Sample records for chz1p regulates h2b

  1. H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation


    Xu, Zhiliang; Song,Zhenhua; Li, Guoping; Tu, Huayu; Liu, Weixiao; Liu, Yujiao; Wang, Pan; Wang, Yuanting; Cui, Xiuhong; Liu, Chao; Shang, Yongliang; de Rooij, Dirk G.; Gao, Fei; Li, Wei


    Meiotic recombination is essential for fertility in most sexually reproducing species, but the molecular mechanisms underlying this process remain poorly understood in mammals. Here, we show that RNF20-mediated H2B ubiquitination is required for meiotic recombination. A germ cell-specific knockout of the H2B ubiquitination E3 ligase RNF20 results in complete male infertility. The Stra8-Rnf20−/− spermatocytes arrest at the pachytene stage because of impaired programmed double-strand break (DSB...

  2. Histone H2B monoubiquitination is involved in the regulation of cutin and wax composition in Arabidopsis thaliana. (United States)

    Ménard, Rozenn; Verdier, Gaëtan; Ors, Mareva; Erhardt, Mathieu; Beisson, Fred; Shen, Wen-Hui


    The plant cuticle is a chemically heterogeneous lipophilic layer composed of a cutin polymer matrix and waxes which covers the aerial parts of plants. This layer plays an essential role in the survival of plants by protecting them from desiccation and (a)biotic stresses. Knowledge on the gene networks and mechanisms regulating the synthesis of cuticle components during organ expansion or stress response remains limited however. Here, using five loss-of-function mutants for histone monoubiquitination, we report on the role of two RING E3 ligases, namely HISTONE MONOUBIQUITINATION 1 and 2 (HUB1 and HUB2), in the selective transcriptional activation of four cuticle biosynthesis genes in Arabidopsis thaliana. Microscopy observations showed that in hub1-6 and hub2-2 mutants irregular epidermal cells and disorganized cuticle layers were present in rosette leaves. Water loss measurements on excised rosettes demonstrated that cuticular permeability was significantly increased in the mutants. Chemical analysis of cuticle components revealed that the wax composition was changed and that cutin 16:0 dicarboxylic acid was significantly reduced in all hub mutants. Analysis of transcript levels of selected genes indicated that LACS2, ATT1 and HOTHEAD involved in cutin biosynthesis and CER1 involved in wax biosynthesis were down-regulated in the hub mutants, while the expression of LACERATA, CER3, CER6 and CER10 remained unchanged. Chromatin immunoprecipitation assays further showed that hub mutants are impaired in dynamic changes of histone H2B monoubiquitination at several loci of down-regulated genes. Taken together, these data establish that the regulation of cuticle composition involves chromatin remodeling by H2B monoubiquitination.

  3. Flowering-Related RING Protein 1 (FRRP1) Regulates Flowering Time and Yield Potential by Affecting Histone H2B Monoubiquitination in Rice (Oryza Sativa). (United States)

    Du, Yiwei; He, Wei; Deng, Changwang; Chen, Xi; Gou, Lanming; Zhu, Fugui; Guo, Wei; Zhang, Jianfu; Wang, Tao


    Flowering time is a critical trait for crops cultivated under various temperature/photoperiod conditions around the world. To understand better the flowering time of rice, we used the vector pTCK303 to produce several lines of RNAi knockdown transgenic rice and investigated their flowering times and other agronomic traits. Among them, the heading date of FRRP1-RNAi knockdown transgenic rice was 23-26 days earlier than that of wild-type plants. FRRP1 is a novel rice gene that encodes a C3HC4-type Really Interesting Novel Gene (RING) finger domain protein. In addition to the early flowering time, FRRP1-RNAi knockdown transgenic rice caused changes on an array of agronomic traits, including plant height, panicle length and grain length. We analyzed the expression of some key genes associated with the flowering time and other agronomic traits in the FRRP1-RNAi knockdown lines and compared with that in wild-type lines. The expression of Hd3a increased significantly, which was the key factor in the early flowering time. Further experiments showed that the level of histone H2B monoubiquitination (H2Bub1) was noticeably reduced in the FRRP1-RNAi knockdown transgenic rice lines compared with wild-type plants and MBP-FRRP1-F1 was capable of self-ubiquitination. The results indicate that Flowering Related RING Protein 1 (FRRP1) is involved in histone H2B monoubiquitination and suggest that FRRP1 functions as an E3 ligase in vivo and in vitro. In conclusion, FRRP1 probably regulates flowering time and yield potential in rice by affecting histone H2B monoubiquitination, which leads to changes in gene expression in multiple processes.

  4. Histone H2B ubiquitylation represses gametogenesis by opposing RSC-dependent chromatin remodeling at the ste11 master regulator locus. (United States)

    Materne, Philippe; Vázquez, Enrique; Sánchez, Mar; Yague-Sanz, Carlo; Anandhakumar, Jayamani; Migeot, Valerie; Antequera, Francisco; Hermand, Damien


    In fission yeast, the ste11 gene encodes the master regulator initiating the switch from vegetative growth to gametogenesis. In a previous paper, we showed that the methylation of H3K4 and consequent promoter nucleosome deacetylation repress ste11 induction and cell differentiation (Materne et al., 2015) but the regulatory steps remain poorly understood. Here we report a genetic screen that highlighted H2B deubiquitylation and the RSC remodeling complex as activators of ste11 expression. Mechanistic analyses revealed more complex, opposite roles of H2Bubi at the promoter where it represses expression, and over the transcribed region where it sustains it. By promoting H3K4 methylation at the promoter, H2Bubi initiates the deacetylation process, which decreases chromatin remodeling by RSC. Upon induction, this process is reversed and efficient NDR (nucleosome depleted region) formation leads to high expression. Therefore, H2Bubi represses gametogenesis by opposing the recruitment of RSC at the promoter of the master regulator ste11 gene.

  5. A positive feedback loop links opposing functions of P-TEFb/Cdk9 and histone H2B ubiquitylation to regulate transcript elongation in fission yeast.

    Directory of Open Access Journals (Sweden)

    Miriam Sansó

    Full Text Available Transcript elongation by RNA polymerase II (RNAPII is accompanied by conserved patterns of histone modification. Whereas histone modifications have established roles in transcription initiation, their functions during elongation are not understood. Mono-ubiquitylation of histone H2B (H2Bub1 plays a key role in coordinating co-transcriptional histone modification by promoting site-specific methylation of histone H3. H2Bub1 also regulates gene expression through an unidentified, methylation-independent mechanism. Here we reveal bidirectional communication between H2Bub1 and Cdk9, the ortholog of metazoan positive transcription elongation factor b (P-TEFb, in the fission yeast Schizosaccharomyces pombe. Chemical and classical genetic analyses indicate that lowering Cdk9 activity or preventing phosphorylation of its substrate, the transcription processivity factor Spt5, reduces H2Bub1 in vivo. Conversely, mutations in the H2Bub1 pathway impair Cdk9 recruitment to chromatin and decrease Spt5 phosphorylation. Moreover, an Spt5 phosphorylation-site mutation, combined with deletion of the histone H3 Lys4 methyltransferase Set1, phenocopies morphologic and growth defects due to H2Bub1 loss, suggesting independent, partially redundant roles for Cdk9 and Set1 downstream of H2Bub1. Surprisingly, mutation of the histone H2B ubiquitin-acceptor residue relaxes the Cdk9 activity requirement in vivo, and cdk9 mutations suppress cell-morphology defects in H2Bub1-deficient strains. Genome-wide analyses by chromatin immunoprecipitation also demonstrate opposing effects of Cdk9 and H2Bub1 on distribution of transcribing RNAPII. Therefore, whereas mutual dependence of H2Bub1 and Spt5 phosphorylation indicates positive feedback, mutual suppression by cdk9 and H2Bub1-pathway mutations suggests antagonistic functions that must be kept in balance to regulate elongation. Loss of H2Bub1 disrupts that balance and leads to deranged gene expression and aberrant cell

  6. Substrate Recognition of Histone H2B by DUBm (United States)

    Henderson, Elizabeth; Berndsen, Christopher; Wolberger, Cynthia


    The SAGA complex is a transcriptional coactivator that regulates gene expression in eukaryotes via histone acetylation and deubiquitination, which are crucial for transcription. Our lab is investigating the SAGA-dependent deubiquitination of histone H2B. The deubiquitinating module (DUBm) of SAGA is comprised of a ubiquitin-specific protease, Ubp8, and three other proteins. It is known that Ubp8 cleaves ubiquitin from histone H2B, however, the specific way in which the enzyme binds to the substrate remains elusive. In order to unravel this mechanism, we attempted to determine the crystal structure of the substrate binding complex. We obtained this substrate by exploiting the techniques of intein chemistry to artificially ubiquitinate a histone H2B peptide, which we then co-crystallized with DUBm. Additionally, we synthesized Ub-K63R-linked chains and Ub-K48-linked chains and co-crystallized them with DUBm.

  7. Histone H2B-IFI16 Recognition of Nuclear Herpesviral Genome Induces Cytoplasmic Interferon-β Responses (United States)

    Iqbal, Jawed; Ansari, Mairaj Ahmed; Kumar, Binod; Dutta, Dipanjan; Roy, Arunava; Chikoti, Leela; Pisano, Gina; Dutta, Sujoy; Veettil, Mohanan Valiya; Chandran, Bala


    IFI16 (gamma-interferon-inducible protein 16), a predominantly nuclear protein involved in transcriptional regulation, also functions as an innate immune response DNA sensor and induces the IL-1β and antiviral type-1 interferon-β (IFN-β) cytokines. We have shown that IFI16, in association with BRCA1, functions as a sequence independent nuclear sensor of episomal dsDNA genomes of KSHV, EBV and HSV-1. Recognition of these herpesvirus genomes resulted in IFI16 acetylation, BRCA1-IFI16-ASC-procaspase-1 inflammasome formation, cytoplasmic translocation, and IL-1β generation. Acetylated IFI16 also interacted with cytoplasmic STING and induced IFN-β. However, the identity of IFI16 associated nuclear proteins involved in STING activation and the mechanism is not known. Mass spectrometry of proteins precipitated by anti-IFI16 antibodies from uninfected endothelial cell nuclear lysate revealed that histone H2B interacts with IFI16. Single and double proximity ligation microscopy, immunoprecipitation, EdU-genome labeled virus infection, and chromatin immunoprecipitation studies demonstrated that H2B is associated with IFI16 and BRCA1 in the nucleus in physiological conditions. De novo KSHV and HSV-1 infection as well as latent KSHV and EBV infection induces the cytoplasmic distribution of H2B-IFI16, H2B-BRCA1 and IFI16-ASC complexes. Vaccinia virus (dsDNA) cytoplasmic replication didn’t induce the redistribution of nuclear H2B-IFI16 or H2B into the cytoplasm. H2B is critical in KSHV and HSV-1 genome recognition by IFI16 during de novo infection. Viral genome sensing by IFI16-H2B-BRCA1 leads to BRCA1 dependent recruitment of p300, and acetylation of H2B and IFI16. BRCA1 knockdown or inhibition of p300 abrogated the acetylation of H2B-IFI16 or H2B. Ran-GTP protein mediated the translocation of acetylated H2B and IFI16 to the cytoplasm along with BRCA1 that is independent of IFI16-ASC inflammasome. ASC knockdown didn’t affect the acetylation of H2B, its cytoplasmic

  8. 78 FR 19098 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program; Delay of Effective Date (United States)


    ... in Occupations Other Than Agriculture or Registered Nursing in the United States (H-2B Workers), and... skill level in the area of intended employment. Pursuant to that now- vacated regulation, the...

  9. MAPKs and Mst1/Caspase-3 pathways contribute to H2B phosphorylation during UVB-induced apoptosis

    Institute of Scientific and Technical Information of China (English)


    Apoptosis is a highly coordinated or programmed cell suicide mechanism in eukaryotes.Histone modification is associated with nuclear events in apoptotic cells.Specifically H2B phosphorylation at serine 14 (Ser14) catalyzed by Mst1 kinase has been linked to chromatin condensation during apoptosis.We report that activation of MAPKs (ERK1/2,JNK1/2 and p38) together with Mst1 and caspase-3 is required for phosphorylation of H2B (Ser14) during ultraviolet B light (UVB)-induced apoptosis.UVB can trigger activation of MAPKs and induce H2B phosphorylation at Ser14 but not acetylation in a time-dependent manner.Inhibition of ERK1/2,JNK1/2 or p38 activity blocked H2B phosphorylation (Ser14).Furthermore,caspase-3 was activated by UVB to regulate Mst1 activity,which phosphorylates H2B at Ser14,leading to chromatin condensation.Full inhibition of caspase-3 activity reduced Mst1 activation and partially inhibited H2B phosphorylation (Ser14),but ERK1/2,JNK1/2 and p38 activities were not affected.Taken together,these data revealed that H2B phosphorylation is regulated by both MAPKs and caspase-3/Mst1 pathways during UVB-induced apoptosis.

  10. FACT Disrupts Nucleosome Structure by Binding H2A-H2B with Conserved Peptide Motifs. (United States)

    Kemble, David J; McCullough, Laura L; Whitby, Frank G; Formosa, Tim; Hill, Christopher P


    FACT, a heterodimer of Spt16 and Pob3, is an essential histone chaperone. We show that the H2A-H2B binding activity that is central to FACT function resides in short acidic regions near the C termini of each subunit. Mutations throughout these regions affect binding and cause correlated phenotypes that range from mild to lethal, with the largest individual contributions unexpectedly coming from an aromatic residue and a nearby carboxylate residue within each domain. Spt16 and Pob3 bind overlapping sites on H2A-H2B, and Spt16-Pob3 heterodimers simultaneously bind two H2A-H2B dimers, the same stoichiometry as the components of a nucleosome. An Spt16:H2A-H2B crystal structure explains the biochemical and genetic data, provides a model for Pob3 binding, and implies a mechanism for FACT reorganization that we confirm biochemically. Moreover, unexpected similarity to binding of ANP32E and Swr1 with H2A.Z-H2B reveals that diverse H2A-H2B chaperones use common mechanisms of histone binding and regulating nucleosome functions.

  11. Genome-wide function of H2B ubiquitylation in promoter and genic regions. (United States)

    Batta, Kiran; Zhang, Zhenhai; Yen, Kuangyu; Goffman, David B; Pugh, B Franklin


    Nucleosomal organization in and around genes may contribute substantially to transcriptional regulation. The contribution of histone modifications to genome-wide nucleosomal organization has not been systematically evaluated. In the present study, we examine the role of H2BK123 ubiquitylation, a key regulator of several histone modifications, on nucleosomal organization at promoter, genic, and transcription termination regions in Saccharomyces cerevisiae. Using high-resolution MNase chromatin immunoprecipitation and sequencing (ChIP-seq), we map nucleosome positioning and occupancy in mutants of the H2BK123 ubiquitylation pathway. We found that H2B ubiquitylation-mediated nucleosome formation and/or stability inhibits the assembly of the transcription machinery at normally quiescent promoters, whereas ubiquitylation within highly active gene bodies promotes transcription elongation. This regulation does not proceed through ubiquitylation-regulated histone marks at H3K4, K36, and K79. Our findings suggest that mechanistically similar functions of H2B ubiquitylation (nucleosome assembly) elicit different functional outcomes on genes depending on its positional context in promoters (repressive) versus transcribed regions (activating).

  12. Nucleosome adaptability conferred by sequence and structural variations in histone H2A-H2B dimers. (United States)

    Shaytan, Alexey K; Landsman, David; Panchenko, Anna R


    Nucleosome variability is essential for their functions in compacting the chromatin structure and regulation of transcription, replication and cell reprogramming. The DNA molecule in nucleosomes is wrapped around an octamer composed of four types of core histones (H3, H4, H2A, H2B). Nucleosomes represent dynamic entities and may change their conformation, stability and binding properties by employing different sets of histone variants or by becoming post-translationally modified. There are many variants of histones H2A and H2B. Specific H2A and H2B variants may preferentially associate with each other resulting in different combinations of variants and leading to the increased combinatorial complexity of nucleosomes. In addition, the H2A-H2B dimer can be recognized and substituted by chaperones/remodelers as a distinct unit, can assemble independently and is stable during nucleosome unwinding. In this review we discuss how sequence and structural variations in H2A-H2B dimers may provide necessary complexity and confer the nucleosome functional variability.

  13. File list: His.PSC.50.H2B.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.PSC.50.H2B.AllCell mm9 Histone H2B Pluripotent stem cell SRX1034714,SRX1034721,...SRX1034715,SRX1034720 ...

  14. 77 FR 28764 - Temporary Non-agricultural Employment of H-2B Aliens in the United States (United States)


    ... H-2B Aliens in the United States AGENCY: Employment and Training Administration, Labor. ] ACTION... Aliens in the United States, published February 21, 2012 (the 2012 H-2B Final Rule). The 2012 H-2B...

  15. (Ubi)quitin' the h2bit: recent insights into the roles of H2B ubiquitylation in DNA replication and transcription. (United States)

    Wright, Duncan E; Kao, Cheng-Fu


    The reversible ubiquitylation of histone H2B has long been known to regulate gene transcription, and is now understood to modulate DNA replication as well. In this review, we describe how recent, genome-wide analyses have demonstrated that this histone mark has further reaching effects on transcription and replication than once thought. We also consider the ongoing efforts to elucidate the molecular mechanisms by which H2B ubiquitylation affects processes on the DNA template, and outline the various hypothetical scenarios.

  16. Genes involved in protein metabolism of the probiotic lactic acid bacterium Lactobacillus delbrueckii UFV H2b20. (United States)

    Do Carmo, A P; da Silva, D F; De Oliveira, M N V; Borges, A C; De Carvalho, A F; De Moraes, C A


    A basic requirement for the prediction of the potential use of lactic acid bacteria (LAB) in the dairy industry is the identification of specific genes involved in flavour-forming pathways. The probiotic Lactobacillus delbrueckii UFV H2b20 was submitted to a genetic characterisation and phylogenetic analysis of genes involved in protein catabolism. Eight genes belonging to this system were identified, which possess a closely phylogenetic relationship to NCFM strains representative, as it was demonstrated for oppC and oppBII, encoding oligopeptide transport system components. PepC, PepN, and PepX might be essential for growth of LAB, probiotic or not, since the correspondent genes are always present, including in L. delbrueckii UFV H2b20 genome. For pepX gene, a probable link between carbohydrate catabolism and PepX expression may exists, where it is regulated by PepR1/CcpA-like, a common feature between Lactobacillus strains and also in L. delbrueckii UFV H2b20. The well conserved evolutionary history of the ilvE gene is evidence that the pathways leading to branched-chain amino acid degradation, such as isoleucine and valine, are similar among L. delbrueckii subsp. bulgaricus strains and L. delbrueckii UFV H2b20. Thus, the involvement of succinate in flavour formation can be attributed to IlvE activity. The presence of aminopeptidase G in L. delbrueckii UFV H2b20 genome, which is absent in several strains, might improve the proteolytic activity and effectiveness. The nucleotide sequence encoding PepG revealed that it is a cysteine endopeptidase, belonging to Peptidase C1 superfamily; sequence analysis showed 99% identity with L. delbrueckii subsp. bulgaricus ATCC 11842 pepG, whereas protein sequence analysis revealed 100% similarity with PepG from the same organism. The present study proposes a schematic model to explain how the proteolytic system of the probiotic L. delbrueckii UFV H2b20 works, based on the components identified so far.

  17. Sperm nuclear histone H2B: correlation with sperm DNA denaturation and DNA stainability

    Institute of Scientific and Technical Information of China (English)

    Armand Zini; Xiaoyang Zhang; Maria San Gabriel


    Aim: To examine the relationship between sperm DNA damage and sperm nuclear histone (H2B) staining. Methods:We evaluated sperm samples from 14 consecutive asthenoteratozoospermic infertile men and six consecutive fertile controls. Sperm nuclear histone (H2B) staining and sperm chromatin integrity (assessed by sperm chromatin structure assay and expressed using the percentage of (I) DNA fragmentation index [%DFI] and (ii) high DNA stainability [%HDS)]) were evaluated. Results: Histone H2B immunocytochemistry demonstrated two nuclear staining patterns: (I) focal punctate staining; and (ii) diffuse staining. Infertile men had a higher mean percentage of spermatozoa exhibiting diffuse H2B staining than did fertile men (7.7% ± 4.6% vs. 1.6% ± 1.2%, respectively, P < 0.01). We observed significant relationships between the proportion of spermatozoa with diffuse nuclear histone staining and both sperm %DFI (r= 0.63, P < 0.01) and sperm %HDS (r= 0.63, P < 0.01). Conclusion: The data demonstrate that infertile men have a higher proportion of spermatozoa with diffuse histone H2B than do fertile men and suggest that sperm DNA damage might, at least in part, be due to abnormally high histone H2B levels.

  18. 77 FR 24225 - Information Collection Approval; Temporary Non-Agricultural Employment of H-2B Aliens in the... (United States)


    ... of H-2B Aliens in the United States AGENCY: Employment and Training Administration, Department of... Employment of H-2B Aliens in the United States; Final Rule. See 77 FR 10038, Feb. 21, 2012. DATES: On April...

  19. Histone crosstalk directed by H2B ubiquitination is required for chromatin boundary integrity.

    Directory of Open Access Journals (Sweden)

    Meiji Kit-Wan Ma


    Full Text Available Genomic maps of chromatin modifications have provided evidence for the partitioning of genomes into domains of distinct chromatin states, which assist coordinated gene regulation. The maintenance of chromatin domain integrity can require the setting of boundaries. The HS4 insulator element marks the 3' boundary of a heterochromatin region located upstream of the chicken β-globin gene cluster. Here we show that HS4 recruits the E3 ligase RNF20/BRE1A to mediate H2B mono-ubiquitination (H2Bub1 at this insulator. Knockdown experiments show that RNF20 is required for H2Bub1 and processive H3K4 methylation. Depletion of RNF20 results in a collapse of the active histone modification signature at the HS4 chromatin boundary, where H2Bub1, H3K4 methylation, and hyperacetylation of H3, H4, and H2A.Z are rapidly lost. A remarkably similar set of events occurs at the HSA/HSB regulatory elements of the FOLR1 gene, which mark the 5' boundary of the same heterochromatin region. We find that persistent H2Bub1 at the HSA/HSB and HS4 elements is required for chromatin boundary integrity. The loss of boundary function leads to the sequential spreading of H3K9me2, H3K9me3, and H4K20me3 over the entire 50 kb FOLR1 and β-globin region and silencing of FOLR1 expression. These findings show that the HSA/HSB and HS4 boundary elements direct a cascade of active histone modifications that defend the FOLR1 and β-globin gene loci from the pervasive encroachment of an adjacent heterochromatin domain. We propose that many gene loci employ H2Bub1-dependent boundaries to prevent heterochromatin spreading.

  20. 76 FR 3451 - Wage Methodology for the Temporary Non-agricultural Employment H-2B Program (United States)


    ... H- 2B program and the optional use of SCA and DBA wages. Comit de Apoyo a los Trabajadores Agricolas... business advocates, business associations, law firms, government agencies, including the Chief Counsel for the Office of Advocacy of the Small Business Association (Chief Counsel for Advocacy, SBA),\\3\\...

  1. Flexibility in crosstalk between H2B ubiquitination and H3 methylation in vivo

    NARCIS (Netherlands)

    Vlaming, Hanneke; van Welsem, Tibor; de Graaf, Erik L; Ontoso, David; Altelaar, A F Maarten; San-Segundo, Pedro A; Heck, Albert J R; van Leeuwen, Fred


    Histone H2B ubiquitination is a dynamic modification that promotes methylation of histone H3K79 and H3K4. This crosstalk is important for the DNA damage response and has been implicated in cancer. Here, we show that in engineered yeast strains, ubiquitins tethered to every nucleosome promote H3K79 a

  2. Flexibility in crosstalk between H2B ubiquitination and H3 methylation in vivo (Corrigendum)

    NARCIS (Netherlands)

    Vlaming, Hanneke; van Welsem, Tibor; de Graaf, Erik L; Ontoso, David; Altelaar, A F Maarten; San-Segundo, Pedro A; Heck, Albert J R; van Leeuwen, Fred


    Histone H2B ubiquitination is a dynamic modification that promotes methylation of histone H3K79 and H3K4. This crosstalk is important for the DNA damage response and has been implicated in cancer. Here, we show that in engineered yeast strains, ubiquitins tethered to every nucleosome promote H3K79 a

  3. Histone H2A and H2B Deubiquitinase in Developmental Disease and Cancer

    Directory of Open Access Journals (Sweden)

    Demeng Chen


    Full Text Available Histone H2A and H2B ubiquitination represents a widely used mechanism for a variety of regulatory transcriptional programs. In this review, structural and functional studies of histone H2A and histone H2B deubiquitinase (DUB, DUB including 2A-DUB, BRCA1-associated protein-1, USP3, UBP8, and USP16, and their role in developmental disease and carcinogenesis were recapitulated. Also the progress in developing small molecular inhibitors targeting DUBs and their application in colon cancer, B-cell lymphoma, and multiple myeloma were summarized. Overall, the study seek to strengthen the understanding on how these DUBs contribute to normal and malignant tissue development thus aiding in improving the design of therapeutic strategies used for diagnosis and prognosis of the disease.

  4. Decreased H2B monoubiquitination and overexpression of ubiquitin-specific protease enzyme 22 in malignant colon carcinoma. (United States)

    Wang, Zijing; Zhu, Linlin; Guo, Tianjiao; Wang, Yiping; Yang, Jinlin


    This study aimed to evaluate the expression of H2B monoubiquitination enzyme (uH2B) and ubiquitin-specific protease enzyme 22 (USP22) in colon carcinoma and establish a correlation between the expression of these enzymes and clinicopathological parameters. The modification levels of uH2B and USP22 in 20 noncancerous and 129 cancerous colon samples were studied by immunohistochemistry. We used a dual-rated semiquantitative method to classify the expression according to 3 levels and analyzed these results. uH2B was abundant in the normal colon epithelium, but its expression was decreased in colon cancers (P colon carcinoma was higher than that in normal tissues (P = .007) and negatively correlated with the degree of differentiation (P = .006), invasion (P = .025), lymph node metastasis (P = .026), and tumor stage (P = .044). uH2B and USP22 expression negatively correlated (r = -0.401, P colon cancer, indicating that uH2B may play an important inhibitory role in carcinogenesis. Increased USP22 expression in colon cancer correlated with reduced uH2B expression, and this expression pattern may contribute to tumor progression.

  5. Detection of histone acetylation levels in the dorsal hippocampus reveals early tagging on specific residues of H2B and H4 histones in response to learning. (United States)

    Bousiges, Olivier; Neidl, Romain; Majchrzak, Monique; Muller, Marc-Antoine; Barbelivien, Alexandra; Pereira de Vasconcelos, Anne; Schneider, Anne; Loeffler, Jean-Philippe; Cassel, Jean-Christophe; Boutillier, Anne-Laurence


    The recent literature provides evidence that epigenetic mechanisms such as DNA methylation and histone modification are crucial to gene transcription linked to synaptic plasticity in the mammalian brain--notably in the hippocampus--and memory formation. We measured global histone acetylation levels in the rat hippocampus at an early stage of spatial or fear memory formation. We found that H3, H4 and H2B underwent differential acetylation at specific sites depending on whether rats had been exposed to the context of a task without having to learn or had to learn about a place or fear therein: H3K9K14 acetylation was mostly responsive to any experimental conditions compared to naive animals, whereas H2B N-terminus and H4K12 acetylations were mostly associated with memory for either spatial or fear learning. Altogether, these data suggest that behavior/experience-dependent changes differently regulate specific acetylation modifications of histones in the hippocampus, depending on whether a memory trace is established or not: tagging of H3K9K14 could be associated with perception/processing of testing-related manipulations and context, thereby enhancing chromatin accessibility, while tagging of H2B N-terminus tail and H4K12 could be more closely associated with the formation of memories requiring an engagement of the hippocampus.

  6. Detection of histone acetylation levels in the dorsal hippocampus reveals early tagging on specific residues of H2B and H4 histones in response to learning.

    Directory of Open Access Journals (Sweden)

    Olivier Bousiges

    Full Text Available The recent literature provides evidence that epigenetic mechanisms such as DNA methylation and histone modification are crucial to gene transcription linked to synaptic plasticity in the mammalian brain--notably in the hippocampus--and memory formation. We measured global histone acetylation levels in the rat hippocampus at an early stage of spatial or fear memory formation. We found that H3, H4 and H2B underwent differential acetylation at specific sites depending on whether rats had been exposed to the context of a task without having to learn or had to learn about a place or fear therein: H3K9K14 acetylation was mostly responsive to any experimental conditions compared to naive animals, whereas H2B N-terminus and H4K12 acetylations were mostly associated with memory for either spatial or fear learning. Altogether, these data suggest that behavior/experience-dependent changes differently regulate specific acetylation modifications of histones in the hippocampus, depending on whether a memory trace is established or not: tagging of H3K9K14 could be associated with perception/processing of testing-related manipulations and context, thereby enhancing chromatin accessibility, while tagging of H2B N-terminus tail and H4K12 could be more closely associated with the formation of memories requiring an engagement of the hippocampus.

  7. 77 FR 10037 - Temporary Non-Agricultural Employment of H-2B Aliens in the United States (United States)


    ... Trabajadores Agricolas (CATA) v. Solis, Civil No. 2:09-cv-240-LP, 2010 WL 3431761 (E.D. Pa. Aug. 30, 2010..., including small business employers, U.S. and H-2B workers, worker advocacy groups, State Workforce...

  8. Resveratrol induces cellular senescence with attenuated mono-ubiquitination of histone H2B in glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Zhen; Xu, Michael S.; Barnett, Tamara L. [Nevada Cancer Institute, Las Vegas, NV 89135 (United States); Xu, C. Wilson, E-mail: [Nevada Cancer Institute, Las Vegas, NV 89135 (United States)


    Research highlights: {yields} Resveratrol induces cellular senescence in glioma cell. {yields} Resveratrol inhibits mono-ubiquitination of histone H2B at K120. {yields} Depletion of RNF20, phenocopies the inhibitory effects of resveratrol. {yields} Mono-ubiquitination of histone H2B at K120 is a novel target of resveratrol. {yields} RNF20 inhibits cellular senescence in proliferating glioma cells. -- Abstract: Resveratrol (3,4',5-trihydroxy-trans-stilbene), a polyphenol naturally occurring in grapes and other plants, has cancer chemo-preventive effects and therapeutic potential. Although resveratrol modulates multiple pathways in tumor cells, how resveratrol or its affected pathways converge on chromatin to mediate its effects is not known. Using glioma cells as a model, we showed here that resveratrol inhibited cell proliferation and induced cellular hypertrophy by transforming spindle-shaped cells to enlarged, irregular and flatten-shaped ones. We further showed that resveratrol-induced hypertrophic cells expressed senescence-associated-{beta}-galactosidase, suggesting that resveratrol-induced cellular senescence in glioma cells. Consistent with these observations, we demonstrated that resveratrol inhibited clonogenic efficiencies in vitro and tumor growth in a xenograft model. Furthermore, we found that acute treatment of resveratrol inhibited mono-ubiquitination of histone H2B at K120 (uH2B) in breast, prostate, pancreatic, lung, brain tumor cells as well as primary human cells. Chronic treatment with low doses of resveratrol also inhibited uH2B in the resveratrol-induced senescent glioma cells. Moreover, we showed that depletion of RNF20, a ubiquitin ligase of histone H2B, inhibited uH2B and induced cellular senescence in glioma cells in vitro, thereby recapitulated the effects of resveratrol. Taken together, our results suggest that uH2B is a novel direct or indirect chromatin target of resveratrol and RNF20 plays an important role in inhibiting cellular

  9. RNF20 Links Histone H2B Ubiquitylation with Inflammation and Inflammation-Associated Cancer (United States)

    Tarcic, Ohad; Pateras, Ioannis S.; Cooks, Tomer; Shema, Efrat; Kanterman, Julia; Ashkenazi, Hadas; Boocholez, Hana; Hubert, Ayala; Rotkopf, Ron; Baniyash, Michal; Pikarsky, Eli; Gorgoulis, Vassilis G.; Oren, Moshe


    Summary Factors linking inflammation and cancer are of great interest. We now report that the chromatin-targeting E3 ubiquitin ligase RNF20/RNF40, driving histone H2B monoubiquitylation (H2Bub1), modulates inflammation and inflammation-associated cancer in mice and humans. Downregulation of RNF20 and H2Bub1 favors recruitment of p65-containing nuclear factor κB (NF-κB) dimers over repressive p50 homodimers and decreases the heterochromatin mark H3K9me3 on a subset of NF-κB target genes to augment their transcription. Concordantly, RNF20+/− mice are predisposed to acute and chronic colonic inflammation and inflammation-associated colorectal cancer, with excessive myeloid-derived suppressor cells (MDSCs) that may quench antitumoral T cell activity. Notably, colons of human ulcerative colitis patients, as well as colorectal tumors, reveal downregulation of RNF20/RNF40 and H2Bub1 in both epithelium and stroma, supporting the clinical relevance of our tissue culture and mouse model findings. PMID:26854224

  10. RNF20 Links Histone H2B Ubiquitylation with Inflammation and Inflammation-Associated Cancer

    Directory of Open Access Journals (Sweden)

    Ohad Tarcic


    Full Text Available Factors linking inflammation and cancer are of great interest. We now report that the chromatin-targeting E3 ubiquitin ligase RNF20/RNF40, driving histone H2B monoubiquitylation (H2Bub1, modulates inflammation and inflammation-associated cancer in mice and humans. Downregulation of RNF20 and H2Bub1 favors recruitment of p65-containing nuclear factor κB (NF-κB dimers over repressive p50 homodimers and decreases the heterochromatin mark H3K9me3 on a subset of NF-κB target genes to augment their transcription. Concordantly, RNF20+/− mice are predisposed to acute and chronic colonic inflammation and inflammation-associated colorectal cancer, with excessive myeloid-derived suppressor cells (MDSCs that may quench antitumoral T cell activity. Notably, colons of human ulcerative colitis patients, as well as colorectal tumors, reveal downregulation of RNF20/RNF40 and H2Bub1 in both epithelium and stroma, supporting the clinical relevance of our tissue culture and mouse model findings.

  11. Dynamics of yeast histone H2A and H2B phosphorylation in response to a double-strand break. (United States)

    Lee, Cheng-Sheng; Lee, Kihoon; Legube, Gaëlle; Haber, James E


    In budding yeast, a single double-strand break (DSB) triggers extensive Tel1 (ATM)- and Mec1 (ATR)-dependent phosphorylation of histone H2A around the DSB, to form γ-H2AX. We describe Mec1- and Tel1-dependent phosphorylation of histone H2B at T129. γ-H2B formation is impaired by γ-H2AX and its binding partner Rad9. High-density microarray analyses show similar γ-H2AX and γ-H2B distributions, but γ-H2B is absent near telomeres. Both γ-H2AX and γ-H2B are strongly diminished over highly transcribed regions. When transcription of GAL7, GAL10 and GAL1 genes is turned off, γ-H2AX is restored within 5 min, in a Mec1-dependent manner; after reinduction of these genes, γ-H2AX is rapidly lost. Moreover, when a DSB is induced near CEN2, γ-H2AX spreads to all other pericentromeric regions, again depending on Mec1. Our data provide new insights in the function and establishment of phosphorylation events occurring on chromatin after DSB induction.

  12. Spt10 and Swi4 Control the Timing of Histone H2A/H2B Gene Activation in Budding Yeast ▿


    Eriksson, Peter R.; Ganguli, Dwaipayan; Clark, David J.


    The expression of the histone genes is regulated during the cell cycle to provide histones for nucleosome assembly during DNA replication. In budding yeast, histones H2A and H2B are expressed from divergent promoters at the HTA1-HTB1 and HTA2-HTB2 loci. Here, we show that the major activator of HTA1-HTB1 is Spt10, a sequence-specific DNA binding protein with a putative histone acetyltransferase (HAT) domain. Spt10 binds to two pairs of upstream activation sequence (UAS) elements in the HTA1-H...

  13. H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast

    LENUS (Irish Health Repository)

    Shieh, Grace S.


    Abstract Background The packaging of DNA into chromatin regulates transcription from initiation through 3\\' end processing. One aspect of transcription in which chromatin plays a poorly understood role is the co-transcriptional splicing of pre-mRNA. Results Here we provide evidence that H2B monoubiquitylation (H2BK123ub1) marks introns in Saccharomyces cerevisiae. A genome-wide map of H2BK123ub1 in this organism reveals that this modification is enriched in coding regions and that its levels peak at the transcribed regions of two characteristic subgroups of genes. First, long genes are more likely to have higher levels of H2BK123ub1, correlating with the postulated role of this modification in preventing cryptic transcription initiation in ORFs. Second, genes that are highly transcribed also have high levels of H2BK123ub1, including the ribosomal protein genes, which comprise the majority of intron-containing genes in yeast. H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3), which functionally correlates with alternative RNA splicing in humans. In addition, the deletion of genes encoding the U2 snRNP subunits, Lea1 or Msl1, in combination with an htb-K123R mutation, leads to synthetic lethality. Conclusion These data suggest that H2BK123ub1 facilitates cross talk between chromatin and pre-mRNA splicing by modulating the distribution of intronic and exonic histone modifications.

  14. 77 FR 24137 - Changes to the Labor Certification Process for the Temporary Non-Agricultural Employment of H-2B... (United States)


    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF LABOR Employment and Training Administration 20 CFR Part 655 RIN 1205-AB58 Changes to the Labor Certification Process for the Temporary Non- Agricultural Employment of H-2B Aliens in the United States; Revisions...

  15. 77 FR 16157 - Changes to the Labor Certification Process for the Temporary Non-Agricultural Employment of H-2B... (United States)


    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF LABOR Employment and Training Administration 20 CFR Part 655 RIN 1205-AB58 Changes to the Labor Certification Process for the Temporary Non- Agricultural Employment of H-2B Aliens in the United States;...

  16. 78 FR 53643 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program; Delay of Effective Date (United States)


    ... in Occupations Other Than Agriculture or Registered Nursing in the United States (H-2B Workers), and... the Occupational Employment Statistics (OES) survey contain tiers that are commensurate with the skill... question into four tiers of wages to correspond to skill levels. The court vacated 20 CFR...

  17. Enhanced stability of histone octamers from plant nucleosomes: role of H2A and H2B histones. (United States)

    Moehs, C P; Baxevanis, A D; Moudrianakis, E N; Spiker, S


    Gel filtration and sedimentation studies have previously established that the vertebrate animal core histone octamer is in equilibrium with an (H3-H4)2 tetramer and an H2A-H2B dimer [Eickbush, T. H., & Moudrianakis, E. N. (1978) Biochemistry 17, 4955-4964; Godfrey, J. E., Eickbush, T. H., & Moudrianakis, E. N. (1980) Biochemistry 19, 1339-1346]. We have investigated the core histone octamer of wheat (Triticum aestivum L.) and have found it to be much more stable than its vertebrate animal counterpart. When vertebrate animal histone octamers are subjected to gel filtration in 2 M NaCl, a trailing peak of H2A-H2B dimer can be clearly resolved from the main octamer peak. When the plant octamer is subjected to the identical procedure, there is no trailing peak of H2A-H2B dimer, but rather a single peak containing the octamer. A sampling across the octamer peak from leading to trailing edge shows no change in the ratio of H2A-H2B to (H3-H4)2. Surprisingly, the plant octamer shows the same stability at 0.6 M NaCl, a salt concentration in which the vertebrate animal octamer dissociates into dimers and tetramers. Equilibrium sedimentation data indicate that the assembly potential of the wheat histones in 2 M NaCl is very high at all protein concentrations above 0.1 mg mL-1. In order to disrupt the forces stabilizing the plant histone octamer at high histone concentrations, the concentration of NaCl must be lowered to approximately 0.3 M.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Monoassociation with Lactobacillus acidophilus UFV-H2b20 stimulates the immune defense mechanisms of germfree mice

    Directory of Open Access Journals (Sweden)

    Neumann E.


    Full Text Available Probiotics are formulations containing live microorganisms or microbial stimulants that have some beneficial influence on the maintenance of a balanced intestinal microbiota and on the resistance to infections. The search for probiotics to be used in prevention or treatment of enteric infections, as an alternative to antibiotic therapy, has gained significant impulse in the last few years. Several studies have demonstrated the beneficial effects of lactic acid bacteria in controlling infection by intestinal pathogens and in boosting the host's nonspecific immune response. Here, we studied the use of Lactobacillus acidophilus UFV-H2b20, a lactic acid bacterium isolated from a human newborn from Viçosa, Minas Gerais, Brazil, as a probiotic. A suspension containing 108 cells of Lactobacillus acidophilus UFV-H2b20 was inoculated into groups of at least five conventional and germfree Swiss mice to determine its capacity to stimulate the host mononuclear phagocytic activity. We demonstrate that this strain can survive the stressing conditions of the intestinal tract in vivo. Moreover, the monoassociation of germfree mice with this strain for seven days improved the host's macrophage phagocytic capacity, as demonstrated by the clearance of a Gram-negative bacterium inoculated intravenously. Monoassociated mice showed an undetectable number of circulating E. coli, while 0.1% of the original inoculum was still present in germfree animals. Mice treated with viable or heat-killed Lactobacillus acidophilus UFV-H2b20 presented similarly improved clearance capacity when compared with germfree controls. In addition, monoassociated mice had twice the amount of Kupffer cells, which are responsible for the clearance of circulating bacteria, compared to germfree controls. These results suggest that the L. acidophilus strain used here stimulates a nonspecific immune response and is a strong candidate to be used as a probiotic.

  19. Closely linked H2B genes in the marine copepod, Tigriopus californicus indicate a recent gene duplication or gene conversion event. (United States)

    Brown, D; Cook, A; Wagner, M; Wells, D


    Two nonallelic histone gene clusters were characterized in the marine copepod, Tigriopus californicus. The DNA sequence of one of the clusters reveals six genes in the contiguous arrangement of H2B, H1, H3, H4, H2B and H2A. The order of genes within the second cluster is H3, H4, H2B and H2A. There is no evidence for the presence of an H1 gene in this cluster. Comparison of the three copepod H2B genes reveals a high degree of similarity between the 5' upstream regions and between the amino terminal halves of the two H2B genes found within the same cluster. From these data we infer that gene duplication and/or gene conversion events occurred within this cluster in the recent past.

  20. Phosphoramidate-Supported Cp*Ir(III) Aminoborane H2 B=NR2 Complexes: Synthesis, Structure, and Solution Dynamics. (United States)

    Drover, Marcus W; Bowes, Eric G; Schafer, Laurel L; Love, Jennifer A; Weller, Andrew S


    Reaction of aminoboranes H2 B=NR2 (R=iPr or Cy) with the cationic Cp*Ir(III) phosphoramidate complex [IrCp*{κ(2) -N,O-Xyl(N)P(O)(OEt)2 }][BAr(F) 4 ] generates the aminoborane complexes [IrCp*(H){κ(1) -N-η(2) -HB-Xyl(N)P(OBHNR2 )(OEt)2 }][BAr(F) 4 ] (R=iPr or Cy) in which coordination of a P=O bond with boron weakens the B=N multiple bond. For these complexes, solution- and solid-state, as well as DFT computational techniques, have been employed to substantiate B-N bond rotation of the coordinated aminoborane.

  1. Partial characterization of ribosomal operons of Lactobacillus delbrueckii UFV H2b20 Caracterização parcial de operons ribossomais de Lactobacillus delbrueckii UFV H2b20

    Directory of Open Access Journals (Sweden)

    Juliana Teixeira de Magalhães


    Full Text Available Ribosomal operons are great tools for microbe community characterization and for microorganisms relationship study, particularly in the case of the acid lactic bacteria. The ribosomal operon of the probiotic strain Lactobacillus delbrueckii UFV H2b20 was partially characterized. A genomic library of this strain was constructed and the clones with partial ribosomal operon were sub-cloned using the shot-gun method for subsequent sequencing with the forward primer. The sequence analysis revealed that the 3' end of the rDNA 16S was following by the short spacer region 1 (16S-23S and that the 3' end of the rDNA 23S was following by the short spacer region 2 (23S-5S, which preceded the rDNA 5S. In the flanking region of the rDNA 5S gene of this operon rrn, a region encoding six tRNAs was detected.Operons ribossomais têm sido instrumentos importantes na caracterização de comunidades microbianas e no estudo de relacionamentos entre microrganismos, principalmente em bactérias do ácido láctico. Operons ribossomais da linhagem probiótica, Lactobacillus delbrueckii UFV H2b20, foram parcialmente caracterizados. Um banco genômico da linhagem foi construído e os clones, contendo parte do operon ribossomal, foram subclonados pelo método de "shot gun", para em seguida serem seqüenciados com primer "forward". As seqüências indicaram a presença da extremidade 3' do rDNA 16S seguida da região espaçadora curta 1 (16S-23S e a presença da extremidade 3' do rDNA 23S seguido da região espaçadora 2 (23S-5S, que por sua vez precedia o rDNA 5S. Adjacente ao gene rDNA 5S deste operon rrn uma região codificadora de 6 tRNAs foi detectada.

  2. Proteome Profiling of Urinary Exosomes Identifies Alpha 1-Antitrypsin and H2B1K as Diagnostic and Prognostic Biomarkers for Urothelial Carcinoma (United States)

    Lin, Shih-Yi; Chang, Chao-Hsiang; Wu, His-Chin; Lin, Ching-Chan; Chang, Kai-Po; Yang, Chi-Rei; Huang, Chi-Ping; Hsu, Wu-Huei; Chang, Chiz-Tzung; Chen, Chao-Jung


    MALDI-TOF spectrometry has not been used for urinary exosome analysis. We used it for determining UC biomarkers. From 2012 to 2015, we enrolled 129 consecutive patients with UC and 62 participants without UC. Exosomes from their urine were isolated, and analyzed through MALDI-TOF spectrometry. Immunohistochemical (IHC) analysis of another 122 UC and 26 non-UC tissues was conducted to verify the discovered biomarkers. Two peaks at m/z 5593 (fragmented peptide of alpha-1-antitrypsin; sensitivity, 50.4%; specificity, 96.9%) and m/z 5947 (fragmented peptide of histone H2B1K sensitivity, 62.0%; specificity, 92.3%) were identified as UC diagnosis exosome biomarkers. UC patients with detectable histone H2B1K showed 2.29- and 3.11-fold increased risks of recurrence and progression, respectively, compared with those with nondetectable histone H2B1K. Verification results of IHC staining revealed significantly higher expression of alpha 1-antitrypsin (p = 0.038) and H2B1K (p = 0.005) in UC tissues than in normal tissues. The expression of alpha 1-antitrypsin and H2B1K in UC tissues was significantly correlated with UC grades (p exosome proteins alpha 1-antitrypsin and histone H2B1K, which are identified through MALDI-TOF analysis, could facilitate rapid diagnosis and prognosis of UC. PMID:27686150

  3. Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation (United States)

    Li, Jasmine; Hardy, Kristine; Phetsouphanh, Chan; Tu, Wen Juan; Sutcliffe, Elissa L.; McCuaig, Robert; Sutton, Christopher R.; Zafar, Anjum; Munier, C. Mee Ling; Zaunders, John J.; Xu, Yin; Theodoratos, Angelo; Tan, Abel; Lim, Pek Siew; Knaute, Tobias; Masch, Antonia; Zerweck, Johannes; Brezar, Vedran; Milburn, Peter J.; Dunn, Jenny; Casarotto, Marco G.; Turner, Stephen J.; Seddiki, Nabila; Kelleher, Anthony D.


    ABSTRACT Memory T cells are characterized by their rapid transcriptional programs upon re-stimulation. This transcriptional memory response is facilitated by permissive chromatin, but exactly how the permissive epigenetic landscape in memory T cells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo human CD4+ T cells, here, we show that the signaling enzyme, protein kinase C theta (PKC-θ) directly relays stimulatory signals to chromatin by binding to transcriptional-memory-responsive genes to induce transcriptional activation. Flanked by permissive histone modifications, these PKC-enriched regions are significantly enriched with NF-κB motifs in ex vivo bulk and vaccinia-responsive human memory CD4+ T cells. Within the nucleus, PKC-θ catalytic activity maintains the Ser536 phosphorylation on the p65 subunit of NF-κB (also known as RelA) and can directly influence chromatin accessibility at transcriptional memory genes by regulating H2B deposition through Ser32 phosphorylation. Furthermore, using a cytoplasm-restricted PKC-θ mutant, we highlight that chromatin-anchored PKC-θ integrates activating signals at the chromatin template to elicit transcriptional memory responses in human memory T cells. PMID:27149922

  4. Dynamics of the formation and loss of boron atoms in a H2/B2H6 microwave plasma (United States)

    Duluard, C. Y.; Aubert, X.; Sadeghi, N.; Gicquel, A.


    For further improvements in doped-diamond deposition technology, an understanding of the complex chemistry in H2/CH4/B2H6 plasmas is of general importance. In this context, a H2/B2H6 plasma ignited by microwave power in a near resonant cavity at high pressure (100-200 mbar) is studied to measure the B-atom density in the ground state. The discharge is ignited in the gas mixture (0-135 ppm B2H6 in H2) by a 2.45 GHz microwave generator, leading to the formation of a hemispheric plasma core, surrounded by a faint discharge halo filling the remaining reactor volume. Measurements with both laser induced fluorescence and resonant absoption with a boron hollow cathode lamp indicate that the B-atom density is higher in the halo than in the plasma core. When the absorption line-of-sight is positioned in the halo, the absorption is so strong that the upper detection limit is reached. To understand the mechanisms of creation and loss of boron atoms, time-resolved absorption measurements have been carried out in a pulsed plasma regime (10 Hz, duty cycle 50%). The study focuses on the influence of the total pressure, the partial pressure of B2H6, as well as the source power, on the growth and decay rates of boron atoms when the plasma is turned off.

  5. Protection by Lactobacillus acidophilus UFV-H2B20 against experimental oral infection with Salmonella enterica subsp. enterica Ser. Typhimurium in gnotobiotic and conventional mice

    Directory of Open Access Journals (Sweden)

    Moura Lilian Nobre


    Full Text Available The ability of Lactobacillus acidophilus UFV-H2B20 to antagonize Salmonella enterica subsp. enterica ser. Typhimurium and to reduce the pathological consequences for the host was determining using conventional and gnotobiotic animals. Conventional NIH mice received daily by gavage a 0.1 ml suspension containing about 10(8 cfu L. acidophilus UFV-H2B20 and germfree animals received a single 0.1 ml dose. The gnotobiotic and conventional groups were infected orally with 10² and 10(5 cfu of S. Typhimurium, respectively, 7 days after the beginning of treatment. Control groups were treated with sterile saline instead of Lactobacillus. Survival data showed a protective effect against the pathogenic bacteria in both conventional and gnotobiotic Lactobacillus-treated mice. L. acidophilus UFV-H2B20 colonized the digestive tract of gnotobiotic mice and the number of viable cells ranged from 10(9 to 10(10 cfu/g of faeces. In both experimental and control gnotobiotic animals, S. Typhimurium became rapidly established at a level ranging from 10(8 to 10(10 cfu/g of faeces and remained at high levels until the animals died or were sacrificed. In conclusion, the previous treatment of mice with L. acidophilus UFV-H2B20 protects the animals against the experimental infection with S. Typhimurium but this protection was not due to the reduction of the pathogenic populations in the intestines.

  6. Neutron scattering studies of the H2a-H2b and (H3-H4)/sub 2/ histone complexes

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, R.D.


    Neutron scattering experiments have shown that both the (H3-H4)/sub 2/ and H2a-H2b histone complexes are quite asymmetric in solution. The (H3-H4)/sub 2/ tetramer is an oblate or flattened structure, with a radius of gyration almost as large as that of the core octamer. If the tetramer is primarily globular, it must have an axial ratio of about 1:5. It is more likely, however, that this asymmetry results in part from N-terminal arms that extend outward approximately within the major plane of the particle. If this is the case, less asymmetric models for the globular part of the tetramer, including a dislocated disk, can be made consistent with the scattering data. The H2a-H2b dimer, on the other hand, is an elongated structure. 48 references, 12 figures, 1 table.

  7. Estudo da resistência a antimicrobianos em Lactobacillus delbrueckii UFV H2b20 submetido a condições de estresse


    Ferreira,Alessandra Barbosa


    A resistência a antimicrobianos e o efeito de peróxido de hidrogênio sobre o crescimento em Lactobacillus delbrueckii UFV H2b20 foram estudados. Os efeitos de choque térmico, choque ácido, exposição a sais biliares e presença de peróxido de hidrogênio sobre a resistência a antimicrobianos nesta bactéria também foram investigados. A determinação do modelo de resistência, pelo método de difusão em meio sólido, indicou que L. delbrueckii UFV H2b20 apresenta resistência a vancomicina, a alguns [B...

  8. Impact of cigarette smoking on histone (H2B) to protamine ratio in human spermatozoa and its relation to sperm parameters. (United States)

    Hamad, M F; Shelko, N; Kartarius, S; Montenarh, M; Hammadeh, M E


    Smoking is strongly associated with abnormalities in histone-to-protamine transition and with alteration of protamine expression in human spermatozoa. A proper protamine to histone ratio is, however, essential for sperm chromatin maturity and DNA integrity. Alterations in these sperm nuclear proteins were observed in infertile men. The present prospective study is aimed at evaluating the possible relationship among smoking, semen quality and the histone-to-protamine transition ratio in mature spermatozoa. Histone H2B and protamine 1 (P1) and 2 (P2) were quantified using acid-urea polyacrylamide gel electrophoresis in the spermatozoa of 35 smokers and 19 non-smokers. Levels of lipid peroxidation marker malondialdehyde (MDA) were measured in seminal plasma by thiobarbituric acid assay. Cotinine concentrations were determined in seminal plasma using an enzyme-linked immunosorbent assay. Histone H2B levels in smokers (292.27 ± 58.24 ng/10(6)) were significantly higher (p = 0.001) than that of non-smokers (109.1 ± 43.70 ng/10(6)), besides, a significant difference (p > 0.0001) was found for the P1 and P2 ratio between smokers (1.71 ± 0.071) and non-smokers (1.05 ± 0.033). The H2B/(H2B+P1 + P2) ratio (0.29 ± 0.71) of smokers were significantly higher (p = sperm count, motility (p = 0.018), vitality (p = 0.009) and membrane integrity (p = 0.0001) than non-smokers. These results reveal that patients who smoke possess a higher proportion of spermatozoa with an alteration of the histone to protamine ratio than patients who do not smoke, and suggest that cigarette smoking may inversely affect male fertility.

  9. Genes involved in lactose catabolism and organic acid production during growth of Lactobacillus delbrueckii UFV H2b20 in skimmed milk. (United States)

    Do Carmo, A P; De Oliveira, M N V; Da Silva, D F; Castro, S B; Borges, A C; De Carvalho, A F; De Moraes, C A


    There are three main reasons for using lactic acid bacteria (LAB) as starter cultures in industrial food fermentation processes: food preservation due to lactic acid production; flavour formation due to a range of organic molecules derived from sugar, lipid and protein catabolism; and probiotic properties attributed to some strains of LAB, mainly of lactobacilli. The aim of this study was to identify some genes involved in lactose metabolism of the probiotic Lactobacillus delbrueckii UFV H2b20, and analyse its organic acid production during growth in skimmed milk. The following genes were identified, encoding the respective enzymes: ldh - lactate dehydrogenase, adhE - Ldb1707 acetaldehyde dehydrogenase, and ccpA-pepR1 - catabolite control protein A. It was observed that L. delbrueckii UFV H2b20 cultivated in different media has the unexpected ability to catabolyse galactose, and to produce high amounts of succinic acid, which was absent in the beginning, raising doubts about the subspecies in question. The phylogenetic analyses showed that this strain can be compared physiologically to L. delbrueckii subsp. bulgaricus and L. delbrueckii subsp. lactis, which are able to degrade lactose and can grow in milk. L. delbrueckii UFV H2b20 sequences have grouped with L. delbrueckii subsp. bulgaricus ATCC 11842 and L. delbrueckii subsp. bulgaricus ATCC BAA-365, strengthening the classification of this probiotic strain in the NCFM group proposed by a previous study. Additionally, L. delbrueckii UFV H2b20 presented an evolutionary pattern closer to that of probiotic Lactobacillus acidophilus NCFM, corroborating the suggestion that this strain might be considered as a new and unusual subspecies among L. delbrueckii subspecies, the first one identified as a probiotic. In addition, its unusual ability to metabolise galactose, which was significantly consumed in the fermentation medium, might be exploited to produce low-browning probiotic Mozzarella cheeses, a desirable property

  10. Construction of HeLa/GFP-Plk1/Cherry-H2B Cells%HeLa/GFP-Plk1/Cherry-H2B稳定细胞系的构建

    Institute of Scientific and Technical Information of China (English)

    李伟; 胥全彬; 江其生; 刘萱; 李平; 曹诚


    Objective: To construct HeLa cells available for study of localization of Polo-like kinase1(Plk1). Methods: Plk1 gene was amplified by PCR and then inserted into vector pRex-EGFP-IRES-Hygro to construct pRex-EGFP-Plk1-IRES-Hygro plasmid. Through retroviral infection, the pRex-EGFP-Plk1-IRES-Hygro and pRex-Cherry-H2B-IRES-Hygro plasmids were transfected into HeLa cells in turn to construct HeLa/GFP-Plk1/Cherry-H2B stable cells. The localization of Plk1 in different mitotic phase was observed under confocal laser scanning microscope. Results: The vector pRex-EGFP-Plk1-IRES-Hygro was verified by enzyme digestion and sequencing. In constructed HeLa/GFP-Plk1/Cherry-H2B stable cells, Plk1 was observed in kinetochores and midbody respective-ly in metaphase and telophase. Conclusion: The constructed HeLa/GFP-Plk1/Cherry-H2B stable cells will benefit the further research on the regulation mechanism of Plk1 in mitosis.%目的:构建可研究Polo样激酶1(Plk1)定位的HeLa细胞系。方法:用PCR方法扩增Plk1基因,定向克隆到pRex-EGFP-IRES-Hygro载体中,构建pRex-EGFP-Plk1-IRES-Hygro表达载体;利用逆转录病毒感染的方法,向HeLa细胞系中依次转染pRex-EGFP-Plk1-IRES-Hygro、pRex-Cherry-H2B-IRES-Hygro,构建Hela/GFP-Plk1/Cher-ry-H2B稳定细胞系;激光共聚焦显微镜观察Hela/GFP-Plk1/Cherry-H2B稳定细胞系在不同有丝细胞分裂期时Plk1的定位。结果:质粒酶切及测序证明pRex-EGFP-Plk1-IRES-Hygro载体构建正确;在Hela/GFP-Plk1/Cherry-H2B稳定细胞系有丝分裂中期和末期时,观察到Plk1分别定位于着丝粒和中间体上。结论:构建了Hela/GFP-Plk1/Cherry-H2B稳定细胞系,为研究Plk1在有丝分裂不同时期的调控机制提供了细胞模型。

  11. Molecular basis and specificity of H2A.Z-H2B recognition and deposition by the histone chaperone YL1. (United States)

    Latrick, Chrysa M; Marek, Martin; Ouararhni, Khalid; Papin, Christophe; Stoll, Isabelle; Ignatyeva, Maria; Obri, Arnaud; Ennifar, Eric; Dimitrov, Stefan; Romier, Christophe; Hamiche, Ali


    H2A.Z, a widely conserved histone variant, is evicted from chromatin by the histone chaperone ANP32E. However, to date, no deposition chaperone for H2A.Z is known in metazoans. Here, we identify YL1 as a specific H2A.Z-deposition chaperone. The 2.7-Å-resolution crystal structure of the human YL1-H2A.Z-H2B complex shows that YL1 binding, similarly to ANP32E binding, triggers an extension of the H2A.Z αC helix. The interaction with YL1 is, however, more extensive and includes both the extended acidic patch and the entire DNA-binding surface of H2A.Z-H2B. Substitution of only four amino acid residues of H2A is sufficient for the formation of an H2A.Z-like interface specifically recognized by YL1. Collectively, our data reveal the molecular basis of H2A.Z-specific recognition by YL1 and shed light on the mechanism of H2A.Z transfer to the nucleosome by the ATP-dependent chromatin-remodeling complexes SRCAP and P400-TIP60.

  12. Differential in vivo clearance and response to secondary heterologous infections by H2(b)-restricted dengue virus-specific CD8+ T cells. (United States)

    Beaumier, Coreen M; Jaiswal, Smita; West, Kim Y; Friberg, Heather; Mathew, Anuja; Rothman, Alan L


    Cytotoxic T lymphocytes (CTL) are hypothesized to play a role in clearance during primary dengue virus (DENV) infections, and contribute to immunopathology during secondary heterologous infections in humans. We previously reported skewed T-cell responses to secondary DENV infection in BALB/c (H-2(d)) mice, reproducing characteristics of human DENV infection. To set the stage for using widely available transgenic and knockout mice, we extended these studies to identify DENV-specific T-cell responses in C57BL/6 (H-2(b)) mice. We identified dominant CD8+ T-cell responses to H-2D(b)-restricted epitopes on the DENV NS4a (aa 249-265) and NS5 (aa 521-537) proteins. High frequencies of IFN-γ- and TNF-α-producing T cells directed at both epitopes were detected following primary infection with all four DENV serotypes, and were augmented by secondary DENV infections. In vivo cytotoxicity assays demonstrated rapid clearance of target cells pulsed with the NS4a peptide; in contrast, NS5 peptide-pulsed target cells were poorly cleared in vivo. These data characterize two H-2(b)-restricted T-cell epitopes displaying divergent in vivo function. These results should facilitate further studies of the in vivo effects of DENV-specific T cells, including the use of genetically modified mouse strains.

  13. Importance of electrostatic interactions in the association of intrinsically disordered histone chaperone Chz1 and histone H2A.Z-H2B.

    Directory of Open Access Journals (Sweden)

    Xiakun Chu

    Full Text Available Histone chaperones facilitate assembly and disassembly of nucleosomes. Understanding the process of how histone chaperones associate and dissociate from the histones can help clarify their roles in chromosome metabolism. Some histone chaperones are intrinsically disordered proteins (IDPs. Recent studies of IDPs revealed that the recognition of the biomolecules is realized by the flexibility and dynamics, challenging the century-old structure-function paradigm. Here we investigate the binding between intrinsically disordered chaperone Chz1 and histone variant H2A.Z-H2B by developing a structure-based coarse-grained model, in which Debye-Hückel model is implemented for describing electrostatic interactions due to highly charged characteristic of Chz1 and H2A.Z-H2B. We find that major structural changes of Chz1 only occur after the rate-limiting electrostatic dominant transition state and Chz1 undergoes folding coupled binding through two parallel pathways. Interestingly, although the electrostatic interactions stabilize bound complex and facilitate the recognition at first stage, the rate for formation of the complex is not always accelerated due to slow escape of conformations with non-native electrostatic interactions at low salt concentrations. Our studies provide an ionic-strength-controlled binding/folding mechanism, leading to a cooperative mechanism of "local collapse or trapping" and "fly-casting" together and a new understanding of the roles of electrostatic interactions in IDPs' binding.

  14. IMAC fractionation in combination with LC-MS reveals H2B and NIF-1 peptides as potential bladder cancer biomarkers. (United States)

    Frantzi, Maria; Zoidakis, Jerome; Papadopoulos, Theofilos; Zürbig, Petra; Katafigiotis, Ioannis; Stravodimos, Konstantinos; Lazaris, Andreas; Giannopoulou, Ioanna; Ploumidis, Achilles; Mischak, Harald; Mullen, William; Vlahou, Antonia


    Improvement in bladder cancer (BC) management requires more effective diagnosis and prognosis of disease recurrence and progression. Urinary biomarkers attract special interest because of the noninvasive means of urine collection. Proteomic analysis of urine entails the adoption of a fractionation methodology to reduce sample complexity. In this study, we applied immobilized metal affinity chromatography in combination with high-resolution LC-MS/MS for the discovery of native urinary peptides potentially associated with BC aggressiveness. This approach was employed toward urine samples from patients with invasive BC, noninvasive BC, and benign urogenital diseases. A total of 1845 peptides were identified, corresponding to a total of 638 precursor proteins. Specific enrichment for proteins involved in nucleosome assembly and for zinc-finger transcription factors was observed. The differential expression of two candidate biomarkers, histone H2B and NIF-1 (zinc finger 335) in BC, was verified in independent sets of urine samples by ELISA and by immunohistochemical analysis of BC tissue. The results collectively support changes in the expression of both of these proteins with tumor progression, suggesting their potential role as markers for discriminating BC stages. In addition, the data indicate a possible involvement of NIF-1 in BC progression, likely as a suppressor and through interactions with Sox9 and HoxA1.

  15. Synthetic peptide immunogens eliciting antibodies to Plasmodium falciparum sporozoite and merozoite surface antigens in H-2b and H-2k mice. (United States)

    Rzepczyk, C M; Csurhes, P A; Lord, R; Matile, H


    Peptides representing conserved (MSA2/1A and MSA2/1B) and variant (MSA2/2, MSA2/6 and MSA2/7) regions of the merozoite surface Ag 2 (MSA2) of Plasmodium falciparum (FCQ-27/PNG isolate) were coupled to either peptide NP(NANP)5NA or peptide C(NANP)6 both of which contained the core sequence (NANP)n. The coupling was done via the N-terminus of one peptide and a cysteine residue on either terminus of the other. BL/10 (H-2b) and B10.BR (H-2k) mice were immunized with these MSA2-(NANP)n conjugates. The mice were also immunized with the unconjugated MSA2 peptides and with NP(NANP)5NA and C(NANP)6. Antibody responses were evaluated by 1) ELISA, in which the MSA2 peptides and C(NANP)6 were used as Ag; 2) immunofluorescence assays (IFAT) against intact sporozoites and merozoites; and 3) immunoblotting experiments against solubilized P. falciparum blood stage proteins. High titer antibodies to (NANP)n were elicited in both BL/10 and B10.BR mice after immunization with all the conjugates except MSA2/7-(NANP)n which gave only a very limited response in B10.BR mice. These antibodies recognized unfixed sporozoites. The conjugates also elicited antibodies to MSA2 as shown by ELISA, IFAT, and immunoblotting except for mice immunized with MSA2/1B-(NANP)n where an anti-MSA2 response was only detectable by immunoblotting. Immunization with unconjugated MSA2 peptides showed that MSA2/2 was immunogenic in both BL/10 and BR.10 mice, with MSA2/6 and MSA2/7 being immunogenic only in BL/10 mice. The antibodies elicited recognized both merozoites and the MSA2 protein. However, the antibody titers were lower overall than those seen when these peptides were used in the conjugated form. No anti-MSA2 antibodies were detected after immunization with MSA2/1A and MSA2/1B. Immunization of mice with the peptide NP(NANP)5NA produced antibodies in BL/10 (H-2b) mice only, and the immunogenicity of this preparation was poor. In contrast, C(NANP)6 produced a strong antibody response in both mouse strains

  16. Reactivity of [M2 (μ-Cl)2 (cod)2 ] (M=Ir, Rh) and [Ru(Cl)2 (cod)(CH3 CN)2 ] with Na[H2 B(bt)2 ]: Formation of Agostic versus Borate Complexes. (United States)

    Bakthavachalam, K; Yuvaraj, K; Zafar, Mohammad; Ghosh, Sundargopal


    Treatment of [M2 (μ-Cl)2 (cod)2 ] (M=Ir and Rh) with Na[H2 B(bt)2 ] (cod=1,5-cyclooctadiene and bt=2-mercaptobenzothiazolyl) at low temperature led to the formation of dimetallaheterocycles [(Mcod)2 (bt)2 ], 1 and 2 (1: M=Ir and 2: M=Rh) and a borate complex [Rh(cod){κ(2) -S,S'-H2 B(bt)2 }], 3. Compounds 1 and 2 are structurally characterized metal analogues of 1,5-cyclooctadiene. Metal-metal bond distances of 3.6195(9) Å in 1 and 3.6749(9) Å in 2 are too long to consider as bonding. In an attempt to generate the Ru analogue of 1 and 2, that is [(Rucod)2 (bt)2 ], we have carried out the reaction of [Ru(Cl)2 (cod)(CH3 CN)2 ] with Na[H2 B(bt)2 ]. Interestingly, the reaction yielded agostic complexes [Ru(cod)L{κ(3) -H,S,S'-H2 B(bt)2 }], 4 and 5 (4: L=Cl; 5: L=C7 H4 NS2 ). One of the key differences between 4 and 5 is the presence of different ancillary ligands at the metal center. The natural bond orbital (NBO) analysis of 1 and 2 shows that there is four lone pairs of electrons on each metal center with a significant amount of d character. Furthermore, the electronic structures and the bonding of these complexes have been established on the ground of quantum-chemical calculations. All of the new compounds were characterized by IR, (1) H, (11) B, (13) C NMR spectroscopy, and X-ray crystallographic analysis.

  17. Two large-scale analyses of Ty1 LTR-retrotransposon de novo insertion events indicate that Ty1 targets nucleosomal DNA near the H2A/H2B interface

    Directory of Open Access Journals (Sweden)

    Bridier-Nahmias Antoine


    Full Text Available Abstract Background Over the years, a number of reports have revealed that Ty1 integration occurs in a 1-kb window upstream of Pol III-transcribed genes with an approximate 80-bp periodicity between each integration hotspot and that this targeting requires active Pol III transcription at the site of integration. However, the molecular bases of Ty1 targeting are still not understood. Findings The publications by Baller et al. and Mularoni et al. in the April issue of Genome Res. report the first high-throughput sequencing analysis of Ty1 de novo insertion events. Their observations converge to the same conclusion, that Ty1 targets a specific surface of the nucleosome at he H2A/H2B interface. Conclusion This discovery is important, and should help identifying factor(s involved in Ty1 targeting. Recent data on transposable elements and retroviruses integration site choice obtained by large-scale analyses indicate that transcription and chromatin structure play an important role in this process. The studies reported in this commentary add a new evidence of the importance of chromatin in integration selectivity that should be of interest for everyone interested in transposable elements integration.

  18. The role of MHC haplotypes H2d/H2b in mouse resistance/susceptibility to cyst formation is influenced by the lineage of infective Toxoplasma gondii strain

    Directory of Open Access Journals (Sweden)

    Marianne G. Resende


    Full Text Available Toxoplasma gondii strains displaying the Type I/III genotype are associated with acquired ocular toxoplasmosis in humans. Here, we used a mice model to characterize some immunological mechanisms involved in host resistance to infection with such strains. We have chosen the Type I/III strains D8, G2 and P-Br, which cause a chronic infection in mice that resembles human toxoplamosis. Mice deficient of molecules MyD88, IFN-gamma, and IL-12 were susceptible to all three parasite strains. This finding indicates the importance of innate mechanisms in controlling infection. On the other hand, MHC haplotype did not influenced resistance/susceptibility; since mice lineages displaying a same genetic background but different MHC haplotypes (H2b or H2d developed similar mortality and cyst numbers after infection with those strains. In contrast, the C57BL/6 genetic background, and not MHC haplotype, was critical for development of intestinal inflammation caused by any of the studied strains. Finally, regarding effector mechanisms, weobserved that B and CD8+ T lymphocytes controlled survival,whereas the inducible nitric oxide synthase influenced cyst numbers in brains of mice infected with Type I/III strains. These findings are relevant to further understanding of the immunologic mechanisms involved in host protection and pathogenesis during infection with T. gondii.Cepas de Toxoplasma gondii que apresentam o genótipo I/III são associadas a toxoplasmose ocular adquirida em humanos. No presente trabalho, nós utilizamos um modelo da doença em camundongos para caracterizar mecanismos imunológicos envolvidos na resistência do hospedeiro à infecção por aquelas cepas. Escolhemos as cepas D8, G2 e P-Br, que causam infecção crônica em camundongos, semelhante à toxoplasmose humana. Camundongos deficientes em MyD88, IFN-G e IL-12 foram susceptíveis a infecções com todas as três linhagens do parasita. Esses dados indicam a importância de mecanismos

  19. Toeplitz and composition operators on H~2 (B_n)

    Institute of Scientific and Technical Information of China (English)

    曹广福; 孙顺华


    The composition operators with closed range on H2( Bn) are characterized, and the Frcdholmness of products of Toeplitz and composition operators discussed. Moreover, using composition operators, the spectra of Toeplitz operators are studied.

  20. Autoimmune-induced preferential depletion of myelin-associated glycoprotein (MAG is genetically regulated in relapsing EAE (B6 × SJL F1 mice

    Directory of Open Access Journals (Sweden)

    Dai Rujuan


    Full Text Available Abstract Background Experimental autoimmune encephalomyelitis (EAE is commonly used to investigate mechanisms of autoimmune-mediated damage to oligodendrocytes, myelin, and axons in multiple sclerosis (MS. Four distinct autoimmune mechanisms with subsequently distinct patterns of demyelination have been recognized in acute MS lesions. EAE correlates for those distinct patterns of MS lesions are unknown. An excessive loss of myelin-associated glycoprotein (MAG, as a result of distal oligodendrogliopathy, is found exclusively in the subtype III lesion. We sought to answer if types of demyelination in acute lesions during onset and relapse of EAE can replicate the specific patterns observed in MS acute lesions. Methods In parental H-2b (C57BL/6, B6 and hybrid H-2b/s [(B6 × SJL F1] EAE mice, we examined spinal cord levels of MOG, MAG, and myelin basic protein (MBP, and compared to levels of axonal neurofilament (NF160 to assess axonal function, and levels of PARPp85 as an indicator of irreversible apoptosis. Results During disease onset, levels of MOG significantly dropped in both strains, although more profoundly in H-2b/s mice. Levels of MOG recovered in relapsing mice of both strains. Regulation of MAG was dissimilar to MOG. Modest loss of MAG was found at disease onset in both strains of mice. Unexpectedly, in relapsing H-2b/s mice, a major depletion of MAG and NF160, accompanied with sharp elevation of PARPp85 levels, was measured. PARPp85 immunoreactivity was observed in cytoplasm and nuclei of some MBP containing cells. Conclusion Taken together, our results show genetically controlled distinct patterns of MOG and MAG depletion, in MOG35–55 induced EAE in H-2b and H-2b/s mice. The data also suggest distinctive immune regulation of acute lesions that develop in relapsing compared to disease onset. A profound depletion of MAG, concomitant with marked depletion of axonal NF160, and sharp elevation of PARPp85 levels, occurred exclusively in

  1. 75 FR 61577 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program (United States)


    ... normal business hours at the Employment and Training Administration (ETA) Office of Policy Development... Agricolas (CATA) v. Solis, Civil No. 2:09-cv-240-LP, 2010 WL 3431761 (E.D. Pa. Aug. 30, 2010), ordered the... a los Trabajadores Agricolas (CATA) v. Solis, 2010 WL 3431761, at *19 n.22, which invalidated...

  2. The Histone H2B Monoubiquitination Regulatory Pathway Is Required for Differentiation of Multipotent Stem Cells

    DEFF Research Database (Denmark)

    Karpiuk, Oleksandra; Najafova, Zeynab; Kramer, Frank;


    Extensive changes in posttranslational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly und...

  3. 20 CFR 655.22 - Obligations of H-2B employers. (United States)


    ... any qualified U.S. worker regardless of race, color, national origin, age, sex, religion, handicap, or... offered wage is not based on commissions, bonuses, or other incentives, unless the employer guarantees...

  4. Menin and RNF20 recruitment is associated with dynamic histone modifications that regulate signal transducer and activator of transcription 1 (STAT1-activated transcription of the interferon regulatory factor 1 gene (IRF1

    Directory of Open Access Journals (Sweden)

    Buro Lauren J


    Full Text Available Abstract Background Signal transducer and activator of transcription (STAT activation of gene expression is both rapid and transient, and when properly executed it affects growth, differentiation, homeostasis and the immune response, but when dysregulated it contributes to human disease. Transcriptional activation is regulated by alterations to the chromatin template. However, the role of histone modification at gene loci that are activated for transcription in response to STAT signaling is poorly defined. Results Using chromatin immunoprecipitation, we profiled several histone modifications during STAT1 activation of the interferon regulatory factor 1 gene (IRF1. Methylated lysine histone proteins H3K4me2, H3K4me3, H3K79me3, H3K36me3 and monoubiquitinated histone ubH2B are dynamic and correlate with interferon (IFNγ induction of STAT1 activity. Chemical inhibition of H3K4 methylation downregulates IRF1 transcription and decreases RNA polymerase II (Pol II occupancy at the IRF1 promoter. MEN1, a component of a complex proteins associated with Set1 (COMPASS-like complex and the hBRE1 component, RNF20, are localized to IRF1 in the uninduced state and are further recruited when IRF1 is activated. RNAi-mediated depletion of RNF20 lowers both ubH2B and H3K4me3, but surprisingly, upregulates IFNγ induced IRF1 transcription. The dynamics of phosphorylation in the C-terminal domain (CTD of Pol II are disrupted during gene activation as well. Conclusions H2B monoubiquitination promotes H3K4 methylation, but the E3 ubiquitin ligase, RNF20, is repressive of inducible transcription at the IRF1 gene locus, suggesting that ubH2B can, directly or indirectly, affect Pol II CTD phosphorylation cycling to exert control on ongoing transcription.

  5. 78 FR 24047 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program, Part 2 (United States)


    ... Comit de Apoyo a los Trabajadores Agricolas v. Solis, which vacated portions of DOL's current prevailing... Department receives available for public inspection during normal business hours at the Employment and...: Kevin J. Cummings, Chief, Business and Foreign Workers Division, Office of Policy and Strategy,...

  6. 78 FR 44054 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program; Proposed Delay of... (United States)


    ... business hours at the Employment and Training Administration (ETA) Office of Policy Development and... Agricolas (CATA) v. Solis, -- F. Supp. 2d --, 2013 WL 1163426 (E.D. Pa. 2013) in which the district...

  7. 76 FR 37686 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program; Amendment of... (United States)


    ... Comit de Apoyo a los Trabajadores Agricolas (CATA) v. Solis, Civil No. 2:09-cv-240-LP (E.D. Pa.), the... also make all the comments it receives available for public inspection during normal business hours at... Department could not phase in a wage regime based upon a desire to alleviate hardship on small...

  8. 76 FR 15129 - Temporary Non-Agricultural Employment of H-2B Aliens in the United States (United States)


    ... it receives available for public inspection during normal business hours at the Employment and... the Eastern District of Pennsylvania in Comit de Apoyo a los Trabajadores Agricolas (CATA) v. Solis... representatives from business, labor and other stakeholders, as part of its annual strategic planning...

  9. 76 FR 14679 - Prevailing Wage Rates for Construction Occupations on Guam for Purposes of the H-2B Temporary... (United States)


    ... SECURITY U.S. Citizenship and Immigration Services RIN 1615-ZA98 Prevailing Wage Rates for Construction... employment will adversely affect the wages and working conditions of similarly employed U.S. workers (i.e... market test on Guam is a determination whether the wages and working conditions offered to U.S....

  10. 76 FR 45667 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program; Amendment of... (United States)


    ... (including potential economic, environmental, public health and safety effects, distributive impacts, and... the benefit of workers and that a negative impact on the employer has an immediate negative effect on... workers for its restaurant could be presented with SCA wage rates for a ``Cook I,'' ``Cook II,''...

  11. SUMO: regulating the regulator

    Directory of Open Access Journals (Sweden)

    Bossis Guillaume


    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.

  12. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre


    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...

  13. Seed dormancy cycling in Arabidopsis: chromatin remodelling and regulation of DOG1 in response to seasonal environmental signals. (United States)

    Footitt, Steven; Müller, Kerstin; Kermode, Allison R; Finch-Savage, William E


    The involvement of chromatin remodelling in dormancy cycling in the soil seed bank (SSB) is poorly understood. Natural variation between the winter and summer annual Arabidopsis ecotypes Cvi and Bur was exploited to investigate the expression of genes involved in chromatin remodelling via histone 2B (H2B) ubiquitination/de-ubiquitination and histone acetylation/deacetylation, the repressive histone methyl transferases CURLY LEAF (CLF) and SWINGER (SWN), and the gene silencing repressor ROS1 (REPRESSOR OF SILENCING1) and promoter of silencing KYP/SUVH4 (KRYPTONITE), during dormancy cycling in the SSB. ROS1 expression was positively correlated with dormancy while the reverse was observed for CLF and KYP/SUVH4. We propose ROS1 dependent repression of silencing and a sequential requirement of CLF and KYP/SUVH4 dependent gene repression and silencing for the maintenance and suppression of dormancy during dormancy cycling. Seasonal expression of H2B modifying genes was correlated negatively with temperature and positively with DOG1 expression, as were histone acetyltransferase genes, with histone deacetylases positively correlated with temperature. Changes in the histone marks H3K4me3 and H3K27me3 were seen on DOG1 (DELAY OF GERMINATION1) in Cvi during dormancy cycling. H3K4me3 activating marks remained stable along DOG1. During relief of dormancy, H3K27me3 repressive marks slowly accumulated and accelerated on exposure to light completing dormancy loss. We propose that these marks on DOG1 serve as a thermal sensing mechanism during dormancy cycling in preparation for light repression of dormancy. Overall, chromatin remodelling plays a vital role in temporal sensing through regulation of gene expression.

  14. Regulating Transplants

    Institute of Scientific and Technical Information of China (English)


    Legislation to determine brain death is viewed as essential in controlling the organ transplant industry Organ transplant represents a very sensitive and complicated issue. Experts say the temporary administrative regulations recently promulgated by the Central Government are an important step, but relevant laws and regulations must follow. Among these, the

  15. 77 FR 59670 - Electronic Filing of H-2A and H-2B Labor Certification Applications Through the iCERT Visa Portal... (United States)


    ... programs administered by the OFLC enable United States (U.S.) employers to employ foreign workers on a..., agents who are subject to the Migrant and Seasonal Agricultural Worker Protection Act must upload copies... qualified U.S. workers for a position for which certification is requested, and whether there would be...

  16. NORM regulations

    Energy Technology Data Exchange (ETDEWEB)

    Gray, P. [ed.


    The author reviews the question of regulation for naturally occuring radioactive material (NORM), and the factors that have made this a more prominent concern today. Past practices have been very relaxed, and have often involved very poor records, the involvment of contractors, and the disposition of contaminated equipment back into commercial service. The rationale behind the establishment of regulations is to provide worker protection, to exempt low risk materials, to aid in scrap recycling, to provide direction for remediation and to examine disposal options. The author reviews existing regulations at federal and state levels, impending legislation, and touches on the issue of site remediation and potential liabilities affecting the release of sites contaminated by NORM.

  17. The PAF complex and Prf1/Rtf1 delineate distinct Cdk9-dependent pathways regulating transcription elongation in fission yeast.

    Directory of Open Access Journals (Sweden)

    Jean Mbogning

    Full Text Available Cyclin-dependent kinase 9 (Cdk9 promotes elongation by RNA polymerase II (RNAPII, mRNA processing, and co-transcriptional histone modification. Cdk9 phosphorylates multiple targets, including the conserved RNAPII elongation factor Spt5 and RNAPII itself, but how these different modifications mediate Cdk9 functions is not known. Here we describe two Cdk9-dependent pathways in the fission yeast Schizosaccharomyces pombe that involve distinct targets and elicit distinct biological outcomes. Phosphorylation of Spt5 by Cdk9 creates a direct binding site for Prf1/Rtf1, a transcription regulator with functional and physical links to the Polymerase Associated Factor (PAF complex. PAF association with chromatin is also dependent on Cdk9 but involves alternate phosphoacceptor targets. Prf1 and PAF are biochemically separate in cell extracts, and genetic analyses show that Prf1 and PAF are functionally distinct and exert opposing effects on the RNAPII elongation complex. We propose that this opposition constitutes a Cdk9 auto-regulatory mechanism, such that a positive effect on elongation, driven by the PAF pathway, is kept in check by a negative effect of Prf1/Rtf1 and downstream mono-ubiquitylation of histone H2B. Thus, optimal RNAPII elongation may require balanced action of functionally distinct Cdk9 pathways.

  18. Trout Stream Special Regulations (United States)

    Minnesota Department of Natural Resources — This layer shows Minnesota trout streams that have a special regulation as described in the 2006 Minnesota Fishing Regulations. Road crossings were determined using...

  19. Hepcidin: regulation of the master iron regulator (United States)

    Rishi, Gautam; Wallace, Daniel F.; Subramaniam, V. Nathan


    Iron, an essential nutrient, is required for many diverse biological processes. The absence of a defined pathway to excrete excess iron makes it essential for the body to regulate the amount of iron absorbed; a deficiency could lead to iron deficiency and an excess to iron overload and associated disorders such as anaemia and haemochromatosis respectively. This regulation is mediated by the iron-regulatory hormone hepcidin. Hepcidin binds to the only known iron export protein, ferroportin (FPN), inducing its internalization and degradation, thus limiting the amount of iron released into the blood. The major factors that are implicated in hepcidin regulation include iron stores, hypoxia, inflammation and erythropoiesis. The present review summarizes our present knowledge about the molecular mechanisms and signalling pathways contributing to hepcidin regulation by these factors. PMID:26182354

  20. General Theories of Regulation

    NARCIS (Netherlands)

    Hertog, J.A. den


    This chapter makes a distinction between three types of theories of regulation: public interest theories, the Chicago theory of regulation and the public choice theories. The Chicago theory is mainly directed at the explanation of economic regulation; public interest theories and public choice theor

  1. Genome-wide integration on transcription factors, histone acetylation and gene expression reveals genes co-regulated by histone modification patterns.

    Directory of Open Access Journals (Sweden)

    Yayoi Natsume-Kitatani

    Full Text Available N-terminal tails of H2A, H2B, H3 and H4 histone families are subjected to posttranslational modifications that take part in transcriptional regulation mechanisms, such as transcription factor binding and gene expression. Regulation mechanisms under control of histone modification are important but remain largely unclear, despite of emerging datasets for comprehensive analysis of histone modification. In this paper, we focus on what we call genetic harmonious units (GHUs, which are co-occurring patterns among transcription factor binding, gene expression and histone modification. We present the first genome-wide approach that captures GHUs by combining ChIP-chip with microarray datasets from Saccharomyces cerevisiae. Our approach employs noise-robust soft clustering to select patterns which share the same preferences in transcription factor-binding, histone modification and gene expression, which are all currently implied to be closely correlated. The detected patterns are a well-studied acetylation of lysine 16 of H4 in glucose depletion as well as co-acetylation of five lysine residues of H3 with H4 Lys12 and H2A Lys7 responsible for ribosome biogenesis. Furthermore, our method further suggested the recognition of acetylated H4 Lys16 being crucial to histone acetyltransferase ESA1, whose essential role is still under controversy, from a microarray dataset on ESA1 and its bypass suppressor mutants. These results demonstrate that our approach allows us to provide clearer principles behind gene regulation mechanisms under histone modifications and detect GHUs further by applying to other microarray and ChIP-chip datasets. The source code of our method, which was implemented in MATLAB (, is available from the supporting page for this paper:


    Energy Technology Data Exchange (ETDEWEB)

    J. GRAF


    This paper proposes a model relationship between the operator engaged in a hazardous activity, the regulator of that activity, and the general public. The roles and responsibilities of each entity are described in a way that allows effective communication flow. The role of the regulator is developed using the steam boiler as an example of a hazard subject to regulation; however, the model applies to any regulated activity. In this model the safety analyst has the extremely important role of communicating sometimes difficult technical information to the regulator in a way that the regulator can provide credible assurance to the general public as to the adequacy of the control of the hazardous activity. The conclusion asserts that acceptance of the model, understanding of the roles and responsibilities and definition of who communicates what information to whom will mitigate frustration on the part of each of the three entities.

  3. Novel regulators of spermatogenesis. (United States)

    Fok, Kin Lam; Chen, Hao; Ruan, Ye Chun; Chan, Hsiao Chang


    Spermatogenesis is a multistep process that supports the production of millions of sperm daily. Understanding of the molecular mechanisms that regulate spermatogenesis has been a major focus for decades. Yet, the regulators involved in different cellular processes of spermatogenesis remain largely unknown. Human diseases that result in defective spermatogenesis have provided hints on the molecular mechanisms regulating this process. In this review, we have summarized recent findings on the function and signaling mechanisms of several genes that are known to be associated with disease or pathological processes, including CFTR, CD147, YWK-II and CT genes, and discuss their potential roles in regulating different processes of spermatogenesis.

  4. Regulation of SUMO Modification

    NARCIS (Netherlands)

    P.M. Knipscheer (Puck Maria)


    textabstractThe small ubiquitin related modifier SUMO is a posttranslational modifier that functions in a wide range of cellular processes like intracellular transport, cell cycle regulation, DNA repair and regulation of transcription. SUMO is an 11 kDa protein and is ligated to its target proteins

  5. Reconceptualizing Civil Regulation

    DEFF Research Database (Denmark)

    Galang, Roberto Martin; Castello, Itziar


    This article re-conceptualizes the notion of civil regulation, through an analysis of 775 projects by firms located in 21 Asian countries, wherein we map the state of civil regulation initiatives in the region. We challenge two established assumptions in the Corporate Social Responsibility litera...

  6. Plant Growth Regulators. (United States)

    Nickell, Louis G.


    Describes the effect of "plant growth regulators" on plants, such as controlling the flowering, fruit development, plant size, and increasing crop yields. Provides a list of plant growth regulators which includes their chemical, common, and trade names, as well as their different use(s). (GA)

  7. Electrical installations and regulations

    CERN Document Server

    Whitfield, J F


    Electrical Installations and Regulations focuses on the regulations that apply to electrical installations and the reasons for them. Topics covered range from electrical science to alternating and direct current supplies, as well as equipment for providing protection against excess current. Cables, wiring systems, and final subcircuits are also considered, along with earthing, discharge lighting, and testing and inspection.Comprised of 12 chapters, this book begins with an overview of electrical installation work, traits of a good electrician, and the regulations governing installations. The r

  8. Volume regulation in epithelia

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Hoffmann, Else Kay


    function of iso-osmotic fluid transport that depends on Na+ recirculation. The causative relationship is discussed for a fluid-absorbing and a fluid-secreting epithelium of which the Na+ recirculation mechanisms have been identified. A large number of transporters and ion channels involved in cell volume...... regulation are cloned. The volume-regulated anion channel (VRAC) exhibiting specific electrophysiological characteristics seems exclusive to serve cell volume regulation. This is contrary to K+ channels as well as cotransporters and exchange mechanisms that may serve both transepithelial transport and cell...

  9. Public regulators and CSR

    DEFF Research Database (Denmark)

    Buhmann, Karin


    for responsible business conduct, connecting to social expectations and bridging to public regulation. This UN guidance has had a significant bearing on how public regulators seek to influence business conduct beyond Human Rights to broader Corporate Social Responsibility (CSR) concerns. Drawing on examples...... of such public regulatory governance, this article explores and explains developments towards a juridification of CSR entailing efforts by public regulators to reach beyond jurisdictional and territorial limitations of conventional public law to address adverse effects of transnational economic activity. Through...

  10. Sport Fishing Regulations (United States)

    US Fish and Wildlife Service, Department of the Interior — The regulations for sport fishing on St. Vincent National Wildlife Refuge are outlined in this document. Fishing is only permitted from sunrise to sunset, and only...

  11. Benchmarking and Regulation

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    . The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  12. Focus on PTEN regulation

    Directory of Open Access Journals (Sweden)

    Miriam eBermudez-Brito


    Full Text Available The role of PTEN as a tumour suppressor has been for a long time attributed to its lipid phosphatase activity against PI(3,4,5P3, the phospholipid product of the class I PI3Ks. Besides its traditional role as a lipid phosphatase at the plasma membrane, a wealth of data has shown that PTEN can function independently of its phosphatase activity and that PTEN also exists and plays a role in the nucleus, in cytoplasmic organelles and extracellularly. Accumulating evidence has shed light on diverse physiological functions of PTEN which are accompanied by a complex regulation of its expression and activity. PTEN levels and function are regulated transcriptionally, post-transcriptionally and post-translationally. PTEN is also sensitive to regulation by its interacting proteins and its localization. Herein, we summarize the current knowledge on mechanisms that regulate the expression and enzymatic activity of PTEN and its role in human diseases.

  13. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    - serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...... of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume......, controlled cell death and cellular migration. Volume regulatory mechanisms has long been in focus for regulating cellular proliferation and my thesis work have been focusing on the role of Cl- channels in proliferation with specific emphasis on ICl, swell. Pharmacological blockage of the ubiquitously...

  14. Worldwide regulations for mycotoxins. (United States)

    van Egmond, Hans P


    Since the discovery of the aflatoxins in the 1960s, regulations have been established in many countries to protect the consumer from the harmful effects of mycotoxins that may contaminate foodstuffs. Various factors play a role in the decision-making process of setting limits for mycotoxins. These include scientific factors such as the availability of toxicological data, survey data, knowledge about the distribution of mycotoxins in commodities, and analytical methodology. Economical and political factors such as commercial interests and sufficiency of food supply have their impact as well. International enquiry's on existing mycotoxin legislation in foodstuffs and animal feedstuffs have been carried out several times in the 1980s and 1990s and details about tolerances, legal basis, responsible authorities, official protocols of analysis and sampling have been published. Recently a comprehensive update on worldwide regulations was published as FAO Food and Nutrition Paper 64. It appeared that at least 77 countries now have specific regulations for mycotoxins, 13 countries are known to have no specific regulations, whereas no data are available for about 50 countries, many of them in Africa. Over the years, a large diversity in tolerance levels for mycotoxins has remained. Some free trade zones (EU, MERCOSUR) are in the process of harmonizing the limits and regulations for mycotoxins in their respective member states, but it is not likely that worldwide harmonized limits for mycotoxins will soon be within reach.

  15. Collaborative Tax Regulation

    DEFF Research Database (Denmark)

    Boll, Karen


    This article shows a new form of regulation within a tax administration where tax administrators abate tax evasion by nudging and motivating consumers to only purchase services from tax compliant businesses. This indirectly closes or forces tax evading businesses to change their practices, because...... their customer bases decline to commercially non-viable levels. The analysis is framed by public governance literature and argues that the regulation is an example of collaborative or interactive governance, because the tax administrators do not regulate non-compliance directly, but activate external...... implications for how tax practitioners think about collaborative and interactive regulatory initiatives. While the tax administration in the study sees the approach as effective, the analysis shows that there are a number of caveats in relation to regularity, public listing, costs and revenue focus...

  16. Staff rules and regulations

    CERN Multimedia

    HR Department


    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: 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 ...

  17. Other-Regulation in Collaborative Groups: Implications for Regulation Quality (United States)

    Rogat, Toni Kempler; Adams-Wiggins, Karlyn R.


    The current study examines variation in other-regulation, conceptualized as efforts by one student to regulate their group's work. This study extends research which has conceptualized other-regulation as temporarily guiding others' conceptual understanding and skill development by broadening the spectrum of other-regulation to include…

  18. The Impact of Regulating Social Science Research with Biomedical Regulations (United States)

    Durosinmi, Brenda Braxton


    The Impact of Regulating Social Science Research with Biomedical Regulations Since 1974 Federal regulations have governed the use of human subjects in biomedical and social science research. The regulations are known as the Federal Policy for the Protection of Human Subjects, and often referred to as the "Common Rule" because 18 Federal…

  19. Nuclear regulation and safety

    Energy Technology Data Exchange (ETDEWEB)

    Hendrie, J.M.


    Nuclear regulation and safety are discussed from the standpoint of a hypothetical country that is in the process of introducing a nuclear power industry and setting up a regulatory system. The national policy is assumed to be in favor of nuclear power. The regulators will have responsibility for economic, reliable electric production as well as for safety. Reactor safety is divided into three parts: shut it down, keep it covered, take out the afterheat. Emergency plans also have to be provided. Ways of keeping the core covered with water are discussed. (DLC)

  20. Legislation and regulation

    Energy Technology Data Exchange (ETDEWEB)



    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 3 of the document contains some details about the Brazilian legislation and regulation, the legislative and regulatory framework, regulatory body and responsibility of the license holder.

  1. Vehicle recycling regulations

    DEFF Research Database (Denmark)

    Smink, Carla


    The number of end-of-life vehicles (ELVs) in the EU is increasing continously. Around 75 percent of an ELV are recyclable metals. The forecast growth in the number of ELVs calls for regulation that aims to minimise the environmental impact of a car. Using Denmark as an example, this article...

  2. Situated bio-regulation

    DEFF Research Database (Denmark)

    Prainsack, Barbara; Wahlberg, Ayo


    Several years ago, both authors engaged in research into bioscience and biomedical regulation in Asian countries. One of us (BP) explored why the regulatory and discursive embedding of human embryonic stem cell in Israel was much more permissive than elsewhere. The other author (AW) sought to und...

  3. Regulation of cholesterol homeostasis

    NARCIS (Netherlands)

    van der Wulp, Mariette Y. M.; Verkade, Henkjan J.; Groen, Albert K.


    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-codin

  4. Regulated Gene Therapy. (United States)

    Breger, Ludivine; Wettergren, Erika Elgstrand; Quintino, Luis; Lundberg, Cecilia


    Gene therapy represents a promising approach for the treatment of monogenic and multifactorial neurological disorders. It can be used to replace a missing gene and mutated gene or downregulate a causal gene. Despite the versatility of gene therapy, one of the main limitations lies in the irreversibility of the process: once delivered to target cells, the gene of interest is constitutively expressed and cannot be removed. Therefore, efficient, safe and long-term gene modification requires a system allowing fine control of transgene expression.Different systems have been developed over the past decades to regulate transgene expression after in vivo delivery, either at transcriptional or post-translational levels. The purpose of this chapter is to give an overview on current regulatory system used in the context of gene therapy for neurological disorders. Systems using external regulation of transgenes using antibiotics are commonly used to control either gene expression using tetracycline-controlled transcription or protein levels using destabilizing domain technology. Alternatively, specific promoters of genes that are regulated by disease mechanisms, increasing expression as the disease progresses or decreasing expression as disease regresses, are also examined. Overall, this chapter discusses advantages and drawbacks of current molecular methods for regulated gene therapy in the central nervous system.

  5. Regulating the private security industry

    CERN Document Server

    Percy, Sarah


    The under-regulation of the private security industry has increasingly become a topic of media and academic interest. This Adelphi Paper enters the debate by explaining why the industry requires further regulation, and what is wrong with the current system. It begins by briefly defining the industry and explaining the need for more effective regulation, before analysing three types of regulation: domestic, international and informal (including self-regulation).

  6. Modification of histones by sugar β-N-acetylglucosamine (GlcNAc) occurs on multiple residues, including histone H3 serine 10, and is cell cycle-regulated. (United States)

    Zhang, Suisheng; Roche, Kevin; Nasheuer, Heinz-Peter; Lowndes, Noel Francis


    The monosaccharide, β-N-acetylglucosamine (GlcNAc), can be added to the hydroxyl group of either serines or threonines to generate an O-linked β-N-acetylglucosamine (O-GlcNAc) residue (Love, D. C., and Hanover, J. A. (2005) Sci. STKE 2005 312, 1-14; Hart, G. W., Housley, M. P., and Slawson, C. (2007) Nature 446, 1017-1022). This post-translational protein modification, termed O-GlcNAcylation, is reversible, analogous to phosphorylation, and has been implicated in many cellular processes. Here, we present evidence that in human cells all four core histones of the nucleosome are substrates for this glycosylation in the relative abundance H3, H4/H2B, and H2A. Increasing the intracellular level of UDP-GlcNAc, the nucleotide sugar donor substrate for O-GlcNAcylation enhanced histone O-GlcNAcylation and partially suppressed phosphorylation of histone H3 at serine 10 (H3S10ph). Expression of recombinant H3.3 harboring an S10A mutation abrogated histone H3 O-GlcNAcylation relative to its wild-type version, consistent with H3S10 being a site of histone O-GlcNAcylation (H3S10glc). Moreover, O-GlcNAcylated histones were lost from H3S10ph immunoprecipitates, whereas immunoprecipitation of either H3K4me3 or H3K9me3 (active or inactive histone marks, respectively) resulted in co-immunoprecipitation of O-GlcNAcylated histones. We also examined histone O-GlcNAcylation during cell cycle progression. Histone O-GlcNAcylation is high in G(1) cells, declines throughout the S phase, increases again during late S/early G(2), and persists through late G(2) and mitosis. Thus, O-GlcNAcylation is a novel histone post-translational modification regulating chromatin conformation during transcription and cell cycle progression.

  7. Regulation of Meiotic Recombination

    Energy Technology Data Exchange (ETDEWEB)

    Gregory p. Copenhaver


    Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system

  8. Probiotics and Appetite Regulation

    DEFF Research Database (Denmark)

    Bjerg, Anne Toksvig

    resistance and blood lipid profile among others. Probiotics which are health promoting bacteria can potentially be used to affect the GM and thereby change metabolic outcomes of the host. Animal studies have shown associations between intake of probiotics and appetite regulation, but currently no human...... studies have investigated this effect. Supplementation with different probiotic strains have been shown to have an effect on blood lipid profiles in both animals and humans and the mechanisms behind have been studied in vitro and in rodents. The aim of the present thesis was to examine in an ex vivo...... intestine, in an animal study and in two human studies the effect of the probiotic bacteria Lactobacillus paracasei subsp. paracasei L. casei W8 (W8) on appetite regulation, blood lipids and blood fatty acids. In addition, it was investigated if W8 had an effect on the fecal microbiota of the human...

  9. Hormonal Regulators of Appetite


    Austin Juliana; Marks Daniel


    Obesity is a significant cause of morbidity and mortality worldwide. There has been a significant worsening of the obesity epidemic mainly due to alterations in dietary intake and energy expenditure. Alternatively, cachexia, or pathologic weight loss, is a significant problem for individuals with chronic disease. Despite their obvious differences, both processes involve hormones that regulate appetite. These hormones act on specific centers in the brain that affect the sensations of hunger a...

  10. Computing Borel's Regulator II

    CERN Document Server

    Choo, Zacky; Sánchez-García, Rubén J; Snaith, Victor P


    In our earlier article we described a power series formula for the Borel regulator evaluated on the odd-dimensional homology of the general linear group of a number field and, concentrating on dimension three for simplicity, described a computer algorithm which calculates the value to any chosen degree of accuracy. In this sequel we give an algorithm for the construction of the input homology classes and describe the results of one cyclotomic field computation.

  11. The regulation of hunting

    DEFF Research Database (Denmark)

    Abildtrup, Jens; Jensen, Frank


    This paper examines a tax/subsidy on hunters based on game population. The tax/subsidy is the difference between actual and optimal population multiplied by an individual, variable tax rate. The tax rate is, among other things, based on the difference between the marginal value of the game...... population to the hunter and the regulator and differences in user costs of the population. The paper shows that the population tax/subsidy secures a first-best optimum....

  12. Improving CS regulations.

    Energy Technology Data Exchange (ETDEWEB)

    Nesse, R.J.; Scheer, R.M.; Marasco, A.L.; Furey, R.


    President Carter issued Executive Order 12044 (3/28/78) that required all Federal agencies to distinguish between significant and insignificant regulations, and to determine whether a regulation will result in major impacts. This study gathered information on the impact of the order and the guidelines on the Office of Conservation and Solar Energy (CS) regulatory practices, investigated problems encountered by the CS staff when implementing the order and guidelines, and recommended solutions to resolve these problems. Major tasks accomplished and discussed are: (1) legislation, Executive Orders, and DOE Memoranda concerning Federal administrative procedures relevant to the development and analysis of regulations within CS reviewed; (2) relevant DOE Orders and Memoranda analyzed and key DOE and CS staff interviewed in order to accurately describe the current CS regulatory process; (3) DOE staff from the Office of the General Counsel, the Office of Policy and Evaluation, the Office of the Environment, and the Office of the Secretary interviewed to explore issues and problems encountered with current CS regulatory practices; (4) the regulatory processes at five other Federal agencies reviewed in order to see how other agencies have approached the regulatory process, dealt with specific regulatory problems, and responded to the Executive Order; and (5) based on the results of the preceding four tasks, recommendations for potential solutions to the CS regulatory problems developed. (MCW)

  13. Taiwan Regulation of Biobanks. (United States)

    Fan, Chien-Te; Hung, Tzu-Hsun; Yeh, Chan-Kun


    This paper introduces legal framework and governance structure in relation to the management and development of biobanks in Taiwan. At first, we briefly describe Taiwan's population, political system and health care system. Secondly, this research introduces biobanking framework of Taiwan including 25 biobanks established with the approval of the Ministry of Health and Welfare. In those biobanks, "Taiwan Biobank" is the first and the largest government-supported biobank which comprises population-based cohort study and disease- oriented study. Since the collection of information, data, and biological specimen of biobanks often involve highly sensitive personal information, in the legal framework of Taiwan, there is a specific regulation, "Human Biobank Management Act" (HBMA), which plays an important role in regulating biobanks in Taiwan. HBMA, the Personal Information Act and other regulations constitute a comprehensive legal and regulatory privacy framework of biobanks. Through the introduction and analysis of the current legal framework applicable to biobanks, we found that there are several challenges that need to be solved appropriately that involve duplicate review systems, the obstacles in the international collaboration, and data sharing between biobanks in Taiwan.

  14. Staff rules and regulations

    CERN Multimedia

    HR Department


    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: 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 m...

  15. Functional role of human NK cell receptor 2B4 (CD244) isoforms. (United States)

    Mathew, Stephen O; Rao, Krithi K; Kim, Jong R; Bambard, Nowland D; Mathew, Porunelloor A


    2B4 (CD244), a member of the signaling lymphocyte-activation molecule (SLAM/CD150), is expressed on all NK cells, a subpopulation of T cells, monocytes and basophils. Human NK cells express two isoforms of 2B4, h2B4-A and h2B4-B that differ in a small portion of the extracellular domain. In the present investigation, we have studied the functions of h2B4-A and h2B4-B. Our study demonstrated that these two isoforms differ in their binding affinity for CD48, which results in differential cytotoxic activity as well as intracellular calcium release by NK cells upon target cell recognition. Analysis of the predicted 3-D structure of the two isoforms showed conformational differences that could account for their differences in binding affinity to CD48. h2B4-A was able to mediate natural cytotoxicity against CD48-expressing K562 target cells and induce intracellular calcium release, whereas h2B4-B showed no effects. NK-92MI, U937, THP-1, KU812, primary monocytes, basophils and NK cells showed expression of both h2B4-A and h2B4-B whereas YT and IL-2-activated NK cells did not show any h2B4-B expression. Stimulation of NK cells through 2B4 resulted in decreased mRNA levels of both h2B4-A and h2B4-B indicating that down-regulation of 2B4 isoforms may be an important factor in controlling NK cell activation during immune responses.

  16. FDA 101: Regulating Biological Products (United States)

    ... Products For Consumers Home For Consumers Consumer Updates FDA 101: Regulating Biological Products Share Tweet Linkedin Pin ... field. back to top What biological products does FDA regulate? The Center for Biologics Evaluation and Research ( ...


    Institute of Scientific and Technical Information of China (English)



    Literal translation and liberal translation are two important methods and both play key roles in translation.However,some textbooks say that most translations are literal translations while others maintain most are liberal ones,besides,some others suggest a combination of the two.This paper focuses on the facts that regulate liberal translation.Because of the differences in culture,society,history,geography,and so on,there exists a great difference between Chinese language and English language,which does naturally lead to the liberal translation.

  18. The regulation of hunting

    DEFF Research Database (Denmark)

    Abildtrup, Jens; Jensen, Frank

    of the individual harvest. However, information about the individual harvest may be costly to obtain. Thus, we may have to look for alternatives to the existing system. This paper proposes a population tax/subsidy as an alternative which is the difference between the actual and optimal population multiplied...... by an individual, variable tax rate. The variable tax rate is, among other things, based on the difference in marginal value of the population between the hunter and the regulator. The paper shows that the population tax/subsidy secures a first-best optimum. Thus, the population tax is a good alternative...

  19. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.


    This report describes accomplishments over the past year on understanding of terpene synthesis in mint plants and sage. Specifically reported are the fractionation of 4-S-limonene synthetase, the enzyme responsible for the first committed step to monoterpene synthesis, along with isolation of the corresponding RNA and DNA cloning of its gene; the localization of the enzyme within the oil glands, regulation of transcription and translation of the synthetase, the pathway to camphor biosynthesis,a nd studies on the early stages and branch points of the isoprenoid pathway.

  20. Wiring regulations in brief

    CERN Document Server

    Tricker, Ray


    Tired of trawling through the Wiring Regs?Perplexed by Part P?Confused by cables, conductors and circuits?Then look no further! This handy guide provides an on-the-job reference source for Electricians, Designers, Service Engineers, Inspectors, Builders, Students, DIY enthusiastsTopic-based chapters link areas of working practice - such as cables, installations, testing and inspection, special locations - with the specifics of the Regulations themselves. This allows quick and easy identification of the official requirements relating to the situati

  1. Environmental regulations and business decisions


    Gray, Wayne B.


    Environmental regulations raise production costs at regulated firms, though in most cases the costs are only a small fraction of a firm’s total costs. Productivity tends to fall, and firms may shift new investment and production to locations with less stringent regulation. However, environmental regulations have had enormous benefits in terms of lives saved and illnesses averted, especially through reductions in airborne particulates. The potential health gains may be even greater in developi...

  2. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.


    During the last grant period, we have completed studies on the key pathways of monoterpene biosynthesis and catabolism in sage and peppermint, and have, by several lines of evidence, deciphered the rate-limiting step of each pathway. We have at least partially purified and characterized the relevant enzymes of each pathway. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation depends upon the balance between biosynthesis and catabolism, and provided supporting evidence that these processes are developmentally-regulated and very closely associated with senescence of the oil glands. Oil gland ontogeny has been characterized at the ultrastructural level. We have exploited foliar-applied bioregulators to delay gland senescence, and have developed tissue explant and cell culture systems to study several elusive aspects of catabolism. We have isolated pure gland cell clusters and localized monoterpene biosynthesis and catabolism within these structures, and have used these preparations as starting materials for the purification to homogeneity of target regulatory'' enzymes. We have thus developed the necessary background knowledge, based on a firm understanding of enzymology, as well as the necessary experimental tools for studying the regulation of monoterpene metabolism at the molecular level. Furthermore, we are now in a position to extend our systematic approach to other terpenoid classes (C[sub 15]-C[sub 30]) produced by oil glands.

  3. The Quality of Regulation

    Directory of Open Access Journals (Sweden)

    Emil BĂLAN


    Full Text Available Good governance also involves the affirmation and practice of some principles that allow the structures of the public space to administrate the general interest in the respect of the democracy and of the state of law pre-requisites, as well as the ones of a good administration: trust and predictability, openness and transparency, responsibility, efficiency and efficacy. The assurance of such desideratum imposes that the rules invested with the force of law, applicable to the juridical rapports to be clear, not equivoques, predictable, to allow both the protection of public interest and the respect of the citizens’ dignity and interests. The evaluation of the quality of regulation represents a necessary process of the appreciation of the impact that juridical norms are intended to produce and measures in which the outcomes of the implementation correspond to the ones established during the stage of formulating the public policy. The study tries to identify ways of evaluating the quality of regulation, valid in a social and political space governed by democratic rules and principles.

  4. Regulations and Procedures Manual

    Energy Technology Data Exchange (ETDEWEB)

    Young, Lydia J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)


    The purpose of the Regulations and Procedures Manual (RPM) is to provide LBNL personnel with a reference to University and Lawrence Berkeley National Laboratory (LBNL or Laboratory) policies and regulations by outlining normal practices and answering most policy questions that arise in the day-to-day operations of Laboratory organizations. Much of the information in this manual has been condensed from detail provided in LBNL procedure manuals, Department of Energy (DOE) directives, and Contract DE-AC02-05CH11231. This manual is not intended, however, to replace any of those documents. RPM sections on personnel apply only to employees who are not represented by unions. Personnel policies pertaining to employees represented by unions may be found in their labor agreements. Questions concerning policy interpretation should be directed to the LBNL organization responsible for the particular policy. A link to the Managers Responsible for RPM Sections is available on the RPM home page. If it is not clear which organization is responsible for a policy, please contact Requirements Manager Lydia Young or the RPM Editor.

  5. Buck/boost regulator (United States)

    Paulkovich, J.; Rodriguez, G. E. (Inventor)


    A voltage regulated DC to DC converter uses an inductor and a capacitor as storage elements. The inductor is composed of two windings having a common junction. A transformer with a center tap connected to the common junction of the two windings is connected at either end of its winding to ground through controlled switches. One winding of the inductor and either end of the transformer winding are connected by power diodes to the capacitor which supplies the output voltage to a load. The other winding of the inductor is connected to a fourth power diode as a clamping diode. Input voltage is supplied to the inductor through a third controlled switch. A pulse width modulator connected to the output of the converter alternately closes and opens the switches connected to either end of the transformer winding and also closes the switch supplying input voltage to the inductor each time either of the switches connected to the ends of the transformer winding are closed. The duty cycle of the closing and opening of the several switches is adjusted by the pulse modulator to regulate the output voltage.

  6. Regulations and Procedures Manual

    Energy Technology Data Exchange (ETDEWEB)

    Young, Lydia [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)


    The purpose of the Regulations and Procedures Manual (RPM) is to provide Laboratory personnel with a reference to University and Lawrence Berkeley National Laboratory policies and regulations by outlining the normal practices and answering most policy questions that arise in the day-to-day operations of Laboratory departments. Much of the information in this manual has been condensed from detail provided in Laboratory procedure manuals, Department of Energy (DOE) directives, and Contract DE-AC02-05CH11231. This manual is not intended, however, to replace any of those documents. The sections on personnel apply only to employees who are not represented by unions. Personnel policies pertaining to employees represented by unions may be found in their labor agreements. Questions concerning policy interpretation should be directed to the department responsible for the particular policy. A link to the Managers Responsible for RPM Sections is available on the RPM home page. If it is not clear which department should be called, please contact the Associate Laboratory Director of Operations.

  7. Circadian rhythms regulate amelogenesis. (United States)

    Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros


    Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of the development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24 h) intervals both at RNA and protein levels. This study also reveals that the two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory stage ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation stage ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stages of amelogenesis might be under circadian control. Changes in clock gene expression patterns might result in significant alterations of enamel apposition and mineralization.

  8. Regulation as delegation

    Directory of Open Access Journals (Sweden)

    Oren Bar-Gill


    Full Text Available Objective to consider the conception of reverse delegation when the government acts a principal and an individual ndash an agent from the point of view of behavioral PrincipalAgent Theory. Methods statistical method sociological polling. Results In diverse areas ndash from retirement savings to consumer credit to prescription drug use to fuel economy and energy efficiency rules to tobacco consumption to food and beverage consumption ndash government makes decisions for us or endeavors to help us make better decisions thus serving as our agent. From the point of view of PrincipalAgent Theory and behavioral PrincipalAgent Theory a great deal of modern regulation can be helpfully evaluated as a hypothetical delegation. Shifting from personal decisions to public goods problems the authors view the idea of reverse delegation with the government as principal and the individuals as agents. They show that the essence of delegation changes depending on the context. The article describes conditions under which various approaches will make sense. Scientific novelty the paper is devoted to the foreign experience of regulation through delegation by the example of a country with developed market economy the USA. It shows the prospects of such approach in solving both the public and the private tasks. Application of PrincipalAgent Theory and behavioral PrincipalAgent Theory is viewed to distinguish between such types of hypothetical delegation as information default rules incentives precommitments mandates and prohibitions. The article considers the benefits and costs of delegation and circumstances in which one or another approach makes sense. Practical significance PrincipalAgent Theory is widely used in economics and political science and can serve as a convenient tool to consider the optimal scale and essence of the assistance rendered to us by the government as our agent. The paper is of interest for the Russian legal science as the institution of

  9. NCAM regulates cell motility

    DEFF Research Database (Denmark)

    Prag, Søren; Lepekhin, Eugene A; Kolkova, Kateryna


    Cell migration is required during development of the nervous system. The regulatory mechanisms for this process, however, are poorly elucidated. We show here that expression of or exposure to the neural cell adhesion molecule (NCAM) strongly affected the motile behaviour of glioma cells...... independently of homophilic NCAM interactions. Expression of the transmembrane 140 kDa isoform of NCAM (NCAM-140) caused a significant reduction in cellular motility, probably through interference with factors regulating cellular attachment, as NCAM-140-expressing cells exhibited a decreased attachment...... to a fibronectin substratum compared with NCAM-negative cells. Ectopic expression of the cytoplasmic part of NCAM-140 also inhibited cell motility, presumably via the non-receptor tyrosine kinase p59(fyn) with which NCAM-140 interacts. Furthermore, we showed that the extracellular part of NCAM acted as a paracrine...

  10. Regulation of Terpene Metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Rodney Croteau


    OAK-B135 Research over the last four years has progressed fairly closely along the lines initially proposed, with progress-driven expansion of Objectives 1, 2 and 3. Recent advances have developed from three research thrusts: 1. Random sequencing of an enriched peppermint oil gland cDNA library has given access to a large number of potential pathway and regulatory genes for test of function; 2. The availability of new DNA probes and antibodies has permitted investigation of developmental regulation and organization of terpenoid metabolism; and 3. The development of a transformation system for peppermint by colleagues at Purdue University has allowed direct transgenic testing of gene function and added a biotechnological component to the project. The current status of each of the original research objectives is outlined below.

  11. Magnetostrictive Pressure Regulating System (United States)

    Richard, James A. (Inventor); Pickens, Herman L. (Inventor)


    A magnetostrictive pressure regulating system includes a magnetostrictive valve that incorporates a magnetostrictive actuator with at least one current-carrying coil disposed thereabout. A pressure force sensor, in fluid communication with the fluid exiting the valve, includes (i) a magnetostrictive material, (ii) a magnetic field generator in proximity to the magnetostrictive material for inducing a magnetic field in and surrounding the magnetostrictive material wherein lines of magnetic flux passing through the magnetostrictive material are defined, and (iii) a sensor positioned adjacent to the magnetostrictive material and in the magnetic field for measuring changes in at least one of flux angle and flux density when the magnetostrictive material experiences an applied force that is aligned with the lines of magnetic flux. The pressure of the fluid exiting the valve causes the applied force. A controller coupled to the sensor and to the current-carrying coil adjusts a current supplied to the current-carrying coil based on the changes so-measured.

  12. Mitosis and its regulation

    Directory of Open Access Journals (Sweden)

    Frías Vázquez Sara


    Full Text Available Cell division by mitosis is essential for the development of organisms and their reproduction; it is also neces- sary that each new cell is genetically identical to that from which it comes. In eukaryotes this is achieved by the presence of complex mechanisms that ensure the integrity of genomic material and their proper segregation during mitosis. The traditional view of mitosis has been divided into different stages that were characterized by morphological studies in dividing cells; advances in molecular biology have led beyond this characterization, so that we now know a range of participant molecules. This article will discuss the process of mitosis, both at the cellular and molecular level and a brief summary of the molecular players that regulate this process.

  13. Regulation of cholesterol homeostasis. (United States)

    van der Wulp, Mariëtte Y M; Verkade, Henkjan J; Groen, Albert K


    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-coding RNA's. The last two decades insight into underlying mechanisms has increased vastly but there are still a lot of unknowns, particularly regarding intracellular cholesterol transport. After decades of concentration on the liver, in recent years the intestine has come into focus as an important control point in cholesterol homeostasis. This review will discuss current knowledge of cholesterol physiology, with emphasis on cholesterol absorption, cholesterol synthesis and fecal excretion, and new (possible) therapeutic options for hypercholesterolemia.

  14. Hormonal Regulators of Appetite

    Directory of Open Access Journals (Sweden)

    Juliana Austin


    Full Text Available Obesity is a significant cause of morbidity and mortality worldwide. There has been a significant worsening of the obesity epidemic mainly due to alterations in dietary intake and energy expenditure. Alternatively, cachexia, or pathologic weight loss, is a significant problem for individuals with chronic disease. Despite their obvious differences, both processes involve hormones that regulate appetite. These hormones act on specific centers in the brain that affect the sensations of hunger and satiety. Mutations in these hormones or their receptors can cause substantial pathology leading to obesity or anorexia. Identification of individuals with specific genetic mutations may ultimately lead to more appropriate therapies targeted at the underlying disease process. Thus far, these hormones have mainly been studied in adults and animal models. This article is aimed at reviewing the hormones involved in hunger and satiety, with a focus on pediatrics.

  15. Hormonal Regulators of Appetite

    Directory of Open Access Journals (Sweden)

    Austin Juliana


    Full Text Available Obesity is a significant cause of morbidity and mortality worldwide. There has been a significant worsening of the obesity epidemic mainly due to alterations in dietary intake and energy expenditure. Alternatively, cachexia, or pathologic weight loss, is a significant problem for individuals with chronic disease. Despite their obvious differences, both processes involve hormones that regulate appetite. These hormones act on specific centers in the brain that affect the sensations of hunger and satiety. Mutations in these hormones or their receptors can cause substantial pathology leading to obesity or anorexia. Identification of individuals with specific genetic mutations may ultimately lead to more appropriate therapies targeted at the underlying disease process. Thus far, these hormones have mainly been studied in adults and animal models. This article is aimed at reviewing the hormones involved in hunger and satiety, with a focus on pediatrics.

  16. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.


    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C[sub 10]) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites of synthesis, and work with bioregulators, indicate that monoterpene production is controlled by terpene cyclases, the enzymes catalyzing the first step of the monoterpene pathway. As the leaf oil glands mature, cyclase levels decline and monoterpene biosynthesis ceases. Yield then decreases as the monoterpenes undergo catabolism by a process involving conversion to a glycoside and transport from the leaf glands to the root. At this site, the terpenoid is oxidatively degraded to acetate that is recycled into other lipid metabolites. During the transition from terpene biosynthesis to catabolism, the oil glands undergo dramatic ultrastructural modification. Degradation of the producing cells results in mixing of previously compartmentized monoterpenes with the catabolic enzymes, ultimately leading to yield decline. This regulatory model is being applied to the formation of other terpenoid classes (C[sub 15] C[sub 20], C[sub 30], C[sub 40]) within the oil glands. Preliminary investigations on the formation of sesquiterpenes (C[sub 15]) suggest that the corresponding cyclases may play a lesser role in determining yield of these products, but that compartmentation effects are important. From these studies, a comprehensive scheme for the regulation of terpene metabolism is being constructed. Results from this project wail have important consequences for the yield and composition of terpenoid natural products that can be made available for industrial exploitation.

  17. Endocannabinoids in cerebrovascular regulation. (United States)

    Benyó, Zoltán; Ruisanchez, Éva; Leszl-Ishiguro, Miriam; Sándor, Péter; Pacher, Pál


    The cerebral blood flow is tightly regulated by myogenic, endothelial, metabolic, and neural mechanisms under physiological conditions, and a large body of recent evidence indicates that inflammatory pathways have a major influence on the cerebral blood perfusion in certain central nervous system disorders, like hemorrhagic and ischemic stroke, traumatic brain injury, and vascular dementia. All major cell types involved in cerebrovascular control pathways (i.e., smooth muscle, endothelium, neurons, astrocytes, pericytes, microglia, and leukocytes) are capable of synthesizing endocannabinoids and/or express some or several of their target proteins [i.e., the cannabinoid 1 and 2 (CB1 and CB2) receptors and the transient receptor potential vanilloid type 1 ion channel]. Therefore, the endocannabinoid system may importantly modulate the regulation of cerebral circulation under physiological and pathophysiological conditions in a very complex manner. Experimental data accumulated since the late 1990s indicate that the direct effect of cannabinoids on cerebral vessels is vasodilation mediated, at least in part, by CB1 receptors. Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g., in conscious restrained animals or during hypoxia and hypercapnia), cannabinoid receptor activation was shown to induce a reduction of the cerebral blood flow, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g., subarachnoid hemorrhage, as well as traumatic and ischemic brain injury), activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation.

  18. Regulation of melanopsin expression. (United States)

    Hannibal, Jens


    Circadian rhythms in mammals are adjusted daily to the environmental day/night cycle by photic input via the retinohypothalamic tract (RHT). Retinal ganglion cells (RGCs) of the RHT constitute a separate light-detecting system in the mammalian retina used for irradiance detection and for transmission to the circadian system and other non-imaging forming processes in the brain. The RGCs of the RHT are intrinsically photosensitive due to the expression of melanopsin, an opsin-like photopigment. This notion is based on anatomical and functional data and on studies of mice lacking melanopsin. Furthermore, heterologous expression of melanopsin in non-neuronal mammalian cell lines was found sufficient to render these cells photosensitive. Even though solid evidence regarding the function of melanopsin exists, little is known about the regulation of melanopsin gene expression. Studies in albino Wistar rats showed that the expression of melanopsin is diurnal at both the mRNA and protein levels. The diurnal changes in melanopsin expression seem, however, to be overridden by prolonged exposure to light or darkness. Significant increase in melanopsin expression was observed from the first day in constant darkness and the expression continued to increase during prolonged exposure in constant darkness. Prolonged exposure to constant light, on the other hand, decreased melanopsin expression to an almost undetectable level after 5 days of constant light. The induction of melanopsin by darkness was even more pronounced if darkness was preceded by light suppression for 5 days. These observations show that dual mechanisms regulate melanopsin gene expression and that the intrinsic light-responsive RGCs in the albino Wistar rat adapt their expression of melanopsin to environmental light and darkness.

  19. Standard types of regulation loops; Chaines de regulation types

    Energy Technology Data Exchange (ETDEWEB)

    Bertrand, M. [ENSAM, Centre d`Enseignement et de Recherche de Lille, 59 - Lille (France)


    The aim of this paper is to give help in the analysis of industrial regulation problems using different types of real installations. The increasing complexity of industrial systems requires the use of a decomposition-recomposition procedure using a scheme with different blocs. Examples are given to help the non-specialist users in the mastery of essential choices and in the distinction between operational and material separations. The examples concern: the heating loop of a central heating installation, the sensors and actuators of industrial systems (the temperature regulation of a tubular furnace, the electro-hydraulic positioning systems used in machine tools, forming, aeronautics etc.., the regulation of a mixing system for hot and cold fluids, and the regulation of a fluidizing system. The usual types of regulation loops are presented with the different steps of the resolution of a regulation problem. (J.S.) 7 refs.

  20. Branded prescription drug fee. Final regulations, temporary regulations, and removal of temporary regulations. (United States)


    This document contains final regulations that provide guidance on the annual fee imposed on covered entities engaged in the business of manufacturing or importing branded prescription drugs. This fee was enacted by section 9008 of the Patient Protection and Affordable Care Act, as amended by section 1404 of the Health Care and Education Reconciliation Act of 2010. This document also withdraws the Branded Prescription Drug Fee temporary regulations and contains new temporary regulations regarding the definition of controlled group that apply beginning on January 1, 2015. The final regulations and the new temporary regulations affect persons engaged in the business of manufacturing or importing certain branded prescription drugs. The text of the temporary regulations in this document also serves as the text of proposed regulations set forth in a notice of proposed rulemaking (REG-123286-14) on this subject in the Proposed Rules section in this issue of the Federal Register.

  1. Regulation of the power sector

    CERN Document Server


    Regulation of the Power Sector is a unified, consistent and comprehensive treatment of the theories and practicalities of regulation in modern power-supply systems. The need for generation to occur at the time of use occasioned by the impracticality of large-scale electricity storage coupled with constant and often unpredictable changes in demand make electricity-supply systems large, dynamic and complex and their regulation a daunting task. Conceptually arranged in four parts, this book addresses both traditional regulatory frameworks and also liberalized and re-regulated environments. First, an introduction gives a full characterization of power supply including engineering, economic and regulatory viewpoints. The second part presents the fundamentals of regulation and the third looks at the regulation of particular components of the power sector in detail. Advanced topics and subjects still open or subject to dispute form the content of the fourth part. In a sector where regulatory design is the key driver...

  2. Nanomaterials: Regulation and Risk Assessment

    DEFF Research Database (Denmark)

    Hansen, Steffen Foss; Grieger, Khara Deanne; Baun, Anders


    The topics of regulation and risk assessment of nanomaterials have never been more relevant and controversial in Europe than they are at this point in time. In this entry, we present and discuss a number of major pieces of legislation relevant for the regulation of nanomaterials, including REACH...... Regulation. Chemical risk assessment provides a fundamental element in support of existing legislation. Risk assessment is normally said to consist of four elements, i.e., hazard identification, dose–response assessment, exposure assessment, and risk characterization. Each of these four elements hold......, the Water Framework Directive, pharmaceuticals regulation, and the Novel Foods Regulation. Current regulation of nanomaterials entail three overall challenges: 1) limitations in regard to terminology and definitions of key terms such as a “substance,” “novel food,” etc.; 2) safety assessment requirements...

  3. Sustainable regulation of construction. (United States)


    The seminar examined the role building codes and regulations can have in promoting a more sustainable approach to construction, particularly through their application to non-industrial building materials. A range of building materials such as straw, bamboo, rammed earth, adobe, and cob (a mixture of clay and chopped straw) were described and illustrated by slides to show their building potential. The current codes have a prime concern to protect the health and safety of people from the built environment. They have been developed almost exclusively for mainstream industrial materials and methods of construction, which makes them difficult to use with alternative, indigenous, or non-industrial building materials, even though those materials may be considered more sustainable. The argument was put forward that with only one-third of the world population living in modern industrial buildings today, it is not sustainable to re-house the remaining rapidly expanding population in high technology dwellings. Many of the low technology building materials and methods now used by the majority of people in the world need only incremental improvement to be equal or superior to many of their industrial replacements. Since these can be more sustainable methods of building, there needs to be an acceptance of the use of alternative materials, particularly in the developing parts of the world, where they are being rejected for less sustainable industrial methods. However, many codes make it difficult to use non-industrial materials; indeed, many of the industrial materials would not meet the demands that must be now met if they were now being introduced as new materials. Consequently, there is a need to develop codes to facilitate the use of a wider range of materials than in current use, and research is needed to assist this development. Sustainable regulation should take into account the full range of real impacts that materials and systems have in areas such as resource use and

  4. Nitrate Reductase: Properties and Regulation

    Institute of Scientific and Technical Information of China (English)


    Nitrate Reductase (NR) is a rating-limit and key enzyme of nitrate assimilation in plants ,so ,NR activity is important for growth,development and the dry matter accumulation of plants. The regulation of NR activity appears to be rather complex and many studies have been devoted to the description of regulation and properties,but in this paper we focus on the properties and regulation of NR in higher plants.

  5. Regulations on Open Government Information

    Institute of Scientific and Technical Information of China (English)



    @@ On April 24, 2007 the State Council promulgated Regulations of the People's Republic of China on Open Government Information (referred to as Regulations below), which will become effective on May 1, 2008. As the first administrative rule of the central government of China that aims to safeguard the public's right to know, the Regulations are of great significance in China's democratization and its establishment of the rule of law.

  6. Regulating regulatory T cells. (United States)

    Le, N T; Chao, N


    Regulatory T cells (Tregs) are a specialized subpopulation of T cells that act to suppress activation of other immune cells and thereby maintain immune system homeostasis, self-tolerance as well as control excessive response to foreign antigens. The mere concept of Tregs was the subject of significant controversy among immunologists for many years owing to the paucity of reliable markers for defining these cells and the ambiguity of the nature and molecular basis of suppressive phenomena. However, recent advances in the molecular characterization of this cell population have firmly established their existence and their vital role in the vertebrate immune system. Of interest, accumulating evidence from both humans and experimental animal models has implicated the involvement of Tregs in the development of graft-versus-host disease (GVHD). The demonstration that Tregs could separate GVHD from graft-versus-tumor (GVT) activity suggests that their immunosuppressive potential could be manipulated to reduce GVHD without detrimental consequence on GVT effect. Although a variety of T lymphocytes with suppressive capabilities have been reported, the two best-characterized subsets are the naturally arising, intrathymic-generated Tregs (natural Tregs) and the peripherally generated, inducible Tregs (inducible Tregs). This review summarizes our current knowledge of the generation, function and regulation of these two populations of Tregs during an immune response. Their role in the development of GVHD and their therapeutic potential for the prevention and treatment of GVHD will also be described.

  7. [Ghrelin: beyond hunger regulation]. (United States)

    Milke García, Maria del Pilar


    Man ingests food to mitigate hunger (mediated by physiological and biochemical signals), satisfy appetite (subjective sensation) and because of psychosocial reasons. Satiation biomarkers (stop feeding) are gastric distention and hormones (CCK, GLP-1) and satiety biomarkers (induce feeding) are food-induced thermogenesis, body temperature, glycaemia and also hormones (insulin, leptin and ghrelin). Oxidative metabolism/body composition, tryptophan/serotonin and proinflammatory cytokines are also implicated on hunger physiology. At the present time, ghrelin is the only known circulating orexigenic with potential on hunger/body weight regulation. It is a neuropeptide (endogenous ligand for the GH secretagogue) recently isolated from the oxyntic mucosa and synthesized mainly in the stomach. Its blood concentration depends on diet, hyperglucemia and adiposity/leptin. It is secreted 1-2 hours preprandially and its concentration decreases drastically during the postprandium. Ghrelin acts on the lateral hypothalamus and theoretically inhibits proinflammatory cytokine secretion and antagonizes leptin. Ghrelin physiologically increases food intake and stimulates adipogenesis, gastrointestinal motility and gastric acid secretion, and has other hormonal and cardiovascular functions. Ghrelin blood concentration is reduced in massive obesity, non-alcoholic steatohepatitis, polycystic ovary syndrome, acromegaly, hypogonadism, ageing, short bowel syndrome and rheumatoid arthritis; and increased in primary or secondary anorexia, starvation, chronic liver disease and celiac disease. Cerebral and peritoneal ghrelin administration (rats) and systemic administration (rats and healthy volunteers, cancer patients or patients on peritoneal dialysis) promotes food consumption and increases adiposity, of utmost importance in the treatment of patients with anorexia.

  8. NCAM regulates cell motility. (United States)

    Prag, Søren; Lepekhin, Eugene A; Kolkova, Kateryna; Hartmann-Petersen, Rasmus; Kawa, Anna; Walmod, Peter S; Belman, Vadym; Gallagher, Helen C; Berezin, Vladimir; Bock, Elisabeth; Pedersen, Nina


    Cell migration is required during development of the nervous system. The regulatory mechanisms for this process, however, are poorly elucidated. We show here that expression of or exposure to the neural cell adhesion molecule (NCAM) strongly affected the motile behaviour of glioma cells independently of homophilic NCAM interactions. Expression of the transmembrane 140 kDa isoform of NCAM (NCAM-140) caused a significant reduction in cellular motility, probably through interference with factors regulating cellular attachment, as NCAM-140-expressing cells exhibited a decreased attachment to a fibronectin substratum compared with NCAM-negative cells. Ectopic expression of the cytoplasmic part of NCAM-140 also inhibited cell motility, presumably via the non-receptor tyrosine kinase p59(fyn) with which NCAM-140 interacts. Furthermore, we showed that the extracellular part of NCAM acted as a paracrine inhibitor of NCAM-negative cell locomotion through a heterophilic interaction with a cell-surface receptor. As we showed that the two N-terminal immunoglobulin modules of NCAM, which are known to bind to heparin, were responsible for this inhibition, we presume that this receptor is a heparan sulfate proteoglycan. A model for the inhibitory effect of NCAM is proposed, which involves competition between NCAM and extracellular components for the binding to membrane-associated heparan sulfate proteoglycan.

  9. 78 FR 31551 - Federal Acquisition Regulation; Submission for OMB Review; Commerce Patent Regulations (United States)


    ... Regulation; Submission for OMB Review; Commerce Patent Regulations AGENCIES: Department of Defense (DOD... approved information collection requirement concerning Department of Commerce patent regulations. A notice... Collection 9000- 0095, Commerce Patent Regulations, by any of the following methods: :...

  10. 76 FR 43585 - Bank Secrecy Act Regulations; Definitions and Other Regulations Relating to Money Services... (United States)


    ... Regulations; Definitions and Other Regulations Relating to Money Services Businesses AGENCY: Treasury... Proposed Rulemaking, Definitions and Other Regulations Relating to Money Services Businesses, 74 FR 22129... to the Bank Secrecy Act Regulations-- Definitions and Other Regulations Relating to Money...

  11. Regulation of gas infrastructure expansion

    NARCIS (Netherlands)

    De Joode, J.


    The topic of this dissertation is the regulation of gas infrastructure expansion in the European Union (EU). While the gas market has been liberalised, the gas infrastructure has largely remained in the regulated domain. However, not necessarily all gas infrastructure facilities – such as gas storag

  12. Novel protein regulates ERK pathway

    Institute of Scientific and Technical Information of China (English)


    @@ The ERK (extracellular signal-regulated kinase) pathway plays a critical role in the vital processes of living cells such as proliferation and differentiation.Recently, CAS scientists in Shanghai have discovered a novel mechanism of spatial regulation on ERK pathway. The result was published in the 4 September issue of the Proceedings of National Academy of Sciences(PNAS).

  13. The Organization of Regulated Production

    DEFF Research Database (Denmark)

    Jansen, Jos; Jeon, Doh-Shin; Menicucci, Domenico


    We analyze the choice between vertical separation (VS) and vertical integration (VI) when two regulated firms produce complementary inputs with correlated costs and are protected by ex post break-even constraints. First, in the absence of collusion the regulator prefers VI (VS) for negative and w...

  14. Regulation of TRPML1 function. (United States)

    Waller-Evans, Helen; Lloyd-Evans, Emyr


    TRPML1 is a ubiquitously expressed cation channel found on lysosomes and late endosomes. Mutations in TRPML1 cause mucolipidosis type IV and it has been implicated in Alzheimer's disease and HIV. However, the mechanisms by which TRPML1 activity is regulated are not well understood. This review summarizes the current understanding of TRPML1 activation and regulation.

  15. Frequency-controlled voltage regulator (United States)

    Mclyman, W. T.


    Converting input ac to higher frequency reduce size and weight and makes possible unique kind of regulation. Since conversion frequency is above range of human hearing, supply generated on audible noise. It also exploits highfrequency conversion features to regulate its output voltage in novel way. Circuit is inherently short-circuit proof.


    Directory of Open Access Journals (Sweden)

    Anna A. Muravyeva


    Full Text Available The paper looks into the diverse aspects of qualifications system regulation, designed for balancing the supply and demand in the labor and educational service markets. Both the objects and mechanisms of such regulation are described. Special attention is given to institutions, involved in regulation of qualifications, and their jurisdiction. Another emphasis is on the industry-related regulation of qualifications which proved to be effective both on the national and European level. Such structures were first established on the national levels to regulate the qualifications and ensure their comparability and compatibility, given the economic globalization and growing labor and academic mobility. The author points out the role of the ministries of education and labor in maintaining a steady qualifications system, and outlines the positive experience of Great Britain using the industry councils for continuing development of qualifications system.

  17. Designing Next Generation Telecom Regulation

    DEFF Research Database (Denmark)

    Henten, Anders; Samarajiva, Rohan

    – ICT convergence regulation and multisector utility regulation. Whatever structure of next generation telecom regulation is adopted, all countries will need to pay much greater attention to the need for increased coordination of policy directions and regulatory activities both across the industries......Continuously expanding applications of information and communication technologies (ICT) are transforming local, national, regional and international economies into network economies, the foundation for information societies. They are being built upon expanded and upgraded national telecom networks...... to creating an environment to foster a massive expansion in the coverage and capabilities of the information infrastructure networks, with national telecom regulators as the key implementers of the policies of reform. The first phase of reform has focused on industry specific telecom policy and regulation...

  18. RNA-guided transcriptional regulation

    Energy Technology Data Exchange (ETDEWEB)

    Church, George M.; Mali, Prashant G.; Esvelt, Kevin M.


    Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

  19. Designing Next Generation Telecom Regulation

    DEFF Research Database (Denmark)

    Henten, Anders; Samarajiva, Rohan; Melody, William H.


    to the regulatory process such as scarcity of regulatory resources and safeguards for regulatory independence, are examined. It is concluded that ICT and media convergence issues are primarily about improving the efficiency of market economies, and how changes in regulation can facilitate this process. Multi......This article critically examines the multiple rationales for telecom, IT, media convergence regulation, on the one hand, and multisector utility regulation, on the other, and the practical questions of implementation they pose, with a view to contributing to informed policy and regulatory decisions....... Both options involve substantive as well as procedural issues, not necessarily separable. The conditions that may affect the creation of convergence and multi-sector regulation, ranging from underlying commonality of inputs and the behaviour of regulated firms to considerations that are specific...


    Directory of Open Access Journals (Sweden)

    Buldykova I. A.


    Full Text Available One of the methods of increasing the productivity of alfalfa is the use of growth regulators, and the use of polymeric compositions of growth regulators, binders with synthesized growth regulators of sim-triazine series is promising with the possibility of creating environmentally friendly technologies for growing alfalfa. Studies have shown that the application of the test on alfalfa growth regulators has a positive effect on growth, physiological and morphogenetic processes, plant resistance to adverse environmental conditions. Intensity impact on plant growth regulators depends on the type of plant growth regulators, concentration and method of application. Processing alfalfa seed growth regulators on germination increases energy 3,0-14,0 % germination on 8,0-17,0 %. Processing plant growth regulators to enhance the growth of plants in height (on the 7th day – 2,6-11,9 % , on the 14th 41,9-48,0 % , the growth of aboveground biomass , expands on the number of productive branches of the 1st ( 24,1-41,3 % and 2nd order (21,7-55,0 %. Pre-sowing seed treatment and plant growth regulators alfalfa sim- triazine series contributed to the increase in seed yield of 15,5 %. On average, the yield of green mass increased by 0,8-2,4 t /ha or 5,2-15,5 % and seed yield at 0,19-0,42 h/ha or 8,7-19, 3 %. Growth regulators of sim-triazine series increase the protein content of the vegetative mass of alfalfa at 3,2-4,6 %

  1. Regulated electricity retailing in Chile

    Energy Technology Data Exchange (ETDEWEB)

    Galetovic, Alexander, E-mail: [Facultad de Ciencias Economicas y Empresariales, Universidad de los Andes, Santiago, Chile. Av. San Carlos de Apoquindo 2200, Las Condes, Santiago (Chile); Munoz, Cristian M., E-mail: [AES Gener and Departamento de Ingenieria Electrica, Universidad Catolica de Chile (Chile)


    While some countries have unbundled distribution and retailing, skeptics argue that the physical attributes of electricity make retailers redundant. Instead, it is claimed that passive pass through of wholesale prices plus regulated charges for transmission and distribution suffice for customers to benefit from competitive generation markets. We review the Chilean experience with regulated retailing and pass through of wholesale prices. We argue that when energy wholesale prices are volatile and prices are stabilized, distortions emerge. Regulated retailers gain little by mitigating or correcting them. On the contrary, sometimes price distortions increase their profits. We estimate the cost of three distortions that neither regulated retailers nor the regulator have shown any interest in correcting. - Highlights: > We review Chile's experience with regulated electricity retailing. > Distortions emerge when energy wholesale prices are volatile and prices stabilized. > Regulated retailers gain little by mitigating or correcting distortions. > Sometimes price distortions increase retailers' profits. > We estimate the cost of three distortions, which retailers have not corrected.

  2. Mental fatigue impairs emotion regulation. (United States)

    Grillon, Christian; Quispe-Escudero, David; Mathur, Ambika; Ernst, Monique


    Because healthy physical and mental functioning depends on the ability to regulate emotions, it is important to identify moderators of such regulations. Whether mental fatigue, subsequent to the depletion of cognitive resources, impairs explicit emotion regulation to negative stimuli is currently unknown. This study explored this possibility. In a within-subject design over 2 separate sessions, healthy individuals performed easy (control session) or difficult (depletion session) cognitive tasks. Subsequently, they were presented with neutral and negative pictures, with instructions to either maintain or regulate (i.e., reduce) the emotions evoked by the pictures. Emotional reactivity was probed with the startle reflex. The negative pictures evoked a similar aversive state in the control and depletion sessions as measured by startle potentiation. However, subjects were able to down-regulate their aversive state only in the control session, not in the depletion session. These results indicate that mental fatigue following performance of cognitive tasks impairs emotion regulation without affecting emotional reactivity. These findings suggest that mental fatigue needs to be incorporated into models of emotion regulation.

  3. Grandfather regulations, new source bias, and state air toxics regulations

    Energy Technology Data Exchange (ETDEWEB)

    Levinson, Arik [University of Wisconsin Economics Department, 1180 Observatory Drive, Madison, WI 53706 (United States)


    This paper uses plant-level data from the Census of Manufactures and the variation in toxic air pollution regulations across states to measure the effects of laws that are more stringent for new sources of pollution than for existing sources (so-called `grandfather` regulations). Of particular interest is the resulting `new source bias` and its effects on capital vintage and investment. Two industries are examined: commercial printing, which has a local product market; and paint manufacturing, which has a more national market. In general, there seem to be no statistically significant differences in capital vintage or investment between plants in states that grandfather new sources of pollution, plants in states that have no air toxics regulations, and plants in states that regulate both new and existing sources

  4. Nanometrology - challenges for health regulation

    Directory of Open Access Journals (Sweden)

    Jailton Carreteiro Damasceno


    Full Text Available The relationship between metrology, nanotechnology and nanoscience and sanitary regulation is discussed from the point of view of its importance and the interrelationship between the themes for the development of products and services involving nanotech-nology. The discussion involves the main techniques for measuring dimensional, chemical and biological properties of materials, and presents some of the challenges for the future. Issues such as processes of standardization and regulation in Europe, U.S. and Brazil are also addressed, providing an overview of how these processes are related to sanitary regulation.

  5. The regulation of ascorbate biosynthesis. (United States)

    Bulley, Sean; Laing, William


    We review the regulation of ascorbate (vitamin C) biosynthesis, focusing on the l-galactose pathway. We discuss the regulation of ascorbate biosynthesis at the level of gene transcription (both repression and enhancement) and translation (feedback inhibition of translation by ascorbate concentration) and discuss the eight proteins that have been demonstrated to date to affect ascorbate concentration in plant tissues. GDP-galactose phosphorylase (GGP) and GDP-mannose epimerase are critical steps that regulate ascorbate biosynthesis. These and other biosynthetic genes are controlled at the transcriptional level, while GGP is also controlled at the translational level. Ascorbate feedback on enzyme activity has not been observed unequivocally.

  6. Emotional regulation strategies and negotiation. (United States)

    Yurtsever, Gülçimen


    This study examined the relationship between profit achievement and emotional regulation strategies, using Kelley's Negotiation Game to measure profit achievement. The game involves bargaining for the prices of three products. Emotional Regulation Strategies were measured by The Emotional Regulation Questionnaire. Scores were obtained from 104 lower level managers of a bank in Turkey. Their average age was 32.0 yr. (SD=3.7), (39 women and 65 men). A correlation of .65 (p<.01) was obtained between scores on profit achievement with scores on Cognitive Reappraisal strategy and -.50 (p<.01) with scores on Suppression strategy.

  7. Voltage Regulators for Photovoltaic Systems (United States)

    Delombard, R.


    Two simple circuits developed to provide voltage regulation for highvoltage (i.e., is greater than 75 volts) and low-voltage (i.e., is less than 36 volts) photovoltaic/battery power systems. Use of these circuits results in voltage regulator small, low-cost, and reliable, with very low power dissipation. Simple oscillator circuit controls photovoltaic-array current to regulate system voltage and control battery charging. Circuit senses battery (and system) voltage and adjusts array current to keep battery voltage from exceeding maximum voltage.

  8. Regulation of TAZ in cancer

    Directory of Open Access Journals (Sweden)

    Xin Zhou


    Full Text Available ABSTRACT TAZ, a transcriptional coactivator with PDZ-binding motif, is encoded by WWTR1 gene (WW domain containing transcription regulator 1. TAZ is tightly regulated in the hippo pathway-dependent and -independent manner in response to a wide range of extracellular and intrinsic signals, including cell density, cell polarity, F-actin related mechanical stress, ligands of G protein-coupled receptors (GPCRs, cellular energy status, hypoxia and osmotic stress. Besides its role in normal tissue development, TAZ plays critical roles in cell proliferation, differentiation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT, and stemness in multiple human cancers. We discuss here the regulators and regulation of TAZ. We also highlight the tumorigenic roles of TAZ and its potential therapeutic impact in human cancers.

  9. Electronic Code of Federal Regulations (United States)

    National Archives and Records Administration — The Electronic Code of Federal Regulations (e-CFR) is the codification of the general and permanent rules published in the Federal Register by the executive...

  10. Network Regulation and Support Schemes

    DEFF Research Database (Denmark)

    Ropenus, Stephanie; Schröder, Sascha Thorsten; Jacobsen, Henrik


    -in tariffs to market-based quota systems, and network regulation approaches, comprising rate-of-return and incentive regulation. National regulation and the vertical structure of the electricity sector shape the incentives of market agents, notably of distributed generators and network operators....... This article seeks to investigate the interactions between the policy dimensions of support schemes and network regulation and how they affect the deployment of distributed generation. Firstly, a conceptual analysis examines how the incentives of the different market agents are affected. In particular......, it will be shown that there frequently exists a trade-off between the creation of incentives for distributed generators and for distribution system operators to facilitate the integration of distributed generation. Secondly, the interaction of these policy dimensions is analyzed, including case studies based...

  11. Self Regulating Fiber Fuel Cell (United States)


    energy numbers are 2.3X and 5.7X the theoretical values for lithium thionyl chloride respectively (1100 Whr/liter and 590 Whr/kg), which has the...REPORT Self Regulating Fiber Fuel Cell 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: Advances in lithium primary battery technology, which serves as the...Prescribed by ANSI Std. Z39.18 - 16-Aug-2010 Self Regulating Fiber Fuel Cell Report Title ABSTRACT Advances in lithium primary battery technology

  12. Money Laundering and its Regulation


    Alberto E. Chong; Florencio López-de-Silanes


    The recent wave of terrorist attacks has increased the attention paid to money laundering activities. Using several methodologies, this paper investigates empirically the determinants of money laundering and its regulation in over 80 countries by assembling a cross-country dataset on proxies for money laundering and the prevalence of feeding activities. The paper additionally constructs specific money laundering regulation indices based on available information on laws and their mechanisms of...

  13. Civilsamfundets ABC: R for Regulering

    DEFF Research Database (Denmark)

    Meyer, Gitte; Lund, Anker Brink


    Hvad er civilsamfundet? Anker Brink Lund og Gitte Meyer fra CBS Center for Civil Society Studies gennemgår civilsamfundet bogstav for bogstav. Vi er nået til R for Regulering.......Hvad er civilsamfundet? Anker Brink Lund og Gitte Meyer fra CBS Center for Civil Society Studies gennemgår civilsamfundet bogstav for bogstav. Vi er nået til R for Regulering....

  14. Mycotoxins – Limits and Regulations



    Since early years, a need has always been felt for some control on the quality of foodstuffs. With the discovery of aflatoxins in the early sixties, health authorities in man countries have become active in establishing regulations to protect their citizens and livestock fro t potential harm caused by mycotoxins. FDA mycotox-ins-in-foods sampling program is continuing with an objective to remove those foods from interstate commerce that contain Aflatoxins “at levels judged to be of regulator ...

  15. 7 CFR 29.29 - Regulations. (United States)


    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Regulations. 29.29 Section 29.29 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... INSPECTION Regulations Definitions § 29.29 Regulations. Rules and regulations of the Secretary under the Act....

  16. 7 CFR 987.48 - Container regulation. (United States)


    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Container regulation. 987.48 Section 987.48... IN RIVERSIDE COUNTY, CALIFORNIA Order Regulating Handling Container Regulation § 987.48 Container regulation. Whenever the Committee deems it advisable to establish a container regulation for any variety...

  17. Precision Adjustable Liquid Regulator (ALR) (United States)

    Meinhold, R.; Parker, M.


    A passive mechanical regulator has been developed for the control of fuel or oxidizer flow to a 450N class bipropellant engine for use on commercial and interplanetary spacecraft. There are several potential benefits to the propulsion system, depending on mission requirements and spacecraft design. This system design enables more precise control of main engine mixture ratio and inlet pressure, and simplifies the pressurization system by transferring the function of main engine flow rate control from the pressurization/propellant tank assemblies, to a single component, the ALR. This design can also reduce the thermal control requirements on the propellant tanks, avoid costly Qualification testing of biprop engines for missions with more stringent requirements, and reduce the overall propulsion system mass and power usage. In order to realize these benefits, the ALR must meet stringent design requirements. The main advantage of this regulator over other units available in the market is that it can regulate about its nominal set point to within +/-0.85%, and change its regulation set point in flight +/-4% about that nominal point. The set point change is handled actively via a stepper motor driven actuator, which converts rotary into linear motion to affect the spring preload acting on the regulator. Once adjusted to a particular set point, the actuator remains in its final position unpowered, and the regulator passively maintains outlet pressure. The very precise outlet regulation pressure is possible due to new technology developed by Moog, Inc. which reduces typical regulator mechanical hysteresis to near zero. The ALR requirements specified an outlet pressure set point range from 225 to 255 psi, and equivalent water flow rates required were in the 0.17 lb/sec range. The regulation output pressure is maintained at +/-2 psi about the set point from a P (delta or differential pressure) of 20 to over 100 psid. Maximum upstream system pressure was specified at 320 psi

  18. Balancing Public and Private Regulation

    Directory of Open Access Journals (Sweden)

    Martijn Scheltema


    Full Text Available Voluntary Sustainability Standards (VSS might develop into a viable alternative to public regulation. However, it turns on the (regulatory circumstances whether that holds true in practice. If public regulation on CSR topics is lacking, governments are unable to agree upon certain topics on a global level or diverging public regulation exists, VSS can be helpful to set global standards. Obviously, private standards will especially be helpful if they are commensurate with local public legislation (and e.g. treaties and/or are accepted by local governments. If one neglects this, numerous domestic structures might exist that frustrate VSS. Furthermore, governments have to remain vigilant as to whether these private regimes do not result in market disruption, consumer detriment or hamper trade. VSS might also compete with public arrangements which might limit the uptake of VSS. However, if public regulation exists VSS might be a viable alternative if compliance with not too compelling public norms by market participants is rather poor and the public policymaker is aiming to incentivize the better performing part of the market to embark on higher standards and thus only desires to regulate the less performing part of the market. However, of paramount importance is the effectiveness of VSS in order to be a viable alternative to public regulation. The effectiveness of VSS should be assessed using an integrated multi-disciplinary (comparative approach entailing legal, impact-assessment, legitimacy, governance and behavioural aspects. Only effective VSS in the aforementioned sense are a true alternative to public regulation.Beyond that, the legal perspective in connection with (the effectiveness of VSS is discussed, featuring FSC and UTZ Certified as an example. It is important from this perspective that VSS have a clear and sufficiently selective objective and sufficiently specific norms, are regularly evaluated, entail ‘conflict of law rules’ and

  19. 77 FR 43082 - Federal Acquisition Regulation; Information Collection; Commerce Patent Regulations (United States)


    ... Regulation; Information Collection; Commerce Patent Regulations AGENCIES: Department of Defense (DOD... approved information collection requirement concerning Department of Commerce patent regulations. Public...: Submit comments identified by Information Collection 9000- 0095, Commerce Patent Regulations, by any...

  20. Cosmetic Regulations: A Comparative Study. (United States)

    Suhag, Jyoti; Dureja, Harish


    The regulatory framework, compliance requirement, efficacy, safety, and marketing of cosmetic products are considered the most important factors for growth of the cosmetic industry. There are different regulatory bodies across the globe that have their own insights for regulation; moreover, governments such as the United States, European Union, and Japan follow a stringent regulatory framework, whereas cosmetics are not so much strictly regulated in countries such as India, Brazil, and China. The alignment of a regulatory framework will play a significant role in the removal of barriers to trade, growth of market at an international level, innovation in the development and presentation of new products, and most importantly safety and efficacy of the marketed products. The present contribution gives insight into the important cosmetic regulations in areas of premarket approval, ingredient control, and labeling and warnings, with a special focus on the cosmetic regulatory environments in the United States, European Union, Japan, and India. Most importantly, the authors highlight the dark side of cosmetics associated with allergic reactions and even skin cancer. The importance of cosmetic regulations has been highlighted by dint of which the society can be healthier, accomplished by more stringent and harmonized regulations.

  1. Progress toward risk informed regulation

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, K.C.


    For the last several years, the NRC, with encouragement from the industry, has been moving in the direction of risk informed regulation. This is consistent with the regulatory principle of efficiency, formally adopted by the Nuclear Regulatory Commission in 1991, which requires that regulatory activities be consistent with the degree of risk reduction they achieve. Probabilistic risk analysis has become the tool of choice for selecting the best of several alternatives. Closely related to risk informed regulation is the development of performance based rules. Such rules focus on the end result to be achieved. They do not specify the process, but instead establish the goals to be reached and how the achievement of those goals is to be judged. The inspection and enforcement activity is based on whether or not the goals have been met. The author goes on to offer comments on the history of the development of this process and its probable development in the future. He also addresses some issues which must be resolved or at least acknowledged. The success of risk informed regulation ultimately depends on having sufficiently reliable data to allow quantification of regulatory alternatives in terms of relative risk. Perhaps the area of human reliability and organizational performance has the greatest potential for improvement in reactor safety. The ability to model human performance is significantly less developed that the ability to model mechanical or electrical systems. The move toward risk informed, performance based regulation provides an unusual, perhaps unique, opportunity to establish a more rational, more effective basis for regulation.

  2. Regulation of Autophagy by Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda, E-mail: [Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)


    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

  3. Guidelines on Building Regulations 2008

    DEFF Research Database (Denmark)

    Thse guidelines clarify and intepret the provisions of the Building Regulations of 2008 (BR08). The Guidelines, which match BR08 in terms of organisation into Parts, are accompanied by the full text of the regulations and the explanatory notes issued by the Danish Enterprise and Construction...... Authority. The Guidelines refer the reader to sources such as relevant standards, instructions and other background material which provides more detailed information. The Guidelines cover the same ground as BR08, including building control regulations, layout, fitting out, structures, fire safety, indoor...... climate, energy consumotion and services. The Guidelines are aimed at all professionals involved in building projects, particularly building design consultants, contractors and municipal application officers....

  4. Molecular regulation of osteoclast activity. (United States)

    Bruzzaniti, Angela; Baron, Roland


    Osteoclasts are multinucleated cells derived from hematopoietic precursors that are primarily responsible for the degradation of mineralized bone during bone development, homeostasis and repair. In various skeletal disorders such as osteoporosis, hypercalcemia of malignancy, tumor metastases and Paget's disease, bone resorption by osteoclasts exceeds bone formation by osteoblasts leading to decreased bone mass, skeletal fragility and bone fracture. The overall rate of osteoclastic bone resorption is regulated either at the level of differentiation of osteoclasts from their monocytic/macrophage precursor pool or through the regulation of key functional proteins whose specific activities in the mature osteoclast control its attachment, migration and resorption. Thus, reducing osteoclast numbers and/or decreasing the bone resorbing activity of osteoclasts are two common therapeutic approaches for the treatment of hyper-resorptive skeletal diseases. In this review, several of the key functional players involved in the regulation of osteoclast activity will be discussed.

  5. Nutritional regulation of fetal growth. (United States)

    Bloomfield, Frank H; Jaquiery, Anne L; Oliver, Mark H


    Fetal growth is largely regulated by nutritional supply. The placenta is responsible for fetal nutrient supply for much of pregnancy, but in early pregnancy nutrition is histiotrophic. Both placental size and efficiency, and fetal growth, may be affected by maternal nutritional state before and during very early pregnancy. In contrast, manipulating maternal nutrition during later stages of pregnancy has a smaller than expected effect on fetal growth. Maternal nutrition before and during early pregnancy also has a greater effect on gestation length than maternal nutrition later in pregnancy, suggesting that nutritional status may regulate both fetal growth trajectory and gestation length and that these two outcomes may be linked. Thus, determination of the nutritional factors regulating fetal growth, and potentially postnatal growth and body phenotype, may lie with the maternal nutritional status even before conception.

  6. Regulation of beta cell replication

    DEFF Research Database (Denmark)

    Lee, Ying C; Nielsen, Jens Høiriis


    Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...

  7. Circadian Regulation of Macronutrient Absorption. (United States)

    Hussain, M Mahmood; Pan, Xiaoyue


    Various intestinal functions exhibit circadian rhythmicity. Disruptions in these rhythms as in shift workers and transcontinental travelers are associated with intestinal discomfort. Circadian rhythms are controlled at the molecular level by core clock and clock-controlled genes. These clock genes are expressed in intestinal cells, suggesting that they might participate in the circadian regulation of intestinal functions. A major function of the intestine is nutrient absorption. Here, we will review absorption of proteins, carbohydrates, and lipids and circadian regulation of various transporters involved in their absorption. A better understanding of circadian regulation of intestinal absorption might help control several metabolic disorders and attenuate intestinal discomfort associated with disruptions in sleep-wake cycles.

  8. Cellular regulation by protein phosphorylation. (United States)

    Fischer, Edmond H


    A historical account of the discovery of reversible protein phosphorylation is presented. This process was uncovered in the mid 1950s in a study undertaken with Edwin G. Krebs to elucidate the complex hormonal regulation of skeletal muscle glycogen phosphorylase. Contrary to the known activation of this enzyme by AMP which serves as an allosteric effector, its hormonal regulation results from a phosphorylation of the protein by phosphorylase kinase following the activation of the latter by Ca(2+) and ATP. The study led to the establishment of the first hormonal cascade of successive enzymatic reactions, kinases acting on kinases, initiated by cAMP discovered by Earl Sutherland. It also showed how two different physiological processes, carbohydrate metabolism and muscle contraction, could be regulated in concert.

  9. Digital Convergence and Content Regulation

    Directory of Open Access Journals (Sweden)

    Michael John Starks


    Full Text Available Broadcasting, Press and Internet journalism systems of distribution are converging: the same infrastructure can deliver all three historically separate services. Reception devices mirror this: the Connected TV, the tablet and the smart phone overlap in their functionality. Service overlaps are evident too, with broadcasters providing online and on-demand services and newspapers developing electronic versions. Does this mean that media regulation policies must converge too?My argument is that they should, though only where historically different communications are now fulfilling a similar function, e.g. broadcaster online services and electronic versions of newspapers. Convergence requires a degree of harmonisation and, to this end, I advocate a review of UK broadcasting's 'due impartiality' requirement and of the UK's application of the public service concept. I also argue for independent self-regulation (rather than state-based regulation of non-public-service broadcasting journalism.

  10. Upstream regulation of mycotoxin biosynthesis. (United States)

    Alkhayyat, Fahad; Yu, Jae-Hyuk


    Mycotoxins are natural contaminants of food and feed products, posing a substantial health risk to humans and animals throughout the world. A plethora of filamentous fungi has been identified as mycotoxin producers and most of these fungal species belong to the genera Aspergillus, Fusarium, and Penicillium. A number of studies have been conducted to better understand the molecular mechanisms of biosynthesis of key mycotoxins and the regulatory cascades controlling toxigenesis. In many cases, the mycotoxin biosynthetic genes are clustered and regulated by one or more pathway-specific transcription factor(s). In addition, as biosynthesis of many secondary metabolites is coordinated with fungal growth and development, there are a number of upstream regulators affecting biosynthesis of mycotoxins in fungi. This review presents a concise summary of the regulation of mycotoxin biosynthesis, focusing on the roles of the upstream regulatory elements governing biosynthesis of aflatoxin and sterigmatocystin in Aspergillus.

  11. Positively regulated bacterial expression systems. (United States)

    Brautaset, Trygve; Lale, Rahmi; Valla, Svein


    Regulated promoters are useful tools for many aspects related to recombinant gene expression in bacteria, including for high-level expression of heterologous proteins and for expression at physiological levels in metabolic engineering applications. In general, it is common to express the genes of interest from an inducible promoter controlled either by a positive regulator or by a repressor protein. In this review, we discuss established and potentially useful positively regulated bacterial promoter systems, with a particular emphasis on those that are controlled by the AraC-XylS family of transcriptional activators. The systems function in a wide range of microorganisms, including enterobacteria, soil bacteria, lactic bacteria and streptomycetes. The available systems that have been applied to express heterologous genes are regulated either by sugars (L-arabinose, L-rhamnose, xylose and sucrose), substituted benzenes, cyclohexanone-related compounds, ε-caprolactam, propionate, thiostrepton, alkanes or peptides. It is of applied interest that some of the inducers require the presence of transport systems, some are more prone than others to become metabolized by the host and some have been applied mainly in one or a limited number of species. Based on bioinformatics analyses, the AraC-XylS family of regulators contains a large number of different members (currently over 300), but only a small fraction of these, the XylS/Pm, AraC/P(BAD), RhaR-RhaS/rhaBAD, NitR/PnitA and ChnR/Pb regulator/promoter systems, have so far been explored for biotechnological applications.

  12. Medical device regulation for manufacturers. (United States)

    McAllister, P; Jeswiet, J


    Manufacturers of medical devices are held to a higher standard than manufacturers of many other products due to the potential severity of the consequences of introducing inferior or unsafe products to the market-place. In Canada, the medical device industry is regulated by Health Canada under the Medical Device Regulations of the Food and Drug Act. The Medical Device Regulations define requirements of medical device design, development and manufacture to ensure that products reaching the public are safe and effective. Health Canada also requires that medical device manufacturers maintain distribution records to ensure that devices can be traced to the source and consumers can be contacted successfully in the event that a device is recalled. Medical devices exported from Canada must be compliant with the regulations of the country of import. The Canadian Medical Device Regulations were based on the Medical Device Directives of the European Union thus facilitating approval of Canadian devices for the European market. The United States Food and Drug Administration has separate and distinct requirements for safety and quality of medical devices. While effort has been made to facilitate approval and trade of Canadian medical devices in the United States and the European Union, obtaining approval from multiple regulatory bodies can result in increased device development time and cost. The Global Harmonization Task Force is an organization composed of members from Japanese, Australian, European, Canadian and American medical device regulatory bodies. This organization was formed with the objective of harmonizing medical device regulations in an effort to facilitate international trade and standardize the quality of medical devices available to all countries. This paper discusses the requirements that must be met by manufacturers when designing and manufacturing medical devices.

  13. TWEAK Negatively Regulates Human Dicer



    The ribonuclease Dicer plays a central role in the microRNA pathway by processing microRNA precursors (pre-microRNAs) into microRNAs, a class of 19- to 24-nucleotide non-coding RNAs that regulate expression of ≈60% of the genes in humans. To gain further insights into the function and regulation of Dicer in human cells, we performed a yeast two-hybrid (Y2HB) screen using human Dicer double-stranded RNA-binding domain (dsRBD) as bait. This approach identified tumor necrosis factor (TNF)-like w...

  14. Epigenetic regulation in cardiac fibrosis

    Institute of Scientific and Technical Information of China (English)

    Li-Ming; Yu; Yong; Xu


    Cardiac fibrosis represents an adoptive response in the heart exposed to various stress cues. While resolution of the fibrogenic response heralds normalization of heart function, persistent fibrogenesis is usually associated with progressive loss of heart function and eventually heart failure. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix proteins, a process the epigenetic machinery plays a pivotal role. In this minireview, we summarize recent advances regarding the epigenetic regulation of cardiac fibrosis focusing on the role of histone and DNA modifications and non-coding RNAs.

  15. Wave Dragon Buoyancy Regulation Study

    DEFF Research Database (Denmark)

    Jakobsen, Jens; Kofoed, Jens Peter

    Wave Dragon is a wave energy converter, which was deployed offshore at Nissum Bredning in Denmark in 2003. The experience gained from operating Wave Dragon during 2003 and 2004 has shown that the buoyancy regulation system can be improved in a number of ways. This study describes the current situ...... situation, and proposes a number of activities in order to improve the buoyancy regulation system. This work was performed under EU ENERGIE contract no. ENK5-CT-2002-00603, and is a contribution to WP 2.3/2.4 and D40/D41....

  16. Regulation of Francisella tularensis Virulence

    Directory of Open Access Journals (Sweden)

    Shipan eDai


    Full Text Available Francisella tularensis is one of the most virulent bacteria known and a Centers for Disease Control and Prevention Category A select agent. It is able to infect a variety of animals and insects and can persist in the environment, thus Francisella spp. must be able to survive in diverse environmental niches. However, F. tularensis has a surprising dearth of sensory and regulatory factors. Recent advancements in the field have identified new functions of encoded transcription factors and greatly expanded our understanding of virulence gene regulation. Here we review the current knowledge of environmental adaptation by F. tularensis, its transcriptional regulators and their relationship to animal virulence.

  17. Transcription regulation mechanisms of bacteriophages (United States)

    Yang, Haiquan; Ma, Yingfang; Wang, Yitian; Yang, Haixia; Shen, Wei; Chen, Xianzhong


    Phage diversity significantly contributes to ecology and evolution of new bacterial species through horizontal gene transfer. Therefore, it is essential to understand the mechanisms underlying phage-host interactions. After initial infection, the phage utilizes the transcriptional machinery of the host to direct the expression of its own genes. This review presents a view on the transcriptional regulation mechanisms of bacteriophages, and its contribution to phage diversity and classification. Through this review, we aim to broaden the understanding of phage-host interactions while providing a reference source for researchers studying the regulation of phage transcription. PMID:25482231

  18. Politics of public utility regulation

    Energy Technology Data Exchange (ETDEWEB)

    Gormley, W.T. Jr.


    Since the early 1970s, energy and telecommunications policies have emerged as increasingly complex and conflictual issues in state government and have, consequently, brought about change in the politics of public utilities regulation. In this analysis, Gormley shows that state public utilities commissions, in determining the rates that can be charged by private utility companies, must confront elected government officials, members of the state bureaucracy, citizens' groups, and the regulated industries themselves in a very visible, highly technical, costly, and controversial process that pits investors against consumers, business groups against residential consumers, consumer groups against environmentalists, and low-income consumers against consumers as a whole.

  19. The role of food intake regulating peptides in cardiovascular regulation. (United States)

    Mikulášková, B; Maletínská, L; Zicha, J; Kuneš, J


    Obesity is a risk factor that worsens cardiovascular events leading to higher morbidity and mortality. However, the exact mechanisms of relation between obesity and cardiovascular events are unclear. Nevertheless, it has been demonstrated that pharmacological therapy for obesity has great potential to improve some cardiovascular problems. Therefore, it is important to determine the common mechanisms regulating both food intake and blood pressure. Several hormones produced by peripheral tissues work together with neuropeptides involved in the regulation of both food intake and blood pressure. Anorexigenic (food intake lowering) hormones such as leptin, glucagon-like peptide-1 and cholecystokinin cooperate with α-melanocyte-stimulating hormone, cocaine- and amphetamine-regulated peptide as well as prolactin-releasing peptide. Curiously their collective actions result in increased sympathetic activity, especially in the kidney, which could be one of the factors responsible for the blood pressure increases seen in obesity. On the other hand, orexigenic (food intake enhancing) peptides, especially ghrelin released from the stomach and acting in the brain, cooperates with orexins, neuropeptide Y, melanin-concentrating hormone and galanin, which leads to decreased sympathetic activity and blood pressure. This paradox should be intensively studied in the future. Moreover, it is important to know that the hypothalamus together with the brainstem seem to be major structures in the regulation of food intake and blood pressure. Thus, the above mentioned regions might be essential brain components in the transmission of peripheral signals to the central effects. In this short review, we summarize the current information on cardiovascular effects of food intake regulating peptides.

  20. Histaminergic regulation of prolactin secretion

    DEFF Research Database (Denmark)

    Knigge, U P


    of DA synthesis and of DA or serotonin (5-HT) receptors inhibit or prevent the PRL stimulatory action of HA infused centrally or systemically. However, other factors regulating PRL secretion (e.g. beta-endorphin, vasoactive intestinal peptide, vasopressin or TRH) may be involved in the mediation...

  1. Temperature: Human Regulating, Ants Conforming (United States)

    Clopton, Joe R.


    Biological processes speed up as temperature rises. Procedures for demonstrating this with ants traveling on trails, and data gathered by students on the Argentine ant ("Linepithema humile") are presented. The concepts of temperature regulation and conformity are detailed with a focus on the processes rather than on terms that label the organisms.

  2. Emotion regulation and successful aging. (United States)

    Suri, Gaurav; Gross, James J


    Despite normative declines in old age, healthy elderly typically report surprisingly high levels of well-being. It is not clear why this is so. A study by Brassen and colleagues suggests that one factor may be reduced responsiveness to regret. These findings highlight the role of emotion regulation in successful aging.

  3. Cell swelling and volume regulation

    DEFF Research Database (Denmark)

    Hoffmann, Else Kay


    The extracellular space in the brain is typically 20% of the tissue volume and is reduced to at least half its size under conditions of neural insult. Whether there is a minimum size to the extracellular space was discussed. A general model for cell volume regulation was presented, followed by a ...

  4. Phytochrome-regulated Gene Expression

    Institute of Scientific and Technical Information of China (English)

    Peter H. Quail


    Identification of all genes involved in the phytochrome (phy)-mediated responses of plants to their light environment is an important goal in providing an overall understanding of light-regulated growth and development. This article highlights and integrates the central findings of two recent comprehensive studies in Arabidopsis that have identified the genome-wide set of phy-regulated genes that respond rapidly to red-light signals upon first exposure of dark-grown seedlings, and have tested the functional relevance to normal seedling photomorphogenesis of an initial subset of these genes. The data: (a) reveal considerable complexity in the channeling of the light signals through the different phy-family members (phyA to phyE) to responsive genes; (b) identify a diversity of transcription-factor-encoding genes as major early, if not primary, targets of phy signaling, and, therefore, as potentially important regulators in the transcriptional-network hierarchy; and (c) identify auxin-related genes as the dominant class among rapidly-regulated, hormone-related genes. However, reverse-genetic functional profiling of a selected subset of these genes reveals that only a limited fraction are necessary for optimal phy-induced seedling deetiolation.

  5. Incentives and regulation in banking

    NARCIS (Netherlands)

    Martynova, N.


    The financial crisis of 2007-2008 has unveiled the hidden flaws in the regulatory framework of the financial sector. The rules of the game established by regulators were not stringent enough and provided bankers with wrong incentives to gamble with depositors’ money. There are two major challenges i

  6. Allosteric regulation of phenylalanine hydroxylase. (United States)

    Fitzpatrick, Paul F


    The liver enzyme phenylalanine hydroxylase is responsible for conversion of excess phenylalanine in the diet to tyrosine. Phenylalanine hydroxylase is activated by phenylalanine; this activation is inhibited by the physiological reducing substrate tetrahydrobiopterin. Phosphorylation of Ser16 lowers the concentration of phenylalanine for activation. This review discusses the present understanding of the molecular details of the allosteric regulation of the enzyme.

  7. Allosteric Regulation of Phenylalanine Hydroxylase


    Fitzpatrick, Paul F.


    The liver enzyme phenylalanine hydroxylase is responsible for conversion of excess phenylalanine in the diet to tyrosine. Phenylalanine hydroxylase is activated by phenylalanine; this activation is inhibited by the physiological reducing substrate tetrahydrobiopterin. Phosphorylation of Ser16 lowers the concentration of phenylalanine for activation. This review discusses the present understanding of the molecular details of the allosteric regulation of the enzyme.

  8. Regulating Collaboration in Teacher Education (United States)

    Dobber, Marjolein; Akkerman, Sanne F.; Verloop, Nico; Vermunt, Jan D.


    Collaboration in teacher education can be seen as a way to prepare student teachers for future social practices at school. When people collaborate with each other, they have to regulate their collaboration. In the Dutch teacher education programme that was investigated, student teachers were members of different types of groups, each of which had…

  9. Liquidity regulation and bank behavior

    NARCIS (Netherlands)

    Bonner, C.


    In response to the 2007-08 financial crisis, the Basel Committee on Banking Supervision proposed two liquidity standards to reinforce banks’ resilience to liquidity risks. The purpose of this thesis is to analyze the impact of liquidity regulation on bank behavior. The first of four main chapters an

  10. Assessing self-regulation strategies

    DEFF Research Database (Denmark)

    de Vet, Emely; de Ridder, Denise T. D.; Stok, Marijn;


    participants were aged between 10 and 17 years. Results: Study 1 resulted in a 24-item questionnaire assessing adolescent-reported use of six specific strategies for healthy eating that represent three general self-regulation approaches. Study 2 showed that the easy-to-administer theory-based TESQ-E has...

  11. The regulation of climate engineering

    NARCIS (Netherlands)

    Reynolds, J.L.


    Intentional interventions in global physical, chemical, and biological systems on a massive scale are receiving increasing attention in hopes of reducing the threat of anthropogenic climate change. Known as climate engineering, or geoengineering, research is moving forward, but regulation remains in

  12. Teaching Students To Regulate Their Own Behavior. (United States)

    Johnson, Lewis R.; Johnson, Christine E.


    Offers strategies for teaching students in all grades self-regulation skills for the purposes of behavior change. Discusses the importance of facilitating generalization, components of self-regulation, steps of self-regulation, selecting a target behavior, graphing and record keeping, and benefits and potential of teaching self-regulation skills.…

  13. The Legal Regulation of Cybersecurity

    Directory of Open Access Journals (Sweden)

    Darius Štitilis


    Full Text Available Cybercrime has become a global phenomenon, which is causing more harm to individual citizens, organizations, society and the state. Most countries in the world compare cybercrime with offences such as terrorism and drug trafficking due to its risks and profitability. Cybersecurity is the central category to fight cybercrime in cyberspace. Therefore, the strategic legal regulation of cybersecurity is one of the most relevant problems in EU, including Lithuania. So far cybersecurity legal regulation analysis in scientific literature has been rather limited. The European Commission, together with the High Representative of the Union for Foreign Affairs and Security Policy, has published a cybersecurity strategy alongside a Commission proposed directive on network and information security (NIS. The cybersecurity strategy – “An Open, Safe and Secure Cyberspace” - represents the EU’s comprehensive vision on how best to prevent and respond to cyber disruptions and attacks. The purpose of its is to further European values of freedom and democracy and ensure the digital economy can safely grow. Specific actions are aimed at enhancing cyber resilience of information systems, reducing cybercrime and strengthening EU international cyber-security policy and cyber defence. The main goal of the paper is to analyze and compare the EU cybersecurity strategy and experience of several foreign countries with the strategic legal regulation of cybersecurity in Lithuania. The article consists of four parts. The first part dealt with the EU cybersecurity strategy. The second part of the article examines the comparative aspect of foreign cybersecurity strategic legal regulation. The third part deals with attempts in Lithuania to draft cybersecurity law and the holistic approach of cybersecurity legal regulation. The fourth part examines Lithuanian cybersecurity strategy and comments on the main probleas related with the strategy. Several different approaches

  14. Regulation of the fungal secretome. (United States)

    McCotter, Sean W; Horianopoulos, Linda C; Kronstad, James W


    The ability of countless representatives of the Kingdom Fungi to adapt to and proliferate in diverse environments is facilitated by regulation of their secretomes to respond to changes in environmental conditions and to mediate interactions with other organisms. Secretome changes often fulfill common functions of nutrient acquisition, facilitation of host/symbiont interactions, cell wall modification, and optimization of the enzyme suite to adapt to new environmental resources. In this review, we expand on our recent work on signaling and the secretome in the pathogenic fungus Cryptococcus neoformans to consider a range of selected examples of regulation of fungal secretomes. These examples include the impact of carbon source and aspects of the response to plant and animal hosts. Additionally, the influence of key protein kinases (e.g., Pka1, Snf1) and transcription factors (e.g., Rim101/PacC) is highlighted to illustrate some underlying regulatory factors influencing the secretome. Although there is a wealth of information about fungal secretomes from both experimentation and genome sequence mining, there are also major gaps in our knowledge about the complete composition of fungal secretomes and mechanisms of dynamic change. For example, a more comprehensive understanding of the composition and regulation of the secretome will require consideration of the emerging roles of unconventional secretion and extracellular vesicles in delivering proteins outside the cell. Overall, changes in the secretome are well documented in diverse fungi and the underlying mechanisms are currently under investigation; however, there remain unknown steps in the regulation of secretory pathways and gaps in understanding the regulation of unconventional secretion, which warrant further research.

  15. Natural Gas Distribution Regulation Natural Gas Distribution Regulation

    Directory of Open Access Journals (Sweden)

    Fernando Salas


    Full Text Available This document discusses the economic content of a set of Ruling affecting the provision of natural gas distribution services in Mexico. As such, it describes the mechanisms proposed in order to ensure economic efficiency in the undertaking of such activity, i.e., competition policies, rate regulation, delimination of licensed geographic regions and design of auction procedures for the granting of distribution franchises. This document discusses the economic content of a set of Ruling affecting the provision of natural gas distribution services in Mexico. As such, it describes the mechanisms proposed in order to ensure economic efficiency in the undertaking of such activity, i.e., competition policies, rate regulation, delimination of licensed geographic regions and design of auction procedures for the granting of distribution franchises.


    Institute of Scientific and Technical Information of China (English)


    Objective To investigate the feasibility of using synbiotics and probiotics to prevent and cure intestinal dysbacteriosis after burn. Methods Burned rats were fed with synbiotics and probiotics reagents, and the amounts of major intestinal florae in caecal contents were detected. Results The major physiological anaerobes were mostly stable, and the conditioned pathogens had no abnormal. Conclusion The micro-ecosystem regulator can quickly supplement the decreased physiological anaerobes caused by burning,and avoid the occurrence of dysbacteriosis.

  17. Microtubule affinity-regulating kinase 4: structure, function, and regulation. (United States)

    Naz, Farha; Anjum, Farah; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz


    MAP/Microtubule affinity-regulating kinase 4 (MARK4) belongs to the family of serine/threonine kinases that phosphorylate the microtubule-associated proteins (MAP) causing their detachment from the microtubules thereby increasing microtubule dynamics and facilitating cell division, cell cycle control, cell polarity determination, cell shape alterations, etc. The MARK4 gene encodes two alternatively spliced isoforms, L and S that differ in their C-terminal region. These isoforms are differentially regulated in human tissues including central nervous system. MARK4L is a 752-residue-long polypeptide that is divided into three distinct domains: (1) protein kinase domain (59-314), (2) ubiquitin-associated domain (322-369), and (3) kinase-associated domain (703-752) plus 54 residues (649-703) involved in the proper folding and function of the enzyme. In addition, residues 65-73 are considered to be the ATP-binding domain and Lys88 is considered as ATP-binding site. Asp181 has been proposed to be the active site of MARK4 that is activated by phosphorylation of Thr214 side chain. The isoform MARK4S is highly expressed in the normal brain and is presumably involved in neuronal differentiation. On the other hand, the isoform MARK4L is upregulated in hepatocarcinoma cells and gliomas suggesting its involvement in cell cycle. Several biological functions are also associated with MARK4 including microtubule bundle formation, nervous system development, and positive regulation of programmed cell death. Therefore, MARK4 is considered as the most suitable target for structure-based rational drug design. Our sequence, structure- and function-based analysis should be helpful for better understanding of mechanisms of regulation of microtubule dynamics and MARK4 associated diseases.

  18. Targeted genome regulation via synthetic programmable transcriptional regulators

    KAUST Repository

    Piatek, Agnieszka Anna


    Regulation of gene transcription controls cellular functions and coordinates responses to developmental, physiological and environmental cues. Precise and efficient molecular tools are needed to characterize the functions of single and multiple genes in linear and interacting pathways in a native context. Modular DNA-binding domains from zinc fingers (ZFs) and transcriptional activator-like proteins (TALE) are amenable to bioengineering to bind DNA target sequences of interest. As a result, ZF and TALE proteins were used to develop synthetic programmable transcription factors. However, these systems are limited by the requirement to re-engineer proteins for each new target sequence. The clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR associated 9 (Cas9) genome editing tool was recently repurposed for targeted transcriptional regulation by inactivation of the nuclease activity of Cas9. Due to the facile engineering, simplicity, precision and amenability to library construction, the CRISPR/Cas9 system is poised to revolutionize the functional genomics field across diverse eukaryotic species. In this review, we discuss the development of synthetic customizable transcriptional regulators and provide insights into their current and potential applications, with special emphasis on plant systems, in characterization of gene functions, elucidation of molecular mechanisms and their biotechnological applications. © 2016 Informa UK Limited, trading as Taylor & Francis Group

  19. Regulating regulator y T cells to achieve transplant tolerance

    Institute of Scientific and Technical Information of China (English)

    Ran Tao; Wayne W. Hancock


    BACKGROUND:Regulatory T cells (Tregs) play crucial roles in both induction and maintenance of tolerance. This active immune regulation may contribute not only to the control of immune responses to self-antigens and thereby prevent autoimmune diseases, but also the control of responses to non-self molecules in adaptive immunity. Numerous experimental and clinical studies indicate that manipulating the balance between regulatory and responder T cells is an effective strategy to control immune responsiveness after transplantation. DATA SOURCES:Literature search was conducted using PubMed on the related subjects. Part of the material was based on the most recent work in the authors' laboratory. RESULTS: We propose some new strategies to achieve transplant tolerance in rodent animals via manipulating Treg function, including using histone deacetylase (HDAC) inhibitor to regulate Foxp3 transcription and enhance Treg suppression, induction of Treg-sparing apoptosis via Nur77, and identiifcation of the co-inhibitory molecule herpes virus entry mediator (HVEM) as an effector molecule for Treg function. CONCLUSION:Regulation of Treg function will deifnitely provide us very promising tools to achieve clinical tolerance in the future.

  20. Regulating health: transcending disciplinary boundaries. (United States)

    Seddon, Toby


    Health and health care problems can be addressed from multiple disciplinary perspectives. This raises challenges for how to do cross-disciplinary scholarship in ways that are still robust, rigorous and coherent. This paper sets out one particular approach to cross-cutting research--regulation--which has proved extremely fertile for scholars working in diverse fields, from coal mine safety to tax compliance. The first part of the paper considers how regulatory ideas might be applied to health and health care research in general. The second part goes on to sketch out how a regulation perspective on one specific area, illicit drug policy, can open up new directions for research. In conclusion, a future research agenda is outlined for regulatory scholarship on health and health care.

  1. Hawking radiation and ultraviolet regulators (United States)

    Hambli, N.; Burgess, C. P.


    Polchinski has argued that the prediction of Hawking radiation must be independent of the details of unknown high-energy physics because the calculation may be performed using ``nice slices,'' for which the adiabatic theorem may be used. If this is so, then any calculation using a manifestly covariant-and so slice-independent-ultraviolet regularization must reproduce the standard Hawking result. We investigate the dependence of the Hawking radiation on such a short-distance regulator by calculating it using a Pauli-Villars regularization scheme. We find that the regulator scale Λ only contributes to the Hawking flux by an amount that is exponentially small in the large variable Λ/TH>>1, where TH is the Hawking temperature, in agreement with Polchinski's arguments. Using the techniques of effective Lagrangians, we demonstrate the robustness of our results. We also solve a technical puzzle concerning the relation between the short-distance singularities of the propagator and the Hawking effect.

  2. Explaining (Missing) Regulator Paradigm Shifts

    DEFF Research Database (Denmark)

    Wigger, Angela; Buch-Hansen, Hubert


    The global financial and economic crisis has prompted some scholars to suggest that a fundamental regulatory shift away from neoliberalism will take place – both in general and in the field of EU competition regulation. This paper shows that so far no radical break with the neoliberal type...... of competition regulation is heaving into sight. It sets out to explain this from the vantage point of a critical political economy perspective, which identifies the circumstances under which a crisis can result in a regulatory paradigm shift. Contrasting the current situation with the shift in EC/EU competition...... capitalism; the social power configuration underpinning the neoliberal order remains unaltered; no clear counter-project has surfaced; the European Commission has been (and remains) in a position to oppose radical changes; and finally, there are no signs of a wider paradigm shift in the EU's regulatory...

  3. Information, Interests, and Environmental Regulation

    DEFF Research Database (Denmark)

    Winter, Søren; May, Peter J.


    This study contributes to the understanding of informational approaches to bringing about compliance with environmental regulations with particular attention to differences in the influence of information provided by different information sources. Based on theorizing from a combination of informa......This study contributes to the understanding of informational approaches to bringing about compliance with environmental regulations with particular attention to differences in the influence of information provided by different information sources. Based on theorizing from a combination...... of information processing and interest group literatures, we develop hypotheses about regulatees' reliance upon and the influence of different sources of information. We test these hypotheses for Danish farmers’ compliance with agro-environmental rules. Our findings show that information plays a role in bringing...

  4. Regulating Power from Supermarket Refrigeration

    DEFF Research Database (Denmark)

    O'Connell, Niamh; Madsen, Henrik; Pinson, Pierre


    This paper presents an analysis of the demand response capabilities of a supermarket refrigeration system, with a particular focus on the suitability for participation in the regulating power market. An ARMAX model of a supermarket refrigeration system is identified using experimental data from...... the Danfoss refrigeration test centre. The complexities of modelling demand response are demonstrated through simulation. Simulations are conducted by placing the identified model in a direct-control demand response architecture, with power reference tracking using model predictive control. The energylimited...... nature of demand response from refrigeration is identified as the key consideration when considering participation in the regulating power market. It is demonstrated that by restricting the operating regions of the supermarket refrigeration system, a simple relationship can be found between the available...

  5. Molecular Mechanisms of Appetite Regulation

    Directory of Open Access Journals (Sweden)

    Ji Hee Yu


    Full Text Available The prevalence of obesity has been rapidly increasing worldwide over the last several decades and has become a major health problem in developed countries. The brain, especially the hypothalamus, plays a key role in the control of food intake by sensing metabolic signals from peripheral organs and modulating feeding behaviors. To accomplish these important roles, the hypothalamus communicates with other brain areas such as the brainstem and reward-related limbic pathways. The adipocyte-derived hormone leptin and pancreatic β-cell-derived insulin inform adiposity to the hypothalamus. Gut hormones such as cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1, and oxyntomodulin transfer satiety signals to the brain and ghrelin relays hunger signals. The endocannabinoid system and nutrients are also involved in the physiological regulation of food intake. In this article, we briefly review physiological mechanisms of appetite regulation.

  6. Various Themes of Myosin Regulation. (United States)

    Heissler, Sarah M; Sellers, James R


    Members of the myosin superfamily are actin-based molecular motors that are indispensable for cellular homeostasis. The vast functional and structural diversity of myosins accounts for the variety and complexity of the underlying allosteric regulatory mechanisms that determine the activation or inhibition of myosin motor activity and enable precise timing and spatial aspects of myosin function at the cellular level. This review focuses on the molecular basis of posttranslational regulation of eukaryotic myosins from different classes across species by allosteric intrinsic and extrinsic effectors. First, we highlight the impact of heavy and light chain phosphorylation. Second, we outline intramolecular regulatory mechanisms such as autoinhibition and subsequent activation. Third, we discuss diverse extramolecular allosteric mechanisms ranging from actin-linked regulatory mechanisms to myosin:cargo interactions. At last, we briefly outline the allosteric regulation of myosins with synthetic compounds.

  7. Regulators of Tfh cell differentiation

    Directory of Open Access Journals (Sweden)

    Gajendra Motiram Jogdand


    Full Text Available The follicular helper T (Tfh cells help is critical for activation of B cells, antibody class switching and germinal center formation. The Tfh cells are characterized by the expression of CXCR5, ICOS, PD-1, Bcl-6, and IL-21. They are involved in clearing infections and are adversely linked with autoimmune diseases and also have a role in viral replication as well as clearance. Tfh cells are generated from naïve CD4 T cells with sequential steps involving cytokine signaling (IL-21, IL-6, IL-12, activin A, migration and positioning in the germinal center by CXCR5, surface receptors (ICOS/ICOSL, SAP/SLAM as well as transcription factor (Bcl-6, c-Maf, STAT3 signaling and repressor miR155. On the other hand Tfh generation is negatively regulated at specific steps of Tfh generation by specific cytokine (IL-2, IL-7, surface receptor (PD-1, CTLA-4, transcription factors Blimp-1, STAT5, T-bet, KLF-2 signaling and repressor miR 146a. Interestingly, miR 17-92 and FOXO1 acts as a positive as well as a negative regulator of Tfh differentiation depending on the time of expression and disease specificity. Tfh cells are also generated from the conversion of other effector T cells as exemplified by Th1 cells converting into Tfh during viral infection. The mechanistic details of effector T cells conversion into Tfh are yet to be clear. To manipulate Tfh cells for therapeutic implication and or for effective vaccination strategies, it is important to know positive and negative regulators of Tfh generation. Hence, in this review we have highlighted and interlinked molecular signaling from cytokines, surface receptors, transcription factors, ubiquitin Ligase and miRNA as positive and negative regulators for Tfh differentiation.

  8. Food Regulation in Biblical Law


    Wilkenfeld, Wendy A.


    Everyone needs to eat, yet most societies and many world religions limit the available food supply by practicing some form of dietary restriction. However, biblical law presents a special case because "few [societies] systematically define all animals as permitted or forbidden and invoke divine authority for the instructions." For at least two thousand years, people have wondered why such a complex and comprehensive system of food regulation as is found in biblical law would fail to offer any...

  9. Hawking Radiation and Ultraviolet Regulators


    Hambli, N.; Burgess, C. P.


    Polchinski has argued that the prediction of Hawking radiation must be independent of the details of unknown high-energy physics because the calculation may be performed using `nice slices', for which the adiabatic theorem may be used. If this is so, then any calculation using a manifestly covariant --- and so slice-independent --- ultraviolet regularization must reproduce the standard Hawking result. We investigate the dependence of the Hawking radiation on such a short-distance regulator by...

  10. Phenotyping jasmonate regulation of senescence. (United States)

    Seltmann, Martin A; Berger, Susanne


    Osmotic stress induces several senescence-like processes in leaves, such as specific changes in gene expression and yellowing. These processes are dependent on the accumulation of jasmonates and on intact jasmonate signaling. This chapter describes the treatment of Arabidopsis thaliana leaves with sorbitol as an osmotic stress agent and the determination of the elicited phenotypes encompassing chlorophyll loss, degradation of plastidial membrane lipids, and induction of genes regulated by senescence and jasmonate.

  11. Regulation Mechanisms of Stomatal Oscillation

    Institute of Scientific and Technical Information of China (English)

    Hui-Min YANG; Jian-Hua ZHANG; Xiao-Yan ZHANG


    Stomata function as the gates between the plant and the atmospheric environment. Stomatal movement, including stomatal opening and closing, controls CO2 absorption as the raw material for photosynthesis and water loss through transpiration. How to reduce water loss and maintain enough CO2 absorption has been an interesting research topic for some time. Simple stomatal opening may elevate CO2 absorption,but, in the meantime, promote the water loss, whereas simple closing of stomatal pores may reduce both water loss and CO2 absorption, resulting in impairment of plant photosynthesis. Both processes are not economical to the plant. As a special rhythmic stomatal movement that usually occurs at smaller stomatal apertures, stomatal oscillation can keep CO2 absorption at a sufficient level and reduce water loss at the same time, suggesting a potential improvement in water use efficiency. Stomatal oscillation is usually found after a sudden change in one environmental factor in relatively constant environments. Many environmental stimuli can induce stomatal oscillation. It appears that, at the physiological level, feedback controls are involved in stomatal oscillation. At the cellular level, possibly two different patterns exist: (i) a quicker responsive pattern; and (ii) a slower response. Both involve water potential changes and water channel regulation, but the mechanisms of regulation of the two patterns are different. Some evidence suggests that the regulation of water channels may play a vital and primary role in stomatal oscillation. The present review summarizes studies on stomatal oscillation and concludes with some discussion regarding the mechanisms of regulation of stomatal oscillation.

  12. Regulation of Rad51 promoter (United States)

    Hine, Christopher M; Li, Hongjie; Xie, Li; Mao, Zhiyong; Seluanov, Andrei; Gorbunova, Vera


    The DNA double-strand break repair and homologous recombination protein Rad51 is overexpressed in the majority of human cancers. This correlates with therapy resistance and decreased patient survival. We previously showed that constructs containing Rad51 promoter fused to a reporter gene are, on average, 850-fold more active in cancer cells than in normal cells. It is not well understood what factors and sequences regulate the Rad51 promoter and cause its high activity in cancerous cells. Here we characterized regulatory regions and examined genetic requirements for oncogenic stimulation of the Rad51 promoter. We identified specific regions responsible for up- and downregulation of the Rad51 promoter in cancerous cells. Furthermore, we show that Rad51 expression is positively regulated by EGR1 transcription factor. We then modeled the malignant transformation process by expressing a set of oncoproteins in normal human fibroblasts. Expression of different combinations of SV40 large T antigen, oncogenic Ras and SV40 small T antigen resulted in step-wise increase in Rad51 promoter activity, with all the 3 oncoproteins together leading to a 47-fold increase in expression. Cumulatively, these results suggest that Rad51 promoter is regulated by multiple factors, and that its expression is gradually activated as cells progress toward malignancy. PMID:24781030

  13. Steroid hormones and sleep regulation. (United States)

    Terán-Pérez, G; Arana-Lechuga, Y; Esqueda-León, E; Santana-Miranda, R; Rojas-Zamorano, J Á; Velázquez Moctezuma, J


    In the search of the sleep substance, many studies have been addressed for different hormones, responsible for sleep-wake cycle regulation. In this article we mentioned the participation of steroid hormones, besides its role regulating sexual behavior, they influence importantly in the sleep process. One of the clearest relationships are that estrogen and progesterone have, that causing changes in sleep patterns associated with the hormonal cycles of women throughout life, from puberty to menopause and specific periods such as pregnancy and the menstrual cycle, including being responsible for some sleep disorders such as hypersomnia and insomnia. Another studied hormone is cortisol, a hormone released in stressful situations, when an individual must react to an extraordinary demand that threatens their survival, but also known as the hormone of awakening because the release peak occurs in the morning, although this may be altered in some sleep disorders like insomnia and mood disorders. Furthermore neurosteroids such as pregnanolone, allopregnanolone and pregnenolone are involved in the generation of slow wave sleep, the effect has been demonstrated in experimental animal studies. Thus we see that the sleep and the endocrine system saved a bidirectional relationship in which depends on each other to regulate different physiological processes including sleep.

  14. Epigenetic microRNA Regulation

    DEFF Research Database (Denmark)

    Wiklund, Erik Digman


    MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that negatively regulate gene expression post-transcriptionally by binding to complementary sequences in the 3’UTR of target mRNAs in the cytoplasm. However, recent evidence suggests that certain miRNAs are enriched in the nucleus......, and their targets do not seem restricted to mRNA 3’UTRs. Therefore, miRNAs are predicted to have a variety functions throughout mammalian cells. MiRNA genes appear to be regulated in much the same way as coding genes, but current insight into transcriptional miRNA control lacks detail, as mapping miRNA promoters...... and confirming transcriptional start sites can be difficult. Epigenetics, gene regulatory and DNA modification mechanisms not involving a change to the primary sequence, have been implied in the regulation of a number of miRNA loci. Both epigenetic and miRNA signatures are broadly altered in cancer...

  15. NRC - regulator of nuclear safety

    Energy Technology Data Exchange (ETDEWEB)



    The U.S. Nuclear Regulatory Commission (NRC) was formed in 1975 to regulate the various commercial and institutional uses of nuclear energy, including nuclear power plants. The agency succeeded the Atomic Energy Commission, which previously had responsibility for both developing and regulating nuclear activities. Federal research and development work for all energy sources, as well as nuclear weapons production, is now conducted by the U.S. Department of Energy. Under its responsibility to protect public health and safety, the NRC has three principal regulatory functions: (1) establish standards and regulations, (2) issue licenses for nuclear facilities and users of nuclear materials, and (3) inspect facilities and users of nuclear materials to ensure compliance with the requirements. These regulatory functions relate to both nuclear power plants and to other uses of nuclear materials - like nuclear medicine programs at hospitals, academic activities at educational institutions, research work, and such industrial applications as gauges and testing equipment. The NRC places a high priority on keeping the public informed of its work. The agency recognizes the interest of citizens in what it does through such activities as maintaining public document rooms across the country and holding public hearings, public meetings in local areas, and discussions with individuals and organizations.

  16. Epigenetic regulation of protein glycosylation. (United States)

    Zoldoš, Vlatka; Grgurević, Srđana; Lauc, Gordan


    Protein N-glycosylation is an ancient metabolic pathway that still exists in all three domains of life (Archaea, Bacteria and Eukarya). The covalent addition of one or more complex oligosaccharides (glycans) to protein backbones greatly diversifies their structures and makes the glycoproteome several orders of magnitude more complex than the proteome itself. Contrary to polypeptides, which are defined by a sequence of nucleotides in the corresponding genes, the glycan part of glycoproteins are encoded in a complex dynamic network of hundreds of proteins, whereby activity is defined by both genetic sequence and the regulation of gene expression. Owing to the complex nature of their biosynthesis, glycans are particularly versatile and apparently a large part of human variation derives from differences in protein glycosylation. Composition of the individual glycome appears to be rather stable, and thus differences in the pattern of glycan synthesis between individuals could originate either from genetic polymorphisms or from stable epigenetic regulation of gene expression in different individuals. Studies of epigenetic modification of genes involved in protein glycosylation are still scarce, but their results indicate that this process might be very important for the regulation of protein glycosylation.

  17. The mother as hidden regulator

    Directory of Open Access Journals (Sweden)

    Annie Panzer


    Full Text Available A human baby is born with a decidedly immature brain, and is absolutely dependent on an intense relationship with its mother (or primary caregiver for brain maturation. In the short term, maternal regulation contributes to a more joyful baby, while in the long term it leads to the internalisation and development of self-regulatory capabilities. The ability to regulate one’s own emotional states is based on the development of right orbitofrontal dominance of dual limbic circuits, i.e. the excitatory sympathetic ventral tegmental circuit, and the inhibitory parasympathetic lateral tegmental circuit. Thus the child will be able to calm down after nigh overwhelming emotions by activating the parasympathetic system, but also to bounce back after setbacks by activating the sympathetic system. The mother influences the parcellation of the two limbic systems and thus the permanent excitation-inhibition autonomic balance of its prefrontal regulatory system. Repeated unregulated emotional states in the practicing period from 12-18 months pave the way for various psychological and psychiatric disorders in adulthood. It is worrisome that many children pass through this critical time in nursery schools, where a shortage of adult staff may lead to the scenario where a child’s emotions are repeatedly not modulated, with dire consequences for the internalisation of its future self-regulating capabilities.

  18. Hate crimes and normative regulation

    Directory of Open Access Journals (Sweden)

    Kovačević Milica


    Full Text Available This paper is primarily devoted to issues related to the normative regulation of hate crimes, with special reference to the regulations of the Republic of Serbia, which are indirectly related to this matter. This kind of crimes are characterized by prejudices that perpetrators have towards injured parties, as members of certain, mostly, minority groups, due to which many hate crimes could be also called crimes of prejudice. In comparative law there are two different basic directions when it comes to regulating hate crimes: separation of hate crimes in a separate category on the one hand, and punishment of perpetrators of criminal acts with the detriment of minority groups through the usual charges of a given criminal justice system, on the other. The author finds that, regardless of the formal response forms, real life suggests that hate crimes can be essentially suppressed only by promoting values such as equality, respect for diversity and tolerance, and by continuous education of public about the danger of hate crimes.

  19. Epigenetic regulation in Parkinson's disease. (United States)

    Labbé, Catherine; Lorenzo-Betancor, Oswaldo; Ross, Owen A


    Recent efforts have shed new light on the epigenetic mechanisms driving gene expression alterations associated with Parkinson's disease (PD) pathogenesis. Changes in gene expression are a well-established cause of PD, and epigenetic mechanisms likely play a pivotal role in regulation. Studies in families with PD harboring duplications and triplications of the SNCA gene have demonstrated that gene dosage is associated with increased expression of both SNCA mRNA and protein, and correlates with a fulminant disease course. Furthermore, it is postulated that even subtle changes in SNCA expression caused by common variation is associated with disease risk. Of note, genome-wide association studies have identified over 30 loci associated with PD with most signals located in non-coding regions of the genome, thus likely influencing transcript expression levels. In health, epigenetic mechanisms tightly regulate gene expression, turning genes on and off to balance homeostasis and this, in part, explains why two cells with the same DNA sequence will have different RNA expression profiles. Understanding this phenomenon will be crucial to our interpretation of the selective vulnerability observed in neurodegeneration and specifically dopaminergic neurons in the PD brain. In this review, we discuss epigenetic mechanisms, such as DNA methylation and histone modifications, involved in regulating the expression of genes relevant to PD, RNA-based mechanisms, as well as the effect of toxins and potential epigenetic-based treatments for PD.

  20. Musical affect regulation in infancy. (United States)

    Trehub, Sandra E; Ghazban, Niusha; Corbeil, Mariève


    Adolescents and adults commonly use music for various forms of affect regulation, including relaxation, revitalization, distraction, and elicitation of pleasant memories. Mothers throughout the world also sing to their infants, with affect regulation as the principal goal. To date, the study of maternal singing has focused largely on its acoustic features and its consequences for infant attention. We describe recent laboratory research that explores the consequences of singing for infant affect regulation. Such work reveals that listening to recordings of play songs can maintain 6- to 9-month-old infants in a relatively contented or neutral state considerably longer than recordings of infant-directed or adult-directed speech. When 10-month-old infants fuss or cry and are highly aroused, mothers' multimodal singing is more effective than maternal speech at inducing recovery from such distress. Moreover, play songs are more effective than lullabies at reducing arousal in Western infants. We explore the implications of these findings along with possible practical applications.

  1. RegulatING chromatin regulators: post-translational modification of the ING family of epigenetic regulators. (United States)

    Satpathy, Shankha; Nabbi, Arash; Riabowol, Karl


    The five human ING genes encode at least 15 splicing isoforms, most of which affect cell growth, differentiation and apoptosis through their ability to alter gene expression by epigenetic mechanisms. Since their discovery in 1996, ING proteins have been classified as type II tumour suppressors on the basis of reports describing their down-regulation and mislocalization in a variety of cancer types. In addition to their regulation by transcriptional mechanisms, understanding the range of PTMs (post-translational modifications) of INGs is important in understanding how ING functions are fine-tuned in the physiological setting and how they add to the repertoire of activities affected by the INGs. In the present paper we review the different PTMs that have been reported to occur on INGs. We discuss the PTMs that modulate ING function under normal conditions and in response to a variety of stresses. We also describe the ING PTMs that have been identified by several unbiased MS-based PTM enrichment techniques and subsequent proteomic analysis. Among the ING PTMs identified to date, a subset has been characterized for their biological significance and have been shown to affect processes including subcellular localization, interaction with enzymatic complexes and ING protein half-life. The present review aims to highlight the emerging role of PTMs in regulating ING function and to suggest additional pathways and functions where PTMs may effect ING function.

  2. Back Bay National Wildlife Refuge regulations (United States)

    US Fish and Wildlife Service, Department of the Interior — This document is a collection of regulations pertaining to the Back Bay National Wildlife Refuge. Most of the regulations concern motor vehicle use on the refuge.

  3. Feedback regulation between autophagy and PKA. (United States)

    Torres-Quiroz, Francisco; Filteau, Marie; Landry, Christian R


    Protein kinase A (PKA) controls diverse cellular processes and homeostasis in eukaryotic cells. Many processes and substrates of PKA have been described and among them are direct regulators of autophagy. The mechanisms of PKA regulation and how they relate to autophagy remain to be fully understood. We constructed a reporter of PKA activity in yeast to identify genes affecting PKA regulation. The assay systematically measures relative protein-protein interactions between the regulatory and catalytic subunits of the PKA complex in a systematic set of genetic backgrounds. The candidate PKA regulators we identified span multiple processes and molecular functions (autophagy, methionine biosynthesis, TORC signaling, protein acetylation, and DNA repair), which themselves include processes regulated by PKA. These observations suggest the presence of many feedback loops acting through this key regulator. Many of the candidate regulators include genes involved in autophagy, suggesting that not only does PKA regulate autophagy but that autophagy also sends signals back to PKA.

  4. Working without limits – reconsidering regulation

    DEFF Research Database (Denmark)

    Jensen, Per Langå


    In the light ofthe development of industry and working conditions present challenges to regulation is presented.......In the light ofthe development of industry and working conditions present challenges to regulation is presented....

  5. Self-tuning regulators. [adaptive control research (United States)

    Astrom, K. J.


    The results of a research project are discussed for self-tuning regulators for active control. An algorithm for the self-tuning regulator is described as being stochastic, nonlinear, time variable, and not trivial.

  6. Tewaukon National Wildlife Refuge: Summer Fishing Regulation (United States)

    US Fish and Wildlife Service, Department of the Interior — This memorandum summarizes the summer fishing regulation for Tewaukon National Wildlife Refuge as submitted to the Federal Register. This regulation defines areas...

  7. Cholinergic regulation of airway inflammation and remodelling

    NARCIS (Netherlands)

    Kolahian, Saeed; Gosens, Reinoud


    Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway disease

  8. Feedback regulation between autophagy and PKA (United States)

    Torres-Quiroz, Francisco; Filteau, Marie; Landry, Christian R


    Protein kinase A (PKA) controls diverse cellular processes and homeostasis in eukaryotic cells. Many processes and substrates of PKA have been described and among them are direct regulators of autophagy. The mechanisms of PKA regulation and how they relate to autophagy remain to be fully understood. We constructed a reporter of PKA activity in yeast to identify genes affecting PKA regulation. The assay systematically measures relative protein-protein interactions between the regulatory and catalytic subunits of the PKA complex in a systematic set of genetic backgrounds. The candidate PKA regulators we identified span multiple processes and molecular functions (autophagy, methionine biosynthesis, TORC signaling, protein acetylation, and DNA repair), which themselves include processes regulated by PKA. These observations suggest the presence of many feedback loops acting through this key regulator. Many of the candidate regulators include genes involved in autophagy, suggesting that not only does PKA regulate autophagy but that autophagy also sends signals back to PKA. PMID:26046386

  9. Securities regulation and implicit penalties

    Directory of Open Access Journals (Sweden)

    Donghua Chen


    Full Text Available The extant literature offers extensive support for the significant role played by institutions in financial markets, but implicit regulation and monitoring have yet to be examined. This study fills this void in the literature by employing unique Chinese datasets to explore the implicit regulation and penalties imposed by the Chinese government in regulating the initial public offering (IPO market. Of particular interest are the economic consequences of underwriting IPO deals for client firms that violate regulatory rules in China’s capital market. We provide evidence to show that the associated underwriters’ reputations are impaired and their market share declines. We further explore whether such negative consequences result from a market disciplinary mechanism or a penalty imposed by the government. To analyze the possibility of a market disciplinary mechanism at work, we investigate (1 the market reaction to other client firms whose IPO deals were underwritten by underwriters associated with a violation at the time the violation was publicly disclosed and (2 the under-pricing of IPO deals undertaken by these underwriters after such disclosure. To analyze whether the government imposes an implicit penalty, we examine the application processing time for future IPO deals underwritten by the associated underwriters and find it to be significantly longer than for IPO deals underwritten by other underwriters. Overall, there is little evidence to suggest that the market penalizes underwriters for the rule-violating behavior of their client firms in China. Instead, the Chinese government implicitly penalizes them by imposing more stringent criteria on and lengthening the processing time of the IPO deals they subsequently underwrite.

  10. Regulated polyploidy in halophilic archaea.

    Directory of Open Access Journals (Sweden)

    Sebastian Breuert

    Full Text Available Polyploidy is common in higher eukaryotes, especially in plants, but it is generally assumed that most prokaryotes contain a single copy of a circular chromosome and are therefore monoploid. We have used two independent methods to determine the genome copy number in halophilic archaea, 1 cell lysis in agarose blocks and Southern blot analysis, and 2 Real-Time quantitative PCR. Fast growing H. salinarum cells contain on average about 25 copies of the chromosome in exponential phase, and their ploidy is downregulated to 15 copies in early stationary phase. The chromosome copy number is identical in cultures with a twofold lower growth rate, in contrast to the results reported for several other prokaryotic species. Of three additional replicons of H. salinarum, two have a low copy number that is not growth-phase regulated, while one replicon even shows a higher degree of growth phase-dependent regulation than the main replicon. The genome copy number of H. volcanii is similarly high during exponential phase (on average 18 copies/cell, and it is also downregulated (to 10 copies as the cells enter stationary phase. The variation of genome copy numbers in the population was addressed by fluorescence microscopy and by FACS analysis. These methods allowed us to verify the growth phase-dependent regulation of ploidy in H. salinarum, and they revealed that there is a wide variation in genome copy numbers in individual cells that is much larger in exponential than in stationary phase. Our results indicate that polyploidy might be more widespread in archaea (or even prokaryotes in general than previously assumed. Moreover, the presence of so many genome copies in a prokaryote raises questions about the evolutionary significance of this strategy.

  11. Securities regulation and implicit penalties

    Institute of Scientific and Technical Information of China (English)

    Donghua; Chen; Yuyan; Guan; Gang; Zhao; Feifei; Wu


    The extant literature offers extensive support for the significant role played by institutions in financial markets,but implicit regulation and monitoring have yet to be examined.This study fills this void in the literature by employing unique Chinese datasets to explore the implicit regulation and penalties imposed by the Chinese government in regulating the initial public offering(IPO) market.Of particular interest are the economic consequences of underwriting IPO deals for client firms that violate regulatory rules in China’s capital market.We provide evidence to show that the associated underwriters’ reputations are impaired and their market share declines.We further explore whether such negative consequences result from a market disciplinary mechanism or a penalty imposed by the government.To analyze the possibility of a market disciplinary mechanism at work,we investigate(1) the market reaction to other client firms whose IPO deals were underwritten by underwriters associated with a violation at the time the violation was publicly disclosed and(2) the under-pricing of IPO deals undertaken by these underwriters after such disclosure.To analyze whether the government imposes an implicit penalty,we examine the application processing time for future IPO deals underwritten by the associated underwriters and find it to be significantly longer than for IPO deals underwritten by other underwriters.Overall,there is little evidence to suggest that the market penalizes underwriters for the rule-violating behavior of their client firms in China.Instead,the Chinese government implicitly penalizes them by imposing more stringent criteria on and lengthening the processing time of the IPO deals they subsequently underwrite.

  12. Regulation of amniotic fluid volume. (United States)

    Beall, M H; van den Wijngaard, J P H M; van Gemert, M J C; Ross, M G


    Water arrives in the mammalian gestation from the maternal circulation across the placenta. It then circulates between the fetal water compartments, including the fetal body compartments, the placenta and the amniotic fluid. Amniotic fluid is created by the flow of fluid from the fetal lung and bladder. A major pathway for amniotic fluid resorption is fetal swallowing; however, in many cases the amounts of fluid produced and absorbed do not balance. A second resorption pathway, the intramembranous pathway (across the amnion to the fetal circulation), has been proposed to explain the maintenance of normal amniotic fluid volume. Amniotic fluid volume is thus a function both of the amount of water transferred to the gestation across the placental membrane, and the flux of water across the amnion. Water flux across biologic membranes may be driven by osmotic or hydrostatic forces; existing data suggest that intramembranous flow in humans is driven by the osmotic difference between the amniotic fluid and the fetal serum. The driving force for placental flow is more controversial, and both forces may be in effect. The mechanism(s) responsible for regulating water flow to and from the amniotic fluid is unknown. In other parts of the body, notably the kidney, water flux is regulated by the expression of aquaporin water channels on the cell membrane. We hypothesize that aquaporins have a role in regulating water flux across both the amnion and the placenta, and present evidence in support of this theory. Current knowledge of gestational water flow is sufficient to allow prediction of fetal outcome when water flow is abnormal, as in twin-twin transfusion syndrome. Further insight into these mechanisms may allow novel treatments for amniotic fluid volume abnormalities with resultant improvement in clinical outcome.

  13. The Cost of Railroad Regulation

    DEFF Research Database (Denmark)

    Federico, Giovanni; Sharp, Paul R.

    We investigate the costs of transportation regulation using the example of agricultural markets in the United States. Using a large database of prices by state of agricultural commodities, we find that the coefficient of variation (as a measure of market integration between states) falls for many...... commodities until the First World War. We demonstrate that this reflected changes in transportation costs which in turn in the long run depended on productivity growth in railroads. 1920 marked a change in this relationship, however, and between the First and Second World Wars we find considerable...

  14. Power electronics converters and regulators

    CERN Document Server

    Dokić, Branko L


    This book is the result of the extensive experience the authors gained through their year-long occupation at the Faculty of Electrical Engineering at the University of Banja Luka. Starting at the fundamental basics of electrical engineering, the book guides the reader into this field and covers all the relevant types of converters and regulators. Understanding is enhanced by the given examples, exercises and solutions. Thus this book can be used as a textbook for students, for self-study or as a reference book for professionals.

  15. Content delivery network and regulation

    Institute of Scientific and Technical Information of China (English)

    PENG Jiu-sheng; LIANG Xiong-jian


    First, this article provides an introduction to the content delivery network (CDN), which has wide prospects but is still in its early stages in China. Second, this article depicts the present situation and the developing characteristics of CDN in China. Elaborating on the above-mentioned two points, this article identifies the numerous problems that are encountered during the development of CDN, such as indistinct service positioning and the hidden troubles of information security.Finally, this article presents several countermeasures for handling the problems, such as opening the market widely,making a rational service positioning, strengthening the regulation on information security, and punishing illegal operations and unfair competition.

  16. Neurobiology of Circadian Rhythm Regulation. (United States)

    Rosenwasser, Alan M; Turek, Fred W


    Over the past few decades, multilevel research has elucidated the basic neuroanatomy, neurochemistry, and molecular neurobiology of the master circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). The circadian timing system is composed of a large number of cellular oscillators located in the SCN, in non-SCN brain structures, and throughout the body. Cellular-level oscillations are generated by a molecular feedback loop in which circadian clock genes rhythmically regulate their own transcription, as well as that of hundreds of clock-controlled genes. The maintenance of proper coordination within this network of cellular- and tissue-level clocks is essential for health and well-being.

  17. Regulation possibilities of biomass combustion (United States)

    Suzdalenko, Vera; Gedrovics, Martins; Zake, Maija; Barmina, Inesa


    The focus of the recent experimental research is to analyze the regulation possibilities of biomass combustion. Three possibilities were chosen as part of this research: a) biomass cofiring with propane, b) swirling flow with re-circulation zone, and c) use of a permanent magnet. The aim of the research is to provide stable, controllable and effective biomass combustion with minimum emissions. The special pilot device was created where biomass can be combusted separately and co-fired with propane. Wood pellets were used during the experiments.

  18. Turbinski regulator za male hidroelektrarne


    Bergoč, Primož


    V pričujočem delu je predstavljen razvoj turbinskega regulatorja za male hidroelektrarne s sinhronskim generatorjem. Turbinski regulator je pomemben člen vsakega hidro agregata, saj je njegova naloga vzdrževati turbino v želeni delovni točki glede na izbran režim obratovanja z reguliranjem odprtja izvršnih členov. Izvršni členi so lahko vodilnik, gonilnik ali iglasti ventil in odrezač, odvisno od vrste turbine. Algoritem turbinskega regulatorja smo izvedli na programirljivem logičnem krmi...

  19. Regulating renewable resources under uncertainty

    DEFF Research Database (Denmark)

    Hansen, Lars Gårn

    Renewable natural resources (like water, fish and wildlife stocks, forests and grazing lands) are critical for the livelihood of millions of people and understanding how they can be managed efficiently is an important economic problem. I show how regulator uncertainty about different economic......) that a pro-quota result under uncertainty about prices and marginal costs is unlikely, requiring that the resource growth function is highly concave locally around the optimum and, 3) that quotas are always preferred if uncertainly about underlying structural economic parameters dominates. These results...

  20. Environmental justice regulations draw fire (United States)

    Showstack, Randy

    Advocates of "environmental justice" say that proposed U.S. Environmental Protection Agency (EPA) regulations are necessary to ensure that an unfair share of industrial facilities and waste plants are not sited in poor and minority communities, as they claim has occurred in the past.However, a number of state and local government agencies, business groups, and Democratic and Republican politicians argue that EPA guidelines—written to put some teeth into the Title VI clause of the Civil Rights Act that prohibits discrimination in all federally funded programs and activities—are unworkable and need to be overhauled.

  1. QB1 - Stochastic Gene Regulation

    Energy Technology Data Exchange (ETDEWEB)

    Munsky, Brian [Los Alamos National Laboratory


    Summaries of this presentation are: (1) Stochastic fluctuations or 'noise' is present in the cell - Random motion and competition between reactants, Low copy, quantization of reactants, Upstream processes; (2) Fluctuations may be very important - Cell-to-cell variability, Cell fate decisions (switches), Signal amplification or damping, stochastic resonances; and (3) Some tools are available to mode these - Kinetic Monte Carlo simulations (SSA and variants), Moment approximation methods, Finite State Projection. We will see how modeling these reactions can tell us more about the underlying processes of gene regulation.

  2. Autonomic Regulation of Splanchnic Circulation

    Directory of Open Access Journals (Sweden)

    Kathleen A Fraser


    Full Text Available The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.

  3. Returning common sense to regulations

    Energy Technology Data Exchange (ETDEWEB)

    Fox, M.R.


    While these sessions of the November 1995 meeting of the American Nuclear Society are being devoted to the Linear Theory of harm from radiation, it must be realized that the low-level radiation issue, as important as it may be, is but a subset of an entire body of environmental issues running afoul of common sense. Cellular phones, electromagnetic fields, asbestos, dioxin, acid rain, and others especially in their public portrayals, some in their regulatory treatment, are based upon exaggerated or misunderstood risks. One must recognize that what lies ahead is an immense effort to revisit the underlying science of the existing regulations of radiation exposures. New evidence has been published, and most importantly, it is now recognized that many of these regulations--promulgated with the best of intentions--have been extraordinarily harmful to the public. In many cases, the harm has been exaggerated, and has created in the public policy arena the notion that the public is at great risk from the smallest sources of radiation. The national cost of compliance with these regulations has been enormous. To the extent that existing environmental regulations are not being moderated, they pose major economic threats to present and future industries involving nuclear materials and technology. These would include the pharmaceutical industries as well as those seeking U.S. isotope markets in separations, purification, labeling, and manufacturing of new radiopharmaceuticals for cancer therapy, diagnosis, pain mitigation, treatment of arthritis, and other new applications. For those who are not aware of the results of recent advances in radiopharmaceuticals, clinical trials have demonstrated an 80% remission rate in the treatment of b-cell lymphoma and leukemia. New isotopes and new isotope technology promise greater effectiveness in the treatment of cancer and other diseases. The regulatory problems and their enormous costs exist at all stages in nuclear medicine, from the

  4. Hard work in soft regulation

    DEFF Research Database (Denmark)

    Hohnen, Pernille; Hasle, Peter; Helbo Jespersen, Anne

    Certified occupational health and safety management (OHSM) systems have become a global instrument in the regulation of work environment. However, their actual impact on occupational health and safety – in particular on ‘softer’ psychosocial areas of the working environment – has been questioned....... This has resulted in recent British attempts to develop publically available guidelines (PAS 1010) to be used together with OHSAS 18001 focusing specifically on psychosocial risk management. The paper discusses these attempts in light of recent sociological theories on the regulatory mechanisms...

  5. MicroRNA Regulation of SIRT1


    Yamakuchi, Munekazu


    SIRT1 is an NAD-dependent deacetylase that regulates stress response pathways. By deacetylating transcription factors and co-factors, SIRT1 modulates metabolism, inflammation, hypoxic responses, circadian rhythms, cell survival, and longevity. Since SIRT1 plays a key role in regulating pathways involved in cardiovascular diseases and metabolic diseases cancer, the regulation of SIRT1 has received intense scrutiny. The post-transcriptional regulation of SIRT1 is mediated by two classes of mole...

  6. VLSI Hybrid DC-DC Regulator


    Cosp Vilella, Jordi; Martínez García, Herminio


    Hybrid DC-DC regulators are structures that combine both a linear voltage regulator and a switching DC-DC converter. The main objective of this hybrid topology is to converge, in a single circuit topology, the best of both alternatives: a small voltage output ripple, which is a common characteristic of linear regulator circuits, and good energy efficiency, as in switching alternatives. While the linear regulator fixes the required output voltage to a fixed value with negligible steady-state r...

  7. 46 CFR 310.67 - Academy regulations. (United States)


    ... 46 Shipping 8 2010-10-01 2010-10-01 false Academy regulations. 310.67 Section 310.67 Shipping... Training of Midshipmen at the United States Merchant Marine Academy § 310.67 Academy regulations. The Superintendent of the Academy is delegated authority to issue all regulations necessary for the accomplishment...

  8. 7 CFR 983.50 - Aflatoxin regulations. (United States)


    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Aflatoxin regulations. 983.50 Section 983.50..., ARIZONA, AND NEW MEXICO Regulations § 983.50 Aflatoxin regulations. The committee shall establish, with the approval of the Secretary, such aflatoxin sampling, analysis, and inspection...

  9. Becoming an Engaged, Self-Regulated Reader. (United States)

    Horner, Sherri L.; Shwery, Craig S.


    Explains how students self-regulate while reading, describing students' personal beliefs of self-efficacy, task value, and motivation and how these beliefs influence their self- regulated reading; discussing the processes of self-regulated reading (goal setting; selection, use, and monitoring of reading strategies; and self-evaluation); and…

  10. 75 FR 10567 - Commerce Acquisition Regulation (CAR) (United States)


    ... Commerce 48 CFR Chapter 13 Commerce Acquisition Regulation (CAR); Final Rule #0;#0;Federal Register / Vol. 75, No. 44 / Monday, March 8, 2010 / Rules and Regulations#0;#0; ] DEPARTMENT OF COMMERCE 48 CFR Chapter 13 RIN 0605-AA26 Commerce Acquisition Regulation (CAR) AGENCY: Department of Commerce...

  11. 76 FR 62630 - Information Security Regulations (United States)


    ... 32 CFR Part 1902 Information Security Regulations AGENCY: Central Intelligence Agency. ACTION: Final rule. SUMMARY: The Central Intelligence agency is removing certain information security regulations... Information security regulations. PART 1902 Sec. 1902.13 0 Accordingly, under the authority of Executive...

  12. Identification of let-7-regulated oncofetal genes

    DEFF Research Database (Denmark)

    Boyerinas, Benjamin; Park, Sun-Mi; Shomron, Noam;


    -regulated at the end of embryonic development. Let-7 is often down-regulated early during cancer development, suggesting that let-7-regulated oncofetal genes (LOG) may become reexpressed in cancer cells. Using comparative bioinformatics, we have identified 12 conserved LOGs that include HMGA2 and IMP-1/CRD-BP. IMP-1...

  13. The Goals for Regulating College Tuition (United States)

    Zeng, Xiaodong


    Regulation refers to governmental restrictions over enterprise in order to protect public interest. Research on governmental regulation in China primarily focuses on public utility, and inadequate attention has been paid to regulating college tuition. Currently, although the educational administrative agencies have successfully kept college…

  14. Emotion Regulation and Depressive Symptoms in Preadolescence (United States)

    Siener, Shannon; Kerns, Kathryn A.


    This study examined associations among several measures of emotion regulation, and their links to depressive symptoms, in a sample of children ages 10-12 years old (N = 87). Both temporal features of emotion regulation and regulation processes involved in the evaluation, monitoring, and modification of emotion were assessed through parent and…

  15. Good Practice Standards – a Regulation Tool

    DEFF Research Database (Denmark)

    Sørensen, Marie Jull


    The purpose of this article is to identify the considerations weighed in regulation with good practice standards. In this article, potential due process problems with regulation via legal standards are identified and compared to other considerations, which this regulation technique meets....

  16. 10 CFR 850.26 - Regulated areas. (United States)


    ... 10 Energy 4 2010-01-01 2010-01-01 false Regulated areas. 850.26 Section 850.26 Energy DEPARTMENT... Regulated areas. (a) If airborne concentrations of beryllium in areas in DOE facilities are measured at or above the action level, the responsible employer must establish regulated areas for those areas. (b)...

  17. Multiplexing regulated traffic streams: design and performance

    NARCIS (Netherlands)

    Kumaran, Krishnan; Mandjes, Michel


    The main network solutions for supporting QoS rely on traf- fic policing (conditioning, shaping). In particular, for IP networks the IETF has developed Intserv (individual flows regulated) and Diffserv (only ag- gregates regulated). The regulator proposed could be based on the (dual) leaky-bucket me

  18. 31 CFR 308.4 - Applicable regulations. (United States)


    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Applicable regulations. 308.4 Section 308.4 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT GENERAL REGULATIONS GOVERNING FULL-PAID...

  19. Regulations Protect Right of Disabled to Employment

    Institute of Scientific and Technical Information of China (English)



    @@ On February 14, 2007, the 169th Executive Meeting of the State Council, China's central government, adopted the Regulations on Employment of the Disabled (hereinafter referred to as the Regulations). The Regulations, which became effective on May 1,comes as an important guarantee for the right of the disabled to work.

  20. Regulated trafficking of the CFTR chloride channel

    NARCIS (Netherlands)

    Braakman, L.J.; Kleizen, B.; Jonge, H.R. de


    The cystic fibrosis transmembrane conductance regulator (CFTR), the ABC transporter encoded by the cystic fibrosis gene, is localized in the apical membrane of epithelial cells where it functions as a cyclic AMP-regulated chloride channel and as a regulator of other ion channels and transporters. Wh

  1. 7 CFR 984.49 - Volume regulation. (United States)


    ... Regulating Handling Marketing Policy § 984.49 Volume regulation. (a) Free, reserve, and export percentages... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... during a marketing year will tend to effectuate the declared policy of the act, he shall establish a...


    Institute of Scientific and Technical Information of China (English)

    Zhao Weigong; Han Xuezhe; Li Xinyou; Guo Xong; Liu Miao


    Objective Bacterial DNA is a pathogen-derived molecule which can regulate the innate immune system by stimulating NF-κB activation. The activity of bacterial DNA relies on its content of unmethylated CpG dinucleotides in particular base contexts("CpG motif"). In light of the pivotal role played by NF-κB in osteoclast differentiation, the ability of CpG oligodeoxynucleotides (CpG ODN) coming from bacterial DNA to modulate osteoclastogenesis was studied. Methods Bone marrow mononuclear cells (BMM) were purified from Balb/c mice, cultured in α-MEM media containing 10% FCS in the presence of mouse M-CSF, with either RANKL or ODNs for 5 days. Osteoclast formation was evaluated on day 5 according to TRAP and May-Grunwald-Giemsa staining. Results CpG ODN alone could induce osteoclast formation in the low degree in BMM culture. The relationship between CpG ODN and RANKL was that CpG ODN could inhibit RANKL-induced osteoclastogenesis when present from the beginning of BMM culture, but strongly increased RANKL-induced osteoclastogenesis in RANKL-pretreated BMMs. Conclusion The mechanism of CpG ODN regulating osteoclast differentiation was bidirectional, which might be a potential therapy for treating metabolic bone disease.

  3. Nickel-responsive transcriptional regulators. (United States)

    Musiani, Francesco; Zambelli, Barbara; Bazzani, Micaela; Mazzei, Luca; Ciurli, Stefano


    Nickel is an essential micronutrient for a large number of living organisms, but it is also a toxic metal ion when it accumulates beyond the sustainable level as it may result if and when its cellular trafficking is not properly governed. Therefore, the homeostasis and metabolism of nickel is tightly regulated through metal-specific protein networks that respond to the available Ni(II) concentration. These are directed by specific nickel sensors, able to couple Ni(II) binding to a change in their DNA binding affinity and/or specificity, thus translating the cellular level of Ni(II) into a modification of the expression of the proteins devoted to modulating nickel uptake, efflux and cellular utilization. This review describes the Ni(II)-dependent transcriptional regulators discovered so far, focusing on their structural features, metal coordination modes and metal binding thermodynamics. Understanding these properties is essential to comprehend how these sensors correlate nickel availability to metal coordination and functional responses. A broad and comparative study, described here, reveals some general traits that characterize the binding stoichiometry and Ni(II) affinity of these metallo-sensors.

  4. Chromatin structure regulates gene conversion.

    Directory of Open Access Journals (Sweden)

    W Jason Cummings


    Full Text Available Homology-directed repair is a powerful mechanism for maintaining and altering genomic structure. We asked how chromatin structure contributes to the use of homologous sequences as donors for repair using the chicken B cell line DT40 as a model. In DT40, immunoglobulin genes undergo regulated sequence diversification by gene conversion templated by pseudogene donors. We found that the immunoglobulin Vlambda pseudogene array is characterized by histone modifications associated with active chromatin. We directly demonstrated the importance of chromatin structure for gene conversion, using a regulatable experimental system in which the heterochromatin protein HP1 (Drosophila melanogaster Su[var]205, expressed as a fusion to Escherichia coli lactose repressor, is tethered to polymerized lactose operators integrated within the pseudo-Vlambda donor array. Tethered HP1 diminished histone acetylation within the pseudo-Vlambda array, and altered the outcome of Vlambda diversification, so that nontemplated mutations rather than templated mutations predominated. Thus, chromatin structure regulates homology-directed repair. These results suggest that histone modifications may contribute to maintaining genomic stability by preventing recombination between repetitive sequences.

  5. Regulation of BLM Nucleolar Localization (United States)

    Tangeman, Larissa; McIlhatton, Michael A.; Grierson, Patrick; Groden, Joanna; Acharya, Samir


    Defects in coordinated ribosomal RNA (rRNA) transcription in the nucleolus cause cellular and organismal growth deficiencies. Bloom’s syndrome, an autosomal recessive human disorder caused by mutated recQ-like helicase BLM, presents with growth defects suggestive of underlying defects in rRNA transcription. Our previous studies showed that BLM facilitates rRNA transcription and interacts with RNA polymerase I and topoisomerase I (TOP1) in the nucleolus. The mechanisms regulating localization of BLM to the nucleolus are unknown. In this study, we identify the TOP1-interaction region of BLM by co-immunoprecipitation of in vitro transcribed and translated BLM segments and show that this region includes the highly conserved nuclear localization sequence (NLS) of BLM. Biochemical and nucleolar co-localization studies using site-specific mutants show that two serines within the NLS (S1342 and S1345) are critical for nucleolar localization of BLM but do not affect the functional interaction of BLM with TOP1. Mutagenesis of both serines to aspartic acid (phospho-mimetic), but not alanine (phospho-dead), results in approximately 80% reduction in nucleolar localization of BLM while retaining the biochemical functions and nuclear localization of BLM. Our studies suggest a role for this region in regulating nucleolar localization of BLM via modification of the two serines within the NLS. PMID:27657136

  6. A laser tube position regulator

    Energy Technology Data Exchange (ETDEWEB)

    Sinyitiro, A.; Norio, K.


    An improved design is patented for a mechanism and method of regulating, with a high degree of accuracy, the position of a laser tube in a gas laser inside the optical resonator formed by external mirrors. The laser tube is held in two holders. Each holder contains an L shaped bracket which supports a semitransparent plate. The plate is positioned so that its center is over the center of the end of the tube which is in the form of a Brewster window. A narrow parallel beam is directed along the tube axis from an external auxiliary laser. The beam passes through the semitransparent mirror of the optical resonator in the adjusted laser, through the first Brewster window, the tube itself, and the second Brewster window and is reflected back in the reverse direction from a fully reflecting mirror in the optical resonator. This provides partial reflection of the beam from the external Brewster mirror surface. The tube position in the holders is regulated continuously so that the luminous spots from the beams reflected off the Brewster windows fall on the semitransparent plates in the center of the latter which is designated as the point of intersection.

  7. Corruption and optimal regulation under common agency

    Directory of Open Access Journals (Sweden)

    Pedro Hemsley


    Full Text Available I show that it is optimal to separate non-benevolent regulators when regulated projects are large. Separation prevents regulators from coordinating to appropriate all of the agent's informational rent when they know the type of the latter; therefore, there is a trade-off between saving on informational rent and efficiency, since the game between the regulators induced by separation causes further distortions when compared to the allocation under one regulator. When the informational rent at stake is large due to the size of the project, separation is the optimal institutional answer.

  8. The Cost of Railroad Regulation

    DEFF Research Database (Denmark)

    Federico, Giovanni; Sharp, Paul R.

    We investigate the costs of transportation regulation using the example of agricultural markets in the United States. Using a large database of prices by state of agricultural commodities, we find that the coefficient of variation (as a measure of market integration between states) falls for many...... commodities until the First World War. We demonstrate that this reflected changes in transportation costs which in turn in the long run depended on productivity growth in railroads. 1920 marked a change in this relationship, however, and between the First and Second World Wars we find considerable...... disintegration of agricultural markets, ultimately as a consequence of the 1920 Transportation Act. We argue that this benefited railroad companies in the 1920s and workers in the 1930s, and we put forward an estimate of the welfare losses for the consumers of railroad services (i.e. agricultural producers...

  9. Regulative mechanisms of chondrocyte adhesion

    DEFF Research Database (Denmark)

    Schmal, Hagen; Mehlhorn, Alexander T; Fehrenbach, Miriam;


    -matrix interaction, as well as collagen type II expression in the cartilage graft after two weeks of in vitro cultivation. Basic fibroblast growth factor (bFGF) treated chondrocytes showed increased adhesion to collagen types I and II, fibronectin, and fibrinogen. Attachment to these investigated proteins......%) increased. A cartilage construct was developed based on a clinically established collagen type I scaffold. In this matrix, more than 80% of the cells could be immobilized by mechanisms of adhesion, filtration, and cell entrapment. Confocal laser microscopy revealed focal adhesion sites as points of cell...... significantly enhanced cell proliferation. Matrix design in cartilage engineering must meet the biological demands of amplified cells, because adhesion of chondrocytes depends on their differentiation status and is regulated by bFGF....

  10. Neuroepigenetic regulation of pathogenic memories

    Directory of Open Access Journals (Sweden)

    Stephanie E. Sillivan


    Full Text Available Our unique collection of memories determines our individuality and shapes our future interactions with the world. Remarkable advances into the neurobiological basis of memory have identified key epigenetic mechanisms that support the stability of memory. Various forms of epigenetic regulation at the levels of DNA methylation, histone modification, and noncoding RNAs can modulate transcriptional and translational events required for memory processes. By changing the cellular profile in the brain’s emotional, reward, and memory circuits, these epigenetic modifications have also been linked to perseverant, pathogenic memories. In this review, we will delve into the relevance of epigenetic dysregulation to pathogenic memory mechanisms by focusing on 2 neuropsychiatric disorders perpetuated by aberrant memory associations: substance use disorder and post-traumatic stress disorder. As our understanding improves, neuroepigenetic mechanisms may someday be harnessed to develop novel therapeutic targets for the treatment of these chronic, relapsing disorders.

  11. Metabolic regulation of circadian clocks. (United States)

    Haydon, Michael J; Hearn, Timothy J; Bell, Laura J; Hannah, Matthew A; Webb, Alex A R


    Circadian clocks are 24-h timekeeping mechanisms, which have evolved in plants, animals, fungi and bacteria to anticipate changes in light and temperature associated with the rotation of the Earth. The current paradigm to explain how biological clocks provide timing information is based on multiple interlocking transcription-translation negative feedback loops (TTFL), which drive rhythmic gene expression and circadian behaviour of growth and physiology. Metabolism is an important circadian output, which in plants includes photosynthesis, starch metabolism, nutrient assimilation and redox homeostasis. There is increasing evidence in a range of organisms that these metabolic outputs can also contribute to circadian timing and might also comprise independent circadian oscillators. In this review, we summarise the mechanisms of circadian regulation of metabolism by TTFL and consider increasing evidence that rhythmic metabolism contributes to the circadian network. We highlight how this might be relevant to plant circadian clock function.

  12. Long noncoding RNAs regulate adipogenesis. (United States)

    Sun, Lei; Goff, Loyal A; Trapnell, Cole; Alexander, Ryan; Lo, Kinyui Alice; Hacisuleyman, Ezgi; Sauvageau, Martin; Tazon-Vega, Barbara; Kelley, David R; Hendrickson, David G; Yuan, Bingbing; Kellis, Manolis; Lodish, Harvey F; Rinn, John L


    The prevalence of obesity has led to a surge of interest in understanding the detailed mechanisms underlying adipocyte development. Many protein-coding genes, mRNAs, and microRNAs have been implicated in adipocyte development, but the global expression patterns and functional contributions of long noncoding RNA (lncRNA) during adipogenesis have not been explored. Here we profiled the transcriptome of primary brown and white adipocytes, preadipocytes, and cultured adipocytes and identified 175 lncRNAs that are specifically regulated during adipogenesis. Many lncRNAs are adipose-enriched, strongly induced during adipogenesis, and bound at their promoters by key transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (CEBPα). RNAi-mediated loss of function screens identified functional lncRNAs with varying impact on adipogenesis. Collectively, we have identified numerous lncRNAs that are functionally required for proper adipogenesis.

  13. Regulation of keratin network organization. (United States)

    Loschke, Fanny; Seltmann, Kristin; Bouameur, Jamal-Eddine; Magin, Thomas M


    Keratins form the major intermediate filament cytoskeleton of epithelia and are assembled from heterodimers of 28 type I and 26 type II keratins in cell- and differentiation-dependent patterns. By virtue of their primary sequence composition, interactions with cell adhesion complexes and components of major signaling cascades, keratins act as targets and effectors of mechanical force and chemical signals to determine cell mechanics, epithelial cohesion and modulate signaling in keratin isotype-specific manners. Therefore, cell-specific keratin expression and organization impact on cell growth, migration and invasion. Here, we review the recent literature, focusing on the question how keratin networks are regulated and how the interplay of keratins with adhesion complexes affects these processes and provides a framework to understand keratins contribution to blistering and inflammatory disorders and to tumor metastasis.

  14. [Regulation of PAI-1 expression]. (United States)

    Wyrzykowska, Paulina; Kasza, Aneta


    PAI-1 (plasminogen activator inhibitor-1) is a member of plasminogen cascade with an inhibitory role in plasmin activation. Plasmin is a protease capable of acting on wide range of substrates and, together with metaloproteinases, is a main proteolytic enzyme. Except its role in plasminogen cascade, PAI-1 has an affinity to vitronectin and uPA/uPAR what involves PAI-1 in cell's motility. PAI-1 gene is regulated in response to cytokines, hormones and many growth factors among which TGFbeta is the most important one. The PAI-1 promoter contains SBE, CAGA box, HRE, ERE, NFkB - binding sites, Sp-1, AP-1 and other. Cooperation between transcription factors bound to promoter and cross-talks between kinases and other upstream proteins decide about gene expression. This work describes the present knowledge in this field.

  15. Molecular Regulation of Fruit Ripening

    Directory of Open Access Journals (Sweden)

    Sonia eOsorio


    Full Text Available Fruit ripening is a highly coordinated developmental process that coincides with seed maturation. The ripening process is regulated by thousands of genes that control progressive softening and/or lignification of pericarp layers, accumulation of sugars, acids, pigments, and release of volatiles. Key to crop improvement is a deeper understanding of the processes underlying fruit ripening. In tomato, mutations blocking the transition to ripe fruits have provided insights into the role of ethylene and its associated molecular networks involved in the control of ripening. However, the role of other plant hormones is still poorly understood. In this review, we describe how plant hormones, transcription factors and epigenetic changes are intimately related to provide a tight control of the ripening process. Recent findings from comparative genomics and system biology approaches are discussed.

  16. Metallochaperones regulate intracellular copper levels.

    Directory of Open Access Journals (Sweden)

    W Lee Pang

    Full Text Available Copper (Cu is an important enzyme co-factor that is also extremely toxic at high intracellular concentrations, making active efflux mechanisms essential for preventing Cu accumulation. Here, we have investigated the mechanistic role of metallochaperones in regulating Cu efflux. We have constructed a computational model of Cu trafficking and efflux based on systems analysis of the Cu stress response of Halobacterium salinarum. We have validated several model predictions via assays of transcriptional dynamics and intracellular Cu levels, discovering a completely novel function for metallochaperones. We demonstrate that in addition to trafficking Cu ions, metallochaperones also function as buffers to modulate the transcriptional responsiveness and efficacy of Cu efflux. This buffering function of metallochaperones ultimately sets the upper limit for intracellular Cu levels and provides a mechanistic explanation for previously observed Cu metallochaperone mutation phenotypes.

  17. Dynamics of bacterial gene regulation (United States)

    Narang, Atul


    The phenomenon of diauxic growth is a classical problem of bacterial gene regulation. The most well studied example of this phenomenon is the glucose-lactose diauxie, which occurs because the expression of the lac operon is strongly repressed in the presence of glucose. This repression is often explained by appealing to molecular mechanisms such as cAMP activation and inducer exclusion. I will begin by analyzing data showing that these molecular mechanisms cannot explain the strong lac repression because they exert a relatively weak effect. I will then present a minimal model accounting only for enzyme induction and dilution, which yields strong repression despite the absence of catabolite repression and inducer exclusion. The model also explains the growth patterns observed in batch and continuous cultures of various bacterial strains and substrate mixtures. The talk will conclude with a discussion of the experimental evidence regarding positive feedback, the key component of the minimal model.


    Directory of Open Access Journals (Sweden)

    Claudia eLieberwirth


    Full Text Available Affiliative social relationships (e.g., among spouses, family members, and friends play an essential role in human society. These relationships affect psychological, physiological, and behavioral functions. As positive and enduring bonds are critical for the overall well-being of humans, it is not surprising that considerable effort has been made to study the neurobiological mechanisms that underlie social bonding behaviors. The present review details the involvement of the nonapeptides, oxytocin (OT and arginine vasopressin (AVP, in the regulation of social bonding in mammals including humans. In particular, we will discuss the role of OT and AVP in the formation of social bonds between partners of a mating pair as well as between parents and their offspring. Furthermore, the role of OT and AVP in the formation of interpersonal bonding involving trust is also discussed.

  19. PDH regulation in skeletal muscle

    DEFF Research Database (Denmark)

    Kiilerich, Kristian

    is determined by the overall content / activity of the regulatory proteins PDH kinase (PDK), of which there are 4 isoforms, and PDH phosphatase (PDP), of which there are 2 isoforms. The overall aim of the PhD project was to elucidate 4 issues. 1: Role of muscle type in resting and exercise-induced PDH...... in arm than leg muscles during exercise in humans may be the result of lower PDH-E1? content and not a muscle type dependent difference in PDH regulation. Both low muscle glycogen and increased plasma FFA are associated with upregulation of PDK4 protein and less exercise-induced increase in PDHa activity...... in human skeletal muscle. It may be noted that the increased PDK4 protein associated with elevated plasma FFA occurs already 2 hours after different dietary intake. A week of physical inactivity (bed rest), leading to whole body glucose intolerance, does not affect muscle PDH-E1? content, or the exercise...

  20. Multiple pathways regulate shoot branching

    Directory of Open Access Journals (Sweden)

    Catherine eRameau


    Full Text Available Shoot branching patterns result from the spatio-temporal regulation of axillary bud outgrowth. Numerous endogenous, developmental and environmental factors are integrated at the bud and plant levels to determine numbers of growing shoots. Multiple pathways that converge to common integrators are most probably involved. We propose several pathways involving not only the classical hormones auxin, cytokinins and strigolactones, but also other signals with a strong influence on shoot branching such as gibberellins, sugars or molecular actors of plant phase transition. We also deal with recent findings about the molecular mechanisms and the pathway involved in the response to shade as an example of an environmental signal controlling branching. We propose the TCP transcription factor TB1/BRC1 and the polar auxin transport stream in the stem as possible integrators of these pathways. We finally discuss how modeling can help to represent this highly dynamic system by articulating knowledges and hypothesis and calculating the phenotype properties they imply.

  1. Regulating Finance After the Crisis

    DEFF Research Database (Denmark)

    Moschella, Manuela; Tsingou, Eleni


    It is now widely recognized that regulatory failures contributed to the onset of the global financial crisis. Redressing such failures has, thus, been a key policy priority in the post-crisis reform agenda at both the domestic and international levels. This special issue investigates the process...... of post-crisis financial regulatory reform in a number of crucial issue areas, including the rules and arrangements that govern financial supervision, offshore financial centers and shadow banking, the financial industry's involvement in global regulatory processes, and macroeconomic modeling. In so doing......, the main purpose of this special issue is to shed light on an often understudied aspect in regulation literature: the variation in the dynamics of regulatory change. Contributors examine the different dynamics of regulatory change observed post-crisis and explain variations by accounting...

  2. [Plant hormones, plant growth regulators]. (United States)

    Végvári, György; Vidéki, Edina


    Plants seem to be rather defenceless, they are unable to do motion, have no nervous system or immune system unlike animals. Besides this, plants do have hormones, though these substances are produced not in glands. In view of their complexity they lagged behind animals, however, plant organisms show large scale integration in their structure and function. In higher plants, such as in animals, the intercellular communication is fulfilled through chemical messengers. These specific compounds in plants are called phytohormones, or in a wide sense, bioregulators. Even a small quantity of these endogenous organic compounds are able to regulate the operation, growth and development of higher plants, and keep the connection between cells, tissues and synergy between organs. Since they do not have nervous and immume systems, phytohormones play essential role in plants' life.

  3. Hard work in soft regulation

    DEFF Research Database (Denmark)

    Hohnen, Pernille; Hasle, Peter; Helbo Jespersen, Anne


    Certified occupational health and safety management (OHSM) systems have become a global instrument in the regulation of work environment (Frick and Wren 2000; Gallagher et al. 2001, Rocha 2010; Robson et al 2007). However, their actual impact on occupational health and safety – in particular...... on ‘softer’ psychosocial areas of the working environment – has been questioned (Hohnen & Hasle 2011; Walters and Frick 2000; Hasle & Zwetsloot 2011). This has resulted in recent British attempts to develop new publically available guidelines (PAS 1010) to be used together with OHSAS 18001 focusing...... specifically on psychosocial risk management attempting to guide and control not only management systems and related procedures but also the concrete work domain in which psychosocial risks are produced, experienced and monitored (Leka 2011). Based on an analysis of OHSAS 18001 and PAS 1010 the present paper...

  4. Analog regulation of metabolic demand

    Directory of Open Access Journals (Sweden)

    Muskhelishvili Georgi


    Full Text Available Abstract Background The 3D structure of the chromosome of the model organism Escherichia coli is one key component of its gene regulatory machinery. This type of regulation mediated by topological transitions of the chromosomal DNA can be thought of as an analog control, complementing the digital control, i.e. the network of regulation mediated by dedicated transcription factors. It is known that alterations in the superhelical density of chromosomal DNA lead to a rich pattern of differential expressed genes. Using a network approach, we analyze these expression changes for wild type E. coli and mutants lacking nucleoid associated proteins (NAPs from a metabolic and transcriptional regulatory network perspective. Results We find a significantly higher correspondence between gene expression and metabolism for the wild type expression changes compared to mutants in NAPs, indicating that supercoiling induces meaningful metabolic adjustments. As soon as the underlying regulatory machinery is impeded (as for the NAP mutants, this coherence between expression changes and the metabolic network is substantially reduced. This effect is even more pronounced, when we compute a wild type metabolic flux distribution using flux balance analysis and restrict our analysis to active reactions. Furthermore, we are able to show that the regulatory control exhibited by DNA supercoiling is not mediated by the transcriptional regulatory network (TRN, as the consistency of the expression changes with the TRN logic of activation and suppression is strongly reduced in the wild type in comparison to the mutants. Conclusions So far, the rich patterns of gene expression changes induced by alterations of the superhelical density of chromosomal DNA have been difficult to interpret. Here we characterize the effective networks formed by supercoiling-induced gene expression changes mapped onto reconstructions of E. coli's metabolic and transcriptional regulatory network. Our

  5. Glycosylation regulates prestin cellular activity. (United States)

    Rajagopalan, Lavanya; Organ-Darling, Louise E; Liu, Haiying; Davidson, Amy L; Raphael, Robert M; Brownell, William E; Pereira, Fred A


    Glycosylation is a common post-translational modification of proteins and is implicated in a variety of cellular functions including protein folding, degradation, sorting and trafficking, and membrane protein recycling. The membrane protein prestin is an essential component of the membrane-based motor driving electromotility changes (electromotility) in the outer hair cell (OHC), a central process in auditory transduction. Prestin was earlier identified to possess two N-glycosylation sites (N163, N166) that, when mutated, marginally affect prestin nonlinear capacitance (NLC) function in cultured cells. Here, we show that the double mutant prestin(NN163/166AA) is not glycosylated and shows the expected NLC properties in the untreated and cholesterol-depleted HEK 293 cell model. In addition, unlike WT prestin that readily forms oligomers, prestin(NN163/166AA) is enriched as monomers and more mobile in the plasma membrane, suggesting that oligomerization of prestin is dependent on glycosylation but is not essential for the generation of NLC in HEK 293 cells. However, in the presence of increased membrane cholesterol, unlike the hyperpolarizing shift in NLC seen with WT prestin, cells expressing prestin(NN163/166AA) exhibit a linear capacitance function. In an attempt to explain this finding, we discovered that both WT prestin and prestin(NN163/166AA) participate in cholesterol-dependent cellular trafficking. In contrast to WT prestin, prestin(NN163/166AA) shows a significant cholesterol-dependent decrease in cell-surface expression, which may explain the loss of NLC function. Based on our observations, we conclude that glycosylation regulates self-association and cellular trafficking of prestin(NN163/166AA). These observations are the first to implicate a regulatory role for cellular trafficking and sorting in prestin function. We speculate that the cholesterol regulation of prestin occurs through localization to and internalization from membrane microdomains by

  6. Microbial Regulation in Gorgonian Corals

    Directory of Open Access Journals (Sweden)

    Laura D. Mydlarz


    Full Text Available Gorgonian corals possess many novel natural products that could potentially mediate coral-bacterial interactions. Since many bacteria use quorum sensing (QS signals to facilitate colonization of host organisms, regulation of prokaryotic cell-to-cell communication may represent an important bacterial control mechanism. In the present study, we examined extracts of twelve species of Caribbean gorgonian corals, for mechanisms that regulate microbial colonization, such as antibacterial activity and QS regulatory activity. Ethanol extracts of gorgonians collected from Puerto Rico and the Florida Keys showed a range of both antibacterial and QS activities using a specific Pseudomonas aeruginosa QS reporter, sensitive to long chain AHLs and a short chain N-acylhomoserine lactones (AHL biosensor, Chromobacterium violaceium. Overall, the gorgonian corals had higher antimicrobial activity against non-marine strains when compared to marine strains. Pseudopterogorgia americana, Pseusopterogorgia acerosa, and Pseudoplexuara flexuosa had the highest QS inhibitory effect. Interestingly, Pseudoplexuara porosa extracts stimulated QS activity with a striking 17-fold increase in signal. The stimulation of QS by P. porosa or other elements of the holobiont may encourage colonization or recruitment of specific microbial species. Overall, these results suggest the presence of novel stimulatory QS, inhibitory QS and bactericidal compounds in gorgonian corals. A better understanding of these compounds may reveal insight into coral-microbial ecology and whether a therapeutic potential exists.

  7. Genome regulation in mammalian cells. (United States)

    Puck, T T; Krystosek, A; Chan, D C


    A theory is presented proposing that genetic regulation in mammalian cells is at least a two-tiered effect; that one level of regulation involves the transition between gene exposure and sequestration; that normal differentiation requires a different spectrum of genes to be exposed in each separate state of differentiation; that the fiber systems of the cell cytoskeleton and the nuclear matrix together control the degree of gene exposure; that specific phosphorylation of these elements causes them to assume a different organizational network and to impose a different pattern of sequestration and exposure on the elements of the genome; that the varied gene phosphorylation mechanisms in the cell are integrated in this function; that attachment of this network system to specific parts of the chromosomes brings about sequestration or exposure of the genes in their neighborhood in a fashion similar to that observed when microtubule elements attach through the kinetochore to the centromeric DNA; that one function of repetitive sequences is to serve as elements for the final attachment of this fibrous network to the specific chromosomal loci; and that at least an important part of the calcium manifestation as a metabolic trigger of different differentiation states involves its acting as a binding agent to centers of electronegativity, in particular proteins and especially phosphorylated groups, so as to change the conformation of the fiber network that ultimately controls gene exposure in the mammalian cell. It would appear essential to determine what abnormal gene exposures and sequestrations are characteristic of each type of cancer; which agonists, if any, will bring about reverse transformation; and whether these considerations can be used in therapy.

  8. Wnt Signaling Regulates Airway Epithelial Stem Cells in Adult Murine Submucosal Glands. (United States)

    Lynch, Thomas J; Anderson, Preston J; Xie, Weiliang; Crooke, Adrianne K; Liu, Xiaoming; Tyler, Scott R; Luo, Meihui; Kusner, David M; Zhang, Yulong; Neff, Traci; Burnette, Daniel C; Walters, Katherine S; Goodheart, Michael J; Parekh, Kalpaj R; Engelhardt, John F


    Wnt signaling is required for lineage commitment of glandular stem cells (SCs) during tracheal submucosal gland (SMG) morphogenesis from the surface airway epithelium (SAE). Whether similar Wnt-dependent processes coordinate SC expansion in adult SMGs following airway injury remains unknown. We found that two Wnt-reporters in mice (BAT-gal and TCF/Lef:H2B-GFP) are coexpressed in actively cycling SCs of primordial glandular placodes and in a small subset of adult SMG progenitor cells that enter the cell cycle 24 hours following airway injury. At homeostasis, these Wnt reporters showed nonoverlapping cellular patterns of expression in the SAE and SMGs. Following tracheal injury, proliferation was accompanied by dynamic changes in Wnt-reporter activity and the analysis of 56 Wnt-related signaling genes revealed unique temporal changes in expression within proximal (gland-containing) and distal (gland-free) portions of the trachea. Wnt stimulation in vivo and in vitro promoted epithelial proliferation in both SMGs and the SAE. Interestingly, slowly cycling nucleotide label-retaining cells (LRCs) of SMGs were spatially positioned near clusters of BAT-gal positive serous tubules. Isolation and culture of tet-inducible H2B-GFP LRCs demonstrated that SMG LRCs were more proliferative than SAE LRCs and culture expanded SMG-derived progenitor cells outcompeted SAE-derived progenitors in regeneration of tracheal xenograft epithelium using a clonal analysis competition assay. SMG-derived progenitors were also multipotent for cell types in the SAE and formed gland-like structures in xenografts. These studies demonstrate the importance of Wnt signals in modulating SC phenotypes within tracheal niches and provide new insight into phenotypic differences of SMG and SAE SCs. Stem Cells 2016.

  9. Erratic Black Hole Regulates Itself (United States)


    New results from NASA's Chandra X-ray Observatory have made a major advance in explaining how a special class of black holes may shut off the high-speed jets they produce. These results suggest that these black holes have a mechanism for regulating the rate at which they grow. Black holes come in many sizes: the supermassive ones, including those in quasars, which weigh in at millions to billions of times the mass of the Sun, and the much smaller stellar-mass black holes which have measured masses in the range of about 7 to 25 times the Sun's mass. Some stellar-mass black holes launch powerful jets of particles and radiation, like seen in quasars, and are called "micro-quasars". The new study looks at a famous micro-quasar in our own Galaxy, and regions close to its event horizon, or point of no return. This system, GRS 1915+105 (GRS 1915 for short), contains a black hole about 14 times the mass of the Sun that is feeding off material from a nearby companion star. As the material swirls toward the black hole, an accretion disk forms. This system shows remarkably unpredictable and complicated variability ranging from timescales of seconds to months, including 14 different patterns of variation. These variations are caused by a poorly understood connection between the disk and the radio jet seen in GRS 1915. Chandra, with its spectrograph, has observed GRS 1915 eleven times since its launch in 1999. These studies reveal that the jet in GRS 1915 may be periodically choked off when a hot wind, seen in X-rays, is driven off the accretion disk around the black hole. The wind is believed to shut down the jet by depriving it of matter that would have otherwise fueled it. Conversely, once the wind dies down, the jet can re-emerge. "We think the jet and wind around this black hole are in a sort of tug of war," said Joseph Neilsen, Harvard graduate student and lead author of the paper appearing in the journal Nature. "Sometimes one is winning and then, for reasons we don

  10. Institutions and Regulations in Innovation Systems

    DEFF Research Database (Denmark)

    Borrás, Susana; Edquist, Charles

    Institutions (including regulations) are constitutive elements of innovation systems, and therefore cornerstones of innovation policy. Focusing on (soft and hard) regulation, the paper identifies the most salient regulatory areas from the perspective of the innovation system. When asking about th...... and re-design of innovation policy, so that policy makers may analyse empirically the social dynamics actually generated by regulation rather than simply assuming deductively their effects....... the effects of regulation on innovation, the paper argues that there are three key issues that need careful empirical analysis; namely, whether regulation is effective and efficient in terms of reducing uncertainty and generating incentives, whether it is able to generate ultimately wider social benefits...... for the innovativeness of the society at large; and the extent to which regulation is adapting to new (social, economic and technological) contexts and is socially legitimate and accepted. These are potentially the three problems that innovation policy needs to address in this area. This provides guidance for the design...

  11. Cap and trade offsets regulation - consultation paper

    Energy Technology Data Exchange (ETDEWEB)



    Due to increasing concerns about the environment, British Columbia has committed to reducing its 2007 greenhouse gas emissions levels by 33% in 2020 and 80% in 2050. To reach those objectives, emissions trading and offset regulations are being developed by the Climate Action Secretariat. The aim of this document is to present a first draft of the regulations to the various stakeholders, including First Nations and the general public, together with the proposed offset eligibility criteria and related process, and to get their feedback. This document is itself part of the 5-phase process of developing the regulations. Following the 45 days during which comments on the proposed regulation were sought, the climate action secretariat will complete legal drafting of the regulations, drawing on help from this stakeholder input, and the regulation will subsequently be implemented. An accompanying response form was attached to this consultation paper.

  12. Endogenous vs. exogenous regulations in the commons

    DEFF Research Database (Denmark)

    Abatayo, Anna Lou; Lynham, John


    endogenous regulations with communication and exogenous regulations without communication. Our results suggest that externally imposed regulations do not crowd out intrinsic motivations in the lab and they confirm that communication facilitates cooperation to reduce extraction.......It is widely believed that there is strong experimental evidence to support the idea that exogenously imposed regulations crowd out the intrinsic motivations of common pool resource (CPR) users to refrain from over-harvesting. We introduce a novel experimental design that attempts to disentangle...... potential confounds in previous experiments. A key feature of our experimental design is to have the exact same regulations chosen endogenously as those that are imposed exogenously. When we compare the same regulations chosen endogenously to those externally imposed, we observe no differences in extraction...

  13. Genome-wide Analysis of Gene Regulation

    DEFF Research Database (Denmark)

    Chen, Yun

    cells are capable of regulating their gene expression, so that each cell can only express a particular set of genes yielding limited numbers of proteins with specialized functions. Therefore a rigid control of differential gene expression is necessary for cellular diversity. On the other hand, aberrant...... gene regulation will disrupt the cell’s fundamental processes, which in turn can cause disease. Hence, understanding gene regulation is essential for deciphering the code of life. Along with the development of high throughput sequencing (HTS) technology and the subsequent large-scale data analysis......, genome-wide assays have increased our understanding of gene regulation significantly. This thesis describes the integration and analysis of HTS data across different important aspects of gene regulation. Gene expression can be regulated at different stages when the genetic information is passed from gene...




    Differences in regulations result in needless destruction of safe food and hamper food trade. The differences are not just the result of the history of food safety regulations, often developed in times before global cooperation, but are also built in new regulations. It may be responses to media hypes or for other reasons, but in most cases the differences cannot be justified scientifically. A major difficulty is that, due to the developments in analytical techniques the number of chemicals t...

  15. Medical devices regulations, standards and practices

    CERN Document Server

    Ramakrishna, Seeram; Wang, Charlene


    Medical Devices and Regulations: Standards and Practices will shed light on the importance of regulations and standards among all stakeholders, bioengineering designers, biomaterial scientists and researchers to enable development of future medical devices. Based on the authors' practical experience, this book provides a concise, practical guide on key issues and processes in developing new medical devices to meet international regulatory requirements and standards. Provides readers with a global perspective on medical device regulationsConcise and comprehensive information on how to desig

  16. Strength in Cognitive Self-Regulation



    Failures in self-regulation are predictive of adverse cognitive, academic and vocational outcomes, yet the interplay between cognition and self-regulation failure remains elusive. Two experiments tested the hypothesis that lapses in self-regulation, as predicted by the strength model, can be induced in individuals using cognitive paradigms and whether such failures are related to cognitive performance. In Experiments 1, the stop-signal task (SST) was used to show reduced behavioral inhibition...

  17. Exploration on ecological regulation of the reservoirs

    Institute of Scientific and Technical Information of China (English)

    Cai Qihua


    Reservoir regulation process in the Yangtze River basin is mainly divided into two types of flood regulation and initiating benefit regulation. The present reservoir management system and operation mode are mainly for dealing with or coordinating of flood control and benefit initiation as well as benefit distribution among various beneficial functions. From the view point of river ecosystem protection, the current regulation mode has two kinds of problems: firstly, most of the reservoir regulation plans do not consider ecosystem protection at downstream of dams and needs of environment protection in reservoir areas; secondly, integrated regulation or management of water resources is ignored. It is very necessary to improve reservoir regulation mode, bearing problems faced by regulation of the Three Gorges reservoir and issues related to cascade development and regulation in Tuojiang and Minjiang River basins in mind. In accordance with the concept of scientific development, and the philosophy of "ensuring a healthy Yangtze River and promoting the har-mony between human and water", taking flood control, benefit initiation and eco-system as a whole, this paper put for-ward the basic consideration to improve reservoir regulation as follows : on the basis of requirements of ecosystem protec-tion at downstream of dams and needs of environment protection in reservoir areas, we should bring the functions of res-ervoir such as flood control and benefit initiation into full play, control the negative influence to the ecosystem at down-stream of dams and the environment in reservoir areas in an endurable scope, and restore the ecosystem and the environ-ment step by step. This paper put forward the relevant regulation process aiming at the idiographic problems such as pro-tection of ecosystem at downstream of dams and environment in reservoir areas, protection of aquatic wildlife species and fish species, regulation of sediment and protection of wetland.

  18. Circuit Regulates Speed Of dc Motor (United States)

    Weaver, Charles; Padden, Robin; Brown, Floyd A., Jr.


    Driving circuit regulates speed of small dc permanent-magnet motor in tape recorder. Two nested feedback loops maintain speed within 1 percent of constant value. Inner loop provides coarse regulation, while outer loop removes most of variation in speed that remains in the presence of regulation by the inner loop. Compares speed of motor with commanded speed and adjusts current supplied to motor accordingly.

  19. Lymphatic Regulation of Cellular Trafficking (United States)

    Jackson, David G.


    Lymphatic vessels play vital roles in immune surveillance and immune regulation by conveying antigen loaded dendritic cells, memory T cells, macrophages and neutrophils from the peripheral tissues to draining lymph nodes where they initiate as well as modify immune responses. Until relatively recently however, there was little understanding of how entry and migration through lymphatic vessels is organized or the specific molecular mechanisms that might be involved. Within the last decade, the situation has been transformed by an explosion of knowledge generated largely through the application of microscopic imaging, transgenic animals, specific markers and function blocking mAbs that is beginning to provide a rational conceptual framework. This article provides a critical review of the recent literature, highlighting seminal discoveries that have revealed the fascinating ultrastructure of leucocyte entry sites in lymphatic vessels, as well as generating controversies over the involvement of integrin adhesion, chemotactic and haptotactic mechanisms in DC entry under normal and inflamed conditions. It also discusses the major changes in lymphatic architecture that occur during inflammation and the different modes of leucocyte entry and trafficking within inflamed lymphatic vessels, as well as presenting a timely update on the likely role of hyaluronan and the major lymphatic endothelial hyaluronan receptor LYVE-1 in leucocyte transit.

  20. Proteinase activity regulation by glycosaminoglycans

    Directory of Open Access Journals (Sweden)

    Tersariol I.L.S.


    Full Text Available There are few reports concerning the biological role and the mechanisms of interaction between proteinases and carbohydrates other than those involved in clotting. It has been shown that the interplay of enzymes and glycosaminoglycans is able to modulate the activity of different proteases and also to affect their structures. From the large number of proteases belonging to the well-known protease families and also the variety of carbohydrates described as widely distributed, only few events have been analyzed more deeply. The term "family" is used to describe a group of proteases in which every member shows an evolutionary relationship to at least one other protease. This relationship may be evident throughout the entire sequence, or at least in that part of the sequence responsible for catalytic activity. The majority of proteases belong to the serine, cysteine, aspartic or metalloprotease families. By considering the existing limited proteolysis process, in addition to the initial idea that the proteinases participate only in digestive processes, it is possible to conclude that the function of the enzymes is strictly limited to the cleavage of intended substrates since the destruction of functional proteins would result in normal tissue damage. In addition, the location as well as the eventual regulation of protease activity promoted by glycosaminoglycans can play an essential role in the development of several physiopathological conditions.

  1. The transcriptional regulation of pluripotency

    Institute of Scientific and Technical Information of China (English)

    Jia-Chi Yeo; Huck-Hui Ng


    The defining features of embryonic stem cells (ESCs) are their self-renewing and pluripotent capacities.Indeed,the ability to give rise into all cell types within the organism not only allows ESCs to function as an ideal in vitro tool to study embryonic development,but also offers great therapeutic potential within the field of regenerative medicine.However,it is also this same remarkable developmental plasticity that makes the efficient control of ESC differentiation into the desired cell type very difficult.Therefore,in order to harness ESCs for clinical applications,a detailed understanding of the molecular and cellular mechanisms controlling ESC pluripotency and lineage commitment is necessary.In this respect,through a variety of transcriptomic approaches,ESC pluripotency has been found to be regulated by a system of ESC-associated transcription factors; and the external signalling environment also acts as a key factor in modulating the ESC transcriptome.Here in this review,we summarize our current understanding of the transcriptional regulatory network in ESCs,discuss how the control of various signalling pathways could influence pluripotency,and provide a future outlook of ESC research.

  2. Oxidative stress and glycemic regulation. (United States)

    Ceriello, A


    Oxidative stress is an acknowledged pathogenetic mechanism in diabetic complications. Hyperglycemia is a widely known cause of enhanced free radical concentration, whereas oxidative stress involvement in glycemic regulation is still debated. Glucose transport is a cascade of events starting from the interaction of insulin with its own receptor at the plasma membrane and ending with intracellular glucose metabolism. In this complex series of events, each step plays an important role and can be inhibited by a negative effect of oxidative stress. Several studies show that an acute increase in the blood glucose level may impair the physiological homeostasis of many systems in living organisms. The mechanisms through which acute hyperglycemia exerts these effects may be identified in the production of free radicals. It has been suggested that insulin resistance may be accompanied by intracellular production of free radicals. In adipocytes cultured in vitro, insulin increases the production of hydrogen peroxide, which has been shown to mimic the action of insulin. These data allow us to hypothesize that a vicious circle between hyperinsulinemia and free radicals could be operating: insulin resistance might cause elevated plasma free radical concentrations, which, in turn, might be responsible for a deterioration of insulin action, with hyperglycemia being a contributory factor. Data supporting this hypothesis are available. Vitamin E improves insulin action in healthy, elderly, and non-insulin-dependent diabetic subjects. Similar results can be obtained by vitamin C administration.

  3. [Central regulation of adenohypophyseal function]. (United States)

    Vigas, M


    The secretion of adenohypophyseal hormones is controlled by hypothalamic hypophysotropic hormones with stimulating (hormone releasing factors) or inhibitory (hormone release inhibiting factors) actions. The release of hypothalamic hormones is regulated by hierarchically higher nerve centres via neurons which liberate neurotransmitters at their endings. The secretion of growth hormone is controlled by hypothalamic hormones, somatotropin releasing factor and somatotropin release-inhibiting factor; of the neurotransmitters, the strongest effects have noradrenaline and dopamine. The release of ACTH is controlled by two stimulating hormones, the ACTH releasing factor and vasopressin, the effects of neurotransmitters are less marked, with the involvement of noradrenaline, serotonin, acetylcholine, gamma aminobutyric acid and other agents. Prolactin release is under the main inhibitory control of hypothalamic dopamine, no release-stimulating hypothalamic factor could be unequivocally demonstrated as yet; likely, several peptides are involved in this mechanism. The release of thyrotropic hormone is stimulated by thyrotropin releasing factor, whereas somatotropin release-inhibiting factor has an inhibitory action. Of the neurotransmitters, the inhibitory effect of dopamine is important; this agent however acts also at the hypophyseal level. External hypothalamic hormones and regulatory neurotransmitters are used in the diagnosis and treatment of neuroendocrine disorders.

  4. [Cosmetic colorants. Toxicology and regulation]. (United States)

    Platzek, T; Krätke, R; Klein, G; Schulz, C


    Some recent publications raised concern over a possible link between hair dye use and the incidence of bladder tumours in a Californian population. The Scientific Committee for Cosmetic Products and Non-Food Products intended for Consumers (SCCNFP) demanded the toxicological testing of all hair dyes used in Europe to exclude any risk. The EU commission initiated corresponding measures. Only safe hair dyes will be included on a positive list while all other hair dyes will be banned. The hair dye lawsone--the dyeing ingredient of henna--was evaluated by the SCCNFP as genotoxic but the BfR came to another conclusion. The regulation of both lawsone and henna remains an open question. Furthermore, some cosmetic colorants were critically discussed. The azo dyes CI 12150, CI 26100, CI 27290 and CI 20170 are allowed for use in cosmetics. On cleavage they form the carcinogenic aromatic amines o-anisidine, 4-aminoazobenzene and 2,4-xylidine, respectively. For three of these dyes the cleavage by human skin bacteria in vitro to the respective arylamine was shown experimentally. Further problems may arise from colorants used for tattoos and permanent makeup. These products up to now are not subject to legislation and there are no regulatory stipulations with respect to health safety and purity for colorants used for these purposes.

  5. Urotensin II in cardiovascular regulation

    Directory of Open Access Journals (Sweden)

    Fraser D Russell


    Full Text Available Fraser D RussellSchool of Health and Sport Sciences, Faculty of Science, Health and Education, University of the Sunshine Coast, Sippy Downs, Queensland, AustraliaAbstract: Cardiovascular function is modulated by neuronal transmitters, circulating hormones, and factors that are released locally from tissues. Urotensin II (UII is an 11 amino acid peptide that stimulates its’ obligatory G protein coupled urotensin II receptors (UT to modulate cardiovascular function in humans and in other animal species, and has been implicated in both vasculoprotective and vasculopathic effects. For example, tissue and circulating concentrations of UII have been reported to increase in some studies involving patients with atherosclerosis, heart failure, hypertension, preeclampsia, diabetes, renal disease and liver disease, raising the possibility that the UT receptor system is involved in the development and/or progression of these conditions. Consistent with this hypothesis, administration of UT receptor antagonists to animal models of cardiovascular disease have revealed improvements in cardiovascular remodelling and hemodynamics. However, recent studies have questioned this contributory role of UII in disease, and have instead postulated a protective effect on the cardiovascular system. For example, high concentrations of circulating UII correlated with improved clinical outcomes in patients with renal disease or myocardial infarction. The purpose of this review is to consider the regulation of the cardiovascular system by UII, giving consideration to methodologies for measurement of plasma concentrations, sites of synthesis and triggers for release.Keywords: urotensin II, cardiovascular disease, heart failure, hypertension

  6. Regulation of microgeneration and microgrids

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Paulo Moises [Escola Superior Tecnologia Viseu, Instituto Politecnico Viseu, Campus Politecnico Repeses, 3504-510 Viseu (Portugal); Matos, Manuel A.; Pecas Lopes, J.A. [INESC Porto, Faculdade de Engenharia da Universidade do Porto, Porto (Portugal)


    The concept of microgrid ({mu}Grid) has been emerging as a way to integrate microgeneration ({mu}G) in low-voltage (LV) networks and simultaneously improve its potential benefits. Technical requirements to connect {mu}grids to LV networks have been studied in order to make this concept technologically feasible and safe to operate. However, the regulatory framework for economic integration of {mu}G and {mu}Grids on distribution systems, despite being crucial, is still an open issue. The main purpose of this paper is to contribute for the development of an appropriate economic regulation framework that removes the barriers to {mu}G and {mu}Grid development. To do so, the relevant costs and benefits resulting from the establishment of {mu}G and {mu}Grid are identified and a methodology for sharing those costs and benefits among the involved economic agents is presented. The only pre-requisite of such a methodology is the existence of a net benefit to all economic agents. (author)

  7. Regulation of microgeneration and microgrids

    Energy Technology Data Exchange (ETDEWEB)

    Moises Costa, Paulo [Escola Superior Tecnologia Viseu, Instituto Politecnico Viseu, Campus Politecnico Repeses, 3504-510 Viseu (Portugal)], E-mail:; Matos, Manuel A.; Pecas Lopes, J.A. [INESC Porto, Faculdade de Engenharia da Universidade do Porto, Porto (Portugal)


    The concept of microgrid ({mu}Grid) has been emerging as a way to integrate microgeneration ({mu}G) in low-voltage (LV) networks and simultaneously improve its potential benefits. Technical requirements to connect {mu}grids to LV networks have been studied in order to make this concept technologically feasible and safe to operate. However, the regulatory framework for economic integration of {mu}G and {mu}Grids on distribution systems, despite being crucial, is still an open issue. The main purpose of this paper is to contribute for the development of an appropriate economic regulation framework that removes the barriers to {mu}G and {mu}Grid development. To do so, the relevant costs and benefits resulting from the establishment of {mu}G and {mu}Grid are identified and a methodology for sharing those costs and benefits among the involved economic agents is presented. The only pre-requisite of such a methodology is the existence of a net benefit to all economic agents.

  8. Redox regulation of mitochondrial biogenesis. (United States)

    Piantadosi, Claude A; Suliman, Hagir B


    The cell renews, adapts, or expands its mitochondrial population during episodes of cell damage or periods of intensified energy demand by the induction of mitochondrial biogenesis. This bigenomic program is modulated by redox-sensitive signals that respond to physiological nitric oxide (NO), carbon monoxide (CO), and mitochondrial reactive oxygen species production. This review summarizes our current ideas about the pathways involved in the activation of mitochondrial biogenesis by the physiological gases leading to changes in the redox milieu of the cell, with an emphasis on the responses to oxidative stress and inflammation. The cell's energy supply is protected from conditions that damage mitochondria by an inducible transcriptional program of mitochondrial biogenesis that operates in large part through redox signals involving the nitric oxide synthase and the heme oxygenase-1/CO systems. These redox events stimulate the coordinated activities of several multifunctional transcription factors and coactivators also involved in the elimination of defective mitochondria and the expression of counterinflammatory and antioxidant genes, such as IL10 and SOD2, as part of a unified damage-control network. The redox-regulated mechanisms of mitochondrial biogenesis schematically outlined in the graphical abstract link mitochondrial quality control to an enhanced capacity to support the cell's metabolic needs while improving its resistance to metabolic failure and avoidance of cell death during periods of oxidative stress.

  9. Metabolic regulation of insulin secretion. (United States)

    Keane, Kevin; Newsholme, Philip


    Regulation of metabolic fuel homeostasis is a critical function of β-cells, which are located in the islets of Langerhans of the animal pancreas. Impairment of this β-cell function is a hallmark of pancreatic β-cell failure and may lead to development of type 2 diabetes mellitus. β-Cells are essentially "fuel sensors" that monitor and react to elevated nutrient load by releasing insulin. This response involves metabolic activation and generation of metabolic coupling factors (MCFs) that relay the nutrient signal throughout the cell and induce insulin biosynthesis and secretion. Glucose is the most important insulin secretagogue as it is the primary fuel source in food. Glucose metabolism is central to generation of MCFs that lead to insulin release, most notably ATP. In addition, other classes of nutrients are able to augment insulin secretion and these include members of the lipid and amino acid family of nutrients. Therefore, it is important to investigate the interplay between glucose, lipid, and amino acid metabolism, as it is this mixed nutrient sensing that generate the MCFs required for insulin exocytosis. The mechanisms by which these nutrients are metabolized to generate MCFs, and how they impact on β-cell insulin release and function, are discussed in detail in this article.

  10. 77 FR 8066 - Semiannual Agenda of Regulations (United States)


    ... nomenclature or address changes), and eliminating those OTS regulations for which other appropriate Federal... or securitization satisfies all of the conditions for sale accounting treatment under...

  11. Reflection amplifiers in self-regulated learning

    NARCIS (Netherlands)

    Verpoorten, Dominique


    Verpoorten, D. (2012). Reflection amplifiers in self-regulated learning. Doctoral thesis. November, 9, 2012, Heerlen, The Netherlands: Open Universiteit (CELSTEC). Datawyse / Universitaire Pers Maastricht.

  12. Exporting licensing regulations affecting US geothermal firms

    Energy Technology Data Exchange (ETDEWEB)


    This document presents a brief introduction and overview of the Department of Commerce's Export Administration Regulations which might affect potential US geothermal goods exporters. It is intended to make US geothermal firms officials aware of the existence of such regulations and to provide them with references, contacts and phone numbers where they can obtain specific and detailed information and assistance. It must be stressed however, that the ultimate responsibility for complying with the above mentioned regulations lies with the exporter who must consult the complete version of the regulations.

  13. Output Regulation of the Arneodo Chaotic System

    Directory of Open Access Journals (Sweden)

    Sundarapandian Vaidyanathan


    Full Text Available This paper solves the problem of regulating the output of the Arneodo chaotic system (1981, which is one of the paradigms of chaotic dynamical systems. Explicitly, using the state feedback control laws, the output of the Arneodo chaotic system is regulated so as to track constant reference signals as well as to track periodic reference signals. The control laws are derived using the regulator equations of Byrnes and Isidori (1990, which provide the solution of the output regulation problem for nonlinear control systems involving neutrally stable exosystem dynamics. Numerical results are shown to verify the results.

  14. Cognitive emotion regulation fails the stress test. (United States)

    Raio, Candace M; Orederu, Temidayo A; Palazzolo, Laura; Shurick, Ashley A; Phelps, Elizabeth A


    Cognitive emotion regulation has been widely shown in the laboratory to be an effective way to alter the nature of emotional responses. Despite its success in experimental contexts, however, we often fail to use these strategies in everyday life where stress is pervasive. The successful execution of cognitive regulation relies on intact executive functioning and engagement of the prefrontal cortex, both of which are rapidly impaired by the deleterious effects of stress. Because it is specifically under stressful conditions that we may benefit most from such deliberate forms of emotion regulation, we tested the efficacy of cognitive regulation after stress exposure. Participants first underwent fear-conditioning, where they learned that one stimulus (CS+) predicted an aversive outcome but another predicted a neutral outcome (CS-). Cognitive regulation training directly followed where participants were taught to regulate fear responses to the aversive stimulus. The next day, participants underwent an acute stress induction or a control task before repeating the fear-conditioning task using these newly acquired regulation skills. Skin conductance served as an index of fear arousal, and salivary α-amylase and cortisol concentrations were assayed as neuroendocrine markers of stress response. Although groups showed no differences in fear arousal during initial fear learning, nonstressed participants demonstrated robust fear reduction following regulation training, whereas stressed participants showed no such reduction. Our results suggest that stress markedly impairs the cognitive regulation of emotion and highlights critical limitations of this technique to control affective responses under stress.

  15. Protein synthesis regulation by leucine

    Directory of Open Access Journals (Sweden)

    Daiana Vianna


    Full Text Available In vivo and in vitro studies have demonstrated that high protein diets affect both protein synthesis and regulation of several cellular processes. The role of amino acids as substrate for protein synthesis has been established in the literature. However, the mechanism by which these amino acids modulate transcription and regulate the mRNA translation via mTOR-dependent signaling pathway has yet to be fully determined. It has been verified that mTOR is a protein responsible for activating a cascade of biochemical intracellular events which result in the activation of the protein translation process. Of the aminoacids, leucine is the most effective in stimulating protein synthesis and reducing proteolysis. Therefore, it promotes a positive nitrogen balance, possibly by favoring the activation of this protein. This amino acid also directly and indirectly stimulates the synthesis and secretion of insulin, enhancing its anabolic cellular effects. Therefore, this review aimed to identify the role of leucine in protein synthesis modulation and to discuss the metabolic aspects related to this aminoacid.Estudos in vivo e in vitro verificaram que dietas hiperprotéicas influenciam a síntese protéica e regulam vários processos celulares. O papel dos aminoácidos como substrato para a síntese de proteínas já está bem evidenciado na literatura, porém as formas como esses aminoácidos modulam a etapa da transcrição e regulam a tradução do RNAm, pela via de sinalização dependente da mTOR, ainda não estão totalmente esclarecidas. Tem-se verificado que a mTOR é uma proteína responsável por ativar uma cascata de eventos bioquímicos intracelulares que culminam na ativação do processo de tradução protéica. Dentre todos os aminoácidos, a leucina é a mais eficaz em estimular a síntese protéica, reduzir a proteólise e, portanto, favorecer o balanço nitrogenado positivo, possivelmente por favorecer a ativação desta proteína. Al

  16. Microenvironmental regulation by fibrillin-1.

    Directory of Open Access Journals (Sweden)

    Gerhard Sengle


    Full Text Available Fibrillin-1 is a ubiquitous extracellular matrix molecule that sequesters latent growth factor complexes. A role for fibrillin-1 in specifying tissue microenvironments has not been elucidated, even though the concept that fibrillin-1 provides extracellular control of growth factor signaling is currently appreciated. Mutations in FBN1 are mainly responsible for the Marfan syndrome (MFS, recognized by its pleiotropic clinical features including tall stature and arachnodactyly, aortic dilatation and dissection, and ectopia lentis. Each of the many different mutations in FBN1 known to cause MFS must lead to similar clinical features through common mechanisms, proceeding principally through the activation of TGFβ signaling. Here we show that a novel FBN1 mutation in a family with Weill-Marchesani syndrome (WMS causes thick skin, short stature, and brachydactyly when replicated in mice. WMS mice confirm that this mutation does not cause MFS. The mutation deletes three domains in fibrillin-1, abolishing a binding site utilized by ADAMTSLIKE-2, -3, -6, and papilin. Our results place these ADAMTSLIKE proteins in a molecular pathway involving fibrillin-1 and ADAMTS-10. Investigations of microfibril ultrastructure in WMS humans and mice demonstrate that modulation of the fibrillin microfibril scaffold can influence local tissue microenvironments and link fibrillin-1 function to skin homeostasis and the regulation of dermal collagen production. Hence, pathogenetic mechanisms caused by dysregulated WMS microenvironments diverge from Marfan pathogenetic mechanisms, which lead to broad activation of TGFβ signaling in multiple tissues. We conclude that local tissue-specific microenvironments, affected in WMS, are maintained by a fibrillin-1 microfibril scaffold, modulated by ADAMTSLIKE proteins in concert with ADAMTS enzymes.

  17. Unity power factor switching regulator (United States)

    Rippel, Wally E. (Inventor)


    A single or multiphase boost chopper regulator operating with unity power factor, for use such as to charge a battery is comprised of a power section for converting single or multiphase line energy into recharge energy including a rectifier (10), one inductor (L.sub.1) and one chopper (Q.sub.1) for each chopper phase for presenting a load (battery) with a current output, and duty cycle control means (16) for each chopper to control the average inductor current over each period of the chopper, and a sensing and control section including means (20) for sensing at least one load parameter, means (22) for producing a current command signal as a function of said parameter, means (26) for producing a feedback signal as a function of said current command signal and the average rectifier voltage output over each period of the chopper, means (28) for sensing current through said inductor, means (18) for comparing said feedback signal with said sensed current to produce, in response to a difference, a control signal applied to the duty cycle control means, whereby the average inductor current is proportionate to the average rectifier voltage output over each period of the chopper, and instantaneous line current is thereby maintained proportionate to the instantaneous line voltage, thus achieving a unity power factor. The boost chopper is comprised of a plurality of converters connected in parallel and operated in staggered phase. For optimal harmonic suppression, the duty cycles of the switching converters are evenly spaced, and by negative coupling between pairs out-of-phase, peak currents through the switches can be reduced while reducing the inductor size and mass.

  18. Endocannabinoid Signaling Regulates Sleep Stability.

    Directory of Open Access Journals (Sweden)

    Matthew J Pava

    Full Text Available The hypnogenic properties of cannabis have been recognized for centuries, but endogenous cannabinoid (endocannabinoid regulation of vigilance states is poorly characterized. We report findings from a series of experiments in mice measuring sleep with polysomnography after various systemic pharmacological manipulations of the endocannabinoid system. Rapid, unbiased scoring of vigilance states was achieved using an automated algorithm that we devised and validated. Increasing endocannabinoid tone with a selective inhibitor of monoacyglycerol lipase (JZL184 or fatty acid amide hydrolase (AM3506 produced a transient increase in non-rapid eye movement (NREM sleep due to an augmentation of the length of NREM bouts (NREM stability. Similarly, direct activation of type 1 cannabinoid (CB1 receptors with CP47,497 increased NREM stability, but both CP47,497 and JZL184 had a secondary effect that reduced NREM sleep time and stability. This secondary response to these drugs was similar to the early effect of CB1 blockade with the antagonist/inverse agonist AM281, which fragmented NREM sleep. The magnitude of the effects produced by JZL184 and AM281 were dependent on the time of day this drug was administered. While activation of CB1 resulted in only a slight reduction in gamma power, CB1 blockade had dramatic effects on broadband power in the EEG, particularly at low frequencies. However, CB1 blockade did not significantly reduce the rebound in NREM sleep following total sleep deprivation. These results support the hypothesis that endocannabinoid signaling through CB1 is necessary for NREM stability but it is not necessary for sleep homeostasis.

  19. Regulation and policy working group

    Energy Technology Data Exchange (ETDEWEB)



    The potential environmental impact of offshore platform disposal can be illustrated by both the numbers of platforms and the complexity of their abandonment options. Some 7,000 platforms are in place worldwide. In the US, approximately a quarter of the platforms are more than 25 years old and in sight of their end of service. In addition, 22,000 miles of pipeline are located on the Outer Continental Shelf (OCS) in the United States. There are more offshore platforms in the U.S. Gulf of Mexico than in any other single area in the world. It is estimated that between October 1995 and December 2000, approximately 665 of the nearly 3,800 existing structures will be removed. Couple this with the mammoth size, the vagaries of the ocean, and the levels of sometimes conflicting international and federal laws, and the magnitude of the challenge to protect the environment becomes clear. The Offshore International Newsletter (11/06/95) stated, {open_quotes}In three of the last four years, annual Gulf of Mexico platform removals have exceeded installations, a trend that will likely continue.{close_quotes} Between 100 and 150 platforms have been removed from the OCS each year for the past six or seven years. As increasing numbers of wells, pipelines, and platforms are decommissioned and disposed of, it is important that the relevant techniques, policies, and regulations be discussed and evaluated. The goal of this workshop is to facilitate and document this discussion in an open, objective, and inclusive way. Since U.S. practices and policies provide precedents for other countries, international participation is encouraged and anticipated.

  20. Regulated trafficking of the CFTR chloride channel. (United States)

    Kleizen, B; Braakman, I; de Jonge, H R


    The cystic fibrosis transmembrane conductance regulator (CFTR), the ABC transporter encoded by the cystic fibrosis gene, is localized in the apical membrane of epithelial cells where it functions as a cyclic AMP-regulated chloride channel and as a regulator of other ion channels and transporters. Whereas a key role of cAMP-dependent phosphorylation in CFTR-channel gating has been firmly established, more recent studies have provided clear evidence for the existence of a second level of cAMP regulation, i.e. the exocytotic recruitment of CFFR to the plasma membrane and its endocytotic retrieval. Regulated trafficking of the CFTR Cl- channel has sofar been demonstrated only in a subset of CFTR-expressing cell types. However, with the introduction of more sensitive methods to measure CFTR cycling and submembrane localization, it might turn out to be a more general phenomenon that could contribute importantly to both the regulation of CFTR-mediated chloride transport itself and to the regulation of other transporters and CFTR-modulated cellular functions. This review aims to summarize the present state of knowledge regarding polarized and regulated CFTR trafficking and endosomal recycling in epithelial cells, to discuss present gaps in our understanding of these processes at the cellular and molecular level, and to consider its possible implications for cystic fibrosis.

  1. 44 CFR 1.7 - Regulations agendas. (United States)


    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Regulations agendas. 1.7 Section 1.7 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Regulations published in April and October of each year. (b) In accordance with 5 U.S.C. 605, the...

  2. Self-regulation in the mining industry

    DEFF Research Database (Denmark)

    Sinding, Knud; Peck, Philip


    Many industries have established their own systems for self-regulation. They often do so when companies involved in the industry operate in countries where financial, technical, environmental and social regulation is weak and when the industry is challenged by legitimacy issues related to behaviour...

  3. Labour and employment regulation in Europe

    DEFF Research Database (Denmark)

    Lind, Jens (ed.); Knudsen, Herman Lyhne (ed.); Jørgensen, Henning (ed.)

    The main focus iof the book is on labour interests, conditions and developments in trade union organisation and  political  regulation of the labour market.......The main focus iof the book is on labour interests, conditions and developments in trade union organisation and  political  regulation of the labour market....

  4. From "smart regulation" to "regulatory arrangements"

    NARCIS (Netherlands)

    Gossum, Van P.; Arts, B.; Verheyen, K.


    When regulators are faced with practical challenges, policy instrument choice theories can help them find the best solution. However, not all such theories are equally helpful. This paper aims to offer regulators a better alternative to the current policy instrument choice theories. We will specific

  5. International Regulation of Central Arctic Ocean Fisheries

    NARCIS (Netherlands)

    Molenaar, E.J.


    Due in particular to the impacts of climate change, the adequacy of the international regulation of Central Arctic Ocean fisheries has come under increasing scrutiny in recent years. As shown in this article, however, international regulation of Central Arctic Ocean fisheries is by no means entirely

  6. 78 FR 45168 - Acquisition Regulations: Export Control (United States)


    ... Parts 925, 952 and 970 RIN 1991-AB99 Acquisition Regulations: Export Control AGENCY: Department of... Department of Energy Acquisition Regulation (DEAR) to add export control requirements applicable to the... business August 23, 2013. ADDRESSES: You may submit comments, identified by ``DEAR: Export Control and...

  7. 15 CFR 2.7 - Supplementary regulations. (United States)


    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Supplementary regulations. 2.7 Section 2.7 Commerce and Foreign Trade Office of the Secretary of Commerce PROCEDURES FOR HANDLING AND... General Counsel for Finance and Litigation may from time to time issue such supplementary regulations...

  8. The Kidney and Acid-Base Regulation (United States)

    Koeppen, Bruce M.


    Since the topic of the role of the kidneys in the regulation of acid base balance was last reviewed from a teaching perspective (Koeppen BM. Renal regulation of acid-base balance. Adv Physiol Educ 20: 132-141, 1998), our understanding of the specific membrane transporters involved in H+, HCO , and NH transport, and especially how these…

  9. Foreign experience of regulating international trade transactions

    Directory of Open Access Journals (Sweden)

    Klymenko L. V.


    Full Text Available The article deals with the international experience of state regulating international trade transactions; nature, directions and contradictions of contemporary processes of globalization are defined; components of regulatory and incentive means in system of state supporting foreign trade activity of commodity producers are considered; general provisions for the improvement of state regulation mechanisms of export-import activities in Ukraine are determined.

  10. Development of a Fluidic Oxygen Regulator (United States)


    IMaJ «aa^^ ■"-i*--’L’ "’"’-—"’"lllMini pp Figure 5a. Breadboard of 0_ Regulator Figure 5b. Breadboard of O , Regulator (second view) 12 "’■■- "max i

  11. 78 FR 70193 - Consumer Leasing (Regulation M) (United States)


    ... CFR Part 213 BUREAU OF CONSUMER FINANCIAL PROTECTION 12 CFR Part 1013 Consumer Leasing (Regulation M) AGENCY: Board of Governors of the Federal Reserve System (Board); and Bureau of Consumer Financial...' regulations that implement the Consumer Leasing Act (CLA). The Dodd- Frank Wall Street Reform and...

  12. 77 FR 69735 - Consumer Leasing (Regulation M) (United States)


    ...-AD94 BUREAU OF CONSUMER FINANCIAL PROTECTION 12 CFR Part 1013 Consumer Leasing (Regulation M) AGENCY: Board of Governors of the Federal Reserve System (Board); and Bureau of Consumer Financial Protection...' regulations that implement the Consumer Leasing Act (CLA). Effective July 21, 2011, the Dodd-Frank Wall...

  13. 78 FR 35195 - Acquisition Regulations: Export Control (United States)


    ... Parts 925, 952, and 970 RIN 1991-AB99 Acquisition Regulations: Export Control AGENCY: Department of... amend the Department of Energy Acquisition Regulation (DEAR) to add export control requirements... ``DEAR: Export Control and RIN 1991-AB99,'' by any of the following methods: Federal eRulemaking...

  14. The Recast Brussels I Regulation and Arbitration

    DEFF Research Database (Denmark)

    Hauberg Wilhelmsen, Louise


    of Justice (ECJ) in the West Tankers case. The predominant interpretation of the existing exclusion of arbitration from the scope of the Regulation entails that a judgment disregarding or breaching an arbitration agreement will circulate in the European Union according to the rules of the Regulation...

  15. Emotion Regulation and Childhood Aggression: Longitudinal Associations (United States)

    Roll, Judith; Koglin, Ute; Petermann, Franz


    Accumulating evidence suggests that emotion dysregulation is associated with psychopathology. This paper provides a review of recent longitudinal studies that investigate the relationship between emotion regulation and aggressive behavior in childhood age. While there is substantial evidence for assuming a close relation of emotion regulation and…

  16. Regulating phosphorus from the agricultural sector

    DEFF Research Database (Denmark)

    Hansen, Line Block; Hansen, Lars Gårn; Rubæk, Gitte Holton


      Loss of phosphorus (P) from agricultural areas is one of the main contributors to eutrophication of water systems in many European countries. Regulatory systems such as ambient taxes or discharge taxes which are suitable for regulation of N are insufficient for regulating P because these systems...

  17. The Lrp family of transcriptional regulators

    NARCIS (Netherlands)

    Brinkman, A.B.; Ettema, T.J.G.; Vos, de W.M.; Oost, van der J.


    Genome analysis has revealed that members of the Lrp family of transcriptional regulators are widely distributed among prokaryotes, both bacteria and archaea. The archetype Leucine-responsive Regulatory Protein from Escherichia coli is a global regulator involved in modulating a variety of metabolic

  18. A Guide to Federal Reserve Regulations. (United States)

    Federal Reserve Bank of New York, NY.

    The Board of Governors of the Federal Reserve System and the Federal Reserve Banks administer more than two dozen regulations affecting a wide variety of financial activities. The regulations concern the functions of the central bank and its relationships with financial institutions, the activities of commercial banks and bank holding companies,…

  19. 44 CFR 1.8 - Regulations review. (United States)


    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Regulations review. 1.8... HOMELAND SECURITY GENERAL RULEMAKING; POLICY AND PROCEDURES General § 1.8 Regulations review. (a) As part... and keep updated a plan for periodic review of existing rules at least within 10 years from date...

  20. Parent-Child Attachment and Emotion Regulation (United States)

    Brumariu, Laura E.


    Given the centrality of both parent-child attachment and emotion regulation in children's development and adjustment, it is important to evaluate the relations between these constructs. This article discusses conceptual and empirical links between attachment and emotion regulation in middle childhood, highlights progress and challenges in the…

  1. Essays on financial fragility and regulation

    NARCIS (Netherlands)

    Ma, K.


    This thesis investigates various issues in regulation, with three chapters on financial fragility and banking regulation, and one chapter on competition policy. Chapter 2 studies banks’ herding driven by their need for market liquidity, highlighting a trade-off between systemic risk and liquidity cr

  2. Self-Regulation and Academic Procrastination. (United States)

    Senecal, Caroline; And Others


    Assesses the role of autonomous self-regulation as a predictor of academic procrastination. Maintains that academic procrastination is often a motivational problem related to fear of failure. Reveals that students with intrinsic reasons for studying procrastinate less than those with less autonomous reasons (for example, external regulation). (MJP)

  3. 75 FR 57690 - Acquisition Regulation: Sustainable Acquisition (United States)


    ... Parts 907, 923, 936, 952, and 970 RIN 1991-AB95 Acquisition Regulation: Sustainable Acquisition AGENCY... (DOE) is amending the Department of Energy Acquisition Regulation (DEAR) to implement Executive Order... to leverage agency acquisitions to foster markets for sustainable technologies and energy...

  4. Test Review: Anger Regulation and Expression Scale (United States)

    Cavlazoglu, Baki; Erdogan, Niyazi; Paine, Taylor; Jones, Meredith


    This review focuses on the Anger Regulation and Expression Scale (ARES) which was developed by DiGiuseppe and Tafrate (2011) and published by Multi-Health Systems Inc. The ARES was designed to be a self-report measure of anger expression and regulation in youth aged 10 to 17 years and was intended to be used in screening, individual assessment,…

  5. 46 CFR 197.535 - Regulated areas. (United States)


    ... 46 Shipping 7 2010-10-01 2010-10-01 false Regulated areas. 197.535 Section 197.535 Shipping COAST... GENERAL PROVISIONS Benzene § 197.535 Regulated areas. (a) Based on the employer's evaluation of the environmental monitoring, whenever the airborne concentration of benzene within an area exceeds or...

  6. The robust regulation problem with robust stability

    NARCIS (Netherlands)

    Cevik, M.K.K.; Schumacher, J.M.


    Among the most common purposes of control are the tracking of reference signals and the rejection of disturbance signals in the face of uncertainties. The related design problem is called the `robust regulation problem'. Here we investigate the trade-off between the robust regulation constraint and

  7. The precautionary principle and chemicals regulation

    DEFF Research Database (Denmark)

    Løkke, Søren


    . Conclusions: It is concluded that the role of the precautionary principle in chemicals regulation will require continued scrutiny in the future shaping of the REACH strategy. Perspectives: Continued development of robust and precaution-based chemicals regulation will have to involve both new data......-generation strategies and new forms of political decision-making, with special attention given to transparency and deliberative policymaking....

  8. Review of economic theories of regulation

    NARCIS (Netherlands)

    den Hertog, J.A.


    This paper reviews the economic theories of regulation. It discusses the public and private interest theories of regulation, as the criticisms that have been leveled at them. The extent to which these theories are also able to account for privatization and deregulation is evaluated and policies invo

  9. Cardiac Vagal Regulation and Early Peer Status (United States)

    Graziano, Paulo A.; Keane, Susan P.; Calkins, Susan D.


    A sample of 341 5 1/2-year-old children participating in an ongoing longitudinal study was the focus of a study on the relation between cardiac vagal regulation and peer status. To assess cardiac vagal regulation, resting measures of respiratory sinus arrhythmia (RSA) and RSA change (suppression) to 3 cognitively and emotionally challenging tasks…

  10. 77 FR 4885 - Patent Compensation Board Regulations (United States)


    ... Part 780 RIN 1990-AA33 Patent Compensation Board Regulations AGENCY: Office of the General Counsel... Patent ] Compensation Board regulations to provide that the Secretary of Energy, or a person acting in that position, shall appoint, as needed, a three member panel to serve as the Patent Compensation...

  11. 12 CFR 618.8300 - General regulation. (United States)


    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false General regulation. 618.8300 Section 618.8300 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM GENERAL PROVISIONS Releasing Information § 618.8300 General regulation. Except as necessary in performing official duties or as authorized in...

  12. 31 CFR 316.3 - Governing regulations. (United States)


    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Governing regulations. 316.3 Section 316.3 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES E §...

  13. Theoretical Issues of the Constitutional Regulation Mechanism (United States)

    Zhussupova, Guldaray B.; Zhailyaubayev, Rassul T.; Ukin, Symbat K.; Shunayeva, Sylu M.; Nurmagambetov, Rachit G.


    The purpose of this research is to define the concept of "constitutional regulation mechanism." The definition of the concept of "constitutional regulation mechanism" will give jurists and legislators a theoretical framework for developing legal sciences, such as the constitutional law and the theory of state and law. The…

  14. Self-Regulation and School Readiness (United States)

    Eisenberg, Nancy; Valiente, Carlos; Eggum, Natalie D.


    Research Findings: In this article, we review research on the relations of self-regulation and its dispositional substrate, effortful control, to variables involved in school success. First, we present a conceptual model in which the relation between self-regulation/effortful control and academic performance is mediated by low maladjustment and…

  15. Drug-induced regulation of target expression

    DEFF Research Database (Denmark)

    Iskar, Murat; Campillos, Monica; Kuhn, Michael;


    further newly identified drug-induced differential regulation of Lanosterol 14-alpha demethylase, Endoplasmin, DNA topoisomerase 2-alpha and Calmodulin 1. The feedback regulation in these and other targets is likely to be relevant for the success or failure of the molecular intervention....

  16. Shale gas development: a smart regulation framework. (United States)

    Konschnik, Katherine E; Boling, Mark K


    Advances in directional drilling and hydraulic fracturing have sparked a natural gas boom from shale formations in the United States. Regulators face a rapidly changing industry comprised of hundreds of players, operating tens of thousands of wells across 30 states. They are often challenged to respond by budget cuts, a brain drain to industry, regulations designed for conventional gas developments, insufficient information, and deeply polarized debates about hydraulic fracturing and its regulation. As a result, shale gas governance remains a halting patchwork of rules, undermining opportunities to effectively characterize and mitigate development risk. The situation is dynamic, with research and incremental regulatory advances underway. Into this mix, we offer the CO/RE framework--characterization of risk, optimization of mitigation strategies, regulation, and enforcement--to design tailored governance strategies. We then apply CO/RE to three types of shale gas risks, to illustrate its potential utility to regulators.

  17. Emotion recognition and regulation in anorexia nervosa. (United States)

    Harrison, Amy; Sullivan, Sarah; Tchanturia, Kate; Treasure, Janet


    It is recognized that emotional problems lie at the core of eating disorders (EDs) but scant attention has been paid to specific aspects such as emotional recognition, regulation and expression. This study aimed to investigate emotion recognition using the Reading the Mind in the Eyes (RME) task and emotion regulation using the Difficulties in Emotion Regulation Scale (DERS) in 20 women with anorexia nervosa (AN) and 20 female healthy controls (HCs). Women with AN had significantly lower scores on RME and reported significantly more difficulties with emotion regulation than HCs. There was a significant negative correlation between total DERS score and correct answers from the RME. These results suggest that women with AN have difficulties with emotional recognition and regulation. It is uncertain whether these deficits result from starvation and to what extent they might be reversed by weight gain alone. These deficits may need to be targeted in treatment.

  18. Dopamine regulates body size in Caenorhabditis elegans. (United States)

    Nagashima, Takashi; Oami, Eitaro; Kutsuna, Natsumaro; Ishiura, Shoichi; Suo, Satoshi


    The nervous system plays a critical role in the regulation of animal body sizes. In Caenorhabditis elegans, an amine neurotransmitter, dopamine, is required for the tactile perception of food and food-dependent behavioral changes, while its role in development is unknown. In this study, we show that dopamine negatively regulates body size through a D2-like dopamine receptor, DOP-3, in C. elegans. Dopamine alters body size without affecting food intake or developmental rate. We also found that dopamine promotes egg-laying, although the regulation of body size by dopamine was not solely caused by this effect. Furthermore, dopamine negatively regulates body size through the suppression of signaling by octopamine and Gq-coupled octopamine receptors, SER-3 and SER-6. Our results demonstrate that dopamine and octopamine regulate the body size of C. elegans and suggest a potential role for perception in addition to ingestion of food for growth.


    Directory of Open Access Journals (Sweden)

    Berinde Mihai


    Full Text Available In a broad sense, the term „competition” defines the relations between economic operators acting on the same market seeking attainment of certain interests in economic freedom conditions. The need for regulations in the area of competition stems from the nature of free, open market economy which is founded on the existence of fair competition between economic agents, competition which must be observed, maintained and protected by the law. Public authorities who issue various regulations should be cautious about how far this role is played in the economy and they way adopted regulations affect competition in the market. Hence, the need for prior assessment relating to the potential effect of a regulation on competition. It was proven in practice that some regulations may lead to measures that may affect competition directly or indirectly by: limiting the number or range of suppliers; limiting supplier capability to compete and reducing interests of suppliers to compete vigorously.

  20. Reflexive regulation of CSR to promote sustainablility

    DEFF Research Database (Denmark)

    Buhmann, Karin

    This article discusses Corporate Social Responsibility (CSR) from the perspective of governmental regulation as a measure to promote public policy interests through public-private regulation intended to influence firms’ self-regulation. Presenting a ‘government case’ for CSR, the connection between...... and the EU CSR Alliance. Focusing on human rights based in international law, it analyses the patterns of negotiation in the MSF and the background for the launch of the CSR Alliance. It shows that analysing public-private regulation of CSR from the perspective of reflexive law theory assists us...... in understanding the mechanisms by which public authorities seek to influence firm’s behaviour through CSR in order to promote public policy objectives. The analysis indicates that to be effective, reflexive regulatory approaches to public-private regulation should pay careful attention to procedural design...

  1. Regulation of Plasma Membrane Recycling by CFTR (United States)

    Bradbury, Neil A.; Jilling, Tamas; Berta, Gabor; Sorscher, Eric J.; Bridges, Robert J.; Kirk, Kevin L.


    The gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) is defective in patients with cystic fibrosis. Although the protein product of the CFTR gene has been proposed to function as a chloride ion channel, certain aspects of its function remain unclear. The role of CFTR in the adenosine 3',5'-monophosphate (cAMP)-dependent regulation of plasma membrane recycling was examined. Adenosine 3',5'-monophosphate is known to regulate endocytosis and exocytosis in chloride-secreting epithelial cells that express CFTR. However, mutant epithelial cells derived from a patient with cystic fibrosis exhibited no cAMP-dependent regulation of endocytosis and exocytosis until they were transfected with complementary DNA encoding wild-type CFTR. Thus, CFTR is critical for cAMP-dependent regulation of membrane recycling in epithelial tissues, and this function of CFTR could explain in part the pleiotropic nature of cystic fibrosis.

  2. Regulated necrosis and its implications in toxicology. (United States)

    Aki, Toshihiko; Funakoshi, Takeshi; Uemura, Koichi


    Recent research developments have revealed that caspase-dependent apoptosis is not the sole form of regulated cell death. Caspase-independent, but genetically regulated, forms of cell death include pyroptosis, necroptosis, parthanatos, and the recently discovered ferroptosis and autosis. Importantly, regulated necrosis can be modulated by small molecule inhibitors/activators, confirming the cell autonomous mechanism of these forms of cell death. The success of small molecule-mediated manipulation of regulated necrosis has produced great changes in the field of cell death research, and has also brought about significant changes in the fields of pharmacology as well as toxicology. In this review, we intend to summarize the modes of regulated cell death other than apoptosis, and discuss their implications in toxicology.

  3. 76 FR 11985 - Acquisition Regulation: Department of Energy Acquisition Regulation, Government Property (United States)


    ... Parts 908, 945, and 970 RIN 1991-AB86 Acquisition Regulation: Department of Energy Acquisition...: The Department of Energy (DOE) is proposing to amend the Department of Energy Acquisition Regulation (DEAR) to conform to the Federal Acquisition Regulation (FAR), remove out-of date government...

  4. 75 FR 75904 - Global Terrorism Sanctions Regulations; Terrorism Sanctions Regulations; Foreign Terrorist... (United States)


    ... Office of Foreign Assets Control 31 CFR Parts 594, 595, and 597 Global Terrorism Sanctions Regulations; Terrorism Sanctions Regulations; Foreign Terrorist Organizations Sanctions Regulations AGENCY: Office of... (``OFAC'') of the U.S. Department of the Treasury is amending the Global Terrorism Sanctions...

  5. Public and private interests in regulation : essays in the law and economics of regulation

    NARCIS (Netherlands)

    Hertog, J.A. den


    The six chapters in this thesis all focus on regulation. Public and private interest theories of regulation are used as a viewpoint and as an instrument to analyse and evaluate particular regulations and policy developments. Furthermore, in the literature there is a debate about the explanatory powe

  6. Female sexuality, regulation and resistance. (United States)

    Khanna, R; Price, J


    India was the context for this discussion of female sexuality, rigid social norms, women's strategies for resistance, the evolution of norms from colonial India, prostitution, myths, and self-help women's activities. Sexuality is a changing set of ideas, and women have contributed to the redefinition. The biological view without consideration of the sociocultural and historical influences proscribes what is deviant and may be used to reinforce patriarchy and colonialism. Management and control of sexuality has been influenced by class, religion, caste, and ethnicity. During the colonial period, women's sexuality and treatment was challenged by the missionaries. The abolishment of "sati" as a traditional practice was used by the British to expand their rule and control over a wider regional area. Attempts were also made to regulate prostitution as means of protecting the health of the British army. The law requiring registration, examination, and commitment for treatment of prostitutes was not adhered to by the women involved. The notion of mothers as irresponsible came into being about 1900, and encouraged abandonment of traditional child- rearing ways for the Western standard of health and hygiene, and lifestyle. In Bengal, motherhood and mother qoddesses became the symbol of the liberation movement. The maternal role could be strengthened through education. The notion of mother and nationhood was supported by the women's movement in Great Britain and the US through positive eugenics ideas of quality race, which supported the ruling elite of British and Indians. Thus, the high class women were to be protected from early marriage, and encouraged to produce children fit to govern; the poor were to be protected from prostitution and overpopulation. Post colonial ideas about sexuality reflected a number of influences both from within and outside India. Health was a focus, and program targets were those who were outside the norm: women with too many children


    Directory of Open Access Journals (Sweden)

    Rafael Rode


    Full Text Available This study aims to assess the cooperative regulation process of forestry producers in comparison to the traditional individual regulation of properties. Twenty (20 forest properties are studied as examples of the development of three forest regulation scenarios: 1 individual regulation, 2 group regulation, and 3 cooperative regulation. The Net Present Value (NPV of each of the scenarios is optimized according to mathematical programming models and compared to a baseline scenario without forest regulation. According to the proposed cooperative regulation, properties had a proportion factor for annual net revenue distribution calculated from results of the baseline scenario. By comparing the NPV maximization results from scenarios 1 and 3 with the non-regulation scenario, the cost for individual regulation is on average 25%, while being only 11% for cooperative regulation, that is, a 14% reduction in property regulation costs. Additionally, cooperative regulation had the advantage of dividing properties into fewer areas when compared to individual regulation.

  8. Incentive Mechanism Design for Public Goods Provision: Price Cap Regulation and Optimal Regulation

    Institute of Scientific and Technical Information of China (English)

    ZHENG Jun-jun; YIN Hong; WANG Xian-jia


    This paper studies the mechanism design that induces firms to provide public goods under two regulatory means: price cap regulation and optimal regulation, respectively. We first outline two models of monopoly regulation with unobservable marginal costs and effort, which can be regard as an optimal problem with dual restrictions. By solving this problem, we get the two optimal regulatory mechanisms to induce the provision of public goods. Further, by comparative statics, the conclusion is drawn that the welfare loss associated with price cap regulation, with respective to optimal regulation, increases more with increase of the expense of public goods.

  9. Social Regulation of Emotion: Messy Layers

    Directory of Open Access Journals (Sweden)

    Arvid eKappas


    Full Text Available Emotions are evolved systems of intra- and interpersonal processes that are regulatory in nature, dealing mostly with issues of personal or social concern. They regulate social interaction and in extension, the social sphere. In turn, processes in the social sphere regulate emotions of individuals and groups. In other words, intrapersonal processes project in the interpersonal space, and inversely, interpersonal experiences deeply influence intrapersonal processes. Thus, I argue that the concepts of emotion generation and regulation should not be artificially separated. Similarly, interpersonal emotions should not be reduced to interacting systems of intraindividual processes. Instead, we can consider emotions at different social levels, ranging from dyads to large scale e-communities. The interaction between these levels is complex and does not only involve influences from one level to the next. In this sense the levels of emotion/regulation are messy and a challenge for empirical study. In this article, I discuss the concepts of emotions and regulation at different intra- and interpersonal levels. I extend the concept of auto-regulation of emotions (Kappas, 2008. 2011a, 2011b to social processes. Furthermore, I argue for the necessity of including mediated communication, particularly in cyberspace in contemporary models of emotion/regulation. Lastly, I suggest the use of concepts from systems dynamics and complex systems to tackle the challenge of the messy layers.

  10. Regulation of chromosomal replication in Caulobacter crescentus. (United States)

    Collier, Justine


    The alpha-proteobacterium Caulobacter crescentus is characterized by its asymmetric cell division, which gives rise to a replicating stalked cell and a non-replicating swarmer cell. Thus, the initiation of chromosomal replication is tightly regulated, temporally and spatially, to ensure that it is coordinated with cell differentiation and cell cycle progression. Waves of DnaA and CtrA activities control when and where the initiation of DNA replication will take place in C. crescentus cells. The conserved DnaA protein initiates chromosomal replication by directly binding to sites within the chromosomal origin (Cori), ensuring that DNA replication starts once and only once per cell cycle. The CtrA response regulator represses the initiation of DNA replication in swarmer cells and in the swarmer compartment of pre-divisional cells, probably by competing with DnaA for binding to Cori. CtrA and DnaA are controlled by multiple redundant regulatory pathways that include DNA methylation-dependent transcriptional regulation, temporally regulated proteolysis and the targeting of regulators to specific locations within the cell. Besides being critical regulators of chromosomal replication, CtrA and DnaA are also master transcriptional regulators that control the expression of many genes, thus connecting DNA replication with other events of the C. crescentus cell cycle.

  11. Rainwater harvesting state regulations and technical resources

    Energy Technology Data Exchange (ETDEWEB)

    Loper, Susan A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)


    Pacific Northwest National Laboratory (PNNL) conducted in-depth research of state-level rainwater harvesting regulations for the Federal Energy Management Program (FEMP) to help federal agencies strategically identify locations conducive to rainwater harvesting projects. Currently, rainwater harvesting is not regulated by the federal government but rather it is up to individual states to regulate the collection and use of rainwater. There is no centralized information on state-level regulations on rainwater harvesting maintained by a federal agency or outside organization. To fill this information gap, PNNL performed detailed internet searches for each state, which included state agencies, universities, Cooperative Extension Offices, city governments, and related organizations. The state-by-state information on rainwater harvesting regulations was compiled and assembled into an interactive map that is color coded by state regulations. The map provides a visual representation of the general types of rainwater harvesting policies across the country as well as general information on the state programs if applicable. The map allows the user to quickly discern where rainwater harvesting is supported and regulated by the state. This map will be available on the FEMP website by September 2015.

  12. Dental hygiene regulation: a global perspective. (United States)

    Johnson, P M


    Occupational regulation of health personnel is important to professional associations and their members, the public that relies on their services and the regulatory agencies responsible for their conduct. There is increasing interest in ensuring that dental hygiene regulation fosters the continuing evolution of the profession and its contribution to oral health. The keynote address for the 2007 Regulatory Forum on Dental Hygiene, this paper discusses the rationale for and issues pertaining to occupational regulation, outlines the evolvement of dental hygiene and identifies regulatory options for the profession. Professional regulation exists to ensure public safety, health and welfare. However, negative political-economic side effects coupled with environmental pressures have resulted in increased scrutiny for health professionals. One such profession is dental hygiene. Its evolution has been dramatic, in particular over the past few decades, as illustrated by its rapidly increasing numbers and broader distribution globally, gradual shift to the baccalaureate as the entry-level educational requirement and increase in postgraduate programs and expanding scope of practice and increased professional autonomy. Regulatory changes have been more gradual. Regulation is mandatory for the vast majority of dental hygienists. Of the options available, the practice act - the most rigorous type, is predominant. Globally, regulation tends to be administered directly by the government (n = 9 countries) more so than indirectly through a dental board (n = 4) or self-regulation (n = 3). Whether regulated directly or indirectly, dental hygienists increasingly are seeking a greater role in shaping their professional future. Self-regulation, its responsibilities, misperceptions and challenges, is examined as an option.

  13. Optimum regulation of grid monopoly in the power trade; Optimal regulering av nettmonopoler i kraftomsetningen

    Energy Technology Data Exchange (ETDEWEB)

    Hope, E.


    The report discusses the organization and behaviour of grid monopolies in the Norwegian power trade and relations to the socio-economic effectiveness. The main attention is laid on analyzing regulation mechanisms and measures leading to an efficient short-term operation and to the investment of optimum production capacity in a long run. Regarding the management, measures are discussed for increasing the efficiency of total power trade by evaluating the existing marketing function of Statnett. Some basic conditions are accounted concerning the regulation problem of grid monopolies with a particular attention to asymmetric information between the authority and the monopoly. In addition, forms of regulation and regulation mechanisms together with the incentive characteristics of these, are discussed. The existing profit regulation principles in relation to an alternative system design such as maximum price regulation combined with standard regulation, are evaluated. 16 refs., 7 figs.

  14. Regulation and Censorship of the Internet


    Okeke, Innocent


    The Internet is probably one of the greatest inventions of mankind and one of the best things that happened in my generation. It has become an integral part of day to day activities and therefore subject to national security in countries around the globe The Internet grows and so does government regulation The key question is now: should government keep regulating the Internet or leave it as it is? Would it be possible to regulate the Internet without interfering with free speech? Who is m...

  15. Epigenetic regulation in male germ cells. (United States)

    Zamudio, Natasha M; Chong, Suyinn; O'Bryan, Moira K


    In recent years, it has become increasingly clear that epigenetic regulation of gene expression is critical during spermatogenesis. In this review, the epigenetic regulation and the consequences of its aberrant regulation during mitosis, meiosis and spermiogenesis are described. The current knowledge on epigenetic modifications that occur during male meiosis is discussed, with special attention on events that define meiotic sex chromosome inactivation. Finally, the recent studies focused on transgenerational and paternal effects in mice and humans are discussed. In many cases, these epigenetic effects resulted in impaired fertility and potentially long-ranging affects underlining the importance of research in this area.

  16. Robust regulation of anaerobic digestion processes. (United States)

    Mailleret, L; Bernard, O; Steyer, J P


    This paper deals with the problem of controlling anaerobic digestion processes. A two-step (i.e. acidogenesis-methanization) mass balance model is considered for a 1 m3 fixed bed digester treating industrial wine distillery wastewater. The control law aims at regulating the organic pollution level while avoiding washout of biomass. To this end, a simple output feedback controller is considered which regulates a variable strongly related to the Chemical Oxygen Demand (COD). Numerical simulations assuming noisy measurements first illustrate the robustness of this control procedure. Then, the regulating procedure is implemented on the considered anaerobic digestion process in order to validate and demonstrate its efficiency in real life experiments.

  17. Bile acids in regulation of intestinal physiology.

    LENUS (Irish Health Repository)

    Keating, Niamh


    In addition to their roles in facilitating lipid digestion and absorption, bile acids are recognized as important regulators of intestinal function. Exposure to bile acids can dramatically influence intestinal transport and barrier properties; in recent years, they have also become appreciated as important factors in regulating cell growth and survival. Indeed, few cells reside within the intestinal mucosa that are not altered to some degree by exposure to bile acids. The past decade saw great advances in the knowledge of how bile acids exert their actions at the cellular and molecular levels. In this review, we summarize the current understanding of the role of bile acids in regulation of intestinal physiology.

  18. Activation and Regulation of Cellular Eicosanoid Biosynthesis

    Directory of Open Access Journals (Sweden)

    Thomas G. Brock


    Full Text Available There is a growing appreciation for the wide variety of physiological responses that are regulated by lipid messengers. One particular group of lipid messengers, the eicosanoids, plays a central role in regulating immune and inflammatory responses in a receptor-mediated fashion. These mediators are related in that they are all derived from one polyunsaturated fatty acid, arachidonic acid. However, the various eicosanoids are synthesized by a wide variety of cell types by distinct enzymatic pathways, and have diverse roles in immunity and inflammation. In this review, the major pathways involved in the synthesis of eicosanoids, as well as key points of regulation, are presented.

  19. Regulation of p21ras activity

    DEFF Research Database (Denmark)

    Lowy, D R; Zhang, K; DeClue, J E


    The ras genes encode GTP/GDP-binding proteins that participate in mediating mitogenic signals from membrane tyrosine kinases to downstream targets. The activity of p21ras is determined by the concentration of GTP-p21ras, which is tightly regulated by a complex array of positive and negative contr...... mechanisms. GAP and NF1 can negatively regulate p21ras activity by stimulating hydrolysis of GTP bound to p21ras. Other cellular factors can positively regulate p21ras by stimulating GDP/GTP exchange....

  20. Smart-grid Investments, Regulation and Organization

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter; Mikkers, Misja


    Grid infrastructure managers worldwide are facing demands for reinvestments in new assets with higher on-grid and off-grid functionality in order to meet new environmental targets. The roles of the current actors will change as the vertical interfaces between regulated and unregulated tasks become...... blurred. In this paper, we characterize some of the effects of new asset investments policy on the network tasks, assets and costs and contrast this with the assumptions of the current economic network regulation. To provide structure, we present a model of investment provision under regulation between...

  1. Towards spatially differentiated regulation of nitrogen

    DEFF Research Database (Denmark)

    Lajer Højberg, Anker; Refsgaard, Jens Christian; Jørgensen, Lisbeth Flindt

    of drains and hydro-biogeochemical conditions in associated riparian lowlands. Hence, a shift of paradigm in regulation practice is needed, whit a cost-effective regulation accounting for this variability and differentiate the regulations/restrictions between resilient and vulnerable areas. However...... on control monitoring of nitrate outputs from agriculture utilising local scale data and knowledge. TReNDS supports a two-tiered approach, where areas subject to further abatement are identified by national screening approaches supported by detailed local studies for the design of optimal measures taking...... advantage of local data and knowledge....

  2. PSD: new regulations and old problems

    Energy Technology Data Exchange (ETDEWEB)

    Terziev, A.J.


    The Prevention of Significant Deterioration (PSD) program is the Clean Air Act of 1977 effort to protect air that is cleaner than the national standards. New PSD regulations were enacted by EPA in 1980. These new regulations, however, do not address or resolve many of the basic conflicts that arose under the original program. Problems encountered in implementing these regulations are identified, including their complexity, efficient allocation of permits, superfluous review, and insufficient data collection. Alternative approaches, such as the establishment of a set of technology-based standards, are recommended.

  3. [Neurochemical mechanisms of sleep regulation]. (United States)


    Sleep is a complex, global and reversible behavioral state of all mammals, that is homeostatically regulated. Generally it is also defined as a rapidly reversible state of immobility and reduced sensory responsiveness. Still, there is no definition that has succeded in satisfying all aspects of sleep. The failure to define sleep as a single behavior lies in several facts: (1) sleep is not a homogenous state, but continuum of number of mixed states; (2) the control mechanisms of sleep are manifested at all levels of biological organization--from genes and intracellular mechanisms to the networks of neuronal populations within the central nervous system that control movement, arousal, autonomic functions, behavior and cognition; (3) the activity and interactions of these neurochemically greatly heterogenous neuronal populations are dependent of two biological rhythms--the circadian rhythm of wake/sleep and periodic cycles of NREM/REM sleep as two main sleep states. There are several levels of sleep control. The brain forebrain areas serve to control neuropsychology of dreaming; thalamo-cortical system controls NREM sleep rhythms, EEG activation and deactivation; hippocampo-cortical system controls memory consolidation; hypothalamic nuclei are the sources of circadian rhythm and sleep onset control; the control of periodic NREM/REM cycling is within the pons. The wake promoting neuronal populations are within the brainstem, midbrain, hypothalamus and basal forebrain. The main pontine wake-promoting centers are the noradrenergic neurons of locus coeruleus, the serotonergic neurons of dorsal raphe nucleus and the cholinerigic neurons of pedunculopontine tegmental nucleus and laterodorsal tegmental nucleus. The reciprocal connections and interactions of these neurons, and their opposite discharge pattern activity from wake to NREM and REM sleep have been the background of reciprocal interaction hypothesis of REM sleep generation. The wake-promoting neurons at the

  4. Metabotropic Regulation of Extrasynaptic GABAA Receptors

    Directory of Open Access Journals (Sweden)

    William Martin Connelly


    Full Text Available A large body of work now shows the importance of GABAA receptor-mediated tonic inhibition in regulating CNS function. However, outside of pathological conditions, there is relatively little evidence that the magnitude of tonic inhibition is itself under regulation. Here we review the mechanisms by which tonic inhibition is known to be modulated, and outline the potential behavioural consequences of this modulation. Specifically, we address the ability of protein kinase A and C to phosphorylate the extrasynaptic receptors responsible for the tonic GABAA current, and how G-protein coupled receptors can regulate tonic inhibition through these effectors. We then speculate about the possible functional consequences of regulating the magnitude of the tonic GABAA current.

  5. Pollution Under Environmental Regulation in Energy Markets

    CERN Document Server

    Gullì, Francesco


    Pollution Under Environmental Regulation in Energy Markets provides a study of environmental regulation when energy markets are imperfectly competitive. This theoretical treatment focuses on three relevant cases of energy markets. First, the residential space heating sector where hybrid regulation such as taxation and emissions trading together are possible. Second, the electricity market where transactions are organized in the form of multi-period auctions. Third, namely natural gas (input) and electricity (output) markets where there is combined imperfect competition in vertical related energy markets.   The development of free or low carbon technologies supported by energy policies, aiming at increasing security of supply, is also explored whilst considering competition policies that reduce market power in energy markets thus improving market efficiency. Pollution Under Environmental Regulation in Energy Markets discusses the key issues of whether imperfect competition can lessen the ability of environmen...

  6. Molecular regulators of phosphate homeostasis in plants. (United States)

    Lin, Wei-Yi; Lin, Shu-I; Chiou, Tzyy-Jen


    An appropriate cellular phosphate (Pi) concentration is indispensable for essential physiological and biochemical processes. To maintain cellular Pi homeostasis, plants have developed a series of adaptive responses to facilitate external Pi acquisition and to limit Pi consumption and to adjust Pi recycling internally when the Pi supply is inadequate. Over the past decade, significant progress has been made toward understanding such regulation at the molecular level. In this review, the focus is on the molecular regulators that mediate cellular Pi concentrations. The regulators are introduced and organized according to their original identification procedures, by the forward genetic approach of mutant screening or by reverse genetic analysis. These genes are involved in Pi uptake, allocation or remobilization or are upstream regulators, such as transcriptional factors or signalling molecules. In the future, integration of current knowledge and exploration of new technology is expected to offer new insights into molecular mechanisms that maintain Pi homeostasis.

  7. Regulation of TET Protein Stability by Calpains

    Directory of Open Access Journals (Sweden)

    Yu Wang


    Full Text Available DNA methylation at the fifth position of cytosine (5mC is an important epigenetic modification that affects chromatin structure and gene expression. Recent studies have established a critical function of the Ten-eleven translocation (Tet family of proteins in regulating DNA methylation dynamics. Three Tet genes have been identified in mammals, and they all encode for proteins capable of oxidizing 5mC as part of the DNA demethylation process. Although regulation of Tet expression at the transcriptional level is well documented, how TET proteins are regulated at posttranslational level is poorly understood. In this study, we report that all three TET proteins are direct substrates of calpains, a family of calcium-dependent proteases. Specifically, calpain1 mediates TET1 and TET2 turnover in mouse ESCs, and calpain2 regulates TET3 level during differentiation. This study provides evidence that TET proteins are subject to calpain-mediated degradation.

  8. Regulation of TET protein stability by calpains. (United States)

    Wang, Yu; Zhang, Yi


    DNA methylation at the fifth position of cytosine (5mC) is an important epigenetic modification that affects chromatin structure and gene expression. Recent studies have established a critical function of the Ten-eleven translocation (Tet) family of proteins in regulating DNA methylation dynamics. Three Tet genes have been identified in mammals, and they all encode for proteins capable of oxidizing 5mC as part of the DNA demethylation process. Although regulation of Tet expression at the transcriptional level is well documented, how TET proteins are regulated at posttranslational level is poorly understood. In this study, we report that all three TET proteins are direct substrates of calpains, a family of calcium-dependent proteases. Specifically, calpain1 mediates TET1 and TET2 turnover in mouse ESCs, and calpain2 regulates TET3 level during differentiation. This study provides evidence that TET proteins are subject to calpain-mediated degradation.

  9. Stringency of environmental regulation and aquaculture growth

    DEFF Research Database (Denmark)

    Gedefaw Abate, Tenaw; Nielsen, Rasmus; Tveterås, Ragnar


    During the last three decades, aquaculture has been the fastest growing animal-food-producing sector in the world, accounting for half of the present seafood supply. However, there is a significant growth disparity among aquaculture-producing countries. The reasons why some countries have achieved...... remarkable growth in aquaculture while others have stagnated or even declined have not been determined. In this article, we investigate whether environmental regulations have an impact on aquaculture growth. Using a cross-country regression analysis, we show that stringent environmental regulations...... are negatively related to aquaculture growth, whereas GDP growth has a positive effect. Countries often face a difficult balancing act between growth and environmental considerations when devising regulations. Our empirical results suggest that stricter environmental regulations in developed countries have...

  10. Regulation of Vascular Function on Posttranscriptional Level

    Directory of Open Access Journals (Sweden)

    Andreas Eisenreich


    Full Text Available Posttranscriptional control of gene expression is crucial for regulating plurality of proteins and functional plasticity of the proteome under (pathophysiologic conditions. Alternative splicing as well as micro (miRNA-mediated mechanisms play an important role for the regulation of protein expression on posttranscriptional level. Both alternative splicing and miRNAs were shown to influence cardiovascular functions, such as endothelial thrombogenicity and the vascular tone, by regulating the expression of several vascular proteins and their isoforms, such as Tissue Factor (TF or the endothelial nitric oxide synthase (eNOS. This review will summarize and discuss the latest findings on the (pathophysiologic role of alternative splicing processes as well as of miRNAs on modulation of vascular functions, such as coagulation, thrombosis, and regulation of the vascular tone.

  11. Code of Federal Regulations Title 21 (United States)

    U.S. Department of Health & Human Services — This database contains the most recent revision from the Government Printing Office (GPO) of the Code of Federal Regulations (CFR) Title 21 - Food and Drugs.

  12. Annual report 2011 the Norwegian energy regulator

    Energy Technology Data Exchange (ETDEWEB)

    Soeiland, Arne; Lund, Per Tore


    The report provides an overview of the current regulation of the electricity and district heating markets in Norway, and explains relevant market developments. An overview of legislative amendments, research work and international participation is also presented in the report (Author)

  13. Molecular regulation of telomerase activity in aging

    Institute of Scientific and Technical Information of China (English)

    Craig Nicholls; He Li; Jian-Qiu Wang; Jun-Ping Liu


    The process of aging is mitigated by the maintenance and repair of chromosome ends (telomeres),resulting in extended lifespan.This review examines the molecular mechanisms underlying the actions and regulation of the enzyme telomerase reverse transcriptase (TERT),which functions as the primary mechanism of telomere maintenance and regulates cellular life expectancy.Underpinning increased cell proliferation,telomerase is also a key factor in facilitating cancer cell immortalization.The review focuses on aspects of hormonal regulations of telomerase,and the intraceilular pathways that converge to regulate telomerase activity with an emphasis on molecular interactions at protein and gene levels.In addition,the basic structure and function of two key telomerase enzyme components-the catalytic subunit TERT and the template RNA (TERC) are discussed briefly.

  14. Opening Innovation in Regulation Inside Government

    DEFF Research Database (Denmark)

    Hartmann, Rasmus Koss; Hienerth, Christoph


    A marked increase in regulation inside government has been a defining feature of public management reform in throughout the Western world over the past thirty years, making regulatory innovation one of the most important forms of innovation in the public sector. The process of regulatory innovation......, however, has been critiqued for resulting in high levels of compliance costs throughout public sector organizations. Concurrently, we show that it has also generally been dominated by a closed and regulator-centered model of innovative development. In this paper, we develop first a concept of user...... of regulation and typology of four forms of user involvement based on the available public management literature. Second, we develop a model of the costs of regulation. We then analyze scenarios of how these four forms can contribute to reducing regulatory costs. We find that user innovation can contribute both...

  15. Reflexive regulation of CSR to promote sustainability

    DEFF Research Database (Denmark)

    Buhmann, Karin


    This article discusses Corporate Social Responsibility (CSR) from the perspective of governmental regulation as a measure to promote public policy interests through public-private regulation intended to influence firms’ self-regulation. Presenting a ‘government case’ for CSR, the connection between...... climate change and environmental sustainability, and social, economic and other human rights lend human rights as part of CSR a potential for meeting some environmental and climate concerns and handling adverse side-effects. The article analyses two EU initiatives: The EU Multi-Stakeholder (MSF) on CSR...... and the EU CSR Alliance. Focusing on human rights based in international law, it analyses the patterns of negotiation in the MSF and the background for the launch of the CSR Alliance. It shows that analysing public-private regulation of CSR from the perspective of reflexive law theory assists us...

  16. Regulation of geothermal energy development in Colorado

    Energy Technology Data Exchange (ETDEWEB)

    Coe, B.A.; Forman, N.A.


    The regulatory system is presented in a format to help guide geothermal energy development. State, local, and federal agencies, legislation, and regulations are presented. Information sources are listed. (MHR)

  17. Clinical comparability and European biosimilar regulations

    NARCIS (Netherlands)

    Schellekens, H.; Moors, Ellen


    Clinical trials required by European regulators to compare biosimilar products with corresponding biologic brands are surplus to requirements and may even be a barrier for the development of biosimilars of more complicated biologics.

  18. Regulation of water balance in mangroves


    Reef, Ruth; Lovelock, Catherine E.


    Background Mangroves are a group of highly salt-tolerant woody plants. The high water use efficiency of mangroves under saline conditions suggests that regulation of water transport is a crucial component of their salinity tolerance.


    Institute of Scientific and Technical Information of China (English)


    @@ The Chinese Government will soon issue an industry policy to regulate the coal-chemicals sector, after a circular in August ordered local authorities to tighten their grip on the approval of new coal-to-petrochemicals projects in China.

  20. Histone variants in plant transcriptional regulation. (United States)

    Jiang, Danhua; Berger, Frédéric


    Chromatin based organization of eukaryotic genome plays a profound role in regulating gene transcription. Nucleosomes form the basic subunits of chromatin by packaging DNA with histone proteins, impeding the access of DNA to transcription factors and RNA polymerases. Exchange of histone variants in nucleosomes alters the properties of nucleosomes and thus modulates DNA exposure during transcriptional regulation. Growing evidence indicates the important function of histone variants in programming transcription during developmental transitions and stress response. Here we review how histone variants and their deposition machineries regulate the nucleosome stability and dynamics, and discuss the link between histone variants and transcriptional regulation in plants. This article is part of a Special Issue entitled: Plant Gene Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer.

  1. Reflexive regulation of CSR to promote sustainablility

    DEFF Research Database (Denmark)

    Buhmann, Karin

    climate change and environmental sustainability, and social, economic and other human rights lend human rights as part of CSR a potential for meeting some environmental and climate concerns and handling adverse side-effects. The article analyses two EU initiatives: The EU Multi-Stakeholder (MSF) on CSR...... in promoting companies’ responsibility with regard to aspects of sustainable development, such as climate impact. Keywords: Sustainable development, sustainable companies, reflexive regulation, climate change, CSR, EU law, public-private regulation, companies' self-regulation...... and the EU CSR Alliance. Focusing on human rights based in international law, it analyses the patterns of negotiation in the MSF and the background for the launch of the CSR Alliance. It shows that analysing public-private regulation of CSR from the perspective of reflexive law theory assists us...

  2. Molecular mechanism and regulation of autophagy

    Institute of Scientific and Technical Information of China (English)

    Ya-ping YANG; Zhong-qin LIANG; Zhen-lun GU; Zheng-hong QIN


    Autophagy is a major cellular pathway for the degradation of long-lived proteins and cytoplasmic organelles in eukaryotic cells. A large number of intracellular/extracellular stimuli, including amino acid starvation and invasion of microorganisms, are able to induce the autophagic response in cells. The discovery of the ATG genes in yeast has greatly advanced our understanding of the molecular mechanisms participating in autophagy and the genes involved in regulating the autophagic pathway. Many yeast genes have mammalian homologs,suggesting that the basic machinery for autophagy has been evolutionarily conserved along the eukaryotic phylum. The regulation of autophagy is a very complex process. Many signaling pathways, including target of rapamycin (TOR) or mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase-I (PI3K-I)/PKB, GTPases, calcium and protein synthesis all play important roles in regulating autophagy. The molecular mechanisms and regulation of autophagy are discussed in this review.

  3. Regulation of monoubiquitinated PCNA by DUB autocleavage

    NARCIS (Netherlands)

    Huang, T.T.; Nijman, S.M.B.; Galardy, P.J.; Cohn, M.A.; Haas, W.; Gygi, S.P.; Ploegh, H.L.; Bernards, R.A.; D'Andrea, A.D.


    Monoubiquitination is a reversible post-translational protein modification that has an important regulatory function in many biological processes, including DNA repair. Deubiquitinating enzymes (DUBs) are proteases that are negative regulators of monoubiquitination, but little is known about their r

  4. Regulation of glucagon secretion by incretins

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Christensen, M; Lund, A;


    Glucagon secretion plays an essential role in the regulation of hepatic glucose production, and elevated fasting and postprandial plasma glucagon concentrations in patients with type 2 diabetes (T2DM) contribute to their hyperglycaemia. The reason for the hyperglucagonaemia is unclear, but recent...... that endogenous GLP-1 plays an important role in regulation of glucagon secretion during fasting as well as postprandially. The mechanisms whereby GLP-1 regulates glucagon secretion are debated, but studies in isolated perfused rat pancreas point to an important role for a paracrine regulation by somatostatin...... studies have shown lack of suppression after oral but preserved suppression after isoglycaemic intravenous glucose, pointing to factors from the gut. Gastrointestinal hormones that are secreted in response to oral glucose include glucagon-like peptide-1 (GLP-1) that strongly inhibits glucagon secretion...


    Directory of Open Access Journals (Sweden)

    Boris Kovalenko


    Full Text Available Government regulation of business is based on the application of different rules of behavior of economic agents. These rules are being developed and implemented at the national and regional levels of economic regulation. At a certain stage of development of national and regional regulations are beginning to constrain the global interaction of the agents of economic development. This trend for the economy of Russia and many countries that have more attention udlyat create market conditions for farming. In order to further the economic development of space postsovetsvkogo gaining positive momentum necessary to reduce control over the actions of economic agents and to create a culture of self-regulation. We see the problem is to establish a balance of government regulation and self-regulation in a single continuum. To this end, studies were carried out the forms and methods of state regulation in the Russian economy, the advantages and disadvantages of self-regulation, self-regulatory organizations proposed classification, formulated the conditions under which self-regulation in the post-may be more effective form of impact on the behavior of economic agents than government regulation. In the article the author offers direction of public-private partnership: financial, logistical and administrative real. The development of public-private partnerships as a mechanism for interaction study of global parties “society - the state – business” in the management of priority areas of the economy.

  6. [On health regulation of synthetic detergents]. (United States)

    Frolova, A D; Sidorin, G I; Lukovnikova, L V; Skhodkina, N I; D'iakova, L I; Shaposhnikova, E S


    The authors present materials on hygienic regulation of such synthetic detergents as "Losk", "Dixan" in air of workplace and populated area, demonstrate results concerning evaluation of "Losk" effects. Discussion covers ways to evaluate chemical load caused by simultaneous emission of synthetic detergents from various environmental objects. For testing reliability of hygienic regulation for complex emission exemplified by "Losk", the authors suggest a model for express evaluation of complex exposure to chemicals.


    Institute of Scientific and Technical Information of China (English)

    Yali DONG; Daizhan CHENG; Huashu QIN


    Output regulation for affine nonlinear systems driven by an exogenous signal is investigated in this paper. In the absence of the standard exosystem hypothesis, we assume availability of the instantaneous values of the exogenous signal and its first time-derivative for use in the control law.For affine nonlinear systems, the necessary and sufficient conditions of the solvability of approximate output regulation problem are obtained. The precise form of the control law is presented under some suitable assumptions.

  8. Towards Systems Biology of Mycotoxin Regulation


    Christof Rampitsch; Rajagopal Subramaniam


    Systems biology is a scientific approach that integrates many scientific disciplines to develop a comprehensive understanding of biological phenomena, thus allowing the prediction and accurate simulation of complex biological behaviors. It may be presumptuous to write about toxin regulation at the level of systems biology, but the last decade of research is leading us closer than ever to this approach. Past research has delineated multiple levels of regulation in the pathways leading to the b...

  9. Maternal regulation and toddlers’ effortful control



    Effortful control is a regulatory component of emotion (Calkins & Hill, 2007). This descriptive study analyzed the relation between maternal co-regulation strategies and children self-regulation strategies in order to evaluate their effortful control skills.19 dyads [mother-child] with children between 18 and 36 months old participated and were divided in three groups, the sample was taken from government´s nurseries. A transversal study with direct observation of the experimental situati...

  10. Metalloproteinases and their regulators in colorectal cancer. (United States)

    van der Jagt, Michel F P; Wobbes, Theo; Strobbe, Luc J A; Sweep, Fred C G J; Span, Paul N


    Metalloproteinases (MPs) such as the matrix metalloproteinases (MMPs) and adamalysins (ADAMs and ADAMTS) are expressed in various stages of colorectal cancer (CRC), and some correlate with survival and prognosis. The MPs are regulated by various factors including EMMPRIN, TIMPs, and RECK. In addition, micro-RNAs are found to be relevant for both MP expression levels and CRC prognostication. Both MPs and their regulators could be potential targets for intervention and therapy in CRC.

  11. Signaling mechanisms for regulation of chemotaxis

    Institute of Scientific and Technical Information of China (English)

    Dianqing WU


    Chemotaxis is a fascinating biological process, through which a cell migrates along a shallow chemoattractant gradient that is less than 5% difference between the anterior and posterior of the cell. Chemotaxis is composed of two independent,but interrelated processes-motility and directionality, both of which are regulated by extracellular stimuli, chemoattractants.In this mini-review, recent progresses in the understanding of the regulation of leukocyte chemotaxis by chemoattractant signaling are reviewed.

  12. Regulation of blood pressure by dopamine receptors. (United States)

    Jose, Pedro A; Eisner, Gilbert M; Felder, Robin A


    Dopamine is an important regulator of blood pressure. Its actions on renal hemodynamics, epithelial transport and humoral agents such as aldosterone, catecholamines, endothelin, prolactin, pro-opiomelanocortin, renin and vasopressin place it in central homeostatic position for regulation of extracellular fluid volume and blood pressure. Dopamine also modulates fluid and sodium intake via actions in the central nervous system and gastrointestinal tract, and by regulation of cardiovascular centers that control the functions of the heart, arteries and veins. Abnormalities in dopamine production and receptor function accompany a high percentage of human essential hypertension and several forms of rodent genetic hypertension. Some dopamine receptor genes and their regulators are in loci linked to hypertension in humans and in rodents. Furthermore, single nucleotide polymorphisms (SNPs) of genes that regulate dopamine receptors, alone or via the interaction with SNPs of genes that regulate the renin-angiotensin system, are associated with human essential hypertension. Each of the five dopamine receptor subtypes (D1, D2, D3, D4 and D5) participates in the regulation of blood pressure by mechanisms specific for the subtype. Some receptors (D2 and D5) influence the central and/or peripheral nervous system; others influence epithelial transport and regulate the secretion and receptors of several humoral agents (e.g., the D1, D3 and D4 receptors interact with the renin-angiotensin system). Modifications of the usual actions of the receptor can produce blood pressure changes. In addition, abnormal functioning of these dopamine receptor subtypes impairs their antioxidant function.

  13. Thermal Regulation of Heat Transfer Processes (United States)


    be approximately 320 m2g-1, 32 times higher than graphite flakes for more efficient heat transfer to the fluid. The evaporation rates of water...AFRL-OSR-VA-TR-2014-0249 THERMAL REGULATION OF HEAT TRANSFER PROCESSES GANG CHEN MASSACHUSETTS INSTITUTE OF TECHNOLOGY Final Report 10/02/2014...Prescribed by ANSI Std. Z39.18 FINAL REPORT FOR FA9550-11-1-0174 THERMAL REGULATION OF HEAT TRANSFER PROCESSES Principal Investigator: Gang Chen

  14. Optimal Bank Regulation and Monetary Policy


    John J. Seater


    A unified model of monetary policy and bank regulation is presented. In accordance with modern banking theory, banks not only intermediate loans and deposits but also provide a financial service affecting aggregate output. Optimal parameter settings for monetary and regulatory policy are derived. New results are that monetary policy affects the expected level as well as the variance of output, bank regulation should change continually in response to the state of the economy, and bank regulati...

  15. Regulation of aleurone development in cereal grains. (United States)

    Becraft, Philip W; Yi, Gibum


    The aleurone layer of cereal grains is important biologically as well as nutritionally and economically. Here, current knowledge on the regulation of aleurone development is reviewed. Recent reports suggest that the control of aleurone development is more complex than earlier models portrayed. Multiple levels of genetic regulation control aleurone cell fate, differentiation, and organization. The hormones auxin and cytokinin can also influence aleurone development. New technical advances promise to facilitate future progress.

  16. Regulation on expert knowledge in radiation protection

    Energy Technology Data Exchange (ETDEWEB)


    The regulation is to be applied to licenses according to paragraphs 3, 15, 16, 20, 20a of the Radiation Protection Law, paragraphs 6, 7, 9 of the Atomic Law, to notices according to paragraphs 4, 17 of the Radiation Protection Law as well as in the prospecting, mining and processing of radioactive minerals. It regulates the extent and evidence of the special knowledge required for radiation protection of radiological safety officers and personnel responsible for radiation protection.

  17. IEE wiring regulations explained and illustrated

    CERN Document Server

    Scaddan, Brian


    The IEE Wiring Regulations Explained and Illustrated, Second Edition discusses the recommendations of the IEE Regulations for the Electrical Equipment of Buildings for the safe selection or erection of wiring installations. The book emphasizes earthing, bonding, protection, and circuit design of electrical wirings. The text reviews the fundamental requirements for safety, earthing systems, the earth fault loop impedance, and supplementary bonding. The book also describes the different types of protection, such as protection against mechanical damage, overcurrent, under voltage (which prevents

  18. 7 CFR 946.51 - Recommendation for regulations. (United States)


    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Recommendation for regulations. 946.51 Section 946.51 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... WASHINGTON Order Regulating Handling Regulation § 946.51 Recommendation for regulations. The committee...

  19. The Regulation of Iron Absorption and Homeostasis (United States)

    Wallace, Daniel F


    Iron is an essential element in biology, required for numerous cellular processes. Either too much or too little iron can be detrimental, and organisms have developed mechanisms for balancing iron within safe limits. In mammals there are no controlled mechanisms for the excretion of excess iron, hence body iron homeostasis is regulated at the sites of absorption, utilisation and recycling. This review will discuss the discoveries that have been made in the past 20 years into advancing our understanding of iron homeostasis and its regulation. The study of iron-associated disorders, such as the iron overload condition hereditary haemochromatosis and various forms of anaemia have been instrumental in increasing our knowledge in this area, as have cellular and animal model studies. The liver has emerged as the major site of systemic iron regulation, being the location where the iron regulatory hormone hepcidin is produced. Hepcidin is a negative regulator of iron absorption and recycling, achieving this by binding to the only known cellular iron exporter ferroportin and causing its internalisation and degradation, thereby reducing iron efflux from target cells and reducing serum iron levels. Much of the research in the iron metabolism field has focussed on the regulation of hepcidin and its interaction with ferroportin. The advances in this area have greatly increased our knowledge of iron metabolism and its regulation and have led to the development of novel diagnostics and therapeutics for iron-associated disorders.


    Directory of Open Access Journals (Sweden)

    Natalia, Gajst


    Full Text Available The French regulation school sets out to carry out an analysis of Capitalism and its transformations, with the purpose of understanding the periods of stable growth and the moments of structural change. The object of this paper consists of carrying out a critical revision of the contributions of this school, concentrating on the conceptual framework that it has developed. For this, in the first place the influences that marked the regulation approach will be reviewed, with special attention on its recovery from the Marxist tradition. Secondly, the ontological and methodological differences between the regulation approach and the neoclassic economy theory will be highlighted. Thirdly, the fundamental concepts of the regulation school will be examined. In fourth place, it will be seen how, from these concepts, the crisis at the beginning of the 1970s was interpreted. In fifth place, how the regulation approach is thought as to the relation between economy and policy. In sixth place, the question of the international dimension will be examined. Finally, the main objections that have been presented to the regulation approach, will be shown and will be evaluated critically.

  1. Histamine and the regulation of body weight

    DEFF Research Database (Denmark)

    Jørgensen, Emilie A; Knigge, Ulrich; Warberg, Jørgen


    Energy intake and expenditure is regulated by a complex interplay between peripheral and central factors. An exhaustive list of peptides and neurotransmitters taking part in this complex regulation of body weight exists. Among these is histamine, which acts as a central neurotransmitter. In the p......Energy intake and expenditure is regulated by a complex interplay between peripheral and central factors. An exhaustive list of peptides and neurotransmitters taking part in this complex regulation of body weight exists. Among these is histamine, which acts as a central neurotransmitter....... In the present article we review current evidence pointing at an important role of histamine in the regulation of appetite and metabolism. Studies using both knockout mouse models as well as pharmacological studies have revealed that histamine acts as an anorexigenic agent via stimulation of histamine H(1......) receptors. One effect of histamine in the regulation of appetite is to act as a mediator of the inhibitory effect of leptin on appetite. It seems that histamine may attenuate and delay the development of leptin resistance in high-fat-diet-induced obesity. Furthermore, histamine may also act to accelerate...

  2. World experience of state regulation of entrepreneurship

    Directory of Open Access Journals (Sweden)

    Bila Iryna S.


    Full Text Available The article analyses tendencies of state regulation of entrepreneurship in EU countries, USA and Japan and identifies state regulation of entrepreneurship as a system, which consists of certain elements, unity and interaction of which determine its efficiency and functionality. Analysis, systematisation and generalisation of experience of state regulation of entrepreneurship in these countries allow making a conclusion that the existing differences in the role of the state in economy are not connected with the degree of state regulation, but are connected with the means used for its realisation. General tendencies of development of relations between the state and entrepreneurial sector allowed identification of main elements of the system of state regulation of entrepreneurship, which include: forecasting, planning and programming socio-economic development; anti-monopoly competitive policy; tax and investment policy; innovation policy and stimulation of R and D (Research and Development. The prospect of further studies is identification of specific features of the system of state regulation of entrepreneurship in the modern Ukrainian economy.

  3. Implicit emotion regulation affects outcome evaluation. (United States)

    Yang, Qiwei; Tang, Ping; Gu, Ruolei; Luo, Wenbo; Luo, Yue-jia


    Efficient implicit emotion regulation processes, which run without awareness, are important for human well-being. In this study, to investigate the influence of implicit emotion regulation on psychological and electrophysiological responses to gains and losses, participants were required to select between two Chinese four-character idioms to match the meaning of the third one before they performed a monetary gambling task. According to whether their meanings were related to emotion regulation, the idioms fell into two categories. Event-related potentials and self-rating emotional experiences to outcome feedback were recorded during the task. Priming emotion regulation reduced subjective emotional experience to both gains and losses and the amplitudes of the feedback-related negativity, while the P3 component was not influenced. According to these results, we suggest that the application of implicit emotion regulation effectively modulated the subjective emotional experience and the motivational salience of current outcomes without the cost of cognitive resources. This study implicates the potential significance of implicit emotion regulation in decision-making processes.

  4. Identifying differentially regulated subnetworks from phosphoproteomic data

    Directory of Open Access Journals (Sweden)

    Tebbe Andreas


    Full Text Available Abstract Background Various high throughput methods are available for detecting regulations at the level of transcription, translation or posttranslation (e.g. phosphorylation. Integrating these data with protein networks should make it possible to identify subnetworks that are significantly regulated. Furthermore, such integration can support identification of regulated entities from often noisy high throughput data. In particular, processing mass spectrometry-based phosphoproteomic data in this manner may expose signal transduction pathways and, in the case of experiments with drug-treated cells, reveal the drug's mode of action. Results Here, we introduce SubExtractor, an algorithm that combines phosphoproteomic data with protein network information from STRING to identify differentially regulated subnetworks and individual proteins. The method is based on a Bayesian probabilistic model combined with a genetic algorithm and rigorous significance testing. The Bayesian model accounts for information about both differential regulation and network topology. The method was tested with artificial data and subsequently applied to a comprehensive phosphoproteomics study investigating the mode of action of sorafenib, a small molecule kinase inhibitor. Conclusions SubExtractor reliably identifies differentially regulated subnetworks from phosphoproteomic data by integrating protein networks. The method can also be applied to gene or protein expression data.

  5. Fascin regulates nuclear actin during Drosophila oogenesis. (United States)

    Kelpsch, Daniel J; Groen, Christopher M; Fagan, Tiffany N; Sudhir, Sweta; Tootle, Tina L


    Drosophila oogenesis provides a developmental system with which to study nuclear actin. During Stages 5-9, nuclear actin levels are high in the oocyte and exhibit variation within the nurse cells. Cofilin and Profilin, which regulate the nuclear import and export of actin, also localize to the nuclei. Expression of GFP-tagged Actin results in nuclear actin rod formation. These findings indicate that nuclear actin must be tightly regulated during oogenesis. One factor mediating this regulation is Fascin. Overexpression of Fascin enhances nuclear GFP-Actin rod formation, and Fascin colocalizes with the rods. Loss of Fascin reduces, whereas overexpression of Fascin increases, the frequency of nurse cells with high levels of nuclear actin, but neither alters the overall nuclear level of actin within the ovary. These data suggest that Fascin regulates the ability of specific cells to accumulate nuclear actin. Evidence indicates that Fascin positively regulates nuclear actin through Cofilin. Loss of Fascin results in decreased nuclear Cofilin. In addition, Fascin and Cofilin genetically interact, as double heterozygotes exhibit a reduction in the number of nurse cells with high nuclear actin levels. These findings are likely applicable beyond Drosophila follicle development, as the localization and functions of Fascin and the mechanisms regulating nuclear actin are widely conserved.

  6. [Regulation of antibiotic biosynthesis in Streptomycetes]. (United States)

    Matseliukh, B P


    The review of literature presents the modern data about cascade regulation of antibiotic biosynthesis in Streptomycetes including basal and global levels. The first regulatory level is presented by related proteins of SARP family playing the role of positive transcription factors of pathway-specific genes of clusters of antibiotic biosynthesis. In their turn these regulatory genes are under the control of higher regulatory level represented by bldA- and A-factor-dependent cascade regulation and two-component signal transduction system (AfsK-AfsR, AbsAl-AbsA2, AfsQ1-AfsQ2 and others), consisting of sensor protein kinase and response regulator protein.Streptomycetes, in contrast to other microorganisms, have dozens of protein kinases and related regulator proteins that testifies to the great importance of protein phosphorylation in regulation of secondary metabolism and morphogenesis in cell response to internal and external signals. The role of camp, ppGpp and other proteins in regulation of antibiotic biosynthesis was also considered in this review.

  7. Sequence Classification: 893787 [

    Lifescience Database Archive (English)

    Full Text Available ociation with SAGA and for H2B deubiquitylation; Sgf11p || ... of SAGA histone acetyltransferase complex, regulates transcription of a subset of SAGA-regulated genes, required for the Ubp8p ass

  8. 34 CFR 661.3 - What regulations apply? (United States)


    ..., DEPARTMENT OF EDUCATION BUSINESS AND INTERNATIONAL EDUCATION PROGRAM General § 661.3 What regulations apply? The following regulations apply to this program: (a) The regulations in 34 CFR part 655. (b)...

  9. Factors that regulate embryonic gustatory development

    Directory of Open Access Journals (Sweden)

    Krimm Robin F


    Full Text Available Abstract Numerous molecular factors orchestrate the development of the peripheral taste system. The unique anatomy/function of the taste system makes this system ideal for understanding the mechanisms by which these factors function; yet the taste system is underutilized for this role. This review focuses on some of the many factors that are known to regulate gustatory development, and discusses a few topics where more work is needed. Some attention is given to factors that regulate epibranchial placode formation, since gustatory neurons are thought to be primarily derived from this region. Epibranchial placodes appear to arise from a pan-placodal region and a number of regulatory factors control the differentiation of individual placodes. Gustatory neuron differentiation is regulated by a series of transcription factors and perhaps bone morphongenic proteins (BMP. As neurons differentiate, they also proliferate such that their numbers exceed those in the adult, and this is followed by developmental death. Some of these cell-cycling events are regulated by neurotrophins. After gustatory neurons become post-mitotic, axon outgrowth occurs. Axons are guided by multiple chemoattractive and chemorepulsive factors, including semaphorins, to the tongue epithelium. Brain derived neurotrophic factor (BDNF, functions as a targeting factor in the final stages of axon guidance and is required for gustatory axons to find and innervate taste epithelium. Numerous factors are involved in the development of gustatory papillae including Sox-2, Sonic hedge hog and Wnt-β-catenin signaling. It is likely that just as many factors regulate taste bud differentiation; however, these factors have not yet been identified. Studies examining the molecular factors that regulate terminal field formation in the nucleus of the solitary tract are also lacking. However, it is possible that some of the factors that regulate geniculate ganglion development, outgrowth, guidance and

  10. Pathway-specific regulation revisited: cross-regulation of multiple disparate gene clusters by PAS-LuxR transcriptional regulators. (United States)

    Vicente, Cláudia M; Payero, Tamara D; Santos-Aberturas, Javier; Barreales, Eva G; de Pedro, Antonio; Aparicio, Jesús F


    PAS-LuxR regulators are highly conserved proteins devoted to the control of antifungal production by binding to operators located in given promoters of polyene biosynthetic genes. The canonical operator of PimM, archetype of this class of regulators, has been used here to search for putative targets of orthologous protein PteF in the genome of Streptomyces avermitilis, finding 97 putative operators outside the pentaene filipin gene cluster (pte). The processes putatively affected included genetic information processing; energy, carbohydrate, and lipid metabolism; DNA replication and repair; morphological differentiation; secondary metabolite biosynthesis; and transcriptional regulation, among others. Seventeen of these operators were selected, and their binding to PimM DNA-binding domain was assessed by electrophoretic mobility shift assays. Strikingly, the protein bound all predicted operators suggesting a direct control over targeted processes. As a proof of concept, we studied the biosynthesis of the ATP-synthase inhibitor oligomycin whose gene cluster included two operators. Regulator mutants showed a severe loss of oligomycin production, whereas gene complementation of the mutant restored phenotype, and gene duplication in the wild-type strain boosted oligomycin production. Comparative gene expression analyses in parental and mutant strains by reverse transcription-quantitative polymerase chain reaction of selected olm genes corroborated production results. These results demonstrate that PteF is able to cross-regulate the biosynthesis of two related secondary metabolites, filipin and oligomycin, but might be extended to all the processes indicated above. This study highlights the complexity of the network of interactions in which PAS-LuxR regulators are involved and opens new possibilities for the manipulation of metabolite production in Streptomycetes.

  11. Adipostatic regulation of motivation and emotion. (United States)

    Davis, Jon F


    The proper maintenance of body weight and mood are two of the most prevalent health issues present in society today. Obese humans display higher levels of mood-related disorders and the causality of such an association is unknown. A common feature of obesity is the imbalance of regulatory hormones which normally act to maintain stable energy balance and body weight. The adiposity hormone leptin is one such signal elevated in obesity with the capacity to dampen feeding behavior through action on brain circuits which regulate appetite and metabolism. Recent evidence suggests that leptin may regulate motivation through its actions within brain reward circuitry. In addition, leptin signaling within central nervous system regions that regulate cognition and emotion elicits anti-depressant like effects. Together, these data indicate that leptin may regulate the decreased motivation and mood present in obesity and depression. This review describes the capacity of leptin to regulate motivation and depression through actions within brain circuits that modulate effort-based behavior and emotion, respectively.

  12. Offshore regulators focus on incentives for safety

    Energy Technology Data Exchange (ETDEWEB)

    Reid, W.


    Strict safety regulations in effect at offshore drilling sites are discussed. The guiding principle in all existing regulation is that while economic or industrial considerations are important, the value and the concern for human life is paramount. Should some tragic event occur at an offshore drilling site that is shown to have been caused by negligence of an operator, there is no question at all that the regulatory authority, in this case the Canada-Newfoundland Offshore Petroleum Board (CNOPB), would take the negligent operator to court. Nevertheless, Canadian authorities remain confident that encouragement of maintaining a safe working environment is likely to be more successful in ensuring workplace safety than threats of punishment. Indeed, Canadian regulators have, in recent times, shown a tendency to move towards performance-based systems, as opposed to the more usual prescriptive or rule-bound regulatory regime. This new approach involves setting targets and giving companies the responsibility to implement measures to reach the targets rather than relying on government instructions. Still, performance-based regulation in Canada is relatively new and some regulations remain prescriptive. Examples are the requirement for two immersion suits and two lifeboat seats for every worker on a drilling unit.

  13. p53 regulates the cardiac transcriptome (United States)

    Mak, Tak W.; Hauck, Ludger; Grothe, Daniela; Billia, Filio


    The tumor suppressor Trp53 (p53) inhibits cell growth after acute stress by regulating gene transcription. The mammalian genome contains hundreds of p53-binding sites. However, whether p53 participates in the regulation of cardiac tissue homeostasis under normal conditions is not known. To examine the physiologic role of p53 in adult cardiomyocytes in vivo, Cre-loxP–mediated conditional gene targeting in adult mice was used. Genome-wide transcriptome analyses of conditional heart-specific p53 knockout mice were performed. Genome-wide annotation and pathway analyses of >5,000 differentially expressed transcripts identified many p53-regulated gene clusters. Correlative analyses identified >20 gene sets containing more than 1,000 genes relevant to cardiac architecture and function. These transcriptomic changes orchestrate cardiac architecture, excitation-contraction coupling, mitochondrial biogenesis, and oxidative phosphorylation capacity. Interestingly, the gene expression signature in p53-deficient hearts confers resistance to acute biomechanical stress. The data presented here demonstrate a role for p53, a previously unrecognized master regulator of the cardiac transcriptome. The complex contributions of p53 define a biological paradigm for the p53 regulator network in the heart under physiological conditions. PMID:28193895

  14. Epigenetic regulation of cystatins in cancer. (United States)

    Rivenbark, Ashley G; Coleman, William B


    Cystatins function as cysteine protease inhibitors, are expressed in numerous cell types, and regulate a number of physiological processes. Four cystatins have been extensively studied: cystatin A, cystatin B, cystatin C, and cystatin M. Aberrant regulation of cystatins occurs in a number of diseases, including cancer and certain neurodegenerative disorders. Recent advances in the understanding of cystatin function suggest that these proteins may regulate promotion or suppression of tumor growth, invasion, and metastasis. Cancer is a disease of abnormal gene expression and cancer cells exhibit aberrant epigenetic events (such as DNA methylation), leading to gene silencing. Cystatins are epigenetically silenced through DNA methylation-dependent mechanisms in several forms of cancer, including breast, pancreatic, brain, and lung. These findings suggest that DNA methylation-dependent epigenetic mechanisms may play an important role in the loss of cystatin gene expression and protein function during neoplastic transformation and/or tumor progression. This review summarizes the biological processes in which cystatins function, focuses on the neoplastic events that involve aberrant regulation of cystatins, and discusses the possible epigenetic regulation of cystatins in cancer.

  15. Tau regulates the subcellular localization of calmodulin

    Energy Technology Data Exchange (ETDEWEB)

    Barreda, Elena Gomez de [Centro de Biologia Molecular ' Severo Ochoa' , CSIC/UAM, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Avila, Jesus, E-mail: [Centro de Biologia Molecular ' Severo Ochoa' , CSIC/UAM, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); CIBER de Enfermedades Neurodegenerativas, 28031 Madrid (Spain)


    Highlights: {yields} In this work we have tried to explain how a cytoplasmic protein could regulate a cell nuclear function. We have tested the role of a cytoplasmic protein (tau) in regulating the expression of calbindin gene. We found that calmodulin, a tau-binding protein with nuclear and cytoplasmic localization, increases its nuclear localization in the absence of tau. Since nuclear calmodulin regulates calbindin expression, a decrease in nuclear calmodulin, due to the presence of tau that retains it at the cytoplasm, results in a change in calbindin expression. -- Abstract: Lack of tau expression in neuronal cells results in a change in the expression of few genes. However, little is known about how tau regulates gene expression. Here we show that the presence of tau could alter the subcellular localization of calmodulin, a protein that could be located at the cytoplasm or in the nucleus. Nuclear calmodulin binds to co-transcription factors, regulating the expression of genes like calbindin. In this work, we have found that in neurons containing tau, a higher proportion of calmodulin is present in the cytoplasm compared with neurons lacking tau and that an increase in cytoplasmic calmodulin correlates with a higher expression of calbindin.

  16. Depolarization-mediated regulation of alternative splicing

    Directory of Open Access Journals (Sweden)

    Alok eSharma


    Full Text Available Alternative splicing in eukaryotes plays an important role in regulating gene expression by selectively including alternative exons. A wealth of information has been accumulated that explains how alternative exons are selected in a developmental stage- or tissue-specific fashion. However, our knowledge of how cells respond to environmental changes to alter alternative splicing is very limited. For example, although a number of alternative exons have been shown to be regulated by calcium level alterations, the underlying mechanisms are not well understood. As calcium signaling in neurons plays a crucial role in essential neuronal functions such as learning and memory formation, it is important to understand how this process is regulated at every level in gene expression. The significance of the dynamic control of alternative splicing in response to changes of calcium levels has been largely unappreciated. In this communication, we will summarize the recent advances in calcium signaling-mediated alternative splicing that have provided some insights into the important regulatory mechanisms. In addition to describing the cis-acting RNA elements on the pre-mRNA molecules that respond to changes of intracellular calcium levels, we will summarize how splicing regulators change and affect alternative splicing in this process. We will also discuss a novel mode of calcium-mediated splicing regulation at the level of chromatin structure and transcription.

  17. Banking Regulation Of Western Balkan Countries

    Directory of Open Access Journals (Sweden)

    Denada Hafizi


    Full Text Available The current global economic crisis has affected the development of banking system in Western Balkan Countries, including Italy and Greece. These effects are expressed with the contraction of lending, fallen of foreign direct investments, fallen of the volume of remittances and fallen of international trade. The banking system continually faces new challenges in a dynamically changing financial system, and this makes difficult theimplementation of bank regulation and supervision.All the countries have improved their banking regulation in order to avoid the contagion effect among banks and banking system in general, effects that get increased especially when banks are engaged in international banking. The standardization of regulatory requirements provides potential solution to the problems of regulating international banking. So, there is a moving through agreements like Basel Accords.For all these countries will be a comparison of regulatory capital to risk-weighted assets ratio and of capital to assets ratio in order to find out how well is capitalized their bankingsystem. The sources of data are the reports of International Monetary Fund for a time series of 2008-2013. In the end there are some conclusions for the main problems that theimplementation of supervision and bank regulation faces.Keywords: Basel Accords, Capital Ratio, Banking Regulation

  18. Hypothalamic neuropeptides and the regulation of appetite. (United States)

    Parker, Jennifer A; Bloom, Stephen R


    Neuropeptides released by hypothalamic neurons play a major role in the regulation of feeding, acting both within the hypothalamus, and at other appetite regulating centres throughout the brain. Where classical neurotransmitters signal only within synapses, neuropeptides diffuse over greater distances affecting both nearby and distant neurons expressing the relevant receptors, which are often extrasynaptic. As well as triggering a behavioural output, neuropeptides also act as neuromodulators: altering the response of neurons to both neurotransmitters and circulating signals of nutrient status. The mechanisms of action of hypothalamic neuropeptides with established roles in feeding, including melanin-concentrating hormone (MCH), the orexins, α-melanocyte stimulating hormone (α-MSH), agouti-gene related protein (AgRP), neuropeptide Y, and oxytocin, are reviewed in this article, with emphasis laid on both their effects on appetite regulating centres throughout the brain, and on examining the evidence for their physiological roles. In addition, evidence for the involvement of several putative appetite regulating hypothalamic neuropeptides is assessed including, ghrelin, cocaine and amphetamine-regulated transcript (CART), neuropeptide W and the galanin-like peptides. This article is part of a Special Issue entitled 'Central control of Food Intake'.

  19. Gasotransmitters: novel regulators of epithelial na(+) transport? (United States)

    Althaus, Mike


    The vectorial transport of Na(+) across epithelia is crucial for the maintenance of Na(+) and water homeostasis in organs such as the kidneys, lung, or intestine. Dysregulated Na(+) transport processes are associated with various human diseases such as hypertension, the salt-wasting syndrome pseudohypoaldosteronism type 1, pulmonary edema, cystic fibrosis, or intestinal disorders, which indicate that a precise regulation of epithelial Na(+) transport is essential. Novel regulatory signaling molecules are gasotransmitters. There are currently three known gasotransmitters: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H(2)S). These molecules are endogenously produced in mammalian cells by specific enzymes and have been shown to regulate various physiological processes. There is a growing body of evidence which indicates that gasotransmitters may also regulate Na(+) transport across epithelia. This review will summarize the available data concerning NO, CO, and H(2)S dependent regulation of epithelial Na(+) transport processes and will discuss whether or not these mediators can be considered as true physiological regulators of epithelial Na(+) transport biology.

  20. Gasotransmitters: Novel regulators of epithelial Na+ transport?

    Directory of Open Access Journals (Sweden)

    Mike eAlthaus


    Full Text Available The vectorial transport of Na+ across epithelia is crucial for the maintenance of Na+ and water homeostasis in organs such as the kidneys, lung or intestine. Dysregulated Na+ transport processes are associated with various human diseases such as hypertension, the salt-wasting syndrome pseudohypoaldosteronism type 1, pulmonary edema, cystic fibrosis or intestinal disorders, which indicate that a precise regulation of epithelial Na+ transport is essential. Novel regulatory signaling molecules are gasotransmitters. There are currently three known gasotransmitters: nitric oxide (NO, carbon monoxide (CO and hydrogen sulfide (H2S. These molecules are endogenously produced in mammalian cells by specific enzymes and have been shown to regulate various physiological processes. There is a growing body of evidence, which indicates that gasotransmitters may also regulate Na+ transport across epithelia. This review will summarize the available data concerning NO, CO and H2S dependent regulation of epithelial Na+ transport processes and will discuss whether or not these mediators can be considered as true physiological regulators of epithelial Na+ transport biology.

  1. Glial Cell Regulation of Rhythmic Behavior (United States)

    Jackson, F. Rob; Ng, Fanny S.; Sengupta, Sukanya; You, Samantha; Huang, Yanmei


    Brain glial cells, in particular astrocytes and microglia, secrete signaling molecules that regulate glia–glia or glia–neuron communication and synaptic activity. While much is known about roles of glial cells in nervous system development, we are only beginning to understand the physiological functions of such cells in the adult brain. Studies in vertebrate and invertebrate models, in particular mice and Drosophila, have revealed roles of glia–neuron communication in the modulation of complex behavior. This chapter emphasizes recent evidence from studies of rodents and Drosophila that highlight the importance of glial cells and similarities or differences in the neural circuits regulating circadian rhythms and sleep in the two models. The chapter discusses cellular, molecular, and genetic approaches that have been useful in these models for understanding how glia–neuron communication contributes to the regulation of rhythmic behavior. PMID:25707272

  2. Iodine chemistry in a reactor regulation

    Energy Technology Data Exchange (ETDEWEB)

    Powers, D.A. [Nuclear Regulatory Commission, Washington, DC (United States). Advisory Committee on Reactor Safeguards


    Radioactive iodine has always been an important consideration in the regulation of nuclear power reactors to assure the health and safety of the public. Regulators adopted conservatively bounding predictions of iodine behavior in the earliest days of the development of nuclear power because there was so little known about either accidents or the chemistry of iodine. Today there is a flood of new information and understanding of the chemistry of iodine under reactor accident conditions. This paper offers some thoughts on how the community of scientists engaged in the study of iodine chemistry can present the results of their work so that it is more immediately adopted by the regulator. It is suggested that the scientific community consider the concept of consensus standards so effectively used within the engineering community to define the status of the study of radioactive iodine chemistry for reactor safety. (author) 9 refs.

  3. Biophysical regulation of stem cell differentiation. (United States)

    Govey, Peter M; Loiselle, Alayna E; Donahue, Henry J


    Bone adaptation to its mechanical environment, from embryonic through adult life, is thought to be the product of increased osteoblastic differentiation from mesenchymal stem cells. In parallel with tissue-scale loading, these heterogeneous populations of multipotent stem cells are subject to a variety of biophysical cues within their native microenvironments. Bone marrow-derived mesenchymal stem cells-the most broadly studied source of osteoblastic progenitors-undergo osteoblastic differentiation in vitro in response to biophysical signals, including hydrostatic pressure, fluid flow and accompanying shear stress, substrate strain and stiffness, substrate topography, and electromagnetic fields. Furthermore, stem cells may be subject to indirect regulation by mechano-sensing osteocytes positioned to more readily detect these same loading-induced signals within the bone matrix. Such paracrine and juxtacrine regulation of differentiation by osteocytes occurs in vitro. Further studies are needed to confirm both direct and indirect mechanisms of biophysical regulation within the in vivo stem cell niche.

  4. Matrix Metalloproteinases as Regulators of Periodontal Inflammation (United States)

    Franco, Cavalla; Patricia, Hernández-Ríos; Timo, Sorsa; Claudia, Biguetti; Marcela, Hernández


    Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the ‘protease web’ is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules—such as cytokines, chemokines, and growth factors, among others—regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation. PMID:28218665

  5. The iron-regulated staphylococcal lipoproteins

    Directory of Open Access Journals (Sweden)

    Jessica eSheldon


    Full Text Available Lipoproteins fulfill diverse roles in antibiotic resistance, adhesion, protein secretion, signaling and sensing, and many also serve as the substrate binding protein (SBP partner to ABC transporters for the acquisition of a diverse array of nutrients including peptides, sugars, and scarcely abundant metals. In the staphylococci, the iron-regulated SBPs are significantly upregulated during iron starvation and function to sequester and deliver iron into the bacterial cell, enabling staphylococci to circumvent iron restriction imposed by the host environment. Accordingly, this subset of lipoproteins has been implicated in staphylococcal pathogenesis and virulence. Lipoproteins also activate the host innate immune response, triggered through Toll-like receptor-2 (TLR2 and, notably, the iron-regulated subset of lipoproteins are particularly immunogenic. In this review, we discuss the iron-regulated staphylococcal lipoproteins with regard to their biogenesis, substrate specificity, and impact on the host innate immune response.

  6. Hormonal Regulation of Leaf Morphogenesis in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Lin-Chuan Li; Ding-Ming Kang; Zhang-Liang Chen; Li-Jia Qu


    Leaf morphogenesis is strictly controlled not only by intrinsic genetic factors, such as transcriptional factors, but also by environmental cues, such as light, water and pathogens. Nevertheless, the molecular mechanism of how leaf rnorphogenesis is regulated by genetic programs and environmental cues is far from clear. Numerous series of events demonstrate that plant hormones, mostly small and simple molecules,play crucial roles in plant growth and development, and in responses of plants to environmental cues such as light. With more and more genetics and molecular evidence obtained from the model plant Arabidopsis,several fundamental aspects of leaf rnorphogenesis including the initiation of leaf primordia, the determination of leaf axes, the regulation of cell division and expansion in leaves have been gradually unveiled.Among these phytohormones, auxin is found to be essential in the regulation of leaf morphogenesis.

  7. Plant nutrient transporter regulation in arbuscular mycorrhizas

    DEFF Research Database (Denmark)

    Burleigh, Stephen; Bechmann, I.E.


    This review discusses the role arbuscular mycorrhizal fungi play in the regulation of plant nutrient transporter genes. Many plant nutrient transporter genes appear to be transcriptionally regulated by a feed-back mechanism that reduces their expression when the plant reaches an optimal level...... of the high-affinity Pi-transporter MtPT2 within mycorrhizal roots of Medicago truncatula was inversely correlated with the concentration of P within the shoots, which suggested that P supply from the fungus influenced this gene's expression. However, there is some evidence that these plant nutrient...... transporters are also down-regulated within mycorrhizal roots by a mechanism not involving nutrient supply by the fungus. Carbon demand by the fungus may be one factor that can influence their expression within mycorrhizal roots....

  8. Free [NADH]/[NAD(+)] regulates sirtuin expression. (United States)

    Gambini, Juan; Gomez-Cabrera, Mari Carmen; Borras, Consuelo; Valles, Soraya L; Lopez-Grueso, Raul; Martinez-Bello, Vladimir E; Herranz, Daniel; Pallardo, Federico V; Tresguerres, Jesus A F; Serrano, Manuel; Viña, Jose


    Sirtuins are deacetylases involved in metabolic regulation and longevity. Our aim was to test the hypothesis that they are subjected to redox regulation by the [NADH]/[NAD(+)] ratio. We used NIH3T3 fibroblasts in culture, Drosophila fed with or without ethanol and exercising rats. In all three models an increase in [NADH]/[NAD(+)] came up with an increased expression of sirtuin mRNA and protein. PGC-1α (a substrate of sirtuins) protein level was significantly increased in fibroblasts incubated with lactate and pyruvate but this effect was lost in fibroblasts obtained from sirtuin-deficient mice. We conclude that the expression of sirtuins is subject to tight redox regulation by the [NADH]/[NAD(+)] ratio, which is a major sensor for metabolite availability conserved from invertebrates to vertebrates.

  9. Risk-based regulation: Challenges and opportunities

    Energy Technology Data Exchange (ETDEWEB)

    Bari, R.A.


    Over the last twenty years, man has witnessed a gradual but steady movement toward increased usage of risk-based methods and results in the regulatory process. The ``risk perspective`` as a supportive view to existing (non-risk-based or deterministic) information used in decision making has a firm foothold now in most countries that regulate nuclear power. Furthermore, in the areas outside the nuclear power field, such as health risk assessment, risk-based information is used increasingly to make decisions on potential impacts of chemical, biological, and radiological exposures. Some of the principal concepts and issues that are pertinent to risk-based regulation are reviewed. There is a growing interest in most countries in the use of risk-based methods and results to facilitate decision-making associated with regulatory processes. A summary is presented of the challenges and opportunities related to expanded use of risk-based regulation.

  10. Physiology of temperature regulation: comparative aspects. (United States)

    Bicego, Kênia C; Barros, Renata C H; Branco, Luiz G S


    Few environmental factors have a larger influence on animal energetics than temperature, a fact that makes thermoregulation a very important process for survival. In general, endothermic species, i.e., mammals and birds, maintain a constant body temperature (Tb) in fluctuating environmental temperatures using autonomic and behavioural mechanisms. Most of the knowledge on thermoregulatory physiology has emerged from studies using mammalian species, particularly rats. However, studies with all vertebrate groups are essential for a more complete understanding of the mechanisms involved in the regulation of Tb. Ectothermic vertebrates-fish, amphibians and reptiles-thermoregulate essentially by behavioural mechanisms. With few exceptions, both endotherms and ectotherms develop fever (a regulated increase in Tb) in response to exogenous pyrogens, and regulated hypothermia (anapyrexia) in response to hypoxia. This review focuses on the mechanisms, particularly neuromediators and regions in the central nervous system, involved in thermoregulation in vertebrates, in conditions of euthermia, fever and anapyrexia.

  11. Regulation of Power Conversion in Fuel Cells

    Institute of Scientific and Technical Information of China (English)

    SHEN Mu-zhong; ZHANG J.; K. Scott


    Here we report a regulation about power conversion in fuel cells. This regulation is expressed as that total power produced by fuel cells is always proportional to the square of the potential difference between the equilibrium potential and work potential. With this regulation we deduced fuel cell performance equation which can describe the potential vs. the current performance curves, namely, polarization curves of fuel cells with three power source parameters: equilibrium potential E0; internal resistance R; and power conversion coefficient K. The concept of the power conversion coefficient is a new criterion to evaluate and compare the characteristics and capacity of different fuel cells. The calculated values obtained with this equation agree with practical performance of different types of fuel cells.

  12. Implementation in International Business Self-Regulation

    DEFF Research Database (Denmark)

    Porter, Tony; Ronit, Karsten


    Self-regulation by business is increasingly common internationally, but the effective implementation of international rules often continues to be seen as something that only states can carry out. We argue that more exclusively private forms of effective implementation can be constructed in self......-regulation. Drawing on research in private international law, public policy implementation and self-regulation, we identify four distinct implementation sequences: monitoring, compliance, adjudication, and sanctioning. These sequences are sometimes constituted in response to deliberate integrated plans, but also come...... together in a decentralized manner. Many international business actors devise ways to carry out the sequences in order to implement rules that are important for them, reflecting a functional logic of implementation that is creative and pragmatic, and together constitute an important stage in the policy...

  13. Regulation of noise in gene expression. (United States)

    Sanchez, Alvaro; Choubey, Sandeep; Kondev, Jane


    The biochemical processes leading to the synthesis of new proteins are random, as they typically involve a small number of diffusing molecules. They lead to fluctuations in the number of proteins in a single cell as a function of time and to cell-to-cell variability of protein abundances. These in turn can lead to phenotypic heterogeneity in a population of genetically identical cells. Phenotypic heterogeneity may have important consequences for the development of multicellular organisms and the fitness of bacterial colonies, raising the question of how it is regulated. Here we review the experimental evidence that transcriptional regulation affects noise in gene expression, and discuss how the noise strength is encoded in the architecture of the promoter region. We discuss how models based on specific molecular mechanisms of gene regulation can make experimentally testable predictions for how changes to the promoter architecture are reflected in gene expression noise.

  14. Chromatin Regulators in Pancreas Development and Diabetes. (United States)

    Campbell, Stephanie A; Hoffman, Brad G


    The chromatin landscape of a cell is dynamic and can be altered by chromatin regulators that control nucleosome placement and DNA or histone modifications. Together with transcription factors, these complexes help dictate the transcriptional output of a cell and, thus, balance cell proliferation and differentiation while restricting tissue-specific gene expression. In this review, we describe current research on chromatin regulators and their roles in pancreas development and the maintenance of mature β cell function, which, once elucidated, will help us better understand how β cell differentiation occurs and is maintained. These studies have so far implicated proteins from several complexes that regulate DNA methylation, nucleosome remodeling, and histone acetylation and methylation that could become promising targets for diabetes therapy and stem cell differentiation.

  15. Plasma membrane regulates Ras signaling networks. (United States)

    Chavan, Tanmay Sanjeev; Muratcioglu, Serena; Marszalek, Richard; Jang, Hyunbum; Keskin, Ozlem; Gursoy, Attila; Nussinov, Ruth; Gaponenko, Vadim


    Ras GTPases activate more than 20 signaling pathways, regulating such essential cellular functions as proliferation, survival, and migration. How Ras proteins control their signaling diversity is still a mystery. Several pieces of evidence suggest that the plasma membrane plays a critical role. Among these are: (1) selective recruitment of Ras and its effectors to particular localities allowing access to Ras regulators and effectors; (2) specific membrane-induced conformational changes promoting Ras functional diversity; and (3) oligomerization of membrane-anchored Ras to recruit and activate Raf. Taken together, the membrane does not only attract and retain Ras but also is a key regulator of Ras signaling. This can already be gleaned from the large variability in the sequences of Ras membrane targeting domains, suggesting that localization, environment and orientation are important factors in optimizing the function of Ras isoforms.

  16. Reliable regulation in decentralised control systems (United States)

    Locatelli, Arturo; Schiavoni, Nicola


    This article addresses the design of decentralised regulators which supply the control systems with signal tracking and disturbance rejection. This property has to be attained, to the maximum possible extent, even when instrumentation faults occur, thus causing the opening of some feedback loops. The problem is tackled for LTI asymptotically stable plants, subject to perturbations, under the assumption that the Laplace transforms of the exogenous signals have multiple poles on the imaginary axis. The proposed regulator is composed of an LTI nominal controller supervised by a reconfiguration block. Once the actions of the reconfiguration block have been settled, the synthesis of the nominal controller is reformulated as a suitable regulation problem. A constructive sufficient condition for its solvability is established. This condition turns out to be also necessary if the exogenous signals are polynomial in time.

  17. Regulating reprogenetics: strategic sacralisation and semantic massage. (United States)

    Mackenzie, Robin


    This paper forms part of the feminist critique of the regulatory consequences of biomedicine's systematic exclusion of the role of women's bodies in the development of reprogenetic technologies. I suggest that strategic use of notions of the sacred to decontextualise and delimit disagreement fosters this marginalisation. Here conceptions of the sacred and sacralisation afford a means by which pragmatic consensus over regulation may be achieved, through the deployment of a bricolage of dense images associated with cultural loyalties to solidify support or exclude contradictory elements. Hence an explicit renegotiation of the symbolic order structuring salient debates is necessary to disrupt and enrich the entrenched and exclusionary dominant discourse over reprogenetic regulation. I draw upon previous analyses of strategic rhetoric associated with the regulation of infertility treatment and embryo research in the United Kingdom, the cultural anthropology of biomedicine and feminist ethnographies of reprogenetics to illustrate these claims.

  18. Cartilage stem cells: regulation of differentiation. (United States)

    Solursh, M


    The developing limb bud is a useful source of cartilage stem cells for studies on the regulation of chondrogenesis. In high density cultures these cells can progress through all stages of chondrogenesis to produce mineralized hypertrophic cartilage. If the cells are maintained in a spherical shape, single stem cells can progress through a similar sequence. The actin cytoskeleton is implicated in the regulation of chondrogenesis since conditions that favor its disruption promote chondrogenesis and conditions that favor actin assembly inhibit chondrogenesis. Since a number of extracellular matrix receptors mediate effects of the extracellular matrix on cytoskeletal organization and some of these receptors are developmentally regulated, it is proposed that matrix receptor expression plays a central role in the divergence of connective tissue cells during development.

  19. Transcriptional Regulation of Plant Secondary Metabolism

    Institute of Scientific and Technical Information of China (English)

    Chang-Qing Yang; Xin Fang; Xiu-Ming Wu; Ying-Bo Mao; Ling-Jian Wang; Xiao-Ya Chen


    Plant secondary metabolites play critical roles in plant-environment interactions.They are synthesized in different organs or tissues at particular developmental stages,and in response to various environmental stimuli,both biotic and abiotic.Accordingly,corresponding genes are regulated at the transcriptional level by multiple transcription factors.Several families of transcription factors have been identified to participate in controlling the biosynthesis and accumulation of secondary metabolites.These regulators integrate internal (often developmental) and external signals,bind to corresponding cis-elements — which are often in the promoter regions — to activate or repress the expression of enzyme-coding genes,and some of them interact with other transcription factors to form a complex.In this review,we summarize recent research in these areas,with an emphasis on newly-identified transcription factors and their functions in metabolism regulation.

  20. Nonredundant requirement for multiple histone modifications for the early anaphase release of the mitotic exit regulator Cdc14 from nucleolar chromatin.

    Directory of Open Access Journals (Sweden)

    William W Hwang


    Full Text Available In Saccharomyces cerevisiae, the conserved phosphatase Cdc14 is required for the exit from mitosis. It is anchored on nucleolar chromatin by the Cfi1/Net1 protein until early anaphase, at which time it is released into the nucleoplasm. Two poorly understood, redundant pathways promote Cdc14 release, the FEAR (Cdc fourteen early release network and the MEN (mitotic exit network. Through the analysis of genetic interactions, we report here a novel requirement for the ubiquitination of histone H2B by the Bre1 ubiquitin ligase in the cell cycle-dependent release of Cdc14 from nucleolar chromatin when the MEN is inactivated. This function for H2B ubiquitination is mediated by its activation of histone H3 methylation on lysines 4 and 79 (meH3K4 and meH3K79 but, surprisingly, is not dependent on the histone deacetylase (HDAC Sir2, which associates with Cdc14 on nucleolar chromatin as part of the RENT complex. We also observed a defect in Cdc14 release in cells lacking H3 lysine 36 methylation (meH3K36 and in cells lacking an HDAC recruited by this modification. These histone modifications represent previously unappreciated factors required for the accessibility to and/or action on nucleolar chromatin of FEAR network components. The nonredundant role for these modifications in this context contrasts with the notion of a highly combinatorial code by which histone marks act to control biological processes.


    Energy Technology Data Exchange (ETDEWEB)



    Environmental regulations can have a significant impact on product use, disposal, and recycling. This report summarizes the basic aspects of current federal, state and international regulations which apply to end-of-life photovoltaic (PV) modules and PV manufacturing scrap destined for disposal or recycling. It also discusses proposed regulations for electronics that may set the ground of what is to be expected in this area in the near future. In the US, several states have started programs to support the recycling of electronic equipment, and materials destined for recycling often are excepted from solid waste regulations during the collection, transfer, storage and processing stages. California regulations are described separately because they are different from those of most other states. International agreements on the movement of waste between different countries may pose barriers to cross-border shipments. Currently waste moves freely among country members of the Organization of Economic Cooperation and Development (OECD), and between the US and the four countries with which the US has bilateral agreements. However, it is expected, that the US will adopt the rules of the Basel Convention (an agreement which currently applies to 128 countries but not the US) and that the Convection's waste classification system will influence the current OECD waste-handling system. Some countries adopting the Basel Convention consider end-of-life electronics to be hazardous waste, whereas the OECD countries consider them to be non-hazardous. Also, waste management regulations potentially affecting electronics in Germany and Japan are mentioned in this report.

  2. Regulators of Slc4 bicarbonate transporter activity

    Directory of Open Access Journals (Sweden)

    Ian M. Thornell


    Full Text Available The Slc4 family of transporters is comprised of anion exchangers (AE1-4, Na-coupled bicarbonate transporters (NCBTs including electrogenic Na/bicarbonate cotransporters (NBCe1 and NBCe2, electroneutral Na/bicarbonate cotransporters (NBCn1 and NBCn2, and the electroneutral Na-driven Cl-bicarbonate exchanger (NDCBE, as well as a borate transporter (BTR1. These transporters regulate intracellular pH (pHi and contribute to steady-state pHi, but are also involved in other physiological processes including CO2 carriage by red blood cells and solute secretion/reabsorption across epithelia. Acid-base transporters function as either acid extruders or acid loaders, with the Slc4 proteins moving HCO3– either into or out of cells. According to results from both molecular and functional studies, multiple Slc4 proteins and/or associated splice variants with similar expected effects on pHi are often found in the same tissue or cell. Such apparent redundancy is likely to be physiologically important. In addition to regulating pHi, a HCO3– transporter contributes to a cell’s ability to fine tune the intracellular regulation of the cotransported/exchanged ion(s (e.g., Na+ or Cl–. In addition, functionally similar transporters or splice variants with different regulatory profiles will optimize pH physiology and solute transport under various conditions or within subcellular domains. Such optimization will depend on activated signaling pathways and transporter expression profiles. In this review, we will summarize and discuss both classical and more recently identified regulators of the Slc4 proteins. Some of these regulators include traditional second messengers, lipids, binding proteins, autoregulatory domains, and less conventional regulators. The material presented will provide insight into the diversity and physiological significance of multiple members within the Slc4 gene family.

  3. Potential environmental regulations for coal liquefaction facilities

    Energy Technology Data Exchange (ETDEWEB)

    Dauzvardis, P.; Gasper, J.; Surles, T.


    Although this report deals with potential regulatory constraints only on development of coal liquids, it should be noted that every basic industry in the national economy is constrained by a myriad of state, local, and federal laws, and many of these existing laws may eventually affect coal liquids development. The American Petroleum Institute has prepared a list of the 12 most generally applicable environmental laws; these are summarized. For the present study, the most comprehensive constraining regulations likely to apply to coal liquefaction were chosen from this list. The choices depended in part upon which laws could be complied with by appropriate facility design. Therefore, for this study, the regulations examined were those covering solid and hazardous wastes and emissions of air and water pollutants. It should be noted that there are at present no emission regulations pertaining specifically to coal liquefaction. A survey of such analogous industries was conducted to identify regulations on air and water pollutants and solid waste disposal that might pertain to coal synfuel plants. The Federal New Source Performance Standards (NSPS) for air and water pollutants were specified where applicable. Wherever federal standards for a particular emission source or pollutant did not exist but appeared necessary, appropriate standards were specified on the basis of state regulations.Estimates of emission and effluent standards that may be applicable to coal liquefaction facilities are presented. Emission standards are defined for coal driers, boilers, process, and combustion equipment and for Claus sulfur plants. Effluent standards are provided for process, boiler, and miscellaneous waste streams. Sources of solid wastes from coal liquefaction and proposed disposal regulations for hazardous wastes are also described.

  4. Regulation and activity of a zinc uptake regulator, Zur, in Corynebacterium diphtheriae. (United States)

    Smith, Kelsy F; Bibb, Lori A; Schmitt, Michael P; Oram, Diana M


    Regulation of metal ion homeostasis is essential to bacterial cell survival, and in most species it is controlled by metal-dependent transcriptional regulators. In this study, we describe a Corynebacterium diphtheriae ferric uptake regulator-family protein, Zur, that controls expression of genes involved in zinc uptake. By measuring promoter activities and mRNA levels, we demonstrate that Zur represses transcription of three genes (zrg, cmrA, and troA) in zinc-replete conditions. All three of these genes have similarity to genes involved in zinc uptake. Transcription of zrg and cmrA was also shown to be regulated in response to iron and manganese, respectively, by mechanisms that are independent of Zur. We demonstrate that the activity of the zur promoter is slightly decreased under low zinc conditions in a process that is dependent on Zur itself. This regulation of zur transcription is distinctive and has not yet been described for any other zur. An adjacent gene, predicted to encode a metal-dependent transcriptional regulator in the ArsR/SmtB family, is transcribed from a separate promoter whose activity is unaffected by Zur. A C. diphtheriae zur mutant was more sensitive to peroxide stress, which suggests that zur has a role in protecting the bacterium from oxidative damage. Our studies provide the first evidence of a zinc specific transcriptional regulator in C. diphtheriae and give new insights into the intricate regulatory network responsible for regulating metal ion concentrations in this toxigenic human pathogen.

  5. Serine/threonine/tyrosine phosphorylation regulates DNA binding of bacterial transcriptional regulators

    DEFF Research Database (Denmark)

    Kalantari, Aida; Derouiche, Abderahmane; Shi, Lei;


    Reversible phosphorylation of bacterial transcriptional regulators (TRs) belonging to the family of two-component systems (TCSs) is a well-established mechanism for regulating gene expression. Recent evidence points to the fact that reversible phosphorylation of bacterial TRs on other types...

  6. Tricornered Kinase Regulates Synapse Development by Regulating the Levels of Wiskott-Aldrich Syndrome Protein.

    Directory of Open Access Journals (Sweden)

    Rajalaxmi Natarajan

    Full Text Available Precise regulation of synapses during development is essential to ensure accurate neural connectivity and function of nervous system. Many signaling pathways, including the mTOR (mechanical Target of Rapamycin pathway operate in neurons to maintain genetically determined number of synapses during development. mTOR, a kinase, is shared between two functionally distinct multi-protein complexes- mTORC1 and mTORC2, that act downstream of Tuberous Sclerosis Complex (TSC. We and others have suggested an important role for TSC in synapse development at the Drosophila neuromuscular junction (NMJ synapses. In addition, our data suggested that the regulation of the NMJ synapse numbers in Drosophila largely depends on signaling via mTORC2. In the present study, we further this observation by identifying Tricornered (Trc kinase, a serine/threonine kinase as a likely mediator of TSC signaling. trc genetically interacts with Tsc2 to regulate the number of synapses. In addition, Tsc2 and trc mutants exhibit a dramatic reduction in synaptic levels of WASP, an important regulator of actin polymerization. We show that Trc regulates the WASP levels largely, by regulating the transcription of WASP. Finally, we show that overexpression of WASP (Wiskott-Aldrich Syndrome Protein in trc mutants can suppress the increase in the number of synapses observed in trc mutants, suggesting that WASP regulates synapses downstream of Trc. Thus, our data provide a novel insight into how Trc may regulate the genetic program that controls the number of synapses during development.

  7. 9 CFR 83.4 - VHS-regulated fish and VHS-regulated areas. (United States)


    ... been isolated in cell culture or other assay determined by the Administrator to be adequate to detect... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false VHS-regulated fish and VHS-regulated areas. 83.4 Section 83.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...

  8. Ikaros: a key regulator of haematopoiesis. (United States)

    Westman, Belinda J; Mackay, Joel P; Gell, David


    Ikaros is an essential transcription factor for normal lymphocyte development. Because of its interaction with a number of closely related factors, Ikaros is required for correct regulation of differentiation and cell proliferation in T- and B-cell lineages. Interestingly, Ikaros appears to function both as a transcriptional repressor and as an activator through its ability to bind a large number of nuclear factors, including components of both histone deacetylase and ATP-dependent chromatin remodelling complexes. In addition, nuclear localisation is important for Ikaros function--unlike most transcription factors, Ikaros is localised to discrete nuclear foci in lymphoid cells, suggesting it employs novel mechanisms to regulate transcription.

  9. Motivation for Compliance with Environmental Regulation

    DEFF Research Database (Denmark)

    Winter, Søren; May, Peter J.


    A combination of calculated, normative, and social motivations as well as awareness of rules and capacity to comply are thought to foster compliance with regulations. Hypotheses about these factors were tested with data concerning Danish farmers’ compliance with agro-environmental regulations....... Three key findings emerge: that farmers’ awareness of rules plays a critical role; that normative and social motivations are as influential as calculated motivations in enhancing compliance; and that inspectors’ enforcement style affects compliance differently from that posited in much of the literature...

  10. The mechanism of protein kinase C regulation

    Institute of Scientific and Technical Information of China (English)

    Julhash U. KAZI


    Protein kinase C (PKC) is a family ofserine/threonine protein kinases that plays a central role in transducing extracellular signals into a variety of intracellular responses ranging from cell proliferation to apoptosis.Nine PKC genes have been identified in the human genome,which encode 10 proteins.Each member of this protein kinase family displays distinct biochemical characteristics and is enriched in different cellular and subcellular locations.Activation of PKC has been implicated in the regulation of cell growth and differentiation.This review summarizes works of the past years in the field of PKC biochemistry that covers regulation and activation mechanism of different PKC isoforms.

  11. Compliance Costs of Regulation for Small Business

    Directory of Open Access Journals (Sweden)

    Phil Lewis


    Full Text Available There has been growing concern about the extent of government regulation in Australia and its impact on small business. This paper examines the results of a survey of small businesses in NSW and Victoria regarding their experiences relating to compliance with government regulation, the costs to business, and factors inhibiting performance. The paper describes the development of the survey instrument, the administration of the survey, a description of the sample, results of the quantitative part of the survey, and an overview of business owners’ comments provided by respondents.

  12. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian


    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  13. Learner Autonomy, Self Regulation and Metacognition

    Directory of Open Access Journals (Sweden)

    Feryal CUBUKCU


    Full Text Available Different theories try to explain why some students are more successful than the others. Phenomenologists (Mc Combs, 1989 study self concepts of the students and find such students prone to achieve more. Attributional Theorists (Dweck, 1986; Weiner, 2005 focus on personal outcome such as effort or ability. Metacognitive theorists (Pressley, 2000; Schunk, Pintrich & Meece, 2007 examine students’ self regulated learning strategies whereas Constructivists (Maxim, 2009; Paris & Byrnes, 1989 believe supportive environments are important to be successful. In this study, the metacognitive theory will be given more importance and the purpose of the article is to find the correlation between self regulation, metacognition and autonomy.

  14. Mechanisms regulating skin immunity and inflammation. (United States)

    Pasparakis, Manolis; Haase, Ingo; Nestle, Frank O


    Immune responses in the skin are important for host defence against pathogenic microorganisms. However, dysregulated immune reactions can cause chronic inflammatory skin diseases. Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease. In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation.

  15. Regulation of cardiomyocyte autophagy by calcium. (United States)

    Shaikh, Soni; Troncoso, Rodrigo; Criollo, Alfredo; Bravo-Sagua, Roberto; García, Lorena; Morselli, Eugenia; Cifuentes, Mariana; Quest, Andrew F G; Hill, Joseph A; Lavandero, Sergio


    Calcium signaling plays a crucial role in a multitude of events within the cardiomyocyte, including cell cycle control, growth, apoptosis, and autophagy. With respect to calcium-dependent regulation of autophagy, ion channels and exchangers, receptors, and intracellular mediators play fundamental roles. In this review, we discuss calcium-dependent regulation of cardiomyocyte autophagy, a lysosomal mechanism that is often cytoprotective, serving to defend against disease-related stress and nutrient insufficiency. We also highlight the importance of the subcellular distribution of calcium and related proteins, interorganelle communication, and other key signaling events that govern cardiomyocyte autophagy.

  16. Self-regulation through Goal Setting

    DEFF Research Database (Denmark)

    Koch, Alexander; Nafziger, Julia

    Goals are an important source of motivation. But little is known about why and how people set them. We address these questions in a model based on two stylized facts from psychology and behavioral economics: i) Goals serve as reference points for performance. ii) Present-biased preferences create...... self-control problems. We show how goals permit self-regulation, but also that they are painful self-disciplining devices. Greater self-control problems therefore lead to stronger self-regulation through goals only up to a certain point. For severely present-biased preferences, the required goal...

  17. Transcriptional Regulation of Heart Development in Zebrafish (United States)

    Lu, Fei; Langenbacher, Adam D.; Chen, Jau-Nian


    Cardiac transcription factors orchestrate the complex cellular and molecular events required to produce a functioning heart. Misregulation of the cardiac transcription program leads to embryonic developmental defects and is associated with human congenital heart diseases. Recent studies have expanded our understanding of the regulation of cardiac gene expression at an additional layer, involving the coordination of epigenetic and transcriptional regulators. In this review, we highlight and discuss discoveries made possible by the genetic and embryological tools available in the zebrafish model organism, with a focus on the novel functions of cardiac transcription factors and epigenetic and transcriptional regulatory proteins during cardiogenesis. PMID:27148546

  18. Regulation of psychic functions in combat sport

    Directory of Open Access Journals (Sweden)

    Klymenko A.I.


    Full Text Available The problems of adjusting of psychical functions are considered in sport. The methods of self-regulation are rotined in sport. The groups of emotional reactions of combat sportsmen are certain. It is set that sporting psychologists and trainers are mainly addressed to training of psychical functions. Also - the system of psychical self-regulation must be complex. It contains affecting physiological reactions and on psychical processes. Five groups of emotional reactions of combat sportsmen are marked. They are directed on development of ability without superfluous emotions to overcome extreme situations in the process of competition activity.

  19. Lipoxins: A Novel Regulator in Embryo Implantation

    Directory of Open Access Journals (Sweden)

    Jing Xiong


    Full Text Available Embryo implantation is essential for mammalian pregnancy, which involves intricate cross-talk between the blastocyst and the maternal endometrium. Recent advances have identified various molecules crucial to implantation and endometrial receptivity, including leukemia inhibitory factor, calcitonin, and homeobox A10. There is a close relationship between implantation and inflammation. Lipoxins, important in the resolution of inflammation, may be a potential regulator in implantation. Here we discuss the hypothesis that lipoxins may work as a novel regulator in embryo implantation and the possible molecular mechanisms.

  20. Environmental regulations handbook for enhanced oil recovery

    Energy Technology Data Exchange (ETDEWEB)

    Madden, M.P. (National Inst. for Petroleum and Energy Research, Bartlesville, OK (United States)); Blatchford, R.P.; Spears, R.B. (Spears and Associates, Inc., Tulsa, OK (United States))


    This handbook is intended to assist owners and operators of enhanced oil recovery (EOR) operations in acquiring some introductory knowledge of the various state agencies, the US Environmental Protection Agency, and the many environmental laws, rules and regulations which can have jurisdiction over their permitting and compliance activities. It is a compendium of summarizations of environmental rules. It is not intended to give readers specific working details of what is required from them, nor can it be used in that manner. Readers of this handbook are encouraged to contact environmental control offices nearest to locations of interest for current regulations affecting them.