

    The apicomplexan parasite Sarcocystis neurona undergoes a complex process of intracellular development, during which many genes are temporally regulated. The described study was undertaken to begin identifying the basic promoter elements that control gene expression in S. neurona. Sequence analysis of the 5'-flanking region of five S. neurona genes revealed a conserved heptanucleotide motif GAGACGC that is similar to the WGAGACG motif described upstream of multiple genes in Toxoplasma gondii. The promoter region for the major surface antigen gene SnSAG1, which contains three heptanucleotide motifs within 135 bases of the transcription start site, was dissected by functional analysis using a dual luciferase reporter assay. These analyses revealed that a minimal promoter fragment containing all three motifs was sufficient to drive reporter molecule expression, with the presence and orientation of the 5'-most heptanucleotide motif being absolutely critical for promoter function. Further studies should help to identify additional sequence elements important for promoter function and for controlling gene expression during intracellular development by this apicomplexan pathogen. PMID:19428678

  9. A short, highly repetitive element in intron -1 of the human c-Ha-ras gene acts as a block to transcriptional readthrough by a viral promoter.

    PubMed Central

    Lowndes, N F; Bushel, P; Mendelsohn, L; Wu, J; Yen, M Y; Allan, M

    1990-01-01

    We have identified a short, highly repetitive element within intron -1 of the human c-Ha-ras gene. This element was found to be transcribed in both orientations and to be homologous to heterogeneous nonpolyadenylated transcripts. The repetitive element blocked transcriptional readthrough from a strong upstream viral promoter but allowed unimpaired readthrough from the c-Has-ras promoter. We suggest that it may serve to prevent excessive transcription into the coding region of the gene under such circumstances as viral insertion. Images PMID:2201911

  10. Promoting College Completion through Leadership among Underrepresented Urban College Students: A Theory of Change and Evaluation of College Retention Outcomes for the Act Six Leadership and Scholarship Initiative

    ERIC Educational Resources Information Center

    Herron, Timothy J.

    2012-01-01

    The Act Six Leadership and Scholarship Initiative is a leadership development and college retention and success program developed by the Northwest Leadership Foundation that provides intensive cohort-based training and support, along with full-tuition, full-need scholarships, to underrepresented urban college students to attend religiously…

  11. The Content Analysis of ACT ASSET: The Validation of an Instrument To Assess the Cognitive Entry Characteristics of College Students in View of Promoting Persistence and Transfer.

    ERIC Educational Resources Information Center

    Talbot, Gilles L.

    The Assessment of Skills for Successful Entry and Transfer (ASSET)--a student advisement and placement service published by American College Testing (ACT) of Iowa City, Iowa--is evaluated. Focus is on determining whether the ASSET is suitable for assessing the cognitive entry characteristics of students entering the College of General and…

  12. 7 CFR 1215.1 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Definitions § 1215.1 Act. Act means the Popcorn Promotion, Research, and Consumer Information Act of 1995, Subtitle E of Title V of...

  13. 7 CFR 1219.1 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.1 Act. Act means the Hass Avocado Promotion, Research, and Information Act of 2000, Public Law 106-387, 7 U.S.C....

  14. 7 CFR 1219.1 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.1 Act. Act means the Hass Avocado Promotion, Research, and Information Act of 2000, Public Law 106-387, 7 U.S.C....

  15. 7 CFR 1219.1 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.1 Act. Act means the Hass Avocado Promotion, Research, and Information Act of 2000, Public Law 106-387, 7 U.S.C....

  16. 7 CFR 1219.1 - Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.1 Act. Act means the Hass Avocado Promotion, Research, and Information Act of 2000, Public Law 106-387, 7 U.S.C....

  17. 7 CFR 1219.1 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE HASS AVOCADO PROMOTION, RESEARCH, AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.1 Act. Act means the Hass Avocado Promotion, Research, and Information Act of 2000, Public Law 106-387, 7 U.S.C....

  18. 7 CFR 1209.1 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209.1 Act. Act means the Mushroom Promotion, Research, and Consumer Information Act of 1990, subtitle B of title XIX...

  19. 7 CFR 1220.101 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.101 Act. The term Act means the Soybean Promotion, Research, and Consumer Information Act, subtitle E of title XIX, of the...

  20. 7 CFR 1220.101 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.101 Act. The term Act means the Soybean Promotion, Research, and Consumer Information Act, subtitle E of title XIX, of the...

  1. 7 CFR 1220.101 - Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.101 Act. The term Act means the Soybean Promotion, Research, and Consumer Information Act, subtitle E of title XIX, of the...

  2. 7 CFR 1220.101 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.101 Act. The term Act means the Soybean Promotion, Research, and Consumer Information Act, subtitle E of title XIX, of the...

  3. 7 CFR 1220.101 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE SOYBEAN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.101 Act. The term Act means the Soybean Promotion, Research, and Consumer Information Act, subtitle E of title XIX, of the...

  4. 7 CFR 1209.1 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209.1 Act. Act means the Mushroom Promotion, Research, and Consumer Information Act of 1990, subtitle B of title XIX...

  5. 7 CFR 1209.1 - Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209.1 Act. Act means the Mushroom Promotion, Research, and Consumer Information Act of 1990, subtitle B of title XIX...

  6. 7 CFR 1209.1 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209.1 Act. Act means the Mushroom Promotion, Research, and Consumer Information Act of 1990, subtitle B of title XIX...

  7. 7 CFR 1209.1 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE MUSHROOM PROMOTION, RESEARCH, AND CONSUMER INFORMATION ORDER Mushroom Promotion, Research, and Consumer Information Order Definitions § 1209.1 Act. Act means the Mushroom Promotion, Research, and Consumer Information Act of 1990, subtitle B of title XIX...

  8. 7 CFR 1230.1 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND CONSUMER INFORMATION Pork Promotion, Research, and Consumer Information Order Definitions § 1230.1 Act. Act means the Pork Promotion, Research, and Consumer Information Act of 1985 (7 U.S.C. 4801-4819) and any...

  9. 7 CFR 1215.1 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Definitions § 1215.1 Act. Act means the Popcorn Promotion, Research, and Consumer Information Act of 1995, Subtitle E of Title V of...

  10. 7 CFR 1215.1 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Definitions § 1215.1 Act. Act means the Popcorn Promotion, Research, and Consumer Information Act of 1995, Subtitle E of Title V of...

  11. 7 CFR 1215.1 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Definitions § 1215.1 Act. Act means the Popcorn Promotion, Research, and Consumer Information Act of 1995, Subtitle E of Title V of...

  12. 7 CFR 1215.1 - Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POPCORN PROMOTION, RESEARCH, AND CONSUMER INFORMATION Popcorn Promotion, Research, and Consumer Information Order Definitions § 1215.1 Act. Act means the Popcorn Promotion, Research, and Consumer Information Act of 1995, Subtitle E of Title V of...

  13. 7 CFR 1210.302 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.302 Act. Act means the Watermelon Research and Promotion Act of 1985 (Title XVI, Subtitle C of Pub. L. 99-198, 99th Congress,...

  14. The UPC2 promoter in Candida albicans contains two cis-acting elements that bind directly to Upc2p, resulting in transcriptional autoregulation.

    PubMed

    Hoot, Samantha J; Brown, Ryan P; Oliver, Brian G; White, Theodore C

    2010-09-01

    In Candida albicans, ergosterol biosynthetic genes, including ERG11, which encodes the target of azole antifungal drugs, are regulated by the transcriptional regulator Upc2p. To initially characterize the promoter of the UPC2 gene, 5' rapid amplification of cDNA ends was used to identify two transcriptional initiation sites upstream of the ATG codon. The regions within the UPC2 promoter required for azole regulation of the UPC2 promoter were then identified using nested deletions fused to a luciferase reporter which were tested for azole inducibility in wild-type (WT) and upc2Delta/upc2Delta strains. Two distinct regions important for azole induction were identified: a Upc2p-dependent region (UDR) between bp -450 and -350 upstream of the ATG codon and a Upc2p-independent region (UIR) between bp -350 and -250 upstream of the ATG codon. Within the UDR, loss or mutation of the sterol response element (SRE), so named because of homology to the Saccharomyces cerevisiae Upc2p binding site, resulted in a decrease in both basal and induced expression in the WT strain but did not affect azole inducibility in the upc2Delta/upc2Delta deletion strain. Gel shift analyses using the DNA binding domain of Upc2p confirmed binding of the protein to two SRE-related sequences within the UPC2 promoter, with strongest binding to the UDR SRE. Detailed gel shift analyses of the UDR SRE shows that Upc2p binds to a bipartite element within the UPC2 promoter, including the previously identified SRE and a new, adjacent element, the short direct repeat (SDR), with partial homology to the SRE. PMID:20656915

  15. A cis-acting element in the promoter of human ether à go-go 1 potassium channel gene mediates repression by calcitriol in human cervical cancer cells.

    PubMed

    Cázares-Ordoñez, V; González-Duarte, R J; Díaz, L; Ishizawa, M; Uno, S; Ortíz, V; Ordoñez-Sánchez, M L; Makishima, M; Larrea, F; Avila, E

    2015-02-01

    The human ether à go-go 1 potassium channel (hEAG1) is required for cell cycle progression and proliferation of cancer cells. Inhibitors of hEAG1 activity and expression represent potential therapeutic drugs in cancer. Previously, we have shown that hEAG1 expression is downregulated by calcitriol in a variety of cancer cells. Herein, we provided evidence on the regulatory mechanism involved in such repressive effect in cells derived from human cervical cancer. Our results indicate that repression by calcitriol occurs at the transcriptional level and involves a functional negative vitamin D response element (nVDRE) E-box type in the hEAG1 promoter. The described mechanism in this work implies that a protein complex formed by the vitamin D receptor-interacting repressor, the vitamin D receptor, the retinoid X receptor, and the Williams syndrome transcription factor interact with the nVDRE in the hEAG1 promoter in the absence of ligand. Interestingly, all of these transcription factors except the vitamin D receptor-interacting repressor are displaced from hEAG1 promoter in the presence of calcitriol. Our results provide novel mechanistic insights into calcitriol mode of action in repressing hEAG1 gene expression. PMID:25495694

  16. Collagen Triple Helix Repeat Containing 1 (CTHRC1) acts via ERK-dependent induction of MMP9 to promote invasion of colorectal cancer cells

    PubMed Central

    Oh, Hyun-Woo; Kim, Kwoneel; Oh, Sang-Seok; Kim, Jong-Tae; Kim, Bo Yeon; Lee, Seon-Jin; Choe, Yong-Kyung; Kim, Dong Hyeok; Kim, Seok-Hyung; Chae, Seoung Wan; Kim, Kwang Dong; Lee, Hee Gu

    2014-01-01

    Collagen triple helix repeat-containing 1 (CTHRC1) is known to be aberrantly upregulated in most human solid tumors, although the functional roles of CTHRC1 in colorectal cancer remain unclear. In this study, we investigated the occurrence of CTHRC1 upregulation and its role in vivo and in vitro. The expression profile and clinical importance of CTHRC1 were examined by reverse transcription-polymerase chain reaction and immunohistochemical analyses in normal and tumor patient samples. CTHRC1 was detectable in normal tissues, but also was highly expressed in tumor specimens. CTHRC1 upregulation was significantly associated with demethylation of the CTHRC1 promoter in colon cancer cell lines and tumor tissues. Clinicopathologic analyses showed that nodal status and expression of CTHRC1 (95% CI 0.999–3.984, p=0.05) were significant prognostic factors for disease-free survival. Promoter CpG methylation and hypermethylation status were measured by bisulfite sequencing and pyrosequencing analysis. Furthermore, we showed that overexpression of CTHRC1 in the SW480 and HT-29 cell lines increased invasiveness, an effect mediated by extracellular signal-regulated kinase (ERK)-dependent upregulation of matrix metalloproteinase 9 (MMP9). Consistent with this, we found that knockdown of CTHRC1 attenuated ERK activation and cancer cell invasivity. These results demonstrate that CTHRC1 expression is elevated in human colon cancer cell lines and clinical specimens, and promotes cancer cell invasivity through ERK-dependent induction of MMP9 expression. Our results further suggest that high levels of CTHRC1 expression are associated with poor clinical outcomes. PMID:24504172

  17. CTHRC1 Acts as a Prognostic Factor and Promotes Invasiveness of Gastrointestinal Stromal Tumors by Activating Wnt/PCP-Rho Signaling1

    PubMed Central

    Ma, Ming-Ze; Zhuang, Chun; Yang, Xiao-Mei; Zhang, Zi-Zhen; Ma, Hong; Zhang, Wen-Ming; You, Haiyan; Qin, Wenxin; Gu, Jianren; Yang, Shengli; Cao, Hui; Zhang, Zhi-Gang

    2014-01-01

    Gastrointestinal stromal tumors (GISTs) are the major gastrointestinal mesenchymal tumors with a variable malignancy ranging from a curable disorder to highly malignant sarcomas. Metastasis and recurrence are the main causes of death in GIST patients. To further explore the mechanism of metastasis and to more accurately estimate the recurrence risk of GISTs after surgery, the clinical significance and functional role of collagen triple helix repeat containing-1 (CTHRC1) in GIST were investigated. We found that CTHRC1 expression was gradually elevated as the risk grade of NIH classification increased, and was closely correlated with disease-free survival and overall survival in 412 GIST patients. In vitro experiments showed that recombinant CTHRC1 protein promoted the migration and invasion capacities of primary GIST cells. A luciferase reporter assay and pull down assay demonstrated that recombinant CTHRC1 protein activated noncanonical Wnt/PCP-Rho signaling but inhibited canonical Wnt signaling. The pro-motility effect of CTHRC1 on GIST cells was reversed by using a Wnt5a neutralizing antibody and inhibitors of Rac1 or ROCK. Taken together, these data indicate that CTHRC1 may serve as a new predictor of recurrence risk and prognosis in post-operative GIST patients and may play an important role in facilitating GIST progression. Furthermore, CTHRC1 promotes GIST cell migration and invasion by activating Wnt/PCP-Rho signaling, suggesting that the CTHRC1-Wnt/PCP-Rho axis may be a new therapeutic target for interventions against GIST invasion and metastasis. PMID:24726140

  18. Inhibitor of differentiation 4 (ID4) acts as an inhibitor of ID-1, -2 and -3 and promotes basic helix loop helix (bHLH) E47 DNA binding and transcriptional activity.

    PubMed

    Sharma, Pankaj; Chinaranagari, Swathi; Chaudhary, Jaideep

    2015-05-01

    The four known ID proteins (ID1-4, Inhibitor of Differentiation) share a homologous helix loop helix (HLH) domain and act as dominant negative regulators of basic-HLH transcription factors. ID proteins also interact with many non-bHLH proteins in complex networks. The expression of ID proteins is increasingly observed in many cancers. Whereas ID-1, ID-2 and ID-3, are generally considered as tumor promoters, ID4 on the contrary has emerged as a tumor suppressor. In this study we demonstrate that ID4 heterodimerizes with ID-1, -2 and -3 and promote bHLH DNA binding, essentially acting as an inhibitor of inhibitors of differentiation proteins. Interaction of ID4 was observed with ID1, ID2 and ID3 that was dependent on intact HLH domain of ID4. Interaction with bHLH protein E47 required almost 3 fold higher concentration of ID4 as compared to ID1. Furthermore, inhibition of E47 DNA binding by ID1 was restored by ID4 in an EMSA binding assay. ID4 and ID1 were also colocalized in prostate cancer cell line LNCaP. The alpha helix forming alanine stretch N-terminal, unique to HLH ID4 domain was required for optimum interaction. Ectopic expression of ID4 in DU145 prostate cancer line promoted E47 dependent expression of CDKNI p21. Thus counteracting the biological activities of ID-1, -2 and -3 by forming inactive heterodimers appears to be a novel mechanism of action of ID4. These results could have far reaching consequences in developing strategies to target ID proteins for cancer therapy and understanding biologically relevant ID-interactions. PMID:25778840

  19. Inhibitor of Differentiation 4 (ID4) Acts as an Inhibitor of ID-1, -2 and -3 and Promotes basic Helix Loop Helix (bHLH) E47 DNA Binding and Transcriptional Activity

    PubMed Central

    Sharma, Pankaj; Chinaranagari, Swathi; Chaudhary, Jaideep

    2015-01-01

    The four known ID proteins (ID1-4, Inhibitor of Differentiation) share a homologous helix loop helix (HLH) domain and act as dominant negative regulators of basic-HLH transcription factors. ID proteins also interact with many non-bHLH proteins in complex networks. The expression of ID proteins is increasingly observed in many cancers. Whereas ID-1, ID-2 and ID-3, are generally considered as tumor promoters, ID4 on the contrary has emerged as a tumor suppressor. In this study we demonstrate that ID4 heterodimerizes with ID-1, -2 and -3 and promote bHLH DNA binding, essentially acting as an inhibitor of inhibitors of differentiation proteins. Interaction of ID4 was observed with ID1, ID2 and ID3 that was dependent on intact HLH domain of ID4. Interaction with bHLH protein E47 required almost 3 fold higher concentration of ID4 as compared to ID1. Furthermore, inhibition of E47 DNA binding by ID1 was restored by ID4 in an EMSA binding assay. ID4 and ID1 were also colocalized in prostate cancer cell line LNCaP. The alpha helix forming alanine stretch N-terminal, unique to HLH ID4 domain was required for optimum interaction. Ectopic expression of ID4 in DU145 prostate cancer line promoted E47 dependent expression of CDKNI p21. Thus counteracting the biological activities of ID-1, -2 and -3 by forming inactive heterodimers appears to be a novel mechanism of action of ID4. These results could have far reaching consequences in developing strategies to target ID proteins for cancer therapy and understanding biologically relevant ID- interactions. PMID:25778840

  20. Chicken ovalbumin upstream-promoter transcription factor (COUP-TF) could act as a transcriptional activator or repressor of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene.

    PubMed Central

    Rodríguez, J C; Ortiz, J A; Hegardt, F G; Haro, D

    1997-01-01

    The chicken ovalbumin upstream-promoter transcription factor (COUP-TF) has a dual effect on the regulation of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase gene. COUP-TF could act as a transcriptional activator or repressor of this gene through different DNA sequences. COUP-TF induces expression of a reporter gene linked to the mitochondrial HMG-CoA synthase gene promoter in human hepatoma HepG2 cells, but represses it in a Leydig tumour cell line (R2C); in both these cell lines the expression of the mitochondrial HMG-CoA synthase gene mimics that of liver and testis. The activation is promoted by a fragment of the gene from coordinates -62 to +28, which contains a GC box and a TATA box, and where no COUP-TF binding site was observed by in vitro DNA binding studies. On the other hand, the COUP-TF inhibitory effect is mainly due to repression of peroxisome-proliferator-activated receptor-dependent activation of the gene, interacting with the region from -104 to -92. To our knowledge this work represents the second example of a target gene for COUP-TF I that could be either activated or repressed by the action of this receptor through different DNA sequences of the same gene. PMID:9291136

  1. The Affordable Care Act and integrated behavioral health programs in community health centers to promote utilization of mental health services among Asian Americans.

    PubMed

    Huang, Susan; Fong, Susana; Duong, Thomas; Quach, Thu

    2016-06-01

    The Affordable Care Act has greatly expanded health care coverage and recognizes mental health as a major priority. However, individuals suffering from mental health disorders still face layered barriers to receiving health care, especially Asian Americans. Integration of behavioral health services within primary care is a viable way of addressing underutilization of mental health services. This paper provides insight into a comprehensive care approach integrating behavioral health services into primary care to address underutilization of mental health services in the Asian American population. True integration of behavioral health services into primary care will require financial support and payment reform to address multi-disciplinary care needs and optimize care coordination, as well as training and workforce development early in medical and mental health training programs to develop the skills that aid prevention, early identification, and intervention. Funding research on evidence-based practice oriented to the Asian American population needs to continue. PMID:27188196

  2. Gibberellin Acts through Jasmonate to Control the Expression of MYB21, MYB24, and MYB57 to Promote Stamen Filament Growth in Arabidopsis

    PubMed Central

    Xiao, Langtao; Soo, Hui Meng; Cheng, Zhiwei; Xie, Daoxin; Peng, Jinrong

    2009-01-01

    Precise coordination between stamen and pistil development is essential to make a fertile flower. Mutations impairing stamen filament elongation, pollen maturation, or anther dehiscence will cause male sterility. Deficiency in plant hormone gibberellin (GA) causes male sterility due to accumulation of DELLA proteins, and GA triggers DELLA degradation to promote stamen development. Deficiency in plant hormone jasmonate (JA) also causes male sterility. However, little is known about the relationship between GA and JA in controlling stamen development. Here, we show that MYB21, MYB24, and MYB57 are GA-dependent stamen-enriched genes. Loss-of-function of two DELLAs RGA and RGL2 restores the expression of these three MYB genes together with restoration of stamen filament growth in GA-deficient plants. Genetic analysis showed that the myb21-t1 myb24-t1 myb57-t1 triple mutant confers a short stamen phenotype leading to male sterility. Further genetic and molecular studies demonstrate that GA suppresses DELLAs to mobilize the expression of the key JA biosynthesis gene DAD1, and this is consistent with the observation that the JA content in the young flower buds of the GA-deficient quadruple mutant ga1-3 gai-t6 rga-t2 rgl1-1 is much lower than that in the WT. We conclude that GA promotes JA biosynthesis to control the expression of MYB21, MYB24, and MYB57. Therefore, we have established a hierarchical relationship between GA and JA in that modulation of JA pathway by GA is one of the prerequisites for GA to regulate the normal stamen development in Arabidopsis. PMID:19325888

  3. TNF{alpha} acting on TNFR1 promotes breast cancer growth via p42/P44 MAPK, JNK, Akt and NF-{kappa}B-dependent pathways

    SciTech Connect

    Rivas, Martin A.; Carnevale, Romina P.; Proietti, Cecilia J.; Rosemblit, Cinthia; Beguelin, Wendy; Salatino, Mariana; Charreau, Eduardo H.; Frahm, Isabel; Sapia, Sandra; Brouckaert, Peter; Elizalde, Patricia V.; Schillaci, Roxana

    2008-02-01

    Tumor necrosis factor {alpha} (TNF{alpha}) enhances proliferation of chemically-induced mammary tumors and of T47D human cell line through not fully understood pathways. Here, we explored the intracellular signaling pathways triggered by TNF{alpha}, the participation of TNF{alpha} receptor (TNFR) 1 and TNFR2 and the molecular mechanism leading to breast cancer growth. We demonstrate that TNF{alpha} induced proliferation of C4HD murine mammary tumor cells and of T47D cells through the activation of p42/p44 MAPK, JNK, PI3-K/Akt pathways and nuclear factor-kappaB (NF-{kappa}B) transcriptional activation. A TNF{alpha}-specific mutein selectively binding to TNFR1 induced p42/p44 MAPK, JNK, Akt activation, NF-{kappa}B transcriptional activation and cell proliferation, just like wild-type TNF{alpha}, while a mutein selective for TNFR2 induced only p42/p44 MAPK activation. Interestingly, blockage of TNFR1 or TNFR2 with specific antibodies was enough to impair TNF{alpha} signaling and biological effect. Moreover, in vivo TNF{alpha} administration supported C4HD tumor growth. We also demonstrated, for the first time, that injection of a selective inhibitor of NF-{kappa}B activity, Bay 11-7082, resulted in regression of TNF{alpha}-promoted tumor. Bay 11-7082 blocked TNF{alpha} capacity to induce cell proliferation and up-regulation of cyclin D1 and of Bcl-x{sub L}in vivo and in vitro. Our results reveal evidence for TNF{alpha} as a breast tumor promoter, and provide novel data for a future therapeutic approach using TNF{alpha} antagonists and NF-{kappa}B pharmacological inhibitors in established breast cancer treatment.

  4. 7 CFR 33.1 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AUTHORITY OF THE EXPORT APPLE ACT Definitions § 33.1 Act. Act and Export Apple Act are synonymous and mean “An act to promote the foreign trade of the United States in apples to protect the reputation of American-grown apples in foreign markets, to prevent deception or misrepresentation as to the quality...

  5. 7 CFR 33.1 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AUTHORITY OF THE EXPORT APPLE ACT Definitions § 33.1 Act. Act and Export Apple Act are synonymous and mean “An act to promote the foreign trade of the United States in apples to protect the reputation of American-grown apples in foreign markets, to prevent deception or misrepresentation as to the quality...

  6. 7 CFR 33.1 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AUTHORITY OF THE EXPORT APPLE ACT Definitions § 33.1 Act. Act and Export Apple Act are synonymous and mean “An act to promote the foreign trade of the United States in apples to protect the reputation of American-grown apples in foreign markets, to prevent deception or misrepresentation as to the quality...

  7. 7 CFR 33.1 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AUTHORITY OF THE EXPORT APPLE ACT Definitions § 33.1 Act. Act and Export Apple Act are synonymous and mean “An act to promote the foreign trade of the United States in apples to protect the reputation of American-grown apples in foreign markets, to prevent deception or misrepresentation as to the quality...

  8. 7 CFR 33.1 - Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AUTHORITY OF THE EXPORT APPLE ACT Definitions § 33.1 Act. Act and Export Apple Act are synonymous and mean “An act to promote the foreign trade of the United States in apples to protect the reputation of American-grown apples in foreign markets, to prevent deception or misrepresentation as to the quality...

  9. Auxin-Independent NAC Pathway Acts in Response to Explant-Specific Wounding and Promotes Root Tip Emergence during de Novo Root Organogenesis in Arabidopsis.

    PubMed

    Chen, Xiaodong; Cheng, Jingfei; Chen, Lyuqin; Zhang, Guifang; Huang, Hai; Zhang, Yijing; Xu, Lin

    2016-04-01

    Plants have powerful regenerative abilities that allow them to recover from damage and survive in nature. De novo organogenesis is one type of plant regeneration in which adventitious roots and shoots are produced from wounded and detached organs. By studying de novo root organogenesis using leaf explants of Arabidopsis (Arabidopsis thaliana), we previously suggested that wounding is the first event that provides signals to trigger the whole regenerative process. However, our knowledge of the role of wounding in regeneration remains limited. In this study, we show that wounding not only triggers the auxin-mediated fate transition of regeneration-competent cells, but also induces the NAC pathway for root tip emergence. The NAC1 transcription factor gene was specifically expressed in response to wounding in the leaf explant, but not in the wounded leaf residue of the source plant. Inhibition of the NAC1 pathway severely affected the emergence of adventitious root tips. However, the NAC1 pathway functioned independently of auxin-mediated cell fate transition and regulates expression of CEP genes, which encode proteins that might have a role in degradation of extensin proteins in the cell wall. Overall, our results suggest that wounding has multiple roles in de novo root organogenesis and that NAC1 acts as one downstream branch in regulating the cellular environment for organ emergence. PMID:26850273

  10. Isolation of cis-acting vaccinia virus DNA fragments promoting the expression of herpes simplex virus thymidine kinase by recombinant viruses.

    PubMed Central

    Vassef, A; Mars, M; Dru, A; Plucienniczak, A; Streeck, R E; Beaud, G

    1985-01-01

    Recombinant TK- vaccinia viruses containing the pBR322 sequence inserted in either orientation within the coding sequence of the viral thymidine kinase gene were constructed. They were characterized by genomic analysis, hybridization studies, reversion to wild-type virus by in vivo recombination, and rescue from their genomes of plasmids which contained all or parts of the pBR322 sequence. TK- cells were infected with one of these recombinant viruses and then transfected with pools of chimeric plasmids composed of a cloned herpes simplex virus thymidine kinase gene which contained upstream inserts of different vaccinia DNA fragments prepared by restriction or sonication. Recombination between homologous pBR322 sequences within infected cells generated selectable recombinant viruses in which expression of the herpes simplex virus thymidine kinase gene was promoted by the upstream vaccinia insert. These viruses were characterized by genomic analysis, hybridization, and in vivo or in vitro phosphorylation of (5-[125I]deoxycytidine as a specific assay for the expressed herpes simplex virus thymidine kinase. Vaccinia DNA inserts were isolated conveniently for transfer to bacteria by rescuing appropriate plasmids from the genome of recombinant viruses. The sequence of 100 nucleotides adjacent to the upstream region of the herpes simplex virus gene was determined in nine different inserts measuring 0.17 to 1.07 kilobase pairs. Images PMID:2989553

  11. Free Sialic Acid Acts as a Signal That Promotes Streptococcus pneumoniae Invasion of Nasal Tissue and Nonhematogenous Invasion of the Central Nervous System.

    PubMed

    Hatcher, Brandon L; Hale, Joanetha Y; Briles, David E

    2016-09-01

    Streptococcus pneumoniae (pneumococcus) is a leading cause of bacterial meningitis and neurological sequelae in children worldwide. Acute bacterial meningitis is widely considered to result from bacteremia that leads to blood-brain barrier breakdown and bacterial dissemination throughout the central nervous system (CNS). Previously, we showed that pneumococci can gain access to the CNS through a nonhematogenous route without peripheral blood infection. This access is thought to occur when the pneumococci in the upper sinus follow the olfactory nerves and enter the CNS through the olfactory bulbs. In this study, we determined whether the addition of exogenous sialic acid postcolonization promotes nonhematogenous invasion of the CNS. Previously, others showed that treatment with exogenous sialic acid post-pneumococcal infection increased the numbers of CFU recovered from an intranasal mouse model of infection. Using a pneumococcal colonization model, an in vivo imaging system, and a multiplex assay for cytokine expression, we demonstrated that sialic acid can increase the number of pneumococci recovered from the olfactory bulbs and brains of infected animals. We also show that pneumococci primarily localize to the olfactory bulb, leading to increased expression levels of proinflammatory cytokines and chemokines. These findings provide evidence that sialic acid can enhance the ability of pneumococci to disseminate into the CNS and provide details about the environment needed to establish nonhematogenous pneumococcal meningitis. PMID:27354445

  12. A 3D Porous Gelatin-Alginate-Based-IPN Acts as an Efficient Promoter of Chondrogenesis from Human Adipose-Derived Stem Cells

    PubMed Central

    Jianu, Dana; Tumbar, Tudorita

    2015-01-01

    Cartilage has limited regeneration potential. Thus, there is an imperative need to develop new strategies for cartilage tissue engineering (CTE) amenable for clinical use. Recent CTE approaches rely on optimal cell-scaffold interactions, which require a great deal of optimization. In this study we attempt to build a novel gelatin- (G-) alginate- (A-) polyacrylamide (PAA) 3D interpenetrating network (IPN) with superior performance in promoting chondrogenesis from human adipose-derived stem cells (hADSCs). We show that our G-A-PAA scaffold is capable of supporting hADSCs proliferation and survival, with no apparent cytotoxic effect. Moreover, we find that after exposure to prochondrogenic conditions a key transcription factor known to induce chondrogenesis, namely, Sox9, is highly expressed in our hADSCs/G-A-PAA bioconstruct, along with cartilage specific markers such as collagen type II, CEP68, and COMP extracellular matrix (ECM) components. These data suggest that our G-A-PAA structural properties and formulation might enable hADSCs conversion towards functional chondrocytes. We conclude that our novel G-A-PAA biomatrix is a good candidate for prospective in vivo CTE applications. PMID:26106422

  13. FANC Pathway Promotes UV-Induced Stalled Replication Forks Recovery by Acting Both Upstream and Downstream Polη and Rev1

    PubMed Central

    Renaud, Emilie; Rosselli, Filippo

    2013-01-01

    To cope with ultraviolet C (UVC)-stalled replication forks and restart DNA synthesis, cells either undergo DNA translesion synthesis (TLS) by specialised DNA polymerases or tolerate the lesions using homologous recombination (HR)-based mechanisms. To gain insight into how cells manage UVC-induced stalled replication forks, we analysed the molecular crosstalk between the TLS DNA polymerases Polη and Rev1, the double-strand break repair (DSB)-associated protein MDC1 and the FANC pathway. We describe three novel functional interactions that occur in response to UVC-induced DNA lesions. First, Polη and Rev1, whose optimal expression and/or relocalisation depend on the FANC core complex, act upstream of FANCD2 and are required for the proper relocalisation of monoubiquitinylated FANCD2 (Ub-FANCD2) to subnuclear foci. Second, during S-phase, Ub-FANCD2 and MDC1 relocalise to UVC-damaged nuclear areas or foci simultaneously but independently of each other. Third, Ub-FANCD2 and MDC1 are independently required for optimal BRCA1 relocalisation. While RPA32 phosphorylation (p-RPA32) and RPA foci formation were reduced in parallel with increasing levels of H2AX phosphorylation and MDC1 foci in UVC-irradiated FANC pathway-depleted cells, MDC1 depletion was associated with increased UVC-induced Ub-FANCD2 and FANCD2 foci as well as p-RPA32 levels and p-RPA32 foci. On the basis of the previous observations, we propose that the FANC pathway participates in the rescue of UVC-stalled replication forks in association with TLS by maintaining the integrity of ssDNA regions and by preserving genome stability and preventing the formation of DSBs, the resolution of which would require the intervention of MDC1. PMID:23365640

  14. Long-Acting PASylated Leptin Ameliorates Obesity by Promoting Satiety and Preventing Hypometabolism in Leptin-Deficient Lep(ob/ob) Mice.

    PubMed

    Bolze, Florian; Morath, Volker; Bast, Andrea; Rink, Nadine; Schlapschy, Martin; Mocek, Sabine; Skerra, Arne; Klingenspor, Martin

    2016-01-01

    Body weight loss of Lep(ob/ob) mice in response to leptin is larger than expected from the reduction in energy intake alone, suggesting a thermogenic action of unknown magnitude. We exploited the superior pharmacological properties of a novel long-acting leptin prepared via PASylation to study the contribution of its anorexigenic and thermogenic effects. PASylation, the genetic fusion of leptin with a conformationally disordered polypeptide comprising 600 Pro/Ala/Ser (PAS) residues, provides a superior way to increase the hydrodynamic volume of the fusion protein, thus retarding kidney filtration and extending plasma half-life. Here a single PAS(600)-leptin injection (300 pmol/g) resulted in a maximal weight reduction of 21% 6 days after application. The negative energy balance of 300 kJ/(4 d) was driven by a decrease in energy intake, whereas energy expenditure remained stable. Mice that were food restricted to the same extent showed an energy deficit of only 220 kJ/(4 d) owing to recurring torpor bouts. Therefore, the anorexigenic effect of PAS(600)-leptin contributes 75% to weight loss, whereas the thermogenic action accounts for 25% by preventing hypometabolism. In a second experiment, just four injections of PAS(600)-leptin (100 pmol/g) administered in 5- to 6-day intervals rectified the Lep(ob/ob) phenotype. In total, 16 nmol of PAS(600)-leptin per mouse triggered a weight loss of 43% within 20 days and normalized hypothermia and glucose homeostasis as well as hepatic steatosis. The beneficial properties of PAS(600)-leptin are substantiated by a comparison with previous studies in which approximately 400 nmol (∼25-fold) unmodified leptin was mandatory to achieve similar improvements. PMID:26492472

  15. Long-Acting Progestin-Only Contraceptives Enhance Human Endometrial Stromal Cell Expressed Neuronal Pentraxin-1 and Reactive Oxygen Species to Promote Endothelial Cell Apoptosis

    PubMed Central

    Guzeloglu-Kayisli, O.; Basar, M.; Shapiro, J. P.; Semerci, N.; Huang, J. S.; Schatz, F.

    2014-01-01

    Context: Despite the absence of progesterone receptor protein in human endometrial endothelial cells (HEECs), endometria of women receiving long-acting progestin-only contraceptives (LAPCs) display reduced uterine blood flow, elevated reactive oxygen species generation, increased angiogenesis, and irregularly distributed, enlarged, fragile microvessels resulting in abnormal uterine bleeding. Objective: We propose that paracrine factors from LAPC-treated human endometrial stromal cells (HESCs) impair HEEC functions by shifting the balance between HEEC viability and death in favor of the latter. Design and Setting: Proliferation, apoptosis, and transcriptome analyses were performed in HEECs treated with conditioned medium supernatant (CMS) derived from HESCs treated with estradiol (E2) ± medroxyprogesterone acetate or etonogestrel under normoxia or hypoxia. Mass spectrometry interrogated the CMS secretome while immunostaining for neuronal pentraxin-1 (NPTX1), cleaved caspase-3, and cytochrome c was performed in cultured HEECs and paired endometria from women using LAPCs. Main Outcome: HEEC apoptosis and its underlying mechanism. Results: HESC CMS from E2 + medroxyprogesterone acetate or E2 + etonogestrel incubations under hypoxia induced HEEC apoptosis (P < .05), whereas mass spectrometry of the CMS revealed increased NPTX1 secretion (P < .05). Endothelial cleaved caspase-3 and stromal NPTX1 immunoreactivity were significantly higher in LAPC-treated endometria (P < .001). Transcriptomics revealed AKT signaling inhibition and mitochondrial dysfunction in HEECs incubated with HESC CMS. In vitro analyses proved that CMS decreased HEEC AKT phosphorylation (P < .05) and that recombinant NPTX1 (P < .05) or NPTX1 + H2O2 (P < .001) increase HEEC apoptosis and cytosolic cytochrome c levels. Conclusions: LAPC-enhanced NPTX1 secretion and reactive oxygen species generation in HESCs impair HEEC survival resulting in a loss in vascular integrity, demonstrating a novel paracrine

  16. Dietary fat and reduced levels of TGFbeta1 act synergistically to promote activation of the vascular endothelium and formation of lipid lesions.

    PubMed

    Grainger, D J; Mosedale, D E; Metcalfe, J C; Böttinger, E P

    2000-07-01

    Transforming growth factor-(beta) (TGF(beta)) has a wide range of activities on vascular cells and inflammatory cells, suggesting it may have different functions during various stages of atherogenesis. We report that mice heterozygous for the deletion of the tgfb1 gene (tgfb1(+/-) mice) have reduced levels of TGF(beta)1 in the artery wall until at least 8 weeks of age. On a normal mouse chow diet, the vascular endothelium of tgfb1(+/-) mice is indistinguishable from wild-type littermates, assessed by morphology and intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression. In contrast, levels of the smooth muscle isoforms of actin and myosin in medial smooth muscle cells of tgfb1(+/-) mice are significantly reduced. Following feeding a cholesterol-enriched diet for 12 weeks, high levels of ICAM-1 and VCAM-1 were detected in the vascular endothelial cells of tgfb1(+/-) mice, but not wild-type mice. Furthermore, marked deposition of lipid into the artery wall was only observed in the tgfb1(+/-) mice on the cholesterol-enriched diet. These vascular lipid lesions were accompanied by local invasion of macrophages. We conclude that deletion of a single allele of the tgfb1 gene results in a reduced level of TGFbeta1 antigen in the aorta together with reduced smooth muscle cell differentiation, whereas the addition of a high fat dietary challenge is required to activate the vascular endothelium and to promote the formation of fatty streaks resembling early atherosclerosis in humans. PMID:10852815

  17. BMX acts downstream of PI3K to promote colorectal cancer cell survival and pathway inhibition sensitizes to the BH3 mimetic ABT-737.

    PubMed

    Potter, Danielle S; Kelly, Paul; Denneny, Olive; Juvin, Veronique; Stephens, Len R; Dive, Caroline; Morrow, Christopher J

    2014-02-01

    Evasion of apoptosis is a hallmark of cancer, and reversing this process by inhibition of survival signaling pathways is a potential therapeutic strategy. Phosphoinositide 3-kinase (PI3K) signaling can promote cell survival and is upregulated in solid tumor types, including colorectal cancer (CRC), although these effects are context dependent. The role of PI3K in tumorigenesis combined with their amenability to specific inhibition makes them attractive drug targets. However, we observed that inhibition of PI3K in HCT116, DLD-1, and SW620 CRC cells did not induce apoptotic cell death. Moreover, these cells were relatively resistant to the Bcl-2 homology domain 3 (BH3) mimetic ABT-737, which directly targets the Bcl-2 family of apoptosis regulators. To test the hypothesis that PI3K inhibition lowers the apoptotic threshold without causing apoptosis per se, PI3K inhibitors were combined with ABT-737. PI3K inhibition enhanced ABT-737-induced apoptosis by 2.3- to 4.5-fold and reduced expression levels of MCL-1, the resistance biomarker for ABT-737. PI3K inhibition enhanced ABT-737-induced apoptosis a further 1.4- to 2.4-fold in CRC cells with small interfering RNA-depleted MCL-1, indicative of additional sensitizing mechanisms. The observation that ABT-737-induced apoptosis was unaffected by inhibition of PI3K downstream effectors AKT and mTOR, implicated a novel PI3K-dependant pathway. To elucidate this, an RNA interference (RNAi) screen of potential downstream effectors of PI3K signaling was conducted, which demonstrated that knockdown of the TEC kinase BMX sensitized to ABT-737. This suggests that BMX is an antiapoptotic downstream effector of PI3K, independent of AKT. PMID:24709422

  18. 7 CFR 35.1 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS EXPORT GRAPES AND PLUMS Definitions § 35.1 Act. Act or Export Grape and Plum Act means “An Act to promote the foreign trade of the United States in grapes and plums, to protect the reputation of American-grown grapes and plums...

  19. 7 CFR 35.1 - Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS EXPORT GRAPES AND PLUMS Definitions § 35.1 Act. Act or Export Grape and Plum Act means “An Act to promote the foreign trade of the United States in grapes and plums, to protect the reputation of American-grown grapes and plums...

  20. 7 CFR 35.1 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS EXPORT GRAPES AND PLUMS Definitions § 35.1 Act. Act or Export Grape and Plum Act means “An Act to promote the foreign trade of the United States in grapes and plums, to protect the reputation of American-grown grapes and plums...

  1. 7 CFR 35.1 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS EXPORT GRAPES AND PLUMS Definitions § 35.1 Act. Act or Export Grape and Plum Act means “An Act to promote the foreign trade of the United States in grapes and plums, to protect the reputation of American-grown grapes and plums...

  2. 7 CFR 35.1 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS EXPORT GRAPES AND PLUMS Definitions § 35.1 Act. Act or Export Grape and Plum Act means “An Act to promote the foreign trade of the United States in grapes and plums, to protect the reputation of American-grown grapes and plums...

  3. Prescription Drug Labeling Promotion Act of 2012

    THOMAS, 112th Congress

    Rep. Markey, Edward J. [D-MA-7

    2012-02-24

    02/24/2012 Referred to the House Committee on Energy and Commerce. (All Actions) Notes: For further action, see S.3187, which became Public Law 112-144 on 7/9/2012. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  4. Promoting Electric Vehicles Act of 2011

    THOMAS, 112th Congress

    Sen. Merkley, Jeff [D-OR

    2011-05-11

    05/19/2011 Committee on Energy and Natural Resources. Hearings held. Hearings printed: S.Hrg. 112-38. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  5. Renewable Electricity Promotion Act of 2010

    THOMAS, 111th Congress

    Sen. Bingaman, Jeff [D-NM

    2010-09-21

    09/22/2010 Read the second time. Placed on Senate Legislative Calendar under General Orders. Calendar No. 576. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  6. n-Alkane and clofibrate, a peroxisome proliferator, activate transcription of ALK2 gene encoding cytochrome P450alk2 through distinct cis-acting promoter elements in Candida maltosa

    SciTech Connect

    Kogure, Takahisa; Takagi, Masamichi; Ohta, Akinori . E-mail: aaohta@mail.ecc.u-tokyo.ac.jp

    2005-04-01

    The ALK2 gene, encoding one of the n-alkane-hydroxylating cytochromes P450 in Candida maltosa, is induced by n-alkanes and a peroxisome proliferator, clofibrate. Deletion analysis of this gene's promoter revealed two cis-acting elements-an n-alkane-responsive element (ARE2) and a clofibrate-responsive element (CRE2)-that partly overlap in sequence but have distinct functions. ARE2-mediated activation responded to n-alkanes but not to clofibrate and was repressed by glucose. CRE2-mediated activation responded to polyunsaturated fatty acids and steroid hormones as well as to peroxisome proliferators but not to n-alkanes, and it was not repressed by glucose. Both elements mediated activation by oleic acid. Mutational analysis demonstrated that three CCG sequences in CRE2 were critical to the activation by clofibrate as well as to the in vitro binding of a specific protein to this element. These findings suggest that ALK2 is induced by peroxisome proliferators and steroid hormones through a specific CRE2-mediated regulatory mechanism.

  7. News Competition: School team launches a rocket Conference: Norway focuses on physics teaching Science on Stage: Canadian science acts take to the stage Particle Physics: Teachers get a surprise at CERN Teaching: Exploring how students learn physics University: Oxford opens doors to science teachers Lasers: Lasers shine light on meeting Science Fair: Malawi promotes science education

    NASA Astrophysics Data System (ADS)

    2010-11-01

    Competition: School team launches a rocket Conference: Norway focuses on physics teaching Science on Stage: Canadian science acts take to the stage Particle Physics: Teachers get a surprise at CERN Teaching: Exploring how students learn physics University: Oxford opens doors to science teachers Lasers: Lasers shine light on meeting Science Fair: Malawi promotes science education

  8. Freedom of Information Act

    USGS Publications Warehouse

    Newman, D.J.

    2012-01-01

    The Freedom of Information Act( FOIA), 5 U.S.C.§ 552, as amended, generally provides that any person has a right to request access to Federal agency records. The USGS proactively promotes information disclosure as inherent to its mission of providing objective science to inform decisionmakers and the general public. USGS scientists disseminate up-to-date and historical scientific data that are critical to addressing national and global priorities.

  9. Acting Atoms.

    ERIC Educational Resources Information Center

    Farin, Susan Archie

    1997-01-01

    Describes a fun game in which students act as electrons, protons, and neutrons. This activity is designed to help students develop a concrete understanding of the abstract concept of atomic structure. (DKM)

  10. ACT Test

    MedlinePlus

    ... this page helpful? Also known as: ACT; Activated Coagulation Time Formal name: Activated Clotting Time Related tests: ... in the blood called platelets and proteins called coagulation factors are activated in a sequence of steps ...

  11. Balancing Acts

    MedlinePlus

    ... Current Issue Past Issues Special Section: Focus on Communication Balancing Acts Past Issues / Fall 2008 Table of ... from the National Institute on Deafness and Other Communication Disorders (NIDCD). It involves simulated trips down the ...

  12. Educational Excellence Act of 1989. Hearing on S. 695 To Promote Excellence in American Education by Recognizing and Rewarding Schools, Teachers, and Students for Their Outstanding Achievements, Enhancing Parental Choice, Encouraging the Study of Science, Mathematics, and Engineering, and for Other Purposes, before the Subcommittee on Education, Arts and Humanities of the Committee on Labor and Human Resources. United States Senate, One Hundred First Congress, First Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Subcommittee on Education, Arts and Humanities.

    The proceedings are presented of the hearing before the Congressional Subcommittee on Education, Arts and the Humanities of the Committee on Labor and Human Resources. They reveal both the strengths and limitations of the proposed Educational Excellence Act of 1989. The proposed act would promote excellence in American education by: recognizing…

  13. 7 CFR 1210.312 - Promotion.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any action taken by the Board, pursuant to the Act, to present a favorable image for watermelons to...

  14. 7 CFR 1210.312 - Promotion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any action taken by the Board, pursuant to the Act, to present a favorable image for watermelons to...

  15. 7 CFR 1210.312 - Promotion.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any action taken by the Board, pursuant to the Act, to present a favorable image for watermelons to...

  16. 7 CFR 1210.312 - Promotion.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE WATERMELON RESEARCH AND PROMOTION PLAN Watermelon Research and Promotion Plan Definitions § 1210.312 Promotion. Promotion means any action taken by the Board, pursuant to the Act, to present a favorable image for watermelons to...

  17. National Energy Act statutes and solar energy

    SciTech Connect

    Howard, J.

    1980-02-01

    The National Energy Act of 1978 contains many provisions that will significantly affect solar technology commercialization and solar energy users. Four of the five statutes that comprise the National Energy Act deserve close attention. The National Energy Conservation Policy Act will promote residential solar installations. The Energy Tax Act will accelerate both residential and commercial solar system applications. The Public Utilities Regulatory Policies Act promotes efficient use of utility resources as well as decentralized power production. And, the Power Plan and Industrial Fuel Use Act places severe restrictions on future burning of petroleum and natural gas, which should lead some operators to build or convert to solar energy systems. Each of the preceding acts are considered in separate sections of this report. Federal regulations issued pursuant to the various provisions are also identified and discussed, and some of the problems with the provisions and regulations are noted.

  18. Act resilient.

    PubMed

    Joseph, Genie; Bice-Stephens, Wynona

    2014-01-01

    Attendees have reported changing from being fearful to serene, from listless to energized, from disengaged to connected, and becoming markedly less anxious in a few weeks. Anecdotally, self-reported stress levels have been reduced by over 50% after just one class. Attendees learn not to be afraid of their feelings by working with emotions in a playful manner. When a person can act angry, but separate himself from his personal story, the emotional energy exists in a separate form that is not attached to specific events, and can be more easily dealt with and neutralized. Attendees are taught to "take out the emotional trash" through expressive comedy. They become less intimated by their own emotional intensity and triggers as they learn how even metaphorical buckets of anger, shame, guilt and hurt can be emotionally emptied. The added benefit is that this is accomplished without the disclosure of personal information of the requirement to reexperience past pain which can trigger its own cascade of stress. PMID:24706248

  19. 7 CFR 1205.10 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE COTTON RESEARCH AND PROMOTION Procedures for Conduct of Sign-up Period Definitions § 1205.10 Act. The term Act means the Cotton Research...

  20. 7 CFR 1280.101 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1280.101 Section 1280.101 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE LAMB PROMOTION, RESEARCH, AND INFORMATION ORDER Lamb Promotion, Research,...

  1. 7 CFR 1260.128 - Act.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Act. 1260.128 Section 1260.128 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BEEF PROMOTION AND RESEARCH Beef Promotion and Research Order Definitions §...

  2. 7 CFR 1260.128 - Act.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Act. 1260.128 Section 1260.128 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BEEF PROMOTION AND RESEARCH Beef Promotion and Research Order Definitions §...

  3. 7 CFR 1260.128 - Act.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Act. 1260.128 Section 1260.128 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BEEF PROMOTION AND RESEARCH Beef Promotion and Research Order Definitions §...

  4. 7 CFR 1260.128 - Act.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Act. 1260.128 Section 1260.128 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BEEF PROMOTION AND RESEARCH Beef Promotion and Research Order Definitions §...

  5. 7 CFR 1260.128 - Act.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Act. 1260.128 Section 1260.128 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BEEF PROMOTION AND RESEARCH Beef Promotion and Research Order Definitions §...

  6. 77 FR 26911 - Processed Raspberry Promotion, Research, and Information Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-08

    ... Service 7 CFR Part 1208 RIN 0581-AC79 Processed Raspberry Promotion, Research, and Information Order... Processed Raspberry Promotion, Research, and Information Order (Order). The program will be implemented under the Commodity Promotion, Research, and Information Act of 1996 (1996 Act). Under the...

  7. Acidosis environment promotes osteoclast formation by acting on the last phase of preosteoclast differentiation: a study to elucidate the action points of acidosis and search for putative target molecules.

    PubMed

    Kato, Kohtaro; Morita, Ikuo

    2011-08-01

    Acidosis promoted tartaric acid-resistant acid phosphatase-positive multinuclear cell (TRAP+MNC) or osteoclast formation. Large osteoclast or TRAP+LMNC formation was observed far more in an acidosis environment than in a physiologically neutral environment. One of the major action points of acidosis was determined to be located in the last phase of preosteoclast differentiation using a co-culture system and a soluble RANKL-dependent bone marrow cell culture system. On-going osteoclast formation in an acidosis environment markedly deteriorated when the medium was replaced with physiologically neutral medium within the first 6h; however, bone marrow cells previously stimulated in an acidosis environment for 9h differentiated into TRAP+LMNC in pH 7.4 medium. Messenger RNA (mRNA) expression levels of DC-STAMP, a key molecule in cell fusion, and NFATc1 did not increase in the acidosis environment compared with those under physiologically neutral conditions. Ruthenium red, a general TRP antagonist, deteriorated acidosis-promoted TRAP+LMNC formation. 4-Alpha-PDD, a TRPV4-specific agonist, added in the last 21 h of preosteoclast differentiation, potentiated TRAP+LMNC formation in a mild acidosis environment, showing synergism between TRPV4 activation and acidosis. RN1734, a TRPV4-specific antagonist, partly inhibited acidosis-promoted TRAP+LMNC formation. We thus narrowed down the major action points of acidosis in osteoclast formation and elucidated the characteristics of this system in detail. Our results show that acidosis effectively uses TRPV4 to drive large-scale cell fusion and also utilizes systems independently of TRPV4. PMID:21575626

  8. 50 Years of U.S. Federal Support to Promote the Health of Mothers, Children and Handicapped Children in America: 1935-1985. A review of Federal Appropriations and Allocations to States for Health and Related Programs of Title V of the Social Security Act of 1935 and the Omnibus Reconciliaton Act of 1981.

    ERIC Educational Resources Information Center

    Magee, Eamon M.; Pratt, Magaret W.

    This document provides information on U.S. federal support for maternal and child health programs from 1935-1985. After a brief history of the Children's Bureau, which was the first unit of the federal government concerned with maternal and child health, funding and allocation formulas for Title V of the Social Security Act of 1935 are examined.…

  9. Promoting Models

    NASA Astrophysics Data System (ADS)

    Li, Qin; Zhao, Yongxin; Wu, Xiaofeng; Liu, Si

    There can be multitudinous models specifying aspects of the same system. Each model has a bias towards one aspect. These models often override in specific aspects though they have different expressions. A specification written in one model can be refined by introducing additional information from other models. The paper proposes a concept of promoting models which is a methodology to obtain refinements with support from cooperating models. It refines a primary model by integrating the information from a secondary model. The promotion principle is not merely an academic point, but also a reliable and robust engineering technique which can be used to develop software and hardware systems. It can also check the consistency between two specifications from different models. A case of modeling a simple online shopping system with the cooperation of the guarded design model and CSP model illustrates the practicability of the promotion principle.

  10. Intracellular Induction of Listeria monocytogenes actA Expression

    PubMed Central

    Shetron-Rama, Lynne M.; Marquis, Hélène; Bouwer, H. G. Archie; Freitag, Nancy E.

    2002-01-01

    Following entry into the host cytosol, the bacterial pathogen Listeria monocytogenes dramatically increases the expression of several key virulence factors. The expression of actA, whose protein product is required for L. monocytogenes actin-based intracellular motility, is increased by more than 200-fold in cytosolic bacteria in comparison to broth-grown cultures. Two distinct promoter elements have been reported to regulate actA expression. One promoter is located immediately upstream of actA coding sequences, while the second promoter is contributed by the upstream mpl gene via the generation of an mpl-actA-plcB transcript. A series of L. monocytogenes mutants were constructed to define the contributions of individual promoter elements to actA expression. The intracellular induction of actA expression was found to be dependent upon the actA proximal promoter; the mpl promoter appeared to contribute to the extracellular induction of actA but did not affect intracellular levels of expression. The actA promoter is dependent upon a regulatory factor known as PrfA for transcriptional activation; however, no increase in actA expression was detected following the introduction of a high-affinity PrfA binding site within the actA promoter. The presence of a mutationally activated form of PrfA, known as PrfA*, increased overall actA expression in broth-grown cultures of both wild-type and actA promoter mutant strains, but the levels of induction observed were still approximately 50-fold lower than those observed for intracellularly grown L. monocytogenes. Collectively, these results indicate that the dramatic induction of actA expression that occurs in the host cell cytosol is mediated through a single promoter element. Furthermore, intracellular induction of actA appears to require additional steps or factors beyond those necessary for the activation and binding of PrfA to the actA promoter. PMID:11854187

  11. Using Data to Promote Equity

    ERIC Educational Resources Information Center

    Shum, Brenda

    2016-01-01

    Data plays a starring role in promoting educational equity, and data-driven decision making begins with good state policies. With the recent passage of the Every Student Succeeds Act (ESSA) and a proposed federal rule to address racial disproportionality in special education, states will shoulder increased responsibility for eliminating…

  12. Promoting Health.

    ERIC Educational Resources Information Center

    Mechanic, David

    1990-01-01

    Argues that culture change or modification of the social structure is necessary for effective health promotion because health behavior is closely tied to basic group structures and processes. Examines the health attitudes of Mormons, low income and minority groups, and developing Islamic nations, emphasizing attitudes towards education and women.…

  13. TaNAC1 acts as a negative regulator of stripe rust resistance in wheat, enhances susceptibility to Pseudomonas syringae, and promotes lateral root development in transgenic Arabidopsis thaliana

    PubMed Central

    Wang, Fengtao; Lin, Ruiming; Feng, Jing; Chen, Wanquan; Qiu, Dewen; Xu, Shichang

    2015-01-01

    Plant-specific NAC transcription factors (TFs) constitute a large family and play important roles in regulating plant developmental processes and responses to environmental stresses, but only some of them have been investigated for effects on disease reaction in cereal crops. Virus-induced gene silencing (VIGS) is an effective strategy for rapid functional analysis of genes in plant tissues. In this study, TaNAC1, encoding a new member of the NAC1 subgroup, was cloned from bread wheat and characterized. It is a TF localized in the cell nucleus, and contains an activation domain in its C-terminal. TaNAC1 was strongly expressed in wheat roots and was involved in responses to infection by the obligate pathogen Puccinia striiformis f. sp. tritici and defense-related hormone treatments such as salicylic acid (SA), methyl jasmonate, and ethylene. Knockdown of TaNAC1 with barley stripe mosaic virus-induced gene silencing (BSMV-VIGS) enhanced stripe rust resistance. TaNAC1-overexpression in Arabidopsis thaliana plants gave enhanced susceptibility, attenuated systemic-acquired resistance to Pseudomonas syringae DC3000, and promoted lateral root development. Jasmonic acid-signaling pathway genes PDF1.2 and ORA59 were constitutively expressed in transgenic plants. TaNAC1 overexpression suppressed the expression levels of resistance-related genes PR1 and PR2 involved in SA signaling and AtWRKY70, which functions as a connection node between the JA- and SA-signaling pathways. Collectively, TaNAC1 is a novel NAC member of the NAC1 subgroup, negatively regulates plant disease resistance, and may modulate plant JA- and SA-signaling defense cascades. PMID:25774162

  14. 27 CFR 6.96 - Consumer promotions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Consumer promotions. 6.96 Section 6.96 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Exceptions § 6.96 Consumer promotions. (a) Coupons. The act by an industry member of furnishing to...

  15. 27 CFR 6.96 - Consumer promotions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Consumer promotions. 6.96 Section 6.96 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Exceptions § 6.96 Consumer promotions. (a) Coupons. The act by an industry member of furnishing to...

  16. 27 CFR 6.96 - Consumer promotions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Consumer promotions. 6.96 Section 6.96 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL âTIED-HOUSEâ Exceptions § 6.96 Consumer promotions. (a) Coupons. The act by an industry member of furnishing to...

  17. 27 CFR 6.96 - Consumer promotions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Consumer promotions. 6.96 Section 6.96 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL âTIED-HOUSEâ Exceptions § 6.96 Consumer promotions. (a) Coupons. The act by an industry member of furnishing to...

  18. 27 CFR 6.96 - Consumer promotions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Consumer promotions. 6.96... OF THE TREASURY LIQUORS âTIED-HOUSEâ Exceptions § 6.96 Consumer promotions. (a) Coupons. The act by an industry member of furnishing to consumers coupons which are redeemable at a retail...

  19. Health promotion capacity mapping: the Korean situation.

    PubMed

    Nam, Eun Woo; Engelhardt, Katrin

    2007-06-01

    Ten years ago the Republic of Korea enacted the National Health Promotion Act, setting the stage for health promotion action in the country. A National Health Promotion Fund was established, financed through tobacco taxes, which is now one of the largest in the world. However, despite abundant financial resources, the infrastructure needed to plan, implement, coordinate and evaluate health promotion efforts is still underdeveloped. Currently, health promotion capacity mapping efforts are emerging in Korea. Two international capacity mapping tools have been used to assess the Korean situation, namely HP-Source and the Health Promotion Capacity Profile, which was developed prior to the sixth Global Conference of Health Promotion, held in August 2005 in Bangkok, Thailand. The article summarizes and discusses the results of the capacity mapping exercise, highlights its challenges and suggest ways to improve the accuracy of health promotion capacity mapping. PMID:17341492

  20. Energy Efficient America Act of 1984

    SciTech Connect

    Not Available

    1984-01-01

    A draft of the Energy Efficient America Act of 1984 was prepared by the Energy Conservation Coalition as a way to promote energy conservation and eliminate waste. The Act is divided into four titles dealing with low-income weatherization, a solar and conservation bank, applicance efficiency, and automobile fuel economy. The sponsors of this initiative describe specific provisions, the background, and the program they would include under the Act. The report includes a form for comment and an opportunity to contribute financial support to the effort.

  1. 76 FR 18422 - Beef Promotion and Research; Reapportionment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-04

    ...This proposed rule would adjust representation on the Cattlemen's Beef Promotion and Research Board (Board), established under the Beef Promotion and Research Act of 1985 (Act), to reflect changes in cattle inventories and cattle and beef imports that have occurred since the most recent Board reapportionment rule became effective in October 2008. These adjustments are required by the Beef......

  2. Energy Independence and Security Act of 2007

    SciTech Connect

    2011-12-30

    An Act passed in 2007 to move the United States toward greater energy independence and security, to increase the production of clean renewable fuels, to protect consumers, to increase the efficiency of products, buildings, and vehicles, to promote research on and deploy greenhouse gas capture and storage options, and to improve the energy performance of the Federal Government, and for other purposes.

  3. ACTS data center

    NASA Astrophysics Data System (ADS)

    Syed, Ali; Vogel, Wolfhard J.

    1993-08-01

    Viewgraphs on ACTS Data Center status report are included. Topics covered include: ACTS Data Center Functions; data flow overview; PPD flow; RAW data flow; data compression; PPD distribution; RAW Data Archival; PPD Audit; and data analysis.

  4. Recovery Act Milestones

    SciTech Connect

    Rogers, Matt

    2009-01-01

    Every 100 days, the Department of Energy is held accountable for a progress report on the American Recovery and Reinvestment Act. Update at 200 days, hosted by Matt Rogers, Senior Advisor to Secretary Steven Chu for Recovery Act Implementation.

  5. ACTS data center

    NASA Technical Reports Server (NTRS)

    Syed, Ali; Vogel, Wolfhard J.

    1993-01-01

    Viewgraphs on ACTS Data Center status report are included. Topics covered include: ACTS Data Center Functions; data flow overview; PPD flow; RAW data flow; data compression; PPD distribution; RAW Data Archival; PPD Audit; and data analysis.

  6. Recovery Act Milestones

    ScienceCinema

    Rogers, Matt

    2013-05-29

    Every 100 days, the Department of Energy is held accountable for a progress report on the American Recovery and Reinvestment Act. Update at 200 days, hosted by Matt Rogers, Senior Advisor to Secretary Steven Chu for Recovery Act Implementation.

  7. Forgetting ACT UP

    ERIC Educational Resources Information Center

    Juhasz, Alexandra

    2012-01-01

    When ACT UP is remembered as the pinnacle of postmodern activism, other forms and forums of activism that were taking place during that time--practices that were linked, related, just modern, in dialogue or even opposition to ACT UP's "confrontational activism"--are forgotten. In its time, ACT UP was embedded in New York City, and a larger world,…

  8. Tryptophan promotes charitable donating

    PubMed Central

    Steenbergen, Laura; Sellaro, Roberta; Colzato, Lorenza S.

    2014-01-01

    The link between serotonin (5-HT) and one of the most important elements of prosocial behavior, charity, has remained largely uninvestigated. In the present study, we tested whether charitable donating can be promoted by administering the food supplement L-Tryptophan (TRP), the biochemical precursor of 5-HT. Participants were compared with respect to the amount of money they donated when given the opportunity to make a charitable donation. As expected, compared to a neutral placebo, TRP appears to increase the participants’ willingness to donate money to a charity. This result supports the idea that the food we eat may act as a cognitive enhancer modulating the way we think and perceive the world and others. PMID:25566132

  9. Iran Human Rights and Democracy Promotion Act of 2011

    THOMAS, 112th Congress

    Rep. Dold, Robert J. [R-IL-10

    2011-05-04

    08/02/2011 Referred to the Subcommittee on Middle East and South Asia . (All Actions) Notes: For further action, see H.R.1905, which became Public Law 112-158 on 8/10/2012. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  10. Promoting health at the community level: thinking globally, acting locally.

    PubMed

    Economos, Christina D; Tovar, Alison

    2012-02-01

    Prevention of childhood obesity is a societal priority. Despite our knowledge about the scope of the problem and the determinants that lead to it, we have yet to produce meaningful declines in obesity rates. Recent attention has been given to interventions that employ multiple strategies across multiple settings involving whole communities given their promising results. The next era of science calls for interdisciplinary teams who will envision a whole system approach to advance the community-based obesity prevention model. This perspective describes some of the more recent discussions of community-based methodologies such as the ANGELO (Analysis Grid for Environments Linked to Obesity) framework, best-practice principles, and a whole system intervention approach to obesity prevention. The proposed required elements to advance community-based research to address childhood obesity are: A systems perspective and approach, training of future leaders in community research methodology and social change, applying transdisciplinary strategies, funding to conduct rigorous trials to determine efficacy and effectiveness, enhanced design and analysis approaches, new and improved tools and methodologies to collect quantitative and qualitative data, enhanced community engagement models and sustainability frameworks, advancement of a bold public policy agenda, economic modeling, and acknowledgment of the approach as viable. To reverse childhood obesity, we need to embrace and integrate complex strategies at multiple levels within communities across the globe. PMID:22799473

  11. Promoting Innovations to 21st Century Careers Act

    THOMAS, 111th Congress

    Rep. Tierney, John F. [D-MA-6

    2009-07-29

    10/22/2009 Referred to the Subcommittee on Higher Education, Lifelong Learning, and Competitiveness. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  12. Promoting Job Creation and Reducing Small Business Burdens Act

    THOMAS, 113th Congress

    Rep. Fitzpatrick, Michael G. [R-PA-8

    2014-09-08

    09/17/2014 Received in the Senate and Read twice and referred to the Committee on Banking, Housing, and Urban Affairs. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  13. Travel Promotion, Enhancement, and Modernization Act of 2014

    THOMAS, 113th Congress

    Rep. Bilirakis, Gus M. [R-FL-12

    2014-04-10

    07/31/2014 Read twice. Placed on Senate Legislative Calendar under General Orders. Calendar No. 521. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  14. Promoting Health as Youth Skills In Classrooms And Life Act

    THOMAS, 112th Congress

    Rep. Fudge, Marcia L. [D-OH-11

    2011-08-12

    11/18/2011 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  15. Marine and Hydrokinetic Renewable Energy Promotion Act of 2011

    THOMAS, 112th Congress

    Rep. Inslee, Jay [D-WA-1

    2011-09-21

    09/19/2012 PERMISSION TO BE ADDED AS A COSPONSOR - Ms. Bonamici asked unanimous consent that she be added as a cosponsor of H.R. 2994 since the original sponsor is no longer a Member of Congress. Agreed to without objection. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  16. Promoting Health as Youth Skills In Classrooms And Life Act

    THOMAS, 113th Congress

    Rep. Fudge, Marcia L. [D-OH-11

    2013-05-23

    07/08/2013 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  17. Concrete Masonry Products Research, Education, and Promotion Act of 2013

    THOMAS, 113th Congress

    Sen. Nelson, Bill [D-FL

    2013-02-28

    12/12/2014 By Senator Rockefeller from Committee on Commerce, Science, and Transportation filed written report. Report No. 113-319. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  18. Promoting Healthy Minds for Safer Communities Act of 2014

    THOMAS, 113th Congress

    Rep. Thompson, Mike [D-CA-5

    2014-05-30

    07/21/2014 Referred to the Subcommittee on Crime, Terrorism, Homeland Security, and Investigations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  19. Critical Minerals and Materials Promotion Act of 2011

    THOMAS, 112th Congress

    Sen. Udall, Mark [D-CO

    2011-02-17

    06/09/2011 Committee on Energy and Natural Resources Subcommittee on Energy. Hearings held. With printed Hearing: S.Hrg. 112-117. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  20. HPV Vaccination's Second Act: Promotion, Competition, and Compulsion

    PubMed Central

    2010-01-01

    Developments regarding human papillomavirus (HPV) vaccines will transform HPV vaccination in the United States while simultaneously raising several new policy and ethical concerns. Policymakers, vaccine manufacturers, and the public health community must now respond to the presence of competing vaccines that are similar but distinct, particularly with respect to genital wart prevention and the benefits of vaccinating males. This work arises in the shadow of the contentious introduction of the HPV vaccine Gardasil (Merck & Co, Inc, Whitehouse Station, NJ) in 2006, particularly the opposition to efforts in many states to require the vaccine for school attendance. I review the current status of HPV vaccine policy in the United States and examine issues of public health ethics and policy central to ongoing and future HPV vaccination programs. PMID:20724671

  1. Internet Freedom, Broadband Promotion, and Consumer Protection Act of 2011

    THOMAS, 112th Congress

    Sen. Cantwell, Maria [D-WA

    2011-01-25

    01/25/2011 Read twice and referred to the Committee on Commerce, Science, and Transportation. (text of measure as introduced: CR S183-185) (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  2. Iran Human Rights and Democracy Promotion Act of 2011

    THOMAS, 112th Congress

    Sen. Kirk, Mark Steven [R-IL

    2011-05-04

    05/04/2011 Read twice and referred to the Committee on Foreign Relations. (All Actions) Notes: For further action, see H.R.1905, which became Public Law 112-158 on 8/10/2012. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  3. United States-Colombia Trade Promotion Agreement Implementation Act

    THOMAS, 112th Congress

    Sen. Baucus, Max [D-MT

    2011-10-03

    09/20/2012 By Senator Baucus from Committee on Finance filed written report. Report No. 112-222. Additional views filed. (All Actions) Notes: For further action, see H.R.3078, which became Public Law 112-42 on 10/21/2011. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  4. United States-Panama Trade Promotion Agreement Implementation Act

    THOMAS, 112th Congress

    Sen. Baucus, Max [D-MT

    2011-10-03

    09/20/2012 By Senator Baucus from Committee on Finance filed written report. Report No. 112-224. Additional views filed. (All Actions) Notes: For further action, see H.R.3079, which became Public Law 112-43 on 10/21/2011. Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  5. Protecting States' Rights to Promote American Energy Security Act

    THOMAS, 113th Congress

    Rep. Flores, Bill [R-TX-17

    2013-07-18

    12/09/2013 Read the second time. Placed on Senate Legislative Calendar under General Orders. Calendar No. 255. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

  6. TAp73 promotes anabolism

    PubMed Central

    Amelio, Ivano; Antonov, Alexey A.; Catani, Maria Valeria; Massoud, Renato; Bernassola, Francesca; Knight, Richard A.; Melino, Gerry; Rufini, Alessandro

    2014-01-01

    Metabolic adaptation has emerged as a hallmark of cancer and a promising therapeutic target, as rapidly proliferating cancer cells adapt their metabolism increasing nutrient uptake and reorganizing metabolic fluxes to support biosynthesis. The transcription factor p73 belongs to the p53-family and regulates tumorigenesis via its two N-terminal isoforms, with (TAp73) or without (ΔNp73) a transactivation domain. TAp73 acts as tumor suppressor, at least partially through induction of cell cycle arrest and apoptosis and through regulation of genomic stability. Here, we sought to investigate whether TAp73 also affects metabolic profiling of cancer cells. Using high throughput metabolomics, we unveil a thorough and unexpected role for TAp73 in promoting Warburg effect and cellular metabolism. TAp73-expressing cells show increased rate of glycolysis, higher amino acid uptake and increased levels and biosynthesis of acetyl-CoA. Moreover, we report an extensive TAp73-mediated upregulation of several anabolic pathways including polyamine and synthesis of membrane phospholipids. TAp73 expression also increases cellular methyl-donor S-adenosylmethionine (SAM), possibly influencing methylation and epigenetics, and promotes arginine metabolism, suggestive of a role in extracellular matrix (ECM) modeling. In summary, our data indicate that TAp73 regulates multiple metabolic pathways that impinge on numerous cellular functions, but that, overall, converge to sustain cell growth and proliferation. PMID:25514460

  7. The Indian Child Welfare Act in the Face of Extinction.

    ERIC Educational Resources Information Center

    Philips, Sloan

    1997-01-01

    Discusses the history, purposes, and provisions of the Indian Child Welfare Act (ICWA); recent high-profile transracial adoption cases; the debate over whether ICWA purposes have been realized; the proposed Adoption Promotion and Stability Act, which would severely limit application of ICWA to adoption cases; and proposed compromise amendments to…

  8. The US Bayh-Dole Act and Revisionism Redux

    ERIC Educational Resources Information Center

    Bremer, Howard; Allen, Joseph; Latker, Norman J.

    2009-01-01

    In the past several years various published papers have questioned whether the Bayh-Dole Act of 1980 (The University and Small Business Patent Procedures Act) has in reality been a determining factor in promoting the transfer of technology from US universities, as has been credited to it. This paper responds to that criticism, presenting facts and…

  9. Indian Child Welfare Act of 1978: Questions and Answers.

    ERIC Educational Resources Information Center

    Administration for Native Americans (DHEW/OHDS), Washington, DC.

    The question and answer booklet highlights the provisions of the Indian Child Welfare Act of 1978 which was designed to protect the best interests of Indian children and to promote the stability and security of Indian tribes and families. The booklet attempts to answer 28 important questions concerning title I of the Act. Examples of questions…

  10. Act II of the Sunshine Act.

    PubMed

    Pham-Kanter, Genevieve

    2014-11-01

    To coincide with the introduction in the United States of the Sunshine Act, Genevieve Pham-Kanter discusses what we need to look for to fight hidden bias and deliberate or unconscious corruption. Please see later in the article for the Editors' Summary. PMID:25369363