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Sample records for regulation cre dated

  1. Commission for Energy regulation (CRE) - Activity report June 2007

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2007 activity report of CRE. Content: A - Towards a single European energy market: Birth of a single European energy market (Origins of Europe of Energy, Emergence of a European energy policy); Main European Community guiding lines (European governance as regards energy, Guiding principles for the internal energy market); European Community activities (European Commission reports, Electricity and gas Regional Initiatives); Organisation and coordination of European regulators (Joint organisation of European regulators, CRE's relations with European Community institutions); CRE's European activities (Regional integration of gas markets, Regional integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, CRE's other European activities); B - CRE action at national level: Grids/networks and infrastructures (General information, Electricity grids, Regulation of gas networks and infrastructures); Markets (Changes in the regulatory and legislative contexts of electricity and natural gas markets, Electricity markets

  2. Commission for Energy regulation (CRE) - Activity report June 2004

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2004 activity report of CRE. Content: A - Opening of the gas and electricity markets for professional customers on 1 July 2004; B - Regulation of the gas market: Gas markets and players (The European environment, The French gas market); Regulation of the gas market (Implementing regulation, Works planned for the coming year; C - Regulation of the electricity market: The electricity markets and players (The European electricity markets, The French electricity market, Monitoring the electricity market); Regulation of the French electricity market (Access to public grid, Cross-border exchanges, Un-bundled accounting principles); The public electricity service in the regulated market (Content of the public service, Public service charges, Electricity production public service financing, Electricity sales tariffs) D - The working of CRE: How CRE exercises its jurisdiction, Tools; E - Appendices: Glossary, Units and conversions, Council of European Energy Regulators, Index of tables and figures.

  3. Commission for Energy regulation (CRE) - Activity report june 2006

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2006 activity report of CRE. Content: A - Opening of the electricity and natural gas markets to household consumers on 1 July 2007: CRE at the service of eligible customers (Information for eligible customers, Improved knowledge of non-household customers); Monitoring of the non-discrimination, transparency and independence of system operators (Drafting and distribution of codes of good conduct for system operators, The necessary improvement of system operator independence); Preparing the practical methods of opening: GTE 2007 and GTG 2007 (The necessary simplification of relations between operators and customers, Achieving a greater level of consumer information and protection, The clearly defined stages of the 'customer pathway', Profiling and settlement mechanisms: turning experience feedback from 2004 to good account); Persisting uncertainties and hurdles (The need for a suitable regulatory and legislative platform, Hurdles to the opening of the household market); B - Regulation of the natural gas market: The gas market in the European context (Increasing weight of

  4. Commission for Energy regulation (CRE) - Activity report June 2005; Commission de regulation de l'energie (CRE) - Rapport d'activite juin 2005

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2005 activity report of CRE. Content: A - The opening of the markets in France and in Europe: The opening of the markets one year after 1 July 2004 (An especially important step, Electricity and gas: a common framework with structural differences, The coexistence of market prices and regulated tariffs); The European texts of 26 June 2003 (Texts to give new impetus, Texts to harmonize the role and powers of national regulators, Texts to guarantee the independence of system operators, Texts to ensure transparent and non-discriminatory access to networks, Texts providing for strengthening of interconnections); The outlook for 2007, a fully open market (1 July 2007: a date set by the directives, Priority given to informing and protecting consumers); B - Regulation of the natural gas market: The gas market in the European context (Europe's dependency on imports is increasing, Gas prices increased considerably across the whole of Europe in 2004, The European gas scene continues to be dominated by a small number of players, Gas infrastructures need to be developed in Europe, The new

  5. Regulation of glycogen metabolism by the CRE-1, RCO-1 and RCM-1 proteins in Neurospora crassa. The role of CRE-1 as the central transcriptional regulator.

    Science.gov (United States)

    Cupertino, Fernanda Barbosa; Virgilio, Stela; Freitas, Fernanda Zanolli; Candido, Thiago de Souza; Bertolini, Maria Célia

    2015-04-01

    The transcription factor CreA/Mig1/CRE-1 is a repressor protein that regulates the use of alternative carbon sources via a mechanism known as Carbon Catabolite Repression (CCR). In Saccharomyces cerevisiae, Mig1 recruits the complex Ssn6-Tup1, the Neurospora crassa RCM-1 and RCO-1 orthologous proteins, respectively, to bind to promoters of glucose-repressible genes. We have been studying the regulation of glycogen metabolism in N. crassa and the identification of the RCO-1 corepressor as a regulator led us to investigate the regulatory role of CRE-1 in this process. Glycogen content is misregulated in the rco-1(KO), rcm-1(RIP) and cre-1(KO) strains, and the glycogen synthase phosphorylation is decreased in all strains, showing that CRE-1, RCO-1 and RCM-1 proteins are involved in glycogen accumulation and in the regulation of GSN activity by phosphorylation. We also confirmed the regulatory role of CRE-1 in CCR and its nuclear localization under repressing condition in N. crassa. The expression of all glycogenic genes is misregulated in the cre-1(KO) strain, suggesting that CRE-1 also controls glycogen metabolism by regulating gene expression. The existence of a high number of the Aspergillus nidulans CreA motif (5'-SYGGRG-3') in the glycogenic gene promoters led us to analyze the binding of CRE-1 to some DNA motifs both in vitro by DNA gel shift and in vivo by ChIP-qPCR analysis. CRE-1 bound in vivo to all motifs analyzed demonstrating that it down-regulates glycogen metabolism by controlling gene expression and GSN phosphorylation. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Commission for Energy regulation (CRE) - Activity report june 2008; Commission de regulation de l'energie (CRE) - Rapport d'activite juin 2008

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate

  7. Deciphering the cis-regulatory elements for XYR1 and CRE1 regulators in Trichoderma reesei.

    Directory of Open Access Journals (Sweden)

    Rafael Silva-Rocha

    Full Text Available In this work, we report the in silico identification of the cis-regulatory elements for XYR1 and CRE1 proteins in the filamentous fungus Trichoderma reesei, two regulators that play a central role in the expression of cellulase genes. Using four datasets of condition-dependent genes from RNA-seq and RT-qPCR experiments, we performed unsupervised motif discovery and found two short motifs resembling the proposed binding consensus for XYR1 and CRE1. Using these motifs, we analysed the presence and arrangement of putative cis-regulatory elements recognized by both regulators and found that shortly spaced sites were more associated with XYR1- and CRE1-dependent promoters than single, high-score sites. Furthermore, the approach used here allowed the identification of the previously reported XYR1-binding sites from cel7a and xyn1 promoters, and we also mapped the potential target sequence for this regulator at the cel6a promoter that has been suggested but not identified previously. Additionally, seven other promoters (for cel7b, cel61a, cel61b, cel3c, cel3d, xyn3 and swo genes presented a putative XYR1-binding site, and strong sites for CRE1 were found at the xyr1 and cel7b promoters. Using the cis-regulatory architectures nearly defined for XYR1 and CRE1, we performed genome-wide identification of potential targets for direct regulation by both proteins and important differences on their functional regulons were elucidated. Finally, we performed binding site mapping on the promoters of differentially expressed genes found in T. reesei mutant strains lacking xyr1 or cre1 and found that indirect regulation plays a key role on their signalling pathways. Taken together, the data provided here sheds new light on the mechanisms for signal integration mediated by XYR1 and CRE1 at cellulase promoters.

  8. Generation of an Rx-tTA: TetOp-Cre knock-in mouse line for doxycycline regulated Cre activity in the Rx expression domain.

    Directory of Open Access Journals (Sweden)

    Timothy F Plageman

    Full Text Available Genetic deletion of mouse genes has played a crucial role in our understanding of embryonic eye development. Transgenic, tissue specific Cre recombinase expression in various eye structures has facilitated these experiments. However, an early expressing, temporally-regulated, optic vesicle-specific Cre line has not been available. In this report, we detail the generation and analysis of a knock-in, inducible Cre line designed to drive recombination specifically within the Rx expression domain. Crossing this line with a reporter line demonstrates that recombination can be mediated within the early optic vesicle and throughout retinal development. Recombination can also be mediated in the Rx-expressing, ventral diencephalon and future posterior pituitary gland. Furthermore, it was demonstrated that dietary doxycycline could effectively modulate Cre activity. This line has the potential to facilitate conditional knock-out experimentation to study early retina and/or posterior pituitary development.

  9. Overlapping CRE and E-box promoter elements can independently regulate COX-2 gene transcription in macrophages.

    Science.gov (United States)

    Mestre, J R; Rivadeneira, D E; Mackrell, P J; Duff, M; Stapleton, P P; Mack-Strong, V; Maddali, S; Smyth, G P; Tanabe, T; Daly, J M

    2001-05-11

    Macrophage cyclooxygenase-2 (COX-2) transcription is mediated through the collaboration of different promoter elements. Here, the role of an overlapping cyclic AMP responsive element (CRE)/E-box was investigated. Nuclear proteins bound both the CRE and E-box, which synergized with other promoter elements to induce COX-2 transcription. Endotoxin induced binding of nuclear proteins to the CRE and E-box and each element independently induced higher COX-2 transcription levels than the overlapping CRE/E-box. Transcription factors associated with the CRE binding complex included c-Jun and CRE binding protein and with the E-box binding complex USF-1; their overexpression significantly induced COX-2 transcription. Therefore, both CRE and E-box promoter elements regulate COX-2 transcription in macrophages.

  10. A CRE1- regulated cluster is responsible for light dependent production of dihydrotrichotetronin in Trichoderma reesei.

    Directory of Open Access Journals (Sweden)

    Alberto Alonso Monroy

    Full Text Available Changing light conditions, caused by the rotation of earth resulting in day and night or growth on the surface or within a substrate, result in considerably altered physiological processes in fungi. For the biotechnological workhorse Trichoderma reesei, regulation of glycoside hydrolase gene expression, especially cellulase expression was shown to be a target of light dependent gene regulation. Analysis of regulatory targets of the carbon catabolite repressor CRE1 under cellulase inducing conditions revealed a secondary metabolite cluster to be differentially regulated in light and darkness and by photoreceptors. We found that this cluster is involved in production of trichodimerol and that the two polyketide synthases of the cluster are essential for biosynthesis of dihydrotrichotetronine (syn. bislongiquinolide or bisorbibutenolide. Additionally, an indirect influence on production of the peptaibol antibiotic paracelsin was observed. The two polyketide synthetase genes as well as the monooxygenase gene of the cluster were found to be connected at the level of transcription in a positive feedback cycle in darkness, but negative feedback in light, indicating a cellular sensing and response mechanism for the products of these enzymes. The transcription factor TR_102497/YPR2 residing within the cluster regulates the cluster genes in a light dependent manner. Additionally, an interrelationship of this cluster with regulation of cellulase gene expression was detected. Hence the regulatory connection between primary and secondary metabolism appears more widespread than previously assumed, indicating a sophisticated distribution of resources either to degradation of substrate (feed or to antagonism of competitors (fight, which is influenced by light.

  11. Decision from the Commission of Electricity Regulation (CRE) dated from June 27, 2002 about a disagreement between Semmaris company and Electricite de France, as manager of the public power distribution grid, relative to the conditions of consideration of the multiplicity of delivery points in the contractual system of access to the grid; Decision de la Commission de Regulation de l'Electricite (CRE) en date du 27 juin 2002 sur un different, qui oppose la societe Semmaris a Electricite de France, en tant que gestionnaire du reseau public de distribution d'electricite, relatif aux conditions de prise en compte de la multiplicite des points de livraison dans le dispositif contractuel d'acces au reseau electrique

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-06-01

    This document presents the analysis made by the French commission of electricity regulation (CRE) about a disagreement between Semmaris company (Rungis, France) and Electricite de France (EdF) concerning the request by Semmaris for the subscription of a single contract of access to the grid for its 18 supply points instead of 9 contracts as proposed by EdF after acceptation of a partial regrouping of some supply points under the same contracts. After examination of the hearings, the CRE requested EdF to establish non-discriminatory objective criteria for the regrouping of different delivery points in a same contract before making a new examination of the disagreement between Semmaris and EdF. (J.S.)

  12. The CRE1 Cytokinin Pathway Is Differentially Recruited Depending on Medicago truncatula Root Environments and Negatively Regulates Resistance to a Pathogen

    Science.gov (United States)

    Laffont, Carole; Rey, Thomas; André, Olivier; Novero, Mara; Kazmierczak, Théophile; Debellé, Frédéric; Bonfante, Paola; Jacquet, Christophe; Frugier, Florian

    2015-01-01

    Cytokinins are phytohormones that regulate many developmental and environmental responses. The Medicago truncatula cytokinin receptor MtCRE1 (Cytokinin Response 1) is required for the nitrogen-fixing symbiosis with rhizobia. As several cytokinin signaling genes are modulated in roots depending on different biotic and abiotic conditions, we assessed potential involvement of this pathway in various root environmental responses. Phenotyping of cre1 mutant roots infected by the Gigaspora margarita arbuscular mycorrhizal (AM) symbiotic fungus, the Aphanomyces euteiches root oomycete, or subjected to an abiotic stress (salt), were carried out. Detailed histological analysis and quantification of cre1 mycorrhized roots did not reveal any detrimental phenotype, suggesting that MtCRE1 does not belong to the ancestral common symbiotic pathway shared by rhizobial and AM symbioses. cre1 mutants formed an increased number of emerged lateral roots compared to wild-type plants, a phenotype which was also observed under non-stressed conditions. In response to A. euteiches, cre1 mutants showed reduced disease symptoms and an increased plant survival rate, correlated to an enhanced formation of lateral roots, a feature previously linked to Aphanomyces resistance. Overall, we showed that the cytokinin CRE1 pathway is not only required for symbiotic nodule organogenesis but also affects both root development and resistance to abiotic and biotic environmental stresses. PMID:25562779

  13. Conditional transgenesis using Dimerizable Cre (DiCre.

    Directory of Open Access Journals (Sweden)

    Nicolas Jullien

    Full Text Available Cre recombinase is extensively used to engineer the genome of experimental animals. However, its usefulness is still limited by the lack of an efficient temporal control over its activity. We have recently developed a conceptually new approach to regulate Cre recombinase, that we have called Dimerizable Cre or DiCre. It is based on splitting Cre into two inactive moieties and fusing them to FKBP12 (FK506-binding protein and FRB (binding domain of the FKBP12-rapamycin associated protein, respectively. These latter can be efficiently hetero-dimerized by rapamycin, leading to the reinstatement of Cre activity. We have been able to show, using in vitro approaches, that this ligand-induced dimerization is an efficient way to regulate Cre activity, and presents a low background activity together with a high efficiency of recombination following dimerization. To test the in vivo performance of this system, we have, in the present work, knocked-in DiCre into the Rosa26 locus of mice. To evaluate the performance of the DiCre system, mice have been mated with indicator mice (Z/EG or R26R and Cre-induced recombination was examined following activation of DiCre by rapamycin during embryonic development or after birth of progenies. No recombination could be observed in the absence of treatment of the animals, indicating a lack of background activity of DiCre in the absence of rapamycin. Postnatal rapamycin treatment (one to five daily injection, 10 mg/kg i.p induced recombination in a number of different tissues of progenies such as liver, heart, kidney, muscle, etc. On the other hand, recombination was at a very low level following in utero treatment of DiCrexR26R mice. In conclusion, DiCre has indeed the potentiality to be used to establish conditional Cre-deleter mice. An added advantage of this system is that, contrary to other modulatable Cre systems, it offers the possibility of obtaining regulated recombination in a combinatorial manner, i.e. induce

  14. An easy method for preparation of Cre-loxP regulated fluorescent adenoviral expression vectors and its application for direct reprogramming into hepatocytes

    Directory of Open Access Journals (Sweden)

    Chitose Kurihara

    2016-12-01

    Full Text Available The recombinant adenoviral gene expression system is a powerful tool for gene delivery. However, it is difficult to obtain high titers of infectious virus, principally due to the toxicity of the expressed gene which affects on virus replication in the host HEK293 cells. To avoid these problems, we generated a Cre-loxP-regulated fluorescent universal vector (termed pAxCALRL. This vector produces recombinant adenoviruses that express the red fluorescent protein (RFP instead of the inserted gene during proliferation, which limits toxicity and can be used to monitor viral replication. Expression of the gene of interest is induced by co-infection with an adenovirus that expresses Cre-recombinase (AxCANCre. Recombinant adenovirus produced by this system that express Hnf4α and Foxa2 were used to reprogram mouse embryo fibroblast (MEF into induced-hepatocyte-like cells (iHep following several rounds of infection, demonstrating the efficacy of this new system.

  15. 77 FR 70885 - Uniform Compliance Date for Food Labeling Regulations

    Science.gov (United States)

    2012-11-28

    ... compliance dates for new food labeling requirements to minimize the economic impact of label changes. On... INFORMATION: I. Background FDA periodically issues regulations requiring changes in the labeling of food. If... periodically have announced uniform compliance dates for new food labeling requirements (see, e.g., the Federal...

  16. 75 FR 71344 - Uniform Compliance Date for Food Labeling Regulations

    Science.gov (United States)

    2010-11-23

    ... date for new meat and poultry product labeling regulations that are issued between January 1, 2011, and December 31, 2012. FSIS periodically announces uniform compliance dates for new meat and poultry product... comments. Mail, including floppy disks or CD-ROMs, and hand- or courier-delivered items: Send to Docket...

  17. 77 FR 76824 - Uniform Compliance Date for Food Labeling Regulations

    Science.gov (United States)

    2012-12-31

    ... compliance date for new meat and poultry product labeling regulations that are issued between January 1, 2013, and December 31, 2014. FSIS periodically announces uniform compliance dates for new meat and poultry..., Washington, DC 20250- 3700. Hand- or courier-delivered items: Send to Docket Clerk, U.S. Department of...

  18. Hydrodynamic Delivery of Cre Protein to Lineage-Mark or Time-Stamp Mouse Hepatocytes In situ

    Science.gov (United States)

    Sonsteng, Katherine M.; Prigge, Justin R.; Talago, Emily A.; June, Ronald K.; Schmidt, Edward E.

    2014-01-01

    Cre-responsive fluorescent marker alleles are powerful tools for cell lineage tracing in mice; however their utility is limited by regulation of Cre activity. When targeting hepatocytes, hydrodynamic delivery of a Cre-expression plasmid can convert Cre-responsive alleles without inducing the intracellular or systemic antiviral responses often associated with viral-derived Cre-expression vectors. In this method, rapid high-volume intravenous inoculation induces hepatocyte-targeted uptake of extracellular molecules. Here we tested whether hydrodynamic delivery of Cre protein or Cre fused to the HIV-TAT cell-penetrating peptide could convert Cre-responsive reporters in hepatocytes of mice. Hydrodynamic delivery of 2 nmol of either Cre or TAT-Cre protein converted the reporter allele in 5 to 20% of hepatocytes. Neither protein gave detectable Cre activity in endothelia, non-liver organs, or non-hepatocyte cells in liver. Using mice homozygous for a Cre-responsive marker that directs red- (Cre-naïve) or green- (Cre-converted) fluorescent proteins to the nucleus, we assessed sub-saturation Cre-activity. One month after hydrodynamic inoculation with Cre protein, 58% of hepatocyte nuclei that were green were also red, indicating that less than half of the hepatocytes that had obtained enough Cre to convert one marker allele to green were able to convert all alleles. For comparison, one month after hydrodynamic delivery of a Cre-expression plasmid with a weak promoter, only 26% of the green nuclei were also red. Our results show that hydrodynamic delivery of Cre protein allows rapid allelic conversion in hepatocytes, but Cre-activity is sub-saturating so many cells will not convert multiple Cre-responsive alleles. PMID:24626158

  19. 76 FR 65999 - Effective Date for Swap Regulation

    Science.gov (United States)

    2011-10-25

    ... latest expiry dates. With respect to provisions covered in the first part of the relief in the July 14... also is proposing to amend the July 14 Order to extend the expiry date of the second part of the relief...

  20. 75 FR 78155 - Uniform Compliance Date for Food Labeling Regulations

    Science.gov (United States)

    2010-12-15

    ... Administration (FDA) is establishing January 1, 2014, as the uniform compliance date for food labeling... compliance dates for new food labeling requirements to minimize the economic impact of label changes. On December 8, 2008, FDA established January 2, 2012, as the uniform compliance date for food labeling...

  1. Split-Cre complementation restores combination activity on transgene excision in hair roots of transgenic tobacco.

    Directory of Open Access Journals (Sweden)

    Mengling Wen

    Full Text Available The Cre/loxP system is increasingly exploited for genetic manipulation of DNA in vitro and in vivo. It was previously reported that inactive ''split-Cre'' fragments could restore Cre activity in transgenic mice when overlapping co-expression was controlled by two different promoters. In this study, we analyzed recombination activities of split-Cre proteins, and found that no recombinase activity was detected in the in vitro recombination reaction in which only the N-terminal domain (NCre of split-Cre protein was expressed, whereas recombination activity was obtained when the C-terminal (CCre or both NCre and CCre fragments were supplied. We have also determined the recombination efficiency of split-Cre proteins which were co-expressed in hair roots of transgenic tobacco. No Cre recombination event was observed in hair roots of transgenic tobacco when the NCre or CCre genes were expressed alone. In contrast, an efficient recombination event was found in transgenic hairy roots co-expressing both inactive split-Cre genes. Moreover, the restored recombination efficiency of split-Cre proteins fused with the nuclear localization sequence (NLS was higher than that of intact Cre in transgenic lines. Thus, DNA recombination mediated by split-Cre proteins provides an alternative method for spatial and temporal regulation of gene expression in transgenic plants.

  2. 24 CFR 1720.25 - Effective date of rules and regulations.

    Science.gov (United States)

    2010-04-01

    ... HOUSING AND URBAN DEVELOPMENT (INTERSTATE LAND SALES REGISTRATION PROGRAM) FORMAL PROCEDURES AND RULES OF... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Effective date of rules and regulations. 1720.25 Section 1720.25 Housing and Urban Development Regulations Relating to Housing and Urban...

  3. Generation of NSE-MerCreMer transgenic mice with tamoxifen inducible Cre activity in neurons.

    Directory of Open Access Journals (Sweden)

    Mandy Ka Man Kam

    Full Text Available To establish a genetic tool for conditional deletion or expression of gene in neurons in a temporally controlled manner, we generated a transgenic mouse (NSE-MerCreMer, which expressed a tamoxifen inducible type of Cre recombinase specifically in neurons. The tamoxifen inducible Cre recombinase (MerCreMer is a fusion protein containing Cre recombinase with two modified estrogen receptor ligand binding domains at both ends, and is driven by the neural-specific rat neural specific enolase (NSE promoter. A total of two transgenic lines were established, and expression of MerCreMer in neurons of the central and enteric nervous systems was confirmed. Transcript of MerCreMer was detected in several non-neural tissues such as heart, liver, and kidney in these lines. In the background of the Cre reporter mouse strain Rosa26R, Cre recombinase activity was inducible in neurons of adult NSE-MerCreMer mice treated with tamoxifen by intragastric gavage, but not in those fed with corn oil only. We conclude that NSE-MerCreMer lines will be useful for studying gene functions in neurons for the conditions that Cre-mediated recombination resulting in embryonic lethality, which precludes investigation of gene functions in neurons through later stages of development and in adult.

  4. Longitudinal Relations between Beliefs Supporting Aggression,Anger Regulation, and Dating Aggression among Early Adolescents.

    Science.gov (United States)

    Sullivan, Terri N; Garthe, Rachel C; Goncy, Elizabeth A; Carlson, Megan M; Behrhorst, Kathryn L

    2017-05-01

    Dating aggression occurs frequently in early to mid-adolescence and has negative repercussions for psychosocial adjustment and physical health. The patterns of behavior learned during this developmental timeframe may persist in future dating relationships, underscoring the need to identify risk factors for this outcome. The current study examined longitudinal relations between beliefs supporting aggression, anger regulation, and dating aggression. Participants were 176 middle school students in sixth, seventh, and eighth grade (50 % female; 82 % African American). No direct effects were found between beliefs supporting reactive or proactive aggression and dating aggression. Beliefs supporting reactive aggression predicted increased rates of anger dysregulation, and beliefs supporting proactive aggression led to subsequent increases in anger inhibition. Anger dysregulation and inhibition were associated with higher frequencies of dating aggression. An indirect effect was found for the relation between beliefs supporting reactive aggression and dating aggression via anger dysregulation. Another indirect effect emerged for the relation between beliefs supporting proactive aggression and dating aggression through anger inhibition. The study's findings suggested that beliefs supporting proactive and reactive aggression were differentially related to emotion regulation processes, and identified anger dysregulation and inhibition as risk factors for dating aggression among adolescents.

  5. 76 FR 57645 - Special Local Regulations for Marine Events; Temporary Change of Dates for Recurring Marine...

    Science.gov (United States)

    2011-09-16

    ... temporary line in the Table to Sec. 100.501 was wrong. This Correction fixes that error. The date and all.... ] FOR FURTHER INFORMATION CONTACT: For information about this correction, contact Kevin d'Eustachio....mil . For information about the original regulation, contact BOSN3 Joseph M. Edge, Coast Guard Sector...

  6. aP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra.

    Science.gov (United States)

    Antonson, Per; Matic, Marko; Portwood, Neil; Kuiper, Raoul V; Bryzgalova, Galyna; Gao, Hui; Windahl, Sara H; Humire, Patricia; Ohlsson, Claes; Berggren, Per-Olof; Gustafsson, Jan-Åke; Dahlman-Wright, Karin

    2014-01-01

    In this study we describe the reproductive phenotypes of a novel mouse model in which Cre-mediated deletion of ERα is regulated by the aP2 (fatty acid binding protein 4) promoter. ERα-floxed mice were crossed with transgenic mice expressing Cre-recombinase under the control of the aP2 promoter to generate aP2-Cre/ERα(flox/flox) mice. As expected, ERα mRNA levels were reduced in adipose tissue, but in addition we also detected an 80% reduction of ERα levels in the hypothalamus of aP2-Cre/ERα(flox/flox) mice. Phenotypic analysis revealed that aP2-Cre/ERα(flox/flox) female mice were infertile. In line with this, aP2-Cre/ERα(flox/flox) female mice did not cycle and presented 3.8-fold elevated estrogen levels. That elevated estrogen levels were associated with increased estrogen signaling was evidenced by increased mRNA levels of the estrogen-regulated genes lactoferrin and aquaporin 5 in the uterus. Furthermore, aP2-Cre/ERα(flox/flox) female mice showed an accumulation of intra-uterine fluid, hydrometra, without overt indications for causative anatomical anomalies. However, the vagina and cervix displayed advanced keratosis with abnormal quantities of accumulating squamous epithelial cells suggesting functional obstruction by keratin plugs. Importantly, treatment of aP2-Cre/ERα(flox/flox) mice with the aromatase inhibitor Letrozole caused regression of the hydrometra phenotype linking increased estrogen levels to the observed phenotype. We propose that in aP2-Cre/ERα(flox/flox) mice, increased serum estrogen levels cause over-stimulation in the uterus and genital tracts resulting in hydrometra and vaginal obstruction.

  7. Emotion Regulation Difficulties Moderate the Association Between Heavy Episodic Drinking and Dating Violence Perpetration Among College Men

    OpenAIRE

    Stappenbeck, Cynthia A.; Davis, Kelly Cue; Cherf, Nicholas; Gulati, Natasha K.; Kajumulo, Kelly F.

    2016-01-01

    Because of high rates of heavy drinking and dating violence (psychological or physical aggression toward a dating partner) among college men, we examined whether emotion regulation difficulties moderated the association between heavy drinking and dating violence perpetration. One hundred and fifty-eight men were recruited from a large northwestern US university between April 2014 and August 2014. Participants completed an online survey that assessed their emotion regulation difficulties as we...

  8. High- and low-affinity cre boxes for CcpA binding in Bacillus subtilis revealed by genome-wide analysis.

    Science.gov (United States)

    Marciniak, Bogumiła C; Pabijaniak, Monika; de Jong, Anne; Dűhring, Robert; Seidel, Gerald; Hillen, Wolfgang; Kuipers, Oscar P

    2012-08-17

    In Bacillus subtilis and its relatives carbon catabolite control, a mechanism enabling to reach maximal efficiency of carbon and energy sources metabolism, is achieved by the global regulator CcpA (carbon catabolite protein A). CcpA in a complex with HPr-Ser-P (seryl-phosphorylated form of histidine-containing protein, HPr) binds to operator sites called catabolite responsive elements, cre. Depending on the cre box position relative to the promoter, the CcpA/HPr-Ser-P complex can either act as a positive or a negative regulator. The cre boxes are highly degenerate semi-palindromes with a lowly conserved consensus sequence. So far, studies aimed at revealing how CcpA can bind such diverse sites were focused on the analysis of single cre boxes. In this study, a genome-wide analysis of cre sites was performed in order to identify differences in cre sequence and position, which determine their binding affinity. The transcriptomes of B. subtilis cultures with three different CcpA expression levels were compared. The higher the amount of CcpA in the cells, the more operons possessing cre sites were differentially regulated. The cre boxes that mediated regulation at low CcpA levels were designated as strong (high affinity) and those which responded only to high amounts of CcpA, as weak (low affinity). Differences in the sequence and position in relation to the transcription start site between strong and weak cre boxes were revealed. Certain residues at specific positions in the cre box as well as, to a certain extent, a more palindromic nature of cre sequences and the location of cre in close vicinity to the transcription start site contribute to the strength of CcpA-dependent regulation. The main factors contributing to cre regulatory efficiencies, enabling subtle differential control of various subregulons of the CcpA regulon, are identified.

  9. High- and low-affinity cre boxes for CcpA binding in Bacillus subtilis revealed by genome-wide analysis

    Directory of Open Access Journals (Sweden)

    Marciniak Bogumiła C

    2012-08-01

    Full Text Available Abstract Background In Bacillus subtilis and its relatives carbon catabolite control, a mechanism enabling to reach maximal efficiency of carbon and energy sources metabolism, is achieved by the global regulator CcpA (carbon catabolite protein A. CcpA in a complex with HPr-Ser-P (seryl-phosphorylated form of histidine-containing protein, HPr binds to operator sites called catabolite responsive elements, cre. Depending on the cre box position relative to the promoter, the CcpA/HPr-Ser-P complex can either act as a positive or a negative regulator. The cre boxes are highly degenerate semi-palindromes with a lowly conserved consensus sequence. So far, studies aimed at revealing how CcpA can bind such diverse sites were focused on the analysis of single cre boxes. In this study, a genome-wide analysis of cre sites was performed in order to identify differences in cre sequence and position, which determine their binding affinity. Results The transcriptomes of B. subtilis cultures with three different CcpA expression levels were compared. The higher the amount of CcpA in the cells, the more operons possessing cre sites were differentially regulated. The cre boxes that mediated regulation at low CcpA levels were designated as strong (high affinity and those which responded only to high amounts of CcpA, as weak (low affinity. Differences in the sequence and position in relation to the transcription start site between strong and weak cre boxes were revealed. Conclusions Certain residues at specific positions in the cre box as well as, to a certain extent, a more palindromic nature of cre sequences and the location of cre in close vicinity to the transcription start site contribute to the strength of CcpA-dependent regulation. The main factors contributing to cre regulatory efficiencies, enabling subtle differential control of various subregulons of the CcpA regulon, are identified.

  10. Disruption of Trichoderma reesei cre2, encoding an ubiquitin C-terminal hydrolase, results in increased cellulase activity

    Directory of Open Access Journals (Sweden)

    Denton Jai A

    2011-11-01

    Full Text Available Abstract Background The filamentous fungus Trichoderma reesei (Hypocrea jecorina is an important source of cellulases for use in the textile and alternative fuel industries. To fully understand the regulation of cellulase production in T. reesei, the role of a gene known to be involved in carbon regulation in Aspergillus nidulans, but unstudied in T. reesei, was investigated. Results The T. reesei orthologue of the A. nidulans creB gene, designated cre2, was identified and shown to be functional through heterologous complementation of a creB mutation in A. nidulans. A T. reesei strain was constructed using gene disruption techniques that contained a disrupted cre2 gene. This strain, JKTR2-6, exhibited phenotypes similar to the A. nidulans creB mutant strain both in carbon catabolite repressing, and in carbon catabolite derepressing conditions. Importantly, the disruption also led to elevated cellulase levels. Conclusions These results demonstrate that cre2 is involved in cellulase expression. Since the disruption of cre2 increases the amount of cellulase activity, without severe morphological affects, targeting creB orthologues for disruption in other industrially useful filamentous fungi, such as Aspergillus oryzae, Trichoderma harzianum or Aspergillus niger may also lead to elevated hydrolytic enzyme activity in these species.

  11. The CreB deubiquitinating enzyme does not directly target the CreA repressor protein in Aspergillus nidulans.

    Science.gov (United States)

    Alam, Md Ashiqul; Kamlangdee, Niyom; Kelly, Joan M

    2017-08-01

    Ubiquitination/deubiquitination pathways are now recognized as key components of gene regulatory mechanisms in eukaryotes. The major transcriptional repressor for carbon catabolite repression in Aspergillus nidulans is CreA, and mutational analysis led to the suggestion that a regulatory ubiquitination/deubiquitination pathway is involved. A key unanswered question is if and how this pathway, comprising CreB (deubiquitinating enzyme) and HulA (ubiquitin ligase) and other proteins, is involved in the regulatory mechanism. Previously, missense alleles of creA and creB were analysed for genetic interactions, and here we extended this to complete loss-of-function alleles of creA and creB, and compared morphological and biochemical phenotypes, which confirmed genetic interaction between the genes. We investigated whether CreA, or a protein in a complex with it, is a direct target of the CreB deubiquitination enzyme, using co-purifications of CreA and CreB, first using strains that overexpress the proteins and then using strains that express the proteins from their native promoters. The Phos-tag system was used to show that CreA is a phosphorylated protein, but no ubiquitination was detected using anti-ubiquitin antibodies and Western analysis. These findings were confirmed using mass spectrometry, which confirmed that CreA was differentially phosphorylated but not ubiquitinated. Thus, CreA is not a direct target of CreB, and nor are proteins that form part of a stable complex with CreA a target of CreB. These results open up new questions regarding the molecular mechanism of CreA repressing activity, and how the ubiquitination pathway involving CreB interacts with this regulatory network.

  12. 75 FR 29886 - Special Local Regulation for Marine Events; Temporary Change of Dates for Recurring Marine Events...

    Science.gov (United States)

    2010-05-28

    ... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulation for Marine Events; Temporary Change of Dates for Recurring Marine Events in the Fifth Coast Guard District AGENCY: Coast Guard, DHS... special local regulations for recurring marine events in the Fifth Coast Guard District. These regulations...

  13. Efficient delivery of Cre-recombinase to neurons in vivo and stable transduction of neurons using adeno-associated and lentiviral vectors

    Directory of Open Access Journals (Sweden)

    Sablitzky Fred

    2004-01-01

    Full Text Available Abstract Background Inactivating genes in vivo is an important technique for establishing their function in the adult nervous system. Unfortunately, conventional knockout mice may suffer from several limitations including embryonic or perinatal lethality and the compensatory regulation of other genes. One approach to producing conditional activation or inactivation of genes involves the use of Cre recombinase to remove loxP-flanked segments of DNA. We have studied the effects of delivering Cre to the hippocampus and neocortex of adult mice by injecting replication-deficient adeno-associated virus (AAV and lentiviral (LV vectors into discrete regions of the forebrain. Results Recombinant AAV-Cre, AAV-GFP (green fluorescent protein and LV-Cre-EGFP (enhanced GFP were made with the transgene controlled by the cytomegalovirus promoter. Infecting 293T cells in vitro with AAV-Cre and LV-Cre-EGFP resulted in transduction of most cells as shown by GFP fluorescence and Cre immunoreactivity. Injections of submicrolitre quantities of LV-Cre-EGFP and mixtures of AAV-Cre with AAV-GFP into the neocortex and hippocampus of adult Rosa26 reporter mice resulted in strong Cre and GFP expression in the dentate gyrus and moderate to strong labelling in specific regions of the hippocampus and in the neocortex, mainly in neurons. The pattern of expression of Cre and GFP obtained with AAV and LV vectors was very similar. X-gal staining showed that Cre-mediated recombination had occurred in neurons in the same regions of the brain, starting at 3 days post-injection. No obvious toxic effects of Cre expression were detected even after four weeks post-injection. Conclusion AAV and LV vectors are capable of delivering Cre to neurons in discrete regions of the adult mouse brain and producing recombination.

  14. Efficient delivery of Cre-recombinase to neurons in vivo and stable transduction of neurons using adeno-associated and lentiviral vectors.

    Science.gov (United States)

    Ahmed, Bushra Y; Chakravarthy, Sridhara; Eggers, Ruben; Hermens, Wim T J M C; Zhang, Jing Ying; Niclou, Simone P; Levelt, Christiaan; Sablitzky, Fred; Anderson, Patrick N; Lieberman, A R; Verhaagen, Joost

    2004-01-30

    Inactivating genes in vivo is an important technique for establishing their function in the adult nervous system. Unfortunately, conventional knockout mice may suffer from several limitations including embryonic or perinatal lethality and the compensatory regulation of other genes. One approach to producing conditional activation or inactivation of genes involves the use of Cre recombinase to remove loxP-flanked segments of DNA. We have studied the effects of delivering Cre to the hippocampus and neocortex of adult mice by injecting replication-deficient adeno-associated virus (AAV) and lentiviral (LV) vectors into discrete regions of the forebrain. Recombinant AAV-Cre, AAV-GFP (green fluorescent protein) and LV-Cre-EGFP (enhanced GFP) were made with the transgene controlled by the cytomegalovirus promoter. Infecting 293T cells in vitro with AAV-Cre and LV-Cre-EGFP resulted in transduction of most cells as shown by GFP fluorescence and Cre immunoreactivity. Injections of submicrolitre quantities of LV-Cre-EGFP and mixtures of AAV-Cre with AAV-GFP into the neocortex and hippocampus of adult Rosa26 reporter mice resulted in strong Cre and GFP expression in the dentate gyrus and moderate to strong labelling in specific regions of the hippocampus and in the neocortex, mainly in neurons. The pattern of expression of Cre and GFP obtained with AAV and LV vectors was very similar. X-gal staining showed that Cre-mediated recombination had occurred in neurons in the same regions of the brain, starting at 3 days post-injection. No obvious toxic effects of Cre expression were detected even after four weeks post-injection. AAV and LV vectors are capable of delivering Cre to neurons in discrete regions of the adult mouse brain and producing recombination.

  15. Emotion Regulation Difficulties Moderate the Association Between Heavy Episodic Drinking and Dating Violence Perpetration Among College Men.

    Science.gov (United States)

    Stappenbeck, Cynthia A; Davis, Kelly Cue; Cherf, Nicholas; Gulati, Natasha K; Kajumulo, Kelly F

    2016-01-01

    Because of high rates of heavy drinking and dating violence (psychological or physical aggression toward a dating partner) among college men, we examined whether emotion regulation difficulties moderated the association between heavy drinking and dating violence perpetration. One hundred and fifty-eight men were recruited from a large northwestern US university between April 2014 and August 2014. Participants completed an online survey that assessed their emotion regulation difficulties as well as their past year history of heavy episodic drinking (HED; consuming 5+ drinks in 2 hours) and dating violence perpetration. Generalized linear models revealed that the positive association between HED and dating violence perpetration was stronger for men with greater impulse control difficulties and for those who reported limited access to emotion regulation strategies. In addition to continued efforts to reduce heavy drinking among college men, interventions targeting emotion regulation difficulties should be incorporated into standard dating violence intervention and prevention efforts to further reduce the likelihood of dating violence perpetration in this population.

  16. A new Cre driver mouse line, Tcf21/Pod1-Cre, targets metanephric mesenchyme.

    Directory of Open Access Journals (Sweden)

    Yoshiro Maezawa

    Full Text Available Conditional gene targeting in mice has provided great insight into the role of gene function in kidney development and disease. Although a number of Cre-driver mouse strains already exist for the kidney, development of additional strains with unique expression patterns is needed. Here we report the generation and validation of a Tcf21/Pod1-Cre driver strain that expresses Cre recombinase throughout the condensing and stromal mesenchyme of developing kidneys and in their derivatives including epithelial components of the nephron and interstitial cells. To test the efficiency of this line, we crossed it to mice transgenic for either loss or gain of function β-catenin conditional alleles. Mice with deletion of β-catenin from Tcf21-expressing cells are born with hypoplastic kidneys, hydroureters and hydronephrosis. By contrast, Tcf21-Cre driven gain of function for β-catenin in mice results in fused midline kidneys and hypoplastic kidneys. Finally, we report the first renal mesenchymal deletion of Patched1 (Ptch1, the receptor for sonic hedgehog (Shh, which results in renal cysts demonstrating a functional role of Shh signaling pathway in renal cystogensis. In summary, we report the generation and validation of a new Cre driver strain that provides robust excision in metanephric mesenchyme.

  17. 75 FR 20294 - Special Local Regulation for Marine Events; Temporary Change of Dates for Recurring Marine Events...

    Science.gov (United States)

    2010-04-19

    ... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulation for Marine Events; Temporary Change of Dates for Recurring Marine Events in the Fifth Coast Guard District AGENCY: Coast Guard, DHS... period of special local regulations for recurring marine events in the Fifth Coast Guard District. These...

  18. 76 FR 36308 - Special Local Regulation for Marine Events; Temporary Change of dates for Recurring Marine Events...

    Science.gov (United States)

    2011-06-22

    ... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulation for Marine Events; Temporary Change of dates for Recurring Marine Events in the Fifth Coast Guard District; Mill Creek, Hampton, VA... the enforcement period of one special local regulation for recurring marine events in the Fifth Coast...

  19. 75 FR 33502 - Special Local Regulation for Marine Events; Temporary Change of Dates for Recurring Marine Events...

    Science.gov (United States)

    2010-06-14

    ... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulation for Marine Events; Temporary Change of Dates for Recurring Marine Events in the Fifth Coast Guard District AGENCY: Coast Guard, DHS... special local regulations for a recurring marine event in the Fifth Coast Guard District. These...

  20. 76 FR 55558 - Special Local Regulation for Marine Events; Temporary Change of Dates for Recurring Marine Events...

    Science.gov (United States)

    2011-09-08

    ... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulation for Marine Events; Temporary Change of Dates for Recurring Marine Events in the Fifth Coast Guard District, John H. Kerr Reservoir... temporarily change the enforcement period of special local regulations for one recurring marine event in the...

  1. CreZOO--the European virtual repository of Cre and other targeted conditional driver strains.

    Science.gov (United States)

    Chandras, Christina; Zouberakis, Michael; Salimova, Ekaterina; Smedley, Damian; Rosenthal, Nadia; Aidinis, Vassilis

    2012-01-01

    The CreZOO (http://www.crezoo.org/) is the European virtual repository of Cre and other targeted conditional driver strains. These mice serve as tools for researchers to selectively 'switch off' gene expression in mouse models to examine gene function and disease pathology. CreZOO aims to capture and disseminate extant and new information on these Cre driver strains, such as genetic background and availability information, and details pertaining promoter, allele, inducibility and expression patterns, which are also presented. All transgenic strains carry detailed information according to MGI's official nomenclature, whereas their availability [e.g. live mice, cryopreserved embryos, sperm and embryonic stem (ES) cells] is clearly indicated with links to European and International databases and repositories (EMMA, MGI/IMSR, MMRRC, etc) and laboratories where the particular mouse strain is available together with the respective IDs. Each promoter/gene includes IDs and direct links to MGI, Entrez Gene, Ensembl, OMIM and RGD databases depending on their species origin, whereas allele information is presented with MGI IDs and active hyperlinks to redirect the user to the respective page in a new tab. The tissue/cell (special) and developmental (temporal) specificity expression patterns are clearly presented, whereas handling and genotyping details (in the form of documents or hyperlinks) together with all relevant publications are clearly presented with PMID(s) and direct PubMed links. CreZOO's design offers a user-friendly query interface and provides instant access to the list of conditional driver strains, promoters and inducibility details. Database access is free of charge and there are no registration requirements for data querying. CreZOO is being developed in the context of the CREATE consortium (http://www.creline.org/), a core of major European and international mouse database holders and research groups involved in conditional mutagenesis. Database URL: http

  2. Deletion of creB in Aspergillus oryzae increases secreted hydrolytic enzyme activity.

    Science.gov (United States)

    Hunter, A J; Morris, T A; Jin, B; Saint, C P; Kelly, J M

    2013-09-01

    Aspergillus oryzae has been used in the food and beverage industry for centuries, and industrial strains have been produced by multiple rounds of selection. Targeted gene deletion technology is particularly useful for strain improvement in such strains, particularly when they do not have a well-characterized meiotic cycle. Phenotypes of an Aspergillus nidulans strain null for the CreB deubiquitinating enzyme include effects on growth and repression, including increased activity levels of various enzymes. We show that Aspergillus oryzae contains a functional homologue of the CreB deubiquitinating enzyme and that a null strain shows increased activity levels of industrially important secreted enzymes, including cellulases, xylanases, amylases, and proteases, as well as alleviated inhibition of spore germination on glucose medium. Reverse transcription-quantitative PCR (RT-qPCR) analysis showed that the increased levels of enzyme activity in both Aspergillus nidulans and Aspergillus oryzae are mirrored at the transcript level, indicating transcriptional regulation. We report that Aspergillus oryzae DAR3699, originally isolated from soy fermentation, has a similar phenotype to that of a creB deletion mutant of the RIB40 strain, and it contains a mutation in the creB gene. Collectively, the results for Aspergillus oryzae, Aspergillus nidulans, Trichoderma reesei, and Penicillium decumbens show that deletion of creB may be broadly useful in diverse fungi for increasing production of a variety of enzymes.

  3. The Effects of Alcohol, Emotion Regulation, and Emotional Arousal on the Dating Aggression Intentions of Men and Women

    OpenAIRE

    Stappenbeck, Cynthia A.; Fromme, Kim

    2013-01-01

    Verbal and physical dating aggression is prevalent among college-aged men and women, especially a pattern of mutual aggression in which both partners engage in aggression. Alcohol intoxication and anger arousal have both been implicated in the occurrence of aggression, and the ability to regulate one’s emotions may interact with both alcohol intoxication and emotional arousal to predict dating aggression. The current study is the first known experimental investigation to examine the effects o...

  4. An Examination of Emotion Regulation and Alcohol Use as Risk Factors for Female-Perpetrated Dating Violence.

    Science.gov (United States)

    Ortiz, Edwin; Shorey, Ryan C; Cornelius, Tara L

    2015-01-01

    Dating violence is a serious problem among college students. Research indicates that females perpetrate as much, if not more, psychological and physical aggression against their dating partners relative to their male counterparts. Unfortunately, there is considerably less research on risk factors for female-perpetrated dating violence, hindering efforts aimed at preventing violence in their relationships. This study examined 2 risk factors for female-perpetrated dating violence, namely alcohol use and emotion regulation, within a sample of undergraduate female college students (N = 379). Using structural equation modeling, results demonstrated that emotion regulation was associated with psychological aggression perpetration, and this was partially mediated by alcohol use. Moreover, a 2-chain mediation was present, such that emotion regulation deficits predicted alcohol use, which in turn predicted psychological aggression, which finally predicted physical aggression. These findings are consistent with theoretical models of dating violence and indicate that intervention programs should focus their efforts on increasing adaptive emotion regulation, decreasing alcohol use, and reducing psychological aggression.

  5. A Study of Plazomicin Compared With Colistin in Patients With Infection Due to Carbapenem-Resistant Enterobacteriaceae (CRE)

    Science.gov (United States)

    2016-10-03

    Bloodstream Infections (BSI) Due to CRE; Hospital-Acquired Bacterial Pneumonia (HABP) Due to CRE; Ventilator-Associated Bacterial Pneumonia (VABP) Due to CRE; Complicated Urinary Tract Infection (cUTI) Due to CRE; Acute Pyelonephritis (AP) Due to CRE

  6. 75 FR 24799 - Special Local Regulation for Marine Events; Temporary Change of Dates for Recurring Marine Events...

    Science.gov (United States)

    2010-05-06

    ... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulation for Marine Events; Temporary Change of Dates for Recurring Marine Events in the Fifth Coast Guard District; Correction ACTION... events in the Fifth Coast Guard District, one on April 17-18, 2010, and one on May 29-30, 2010. That...

  7. 76 FR 37293 - Special Local Regulation for Marine Events; Temporary Change of Dates for Recurring Marine Events...

    Science.gov (United States)

    2011-06-27

    ... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulation for Marine Events; Temporary Change of Dates for Recurring Marine Events in the Fifth Coast Guard District, John H. Kerr Reservoir... event in the Fifth Coast Guard District, specifically, the ``Clarksville Hydroplane Challenge...

  8. 75 FR 17103 - Special Local Regulation for Marine Event; Temporary Change of Dates for Recurring Marine Event...

    Science.gov (United States)

    2010-04-05

    ... 100.501 is effective annually for the Maryland Swim for Life marine event. The event is an open water... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulation for Marine Event; Temporary Change of Dates for Recurring Marine Event in the Fifth Coast Guard District AGENCY: Coast Guard, DHS...

  9. 77 FR 14959 - Special Local Regulation for Marine Event; Temporary Change of Dates for Recurring Marine Events...

    Science.gov (United States)

    2012-03-14

    ... Coast Guard Sector--Captain of the Port Zone, please see 33 CFR 3.25. Because event planners notified... USNA Crew Races. This regulation proposes to temporarily change the enforcement date from ``March--last... ``June--last Saturday and Sunday'' to ``July 14 and 15, 2012.'' The Virginia/Carolina Racing Association...

  10. Modified Cre-loxP Recombination in Aspergillus oryzae by Direct Introduction of Cre Recombinase for Marker Gene Rescue

    Science.gov (United States)

    Masaki, Kazuo; Gomi, Katsuya; Iefuji, Haruyuki

    2012-01-01

    Marker rescue is an important molecular technique that enables sequential gene deletions. The Cre-loxP recombination system has been used for marker gene rescue in various organisms, including aspergilli. However, this system requires many time-consuming steps, including construction of a Cre expression plasmid, introduction of the plasmid, and Cre expression in the transformant. To circumvent this laborious process, we investigated a method wherein Cre could be directly introduced into Aspergillus oryzae protoplasts on carrier DNA such as a fragment or plasmid. In this study, we define the carrier DNA (Cre carrier) as a carrier for the Cre enzyme. A mixture of commercial Cre and nucleic acids (e.g., pUG6 plasmid) was introduced into A. oryzae protoplasts using a modified protoplast-polyethylene glycol method, resulting in the deletion of a selectable marker gene flanked by loxP sites. By using this method, we readily constructed a marker gene-rescued strain lacking ligD to optimize homologous recombination. Furthermore, we succeeded in integrative recombination at a loxP site in A. oryzae. Thus, we developed a simple method to use the Cre-loxP recombination system in A. oryzae by direct introduction of Cre into protoplasts using DNA as a carrier for the enzyme. PMID:22504800

  11. 46 CFR 550.508 - Publication, content, and effective date of regulation.

    Science.gov (United States)

    2010-10-01

    ... RESTRICTIVE FOREIGN MARITIME PRACTICES REGULATIONS TO ADJUST OR MEET CONDITIONS UNFAVORABLE TO SHIPPING IN THE... regulation. The Commission shall incorporate in any regulations adopted under the rules of this part a.... Except where conditions warrant and for good cause, regulations promulgated under the rules of this part...

  12. CRE communication on the work of the GTE 2007 and GTG 2007

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-09-15

    The work conducted in the first half of 2006 by the Electricity Working Group (GTE) and Gas Working Group (GTG) consultation bodies set up by the Commission de regulation de l'energie (CRE), has specified the practical conditions for market operation defined in CRE communication of 10 January 2006. The CRE decision of 26 May 2005, has led to the creation of a consumer committee within the GTE and GTG allowing the expectations of gas and electricity consumers to be given greater consideration. During the first half of 2006, this consumer committee defined consumers needs in terms of information and protection, and set recommendations, whose application is one of the priorities over the coming months. The consumer committee has become a plenary committee for gas and electricity consumers, with the same stature as the GTE and GTG plenary committees. Following a round table with the players on 14 September 2006, CRE presents the decisions made and guidelines adopted for the coming months in this communication. (author)

  13. Germ-line recombination activity of the widely used hGFAP-Cre and nestin-Cre transgenes.

    Directory of Open Access Journals (Sweden)

    Jiong Zhang

    Full Text Available Herein we demonstrate with PCR, immunodetection and reporter gene approaches that the widely used human Glial Fibrillary Acidic Protein (hGFAP-Cre transgene exhibits spontaneous germ-line recombination activity in leading to deletion in brain, heart and tail tissue with high frequency. The ectopic activity of hGFAP-Cre requires a rigorous control. We likewise observed that a second widely used nestin-Cre transgene shows germ-line deletion. Here we describe procedures to identify mice with germ-line recombination mediated by the hGFAP-Cre and nestin-Cre transgenes. Such control is essential to avoid pleiotropic effects due to germ-line deletion of loxP-flanked target genes and to maintain the CNS-restricted deletion status in transgenic mouse colonies.

  14. The Effects of Alcohol, Emotion Regulation, and Emotional Arousal on the Dating Aggression Intentions of Men and Women

    Science.gov (United States)

    Stappenbeck, Cynthia A; Fromme, Kim

    2013-01-01

    Verbal and physical dating aggression is prevalent among college-aged men and women, especially a pattern of mutual aggression in which both partners engage in aggression. Alcohol intoxication and anger arousal have both been implicated in the occurrence of aggression, and the ability to regulate one’s emotions may interact with both alcohol intoxication and emotional arousal to predict dating aggression. The current study is the first known experimental investigation to examine the effects of alcohol intoxication, alcohol expectancies, emotion regulation, and emotional arousal on dating aggression. Participants were randomized to receive alcohol (n=48), placebo (n=48), or no alcohol (n=48). Intoxicated men and women expressed more verbal and physical aggression intentions than those in the no alcohol condition, and individuals in the placebo condition did not significantly differ from those in the alcohol and no alcohol conditions. These results suggest that the pharmacological effects of alcohol were important to the occurrence of dating aggression, whereas the effects of expectancy are less clear. Among those less able to engage in cognitive reappraisal, individuals who consumed alcohol or believed they consumed alcohol expressed more verbal and physical aggression intentions than those who received no alcohol. Those with higher arousal who were better able to suppress their emotions expressed fewer verbal and physical aggression intentions than those with lower arousal. In addition to reducing alcohol consumption, interventions to prevent dating aggression might incorporate emotion regulation skills, with a focus on understanding the circumstances in which cognitive reappraisal and emotion suppression are relatively more effective. PMID:23586449

  15. The effects of alcohol, emotion regulation, and emotional arousal on the dating aggression intentions of men and women.

    Science.gov (United States)

    Stappenbeck, Cynthia A; Fromme, Kim

    2014-03-01

    Verbal and physical dating aggression is prevalent among college-aged men and women, especially a pattern of mutual aggression in which both partners engage in aggression. Alcohol intoxication and anger arousal have been implicated in the occurrence of aggression, and the ability to regulate one's emotions may interact with both alcohol intoxication and emotional arousal to predict dating aggression. The current study is the first known experimental investigation to examine the effects of alcohol intoxication, alcohol expectancies, emotion regulation, and emotional arousal on dating aggression. Participants were randomized to receive alcohol (n = 48), placebo (n = 48), or no alcohol (n = 48). Intoxicated men and women expressed more verbal and physical aggression intentions than those in the no-alcohol condition, and individuals in the placebo condition did not significantly differ from those in the alcohol and no-alcohol conditions. These results suggest that the pharmacological effects of alcohol were important to the occurrence of dating aggression, whereas the effects of expectancy are less clear. Among those less able to engage in cognitive reappraisal, individuals who consumed or believed they consumed alcohol expressed more verbal and physical aggression intentions than those who received no alcohol. Those with higher arousal who were better able to suppress their emotions expressed fewer verbal and physical aggression intentions than those with lower arousal. In addition to reducing alcohol consumption, interventions for dating aggression might incorporate emotion regulation skills, with a focus on understanding the circumstances in which cognitive reappraisal and emotion suppression are relatively more effective. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  16. Mutants of Cre recombinase with improved accuracy

    Science.gov (United States)

    Eroshenko, Nikolai; Church, George M.

    2013-01-01

    Despite rapid advances in genome engineering technologies, inserting genes into precise locations in the human genome remains an outstanding problem. It has been suggested that site-specific recombinases can be adapted towards use as transgene delivery vectors. The specificity of recombinases can be altered either with directed evolution or via fusions to modular DNA-binding domains. Unfortunately, both wildtype and altered variants often have detectable activities at off-target sites. Here we use bacterial selections to identify mutations in the dimerization surface of Cre recombinase (R32V, R32M, and 303GVSdup) that improve the accuracy of recombination. The mutants are functional in bacteria, in human cells, and in vitro (except for 303GVSdup, which we did not purify), and have improved selectivity against both model off-target sites and the entire E. coli genome. We propose that destabilizing binding cooperativity may be a general strategy for improving the accuracy of dimeric DNA-binding proteins. PMID:24056590

  17. 7 CFR 999.1 - Regulation governing the importation of dates.

    Science.gov (United States)

    2010-01-01

    ... of the Consumer and Marketing Service, United States Department of Agriculture, Washington, DC 20250... thereafter, either an onboard bill of lading designating the lots to be inspected by USDA inspectors and... importer. Each wholesaler or other reseller of dates for processing should, for his protection, obtain from...

  18. 76 FR 44877 - Special Local Regulations for Marine Events; Temporary Change of Dates for Recurring Marine...

    Science.gov (United States)

    2011-07-27

    ... Local Regulation is necessary to provide for the safety of life on navigable waters during the event... North Carolina. The Triathlon consists of three events: a running portion, a bike-riding portion, and a... Beach. A special local regulation is effective annually to create a safety zone for the swimming portion...

  19. 77 FR 43511 - Special Local Regulations for Marine Events, Temporary Change of Dates for Recurring Marine...

    Science.gov (United States)

    2012-07-25

    ... Carolina. This Special Local Regulation is necessary to provide for the safety of life on navigable waters... North Carolina. The Triathlon consists of three events: a running portion, a bike-riding portion, and a... Beach. A special local regulation is effective annually to create a safety zone for the swimming portion...

  20. 77 FR 30929 - Special Local Regulations for Marine Events, Temporary Change of Dates for Recurring Marine...

    Science.gov (United States)

    2012-05-24

    ... Beach, North Carolina. This Special Local Regulation is necessary to provide for the safety of life on... consists of three events: A running portion, a bike-riding portion, and a swimming portion. The swimming... regulation is effective annually to create a safety zone for the swimming portion of the Triathlon. The...

  1. Flavonoids and Auxin Transport Inhibitors Rescue Symbiotic Nodulation in the Medicago truncatula Cytokinin Perception Mutant cre1

    Science.gov (United States)

    Ng, Jason Liang Pin; Hassan, Samira; Truong, Thy T.; Hocart, Charles H.; Laffont, Carole; Frugier, Florian; Mathesius, Ulrike

    2015-01-01

    Initiation of symbiotic nodules in legumes requires cytokinin signaling, but its mechanism of action is largely unknown. Here, we tested whether the failure to initiate nodules in the Medicago truncatula cytokinin perception mutant cre1 (cytokinin response1) is due to its altered ability to regulate auxin transport, auxin accumulation, and induction of flavonoids. We found that in the cre1 mutant, symbiotic rhizobia cannot locally alter acro- and basipetal auxin transport during nodule initiation and that these mutants show reduced auxin (indole-3-acetic acid) accumulation and auxin responses compared with the wild type. Quantification of flavonoids, which can act as endogenous auxin transport inhibitors, showed a deficiency in the induction of free naringenin, isoliquiritigenin, quercetin, and hesperetin in cre1 roots compared with wild-type roots 24 h after inoculation with rhizobia. Coinoculation of roots with rhizobia and the flavonoids naringenin, isoliquiritigenin, and kaempferol, or with the synthetic auxin transport inhibitor 2,3,5,-triiodobenzoic acid, rescued nodulation efficiency in cre1 mutants and allowed auxin transport control in response to rhizobia. Our results suggest that CRE1-dependent cytokinin signaling leads to nodule initiation through the regulation of flavonoid accumulation required for local alteration of polar auxin transport and subsequent auxin accumulation in cortical cells during the early stages of nodulation. PMID:26253705

  2. Targeting of GFP-Cre to the mouse Cyp11a1 locus both drives cre recombinase expression in steroidogenic cells and permits generation of Cyp11a1 knock out mice.

    Directory of Open Access Journals (Sweden)

    Laura O'Hara

    Full Text Available To permit conditional gene targeting of floxed alleles in steroidogenic cell-types we have generated a transgenic mouse line that expresses Cre Recombinase under the regulation of the endogenous Cytochrome P450 side chain cleavage enzyme (Cyp11a1 promoter. Mice Carrying the Cyp11a1-GC (GFP-Cre allele express Cre Recombinase in fetal adrenal and testis, and adrenal cortex, testicular Leydig cells (and a small proportion of Sertoli cells, theca cells of the ovary, and the hindbrain in postnatal life. Circulating testosterone concentration is unchanged in Cyp11(+/GC males, suggesting steroidogenesis is unaffected by loss of one allele of Cyp11a1, mice are grossly normal, and Cre Recombinase functions to recombine floxed alleles of both a YFP reporter gene and the Androgen Receptor (AR in steroidogenic cells of the testis, ovary, adrenal and hindbrain. Additionally, when bred to homozygosity (Cyp11a1(GC/GC , knock-in of GFP-Cre to the endogenous Cyp11a1 locus results in a novel mouse model lacking endogenous Cyp11a1 (P450-SCC function. This unique dual-purpose model has utility both for those wishing to conditionally target genes within steroidogenic cell types and for studies requiring mice lacking endogenous steroid hormone production.

  3. Strict control of telomerase activation using Cre-mediated inversion

    Directory of Open Access Journals (Sweden)

    Harrington Lea

    2006-02-01

    Full Text Available Abstract Background Human cells appear exquisitely sensitive to the levels of hTERT expression, the telomerase reverse transcriptase. In primary cells that do not express hTERT, telomeres erode with each successive cell division, leading to the eventual loss of telomere DNA, an induction of a telomere DNA damage response, and the onset of cellular senescence or crisis. In some instances, an average of less than one appropriately spliced hTERT transcript per cell appears sufficient to restore telomerase activity and telomere maintenance, and overcome finite replicative capacity. Results To underscore this sensitivity, we showed that a widely used system of transcriptional induction involving ecdysone (muristerone led to sufficient expression of hTERT to immortalize human fibroblasts, even in the absence of induction. To permit tightly regulated expression of hTERT, or any other gene of interest, we developed a method of transcriptional control using an invertible expression cassette flanked by antiparallel loxP recombination sites. When introduced into human fibroblasts with the hTERT cDNA positioned in the opposite orientation relative to a constitutively active promoter, no telomerase activity was detected, and the cell population retained a mortal phenotype. Upon inversion of the hTERT cDNA to a transcriptionally competent orientation via the action of Cre recombinase, cells acquired telomerase activity, telomere DNA was replenished, and the population was immortalized. Further, using expression of a fluorescent protein marker, we demonstrated the ability to repeatedly invert specific transcripts between an active and inactive state in an otherwise isogenic cell background. Conclusion This binary expression system thus provides a useful genetic means to strictly regulate the expression of a given gene, or to control the expression of at least two different genes in a mutually exclusive manner.

  4. Heat-inducible Cre-lox system for marker excision in transgenic rice

    Indian Academy of Sciences (India)

    The present study assessed the efficacy of a heat-inducible cre gene for conditional removal of the marker gene from a rice genome via Cre-lox recombination. A cre gene controlled by the soybean heat-shock promoter was introduced into the rice genome along with the recombination target (lox) construct. Cre-mediated ...

  5. Long-term Cre-mediated Retrograde Tagging of Neurons Using a Novel Recombinant Pseudorabies Virus

    Directory of Open Access Journals (Sweden)

    Hassana eOyibo

    2014-09-01

    Full Text Available Brain regions contain diverse populations of neurons that project to different long-range targets. The study of these subpopulations in circuit function and behavior requires a toolkit to characterize and manipulate their activity in vivo. We have developed a novel set of reagents based on Pseudorabies Virus (PRV for efficient and long-term genetic tagging of neurons based on their projection targets. By deleting IE180, the master transcriptional regulator in the PRV genome, we have produced a mutant virus capable of infection and transgene expression in neurons but unable to replicate in or spread from those neurons. IE180-null mutants showed no cytotoxicity, and infected neurons exhibited normal physiological function more than 45 days after infection, indicating the utility of these engineered viruses for chronic experiments. To enable rapid and convenient construction of novel IE180-null recombinants, we engineered a bacterial artificial chromosome (BAC shuttle-vector system for moving new constructs into the PRV IE180-null genome. Using this system we generated an IE180-null recombinant virus expressing the site-specific recombinase Cre. This Cre-expressing virus (PRV-hSyn-Cre efficiently and robustly infects neurons in vivo and activates transgene expression from Cre-dependent vectors in local and retrograde projecting populations of neurons in the mouse. We also generated an assortment of recombinant viruses expressing fluorescent proteins (mCherry, EGFP, ECFP. These viruses exhibit long-term labeling of neurons in vitro but transient labeling in vivo. Together these novel IE180-null PRV reagents expand the toolkit for targeted gene expression in the brain, facilitating functional dissection of neuronal circuits in vivo.

  6. Heterogeneous transgene expression in the retinas of the TH-RFP, TH-Cre, TH-BAC-Cre and DAT-Cre mouse lines.

    Science.gov (United States)

    Vuong, H E; Pérez de Sevilla Müller, L; Hardi, C N; McMahon, D G; Brecha, N C

    2015-10-29

    Transgenic mouse lines are essential tools for understanding the connectivity, physiology and function of neuronal circuits, including those in the retina. This report compares transgene expression in the retina of a tyrosine hydroxylase (TH)-red fluorescent protein (RFP) mouse line with three catecholamine-related Cre recombinase mouse lines [TH-bacterial artificial chromosome (BAC)-, TH-, and dopamine transporter (DAT)-Cre] that were crossed with a ROSA26-tdTomato reporter line. Retinas were evaluated and immunostained with commonly used antibodies including those directed to TH, GABA and glycine to characterize the RFP or tdTomato fluorescent-labeled amacrine cells, and an antibody directed to RNA-binding protein with multiple splicing to identify ganglion cells. In TH-RFP retinas, types 1 and 2 dopamine (DA) amacrine cells were identified by their characteristic cellular morphology and type 1 DA cells by their expression of TH immunoreactivity. In the TH-BAC-, TH-, and DAT-tdTomato retinas, less than 1%, ∼ 6%, and 0%, respectively, of the fluorescent cells were the expected type 1 DA amacrine cells. Instead, in the TH-BAC-tdTomato retinas, fluorescently labeled AII amacrine cells were predominant, with some medium diameter ganglion cells. In TH-tdTomato retinas, fluorescence was in multiple neurochemical amacrine cell types, including four types of polyaxonal amacrine cells. In DAT-tdTomato retinas, fluorescence was in GABA immunoreactive amacrine cells, including two types of bistratified and two types of monostratified amacrine cells. Although each of the Cre lines was generated with the intent to specifically label DA cells, our findings show a cellular diversity in Cre expression in the adult retina and indicate the importance of careful characterization of transgene labeling patterns. These mouse lines with their distinctive cellular labeling patterns will be useful tools for future studies of retinal function and visual processing. Published by Elsevier

  7. CRISPR/Cas9-mediated targeting of the Rosa26 locus produces Cre reporter rat strains for monitoring Cre-loxP-mediated lineage tracing.

    Science.gov (United States)

    Ma, Yuanwu; Yu, Lei; Pan, Shuo; Gao, Shan; Chen, Wei; Zhang, Xu; Dong, Wei; Li, Jing; Zhou, Rui; Huang, Lan; Han, Yunlin; Bai, Lin; Zhang, Li; Zhang, Lianfeng

    2017-10-01

    The rat is an important laboratory animal for physiological, toxicological and pharmacological studies. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) is a simple and efficient tool to generate precise genetic modifications in rats, which will promote the accumulation of genetic resources and enable more precise studies of gene function. To monitor Cre-loxP-mediated excision in vivo, we generated a Cre reporter rat strain (Rosa26-imCherry) by knockin of a Cre reporter cassette at the Rosa26 locus using CRISPR/Cas9. Rosa26-imCherry rats exhibited inducible expression of the mCherry cassette (imCherry) using the Cre-loxP system, whereas normal rats exhibited ubiquitous expression of eGFP but not mCherry in the whole body. Injection of adeno-associated virus serotype 9-Cre into the hippocampus and skeletal muscle resulted in mCherry expression in virus-infected cells. Cre-loxP-mediated mCherry expression was then evaluated by crossing Rosa26-imCherry rats with transgenic rats ubiquitously expressing CAG-Cre, heart-specific α-MHC-Cre transgenic rats and liver-specific Alb-Cre knockin rats. Finally, using the established system the expression pattern of Cre driven by two endogenous gene promoters (Wfs1-Cre knockin rat, FabP2-Cre knockin rat) was traced. In summary, we demonstrated excision of the loxP-flanked allele in Rosa26-imCherry rats via activation of mCherry expression in the presence of Cre recombinase. This newly established Rosa26-imCherry rat strain represents a useful tool to facilitate Cre-expression pattern determination and tracing experiments. © 2017 Federation of European Biochemical Societies.

  8. CDC Vital Signs: Making Health Care Safer -- Stop Infections from Lethal CRE Germs Now

    Science.gov (United States)

    ... Program (EIP). Providing CRE outbreak support such as staff expertise, prevention guidelines, tools, and lab testing to states and facilities. Developing detection methods and prevention programs to control CRE. CDC's "Detect and Protect" effort supports regional ...

  9. Preserved dopaminergic homeostasis and dopamine-related behaviour in hemizygous TH-Cre mice

    DEFF Research Database (Denmark)

    Thomsen, Annika Højrup Runegaard; Jensen, Kathrine L; Fitzpatrick, Ciarán M

    2017-01-01

    assessment of the dopaminergic system in hemizygous tyrosine hydroxylase (TH)-Cre mice in comparison to wild-type (WT) controls. Our data show that TH-Cre mice display preserved dopaminergic homeostasis with unaltered levels of TH and dopamine as well as unaffected dopamine turnover in striatum. TH-Cre mice...

  10. Visualisation of Kiss1 Neurone Distribution Using a Kiss1-CRE Transgenic Mouse.

    Science.gov (United States)

    Yeo, S-H; Kyle, V; Morris, P G; Jackman, S; Sinnett-Smith, L C; Schacker, M; Chen, C; Colledge, W H

    2016-11-01

    Kisspeptin neuropeptides are encoded by the Kiss1 gene and play a critical role in the regulation of the mammalian reproductive axis. Kiss1 neurones are found in two locations in the rodent hypothalamus: one in the arcuate nucleus (ARC) and another in the RP3V region, which includes the anteroventral periventricular nucleus (AVPV). Detailed mapping of the fibre distribution of Kiss1 neurones will help with our understanding of the action of these neurones in other regions of the brain. We have generated a transgenic mouse in which the Kiss1 coding region is disrupted by a CRE-GFP transgene so that expression of the CRE recombinase protein is driven from the Kiss1 promoter. As expected, mutant mice of both sexes are sterile with hypogonadotrophic hypogonadism and do not show the normal rise in luteinising hormone after gonadectomy. Mutant female mice do not develop mature Graafian follicles or form corpora lutea consistent with ovulatory failure. Mutant male mice have low blood testosterone levels and impaired spermatogenesis beyond the meiosis stage. Breeding Kiss-CRE heterozygous mice with CRE-activated tdTomato reporter mice allows fluorescence visualisation of Kiss1 neurones in brain slices. Approximately 80-90% of tdTomato positive neurones in the ARC were co-labelled with kisspeptin and expression of tdTomato in the AVPV region was sexually dimorphic, with higher expression in females than males. A small number of tdTomato-labelled neurones was also found in other locations, including the lateral septum, the anterodorsal preoptic nucleus, the amygdala, the dorsomedial and ventromedial hypothalamic nuclei, the periaquaductal grey, and the mammillary nucleus. Three dimensional visualisation of Kiss1 neurones and fibres by CLARITY processing of whole brains showed an increase in ARC expression during puberty and higher numbers of Kiss1 neurones in the caudal region of the ARC compared to the rostral region. ARC Kiss1 neurones sent fibre projections to several

  11. Consultation organised by CRE and CREG on the France-Belgium interconnection; Consultation organisee par la CRE et la CREG relative a la gestion de l'interconnexion France-Belgique

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-07-01

    In June 2002, RTE and ELIA put forward a proposal to CRE and CREG for setting up a new joint mechanism for allocating capacity on the Franco-Belgian border. As it contained a number of improvements, the regulators authorised its use as from July 1, 2002. At the same time, they announced that users would be consulted during Autumn 2002 on the way RTE's and ELIA's commitments had been reflected in contractual terms, the transparency of the allocation process, the new mechanism's overall efficiency and the possibility of allocating capacity on an annual basis. CRE and CREG ask everybody concerned by electricity transfers between France and Belgium to give his or her opinion on the way in which the interconnections new operating conditions contribute at present, or could contribute in the future, to developing fair and efficient competition on European Union electricity markets. (author)

  12. The Role of Shame, Anger, and Affect Regulation in Men's Perpetration of Psychological Abuse in Dating Relationships

    Science.gov (United States)

    Harper, Felicity W. K.; Austin, Amanda G.; Cercone, Jennifer J.; Arias, Ileana

    2005-01-01

    This study determines the relationships between shame, anger, and men's perpetration of psychological abuse in dating relationships. The authors' hypothesize the connection between shame proneness and men's use of psychological abuse with a dating partner, with anger's mediating in this relationship. In addition, the authors' hypothesize that…

  13. CcpA represses the expression of the divergent cit operons of Enterococcus faecalis through multiple cre sites.

    Science.gov (United States)

    Suárez, Cristian A; Blancato, Víctor S; Poncet, Sandrine; Deutscher, Josef; Magni, Christian

    2011-10-11

    In Enterococcus faecalis the genes encoding the enzymes involved in citrate metabolism are organized in two divergent operons, citHO and oadHDB-citCDEFX-oadA-citMG (citCL locus). Expression of both operons is specifically activated by adding citrate to the medium. This activation is mediated by binding of the GntR-like transcriptional regulator (CitO) to the cis-acting sequences located in the cit intergenic region. Early studies indicated that citrate and glucose could not be co-metabolized suggesting some form of catabolite repression, however the molecular mechanism remained unknown. In this study, we observed that the citHO promoter is repressed in the presence of sugars transported by the Phosphoenolpyruvate:carbohydrate Phosphotranserase System (PTS sugars). This result strongly suggested that Carbon Catabolic Repression (CCR) impedes the expression of the activator CitO and the subsequent induction of the cit pathway. In fact, we demonstrate that CCR is acting on both promoters. It is partially relieved in a ccpA-deficient E. faecalis strain indicating that a CcpA-independent mechanism is also involved in regulation of the two operons. Furthermore, sequence analysis of the citH/oadH intergenic region revealed the presence of three putative catabolite responsive elements (cre). We found that they are all active and able to bind the CcpA/P-Ser-HPr complex, which downregulates the expression of the cit operons. Systematic mutation of the CcpA/P-Ser-HPr binding sites revealed that cre1 and cre2 contribute to citHO repression, while cre3 is involved in CCR of citCL. In conclusion, our study establishes that expression of the cit operons in E. faecalis is controlled by CCR via CcpA-dependent and -independent mechanisms.

  14. A Nestin-cre transgenic mouse is insufficient for recombination in early embryonic neural progenitors

    Directory of Open Access Journals (Sweden)

    Huixuan Liang

    2012-09-01

    Nestin-cre transgenic mice have been widely used to direct recombination to neural stem cells (NSCs and intermediate neural progenitor cells (NPCs. Here we report that a readily utilized, and the only commercially available, Nestin-cre line is insufficient for directing recombination in early embryonic NSCs and NPCs. Analysis of recombination efficiency in multiple cre-dependent reporters and a genetic mosaic line revealed consistent temporal and spatial patterns of recombination in NSCs and NPCs. For comparison we utilized a knock-in Emx1cre line and found robust recombination in NSCs and NPCs in ventricular and subventricular zones of the cerebral cortices as early as embryonic day 12.5. In addition we found that the rate of Nestin-cre driven recombination only reaches sufficiently high levels in NSCs and NPCs during late embryonic and early postnatal periods. These findings are important when commercially available cre lines are considered for directing recombination to embryonic NSCs and NPCs.

  15. Tie-1-directed expression of Cre recombinase in endothelial cells of embryoid bodies and transgenic mice

    DEFF Research Database (Denmark)

    Gustafsson, E; Brakebusch, C; Hietanen, K

    2001-01-01

    Tissue-specific gene inactivation using the Cre-loxP system has become an important tool to unravel functions of genes when the conventional null mutation is lethal. We report here the generation of a transgenic mouse line expressing Cre recombinase in endothelial cells. In order to avoid...... the production and screening of multiple transgenic lines we used embryonic stem cell and embryoid body technology to identify recombinant embryonic stem cell clones with high, endothelial-specific Cre activity. One embryonic stem cell clone that showed high Cre activity in endothelial cells was used to generate...... germline chimeras. The in vivo efficiency and specificity of the transgenic Cre was analysed by intercrossing the tie-1-Cre line with the ROSA26R reporter mice. At initial stages of vascular formation (E8-9), LacZ staining was detected in almost all cells of the forming vasculature. Between E10 and birth...

  16. Generation of ER{alpha}-floxed and knockout mice using the Cre/LoxP system

    Energy Technology Data Exchange (ETDEWEB)

    Antonson, P., E-mail: per.antonson@ki.se [Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 83 Huddinge (Sweden); Omoto, Y.; Humire, P. [Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 83 Huddinge (Sweden); Gustafsson, J.-A. [Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 83 Huddinge (Sweden); Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204 (United States)

    2012-08-10

    Highlights: Black-Right-Pointing-Pointer ER{alpha} floxed and knockout mice were generated. Black-Right-Pointing-Pointer Disruption of the ER{alpha} gene results in sterility in both male and female mice. Black-Right-Pointing-Pointer ER{alpha}{sup -/-} mice have ovaries with hemorrhagic follicles and hypoplastic uterus. Black-Right-Pointing-Pointer Female ER{alpha}{sup -/-} mice develop obesity. -- Abstract: Estrogen receptor alpha (ER{alpha}) is a nuclear receptor that regulates a range of physiological processes in response to estrogens. In order to study its biological role, we generated a floxed ER{alpha} mouse line that can be used to knock out ER{alpha} in selected tissues by using the Cre/LoxP system. In this study, we established a new ER{alpha} knockout mouse line by crossing the floxed ER{alpha} mice with Cre deleter mice. Here we show that genetic disruption of the ER{alpha} gene in all tissues results in sterility in both male and female mice. Histological examination of uterus and ovaries revealed a dramatically atrophic uterus and hemorrhagic cysts in the ovary. These results suggest that infertility in female mice is the result of functional defects of the reproductive tract. Moreover, female knockout mice are hyperglycemic, develop obesity and at the age of 4 months the body weight of these mice was more than 20% higher compared to wild type littermates and this difference increased over time. Our results demonstrate that ER{alpha} is necessary for reproductive tract development and has important functions as a regulator of metabolism in females.

  17. A pink mouse reports the switch from red to green fluorescence upon Cre-mediated recombination

    OpenAIRE

    Hartwich Heiner; Satheesh Somisetty V; Nothwang Hans

    2012-01-01

    Abstract Background Targeted genetic modification in the mouse becomes increasingly important in biomedical and basic science. This goal is most often achieved by use of the Cre/loxP system and numerous Cre-driver mouse lines are currently generated. Their initial characterization requires reporter mouse lines to study the in vivo spatiotemporal activity of Cre. Findings Here, we report a dual fluorescence reporter mouse line, which switches expression from the red fluorescent protein mCherry...

  18. Drug Pricing Program Ceiling Price and Manufacturer Civil Monetary Penalties Regulation. Final rule; further delay of effective date.

    Science.gov (United States)

    2017-09-29

    The Health Resources and Services Administration (HRSA) administers section 340B of the Public Health Service Act (PHSA), known as the "340B Drug Pricing Program" or the "340B Program." HRSA published a final rule on January 5, 2017, that set forth the calculation of the ceiling price and application of civil monetary penalties. The final rule applied to all drug manufacturers that are required to make their drugs available to covered entities under the 340B Program. On August 21, 2017, HHS solicited comments on further delaying the effective date of the January 5, 2017, final rule to July 1, 2018 (82 FR 39553). HHS proposed this action to allow a more deliberate process of considering alternative and supplemental regulatory provisions and to allow for sufficient time for additional rulemaking. After consideration of the comments received on the proposed rule, HHS is delaying the effective date of the January 5, 2017, final rule, to July 1, 2018.

  19. 340B Drug Pricing Program Ceiling Price and Manufacturer Civil Monetary Penalties Regulation. Final rule; further delay of effective date.

    Science.gov (United States)

    2017-05-19

    The Health Resources and Services Administration (HRSA) administers section 340B of the Public Health Service Act (PHSA), referred to as the "340B Drug Pricing Program" or the "340B Program." HRSA published a final rule on January 5, 2017, that set forth the calculation of the ceiling price and application of civil monetary penalties. The final rule applied to all drug manufacturers that are required to make their drugs available to covered entities under the 340B Program. In accordance with a January 20, 2017, memorandum from the Assistant to the President and Chief of Staff, entitled "Regulatory Freeze Pending Review," HRSA issued an interim final rule that delayed the effective date of the final rule published in the Federal Register (82 FR 1210, (January 5, 2017)) to May 22, 2017. HHS invited commenters to provide their views on whether a longer delay of the effective date to October 1, 2017, would be more appropriate. After consideration of the comments received on the interim final rule, HHS is delaying the effective date of the January 5, 2017 final rule, to October 1, 2017.

  20. A CaMK cascade activates CRE-mediated transcription in neurons of Caenorhabditis elegans

    Science.gov (United States)

    Kimura, Yoshishige; Corcoran, Ethan E.; Eto, Koh; Gengyo-Ando, Keiko; Muramatsu, Masa-aki; Kobayashi, Ryoji; Freedman, Jonathan H.; Mitani, Shohei; Hagiwara, Masatoshi; Means, Anthony R.; Tokumitsu, Hiroshi

    2002-01-01

    Calcium (Ca2+) signals regulate a diverse set of cellular responses, from proliferation to muscular contraction and neuro-endocrine secretion. The ubiquitous Ca2+ sensor, calmodulin (CaM), translates changes in local intracellular Ca2+ concentrations into changes in enzyme activities. Among its targets, the Ca2+/CaM-dependent protein kinases I and IV (CaMKs) are capable of transducing intraneuronal signals, and these kinases are implicated in neuronal gene regulation that mediates synaptic plasticity in mammals. Recently, the cyclic AMP response element binding protein (CREB) has been proposed as a target for a CaMK cascade involving not only CaMKI or CaMKIV, but also an upstream kinase kinase that is also CaM regulated (CaMKK). Here, we report that all components of this pathway are coexpressed in head neurons of Caenorhabditis elegans. Utilizing a transgenic approach to visualize CREB-dependent transcription in vivo, we show that this CaMK cascade regulates CRE-mediated transcription in a subset of head neurons in living nematodes. PMID:12231504

  1. Synthesis of the investment program proposals submitted by RTE to CRE's approval; Synthese des propositions de programme d'investissement soumises par RTE a l'approbation de la CRE

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    Conformably to the French law from February 10, 2000, the French commission of electricity regulation (CRE) must proceed to the examination of the proposals submitted by the electricity transportation network (RTE) for the approval of its 2002 investments program devoted to the power grid. The main lines of the proposals submitted by RTE are described in this document: 1 - strategy of grid development (methodology, interconnections), 2 - methods of evaluation and selection of regional projects (replacement and development projects), 3 - main projects retained (main transportation network and interconnections, regional networks, remote control and safety systems), 4 - program financing plan. (J.S.)

  2. Improved α-Amylase Production by Dephosphorylation Mutation of CreD, an Arrestin-Like Protein Required for Glucose-Induced Endocytosis of Maltose Permease and Carbon Catabolite Derepression in Aspergillus oryzae.

    Science.gov (United States)

    Tanaka, Mizuki; Hiramoto, Tetsuya; Tada, Hinako; Shintani, Takahiro; Gomi, Katsuya

    2017-07-01

    Aspergillus oryzae produces copious amount of amylolytic enzymes, and MalP, a major maltose permease, is required for the expression of amylase-encoding genes. The expression of these genes is strongly repressed by carbon catabolite repression (CCR) in the presence of glucose. MalP is transported from the plasma membrane to the vacuole by endocytosis, which requires the homolog of E6-AP carboxyl terminus ubiquitin ligase HulA, an ortholog of yeast Rsp5. In yeast, arrestin-like proteins mediate endocytosis as adaptors of Rsp5 and transporters. In the present study, we examined the involvement of CreD, an arrestin-like protein, in glucose-induced MalP endocytosis and CCR of amylase-encoding genes. Deletion of creD inhibited the glucose-induced endocytosis of MalP, and CreD showed physical interaction with HulA. Phosphorylation of CreD was detected by Western blotting, and two serine residues were determined as the putative phosphorylation sites. However, the phosphorylation state of the serine residues did not regulate MalP endocytosis and its interaction with HulA. Although α-amylase production was significantly repressed by creD deletion, both phosphorylation and dephosphorylation mimics of CreD had a negligible effect on α-amylase activity. Interestingly, dephosphorylation of CreD was required for CCR relief of amylase genes that was triggered by disruption of the deubiquitinating enzyme-encoding gene creB The α-amylase activity of the creB mutant was 1.6-fold higher than that of the wild type, and the dephosphorylation mimic of CreD further improved the α-amylase activity by 2.6-fold. These results indicate that a combination of the dephosphorylation mutation of CreD and creB disruption increased the production of amylolytic enzymes in A. oryzae IMPORTANCE In eukaryotes, glucose induces carbon catabolite repression (CCR) and proteolytic degradation of plasma membrane transporters via endocytosis. Glucose-induced endocytosis of transporters is mediated by

  3. Lactation Defect in a Widely Used MMTV-Cre Transgenic Line of Mice

    Science.gov (United States)

    Yuan, Taichang; Wang, Yongping; Pao, Lily; Anderson, Steve M.; Gu, Haihua

    2011-01-01

    Background MMTV-Cre mouse lines have played important roles in our understanding about the functions of numerous genes in mouse mammary epithelial cells during mammary gland development and tumorigenesis. However, numerous studies have not included MMTV-Cre mice as controls, and many investigators have not indicated which of the different MMTV-Cre founder lines were used in their studies. Here, we describe a lactation defect that severely limits the use of one of the most commonly used MMTV-Cre founder lines. Methodology/Principal Findings To explore the role of protein tyrosine phosphatase Shp1 in mammary gland development, mice bearing the floxed Shp1 gene were crossed with MMTV-Cre mice and mammary gland development was examined by histological and biochemical techniques, while lactation competency was assessed by monitoring pup growth. Surprisingly, both the Shp1fl/+;MMTV-Cre and MMTV-Cre female mice displayed a severe lactation defect when compared to the Shp1 fl/+ control mice. Histological and biochemical analyses reveal that female mice expressing the MMTV-Cre transgene, either alone or in combination with floxed genes, exhibit defects in lobuloalveolar expansion, presence of large cytoplasmic lipid droplets in luminal alveolar epithelial cells postpartum, and precocious induction of involution. Using a PCR-based genotyping method, the three different founder lines can be distinguished, and we determined that the MMTV-Cre line A, the most widely used MMTV-Cre founder line, exhibits a profound lactation defect that limits its use in studies on mammary gland development. Conclusions/Significance The identification of a lactation defect in the MMTV-Cre line A mice indicates that investigators must use MMTV-Cre alone mice as control in studies that utilize Cre recombinase to excise genes of interest from mammary epithelial cells. Our results also suggest that previous results obtained in studies using the MMTV-Cre line A line should be re-evaluated if the

  4. Tg(Th-CreFI172Gsat (Th-Cre defines neurons that are required for full hypercapnic and hypoxic reflexes

    Directory of Open Access Journals (Sweden)

    Jenny J. Sun

    2017-08-01

    Full Text Available The catecholaminergic (CA system has been implicated in many facets of breathing control and offers an important target to better comprehend the underlying etiologies of both developmental and adult respiratory pathophysiologies. Here, we used a noninvasive DREADD-based pharmacogenetic approach to acutely perturb Tg(Th-CreFI172Gsat (Th-Cre-defined neurons in awake and unrestrained mice in an attempt to characterize CA function in breathing. We report that clozapine-N-oxide (CNO-DREADD-mediated inhibition of Th-Cre-defined neurons results in blunted ventilatory responses under respiratory challenge. Under a hypercapnic challenge (5% CO2/21% O2/74% N2, perturbation of Th-Cre neurons results in reduced fR, and . Under a hypoxic challenge (10% O2/90% N2, we saw reduced fR, and , in addition to instability in both interbreath interval and tidal volume, resulting in a Cheyne-Stokes-like respiratory pattern. These findings demonstrate the necessity of Th-Cre-defined neurons for the hypercapnic and hypoxic ventilatory responses and breathing stability during hypoxia. However, given the expanded non-CA expression domains of the Tg(Th-CreFI172Gsat mouse line found in the brainstem, full phenotypic effect cannot be assigned solely to CA neurons. Nonetheless, this work identifies a key respiratory population that may lead to further insights into the circuitry that maintains respiratory stability in the face of homeostatic challenges.

  5. Generation of Shox2-Cre allele for tissue specific manipulation of genes in the developing heart, palate, and limb

    OpenAIRE

    Sun, Cheng; Zhang, Tao; Liu, Chao; Gu, Shuping; Chen, YiPing

    2013-01-01

    Shox2 is expressed in several developing organs in a tissue specific manner in both mice and humans, including the heart, palate, limb, and nervous system. To better understand the spatial and temporal expression patterns of Shox2 and to systematically dissect the genetic cascade regulated by Shox2, we created Shox2-LacZ and Shox2-Cre knock-in mouse lines. We show that the Shox2-LacZ allele expresses beta-galactosidase reporter gene in a fashion that recapitulates the endogenous Shox2 express...

  6. Cytokeratin 19 promoter directs the expression of Cre recombinase in various epithelia of transgenic mice.

    Science.gov (United States)

    Zhao, Gui-Feng; Zhao, Shuang; Liu, Jia-Jie; Wu, Ji-Cheng; He, Hao-Yu; Ding, Xiao-Qing; Yu, Xue-Wen; Huang, Ke-Qiang; Li, Zhi-Jie; Zheng, Hua-Chuan

    2017-03-14

    Cytokeratin 19 (K19) is expressed in various differentiated cells, including gastric, intestinal and bronchial epithelial cells, and liver duct cells. Here, we generated a transgenic mouse line, K19-Cre, in which the expression of Cre recombinase was controlled by the promoter of K19. To test the tissue distribution and excision activity of Cre recombinase, K19-Cre transgenic mice were bred with Rosa26 reporter strain and a mouse strain that carries PTEN conditional alleles (PTENLoxp/Loxp). At mRNA level, Cre was strongly expressed in the stomach, lung and intestine, while in stomach, lung, and liver at protein level. The immunoreactivity to Cre was strongly observed the cytoplasm of gastric, bronchial and intestinal epithelial cells. Cre activity was detectable in gastric, bronchial and intestinal epithelial cells, according to LacZ staining. In K19-Cre/PTEN Loxp/Loxp mice, PTEN was abrogated in stomach, intestine, lung, liver and breast, the former two of which were verified by in situ PCR. There appeared breast cancer with PTEN loss. These data suggest that K19 promoter may be a useful tool to study the pathophysiological functions of cytokeratin 19-positive cells, especially gastrointestinal epithelial cells. Cell specificity of neoplasia is not completely attributable to the cell-specific expression of oncogenes and cell-specific loss of tumor suppressor genes.

  7. Promiscuous recombination of LoxP alleles during gametogenesis in cornea Cre driver mice

    Science.gov (United States)

    Weng, Daniel Y.; Zhang, Yujin; Hayashi, Yasuhito; Kuan, Chia-Yi; Liu, Chia-Yang; Babcock, George; Weng, Wei-Lan; Schwemberger, Sandy

    2008-01-01

    Purpose To examine whether promiscuous Cre/LoxP recombination happens during gametogenesis in double transgenic mice carrying LoxP modified alleles and Cre transgene driven by tissue-specific promoter outside the gonads of adult mice. Methods Cre driver mice were crossbred with reporter mouse lines (e.g., ZEG and Rosa26R) to obtain Cre/ZEG and Cre/Rosa26R double transgenic mice. The frequency of promiscuous LoxP/Cre recombination was determined by the expression of second reporter genes in the offspring of double transgenic mice. Results The frequency of promiscuous LoxP/Cre recombination varied in different lines of Cre driver mice and in the sex of the same driver mice with higher penetrance in male than in female double transgenic mice. Polymerase chain reaction (PCR) and recombination analysis demonstrate that the recombination of floxed allele occurs during the transition from spermatogonia (diploid) to primary spermatocyte (tetraploid) in the testis. Thereby, target-floxed allele(s) may be ubiquitously ablated in experimental animals intended for tissue-specific gene deletion. Conclusions Gametogenesis-associated recombination should always be examined in tissue-specific gene ablation studies. PMID:18385792

  8. Effects of CreERT2, 4-OH Tamoxifen, and Gender on CFU-F Assays.

    Directory of Open Access Journals (Sweden)

    Sophie L McHaffie

    Full Text Available Gene function in stem cell maintenance is often tested by inducing deletion via the Cre-loxP system. However, controls for Cre and other variables are frequently not included. Here we show that when cultured in the presence of 4-OH tamoxifen, bone and marrow cells containing the CreERT2 construct have a reduced colony forming ability. Inactive CreERT2 recombinase, however, has the opposite effect. Young female marrow cells containing the inactive CreERT2 construct grew more colonies than cells lacking the construct altogether. Young female control marrow cells (i.e., negative for CreERT2 also produced significantly greater colony numbers when cultured with 4-OH tamoxifen, compared with the ethanol vehicle control. In conclusion, we report that the use of the Cre-loxP system is inadvisable in combination with CFU-F assays, and that appropriate controls should be in place to extend the future use of Cre-loxP in alternate assays.

  9. 77 FR 25070 - Special Local Regulation for Marine Events; Temporary Change of Dates for Recurring Marine Events...

    Science.gov (United States)

    2012-04-27

    ..., swim races and holiday parades. For a description of the geographical area of each Coast Guard Sector... the vicinity of Ocean City, Maryland from 11 a.m. until 5 p.m. on May 13, 2012. If you think that your... think it qualifies and how and to what degree this rule would economically affect it. This regulation...

  10. 76 FR 1564 - Special Local Regulation for Marine Event; Temporary Change of Dates for Recurring Marine Event...

    Science.gov (United States)

    2011-01-11

    ... Seminar,'' sponsored by the U.S. Naval Academy, on the waters of the Severn River at Annapolis, MD. The.... Naval Academy, on the waters of the Severn River at Annapolis, MD. The regulation at 33 CFR 100.501 is..., 2011. The U.S. Naval Academy, which is the sponsor for this event, intends to hold this event annually...

  11. Dating Techniques

    Indian Academy of Sciences (India)

    Absolute dating technique (such as stylistic affiliation, association with datable deposits, amino acid study of protein in pigments, and direct radiocarbon dating of the organic fraction of pigments or desert varnish).

  12. A CRE/AP-1-like motif is essential for induced syncytin-2 expression and fusion in human trophoblast-like model.

    Directory of Open Access Journals (Sweden)

    Chirine Toufaily

    Full Text Available Syncytin-2 is encoded by the envelope gene of Endogenous Retrovirus-FRD (ERVFRD-1 and plays a critical role in fusion of placental trophoblasts leading to the formation of the multinucleated syncytiotrophoblast. Its expression is consequently regulated in a strict manner. In the present study, we have identified a forskolin-responsive region located between positions -300 to -150 in the Syncytin-2 promoter region. This 150 bp region in the context of a minimal promoter mediated an 80-fold induction of promoter activity following forskolin stimulation. EMSA analyses with competition experiments with nuclear extracts from forskolin-stimulated BeWo cells demonstrated that the -211 to -177 region specifically bound two forskolin-induced complexes, one of them containing a CRE/AP-1-like motif. Site-directed mutagenesis of the CRE/AP-1 binding site in the context of the Syncytin-2 promoter or a heterologous promoter showed that this motif was mostly essential for forskolin-induced promoter activity. Transfection experiments with dominant negative mutants and constitutively activated CREB expression vectors in addition to Chromatin Immunoprecipitation suggested that a CREB family member, CREB2 was binding and acting through the CRE/AP-1 motif. We further demonstrated the binding of JunD to this same motif. Similar to forskolin and soluble cAMP, CREB2 and JunD overexpression induced Syncytin-2 promoter activity in a CRE/AP-1-dependent manner and Syncytin-2 expression. In addition, BeWo cell fusion was induced by both CREB2 and JunD overexpression, while being repressed following silencing of either gene. These results thereby demonstrate that induced expression of Syncytin-2 is highly dependent on the interaction of bZIP-containing transcription factors to a CRE/AP-1 motif and that this element is important for the regulation of Syncytin-2 expression, which results in the formation of the peripheral syncytiotrophoblast layer.

  13. Cell type-specific manipulation with GFP-dependent Cre recombinase.

    Science.gov (United States)

    Tang, Jonathan C Y; Rudolph, Stephanie; Dhande, Onkar S; Abraira, Victoria E; Choi, Seungwon; Lapan, Sylvain W; Drew, Iain R; Drokhlyansky, Eugene; Huberman, Andrew D; Regehr, Wade G; Cepko, Constance L

    2015-09-01

    There are many transgenic GFP reporter lines that allow the visualization of specific populations of cells. Using such lines for functional studies requires a method that transforms GFP into a molecule that enables genetic manipulation. We developed a method that exploits GFP for gene manipulation, Cre recombinase dependent on GFP (CRE-DOG), a split component system that uses GFP and its derivatives to directly induce Cre/loxP recombination. Using plasmid electroporation and AAV viral vectors, we delivered CRE-DOG to multiple GFP mouse lines, which led to effective recombination selectively in GFP-labeled cells. Furthermore, CRE-DOG enabled optogenetic control of these neurons. Beyond providing a new set of tools for manipulation of gene expression selectively in GFP(+) cells, we found that GFP can be used to reconstitute the activity of a protein not known to have a modular structure, suggesting that this strategy might be applicable to a wide range of proteins.

  14. Dual fluorescent reporter pig for Cre recombination: transgene placement at the ROSA26 locus.

    Directory of Open Access Journals (Sweden)

    Shun Li

    Full Text Available We are extending the Cre/loxP site-specific recombination system to pigs, focussing on conditional and tissue-specific expression of oncogenic mutations to model human cancers. Identifying the location, pattern and extent of Cre recombination in vivo is an important aspect of this technology. Here we report pigs with a dual fluorochrome cassette under the control of the strong CAG promoter that switches expression after Cre-recombination, from membrane-targeted tandem dimer Tomato to membrane-targeted green fluorescent protein. The reporter cassette was placed at the porcine ROSA26 locus by conventional gene targeting using primary mesenchymal stem cells, and animals generated by nuclear transfer. Gene targeting efficiency was high, and analysis of foetal organs and primary cells indicated that the reporter is highly expressed and functional. Cre reporter pigs will provide a multipurpose indicator of Cre recombinase activity, an important new tool for the rapidly expanding field of porcine genetic modification.

  15. Radiocarbon Dating

    Energy Technology Data Exchange (ETDEWEB)

    Buchholz, B A

    2007-12-20

    Radiocarbon dating can be used to determine the age of objects that contain components that were once alive. In the case of human remains, a radiocarbon date can distinguish between a crime scene and an archeological site. Documents, museum artifacts and art objects can be dated to determine if their age is correct for the historical context. A radiocarbon date does not confirm authenticity, but it can help identify a forgery.

  16. Dating Violence

    Science.gov (United States)

    Stader, David L.

    2011-01-01

    Dating violence is a form of student-on-student victimization and is a serious school safety issue. Research indicates that at a minimum, 10 percent of high school students are victims of dating violence in one form or another. Among female high school students that date, some data indicate that as many as 30 percent may be victims of dating…

  17. Generation of a transgenic mouse for colorectal cancer research with intestinal cre expression limited to the large intestine

    National Research Council Canada - National Science Library

    Xue, Yingben; Johnson, Robert; Desmet, Marsha; Snyder, Paul W; Fleet, James C

    2010-01-01

    .... We sought to create a transgenic mouse with Cre recombinase (Cre) expression limited to the epithelial cells of the large intestine and used this model to study colon cancer driven by adenomatosis polyposis coli (APC) gene inactivation...

  18. GFAP-Cre-mediated transgenic activation of Bmi1 results in pituitary tumors.

    Directory of Open Access Journals (Sweden)

    Bart A Westerman

    Full Text Available Bmi1 is a member of the polycomb repressive complex 1 and plays different roles during embryonic development, depending on the developmental context. Bmi1 over expression is observed in many types of cancer, including tumors of astroglial and neural origin. Although genetic depletion of Bmi1 has been described to result in tumor inhibitory effects partly through INK4A/Arf mediated senescence and apoptosis and also through INK4A/Arf independent effects, it has not been proven that Bmi1 can be causally involved in the formation of these tumors. To see whether this is the case, we developed two conditional Bmi1 transgenic models that were crossed with GFAP-Cre mice to activate transgenic expression in neural and glial lineages. We show here that these mice generate intermediate and anterior lobe pituitary tumors that are positive for ACTH and beta-endorphin. Combined transgenic expression of Bmi1 together with conditional loss of Rb resulted in pituitary tumors but was insufficient to induce medulloblastoma therefore indicating that the oncogenic function of Bmi1 depends on regulation of p16(INK4A/Rb rather than on regulation of p19(ARF/p53. Human pituitary adenomas show Bmi1 overexpression in over 50% of the cases, which indicates that Bmi1 could be causally involved in formation of these tumors similarly as in our mouse model.

  19. The Pax3-Cre transgene exhibits a rostrocaudal gradient of expression in the skeletal muscle lineage.

    Science.gov (United States)

    Jarad, George; Miner, Jeffrey H

    2009-01-01

    Pax3-Cre (P3Pro-Cre) transgenic mice have been used for conditional gene deletion and/or lineage tracing in derivatives of neural crest, neural tube, metanephric mesenchyme, and ureteric mesenchyme. However, the extent of its expression in skeletal muscle has not been reported. We investigated the expression of P3Pro-Cre in the skeletal muscle lineage using the R26R reporter and found an unexpected rostrocaudal gradient of expression. By X-gal staining, head, neck, forelimb, diaphragm, and most of the chest wall muscles did not show evidence of Cre expression, whereas all muscle groups posterior of the diaphragm stained blue. Intercostal muscles exhibited a rostrocaudal gradient of staining. The consistency of this expression pattern was demonstrated by using P3Pro-Cre to mutate a conditional dystroglycan allele. The result was loss of dystroglycan from caudal muscles, which exhibited the histological signs of muscle fiber injury and regeneration characteristic of muscular dystrophy. The lack of dystroglycan in regenerating myofibers suggests that the P3Pro-Cre transgene is active in satellite cells and/or in their precursors. In contrast, rostral muscles, including feeding and breathing muscles, maintained dystroglycan expression and were spared from disease. Accordingly, the mutants were viable for over a year. Its unique gradient of activity makes the P3Pro-Cre transgene a previously unappreciated yet powerful tool for manipulating gene expression in skeletal muscle and its precursors.

  20. Somatostatin-IRES-Cre Mice: Between Knockout and Wild-Type?

    Directory of Open Access Journals (Sweden)

    Cécile Viollet

    2017-06-01

    Full Text Available The neuropeptide somatostatin (SOM is widely expressed in rodent brain and somatostatin-IRES-Cre (SOM-cre mouse strains are increasingly used to unravel the physiology of SOM-containing neurons. However, while knock-in targeting strategy greatly improves Cre-Lox system accuracy, recent reports have shown that genomic insertion of Cre construct per se can markedly affect physiological function. We show that Cre transgene insertion into the 3′UTR of the somatostatin gene leads to the selective and massive depletion of endogenous SOM in all tested brain regions. It also strongly impacts SOM-related neuroendocrine responses in a similar manner to what has been reported for SST KO mice: increased corticosterone levels after 30-min restraint stress, decreased amplitude and regularity of ultradian growth hormone secretory patterns accompanied by changes in sexually dimorphic liver gene expression (serpina1, Cyp2b9, Cyp2a4, Cyp2d9, and Cyp7b1. In addition to demonstrating the need for examination of the consequences of Cre transgenesis, these results also reveal how this SOM-cre strain may be a useful tool in studying the functional consequences of moderate to low SOM levels as reported in neurological and psychiatric disorders.

  1. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse.

    Science.gov (United States)

    Caldeira, Vanessa; Dougherty, Kimberly J; Borgius, Lotta; Kiehn, Ole

    2017-01-27

    Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype and progenitor domain, but does not overlap with the Shox2 non-V2a population. We also show that Hb9::Cre-derived INs include the comparatively small medial population of INs which continues to express Hb9 postnatally. When excitatory neurotransmission is selectively blocked by deleting Vglut2 from Hb9::Cre-derived INs, there is no difference in left-right and/or flexor-extensor phasing between these cords and controls, suggesting that excitatory Hb9::Cre-derived INs do not affect pattern generation. In contrast, the frequencies of locomotor activity are significantly lower in cords from Hb9::Cre-Vglut2(Δ/Δ) mice than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion.

  2. Endogenous n-3 Polyunsaturated Fatty Acids Delay Progression of Pancreatic Ductal Adenocarcinoma in Fat-1-p48Cre/+-LSL-KrasG12D/+ Mice

    Directory of Open Access Journals (Sweden)

    Altaf Mohammed

    2012-12-01

    Full Text Available Preclinical studies suggest that diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs may be beneficial for prevention of pancreatic cancer. Nutritional intervention studies are often complex, and there is no clear evidence, without potential confounding factors, on whether conversion of n-6 PUFAs to n-3 PUFAs in pancreatic tissues would provide protection. Experiments were designed using n-3 fatty acid desaturase (Fat-1 transgenic mice, which can convert n-6 PUFA to n-3 FAs endogenously, to determine the impact of n-3 PUFAs on pancreatic intraepithelial neoplasms (PanINs and their progression to pancreatic ductal adenocarcinoma (PDAC. Six-weekold female p48Cre/+-LSL-KrasG12D/+ andcompoundFat-1-p48Cre/+-LSL-KrasG12D/+ mice were fed (AIN-76A diets containing 10% safflower oil for 35 weeks. Pancreata were evaluated histopathologically for PanINs and PDAC. Results showed a dramatic reduction in incidence of PDAC (84%; P 85%; P < .05–0.01 in pancreas of compound transgenic mice than in those of p48Cre/+-LSL-KrasG12D/+ mice. Molecular analysis of the pancreas showed a significant down-regulation of proliferating cell nuclear antigen, cyclooxygenase-2, 5-lipoxygenase (5-LOX, 5-LOX-activating protein, Bcl-2, and cyclin D1 expression levels in Fat-1-p48Cre/+-LSL-KrasG12D/+ mice compared to p48Cre/+-LSL-KrasG12D/+ mice. These data highlight the promise of dietary n-3 FAs for chemoprevention of pancreatic cancer in high-risk individuals.

  3. date extended

    Indian Academy of Sciences (India)

    C A L AN DER OF EVENTS. Date of issue of bid document : 2016 September 21. Extended Due date and Time for Receipt of Tender : Up to 2016 October 17, Time 13:00 Hrs. Date and Time of opening of bid : 2016 October 17, Time 15:00 Hrs. Cost of Bid Document : Rs. 100/- only (Non-refundable). Earnest Money Deposit ...

  4. Physiological characterisation of recombinant Aspergillus nidulans strains with different creA genotypes expressing A-oryzae alpha-amylase

    DEFF Research Database (Denmark)

    Agger, Teit; Petersen, J.B.; O'Connor, S.M.

    2002-01-01

    The physiology of three strains of Aspergillus nidulans was examined-a creA deletion strain, a wild type creA genotype and a strain containing extra copies of the creA gene, all producing Aspergillus oryzae alpha-amylase. The strains were cultured in batch and continuous cultivations...

  5. Novel migrating mouse neural crest cell assay system utilizing P0-Cre/EGFP fluorescent time-lapse imaging

    Directory of Open Access Journals (Sweden)

    Kawakami Minoru

    2011-11-01

    Full Text Available Abstract Background Neural crest cells (NCCs are embryonic, multipotent stem cells. Their long-range and precision-guided migration is one of their most striking characteristics. We previously reported that P0-Cre/CAG-CAT-lacZ double-transgenic mice showed significant lacZ expression in tissues derived from NCCs. Results In this study, by embedding a P0-Cre/CAG-CAT-EGFP embryo at E9.5 in collagen gel inside a culture glass slide, we were able to keep the embryo developing ex vivo for more than 24 hours; this development was with enough NCC fluorescent signal intensity to enable single-cell resolution analysis, with the accompanying NCC migration potential intact and with the appropriate NCC response to the extracellular signal maintained. By implantation of beads with absorbed platelet-derived growth factor-AA (PDGF-AA, we demonstrated that PDGF-AA acts as an NCC-attractant in embryos. We also performed assays with NCCs isolated from P0-Cre/CAG-CAT-EGFP embryos on culture plates. The neuromediator 5-hydroxytryptamine (5-HT has been known to regulate NCC migration. We newly demonstrated that dopamine, in addition to 5-HT, stimulated NCC migration in vitro. Two NCC populations, with different axial levels of origins, showed unique distribution patterns regarding migration velocity and different dose-response patterns to both 5-HT and dopamine. Conclusions Although avian species predominated over the other species in the NCC study, our novel system should enable us to use mice to assay many different aspects of NCCs in embryos or on culture plates, such as migration, division, differentiation, and apoptosis.

  6. Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain

    OpenAIRE

    Deverman, Benjamin E.; Pravdo, Piers L.; Simpson, Bryan P.; Kumar, Sripriya Ravindra; Chan, Ken Y.; Banerjee, Abhik; Wu, Wei-Li; Yang, Bin; Huber, Nina; Pasca, Sergiu P.; Gradinaru, Viviana

    2016-01-01

    Recombinant adeno-associated viruses (rAAVs) are commonly used vehicles for in vivo gene transfer 1-6 . However, the tropism repertoire of naturally occurring AAVs is limited, prompting a search for novel AAV capsids with desired characteristics 7-13 . Here we describe a capsid selection method, called Cre-recombination-based AAV targeted evolution (CREATE), that enables the development of AAV capsids that more efficiently transduce defined Cre-expressing cell populations in vivo. We use CREA...

  7. Cardiac fibrosis in mice expressing an inducible myocardial-specific Cre driver

    Directory of Open Access Journals (Sweden)

    Jonas Lexow

    2013-11-01

    Tamoxifen-inducible Cre-mediated manipulation of animal genomes has achieved wide acceptance over the last decade, with numerous important studies heavily relying on this technique. Recently, a number of groups have reported transient complications of using this protocol in the heart. In the present study we observed a previously unreported focal fibrosis and depressed left-ventricular function in tamoxifen-treated αMHC-MerCreMer-positive animals in a Tβ4shRNAflox × αMHC-MerCreMer cross at 6–7 weeks following standard tamoxifen treatment, regardless of the presence of the floxed transgene. The phenotype was reproduced by treating mice from the original αMHC-MerCreMer strain with tamoxifen. In the acute phase after tamoxifen treatment, cell infiltration into the myocardium was accompanied by increased expression of pro-inflammatory cytokines (IL-1β, IL-6, TNFα, IFNγ, Ccl2 and markers of hypertrophy (ANF, BNP, Col3a1. These observations highlight the requirement for including tamoxifen-treated MerCreMer littermate controls to avert misinterpretation of conditional mutant phenotypes. A survey of the field as well as the protocols presented here suggests that controlling the parameters of tamoxifen delivery is important in avoiding the chronic MerCreMer-mediated cardiac phenotype reported here.

  8. Monodispersity of recombinant Cre recombinase correlates with its effectiveness in vivo

    Directory of Open Access Journals (Sweden)

    Edenhofer Frank

    2009-09-01

    Full Text Available Abstract Background Cre recombinase is a common reagent used for the in vivo on/off switching of the expression of target genes flanked by loxP sites. In particular, recombinant TAT-Cre fusion constructs purified from bacteria have been used to promote the cell uptake of the enzyme. However, the recovery of active TAT-Cre remains a demanding process and its specific activity varies significantly among batches, making difficult data comparison. Results We noticed a strong correlation between recombinase activity and enzyme monodispersity. The existence of such correlation enabled us to indirectly monitor the TAT-Cre recombinase activity during the multi-step purification process by measuring its monodispersity, a parameter detectable by means of a spectrofluorimetric assay that allows the calculation of the Aggregation Index (AI in an easy and rapid way. AI values were recorded after each purification passage to identify the critical steps and to choose optimal alternatives for chromatographic conditions, desalting procedures, and protocols for bacterial endotoxin removal. Furthermore, the effect of metal ions and temperature on TAT-Cre aggregation and inactivation was characterized in vitro. Finally, we optimized the enzyme delivery protocol in vivo by following the accumulation tuning of the reporter protein β-catenin. Conclusion A rational purification protocol for TAT-Cre has been developed by choosing the options that minimize the enzyme aggregation. Our data suggest that AI measurement should support the optimization of any protocol aiming at the recovery of monodispersed protein.

  9. Cre-loxP-Mediated Recombination: General Principles and Experimental Considerations.

    Science.gov (United States)

    McLellan, Micheal A; Rosenthal, Nadia A; Pinto, Alexander R

    2017-03-02

    The cre-loxP-mediated recombination system (the "cre-loxP system") is an integral experimental tool for mammalian genetics and cell biology. Use of the system has greatly expanded our ability to precisely interrogate gene function in the mouse, providing both spatial and temporal control of gene expression. This has been largely due to the simplicity of its use and its adaptability to address diverse biological questions. While the use of the cre-loxP system is becoming increasingly widespread, in particular because of growing availability of conditional mouse mutants, many considerations need to be taken into account when utilizing the cre-loxP system. This review provides an overview of the cre-loxP system and its various permutations. It addresses the limitations of cre-loxP technology and related considerations for experimental design, and it discusses alternative strategies for site-specific genetic recombination and integration. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  10. Online dating

    OpenAIRE

    Pilecká, Jarmila

    2014-01-01

    The usage of online dating sides has increased in last few decades. This kind of meeting potential new partner is specific in many ways. Especially in communication, ways of selection and initiation of the relationship online. The reduction of information is another phenomenon in this kind of interaction as a result of creating impression. This contains lying and deception in self-presentation on online dating sides as well. Analysis of data suggests, that men tell lies more than women. They ...

  11. Structural and functional characterization of the coxsackievirus B3 CRE(2C): role of CRE(2C) in negative- and positive-strand RNA synthesis.

    NARCIS (Netherlands)

    Ooij, M.J. van; Vogt, D.A.; Paul, A.; Castro, C.; Kuijpers, J.M.; Kuppeveld, F.J.M. van; Cameron, C.E.; Wimmer, E.; Andino, R.; Melchers, W.J.G.

    2006-01-01

    A stem-loop element located within the 2C-coding region of the coxsackievirus B3 (CVB3) genome has been proposed to function as a cis-acting replication element (CRE). It is shown here that disruption of this structure indeed interfered with viral RNA replication in vivo and abolished uridylylation

  12. Unexpected severe consequences of Pikfyve deletion by aP2- or Aq-promoter-driven Cre expression for glucose homeostasis and mammary gland development.

    Science.gov (United States)

    Ikonomov, Ognian C; Sbrissa, Diego; Delvecchio, Khortnal; Rillema, James A; Shisheva, Assia

    2016-06-01

    Systemic deficiency of PIKfyve, the evolutionarily conserved phosphoinositide kinase synthesizing cellular PtdIns5P and PtdIns(3,5)P2 and implicated in insulin signaling, causes early embryonic death in mice. In contrast, mice with muscle-specific Pikfyve disruption have normal lifespan but exhibit early-age whole-body glucose intolerance and muscle insulin resistance, thus establishing the key role of muscle PIKfyve in glucose homeostasis. Fat and muscle tissues control postprandial glucose clearance through different mechanisms, raising questions as to whether adipose Pikfyve disruption will also trigger whole-body metabolic abnormalities, and if so, what the mechanism might be. To clarify these issues, here we have characterized two new mouse models with adipose tissue disruption of Pikfyve through Cre recombinase expression driven by adipose-specific aP2- or adiponectin (Aq) promoters. Whereas both mouse lines were ostensibly normal until adulthood, their glucose homeostasis and systemic insulin sensitivity were severely dysregulated. These abnormalities stemmed in part from accelerated fat-cell lipolysis and elevated serum FFA Intriguingly, aP2-Cre-PIKfyve(fl/fl) but not Aq-Cre-PIKfyve(fl/fl) females had severely impaired pregnancy-induced mammary gland differentiation and lactogenesis, consistent with aP2-Cre-mediated Pikfyve excision in nonadipogenic tissues underlying this defect. Intriguingly, whereas mammary glands from postpartum control and Aq-Cre-PIKfyve(fl/fl) mice or ex vivo mammary gland explants showed profound upregulation of PIKfyve protein levels subsequent to prolactin receptor activation, such increases were not apparent in aP2-Cre-PIKfyve(fl/fl) females. Collectively, our data identify for the first time that adipose tissue Pikfyve plays a key role in the mechanisms regulating glucose homeostasis and that the PIKfyve pathway is critical in mammary epithelial differentiation during pregnancy and lactogenesis downstream of prolactin receptor

  13. Heme oxygenase-1 expression protects the heart from acute injury caused by inducible Cre recombinase.

    Science.gov (United States)

    Hull, Travis D; Bolisetty, Subhashini; DeAlmeida, Angela C; Litovsky, Silvio H; Prabhu, Sumanth D; Agarwal, Anupam; George, James F

    2013-08-01

    The protective effect of heme oxygenase-1 (HO-1) expression in cardiovascular disease has been previously demonstrated using transgenic animal models in which HO-1 is constitutively overexpressed in the heart. However, the temporal requirements for protection by HO-1 induction relative to injury have not been investigated, but are essential to employ HO-1 as a therapeutic strategy in human cardiovascular disease states. Therefore, we generated mice with cardiac-specific, tamoxifen (TAM)-inducible overexpression of a human HO-1 (hHO-1) transgene (myosin heavy chain (MHC)-HO-1 mice) by breeding mice with cardiac-specific expression of a TAM-inducible Cre recombinase (MHC-Cre mice), with mice containing an hHO-1 transgene preceded by a floxed-stop signal. MHC-HO-1 mice overexpress HO-1 mRNA and the enzymatically active protein following TAM administration (40 mg/kg body weight on 2 consecutive days). In MHC-Cre controls, TAM administration leads to severe, acute cardiac toxicity, cardiomyocyte necrosis, and 80% mortality by day 3. This cardiac toxicity is accompanied by a significant increase in inflammatory cells in the heart that are predominantly neutrophils. In MHC-HO-1 mice, HO-1 overexpression ameliorates the depression of cardiac function and high mortality rate observed in MHC-Cre mice following TAM administration and attenuates cardiomyocyte necrosis and neutrophil infiltration. These results highlight that HO-1 induction is sufficient to prevent the depression of cardiac function observed in mice with TAM-inducible Cre recombinase expression by protecting the heart from necrosis and neutrophil infiltration. These findings are important because MHC-Cre mice are widely used in cardiovascular research despite the limitations imposed by Cre-induced cardiac toxicity, and also because inflammation is an important pathological component of many human cardiovascular diseases.

  14. Conditional Wwox deletion in mouse mammary gland by means of two Cre recombinase approaches.

    Directory of Open Access Journals (Sweden)

    Brent W Ferguson

    Full Text Available Loss of WWOX expression has been reported in many different cancers including breast cancer. Elucidating the function of this gene in adult tissues has not been possible with full Wwox knockout models. Here we characterize the first conditional models of Wwox ablation in mouse mammary epithelium utilizing two transgenic lines expressing Cre recombinase, keratin 5-Cre (BK5-Cre and MMTV-Cre. In the BK5-Cre model we observed very efficient Wwox ablation in KO mammary glands. However, BK5-Cre Wwox KO animals die prematurely for unknown reasons. In the MMTV-Cre model we observed significant ablation of Wwox in mammary epithelium with no effect on survival. In both of these models we found that Wwox deletion resulted in impaired mammary branching morphogenesis. We demonstrate that loss of Wwox is not carcinogenic in our KO models. Furthermore, no evidence of increase proliferation or development of premalignant lesions was observed. In none of the models did loss of a single Wwox allele (i.e. haploinsufficiency have any observable phenotypic effect in mammary gland. To better understand the function of Wwox in the mammary gland, transcriptome profiling was performed. We observed that Wwox ablation results in the deregulation of genes involved in various cellular processes. We found that expression of the non-canonical Wnt ligand, Wnt5a, was significantly upregulated in Wwox KO mammary epithelium. Interestingly, we also determined that components of the Jak/Stat3 signaling pathway were upregulated in KO mice and this correlated with a very robust increase in phospho-Stat3 signaling, which warrants further testing. Even though the loss of Wwox expression in breast and other cancers is very well documented, our findings suggest that Wwox does not act as a classical tumor suppressor as previously thought.

  15. 19 CFR 351.701 - Applicability dates.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Applicability dates. 351.701 Section 351.701... DUTIES Applicability Dates § 351.701 Applicability dates. The regulations contained in this part 351... governed by the regulations in effect on the date the petitions were filed or requests were made for those...

  16. 7 CFR 987.5 - Dates.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Dates. 987.5 Section 987.5 Agriculture Regulations of... Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DOMESTIC DATES PRODUCED OR PACKED IN RIVERSIDE COUNTY, CALIFORNIA Order Regulating Handling Definitions § 987.5 Dates. Dates means the Deglet...

  17. Direct Dating

    Indian Academy of Sciences (India)

    For example, rock engravings and paintings are partially covered with lichens which are slow – growing, long – ranging and increase in diameter at a constant rate. The technique depends upon development of a specific lichen growth curve by measuring lichen thallus diameters on dated rock surfaces. This can then be ...

  18. Cre Fused with RVG Peptide Mediates Targeted Genome Editing in Mouse Brain Cells In Vivo.

    Science.gov (United States)

    Zou, Zhiyuan; Sun, Zhaolin; Li, Pan; Feng, Tao; Wu, Sen

    2016-12-14

    Cell penetrating peptides (CPPs) are short peptides that can pass through cell membranes. CPPs can facilitate the cellular entry of proteins, macromolecules, nanoparticles and drugs. RVG peptide (RVG hereinafter) is a 29-amino-acid CPP derived from a rabies virus glycoprotein that can cross the blood-brain barrier (BBB) and enter brain cells. However, whether RVG can be used for genome editing in the brain has not been reported. In this work, we combined RVG with Cre recombinase for bacterial expression. The purified RVG-Cre protein cut plasmids in vitro and traversed cell membranes in cultured Neuro2a cells. By tail vein-injecting RVG-Cre into Cre reporter mouse lines mTmG and Rosa26lacZ, we demonstrated that RVG-Cre could target brain cells and achieve targeted somatic genome editing in adult mice. This direct delivery of the gene-editing enzyme protein into mouse brains with RVG is much safer than plasmid- or viral-based methods, holding promise for further applications in the treatment of various brain diseases.

  19. Cell-Specific Cre Strains For Genetic Manipulation in Salivary Glands.

    Directory of Open Access Journals (Sweden)

    Eri O Maruyama

    Full Text Available The secretory acinar cells of the salivary gland are essential for saliva secretion, but are also the cell type preferentially lost following radiation treatment for head and neck cancer. The source of replacement acinar cells is currently a matter of debate. There is evidence for the presence of adult stem cells located within specific ductal regions of the salivary glands, but our laboratory recently demonstrated that differentiated acinar cells are maintained without significant stem cell contribution. To enable further investigation of salivary gland cell lineages and their origins, we generated three cell-specific Cre driver mouse strains. For genetic manipulation in acinar cells, an inducible Cre recombinase (Cre-ER was targeted to the prolactin-induced protein (Pip gene locus. Targeting of the Dcpp1 gene, encoding demilune cell and parotid protein, labels intercalated duct cells, a putative site of salivary gland stem cells, and serous demilune cells of the sublingual gland. Duct cell-specific Cre expression was attempted by targeting the inducible Cre to the Tcfcp2l1 gene locus. Using the R26Tomato Red reporter mouse, we demonstrate that these strains direct inducible, cell-specific expression. Genetic tracing of acinar cells using PipGCE supports the recent finding that differentiated acinar cells clonally expand. Moreover, tracing of intercalated duct cells expressing DcppGCE confirms evidence of duct cell proliferation, but further analysis is required to establish that renewal of secretory acinar cells is dependent on stem cells within these ducts.

  20. Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny.

    Science.gov (United States)

    Calaminus, Simon D J; Guitart, Amelie V; Guitart, Amelie; Sinclair, Amy; Schachtner, Hannah; Watson, Steve P; Holyoake, Tessa L; Kranc, Kamil R; Machesky, Laura M

    2012-01-01

    The development of a megakaryocyte lineage specific Cre deleter, using the Pf4 (CXCL4) promoter (Pf4-Cre), was a significant step forward in the specific analysis of platelet and megakaryocyte cell biology. However, in the present study we have employed a sensitive reporter-based approach to demonstrate that Pf4-Cre also recombines in a significant proportion of both fetal liver and bone marrow hematopoietic stem cells (HSCs), including the most primitive fraction containing the long-term repopulating HSCs. Consequently, we demonstrate that Pf4-Cre activity is not megakaryocyte lineage-specific but extends to other myeloid and lymphoid lineages at significant levels between 15-60%. Finally, we show for the first time that Pf4 transcripts are present in adult HSCs and primitive hematopoietic progenitor cells. These results have fundamental implications for the use of the Pf4-Cre mouse model and for our understanding of a possible role for Pf4 in the development of the hematopoietic lineage.

  1. Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny.

    Directory of Open Access Journals (Sweden)

    Simon D J Calaminus

    Full Text Available The development of a megakaryocyte lineage specific Cre deleter, using the Pf4 (CXCL4 promoter (Pf4-Cre, was a significant step forward in the specific analysis of platelet and megakaryocyte cell biology. However, in the present study we have employed a sensitive reporter-based approach to demonstrate that Pf4-Cre also recombines in a significant proportion of both fetal liver and bone marrow hematopoietic stem cells (HSCs, including the most primitive fraction containing the long-term repopulating HSCs. Consequently, we demonstrate that Pf4-Cre activity is not megakaryocyte lineage-specific but extends to other myeloid and lymphoid lineages at significant levels between 15-60%. Finally, we show for the first time that Pf4 transcripts are present in adult HSCs and primitive hematopoietic progenitor cells. These results have fundamental implications for the use of the Pf4-Cre mouse model and for our understanding of a possible role for Pf4 in the development of the hematopoietic lineage.

  2. Nationwide Surveillance of Clinical Carbapenem-resistant Enterobacteriaceae (CRE Strains in China

    Directory of Open Access Journals (Sweden)

    Rong Zhang

    2017-05-01

    Full Text Available The increasing incidence of carbapenem-resistant Enterobacteriaceae (CRE - mediated hospital infections in China prompted a need to investigate the genetic basis of emergence of such strains. A nationwide survey was conducted in China covering a total of 1105 CRE strains collected from 25 geographical locales with results showing that acquisition of two carbapenemase genes, blaKPC-2 and blaNDM, was responsible for phenotypic resistance in 90% of the CRE strains tested (58% and 32% respectively, among which several major strain types, such as ST11 of K. pneumoniae and ST131/ST167 of E. coli, were identified, suggesting that dissemination of specific resistant clones is mainly responsible for emergence of new CRE strains. Prevalence of the fosA3 gene which mediates fosfomycin resistance, was high, while the colistin resistance determinant mcr-1 was rarely present in these isolates. Consistently, the majority of the blaNDM-bearing plasmids recoverable from the test strains belonged to IncX3, which contained a common core structure, blaNDM-blaMBL-trpF. Likewise, the core structure of ISKpn27-blaKPC-2-ISKpn2 was observed among plasmids harboring the blaKPC-2 gene, although they were genetically more divergent. In conclusion, the increasing prevalence of CRE strains in China is attributed to dissemination of conservative mobile elements carrying blaNDM or blaKPC-2 on conjugative and non-conjugative plasmids.

  3. Molecular switch of Cre/loxP for radiation modulated gene therapy on hepatoma

    Science.gov (United States)

    Hsieh, Ya-Ju; Chen, Fu-Du; Wang, Fu Hui; Ke, Chien Chih; Wang, Hsin-Ell; Liu, Ren-Shyan

    2007-02-01

    For the purpose of enhancement of AFP promoter for the use of radiation modulated gene therapy for hepatocellular carcinoma (HCC), we combined hepatitis B virus (HBV) enhancer II with AFP promoter which shows the selectivity to the target cells to control the Cre/loxP system. Different gene constructs, pE4luc, pE4Tk, EIIAPA-Cre, E4CMV-STOP-Tk and chimeric promoters combined with HBV enhancer were constructed and transfected into HepG2, HeLa and NIH-3T3 cell lines. Cell experiments revealed that E4 enhancer responses to radiation best after 60 h irradiation at a dose range of 5-7 Gy in HepG2 stable clone. The EIIAPA promoter provided high specificity to hepatoma and activated the Cre downstream and removed the stop cassette only in hepatoma cells. After removal of the stop cassette, the E4 response to radiation could encode more Tk protein and kill more tumor cells. In summary, the chimeric EIIAPA promoter can stringently control the expression of Cre recombinase only in HCC. The radiation effect of the EIIAPA-Cre and E4CMV-STOP-Tk system shows promising results in terms of cell survival of HCC.

  4. BIOCHEMICAL AND PHYLOGENETIC STUDIES OF CreD OF Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Muhammad Tausif Chaudhry

    2015-06-01

    Full Text Available CreD characterized as Mg2+-dependent phosphohydrolase with conserved HD domain was involved in 4-cresol metabolism in Corynebacterium glutamicum. Native molecular mass of 54 kDa suggested that the biological unit is a dimer. No deoxynucleotide triphosphate triphosphohydrolase (dNTPase activity was detected for CreD. The apparent Km and Vmax values for 4-nitrophenyl phosphate were 0.35 mM and 16.23 M min-1 mg-1, respectively, while calculated values for kcat and kcat/Km were 0.4 s-1 and 1.14103 M-1 s-1, respectively. Among thiol group inhibitors, iodoacetic acid significantly inhibited phosphohydrolase activity. Sequence identity and phylogenetic analysis suggested universal existence of CreD homologues. Involvement of HD-domain hydrolase in aromatic degradation has not been reported before.

  5. Efficient B cell depletion via diphtheria toxin in CD19-Cre/iDTR mice.

    Directory of Open Access Journals (Sweden)

    Filiz Demircik

    Full Text Available B cells were first discovered as antibody producing cells, as B-1 B cells and finally as effector cells. In recent years their capacity to serve as antigen presenting cells is increasingly appreciated, and better tools are needed to study their function. We have previously described a new mouse model, the iDTR mice, that allow for the Cre-mediated expression of the diphtheria toxin receptor, thus rendering cells that express the Cre-recombinase sensitivity to diphtheria toxin. Herein we describe a new mouse line, the B-DTR mice, where the CD19-Cre was crossed to the iDTR mice. B-DTR allows for the efficient and cost-effective depletion of different B cell subpopulations, but only partially plasma cells. These mice can therefore be used to study the importance of B cells versus plasma cells in different immune responses and autoimmune diseases.

  6. PREPARATION OF PLANT TRANSFORMATION VECTOR CONTAINING “SELF-EXCISION” CRE/LOXP SYSTEM

    Directory of Open Access Journals (Sweden)

    Jana Moravčíková

    2012-02-01

    Full Text Available This work is focused on preparation of the plant transformation vector pZP6 containing “self-excision” Cre/loxP system. The T-DNA of binary vector consists of the cre recombinase gene driven by the Arabidopsis DLL promoter and the nptII expression unit flanked by two loxP sites in direct orientation. The gus reporter gene controlled by the double CaMV 35S promoter was placed out of the loxP embedded DNA. To confirm functionality of the Cre/loxP system, the pZP6 was analyzed for correct removal of the loxP embedded sequence in E. coli. The pZP6 was transformed into two bacterial strains A. tumefaciens AGLO and LBA 4404. Its stability in agrobacteria was evaluated by restriction analyses.

  7. Cre/lox-mediated marker gene excision in transgenic maize (Zea mays L.) plants.

    Science.gov (United States)

    Zhang, W; Subbarao, S; Addae, P; Shen, A; Armstrong, C; Peschke, V; Gilbertson, L

    2003-11-01

    After the initial transformation and tissue culture process is complete, selectable marker genes, which are used in virtually all transformation approaches, are not required for the expression of the gene of interest in the transgenic plants. There are several advantages to removing the selectable marker gene after it is no longer needed, such as enabling the reuse of selectable markers and simplifying transgene arrays. We have tested the Cre/ lox system from bacteriophage P1 for its ability to precisely excise stably integrated marker genes from chromosomes in transgenic maize plants. Two strategies, crossing and autoexcision, have been tested and demonstrated. In the crossing strategy, plants expressing the Cre recombinase are crossed with plants bearing a transgene construct in which the selectable marker gene is flanked by directly repeated lox sites. Unlike previous reports in which incomplete somatic and germline excision were common, in our experiments complete somatic and germline marker gene excision occurred in the F(1) plants from most crosses with multiple independent Cre and lox lines. In the autoexcision strategy, the cre gene, under the control of a heat shock-inducible promoter, is excised along with the nptII marker gene. Our results show that a transient heat shock treatment of primary transgenic callus is sufficient for inducing cre and excising the cre and nptII genes. Genetic segregation and molecular analysis confirmed that marker gene removal is precise, complete and stable. The autoexcision strategy provides a way of removing the selectable marker gene from callus or other tissues such as embryos and kernels.

  8. A pink mouse reports the switch from red to green fluorescence upon Cre-mediated recombination

    Directory of Open Access Journals (Sweden)

    Hartwich Heiner

    2012-06-01

    Full Text Available Abstract Background Targeted genetic modification in the mouse becomes increasingly important in biomedical and basic science. This goal is most often achieved by use of the Cre/loxP system and numerous Cre-driver mouse lines are currently generated. Their initial characterization requires reporter mouse lines to study the in vivo spatiotemporal activity of Cre. Findings Here, we report a dual fluorescence reporter mouse line, which switches expression from the red fluorescent protein mCherry to eGFP after Cre-mediated recombination. Both fluorescent proteins are expressed from the ubiquitously active and strong CAGGS promoter. Among the founders, we noticed a pink mouse line, expressing high levels of the red fluorescent protein mCherry throughout the entire body. Presence of mCherry in the living animal as well as in almost all organs was clearly visible without optical equipment. Upon Cre-activity, mCherry expression was switched to eGFP, demonstrating functionality of this reporter mouse line. Conclusions The pink mouse presented here is an attractive novel reporter line for fluorescence-based monitoring of Cre-activity. The high expression of mCherry, which is visible to the naked eye, facilitates breeding and crossing, as no genotyping is required to identify mice carrying the reporter allele. The presence of two fluorescent proteins allows in vivo monitoring of recombined and non-recombined cells. Finally, the pink mouse is an eye-catching animal model to demonstrate the power of transgenic techniques in teaching courses.

  9. Highly Efficient Sex Chromosome Interchanges Produced By I-CreI Expression in Drosophila

    OpenAIRE

    Maggert, Keith A; Golic, Kent G

    2005-01-01

    The homing endonuclease I-CreI recognizes a site in the gene encoding the 23S rRNA of Chlamydomonas reinhardtii. A very similar sequence is present in the 28S rRNA genes that are located on the X and Y chromosomes of Drosophila melanogaster. In this work we show that I-CreI expression in Drosophila is capable of causing induced DNA damage and eliciting cell cycle arrest. Expression also caused recombination between the X and Y chromosomes in the heterochromatic regions where the rDNA is locat...

  10. Transgenic Mice Expressing a Ligand-Inducible Cre Recombinase in Osteoblasts and Odontoblasts

    Science.gov (United States)

    Kim, Jung-Eun; Nakashima, Kazuhisa; de Crombrugghe, Benoit

    2004-01-01

    The skeleton supports body structures in vertebrates and helps maintain calcium homeostasis throughout life. Disruption of genes involved in mammalian bone formation has often led to embryonic lethality, hence preventing study of these genes’ role in adult animals. To develop a usable tool for such study, we generated transgenic mice in which a 2.3-kb mouse Col1a1 proximal promoter, which is active in all osteoblasts, drives a transgene coding for a polypeptide consisting of Cre recombinase fused to a mutated ligand-binding domain of the estrogen receptor. In this Col1a1-CreERT2 mouse line, expression patterns of the transgene and of the resulting Cre-mediated DNA recombination are analyzed by crossing with ROSA26 reporter mice and by measurement of β-galactosidase activity and X-gal staining. Exposure to 4-hydroxytamoxifen induced Cre-mediated recombination in osteoblasts in virtually all bones and in odontoblasts in teeth of both embryos and postnatal mice. The generation of these transgenic mice provides a new and important tool with which to study the function of specific genes in bone and tooth physiology and diseases in intact animals after birth. PMID:15579432

  11. STIM1fl/fl Ksp-Cre Mouse has Impaired Renal Water Balance

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    Liudmila Cebotaru

    2016-06-01

    Full Text Available Background/AIM: STIM1 is as an essential component in store operated Ca2+ entry. However give the paucity of information on the role of STIM1 in kidney, the aim was to study the function of STIM1 in the medulla of the kidney. Methods: we crossed a Ksp-cre mouse with another mouse containing two loxP sites flanking Exon 6 of STIM1. The Ksp-cre mouse is based upon the Ksp-cadherin gene promoter which expresses cre recombinase in developing nephrons, collecting ducts (SD and thick ascending limbs (TAL of the loop of Henle. Results: The offspring of these mice are viable without gross morphological changes, however, we noticed that the STIM1 Ksp-cre knockout mice produced more urine compared to control. To examine this more carefully, we fed mice low (LP and high protein (HP diets respectively. When mice were fed HP diet STIM1 ko mice had significantly increased urinary volume and lower specific gravity compared to wt mice. In STIM1 ko mice fed HP diet urine creatinine and urea were significantly lower compared to wt mice fed HP diet, however the fractional excretion was the same. Conclusion: These data support the idea that STIM1 ko mice have impaired urinary concentrating ability when challenged with HP diet is most likely caused by impaired Ca2+-dependent signal transduction through the vasopressin receptor cascade.

  12. Robust cre-mediated recombination in small intestinal stem cells utilizing the olfm4 locus

    NARCIS (Netherlands)

    Schuijers, Jurian; van der Flier, Laurens G; van Es, Johan; Clevers, Hans

    2014-01-01

    The epithelium of the small intestine is the most rapidly self-renewing tissue in mammals. We previously demonstrated the existence of a long-lived pool of cycling stem cells defined by Lgr5 expression at the bottom of intestinal crypts. An Lgr5-eGFP-IRES-CreERT2 knockin allele has been instrumental

  13. The FEM simulation of continuous rotary extrusion (CRE) of aluminum alloy AA3003

    Science.gov (United States)

    Rajendran, Nijenthan; Valberg, Henry; Misiolek, Wojciech Z.

    2017-10-01

    Continuous Rotary Extrusion (CRE) process is also known in literature under Conform TM name and it is mainly used for the continuous extrusion of Aluminum and Copper alloys. CRE use a feedstock in the form of rod, powders and chips, which are fed into the groove of the rotating wheel. As the wheel rotates the feedstock moves along with it due to friction with the wheel. Once the feedstock reaches the abutment the material deforms plastically and it is extruded through the die. CRE has lot to offer when compared to other more conventional extrusion processes such as low energy input, no limit in billet length as it is a continuous process as well as improved material physical properties due to plastic deformation under constant parameters. In this work a FEM model has been developed using Deform TM 3D, to study the metal flow and state variables of AA3003 CRE extrusion. The effect of extrusion wheel velocity has been investigated. The results show that increase in wheel velocity will heat up the feedstock metal due to high shear deformation and higher friction, which significantly changes metal flow conditions at the die exit.

  14. Sox9- and Scleraxis-Cre Lineage Fate Mapping in Aortic and Mitral Valve Structures

    Directory of Open Access Journals (Sweden)

    Blair F. Austin

    2014-09-01

    Full Text Available Heart valves are complex structures composed of a heterogeneous population of valve interstitial cells (VICs, an overlying endothelium and highly organized layers of extracellular matrix. Alterations in valve homeostasis are characteristic of dysfunction and disease, however the mechanisms that initiate and promote valve pathology are poorly understood. Advancements have been largely hindered by the limited availability of tools for gene targeting in heart valve structures during embryogenesis and after birth. We have previously shown that the transcription factors Sox9 and Scleraxis (Scx are required for heart valve formation and in this study we describe the recombination patterns of Sox9- and Scx-Cre lines at differential time points in aortic and mitral valve structures. In ScxCre; ROSA26GFP mice, recombination is undetected in valve endothelial cells (VECs and low in VICs during embryogenesis. However, recombination increases in VICs from post natal stages and by 4 weeks side-specific patterns are observed. Using the inducible Sox9CreERT2 system, we observe recombination in VECs and VICs in the embryo, and high levels are maintained through post natal and juvenile stages. These Cre-drivers provide the field with new tools for gene targeting in valve cell lineages during differential stages of embryonic and post natal maturation and maintenance.

  15. High-fidelity Glucagon-CreER mouse line generated by CRISPR-Cas9 assisted gene targeting

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    Amanda M. Ackermann

    2017-03-01

    Conclusions: We successfully derived a Gcg-CreERT2 mouse line that expresses CreERT2 in pancreatic α-cells and enteroendocrine L-cells without disrupting preproglucagon gene expression. These mice will be a useful tool for performing temporally controlled genetic manipulation specifically in these cell types.

  16. NF1 Is an Effector and Regulator of the GPCR Signaling in the Nervous System

    Science.gov (United States)

    2015-04-01

    of NF1 by infecting differentiated cultures with AAV carrying Cre recombinase (Task 2 A and B). We used these cultures along with uninfected...activation and regulation of its signaling to downstream protein kinases (Task 3). We infected neurons with the AAV virus encoding Cre-recombinase...cultured striatal neurons on MAPK signaling. Cultured neurons from NF1flx/flx mice were infected with either AAV -Cre deleting NF1 or control AAV

  17. Altered Baseline and Nicotine-Mediated Behavioral and Cholinergic Profiles in ChAT-Cre Mouse Lines.

    Science.gov (United States)

    Chen, Edison; Lallai, Valeria; Sherafat, Yasmine; Grimes, Nickolas P; Pushkin, Anna N; Fowler, J P; Fowler, Christie D

    2018-01-25

    The recent development of transgenic rodent lines expressing cre recombinase in a cell-specific manner, along with advances in engineered viral vectors, has permitted in-depth investigations into circuit function. However, emerging evidence has begun to suggest that genetic modifications may introduce unexpected caveats. In the current studies, we sought to extensively characterize male and female mice from both the ChAT (BAC) -Cre mouse line, created with the bacterial artificial chromosome (BAC) method, and ChAT (IRES) -Cre mouse line, generated with the internal ribosome entry site (IRES) method. ChAT (BAC) -Cre transgenic and wildtype mice did not differ in general locomotor behavior, anxiety measures, drug-induced cataplexy, nicotine-mediated hypolocomotion, or operant food training. However, ChAT (BAC) -Cre transgenic mice did exhibit significant deficits in intravenous nicotine self-administration, which paralleled an increase in vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) hippocampal expression. For the ChAT (IRES) -Cre line, transgenic mice exhibited deficits in baseline locomotor, nicotine-mediated hypolocomotion, and operant food training compared to wildtype and hemizygous littermates. No differences among ChAT (IRES) -Cre wildtype, hemizygous and transgenic littermates were found in anxiety measures, drug-induced cataplexy, and nicotine self-administration. Given that increased cre expression was present in the ChAT (IRES) -Cre transgenic mice, as well as a decrease in ChAT expression in the hippocampus, altered neuronal function may underlie behavioral phenotypes. In contrast, ChAT (IRES) -Cre hemizygous mice were more similar to wildtype mice in both protein expression and the majority of behavioral assessments. As such, interpretation of data derived from ChAT-Cre rodents must consider potential limitations dependent on the line and/or genotype employed in research investigations. SIGNIFICANCE STATEMENT Altered

  18. Overview of BioCreAtIvE: critical assessment of information extraction for biology

    Directory of Open Access Journals (Sweden)

    Hirschman Lynette

    2005-05-01

    Full Text Available Abstract Background The goal of the first BioCreAtIvE challenge (Critical Assessment of Information Extraction in Biology was to provide a set of common evaluation tasks to assess the state of the art for text mining applied to biological problems. The results were presented in a workshop held in Granada, Spain March 28–31, 2004. The articles collected in this BMC Bioinformatics supplement entitled "A critical assessment of text mining methods in molecular biology" describe the BioCreAtIvE tasks, systems, results and their independent evaluation. Results BioCreAtIvE focused on two tasks. The first dealt with extraction of gene or protein names from text, and their mapping into standardized gene identifiers for three model organism databases (fly, mouse, yeast. The second task addressed issues of functional annotation, requiring systems to identify specific text passages that supported Gene Ontology annotations for specific proteins, given full text articles. Conclusion The first BioCreAtIvE assessment achieved a high level of international participation (27 groups from 10 countries. The assessment provided state-of-the-art performance results for a basic task (gene name finding and normalization, where the best systems achieved a balanced 80% precision / recall or better, which potentially makes them suitable for real applications in biology. The results for the advanced task (functional annotation from free text were significantly lower, demonstrating the current limitations of text-mining approaches where knowledge extrapolation and interpretation are required. In addition, an important contribution of BioCreAtIvE has been the creation and release of training and test data sets for both tasks. There are 22 articles in this special issue, including six that provide analyses of results or data quality for the data sets, including a novel inter-annotator consistency assessment for the test set used in task 2.

  19. Transgenic mice for a tamoxifen-induced, conditional expression of the Cre recombinase in osteoclasts.

    Directory of Open Access Journals (Sweden)

    Maria Arantzazu Sanchez-Fernandez

    Full Text Available BACKGROUND: Studies on osteoclasts, the bone resorbing cells, have remained limited due to the lack of transgenic mice allowing the conditional knockout of genes in osteoclasts at any time during development or adulthood. METHODOLOGY/PRINCIPAL FINDING: We report here on the generation of transgenic mice which specifically express a tamoxifen-inducible Cre recombinase in osteoclasts. These mice, generated on C57BL/6 and FVB background, express a fusion Cre recombinase-ERT2 protein whose expression is driven by the promoter of cathepsin K (CtsK, a gene highly expressed in osteoclasts. We tested the cellular specificity of Cre activity in CtsKCreERT2 strains by breeding with Rosa26LacZ reporter mice. PCR and histological analyses of the CtsKCreERT2LacZ positive adult mice and E17.5 embryos show that Cre activity is restricted largely to bone tissue. In vitro, primary osteoclasts derived from the bone marrow of CtsKCreERT2+/-LacZ+/- adult mice show a Cre-dependent β-galactosidase activity after tamoxifen stimulation. CONCLUSIONS/SIGNIFICANCE: We have generated transgenic lines that enable the tamoxifen-induced, conditional deletion of loxP-flanked genes in osteoclasts, thus circumventing embryonic and postnatal gene lethality and avoiding gene deletion in other cell types. Such CtsKCreERT2 mice provide a convenient tool to study in vivo the different facets of osteoclast function in bone physiology during different developmental stages and adulthood of mice.

  20. 39 CFR 601.101 - Effective date.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Effective date. 601.101 Section 601.101 Postal... RIGHTS OTHER THAN PATENTS PURCHASING OF PROPERTY AND SERVICES § 601.101 Effective date. These regulations... that date will be governed by the regulations in effect at the time the solicitation was issued. ...

  1. 33 CFR 239.9 - Effective date.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Effective date. 239.9 Section 239....9 Effective date. These regulations are applicable to all projects not approved by OCE prior to the date of this regulation. ...

  2. Targeted deletion of RANKL in M cell inducer cells by the Col6a1-Cre driver.

    Science.gov (United States)

    Nagashima, Kazuki; Sawa, Shinichiro; Nitta, Takeshi; Prados, Alejandro; Koliaraki, Vasiliki; Kollias, George; Nakashima, Tomoki; Takayanagi, Hiroshi

    2017-11-04

    The gut-associated lymphoid tissues (GALTs), including Peyer's patches (PPs), cryptopatches (CPs) and isolated lymphoid follicles (ILFs), establish a host-microbe symbiosis by the promotion of immune reactions against gut microbes. Microfold cell inducer (MCi) cells in GALTs are the recently identified mesenchymal cells that express the cytokine RANKL and initiate bacteria-specific immunoglobulin A (IgA) production via induction of microfold (M) cell differentiation. In the previous study, the Twist2-Cre driver was utilized for gene deletion in mesenchymal cells including MCi cells. In order to investigate MCi cells more extensively, it will be necessary to develop experimental tools in addition to the Twist2-Cre driver mice and characterize such drivers in specificity and efficiency. Here we show that M cell differentiation and IgA production are impaired in the targeted deletion of RANKL by the Col6a1-Cre driver. We compared Col6a1-Cre with Twist2-Cre in terms of the specificity for mesenchymal cells in GALTs. Col6a1-Cre CAG-CAT-EGFP mice exhibited EGFP expression in podoplanin+CD31- cells including MCi cells, while Twist2-Cre mice were shown to target endothelial cells and podoplanin+CD31- cells. Tnfsf11fl/ΔCol6a1-Cre mice exhibited the absence of M cells and severe IgA reduction together with an alteration in gut microbial composition. Moreover, we analyzed germ free mice to test whether changes in the microbiota are the cause of M cell deficiency. M cell differentiation was normal in the CPs/ILFs of germ free mice, indicating that MCi cells induce M cells independently of microbial colonization. This study demonstrates that Col6a1-Cre driver mice are as useful as Twist2-Cre driver mice for functional analyses of GALT-resident mesenchymal cells, including MCi cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 10 CFR 2.807 - Effective date.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Effective date. 2.807 Section 2.807 Energy NUCLEAR... § 2.807 Effective date. The notice of adoption of a regulation will specify the effective date... relieving from restrictions, will be made not less than thirty (30) days prior to the effective date unless...

  4. Tamoxifen-Induced Cre-loxP Recombination Is Prolonged in Pancreatic Islets of Adult Mice.

    Directory of Open Access Journals (Sweden)

    Rachel B Reinert

    Full Text Available Tamoxifen (Tm-inducible Cre recombinases are widely used to perform gene inactivation and lineage tracing studies in mice. Although the efficiency of inducible Cre-loxP recombination can be easily evaluated with reporter strains, the precise length of time that Tm induces nuclear translocation of CreER(Tm and subsequent recombination of a target allele is not well defined, and difficult to assess. To better understand the timeline of Tm activity in vivo, we developed a bioassay in which pancreatic islets with a Tm-inducible reporter (from Pdx1(PB-CreER(Tm;R26R(lacZ mice were transplanted beneath the renal capsule of adult mice previously treated with three doses of 1 mg Tm, 8 mg Tm, or corn oil vehicle. Surprisingly, recombination in islet grafts, as assessed by expression of the β-galactosidase (β-gal reporter, was observed days or weeks after Tm treatment, in a dose-dependent manner. Substantial recombination occurred in islet grafts long after administration of 3×8 mg Tm: in grafts transplanted 48 hours after the last Tm injection, 77.9±0.4% of β-cells were β-gal+; in β-cells placed after 1 week, 46.2±5.0% were β-gal+; after 2 weeks, 26.3±7.0% were β-gal+; and after 4 weeks, 1.9±0.9% were β-gal+. Islet grafts from mice given 3×1 mg Tm showed lower, but notable, recombination 48 hours (4.9±1.7% and 1 week (4.5±1.9% after Tm administration. These results show that Tm doses commonly used to induce Cre-loxP recombination may continue to label significant numbers of cells for weeks after Tm treatment, possibly confounding the interpretation of time-sensitive studies using Tm-dependent models. Therefore, investigators developing experimental approaches using Tm-inducible systems should consider both maximal recombination efficiency and the length of time that Tm-induced Cre-loxP recombination occurs.

  5. The effect of CreA in glucose and xylose catabolism in Aspergillus nidulans

    DEFF Research Database (Denmark)

    Prathumpai, Wai; Mcintyre, Mhairi; Nielsen, Jens

    2004-01-01

    The catabolism of glucose and xylose was studied in a wild type and creA deleted (carbon catabolite de-repressed) strain of Aspergillus nidulans. Both strains were cultivated in bioreactors with either glucose or xylose as the sole carbon source, or in the presence of both sugars....... In the cultivations on single carbon sources, it was demonstrated that xylose acted as a carbon catabolite repressor (xylose cultivations), while the enzymes in the xylose utilisation pathway were also subject to repression in the presence of glucose (glucose cultivations). In the wild type strain growing...... on the sugar mixture, glucose repression of xylose utilisation was observed; with xylose utilisation occurring only after glucose was depleted. This phenomenon was not seen in the creA deleted strain, where glucose and xylose were catabolised simultaneously. Measurement of key metabolites and the activities...

  6. Ubiquitous transgene expression and Cre-based recombination driven by the ubiquitin promoter in zebrafish

    Science.gov (United States)

    Mosimann, Christian; Kaufman, Charles K.; Li, Pulin; Pugach, Emily K.; Tamplin, Owen J.; Zon, Leonard I.

    2011-01-01

    Molecular genetics approaches in zebrafish research are hampered by the lack of a ubiquitous transgene driver element that is active at all developmental stages. Here, we report the isolation and characterization of the zebrafish ubiquitin (ubi) promoter, which drives constitutive transgene expression during all developmental stages and analyzed adult organs. Notably, ubi expresses in all blood cell lineages, and we demonstrate the application of ubi-driven fluorophore transgenics in hematopoietic transplantation experiments to assess true multilineage potential of engrafted cells. We further generated transgenic zebrafish that express ubiquitous 4-hydroxytamoxifen-controlled Cre recombinase activity from a ubi:creERt2 transgene, as well as ubi:loxP-EGFP-loxP-mCherry (ubi:Switch) transgenics and show their use as a constitutive fluorescent lineage tracing reagent. The ubi promoter and the transgenic lines presented here thus provide a broad resource and important advancement for transgenic applications in zebrafish. PMID:21138979

  7. Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development

    Directory of Open Access Journals (Sweden)

    Matthew R. McCann

    2012-01-01

    Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months. Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration.

  8. Being a Learner Using Social Media in School: The Case of Space2cre8

    Science.gov (United States)

    Vasbø, Kristin Beate; Silseth, Kenneth; Erstad, Ola

    2014-01-01

    The aim of this article is to gain knowledge about what it means to be a learner using social media in an educational setting. The article presents an ethnographic study of students in a multiethnic community in Oslo who participate in a social networking site called Space2cre8 (S28). In this article, we set out to explore the kind of space for…

  9. Utilizing the CreA Gene to Better Understand Carbon Flux in Fungi

    Energy Technology Data Exchange (ETDEWEB)

    Annecharico, Matthew D.; Baker, Scott E.

    2005-01-01

    Carbon catabolite repression (CCR) is a system which represses the synthesis of enzymes required for certain carbon sources when more favored carbon sources are present. Fungal enzymes are useful in various industrial applications such as the degradation of bi-product biomass produced in many areas of manufacturing and production. For example, the basidiomycete, Phanerochaete chrysosporium, a filamentous fungus, produces a number of lignin peroxidases (LiPs) such as an extra-cellular lignin-modifying protein and manganese-dependent peroxidase (MnPs). The LiPs secreted by P. chrysosporium are able to break down lignin, one of the main substances of wood, while leaving the cellulose behind. These enzymes are capable of degrading toxic waste as well as biomass waste. Through polysaccharide hydrolysis and lignin utilization, biobased products and biofuels can be processed from biomass instead of petroleum, which is more environmentally sound than current fuel options. Previous research in the fungal phylum, Ascomyces has shown that the creA gene is an important gene that controls various enzymes which have key roles in controlling carbon utilization by fungi. We hypothesize that there are similarities across all fungi in the mechanism by which carbon flux is controlled and that orthologs of the creA gene exist in all fungal phyla. A COnsensus-DEgenerate Hybrid Oligonucleotide Primers (CODEHOP) polymerase chain reaction (PCR) strategy was used to isolate genomic fragments of the creA gene from a variety of fungi with the objective to design and utilize a method for isolation of the creA gene from a wide range of fungi.

  10. Highly efficient sex chromosome interchanges produced by I-CreI expression in Drosophila.

    Science.gov (United States)

    Maggert, Keith A; Golic, Kent G

    2005-11-01

    The homing endonuclease I-CreI recognizes a site in the gene encoding the 23S rRNA of Chlamydomonas reinhardtii. A very similar sequence is present in the 28S rRNA genes that are located on the X and Y chromosomes of Drosophila melanogaster. In this work we show that I-CreI expression in Drosophila is capable of causing induced DNA damage and eliciting cell cycle arrest. Expression also caused recombination between the X and Y chromosomes in the heterochromatic regions where the rDNA is located, presumably as a result of a high frequency of double-strand breaks in these regions. Approximately 20% of the offspring of males expressing I-CreI showed exceptional inheritance of X- and Y-linked markers, consistent with chromosome exchange at rDNA loci. Cytogenetic analysis confirmed the structures of many of these products. Exchange between the X and Y chromosomes can be induced in males and females to produce derivative-altered Y chromosomes, attached-XY, and attached-X chromosomes. This method has advantages over the traditional use of X rays for generating X-Y interchanges because it is very frequent and it generates predictable products.

  11. Generation of eGFP and Cre knockin rats by CRISPR/Cas9.

    Science.gov (United States)

    Ma, Yuanwu; Ma, Jing; Zhang, Xu; Chen, Wei; Yu, Lei; Lu, Yingdong; Bai, Lin; Shen, Bin; Huang, Xingxu; Zhang, Lianfeng

    2014-09-01

    The type II bacterial CRISPR/Cas [clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)] system is a very valuable genome engineering tool, which has been widely used in genome editing of a variety of organisms. Previously, we generated floxed alleles in rats by CRISPR/Cas9. Here, we successfully use a two-cut strategy with one circular vector, which contains the exogenous cDNAs with homology arm regions, in generating knockin rats at the Trdmt1, Nestin and Cck loci. The efficiency of CRISPR/Cas9-mediated knockin was up to 54%. Furthermore, by crossing the Nestin-Cre rat with the Dnmt3b floxed rat and Cck-Cre with the Dnmt1 floxed rat, we detected Cre/loxP-mediated recombination in the F1 generation of rats. We also show that the knockin alleles were germline transmitted. These results provided a simple and flexible engineering strategy for the establishment of knockin rats. © 2014 FEBS.

  12. All-in-one construct for genome engineering using Cre-lox technology.

    Science.gov (United States)

    Mariscal, Ana M; González-González, Luis; Querol, Enrique; Piñol, Jaume

    2016-06-01

    Mycoplasma genitalium is an appealing model of a minimal cell and synthetic biology study, and it was one of the first organisms whose genome was fully sequenced and chemically synthesized. Despite its usefulness as a model organism, many genetic tools well established for other microorganisms are not currently available in mycoplasmas. We have developed several vectors to adapt the Cre-lox technology for genome engineering in M. genitalium, providing an all-in-one construct that could be also useful to obtain unmarked genetic modifications in many other slow growing microorganisms. This construct contains a modified promoter sequence based in TetR system that exhibits an enhanced control on Cre recombinase expression, virtually abolishing the presence of this recombinase in the absence of inducer. This allows to introduce the Cre recombinase gene and the desired genetic modification in a single transformation step. In addition, this inducible promoter may be a very promising tool for a wide range of molecular applications. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  13. Reactions of Cre with methylphosphonate DNA: similarities and contrasts with Flp and vaccinia topoisomerase.

    Directory of Open Access Journals (Sweden)

    Chien-Hui Ma

    2009-09-01

    Full Text Available Reactions of vaccinia topoisomerase and the tyrosine site-specific recombinase Flp with methylphosphonate (MeP substituted DNA substrates, have provided important insights into the electrostatic features of the strand cleavage and strand joining steps catalyzed by them. A conserved arginine residue in the catalytic pentad, Arg-223 in topoisomerase and Arg-308 in Flp, is not essential for stabilizing the MeP transition state. Topoisomerase or its R223A variant promotes cleavage of the MeP bond by the active site nucleophile Tyr-274, followed by the rapid hydrolysis of the MeP-tyrosyl intermediate. Flp(R308A, but not wild type Flp, mediates direct hydrolysis of the activated MeP bond. These findings are consistent with a potential role for phosphate electrostatics and active site electrostatics in protecting DNA relaxation and site-specific recombination, respectively, against abortive hydrolysis.We have examined the effects of DNA containing MeP substitution in the Flp related Cre recombination system. Neutralizing the negative charge at the scissile position does not render the tyrosyl intermediate formed by Cre susceptible to rapid hydrolysis. Furthermore, combining the active site R292A mutation in Cre (equivalent to the R223A and R308A mutations in topoisomerase and Flp, respectively with MeP substitution does not lead to direct hydrolysis of the scissile MeP bond in DNA. Whereas Cre follows the topoisomerase paradigm during the strand cleavage step, it follows the Flp paradigm during the strand joining step.Collectively, the Cre, Flp and topoisomerase results highlight the contribution of conserved electrostatic complementarity between substrate and active site towards transition state stabilization during site-specific recombination and DNA relaxation. They have potential implications for how transesterification reactions in nucleic acids are protected against undesirable abortive side reactions. Such protective mechanisms are significant

  14. A multifunctional teal-fluorescent Rosa26 reporter mouse line for Cre- and Flp-mediated recombination.

    Science.gov (United States)

    Imayoshi, Itaru; Hirano, Kyoko; Sakamoto, Masayuki; Miyoshi, Goichi; Imura, Tetsuya; Kitano, Satsuki; Miyachi, Hitoshi; Kageyama, Ryoichiro

    2012-05-01

    Reporters of Cre and/or Flp activity are important for defining the spatial and temporal extent of Cre/Flp-mediated recombination. Here, we describe R26-CAG-LF-mTFP1, a multifunctional fluorescent reporter mouse that strongly expresses mTFP1 (bright teal fluorescent protein) after Cre- and Flp-mediated recombination. To meet the need for single recombinase-mediated reporter expression, we generated derivatives of R26-CAG-LF-mTFP1. The germline excision of the Frt-flanked stop cassette in R26-CAG-LF-mTFP1 generated a Cre-dependent reporter (R26-CAG-LoxP-mTFP1). Similarly, R26-CAG-FRT-mTFP1, in which the loxP-flanked stop cassette was excised in the germline, requires only Flp to activate mTFP1 expression. Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  15. Temporal control of gene deletion in sensory ganglia using a tamoxifen-inducible Advillin-Cre-ERT2 recombinase mouse

    Directory of Open Access Journals (Sweden)

    Lau Joanne

    2011-12-01

    Full Text Available Abstract Background Tissue-specific gene deletion has proved informative in the analysis of pain pathways. Advillin has been shown to be a pan-neuronal marker of spinal and cranial sensory ganglia. We generated BAC transgenic mice using the Advillin promoter to drive a tamoxifen-inducible CreERT2 recombinase construct in order to be able to delete genes in adult animals. We used a floxed stop ROSA26LacZ reporter mouse to examine functional Cre expression, and analysed the behaviour of mice expressing Cre recombinase. Results We used recombineering to introduce a CreERT2 cassette in place of exon 2 of the Advillin gene into a BAC clone (RPCI23-424F19 containing the 5' region of the Advillin gene. Transgenic mice were generated using pronuclear injection. The resulting AvCreERT2 transgenic mice showed a highly specific expression pattern of Cre activity after tamoxifen induction. Recombinase activity was confined to sensory neurons and no expression was found in other organs. Less than 1% of neurons showed Cre expression in the absence of tamoxifen treatment. Five-day intraperitoneal treatment with tamoxifen (2 mg per day induced Cre recombination events in ≈90% of neurons in dorsal root and cranial ganglia. Cell counts of dorsal root ganglia (DRG from transgenic animals with or without tamoxifen treatment showed no neuronal cell loss. Sensory neurons in culture showed ≈70% induction after 3 days treatment with tamoxifen. Behavioural tests showed no differences between wildtype, AvCreERT2 and tamoxifen-treated animals in terms of motor function, responses to light touch and noxious pressure, thermal thresholds as well as responses to inflammatory agents. Conclusions Our results suggest that the inducible pan-DRG AvCreERT2 deleter mouse strain is a useful tool for studying the role of individual genes in adult sensory neuron function. The pain phenotype of the Cre-induced animal is normal; therefore any alterations in pain processing can be

  16. Establishment of a Cre/loxP recombination system for N-terminal epitope tagging of genes in Tetrahymena

    OpenAIRE

    Mochizuki Kazufumi; Vogt Alexander; Busch Clara

    2010-01-01

    Abstract Background Epitope tagging is a powerful strategy to study the function of proteins. Although tools for C-terminal protein tagging in the ciliated protozoan Tetrahymena thermophila have been developed, N-terminal protein tagging in this organism is still technically demanding. Results In this study, we have established a Cre/loxP recombination system in Tetrahymena and have applied this system for the N-terminal epitope tagging of Tetrahymena genes. Cre can be expressed in Tetrahymen...

  17. Efficient elimination of selectable marker genes from the plastid genome by the CRE-lox site-specific recombination system.

    Science.gov (United States)

    Corneille, S; Lutz, K; Svab, Z; Maliga, P

    2001-07-01

    Incorporation of a selectable marker gene during transformation is essential to obtain transformed plastids. However, once transformation is accomplished, having the marker gene becomes undesirable. Here we report on adapting the P1 bacteriophage CRE-lox site-specific recombination system for the elimination of marker genes from the plastid genome. The system was tested by the elimination of a negative selectable marker, codA, which is flanked by two directly oriented lox sites (>codA>). Highly efficient elimination of >codA> was triggered by introduction of a nuclear-encoded plastid-targeted CRE by Agrobacterium transformation or via pollen. Excision of >codA> in tissue culture cells was frequently accompanied by a large deletion of a plastid genome segment which includes the tRNA-ValUAC gene. However, the large deletions were absent when cre was introduced by pollination. Thus pollination is our preferred protocol for the introduction of cre. Removal of the >codA> coding region occurred at a dramatic speed, in striking contrast to the slow and gradual build-up of transgenic copies during plastid transformation. The nuclear cre gene could subsequently be removed by segregation in the seed progeny. The modified CRE-lox system described here will be a highly efficient tool to obtain marker-free transplastomic plants.

  18. Restoring pollen fertility in transgenic male-sterile eggplant by Cre/loxp-mediated site-specific recombination system

    Directory of Open Access Journals (Sweden)

    Bihao Cao

    2010-01-01

    Full Text Available This study was designed to control plant fertility by cell lethal gene Barnase expressing at specific developmental stage and in specific tissue of male organ under the control of Cre/loxP system, for heterosis breeding, producing hybrid seed of eggplant. The Barnase-coding region was flanked by loxP recognition sites for Cre-recombinase. The eggplant inbred/pure line ('E-38' was transformed with Cre gene and the inbred/pure line ('E-8' was transformed with the Barnase gene situated between loxp. The experiments were done separately, by means of Agrobacterium co-culture. Four T0-plants with the Barnase gene were obtained, all proved to be male-sterile and incapable of producing viable pollen. Flowers stamens were shorter, but the vegetative phenotype was similar to wild-type. Five T0-plants with the Cre gene developed well, blossomed out and set fruit normally. The crossing of male-sterile Barnase-plants with Cre expression transgenic eggplants resulted in site-specific excision with the male-sterile plants producing normal fruits. With the Barnase was excised, pollen fertility was fully restored in the hybrids. The phenotype of these restored plants was the same as that of the wild-type. Thus, the Barnase and Cre genes were capable of stable inheritance and expression in progenies of transgenic plants.

  19. Generation of a Tlx1(CreER-Venus) knock-in mouse strain for the study of spleen development.

    Science.gov (United States)

    Nakahara, Ryo; Kawai, Yasuhiro; Oda, Akihisa; Nishimura, Miyuki; Murakami, Akikazu; Azuma, Takachika; Kaifu, Tomonori; Goitsuka, Ryo

    2014-11-01

    The spleen is a lymphoid organ that serves as a unique niche for immune reactions, extramedullary hematopoiesis, and the removal of aged erythrocytes from the circulation. While much is known about the immunological functions of the spleen, the mechanisms governing the development and organization of its stromal microenvironment remain poorly understood. Here we report the generation and analysis of a Tlx1(Cre) (ER) (-Venus) knock-in mouse strain engineered to simultaneously express tamoxifen-inducible CreER(T2) and Venus fluorescent protein under the control of regulatory elements of the Tlx1 gene, which encodes a transcription factor essential for spleen development. We demonstrated that Venus as well as CreER expression recapitulates endogenous Tlx1 transcription within the spleen microenvironment. When Tlx1(Cre) (ER) (-Venus) mice were crossed with the Cre-inducible reporter strain, Tlx1-expressing cells as well as their descendants were specifically labeled following tamoxifen administration. We also showed by cell lineage tracing that asplenia caused by Tlx1 deficiency is attributable to altered contribution of mesenchymal cells in the spleen anlage to the pancreatic mesenchyme. Thus, Tlx1(Cre) (ER) (-Venus) mice represent a new tool for lineage tracing and conditional gene manipulation of spleen mesenchymal cells, essential approaches for understanding the molecular mechanisms of spleen development. © 2014 Wiley Periodicals, Inc.

  20. The phenylquinazoline compound S-4893 is a non-competitive cytokinin antagonist that targets Arabidopsis cytokinin receptor CRE1 and promotes root growth in Arabidopsis and rice.

    Science.gov (United States)

    Arata, Yuto; Nagasawa-Iida, Asako; Uneme, Hideki; Nakajima, Hiroki; Kakimoto, Tatsuo; Sato, Ryo

    2010-12-01

    We identified two phenylquinazoline compounds in a large-scale screening for cytokinin antagonists in yeast expressing the Arabidopsis cytokinin receptor cytokinin response 1/histidine kinase 4 (CRE1). After chemical modifications, we obtained compound S-4893, which non-competitively inhibited binding of the natural ligand 2-isopentenyladenine to CRE1. S-4893 antagonized cytokinin-induced activation of the Arabidopsis response regulator 5 promoter in Arabidopsis. Importantly, S-4893 had no detectable intrinsic cytokinin agonist activity in Arabidopsis or in the transformed yeast system. Cytokinin bioassay further demonstrated that S-4893 antagonized cytokinin-induced stimulation of callus formation and inhibition of root elongation. S-4893 also promoted seminal, crown and lateral root growth in rice, suggesting that S-4893 could potentially promote root growth in a variety of agronomically important plants. We believe S-4893 will be a useful tool in functional studies of cytokinin action in a wide range of plants and a lead compound for the development of useful root growth promoters in agriculture.

  1. 34 CFR 105.42 - Effective date.

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    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Effective date. 105.42 Section 105.42 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF EDUCATION... DEPARTMENT OF EDUCATION § 105.42 Effective date. The effective date of this part is October 9, 1990. ...

  2. 29 CFR 452.137 - Effective dates.

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    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Effective dates. 452.137 Section 452.137 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR LABOR-MANAGEMENT STANDARDS... OF 1959 Dates and Scope of Application § 452.137 Effective dates. (a) Section 404 states when the...

  3. 10 CFR 784.13 - Effective dates.

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    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Effective dates. 784.13 Section 784.13 Energy DEPARTMENT OF ENERGY PATENT WAIVER REGULATION § 784.13 Effective dates. Waivers shall be effective on the following dates: (a) For advance waivers of identified inventions, i.e., inventions conceived prior to the...

  4. 46 CFR 272.44 - Dates.

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    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Dates. 272.44 Section 272.44 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS AFFECTING SUBSIDIZED VESSELS AND OPERATORS REQUIREMENTS... Examination, Audit, Review and Appeal Procedures § 272.44 Dates. The dates noted on the letters or...

  5. 45 CFR 146.125 - Applicability dates.

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    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Applicability dates. 146.125 Section 146.125..., and Limitations on Preexisting Condition Exclusion Periods § 146.125 Applicability dates. Section 144... or after July 1, 2005. Until the applicability date for this regulation, plans and issuers are...

  6. 7 CFR 1000.90 - Dates.

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    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Dates. 1000.90 Section 1000.90 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Miscellaneous Provisions § 1000.90 Dates. If a date required for a payment contained in a Federal milk order...

  7. 25 CFR 213.48 - Effective date.

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    ... FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING Removal of Restrictions § 213.48 Effective date. The regulations in this part shall become effective and in full force from and after the date of approval (Apr. 27... 25 Indians 1 2010-04-01 2010-04-01 false Effective date. 213.48 Section 213.48 Indians BUREAU OF...

  8. The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB

    Directory of Open Access Journals (Sweden)

    Kandel Eric R

    2012-05-01

    Full Text Available Abstract The analysis of the contributions to synaptic plasticity and memory of cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB has recruited the efforts of many laboratories all over the world. These are six key steps in the molecular biological delineation of short-term memory and its conversion to long-term memory for both implicit (procedural and explicit (declarative memory. I here first trace the background for the clinical and behavioral studies of implicit memory that made a molecular biology of memory storage possible, and then detail the discovery and early history of these six molecular steps and their roles in explicit memory.

  9. The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB.

    Science.gov (United States)

    Kandel, Eric R

    2012-05-14

    The analysis of the contributions to synaptic plasticity and memory of cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB has recruited the efforts of many laboratories all over the world. These are six key steps in the molecular biological delineation of short-term memory and its conversion to long-term memory for both implicit (procedural) and explicit (declarative) memory. I here first trace the background for the clinical and behavioral studies of implicit memory that made a molecular biology of memory storage possible, and then detail the discovery and early history of these six molecular steps and their roles in explicit memory.

  10. Imaging Voltage in Genetically Defined Neuronal Subpopulations with a Cre Recombinase-Targeted Hybrid Voltage Sensor.

    Science.gov (United States)

    Bayguinov, Peter O; Ma, Yihe; Gao, Yu; Zhao, Xinyu; Jackson, Meyer B

    2017-09-20

    Genetically encoded voltage indicators create an opportunity to monitor electrical activity in defined sets of neurons as they participate in the complex patterns of coordinated electrical activity that underlie nervous system function. Taking full advantage of genetically encoded voltage indicators requires a generalized strategy for targeting the probe to genetically defined populations of cells. To this end, we have generated a mouse line with an optimized hybrid voltage sensor (hVOS) probe within a locus designed for efficient Cre recombinase-dependent expression. Crossing this mouse with Cre drivers generated double transgenics expressing hVOS probe in GABAergic, parvalbumin, and calretinin interneurons, as well as hilar mossy cells, new adult-born neurons, and recently active neurons. In each case, imaging in brain slices from male or female animals revealed electrically evoked optical signals from multiple individual neurons in single trials. These imaging experiments revealed action potentials, dynamic aspects of dendritic integration, and trial-to-trial fluctuations in response latency. The rapid time response of hVOS imaging revealed action potentials with high temporal fidelity, and enabled accurate measurements of spike half-widths characteristic of each cell type. Simultaneous recording of rapid voltage changes in multiple neurons with a common genetic signature offers a powerful approach to the study of neural circuit function and the investigation of how neural networks encode, process, and store information. SIGNIFICANCE STATEMENT Genetically encoded voltage indicators hold great promise in the study of neural circuitry, but realizing their full potential depends on targeting the sensor to distinct cell types. Here we present a new mouse line that expresses a hybrid optical voltage sensor under the control of Cre recombinase. Crossing this line with Cre drivers generated double-transgenic mice, which express this sensor in targeted cell types. In

  11. 29 CFR 697.4 - Effective dates.

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    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Effective dates. 697.4 Section 697.4 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS INDUSTRIES IN AMERICAN SAMOA § 697.4 Effective dates. The wage rates specified in § 697.2 shall be effective on October...

  12. 48 CFR 6301.6 - Effective date.

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    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Effective date. 6301.6 Section 6301.6 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION BOARD OF CONTRACT APPEALS BOARD OF CONTRACT APPEALS 6301.6 Effective date. This chapter shall apply to all appeals relating...

  13. Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain.

    Science.gov (United States)

    Deverman, Benjamin E; Pravdo, Piers L; Simpson, Bryan P; Kumar, Sripriya Ravindra; Chan, Ken Y; Banerjee, Abhik; Wu, Wei-Li; Yang, Bin; Huber, Nina; Pasca, Sergiu P; Gradinaru, Viviana

    2016-02-01

    Recombinant adeno-associated viruses (rAAVs) are commonly used vehicles for in vivo gene transfer. However, the tropism repertoire of naturally occurring AAVs is limited, prompting a search for novel AAV capsids with desired characteristics. Here we describe a capsid selection method, called Cre recombination-based AAV targeted evolution (CREATE), that enables the development of AAV capsids that more efficiently transduce defined Cre-expressing cell populations in vivo. We use CREATE to generate AAV variants that efficiently and widely transduce the adult mouse central nervous system (CNS) after intravenous injection. One variant, AAV-PHP.B, transfers genes throughout the CNS with an efficiency that is at least 40-fold greater than that of the current standard, AAV9 (refs. 14,15,16,17), and transduces the majority of astrocytes and neurons across multiple CNS regions. In vitro, it transduces human neurons and astrocytes more efficiently than does AAV9, demonstrating the potential of CREATE to produce customized AAV vectors for biomedical applications.

  14. Comparison of Three Cre-LoxP Based Paired-End Library Construction Methods

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Ze; Nath, Nandita; Tritt, Andrew; Liang, Shoudan; Han, James; Pennacchio, Len; Chen, Feng

    2013-03-26

    Paired-end library sequencing has been proven useful in scaffold construction during de novo whole genome shotgun assembly. The ability of generating mate pairs with > 8 Kb insert sizes is especially important for genomes containing long repeats. To make mate paired libraries for next generation sequencing, DNA fragments need to be circularized to bring the ends together. There are several methods that can be used for DNA circulation, namely ligation, hybridization and Cre-LoxP recombination. With higher circularization efficiency with large insert DNA fragments, Cre-LoxP recombination method generally has been used for constructing >8 kb insert size paired-end libraries. Second fragmentation step is also crucial for maintaining high library complexity and uniform genome coverage. Here we will describe the following three fragmentation methods: restriction enzyme digestion, random shearing and nick translation. We will present the comparison results for these three methods. Our data showed that all three methods are able to generate paired-end libraries with greater than 20 kb insert. Advantages and disadvantages of these three methods will be discussed as well.

  15. Date Rape (For Teens)

    Science.gov (United States)

    ... Breath? Talking to Your Parents - or Other Adults Date Rape KidsHealth > For Teens > Date Rape Print A ... Yourself Getting Help Reporting a Rape What Is Date Rape? When people think of rape , they might ...

  16. Agrobacterium-mediated transformation of maize (Zea mays) with Cre-lox site specific recombination cassettes in BIBAC vectors.

    Science.gov (United States)

    Vega, Juan M; Yu, Weichang; Han, Fangpu; Kato, Akio; Peters, Eric M; Zhang, Zhanyuan J; Birchler, James A

    2008-04-01

    The Cre/loxP site-specific recombination system has been applied in various plant species including maize (Zea mays) for marker gene removal, gene targeting, and functional genomics. A BIBAC vector system was adapted for maize transformation with a large fragment of genetic material including a herbicide resistance marker gene, a 30 kb yeast genomic fragment as a marker for fluorescence in situ hybridization (FISH), and a 35S-lox-cre recombination cassette. Seventy-five transgenic lines were generated from Agrobacterium-mediated transformation of a maize Hi II line with multiple B chromosomes. Eighty-four inserts have been localized among all 10 A chromosome pairs by FISH using the yeast DNA probe together with a karyotyping cocktail. No inserts were found on the B chromosomes; thus a bias against the B chromosomes by the Agrobacterium-mediated transformation was revealed. The expression of a cre gene was confirmed in 68 of the 75 transgenic lines by a reporter construct for cre/lox mediated recombination. The placement of the cre/lox site-specific recombination system in many locations in the maize genome will be valuable materials for gene targeting and chromosome engineering.

  17. Development of CRTEIL and CETRIZ, Cre-loxP-Based Systems, Which Allow Change of Expression of Red to Green or Green to Red Fluorescence upon Transfection with a Cre-Expression Vector

    OpenAIRE

    Masato Ohtsuka; Takayuki Warita; Takayuki Sakurai; Satoshi Watanabe; Hidetoshi Inoko; Masahiro Sato

    2009-01-01

    We developed Cre-loxP-based systems, termed CRTEIL and CETRIZ, which allow gene switching in a noninvasive manner. Single transfection with pCRTEIL resulted in predominant expression of red fluorescence. Cotransfection with pCRTEIL and Cre-expression plasmid (pCAG/NCre) caused switching from red to green fluorescence. Similarly, cotransfection with pCETRIZ and pCAG/NCre resulted in change of green to red fluorescence. These noninvasive systems will be useful in cell lineage analysis, since de...

  18. Establishment of a Cre/loxP recombination system for N-terminal epitope tagging of genes in Tetrahymena.

    Science.gov (United States)

    Busch, Clara Jana-Lui; Vogt, Alexander; Mochizuki, Kazufumi

    2010-07-13

    Epitope tagging is a powerful strategy to study the function of proteins. Although tools for C-terminal protein tagging in the ciliated protozoan Tetrahymena thermophila have been developed, N-terminal protein tagging in this organism is still technically demanding. In this study, we have established a Cre/loxP recombination system in Tetrahymena and have applied this system for the N-terminal epitope tagging of Tetrahymena genes. Cre can be expressed in Tetrahymena and localizes to the macronucleus where it induces precise recombination at two loxP sequences in direct orientation in the Tetrahymena macronuclear chromosome. This Cre/loxP recombination can be used to remove a loxP-flanked drug-resistance marker from an N-terminal tagging construct after it is integrated into the macronucleus. The system established in this study allows us to express an N-terminal epitope tagged gene from its own endogenous promoter in Tetrahymena.

  19. 12 CFR 334.28 - Effective date, compliance date, and prospective application.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Effective date, compliance date, and prospective application. 334.28 Section 334.28 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY FAIR CREDIT REPORTING Affiliate Marketing § 334.28 Effective date...

  20. 12 CFR 717.28 - Effective date, compliance date, and prospective application.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Effective date, compliance date, and prospective application. 717.28 Section 717.28 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS FAIR CREDIT REPORTING Affiliate Marketing § 717.28 Effective date...

  1. Efficient Construction of Large Genomic Deletion in Agrobacterium tumefaciens by Combination of Cre/loxP System and Triple Recombineering.

    Science.gov (United States)

    Liu, Zhengqiang; Xie, Yali; Zhang, Xu; Hu, Xiaofeng; Li, Yusheng; Ding, Xuezhi; Xia, Liqiu; Hu, Shengbiao

    2016-04-01

    In order to develop an efficient system for deleting genomic segment in Agrobacterium tumefaciens to analyze gene functions and construct marker gene-free recombinant strains, a Cre recombinase expression plasmid was constructed by placing its encoding gene under the control of Ptet promoter and cloning into the plasmid replicable in both A. tumefaciens and E. coli. Triple recombineering was applied to efficiently construct integrative vectors which were used to introduce loxP sites and selection markers into the chromosome of A. tumefaciens. Cre recombinase could be properly induced by anhydrotetracycline in A. tumefaciens, which was revealed by the fact that kanamycin resistance gene flanked by two parallel loxP sites was excised from the genome of A. tumefaciens with virtually 100% efficiency. And what is more, an A. tumefaciens mutant carrying large-deletion (~85 kb) in genome was successfully constructed by Cre/loxP system. Here, we described the application of combination of Cre/loxP system and triple recombineering to efficiently excise genomic segment in A. tumefaciens, which also would facilitate efficient construction of multiple gene disruptions in A. tumefaciens.

  2. Osterix-Cre Labeled Progenitor Cells Contribute to the Formation and Maintenance of the Bone Marrow Stroma

    Science.gov (United States)

    Liu, Yaling; Strecker, Sara; Wang, Liping; Kronenberg, Mark S.; Wang, Wen; Rowe, David W.; Maye, Peter

    2013-01-01

    We have carried out fate mapping studies using Osterix-EGFPCre and Osterix-CreERt animal models and found Cre reporter expression in many different cell types that make up the bone marrow stroma. Constitutive fate mapping resulted in the labeling of different cellular components located throughout the bone marrow, whereas temporal fate mapping at E14.5 resulted in the labeling of cells within a region of the bone marrow. The identity of cell types marked by constitutive and temporal fate mapping included osteoblasts, adipocytes, vascular smooth muscle, perineural, and stromal cells. Prolonged tracing of embryonic precursors labeled at E14.5dpc revealed the continued existence of their progeny up to 10 months of age, suggesting that fate mapped, labeled embryonic precursors gave rise to long lived bone marrow progenitor cells. To provide further evidence for the marking of bone marrow progenitors, bone marrow cultures derived from Osterix-EGFPCre/Ai9 mice showed that stromal cells retained Cre reporter expression and yielded a FACS sorted population that was able to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and into osteoblasts, adipocytes, and perivascular stromal cells after transplantation. Collectively, our studies reveal the developmental process by which Osterix-Cre labeled embryonic progenitors give rise to adult bone marrow progenitors which establish and maintain the bone marrow stroma. PMID:23951132

  3. Dating as leisure

    OpenAIRE

    Flambard, Véronique; Vaillant, Nicolas Gérard; Wolff, François-Charles

    2010-01-01

    Partner selection occurs naturally and informally, but it may also be organized through commercial intermediaries facilitating mating and dating. This paper focuses on the relationship between online dating and the business cycle . We rely on monthly data covering the period from January 2004 to August 2008 on the demand for online dating in France to study whether economic recession tends to stimulate the online dating industry. We find that during economic downturns, people tend to to incre...

  4. Impaired Ca(2+ signaling in β-cells lacking leptin receptors by Cre-loxP recombination.

    Directory of Open Access Journals (Sweden)

    Eva Tudurí

    Full Text Available Obesity is a major risk factor for diabetes and is typically associated with hyperleptinemia and a state of leptin resistance. The impact of chronically elevated leptin levels on the function of insulin-secreting β-cells has not been elucidated. We previously generated mice lacking leptin signaling in β-cells by using the Cre-loxP strategy and showed that these animals develop increased body weight and adiposity, hyperinsulinemia, impaired glucose-stimulated insulin secretion and insulin resistance. Here, we performed several in vitro studies and observed that β-cells lacking leptin signaling in this model are capable of properly metabolizing glucose, but show impaired intracellular Ca(2+ oscillations and lack of synchrony within the islets in response to glucose, display reduced response to tolbutamide and exhibit morphological abnormalities including increased autophagy. Defects in intracellular Ca(2+ signaling were observed even in neonatal islets, ruling out the possible contribution of obesity to the β-cell irregularities observed in adults. In parallel, we also detected a disrupted intracellular Ca(2+ pattern in response to glucose and tolbutamide in control islets from adult transgenic mice expressing Cre recombinase under the rat insulin promoter, despite these animals being glucose tolerant and secreting normal levels of insulin in response to glucose. This unexpected observation impeded us from discerning the consequences of impaired leptin signaling as opposed to long-term Cre expression in the function of insulin-secreting cells. These findings highlight the need to generate improved Cre-driver mouse models or new tools to induce Cre recombination in β-cells.

  5. 31 CFR 226.7 - Effective date.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Effective date. 226.7 Section 226.7 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE... LOAN DEPOSITARIES § 226.7 Effective date. The provisions of this part become effective November 2, 1978. ...

  6. 31 CFR 357.1 - Effective date.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Effective date. 357.1 Section 357.1 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE... AND BILLS HELD IN LEGACY TREASURY DIRECT General Information § 357.1 Effective date. Subpart B of this...

  7. 7 CFR 1485.24 - Applicability date.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Applicability date. 1485.24 Section 1485.24 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT... FOREIGN MARKETS FOR AGRICULTURAL COMMODITIES Market Access Program § 1485.24 Applicability date. This...

  8. 7 CFR 1730.65 - Effective dates.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Effective dates. 1730.65 Section 1730.65 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE... dates. (a) All electric program borrowers with an approved electric program loan as of July 8, 2009...

  9. 48 CFR 3001.301-71 - Effective date.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Effective date. 3001.301... Acquisition Regulations 3001.301-71 Effective date. Unless otherwise stated: (a) HSAR changes apply to solicitations issued on or after the effective date of the change; (b) Contracting officers may, at their...

  10. Transgenic mice exhibiting inducible and spontaneous Cre activities driven by a bovine keratin 5 promoter that can be used for the conditional analysis of basal epithelial cells in multiple organs

    Directory of Open Access Journals (Sweden)

    Liang Chih-Chia

    2009-01-01

    Full Text Available Abstract Background Cre/loxP-mediated genetic modification is the most widely used conditional genetic approach used in the mouse. Engineered Cre and the mutated ligand-binding domain of estrogen receptor fusion recombinase (CreERT allow temporal control of Cre activity. Results In this study, we have generated two distinct transgenic mouse lines expressing CreERT, which show 4-hydroxytamoxifen (4-OHT-inducible and spontaneous (4-OHT-independent Cre activities, referred to Tg(BK5-CreERTI and Tg(BK5-CreERTS, respectively. The transgenic construct is driven by the bovine Keratin 5 promoter, which is active in the basal epithelial lineage of stratified and pseudo-stratified epithelium across multiple organs. Despite the difference in 4-OHT dependency, the Tg(BK5-CreERTI and Tg(BK5-CreERTS mouse lines shared similar Cre-mediated recombination among various organs, except for unique mammary epithelial Cre activity in Tg(BK5-CreERTS females. Conclusion These two new transgenic mouse lines for the analysis of basal epithelial function and for the genetic modification have been created allowing the identification of these cell lineages and analysis of their differentiation during embryogenesis, during perinatal development and in adult mice.

  11. Cyclic AMP induces IPC leukemia cell apoptosis via CRE-and CDK-dependent Bim transcription.

    Science.gov (United States)

    Huseby, S; Gausdal, G; Keen, T J; Kjærland, E; Krakstad, C; Myhren, L; Brønstad, K; Kunick, C; Schwede, F; Genieser, H-G; Kleppe, R; Døskeland, S O

    2011-12-08

    The IPC-81 cell line is derived from the transplantable BNML model of acute myelogenic leukemia (AML), known to be a reliable predictor of the clinical efficiency of antileukemic agents, like the first-line AML anthracycline drug daunorubicin (DNR). We show here that cAMP acted synergistically with DNR to induce IPC cell death. The DNR-induced death differed from that induced by cAMP by (1) not involving Bim induction, (2) being abrogated by GSK3β inhibitors, (3) by being promoted by the HSP90/p23 antagonist geldanamycin and truncated p23 and (4) by being insensitive to the CRE binding protein (CREB) antagonist ICER and to cyclin-dependent protein kinase (CDK) inhibitors. In contrast, the apoptosis induced by cAMP correlated tightly with Bim protein expression. It was abrogated by Bim (BCL2L11) downregulation, whether achieved by the CREB antagonist ICER, by CDK inhibitors, by Bim-directed RNAi, or by protein synthesis inhibitor. The forced expression of BimL killed IPC-81(WT) cells rapidly, Bcl2-overexpressing cells being partially resistant. The pivotal role of CREB and CDK activity for Bim transcription is unprecedented. It is also noteworthy that newly developed cAMP analogs specifically activating PKA isozyme I (PKA-I) were able to induce IPC cell apoptosis. Our findings support the notion that AML cells may possess targetable death pathways not exploited by common anti-cancer agents.

  12. Tracking proliferative history in lymphocyte development with cre-mediated sister chromatid recombination.

    Directory of Open Access Journals (Sweden)

    Baojun Zhang

    2013-10-01

    Full Text Available Tracking and isolating live cells based on their proliferative history in live animals remains a technical challenge in animal studies. We have designed a genetic marking system for tracking the proliferative frequency and history of lymphocytes during their development and homeostatic maintenance. This system is based on activation of a fluorescent marker after Cre-dependent recombination between sister chromatids at a specially designed tandem loxP site, named Tlox. We have demonstrated the utility of the Tlox system in tracking proliferative windows of B and T lymphocyte development. We have further applied the Tlox system in the analysis of the proliferative behavior and homeostatic maintenance of Vγ1.1 positive γδ T cells. Our data show that Vγ1.1 T cells generated in neonatal but not adult life are able to expand in the thymus. The expanded Vγ1.1 T cells are preferentially maintained in the liver but not in lymphoid organs. It has been shown that numbers of Vγ1.1 T cells were dramatically increased in the lymphoid organs of Id3 deficient mice. By combining BrdU and Tlox assays we show that this phenotype is primarily due to enhanced neonatal expansion and subsequent retention of Vγ1.1 T cells. Thus, the Tlox system provides a new genetic tool to track clonal expansion within a defined cell population or tissue type in live animals.

  13. Correlates of minimal dating.

    Science.gov (United States)

    Leck, Kira

    2006-10-01

    Researchers have associated minimal dating with numerous factors. The present author tested shyness, introversion, physical attractiveness, performance evaluation, anxiety, social skill, social self-esteem, and loneliness to determine the nature of their relationships with 2 measures of self-reported minimal dating in a sample of 175 college students. For women, shyness, introversion, physical attractiveness, self-rated anxiety, social self-esteem, and loneliness correlated with 1 or both measures of minimal dating. For men, physical attractiveness, observer-rated social skill, social self-esteem, and loneliness correlated with 1 or both measures of minimal dating. The patterns of relationships were not identical for the 2 indicators of minimal dating, indicating the possibility that minimal dating is not a single construct as researchers previously believed. The present author discussed implications and suggestions for future researchers.

  14. Dating the Crucifixion

    Science.gov (United States)

    Humphreys, Colin J.; Waddington, W. G.

    1983-12-01

    The date of the Crucifixion has been debated for many years, but there has been no agreement on the year nor the day. Astronomical calculations have now been used to reconstruct the Jewish calendar in the first century AD and to date a lunar eclipse that biblical and other references suggest followed the Crucifixion. The evidence points to Friday 3 April AD 33 as the date when Jesus Christ died.

  15. Dermal Delivery of Constructs Encoding Cre Recombinase to Induce Skin Tumors in PtenLoxP/LoxP;BrafCA/+ Mice

    Directory of Open Access Journals (Sweden)

    Marcel A. Deken

    2016-12-01

    Full Text Available Current genetically-engineered mouse melanoma models are often based on Tyr::CreERT2-controlled MAPK pathway activation by the BRAFV600E mutation and PI3K pathway activation by loss of PTEN. The major drawback of these models is the occurrence of spontaneous tumors caused by leakiness of the Tyr::CreERT2 system, hampering long-term experiments. To address this problem, we investigated several approaches to optimally provide local delivery of Cre recombinase, including injection of lentiviral particles, DNA tattoo administration and particle-mediated gene transfer, to induce melanomas in PtenLoxP/LoxP;BrafCA/+ mice lacking the Tyr::CreERT2 allele. We found that dermal delivery of the Cre recombinase gene under the control of a non-specific CAG promoter induced the formation of melanomas, but also keratoacanthoma and squamous cell carcinomas. Delivery of Cre recombinase DNA under the control of melanocyte-specific promoters in PtenLoxP/LoxP;BrafCA/+ mice resulted in sole melanoma induction. The growth rate and histological features of the induced tumors were similar to 4-hydroxytamoxifen-induced tumors in Tyr::CreERT2;PtenLoxP/LoxP;BrafCA/+ mice, while the onset of spontaneous tumors was prevented completely. These novel induction methods will allow long-term experiments in mouse models of skin malignancies.

  16. 50 CFR 216.201 - Effective dates.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF COMMERCE MARINE MAMMALS REGULATIONS GOVERNING THE TAKING AND IMPORTING OF MARINE MAMMALS Taking of Marine Mammals Incidental to Construction and Operation of Offshore Oil and Gas Facilities in the U.S. Beaufort Sea § 216.201 Effective dates. Regulations in this subpart are effective from April 6...

  17. 31 CFR 800.210 - Effective date.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Effective date. 800.210 Section 800.210 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF INVESTMENT SECURITY, DEPARTMENT OF THE TREASURY REGULATIONS PERTAINING TO MERGERS, ACQUISITIONS, AND...

  18. Interleukin-6 deletion in mice driven by aP2-Cre-ERT2 prevents against high-fat diet-induced gain weight and adiposity in female mice.

    Science.gov (United States)

    Navia, B; Ferrer, B; Giralt, M; Comes, G; Carrasco, J; Molinero, A; Quintana, A; Leclerc, J; Viollet, B; Señarís, R M; Hidalgo, J

    2014-08-01

    Interleukin-6 (IL-6) is a major cytokine controlling body weight and metabolism, but because many types of cells can synthesize and respond to IL-6 considerable uncertainty still exists about the mechanisms underlying IL-6 effects. Therefore, the aim of this study was to analyse the effects of tissue-specific deletion of IL-6 using a fatty acid binding protein (aP2) promoter-Cre inducible system (aP2-Cre-ERT2). Tissue-specific IL-6 KO mice (aP2-IL-6 KO mice) were produced upon tamoxifen administration and were fed a high-fat diet (HFD, 58.4% kcal from fat) or a control diet (18%) for 14 weeks. aP2-IL-6 KO female mice on a HFD gained less weight and adiposity than littermate wild-type mice, but these effects were not observed in males. Hypothalamic factors such as NPY and AgRP showed a pattern of expression consistent with this sex-specific phenotype. PGC-1α expression was increased in several tissues in aP2-IL-6 KO female mice, which is compatible with increased energy expenditure. Serum leptin, insulin, glucose, cholesterol and triglycerides levels were increased by HFD, and in females IL-6 deficiency reversed this effect in the case of insulin and cholesterol. HFD induced impaired responses to insulin and glucose tolerance tests, but no significant differences between genotypes were observed. The present results demonstrate that deletion of IL-6 driven by aP2-Cre regulates body weight, body fat and metabolism in a sex-specific fashion. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  19. Establishment of a Cre/loxP recombination system for N-terminal epitope tagging of genes in Tetrahymena

    Directory of Open Access Journals (Sweden)

    Mochizuki Kazufumi

    2010-07-01

    Full Text Available Abstract Background Epitope tagging is a powerful strategy to study the function of proteins. Although tools for C-terminal protein tagging in the ciliated protozoan Tetrahymena thermophila have been developed, N-terminal protein tagging in this organism is still technically demanding. Results In this study, we have established a Cre/loxP recombination system in Tetrahymena and have applied this system for the N-terminal epitope tagging of Tetrahymena genes. Cre can be expressed in Tetrahymena and localizes to the macronucleus where it induces precise recombination at two loxP sequences in direct orientation in the Tetrahymena macronuclear chromosome. This Cre/loxP recombination can be used to remove a loxP-flanked drug-resistance marker from an N-terminal tagging construct after it is integrated into the macronucleus. Conclusions The system established in this study allows us to express an N-terminal epitope tagged gene from its own endogenous promoter in Tetrahymena.

  20. Understanding Teen Dating Violence

    Science.gov (United States)

    ... public health problems like dating violence. Step 1: Define the problem Before we can prevent dating violence, we need ... and who it affects. CDC learns about a problem by gathering and studying ... and supports research to answer this question. Step 3: Develop and ...

  1. Date Palm Germplasm

    Science.gov (United States)

    This book chapter reviews date palm genetic resources and their conservation. Date palm (Phoenix dactylifera) is an important food crop in the Middle East and North Africa. Its center of origin and diversity most probably is the area near Iraq/Iran. From there, it spread throughout its present range...

  2. Dating and Sexual Feelings

    Science.gov (United States)

    ... sex It’s not too late to stop having sex Could I be gay? Dating older guys Staying safe when dating What about masturbation? What teens are saying about sex top You may get lots of messages about ...

  3. Second Quaternary dating workshop

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-11-01

    The second Quaternary dating methods workshop was held at Lucas Heights and sponsored by ANSTO and AINSE. Topics covered include, isotope and thermoluminescence dating, usage of accelerator and thermal ionisation mass spectrometry in environmental studies emphasizing on the methodologies used and sample preparation

  4. 12 CFR 222.28 - Effective date, compliance date, and prospective application.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Effective date, compliance date, and prospective application. 222.28 Section 222.28 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM FAIR CREDIT REPORTING (REGULATION V) Affiliate Marketing § 222.28...

  5. Online dating and education

    Directory of Open Access Journals (Sweden)

    Yvonne Fritze

    2012-11-01

    Full Text Available Taking its inspiration from Luhmann's communication theory, this article looks at online dating from the perspective of teaching and education. While Eros obviously plays an important role in regenerating the desire to communicate, this ardour is often absent from the domain of net-based teaching. The article explores those features of online dating characteristic of distance dialogue, and discusses the extent to which these can be transferred to communication in the teaching context. We further argue that participation in online dating increases communicators' competence and self-reflection.

  6. Insights into the preferential order of strand exchange in the Cre/loxP recombinase system: impact of the DNA spacer flanking sequence and flexibility

    Science.gov (United States)

    Abi-Ghanem, Josephine; Samsonov, Sergey A.; Pisabarro, M. Teresa

    2015-03-01

    The Cre/loxP system is widely used as a genetic tool to manipulate DNA. Cre recombinase catalyzes site-specific recombination between 34 bp loxP sites. Each loxP site is recognized by two Cre molecules assuming a cleaving (CreC) and non-cleaving (CreNC) activity. Despite the symmetry in the sequences of the arms of loxP, available biochemical data show strong evidence that the recombination reaction is asymmetric with a preferred strand exchange order. The asymmetry comes from the spacer separating the two sets of palindromic arms of the loxP sequence. However, it remains to be understood how this preferential order is established. We apply computational structure-based methods and perform a thorough detailed analysis of available structural and biochemical information on the Cre/loxP system in order to investigate such asymmetry in the recombination, and we propose a rationale to explain the determinants favoring the strand exchange order. We show that the structural properties of the DNA flanking sequence of the spacer guide the recombination, and we establish the role of residues R118, R121 and K122 from CreC, which contact the spacer region and by clamping the DNA inhibit the cleavage on the second arm of loxP. Our studies give an atomistic insight on the synapsis state of the recombination process in the Cre/loxP system and highlight the importance of the flexibility and other intrinsic properties of the flanking regions of the DNA spacer to establish a preferential strand exchange order.

  7. NAIP 2014 Image Dates

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — This map is produced by the Aerial Phtography Field Office (APFO) to show the image acquisition dates for the 2014 National Agriculture Imagery Program (NAIP)...

  8. NAIP 2012 Image Dates

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — This map is produced by the Aerial Phtography Field Office (APFO) to show the image acquisition dates for the 2012 National Agriculture Imagery Program (NAIP)...

  9. Food Product Dating

    Science.gov (United States)

    ... Standard Forms FSIS United States Department of Agriculture Food Safety and Inspection Service About FSIS District Offices ... Web Content Viewer (JSR 286) Actions ${title} Loading... Food Product Dating "Best if Used By" is a ...

  10. NAIP 2011 Image Dates

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — This map is produced by the Aerial Phtography Field Office (APFO) to show the image acquisition dates for the 2011 National Agriculture Imagery Program (NAIP)...

  11. NAIP 2013 Image Dates

    Data.gov (United States)

    Farm Service Agency, Department of Agriculture — This map is produced by the Aerial Phtography Field Office (APFO) to show the image acquisition dates for the 2013 National Agriculture Imagery Program (NAIP)...

  12. Online dating and education

    OpenAIRE

    Fritze, Yvonne; Nordkvelle, Yngve Troye

    2012-01-01

    Taking its inspiration from Luhmann’s communication theory, this article looks at online dating from the perspective of teaching and education. While Eros obviously plays an important role in regenerating the desire to communicate, this ardour is often absent from the domain of net-based teaching. The article explores those features of online dating characteristic of distance dialogue, and discusses the extent to which these can be transferred to communication in the teaching context. We furt...

  13. Nestin-Cre mice are affected by hypopituitarism, which is not due to significant activity of the transgene in the pituitary gland.

    Directory of Open Access Journals (Sweden)

    Christophe Galichet

    2010-07-01

    Full Text Available Nestin-Cre mice express Cre recombinase under control of the rat nestin promoter and central nervous system (CNS enhancer. While endogenous Nestin is expressed in some other tissues including the pituitary gland, Nestin-Cre mice induce recombination predominantly in the CNS. For this reason, they have been widely used to explore gene function or cell fate in the latter. Pituitary hormonal deficiencies, or hypopituitarism, are associated with a wide range of symptoms and with a significant morbidity. These can have a neural and/or a pituitary origin as the gland's secretions are controlled by the hypothalamus. We report here that Nestin-Cre mice themselves are affected by mild hypopituitarism. Hence, physiological consequences are expected, especially in combination with defects resulting from Cre mediated deletion of any gene under investigation. To further investigate the origin of this phenotype, we re-examined the activity of the transgene. We compared it with expression of Nestin itself in the context of the hypothalamo-pituitary axis, especially in the light of a recent report showing pituitary Nestin-Cre activity, which contrasts with previous data. Our results disagree with those of this recent study and do not support the claim that Nestin positive cells are present in the pituitary anlagen, the Rathke's pouch (RP. Moreover we did not observe any significant activity in the post-natal pituitary, in agreement with the initial report.

  14. Nestin-Cre Mice Are Affected by Hypopituitarism, Which Is Not Due to Significant Activity of the Transgene in the Pituitary Gland

    Science.gov (United States)

    Galichet, Christophe; Lovell-Badge, Robin; Rizzoti, Karine

    2010-01-01

    Nestin-Cre mice express Cre recombinase under control of the rat nestin promoter and central nervous system (CNS) enhancer. While endogenous Nestin is expressed in some other tissues including the pituitary gland, Nestin-Cre mice induce recombination predominantly in the CNS. For this reason, they have been widely used to explore gene function or cell fate in the latter. Pituitary hormonal deficiencies, or hypopituitarism, are associated with a wide range of symptoms and with a significant morbidity. These can have a neural and/or a pituitary origin as the gland's secretions are controlled by the hypothalamus. We report here that Nestin-Cre mice themselves are affected by mild hypopituitarism. Hence, physiological consequences are expected, especially in combination with defects resulting from Cre mediated deletion of any gene under investigation. To further investigate the origin of this phenotype, we re-examined the activity of the transgene. We compared it with expression of Nestin itself in the context of the hypothalamo-pituitary axis, especially in the light of a recent report showing pituitary Nestin-Cre activity, which contrasts with previous data. Our results disagree with those of this recent study and do not support the claim that Nestin positive cells are present in the pituitary anlagen, the Rathke's pouch (RP). Moreover we did not observe any significant activity in the post-natal pituitary, in agreement with the initial report. PMID:20625432

  15. Generation of a tenascin-C-CreER2 knockin mouse line for conditional DNA recombination in renal medullary interstitial cells.

    Directory of Open Access Journals (Sweden)

    Wenjuan He

    Full Text Available Renal medullary interstitial cells (RMIC are specialized fibroblast-like cells that exert important functions in maintaining body fluid homeostasis and systemic blood pressure. Here, we generated a RMIC specific tenascin-C promoter driven inducible CreER2 knockin mouse line with an EGFP reporter. Similar as endogenous tenascin-C expression, the reporter EGFP expression in the tenascin-C-CreER2(+/- mice was observed in the inner medulla of the kidney, and co-localized with COX2 but not with AQP2 or AQP1, suggesting selective expression in RMICs. After recombination (tenascin-C-CreER2(+/-/ROSA26-lacZ(+/- mice + tamoxifen, β-gal activity was restricted to the cells in the inner medulla of the kidney, and didn't co-localize with AQP2, consistent with selective Cre recombinase activity in RMICs. Cre activity was not obvious in other major organs or without tamoxifen treatment. This inducible RMIC specific Cre mouse line should therefore provide a novel tool to manipulate genes of interest in RMICs.

  16. Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response.

    Science.gov (United States)

    Fu, Lingchen; Kilberg, Michael S

    2013-02-15

    Mammalian cells respond to amino acid deprivation through multiple signaling pathways referred to as the amino acid response (AAR). Transcription factors mediate the AAR after their activation by several mechanisms; examples include translational control (activating transcription factor 4, ATF4), phosphorylation (p-cJUN), and transcriptional control (ATF3). ATF4 induces ATF3 transcription through a promoter-localized C/EBP-ATF response element (CARE). The present report characterizes an ATF/CRE site upstream of the CARE that also contributes to AAR-induced ATF3 transcription. ATF4 binds to the ATF/CRE and CARE sequences and both are required for a maximal response to ATF4 induction. ATF3, which antagonizes ATF4 and represses its own gene, also exhibited binding activity to the ATF/CRE and CARE sequences. The AAR resulted in elevated total cJUN and p-cJUN protein levels and both forms exhibited binding activity to the ATF/CRE and CARE ATF3 sequences. Knockdown of AAR-enhanced cJUN expression blocked induction of the ATF3 gene and mutation of either the ATF/CRE or the CARE site prevented the cJUN-dependent increase in ATF3-driven luciferase activity. The results indicate that both increased cJUN and the cis-acting ATF/CRE sequence within the ATF3 promoter contribute to the transcriptional activation of the gene during the AAR.

  17. Dating fossil opal phytoliths

    Energy Technology Data Exchange (ETDEWEB)

    Lentfer, C.; Boyd, B. [Southern Cross University, Lismore, NSW (Australia). School of Resource Science and Management; Torrence, R. [Australian Museum, Sydney, NSW (Australia). Division of Anthropology

    1999-11-01

    Full text: Opal phytoliths are microscopic silica bodies formed by the precipitation of hydrated silica dioxide (SiO{sub 2}nH{sub 2}0) in, around and between cell walls. They are relatively resistant to degradation in most environments and thus, can occur in large quantities in palaeosediments. Consequently, they are valuable tools for environmental reconstruction. Furthermore, phytoliths are often the only recoverable organic material in well oxidised sediments, the occluded carbon provides the opportunity for dating sediment whose ages have previously been difficult to determine, and thus, increase the potential for fine resolution determination of environmental change. This poster describes the results of an investigation assessing the viability of AMS radiocarbon dating of fossil phytolith inclusions using samples from Garua Island, West New Britain, PNG. Thirteen phytolith samples, isolated from sediments previously dated using tephrastratigraphy and C14 dating of macroremains of nutshells and wood charcoal, were used in the analysis. As a control measure, thirteen parallel samples of microscopic charcoal were also dated using AMS. The results show that the AMS dates for the microscopic charcoal samples are consistent with ages anticipated from the other dating methods, for all but one sample. However, the dates for eight of the thirteen phytolith samples are considerably younger than expected. This bias could be explained by several factors, including downwashing of phytolith through soils, bioturbation, carbon exchange through the siliceous matrix of the phytolith bodies, and contamination from extraneous sources of modern carbon retained in the samples. Research is currently focusing on the investigation of these issues and selected samples are in the process of being retreated with strong oxidising agents to clear contaminants prior to re-dating. Further to this, a full investigation of one profile with a long sequence is underway. High concentrations of

  18. 46 CFR 151.01-30 - Effective date.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Effective date. 151.01-30 Section 151.01-30 Shipping... BULK LIQUID HAZARDOUS MATERIAL CARGOES General § 151.01-30 Effective date. (a) The regulations in this... effective ninety (90) days after the date of publication in the Federal Register unless the Commandant shall...

  19. 76 FR 77831 - 2012 Presidential Candidate Matching Fund Submission Dates and Post Date of Ineligibility Dates...

    Science.gov (United States)

    2011-12-14

    ... 2012 Presidential Candidate Matching Fund Submission Dates and Post Date of Ineligibility Dates To...: Notice of matching fund submission dates and submission dates for statements of net outstanding campaign... fund submission dates for publicly funded 2012 presidential primary candidates. Eligible candidates may...

  20. 48 CFR 9904.402-63 - Effective date.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Effective date. 9904.402-63 Section 9904.402-63 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.402-63 Effective date. This Standard is effective as of...

  1. 48 CFR 9904.405-63 - Effective date.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Effective date. 9904.405-63 Section 9904.405-63 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.405-63 Effective date. This Standard is effective as of...

  2. 48 CFR 9904.401-63 - Effective date.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Effective date. 9904.401-63 Section 9904.401-63 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.401-63 Effective date. This Standard is effective as of...

  3. 48 CFR 9904.407-63 - Effective date.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Effective date. 9904.407-63 Section 9904.407-63 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.407-63 Effective date. This Standard is effective as of...

  4. 48 CFR 9904.406-63 - Effective date.

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    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Effective date. 9904.406-63 Section 9904.406-63 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.406-63 Effective date. This Standard is effective as of...

  5. 48 CFR 9904.403-63 - Effective date.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Effective date. 9904.403-63 Section 9904.403-63 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.403-63 Effective date. This Standard is effective as of...

  6. 48 CFR 9904.404-63 - Effective date.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Effective date. 9904.404-63 Section 9904.404-63 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE... ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.404-63 Effective date. (a) This Standard is effective...

  7. High burden of Carbapenem-resistant Enterobacteriaceae (CRE fecal carriage at a teaching hospital: cost-effectiveness of screening in low-resource setting

    Directory of Open Access Journals (Sweden)

    Abdul Rahman Zaidah

    2017-05-01

    Full Text Available Abstract Background Infections by multidrug-resistant gram-negative bacteria (MDR-GNB have been continuously growing and pose challenge to health institution globally. Carbapenem-resistant Enterobacteriacea (CRE was identified as one of the MDR-GNB which has limited treatment options and higher mortality compared to those of sensitive strains. We report an increased burden of CRE fecal carriage at a hospital in the North-eastern region of Malaysia. Methods A retrospective descriptive study from August 2013 to December 2015 was conducted in the Medical Microbiology & Parasitology laboratory of Hospital Universiti Sains Malaysia, which is a tertiary teaching hospital with more than 700 beds. This hospital treats patients with various medical and surgical conditions. Suspected CRE from any clinical specimens received by the laboratory was identified and confirmed using standard protocols. Polymerase chain reaction (PCR assay was performed to determine the genotype. Results Altogether, 8306 Enterobacteriaceae was isolated from various clinical specimens during the study period and 477/8306 (5.74% were CRE. Majority of the isolated CRE were Klebsiella [408/477, (85.5%], of which Klebsiella pneumoniae was the predominant species, 388/408 (95%. CRE were mainly isolated from rectal swab (screening, 235/477 (49.3%; urine, 76/477 (15.9%; blood, 46/477 (9.6% and about 7.1% from tracheal aspirate. One hundred and thirty-six isolates were subjected to genotype determination and., 112/136 (82.4% showed positive detection of New Delhi metallo-β-lactamase 1 (NDM-1 gene (bla NDM1. Conclusion The study noted a high numbers of CRE isolated especially from rectal swabs. Active screening results in significant cost pressures and therefore should be revisited and revised, especially in low resource settings.

  8. Iranian dates and ethnic date-based products

    OpenAIRE

    Vahid M. Karizaki

    2017-01-01

    Background: The origins of date production and use in Iran go back to about 4000 bc. Today, more than 400 types of date and various kinds of date-based foods are consumed by the Iranian people. This study aimed at documenting the information about date and date-based products in Iranian cuisine. Methods: The required data were determined by interviews with the farmers, domestic people, consumers, producers, and sellers of dates. In addition, online databases and scientific articles were sc...

  9. Biodiversity of date palm

    Science.gov (United States)

    The date palm (Phoenix dactylifera) is the dominant component upon which the sustainable biophysical and socio-economic structures of the oasis ecosystem are based; a fruit tree with unique nutritional, biochemical and biophysical characteristics, a rich source of aesthetic and cultural values, and ...

  10. Date palm: Production

    Science.gov (United States)

    The future of date palm, as a dioecious, monocot fruit tree largely depends on (1) developing advanced knowledge and information about the dynamics, management, and sustainability of the tree as a central component of the oasis agro-ecosystem, and (2) in-depth understanding of the genetic diversity ...

  11. Confronting Dating Violence.

    Science.gov (United States)

    McNulty, Raymond J.; Heller, Daniel A.; Binet, Tracy

    1997-01-01

    To be safe havens for children, schools cannot address the intellect only. Brattleboro (Vermont) Union High School went beyond academics by sponsoring a performance of "The Yellow Dress," a powerful one-woman play about a teenage victim of dating violence. The production challenged participants to unite school and community, intellect…

  12. Flirting in Online Dating

    DEFF Research Database (Denmark)

    Mortensen, Kristine Køhler

    2017-01-01

    Various fields have examined the activity of flirting, predominantly based on experimental and reported data; the interactional workings are therefore often overlooked. Based on emails and chats from two Danish online dating sites, this article investigates how users negotiate romantic connections...

  13. DNA Hasar Analizinde Tek Hücre Jel Elektroforezi (Komet Yöntemi)

    OpenAIRE

    Durmaz, Ayşen; Dikmen, Nurten; Gündüz, Cumhur

    2014-01-01

    "Single cell gel electrophoresis (SCGE)", also called "Comet Assay", is a sensitive, reliable and rapid technique for quantifying and analyzing DNA damage in individual cells. The comet assay is widely used in living cells, researches and the applications on comet assay is becoming broader day by day. To date, the comet assay has been used for a variety of applications, including genotoxic and cytotoxic agent analyses, environmental toxicolo...

  14. Detection of epithelial to mesenchymal transition in airways of a bleomycin induced pulmonary fibrosis model derived from an α-smooth muscle actin-Cre transgenic mouse

    Directory of Open Access Journals (Sweden)

    Yang Xiao

    2007-01-01

    Full Text Available Abstract Background Epithelial to mesenchymal transition (EMT in alveolar epithelial cells (AECs has been widely observed in patients suffering interstitial pulmonary fibrosis. In vitro studies have also demonstrated that AECs could convert into myofibroblasts following exposure to TGF-β1. In this study, we examined whether EMT occurs in bleomycin (BLM induced pulmonary fibrosis, and the involvement of bronchial epithelial cells (BECs in the EMT. Using an α-smooth muscle actin-Cre transgenic mouse (α-SMA-Cre/R26R strain, we labelled myofibroblasts in vivo. We also performed a phenotypic analysis of human BEC lines during TGF-β1 stimulation in vitro. Methods We generated the α-SMA-Cre mouse strain by pronuclear microinjection with a Cre recombinase cDNA driven by the mouse α-smooth muscle actin (α-SMA promoter. α-SMA-Cre mice were crossed with the Cre-dependent LacZ expressing strain R26R to produce the double transgenic strain α-SMA-Cre/R26R. β-galactosidase (βgal staining, α-SMA and smooth muscle myosin heavy chains immunostaining were carried out simultaneously to confirm the specificity of expression of the transgenic reporter within smooth muscle cells (SMCs under physiological conditions. BLM-induced peribronchial fibrosis in α-SMA-Cre/R26R mice was examined by pulmonary βgal staining and α-SMA immunofluorescence staining. To confirm in vivo observations of BECs undergoing EMT, we stimulated human BEC line 16HBE with TGF-β1 and examined the localization of the myofibroblast markers α-SMA and F-actin, and the epithelial marker E-cadherin by immunofluorescence. Results βgal staining in organs of healthy α-SMA-Cre/R26R mice corresponded with the distribution of SMCs, as confirmed by α-SMA and SM-MHC immunostaining. BLM-treated mice showed significantly enhanced βgal staining in subepithelial areas in bronchi, terminal bronchioles and walls of pulmonary vessels. Some AECs in certain peribronchial areas or even a small

  15. 24 CFR 100.148 - Effective date.

    Science.gov (United States)

    2010-04-01

    ... DISCRIMINATORY CONDUCT UNDER THE FAIR HOUSING ACT Discrimination in Residential Real Estate-Related Transactions... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Effective date. 100.148 Section 100.148 Housing and Urban Development Regulations Relating to Housing and Urban Development OFFICE OF...

  16. Dating fractures in infants

    Energy Technology Data Exchange (ETDEWEB)

    Halliday, K.E., E-mail: kath.halliday@nuh.nhs.uk [Department of Radiology, Nottingham University Hospitals, Queen' s Medical Centre, Nottingham (United Kingdom); Broderick, N.J.; Somers, J.M. [Department of Radiology, Nottingham University Hospitals, Queen' s Medical Centre, Nottingham (United Kingdom); Hawkes, R. [Department of Radiology, Paul O' Gorman Building, Bristol (United Kingdom)

    2011-11-15

    Aim: To document the timing of the appearance of the radiological features of fracture healing in a group of infants in which the date of injury was known and to assess the degree of interobserver agreement. Materials and methods: Three paediatric radiologists independently assessed 161 images of 37 long bone fractures in 31 patients aged 0-44 months. The following features were assessed: soft-tissue swelling, subperiosteal new bone formation (SPNBF), definition of fracture line, presence or absence of callus, whether callus was well or ill defined, and the presence of endosteal callus. Results: Agreement between observers was only moderate for all discriminators except SPNBF. SPNBF was invariably seen after 11 days but was uncommon before this time even in the very young. In one case SPNBF was seen at 4 days. Conclusion: With the exception of SPNBF, the criteria relied on to date fractures are either not reproducible or are poor discriminators of fracture age.

  17. Upregulation of CREM/ICER suppresses wound endothelial CRE-HIF-1α-VEGF-dependent signaling and impairs angiogenesis in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Milad S. Bitar

    2015-01-01

    Full Text Available Impaired angiogenesis and endothelial dysfunction in type 2 diabetes constitute dominant risk factors for non-healing wounds and most forms of cardiovascular disease. We propose that diabetes shifts the ‘angiogenic balance’ in favor of an excessive anti-angiogenic phenotype. Herein, we report that diabetes impairs in vivo sponge angiogenic capacity by decreasing VEGF expression and fibrovascular invasion, and reciprocally enhances the formation of angiostatic molecules, such as thrombospondins, NFκB and FasL. Defective in vivo angiogenesis prompted cellular studies in cultured endothelial cells derived from subcutaneous sponge implants (SIECs of control and Goto-Kakizaki rats. Ensuing data from diabetic SIECs demonstrated a marked upregulation in cAMP-PKA-CREB signaling, possibly stemming from increased expression of adenylyl cyclase isoforms 3 and 8, and decreased expression of PDE3. Mechanistically, we found that oxidative stress and PKA activation in diabetes enhanced CREM/ICER expression. This reduces IRS2 cellular content by inhibiting cAMP response element (CRE transcriptional activity. Consequently, a decrease in the activity of Akt-mTOR ensued with a concomitant reduction in the total and nuclear protein levels of HIF-1α. Limiting HIF-1α availability for the specific hypoxia response elements in diabetic SIECs elicited a marked reduction in VEGF expression, both at the mRNA and protein levels. These molecular abnormalities were illustrated functionally by a defect in various pro-angiogenic properties, including cell proliferation, migration and tube formation. A genetic-based strategy in diabetic SIECs using siRNAs against CREM/ICER significantly augmented the PKA-dependent VEGF expression. To this end, the current data identify the importance of CREM/ICER as a negative regulator of endothelial function and establish a link between CREM/ICER overexpression and impaired angiogenesis during the course of diabetes. Moreover, it could

  18. Proglucagon Promoter Cre-Mediated AMPK Deletion in Mice Increases Circulating GLP-1 Levels and Oral Glucose Tolerance.

    Directory of Open Access Journals (Sweden)

    Sophie R Sayers

    Full Text Available Enteroendocrine L-cells synthesise and release the gut hormone glucagon-like peptide-1 (GLP-1 in response to food transit. Deletion of the tumour suppressor kinase LKB1 from proglucagon-expressing cells leads to the generation of intestinal polyps but no change in circulating GLP-1 levels. Here, we explore the role of the downstream kinase AMP-activated protein kinase (AMPK in these cells.Loss of AMPK from proglucagon-expressing cells was achieved using a preproglucagon promoter-driven Cre (iGluCre to catalyse recombination of floxed alleles of AMPKα1 and α2. Oral and intraperitoneal glucose tolerance were measured using standard protocols. L-cell mass was measured by immunocytochemistry. Hormone and peptide levels were measured by electrochemical-based luminescence detection or radioimmunoassay.Recombination with iGluCre led to efficient deletion of AMPK from intestinal L- and pancreatic alpha-cells. In contrast to mice rendered null for LKB1 using the same strategy, mice deleted for AMPK displayed an increase (WT: 0.05 ± 0.01, KO: 0.09±0.02%, p<0.01 in L-cell mass and elevated plasma fasting (WT: 5.62 ± 0.800 pg/ml, KO: 14.5 ± 1.870, p<0.01 and fed (WT: 15.7 ± 1.48pg/ml, KO: 22.0 ± 6.62, p<0.01 GLP-1 levels. Oral, but not intraperitoneal, glucose tolerance was significantly improved by AMPK deletion, whilst insulin and glucagon levels were unchanged despite an increase in alpha to beta cell ratio (WT: 0.23 ± 0.02, KO: 0.33 ± 0.03, p<0.01.AMPK restricts L-cell growth and GLP-1 secretion to suppress glucose tolerance. Targeted inhibition of AMPK in L-cells may thus provide a new therapeutic strategy in some forms of type 2 diabetes.

  19. Self-excising Cre/mutant lox marker recycling system for multiple gene integrations and consecutive gene deletions in Aspergillus oryzae.

    Science.gov (United States)

    Zhang, Silai; Ban, Akihiko; Ebara, Naoki; Mizutani, Osamu; Tanaka, Mizuki; Shintani, Takahiro; Gomi, Katsuya

    2017-04-01

    In this study, we developed a self-excising Cre/loxP-mediated marker recycling system with mutated lox sequences to introduce a number of biosynthetic genes into Aspergillus oryzae. To construct the self-excising marker cassette, both the selectable marker, the Aspergillus nidulans adeA gene, and the Cre recombinase gene (cre), conditionally expressed by the xylanase-encoding gene promoter, were designed to be located between the mutant lox sequences, lox66 and lox71. However, construction of the plasmid failed, possibly owing to a slight expression of cre downstream of the fungal gene promoter in Escherichia coli. Hence, to avoid the excision of the cassette in E. coli, a 71-bp intron of the A. oryzae xynG2 gene was inserted into the cre gene. The A. oryzae adeA deletion mutant was transformed with the resulting plasmid in the presence of glucose, and the transformants were cultured in medium containing xylose as the sole carbon source. PCR analysis of genomic DNA from resultant colonies revealed the excision of both the marker and Cre expression construct, indicating that the self-excising marker cassette was efficient at removing the selectable marker. Using the marker recycling system, hyperproduction of kojic acid could be achieved in A. oryzae by the introduction of two genes that encode oxidoreductase and transporter. Furthermore, we also constructed an alternative marker recycling cassette bearing the A. nidulans pyrithiamine resistant gene (ptrA) as a dominant selectable marker. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  20. Dating Violence among College Students

    Science.gov (United States)

    Iconis, Rosemary

    2013-01-01

    Dating violence is a significant problem on college campuses. More than one-fifth of the undergraduate dating population are physically abused by their dating partners and an even greater percentage are psychologically abused. Researchers have identified risk factors for college student dating violence. Preventive interventions are strongly…

  1. 210Pb dating

    Science.gov (United States)

    Swarzenski, Peter W.

    2014-01-01

    Roughly fifty years ago, a small group of scientists from Belgium and the United States, trying to better constrain ice sheet accumulation rates, attempted to apply what was then know about environmental lead as a potential geochronometer. Thus Goldberg (1963) developed the first principles of the 210Pb dating method, which was soon followed by a paper by Crozaz et al. (1964), who examined accumulation history of Antarctic snow using 210Pb. Shortly thereafter, Koide et al. (1972, 1973) adapted this technique to unravel sediment deposition and accumulation records in deep-sea environments. Serendipitously, they chose to work in a deep basin off California, where an independent and robust age model had already been developed. Krishanswami et al. (1971) extended the use of this technique to lacustrine deposits to reconstruct depositional histories of lake sediment, and maybe more importantly, contaminant inputs and burial. Thus, the powerful tool for dating recent (up to about one century old) sediment deposits was established and soon widely adopted. Today almost all oceanographic or limnologic studies that address recent depositional reconstructions employ 210Pb as one of several possible geochronometers (Andrews et al., 2009; Gale, 2009; Baskaran, 2011; Persson and Helms, 2011). This paper presents a short overview of the principles of 210Pb dating and provides a few examples that illustrate the utility of this tracer in contrasting depositional systems. Potential caveats and uncertainties (Appleby et al., 1986; Binford, 1990; Binford et al., 1993; Smith, 2001; Hancock et al., 2002) inherent to the use and interpretation of 210Pb-derived age-models are also introduced. Recommendations as to best practices for most reliable uses and reporting are presented in the summary.

  2. Vulcanism and Radiocarbon Dates

    Science.gov (United States)

    Libby, L. M.; Libby, W. F.

    1972-10-01

    We consider whether the long term perturbation of radiocarbon dates, which is known to be approximately a sin function of period about 8000 years and amplitude of about 8% peak-to-peak, could have been caused in any major part by vulcanism. We conclude that this is not the case. On the contrary, present day volcanoes are a far less important source of inert CO{sub 2} (about 100 fold less) than is man's burning of fossil fuels which has caused the Suess dilution of about 2%. (auth)

  3. TRANSFORMATION EFFECTIVENESS FOR ARABIDOPSIS THALIANA PLANTS BY DNA-CONSTRUCTIONS WITH SITE-SPECIFIC RECOMBINASE SYSTEM Cre/loxP

    Directory of Open Access Journals (Sweden)

    A. S. Sekan

    2015-02-01

    Full Text Available Using of new approach with site-specific recombinase system Cre/loxP under the control of 35S-promoter to generate marker-free genetically modified plants was developed. The analysis of recombinase system was carried out during the next generation of Arabidopsis thaliana plants, produced by agrobacterium transformation method. For this purpose two types of DNA-constructions were used for establishing better variant. The histochemical analysis of the plants progeny T1 transformed by both construct types was described. As a result of our work, it was established that the amount of marker-free transformants was arising during every next transformation offspring independently of the used construct type. The new strategy provides a simple and rapid way to eliminate swelective and marker genes.

  4. A 3D Searchable Database of Transgenic Zebrafish Gal4 and Cre Lines for Functional Neuroanatomy Studies.

    Science.gov (United States)

    Marquart, Gregory D; Tabor, Kathryn M; Brown, Mary; Strykowski, Jennifer L; Varshney, Gaurav K; LaFave, Matthew C; Mueller, Thomas; Burgess, Shawn M; Higashijima, Shin-Ichi; Burgess, Harold A

    2015-01-01

    Transgenic methods enable the selective manipulation of neurons for functional mapping of neuronal circuits. Using confocal microscopy, we have imaged the cellular-level expression of 109 transgenic lines in live 6 day post fertilization larvae, including 80 Gal4 enhancer trap lines, 9 Cre enhancer trap lines and 20 transgenic lines that express fluorescent proteins in defined gene-specific patterns. Image stacks were acquired at single micron resolution, together with a broadly expressed neural marker, which we used to align enhancer trap reporter patterns into a common 3-dimensional reference space. To facilitate use of this resource, we have written software that enables searching for transgenic lines that label cells within a selectable 3-dimensional region of interest (ROI) or neuroanatomical area. This software also enables the intersectional expression of transgenes to be predicted, a feature which we validated by detecting cells with co-expression of Cre and Gal4. Many of the imaged enhancer trap lines show intrinsic brain-specific expression. However, to increase the utility of lines that also drive expression in non-neuronal tissue we have designed a novel UAS reporter, that suppresses expression in heart, muscle, and skin through the incorporation of microRNA binding sites in a synthetic 3' untranslated region. Finally, we mapped the site of transgene integration, thus providing molecular identification of the expression pattern for most lines. Cumulatively, this library of enhancer trap lines provides genetic access to 70% of the larval brain and is therefore a powerful and broadly accessible tool for the dissection of neural circuits in larval zebrafish.

  5. Commission of energy regulation. 2004 activity report; Commission de regulation de l'energie. Rapport d'activite 2004

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-07-01

    The commission of energy regulation (CRE) is an independent administrative authority in charge of the control of the operation of gas and electricity markets. This document is the fifth activity report of CRE and covers the July 1, 2003 - June 30, 2004 period, which corresponds to the era of opening of energy markets as a consequence of the enforcement of the June 26, 2003 European directive. In the framework of the stakes made by energy markets liberalization, this document presents the situation of the gas and electricity markets during this period (European framework, regulation of both markets, public utility mission..) and describes CRE's means for the monitoring of these markets. (J.S.)

  6. Laboratory for Radiokrypton Dating

    Science.gov (United States)

    Lu, Z.; Bailey, K.; Jiang, W.; Müller, P.; O'Connor, T. P.; Zappala, J. C.

    2013-12-01

    Due to its simple production and transport processes in the terrestrial environment, the long-lived noble-gas isotope 81Kr (half-life = 230 kyr) is the ideal tracer for studying old water and ice in the age range of 10^5-10^6 years, a range beyond the reach of 14C. 81Kr dating, a concept pursued in the past four decades by numerous laboratories employing a variety of techniques, is now available for the first time to the earth science community at large. This is made possible by the development of ATTA-3 (Jiang et al., GCA 91, 1-6; 2012), an efficient and selective atom counter based on the Atom Trap Trace Analysis method (Chen et al., Science 286, 1139-1141; 1999). The instrument is capable of measuring both 81Kr/Kr and 85Kr/Kr ratios of environmental samples in the range of 10^-14-10^-10. For 81Kr-dating in the age range of 150 - 1,500 kyr, the required sample size is 5 - 10 micro-L STP of krypton gas, which can be extracted from approximately 100 - 200 kg of water or 40 - 80 kg of ice. For 85Kr/Kr analysis, the required sample size is generally smaller by an order of magnitude because of the isotope's higher initial abundance in the atmosphere. The Laboratory for Radiokrypton Dating is currently equipped to analyze up to 120 samples per year. With future equipment upgrades, this limit can be increased as demand grows. In the period since November 2011, the Laboratory has measured both 81Kr/Kr and 85Kr/Kr ratios in over 50 samples that had been extracted by collaborators from six different continents. The samples were from groundwater wells in the Great Artesian Basin (Australia), Guarani Aquifer (Brazil), and Locust Grove (Maryland); from brine wells of the Waste Isolation Pilot Plant (New Mexico); from geothermal steam vents in Yellowstone National Park; from near-surface ice at Taylor Glacier, Antarctica; and from deep mines in South Africa. Sample collection and purification was performed by groups including the University of Illinois at Chicago, University

  7. Aeromonas hydrophila AmpH and CepH beta-lactamases: derepressed expression in mutants of Escherichia coli lacking creB.

    Science.gov (United States)

    Avison, M B; Niumsup, P; Walsh, T R; Bennett, P M

    2000-11-01

    The class 1 cephalosporinase (CepH) and class 2d oxacillinase (AmpH) from an Aeromonas hydrophila clinical isolate, strain T429125, have been cloned and sequenced. Both enzymes are typical of their equivalents in other species of Aeromonas Both cloned beta-lactamase genes were expressed at a low level in a standard laboratory Escherichia coli strain, but when cloned into a cre deletion E. coli mutant, they were expressed at significantly higher levels. Specific disruption of the creB gene resulted in similar increased levels of beta-lactamase expression, so it was concluded that CreB represses the transcription of ampH and cepH in a cre(+) E. coli strain. The expression of cepH was four times that of ampH in the deltacre mutant because of an additional factor encoded on the cloned T429125 chromosomal fragment containing cepH. This factor was able to trans-activate expression of co-resident ampH in the deltacre mutant such that expression of the two genes was approximately equal. The entire cepH-containing fragment was sequenced, but it contained no genes that were obviously related to any known class of DNA-binding protein.

  8. Excision of a selectable marker gene in transgenic banana using a Cre/lox system controlled by an embryo specific promoter.

    Science.gov (United States)

    Chong-Pérez, Borys; Reyes, Maritza; Rojas, Luis; Ocaña, Bárbara; Ramos, Adolfo; Kosky, Rafael G; Angenon, Geert

    2013-09-01

    Antibiotic and herbicide resistance genes have been used in transgene technology as powerful selection tools. Nonetheless, once transgenic events have been obtained their presence is no longer needed and can even be undesirable. In this work, we have developed a system to excise the selectable marker and the cre recombinase genes from transgenic banana cv. 'Grande Naine' (Musa AAA). To achieve this, the embryo specific REG-2 promoter was isolated from rice and its expression pattern in banana cell clumps, somatic embryos and regenerated plantlets was characterized by using a pREG2::uidA fusion construct. Subsequently, the REG-2 promoter was placed upstream of the cre gene, conferring Cre functionality in somatic embryos and recombination of lox sites resulting in excision of the selectable marker and cre genes. PCR analysis revealed that 41.7 % of the analysed transgenic plants were completely marker free, results that were thereafter confirmed by Southern blot hybridization. These results demonstrate the feasibility of using developmentally controlled promoters to mediate marker excision in banana. This system does not require any extra handling compared to the conventional transformation procedure and might be useful in other species regenerating through somatic embryogenesis.

  9. α-Fetoprotein promoter-driven Cre/LoxP-switched RNA interference for hepatocellular carcinoma tissue-specific target therapy.

    Directory of Open Access Journals (Sweden)

    Yuan-Fei Peng

    Full Text Available RNA interference (RNAi has recently emerged as a potential treatment modality for hepatocellular carcinoma (HCC therapy, but the lack of cellular targets and sustained efficacy limits its application. The purpose of this study is to develop an HCC tissue-specific RNAi system and investigate its possibility for HCC treatment.Two different HCC-specific RNAi systems in which therapeutic miRNA or shRNA against target gene (Beclin 1 was directly or indirectly driven by alpha-fetoprotein promoter (AFP-miRNA and AFP-Cre/LoxP-shRNA were constructed. Human HCC cell lines (HepG2, Hep3B and HCCLM3 and non-HCC cell lines (L-02, Hela and SW1116 were infected with the systems. The effectiveness and tissue-specificity of the systems were examined by Q-PCR and western blot analysis. The efficacy of the systems was further tested in mouse model of HCC by intravenous or intratumoral administration. The feasibility of the system for HCC treatment was evaluated by applying the system as adjuvant therapy to enhance sorafenib treatment. An AFP-Cre/LoxP-shRNA system targeting Atg5 gene (AFP-Cre/LoxP-shRNA-Atg5 was constructed and its efficacy in sensitizing HCC cells (MHCC97L/PLC to sorafenib treatment was examined by apoptosis assay in vitro and tumorigenesis assay in vivo.The AFP-miRNA system could silence target gene (Beclin 1 but required a high titer which was lethal to target cells. The AFP-Cre/LoxP-shRNA system could efficiently knockdown target gene while maintain high HCC specificity. Intratumoral injection of the AFP-Cre/LoxP-shRNA system could efficiently silence target gene (Beclin 1 in vivo while intravenous administration could not. The AFP-Cre/LoxP-shRNA system target Atg5 gene could significantly sensitize MHCC97L/PLC cells to sorafenib-induced apoptosis in vitro and tumor growth suppression in vivo.An efficient HCC tissue-specific RNAi system (AFP-Cre/LoxP-shRNA was successfully established. The system provides a usable tool for HCC-specific RNAi

  10. 7 CFR 201.30a - Date of test.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT... germination test was completed and the date of transportation or delivery for transportation in interstate...

  11. 29 CFR 4062.5 - Net worth record date.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Net worth record date. 4062.5 Section 4062.5 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION LIABILITY LIABILITY FOR... to or abuse of the plan termination insurance system, may establish as the net worth record date an...

  12. 26 CFR 301.9000-7 - Effective date.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Effective date. 301.9000-7 Section 301.9000-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) PROCEDURE AND... Effective date. These regulations are applicable on February 14, 2005. ...

  13. 26 CFR 1.383-0 - Effective date.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Effective date. 1.383-0 Section 1.383-0 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.383-0 Effective date. (a) The regulations under section 383 (other...

  14. Violence in Adolescent Dating Relationships

    Science.gov (United States)

    Jouriles, Ernest N.; Platt, Cora; McDonald, Renee

    2009-01-01

    Beginning with a definition of dating and dating violence among adolescents, this article explores the factors which impact such violence. It concludes with a review of two school-based prevention/intervention programs (Safe Dates and The Youth Relationships Project). (Contains 1 table.)

  15. Mikroskop görüntüsünde otomatik embriyonik kök hücre tespiti ve sayımı

    Directory of Open Access Journals (Sweden)

    Gökçen Çetinel

    2016-08-01

    Full Text Available Mikroskop altında hücre sayımı, bir uzman tarafından mikroskop merceğine sürekli bakılarak veya otomatik hücre sayımı yöntemleri kullanılarak yapılabilmektedir. Sayım uzman tarafından yapıldığında oldukça yorucu, uzun süren ve düşük doğruluğa sahip bir işlem haline gelmektedir. Bunun dışında hücre sayımını zorlaştrıan ve doğruluğu düşüren başka etkenler de mevcuttur. Bu nedenle, hücre sayımının otomatik bir şekilde yapılması ve sunulan sayım yöntemlerinin iyileştirilmesi gerekmektedir. Bu çalışmada, flüoresans mikroskop görüntüsünde otomatik hücre tespiti ve sayımı için bir yöntem sunulmuştur. Yöntemin tüm adımları açıklanmıştır. Sunulan yöntemin etkinliği birçok farklı durum için simülasyon programları vasıtasıyla test edilmiş, yöntemin başarıya ulaştığı ve gelecek vadeden bir çalışma olduğu gösterilmiştir.

  16. Regulation of Energy Balance via BDNF Expressed in Nonparaventricular Hypothalamic Neurons.

    Science.gov (United States)

    Yang, Haili; An, Juan Ji; Sun, Chao; Xu, Baoji

    2016-05-01

    Brain-derived neurotrophic factor (BDNF) expressed in the paraventricular hypothalamus (PVH) has been shown to play a key role in regulating energy intake and energy expenditure. BDNF is also expressed in other hypothalamic nuclei; however, the role in the control of energy balance for BDNF produced in these structures remains largely unknown. We found that deleting the Bdnf gene in the ventromedial hypothalamus (VMH) during embryogenesis using the Sf1-Cre transgene had no effect on body weight in mice. In contrast, deleting the Bdnf gene in the adult VMH using Cre-expressing virus led to significant hyperphagia and obesity. These observations indicate that the lack of a hyperphagia phenotype in the Sf1-Cre/Bdnf mutant mice is likely due to developmental compensation. To investigate the role of BDNF expressed in other hypothalamic areas, we employed the hypothalamus-specific Nkx2.1-Cre transgene to delete the Bdnf gene. We found that the Nkx2.1-Cre transgene could abolish BDNF expression in many hypothalamic nuclei, but not in the PVH, and that the resulting mutant mice developed modest obesity due to reduced energy expenditure. Thus, BDNF produced in the VMH plays a role in regulating energy intake. Furthermore, BDNF expressed in hypothalamic areas other than PVH and VMH is also involved in the control of energy expenditure.

  17. node.dating: dating ancestors in phylogenetic trees in R.

    Science.gov (United States)

    Jones, Bradley R; Poon, Art F Y

    2017-03-15

    Phylogenetic trees encode the evolutionary distances between species or populations. With sufficient information, these evolutionary distances can be rescaled over time to provide estimates of the dates of the most recent ancestors of the species. Here we present the R program node.dating, divergence-time analysis software, which uses a maximum-likelihood method to estimate the dates of the internal nodes of a phylogenetic tree. node.dating is available as a part of the R v3.30 package ape v4.0 (cran.r-project.org). node.dating is also available in the GitHub repository: https://github.com/brj1/node.dating , along with supplementary software and tests. brj1@sfu.ca. Supplementary data are available at Bioinformatics online.

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  19. Growth factor independence 1b (gfi1b is important for the maturation of erythroid cells and the regulation of embryonic globin expression.

    Directory of Open Access Journals (Sweden)

    Lothar Vassen

    Full Text Available Growth factor independence 1b (GFI1B is a DNA binding repressor of transcription with vital functions in hematopoiesis. Gfi1b-null embryos die at midgestation very likely due to defects in erythro- and megakaryopoiesis. To analyze the full functionality of Gfi1b, we used conditionally deficient mice that harbor floxed Gfi1b alleles and inducible (Mx-Cre, Cre-ERT or erythroid specific (EpoR-Cre Cre expressing transgenes. In contrast to the germline knockout, EpoR-Cre mediated erythroid specific ablation of Gfi1b allows full gestation, but causes perinatal lethality with very few mice surviving to adulthood. Both the embryonic deletion of Gfi1b by EpoR-Cre and the deletion in adult mice by Mx-Cre or Cre-ERT leads to reduced numbers of erythroid precursors, perturbed and delayed erythroid maturation, anemia and extramedullary erythropoiesis. Global expression analyses showed that the Hba-x, Hbb-bh1 and Hbb-y embryonic globin genes were upregulated in Gfi1b deficient TER119+ fetal liver cells over the gestation period from day 12.5-17.5 p.c. and an increased level of Hbb-bh1 and Hbb-y embryonic globin gene expression was even maintained in adult Gfi1b deficient mice. While the expression of Bcl11a, a regulator of embryonic globin expression was not affected by Gfi1b deficiency, the expression of Gata1 was reduced and the expression of Sox6, also involved in globin switch, was almost entirely lost when Gfi1b was absent. These findings establish Gfi1b as a regulator of embryonic globin expression and embryonic and adult erythroid maturation.

  20. A 3D searchable database of transgenic zebrafish Gal4 and Cre lines for functional neuroanatomy studies

    Directory of Open Access Journals (Sweden)

    Gregory D Marquart

    2015-11-01

    Full Text Available Transgenic methods enable the selective manipulation of neurons for functional mapping of neuronal circuits. Using confocal microscopy, we have imaged the cellular-level expression of 109 transgenic lines in live 6 day post fertilization larvae, including 80 Gal4 enhancer trap lines, 9 Cre enhancer trap lines and 20 transgenic lines that express fluorescent proteins in defined gene-specific patterns. Image stacks were acquired at single micron resolution, together with a broadly expressed neural marker, which we used to align enhancer trap reporter patterns into a common 3-dimensional reference space. To facilitate use of this resource, we have written software that enables searching for transgenic lines that label cells within a selectable 3-dimensional region of interest or neuroanatomical area. Many of the imaged enhancer trap lines show intrinsic brain-specific expression. However, to increase the utility of lines that also drive expression in non-neuronal tissue we have designed a novel UAS reporter, that suppresses expression in heart, muscle and skin through the incorporation of microRNA binding sites in a synthetic 3' untranslated region. Finally, we mapped the site of transgene integration, thus providing molecular identification of the expression pattern for most lines. Cumulatively, this library of enhancer trap lines provides genetic access to 70 % of the larval brain and is therefore a powerful and broadly accessible tool for the dissection of neural circuits in larval zebrafish.

  1. A set of vectors for introduction of antibiotic resistance genes by in vitro Cre-mediated recombination

    Directory of Open Access Journals (Sweden)

    Vassetzky Yegor S

    2008-12-01

    Full Text Available Abstract Background Introduction of new antibiotic resistance genes in the plasmids of interest is a frequent task in molecular cloning practice. Classical approaches involving digestion with restriction endonucleases and ligation are time-consuming. Findings We have created a set of insertion vectors (pINS carrying genes that provide resistance to various antibiotics (puromycin, blasticidin and G418 and containing a loxP site. Each vector (pINS-Puro, pINS-Blast or pINS-Neo contains either a chloramphenicol or a kanamycin resistance gene and is unable to replicate in most E. coli strains as it contains a conditional R6Kγ replication origin. Introduction of the antibiotic resistance genes into the vector of interest is achieved by Cre-mediated recombination between the replication-incompetent pINS and a replication-competent target vector. The recombination mix is then transformed into E. coli and selected by the resistance marker (kanamycin or chloramphenicol present in pINS, which allows to recover the recombinant plasmids with 100% efficiency. Conclusion Here we propose a simple strategy that allows to introduce various antibiotic-resistance genes into any plasmid containing a replication origin, an ampicillin resistance gene and a loxP site.

  2. Study of muscle cell dedifferentiation after skeletal muscle injury of mice with a Cre-Lox system.

    Directory of Open Access Journals (Sweden)

    Xiaodong Mu

    2011-02-01

    Full Text Available Dedifferentiation of muscle cells in the tissue of mammals has yet to be observed. One of the challenges facing the study of skeletal muscle cell dedifferentiation is the availability of a reliable model that can confidentially distinguish differentiated cell populations of myotubes and non-fused mononuclear cells, including stem cells that can coexist within the population of cells being studied.In the current study, we created a Cre/Lox-β-galactosidase system, which can specifically tag differentiated multinuclear myotubes and myotube-generated mononuclear cells based on the activation of the marker gene, β-galactosidase. By using this system in an adult mouse model, we found that β-galactosidase positive mononuclear cells were generated from β-galactosidase positive multinuclear myofibers upon muscle injury. We also demonstrated that these mononuclear cells can develop into a variety of different muscle cell lineages, i.e., myoblasts, satellite cells, and muscle derived stem cells.These novel findings demonstrated, for the first time, that cellular dedifferentiation of skeletal muscle cells actually occurs in mammalian skeletal muscle following traumatic injury in vivo.

  3. 5-HT inhibition of rat insulin 2 promoter Cre recombinase transgene and proopiomelanocortin neuron excitability in the mouse arcuate nucleus.

    Science.gov (United States)

    Hisadome, K; Smith, M A; Choudhury, A I; Claret, M; Withers, D J; Ashford, M L J

    2009-03-03

    A number of anti-obesity agents have been developed that enhance hypothalamic 5-HT transmission. Various studies have demonstrated that arcuate neurons, which express proopiomelanocortin peptides (POMC neurons), and neuropeptide Y with agouti-related protein (NPY/AgRP) neurons, are components of the hypothalamic circuits responsible for energy homeostasis. An additional arcuate neuron population, rat insulin 2 promoter Cre recombinase transgene (RIPCre) neurons, has recently been implicated in hypothalamic melanocortin circuits involved in energy balance. It is currently unclear how 5-HT modifies neuron excitability in these local arcuate neuronal circuits. We show that 5-HT alters the excitability of the majority of mouse arcuate RIPCre neurons, by either hyperpolarization and inhibition or depolarization and excitation. RIPCre neurons sensitive to 5-HT, predominantly exhibit hyperpolarization and pharmacological studies indicate that inhibition of neuronal firing is likely to be through 5-HT(1F) receptors increasing current through a voltage-dependent potassium conductance. Indeed, 5-HT(1F) receptor immunoreactivity co-localizes with RIPCre green fluorescent protein expression. A minority population of POMC neurons also respond to 5-HT by hyperpolarization, and this appears to be mediated by the same receptor-channel mechanism. As neither POMC nor RIPCre neuronal populations display a common electrical response to 5-HT, this may indicate that sub-divisions of POMC and RIPCre neurons exist, perhaps serving different outputs.

  4. Cell-Type-Specific Circuit Connectivity of Hippocampal CA1 Revealed through Cre-Dependent Rabies Tracing

    Directory of Open Access Journals (Sweden)

    Yanjun Sun

    2014-04-01

    Full Text Available We developed and applied a Cre-dependent, genetically modified rabies-based tracing system to map direct synaptic connections to specific CA1 neuron types in the mouse hippocampus. We found common inputs to excitatory and inhibitory CA1 neurons from CA3, CA2, the entorhinal cortex (EC, the medial septum (MS, and, unexpectedly, the subiculum. Excitatory CA1 neurons receive inputs from both cholinergic and GABAergic MS neurons, whereas inhibitory neurons receive a great majority of inputs from GABAergic MS neurons. Both cell types also receive weaker input from glutamatergic MS neurons. Comparisons of inputs to CA1 PV+ interneurons versus SOM+ interneurons showed similar strengths of input from the subiculum, but PV+ interneurons received much stronger input than SOM+ neurons from CA3, the EC, and the MS. Thus, rabies tracing identifies hippocampal circuit connections and maps how the different input sources to CA1 are distributed with different strengths on each of its constituent cell types.

  5. Using the cre-lox recombination system to assess functional impairment caused by amino acid substitutions in yeast proteins

    Directory of Open Access Journals (Sweden)

    Shirley Renee L.

    2004-01-01

    Full Text Available A method was developed to assess the functional significance of a sequence motif in yeast Upf3p, a protein required for nonsense-mediated mRNA decay (NMD. The motif lies at the edge of the Upf3p-Upf2p interaction domain, but at the same time resembles the canonical leucine-rich nuclear export sequence (NES found in proteins that bind Crm1p exportin. To test the function of the putative NES, site-directed mutations that cause substitutions of conserved NES-A residues were first selected to identify hypermorphic alleles. Next, a portable Crm1p-binding NES from HIV-1 Rev protein that functions in yeast was fused en masse to the C-terminus of variant Upf3 proteins using loxP sites recognized by bacterial cre-recombinase. Finally, variant Upf3-Rev proteins that were functional in NMD were selected and examined for the types of amino acid substitutions present in NES-A. The mutational analysis revealed that amino acid substitutions in the Upf3 NES impair both nuclear export and the Upf2p-Upf3p interaction, both of which are required for Upf3p to function in NMD. The method described in this report could be modified for the genetic analysis of a variety of portable protein domains.

  6. CRE Solvability, Nonlocal Symmetry and Exact Interaction Solutions of the Fifth-Order Modified Korteweg-de Vries Equation

    Science.gov (United States)

    Cheng, Wen-Guang; Qiu, De-Qin; Yu, Bo

    2017-06-01

    This paper is concerned with the fifth-order modified Korteweg-de Vries (fmKdV) equation. It is proved that the fmKdV equation is consistent Riccati expansion (CRE) solvable. Three special form of soliton-cnoidal wave interaction solutions are discussed analytically and shown graphically. Furthermore, based on the consistent tanh expansion (CTE) method, the nonlocal symmetry related to the consistent tanh expansion (CTE) is investigated, we also give the relationship between this kind of nonlocal symmetry and the residual symmetry which can be obtained with the truncated Painlevé method. We further study the spectral function symmetry and derive the Lax pair of the fmKdV equation. The residual symmetry can be localized to the Lie point symmetry of an enlarged system and the corresponding finite transformation group is computed. Supported by National Natural Science Foundation of China under Grant No. 11505090, and Research Award Foundation for Outstanding Young Scientists of Shandong Province under Grant No. BS2015SF009

  7. 29 CFR 2584.8477(e)-7 - Effective date.

    Science.gov (United States)

    2010-07-01

    ... Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR FIDUCIARY RESPONSIBILITY UNDER THE FEDERAL EMPLOYEES' RETIREMENT SYSTEM ACT OF 1986 RULES AND REGULATIONS FOR THE ALLOCATION OF FIDUCIARY RESPONSIBILITY § 2584.8477(e)-7 Effective date. This section is...

  8. Numb regulates acinar cell dedifferentiation and survival during pancreatic damage and acinar-to-ductal metaplasia.

    Science.gov (United States)

    Greer, Renee L; Staley, Binnaz K; Liou, Angela; Hebrok, Matthias

    2013-11-01

    Pancreatic ductal adenocarcinoma (PDA) is a leading cause of cancer-related death. Through the process of acinar-to-ductal metaplasia (ADM), pancreatic acinar cells give rise to pancreatic intraepithelial neoplasia (PanIN), the most common precursor of PDA. However, even when Kras is activated in a majority of acinar cells, ADM and subsequent development of PanINs is inefficient in the absence of additional stresses. Numb regulates cell junctions, integrins, and the activity of embryonic signaling pathways; therefore, we investigated its effects on acinar cell dedifferentiation, regeneration, and metaplasia. We used mouse models of pancreatic regeneration and PDA as well as mice with loss-of-function alleles of Numb (p48Cre/p48Cre(ER);Numb(f/f) and p48Cre/p48Cre(ER);Kras(G12D);Numb(f/f) mice) to study the roles of Numb in pancreatic regeneration and ADM. Loss of Numb resulted in premature dedifferentiation of acinar cells in response to injury due to administration of the cholecystokinin analogue cerulein and interfered with acinar cell regeneration. Numb was found to regulate multiple signaling pathways in acinar cells during cerulein-induced pancreatitis. Disruption of Numb accelerated and destabilized ADM in the context of oncogenic Kras (in p48Cre;Kras(G12D);Numb(f/f) and p48Cre(ER);Kras(G12D);Numb(f/f) mice). Numb is an important regulator of acinar cell differentiation and viability during metaplasia. In mice with pancreatitis or pancreatic injury, elimination of Numb causes dedifferentiated acinar cells to undergo apoptosis, and this is not mitigated by oncogenic Kras. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Hypoxia inducible factor-2α regulates the development of retinal astrocytic network by maintaining adequate supply of astrocyte progenitors.

    Directory of Open Access Journals (Sweden)

    Li-Juan Duan

    Full Text Available Here we investigate the role of hypoxia inducible factor (HIF-2α in coordinating the development of retinal astrocytic and vascular networks. Three Cre mouse lines were used to disrupt floxed Hif-2α, including Rosa26(CreERT2, Tie2(Cre, and GFAP(Cre. Global Hif-2α disruption by Rosa26(CreERT2 led to reduced astrocytic and vascular development in neonatal retinas, whereas endothelial disruption by Tie2(Cre had no apparent effects. Hif-2α deletion in astrocyte progenitors by GFAP(Cre significantly interfered with the development of astrocytic networks, which failed to reach the retinal periphery and were incapable of supporting vascular development. Perplexingly, the abundance of strongly GFAP(+ mature astrocytes transiently increased at P0 before they began to lag behind the normal controls by P3. Pax2(+ and PDGFRα(+ astrocytic progenitors and immature astrocytes were dramatically diminished at all stages examined. Despite decreased number of astrocyte progenitors, their proliferation index or apoptosis was not altered. The above data can be reconciled by proposing that HIF-2α is required for maintaining the supply of astrocyte progenitors by slowing down their differentiation into non-proliferative mature astrocytes. HIF-2α deficiency in astrocyte progenitors may accelerate their differentiation into astrocytes, a change which greatly interferes with the replenishment of astrocyte progenitors due to insufficient time for proliferation. Rapidly declining progenitor supply may lead to premature cessation of astrocyte development. Given that HIF-2α protein undergoes oxygen dependent degradation, an interesting possibility is that retinal blood vessels may regulate astrocyte differentiation through their oxygen delivery function. While our findings support the consensus that retinal astrocytic template guides vascular development, they also raise the possibility that astrocytic and vascular networks may mutually regulate each other

  10. Cyclic strain causes heterogeneous induction of transcription factors, AP-1, CRE binding protein and NF-kB, in endothelial cells: species and vascular bed diversity.

    Science.gov (United States)

    Du, W; Mills, I; Sumpio, B E

    1995-12-01

    Recent studies demonstrate that cyclic strain stimulates protein kinase C in bovine aortic endothelial cells (BAEC) as well as the induction of immediate early genes and the transcription factor activator protein-1 (AP-1) in human umbilical vein endothelial cells (HUVEC). The objective of this study was to determine whether transcriptional factor induction in endothelial cells (EC) exposed to strain is the same with regard to the species and vascular bed they are derived from. Evidence for a heterogeneous response for growth, orientation and prostacyclin secretion has been obtained for a variety of EC exposed to cyclic strain. In this study, we investigated cyclic strain mediated induction of transcription factors, AP-1, cAMP response element binding protein (CRE) and nuclear factor kB (NF-kB) in cultured EC from HUVEC, human aorta (HAEC), and BAEC. EC were exposed to 10% average strain at 60 cpm for up to 24 h. At varying time points, nuclear protein was extracted and analyzed for production of AP-1, CRE and NF-kB by electromobility shift assay. The results demonstrate that EC exposure to cyclic strain leads to a significant induction of AP-1, CRE and NF-kB in HAEC and HUVEC, but not in BAEC. Furthermore, these findings are in marked contrast to the previously described shear stress induced activation of AP-1 and NF-kB in BAEC. There was also a temporal difference in their response such that stretch-induced activation of AP-1 and NF-kB peaked at 4 h, whereas CRE increased in a biphasic manner at 15 min and 24 h. These results may partially explain the divergent effects of cyclic strain on EC gene expression and phenotype in EC from different vascular beds and species and underscore the difference in EC response to cyclic strain and shear stress.

  11. Heat shock induced excision of selectable marker genes in transgenic banana by the Cre-lox site-specific recombination system.

    Science.gov (United States)

    Chong-Pérez, Borys; Kosky, Rafael G; Reyes, Maritza; Rojas, Luis; Ocaña, Bárbara; Tejeda, Marisol; Pérez, Blanca; Angenon, Geert

    2012-06-30

    Selectable marker genes are indispensable for efficient production of transgenic events, but are no longer needed after the selection process and may cause public concern and technological problems. Although several gene excision systems exist, few have been optimized for vegetatively propagated crops. Using a Cre-loxP auto-excision strategy, we obtained transgenic banana plants cv. Grande Naine (Musa AAA) devoid of the marker gene used for selection. We used T-DNA vectors with the cre recombinase gene under control of a heat shock promoter and selectable marker gene cassettes placed between two loxP sites in direct orientation, and a gene of interest inserted outside of the loxP sites. Heat shock promoters pGmHSP17.6-L and pHSP18.2, from soybean and Arabidopsis respectively, were tested. A transient heat shock treatment of primary transgenic embryos was sufficient for inducing cre and excising cre and the marker genes. Excision efficiency, as determined by PCR and Southern hybridization was 59.7 and 40.0% for the GmHSP17.6-L and HSP18.2 promoters, respectively. Spontaneous excision was not observed in 50 plants derived from untreated transgenic embryos. To our knowledge this is the first report describing an efficient marker gene removal system for banana. The method described is simple and might be generally applicable for the production of marker-free transgenic plants of many crop species. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Foxc2CreERT2knock-in mice mark stage-specific Foxc2-expressing cells during mouse organogenesis.

    Science.gov (United States)

    Amin, Mohammed Badrul; Miura, Naoyuki; Uddin, Mohammad Khaja Mafij; Islam, Mohammod Johirul; Yoshida, Nobuaki; Iseki, Sachiko; Kume, Tsutomu; Trainor, Paul A; Saitsu, Hirotomo; Aoto, Kazushi

    2017-01-01

    Foxc2, a member of the winged helix transcription factor family, is essential for eye, calvarial bone, cardiovascular and kidney development in mice. Nevertheless, how Foxc2-expressing cells and their descendent cells contribute to the development of these tissues and organs has not been elucidated. Here, we generated a Foxc2 knock-in (Foxc2 CreERT2 ) mouse, in which administration of estrogen receptor antagonist tamoxifen induces nuclear translocation of Cre recombinase in Foxc2-expressing cells. By crossing with ROSA-LacZ reporter mice (Foxc2 CreERT2 ; R26R), the fate of Foxc2 positive (Foxc2 + ) cells was analyzed through LacZ staining at various embryonic stages. We found Foxc2 + cell descendants in the supraoccipital and exoccipital bone in E18.5 embryos, when tamoxifen was administered at embryonic day (E) 8.5. Furthermore, Foxc2 + descendant cranial neural crest cells at E8-10 were restricted to the corneal mesenchyme, while Foxc2 + cell derived cardiac neural crest cells at E6-12 were found in the aorta, pulmonary trunk and valves, and endocardial cushions. Foxc2 + cell descendant contributions to the glomerular podocytes in the kidney were also observed following E6.5 tamoxifen treatment. Our results are consistent with previous reports of Foxc2 expression during early embryogenesis and the Foxc2 CreERT2 mouse provides a tool to investigate spatiotemporal roles of Foxc2 and contributions of Foxc2 + expressing cells during mouse embryogenesis. © 2016 Japanese Teratology Society.

  13. National Date Palm Germplasm Repository

    Science.gov (United States)

    The National Clonal Germplasm Repository for Citrus & Dates (NCGRCD), located in Riverside, California USA, is a project of the Agricultural Research Service (ARS) of the United States Department of Agriculture (USDA). The NCGRCD maintains a collection of germplasm of date palm (Phoneix dactylifera ...

  14. 75 FR 16516 - Dates Correction

    Science.gov (United States)

    2010-04-01

    ... From the Federal Register Online via the Government Publishing Office ] NATIONAL ARCHIVES AND RECORDS ADMINISTRATION Office of the Federal Register Dates Correction Correction In the Notices section... through 15499, the date at the top of each page is corrected to read ``Monday, March 29, 2010''. This...

  15. A Trp53fl/flPtenfl/fl mouse model of undifferentiated pleomorphic sarcoma mediated by adeno-Cre injection and in vivo bioluminescence imaging.

    Directory of Open Access Journals (Sweden)

    Marisa R Buchakjian

    Full Text Available Genetic mouse models of soft tissue sarcoma provide critical insights into disease pathophysiology, which are oftentimes unable to be extracted from human tumor samples or xenograft models. In this study we describe a mouse model of soft tissue sarcoma mediated by adenoviral-Cre recombinase injection into Trp53fl/fl/Ptenfl/fl lox-stop-lox luciferase mice. Injection of adenovirus expressing Cre recombinase, either subcutaneously or intramuscularly in two experimental groups, results in viral infection and gene recombination with 100% penetrance within the first 24 hours following injection. Luciferase expression measured by real-time bioluminescence imaging increases over time, with an initial robust increase following viral injection, followed by a steady rise over the next several weeks as primary tumors develop and grow. Intramuscular injections were more commonly associated with evidence of systemic viral distribution than subcutaneous injections. All mice developed soft tissue sarcomas at the primary injection site, with histological examination identifying 93% of tumors as invasive pleomorphic sarcomas based on microscopic morphology and immunohistochemical expression of sarcoma markers. A lymphocytic infiltrate was present in 64% of the sarcomas in this immunocompetent model and 71% of tumors expressed PD-L1. This is the first report of a viral-Cre mediated Trp53/Pten mouse model of undifferentiated pleomorphic sarcoma. The bioluminescence imaging feature, along with high penetrance of the model and its immunological characteristics, makes it suited for pre-clinical studies of soft tissue sarcoma.

  16. High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expression.

    Directory of Open Access Journals (Sweden)

    Sandra J Kuhlman

    2008-04-01

    Full Text Available We describe a method that combines Cre-recombinase knockin mice and viral-mediated gene transfer to genetically label and functionally manipulate specific neuron types in the mouse brain. We engineered adeno-associated viruses (AAVs that express GFP, dsRedExpress, or channelrhodopsin (ChR2 upon Cre/loxP recombination-mediated removal of a transcription-translation STOP cassette. Fluorescent labeling was sufficient to visualize neuronal structures with synaptic resolution in vivo, and ChR2 expression allowed light activation of neuronal spiking. The structural dynamics of a specific class of neocortical neuron, the parvalbumin-containing (Pv fast-spiking GABAergic interneuron, was monitored over the course of a week. We found that although the majority of Pv axonal boutons were stable in young adults, bouton additions and subtractions on axonal shafts were readily observed at a rate of 10.10% and 9.47%, respectively, over 7 days. Our results indicate that Pv inhibitory circuits maintain the potential for structural re-wiring in post-adolescent cortex. With the generation of an increasing number of Cre knockin mice and because viral transfection can be delivered to defined brain regions at defined developmental stages, this strategy represents a general method to systematically visualize the structure and manipulate the function of different cell types in the mouse brain.

  17. Biological, familial, and peer influences on dating in early adolescence.

    Science.gov (United States)

    Friedlander, Laura J; Connolly, Jennifer A; Pepler, Debra J; Craig, Wendy M

    2007-12-01

    The current study examined the joint contributions of pubertal maturation, parental monitoring, involvement in older peer groups, peer dating, and peer delinquency on dating in a sample of early adolescent boys and girls. The sample consisted of 784 adolescents (394 boys, 390 girls) enrolled in grades 5, 6, and 7 who were followed for one year. In addition to measures of pubertal maturation and parental monitoring, adolescents and their peer group members completed indices of dating and delinquency. Average dating and delinquency scores for each participant's peer group network were computed. Results indicated that it was the combination of pubertal maturation, peer delinquency, and peer dating that explained increases in early dating. For boys only, parental monitoring was a significant predictor. The more knowledgeable parents were about their boys' activities, the lower the number of dating activities reported. These results highlight the importance of considering the joint effects of these biological and social predictors in understanding early dating. When rapid changes occur in all three domains, early dating is most likely to ensue. The findings of this study have practical importance. Parents and professionals who work closely with youth should attend to the special vulnerability of early maturing adolescents in the face of peer pressure and to the important role of parental monitoring in regulating dating activities.

  18. Targeted deletion of Sox10 by Wnt1-cre defects neuronal migration and projection in the mouse inner ear.

    Directory of Open Access Journals (Sweden)

    YanYan Mao

    Full Text Available Sensory nerves of the brainstem are mostly composed of placode-derived neurons, neural crest-derived neurons and neural crest-derived Schwann cells. This mixed origin of cells has made it difficult to dissect interdependence for fiber guidance. Inner ear-derived neurons are known to connect to the brain after delayed loss of Schwann cells in ErbB2 mutants. However, the ErbB2 mutant related alterations in the ear and the brain compound interpretation of the data. We present here a new model to evaluate exclusively the effect of Schwann cell loss on inner ear innervation. Conditional deletion of the neural crest specific transcription factor, Sox10, using the rhombic lip/neural crest specific Wnt1-cre driver spares Sox10 expression in the ear. We confirm that neural crest-derived cells provide a stop signal for migrating spiral ganglion neurons. In the absence of Schwann cells, spiral ganglion neurons migrate into the center of the cochlea and even out of the ear toward the brain. Spiral ganglion neuron afferent processes reach the organ of Corti, but many afferent fibers bypass the organ of Corti to enter the lateral wall of the cochlea. In contrast to this peripheral disorganization, the central projection to cochlear nuclei is normal. Compared to ErbB2 mutants, conditional Sox10 mutants have limited cell death in spiral ganglion neurons, indicating that the absence of Schwann cells alone contributes little to the embryonic survival of neurons. These data suggest that neural crest-derived cells are dispensable for all central and some peripheral targeting of inner ear neurons. However, Schwann cells provide a stop signal for migratory spiral ganglion neurons and facilitate proper targeting of the organ of Corti by spiral ganglion afferents.

  19. Diphtheria toxin treatment of Pet-1-Cre floxed diphtheria toxin receptor mice disrupts thermoregulation without affecting respiratory chemoreception

    Science.gov (United States)

    Cerpa, Verónica; Gonzalez, Amalia; Richerson, George B.

    2014-01-01

    In genetically-modified Lmx1bf/f/p mice, selective deletion of LMX1B in Pet-1 expressing cells leads to failure of embryonic development of serotonin (5-HT) neurons. As adults, these mice have a decreased hypercapnic ventilatory response and abnormal thermoregulation. This mouse model has been valuable in defining the normal role of 5-HT neurons, but it is possible that developmental compensation reduces the severity of observed deficits. Here we studied mice genetically modified to express diphtheria toxin receptors (DTR) on Pet-1 expressing neurons (Pet-1-Cre/Floxed DTR or Pet1/DTR mice). These mice developed with a normal complement of 5-HT neurons. As adults, systemic treatment with 2 – 35 μg diphtheria toxin (DT) reduced the number of tryptophan hydroxylase immunoreactive (TpOH-ir) neurons in the raphe nuclei and ventrolateral medulla by 80%. There were no effects of DT on baseline ventilation (VE) or the ventilatory response to hypercapnia or hypoxia. At an ambient temperature (TA) of 24°C, all Pet1/DTR mice dropped their body temperature (TB) below 35°C after DT treatment, but the latency was shorter in males than females (3.0 ± 0.37 vs 4.57 ± 0.29 days, respectively; p thermoregulation, in males more than females. In comparison to models with deficient embryonic development of 5-HT neurons, acute deletion of 5-HT neurons in adults leads to a greater defect in thermoregulation, suggesting that significant developmental compensation can occur. PMID:25171790

  20. How can Cre.eight – an online t-shirt brand – increase brand awareness and sales, in Portuguese market, through its main social media networking sites : Facebook and Instagram?

    OpenAIRE

    Ferraz, Pedro Filgueiras Soares

    2016-01-01

    Cre.eight is an online t-shirt brand founded by Pedro Ferraz in 2015. This dissertation has the objective of studying Cre.eight and understanding the importance of Facebook and Instagram as means of increasing brand awareness and sales. The relevance of social media networking sites for the millennial generation was evaluated, along with the tools that these platforms posses for up-rising brands. An outlined analysis of Facebook and Instagram and their power as communication ch...

  1. Date stones in broiler's feeding

    Directory of Open Access Journals (Sweden)

    Gualtieri, M.

    1990-01-01

    Full Text Available To evaluate date stones as dietary component for broilers, two trials were carried out. In the first trial, Tunisian Deglet date stones were used and in the second one, stones were the waste product of an Italian distillery. One-day-old Arbor Acres chickens were cage reared and fed for 6 weeks on 4 experimental diets, which were formulated to be isonitrogenous and isocaloric and differed in cereal component (maize or low tannin sorghum and in inclusion level (0 or 10 % of ground date stones. Birds ' performances were slightly different in the two trials, but overall results indicate that date stones are suitable for use in broiler's feeding under such conditions.

  2. Microscale radiocarbon dating of paintings

    Energy Technology Data Exchange (ETDEWEB)

    Hendriks, Laura; Hajdas, Irka; McIntyre, Cameron [ETH Zurich, Ion Beam Physics, Zurich (Switzerland); Kueffner, Markus; Ferreira, Ester S.B. [SIK-ISEA, Zurich, Zurich (Switzerland); Scherrer, Nadim C. [Bern University of Applied Sciences, HKB, Bern (Switzerland)

    2016-03-15

    In this paper, radiocarbon dating of paintings using minimal sample sizes has been investigated, in an effort to address the problem of limited access to sample material in paintings. {sup 14}C analyses were conducted on signed and dated paintings from two Swiss artists of the twentieth century. The selected paintings dated from the 1930s and 1960s, provided the opportunity to evaluate the dating accuracy on paintings realized before and after 1950 AD when the {sup 14}C bomb peak was created, as a result of the nuclear tests conducted in the 1950/1960s. The work focused on the one hand on minimizing the size of the canvas sample required for accelerator mass spectrometer radiocarbon measurement on the gas ion source of the MICADAS and, on the other hand, on testing the possibility of dating the organic binder of the paint. Following careful characterization of the paint composition by X-ray fluorescence spectroscopy, Fourier transformed infrared spectroscopy, and Raman spectroscopy, paints containing no other carbon source than the natural organic binder were identified and dated. (orig.)

  3. Radiocarbon dating of iron artefacts

    Energy Technology Data Exchange (ETDEWEB)

    Cresswell, R. [Australian National Univ., Canberra, ACT (Australia). Dept. of Nuclear Physics

    1997-12-31

    Iron artefacts are generally dated by association or on stylistic grounds. This may not give a true indication of the date of manufacture, or may not be possible if the piece is out of context, ambiguous in style, or a copy. Obtaining a direct date on the artefact would be preferable. During the processes of manufacture, carbon is incorporated into the iron from the fuel source. If the fuel is of a material containing contemporaneous carbon, i.e. has an ambient radiocarbon signature, e.g. charcoal, then we may reliably radiocarbon date the artefact by extracting this carbon. Care must be taken, however, to ensure that re-working has not introduced multiple sources of carbon that would give an erroneous date. Detailed chemical analysis must precede radiocarbon analysis. Sample size is determined by carbon content, and before the advent of accelerator mass spectrometry, several tens of grams of carbon were required for radiocarbon dating (van der Merwe, 1969), prohibiting this method except for high-carbon cast-irons and bulk samples, e.g. caches of nails. AMS permits the analysis of sub-gram pieces of iron (Cresswell, 1991), thereby permitting the analysis of museum pieces with only minimal loss of material, and small fragments of iron recovered from archaeological sites. A few examples are given to illustrate these points. Paper no. 41; Extended abstract. 6 refs.

  4. ERK phosphorylation regulates sleep and plasticity in Drosophila.

    Directory of Open Access Journals (Sweden)

    William M Vanderheyden

    Full Text Available Given the relationship between sleep and plasticity, we examined the role of Extracellular signal-regulated kinase (ERK in regulating baseline sleep, and modulating the response to waking experience. Both sleep deprivation and social enrichment increase ERK phosphorylation in wild-type flies. The effects of both sleep deprivation and social enrichment on structural plasticity in the LNvs can be recapitulated by expressing an active version of ERK (UAS-ERK(SEM pan-neuronally in the adult fly using GeneSwitch (Gsw Gsw-elav-GAL4. Conversely, disrupting ERK reduces sleep and prevents both the behavioral and structural plasticity normally induced by social enrichment. Finally, using transgenic flies carrying a cAMP response Element (CRE-luciferase reporter we show that activating ERK enhances CRE-Luc activity while disrupting ERK reduces it. These data suggest that ERK phosphorylation is an important mediator in transducing waking experience into sleep.

  5. Dating

    African Journals Online (AJOL)

    Among its other ills, the Internet has widened children's access to pornography with its estimated over 28,000 sex-oriented and porn sites on the www; child moles- tation (Ota, 1997:3029); promoted gambling (New York Times, 199718;. Gruenwald, l998az238); encouraged terrorism with the influx of uncensored ...

  6. 75 FR 33166 - Extension of Expiration Dates for Several Body System Listings

    Science.gov (United States)

    2010-06-11

    ... ADMINISTRATION 20 CFR Part 404 RIN 0960-AH20 Extension of Expiration Dates for Several Body System Listings... dates of the following body systems in the Listing of Impairments (listings) in our regulations... evaluation processes for initial claims and continuing disability reviews. DATES: This final rule is...

  7. 77 FR 35264 - Extension of Expiration Dates for Several Body System Listings

    Science.gov (United States)

    2012-06-13

    ... ADMINISTRATION 20 CFR Part 404 RIN 0960-AH49 Extension of Expiration Dates for Several Body System Listings... dates of the following body systems in the Listing of Impairments (listings) in our regulations: Growth... evaluation processes for initial claims and continuing disability reviews. DATES: This final rule is...

  8. Linguistic Dating of Biblical Texts

    DEFF Research Database (Denmark)

    Ehrensvärd, Martin Gustaf

    2003-01-01

    For two centuries, scholars have pointed to consistent differences in the Hebrew of certain biblical texts and interpreted these differences as reflecting the date of composition of the texts. Until the 1980s, this was quite uncontroversial as the linguistic findings largely confirmed the chronol......For two centuries, scholars have pointed to consistent differences in the Hebrew of certain biblical texts and interpreted these differences as reflecting the date of composition of the texts. Until the 1980s, this was quite uncontroversial as the linguistic findings largely confirmed...... the chronology of the texts established by other means: the Hebrew of Genesis-2 Kings was judged to be early and that of Esther, Daniel, Ezra, Nehemiah, and Chronicles to be late. In the current debate where revisionists have questioned the traditional dating, linguistic arguments in the dating of texts have...... come more into focus. The study critically examines some linguistic arguments adduced to support the traditional position, and reviewing the arguments it points to weaknesses in the linguistic dating of EBH texts to pre-exilic times. When viewing the linguistic evidence in isolation it will be clear...

  9. Mechanosensory and ATP Release Deficits following Keratin14-Cre-Mediated TRPA1 Deletion Despite Absence of TRPA1 in Murine Keratinocytes.

    Directory of Open Access Journals (Sweden)

    Katherine J Zappia

    Full Text Available Keratinocytes are the first cells that come into direct contact with external tactile stimuli; however, their role in touch transduction in vivo is not clear. The ion channel Transient Receptor Potential Ankyrin 1 (TRPA1 is essential for some mechanically-gated currents in sensory neurons, amplifies mechanical responses after inflammation, and has been reported to be expressed in human and mouse skin. Other reports have not detected Trpa1 mRNA transcripts in human or mouse epidermis. Therefore, we set out to determine whether selective deletion of Trpa1 from keratinocytes would impact mechanosensation. We generated K14Cre-Trpa1fl/fl mice lacking TRPA1 in K14-expressing cells, including keratinocytes. Surprisingly, Trpa1 transcripts were very poorly detected in epidermis of these mice or in controls, and detection was minimal enough to preclude observation of Trpa1 mRNA knockdown in the K14Cre-Trpa1fl/fl mice. Unexpectedly, these K14Cre-Trpa1fl/fl mice nonetheless exhibited a pronounced deficit in mechanosensitivity at the behavioral and primary afferent levels, and decreased mechanically-evoked ATP release from skin. Overall, while these data suggest that the intended targeted deletion of Trpa1 from keratin 14-expressing cells of the epidermis induces functional deficits in mechanotransduction and ATP release, these deficits are in fact likely due to factors other than reduction of Trpa1 expression in adult mouse keratinocytes because they express very little, if any, Trpa1.

  10. 21 CFR 870.3 - Effective dates of requirement for premarket approval.

    Science.gov (United States)

    2010-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES General Provisions § 870.3 Effective dates of... (premarket approval) shall not be commercially distributed after the date shown in the regulation classifying... FDA must promulgate a regulation under section 515(b) of the act requiring such approval, except as...

  11. 78 FR 73696 - Extension of Expiration Date for Mental Disorders Body System Listings; Correction

    Science.gov (United States)

    2013-12-09

    ... date of the Mental Disorders body system in the Listing of Impairments (listings) in our regulations... Mental Disorders body system in the Listing of Impairments (listings) in our regulations. In this final... ADMINISTRATION 20 CFR Part 404 RIN 0960-AH62 Extension of Expiration Date for Mental Disorders Body System...

  12. ESR dating of fault rocks

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hee Kwon [Kangwon National Univ., Chuncheon (Korea, Republic of)

    2002-03-15

    Past movement on faults can be dated by measurement of the intensity of ESR signals in quartz. These signals are reset by local lattice deformation and local frictional heating on grain contacts at the time of fault movement. The ESR signals then trow back as a result of bombardment by ionizing radiation from surrounding rocks. The age is obtained from the ratio of the equivalent dose, needed to produce the observed signal, to the dose rate. Fine grains are more completely reset during faulting, and a plot of age vs grain size shows a plateau for grains below critical size : these grains are presumed to have been completely zeroed by the last fault activity. We carried out ESR dating of fault rocks collected from the Yangsan fault system. ESR dates from the this fault system range from 870 to 240 ka. Results of this research suggest that long-term cyclic fault activity continued into the pleistocene.

  13. Expression, regulation and putative nutrient-sensing function of taste GPCRs in the heart.

    Directory of Open Access Journals (Sweden)

    Simon R Foster

    Full Text Available G protein-coupled receptors (GPCRs are critical for cardiovascular physiology. Cardiac cells express >100 nonchemosensory GPCRs, indicating that important physiological and potential therapeutic targets remain to be discovered. Moreover, there is a growing appreciation that members of the large, distinct taste and odorant GPCR families have specific functions in tissues beyond the oronasal cavity, including in the brain, gastrointestinal tract and respiratory system. To date, these chemosensory GPCRs have not been systematically studied in the heart. We performed RT-qPCR taste receptor screens in rodent and human heart tissues that revealed discrete subsets of type 2 taste receptors (TAS2/Tas2 as well as Tas1r1 and Tas1r3 (comprising the umami receptor are expressed. These taste GPCRs are present in cultured cardiac myocytes and fibroblasts, and by in situ hybridization can be visualized across the myocardium in isolated cardiac cells. Tas1r1 gene-targeted mice (Tas1r1(Cre/Rosa26(tdRFP strikingly recapitulated these data. In vivo taste receptor expression levels were developmentally regulated in the postnatal period. Intriguingly, several Tas2rs were upregulated in cultured rat myocytes and in mouse heart in vivo following starvation. The discovery of taste GPCRs in the heart opens an exciting new field of cardiac research. We predict that these taste receptors may function as nutrient sensors in the heart.

  14. The complexity behind the date

    CERN Multimedia

    2009-01-01

    For the waiting world, and indeed for most of us here at CERN, ‘the LHC schedule’ simply means the date that the LHC will restart - and we only take notice when that end-date changes. But in fact the schedule is a constantly evolving intricate document coordinating all the repairs, consolidation and commissioning in every part of the machine. So, what actually goes on behind the scenes in timing and planning all the work on one of the most complex scientific instruments ever built?

  15. Tariff proposal of the Commission of energy regulation from February 28, 2008 for the use of public natural gas distribution networks; Proposition tarifaire de la Commission de regulation de l'energie du 28 fevrier 2008 pour l'utilisation des reseaux publics de distribution de gaz naturel

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    With the complete opening of natural gas markets to competition and the legal separation of distribution networks, Gaz de France Reseau Distribution requested the implementation of a new tariff of use of gas distribution networks to the Commission of energy regulation (CRE). A new tariff of networks utilisation has thus been proposed by CRE after a public consultation and the audition of gas suppliers. This tariff foresees a 5.6% increase of the present day tariff by July 1, 2008. The impact on the end-users' gas retail price will be a 1.5% rise of the regulated tariff. (J.S.)

  16. 21 CFR 1312.25 - Expiration date.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Expiration date. 1312.25 Section 1312.25 Food and... SUBSTANCES Exportation of Controlled Substances § 1312.25 Expiration date. An export permit shall not be valid after the date specified therein, which date shall conform to the expiration date specified in the...

  17. Peer Group Influences on Adolescent Dating Aggression

    Science.gov (United States)

    Connolly, Jennifer; Friedlander, Laura

    2009-01-01

    The peer group is a critical social context for dating and romantic relationships. Peer groups provide opportunities to meet potential dating partners and set norms for acceptable dating behaviors. This article explores how peer groups influence dating and dating aggression, as well as how they can be used in prevention efforts. It also reviews…

  18. Online Dating and Conjugal Bereavement

    Science.gov (United States)

    Young, Dannagal Goldthwaite; Caplan, Scott E.

    2010-01-01

    This study examined self-presentation in the online dating profiles of 241 widowed and 280 divorced individuals between 18 and 40 years old. A content analysis of open-ended user-generated profiles assessed the presence or absence of various themes, including the user's marital status, the backstory of their lost relationship, and whether they…

  19. Luminescence dating of delta sediments

    NARCIS (Netherlands)

    Chamberlain, Elizabeth L.; Wallinga, Jakob; Reimann, Tony; Goodbred, Steven L.; Steckler, Michael S.; Shen, Zhixiong; Sincavage, Ryan

    2017-01-01

    Deltas where luminescence dating is most essential due to organic-poor geologic records are also those where it is often most challenging due to unsuitable luminescence properties of quartz grains, associated with rapid production of young clastic sediment. One example is the

  20. Deciphering Cis-Regulatory Element Mediated Combinatorial Regulation in Rice under Blast Infected Condition.

    Science.gov (United States)

    Deb, Arindam; Kundu, Sudip

    2015-01-01

    Combinations of cis-regulatory elements (CREs) present at the promoters facilitate the binding of several transcription factors (TFs), thereby altering the consequent gene expressions. Due to the eminent complexity of the regulatory mechanism, the combinatorics of CRE-mediated transcriptional regulation has been elusive. In this work, we have developed a new methodology that quantifies the co-occurrence tendencies of CREs present in a set of promoter sequences; these co-occurrence scores are filtered in three consecutive steps to test their statistical significance; and the significantly co-occurring CRE pairs are presented as networks. These networks of co-occurring CREs are further transformed to derive higher order of regulatory combinatorics. We have further applied this methodology on the differentially up-regulated gene-sets of rice tissues under fungal (Magnaporthe) infected conditions to demonstrate how it helps to understand the CRE-mediated combinatorial gene regulation. Our analysis includes a wide spectrum of biologically important results. The CRE pairs having a strong tendency to co-occur often exhibit very similar joint distribution patterns at the promoters of rice. We couple the network approach with experimental results of plant gene regulation and defense mechanisms and find evidences of auto and cross regulation among TF families, cross-talk among multiple hormone signaling pathways, similarities and dissimilarities in regulatory combinatorics between different tissues, etc. Our analyses have pointed a highly distributed nature of the combinatorial gene regulation facilitating an efficient alteration in response to fungal attack. All together, our proposed methodology could be an important approach in understanding the combinatorial gene regulation. It can be further applied to unravel the tissue and/or condition specific combinatorial gene regulation in other eukaryotic systems with the availability of annotated genomic sequences and suitable

  1. Deciphering Cis-Regulatory Element Mediated Combinatorial Regulation in Rice under Blast Infected Condition.

    Directory of Open Access Journals (Sweden)

    Arindam Deb

    Full Text Available Combinations of cis-regulatory elements (CREs present at the promoters facilitate the binding of several transcription factors (TFs, thereby altering the consequent gene expressions. Due to the eminent complexity of the regulatory mechanism, the combinatorics of CRE-mediated transcriptional regulation has been elusive. In this work, we have developed a new methodology that quantifies the co-occurrence tendencies of CREs present in a set of promoter sequences; these co-occurrence scores are filtered in three consecutive steps to test their statistical significance; and the significantly co-occurring CRE pairs are presented as networks. These networks of co-occurring CREs are further transformed to derive higher order of regulatory combinatorics. We have further applied this methodology on the differentially up-regulated gene-sets of rice tissues under fungal (Magnaporthe infected conditions to demonstrate how it helps to understand the CRE-mediated combinatorial gene regulation. Our analysis includes a wide spectrum of biologically important results. The CRE pairs having a strong tendency to co-occur often exhibit very similar joint distribution patterns at the promoters of rice. We couple the network approach with experimental results of plant gene regulation and defense mechanisms and find evidences of auto and cross regulation among TF families, cross-talk among multiple hormone signaling pathways, similarities and dissimilarities in regulatory combinatorics between different tissues, etc. Our analyses have pointed a highly distributed nature of the combinatorial gene regulation facilitating an efficient alteration in response to fungal attack. All together, our proposed methodology could be an important approach in understanding the combinatorial gene regulation. It can be further applied to unravel the tissue and/or condition specific combinatorial gene regulation in other eukaryotic systems with the availability of annotated genomic

  2. 76 FR 35372 - Effective Date for Swap Regulation

    Science.gov (United States)

    2011-06-17

    ...) Protection of market participants and the public; (2) efficiency, competitiveness, and financial integrity of... manipulative. 2. Efficiency, Competition, and Financial Integrity Although the Dodd-Frank Act establishes a... transition will promote ] market efficiency, competition, and financial integrity. 3. Price Discovery As...

  3. Ice Core Dating Software for Interactive Dating of Ice Cores

    Science.gov (United States)

    Kurbatov, A. V.; Mayewski, P. A.; Abdul Jawad, B. S.

    2005-12-01

    Scientists involved in ice core dating are well familiar with the problem of identification and recording the depth of annual signals using stable isotopes, glaciochemistry, ECM (electrical conductivity), DEP (dielectric properties) and particle counter data. Traditionally all parameters used for ice core dating were plotted as a function of depth, printed and after years were marked on the paper, converted to depth vs. age time scale. To expedite this tedious and manual process we developed interactive computer software, Ice core Dating (ICD) program. ICD is written in Java programming language, and uses GPL and GPL site licensed graphic libraries. The same 3.5 Mb in size pre-compiled single jar file, that includes all libraries and application code, was successfully tested on WinOS, Mac OSX, Linux, and Solaris operating systems running Java VM version 1.4. We have followed the modular design philosophy in our source code so potential integration with other software modules, data bases and server side distributed computer environments can be easily implemented. We expect to continue development of new suites of tools for easy integration of ice core data with other available time proxies. ICD is thoroughly documented and comes with a technical reference and cookbook that explains the purpose of the software and its many features, and provides examples to help new users quickly become familiar with the operation and philosophy of the software. ICD is available as a free download from the Climate Change Institute web site ( under the terms of GNU GPL public license.

  4. The Application of NHEJ-CRISPR/Cas9 and Cre-Lox System in the Generation of Bivalent Duck Enteritis Virus Vaccine against Avian Influenza Virus

    Directory of Open Access Journals (Sweden)

    Pengxiang Chang

    2018-02-01

    Full Text Available Duck-targeted vaccines to protect against avian influenza are critically needed to aid in influenza disease control efforts in regions where ducks are endemic for highly pathogenic avian influenza (HPAI. Duck enteritis virus (DEV is a promising candidate viral vector for development of vaccines targeting ducks, owing to its large genome and narrow host range. The clustered regularly interspaced palindromic repeats (CRISPR/Cas9 system is a versatile gene-editing tool that has proven beneficial for gene modification and construction of recombinant DNA viral vectored vaccines. Currently, there are two commonly used methods for gene insertion: non-homologous end-joining (NHEJ and homology-directed repair (HDR. Owing to its advantages in efficiency and independence from molecular requirements of the homologous arms, we utilized NHEJ-dependent CRISPR/Cas9 to insert the influenza hemagglutinin (HA antigen expression cassette into the DEV genome. The insert was initially tagged with reporter green fluorescence protein (GFP, and a Cre-Lox system was later used to remove the GFP gene insert. Furthermore, a universal donor plasmid system was established by introducing double bait sequences that were independent of the viral genome. In summary, we provide proof of principle for generating recombinant DEV viral vectored vaccines against the influenza virus using an integrated NHEJ-CRISPR/Cas9 and Cre-Lox system.

  5. 7 CFR 4280.37 - Application forms and filing dates.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Application forms and filing dates. 4280.37 Section 4280.37 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE LOANS AND GRANTS Rural Economic Development...

  6. 48 CFR 9904.409-63 - Effective date.

    Science.gov (United States)

    2010-10-01

    ...-63 Section 9904.409-63 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.409-63 Effective date. (a) This Standard is effective...

  7. 76 FR 68373 - Proposed Revision to Vintage Date Requirements

    Science.gov (United States)

    2011-11-04

    ..., Labeling, Packaging and containers, Reporting and recordkeeping requirements, Trade practices, Wine.... SUMMARY: The Alcohol and Tobacco Tax and Trade Bureau proposes to amend its wine labeling regulations to allow a vintage date to appear on a wine that is labeled with a country as an appellation of origin. The...

  8. Adolescent Bullying, Dating, and Mating

    Directory of Open Access Journals (Sweden)

    Anthony A. Volk

    2015-11-01

    Full Text Available Traditionally believed to be the result of maladaptive development, bullying perpetration is increasingly being viewed as a potentially adaptive behavior. We were interested in determining whether adolescents who bully others enjoy a key evolutionary benefit: increased dating and mating (sexual opportunities. This hypothesis was tested in two independent samples consisting of 334 adolescents and 144 university students. The data partly supported our prediction that bullying, but not victimization, would predict dating behavior. The data for sexual behavior more clearly supported our hypothesis that bullying behavior predicts an increase in sexual opportunities even when accounting for age, sex, and self-reports of attractiveness, likeability, and peer victimization. These results are generally congruent with the hypothesis that bullying perpetration is, at least in part, an evolutionary adaptive behavior.

  9. Linguistic dating of biblical texts

    DEFF Research Database (Denmark)

    Young, Ian; Rezetko, Robert; Ehrensvärd, Martin Gustaf

    Since the beginning of critical scholarship biblical texts have been dated using linguistic evidence. In recent years this has become a controversial topic, especially with the publication of Ian Young (ed.), Biblical Hebrew: Studies in Chronology and Typology (2003). However, until now there has...... been no introduction and comprehensive study of the field. Volume 1 introduces the field of linguistic dating of biblical texts, particularly to intermediate and advanced students of biblical Hebrew who have a reasonable background in the language, having completed at least an introductory course...... in this volume are: What is it that makes Archaic Biblical Hebrew archaic , Early Biblical Hebrew early , and Late Biblical Hebrew late ? Does linguistic typology, i.e. different linguistic characteristics, convert easily and neatly into linguistic chronology, i.e. different historical origins? A large amount...

  10. Current topics in ESR dating

    Energy Technology Data Exchange (ETDEWEB)

    Skinner, Anne R., E-mail: Anne.R.Skinner@williams.edu [Williams College, Williamstown, MA (United States)

    2011-09-15

    After over 25 years, the use of electron spin resonance (ESR) is well-established in dating sites of geological, paleontological and archaeological interest. Like any scientific technique, there have been changes in understanding and in methodology. Improvements have not, however, changed the observation that external dose calculations are still a significant source of uncertainty in ages. Examples from Europe, Africa and the Americans illustrate this point. For Pradayrol Cave (France), the occupation age, 330 ka, is unchallenged, making this the oldest known Neanderthal site in France. For Roc de Marsal, also in France, on the other hand, discrepancies between TL and sedimentary dose rates imply substantial differences in interpretation. In the Western Egyptian Desert, where artifacts and datable material are not well-correlated, the dating results show consistency with expectations based on global climate change, even in deflated sites. Climate change is also the question in geological studies in the Bahamas where, despite concerns about cosmic dose history, ESR dates confirm other evidence for sea level changes. We show that an uncertain age is not the same as an impossible one.

  11. ESR dating of fault rocks

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hee Kwon [Kangwon National Univ., Chuncheon (Korea, Republic of)

    2003-02-15

    Past movement on faults can be dated by measurement of the intensity of ESR signals in quartz. These signals are reset by local lattice deformation and local frictional heating on grain contacts at the time of fault movement. The ESR signals then grow back as a result of bombardment by ionizing radiation from surrounding rocks. The age is obtained from the ratio of the equivalent dose, needed to produce the observed signal, to the dose rate. Fine grains are more completely reset during faulting, and a plot of age vs. grain size shows a plateau for grains below critical size; these grains are presumed to have been completely zeroed by the last fault activity. We carried out ESR dating of fault rocks collected near the Gori nuclear reactor. Most of the ESR signals of fault rocks collected from the basement are saturated. This indicates that the last movement of the faults had occurred before the Quaternary period. However, ESR dates from the Oyong fault zone range from 370 to 310 ka. Results of this research suggest that long-term cyclic fault activity of the Oyong fault zone continued into the Pleistocene.

  12. REGULATION OF BLOOD PRESSURE, APPETITE AND GLUCOSE BY LEPTIN AFTER INACTIVATION OF INSULIN RECEPTOR SUBSTRATE 2 (IRS2) SIGNALING IN THE ENTIRE BRAIN OR IN POMC NEURONS

    Science.gov (United States)

    do Carmo, Jussara M.; da Silva, Alexandre A.; Wang, Zhen; Freeman, Nathan J.; Alsheik, Ammar J.; Adi, Ahmad; Hall, John E.

    2016-01-01

    Insulin receptor substrate 2 (IRS2) is one of three major leptin receptor signaling pathways, but its role in mediating the chronic effects of leptin on blood pressure, food intake and glucose regulation is unclear. We tested if genetic inactivation of IRS2 in the entire brain (IRS2/Nestin-cre mice) or specifically in proopiomelanocortin (POMC) neurons (IRS2/POMC-cre mice) attenuates the chronic cardiovascular, metabolic and antidiabetic effects of leptin. Mice were instrumented with telemetry probes for measurement of blood pressure (BP) and heart rate (HR) and with venous catheters for intravenous infusions. After a 5-day control period, mice received leptin infusion (2 µg/kg/min) for 7 days. Compared to control IRS2flox/flox mice, IRS2/POMC-cre mice had similar body weight and food intake (33±1 vs. 35±1g and 3.6±0.5 vs. 3.8±0.2 g/day) but higher MAP and HR (110±2 vs. 102±2 mmHg and 641±9 vs. 616±5 bpm). IRS2/Nestin-cre mice were heavier (38±2 g), slightly hyperphagic (4.5±1.0 g/day), and had higher MAP and HR (108±2 mmHg and 659±9 bpm) compared to control mice. Leptin infusion gradually increased MAP despite decreasing food intake by 31% in IRS2flox/flox as well as in Nestin-cre control mice. In contrast, leptin infusion did not change MAP in IRS2/Nestin-cre or IRS2/POMC-cre mice. The anorexic and antidiabetic effects of leptin, however, were similar in all 3 groups. These results indicate that IRS2 signaling in the CNS, and particularly in POMC neurons, is essential for the chronic actions of leptin to raise MAP but not for its anorexic or antidiabetic effects. PMID:26628674

  13. Dating Infidelity: Behaviors, Reasons and Consequences.

    Science.gov (United States)

    Roscoe, Bruce; And Others

    1988-01-01

    Surveyed older adolescents (N=247) regarding behaviors which constitute infidelity in a dating relationship, reasons for a dating partner to be unfaithful, and reactions to a dating partner's infidelity. Found responses to dating infidelity and extramarital affairs similar with regard to behaviors, causes and consequences. Results suggest…

  14. 11 CFR 7.28 - Hearing date.

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Hearing date. 7.28 Section 7.28 Federal... for Administrative Enforcement Proceedings § 7.28 Hearing date. (a) Setting of date by examiner. The examiner shall set the hearing at a reasonable time, date, and place. (b) Considerations. Whenever...

  15. 18 CFR 11.7 - Effective date.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Effective date. 11.7... Dams § 11.7 Effective date. All annual charges imposed under this subpart will be computed beginning on the effective date of the license unless some other date is fixed in the license. ...

  16. 40 CFR 469.21 - Compliance dates.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Compliance dates. 469.21 Section 469....21 Compliance dates. The compliance date for the BAT fluoride limitation is as soon as possible as determined by the permit writer but in no event later than November 8, 1985. The compliance date for PSES for...

  17. School Counselors' Role in Dating Violence Intervention

    Science.gov (United States)

    Craigen, Laurie M.; Sikes, April; Healey, Amanda; Hays, Danica

    2009-01-01

    Dating violence among adolescents is a major public health concern. The purpose of this paper is to examine five factors of which school counselors must be aware in order to recognize, intervene, and report incidence of dating violence. These factors are (a) understanding the diverse definitions of dating violence, (b) recognizing dating violence…

  18. Etiology of Teen Dating Violence among Adolescent Children of Alcoholics.

    Science.gov (United States)

    Livingston, Jennifer A; Eiden, Rina D; Lessard, Jared; Casey, Meghan; Henrie, James; Leonard, Kenneth E

    2018-03-01

    Family processes in early life have been implicated in adolescent involvement in teen dating violence, yet the developmental pathways through which this occurs are not well understood. In this study, etiological pathways from parental psychopathology and marital conflict in infancy to involvement in dating violence in late adolescence were examined in a sample of children at high-risk due to parental alcohol problems. Families (N = 227) recruited when the child was 12 months of age were assessed at 12-, 24-, 36-months, kindergarten, 6th, 8th, and 12th grades. Slightly more than half of the children were female (51%) and the majority were of European American descent (91%). Parental psychopathology in infancy was indirectly associated with teen dating violence in late adolescence via low maternal warmth and self-regulation in early childhood, externalizing behavior from kindergarten to early adolescence, and sibling problems in middle childhood. Marital conflict was also indirectly associated with teen dating violence via child externalizing behavior. Maternal warmth and sensitivity in early childhood emerged as an important protective factor and was associated with reduced marital conflict and increased child self-regulation in the preschool years as well as increased parental monitoring in middle childhood and early adolescence. Family processes occurring in the preschool years and in middle childhood appear to be critical periods for creating conditions that contribute to dating violence risk in late adolescence. These findings underscore the need for early intervention and prevention with at-risk families.

  19. The Interpersonal Communication Of Spouse Through Taaruf Online Dating

    OpenAIRE

    Lucy Pujasari Supratman; Permata Mardianti

    2016-01-01

    The development of social networking has revealed new opportunities for all varieties of internet sites that offer online dating services/online dating . One of them is the site of rumahtaaruf.com. During the process of matchmaking in rumahtaaruf.com., each candidate areis accompanied by a mediator who acts as an intermediary for both parties. Their role are job of mediator is to regulate and monitor the way of taaruf based on Islamic shari'a. This study focuses on the motive that underlying ...

  20. Near-infrared fluorescent protein iRFP713 as a reporter protein for optogenetic vectors, a transgenic Cre-reporter rat, and other neuronal studies.

    Science.gov (United States)

    Richie, Christopher T; Whitaker, Leslie R; Whitaker, Keith W; Necarsulmer, Julie; Baldwin, Heather A; Zhang, Yajun; Fortuno, Lowella; Hinkle, Josh J; Koivula, Pyry; Henderson, Mark J; Sun, Wenzhi; Wang, Kai; Smith, Jeffrey C; Pickel, Jim; Ji, Na; Hope, Bruce T; Harvey, Brandon K

    2017-06-01

    The use of genetically-encoded fluorescent reporters is essential for the identification and observation of cells that express transgenic modulatory proteins. Near-infrared (NIR) fluorescent proteins have superior light penetration through biological tissue, but are not yet widely adopted. Using the near-infrared fluorescent protein, iRFP713, improves the imaging resolution in thick tissue sections or the intact brain due to the reduced light-scattering at the longer, NIR wavelengths used to image the protein. Additionally, iRFP713 can be used to identify transgenic cells without photobleaching other fluorescent reporters or affecting opsin function. We have generated a set of adeno-associated vectors in which iRFP713 has been fused to optogenetic channels, and can be expressed constitutively or Cre-dependently. iRFP713 is detectable when expressed in neurons both in vitro and in vivo without exogenously supplied chromophore biliverdin. Neuronally-expressed iRFP713 has similar properties to GFP-like fluorescent proteins, including the ability to be translationally fused to channelrhodopsin or halorhodopsin, however, it shows superior photostability compared to EYFP. Furthermore, electrophysiological recordings from iRFP713-labeled cells compared to cells labeled with mCherry suggest that iRFP713 cells are healthier and therefore more stable and reliable in an ex vivo preparation. Lastly, we have generated a transgenic rat that expresses iRFP713 in a Cre-dependent manner. Overall, we have demonstrated that iRFP713 can be used as a reporter in neurons without the use of exogenous biliverdin, with minimal impact on viability and function thereby making it feasible to extend the capabilities for imaging genetically-tagged neurons in slices and in vivo. Published by Elsevier B.V.

  1. Sexual assault in dating relationships.

    Science.gov (United States)

    Rhynard, J; Krebs, M; Glover, J

    1997-03-01

    This article focuses on acquaintance rape, which under Canadian law constitutes a form of sexual assault. Frequency of acquaintance rape often is underestimated due to under-reporting, resulting in a local perception that acquaintance rape rarely occurs in a small Canadian community. A survey was conducted to determine whether acquaintance rape does occur in this community. One hundred sixty-four male and female students from grades 8-12 completed a questionnaire. Twenty-six percent of respondents reported being forced into some type of sexual activity. Based on the survey, this article explores the type of force used, the relationship between acquaintance rape and use of alcohol and drugs, and the relationship between acquaintance rape and the ability to indicate to a partner to stop a behavior. Results confirmed a need to develop programs to prevent rather than merely respond to issues of sexual assault on a date.

  2. Retrospective Birth Dating of Cells

    Energy Technology Data Exchange (ETDEWEB)

    L.Spalding, K; Bhardwaj, R D; Buchholz, B A; Druid, H; Frisen, J

    2005-04-19

    The generation of cells in the human body has been difficult to study and our understanding of cell turnover is limited. Extensive testing of nuclear weapons resulted in a dramatic global increase in the levels of the isotope {sup 14}C in the atmosphere, followed by an exponential decrease after the test ban treaty in 1963. We show that the level of {sup 14}C in genomic DNA closely parallels atmospheric levels, and can be used to establish the time point when the DNA was synthesized and cells were born. We use this strategy to determine the age of cells in the cortex of the adult human brain, and show that whereas non-neuronal cells are exchanged, occipital neurons are as old as the individual, supporting the view that postnatal neurogenesis does not take place in this region. Retrospective birth dating is a generally applicable strategy that can be used to measure cell turnover in man under physiological and pathological conditions.

  3. Blind-date Conversation Joining

    Directory of Open Access Journals (Sweden)

    Luca Cesari

    2013-07-01

    Full Text Available We focus on a form of joining conversations among multiple parties in service-oriented applications where a client may asynchronously join an existing conversation without need to know in advance any information about it. More specifically, we show how the correlation mechanism provided by orchestration languages enables a form of conversation joining that is completely transparent to clients and that we call 'blind-date joining'. We provide an implementation of this strategy by using the standard orchestration language WS-BPEL. We then present its formal semantics by resorting to COWS, a process calculus specifically designed for modelling service-oriented applications. We illustrate our approach by means of a simple, but realistic, case study from the online games domain.

  4. Deciphering the Neuronal Circuitry Controlling Local Blood Flow in the Cerebral Cortex with Optogenetics in PV::Cre Transgenic Mice

    Science.gov (United States)

    Urban, Alan; Rancillac, Armelle; Martinez, Lucie; Rossier, Jean

    2012-01-01

    Although it is know since more than a century that neuronal activity is coupled to blood supply regulation, the underlying pathways remains to be identified. In the brain, neuronal activation triggers a local increase of cerebral blood flow (CBF) that is controlled by the neurogliovascular unit composed of terminals of neurons, astrocytes, and blood vessel muscles. It is generally accepted that the regulation of the neurogliovascular unit is adjusted to local metabolic demand by local circuits. Today experimental data led us to realize that the regulatory mechanisms are more complex and that a neuronal system within the brain is devoted to the control of local brain-blood flow. Recent optogenetic experiments combined with functional magnetic resonance imaging have revealed that light stimulation of neurons expressing the calcium binding protein parvalbumin (PV) is associated with positive blood oxygen level-dependent (BOLD) signal in the corresponding barrel field but also with negative BOLD in the surrounding deeper area. Here, we demonstrate that in acute brain slices, channelrhodopsin-2 (ChR2) based photostimulation of PV containing neurons gives rise to an effective contraction of penetrating arterioles. These results support the neurogenic hypothesis of a complex distributed nervous system controlling the CBF. PMID:22715327

  5. Role of proopiomelanocortin neuron Stat3 in regulating arterial pressure and mediating the chronic effects of leptin.

    Science.gov (United States)

    Dubinion, John H; do Carmo, Jussara M; Adi, Ahmad; Hamza, Shereen; da Silva, Alexandre A; Hall, John E

    2013-05-01

    Although signal transducer and activator of transcription 3 (Stat3) is a key second messenger by which leptin regulates appetite and body weight, its role in specific neuronal populations in metabolic regulation and in mediating the chronic effects of leptin on blood pressure is unknown. The current study tested the hypothesis that Stat3 signaling in proopiomelanocortin (POMC) neurons mediates the chronic effects of leptin on mean arterial pressure (MAP), as well as on glucose regulation, energy expenditure, and food intake. Stat3(flox/flox) mice were crossed with POMC-Cre mice to generate mice with Stat3 deletion specifically in POMC neurons (Stat3(flox/flox)/POMC-Cre). Oxygen consumption (Vo2), carbon dioxide respiration (Vco2), motor activity, heat production, food intake, and MAP were measured 24 hours/d. After baseline measurements, leptin was infused (4 μg/kg per min, IP) for 7 days. Stat3(flox/flox)/POMC-Cre mice were hyperphagic, heavier, and had increased respiratory quotients compared with control Stat3(flox/flox) mice. Baseline MAP was not different between the groups, and chronic leptin infusion reduced food intake similarly in both groups (27 versus 29%). Vo2, Vco2, and heat production responses to leptin were not significantly different in control and Stat3(flox/flox)/POMC-Cre mice. However, leptin-mediated increases in MAP were completely abolished, and blood pressure responses to acute air-jet stress were attenuated in male Stat3(flox/flox)/POMC-Cre mice. These results indicate that Stat3 signaling in POMC neurons is essential for leptin-mediated increases in MAP, but not for anorexic or thermogenic effects of leptin.

  6. Role of Shp2 in forebrain neurons in regulating metabolic and cardiovascular functions and responses to leptin

    Science.gov (United States)

    do Carmo, Jussara M.; da Silva, Alexandre A.; Sessums, Price O.; Ebaady, Sabira H.; Pace, Benjamin R.; Rushing, John S.; Davis, Mark T.; Hall, John E.

    2014-01-01

    Objective We examined whether deficiency of Shp2 signaling in forebrain neurons alters metabolic and cardiovascular regulation under various conditions and if it attenuates the anorexic and cardiovascular effects of leptin. We also tested whether forebrain Shp2 deficiency alters blood pressure (BP) and heart rate (HR) responses to acute stress. Design Forebrain Shp2-/- mice were generated by crossing Shp2flox/flox mice with CamKIIα-cre mice. At 22 to 24 weeks of age, mice were instrumented for telemetry for measurement of BP, HR and body temperature (BT). Oxygen consumption (VO2), energy expenditure and motor activity were monitored by indirect calorimetry. Results Shp2/CamKIIα-cre mice were heavier (46±3 vs 32±1 g), hyperglycemic, hyperleptinemic, hyperinsulinemic, and hyperphagic compared to Shp2flox/flox control mice. Shp2/CamKIIα-cre mice exhibited reduced food intake responses to fasting/refeeding and impaired regulation of BT when exposed to 15°C and 30°C ambient temperatures. Despite being obese and having many features of metabolic syndrome, Shp2/CamKIIα-cre mice had similar daily average BP and HR compared to Shp2flox/flox mice (112±2 vs 113±1 mmHg and 595±34 vs 650±40 bpm), but exhibited increased BP and HR responses to cold exposure and acute air-jet stress test. Leptin's ability to reduce food intake and to raise BP were markedly attenuated in Shp2/CamKIIα-cre mice. Conclusion These results suggest that forebrain Shp2 signaling regulates food intake, appetite responses to caloric deprivation, and thermogenic control of body temperature during variations in ambient temperature. Deficiency of Shp2 signaling in the forebrain is associated with augmented cardiovascular responses to cold and acute stress but attenuated BP responses to leptin. PMID:24030516

  7. The ERK1/2 pathway regulates testosterone synthesis by coordinately regulating the expression of steroidogenic genes in Leydig cells.

    Science.gov (United States)

    Matzkin, Maria Eugenia; Yamashita, Soichi; Ascoli, Mario

    2013-05-06

    Adult mice with a Leydig cell specific deletion of MAPK kinase (MEK) 1 and 2 (Mek1(f)(/)(f);Mek2(-/-);Cre(+)) mice display Leydig cell hypoplasia and hypergonadotropic hypogonadism. We used radioimmunoassays and quantitative PCR to evaluate the function and expression of the Leydig cell genes involved in the conversion of cholesterol to testosterone (Star, Cyp11a1, Hsd3b6, Cyp17a1 and Hsd17b3), androgen metabolism (Srda1 and Dhrs9), and four transcription factors (Creb1, Nr5a1, Nr4a1 and Nr0b1) that regulate the expression of steroidogenic genes. We show that Star, Hsd3b6, Cyp17a1 and Hsd17b3 are downregulated in Ledyig cells of adult Mek1(f)(/)(f);Mek2(-/-);Cre(+) mice whereas Srda1 and Dhrs9 are upregulated and Creb1, Nr5a1, Nr4a1 and Nr0b1 are unchanged or upregulated. Functionally, all the downregulated genes but none of the upregulated genes contribute to the decrease in testosterone synthesis in Leydig cells of adult Mek1(f)(/)(f);Mek2(-/-);Cre(+) mice because they produce low testosterone and dihydrotestosterone when stimulated with hCG or when incubated with testosterone precursors such as progesterone or androstenedione. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. 40 CFR 62.4626 - Effective date.

    Science.gov (United States)

    2010-07-01

    ... Phosphate Fertilizer Plants § 62.4626 Effective date. (a) The effective date of the portion of the plan applicable to phosphate fertilizer plants is July 12, 1982. Fluoride Emissions From Existing Primary Aluminum...

  9. Analisis Faktor Pendorong dalam Melakukan Online Dating

    OpenAIRE

    Maharani, Safira; Manalu, S. Rouli

    2017-01-01

    This study aimed to find the main factor that motivates users to use online dating, especially for Indonesian users. The development of internet technology raises a new phenomenon, called online dating. Online dating is a way to find someone for romantical or sexual relationship on the internet, mostly using online dating application or website. This study uses some previous research that discussed about individual motivation of having cyber-relationship. The result of those factors grouped i...

  10. 78 FR 54147 - Domestic Dates Produced or Packed in Riverside County, California; Decreased Assessment Rate

    Science.gov (United States)

    2013-09-03

    ... industry plans to shift its marketing programs to the State marketing program, the California Date... / Tuesday, September 3, 2013 / Rules and Regulations#0;#0; ] DEPARTMENT OF AGRICULTURE Agricultural Marketing Service 7 CFR Part 987 Domestic Dates Produced or Packed in Riverside County, California...

  11. Memory for time: how people date events

    NARCIS (Netherlands)

    Janssen, S.M.J.; Chessa, A.G.; Murre, J.M.J.

    2006-01-01

    The effect of different formats on the accuracy of dating news and the distribution of personal events was examined in four conditions. In the first, participants had to date events in the absolute time format (e.g., "July 2004"), and in the second, they had to date events in the relative time

  12. 20 CFR 217.16 - Filing date.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Filing date. 217.16 Section 217.16 Employees... LUMP SUM Filing An Application § 217.16 Filing date. An application filed in a manner and form acceptable to the Board is officially filed with the Board on the earliest of the following dates: (a) On the...

  13. 40 CFR 469.11 - Compliance dates.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Compliance dates. 469.11 Section 469... Compliance dates. The compliance deadline for the BAT fluoride limitation shall be as soon as possible as... determined by the permit writer, but in no event later than July 1, 1984. The compliance date for PSES for...

  14. 20 CFR 323.7 - Effective date.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Effective date. 323.7 Section 323.7 Employees... NONGOVERNMENTAL PLANS FOR UNEMPLOYMENT OR SICKNESS INSURANCE § 323.7 Effective date. (a) This part shall not apply to a plan approved by the Director of Unemployment and Sickness Insurance prior to the effective date...

  15. 40 CFR 57.106 - Expiration date.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Expiration date. 57.106 Section 57.106 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) PRIMARY NONFERROUS SMELTER ORDERS General § 57.106 Expiration date. Each NSO shall state its expiration date. No NSO...

  16. 33 CFR 106.110 - Compliance dates.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Compliance dates. 106.110 Section... MARINE SECURITY: OUTER CONTINENTAL SHELF (OCS) FACILITIES General § 106.110 Compliance dates. (a) On or... TWIC under this part may enroll beginning after the date set by the Coast Guard in a Notice to be...

  17. 40 CFR 51.1004 - Attainment dates.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 2 2010-07-01 2010-07-01 false Attainment dates. 51.1004 Section 51....5 National Ambient Air Quality Standards § 51.1004 Attainment dates. (a) Consistent with section 172(a)(2)(A) of the Act, the attainment date for an area designated nonattainment for the PM2.5 NAAQS...

  18. 38 CFR 8a.3 - Effective date.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Effective date. 8a.3... INSURANCE § 8a.3 Effective date. (a) Where the grant was approved prior to August 11, 1971, VMLI shall be effective August 11, 1971, if on that date, the eligible veteran was obligated under a mortgage loan, and...

  19. 49 CFR 571.8 - Effective date.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 6 2010-10-01 2010-10-01 false Effective date. 571.8 Section 571.8 Transportation..., DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR VEHICLE SAFETY STANDARDS General § 571.8 Effective date. (a) Firefighting vehicles. Notwithstanding the effective date provisions of the motor vehicle safety standards in...

  20. 33 CFR 105.115 - Compliance dates.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Compliance dates. 105.115 Section... MARITIME SECURITY: FACILITIES General § 105.115 Compliance dates. (a) On or before December 31, 2003... required to obtain a TWIC under this part may enroll beginning after the date set by the Coast Guard in a...

  1. 49 CFR 214.305 - Compliance dates.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Compliance dates. 214.305 Section 214.305..., DEPARTMENT OF TRANSPORTATION RAILROAD WORKPLACE SAFETY Roadway Worker Protection § 214.305 Compliance dates. Each program adopted by a railroad shall comply not later than the date specified in the following...

  2. 40 CFR 745.81 - Effective dates.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Effective dates. 745.81 Section 745.81... Effective dates. Link to an amendment published at 75 FR 24818, May 6, 2010. (a) Training, certification and... Right: Important Lead Hazard Information for Families, Child Care Providers and Schools. After that date...

  3. 40 CFR 280.91 - Compliance dates.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Compliance dates. 280.91 Section 280... (UST) Financial Responsibility § 280.91 Compliance dates. Owners of petroleum underground storage tanks are required to comply with the requirements of this subpart by the following dates: (a) All petroleum...

  4. 40 CFR 425.05 - Compliance dates.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Compliance dates. 425.05 Section 425... STANDARDS LEATHER TANNING AND FINISHING POINT SOURCE CATEGORY General Provisions § 425.05 Compliance dates. The compliance date for new source performance standards (NSPS) and pretreatment standards for new...

  5. 1 CFR 20.7 - Deadline dates.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Deadline dates. 20.7 Section 20.7 General... DOCUMENTS HANDLING OF THE UNITED STATES GOVERNMENT MANUAL STATEMENTS § 20.7 Deadline dates. The Manual is... basis. Therefore, agencies must comply with the deadline dates established by the Director of the...

  6. 18 CFR 1308.7 - Effective date.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Effective date. 1308.7... General Matters § 1308.7 Effective date. Subject to § 1308.3(a), this part applies to any TVA contract having an effective date on or after March 1, 1979. ...

  7. 7 CFR 1421.101 - Maturity dates.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Maturity dates. 1421.101 Section 1421.101 Agriculture... Maturity dates. (a)(1) All marketing assistance loans shall mature on demand by CCC and no later than the... filed and disbursed except, for transferred marketing assistance loan collateral. The maturity date for...

  8. 42 CFR 435.914 - Effective date.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Effective date. 435.914 Section 435.914 Public... Eligibility § 435.914 Effective date. (a) The agency must make eligibility for Medicaid effective no later... during that month. (c) The State plan must specify the date on which eligibility will be made effective...

  9. 36 CFR 1258.16 - Effective date.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Effective date. 1258.16... AVAILABILITY AND USE FEES § 1258.16 Effective date. The fees in this part are effective on October 1, 2007. If your order was received by NARA before this effective date, we will charge the fees in effect at the...

  10. 76 FR 34618 - Domestic Dates Produced or Packed in Riverside County, CA; Proposed Amendments to Marketing Order

    Science.gov (United States)

    2011-06-14

    ... Agricultural Marketing Service 7 CFR Part 987 Domestic Dates Produced or Packed in Riverside County, CA.... SUMMARY: Five amendments to Marketing Agreement and Order No.987 which regulates the handling of domestic... (7 CFR part 987), regulating the handling of domestic dates produced or packed in Riverside County...

  11. Disparities and Trends in Door-to-Needle Time: The FL-PR CReSD Study (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities).

    Science.gov (United States)

    Oluwole, Sofia A; Wang, Kefeng; Dong, Chuanhui; Ciliberti-Vargas, Maria A; Gutierrez, Carolina M; Yi, Li; Romano, Jose G; Perez, Enmanuel; Tyson, Brittany Ann; Ayodele, Maranatha; Asdaghi, Negar; Gardener, Hannah; Rose, David Z; Garcia, Enid J; Zevallos, Juan Carlos; Foster, Dianne; Robichaux, Mary; Waddy, Salina P; Sacco, Ralph L; Rundek, Tatjana

    2017-08-01

    In the United States, about half of acute ischemic stroke patients treated with tPA (tissue-type plasminogen activator) receive treatment within 60 minutes of hospital arrival. We aimed to determine the proportion of patients receiving tPA within 60 minutes (door-to-needle time [DTNT] ≤60) and 45 minutes (DTNT ≤45) of hospital arrival by race/ethnicity and sex and to identify temporal trends in DTNT ≤60 and DTNT ≤45. Among 65 654 acute ischemic stroke admissions in the National Institute of Neurological Disorders and Stroke-funded FL-PR CReSD study (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities) from 2010 to 2015, we included 6181 intravenous tPA-treated cases (9.4%). Generalized estimating equations were used to determine predictors of DTNT ≤60 and DTNT ≤45. DTNT ≤60 was achieved in 42% and DTNT ≤45 in 18% of cases. After adjustment, women less likely received DTNT ≤60 (odds ratio, 0.81; 95% confidence interval, 0.72-0.92) and DTNT ≤45 (odds ratio, 0.73; 95% confidence interval, 0.57-0.93). Compared with Whites, Blacks less likely had DTNT ≤45 during off hours (odds ratio, 0.68; 95% confidence interval, 0.47-0.98). Achievement of DTNT ≤60 and DTNT ≤45 was highest in South Florida (50%, 23%) and lowest in West Central Florida (28%, 11%). In the FL-PR CReSD, achievement of DTNT ≤60 and DTNT ≤45 remains low. Compared with Whites, Blacks less likely receive tPA treatment within 45 minutes during off hours. Treatment within 60 and 45 minutes is lower in women compared with men and lowest in West Central Florida compared with other Florida regions and Puerto Rico. Further research is needed to identify reasons for delayed thrombolytic treatment in women and Blacks and factors contributing to regional disparities in DTNT. © 2017 American Heart Association, Inc.

  12. Synergistic and Dose-Controlled Regulation of Cellulase Gene Expression in Penicillium oxalicum

    Science.gov (United States)

    Li, Zhonghai; Yao, Guangshan; Wu, Ruimei; Gao, Liwei; Kan, Qinbiao; Liu, Meng; Yang, Piao; Liu, Guodong; Qin, Yuqi; Song, Xin; Zhong, Yaohua; Fang, Xu; Qu, Yinbo

    2015-01-01

    Filamentous fungus Penicillium oxalicum produces diverse lignocellulolytic enzymes, which are regulated by the combinations of many transcription factors. Here, a single-gene disruptant library for 470 transcription factors was constructed and systematically screened for cellulase production. Twenty transcription factors (including ClrB, CreA, XlnR, Ace1, AmyR, and 15 unknown proteins) were identified to play putative roles in the activation or repression of cellulase synthesis. Most of these regulators have not been characterized in any fungi before. We identified the ClrB, CreA, XlnR, and AmyR transcription factors as critical dose-dependent regulators of cellulase expression, the core regulons of which were identified by analyzing several transcriptomes and/or secretomes. Synergistic and additive modes of combinatorial control of each cellulase gene by these regulatory factors were achieved, and cellulase expression was fine-tuned in a proper and controlled manner. With one of these targets, the expression of the major intracellular β-glucosidase Bgl2 was found to be dependent on ClrB. The Bgl2-deficient background resulted in a substantial gene activation by ClrB and proved to be closely correlated with the relief of repression mediated by CreA and AmyR during cellulase induction. Our results also signify that probing the synergistic and dose-controlled regulation mechanisms of cellulolytic regulators and using it for reconstruction of expression regulation network (RERN) may be a promising strategy for cellulolytic fungi to develop enzyme hyper-producers. Based on our data, ClrB was identified as focal point for the synergistic activation regulation of cellulase expression by integrating cellulolytic regulators and their target genes, which refined our understanding of transcriptional-regulatory network as a “seesaw model” in which the coordinated regulation of cellulolytic genes is established by counteracting activators and repressors. PMID:26360497

  13. 12 CFR 571.28 - Effective date, compliance date, and prospective application.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Effective date, compliance date, and prospective application. 571.28 Section 571.28 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY FAIR CREDIT REPORTING Affiliate Marketing § 571.28 Effective date, compliance date, and...

  14. 12 CFR 41.28 - Effective date, compliance date, and prospective application.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Effective date, compliance date, and prospective application. 41.28 Section 41.28 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY FAIR CREDIT REPORTING Affiliate Marketing § 41.28 Effective date, compliance date, and prospective...

  15. Cultivar-Dependent Direct Organogenesis of Date Palm from Shoot Tip Explants.

    Science.gov (United States)

    Abahmane, Larbi

    2017-01-01

    A number of public and private laboratories are working on date palm micropropagation to meet the increasing worldwide demand for date palm planting material. A standardized direct organogenesis protocol exists for the production of date palm plantlets to maintain the genetic fidelity of regenerated plants. Organogenesis has the advantage of using low concentrations of plant growth regulators and avoiding the callus phase. In addition, direct regeneration of vegetative buds minimizes the risk of somaclonal variation among plant regenerants. However, in vitro multiplication cycles should be limited in duration by frequent renewal of plant material. This chapter describes a simple and routine organogenesis protocol for date palm multiplication using shoot tip explants.

  16. Disruption of SATB2 or its long-range cis-regulation by SOX9 causes a syndromic form of Pierre Robin sequence.

    Science.gov (United States)

    Rainger, Jacqueline K; Bhatia, Shipra; Bengani, Hemant; Gautier, Philippe; Rainger, Joe; Pearson, Matt; Ansari, Morad; Crow, Jayne; Mehendale, Felicity; Palinkasova, Bozena; Dixon, Michael J; Thompson, Pamela J; Matarin, Mar; Sisodiya, Sanjay M; Kleinjan, Dirk A; Fitzpatrick, David R

    2014-05-15

    Heterozygous loss-of-function (LOF) mutations in the gene encoding the DNA-binding protein, SATB2, result in micrognathia and cleft palate in both humans and mice. In three unrelated individuals, we show that translocation breakpoints (BPs) up to 896 kb 3' of SATB2 polyadenylation site cause a phenotype which is indistinguishable from that caused by SATB2 LOF mutations. This syndrome comprises long nose, small mouth, micrognathia, cleft palate, arachnodactyly and intellectual disability. These BPs map to a gene desert between PLCL1 and SATB2. We identified three putative cis-regulatory elements (CRE1-3) using a comparative genomic approach each of which would be placed in trans relative to SATB2 by all three BPs. CRE1-3 each bind p300 and mono-methylated H3K4 consistent with enhancer function. In silico analysis suggested that CRE1-3 contain one or more conserved SOX9-binding sites, and this binding was confirmed using chromatin immunoprecipitation on cells derived from mouse embryonic pharyngeal arch. Interphase bacterial artificial chromosome fluorescence in situ hybridization measurements in embryonic craniofacial tissues showed that the orthologous region in mice exhibits Satb2 expression-dependent chromatin decondensation consistent with Satb2 being a target gene of CRE1-3. To assess their in vivo function, we made multiple stable reporter transgenic lines for each enhancer in zebrafish. CRE2 was shown to drive SATB2-like expression in the embryonic craniofacial region. This expression could be eliminated by mutating the SOX9-binding site of CRE2. These observations suggest that SATB2 and SOX9 may be acting together via complex cis-regulation to coordinate the growth of the developing jaw.

  17. Dating for Older Women: Experiences and Meanings of Dating in Later Life

    Science.gov (United States)

    Watson, Wendy K.; Stelle, Charlie

    2013-01-01

    Research over the last 20 years has provided an increased understanding of intimate relationships in later life; however, dating in later life remains largely unexplored. The purpose of this study was to examine the meanings of dating for women in later life. In this study, dating was examined through semistructured, in-depth interviews with 14 women ages 64 to 77 who had all dated in later life. Themes that emerged from an interpretative phenomenological analysis included multiple meanings of dating in later life, how dating in later life compared to earlier points in life, and dating in the future. PMID:21767089

  18. La credibilidad de los medios de Comunicación de masas: una aproximación desde el Modelo de Marca Creíble

    Directory of Open Access Journals (Sweden)

    Cristina Calvo-Porral

    Full Text Available Este estudio tiene por objetivo investigar, en el entorno actual de los medios de Comunicación, la relación entre el valor de marca de los medios de Comunicación desde el enfoque del consumidor y su credibilidad, aplicando el Modelo de Marca Creíble para analizar cómo la audiencia elabora un juicio sobre la credibilidad de los medios. Los datos recogidos mediante un cuestionario estructurado sobre las percepciones de los consumidores, se analizaron mediante un modelo de ecuaciones estructurales. Nuestros resultados sugieren la existencia de una relación positiva entre el valor de marca de los medios de Comunicación y su credibilidad, mostrando que tanto la imagen o asociaciones, juntamente com la lealtad, ejercen la mayor influencia sobre el valor de los medios de Comunicación. Por tanto, la credibilidad de los medios de Comunicación implica una mejora de los procesos y de la propia imagen de éstos, así como el desarrollo de nuevas formas de tratamiento de las noticias y de las necesidades de información de la audiencia.

  19. Suggested terminology for Quaternary dating methods

    Science.gov (United States)

    Colman, Steven M.; Pierce, K.L.; Birkeland, P.W.

    1987-01-01

    Classification of Quaternary dating methods should be based on the level of quantitative information and the degree of confidence contained in the age estimates produced by the dating methods. We recommend the use of the terms numerical-age, calibrated-age, relative-age, and correlated-age to describe these levels. We also classify dating methods by type into sideral, isotopic, radiogenic, chemical and biological, geomorphic, and correlation methods. The use of "absolute" is inappropriate for most dating methods, and should be replaced by "numerical." The use of "date" should be minimized in favor of "age" or "age estimate." We recommend use of the abbreviations ka and Ma for most ages; calender dates can be used where appropriate and yr B.P. can be used for radiocarbon ages. ?? 1987.

  20. 17 CFR 240.12d1-4 - Date of receipt of certification by Commission.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Date of receipt of certification by Commission. 240.12d1-4 Section 240.12d1-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities Exchange Act...

  1. Conditional reverse tet-transactivator mouse strains for the efficient induction of TRE-regulated transgenes in mice.

    Directory of Open Access Journals (Sweden)

    Lukas E Dow

    Full Text Available Tetracycline or doxycycline (dox-regulated control of genetic elements allows inducible, reversible and tissue specific regulation of gene expression in mice. This approach provides a means to investigate protein function in specific cell lineages and at defined periods of development and disease. Efficient and stable regulation of cDNAs or non-coding elements (e.g. shRNAs downstream of the tetracycline-regulated element (TRE requires the robust expression of a tet-transactivator protein, commonly the reverse tet-transactivator, rtTA. Most rtTA strains rely on tissue specific promoters that often do not provide sufficient rtTA levels for optimal inducible expression. Here we describe the generation of two mouse strains that enable Cre-dependent, robust expression of rtTA3, providing tissue-restricted and consistent induction of TRE-controlled transgenes. We show that these transgenic strains can be effectively combined with established mouse models of disease, including both Cre/LoxP-based approaches and non Cre-dependent disease models. The integration of these new tools with established mouse models promises the development of more flexible genetic systems to uncover the mechanisms of development and disease pathogenesis.

  2. Regulating the regulators : accountability of Australian regulators

    National Research Council Canada - National Science Library

    Bird, Joanna

    2011-01-01

    Accountability of Australian regulators - Australian Securities and Investments Commission - Australian Prudential Regulation Authority - concept of 'accountability' - mechanisms for accountability...

  3. Peer Involvement in Adolescent Dating Violence

    Science.gov (United States)

    Stephenson, Pam S.; Martsolf, Donna; Draucker, Claire Burke

    2013-01-01

    This study investigated the ways in which peers are involved in adolescent dating violence. Eighty-eight young adults aged 18-21 were interviewed and asked to reflect on aggressive dating relationships they experienced as teens. The researchers used grounded theory to analyze the data. Findings showed that male and female peers were involved in…

  4. Date palm production and pest management challenges

    Science.gov (United States)

    Abstract: Date palm, Phoenix dactylifera, is a monocotyledonous species belong- ing to the palm family (Arecaceae or Palmae) which is perennial and dioecious and cultivated mostly in the arid regions of the world. Date palm is important to the agrarian economy of several countries, with the ability ...

  5. 38 CFR 21.4135 - Discontinuance dates.

    Science.gov (United States)

    2010-07-01

    ...(g), 3532(e)) (n) Fugitive felons: veterans eligible under 38 U.S.C. chapter 32. VA will not award..., during which the veteran is a fugitive felon. The date of discontinuance of an award of educational assistance allowance to a veteran who is a fugitive felon is the later of— (1) The date of the warrant for...

  6. 38 CFR 21.7135 - Discontinuance dates.

    Science.gov (United States)

    2010-07-01

    ..., 3676, 3680A(a)) (aa) Fugitive felons. (1) VA will not award educational assistance allowance to an... felon. The date of discontinuance of an award of educational assistance allowance to a veteran who is a fugitive felon is the later of— (i) The date of the warrant for the arrest of the felon; or (ii) December...

  7. 32 CFR 270.3 - Effective date.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Effective date. 270.3 Section 270.3 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS... Effective date. This part is effective on May 15, 1997. ...

  8. 42 CFR 489.104 - Effective dates.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Effective dates. 489.104 Section 489.104 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... dates. These provisions apply to services furnished on or after December 1, 1991 payments made under...

  9. 18 CFR 808.19 - Effective date.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Effective date. 808.19 Section 808.19 Conservation of Power and Water Resources SUSQUEHANNA RIVER BASIN COMMISSION HEARINGS AND ENFORCEMENT ACTIONS Compliance and Enforcement § 808.19 Effective date. This part shall be effective on...

  10. Strategies for Family Facilitation of Play Dates

    Science.gov (United States)

    Chambers, Cynthia R.; Horn, Eva M.

    2010-01-01

    Play dates can serve several functions for young children, including children with social difficulties, such as developmental delays, behavioral disorders, autism spectrum disorders, and shyness. Play dates provide children with additional opportunities to be around peers and to practice skills associated with peer play interactions. Play dates…

  11. 18 CFR 807.4 - Effective date.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Effective date. 807.4 Section 807.4 Conservation of Power and Water Resources SUSQUEHANNA RIVER BASIN COMMISSION WATER WITHDRAWAL REGISTRATION § 807.4 Effective date. This part shall be effective on January 1, 2007. ...

  12. 11 CFR 9006.2 - Filing dates.

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Filing dates. 9006.2 Section 9006.2 Federal Elections FEDERAL ELECTION COMMISSION PRESIDENTIAL ELECTION CAMPAIGN FUND: GENERAL ELECTION FINANCING REPORTS AND RECORDKEEPING § 9006.2 Filing dates. The reports required to be filed under 11 CFR 9006.1...

  13. 40 CFR 745.339 - Effective date.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Effective date. 745.339 Section 745.339 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT... Programs § 745.339 Effective date. States and Indian Tribes may seek authorization to administer and...

  14. 10 CFR 1023.102 - Effective date.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Effective date. 1023.102 Section 1023.102 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) CONTRACT APPEALS Rules of the Board of Contract Appeals § 1023.102 Effective date. The rules of the Board of Contract Appeals shall apply to all proceedings filed on or after...

  15. 32 CFR 191.10 - Effective date.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Effective date. 191.10 Section 191.10 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS THE DOD CIVILIAN EQUAL EMPLOYMENT OPPORTUNITY (EEO) PROGRAM § 191.10 Effective date. This part is...

  16. 44 CFR 206.17 - Effective date.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Effective date. 206.17 Section 206.17 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE General § 206.17 Effective date. These...

  17. 40 CFR 63.1501 - Dates.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Dates. 63.1501 Section 63.1501 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL... Hazardous Air Pollutants for Secondary Aluminum Production General § 63.1501 Dates. (a) The owner or...

  18. 40 CFR 63.1545 - Compliance dates.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Compliance dates. 63.1545 Section 63.1545 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... for Hazardous Air Pollutants for Primary Lead Smelting § 63.1545 Compliance dates. (a) Each owner or...

  19. 32 CFR 242a.8 - Effective date.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Effective date. 242a.8 Section 242a.8 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS... § 242a.8 Effective date. This part shall become effective on March 12, 1977. ...

  20. 40 CFR 745.239 - Effective dates.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Effective dates. 745.239 Section 745.239 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT... § 745.239 Effective dates. This subpart L shall apply in any State or Indian Country that does not have...

  1. 40 CFR 745.102 - Effective dates.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Effective dates. 745.102 Section 745.102 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT... dates. The requirements in this subpart take effect in the following manner: (a) For owners of more than...

  2. Dating violence and suicidal behavior in adolescents.

    Science.gov (United States)

    Holmes, Kristin; Sher, Leo

    2013-01-01

    The aim of this paper is to assess the possible consequences of adolescent physical, emotional and sexual dating violence through a review of the literature on the topic. An electronic search of major biomedical bibliographic databases (Pubmed, ISI, PsycINFO) was used to retrieve articles providing information on the prevalence rates, risk factors, associated consequences and possible preventive measures for adolescent dating violence across different populations. Currently, there have been few longitudinal studies conducted to identify potential risk factors for entering a violent dating relationship in adolescence. Risky behaviors such as early sexual intercourse may predispose someone for victimization. Dating violence itself is also a predictor of future dating violence. Adolescent dating violence was associated with an increase in other violence-related behaviors, substance use, depression, poorer educational outcomes, posttraumatic stress, unhealthy weight control and risky sexual behavior. The association between adolescent dating violence and an increase in suicidal behavior is a major public health concern. Future research should focus on longitudinal studies so that a causal relationship between dating violence and suicidality may be better understood.

  3. Teen Dating Violence Prevention Program Assessment

    Science.gov (United States)

    Lucas, Quincy Arrianna Rose

    2013-01-01

    The American Psychological Association (APA) has identified the prevention of and intervention in relationship violence as a top priority (APA, n.d.). According to the Center for Disease Control and Prevention's 2012 Teen Dating Violence Fact Sheet, dating violence is a serious problem in the United States. In accordance with Foshee et al. (1998):…

  4. Cre-/IoxP-Mediated Recombination between the SIL and SCL Genes Leads to a Block in T-Cell Development at the CD4-CD8- to CD4+CD8+ Transition

    Directory of Open Access Journals (Sweden)

    Yue Cheng

    2007-04-01

    Full Text Available In the most common form of stem cell leukemia (SCL gene rearrangement, an interstitial deletion of 82 kb brings SCL under the control of regulatory elements that normally govern expression of the ubiquitously expressed SCL interrupting locus (SIL gene, which is located directly upstream of SCL. To investigate the effect of this fusion in a mouse model, a bacterial artificial chromosome (BAC clone containing both human SIL and SCL genes was isolated, and IoxP sites were inserted into intron 1 of both the SIL and SCL genes, corresponding to the sites at which recombination occurs in human T-cell acute lymphocytic leukemia patients. This BAC clone was used to generate transgenic SILIoxloxSCL mice. These transgenic mice were subsequently bred to Lck-Cre mice that express the Cre recombinase specifically in the thymus. The BAC transgene was recombined between the two IoxP sites in over 50% of the thymocytes from SILIoxloxSCL/Cre double-transgenic mice, bringing the SCL gene under the direct control of SIL regulatory elements. Aberrant SCL gene expression in the thymus was verified by reverse transcription- polymerase chain reaction. Using FACS analysis, we found that mice carrying both SILIoxloxSCL and Cre transgenes have increased CD4-/CD8- thymocytes compared with transgenenegative mice. In the spleen, these transgenic mice show a marked reduction in the number of mature CD4+ or CD8+ cells. These results demonstrate that conditional activation of SCL under control of SIL regulatory elements can impair normal T-cell development.

  5. Ambiguity and violence in adolescent dating relationships.

    Science.gov (United States)

    Draucker, Claire Burke; Martsolf, Donna; Stephenson, Pam Shockey

    2012-08-01

    Little is known about dyadic processes that lead to adolescent dating violence. The purpose of this study was to examine the phenomenon of relationship ambiguity in adolescent dating relationships to better understand how ambiguity contributes to violence and aggression between dating partners. Data were drawn from 88 narratives of young adults who had participated in a study on adolescent dating violence. Interpretive phenomenology was used to produce an in-depth description of the phenomenon of relationship ambiguity. Relationship ambiguity results in differing expectations between partners regarding closeness and intimacy, fidelity, and obligation. These differences lead to conflicts that set the stage for violence and aggression in adolescent dating relationships. A series of recommendations for clinicians working with adolescents are presented. © 2012 Wiley Periodicals, Inc.

  6. HMGA1 expression levels are elevated in pancreatic intraepithelial neoplasia cells in the Ptf1a-Cre; LSL-KrasG12D transgenic mouse model of pancreatic cancer.

    Science.gov (United States)

    Veite-Schmahl, Michelle J; Joesten, William C; Kennedy, Michael A

    2017-08-22

    Pancreatic cancer is currently the third leading cause of cancer deaths in the United States and it is predicted to become the second by the year 2030. High-mobility group A1 protein (HMGA1) is an oncogenic transcription factor, localised and active in cell nuclei, that is linked to tumour progression in many human cancers, including pancreatic cancer. Overexpression of HMGA1 renders cancer cells resistant to chemotherapy. Although the Ptf1a-Cre; LSL-KrasG12D transgenic mouse is perhaps the most widely utilised animal model for human pancreatic cancer, expression levels of HMGA1 in pancreata from this mouse model have not been characterised. Quantitative immunohistochemical analysis was used to determine nuclear HMGA1 levels in pancreatic tissue sections from Ptf1a-Cre; LSL-KrasG12D mice aged 5, 11, and 15 months. The H Score method was used for quantitative analysis. The HMGA1 levels were significantly elevated in pancreatic intraepithelial neoplasia (PanIN) epithelia compared with untransformed acinar tissues or fibroinflammatory stroma. The PanINs have long been regarded as precancerous precursors to pancreatic adenocarcinoma. Significantly elevated HMGA1 levels observed in the nuclei of PanINs in Ptf1a-Cre; LSL-KrasG12D mice validate this animal model for investigating the role that HMGA1 plays in cancer progression and testing therapeutic approaches targeting HMGA1 in human cancers.

  7. TCreERT2, a transgenic mouse line for temporal control of Cre-mediated recombination in lineages emerging from the primitive streak or tail bud.

    Science.gov (United States)

    Anderson, Matthew J; Naiche, L A; Wilson, Catherine P; Elder, Cindy; Swing, Deborah A; Lewandoski, Mark

    2013-01-01

    The study of axis extension and somitogenesis has been greatly advanced through the use of genetic tools such as the TCre mouse line. In this line, Cre is controlled by a fragment of the T (Brachyury) promoter that is active in progenitor cells that reside within the primitive streak and tail bud and which give rise to lineages emerging from these tissues as the embryonic axis extends. However, because TCre-mediated recombination occurs early in development, gene inactivation can result in an axis truncation that precludes the study of gene function in later or more posterior tissues. To address this limitation, we have generated an inducible TCre transgenic mouse line, called TCreERT2, that provides temporal control, through tamoxifen administration, in all cells emerging from the primitive streak or tail bud throughout development. TCreERT2 activity is mostly silent in the absence of tamoxifen and, in its presence, results in near complete recombination of emerging mesoderm from E7.5 through E13.5. We demonstrate the utility of the TCreERT2 line for determining rate of posterior axis extension and somite formation, thus providing the first in vivo tool for such measurements. To test the usefulness of TCreERT2 for genetic manipulation, we demonstrate that an early deletion of ß-Catenin via TCreERT2 induction phenocopies the TCre-mediated deletion of ß-Catenin defect, whereas a later induction bypasses this early phenotype and produces a similar defect in more caudal tissues. TCreERT2 provides a useful and novel tool for the control of gene expression of emerging embryonic lineages throughout development.

  8. Inhibition of Pancreatic Intraepithelial Neoplasia Progression to Carcinoma by Nitric Oxide-Releasing Aspirin in p48Cre/+-LSL-KrasG12D/+ Mice

    Directory of Open Access Journals (Sweden)

    Chinthalapally V. Rao

    2012-09-01

    Full Text Available Nitric oxide-releasing aspirin (NO-aspirin represents a novel class of promising chemopreventive agents. Unlike conventional nonsteroidal anti-inflammatory drugs, NO-aspirin seems to be free of adverse effects while retaining the beneficial activities of its parent compound. The effect of NO-aspirin on pancreatic carcinogenesis was investigated by assessing the development of precursor pancreatic lesions and adenocarcinomas in KrasG12D/+ transgenic mice that recapitulate human pancreatic cancer progression. Six-week-old male p48Cre/+-LSL-KrasG12D/+ transgenic mice (20 per group were fed diets containing 0, 1000, or 2000 ppm NO-aspirin. The development of pancreatic tumors was monitored by positron emission tomography imaging. All mice were killed at the age of 41 weeks and assessed for pancreatic intraepithelial neoplasia (PanIN and pancreatic ductal adenocarcinoma (PDAC and for molecular changes in the tumors. Our results reveal that NO-aspirin at 1000 and 2000 ppm significantly suppressed pancreatic tumor weights, PDAC incidence, and carcinoma in situ (PanIN-3 lesions. The degree of inhibition of PanIN-3 and carcinoma was more pronounced with NO-aspirin at 1000 ppm (58.8% and 48%, respectively than with 2000 ppm (47% and 20%, respectively. NO-aspirin at 1000 ppm significantly inhibited the spread of carcinoma in the pancreas (∼97%; P < .0001. Decreased expression of cyclooxygenase (COX; with ∼42% inhibition of total COX activity, inducible nitric oxide synthase, proliferating cell nuclear antigen, Bcl-2, cyclin D1, and β-catenin was observed, with induction of p21, p38, and p53 in the pancreas of NO-aspirin-treated mice. These results suggest that low-dose NO-aspirin possesses inhibitory activity against pancreatic carcinogenesis by modulating multiple molecular targets.

  9. Store-operated Ca2+ entry regulates Ca2+-activated chloride channels and eccrine sweat gland function.

    Science.gov (United States)

    Concepcion, Axel R; Vaeth, Martin; Wagner, Larry E; Eckstein, Miriam; Hecht, Lee; Yang, Jun; Crottes, David; Seidl, Maximilian; Shin, Hyosup P; Weidinger, Carl; Cameron, Scott; Turvey, Stuart E; Issekutz, Thomas; Meyts, Isabelle; Lacruz, Rodrigo S; Cuk, Mario; Yule, David I; Feske, Stefan

    2016-11-01

    Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release-activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel-deficient patients and mice with ectodermal tissue-specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development. SOCE was absent in agonist-stimulated sweat glands from Orai1K14Cre and Stim1/2K14Cre mice and human sweat gland cells lacking ORAI1 or STIM1 expression. In Orai1K14Cre mice, abolishment of SOCE was associated with impaired chloride secretion by primary murine sweat glands. In human sweat gland cells, SOCE mediated by ORAI1 was necessary for agonist-induced chloride secretion and activation of the Ca2+-activated chloride channel (CaCC) anoctamin 1 (ANO1, also known as TMEM16A). By contrast, expression of TMEM16A, the water channel aquaporin 5 (AQP5), and other regulators of sweat gland function was normal in the absence of SOCE. Our findings demonstrate that Ca2+ influx via store-operated CRAC channels is essential for CaCC activation, chloride secretion, and sweat production in humans and mice.

  10. Ciliary neurotrophic factor receptor regulation of adult forebrain neurogenesis.

    Science.gov (United States)

    Lee, Nancy; Batt, Myra K; Cronier, Brigitte A; Jackson, Michele C; Bruno Garza, Jennifer L; Trinh, Dennis S; Mason, Carter O; Spearry, Rachel P; Bhattacharya, Shayon; Robitz, Rachel; Nakafuku, Masato; MacLennan, A John

    2013-01-16

    Appropriately targeted manipulation of endogenous neural stem progenitor (NSP) cells may contribute to therapies for trauma, stroke, and neurodegenerative disease. A prerequisite to such therapies is a better understanding of the mechanisms regulating adult NSP cells in vivo. Indirect data suggest that endogenous ciliary neurotrophic factor (CNTF) receptor signaling may inhibit neuronal differentiation of NSP cells. We challenged subventricular zone (SVZ) cells in vivo with low concentrations of CNTF to anatomically characterize cells containing functional CNTF receptors. We found that type B "stem" cells are highly responsive, whereas type C "transit-amplifying" cells and type A neuroblasts are remarkably unresponsive, as are GFAP(+) astrocytes found outside the SVZ. CNTF was identified in a subset of type B cells that label with acute BrdU administration. Disruption of in vivo CNTF receptor signaling in SVZ NSP cells, with a "floxed" CNTF receptor α (CNTFRα) mouse line and a gene construct driving Cre recombinase (Cre) expression in NSP cells, led to increases in SVZ-associated neuroblasts and new olfactory bulb neurons, as well as a neuron subtype-specific, adult-onset increase in olfactory bulb neuron populations. Adult-onset receptor disruption in SVZ NSP cells with a recombinant adeno-associated virus (AAV-Cre) also led to increased neurogenesis. However, the maintenance of type B cell populations was apparently unaffected by the receptor disruption. Together, the data suggest that endogenous CNTF receptor signaling in type B stem cells inhibits adult neurogenesis, and further suggest that the regulation may occur in a neuron subtype-specific manner.

  11. Longitudinal relationships between individual and class norms supporting dating violence and perpetration of dating violence.

    Science.gov (United States)

    Taylor, Katherine A; Sullivan, Terri N; Farrell, Albert D

    2015-03-01

    Dating violence is commonly perpetrated in adolescence, making it imperative to understand risk factors in order to inform prevention efforts. Although individual norms supporting dating violence are strongly related to its perpetration, few studies have examined their longitudinal impact. Moreover, the influence of class norms (i.e., norms for students in the same grade, cohort, and school) supporting dating violence on perpetration has rarely been studied. The current study examined longitudinal relationships between individual and class norms supporting dating violence and perpetration of physical and psychological dating violence. Participants were two cohorts of sixth graders from 37 schools who were in dating relationships at Wave 1 and 6 months later at Wave 2 (N = 2,022; 43% female; 52% African American, 21% Latino/a, 20% White, and 7% other). The analyses used a multilevel approach, with students represented at Level 1 and classes (n = 74) at Level 2. The models tested direct effects of Wave 1 individual and class norms supporting dating violence on subsequent changes in perpetration of dating violence at Wave 2 and the extent to which gender moderated these relationships. The findings indicated that greater individual norms supporting male dating violence predicted greater change in perpetration of physical and psychological dating violence and greater individual norms supporting female dating violence predicted greater change in perpetration of psychological dating violence. Greater class norms supporting male dating violence predicted greater change in perpetration of physical dating violence; whereas greater class norms supporting female dating violence predicted less change in perpetration of physical dating violence. These findings highlight the need to address norms in early adolescence.

  12. Dating for Older Women: Experiences and Meanings of Dating in Later Life

    OpenAIRE

    Watson, Wendy K.; Stelle, Charlie

    2011-01-01

    Research over the last 20 years has provided an increased understanding of intimate relationships in later life; however, dating in later life remains largely unexplored. The purpose of this study was to examine the meanings of dating for women in later life. In this study, dating was examined through semistructured, in-depth interviews with 14 women ages 64 to 77 who had all dated in later life. Themes that emerged from an interpretative phenomenological analysis included multiple meanings o...

  13. Date palm micropropagation: Advances and applications

    Directory of Open Access Journals (Sweden)

    Jameel Mohammed Al-Khayri

    Full Text Available ABSTRACT Date palm (Phoenix dactylifera L. is a fruit tree resilient to adverse climatic conditions predominating in hot arid regions of the Middle East and North Africa. The date fruit contains numerous chemical components that possess high nutritional and medicinal values. Traditional propagation by offshoots is inefficient to satisfy current demands for date palm trees. Alternatively, micropropagation provides an efficient means for large-scale propagation of date palm cultivars. Both somatic embryogenesis and organogenesis, either directly or indirectly though the callus phase, have been demonstrated in date palm in vitro regeneration. Culture initiation commonly utilizes shoot-tip explants isolated from young offshoots. Recently, the immature inflorescences of adult trees were utilized as an alternative nondestructive source of explants. In addition to the nature of the explant used, successful plant regeneration depends on the cultivar, composition of the culture medium and physical status. Challenges of date palm micropropagation include long in vitro cycle, latent contamination, browning, somaclonal variation as well as ex vitro acclimatization and transplanting. A remarkable amount of research investigating these factors has led to optimized protocols for the micropropagation of numerous commercially important cultivars. This has encouraged the development of several international commercial tissue culture laboratories. Molecular characterization provides an assurance of genetic conformity of regenerated plantlets, a key feature for commercial production. This article describes date palm micropropagation protocols and also discusses recent achievements with respect to somaclonal variation, molecular markers, cryopreservation and future prospects.

  14. Preliminary Report on Practice Dating and Feedback as Treatment for College Dating Problems

    Science.gov (United States)

    Christensen, Andrew; Arkowitz, Hal

    1974-01-01

    Fourteen make and 14 female undergraduates who volunteered for a program to increase their dating effectiveness were matched for six dates, each date with a different opposite-sex subject. Heterosexual interaction frequency and subjective measures of comfort increased significantly with treatment. (Author)

  15. A Phenomenological Investigation of Adolescent Dating Relationships and Dating Violence Counseling Interventions

    Science.gov (United States)

    Hays, Danica G.; Michel, Rebecca E.; Cole, Rebekah F.; Emelianchik, Kelly; Forman, Julia; Lorelle, Sonya; McBride, Rebecca; Sikes, April

    2011-01-01

    Despite the prevalence of dating violence, incidences often go unreported due to a lack of awareness among students as to appropriate dating behaviors. This phenomenology investigated how adolescents conceptualize and experience dating relationships. We explored adolescent females' definitions of healthy and abusive relationships, experiences with…

  16. Optically stimulated luminescence dating of young sediments

    DEFF Research Database (Denmark)

    Madsen, Anni Tindahl; Murray, Andrew S.

    2009-01-01

    of OSL dating, outlines the problems specific to the dating of young material, and then uses recent applications to young sediments to illustrate the greatly increased scope and potential of the method in geomorphology and the geology of recent deposits. The overall reliability of this new generation...... for determining the time of deposition of water-lain sediments from the coastal zone, and aeolian deposits from both coastal and inland environments. Our conclusion is supported by the growing popularity of OSL dating in geomorphology and geology...

  17. TL and EPR dating: some applications

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, S. [Institute of Physics, University of Sao Paulo, Sao Paulo (Brazil)

    2006-07-01

    The intensity of thermoluminescence light emitted by a crystal is a function of radiation dose. The number of defects or of radicals in a crystal or organic substances is also a function of radiation dose. Since such defects or radicals present EPR signals, the EPR intensity is also a function of radiation dose. These facts are basis for radiation dosimetry and can be applied in dating of archaeological potteries or other materials, as well as in dating geological substances such as sediments, caves speleothemes, animal teeth and bones. Recent investigation on sensitized quartz based dosimeters and dating calcite covering ancient wall painting to find early settlers in Brazil will be presented. (Author)

  18. CTGF mediates Smad-dependent transforming growth factor β signaling to regulate mesenchymal cell proliferation during palate development.

    Science.gov (United States)

    Parada, Carolina; Li, Jingyuan; Iwata, Junichi; Suzuki, Akiko; Chai, Yang

    2013-09-01

    Transforming growth factor β (TGF-β) signaling plays crucial functions in the regulation of craniofacial development, including palatogenesis. Here, we have identified connective tissue growth factor (Ctgf) as a downstream target of the TGF-β signaling pathway in palatogenesis. The pattern of Ctgf expression in wild-type embryos suggests that it may be involved in key processes during palate development. We found that Ctgf expression is downregulated in both Wnt1-Cre; Tgfbr2(fl/fl) and Osr2-Cre; Smad4(fl/fl) palates. In Tgfbr2 mutant embryos, downregulation of Ctgf expression is associated with p38 mitogen-activated protein kinase (MAPK) overactivation, whereas loss of function of Smad4 itself leads to downregulation of Ctgf expression. We also found that CTGF regulates its own expression via TGF-β signaling. Osr2-Cre; Smad4(fl/fl) mice exhibit a defect in cell proliferation similar to that of Tgfbr2 mutant mice, as well as cleft palate. We detected no alteration in bone morphogenetic protein (BMP) downstream targets in Smad4 mutant palates, suggesting that the reduction in cell proliferation is due to defective transduction of TGF-β signaling via decreased Ctgf expression. Significantly, an exogenous source of CTGF was able to rescue the cell proliferation defect in both Tgfbr2 and Smad4 mutant palates. Collectively, our data suggest that CTGF regulates proliferation as a mediator of the canonical pathway of TGF-β signaling during palatogenesis.

  19. Fibroblast growth factor 9 (FGF9)-pituitary homeobox 2 (PITX2) pathway mediates transforming growth factor β (TGFβ) signaling to regulate cell proliferation in palatal mesenchyme during mouse palatogenesis.

    Science.gov (United States)

    Iwata, Jun-ichi; Tung, Lily; Urata, Mark; Hacia, Joseph G; Pelikan, Richard; Suzuki, Akiko; Ramenzoni, Liza; Chaudhry, Obaid; Parada, Carolina; Sanchez-Lara, Pedro A; Chai, Yang

    2012-01-20

    Cleft palate represents one of the most common congenital birth defects. Transforming growth factor β (TGFβ) signaling plays crucial functions in regulating craniofacial development, and loss of TGFβ receptor type II in cranial neural crest cells leads to craniofacial malformations, including cleft palate in mice (Tgfbr2(fl/fl);Wnt1-Cre mice). Here we have identified candidate target genes of TGFβ signaling during palatal formation. These target genes were selected based on combining results from gene expression profiles of embryonic day 14.5 palates from Tgfbr2(fl/fl);Wnt1-Cre mice and previously identified cleft palate phenotypes in genetically engineered mouse models. We found that fibroblast growth factor 9 (Fgf9) and transcription factor pituitary homeobox 2 (Pitx2) expressions are significantly down-regulated in the palate of Tgfbr2(fl/fl);Wnt1-Cre mice, and Fgf9 and Pitx2 loss of function mutations result in cleft palate in mice. Pitx2 expression is down-regulated by siRNA knockdown of Fgf9, suggesting that Fgf9 is upstream of Pitx2. We detected decreased expression of both cyclins D1 and D3 in the palates of Tgfbr2(fl/fl);Wnt1-Cre mice, consistent with the defect in cell proliferation. Significantly, exogenous FGF9 restores expression of cyclins D1 and D3 in a Pitx2-dependent manner and rescues the cell proliferation defect in the palatal mesenchyme of Tgfbr2(fl/fl);Wnt1-Cre mice. Our study indicates that a TGFβ-FGF9-PITX2 signaling cascade regulates cranial neural crest cell proliferation during palate formation.

  20. Pten Regulates Epithelial Cytodifferentiation during Prostate Development

    DEFF Research Database (Denmark)

    Lokody, Isabel B; Francis, Jeffrey C; Gardiner, Jennifer R

    2015-01-01

    Gene expression and functional studies have indicated that the molecular programmes involved in prostate development are also active in prostate cancer. PTEN has been implicated in human prostate cancer and is frequently mutated in this disease. Here, using the Nkx3.1:Cre mouse strain and a genetic...... deletion approach, we investigate the role of Pten specifically in the developing mouse prostate epithelia. In contrast to its role in other developing organs, this gene is dispensable for the initial developmental processes such as budding and branching. However, as cytodifferentiation progresses...... that are shared with Pten mutant prostate cancer models, including a decrease in androgen receptor regulated genes. In depth analysis of the phenotype of these mice during development revealed that loss of Pten leads to the precocious differentiation of epithelial cells towards a luminal cell fate. This study...

  1. SUMO: regulating the regulator

    Directory of Open Access Journals (Sweden)

    Bossis Guillaume

    2006-06-01

    Full Text Available Abstract Post-translational modifiers of the SUMO (Small Ubiquitin-related Modifier family have emerged as key regulators of protein function and fate. While the past few years have seen an enormous increase in knowledge on SUMO enzymes, substrates, and consequences of modification, regulation of SUMO conjugation is far from being understood. This brief review will provide an overview on recent advances concerning (i the interplay between sumoylation and other post-translational modifications at the level of individual targets and (ii global regulation of SUMO conjugation and deconjugation.

  2. Coconut, date and oil palm genomics

    Science.gov (United States)

    A review of genomics research is presented for the three most economically important palm crops, coconut (Cocos nucifera), date palm (Phoenix dactylifera) and oil palm (Elaeis guineensis), encompassing molecular markers studies of genetic diversity, genetic mapping, quantitative trait loci discovery...

  3. Amtrak's strategic business plan : progress to date

    Science.gov (United States)

    1996-07-24

    To address its financial crisis and make its operations more efficient, in 1995 : Amtrak undertook a major corporate restructuring, along with developing its : Strategic Business Plan. This report (1) reviews Amtrak's success to date in : achieving f...

  4. Substance Use and Physical Dating Violence

    Science.gov (United States)

    Reyes, H. Luz McNaughton; Foshee, Vangie A.; Tharp, Andra T.; Ennett, Susan T.; Bauer, Daniel J.

    2015-01-01

    Introduction Theoretic models suggest that associations between substance use and dating violence perpetration may vary in different social contexts, but few studies have examined this proposition. The current study examined whether social control and violence in the neighborhood, peer, and family contexts moderate the associations between substance use (heavy alcohol use, marijuana, and hard drug use) and adolescent physical dating violence perpetration. Methods Adolescents in the eighth, ninth, and tenth grades completed questionnaires in 2004 and again four more times until 2007 when they were in the tenth, 11th and 12th grades. Multilevel analysis was used to examine interactions between each substance and measures of neighborhood, peer, and family social control and violence as within-person (time-varying) predictors of physical dating violence perpetration across eighth through 12th grade (N=2,455). Analyses were conducted in 2014. Results Physical dating violence perpetration increased at time points when heavy alcohol and hard drug use were elevated; these associations were weaker when neighborhood social control was higher and stronger when family violence was higher. Also, the association between heavy alcohol use and physical dating violence perpetration was weaker when teens had more-prosocial peer networks and stronger when teens’ peers reported more physical dating violence. Conclusions Linkages between substance use and physical dating violence perpetration depend on substance use type and levels of contextual violence and social control. Prevention programs that address substance use–related dating violence should consider the role of social contextual variables that may condition risk by influencing adolescents’ aggression propensity. PMID:26296445

  5. Reduction of date microbial load with ozone

    Science.gov (United States)

    Farajzadeh, Davood; Qorbanpoor, Ali; Rafati, Hasan; Isfeedvajani, Mohsen Saberi

    2013-01-01

    Background: Date is one of the foodstuffs that are produced in tropical areas and used worldwide. Conventionally, methyl bromide and phosphine are used for date disinfection. The toxic side effects of these usual disinfectants have led food scientists to consider safer agents such as ozone for disinfection, because food safety is a top priority. The present study was performed to investigate the possibility of replacing common conventional disinfectants with ozone for date disinfection and microbial load reduction. Materials and Methods: In this experimental study, date samples were ozonized for 3 and 5 hours with 5 and 10 g/h concentrations and packed. Ozonized samples were divided into two groups and kept in an incubator which was maintained at 25°C and 40°C for 9 months. During this period, every 3 month, microbial load (bacteria, mold, and yeast) were examined in ozonized and non-ozonized samples. Results: This study showed that ozonization with 5 g/h for 3 hours, 5 g/h for 5 hours, 10 g/h for 3 hours, and 10 g/h for 5 hours leads to about 25%, 25%, 53%, and 46% reduction in date mold and yeast load and about 6%, 9%, 76%, and 74.7% reduction in date bacterial load at baseline phase, respectively. Appropriate concentration and duration of ozonization for microbial load reduction were 10 g/h and 3 hours. Conclusion: Date ozonization is an appropriate method for microbial load reduction and leads to an increase in the shelf life of dates. PMID:24124432

  6. 77 FR 44045 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-60; Introduction

    Science.gov (United States)

    2012-07-26

    ... Internet at http://www.regulations.gov . DATES: For effective dates and comment dates see separate... Administration 48 CFR Chapter 1 Federal Acquisition Regulation; Final Rules #0;#0;Federal Register / Vol. 77 , No. 144 / Thursday, July 26, 2012 / Rules and Regulations#0;#0; ] DEPARTMENT OF DEFENSE GENERAL SERVICES...

  7. 77 FR 69713 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-62; Introduction

    Science.gov (United States)

    2012-11-20

    ... available via the Internet at http://www.regulations.gov . DATES: For effective dates and comment dates see... Space Administration 48 CFR Chapter 1 Federal Acquisition Regulation; Final Rules #0;#0;Federal Register / Vol. 77 , No. 224 / Tuesday, November 20, 2012 / Rules and Regulations#0;#0; ] DEPARTMENT OF DEFENSE...

  8. In Vitro Cryopreservation of Date Palm Caulogenic Meristems.

    Science.gov (United States)

    Fki, Lotfi; Chkir, Olfa; Kriaa, Walid; Nasri, Ameni; Baklouti, Emna; Masmoudi, Raja B; Rival, Alain; Drira, Noureddine; Panis, Bart

    2017-01-01

    Cryopreservation is the technology of choice not only for plant genetic resource preservation but also for virus eradication and for the efficient management of large-scale micropropagation. In this chapter, we describe three cryopreservation protocols (standard vitrification, droplet vitrification, and encapsulation vitrification) for date palm highly proliferating meristems that are initiated from vitro-cultures using plant growth regulator-free MS medium. The positive impact of sucrose preculture and cold hardening treatments on survival rates is significant. Regeneration rates obtained with standard vitrification, encapsulation-vitrification, and droplet-vitrification protocols can reach 30, 40, and 70%, respectively. All regenerated plants from non-cryopreserved or cryopreserved explants don't show morphological variation by maintaining genetic integrity without adverse effect of cryogenic treatment. Cryopreservation of date palm vitro-cultures enables commercial tissue culture laboratories to move to large-scale propagation from cryopreserved cell lines producing true-to-type plants after clonal field-testing trials. When comparing the cost of cryostorage and in-field conservation of date palm cultivars, tissue cryopreservation is the most cost-effective. Moreover, many of the risks linked to field conservation like erosion due to climatic, edaphic, and phytopathologic constraints are circumvented.

  9. Bullying Predicts Reported Dating Violence and Observed Qualities in Adolescent Dating Relationships.

    Science.gov (United States)

    Ellis, Wendy E; Wolfe, David A

    2015-10-01

    The relationship between reported bullying, reported dating violence, and dating relationship quality measured through couple observations was examined. Given past research demonstrating similarity between peer and dating contexts, we expected that bullying would predict negative dating experiences. Participants with dating experience (n = 585; 238 males, M(age) = 15.06) completed self-report assessments of bullying and dating violence perpetration and victimization. One month later, 44 opposite-sex dyads (M(age) = 15.19) participated in behavioral observations. In 10-min sessions, couples were asked to rank and discuss areas of relationship conflict while being video-recorded. Qualities of the relationship were later coded by trained observers. Regression analysis revealed that bullying positively predicted dating violence perpetration and victimization. Self-reported bullying also predicted observations of lower relationship support and higher withdrawal. Age and gender interactions further qualified these findings. The bullying of boys, but not girls, was significantly related to dating violence perpetration. Age interactions showed that bullying was positively predictive of dating violence perpetration and victimization for older, but not younger adolescents. Positive affect was also negatively predicted by bullying, but only for girls. These findings add to the growing body of evidence that adolescents carry forward strategies learned in the peer context to their dating relationships. © The Author(s) 2014.

  10. Effect of processing of dates into date juice concentrate and appraisal of its quality characteristics.

    Science.gov (United States)

    Kulkarni, S G; Vijayanand, P; Shubha, L

    2010-03-01

    Date palm (Phoenix dactylifera) is widely cultivated in Kutch district of Gujarat and the fruits are harvested at immature stage before the onset of monsoon to prevent spoilage. The immature date fruits with less commercial value were used for processing into date juice concentrate. Immature dates were crushed and treated with 0.1% pectinase enzyme for 120 min to obtain maximum juice. Date juice was found to be rich in reducing sugars (16.1%) and total sugars (18.3%). Juice was pasteurized at 85°C to inactivate the enzyme, cooled and centrifuged at 3000 rpm to get clear juice. The juice was concentrated in a thin film evaporator to a total soluble solids (TSS) of 76°Brix in 2 passes. Chemical composition of date juice during different stages of concentration was determined. Date juice concentrate was packed in low density polyethylene bags of size (22 cm × 14 cm) and frozen in blast freezer at -40°C and stored at -20°C. Storage of date juice concentrate at -20°C for 6 months indicated no significant changes in TSS, acidity, ascorbic acid, total sugars and pH. Hunter colour lightness L, and redness a values of date juice concentrate decreased whereas b values increased during storage. Date juice concentrate was stable during 6 months storage could be reconstituted for preparing ready-to-serve beverages with acceptable sensory quality.

  11. Date Attachable Offline Electronic Cash Scheme

    Directory of Open Access Journals (Sweden)

    Chun-I Fan

    2014-01-01

    Full Text Available Electronic cash (e-cash is definitely one of the most popular research topics in the e-commerce field. It is very important that e-cash be able to hold the anonymity and accuracy in order to preserve the privacy and rights of customers. There are two types of e-cash in general, which are online e-cash and offline e-cash. Both systems have their own pros and cons and they can be used to construct various applications. In this paper, we pioneer to propose a provably secure and efficient offline e-cash scheme with date attachability based on the blind signature technique, where expiration date and deposit date can be embedded in an e-cash simultaneously. With the help of expiration date, the bank can manage the huge database much more easily against unlimited growth, and the deposit date cannot be forged so that users are able to calculate the amount of interests they can receive in the future correctly. Furthermore, we offer security analysis and formal proofs for all essential properties of offline e-cash, which are anonymity control, unforgeability, conditional-traceability, and no-swindling.

  12. Date Attachable Offline Electronic Cash Scheme

    Science.gov (United States)

    Sun, Wei-Zhe; Hau, Hoi-Tung

    2014-01-01

    Electronic cash (e-cash) is definitely one of the most popular research topics in the e-commerce field. It is very important that e-cash be able to hold the anonymity and accuracy in order to preserve the privacy and rights of customers. There are two types of e-cash in general, which are online e-cash and offline e-cash. Both systems have their own pros and cons and they can be used to construct various applications. In this paper, we pioneer to propose a provably secure and efficient offline e-cash scheme with date attachability based on the blind signature technique, where expiration date and deposit date can be embedded in an e-cash simultaneously. With the help of expiration date, the bank can manage the huge database much more easily against unlimited growth, and the deposit date cannot be forged so that users are able to calculate the amount of interests they can receive in the future correctly. Furthermore, we offer security analysis and formal proofs for all essential properties of offline e-cash, which are anonymity control, unforgeability, conditional-traceability, and no-swindling. PMID:24982931

  13. Dating phylogenies with sequentially sampled tips.

    Science.gov (United States)

    Stadler, Tanja; Yang, Ziheng

    2013-09-01

    We develop a Bayesian Markov chain Monte Carlo (MCMC) algorithm for estimating divergence times using sequentially sampled molecular sequences. This type of data is commonly collected during viral epidemics and is sometimes available from different species in ancient DNA studies. We derive the distribution of ages of nodes in the tree under a birth-death-sequential-sampling (BDSS) model and use it as the prior for divergence times in the dating analysis. We implement the prior in the MCMCtree program in the PAML package for divergence dating. The BDSS prior is very flexible and, with different parameters, can generate trees of very different shapes, suitable for examining the sensitivity of posterior time estimates. We apply the method to a data set of SIV/HIV-2 genes in comparison with a likelihood-based dating method, and to a data set of influenza H1 genes from different hosts in comparison with the Bayesian program BEAST. We examined the impact of tree topology on time estimates and suggest that multifurcating consensus trees should be avoided in dating analysis. We found posterior time estimates for old nodes to be sensitive to the priors on times and rates and suggest that previous Bayesian dating studies may have produced overconfident estimates.

  14. Date attachable offline electronic cash scheme.

    Science.gov (United States)

    Fan, Chun-I; Sun, Wei-Zhe; Hau, Hoi-Tung

    2014-01-01

    Electronic cash (e-cash) is definitely one of the most popular research topics in the e-commerce field. It is very important that e-cash be able to hold the anonymity and accuracy in order to preserve the privacy and rights of customers. There are two types of e-cash in general, which are online e-cash and offline e-cash. Both systems have their own pros and cons and they can be used to construct various applications. In this paper, we pioneer to propose a provably secure and efficient offline e-cash scheme with date attachability based on the blind signature technique, where expiration date and deposit date can be embedded in an e-cash simultaneously. With the help of expiration date, the bank can manage the huge database much more easily against unlimited growth, and the deposit date cannot be forged so that users are able to calculate the amount of interests they can receive in the future correctly. Furthermore, we offer security analysis and formal proofs for all essential properties of offline e-cash, which are anonymity control, unforgeability, conditional-traceability, and no-swindling.

  15. Auspicious birth dates among Chinese in California.

    Science.gov (United States)

    Almond, Douglas; Chee, Christine Pal; Sviatschi, Maria Micaela; Zhong, Nan

    2015-07-01

    The number eight is considered lucky in Chinese culture, e.g. the Beijing Olympics began at 8:08 pm on 8/8/2008. Given the potential for discretion in selecting particular dates of labor induction or scheduled Cesarean section (C-section), we consider whether Chinese-American births in California occur disproportionately on the 8th, 18th, or 28th day of the month. We find 2.3% "too many" Chinese births on these auspicious birth dates, whereas Whites show no corresponding increase. The increase in Chinese births is driven by higher parity C-sections: the number of repeat C-sections is 6% "too high" on auspicious birth dates. Sons born to Chinese parents account for the entire increase; daughter deliveries do not seem to be timed to achieve "lucky" birth dates. We also find avoidance of repeat C-section deliveries on the 4th, 14th, and 24th of the month, considered unlucky in Chinese culture. Finally, we replicate earlier work finding that Friday the 13th delivery dates are avoided and document a particularly large decrease among Chinese. For Whites and Chinese in California, mothers with higher levels of education are particularly likely to avoid delivering on the 13th. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Emotion regulation moderates the association between empathy and prosocial behavior

    National Research Council Canada - National Science Library

    Lockwood, Patricia L; Seara-Cardoso, Ana; Viding, Essi

    2014-01-01

    .... However, studies to date have not simultaneously explored the associations between different empathic processes and prosocial behaviour, nor whether different types of emotion regulation strategies (e.g...

  17. TAK1 Regulates Cartilage and Joint Development via the MAPK and BMP Signaling Pathways

    Science.gov (United States)

    Gunnell, Lea M; Jonason, Jennifer H; Loiselle, Alayna E; Kohn, Anat; Schwarz, Edward M; Hilton, Matthew J; O'Keefe, Regis J

    2010-01-01

    The importance of canonical transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling during cartilage and joint development is well established, but the necessity for noncanonical (SMAD-independent) signaling during these processes is largely unknown. TGF-β activated kinase 1 (TAK1) is a MAP3K activated by TGF-β, BMP, and other mitogen-activated protein kinase (MAPK) signaling components. We set out to define the potential role for noncanonical, TAK1-mediated signaling in cartilage and joint development via deletion of Tak1 in chondrocytes (Col2Cre;Tak1f/f) and the developing limb mesenchyme (Prx1Cre;Tak1f/f). Deletion of Tak1 in chondrocytes resulted in novel embryonic developmental cartilage defects including decreased chondrocyte proliferation, reduced proliferating chondrocyte survival, delayed onset of hypertrophy, reduced Mmp13 expression, and a failure to maintain interzone cells of the elbow joint, which were not observed previously in another Col2Cre;Tak1f/f model. Deletion of Tak1 in limb mesenchyme resulted in widespread joint fusions likely owing to the differentiation of interzone cells to the chondrocyte lineage. The Prx1Cre;Tak1f/f model also allowed us to identify novel columnar chondrocyte organization and terminal maturation defects owing to the interplay between chondrocytes and the surrounding mesenchyme. Furthermore, both our in vivo models and in vitro cell culture studies demonstrate that loss of Tak1 results in impaired activation of the downstream MAPK target p38, as well as diminished activation of the BMP/SMAD signaling pathway. Taken together, these data demonstrate that TAK1 is a critical regulator of both MAPK and BMP signaling and is necessary for proper cartilage and joint development. © 2010 American Society for Bone and Mineral Research. PMID:20213696

  18. Direct and indirect regulation of spinal cord Ia afferent terminal formation by the γ-Protocadherins

    Directory of Open Access Journals (Sweden)

    Tuhina ePrasad

    2011-12-01

    Full Text Available The Pcdh-γ gene cluster encodes 22 protocadherin adhesion molecules that interact as homophilic multimers and critically regulate synaptogenesis and apoptosis of interneurons in the developing spinal cord. Unlike interneurons, the two primary components of the monosynaptic stretch reflex circuit, dorsal root ganglion sensory neurons and ventral motor neurons, do not undergo excessive apoptosis in Pcdh-γdel/del null mutants, which die shortly after birth. However, as we show here, mutants exhibit severely disorganized Ia proprioceptive afferent terminals in the ventral horn. In contrast to the fine net-like pattern observed in wild-type mice, central Ia terminals in Pcdh-γ mutants are expanded, clumped, and fill the space between individual motor neurons; quantitative analysis shows a ~2.5 fold increase in the area of terminals. Concomitant with this, there is a 70% loss of the collaterals that Ia afferents extend to ventral interneurons, many of which undergo apoptosis in the mutants. The Ia afferent phenotype is ameliorated, though not entirely rescued, when apoptosis is blocked in Pcdh-γ null mice by introduction of a Bax null allele. This indicates that loss of ventral interneurons, which act as intermediate Ia afferent targets, contributes to the disorganization of terminals on motor pools. Restricted mutation of the Pcdh-γ cluster using conditional mutants and multiple Cre transgenic lines (Wnt1-Cre for sensory neurons; Pax2-Cre for ventral interneurons; Hb9-Cre for motor neurons also revealed a direct requirement for the γ-Pcdhs in Ia neurons and ventral interneurons, but not in motor neurons themselves. Together, these genetic manipulations indicate that the γ-Pcdhs are required for the formation of the Ia afferent circuit in two ways: First, they control the survival of ventral interneurons that act as intermediate Ia targets; and second, they provide a homophilic molecular cue between Ia afferents and target ventral interneurons.

  19. Optically stimulated luminescence dating of rock surfaces

    DEFF Research Database (Denmark)

    Sohbati, Reza

    There are many examples of rock surfaces, rock art and stone structures whose ages are of great importance to the understanding of various phenomena in geology, climatology and archaeology. Optically stimulated luminescence (OSL) dating is a well-established chronological tool that has successfully...... determined the depositional age of a wide variety of fine-grained sediments, from several years to several hundred thousands of years. However, there is no routine OSL dating method applicable to larger clasts such as cobbles, boulders and other rock surfaces. Here the application of quartz OSL to the dating...... of rock surfaces is successfully tested by application to two different quartz-rich rock types (sandstone and quartzite). Together with the measurement of infrared stimulated luminescence (IRSL) signals as a function of depth into the surface of different granites it is clear that both OSL and IRSL can...

  20. Fixing Images Observation Dates Thanks to Asteroids

    Science.gov (United States)

    Derriere, S.

    2015-09-01

    An important piece of metadata for any astronomical image is the date and time at which it was observed (and the exposure time). Unfortunately, the values of the observation epoch found in the FITS headers of digitized photographic plates, for example, are not always accurate. There can be many different sources of error: mistakes in the original observation log, errors when converting between different dates and time format (calendar date, Julian days, decimal years, etc.). We present in this paper an analysis of the different values that can be found for the observation epoch of several image sets in various metadata sources. We show how the presence of known asteroids in the field of view can be used to recover the correct time values with a good accuracy.

  1. Carbon Catabolite Repression Regulates the Production of the Unique Volatile Sodorifen of Serratia plymuthica 4Rx13

    Directory of Open Access Journals (Sweden)

    Nancy Magnus

    2017-12-01

    Full Text Available Microorganisms are capable of synthesizing a plethora of secondary metabolites including the long-overlooked volatile organic compounds. Little knowledge has been accumulated regarding the regulation of the biosynthesis of such mVOCs. The emission of the unique compound sodorifen of Serratia plymuthica isolates was significantly reduced in minimal medium with glucose, while succinate elevated sodorifen release. The hypothesis of carbon catabolite repression (CCR acting as a major control entity on the synthesis of mVOCs was proven by genetic evidence. Central components of the typical CCR of Gram-negative bacteria such as the adenylate cyclase (CYA, the cAMP binding receptor protein (CRP, and the catabolite responsive element (CRE were removed by insertional mutagenesis. CYA, CRP, CRE1 mutants revealed a lower sodorifen release. Moreover, the emission potential of other S. plymuthica isolates was also evaluated.

  2. Dating Petroglyphs from Fugoppe Cave, Japan

    Directory of Open Access Journals (Sweden)

    Masaru Ogawa

    2014-01-01

    Full Text Available For over 20 years, I have tried to establish a relative date for petroglyphs in Fugoppe Cave, Japan. Unsuspected amidst debris accumulating from about 1300 years ago, the petroglyphs were rediscovered accidentally in 1950. From an analysis of petroglyphs on fallen rocks scattered randomly on the site floor, I argue that the artworks date from ca.1900 years ago. The cave itself, formed by wave action, saw its main occupation by pottery-making people from 1700–1500 years ago; although the petroglyphs on the rock walls predated their occupation, it seems unlikely that the occupants attached any meaning to them.

  3. The freshwater reservoir effect in radiocarbon dating

    DEFF Research Database (Denmark)

    Philippsen, Bente

    2013-01-01

    effect on radiocarbon dating in an estuarine environment is examined. Here, freshwater influence causes reservoir ages to vary between 250 and 700 14C years during the period 5400 BC - AD 700. The examples in this study show clearly that the freshwater reservoir effect can seriously corrupt radiocarbon...... for radiocarbon dating of Mesolithic pottery from inland sites of the Ertebølle culture in Northern Germany. The surprisingly old ages of the earliest pottery most probably are caused by a freshwater reservoir effect. In a sediment core from the Limfjord, northern Denmark, the impact of the freshwater reservoir...

  4. Bilzingsleben archaeological site: new dating evidence

    Energy Technology Data Exchange (ETDEWEB)

    Schwarcz, H.P.; Gruen, R.; Latham, A.G.; Mania, D.; Brunnacker, K.

    1988-02-01

    New absolute dates have been obtained for the Bilzingsleben (D.D.R.) archaeological site, using uranium-series analyses of travertine, and electron spin resonance (ESR) analyses of travertine and tooth enamel of rhinoceros. The results indicate that the site was apparently occupied during interglacial isotope stages 9 or 11. The surrounding terrain has been subsequently dissected by at least three discrete stages of fluvial erosion during succeeding glacial stages. Bilzingsleben is thus shown to be significantly older than the Lower Travertine at the nearby site of Ehringsdorf, assigned to isotope stage 7 by uranium-series dating. The latter assignment is confirmed by new ESR data presented here.

  5. Computational Age Dating of Special Nuclear Materials

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2012-06-30

    This slide-show presented an overview of the Constrained Progressive Reversal (CPR) method for computing decays, age dating, and spoof detecting. The CPR method is: Capable of temporal profiling a SNM sample; Precise (compared with known decay code, such a ORIGEN); Easy (for computer implementation and analysis). We have illustrated with real SNM data using CPR for age dating and spoof detection. If SNM is pure, may use CPR to derive its age. If SNM is mixed, CPR will indicate that it is mixed or spoofed.

  6. Regulation of Blood Pressure, Appetite, and Glucose by Leptin After Inactivation of Insulin Receptor Substrate 2 Signaling in the Entire Brain or in Proopiomelanocortin Neurons.

    Science.gov (United States)

    do Carmo, Jussara M; da Silva, Alexandre A; Wang, Zhen; Freeman, Nathan J; Alsheik, Ammar J; Adi, Ahmad; Hall, John E

    2016-02-01

    Insulin receptor substrate 2 (IRS2) is one of the 3 major leptin receptor signaling pathways, but its role in mediating the chronic effects of leptin on blood pressure, food intake, and glucose regulation is unclear. We tested whether genetic inactivation of IRS2 in the entire brain (IRS2/Nestin-cre mice) or specifically in proopiomelanocortin (POMC) neurons (IRS2/POMC-cre mice) attenuates the chronic cardiovascular, metabolic, and antidiabetic effects of leptin. Mice were instrumented with telemetry probes for measurement of blood pressure and heart rate and with venous catheters for intravenous infusions. After a 5-day control period, mice received leptin infusion (2 μg/kg per minute) for 7 days. Compared with control IRS2(flox/flox) mice, IRS2/POMC-cre mice had similar body weight and food intake (33±1 versus 35±1 g and 3.6±0.5 versus 3.8±0.2 g per day) but higher mean arterial pressure (MAP) and heart rate (110±2 versus 102±2 mm Hg and 641±9 versus 616±5 bpm). IRS2/Nestin-cre mice were heavier (38±2 g), slightly hyperphagic (4.5±1.0 g per day), and had higher MAP and heart rate (108±2 mm Hg and 659±9 bpm) compared with control mice. Leptin infusion gradually increased MAP despite decreasing food intake by 31% in IRS2(flox/flox) and in Nestin-cre control mice. In contrast, leptin infusion did not change MAP in IRS2/Nestin-cre or IRS2/POMC-cre mice. The anorexic and antidiabetic effects of leptin, however, were similar in all 3 groups. These results indicate that IRS2 signaling in the central nervous system, and particularly in POMC neurons, is essential for the chronic actions of leptin to raise MAP but not for its anorexic or antidiabetic effects. © 2015 American Heart Association, Inc.

  7. 46 CFR 160.066-10 - Expiration date.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Expiration date. 160.066-10 Section 160.066-10 Shipping....066-10 Expiration date. Each approved signal must have an expiration date marked on it. That date must not be more than forty-two months from date of manufacture. ...

  8. 38 CFR 21.4131 - Commencing dates.

    Science.gov (United States)

    2010-07-01

    ... jail. (Authority: 38 U.S.C. 3482(g), 3532(e)) (i) Fugitive felons. An award of educational assistance... arrest of the felon is cleared by— (1) Arrest; (2) Surrendering to the issuing authority; (3) Dismissal; or (4) Court documents (dated after the warrant for the arrest of the felon) showing the individual...

  9. 16 CFR 602.1 - Effective dates.

    Science.gov (United States)

    2010-01-01

    ... Commercial Practices FEDERAL TRADE COMMISSION THE FAIR CREDIT REPORTING ACT FAIR AND ACCURATE CREDIT TRANSACTIONS ACT OF 2003 § 602.1 Effective dates. (a)-(b) (c) The applicable provisions of the Fair and... implement the applicable provision of the FACT Act or the applicable provision of the Fair Credit Reporting...

  10. 21 CFR 211.137 - Expiration dating.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Expiration dating. 211.137 Section 211.137 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Packaging and Labeling Control...

  11. The False Security of Blind Dates

    Science.gov (United States)

    Cimino, J.J.

    2012-01-01

    Background The reuse of clinical data for research purposes requires methods for the protection of personal privacy. One general approach is the removal of personal identifiers from the data. A frequent part of this anonymization process is the removal of times and dates, which we refer to as “chrononymization.” While this step can make the association with identified data (such as public information or a small sample of patient information) more difficult, it comes at a cost to the usefulness of the data for research. Objectives We sought to determine whether removal of dates from common laboratory test panels offers any advantage in protecting such data from re-identification. Methods We obtained a set of results for 5.9 million laboratory panels from the National Institutes of Health’s (NIH) Biomedical Translational Research Information System (BTRIS), selected a random set of 20,000 panels from the larger source sets, and then identified all matches between the sets. Results We found that while removal of dates could hinder the re-identification of a single test result, such removal had almost no effect when entire panels were used. Conclusions Our results suggest that reliance on chrononymization provides a false sense of security for the protection of laboratory test results. As a result of this study, the NIH has chosen to rely on policy solutions, such as strong data use agreements, rather than removal of dates when reusing clinical data for research purposes. PMID:23646086

  12. 38 CFR 21.9635 - Discontinuance dates.

    Science.gov (United States)

    2010-07-01

    ... study, and the course loses its accreditation (or the institution of higher learning offering the course...) VOCATIONAL REHABILITATION AND EDUCATION Post-9/11 GI Bill Payments-Educational Assistance § 21.9635... be the last date of the period covered by the lump sum payment. (2) If the institution of higher...

  13. Dating violence among gay men in China.

    Science.gov (United States)

    Yu, Yong; Xiao, Shuiyuan; Liu, Kirin Qilin

    2013-08-01

    This is the first study on the prevalence of dating violence and threats of being forced to "come out of the closet" among Chinese gay men. Data on social demographic information and the experience of dating violence, including types of abuse, threats of "outing," and the gender of abusers were collected from 418 gay men and 330 heterosexual men by self-administered questionnaires. Mann-Whitney U test, χ(2) test, and multivariate logistic regression analyses were used to test group differences. Up to 32.8% of the gay men had experienced one abuse or more. Among those experiencing abuse, 83.9% of the gay men never told anyone about their abuse. The experience of any form of abuse by gay men was 5.07 times higher than the rate of abuse among heterosexual men controlling for age in logistic regression models. In addition, 12.4% of the gay men have experienced the threat of being outed. Overall, dating violence is more prevalent in gay men than in heterosexuals. Efforts to prevent dating violence, especially among gay men, should be made in China.

  14. Dating experiences of bullies in early adolescence.

    Science.gov (United States)

    Connolly, J; Pepler, D; Craig, W; Taradash, A

    2000-11-01

    In this study, 196 young adolescents who reported that they bullied their peers were identified out of a sample of 1,758 students in Grades 5 through 8. After selecting from the total sample a group of nonbullying youth who were matched on gender, school, and grade, a comparison was made of the groups' dating experiences, quality of friend and boyfriend or girlfriend relationships, and acts of physical and social aggression. The results indicated that bullies started dating earlier and engaged in more advanced dyadic dating than comparison adolescents. Bullies were highly relationship oriented, yet their views of their friends and boyfriends or girlfriends were less positive and less equitable than the comparison adolescents. Finally, bullies were more likely to report physical and social aggression with their boyfriends or girlfriends. Although the bullies reported more advanced pubertal development, this factor did not fully account for their dating precocity and negative romantic relationships. The results confirmed our hypotheses that adolescents whose peer relationships are characterized by bullying are at risk in their development of healthy romantic relationships.

  15. ESR dating of the fault rocks

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hee Kwon [Kangwon National Univ., Chuncheon (Korea, Republic of)

    2004-01-15

    Past movement on faults can be dated by measurement of the intensity of ESR signals in quartz. These signals are reset by local lattice deformation and local frictional heating on grain contacts at the time of fault movement. The ESR signals then grow back as a result of bombardment by ionizing radiation from surrounding rocks. The age is obtained from the ratio of the equivalent dose, needed to produce the observed signal, to the dose rate. Fine grains are more completely reset during faulting, and a plot of age vs, grain size shows a plateau for grains below critical size : these grains are presumed to have been completely zeroed by the last fault activity. We carried out ESR dating of fault rocks collected near the Ulzin nuclear reactor. ESR signals of quartz grains separated from fault rocks collected from the E-W trend fault are saturated. This indicates that the last movement of these faults had occurred before the quaternary period. ESR dates from the NW trend faults range from 300ka to 700ka. On the other hand, ESR date of the NS trend fault is about 50ka. Results of this research suggest that long-term cyclic fault activity near the Ulzin nuclear reactor continued into the pleistocene.

  16. ESTIMATION OF PLANTING DATES FOR ROSELLE (HIBISCUS ...

    African Journals Online (AJOL)

    thinkexploitsint'l

    2011-06-11

    Jun 11, 2011 ... colourings have continued to attract the attention of food and beverages manufacturers, and ... In spite of these medicinal and food values, roselle cultivation is limited in .... While the planting dates Significantly influenced the number of branches produced per roselle plant at 8, 12 and 16 WAP, the effects of.

  17. Radiocarbon dating of ancient rock paintings

    Energy Technology Data Exchange (ETDEWEB)

    Ilger, W.A.; Hyman, M.; Rowe, M.W. [Texas A and M Univ., College Station, TX (United States). Dept. of Chemistry; Southon, J. [Lawrence Livermore National Lab., CA (United States)

    1995-06-20

    This report presents progress made on a technique for {sup 14}C dating pictographs. A low-temperature oxygen plasma is used coupled with high-vacuum technologies to selectively remove C-containing material in the paints without contamination from inorganic carbon from rock substrates or accretions.

  18. Practice Dating Program for University Students

    Science.gov (United States)

    Hutchinson, Gail E.

    1978-01-01

    Upon attending university, students often leave behind the parents and close friends who have provided emotional support and now face large classes and grade competition. Dating is one way students can help to overcome social and emotional isolation. The author discusses some of the work with college student nondating. (Author/JEL)

  19. Dating Violence among High School Students.

    Science.gov (United States)

    Bergman, Libby

    1992-01-01

    Surveyed students (n=631) from rural, suburban, and inner-city high schools regarding sexual, physical, and verbal dating violence. Proportion of females reporting sexual violence was 15.5%; proportion reporting physical violence was same. Proportion of males reporting violence was lower. Significant correlates of violence included dating…

  20. Historical Analysis of College Campus Interracial Dating

    Science.gov (United States)

    Firmin, Michael W.; Firebaugh, Stephanie

    2008-01-01

    Interracial dating on American campuses has had a relatively stormy past. Until the past three decades or so, it was outlawed in some states. Southern institutions, in particular, such as the infamous Bob Jones University have made this issue divisive even among their own constituencies. Age and generation seem to be cogent factors with younger…

  1. 45 CFR 1306.2 - Effective dates.

    Science.gov (United States)

    2010-10-01

    ... 1, 1995, at which time they must comply with the three and one-half hour minimum class time..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START PROGRAM HEAD START STAFFING REQUIREMENTS AND PROGRAM OPTIONS General § 1306.2 Effective dates. (a) Except...

  2. 40 CFR 141.6 - Effective dates.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Effective dates. 141.6 Section 141.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL... measuring dalapon, dinoseb, diquat, endothall, endrin, glyphosate, oxamyl, picloram, simazine, benzo(a...

  3. Physical Dating Aggression Growth during Adolescence

    Science.gov (United States)

    Nocentini, Annalaura; Menesini, Ersilia; Pastorelli, Concetta

    2010-01-01

    The development of Physical Dating Aggression from the age of 16 to 18 years was investigated in relation to time-invariant predictors (gender, parental education, family composition, number of partners) and to time-varying effects of delinquent behavior and perception of victimization by the partner. The sample consisted of 181 adolescents with a…

  4. The unexpected truth about dates and hypoglycemia.

    Science.gov (United States)

    Yasawy, Mohammed I

    2016-01-01

    Dates are a concentrated source of essential nutrients, vitamins, minerals, and carbohydrates (CHOs), which are necessary for the maintenance of optimum health. Most of the CHOs in dates come from sugars including glucose and fructose. Dates are commonly consumed in Saudi Arabia, particularly at the time of breaking the fast to provide instant energy and maintain blood sugar level. However, dates may cause hypoglycemia in a rare condition named as heredity fructose intolerance (HFI), and a few families have been to see us with a history of that nature. This is to report the preliminary results of an on-going study of a group of patients who get symptoms of hypoglycemia following the ingestion of dates and have suffered for years without an accurate diagnosis. This report is based on three patients, from the same family, living in a date growing region of the Kingdom of Saudi Arabia (KSA). The patients had been to several medical centers without getting any definite answers or diagnosis until they were referred to the Gastroenterology Clinic of King Fahd Hospital of the University, Al-Khobar, KSA. The data were obtained by careful history and laboratory investigations, and a final diagnosis of HFI made on fructose intolerance test (FIT). The patients reported that they had avoided eating dates because of various symptoms, such as bloating, nausea, and even hypoglycemia when larger amounts were consumed. Their other symptoms included sleepiness, sweating, and shivering. After full examinations and necessary laboratory tests based on the above symptoms, FIT was performed and the patients were diagnosed with HFI. They were referred to a dietitian who advised a fructose-free diet. They felt well and were free of symptoms. HFI may remain undiagnosed until adulthood and may lead to disastrous complications and even death. The diagnosis can only be suspected after a careful dietary history is taken supported by FIT. This can prevent serious complications. Restricting

  5. The unexpected truth about dates and hypoglycemia

    Directory of Open Access Journals (Sweden)

    Mohammed I Yasawy

    2016-01-01

    Full Text Available Background: Dates are a concentrated source of essential nutrients, vitamins, minerals, and carbohydrates (CHOs, which are necessary for the maintenance of optimum health. Most of the CHOs in dates come from sugars including glucose and fructose. Dates are commonly consumed in Saudi Arabia, particularly at the time of breaking the fast to provide instant energy and maintain blood sugar level. However, dates may cause hypoglycemia in a rare condition named as heredity fructose intolerance (HFI, and a few families have been to see us with a history of that nature. This is to report the preliminary results of an on-going study of a group of patients who get symptoms of hypoglycemia following the ingestion of dates and have suffered for years without an accurate diagnosis. Methodology: This report is based on three patients, from the same family, living in a date growing region of the Kingdom of Saudi Arabia (KSA. The patients had been to several medical centers without getting any definite answers or diagnosis until they were referred to the Gastroenterology Clinic of King Fahd Hospital of the University, Al-Khobar, KSA. The data were obtained by careful history and laboratory investigations, and a final diagnosis of HFI made on fructose intolerance test (FIT. Results: The patients reported that they had avoided eating dates because of various symptoms, such as bloating, nausea, and even hypoglycemia when larger amounts were consumed. Their other symptoms included sleepiness, sweating, and shivering. After full examinations and necessary laboratory tests based on the above symptoms, FIT was performed and the patients were diagnosed with HFI. They were referred to a dietitian who advised a fructose-free diet. They felt well and were free of symptoms. Conclusion: HFI may remain undiagnosed until adulthood and may lead to disastrous complications and even death. The diagnosis can only be suspected after a careful dietary history is taken supported by

  6. Up-Dating: Ratings of Perceived Dating Success Are Better Online than Offline.

    Science.gov (United States)

    Fullwood, Chris; Attrill-Smith, Alison

    2017-06-28

    The primary aims of this study were to test whether perceived dating success would differ between offline and online zero-acquaintance dating contexts and to investigate the role that self-esteem might play in these evaluations. Participants were presented with the same photos of targets in either an offline or online dating scenario and rated their chances of dating success along with their perceptions of how attractive they thought the target would consider them. Higher self-esteem individuals believed they would be rated as more attractive. There was an overall perception that, irrespective of self-esteem level, meeting online would lead to better chances of dating success. These findings are considered in relation to an increased ability to more precisely manage impressions and develop an image of the self which would be evaluated more positively online.

  7. Internet dating as a project: the commodification and rationalisation of online dating

    Directory of Open Access Journals (Sweden)

    Tjaša Žakelj

    2015-04-01

    Full Text Available Based on qualitative empirical data from two studies on Internet dating in Slovenia, this paper discusses the social contexts of the Internet dating of heterosexual men and women and homosexual men. Special attention is given to different aspects of the commodification and rationalisation of dating in the process of forming potential (romantic partnerships. First, we discuss our respondents’ reasons for using the Internet to get in touch with potential (romantic partners. Second, we focus on the demands and strategies of targeted market- ing in personal profile writing and, finally, on the process of selecting potential partners. Our study shows that the primary understanding of Internet dating among people who engage in it is its economic nature. Together with targeted marketing and the predeter- mined criteria for choosing interesting others, Internet dating can thus be understood as a market that encourages rationalisation and commodification in the process of forming intimate relationships.

  8. Witnessing Interparental Violence and Acceptance of Dating Violence as Predictors for Teen Dating Violence Victimization.

    Science.gov (United States)

    Karlsson, Marie E; Temple, Jeff R; Weston, Rebecca; Le, Vi Donna

    2016-04-01

    We examined the association between witnessing interparental violence, attitudes about dating violence, and physical and psychological teen dating violence (TDV) victimization. Participants were 918 teens with dating experience. Witnessing interparental violence and acceptance of dating violence were significant predictors of TDV victimization. Acceptance of dating violence was also a partial mediator between witnessing interparental violence and TDV victimization. Witnessing mother-to-father violence and acceptance of female-perpetrated violence were the most consistent predictors. TDV programs aiming to prevent victimization could benefit from targeting youth exposed to father-to-mother and mother-to-father violence, targeting attitudes about violence, and tailoring interventions to gender-specific risk factors. © The Author(s) 2015.

  9. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

  10. Optically stimulated luminescence dating at Rose Cottage Cave

    CSIR Research Space (South Africa)

    Pienaar, M

    2008-01-01

    Full Text Available Six Optically stimulated luminescence (OSL) dates are compared with stratigraphically associated C-14 dates from Rose Cottage Cave. The OSL dates overlap the accepted C-14 chronology except for one sample that overestimates the expected age...

  11. Retinoic acid signalling in thymocytes regulates T cell development

    DEFF Research Database (Denmark)

    Wendland, Kerstin; Sitnik, Katarzyna Maria; Kotarsky, Knut

    The Vitamin A derivative retinoic acid (RA) has emerged as an important regulator of peripheral T cell responses. However, whether there is endogenous retinoic acid receptor (RAR) signaling in developing thymocytes and the potential impact of such signals in thymocyte development remains unclear...... further enhanced in recently generated CD69+ CD4+ SP cells. To address the potential biological significance of RA signaling in developing thymocytes, we evaluated T cell development in CD4Cre-dnRAR mice, where RA signaling is blocked in thymocytes from the CD4+CD8+ double positive (DP) stage onwards due...... of this cell subset. Collectively, our data suggest a direct role for RA signaling in regulating thymocyte homeostasis and T cell development....

  12. 40 CFR 72.69 - Issuance and effective date of acid rain permits.

    Science.gov (United States)

    2010-07-01

    ...) AIR PROGRAMS (CONTINUED) PERMITS REGULATION Federal Acid Rain Permit Issuance Procedures § 72.69 Issuance and effective date of acid rain permits. (a) After the close of the public comment period, the Administrator will issue or deny an Acid Rain permit. The Administrator will serve a copy of any Acid Rain...

  13. 77 FR 75780 - Nondisplacement of Qualified Workers Under Service Contracts; Effective Date

    Science.gov (United States)

    2012-12-21

    ... after the effective date of regulations issued by the Federal Acquisition Regulatory Council (FARC) to... (FARC Final Rule). The Department of Labor Final Rule provided that it would not be effective until the FARC issued the FARC Final Rule, and that as a result, the Department of Labor would publish a notice...

  14. PTEN regulates lung endodermal morphogenesis through MEK/ERK pathway.

    Science.gov (United States)

    Xing, Yiming; Wang, Runming; Li, Changgong; Minoo, Parviz

    2015-12-01

    Pten is a multifunctional tumor suppressor. Deletions and mutations in the Pten gene have been associated with multiple forms of human cancers. Pten is a central regulator of several signaling pathways that influences multiple cellular functions. One such function is in cell motility and migration, although the precise mechanism remains unknown. In this study, we deleted Pten in the embryonic lung epithelium using Gata5-cre mice. Absence of Pten blocked branching morphogenesis and ERK and AKT phosphorylation at E12.5. In an explant model, Pten(Δ/Δ) mesenchyme-free embryonic lung endoderm failed to branch. Inhibition of budding in Pten(Δ/Δ) explants was associated with major changes in cell migration, while cell proliferation was not affected. We further examined the role of ERK and AKT in branching morphogenesis by conditional, endodermal-specific mutants which blocked ERK or AKT phosphorylation. MEK(DM/+); Gata5-cre (blocking of ERK phosphorylation) lung showed more severe phenotype in branching morphogenesis. The inhibition of budding was also associated with disruption of cell migration. Thus, the mechanisms by which Pten is required for early endodermal morphogenesis may involve ERK, but not AKT, mediated cell migration. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Notch Regulates Macrophage-Mediated Inflammation in Diabetic Wound Healing

    Directory of Open Access Journals (Sweden)

    Andrew S. Kimball

    2017-06-01

    Full Text Available Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect (DNMAMLfloxedLyz2Cre+ demonstrated delayed early healing (days 1–3 and wound macrophages had decreased inflammatory gene expression. In our physiologic murine model of type 2 diabetes (T2D, Notch receptor expression was significantly increased in wound macrophages on day 6, following the initial inflammatory phase of wound healing, corresponding to increased inflammatory cytokine expression. This increase in Notch1 and Notch2 was also observed in human monocytes from patients with T2D. Further, in prediabetic mice with a genetic Notch signaling defect (DNMAMLfloxedLyz2Cre+ on a high-fat diet, improved wound healing was seen at late time points (days 6–7. These findings suggest that Notch is critical for the early inflammatory phase of wound healing and directs production of macrophage-dependent inflammatory mediators. These results identify that canonical Notch signaling is important in directing macrophage function in wound repair and define a translational target for the treatment of non-healing diabetic wounds.

  16. Regulators of G protein signaling 12 promotes osteoclastogenesis in bone remodeling and pathological bone loss.

    Science.gov (United States)

    Yuan, X; Cao, J; Liu, T; Li, Y-P; Scannapieco, F; He, X; Oursler, M J; Zhang, X; Vacher, J; Li, C; Olson, D; Yang, S

    2015-12-01

    Regulators of G protein signaling (Rgs) have pivotal roles in controlling various cellular processes, such as cell differentiation. How Rgs proteins regulate osteoclast (OC) differentiation, function and bone homeostasis is poorly understood. It was previously demonstrated that Rgs12, the largest protein in the Rgs family, is predominantly expressed in OCs and regulates OC differentiation in vitro. To further understand the role and mechanism of Rgs12 in OC differentiation and bone diseases in vivo, we created OC-targeted Rgs12 knockout mice by using inducible Mx1-Cre and CD11b-Cre. Deletion of Rgs12 in hematopoietic cells or specifically in OC precursors resulted in increased bone mass with decreased OC numbers. Loss of Rgs12 impaired OC differentiation and function with impaired Ca(2+) oscillations and reduced nuclear factor of activated T cells (NFAT) 2 expression. The introduction of wild-type osteoblasts did not rescue the defective osteoclastogenesis. Ectopic expression of NFAT2 rescued defective OC differentiation in CD11b;Rgs12(fl/fl) cells and promoted normal OC differentiation. Moreover, deletion of Rgs12 significantly inhibited pathological osteoclastogenesis and bone destruction in Rgs12-deficient mice that were subjected to ovariectomy and lipodysaccharide for bone loss. Thus our findings demonstrate that Rgs12 is an important regulator in OC differentiation and function and identify Rgs12 as a potential therapeutic target for osteoporosis and inflammation-induced bone loss.

  17. DNMT1 is a Required Genomic Regulator for Murine Liver Histogenesis and Regeneration

    DEFF Research Database (Denmark)

    Kaji, Kosuke; Factor, Valentina M; Andersen, Jesper B

    2016-01-01

    DNA methyltransferase 1 (DNMT1) is an essential regulator maintaining both epigenetic reprogramming during DNA replication and genome stability. We investigated the role of DNMT1 in the regulation of postnatal liver histogenesis under homeostasis and stress conditions. We generated Dnmt1 conditio......DNA methyltransferase 1 (DNMT1) is an essential regulator maintaining both epigenetic reprogramming during DNA replication and genome stability. We investigated the role of DNMT1 in the regulation of postnatal liver histogenesis under homeostasis and stress conditions. We generated Dnmt1...... hepatocytes caused global hypomethylation, enhanced DNA damage response and initiated a senescence state causing a progressive inability to maintain tissue homeostasis and proliferate in response to injury. The liver regenerated via activation and repopulation from progenitors due to lineage......-dependent differences in Alb-Cre expression, providing a basis for selection of less mature and therefore less damaged HPC progeny. Consistently, an efficient knockdown of Dnmt1 in cultured HPCs caused severe DNA damage, cell cycle arrest, senescence and cell death. Mx1-Cre-driven deletion of Dnmt1 in adult quiescent...

  18. The freshwater reservoir effect in radiocarbon dating

    DEFF Research Database (Denmark)

    Philippsen, Bente

    case studies will show the degree of variability of the freshwater reservoir effect over short and long timescales. Radiocarbon dating of recent water samples, aquatic plants and animals, shows that age differences of up to 2000 years can occur within one river. In the Limfjord, freshwater influence......The freshwater reservoir effect can result in too high radiocarbon ages of samples from lakes and rivers, including the bones of people whose subsistence was based on freshwater fish, and pottery in which fish was cooked. In my talk, I will explain the causes and consequences of this effect. Two...... caused reservoir ages to vary between 250 and 700 years during the period 5400 BC - AD 700. Finally, I will discuss the implications of the freshwater reservoir effect for radiocarbon dating of Mesolithic pottery from inland sites of the Ertebølle culture in Northern Germany....

  19. Radiocarbon dating prehistoric pottery from Northern Europe

    DEFF Research Database (Denmark)

    Philippsen, Bente; Craig, Oliver; Heron, Carl

    2012-01-01

    ” (charred deposits from the outer side of sherds), plant remains from inside the clay matrix, and lipids extracted from the ceramic matrix. All of these are potentially problematic media for AMS dating: ‘Foodcrusts’ and absorbed lipids can appear too old because of the marine or freshwater reservoir effect....... These are hunter/fisher/gatherer sites located in coastal or riverine setting and correspond to some of the earliest pottery bearing sites in this region. We have chosen to radiocarbon date different fractions on the pottery including “foodcrusts” (charred deposits from the inner surface of sherds), “soot......, such as when aquatic products have been prepared in the pottery. Soot can derive from old wood that was used for the hearth fire, or from (potentially aquatic) food that boiled over. Plant remains may have been present in the clay for a long time before manufacture of the pottery. Post-depositional...

  20. Should precise numerical dating overrule glacial geomorphology?

    Science.gov (United States)

    Winkler, Stefan

    2016-04-01

    Numerical age dating techniques, namely different types of terrestrial cosmogenic nuclide dating (TCND), have achieved an impressive progress in both laboratory precision and regional calibration models during the past few decades. It is now possible to apply precise TCND even to young landforms like Late Holocene moraines, a task seemed hardly achievable just about 15 years ago. An increasing number of studies provide very precise TCND ages for boulders from Late Holocene moraines enabling related reconstruction of glacier chronologies and the interpretation of these glacial landforms in a palaeoclimatological context. These studies may also solve previous controversies about different ages assigned to moraines obtained by different dating techniques, for example relative-age dating techniques or techniques combining relative-age dating with few fixed points derived from numerical age dating. There are a few cases, for example Mueller Glacier and nearby long debris-covered valley glacier in Aoraki/Mt.Cook National Park (Southern Alps, New Zealand), where the apparent "supremacy" of TCND-ages seem to overrule glacial geomorphological principles. Enabled by a comparatively high number of individual boulders precisely dated by TCND, moraine ridges on those glacier forelands have been primarily clustered on basis of these boulder ages rather than on their corresponding morphological position. To the extreme, segments of a particular moraine complex morphologically and sedimentologically proven to be formed during one event have become split and classified as two separate "moraines" on different parts of the glacier foreland. One ledge of another moraine complex contains 2 TCND-sampled boulders apparently representing two separate "moraines"-clusters of an age difference in the order of 1,500 years. Although recently criticism has been raised regarding the non-contested application of the arithmetic mean for calculation of TCND-ages for individual moraines, this

  1. AGAR PENULISAN RESEP TETAP UP TO DATE

    Directory of Open Access Journals (Sweden)

    Rahmatini Rahmatini

    2009-09-01

    Full Text Available AbstrakResep adalah suatu permintaan tertulis dari dokter, dokter gigi atau dokter hewan kepada apoteker untuk membuatkan obat dalam bentuk sediaan tertentu dan menyerahkannya kepada pasien. Resep merupakan perwujudan akhir dari kompetensi, pengetahuan dan keahlian dokter dalam menerapkan pengetahuannya dalam bidang farmakologi dan terapi.Penulisan resep harus ditulis dengan jelas sehingga dapat dibaca oleh petugas di apotek. Resep yang ditulis dengan tidak jelas akan menimbulkan terjadinya kesalahan saat peracikan / penyiapan obat dan penggunaan obat yang diresepkan.Ilmu pengetahuan tentang obat selalu berubah, obat – obat baru selalu muncul di pasaran.Secara umum, seorang dokter harus mengikuti perkembangan dalam terapi obat. Bila muncul efek samping akibat obat yang seharusnya diketahui dan dapat dicegah oleh dokter, maka dokter akan berhadapan dengan hukum.Agar penulisan resep tetap up to date, seorang dokter harus mengumpulkan berbagai informasi yang tersedia. Sumber informasi yang dapat digunakan adalah : Buku acuan, Kompendium obat, Daftar Obat Esensial Nasional (DOEN dan Pedoman terapi, Buletin obat, Jurnal Kedokteran, Pusat informasi obat,Informasi melalui komputer, Sumber informasi dari industri farmasi, dan informasi lisan.Bandingkan kelebihan dan kekurangan berbagai sumber informasi. Tugas seorang dokter adalah melakukan cara terbaik untuk tetap up to date dengan mendaftar sumber informasi yang dapat dimanfaatkan. Carilah sedikitnya satu dari yang berikut ini : (1 jurnal kedokteran: (2 buletin obat; (3 buku acuan farmakologi atau acuan klinis; (4 komisi terapi maupun konsultan, atau lulusan pasca sarjana farmakologi. Dengan bekal pengetahuan dan kemampuan untuk melakukan penilaian secara kritis setiap bentuk informasi, diharapkan dokter tetap up to date dalam menulis resepKata kunci : Resep – up to- date.Abstract Prescription is a written request from a doctor, dentist or veterinarian to the pharmacist to make a particular drug

  2. The freshwater reservoir effect in radiocarbon dating

    OpenAIRE

    Philippsen, Bente

    2012-01-01

    The freshwater reservoir effect can result in too high radiocarbon ages of samples from lakes and rivers, including the bones of people whose subsistence was based on freshwater fish, and pottery in which fish was cooked. In my talk, I will explain the causes and consequences of this effect. Two case studies will show the degree of variability of the freshwater reservoir effect over short and long timescales. Radiocarbon dating of recent water samples, aquatic plants and animals, shows that a...

  3. A Simple Example of Radioactive Dating

    Science.gov (United States)

    Brown, Todd

    2014-01-01

    Although nuclear half-life is vital to physics and physical science, and to sensitive societal issues from nuclear waste to the age of the Earth, a true lab on half-life is almost never done at the college or high school level. Seldom are students able to use radioactivity to actually date when an object came into being, as is done in this…

  4. {sup 14}C AMS dating Yongcheon cave

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J.H., E-mail: jefflee@snu.ac.kr [AMS Lab., NCIRF, Seoul National University, Seoul 151-742 (Korea, Republic of); Choe, K. [AMS Lab., NCIRF, Seoul National University, Seoul 151-742 (Korea, Republic of); Kim, J.C. [Dept. of Physics and Astronomy, Seoul National University, Seoul 151-742 (Korea, Republic of); Choi, S.H.; Kang, J.; Song, S.; Song, Y.M. [AMS Lab., NCIRF, Seoul National University, Seoul 151-742 (Korea, Republic of); Jang, J.G. [Jeju National Museum, Jeju 690-782 (Korea, Republic of)

    2013-01-15

    The biggest island in South Korea is Jeju Island, which lies 80 km south of the mainland and has one shield volcano, Mt. Halla. The volcanic island and its lava tubes were added to the world heritage list by UNESCO in 2007. Among the many lava tubes on the island, a unique cave had been accidentally found in 2005 while some workers were replacing a telephone pole. Until the discovery, it had been completely isolated from the outside by naturally-built sand blocks. Yongcheon cave is a lime-decorated lava tube showing both the properties of a volcanic lava tube and a limestone cave. This cave, about 3 km in length, is acknowledged to be the best of this type in the world and includes a large clean-water lake, lava falls, and richly developed speleothems inside it. Even though there is archaeological evidence from well preserved pottery that ancient people entered this place, the preservation of artifacts was ensured by a geological change that made later entrance difficult. We have collected charcoal samples scattered around the cave and dated them using AMS. Ages were in the range of ca. 1570-1260 BP (A.D. 340-880) and this corresponds to the Ancient Three Kingdoms and the Unified Silla era in Korean history. The {sup 14}C AMS measurement results presented in this paper on wood charcoal provide precise dates which will be very useful not only to clarify the nature of human activities in this cave but also to provide reference dates when comparing other dating methods.

  5. Carbon-14 Bomb-Pulse Dating

    Energy Technology Data Exchange (ETDEWEB)

    Buchholz, B A

    2007-12-16

    Atmospheric testing of nuclear weapons during the 1950s and early 1960s doubled the concentration of carbon-14 atmosphere and created a pulse that labeled everything alive in the past 50 years as carbon moved up the food chain. The variation in carbon-14 concentration in time is well-documented and can be used to chronologically date all biological materials since the mid-1950s.

  6. The Interpersonal Communication Of Spouse Through Taaruf Online Dating

    Directory of Open Access Journals (Sweden)

    Lucy Pujasari Supratman

    2016-12-01

    Full Text Available The development of social networking has revealed new opportunities for all varieties of internet sites that offer online dating services/online dating . One of them is the site of rumahtaaruf.com. During the process of matchmaking in rumahtaaruf.com., each candidate areis accompanied by a mediator who acts as an intermediary for both parties. Their role are job of mediator is to regulate and monitor the way of taaruf based on Islamic shari'a. This study focuses on the motive that underlying the attitudes of women and men who chosen spouses under the site services of rumahtaaruf.com. This study used a qualitative method with phenomenological approach. The data were obtained through interviews and observations. The informants were couples who have been married once brought together by Rrumahtaaruf.com administrator. The results showed that the motive prospective couples to choose rumahtaaruf.com was based on education, age, occupation , physical attraction, response of family and culture.

  7. Preference Versus Choice in Online Dating.

    Science.gov (United States)

    Whyte, Stephen; Torgler, Benno

    2017-03-01

    This study explores factors that influence matches of online dating participants' stated preference for particular characteristics in a potential partner and compares these with the characteristics of the online daters actually contacted. The nature of online dating facilitates exploration of the differences between stated preference and actual choice by participants, as online daters willingly provide a range of demographics on their ideal partner. Using data from the Australian dating website RSVP, we analyze 219,013 contact decisions. We conduct a multivariate analysis using the number of matched variables between the participants' stated preference and the characteristics of the individuals contacted. We find that factors such as a person's age, their education level, and a more social personality all increase the number of factors they choose in a potential partner that match their original stated preference. Males (relative to females) appear to match fewer characteristics when contacting potential love interests. Conversely, age interaction effects demonstrate that males in their late 60's are increasingly more selective (than females) regarding who they contact. An understanding of how technology (the Internet) is impacting human mating patterns and the psychology behind the participants informs the wider social science of human behavior in large-scale decision settings.

  8. ESR dating at Mezmaiskaya Cave, Russia

    Energy Technology Data Exchange (ETDEWEB)

    Skinner, A.R. [Department of Chemistry, Williams College, Williamstown, MA, 01267 (United States)]. E-mail: anne.r.skinner@williams.edu; Blackwell, B.A.B. [Department of Chemistry, Williams College, Williamstown, MA, 01267 (United States); Martin, Sara [Department of Chemistry, Williams College, Williamstown, MA, 01267 (United States); Ortega, A. [RFK Science Research Institute, Flushing, NY, 11366 (United States); Blickstein, J.I.B. [RFK Science Research Institute, Flushing, NY, 11366 (United States); Golovanova, L.V. [Laboratory of Prehistory, St. Petersburg (Russian Federation); Doronichev, V.B. [Laboratory of Prehistory, St. Petersburg (Russian Federation)

    2005-02-01

    Mezmaiskaya Cave has yielded more than 10,000 artifacts, thousands of very well preserved faunal remains, and hominin remains, found in seven Middle Paleolithic (Mousterian) and three Upper Paleolithic levels. A complete Neanderthal infant skeleton was preserved in anatomical juxtaposition lying on a large limestone block, overlain by the earliest Mousterian layer, Layer 3. Twenty-four skull fragments from a 1-2 year-old Neanderthal infant, showing post-mortem deformation, occurred in a pit originating in the Mousterian Layer 2 and penetrating into underlying layers 2A and 2B(1). Bone from Layer 2A was dated by AMS {sup 14}C at 35.8-36.3{+-}0.5 kyr BP. Direct dating of Neanderthal bone from Layer 3 gave an age of 29 kyr, but that is now considered to be due to contamination by modern carbon. Fourteen large mammal teeth from Layers 2 through 3 have been dated by standard electron spin resonance (ESR). Low U concentrations in both the enamel and dentine ensure that ESR ages do not depend significantly on the U uptake model, but do depend strongly on the sedimentary dose rates. Assuming a sedimentary water concentration equal to 20 wt%, ESR ages for the Mousterian layers range from 36.2 to 73.0{+-}5.0 ka.

  9. Workshop on dating old ground water

    Energy Technology Data Exchange (ETDEWEB)

    1978-01-01

    A workshop on methods which might be used to date very old ground water was held on March 16--18, 1978, in Tucson, Arizona. The workshop was sponsored by the Office of Waste Isolation of Union Carbide Corporation as part of studies supported by the United States Department of Energy which are designed to evaluate the safety of proposed subsurface repositories for nuclear waste. The workshop was convened by the College of Earth Sciences of the University of Arizona with the cooperation of other university departments, particularly the Department of Physics. The dating of ground water in the vicinity of nuclear repositories is a critical aspect of the safety evaluation of these repositories. The age of the water gives an indication of past rates of water movement which in turn will help evaluate the likelihood of future migration of radionuclides from a given repository. Despite this rather obvious practical application, most of the workshop time was devoted to difficult technical questions related to the actual dating of the water.

  10. Predictors of dating violence: a multivariate analysis.

    Science.gov (United States)

    Bookwala, J; Frieze, I H; Smith, C; Ryan, K

    1992-01-01

    A multivariate approach was used to determine the pattern of predictors associated with engaging in dating violence. Predictors were selected whose relationship to dating violence has been established by earlier research: attitudes toward violence, sex-role attitudes, romantic jealousy, general levels of interpersonal aggression, verbal aggression, and verbal and physical aggression received from one's partner. Participants included 305 introductory psychology student volunteers (227 females and 78 males) who completed a set of scales related to dating relationships. Expecting different patterns of predictors to emerge for men and women, we performed separate multiple regression analyses for each. Of the set of predictors employed, receipt of physical violence from one's partner emerged as the largest predictor of expressed violence for both men and women. In addition, higher scores on attitudes toward violence and verbal aggression, and less traditional sex-role attitudes emerged as significant predictors of expressed violence for men. For women, less accepting attitudes toward violence, more traditional sex-role attitudes, feelings of romantic jealousy, higher general levels of interpersonal aggression, and verbal aggression were predictive of expressed violence. The implications of our findings for future research are discussed.

  11. Staff rules and regulations

    CERN Multimedia

    HR Department

    2007-01-01

    The 11th edition of the Staff Rules and Regulations, dated 1 January 2007, adopted by the Council and the Finance Committee in December 2006, is currently being distributed to departmental secretariats. The Staff Rules and Regulations, together with a summary of the main modifications made, will be available, as from next week, on the Human Resources Department's intranet site: http://cern.ch/hr-web/internal/admin_services/rules/default.asp The main changes made to the Staff Rules and Regulations stem from the five-yearly review of employment conditions of members of the personnel. The changes notably relate to: the categories of members of the personnel (e.g. removal of the local staff category); the careers structure and the merit recognition system; the non-residence, installation and re-installation allowances; the definition of family, family allowances and family-related leave; recognition of partnerships; education fees. The administrative circulars, some of which are being revised following the ...

  12. Casual dating online: sexual norms and practices on French heterosexual dating sites

    OpenAIRE

    Bergström, Marie

    2011-01-01

    "Während über das Internet vermittelte gelegentliche Treffen zwischen homosexuellen Männern bereits ein etablierter Forschungsgegenstand in den Sozialwissenschaften sind, ist die Forschung zu heterosexuellem Online-Dating größtenteils auf die Suche nach romantischen Langzeitbeziehungen fokussiert. Der vorliegende Artikel will damit beginnen, diese Forschungslücke zu füllen, indem er den möglichen neuen sexuellen Bereich untersucht, der durch heterosexuelle Online-Dating-Plattformen entsteht. ...

  13. Plutonium age dating (production date measurement) by inductively coupled plasma mass spectrometry

    OpenAIRE

    Varga, Zsolt; Nicholl, Adrian; Wallenius, Maria; Mayer, Klaus

    2015-01-01

    This paper describes rapid methods for the determination of the production date (age dating) of plutonium (Pu) materials by inductively coupled plasma mass spectrometry (ICP-MS) for nuclear forensic and safeguards purposes. One of the presented methods is a rapid, direct measurement without chemical separation using 235U/239Pu and 236U/240Pu chronometers. The other method comprises a straightforward extraction chromatographic separation, followed by ICP-MS measurement for the 234U/238Pu, 235U...

  14. Cyber dating abuse: prevalence, context, and relationship with offline dating aggression.

    Science.gov (United States)

    Borrajo, E; Gámez-Guadix, M; Calvete, E

    2015-04-01

    The use of information and communication technologies (ICT) as tools to intimidate, harass, and control the partner has been, so far, little studied in the literature. The aim of this study was to determine the extension and sex differences of victimization of cyber dating abuse, as well as the context in which it occurs, and its relationship with offline psychological and physical aggressions. The sample consisted of 433 college students ages 18 to 30 years. The results showed that over 50% of the participants had been victims of some type of cyber dating abuse in the last six months. The most common behavior was the use of ICT to control the partner. Also, victims of cyber dating abuse were victimized repeatedly, an average of 23 times in the last six months. The data also showed that cyber dating abuse appear usually in a context of jealousy. Finally, the results revealed a significant relationship between cyber dating abuse and offline psychological dating aggressions. Limitations and future lines of research are discussed.

  15. 50 CFR 10.4 - When regulations apply.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 1 2010-10-01 2010-10-01 false When regulations apply. 10.4 Section 10.4... GENERAL PROVISIONS Introduction § 10.4 When regulations apply. The regulations of this subchapter B shall apply to all matters arising after the effective date of such regulations, with the following exceptions...

  16. 77 FR 27548 - Federal Acquisition Regulation; Free Trade Agreement-Colombia

    Science.gov (United States)

    2012-05-10

    ... 9000-AM24 Federal Acquisition Regulation; Free Trade Agreement--Colombia AGENCY: Department of Defense... Acquisition Regulation (FAR) to implement the United States- Colombia Trade Promotion Agreement. This Trade... eligible products and services from Colombia. DATES: Effective Date: May 15, 2012. Comment Date: Interested...

  17. 21 CFR 610.50 - Date of manufacture.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Date of manufacture. 610.50 Section 610.50 Food... GENERAL BIOLOGICAL PRODUCTS STANDARDS Dating Period Limitations § 610.50 Date of manufacture. The date of manufacture shall be determined as follows: (a) For products for which an official standard of potency is...

  18. 46 CFR 188.10-1 - Anniversary date.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Anniversary date. 188.10-1 Section 188.10-1 Shipping... PROVISIONS Definition of Terms Used in This Subchapter § 188.10-1 Anniversary date. The term anniversary date means the day and the month of each year, which corresponds to the date of expiration of the Certificate...

  19. 26 CFR 1.771-1 - Effective date.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Effective date. 1.771-1 Section 1.771-1 Internal... TAXES Effective Date for Subchapter K, Chapter 1 of the Code § 1.771-1 Effective date. (a) General rule.... Certain provisions of section 771 apply after specific dates in 1954, as follows: (1) Adoption of taxable...

  20. Dating Practices and Patterns of Disclosure among in-School ...

    African Journals Online (AJOL)

    Dating relationships are central to adolescents' lives. Dating and romance are major topics of adolescents' conversations and are linked to both positive and negative emotions. This study examined dating patterns, dating disclosure and parent's awareness in Ibadan metropolis using a mixed method design and found that ...

  1. Dating Violence among High School Students in Southeastern North Carolina

    Science.gov (United States)

    Kim-Godwin, Yeoun Soo; Clements, Carrie; McCuiston, Ashley M.; Fox, Jane A.

    2009-01-01

    Adolescents are a high-risk group for dating violence. Using the Youth Risk Behavior Survey data, this study examined the associations among dating violence (including physical dating violence [PDV] and sexual dating violence [SDV]) and selected health risk behaviors among 375 and 372 high school students, in 2005 and 2007, respectively, in…

  2. High- and low-affinity cre boxes for CcpA binding in Bacillus subtilis revealed by genome-wide analysis

    NARCIS (Netherlands)

    Marciniak, Bogumila C.; Pabijaniak, Monika; de Jong, Anne; Dűhring, Robert; Seidel, Gerald; Hillen, Wolfgang; Kuipers, Oscar P.

    2012-01-01

    Background: In Bacillus subtilis and its relatives carbon catabolite control, a mechanism enabling to reach maximal efficiency of carbon and energy sources metabolism, is achieved by the global regulator CcpA (carbon catabolite protein A). CcpA in a complex with HPr-Ser-P (seryl-phosphorylated form

  3. Direct dating of hominids using ESR and U-series dating

    Energy Technology Data Exchange (ETDEWEB)

    Gruen, R. [Australian National University, Canberra, ACT (Australia). Research School of Earth Science

    1999-11-01

    Full text: Dating studies on palaeoanthropological sites is usually carried out on material associated with the human remains, such as the sediment, charcoal or other fauna rather than the human specimen itself. The reason lies in the fact that most dating techniques are destructive and because the hominid remains are too rare to be sacrificed for dating. This indirect dating approach is in many cases not satisfactory, because:(i) the human remains are often buried into the sediments and the association with other materials is uncertain (e.g. Skhul, Qafzeh, etc.);(ii) faunal remains or minerals from the sediment are re-worked from older deposits (see e.g. present discussion of the age of the Homo erectus remains in Indonesia);(iii) the hominid specimen was discovered at a time when no careful excavations were carried out and it is impossible to correlate the specimen with other datable material (nearly 90% of all palaeoanthropological specimen). For example, the hominid burial site of Qafzeh in Israel has been dated by several independent dating laboratories with a multitude of methods. However, the data are still not accepted by some because the dating has not been carried out on the hominid specimen. Until recently, hominid fossils could only be dated by radiocarbon. This method reaches back to about 40,000 years. As a consequence, all the older fossils could not be analysed and many important questions in our understanding of human evolution could not be addressed. Human remains are scarce and extremely valuable, therefore any sort of destruction has to be kept to an absolute minimum. This is of particular importance in Australia where any human fossils are sacred. Thus, for the analysis of hominid material it was necessary to develop a more or less non-destructive techniques. This has been accomplished in recent years by the application of ESR dating of tooth enamel and a combination of gamma spectrometric and TIMS U-series dating of bones. The examples of

  4. Asian American dating: important factors in partner choice.

    Science.gov (United States)

    Mok, T A

    1999-05-01

    The majority of research on romantic relationships has tended to focus on marriage, with relatively less attention paid to dating. This study examined the relationship between Asian American dating, both interracial and intraracial, and a variety of factors thought to be associated with dating in this population, including acculturation, ethnic identity, attractiveness, interracial dating experience, ethnicity of friends, parental influence over dating, and density. Participants were administered measures of these variables and were asked questions regarding their likelihood of dating both Asian Americans and White Americans. An interesting pattern of results emerged when the variables were put into regression equations to predict both interracial and intraracial dating. Findings are presented and implications discussed.

  5. In Search of Teen Dating Violence Typologies.

    Science.gov (United States)

    Reidy, Dennis E; Ball, Barbara; Houry, Debra; Holland, Kristin M; Valle, Linda A; Kearns, Megan C; Marshall, Khiya J; Rosenbluth, Barri

    2016-02-01

    The goal of the present research was to identify distinct latent classes of adolescents that commit teen dating violence (TDV) and assess differences on demographic, behavioral, and attitudinal correlates. Boys and girls (N = 1,149; Mage = 14.3; Grades 6-12) with a history of violence exposure completed surveys assessing six indices of TDV in the preceding 3 months. Indices of TDV included controlling behaviors, psychological TDV, physical TDV, sexual TDV, fear/intimidation, and injury. In addition, adolescents provided demographic and dating history information and completed surveys assessing attitudes condoning violence, relationship skills and knowledge, and reactive/proactive aggression. Latent class analysis indicated a three-class solution wherein the largest class of students was nonviolent on all indices ("nonaggressors") and the smallest class of students demonstrated high probability of nearly all indices of TDV ("multiform aggressors"). In addition, a third class of "emotional aggressors" existed for which there was a high probability of controlling and psychological TDV but low likelihood of any other form of TDV. Multiform aggressors were differentiated from emotional and nonaggressors on the use of self-defense in dating relationships, attitudes condoning violence, and proactive aggression. Emotional aggressors were distinguished from nonaggressors on nearly all measured covariates. Evidence indicates that different subgroups of adolescents engaging in TDV exist. In particular, a small group of youth engaging in multiple forms of TDV can be distinguished from a larger group of youth that commit acts of TDV restricted to emotional aggression (i.e., controlling and psychological) and most youth that do not engage in TDV. Published by Elsevier Inc.

  6. Soils as relative-age dating tools

    Science.gov (United States)

    Markewich, Helaine Walsh; Pavich, Milan J.; Wysocki, Douglas A.

    2017-01-01

    Soils develop at the earth's surface via multiple processes that act through time. Precluding burial or disturbance, soil genetic horizons form progressively and reflect the balance among formation processes, surface age, and original substrate composition. Soil morphology provides a key link between process and time (soil age), enabling soils to serve as both relative and numerical dating tools for geomorphic studies and landscape evolution. Five major factors define the contemporary state of all soils: climate, organisms, topography, parent material, and time. Soils developed on similar landforms and parent materials within a given landscape comprise what we term a soil/landform/substrate complex. Soils on such complexes that differ in development as a function of time represent a soil chronosequence. In a soil chronosequence, time constitutes the only independent formation factor; the other factors act through time. Time dictates the variations in soil development or properties (field or laboratory measured) on a soil/landform/substrate complex. Using a dataset within the chronosequence model, we can also formulate various soil development indices based upon one or a combination of soil properties, either for individual soil horizons or for an entire profile. When we evaluate soil data or soil indices mathematically, the resulting equation creates a chronofunction. Chronofunctions help quantify processes and mechanisms involved in soil development, and relate them mathematically to time. These rigorous kinds of comparisons among and within soil/landform complexes constitute an important tool for relative-age dating. After determining one or more absolute ages for a soil/landform complex, we can calculate quantitative soil formation, and or landform-development rates. Multiple dates for several complexes allow rate calculations for soil/landform-chronosequence development and soil-chronofunction calibration.

  7. Zechariah and the Dating of Biblical Hebrew

    DEFF Research Database (Denmark)

    Ehrensvärd, Martin Gustaf

    2006-01-01

    The data presented in the article indicate clearly that the ability to write proper EBH did not end with the exile; but when did it end? In the course of the fifth century, or the fourth century, or even later? This is difficult to resolve, on linguistic grounds. On linguistic grounds, can we say...... conclusions of most biblical scholars. Considering only linguistic data, texts in EBH could have been composed after the exile. Other, non-linguistic considerations can make this unlikely, but we can raise no objections from a linguistic viewpoint to such a dating....

  8. Suitability of Ostrich eggshell for radiocarbon dating

    CSIR Research Space (South Africa)

    Vogel, JC

    2001-01-01

    Full Text Available sample we also analyzed the organic contents of the egg—a mixture of the egg white and yolk. Also given is the 14C content of the carbon dioxide of the atmosphere in the month in which the eggs were laid. This closely reflects the 14C content... deposits cannot be guaranteed. A more direct approach would be to ana- lyze modern ostrich eggs of which the date of laying is known. It is necessary to know exactly when the eggs were laid because the elevated 14C content of the environment caused...

  9. Timing of last deglaciation in the Cantabrian Mountains (Iberian Peninsula; North Atlantic Region) based on in situ-produced 10Be exposure dating

    Science.gov (United States)

    Rodríguez-Rodríguez, Laura; Jiménez-Sánchez, Montserrat; Domínguez-Cuesta, María José; Rinterknecht, Vincent; Pallàs, Raimon; Aumaître, Georges; Bourlès, Didier L.; Keddadouche, Karim; Aster Team

    2017-09-01

    The Last Glacial Termination led to major changes in ice sheet coverage that disrupted global patterns of atmosphere and ocean circulation. Paleoclimate records from Iberia suggest that westerly episodes played a key role in driving heterogeneous climate in the North Atlantic Region. We used 10Be Cosmic Ray Exposure (CRE) dating to explore the glacier response of small mountain glaciers (ca. 5 km2) that developed on the northern slope of the Cantabrian Mountains (Iberian Peninsula), an area directly under the influence of the Atlantic westerly winds. We analyzed twenty boulders from three moraines and one rock glacier arranged as a recessional sequence preserved between 1150 and 1540 m above sea level (a.s.l.) in the Monasterio valley (Redes Natural Park). Results complement previous chronologic data based on radiocarbon and optically stimulated luminescence from the Monasterio valley, which suggest a local Glacial Maximum (local GM) prior to 33 ka BP and a long-standing glacier advance at 24 ka coeval to the global Last Glacial Maximum (LGM). Resultant 10Be CRE ages suggest a progressive retreat and thinning of the Monasterio glacier over the time interval 18.1-16.7 ka. This response is coeval with the Heinrich Stadial 1, an extremely cold and dry climate episode initiated by a weakening of the Atlantic Meridional Overturning Circulation (AMOC). Glacier recession continued through the Bølling/Allerød period as indicate the minimum exposure ages obtained from a cirque moraine and a rock glacier nested within this moraine, which yielded ages of 14.0 and 13.0 ka, respectively. Together, they suggest that the Monasterio glacier experienced a gradual transition from glacier to rock glacier activity as the AMOC started to strengthen again. Glacial evidence ascribable to the Younger Dryas cooling was not dated in the Monasterio valley, but might have occurred at higher elevations than evidence dated in this work. The evolution of former glaciers documented in the

  10. A review of the literature on dating violence prevention programs

    OpenAIRE

    蓮井, 江利香

    2012-01-01

    The purpose of this study was to review the previous studies on dating violence prevention programs. Recent researches on Japanese dating violence and the prevalence rates for Japanese dating violence were discussed before the review of literature on prevention programs for dating violence. The search strategy began with electronic databases such as Journals@Ovid, PsycARTICLES, and CiNii (Citation Information by NII,) etc. The review revealed that there were few studies on dating violence pre...

  11. Assessing the effects of Families for Safe Dates, a family-based teen dating abuse prevention program.

    Science.gov (United States)

    Foshee, Vangie A; McNaughton Reyes, Heath Luz; Ennett, Susan T; Cance, Jessica D; Bauman, Karl E; Bowling, J Michael

    2012-10-01

    To examine the effects of a family-based teen dating abuse prevention program, Families for Safe Dates, primarily on outcomes related to testing the conceptual underpinnings of the program including (1) factors motivating and facilitating caregiver engagement in teen dating abuse prevention activities, and 2) risk factors for teen dating abuse, and secondarily on dating abuse behaviors. Families were recruited nationwide using listed telephone numbers. Caregivers and teens completed baseline and 3-month follow-up telephone interviews (n = 324). Families randomly allocated to treatment condition received the Families for Safe Dates program including six mailed activity booklets followed-up by health educator telephone calls. There were significant (teen dating abuse prevention activities including caregiver perceived severity of dating abuse, response efficacy for preventing dating abuse, self-efficacy for talking about dating abuse, knowledge of dating abuse, acceptance of dating abuse, communication skills with the teen, and belief in the importance of involvement in their male (but not female) teen's dating. The latter effect was the only one moderated by sex of the teen. The targeted risk factor affected by the program was teen acceptance of dating abuse. Treatment was also significantly associated with less physical dating abuse victimization. Modifications to the program are warranted, but overall, the findings are very favorable for the first family-based teen dating abuse prevention program to be evaluated. Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  12. Dating Norms and Dating Violence among Ninth Graders in Northeast Georgia: Reports from Student Surveys and Focus Groups

    Science.gov (United States)

    Reeves, Patricia M.; Orpinas, Pamela

    2012-01-01

    This mixed-methods study describes the norms supporting male-to-female and female-to-male dating violence in a diverse sample of ninth graders. The quantitative study, based on student surveys (n = 624), compared norms supporting dating violence by sex, race/ethnicity, and dating status, and it examined the relation between dating violence norms…

  13. The Rate of Cyber Dating Abuse among Teens and How It Relates to Other Forms of Teen Dating Violence

    Science.gov (United States)

    Zweig, Janine M.; Dank, Meredith; Yahner, Jennifer; Lachman, Pamela

    2013-01-01

    To date, little research has documented how teens might misuse technology to harass, control, and abuse their dating partners. This study examined the extent of cyber dating abuse--abuse via technology and new media--in youth relationships and how it relates to other forms of teen dating violence. A total of 5,647 youth from ten schools in three…

  14. Characterization and evolution of conserved MicroRNA through duplication events in date palm (Phoenix dactylifera).

    Science.gov (United States)

    Xiao, Yong; Xia, Wei; Yang, Yaodong; Mason, Annaliese S; Lei, Xintao; Ma, Zilong

    2013-01-01

    MicroRNAs (miRNAs) are important regulators of gene expression at the post-transcriptional level in a wide range of species. Highly conserved miRNAs regulate ancestral transcription factors common to all plants, and control important basic processes such as cell division and meristem function. We selected 21 conserved miRNA families to analyze the distribution and maintenance of miRNAs. Recently, the first genome sequence in Palmaceae was released: date palm (Phoenix dactylifera). We conducted a systematic miRNA analysis in date palm, computationally identifying and characterizing the distribution and duplication of conserved miRNAs in this species compared to other published plant genomes. A total of 81 miRNAs belonging to 18 miRNA families were identified in date palm. The majority of miRNAs in date palm and seven other well-studied plant species were located in intergenic regions and located 4 to 5 kb away from the nearest protein-coding genes. Sequence comparison showed that 67% of date palm miRNA members were present in duplicated segments, and that 135 pairs of miRNA-containing segments were duplicated in Arabidopsis, tomato, orange, rice, apple, poplar and soybean with a high similarity of non coding sequences between duplicated segments, indicating genomic duplication was a major force for expansion of conserved miRNAs. Duplicated miRNA pairs in date palm showed divergence in pre-miRNA sequence and in number of promoters, implying that these duplicated pairs may have undergone divergent evolution. Comparisons between date palm and the seven other plant species for the gain/loss of miR167 loci in an ancient segment shared between monocots and dicots suggested that these conserved miRNAs were highly influenced by and diverged as a result of genomic duplication events.

  15. Ensilage of cardboard and date palm leaves.

    Science.gov (United States)

    Baroon, Z; El-Nawawy, A S; Al-Othman, A

    2004-01-01

    Eight treatments of cardboard (CB) and date palm leaves (DPL) with or without alkali treatments plus molasses, dates, and ammonium sulfate were ensiled in laboratory silos. Latobacillus plantarum and Saccharomyces cerevisiae inoculants were added at an application rate of 10(5) cfu/g of silage to study their possible influence on the fermentation process. Silos were sealed and incubated at 30 degrees C. The anaerobic ensiling was evaluated for chemical and microbiological variables by opening the silos after 30, 60, and 90 days. After 90 days, significantly low pH values (5.2-3.5) were obtained. The percentages of hemicellulose, cellulose, lignin, and ash were determined. Concentrations of reducing sugars, ether extract, and crude protein tended to be acceptable among treatments. Silages showed a significantly high lactic acid concentration (up to 4.3%) and only traces of butyric acid (below 1%). Also changes in acetic and propionic acids concentrations were determined. Lactobacillus populations remained almost static while yeast and molds populations tended to be lower after 90 days of ensilage. Neither alkali treatment nor microbial inoculants showed a relationship with the ensiling process. Thus, overall, it was concluded that CB and DPL can be effectively ensiled and the resultant silages are acceptable to merit their use as ruminant feed in arid regions.

  16. Dating phylogenies with hybrid local molecular clocks.

    Directory of Open Access Journals (Sweden)

    Stéphane Aris-Brosou

    Full Text Available BACKGROUND: Because rates of evolution and species divergence times cannot be estimated directly from molecular data, all current dating methods require that specific assumptions be made before inferring any divergence time. These assumptions typically bear either on rates of molecular evolution (molecular clock hypothesis, local clocks models or on both rates and times (penalized likelihood, Bayesian methods. However, most of these assumptions can affect estimated dates, oftentimes because they underestimate large amounts of rate change. PRINCIPAL FINDINGS: A significant modification to a recently proposed ad hoc rate-smoothing algorithm is described, in which local molecular clocks are automatically placed on a phylogeny. This modification makes use of hybrid approaches that borrow from recent theoretical developments in microarray data analysis. An ad hoc integration of phylogenetic uncertainty under these local clock models is also described. The performance and accuracy of the new methods are evaluated by reanalyzing three published data sets. CONCLUSIONS: It is shown that the new maximum likelihood hybrid methods can perform better than penalized likelihood and almost as well as uncorrelated Bayesian models. However, the new methods still tend to underestimate the actual amount of rate change. This work demonstrates the difficulty of estimating divergence times using local molecular clocks.

  17. Tie-2Cre mediated deletion of the vitamin D receptor gene leads to improved skeletal muscle insulin sensitivity and glucose tolerance.

    Science.gov (United States)

    Ni, Wei; Glenn, Denis J; Gardner, David G

    2016-11-01

    A variety of studies have suggested that vitamin D may play a palliative role in improving insulin secretion and glucose tolerance. Endothelial cells of the microcirculation are thought to play an important role in regulating both insulin secretion and insulin sensitivity in target tissues. We have selectively deleted the vitamin D receptor (VDR) gene in endothelial cells of the murine vasculature. These mice demonstrate improved glucose tolerance, improved insulin sensitivity in skeletal muscle, but not in liver, and a reduction in expression and secretion of insulin in the pancreatic islets. Collectively, these data, taken within the context of recent publications in this field, suggest that the endothelial cell VDR plays a tonic inhibitory role in regulating glucose disposal and could prove to be a factor in controlling glucose homeostasis in the intact organism. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Topology, divergence dates, and macroevolutionary inferences vary between different tip-dating approaches applied to fossil theropods (Dinosauria)

    OpenAIRE

    Bapst, D. W.; Wright, A.M; Matzke, N. J.; Lloyd, G.T.

    2016-01-01

    Dated phylogenies of fossil taxa allow palaeobiologists to estimate the timing of major divergences and placement of extinct lineages, and to test macroevolutionary hypotheses. Recently developed Bayesian ?tip-dating? methods simultaneously infer and date the branching relationships among fossil taxa, and infer putative ancestral relationships. Using a previously published dataset for extinct theropod dinosaurs, we contrast the dated relationships inferred by several tip-dating approaches and...

  19. Bmpr1a is required for proper migration of the AVE through regulation of Dkk1 expression in the pre-streak mouse embryo.

    Science.gov (United States)

    Miura, Shigeto; Singh, Ajeet Pratap; Mishina, Yuji

    2010-05-01

    Here, we report a novel mechanism regulating migration of the anterior visceral endoderm (AVE) by BMP signaling through BMPRIA. In Bmpr1a-deficient (Bmpr-null) embryos, the AVE does not migrate at all. In embryos with an epiblast-specific deletion of Bmpr1a (Bmpr1a(null/flox); Sox2Cre embryos), the AVE cells migrate randomly from the distal end of embryos, resulting in an expansion of the AVE. Dkk1, which is normally expressed in the anterior proximal visceral endoderm (PxVE), is downregulated in Bmpr-null embryos, whereas it is circumferentially expressed in Bmpr1a(null/flox); Sox2Cre embryos at E5.75-6.5. These results demonstrate an association of the position of Dkk1 expressing cells with direction of the migration of AVE. In Bmpr1a(null/flox); Sox2Cre embryos, a drastic decrease of WNT signaling is observed at E6.0. Addition of WNT3A to the culture of Bmpr1a(null/flox); Sox2Cre embryos at E5.5 restores expression patterns of Dkk1 and Cer1. These data indicate that BMP signaling in the epiblast induces Wnt3 and Wnt3a expression to maintain WNT signaling in the VE, resulting in downregulation of Dkk1 to establish the anterior expression domain. Thus, our results suggest that BMP signaling regulates the expression patterns of Dkk1 for anterior migration of the AVE. Published by Elsevier Inc.

  20. Klotho expression in long bones regulates FGF23 production during renal failure.

    Science.gov (United States)

    Kaludjerovic, Jovana; Komaba, Hirotaka; Sato, Tadatoshi; Erben, Reinhold G; Baron, Roland; Olauson, Hannes; Larsson, Tobias E; Lanske, Beate

    2017-05-01

    Circulating levels of bone-derived fibroblast growth factor 23 (FGF23) increase early during acute and chronic kidney disease and are associated with adverse outcomes. Membrane-bound Klotho acts as a permissive coreceptor for FGF23, and its expression was recently found in osteoblasts/osteocytes. We hypothesized that Klotho in bone cells is part of an autocrine feedback loop that regulates FGF23 expression during renal failure. Thus, we induced renal failure in mice with targeted deletion of Klotho in long bones. Uremic wild-type (KLfl/fl ) and knockout (Prx1-Cre;KLfl/fl ) mice both responded with reduced body weight, kidney atrophy, hyperphosphatemia, and increased bone turnover. Importantly, long bones of Prx1-Cre;KLfl/fl mice but not their axial skeleton failed to increase FGF23 expression as observed in uremic KLfl/fl mice. Consequently, Prx1-Cre;KLfl/fl mice had significantly lower serum FGF23 and parathyroid hormone levels, and higher renal 1-α-hydroxylase expression, serum 1,25-dihydroxyvitamin D, and calcium levels than KLfl/fl mice. These results were confirmed in two independent models of renal failure, adenine diet induced and 5/6 nephrectomy. Moreover, FGF23-treated bone cells required Klotho to increase FGF23 mRNA and ERK phosphorylation. In summary, our novel findings show that Klotho in bone is crucial for inducing FGF23 production upon renal failure. We propose the presence of an autocrine feedback loop in which Klotho senses the need for FGF23.-Kaludjerovic, J., Komaba, H., Sato, T., Erben, R. G., Baron, R., Olauson, H., Larsson, T. E., Lanske, B. Klotho expression in long bones regulates FGF23 production during renal failure. © FASEB.