Sample records for tieg1 regulates bmal1

  1. Possible role of TIEG1 as a feedback regulator of myostatin and TGF-{beta} in myoblasts

    SciTech Connect

    Miyake, Masato; Hayashi, Shinichiro; Iwasaki, Shunsuke; Chao, Guozheng; Takahashi, Hideyuki; Watanabe, Kouichi; Ohwada, Shyuichi; Aso, Hisashi [Laboratory of Functional Morphology, Department of Animal Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-Ku, Sendai 981-8555 (Japan)] [Laboratory of Functional Morphology, Department of Animal Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-Ku, Sendai 981-8555 (Japan); Yamaguchi, Takahiro, E-mail: ty1010@bios.tohoku.ac.jp [Laboratory of Functional Morphology, Department of Animal Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-Ku, Sendai 981-8555 (Japan)] [Laboratory of Functional Morphology, Department of Animal Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-Ku, Sendai 981-8555 (Japan)

    2010-03-19

    Myostatin and TGF-{beta} negatively regulate skeletal muscle development and growth. Both factors signal through the Smad2/3 pathway. However, the regulatory mechanism of myostatin and TGF-{beta} signaling remains unclear. TGF-{beta} inducible early gene (TIEG) 1 is highly expressed in skeletal muscle and has been implicated in the modulation of TGF-{beta} signaling. These findings prompted us to investigate the effect of TIEG1 on myostatin and TGF-{beta} signaling using C2C12 myoblasts. Myostatin and TGF-{beta} induced the expression of TIEG1 and Smad7 mRNAs, but not TIEG2 mRNA, in proliferating C2C12 cells. When differentiating C2C12 myoblasts were stimulated by myostatin, TIEG1 mRNA was up-regulated at a late stage of differentiation. In contrast, TGF-{beta} enhanced TIEG1 expression at an early stage. Overexpression of TIEG1 prevented the transcriptional activation of Smad by myostatin and TGF-{beta} in both proliferating or differentiating C2C12 cells, but the expression of Smad2 and Smad7 mRNAs was not affected. Forced expression of TIEG1 inhibited myogenic differentiation but did not cause more inhibition than the empty vector in the presence of myostatin or TGF-{beta}. These results demonstrate that TIEG1 is one possible feedback regulator of myostatin and TGF-{beta} that prevents excess action in myoblasts.

  2. TGF?2 regulates hypothalamic Trh expression through the TGF? inducible early gene-1 (TIEG1) during fetal development

    PubMed Central

    Martínez-Armenta, Miriam; de León-Guerrero, Sol Díaz; Catalán, Ana; Alvarez-Arellano, Lourdes; Uribe, Rosa Maria; Subramaniam, Malayannan; Charli, Jean-Louis; Pérez-Martínez, Leonor

    2015-01-01

    The hypothalamus regulates the homeostasis of the organism by controlling hormone secretion from the pituitary. The molecular mechanisms that regulate the differentiation of the hypothalamic thyrotropin-releasing hormone (TRH) phenotype are poorly understood. We have previously shown that Klf10 or TGF? inducible early gene-1 (TIEG1) is enriched in fetal hypothalamic TRH neurons. Here, we show that expression of TGF? isoforms (1–3) and both TGF? receptors (T?RI and II) occurs in the hypothalamus concomitantly with the establishment of TRH neurons during late embryonic development. TGF?2 induces Trh expression via a TIEG1 dependent mechanism. TIEG1 regulates Trh expression through an evolutionary conserved GC rich sequence on the Trh promoter. Finally, in mice deficient in TIEG1, Trh expression is lower than in wild type animals at embryonic day 17. These results indicate that TGF? signaling, through the upregulation of TIEG1, plays an important role in the establishment of Trh expression in the embryonic hypothalamus. PMID:25448845

  3. Nuclear envelope protein MAN1 regulates clock through BMAL1

    PubMed Central

    Lin, Shu-Ting; Zhang, Luoying; Lin, Xiaoyan; Zhang, Linda Chen; Garcia, Valentina Elizabeth; Tsai, Chen-Wei; Ptá?ek, Louis; Fu, Ying-Hui

    2014-01-01

    Circadian clocks serve as internal pacemakers that influence many basic homeostatic processes; consequently, the expression and function of their components are tightly regulated by intricate networks of feedback loops that fine-tune circadian processes. Our knowledge of these components and pathways is far from exhaustive. In recent decades, the nuclear envelope has emerged as a global gene regulatory machine, although its role in circadian regulation has not been explored. We report that transcription of the core clock component BMAL1 is positively modulated by the inner nuclear membrane protein MAN1, which directly binds the BMAL1 promoter and enhances its transcription. Our results establish a novel connection between the nuclear periphery and circadian rhythmicity, therefore bridging two global regulatory systems that modulate all aspects of bodily functions. DOI: http://dx.doi.org/10.7554/eLife.02981.001 PMID:25182847

  4. Dual role of the CLOCK\\/BMAL1 circadian complex in transcriptional regulation

    Microsoft Academic Search

    Roman V. Kondratov; Rashmi K. Shamanna; Anna A. Kondratova; Victoria Y. Gorbachev; Marina P. Antoch

    2006-01-01

    The basic helix-loop-helix (bHLH) -PAS domain containing transcription factors CLOCK and BMAL1 are two major components of the circadian molecular oscillator. It is known that the CLOCK\\/BMAL1 complex positively regulates the activity of E-box containing promoters. Here we demonstrate that the CLOCK\\/BMAL1 complex can also suppress the activity of some promoters upon its interaction with CRYPTOCHROME (CRY). Such a dual

  5. Cryptochrome and Period Proteins Are Regulated by the CLOCK/BMAL1 Gene: Crosstalk between the PPARs/RXR?-Regulated and CLOCK/BMAL1-Regulated Systems

    PubMed Central

    Nakamura, Koh-ichi; Inoue, Ikuo; Takahashi, Seiichiro; Komoda, Tsugikazu; Katayama, Shigehiro

    2008-01-01

    Feeding and the circadian system regulate lipid absorption and metabolism, and the expression of enzymes involved in lipid metabolism is believed to be directly controlled by the clock system. To investigate the interaction between the lipid metabolism system and the circadian system, we analyzed the effect of a CLOCK/BMAL1 heterodimer on the transcriptional regulation of PPAR-controlled genes through PPAR response elements (PPREs). Transcription of acyl-CoA oxidase, cellular retinol binding protein II (CRBPII), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase was altered by CLOCK/BMAL1, and transcriptional activity via PPRE by PPARs/RXR? was enhanced by CLOCK/BMAL1 and/or by PPARs ligand/activators. We also found that CLOCK/BMAL1-mediated transcription of period (PER) and cryptochrome (CRY) was modulated by PPAR?/RXR?. These results suggest that there may be crosstalk between the PPARs/RXR?-regulated system and the CLOCK/BMAL1-regulated system. PMID:18317514

  6. The Circadian Protein BMAL1 Regulates Translation in Response to S6K1-Mediated Phosphorylation.

    PubMed

    Lipton, Jonathan O; Yuan, Elizabeth D; Boyle, Lara M; Ebrahimi-Fakhari, Darius; Kwiatkowski, Erica; Nathan, Ashwin; Güttler, Thomas; Davis, Fred; Asara, John M; Sahin, Mustafa

    2015-05-21

    The circadian timing system synchronizes cellular function by coordinating rhythmic transcription via a transcription-translational feedback loop. How the circadian system regulates gene expression at the translational level remains a mystery. Here, we show that the key circadian transcription factor BMAL1 associates with the translational machinery in the cytosol and promotes protein synthesis. The mTOR-effector kinase, ribosomal S6 protein kinase 1 (S6K1), an important regulator of translation, rhythmically phosphorylates BMAL1 at an evolutionarily conserved site. S6K1-mediated phosphorylation is critical for BMAL1 to both associate with the translational machinery and stimulate protein synthesis. Protein synthesis rates demonstrate circadian oscillations dependent on BMAL1. Thus, in addition to its critical role in circadian transcription, BMAL1 is a translation factor that links circadian timing and the mTOR signaling pathway. More broadly, these results expand the role of the circadian clock to the regulation of protein synthesis. PMID:25981667

  7. Cryptochrome 1 regulates the circadian clock through dynamic interactions with the BMAL1 C terminus.

    PubMed

    Xu, Haiyan; Gustafson, Chelsea L; Sammons, Patrick J; Khan, Sanjoy K; Parsley, Nicole C; Ramanathan, Chidambaram; Lee, Hsiau-Wei; Liu, Andrew C; Partch, Carrie L

    2015-06-01

    The molecular circadian clock in mammals is generated from transcriptional activation by the bHLH-PAS transcription factor CLOCK-BMAL1 and subsequent repression by PERIOD and CRYPTOCHROME (CRY). The mechanism by which CRYs repress CLOCK-BMAL1 to close the negative feedback loop and generate 24-h timing is not known. Here we show that, in mouse fibroblasts, CRY1 competes for binding with coactivators to the intrinsically unstructured C-terminal transactivation domain (TAD) of BMAL1 to establish a functional switch between activation and repression of CLOCK-BMAL1. TAD mutations that alter affinities for co-regulators affect the balance of repression and activation to consequently change the intrinsic circadian period or eliminate cycling altogether. Our results suggest that CRY1 fulfills its role as an essential circadian repressor by sequestering the TAD from coactivators, and they highlight regulation of the BMAL1 TAD as a critical mechanism for establishing circadian timing. PMID:25961797

  8. Glucagon-CREB/CRTC2 signaling cascade regulates hepatic BMAL1 protein.

    PubMed

    Sun, Xiujie; Dang, Fabin; Zhang, Deyi; Yuan, Yuan; Zhang, Cui; Wu, Yuting; Wang, Yiguo; Liu, Yi

    2015-01-23

    Energy metabolism follows a diurnal pattern responding to the cycles of light and food exposures. Although food availability is a potent synchronizer of peripheral circadian clock in mammals, the underlying mechanism remains elusive. Here, we found that the temporal signals of fasting and refeeding hormones regulate the transcription of Bmal1, a key transcription activator of molecular clock, in the liver. During fasting, glucagon, a major fasting hormone, activates CREB/CRTC2 transcriptional complex that is recruited to Bmal1 promoter to induce its expression. Furthermore, we showed that CRTC2 is required for basal transcriptional regulation of Bmal1 by experiments using either adenovirus-mediated CRTC2 RNAi knockdown or primary Crtc2 null hepatocytes. On the other hand, insulin suppresses fasting-induced Bmal1 expression by inhibiting CRTC2 activity after refeeding. Taken together, our results indicate CRTC2 as a key component of the circadian oscillator that integrates the mammalian clock and energy metabolism. PMID:25480789

  9. Synergistic regulation of the mouse orphan nuclear receptor SHP gene promoter by CLOCK-BMAL1 and LRH-1

    SciTech Connect

    Oiwa, Ako [Shinshu University Graduate School of Medicine, Institute on Aging and Adaptation, Department of Aging Medicine and Geriatrics, Matsumoto 390-8621 (Japan); Kakizawa, Tomoko [Shinshu University Graduate School of Medicine, Institute on Aging and Adaptation, Department of Aging Medicine and Geriatrics, Matsumoto 390-8621 (Japan)]. E-mail: tkaki@hsp.md.shinshu-u.ac.jp; Miyamoto, Takahide [Shinshu University Graduate School of Medicine, Institute on Aging and Adaptation, Department of Aging Medicine and Geriatrics, Matsumoto 390-8621 (Japan); Yamashita, Koh [Shinshu University Graduate School of Medicine, Institute on Aging and Adaptation, Department of Aging Medicine and Geriatrics, Matsumoto 390-8621 (Japan); Jiang, Wei [Department of Endocrinology, First Clinical College, Harbin Medical University, 150001 (China); Takeda, Teiji [Shinshu University Graduate School of Medicine, Institute on Aging and Adaptation, Department of Aging Medicine and Geriatrics, Matsumoto 390-8621 (Japan); Suzuki, Satoru [Shinshu University Graduate School of Medicine, Institute on Aging and Adaptation, Department of Aging Medicine and Geriatrics, Matsumoto 390-8621 (Japan); Hashizume, Kiyoshi [Shinshu University Graduate School of Medicine, Institute on Aging and Adaptation, Department of Aging Medicine and Geriatrics, Matsumoto 390-8621 (Japan)

    2007-02-23

    Small heterodimer partner (SHP; NR0B2) is an orphan nuclear receptor and acts as a repressor for wide variety of nuclear hormone receptors. We demonstrated here that mouse SHP mRNA showed a circadian expression pattern in the liver. Transient transfection of the mSHP promoter demonstrated that CLOCK-BMAL1, core circadian clock components, bound to E-box (CACGTG), and stimulated the promoter activity by 4-fold. Liver receptor homologue-1 (LRH-1; NR5A2) stimulated the mSHP promoter, and CLOCK-BMAL1 synergistically enhanced the LRH-1-mediated transactivation. Interestingly, SHP did not affect the CLOCK-BMAL1-mediated promoter activity, but strongly repressed the synergistic activation of CLOCK-BMAL1 and LRH-1. Furthermore, in vitro pull-down assays revealed the existence of direct protein-protein interaction between LRH-1 and CLOCK. In summary, this study shows that CLOCK-BMAL1, LRH-1 and SHP coordinately regulate the mSHP gene to generate the circadian oscillation. The cyclic expression of mSHP may affect daily activity of other nuclear receptors and contribute to circadian liver functions.

  10. TIEG1-null tenocytes display age-dependent differences in their gene expression, adhesion, spreading and proliferation properties

    SciTech Connect

    Haddad, Oualid; Gumez, Laurie [Laboratoire de Biomecanique et Bioingenierie UMR CNRS 6600, Universite de Technologie de Compiegne, Compiegne (France)] [Laboratoire de Biomecanique et Bioingenierie UMR CNRS 6600, Universite de Technologie de Compiegne, Compiegne (France); Hawse, John R.; Subramaniam, Malayannan; Spelsberg, Thomas C. [Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN (United States)] [Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN (United States); Bensamoun, Sabine F., E-mail: sabine.bensamoun@utc.fr [Laboratoire de Biomecanique et Bioingenierie UMR CNRS 6600, Universite de Technologie de Compiegne, Compiegne (France)

    2011-07-15

    The remodeling of extracellular matrix is a crucial mechanism in tendon development and the proliferation of fibroblasts is a key factor in this process. The purpose of this study was to further elucidate the role of TIEG1 in mediating important tenocyte properties throughout the aging process. Wildtype and TIEG1 knockout tenocytes adhesion, spreading and proliferation were characterized on different substrates (fibronectin, collagen type I, gelatin and laminin) and the expression levels of various genes known to be involved with tendon development were analyzed by RT-PCR. The experiments revealed age-dependent and substrate-dependent properties for both wildtype and TIEG1 knockout tenocytes. Taken together, our results indicate an important role for TIEG1 in regulating tenocytes adhesion, spreading, and proliferation throughout the aging process. Understanding the basic mechanisms of TIEG1 in tenocytes may provide valuable information for treating multiple tendon disorders.

  11. Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN.

    PubMed

    Shende, Vikram R; Neuendorff, Nichole; Earnest, David J

    2013-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional modulators by regulating stability or translation of target mRNAs. Recent studies have implicated miRNAs in the regulation of mammalian circadian rhythms. To explore the role of miRNAs in the post-transcriptional modulation of core clock genes in the master circadian pacemaker, we examined miR-142-3p for evidence of circadian expression in the suprachiasmatic nuclei (SCN), regulation of its putative clock gene target Bmal1 via specific binding sites in the 3' UTR and overexpression-induced changes in the circadian rhythm of BMAL1 protein levels in SCN cells. In mice exposed to constant darkness (DD), miR-142-3p levels in the SCN were characterized by circadian rhythmicity with peak expression during early subjective day at CT 3. Mutagenesis studies indicate that two independent miRNA recognition elements located at nucleotides 1-7 and 335-357 contribute equally to miR-142-3p-induced repression of luciferase-reported Bmal1 3' UTR activity. Importantly, overexpression of miR-142-3p in immortalized SCN cells abolished circadian variation in endogenous BMAL1 protein levels in vitro. Collectively, our results suggest that miR-142-3p may play a role in the post-transcriptional modulation of Bmal1 and its oscillatory regulation in molecular feedback loops mediating SCN circadian function. PMID:23755214

  12. Role of miR-142-3p in the Post-Transcriptional Regulation of the Clock Gene Bmal1 in the Mouse SCN

    PubMed Central

    Shende, Vikram R.; Neuendorff, Nichole; Earnest, David J.

    2013-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional modulators by regulating stability or translation of target mRNAs. Recent studies have implicated miRNAs in the regulation of mammalian circadian rhythms. To explore the role of miRNAs in the post-transcriptional modulation of core clock genes in the master circadian pacemaker, we examined miR-142-3p for evidence of circadian expression in the suprachiasmatic nuclei (SCN), regulation of its putative clock gene target Bmal1 via specific binding sites in the 3? UTR and overexpression-induced changes in the circadian rhythm of BMAL1 protein levels in SCN cells. In mice exposed to constant darkness (DD), miR-142-3p levels in the SCN were characterized by circadian rhythmicity with peak expression during early subjective day at CT 3. Mutagenesis studies indicate that two independent miRNA recognition elements located at nucleotides 1–7 and 335–357 contribute equally to miR-142-3p-induced repression of luciferase-reported Bmal1 3? UTR activity. Importantly, overexpression of miR-142-3p in immortalized SCN cells abolished circadian variation in endogenous BMAL1 protein levels in vitro. Collectively, our results suggest that miR-142-3p may play a role in the post-transcriptional modulation of Bmal1 and its oscillatory regulation in molecular feedback loops mediating SCN circadian function. PMID:23755214

  13. Gender dimorphism in the role of cycle (BMAL1) in rest, rest regulation, and longevity in Drosophila melanogaster.

    PubMed

    Hendricks, Joan C; Lu, Sumei; Kume, Kazuhiko; Yin, Jerry C P; Yang, Zhaohai; Sehgal, Amita

    2003-02-01

    The central clock is generally thought to provide timing information for rest/activity but not to otherwise participate in regulation of these states. To test the hypothesis that genes that are components of the molecular clock also regulate rest, the authors quantified the duration and intensity of consolidated rest and activity for the four viable Drosophila mutations of the central clock that lead to arrhythmic locomotor behavior and for the pdf mutant that lacks pigment-dispersing factor, an output neuropeptide. Only the cycle (cyc01) and Clock (Clk(Jrk)) mutants had abnormalities that mapped to the mutant locus, namely, decreased consolidated rest and grossly extended periods of activity. All mutants with the exception of the cyc01 fly exhibited a qualitatively normal compensatory rebound after rest deprivation. This abnormal response in cyc01 was sexually dimorphic, being reduced or absent in males and exaggerated in females. Finally, the cyc01 mutation shortened the life span of male flies. These data indicate that cycle regulates rest and life span in male Drosophila. PMID:12568241

  14. BMAL1 and CLOCK, Two Essential Components of the Circadian Clock, Are Involved in Glucose Homeostasis

    Microsoft Academic Search

    R. Daniel Rudic; Peter McNamara; Anne-Maria Curtis; Raymond C. Boston; Satchidananda Panda; John B. Hogenesch; Garret A. FitzGerald

    2004-01-01

    Circadian timing is generated through a unique series of autoregulatory interactions termed the molecular clock. Behavioral rhythms subject to the molecular clock are well characterized. We demonstrate a role for Bmal1 and Clock in the regulation of glucose homeostasis. Inactivation of the known clock components Bmal1 (Mop3) and Clock suppress the diurnal variation in glucose and triglycerides. Gluconeogenesis is abolished

  15. Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1 and circadian period

    PubMed Central

    Onishi, Yoshiaki; Kawano, Yasuhiro

    2012-01-01

    The Bmal1 gene is essential for the circadian system, and its promoter has a unique open chromatin structure. We examined the mechanism of topoisomerase I (Top1) to understand the role of the unique chromatin structure in Bmal1 gene regulation. Camptothecin, a Top1 inhibitor, and Top1 small interfering RNA (siRNA) enhanced Baml1 transcription and lengthened its circadian period. Top1 is located at an intermediate region between two ROREs that are critical cis-elements of circadian transcription and the profile of Top1 binding indicated anti-phase circadian oscillation of Bmal1 transcription. Promoter assays showed that the Top1-binding site is required for transcriptional suppression and that it functions cooperatively with the distal RORE, supporting that Bmal1 transcription is upregulated by Top1 inhibition. A DNA fragment between the ROREs, where the Top1-binding site is located, behaved like a right-handed superhelical twist, and modulation of Top1 activity by camptothecin and Top1 siRNA altered the footprint profile, indicating modulation of the chromatin structure. These data indicate that Top1 modulates the chromatin structure of the Bmal1 promoter, regulates Bmal1 transcription and influences the circadian period. PMID:22904072

  16. Cardiomyocyte-specific BMAL1 plays critical roles in metabolism, signaling, and maintenance of contractile function of the heart.

    PubMed

    Young, Martin E; Brewer, Rachel A; Peliciari-Garcia, Rodrigo A; Collins, Helen E; He, Lan; Birky, Tana L; Peden, Bradley W; Thompson, Emily G; Ammons, Billy-Joe; Bray, Molly S; Chatham, John C; Wende, Adam R; Yang, Qinglin; Chow, Chi-Wing; Martino, Tami A; Gamble, Karen L

    2014-08-01

    Circadian clocks are cell autonomous, transcriptionally based, molecular mechanisms that confer the selective advantage of anticipation, enabling cells/organs to respond to environmental factors in a temporally appropriate manner. Critical to circadian clock function are 2 transcription factors, CLOCK and BMAL1. The purpose of the present study was to reveal novel physiologic functions of BMAL1 in the heart, as well as to determine the pathologic consequences of chronic disruption of this circadian clock component. To address this goal, we generated cardiomyocyte-specific Bmal1 knockout (CBK) mice. Following validation of the CBK model, combined microarray and in silico analyses were performed, identifying 19 putative direct BMAL1 target genes, which included a number of metabolic (e.g., ?-hydroxybutyrate dehydrogenase 1 [Bdh1]) and signaling (e.g., the p85? regulatory subunit of phosphatidylinositol 3-kinase [Pik3r1]) genes. Results from subsequent validation studies were consistent with regulation of Bdh1 and Pik3r1 by BMAL1, with predicted impairments in ketone body metabolism and signaling observed in CBK hearts. Furthermore, CBK hearts exhibited depressed glucose utilization, as well as a differential response to a physiologic metabolic stress (i.e., fasting). Consistent with BMAL1 influencing critical functions in the heart, echocardiographic, gravimetric, histologic, and molecular analyses revealed age-onset development of dilated cardiomyopathy in CBK mice, which was associated with a severe reduction in life span. Collectively, our studies reveal that BMAL1 influences metabolism, signaling, and contractile function of the heart. PMID:25238855

  17. Histone demethylase JARID1B/KDM5B is a corepressor of TIEG1/KLF10.

    PubMed

    Kim, Joanna; Shin, Sook; Subramaniam, Malayannan; Bruinsma, Elizabeth; Kim, Tae-Dong; Hawse, John R; Spelsberg, Thomas C; Janknecht, Ralf

    2010-10-22

    JARID1B/KDM5B (jumonji AT-rich interactive domain 1B/lysine-specific demethylase 5B) is an enzyme that efficiently removes methyl residues from trimethylated lysine 4 on histone H3, a pivotal mark for active chromatin. TIEG1/KLF10 (transforming growth factor-? inducible early gene-1/Krüppel-like transcription factor 10) is a zinc-finger transcription factor that is involved in bone metabolism and exerts antiproliferative activity. Here, we found that TIEG1 interacts with JARID1B. In particular, the repression domains of TIEG1 bind to the C-terminus of JARID1B. Moreover, overexpression of JARID1B augments TIEG1 to repress transcription of Smad7, an inhibitor of the TGF-? (transforming growth factor-?) signaling pathway. Conversely, JARID1B knock-down leads to increased Smad7 mRNA levels. Thus, TIEG1 and JARID1B may cooperate to suppress tumorigenesis by enhancing TGF-? signaling. Notably, both TIEG1 and JARID1B are downregulated in melanomas, suggesting that they indeed cooperate physiologically. In conclusion, JARID1B is the first TIEG1 corepressor identified, explaining how TIEG1 represses transcription through inducing histone H3 lysine 4 demethylation, which may be important for TIEG1 function in both normal and cancer cells. PMID:20863814

  18. Loss of BMAL1 in ovarian steroidogenic cells results in implantation failure in female mice.

    PubMed

    Liu, Yan; Johnson, Brian P; Shen, Anna L; Wallisser, Jacqueline A; Krentz, Kathy J; Moran, Susan M; Sullivan, Ruth; Glover, Edward; Parlow, Albert F; Drinkwater, Norman R; Schuler, Linda A; Bradfield, Christopher A

    2014-09-30

    The circadian clock plays a significant role in many aspects of female reproductive biology, including estrous cycling, ovulation, embryonic implantation, onset of puberty, and parturition. In an effort to link cell-specific circadian clocks to their specific roles in female reproduction, we used the promoter that controls expression of Steroidogenic Factor-1 (SF1) to drive Cre-recombinase-mediated deletion of the brain muscle arnt-like 1 (Bmal1) gene, known to encode an essential component of the circadian clock (SF1-Bmal1(-/-)). The resultant SF1-Bmal1(-/-) females display embryonic implantation failure, which is rescued by progesterone supplementation, or bilateral or unilateral transplantation of wild-type ovaries into SF1-Bmal1(-/-) dams. The observation that the central clock, and many other peripheral clocks, are fully functional in this model allows the assignment of the implantation phenotype to the clock in ovarian steroidogenic cells and distinguishes it from more general circadian related systemic pathology (e.g., early onset arthropathy, premature aging, ovulation, late onset of puberty, and abnormal estrous cycle). Our ovarian transcriptome analysis reveals that deletion of ovarian Bmal1 disrupts expression of transcripts associated with the circadian machinery and also genes critical for regulation of progesterone production, such as steroidogenic acute regulatory factor (Star). Overall, these data provide a powerful model to probe the interlocking and synergistic network of the circadian clock and reproductive systems. PMID:25225411

  19. Increased Superoxide and Endothelial NO Synthase Uncoupling in Blood Vessels of Bmal1-Knockout Mice

    PubMed Central

    Anea, Ciprian B.; Cheng, Bo; Sharma, Shruti; Kumar, Sanjiv; Caldwell, R. William; Yao, Lin; Ali, M. Irfan; Merloiu, Ana M.; Stepp, David W.; Black, Stephen M.; Fulton, David J.R.; Rudic, R. Daniel

    2013-01-01

    Rationale Disruption of the circadian clock in mice produces vascular dysfunction as evidenced by impairments in endothelium-dependent signaling, vasomotion, and blood vessel remodeling. Although the altered function of endothelial NO synthase and the overproduction of reactive oxygen species are central to dysfunction of the endothelium, to date, the impact of the circadian clock on endothelial NO synthase coupling and vascular reactive oxygen species production is not known. Objective The goals of the present study were to determine whether deletion of a critical component of the circadian clock, Bmal1, can influence endothelial NO synthase coupling and reactive oxygen species levels in arteries from Bmal1-knockout (KO) mice. Methods and Results Endothelial function was reduced in aortae from Bmal1-KO mice and improved by scavenging reactive oxygen species with polyethylene glycol-superoxide dismutase and nonselectively inhibiting cyclooxygenase isoforms with indomethacin. Aortae from Bmal1-KO mice exhibited enhanced superoxide levels as determined by electron paramagnetic resonance spectroscopy and dihydroethidium fluorescence, an elevation that was abrogated by administration of nitro-L -arginine methyl ester. High-performance liquid chromatography analysis revealed a reduction in tetrahydrobiopterin and an increase in dihydrobiopterin levels in the lung and aorta of Bmal1-KO mice, whereas supplementation with tetrahydrobiopterin improved endothelial function in the circadian clock KO mice. Furthermore, levels of tetrahydrobiopterin, dihydrobiopterin, and the key enzymes that regulate biopterin bioavailability, GTP cyclohydrolase and dihydrofolate reductase exhibited a circadian expression pattern. Conclusions Having an established influence in the metabolic control of glucose and lipids, herein, we describe a novel role for the circadian clock in metabolism of biopterins, with a significant impact in the vasculature, to regulate coupling of endothelial NO synthase, production of superoxide, and maintenance of endothelial function. (Circ Res. 2012; 111:1157–1165.) PMID:22912383

  20. Quantitative Analyses of Cryptochrome-mBMAL1 Interactions

    PubMed Central

    Czarna, Anna; Breitkreuz, Helena; Mahrenholz, Carsten C.; Arens, Julia; Strauss, Holger M.; Wolf, Eva

    2011-01-01

    The mammalian cryptochromes mCRY1 and mCRY2 act as transcriptional repressors within the 24-h transcription-translational feedback loop of the circadian clock. The C-terminal tail and a preceding predicted coiled coil (CC) of the mCRYs as well as the C-terminal region of the transcription factor mBMAL1 are involved in transcriptional feedback repression. Here we show by fluorescence polarization and isothermal titration calorimetry that purified mCRY1/2CCtail proteins form stable heterodimeric complexes with two C-terminal mBMAL1 fragments. The longer mBMAL1 fragment (BMAL490) includes Lys-537, which is rhythmically acetylated by mCLOCK in vivo. mCRY1 (but not mCRY2) has a lower affinity to BMAL490 than to the shorter mBMAL1 fragment (BMAL577) and a K537Q mutant version of BMAL490. Using peptide scan analysis we identify two mBMAL1 binding epitopes within the coiled coil and tail regions of mCRY1/2 and document the importance of positively charged mCRY1 residues for mBMAL1 binding. A synthetic mCRY coiled coil peptide binds equally well to the short and to the long (wild-type and K537Q mutant) mBMAL1 fragments. In contrast, a peptide including the mCRY1 tail epitope shows a lower affinity to BMAL490 compared with BMAL577 and BMAL490(K537Q). We propose that Lys-537mBMAL1 acetylation enhances mCRY1 binding by affecting electrostatic interactions predominantly with the mCRY1 tail. Our data reveal different molecular interactions of the mCRY1/2 tails with mBMAL1, which may contribute to the non-redundant clock functions of mCRY1 and mCRY2. Moreover, our study suggests the design of peptidic inhibitors targeting the interaction of the mCRY1 tail with mBMAL1. PMID:21521686

  1. Food anticipation in Bmal1-/- and AAV-Bmal1 rescued mice: a reply to Fuller et al

    PubMed Central

    Mistlberger, Ralph E; Buijs, Ruud M; Challet, Etienne; Escobar, Carolina; Landry, Glenn J; Kalsbeek, Andries; Pevet, Paul; Shibata, Shigenobu

    2009-01-01

    Evidence that circadian food-anticipatory activity and temperature rhythms are absent in Bmal1 knockout mice and rescued by restoration of Bmal1 expression selectively in the dorsomedial hypothalamus was published in 2008 by Fuller et al and critiqued in 2009 by Mistlberger et al. Fuller et al have responded to the critique with new information. Here we update our critique in the light of this new information. We also identify and correct factual and conceptual errors in the Fuller et al response. We conclude that the original results of Fuller et al remain inconclusive and fail to clarify the role of Bmal1 or the dorsomedial hypothalamus in the generation of food-entrainable rhythms in mice. PMID:19664274

  2. Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway.

    PubMed

    Hwang, Jae-Woong; Sundar, Isaac K; Yao, Hongwei; Sellix, Michael T; Rahman, Irfan

    2014-01-01

    Patients with obstructive lung diseases display abnormal circadian rhythms in lung function. We determined the mechanism whereby environmental tobacco/cigarette smoke (CS) modulates expression of the core clock gene BMAL1, through Sirtuin1 (SIRT1) deacetylase during lung inflammatory and injurious responses. Adult C57BL6/J and various mice mutant for SIRT1 and BMAL1 were exposed to both chronic (6 mo) and acute (3 and 10 d) CS, and we measured the rhythmic expression of clock genes, circadian rhythms of locomotor activity, lung function, and inflammatory and emphysematous responses in the lungs. CS exposure (100-300 mg/m(3) particulates) altered clock gene expression and reduced locomotor activity by disrupting the central and peripheral clocks and increased lung inflammation, causing emphysema in mice. BMAL1 was acetylated and degraded in the lungs of mice exposed to CS and in patients with chronic obstructive pulmonary disease (COPD), compared with lungs of the nonsmoking controls, linking it mechanistically to CS-induced reduction of SIRT1. Targeted deletion of Bmal1 in lung epithelium augmented inflammation in response to CS, which was not attenuated by the selective SIRT1 activator SRT1720 (EC50=0.16 ?M) in these mice. Thus, the circadian clock, specifically the enhancer BMAL1 in epithelium, plays a pivotal role, mediated by SIRT1-dependent BMAL1, in the regulation of CS-induced lung inflammatory and injurious responses. PMID:24025728

  3. Histone demethylase JARID1B\\/KDM5B is a corepressor of TIEG1\\/KLF10

    Microsoft Academic Search

    Joanna Kim; Sook Shin; Malayannan Subramaniam; Elizabeth Bruinsma; Tae-Dong Kim; John R. Hawse; Thomas C. Spelsberg; Ralf Janknecht

    2010-01-01

    JARID1B\\/KDM5B (jumonji AT-rich interactive domain 1B\\/lysine-specific demethylase 5B) is an enzyme that efficiently removes methyl residues from trimethylated lysine 4 on histone H3, a pivotal mark for active chromatin. TIEG1\\/KLF10 (transforming growth factor-? inducible early gene-1\\/Krüppel-like transcription factor 10) is a zinc-finger transcription factor that is involved in bone metabolism and exerts antiproliferative activity. Here, we found that TIEG1 interacts

  4. Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway

    PubMed Central

    Hwang, Jae-Woong; Sundar, Isaac K.; Yao, Hongwei; Sellix, Michael T.; Rahman, Irfan

    2014-01-01

    Patients with obstructive lung diseases display abnormal circadian rhythms in lung function. We determined the mechanism whereby environmental tobacco/cigarette smoke (CS) modulates expression of the core clock gene BMAL1, through Sirtuin1 (SIRT1) deacetylase during lung inflammatory and injurious responses. Adult C57BL6/J and various mice mutant for SIRT1 and BMAL1 were exposed to both chronic (6 mo) and acute (3 and 10 d) CS, and we measured the rhythmic expression of clock genes, circadian rhythms of locomotor activity, lung function, and inflammatory and emphysematous responses in the lungs. CS exposure (100–300 mg/m3 particulates) altered clock gene expression and reduced locomotor activity by disrupting the central and peripheral clocks and increased lung inflammation, causing emphysema in mice. BMAL1 was acetylated and degraded in the lungs of mice exposed to CS and in patients with chronic obstructive pulmonary disease (COPD), compared with lungs of the nonsmoking controls, linking it mechanistically to CS-induced reduction of SIRT1. Targeted deletion of Bmal1 in lung epithelium augmented inflammation in response to CS, which was not attenuated by the selective SIRT1 activator SRT1720 (EC50=0.16 ?M) in these mice. Thus, the circadian clock, specifically the enhancer BMAL1 in epithelium, plays a pivotal role, mediated by SIRT1-dependent BMAL1, in the regulation of CS-induced lung inflammatory and injurious responses.— Hwang, J.-W., Sundar, I. K., Yao, H., Sellix, M. T., Rahman, I. Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway. PMID:24025728

  5. Genomic Convergence among ERR?, PROX1, and BMAL1 in the Control of Metabolic Clock Outputs

    PubMed Central

    Dufour, Catherine R.; Levasseur, Marie-Pier; Pham, Nguyen Hoai Huong; Eichner, Lillian J.; Wilson, Brian J.; Charest-Marcotte, Alexis; Duguay, David; Poirier-Héon, Jean-François; Cermakian, Nicolas; Giguère, Vincent

    2011-01-01

    Metabolic homeostasis and circadian rhythms are closely intertwined biological processes. Nuclear receptors, as sensors of hormonal and nutrient status, are actively implicated in maintaining this physiological relationship. Although the orphan nuclear receptor estrogen-related receptor ? (ERR?, NR3B1) plays a central role in the control of energy metabolism and its expression is known to be cyclic in the liver, its role in temporal control of metabolic networks is unknown. Here we report that ERR? directly regulates all major components of the molecular clock. ERR?-null mice also display deregulated locomotor activity rhythms and circadian period lengths under free-running conditions, as well as altered circulating diurnal bile acid and lipid profiles. In addition, the ERR?-null mice exhibit time-dependent hypoglycemia and hypoinsulinemia, suggesting a role for ERR? in modulating insulin sensitivity and glucose handling during the 24-hour light/dark cycle. We also provide evidence that the newly identified ERR? corepressor PROX1 is implicated in rhythmic control of metabolic outputs. To help uncover the molecular basis of these phenotypes, we performed genome-wide location analyses of binding events by ERR?, PROX1, and BMAL1, an integral component of the molecular clock. These studies revealed the existence of transcriptional regulatory loops among ERR?, PROX1, and BMAL1, as well as extensive overlaps in their target genes, implicating these three factors in the control of clock and metabolic gene networks in the liver. Genomic convergence of ERR?, PROX1, and BMAL1 transcriptional activity thus identified a novel node in the molecular circuitry controlling the daily timing of metabolic processes. PMID:21731503

  6. Shifting the Circadian Rhythm of Feeding in Mice Induces Gastrointestinal, Metabolic and Immune Alterations Which Are Influenced by Ghrelin and the Core Clock Gene Bmal1

    PubMed Central

    Laermans, Jorien; Broers, Charlotte; Beckers, Kelly; Vancleef, Laurien; Steensels, Sandra; Thijs, Theo; Tack, Jan; Depoortere, Inge

    2014-01-01

    Background In our 24-hour society, an increasing number of people are required to be awake and active at night. As a result, the circadian rhythm of feeding is seriously compromised. To mimic this, we subjected mice to restricted feeding (RF), a paradigm in which food availability is limited to short and unusual times of day. RF induces a food-anticipatory increase in the levels of the hunger hormone ghrelin. We aimed to investigate whether ghrelin triggers the changes in body weight and gastric emptying that occur during RF. Moreover, the effect of genetic deletion of the core clock gene Bmal1 on these physiological adaptations was studied. Methods Wild-type, ghrelin receptor knockout and Bmal1 knockout mice were fed ad libitum or put on RF with a normal or high-fat diet (HFD). Plasma ghrelin levels were measured by radioimmunoassay. Gastric contractility was studied in vitro in muscle strips and in vivo (13C breath test). Cytokine mRNA expression was quantified and infiltration of immune cells was assessed histologically. Results The food-anticipatory increase in plasma ghrelin levels induced by RF with normal chow was abolished in HFD-fed mice. During RF, body weight restoration was facilitated by ghrelin and Bmal1. RF altered cytokine mRNA expression levels and triggered contractility changes resulting in an accelerated gastric emptying, independent from ghrelin signaling. During RF with a HFD, Bmal1 enhanced neutrophil recruitment to the stomach, increased gastric IL-1? expression and promoted gastric contractility changes. Conclusions This is the first study demonstrating that ghrelin and Bmal1 regulate the extent of body weight restoration during RF, whereas Bmal1 controls the type of inflammatory infiltrate and contractility changes in the stomach. Disrupting the circadian rhythm of feeding induces a variety of diet-dependent metabolic, immune and gastrointestinal alterations, which may explain the higher prevalence of obesity and immune-related gastrointestinal disorders among shift workers. PMID:25329803

  7. Dietary proanthocyanidins modulate BMAL1 acetylation, Nampt expression and NAD levels in rat liver.

    PubMed

    Ribas-Latre, Aleix; Baselga-Escudero, Laura; Casanova, Ester; Arola-Arnal, Anna; Salvadó, M-Josepa; Bladé, Cinta; Arola, Lluís

    2015-01-01

    Metabolism follows circadian rhythms, which are driven by peripheral clocks. Clock genes in the liver are entrained by daytime meals and food components. Proanthocyanidins (PAs), the most abundant flavonoids in the human diet, modulate lipid and glucose metabolism. The aim of this study was to determine whether PAs could adjust the clock system in the liver. Male Wistar rats were orally gavaged with 250?mg grape seed proanthocyanidin extract (GSPE)/kg body weight at zeitgeber time (ZT) 0 (light turned on), at ZT12 (light turned off), or before a 6?hour jet-lag and sacrificed at different times. The 24?hour rhythm of clock-core and clock-controlled gene expression indicated that nicotinamide phosphoribosyltransferase (Nampt) was the most sensitive gene to GSPE. However, Nampt was repressed or overexpressed after GSPE administration at ZT0 or ZT12, respectively. NAD levels, which are controlled by Nampt and also exhibit circadian rhythm, decreased or increased according to Nampt expression. Moreover, the ratio of acetylated Bmal1, that directly drives Nampt expression, only increased when GSPE was administered at ZT12. Therefore, GSPE modulated the clock system in the liver, suggesting that PAs can regulate lipid and glucose metabolism by adjusting the circadian rhythm in the liver. PMID:26051626

  8. Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock.

    PubMed

    DiTacchio, Luciano; Le, Hiep D; Vollmers, Christopher; Hatori, Megumi; Witcher, Michael; Secombe, Julie; Panda, Satchidananda

    2011-09-30

    In animals, circadian oscillators are based on a transcription-translation circuit that revolves around the transcription factors CLOCK and BMAL1. We found that the JumonjiC (JmjC) and ARID domain-containing histone lysine demethylase 1a (JARID1a) formed a complex with CLOCK-BMAL1, which was recruited to the Per2 promoter. JARID1a increased histone acetylation by inhibiting histone deacetylase 1 function and enhanced transcription by CLOCK-BMAL1 in a demethylase-independent manner. Depletion of JARID1a in mammalian cells reduced Per promoter histone acetylation, dampened expression of canonical circadian genes, and shortened the period of circadian rhythms. Drosophila lines with reduced expression of the Jarid1a homolog, lid, had lowered Per expression and similarly altered circadian rhythms. JARID1a thus has a nonredundant role in circadian oscillator function. PMID:21960634

  9. Effect of Resveratrol, a SIRT1 Activator, on the Interactions of the CLOCK/BMAL1 Complex

    PubMed Central

    Park, Insung; Lee, Yool; Kim, Hee-Dae

    2014-01-01

    Background In mammals, the CLOCK/BMAL1 heterodimer is a key transcription factor complex that drives the cyclic expression of clock-controlled genes involved in various physiological functions and behavioral consequences. Recently, a growing number of studies have reported a molecular link between the circadian clock and metabolism. In the present study, we explored the regulatory effects of SIRTUIN1 (SIRT1), an NAD+-dependent deacetylase, on CLOCK/BMAL1-mediated clock gene expression. Methods To investigate the interaction between SIRT1 and CLOCK/BMAL1, we conducted bimolecular fluorescence complementation (BiFC) analyses supplemented with immunocytochemistry assays. BiFC experiments employing deletion-specific mutants of BMAL1 were used to elucidate the specific domains that are necessary for the SIRT1-BMAL1 interaction. Additionally, luciferase reporter assays were used to delineate the effects of SIRT1 on circadian gene expression. Results BiFC analysis revealed that SIRT1 interacted with both CLOCK and BMAL1 in most cell nuclei. As revealed by BiFC assays using various BMAL1 deletion mutants, the PAS-B domain of BMAL1 was essential for interaction with SIRT1. Activation of SIRT1 with resveratrol did not exert any significant change on the interaction with the CLOCK/BMAL1 complex. However, promoter analysis using Per1-Luc and Ebox-Luc reporters showed that SIRT1 significantly downregulated both promoter activities. This inhibitory effect was intensified by treatment with resveratrol, indicating a role for SIRT1 and its activator in CLOCK/BMAL1-mediated transcription of clock genes. Conclusion These results suggest that SIRT1 may form a regulatory complex with CLOCK/BMAL1 that represses clock gene expression, probably via deacetylase activity. PMID:25309798

  10. A positive feedback loop links circadian clock factor CLOCK-BMAL1 to the basic transcriptional machinery

    PubMed Central

    Lande-Diner, Laura; Boyault, Cyril; Kim, Jin Young; Weitz, Charles J.

    2013-01-01

    Circadian clocks in mammals are built on a negative feedback loop in which the heterodimeric transcription factor circadian locomotor output cycles kaput (CLOCK)-brain, muscle Arnt-like 1 (BMAL1) drives the expression of its own inhibitors, the PERIOD and CRYPTOCHROME proteins. Reactivation of CLOCK-BMAL1 occurs at a specific time several hours after PERIOD and CRYPTOCHROME protein turnover, but the mechanism underlying this process is unknown. We found that mouse BMAL1 complexes include TRAP150 (thyroid hormone receptor-associated protein-150; also known as THRAP3). TRAP150 is a selective coactivator for CLOCK-BMAL1, which oscillates under CLOCK-BMAL1 transcriptional control. TRAP150 promotes CLOCK-BMAL1 binding to target genes and links CLOCK-BMAL1 to the transcriptional machinery at target-gene promoters. Depletion of TRAP150 caused low-amplitude, long-period rhythms, identifying it as a positive clock element. The activity of TRAP150 defines a positive feedback loop within the clock and provides a potential mechanism for timing the reactivation of circadian transcription. PMID:24043798

  11. Influence of aging on Bmal1 and Per2 expression in extra-SCN oscillators in hamster brain.

    PubMed

    Duncan, Marilyn J; Prochot, Jeffrey R; Cook, Daniel H; Tyler Smith, J; Franklin, Kathleen M

    2013-01-23

    Deletion of the core clock gene, Bmal1, ablates circadian rhythms and accelerates aging, leading to cognitive deficits and tissue atrophy (e.g., skeletal muscle) (Kondratov et al., 2006, Kondratova et al., 2010). Although normal aging has been shown to attenuate Bmal1 expression in the master circadian pacemaker in the suprachiasmatic nucleus (SCN), relatively little is known about age-related changes in Bmal1 expression in other tissues, where Bmal1 may have multiple functions. This study tested the hypothesis that aging reduces Bmal1 expression in extra-SCN oscillators including brain substrates for memory and in skeletal muscle. Brains and gastrocnemius muscles were collected from young (3-5 months) and old hamsters (17-21 months) euthanized at four times of day. Bmal1 mRNA expression was determined by conducting in situ hybridization on brain sections or real-time PCR on muscle samples. The results showed age-related attenuation of Bmal1 expression in many brain regions, and included loss of diurnal rhythms in the hippocampal CA2 and CA3 subfields, but no change in muscle. In situ hybridization for Per2 mRNA was also conducted and showed age-related reduction of diurnal rhythm amplitude selectively in the hippocampal CA1 and DG subfields. In conclusion, aging has tissue-dependent effects on Bmal1 expression in extra-SCN oscillators. These finding on normal aging will provide a reference for comparing potential changes in Bmal1 and Per2 expression in age-related pathologies. In conjunction with previous reports, the results suggest the possibility that attenuation of clock gene expression in some brain regions (the hippocampus, cingulate cortex and SCN) may contribute to age-related cognitive deficits. PMID:23159832

  12. Palmitate Inhibits SIRT1-Dependent BMAL1/CLOCK Interaction and Disrupts Circadian Gene Oscillations in Hepatocytes

    PubMed Central

    Tong, Xin; Zhang, Deqiang; Arthurs, Blake; Li, Pei; Durudogan, Leigh; Gupta, Neil; Yin, Lei

    2015-01-01

    Elevated levels of serum saturated fatty acid palmitate have been shown to promote insulin resistance, increase cellular ROS production, and trigger cell apoptosis in hepatocytes during the development of obesity. However, it remains unclear whether palmitate directly impacts the circadian clock in hepatocytes, which coordinates nutritional inputs and hormonal signaling with downstream metabolic outputs. Here we presented evidence that the molecular clock is a novel target of palmitate in hepatocytes. Palmitate exposure at low dose inhibits the molecular clock activity and suppresses the cyclic expression of circadian targets including Dbp, Nr1d1 and Per2 in hepatocytes. Palmitate treatment does not seem to alter localization or reduce protein expression of BMAL1 and CLOCK, the two core components of the molecular clock in hepatocytes. Instead, palmitate destabilizes the protein-protein interaction between BMAL1-CLOCK in a dose and time-dependent manner. Furthermore, we showed that SIRT1 activators could reverse the inhibitory action of palmitate on BMAL1-CLOCK interaction and the clock gene expression, whereas inhibitors of NAD synthesis mimic the palmitate effects on the clock function. In summary, our findings demonstrated that palmitate inhibits the clock function by suppressing SIRT1 function in hepatocytes. PMID:26075729

  13. Dual modes of CLOCK:BMAL1 inhibition mediated by Cryptochrome and Period proteins in the mammalian circadian clock

    PubMed Central

    Ye, Rui; Selby, Cristopher P.; Chiou, Yi-Ying; Ozkan-Dagliyan, Irem; Gaddameedhi, Shobhan

    2014-01-01

    The mammalian circadian clock is based on a transcription–translation feedback loop (TTFL) in which CLOCK and BMAL1 proteins act as transcriptional activators of Cryptochrome and Period genes, which encode proteins that repress CLOCK–BMAL1 with a periodicity of ?24 h. In this model, the mechanistic roles of CRY and PER are unclear. Here, we used a controlled targeting system to introduce CRY1 or PER2 into the nuclei of mouse cells with defined circadian genotypes to characterize the functions of CRY and PER. Our data show that CRY is the primary repressor in the TTFL: It binds to CLOCK–BMAL1 at the promoter and inhibits CLOCK–BMAL1-dependent transcription without dissociating the complex (“blocking”-type repression). PER alone has no effect on CLOCK–BMAL1-activated transcription. However, in the presence of CRY, nuclear entry of PER inhibits transcription by displacing CLOCK–BMAL1 from the promoter (“displacement”-type repression). In light of these findings, we propose a new model for the mammalian circadian clock in which the negative arm of the TTFL proceeds by two different mechanisms during the circadian cycle. PMID:25228643

  14. 2,2,2-Trichloroethanol lengthens the circadian period of Bmal1-driven circadian bioluminescence rhythms in U2OS cells.

    PubMed

    Gao, Jie; Yang, Caixia; Ding, Hui; Zhang, Yanli; Xue, Jinhua; Cai, Yanning

    2015-07-01

    2,2,2-Trichloroethanol (TCOH) is responsible for the pharmacological actions of chloral hydrate (CH), and is a major metabolite of trichloroethylene. Human exposure to TCOH is known to be increasing. Recently, it was reported that TCOH causes a significant phase delay of Per2 expression in mouse liver when injected daily over the course of several days. However, it is not clear whether TCOH directly modulates the molecular clock. In the present study we used a cell-based assay system to test this possibility. We found that the daily oscillation period of Bmal1 was lengthened to 3 h following treatment with 1.5 mM TCOH, and increased to 5 h with 3 mM TCOH treatment. However, low concentrations of TCOH had no noticeable effects. The effect of TCOH on Per2 oscillation was marginal. Interestingly, serum from rats anesthetized with CH also modulated Bmal1 period, suggesting that exposure to anesthesia should be taken into consideration for circadian rhythm studies. In summary, our study reveals a direct regulation of TCOH on molecular clock. PMID:25956065

  15. Dynamical mechanism of Bmal 1 / Rev- erb? loop in circadian clock

    NASA Astrophysics Data System (ADS)

    Li, Ying; Liu, Zengrong

    2015-07-01

    In mammals, the circadian clock is driven by multiple integrated transcriptional feedback loops involving three kinds of central clock-controlled elements (CCEs): E-boxes, D-boxes and ROR-elements. With the aid of CCEs, the concentrations of the active proteins are approximated by the delayed concentrations of mRNAs, which simplifies the circadian system drastically. The regulatory loop composed by BMAL1 and REV-ERB- ? plays important roles in circadian clock. With delay differential equations, we gave a mathematical model of this loop and investigated its dynamical mechanisms. Specially, we theoretically provided the sufficient conditions for sustained oscillation of the loop with Hopf bifurcation theory. The total of delays determines the emergence of oscillators, which explains the crucial roles of delays in circadian clock revealed by biological experiments. Numerically, we studied the amplitude and period against the variations of delays and the degradation rates. The different sensitivities of amplitude and period on these factors provide ideas to adjust the amplitude or period of circadian oscillators.

  16. A meeting of two chronobiological systems: circadian proteins Period1 and BMAL1 modulate the human hair cycle clock.

    PubMed

    Al-Nuaimi, Yusur; Hardman, Jonathan A; Bíró, Tamás; Haslam, Iain S; Philpott, Michael P; Tóth, Balázs I; Farjo, Nilofer; Farjo, Bessam; Baier, Gerold; Watson, Rachel E B; Grimaldi, Benedetto; Kloepper, Jennifer E; Paus, Ralf

    2014-03-01

    The hair follicle (HF) is a continuously remodeled mini organ that cycles between growth (anagen), regression (catagen), and relative quiescence (telogen). As the anagen-to-catagen transformation of microdissected human scalp HFs can be observed in organ culture, it permits the study of the unknown controls of autonomous, rhythmic tissue remodeling of the HF, which intersects developmental, chronobiological, and growth-regulatory mechanisms. The hypothesis that the peripheral clock system is involved in hair cycle control, i.e., the anagen-to-catagen transformation, was tested. Here we show that in the absence of central clock influences, isolated, organ-cultured human HFs show circadian changes in the gene and protein expression of core clock genes (CLOCK, BMAL1, and Period1) and clock-controlled genes (c-Myc, NR1D1, and CDKN1A), with Period1 expression being hair cycle dependent. Knockdown of either BMAL1 or Period1 in human anagen HFs significantly prolonged anagen. This provides evidence that peripheral core clock genes modulate human HF cycling and are an integral component of the human hair cycle clock. Specifically, our study identifies BMAL1 and Period1 as potential therapeutic targets for modulating human hair growth. PMID:24005054

  17. Bmal1 and Beta cell clock are required for adaptation to circadian disruption, and their loss of function leads to oxidative stress-induced Beta cell failure in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian disruption has deleterious effects on metabolism. Global deletion of Bmal1, a core clock gene, results in Beta cell dysfunction and diabetes. However, it is unknown if this is due to loss of cell-autonomous function of Bmal1 in Beta cells. To address this, we generated mice with Beta cell ...

  18. Functional and structural analyses of cryptochrome. Vertebrate CRY regions responsible for interaction with the CLOCK:BMAL1 heterodimer and its nuclear localization.

    PubMed

    Hirayama, Jun; Nakamura, Haruki; Ishikawa, Tomoko; Kobayashi, Yuri; Todo, Takeshi

    2003-09-12

    Mouse mCRY1 and zebrafish zCRY1a and zCRY3 belong to the DNA photolyase/Cryptochrome family. mCRY1 and zCRY1a repress CLOCK:BMAL1-mediated transcription, whereas zCRY3 does not. Reciprocal chimeras between zCRY1a and zCRY3 were generated to determine the zCRY1a regions responsible for nuclear translocation, interaction with the CLOCK:BMAL1 heterodimer, and repression of CLOCK:BMAL1-mediated transcription. Three regions, RD-2a-(126-196), RD-1-(197-263), and RD-2b-(264-293), were identified. Proteins in this family consist of an N-terminal alpha/beta domain and a C-terminal helical domain connected by an interdomain loop. RD-2a is within this loop, RD-1 is at the N-terminal 50 amino acids, and RD-2b at the following 31 amino acid residues of the helical domain. Either RD-2a or RD-1 is required for interaction with the CLOCK: BMAL1 heterodimer, and either RD-1 or RD-2b is required for the nuclear translocation of CRY. Both of these functions are prerequisites for the transcriptional repressor activity. The functional nuclear localizing signal in the RD-2b region also was identified. The sequence is well conserved among repressor-type CRYs, including mCRY1. Mutations in the nuclear localizing signal of mCRY1 reduce the extent of its nuclear localization. These findings show that both nuclear localization and interaction with the CLOCK:BMAL heterodimer are essential for transcriptional repression by CRY. PMID:12832412

  19. The effect of new monochromatic light regimes on egg production and expression of the circadian gene BMAL1 in pigeons1.

    PubMed

    Wang, Y; Ding, J T; Yang, H M; Cao, W; Li, Y B

    2015-05-01

    We examined the effect of monochromatic light supplementation on pigeon reproductive performance and on the expression of the brain and muscle aryl hydrocarbon receptor nuclear translocator-like (BMAL1) protein in the hypothalamic-pituitary-gonadal (HPG) axis. White King pigeons were selected randomly from 4 lofts (510 pairs/loft) with 3 subgroups/loft. The lofts were exposed to one of 4 light treatments for 3 months administered in the morning and evening as follows: blue light (480 nm), green light (540 nm), red light (660 nm), and control white light. The laying rate, fertility rate, and birth rate were recorded. After 3 months, 48 birds were selected randomly from the 4 lofts (6 females and 6 males from each loft), sacrificed, and the HPG axis was isolated. Following exposure to red light, laying rate was greater than the control group (P = 0.013), but there were no significant differences in the fertility rate (P = 0.41) or birth rate (P = 0.66). Expression of BMAL1 in the hypothalamus was unaffected by the light regime but was greater in the pituitary of females exposed to red light (P = 0.046) and in the pituitary of males exposed to the control white light (P = 0.059). The change in BMAL1 expression in the pituitary of females was negatively correlated with birth rate in monochromatic light (P = 0.021). We suggest that reproductive performance of pigeons is improved by light supplementation in the morning and evening. According to these data, 100 pigeons exposed to red light could lay 26.68 more eggs per month than the control group. Additionally, BMAL1 expression in the HPG axis of pigeons exposed to monochromatic light correlated with birth rate. PMID:25701204

  20. Circadian Proteins CLOCK and BMAL1 in the Chromatoid Body, a RNA Processing Granule of Male Germ Cells

    Microsoft Academic Search

    Rita L. Peruquetti; Sara de Mateo; Paolo Sassone-Corsi

    2012-01-01

    Spermatogenesis is a complex differentiation process that involves genetic and epigenetic regulation, sophisticated hormonal control, and extensive structural changes in male germ cells. RNA nuclear and cytoplasmic bodies appear to be critical for the progress of spermatogenesis. The chromatoid body (CB) is a cytoplasmic organelle playing an important role in RNA post-transcriptional and translation regulation during the late steps of

  1. Circadian Proteins CLOCK and BMAL1 in the Chromatoid Body, a RNA Processing Granule of Male Germ Cells

    E-print Network

    Peruquetti, Rita L; de Mateo, Sara; Sassone-Corsi, Paolo; Tora, Laszlo

    2012-01-01

    cells seem to play important roles during the gametogenesis process [cells, is characterized by a number of unique and remarkable features. This processprocess that involves genetic and epigenetic regulation, sophisticated hormonal control, and extensive structural changes in male germ cells.

  2. Regulation of Circadian Behavior and Metabolism by Rev-erb? and Rev-erb?

    PubMed Central

    Cho, Han; Zhao, Xuan; Hatori, Megumi; Yu, Ruth T.; Barish, Grant D.; Lam, Michael T.; Chong, Ling-Wa; DiTacchio, Luciano; Atkins, Annette R.; Glass, Christopher K.; Liddle, Christopher; Auwerx, Johan; Downes, Michael; Panda, Satchidananda; Evans, Ronald M.

    2012-01-01

    The circadian clock acts at the genomic level to coordinate internal behavioral and physiologic rhythms via the CLOCK-BMAL transcriptional heterodimer. Although the nuclear receptors REV-ERB? and ? have been proposed to form an accessory feedback loop that contributes to clock function1,2, their precise roles and importance remain unresolved. To establish their regulatory potential we generated comparative cistromes of both REV-ERB isoforms, which revealed shared recognition at over 50% of their total sites and extensive overlap with the master circadian regulator BMAL1. While Rev-erb? has been shown to directly regulate Bmal1 expression1,2, the cistromic analysis reveals a direct connection between Bmal1 and Rev-erb? and ? regulatory circuits than previously suspected. Genes within the intersection of the BMAL1, REV-ERB? and REV-ERB? cistromes are highly enriched for both clock and metabolic functions. As predicted by the cistromic analysis, dual depletion of Rev-erb?/? function by creating double-knockout mice (DKOs) profoundly disrupted circadian expression of core circadian clock and lipid homeostatic gene networks. As a result, DKOs show strikingly altered circadian wheel-running behavior and deregulated lipid metabolism. These data now ally Rev-erb?/? with Per, Cry and other components of the principal feedback loop that drives circadian expression and suggest a more integral mechanism for the coordination of circadian rhythm and metabolism. PMID:22460952

  3. JNK regulates the photic response of the mammalian circadian clock.

    PubMed

    Yoshitane, Hikari; Honma, Sato; Imamura, Kiyomichi; Nakajima, Hiroto; Nishide, Shin-ya; Ono, Daisuke; Kiyota, Hiroshi; Shinozaki, Naoya; Matsuki, Hirokazu; Wada, Naoya; Doi, Hirofumi; Hamada, Toshiyuki; Honma, Ken-ichi; Fukada, Yoshitaka

    2012-05-01

    The posttranslational regulation of mammalian clock proteins has been assigned a time-keeping function, but seems to have more essential roles. Here we show that c-Jun N-terminal kinase (JNK), identified by inhibitor screening of BMAL1 phosphorylation at Ser 520/Thr 527/Ser 592, confers dynamic regulation on the clock. Knockdown of JNK1 and JNK2 abrogates BMAL1 phosphorylation and lengthens circadian period in fibroblasts. Mice deficient for neuron-specific isoform JNK3 have altered behavioural rhythms, with longer free-running period and compromised phase shifts to light. The locomotor rhythms are insensitive to intensity variance of constant light, deviating from Aschoff's rule. Thus, JNK regulates a core characteristic of the circadian clock by controlling the oscillation speed and the phase in response to light. PMID:22441692

  4. Opposing actions of Per1 and Cry2 in the regulation of Per1 target gene expression in the liver and kidney

    PubMed Central

    Richards, Jacob; All, Sean; Skopis, George; Cheng, Kit-Yan; Compton, Brandy; Srialluri, Nitya; Stow, Lisa; Jeffers, Lauren A.

    2013-01-01

    Mounting evidence suggests that the circadian clock plays an integral role in the regulation of many physiological processes including blood pressure, renal function, and metabolism. The canonical molecular clock functions via activation of circadian target genes by Clock/Bmal1 and repression of Clock/Bmal1 activity by Per1–3 and Cry1/2. However, we have previously shown that Per1 activates genes important for renal sodium reabsorption, which contradicts the canonical role of Per1 as a repressor. Moreover, Per1 knockout (KO) mice exhibit a lowered blood pressure and heavier body weight phenotype similar to Clock KO mice, and opposite that of Cry1/2 KO mice. Recent work has highlighted the potential role of Per1 in repression of Cry2. Therefore, we postulated that Per1 potentially activates target genes through a Cry2-Clock/Bmal1-dependent mechanism, in which Per1 antagonizes Cry2, preventing its repression of Clock/Bmal1. This hypothesis was tested in vitro and in vivo. The Per1 target genes ?ENaC and Fxyd5 were identified as Clock targets in mpkCCDc14 cells, a model of the renal cortical collecting duct. We identified PPAR? and DEC1 as novel Per1 targets in the mouse hepatocyte cell line, AML12, and in the liver in vivo. Per1 knockdown resulted in upregulation of Cry2 in vitro, and this result was confirmed in vivo in mice with reduced expression of Per1. Importantly, siRNA-mediated knockdown of Cry2 and Per1 demonstrated opposing actions for Cry2 and Per1 on Per1 target genes, supporting the potential Cry2-Clock/Bmal1-dependent mechanism underlying Per1 action in the liver and kidney. PMID:23824961

  5. Opposing actions of Per1 and Cry2 in the regulation of Per1 target gene expression in the liver and kidney.

    PubMed

    Richards, Jacob; All, Sean; Skopis, George; Cheng, Kit-Yan; Compton, Brandy; Srialluri, Nitya; Stow, Lisa; Jeffers, Lauren A; Gumz, Michelle L

    2013-10-01

    Mounting evidence suggests that the circadian clock plays an integral role in the regulation of many physiological processes including blood pressure, renal function, and metabolism. The canonical molecular clock functions via activation of circadian target genes by Clock/Bmal1 and repression of Clock/Bmal1 activity by Per1-3 and Cry1/2. However, we have previously shown that Per1 activates genes important for renal sodium reabsorption, which contradicts the canonical role of Per1 as a repressor. Moreover, Per1 knockout (KO) mice exhibit a lowered blood pressure and heavier body weight phenotype similar to Clock KO mice, and opposite that of Cry1/2 KO mice. Recent work has highlighted the potential role of Per1 in repression of Cry2. Therefore, we postulated that Per1 potentially activates target genes through a Cry2-Clock/Bmal1-dependent mechanism, in which Per1 antagonizes Cry2, preventing its repression of Clock/Bmal1. This hypothesis was tested in vitro and in vivo. The Per1 target genes ?ENaC and Fxyd5 were identified as Clock targets in mpkCCDc14 cells, a model of the renal cortical collecting duct. We identified PPAR? and DEC1 as novel Per1 targets in the mouse hepatocyte cell line, AML12, and in the liver in vivo. Per1 knockdown resulted in upregulation of Cry2 in vitro, and this result was confirmed in vivo in mice with reduced expression of Per1. Importantly, siRNA-mediated knockdown of Cry2 and Per1 demonstrated opposing actions for Cry2 and Per1 on Per1 target genes, supporting the potential Cry2-Clock/Bmal1-dependent mechanism underlying Per1 action in the liver and kidney. PMID:23824961

  6. Genetic interaction of Per1 and Dec1/2 in the regulation of circadian locomotor activity.

    PubMed

    Bode, Brid; Shahmoradi, Ali; Taneja, Reshma; Rossner, Moritz J; Oster, Henrik

    2011-12-01

    In mammals, 24-h rhythms are controlled by a hierarchical system of endogenous clocks, with a circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus that synchronizes peripheral oscillators throughout the body. The molecular clock machinery is regulated by interlocked transcriptional translational feedback loops (TTLs). The core TTL includes the transcriptional modulators PER (1-3) and CRY (1/2) that feed back on their own expression by interaction with CLOCK/BMAL1. An accessory loop involving the transcription factors DEC1 and DEC2 has been described that also impinges on CLOCK/BMAL1-mediated transactivation. In Drosophila, the DEC ortholog CWO shows synergistic activity to PER. This prompted the authors to analyze PER1-DEC interaction in the mammalian SCN. They generated Per1/Dec double and triple mutant mice to monitor activity rhythms under entrained and free-running conditions. Furthermore, they analyzed expression of the clock genes Per2, Rev-Erb?, and Bmal1 in wild-type and Per1/Dec mutant SCN by in situ hybridization. The experiments reveal a critical role for Per1-Dec interaction in regulating activity phase under entrained conditions. In constant darkness, a synergistic function for Per1 and Dec1/2 in period regulation was found, correlating with disrupted clock gene mRNA levels in the SCN. Luciferase reporter gene assays indicate an activatory function of DECs on Bmal1 expression. Together, the results suggest a partially redundant and bidirectional regulatory function for the 2 Dec genes in the TTL and a conservation of Per-Dec (Cwo) synergism between vertebrate and invertebrate clocks. PMID:22215611

  7. Astakine 2—the Dark Knight Linking Melatonin to Circadian Regulation in Crustaceans

    PubMed Central

    Watthanasurorot, Apiruck; Saelee, Netnapa; Phongdara, Amornrat; Roytrakul, Sittiruk; Jiravanichpaisal, Pikul; Söderhäll, Kenneth; Söderhäll, Irene

    2013-01-01

    Daily, circadian rhythms influence essentially all living organisms and affect many physiological processes from sleep and nutrition to immunity. This ability to respond to environmental daily rhythms has been conserved along evolution, and it is found among species from bacteria to mammals. The hematopoietic process of the crayfish Pacifastacus leniusculus is under circadian control and is tightly regulated by astakines, a new family of cytokines sharing a prokineticin (PROK) domain. The expression of AST1 and AST2 are light-dependent, and this suggests an evolutionarily conserved function for PROK domain proteins in mediating circadian rhythms. Vertebrate PROKs are transmitters of circadian rhythms of the suprachiasmatic nucleus (SCN) in the brain of mammals, but the mechanism by which they function is unknown. Here we demonstrate that high AST2 expression is induced by melatonin in the brain. We identify RACK1 as a binding protein of AST2 and further provide evidence that a complex between AST2 and RACK1 functions as a negative-feedback regulator of the circadian clock. By DNA mobility shift assay, we showed that the AST2-RACK1 complex will interfere with the binding between BMAL1 and CLK and inhibit the E-box binding activity of the complex BMAL1-CLK. Finally, we demonstrate by gene knockdown that AST2 is necessary for melatonin-induced inhibition of the complex formation between BMAL1 and CLK during the dark period. In summary, we provide evidence that melatonin regulates AST2 expression and thereby affects the core clock of the crustacean brain. This process may be very important in all animals that have AST2 molecules, i.e. spiders, ticks, crustaceans, scorpions, several insect groups such as Hymenoptera, Hemiptera, and Blattodea, but not Diptera and Coleoptera. Our findings further reveal an ancient evolutionary role for the prokineticin superfamily protein that links melatonin to direct regulation of the core clock gene feedback loops. PMID:23555281

  8. Astakine 2--the dark knight linking melatonin to circadian regulation in crustaceans.

    PubMed

    Watthanasurorot, Apiruck; Saelee, Netnapa; Phongdara, Amornrat; Roytrakul, Sittiruk; Jiravanichpaisal, Pikul; Söderhäll, Kenneth; Söderhäll, Irene

    2013-03-01

    Daily, circadian rhythms influence essentially all living organisms and affect many physiological processes from sleep and nutrition to immunity. This ability to respond to environmental daily rhythms has been conserved along evolution, and it is found among species from bacteria to mammals. The hematopoietic process of the crayfish Pacifastacus leniusculus is under circadian control and is tightly regulated by astakines, a new family of cytokines sharing a prokineticin (PROK) domain. The expression of AST1 and AST2 are light-dependent, and this suggests an evolutionarily conserved function for PROK domain proteins in mediating circadian rhythms. Vertebrate PROKs are transmitters of circadian rhythms of the suprachiasmatic nucleus (SCN) in the brain of mammals, but the mechanism by which they function is unknown. Here we demonstrate that high AST2 expression is induced by melatonin in the brain. We identify RACK1 as a binding protein of AST2 and further provide evidence that a complex between AST2 and RACK1 functions as a negative-feedback regulator of the circadian clock. By DNA mobility shift assay, we showed that the AST2-RACK1 complex will interfere with the binding between BMAL1 and CLK and inhibit the E-box binding activity of the complex BMAL1-CLK. Finally, we demonstrate by gene knockdown that AST2 is necessary for melatonin-induced inhibition of the complex formation between BMAL1 and CLK during the dark period. In summary, we provide evidence that melatonin regulates AST2 expression and thereby affects the core clock of the crustacean brain. This process may be very important in all animals that have AST2 molecules, i.e. spiders, ticks, crustaceans, scorpions, several insect groups such as Hymenoptera, Hemiptera, and Blattodea, but not Diptera and Coleoptera. Our findings further reveal an ancient evolutionary role for the prokineticin superfamily protein that links melatonin to direct regulation of the core clock gene feedback loops. PMID:23555281

  9. p53 Regulates Period2 Expression and the Circadian Clock

    PubMed Central

    Miki, Takao; Matsumoto, Tomoko; Zhao, Zhaoyang; Lee, Cheng Chi

    2013-01-01

    The mechanistic interconnectivity between circadian regulation and the genotoxic stress response remains poorly understood. Here we show that the expression of Period 2 (Per2), a circadian regulator, is directly regulated by p53 binding to a response element in the Per2 promoter. This p53 response element is evolutionarily conserved and overlaps with the E-Box element critical for BMAL1/CLOCK binding and its transcriptional activation of Per2 expression. Our studies reveal that p53 blocks BMAL1/CLOCK binding to the Per2 promoter leading to repression of Per2 expression. In the suprachiasmatic nucleus (SCN), p53 expression and its binding to the Per2 promoter are under circadian control. Per2 expression in the SCN is altered by p53 deficiency or stabilization of p53 by Nutlin-3. Behaviorally, p53?/? mice have a shorter period length that lacks stability and they exhibit impaired photo-entrainment to a light pulse under a free-running state. Our studies demonstrate that p53 modulates mouse circadian behavior. PMID:24051492

  10. Class IIa histone deacetylases are conserved regulators of circadian function.

    PubMed

    Fogg, Paul C M; O'Neill, John S; Dobrzycki, Tomasz; Calvert, Shaun; Lord, Emma C; McIntosh, Rebecca L L; Elliott, Christopher J H; Sweeney, Sean T; Hastings, Michael H; Chawla, Sangeeta

    2014-12-01

    Class IIa histone deacetylases (HDACs) regulate the activity of many transcription factors to influence liver gluconeogenesis and the development of specialized cells, including muscle, neurons, and lymphocytes. Here, we describe a conserved role for class IIa HDACs in sustaining robust circadian behavioral rhythms in Drosophila and cellular rhythms in mammalian cells. In mouse fibroblasts, overexpression of HDAC5 severely disrupts transcriptional rhythms of core clock genes. HDAC5 overexpression decreases BMAL1 acetylation on Lys-537 and pharmacological inhibition of class IIa HDACs increases BMAL1 acetylation. Furthermore, we observe cyclical nucleocytoplasmic shuttling of HDAC5 in mouse fibroblasts that is characteristically circadian. Mutation of the Drosophila homolog HDAC4 impairs locomotor activity rhythms of flies and decreases period mRNA levels. RNAi-mediated knockdown of HDAC4 in Drosophila clock cells also dampens circadian function. Given that the localization of class IIa HDACs is signal-regulated and influenced by Ca(2+) and cAMP signals, our findings offer a mechanism by which extracellular stimuli that generate these signals can feed into the molecular clock machinery. PMID:25271152

  11. Class IIa Histone Deacetylases Are Conserved Regulators of Circadian Function*

    PubMed Central

    Fogg, Paul C. M.; O'Neill, John S.; Dobrzycki, Tomasz; Calvert, Shaun; Lord, Emma C.; McIntosh, Rebecca L. L.; Elliott, Christopher J. H.; Sweeney, Sean T.; Hastings, Michael H.; Chawla, Sangeeta

    2014-01-01

    Class IIa histone deacetylases (HDACs) regulate the activity of many transcription factors to influence liver gluconeogenesis and the development of specialized cells, including muscle, neurons, and lymphocytes. Here, we describe a conserved role for class IIa HDACs in sustaining robust circadian behavioral rhythms in Drosophila and cellular rhythms in mammalian cells. In mouse fibroblasts, overexpression of HDAC5 severely disrupts transcriptional rhythms of core clock genes. HDAC5 overexpression decreases BMAL1 acetylation on Lys-537 and pharmacological inhibition of class IIa HDACs increases BMAL1 acetylation. Furthermore, we observe cyclical nucleocytoplasmic shuttling of HDAC5 in mouse fibroblasts that is characteristically circadian. Mutation of the Drosophila homolog HDAC4 impairs locomotor activity rhythms of flies and decreases period mRNA levels. RNAi-mediated knockdown of HDAC4 in Drosophila clock cells also dampens circadian function. Given that the localization of class IIa HDACs is signal-regulated and influenced by Ca2+ and cAMP signals, our findings offer a mechanism by which extracellular stimuli that generate these signals can feed into the molecular clock machinery. PMID:25271152

  12. p75 Neurotrophin Receptor Is a Clock Gene That Regulates Oscillatory Components of Circadian and Metabolic Networks

    PubMed Central

    Baeza-Raja, Bernat; Eckel-Mahan, Kristin; Zhang, Luoying; Vagena, Eirini; Tsigelny, Igor F.; Sassone-Corsi, Paolo; Ptá?ek, Louis J.

    2013-01-01

    The p75 neurotrophin receptor (p75NTR) is a member of the tumor necrosis factor receptor superfamily with a widespread pattern of expression in tissues such as the brain, liver, lung, and muscle. The mechanisms that regulate p75NTR transcription in the nervous system and its expression in other tissues remain largely unknown. Here we show that p75NTR is an oscillating gene regulated by the helix-loop-helix transcription factors CLOCK and BMAL1. The p75NTR promoter contains evolutionarily conserved noncanonical E-box enhancers. Deletion mutagenesis of the p75NTR-luciferase reporter identified the ?1039 conserved E-box necessary for the regulation of p75NTR by CLOCK and BMAL1. Accordingly, gel-shift assays confirmed the binding of CLOCK and BMAL1 to the p75NTR?1039 E-box. Studies in mice revealed that p75NTR transcription oscillates during dark and light cycles not only in the suprachiasmatic nucleus (SCN), but also in peripheral tissues including the liver. Oscillation of p75NTR is disrupted in Clock-deficient and mutant mice, is E-box dependent, and is in phase with clock genes, such as Per1 and Per2. Intriguingly, p75NTR is required for circadian clock oscillation, since loss of p75NTR alters the circadian oscillation of clock genes in the SCN, liver, and fibroblasts. Consistent with this, Per2::Luc/p75NTR?/? liver explants showed reduced circadian oscillation amplitude compared with those of Per2::Luc/p75NTR+/+. Moreover, deletion of p75NTR also alters the circadian oscillation of glucose and lipid homeostasis genes. Overall, our findings reveal that the transcriptional activation of p75NTR is under circadian regulation in the nervous system and peripheral tissues, and plays an important role in the maintenance of clock and metabolic gene oscillation. PMID:23785138

  13. Nascent-Seq reveals novel features of mouse circadian transcriptional regulation

    PubMed Central

    Menet, Jerome S; Rodriguez, Joseph; Abruzzi, Katharine C; Rosbash, Michael

    2012-01-01

    A substantial fraction of the metazoan transcriptome undergoes circadian oscillations in many cells and tissues. Based on the transcription feedback loops important for circadian timekeeping, it is commonly assumed that this mRNA cycling reflects widespread transcriptional regulation. To address this issue, we directly measured the circadian dynamics of mouse liver transcription using Nascent-Seq (genome-wide sequencing of nascent RNA). Although many genes are rhythmically transcribed, many rhythmic mRNAs manifest poor transcriptional rhythms, indicating a prominent contribution of post-transcriptional regulation to circadian mRNA expression. This analysis of rhythmic transcription also showed that the rhythmic DNA binding profile of the transcription factors CLOCK and BMAL1 does not determine the transcriptional phase of most target genes. This likely reflects gene-specific collaborations of CLK:BMAL1 with other transcription factors. These insights from Nascent-Seq indicate that it should have broad applicability to many other gene expression regulatory issues. DOI: http://dx.doi.org/10.7554/eLife.00011.001 PMID:23150795

  14. Transcriptional Regulation via Nuclear Receptor Crosstalk Required for the Drosophila Circadian Clock.

    PubMed

    Jaumouillé, Edouard; Machado Almeida, Pedro; Stähli, Patrick; Koch, Rafael; Nagoshi, Emi

    2015-06-01

    Circadian clocks in large part rely on transcriptional feedback loops. At the core of the clock machinery, the transcriptional activators CLOCK/BMAL1 (in mammals) and CLOCK/CYCLE (CLK/CYC) (in Drosophila) drive the expression of the period (per) family genes. The PER-containing complexes inhibit the activity of CLOCK/BMAL1 or CLK/CYC, thereby forming a negative feedback loop [1]. In mammals, the ROR and REV-ERB family nuclear receptors add positive and negative transcriptional regulation to this core negative feedback loop to ensure the generation of robust circadian molecular oscillation [2]. Despite the overall similarities between mammalian and Drosophila clocks, whether comparable mechanisms via nuclear receptors are required for the Drosophila clock remains unknown. We show here that the nuclear receptor E75, the fly homolog of REV-ERB ? and REV-ERB ?, and the NR2E3 subfamily nuclear receptor UNF are components of the molecular clocks in the Drosophila pacemaker neurons. In vivo assays in conjunction with the in vitro experiments demonstrate that E75 and UNF bind to per regulatory sequences and act together to enhance the CLK/CYC-mediated transcription of the per gene, thereby completing the core transcriptional feedback loop necessary for the free-running clockwork. Our results identify a missing link in the Drosophila clock and highlight the significance of the transcriptional regulation via nuclear receptors in metazoan circadian clocks. PMID:26004759

  15. Transcriptional Regulation via Nuclear Receptor Crosstalk Required for the Drosophila Circadian Clock

    PubMed Central

    Jaumouillé, Edouard; Machado Almeida, Pedro; Stähli, Patrick; Koch, Rafael; Nagoshi, Emi

    2015-01-01

    Summary Circadian clocks in large part rely on transcriptional feedback loops. At the core of the clock machinery, the transcriptional activators CLOCK/BMAL1 (in mammals) and CLOCK/CYCLE (CLK/CYC) (in Drosophila) drive the expression of the period (per) family genes. The PER-containing complexes inhibit the activity of CLOCK/BMAL1 or CLK/CYC, thereby forming a negative feedback loop [1]. In mammals, the ROR and REV-ERB family nuclear receptors add positive and negative transcriptional regulation to this core negative feedback loop to ensure the generation of robust circadian molecular oscillation [2]. Despite the overall similarities between mammalian and Drosophila clocks, whether comparable mechanisms via nuclear receptors are required for the Drosophila clock remains unknown. We show here that the nuclear receptor E75, the fly homolog of REV-ERB ? and REV-ERB ?, and the NR2E3 subfamily nuclear receptor UNF are components of the molecular clocks in the Drosophila pacemaker neurons. In vivo assays in conjunction with the in vitro experiments demonstrate that E75 and UNF bind to per regulatory sequences and act together to enhance the CLK/CYC-mediated transcription of the per gene, thereby completing the core transcriptional feedback loop necessary for the free-running clockwork. Our results identify a missing link in the Drosophila clock and highlight the significance of the transcriptional regulation via nuclear receptors in metazoan circadian clocks. PMID:26004759

  16. The RelB subunit of NF?B acts as a negative regulator of circadian gene expression.

    PubMed

    Bellet, Marina M; Zocchi, Loredana; Sassone-Corsi, Paolo

    2012-09-01

    The circadian system controls a large array of physiological and metabolic functions. The molecular organization of the circadian clock is complex, involving various elements organized in feedback regulatory loops. Here we demonstrate that the RelB subunit of NF?B acts as a repressor of circadian transcription. RelB physically interacts with the circadian activator BMAL1 in the presence of CLOCK to repress circadian gene expression at the promoter of the clock-controlled gene Dbp. The repression is independent of the circadian negative regulator CRY. Notably, RelB -/- fibroblasts have profound alterations of circadian genes expression. These findings reveal a previously unforeseen function for RelB as an important regulator of the mammalian circadian system in fibroblasts. PMID:22894897

  17. The RelB subunit of NF?B acts as a negative regulator of circadian gene expression

    PubMed Central

    Bellet, Marina M.; Zocchi, Loredana; Sassone-Corsi, Paolo

    2012-01-01

    The circadian system controls a large array of physiological and metabolic functions. The molecular organization of the circadian clock is complex, involving various elements organized in feedback regulatory loops. Here we demonstrate that the RelB subunit of NF?B acts as a repressor of circadian transcription. RelB physically interacts with the circadian activator BMAL1 in the presence of CLOCK to repress circadian gene expression at the promoter of the clock-controlled gene Dbp. The repression is independent of the circadian negative regulator CRY. Notably, RelB ?/? fibroblasts have profound alterations of circadian genes expression. These findings reveal a previously unforeseen function for RelB as an important regulator of the mammalian circadian system in fibroblasts. PMID:22894897

  18. Regulation of period 1 expression in cultured rat pineal

    NASA Technical Reports Server (NTRS)

    Fukuhara, Chiaki; Dirden, James C.; Tosini, Gianluca

    2002-01-01

    The aim of the present study was to investigate the in vitro expression of Period 1 (Per1), Period 2 (Per2) and arylalkylamine N-acetyltransferase (AA-NAT) genes in the rat pineal gland to understand the mechanism(s) regulating the expression of these genes in this organ. Pineals, when maintained in vitro for 5 days, did not show circadian rhythmicity in the expression of any of the three genes monitored. Norepinephrine (NE) induced AA-NAT and Per1, whereas its effect on Per2 was negligible. Contrary to what was observed in other systems, NE stimulation did not induce circadian expression of Per1. The effect of NE on Per1 level was dose- and receptor subtype-dependent, and both cAMP and cGMP induced Per1. Per1 was not induced by repeated NE - or forskolin - stimulation. Protein synthesis was not necessary for NE-induced Per1, but it was for reduction of Per1 following NE stimulation. Per1 transcription in pinealocytes was activated by BMAL1/CLOCK. Our results indicate that important differences are present in the regulation of these genes in the mammalian pineal. Copyright 2002 S. Karger AG, Basel.

  19. CLOCK-Controlled Polyphonic Regulation of Circadian Rhythms through Canonical and Noncanonical E-Boxes

    PubMed Central

    Yoshitane, Hikari; Ozaki, Haruka; Terajima, Hideki; Du, Ngoc-Hien; Suzuki, Yutaka; Fujimori, Taihei; Kosaka, Naoki; Shimba, Shigeki; Sugano, Sumio; Takagi, Toshihisa

    2014-01-01

    In mammalian circadian clockwork, the CLOCK-BMAL1 complex binds to DNA enhancers of target genes and drives circadian oscillation of transcription. Here we identified 7,978 CLOCK-binding sites in mouse liver by chromatin immunoprecipitation-sequencing (ChIP-Seq), and a newly developed bioinformatics method, motif centrality analysis of ChIP-Seq (MOCCS), revealed a genome-wide distribution of previously unappreciated noncanonical E-boxes targeted by CLOCK. In vitro promoter assays showed that CACGNG, CACGTT, and CATG(T/C)G are functional CLOCK-binding motifs. Furthermore, we extensively revealed rhythmically expressed genes by poly(A)-tailed RNA-Seq and identified 1,629 CLOCK target genes within 11,926 genes expressed in the liver. Our analysis also revealed rhythmically expressed genes that have no apparent CLOCK-binding site, indicating the importance of indirect transcriptional and posttranscriptional regulations. Indirect transcriptional regulation is represented by rhythmic expression of CLOCK-regulated transcription factors, such as Krüppel-like factors (KLFs). Indirect posttranscriptional regulation involves rhythmic microRNAs that were identified by small-RNA-Seq. Collectively, CLOCK-dependent direct transactivation through multiple E-boxes and indirect regulations polyphonically orchestrate dynamic circadian outputs. PMID:24591654

  20. Bioinformatics analysis of transcriptional regulation of circadian genes in rat liver

    PubMed Central

    2014-01-01

    Background The circadian clock is a critical regulator of biological functions controlling behavioral, physiological and biochemical processes. Because the liver is the primary regulator of metabolites within the mammalian body and the disruption of circadian rhythms in liver is associated with severe illness, circadian regulators would play a strong role in maintaining liver function. However, the regulatory structure that governs circadian dynamics within the liver at a transcriptional level remains unknown. To explore this aspect, we analyzed hepatic transcriptional dynamics in Sprague-Dawley rats over a period of 24 hours to assess the genome-wide responses. Results Using an unsupervised consensus clustering method, we identified four major gene expression clusters, corresponding to central carbon and nitrogen metabolism, membrane integrity, immune function, and DNA repair, all of which have dynamics which suggest regulation in a circadian manner. With the assumption that transcription factors (TFs) that are differentially expressed and contain CLOCK:BMAL1 binding sites on their proximal promoters are likely to be clock-controlled TFs, we were able to use promoter analysis to putatively identify additional clock-controlled TFs besides PARF and RORA families. These TFs are both functionally and temporally related to the clusters they regulate. Furthermore, we also identified significant sets of clock TFs that are potentially transcriptional regulators of gene clusters. Conclusions All together, we were able to propose a regulatory structure for circadian regulation which represents alternative paths for circadian control of different functions within the liver. Our prediction has been affirmed by functional and temporal analyses which are able to extend for similar studies. PMID:24666587

  1. Regulation of clock-controlled genes in mammals.

    PubMed

    Bozek, Katarzyna; Relógio, Angela; Kielbasa, Szymon M; Heine, Markus; Dame, Christof; Kramer, Achim; Herzel, Hanspeter

    2009-01-01

    The complexity of tissue- and day time-specific regulation of thousands of clock-controlled genes (CCGs) suggests that many regulatory mechanisms contribute to the transcriptional output of the circadian clock. We aim to predict these mechanisms using a large scale promoter analysis of CCGs.Our study is based on a meta-analysis of DNA-array data from rodent tissues. We searched in the promoter regions of 2065 CCGs for highly overrepresented transcription factor binding sites. In order to compensate the relatively high GC-content of CCG promoters, a novel background model to avoid a bias towards GC-rich motifs was employed. We found that many of the transcription factors with overrepresented binding sites in CCG promoters exhibit themselves circadian rhythms. Among the predicted factors are known regulators such as CLOCKratioBMAL1, DBP, HLF, E4BP4, CREB, RORalpha and the recently described regulators HSF1, STAT3, SP1 and HNF-4alpha. As additional promising candidates of circadian transcriptional regulators PAX-4, C/EBP, EVI-1, IRF, E2F, AP-1, HIF-1 and NF-Y were identified. Moreover, GC-rich motifs (SP1, EGR, ZF5, AP-2, WT1, NRF-1) and AT-rich motifs (MEF-2, HMGIY, HNF-1, OCT-1) are significantly overrepresented in promoter regions of CCGs. Putative tissue-specific binding sites such as HNF-3 for liver, NKX2.5 for heart or Myogenin for skeletal muscle were found. The regulation of the erythropoietin (Epo) gene was analysed, which exhibits many binding sites for circadian regulators. We provide experimental evidence for its circadian regulated expression in the adult murine kidney. Basing on a comprehensive literature search we integrate our predictions into a regulatory network of core clock and clock-controlled genes. Our large scale analysis of the CCG promoters reveals the complexity and extensiveness of the circadian regulation in mammals. Results of this study point to connections of the circadian clock to other functional systems including metabolism, endocrine regulation and pharmacokinetics. PMID:19287494

  2. Regulation of Clock-Controlled Genes in Mammals

    PubMed Central

    Kielbasa, Szymon M.; Heine, Markus; Dame, Christof; Kramer, Achim; Herzel, Hanspeter

    2009-01-01

    The complexity of tissue- and day time-specific regulation of thousands of clock-controlled genes (CCGs) suggests that many regulatory mechanisms contribute to the transcriptional output of the circadian clock. We aim to predict these mechanisms using a large scale promoter analysis of CCGs. Our study is based on a meta-analysis of DNA-array data from rodent tissues. We searched in the promoter regions of 2065 CCGs for highly overrepresented transcription factor binding sites. In order to compensate the relatively high GC-content of CCG promoters, a novel background model to avoid a bias towards GC-rich motifs was employed. We found that many of the transcription factors with overrepresented binding sites in CCG promoters exhibit themselves circadian rhythms. Among the predicted factors are known regulators such as CLOCK?BMAL1, DBP, HLF, E4BP4, CREB, ROR? and the recently described regulators HSF1, STAT3, SP1 and HNF-4?. As additional promising candidates of circadian transcriptional regulators PAX-4, C/EBP, EVI-1, IRF, E2F, AP-1, HIF-1 and NF-Y were identified. Moreover, GC-rich motifs (SP1, EGR, ZF5, AP-2, WT1, NRF-1) and AT-rich motifs (MEF-2, HMGIY, HNF-1, OCT-1) are significantly overrepresented in promoter regions of CCGs. Putative tissue-specific binding sites such as HNF-3 for liver, NKX2.5 for heart or Myogenin for skeletal muscle were found. The regulation of the erythropoietin (Epo) gene was analysed, which exhibits many binding sites for circadian regulators. We provide experimental evidence for its circadian regulated expression in the adult murine kidney. Basing on a comprehensive literature search we integrate our predictions into a regulatory network of core clock and clock-controlled genes. Our large scale analysis of the CCG promoters reveals the complexity and extensiveness of the circadian regulation in mammals. Results of this study point to connections of the circadian clock to other functional systems including metabolism, endocrine regulation and pharmacokinetics. PMID:19287494

  3. Gene Model 129 (Gm129) Encodes a Novel Transcriptional Repressor That Modulates Circadian Gene Expression*

    PubMed Central

    Annayev, Yunus; Adar, Sheera; Chiou, Yi-Ying; Lieb, Jason D.; Sancar, Aziz; Ye, Rui

    2014-01-01

    The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK·BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK·BMAL1·CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized protein that directly interacts with BMAL1 and represses CLOCK·BMAL1 activity. In vitro and in vivo protein-DNA interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK·BMAL1 complex on DNA. Although Gm129?/? or Cry1?/? Gm129?/? mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit a significant phase delay compared with control. Our results suggest that, in addition to CRYs and PERs, the GM129 protein contributes to the transcriptional feedback loop by modulating CLOCK·BMAL1 activity as a transcriptional repressor. PMID:24385426

  4. Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion.

    PubMed

    Chatterjee, Somik; Yin, Hongshan; Nam, Deokhwa; Li, Yong; Ma, Ke

    2015-02-01

    Circadian clock is an evolutionarily conserved timing mechanism governing diverse biological processes and the skeletal muscle possesses intrinsic functional clocks. Interestingly, although the essential clock transcription activator, Brain and muscle Arnt-like 1 (Bmal1), participates in maintenance of muscle mass, little is known regarding its role in muscle growth and repair. In this report, we investigate the in vivo function of Bmal1 in skeletal muscle regeneration using two muscle injury models. Bmal1 is highly up-regulated by cardiotoxin injury, and its genetic ablation significantly impairs regeneration with markedly suppressed new myofiber formation and attenuated myogenic induction. A similarly defective regenerative response is observed in Bmal1-null mice as compared to wild-type controls upon freeze injury. Lack of satellite cell expansion accounts for the regeneration defect, as Bmal1(-/-) mice display significantly lower satellite cell number with nearly abolished induction of the satellite cell marker, Pax7. Furthermore, satellite cell-derived primary myoblasts devoid of Bmal1 display reduced growth and proliferation ex vivo. Collectively, our results demonstrate, for the first time, that Bmal1 is an integral component of the pro-myogenic response that is required for muscle repair. This mechanism may underlie its role in preserving adult muscle mass and could be targeted therapeutically to prevent muscle-wasting diseases. PMID:25218946

  5. [Molecular oscillatory machinery of circadian rhythms].

    PubMed

    Yamaguchi, Yoshiaki; Okamura, Hitoshi

    2012-07-01

    Many metabolic and physiological processes display daily rhythms oscillated by the internal circadian clock system. This rhythm is generated by interlocked transcription-(post) translation feedback loops of clock genes: the core oscillatory loop, being composed of CLOCK/BMAL1 heterodimer activating the expressions of PER and CRY that directly repress CLOCK/BMAL1, is accompanied by accessory loops consisted with REV-ERB nuclear receptor repressing Bmal1 or with DBP competing with E4BP4 on D-box site. These clock proteins are regulated by phosphorylation and ubiquitination (PER/CRY), and acetylation (CLOCK/BMAL1). Recently, a deacetylating protein SIRT1 mediated metabolic pathway is discovered to be interlocked with core oscillatory loop via Nampt expression, a late-limiting enzyme in NAD+ salvage pathway. Since many key-step enzymes of metabolisms are regulated by the circadian clock, circadian clock system may intimately link to cellular metabolism. PMID:22844791

  6. Clock-controlled output gene Dbp is a regulator of Arnt/Hif-1? gene expression in pancreatic islet ?-cells

    SciTech Connect

    Nakabayashi, Hiroko; Ohta, Yasuharu, E-mail: yohta@yamaguchi-u.ac.jp; Yamamoto, Masayoshi; Susuki, Yosuke; Taguchi, Akihiko; Tanabe, Katsuya; Kondo, Manabu; Hatanaka, Masayuki; Nagao, Yuko; Tanizawa, Yukio, E-mail: tanizawa@yamaguchi-u.ac.jp

    2013-05-03

    Highlights: •Arnt mRNA expressed in a circadian manner in mouse pancreatic islets. •Expressions of Dbp and Arnt damped in the islets of a diabetic model mouse. •DBP and E4BP4 regulate Arnt promoter activity by direct binding. •Arnt may have a role in connecting circadian rhythm and metabolism. -- Abstract: Aryl hydrocarbon receptor nuclear translocator (ARNT)/hypoxia inducible factor-1? (HIF-1?) has emerged as a potential determinant of pancreatic ?-cell dysfunction and type 2 diabetes in humans. An 82% reduction in Arnt expression was observed in islets from type 2 diabetic donors as compared to non-diabetic donors. However, few regulators of Arnt expression have been identified. Meanwhile, disruption of the clock components CLOCK and BMAL1 is known to result in hypoinsulinemia and diabetes, but the molecular details remain unclear. In this study, we identified a novel molecular connection between Arnt and two clock-controlled output genes, albumin D-element binding protein (Dbp) and E4 binding protein 4 (E4bp4). By conducting gene expression studies using the islets of Wfs1{sup ?/?} A{sup y}/a mice that develop severe diabetes due to ?-cell apoptosis, we demonstrated clock-related gene expressions to be altered in the diabetic mice. Dbp mRNA decreased by 50%, E4bp4 mRNA increased by 50%, and Arnt mRNA decreased by 30% at Zeitgever Time (ZT) 12. Mouse pancreatic islets exhibited oscillations of clock gene expressions. E4BP4, a D-box negative regulator, oscillated anti-phase to DBP, a D-box positive regulator. We also found low-amplitude circadian expression of Arnt mRNA, which peaked at ZT4. Over-expression of DBP raised both mRNA and protein levels of ARNT in HEK293 and MIN6 cell lines. Arnt promoter-driven luciferase reporter assay in MIN6 cells revealed that DBP increased Arnt promoter activity by 2.5-fold and that E4BP4 competitively inhibited its activation. In addition, on ChIP assay, DBP and E4BP4 directly bound to D-box elements within the Arnt promoter in MIN6 cells. These results suggest that in mouse pancreatic islets mRNA expression of Arnt fluctuates significantly in a circadian manner and that the down-regulation of Dbp and up-regulation E4bp4 contribute to direct suppression of Arnt expression in diabetes.

  7. SRC-2 Is an Essential Coactivator for Orchestrating Metabolism and Circadian Rhythm

    PubMed Central

    Stashi, Erin; Lanz, Rainer B.; Mao, Jianqiang; Michailidis, George; Zhu, Bokai; Kettner, Nicole M.; Putluri, Nagireddy; Reineke, Erin L.; Reineke, Lucas C.; Dasgupta, Subhamoy; Dean, Adam; Stevenson, Connor R.; Sivasubramanian, Natarajan; Sreekumar, Arun; DeMayo, Francesco; York, Brian; Fu, Loning; O'Malley, Bert W.

    2014-01-01

    SUMMARY Synchrony of the mammalian circadian clock is achieved by complex transcriptional and translational feedback loops centered on the BMAL1: CLOCK heterodimer. Modulation of circadian feedback loops is essential for maintaining rhythmicity, yet the role of transcriptional coactivators in driving BMAL1:CLOCK transcriptional networks is largely unexplored. Here, we show diurnal hepatic steroid receptor coactivator 2 (SRC-2) recruitment to the genome that extensively overlaps with the BMAL1 cistrome during the light phase, targeting genes that enrich for circadian and metabolic processes. Notably, SRC-2 ablation impairs wheel-running behavior, alters circadian gene expression in several peripheral tissues, alters the rhythmicity of the hepatic metabolome, and deregulates the synchronization of cell-autonomous metabolites. We identify SRC-2 as a potent coregulator of BMAL1:CLOCK and find that SRC-2 targets itself with BMAL1:CLOCK in a feedforward loop. Collectively, our data suggest that SRC-2 is a transcriptional coactivator of the BMAL1:CLOCK oscillators and establish SRC-2 as a critical positive regulator of the mammalian circa-dian clock. PMID:24529706

  8. Library Regulations Library Regulations

    E-print Network

    Birmingham, University of

    REGULATIONS Preamble: The Library Regulations apply to all users of library facilities managed on behalf by the Director of Library Services. All use of computing and network facilities within those facilities managed-13 Library Regulations `Service' is deemed to include any system whereby Library Services provides access

  9. Regulation XVI: GENERAL UNIVERSITY REGULATIONS

    E-print Network

    Regulation XVI: GENERAL UNIVERSITY REGULATIONS APPLICATION AND INTERPRETATION 1. Unless stated otherwise, these and the following Regulations apply to students in all Faculties, including the International Faculty: General Regulations for First Degrees; General Regulations for Higher Degrees

  10. 1 University Regulations UNIVERSITY REGULATIONS

    E-print Network

    Vertes, Akos

    1 University Regulations UNIVERSITY REGULATIONS Students enrolled in the University are required to conform to the following regulations and to comply with the requirements and regulations of the school only under the regulations and requirements in force at the time of return. If a student knowingly

  11. Sleep and Circadian Rhythm Regulation in Early Parkinson Disease

    PubMed Central

    Nawarathna, Upekshani; Fisher, Kate; Shneerson, John M.; Reddy, Akhilesh B.; Barker, Roger A.

    2014-01-01

    IMPORTANCE Sleep disturbances are recognized as a common nonmotor complaint in Parkinson disease but their etiology is poorly understood. OBJECTIVE To define the sleep and circadian phenotype of patients with early-stage Parkinson disease. DESIGN, SETTING, AND PARTICIPANTS Initial assessment of sleep characteristics in a large population-representative incident Parkinson disease cohort (N=239) at the University of Cambridge, England, followed by further comprehensive case-control sleep assessments in a subgroup of these patients (n=30) and matched controls (n=15). MAIN OUTCOMES AND MEASURES Sleep diagnoses and sleep architecture based on polysomnography studies, actigraphy assessment, and 24-hour analyses of serum cortisol, melatonin, and peripheral clock gene expression (Bmal1, Per2, and Rev-Erb?). RESULTS Subjective sleep complaints were present in almost half of newly diagnosed patients and correlated significantly with poorer quality of life. Patients with Parkinson disease exhibited increased sleep latency (P = .04), reduced sleep efficiency (P = .008), and reduced rapid eye movement sleep (P = .02). In addition, there was a sustained elevation of serum cortisol levels, reduced circulating melatonin levels, and altered Bmal1 expression in patients with Parkinson disease compared with controls. CONCLUSIONS AND RELEVANCE Sleep dysfunction seen in early Parkinson disease may reflect a more fundamental pathology in the molecular clock underlying circadian rhythms. PMID:24687146

  12. [Dyslipidemia induced disorder of circadian rhythm].

    PubMed

    Shimba, Shigeki

    2013-12-01

    Several epidemiological studies have suggested that the perturbation of circadian rhythm has adverse metabolic consequences (e.g., dyslipidemia) in humans. At the molecular level, circadian rhythms are encoded by an autoregulatory loop composed of a set of transcription activators (BMAL1/CLOCK) that induce expression of repressors (PER/CRY). The mammalian molecular clock is not only expressed within the master suprachiasmatic nucleus pacemaker neurons, but also within nearly all cells. In addition to this core loop, BMAL1/CLOCK also induce expression of the orphan nuclear hormone receptor, which modulates Bmal1 transcription. Disruption of clock genes results in metabolic deregulation in mice. In this article, the roles of clock genes in the regulation of metabolism were summarized based on the phenotypes of the knockout mice. PMID:24437265

  13. [The roles of clock genes in obesity].

    PubMed

    Shimba, Shigeki

    2013-02-01

    Several epidemiological studies have suggested that the perturbation of circadian rhythm has adverse metabolic consequences (e.g., obesity) in humans. At the molecular level, circadian rhythms are encoded by an autoregulatory loop composed of a set of transcription activators (BMAL1/CLOCK) that induce expression of repressors (PER/CRY). The mammalian molecular clock is not only expressed within the master suprachiasmatic nucleus pacemaker neurons, but also within nearly all cells. In addition to this core loop, BMAL1/CLOCK also induce expression of the orphan nuclear hormone receptor, which modulates Bmal1 transcription. Disruption of clock genes results in metabolic dysregulation in mice. In this article, the roles of clock genes in the regulation of metabolism were summarized based on the phenotypes of the knockout mice. PMID:23631200

  14. Biotechnology regulation

    SciTech Connect

    Not Available

    1985-01-01

    Testimony and hearings in support of biotechnology regulation. Before The Subcommittee On Oversight And Investigations Of The Committee On Energy And Commerce House Of Representatives are presented. Special consideration is given to the regulation of genetic engineering.

  15. The adipocyte clock controls brown adipogenesis through the TGF-Beta and BMP signaling pathways

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The molecular clock is intimately linked to metabolic regulation, and brown adipose tissue plays a key role in energy homeostasis. However, whether the cell-intrinsic clock machinery participates in brown adipocyte development is unknown. Here, we show that Bmal1 (also known as ARNTL), the essential...

  16. Roles of CLOCK phosphorylation in suppression of E-box-dependent transcription.

    PubMed

    Yoshitane, Hikari; Takao, Toshifumi; Satomi, Yoshinori; Du, Ngoc-Hien; Okano, Toshiyuki; Fukada, Yoshitaka

    2009-07-01

    In mammalian circadian clockwork, the CLOCK-BMAL1 heterodimer activates E-box-dependent transcription, while its activity is suppressed by circadian binding with negative regulators, such as CRYs. Here, we found that the CLOCK protein is kept mostly in the phosphorylated form throughout the day and is partly hyperphosphorylated in the suppression phase of E-box-dependent transcription in the mouse liver and NIH 3T3 cells. Coexpression of CRY2 in NIH 3T3 cells inhibited the phosphorylation of CLOCK, whereas CIPC coexpression markedly stimulated phosphorylation, indicating that CLOCK phosphorylation is regulated by a combination of the negative regulators in the suppression phase. CLOCK-BMAL1 purified from the mouse liver was subjected to tandem mass spectrometry analysis, which identified Ser38, Ser42, and Ser427 as in vivo phosphorylation sites of CLOCK. Ser38Asp and Ser42Asp mutations of CLOCK additively and markedly weakened the transactivation activity of CLOCK-BMAL1, with downregulation of the nuclear amount of CLOCK and the DNA-binding activity. On the other hand, CLOCK Delta 19, lacking the CIPC-binding domain, was far less phosphorylated and much more stabilized than wild-type CLOCK in vivo. Calyculin A treatment of cultured NIH 3T3 cells promoted CLOCK phosphorylation and facilitated its proteasomal degradation. Together, these results show that CLOCK phosphorylation contributes to the suppression of CLOCK-BMAL1-mediated transactivation through dual regulation: inhibition of CLOCK activity and promotion of its degradation. PMID:19414601

  17. Regulation XVII: GENERAL REGULATIONS FOR FIRST DEGREES

    E-print Network

    Regulation XVII: GENERAL REGULATIONS FOR FIRST DEGREES SCOPE OF THESE REGULATIONS4 1. These Regulations apply, subject to any different provision in the Regulations for a particular programme of study programme of study is designated as a non-modular programme, Regulation 14 and subsequent Regulations

  18. Regulations & Policies Regulations & Policies for Undergraduates

    E-print Network

    Howie, Jim

    Regulations & Policies Regulations & Policies for Undergraduates If you are arriving with these regulations if they are relevant to you. They can be downloaded from: www.hw.ac.uk/ordinances/regulations.pdf General Regulation Regulation 1 Modular First Degrees Regulation 3 Degree of Bachelor in Combined

  19. Gene Regulation

    NSDL National Science Digital Library

    Robert Frederick (AAAS; )

    2008-03-28

    In this video introduction, Perspective author John Mattick, Stephen Buratowski, and Science editor Guy Riddihough discuss the new and increasing understanding of how RNA regulates DNA, and how RNA may have been the original molecule of life.

  20. Government Regulation

    E-print Network

    Ashford, Nicholas

    2005-01-01

    Abstract. Interest in the use of so-called voluntary approaches to supplement or replace formal environmental regulation is on the rise, both in Europe and in the United States. These approaches fall into two general ...

  1. Circadian clock components in the rat neocortex: daily dynamics, localization and regulation.

    PubMed

    Rath, Martin F; Rohde, Kristian; Fahrenkrug, Jan; Møller, Morten

    2013-03-01

    The circadian master clock of the mammalian brain resides in the suprachiasmatic nucleus (SCN) of the hypothalamus. At the molecular level, the clock of the SCN is driven by a transcriptional/posttranslational autoregulatory network with clock gene products as core elements. Recent investigations have shown the presence of peripheral clocks in extra-hypothalamic areas of the central nervous system. However, knowledge on the clock gene network in the cerebral cortex is limited. We here show that the mammalian clock genes Per1, Per2, Per3, Cry1, Cry2, Bmal1, Clock, Nr1d1 and Dbp are expressed in the rat neocortex. Among these, Per1, Per2, Per3, Cry1, Bmal1, Nr1d1 and Dbp were found to exhibit daily rhythms. The amplitude of circadian oscillation in neocortical clock gene expression was damped and the peak delayed as compared with the SCN. Lesions of the SCN revealed that rhythmic clock gene expression in the neocortex is dependent on the SCN. In situ hybridization and immunohistochemistry showed that products of the canonical clock gene Per2 are located in perikarya throughout all areas of the neocortex. These findings show that local circadian oscillators driven by the SCN reside within neurons of the neocortex. PMID:22527123

  2. THESIS MANUAL UNIVERSITY REGULATIONS

    E-print Network

    de Lijser, Peter

    THESIS MANUAL UNIVERSITY REGULATIONS AND FORMAT GUIDELINES Revised Summer 2012 Published..................................................................................................................................1 University Regulations

  3. THESIS MANUAL UNIVERSITY REGULATIONS

    E-print Network

    de Lijser, Peter

    THESIS MANUAL UNIVERSITY REGULATIONS AND FORMAT GUIDELINES Revised Spring 2013 Published..................................................................................................................................1 University Regulations

  4. Regulation 29: Other Regulations concerning the University site and buildings, Computing Regulations and Miscellaneous Administrative Regulations

    E-print Network

    Sussex, University of

    Regulation 29: Other Regulations concerning the University site and buildings, Computing Regulations and Miscellaneous Administrative Regulations 190 nuisance to occupants, except in designated (Vehicle Operators and Penalty Notices) Regulations; (iii) allow smoking in designated study bedrooms

  5. Regulation XVIII: GENERAL REGULATIONS FOR HIGHER DEGREES,

    E-print Network

    Regulation XVIII: GENERAL REGULATIONS FOR HIGHER DEGREES, POSTGRADUATE DIPLOMAS AND POSTGRADUATE CERTIFICATES SCOPE OF THESE REGULATIONS 1. These Regulations apply to the Degree of PhD in all Faculties in all Faculties Postgraduate Certificates in all Faculties. 2. These Regulations are subject

  6. Charge regulation circuit

    DOEpatents

    Ball, Don G. (Livermore, CA)

    1992-01-01

    A charge regulation circuit provides regulation of an unregulated voltage supply in the range of 0.01%. The charge regulation circuit is utilized in a preferred embodiment in providing regulated voltage for controlling the operation of a laser.

  7. Modelling regulations Completing an incomplete regulation

    E-print Network

    van der Torre, Leon

    Objectives Modelling regulations Completing an incomplete regulation Examples Discussion Consistency and Completeness of Regulations Laurence Cholvy1 St´ephanie Roussel1,2 1ONERA Centre de Toulouse 2ISAE, Toulouse NorMAS 2008, Luxembourg, July 2008 cholvy Consistency and Completeness of Regulations

  8. Circadian clock, cancer and lipid metabolism

    Microsoft Academic Search

    Norio Ishida

    2007-01-01

    Genetic analysis has revealed that mammalian circadian oscillator is driven by a cell autonomous transcription\\/translation-based negative feedback loop, wherein positive elements (CLOCK and BMAL1) induce the expression of negative regulators (Periods, CRY1 and CRY2) that inhibit the transactivation of positive regulators. Recent research reveals that this clock feedback loop affects many aspects of our physiology, such as cell cycle and

  9. Taxation by Regulation

    Microsoft Academic Search

    Richard A. Posner

    1971-01-01

    Students of the regulated industries often assume that regulation is designed either to approximate the results of competition or to protect the regulated firms from competition. But neither view explains adequately a number of important phenomena of regulation and regulated industries. Foremost among them is the prevalence of \\

  10. Regulations UNIVERSITY OF BIRMINGHAM

    E-print Network

    Birmingham, University of

    Regulations 2013-14 1 UNIVERSITY OF BIRMINGHAM REGULATIONS OF THE UNIVERSITY OF BIRMINGHAM SECTION 8 - STUDENT CONDUCT Executive Brief Sets out the principles and Regulations to be followed in cases;Regulations 2013-14 2 Section 8: Student Conduct 8.1 Introduction 8.1.1 These Regulations apply to all

  11. CIPC is a mammalian circadian clock protein without invertebrate homologues.

    PubMed

    Zhao, Wen-Ning; Malinin, Nikolay; Yang, Fu-Chia; Staknis, David; Gekakis, Nicholas; Maier, Bert; Reischl, Silke; Kramer, Achim; Weitz, Charles J

    2007-03-01

    At the core of the mammalian circadian clock is a feedback loop in which the heterodimeric transcription factor CLOCK-Brain, Muscle Arnt-like-1 (BMAL1) drives expression of its negative regulators, periods (PERs) and cryptochromes (CRYs). Here, we provide evidence that CLOCK-Interacting Protein, Circadian (CIPC) is an additional negative-feedback regulator of the circadian clock. CIPC exhibits circadian regulation in multiple tissues, and it is a potent and specific inhibitor of CLOCK-BMAL1 activity that functions independently of CRYs. CIPC-CLOCK protein complexes are present in vivo, and depletion of endogenous CIPC shortens the circadian period length. CIPC is unrelated to known proteins and has no recognizable homologues outside vertebrates. Our results suggest that negative feedback in the mammalian circadian clock is divided into distinct pathways, and that the addition of new genes has contributed to the complexity of vertebrate clocks. PMID:17310242

  12. Regulation 28: Library REGULATION 28: LIBRARY

    E-print Network

    Sussex, University of

    consideration. 16. The Library is a public building. Do not leave personal belongings unattended at any time. WeRegulation 28: Library 180 REGULATION 28: LIBRARY The purpose of this Regulation is to safeguard the common interests of all Library users. All persons are admitted on the understanding that they have read

  13. MicroRNA 22 Regulates Cell Cycle Length in Cerebellar Granular Neuron Precursors

    PubMed Central

    Berenguer, Jordi; Herrera, Antonio; Vuolo, Laura; Torroba, Blanca; Llorens, Franc; Sumoy, Lauro

    2013-01-01

    During cerebellum development, Sonic hedgehog (Shh)-induced proliferation of cerebellar granular neuronal precursors (CGNPs) is potently inhibited by bone morphogenetic proteins (BMPs). We have previously reported the upregulation of TIEG-1 and Mash1, two antimitotic factors that modulate MYCN transcription and N-Myc activity, in response to BMP2. To gain further insight into the BMP antimitotic mechanism, we used microRNA (miRNA) arrays to compare the miRNAs of CGNPs proliferating in response to Shh with those of CGNPs treated with Shh plus BMP2. The array analysis revealed that miRNA 11 (miR-22) levels significantly increased in cells treated with BMP2. Additionally, in P7 mouse cerebellum, miR-22 distribution mostly recapitulated the combination of BMP2 and BMP4 expression patterns. Accordingly, in CGNP cultures, miR-22 overexpression significantly reduced cell proliferation, whereas miR-22 suppression diminished BMP2 antiproliferative activity. In contrast to BMP2, miR-22 did not induce neural differentiation but instead significantly increased cell cycle length. Consistent with the central role played by N-myc on CGNP proliferation, Max was revealed as a direct target of miR-22, and miR-22 expression caused a significant reduction of Max protein levels and N-myc/Max-dependent promoter activity. Therefore, we conclude that, in addition to the previously described mechanisms, miR-22 plays a specific role on downstream BMPs through cerebellum growth. PMID:23671190

  14. Multimedia regulated chemicals

    SciTech Connect

    Lee, C.C.; Huffman, G.L. [Environmental Protection Agency, Cincinnati, OH (United States). National Risk Management Research Lab.; Mao, Y.L. [Soochow Univ., Taipei (Taiwan, Province of China). Dept. of Chemistry

    1999-10-01

    This article examines those chemicals that are listed in either environmental laws or regulations. Its objective is to help readers determine which laws regulate what types of chemicals and which types of chemicals are regulated by what laws. It is multimedia in scope, describing the various chemicals that are regulated in the different media (i.e., air, water, or land).

  15. State Licensing and Regulation Information

    MedlinePLUS

    ... State Licensing and Regulation Information State Licensing and Regulation Information States are contacted at least twice per ... on state below to view state information. Alabama Regulations Read More Alaska Regulations Read More Arizona Regulations ...

  16. Fragile X-Related Proteins Regulate Mammalian Circadian Behavioral Rhythms

    PubMed Central

    Zhang, Jing; Fang, Zhe; Jud, Corinne; Vansteensel, Mariska J.; Kaasik, Krista; Lee, Cheng Chi; Albrecht, Urs; Tamanini, Filippo; Meijer, Johanna H.; Oostra, Ben A.; Nelson, David L.

    2008-01-01

    Fragile X syndrome results from the absence of the fragile X mental retardation 1 (FMR1) gene product (FMRP). FMR1 has two paralogs in vertebrates: fragile X related gene 1 and 2 (FXR1 and FXR2). Here we show that Fmr1/Fxr2 double knockout (KO) and Fmr1 KO/Fxr2 heterozygous animals exhibit a loss of rhythmic activity in a light:dark (LD) cycle, and that Fmr1 or Fxr2 KO mice display a shorter free-running period of locomotor activity in total darkness (DD). Molecular analysis and in vitro electrophysiological studies suggest essentially normal function of cells in the suprachiasmatic nucleus (SCN) in Fmr1/Fxr2 double KO mice. However, the cyclical patterns of abundance of several core clock component messenger (m) RNAs are altered in the livers of double KO mice. Furthermore, FXR2P alone or FMRP and FXR2P together can increase PER1- or PER2-mediated BMAL1-Neuronal PAS2 (NPAS2) transcriptional activity in a dose-dependent manner. These data collectively demonstrate that FMR1 and FXR2 are required for the presence of rhythmic circadian behavior in mammals and suggest that this role may be relevant to sleep and other behavioral alterations observed in fragile X patients. PMID:18589395

  17. The NAD +Dependent Deacetylase SIRT1 Modulates CLOCK-Mediated Chromatin Remodeling and Circadian Control

    Microsoft Academic Search

    Yasukazu Nakahata; Milota Kaluzova; Benedetto Grimaldi; Saurabh Sahar; Jun Hirayama; Danica Chen; Leonard P. Guarente; Paolo Sassone-Corsi

    2008-01-01

    SUMMARY Circadian rhythms govern a large array of metabolic and physiological functions. The central clock protein CLOCK has HAT properties. It directs acety- lation of histone H3 and of its dimerization partner BMAL1 at Lys537, an event essential for circadian function. We show that the HDAC activity of the NAD+-dependent SIRT1 enzyme is regulated in a cir- cadian manner, correlating

  18. Profiling of Circadian Genes Expressed in the Uterus Endometrial Stromal Cells of Pregnant Rats as Revealed by DNA Microarray Coupled with RNA Interference

    PubMed Central

    Tasaki, Hirotaka; Zhao, Lijia; Isayama, Keishiro; Chen, Huatao; Nobuhiko Yamauchi; Yasufumi Shigeyoshi; Hashimoto, Seiichi; Hattori, Masa-aki

    2013-01-01

    The peripheral circadian oscillator plays an essential role in synchronizing local physiology to operate in a circadian manner via regulation of the expression of clock-controlled genes. The present study aimed to evaluate the circadian rhythms of clock genes and clock-controlled genes expressed in the rat uterus endometrial stromal cells (UESCs) during the stage of implantation by a DNA microarray. Of 12,252 genes showing significantly expression, 7,235 genes displayed significant alterations. As revealed by the biological pathway analysis using the database for annotation, visualization, and integrated discovery online annotation software, genes were involved in cell cycle, glutathione metabolism, MAPK signaling pathway, fatty acid metabolism, ubiquitin mediated proteolysis, focal adhesion, and PPAR signaling pathway. The clustering of clock genes were mainly divided into four groups: the first group was Ror?, Timeless, Npas2, Bmal1, Id2, and Cry2; the second group Per1, Per2, Per3, Dec1, Tef, and Dbp; the third group Bmal2, Cry1, E4bp4, Ror?, and Clock; the fourth group Rev-erb?. Eleven implantation-related genes and 24 placenta formation-related genes displayed significant alterations, suggesting that these genes involved in implantation and placenta formation are controlled under circadian clock. Some candidates as clock-controlled genes were evaluated by using RNA interference to Bmal1 mRNA. Down-regulation of Igf1 gene expression was observed by Bmal1 silencing, whereas the expression of Inh?a was significantly increased. During active oscillation of circadian clock, the apoptosis-related genes Fas and Caspase3 remained no significant changes, but they were significantly increased by knockdown of Bmal1 mRNA. These results indicate that clock-controlled genes are up- or down-regulated in rat UESCs during the stage of decidualization. DNA microarray analysis coupled with RNA interference will be helpful to understand the physiological roles of some oscillating genes in blastocyst implantation and placenta formation. PMID:23847593

  19. Regulation and Administered Contracts

    Microsoft Academic Search

    Victor P. Goldberg

    1976-01-01

    This paper explores the ramifications of introducing administered contracts -- long term, collective contractual relationships -- into economic analysis with attention being focused on the implicit regulatory contract. The perspective afforded by the administered contracts framework suggests that the economist's case against regulation has been overstated. Many of the problems associated with regulation lie in what is being regulated, not

  20. Workshop in Regulation &

    E-print Network

    Lin, Xiaodong

    -353-5761 973-353-1348 (fax) #12;10/8/03 ADVANCED WORKSHOP IN REGULATION AND COMPETITION Networking Industries­telecommunications10/8/03 Advanced Workshop in Regulation & Competition 2003-2004 Who Says Network Industries Conference San Diego, California, June 23-25, 2004 CENTER FOR RESEARCH IN REGULATED INDUSTRIES crri

  1. Cyclin dependent kinase regulation

    Microsoft Academic Search

    Emma Lees

    1995-01-01

    Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and their activities are consequently tightly regulated. Recent developments in the field of CDK regulation have included the discovery and characterization of CDK inhibitors. These developments have had an impact on our understanding of how other signalling pathways may be linked to the cell cycle machinery.

  2. Computer Use Regulation Introduction

    E-print Network

    Liu, Paul

    Computer Use Regulation #12;Introduction · The following training materials will reference the contents of the Computer Use Regulations, but should not serve as a substitute for reading the actual responsibilities NCSU employees have under the regulations. · North Carolina State University's computer networks

  3. Price regulation and quality

    Microsoft Academic Search

    Dennis L. Weisman

    2005-01-01

    A growing concern on the part of regulators in the telecommunications and electric power industries is that the adoption of price-cap regulation may weaken incentives for investment in service quality. This analysis reveals that participation by the regulated firm in complementary, competitive markets may serve to temper this incentive. Paradoxically, commonly used revenue-share penalties can (actually) serve to reduce investment

  4. TEACHING AND EXAMINATION REGULATIONS

    E-print Network

    TEACHING AND EXAMINATION REGULATIONS (see Article 7.13 of the Higher Education and Research Act 2013-2014 Page #12;Most important changes in comparison with the teaching and examination regulations - General 4 Article 1 - Areas to which the regulations apply 4 Article 2 - Definitions of terms used 4

  5. TEACHING AND EXAMINATION REGULATIONS

    E-print Network

    TEACHING AND EXAMINATION REGULATIONS (see Article 7.13 ofthe Higher Education and Research Act Engineering 2013-2014 Page #12;Most important ctianges with regard to the teaching and examination regulations - Areas to which the regulations apply 4 Article 2 - Definitions of terms used 4 Article 3 - The programme

  6. California Energy Commission REGULATIONS

    E-print Network

    California Energy Commission REGULATIONS FINAL STATEMENT OF REASONS ENFORCEMENT PROCEDURES of Regulations Title 20, Division 2, Chapter 13, Sections 3200 through 3208, and Chapter 2, Article 4, Section by Government Code section 11346.9(a) for the California Energy Commission (Energy Commission) regulations

  7. Emotion Regulation CONCEPTUAL FOUNDATIONS

    E-print Network

    Gross, James J.

    CHAPTER 1 Emotion Regulation CONCEPTUAL FOUNDATIONS JAMES J. GROSS ROSS A. THOMPSON Standing, paper or plastic are made. Quotidian acts of emotion regulation such as this constitute one important- changes that require us to regulate how emotions are experienced and expressed. But what do people do

  8. 3 Library Regulations Definitions

    E-print Network

    Mottram, Nigel

    3 Library Regulations Definitions In Regulation 3: 'Library' means the University Library as defined in Regulation 3.1; 'Library staff' means the staff of the University Library; 'Librarian' means the University Librarian and Head of Information Resources Directorate or nominee; `Library Committee' means

  9. Intrinsically Disordered Proteins: Regulation and Disease Regulation of IDPs

    E-print Network

    Babu, M. Madan

    31st Jan 2011 Intrinsically Disordered Proteins: Regulation and Disease Regulation of IDPs M. Madan ...........................................................................................................................................................................1 2. The need for regulating IDPs.................................................................................................................................................1 3. General principles of IDP regulation

  10. Load regulating expansion fixture

    DOEpatents

    Wagner, L.M.; Strum, M.J.

    1998-12-15

    A free standing self contained device for bonding ultra thin metallic films, such as 0.001 inch beryllium foils is disclosed. The device will regulate to a predetermined load for solid state bonding when heated to a bonding temperature. The device includes a load regulating feature, whereby the expansion stresses generated for bonding are regulated and self adjusting. The load regulator comprises a pair of friction isolators with a plurality of annealed copper members located therebetween. The device, with the load regulator, will adjust to and maintain a stress level needed to successfully and economically complete a leak tight bond without damaging thin foils or other delicate components. 1 fig.

  11. Load regulating expansion fixture

    DOEpatents

    Wagner, Lawrence M. (San Jose, CA); Strum, Michael J. (San Jose, CA)

    1998-01-01

    A free standing self contained device for bonding ultra thin metallic films, such as 0.001 inch beryllium foils. The device will regulate to a predetermined load for solid state bonding when heated to a bonding temperature. The device includes a load regulating feature, whereby the expansion stresses generated for bonding are regulated and self adjusting. The load regulator comprises a pair of friction isolators with a plurality of annealed copper members located therebetween. The device, with the load regulator, will adjust to and maintain a stress level needed to successfully and economically complete a leak tight bond without damaging thin foils or other delicate components.

  12. Cancer/Testis Antigen PASD1 Silences the Circadian Clock.

    PubMed

    Michael, Alicia K; Harvey, Stacy L; Sammons, Patrick J; Anderson, Amanda P; Kopalle, Hema M; Banham, Alison H; Partch, Carrie L

    2015-06-01

    The circadian clock orchestrates global changes in transcriptional regulation on a daily basis via the bHLH-PAS transcription factor CLOCK:BMAL1. Pathways driven by other bHLH-PAS transcription factors have a homologous repressor that modulates activity on a tissue-specific basis, but none have been identified for CLOCK:BMAL1. We show here that the cancer/testis antigen PASD1 fulfills this role to suppress circadian rhythms. PASD1 is evolutionarily related to CLOCK and interacts with the CLOCK:BMAL1 complex to repress transcriptional activation. Expression of PASD1 is restricted to germline tissues in healthy individuals but can be induced in cells of somatic origin upon oncogenic transformation. Reducing PASD1 in human cancer cells significantly increases the amplitude of transcriptional oscillations to generate more robust circadian rhythms. Our results describe a function for a germline-specific protein in regulation of the circadian clock and provide a molecular link from oncogenic transformation to suppression of circadian rhythms. PMID:25936801

  13. Circadian rhythmicity of active GSK3 isoforms modulates molecular clock gene rhythms in the suprachiasmatic nucleus.

    PubMed

    Besing, Rachel C; Paul, Jodi R; Hablitz, Lauren M; Rogers, Courtney O; Johnson, Russell L; Young, Martin E; Gamble, Karen L

    2015-04-01

    The suprachiasmatic nucleus (SCN) drives and synchronizes daily rhythms at the cellular level via transcriptional-translational feedback loops comprising clock genes such as Bmal1 and Period (Per). Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, phosphorylates at least 5 core clock proteins and shows diurnal variation in phosphorylation state (inactivation) of the GSK3? isoform. Whether phosphorylation of the other primary isoform (GSK3?) varies across the subjective day-night cycle is unknown. The purpose of this study was to determine if the endogenous rhythm of GSK3 (? and ?) phosphorylation is critical for rhythmic BMAL1 expression and normal amplitude and periodicity of the molecular clock in the SCN. Significant circadian rhythmicity of phosphorylated GSK3 (? and ?) was observed in the SCN from wild-type mice housed in constant darkness for 2 weeks. Importantly, chronic activation of both GSK3 isoforms impaired rhythmicity of the GSK3 target BMAL1. Furthermore, chronic pharmacological inhibition of GSK3 with 20 µM CHIR-99021 enhanced the amplitude and shortened the period of PER2::luciferase rhythms in organotypic SCN slice cultures. These results support the model that GSK3 activity status is regulated by the circadian clock and that GSK3 feeds back to regulate the molecular clock amplitude in the SCN. PMID:25724980

  14. Hepcidin: regulation of the master iron regulator

    PubMed Central

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

    2015-01-01

    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:25826005

  15. General Qualification Regulations (Declared Qualifications)

    E-print Network

    Bandara, Arosha

    General Qualification Regulations (Declared Qualifications) Revised July 2012, effective from 1 August 2012 The General Qualification Regulations should not be read in isolation. It is important that you read them in conjunction with the following documents. · Module Regulations · The regulations

  16. Responsibilities Rules and regulations for

    E-print Network

    Johannesson, Henrik

    Rights and Responsibilities Rules and regulations for studies at Göteborg University Ratified.injury.insurance...............................................................................12 Disciplinary.measures.and.suspension.from.studies......12 Regulations ­ Rules and regulations for studies at Göteborg University usually known as Rules and regulations

  17. Pressure reducing regulator

    DOEpatents

    Whitehead, John C. (Davis, CA); Dilgard, Lemoyne W. (Willits, CA)

    1995-01-01

    A pressure reducing regulator that controls its downstream or outlet pressure to a fixed fraction of its upstream or inlet pressure. The regulator includes a housing which may be of a titanium alloy, within which is located a seal or gasket at the outlet end which may be made of annealed copper, a rod, and piston, each of which may be made of high density graphite. The regulator is insensitive to temperature by virtue of being without a spring or gas sealed behind a diaphragm, and provides a reference for a system in which it is being used. The rod and piston of the regulator are constructed, for example, to have a 1/20 ratio such that when the downstream pressure is less than 1/20 of the upstream pressure the regulator opens and when the downstream pressure exceeds 1/20 of the upstream pressure the regulator closes.

  18. Pressure reducing regulator

    DOEpatents

    Whitehead, J.C.; Dilgard, L.W.

    1995-10-10

    A pressure reducing regulator that controls its downstream or outlet pressure to a fixed fraction of its upstream or inlet pressure is disclosed. The regulator includes a housing which may be of a titanium alloy, within which is located a seal or gasket at the outlet end which may be made of annealed copper, a rod, and piston, each of which may be made of high density graphite. The regulator is insensitive to temperature by virtue of being without a spring or gas sealed behind a diaphragm, and provides a reference for a system in which it is being used. The rod and piston of the regulator are constructed, for example, to have a 1/20 ratio such that when the downstream pressure is less than 1/20 of the upstream pressure the regulator opens and when the downstream pressure exceeds 1/20 of the upstream pressure the regulator closes. 10 figs.

  19. Plant Growth Regulation

    NSDL National Science Digital Library

    This page authored by Jim Bidlack, University of Central Oklahoma, based on original activities by Long Ashton Research Station, KScience, Cynthia Herbrandson, Kellogg Community College, Ross Koning, Eastern Connecticut State University, and A.G. Scientific, Inc.

    Plant growth regulators, including auxin, gibberellin, cytokinin, abscisic acid, and ethylene, are investigated in this learning activity to demonstrate how these chemicals (hormones) affect plant growth and development.

  20. Regulation of natural monopolies

    E-print Network

    Joskow, Paul L.

    2005-01-01

    This chapter provides a comprehensive overview of the theoretical and empirical literature on the regulation of natural monopolies. It covers alternative definitions of natural monopoly, regulatory goals, alternative ...

  1. Men and women differ in their diurnal expression of monocyte peroxisome proliferator-activated receptor-? in the fed but not in the fasted state.

    PubMed

    Wege, Nicole; Schutkowski, Alexandra; Boenn, Markus; Bialek, Joanna; Schlitt, Axel; Noack, Frank; Grosse, Ivo; Stangl, Gabriele I

    2015-07-01

    Peroxisome proliferator-activated receptor-? (PPAR?) plays a pivotal role in regulating metabolic response to fasting and is an inhibitor of inflammatory pathways in immune cells. It represents a therapeutic target for treatment of several diseases, mainly hyperlipidemia. To shed light on PPAR? expression changes in response to fasting, young healthy male and female volunteers were fed or fasted for 24 hours. Monocytes were analyzed every 2 hours to compile both profiles of mRNA and protein expression of PPAR? and its interactive partner, the circadian pacemaker brain and muscle aryl hydrocarbon receptor nuclear translocator like-1 (BMAL1). We found that women change their diurnal expression profiles of PPAR? and BMAL1 when switching from the fed to the fasted state, whereas men do not. Interestingly, the PPAR? and BMAL1 profiles of men and women in the fed state are different, whereas the profiles in the fasted state are virtually identical. The finding of diametrically opposite responses of male and female PPAR? expression in the fed state might have practical implication in human medicine as PPAR? activators like fibrates are used for the therapy of chronic lymphocytic leukemia, microvascular complications in diabetes, and kidney diseases.-Wege, N., Schutkowski, A., Boenn, M., Bialek, J., Schlitt, A., Noack, F., Grosse, I., Stangl, G. I. Men and women differ in their diurnal expression of monocyte peroxisome proliferator-activated receptor-? in the fed but not in the fasted state. PMID:25825462

  2. A baculovirus photolyase with DNA repair activity and circadian clock regulatory function.

    PubMed

    Biernat, Magdalena A; Eker, André P M; van Oers, Monique M; Vlak, Just M; van der Horst, Gijsbertus T J; Chaves, Inês

    2012-02-01

    Cryptochromes and photolyases belong to the same family of flavoproteins but, despite being structurally conserved, display distinct functions. Photolyases use visible light to repair ultraviolet-induced DNA damage. Cryptochromes, however, function as blue-light receptors, circadian photoreceptors, or repressors of the CLOCK/BMAL1 heterodimer, the transcription activator controlling the molecular circadian clock. Here, we present evidence that the functional divergence between cryptochromes and photolyases is not so univocal. Chrysodeixis chalcites nucleopolyhedrovirus possesses 2 photolyase-like genes: phr1 and phr2. We show that PHR1 and PHR2 are able to bind the CLOCK protein. Only for PHR2, however, the physical interaction with CLOCK represses CLOCK/BMAL1-driven transcription. This result shows that binding of photolyase per se is not sufficient to inhibit the CLOCK/BMAL1 heterodimer. PHR2, furthermore, affects the oscillation of immortalized mouse embryonic fibroblasts, suggesting that PHR2 can regulate the molecular circadian clock. These findings are relevant for further understanding the evolution of cryptochromes and photolyases as well as behavioral changes induced in insects by baculoviruses. PMID:22306969

  3. Expression of clock genes in patients with colorectal cancer.

    PubMed

    Karantanos, Theodoros; Theodoropoulos, George; Gazouli, Maria; Vaiopoulou, Anna; Karantanou, Christina; Lymberi, Maria; Pektasides, Dimitrios

    2013-05-27

    Recent studies have demonstrated the influence of clock genes in cell cycle regulation, cell proliferation, apoptosis and DNA damage recognition and repair. There is evidence suggesting the implication of clock genes in colorectal cancer (CRC) development and progression. The aim of this study is to evaluate the expression levels of clock genes in CRC and correlate them with patients' prognosis. Forty-two CRC samples (from 24 males and 18 females), their paired noncancerous tissues and 8 biopsies from healthy individuals were included. Quantitative real-time PCR was used to examine the expression levels of CLOCK1, BMAL1, PER1, PER2 and PER3 genes in all the samples. In the cancerous tissues CLOCK1 (p<0.0001) and BMAL1 (p<0.0001) expression levels were higher, while PER1 (p<0.0024) and PER3 (p<0.0001) expression levels were lower compared to matched healthy tissues. No difference was observed in the expression levels of PER2 (p=0.99). No correlation was found between clock gene expression and patients' clinicopathological characteristics or prognosis. The results suggest abnormal expression of CLOCK1, BMAL1, PER1 and PER3 genes in CRC but no correlation with patients' prognosis. PMID:23712462

  4. REGULATION I: Responsibility for Creation and Amendment of Regulations

    E-print Network

    REGULATION I: Responsibility for Creation and Amendment of Regulations 1. In accordance with Article 14 of the Charter, the Council shall have the power to make, amend or repeal Regulations. 2 of the Regulations and the delegation of such power pursuant to Regulation II (7.2) by the Council to Senate

  5. RHUL Research Degree Regulations 2013/14 Research Degree Regulations

    E-print Network

    Sheldon, Nathan D.

    RHUL Research Degree Regulations 2013/14 Research Degree Regulations Programmes of study Period of registration Appendix 1: Regulations Governing the Master by Research programmes Appendix 2: Regulations Governing the Doctor of Clinical Psychology (DClinPsy) Appendix 3: Regulations Governing the Doctorate

  6. Workshop in Regulation &

    E-print Network

    Lin, Xiaodong

    Regulation." Victor Glass, NECA, Comments January 14, 2011 Smart Grid and Regulatory Issues Location: Rutgers Smart Grid and Regulatory Issues April 1, 2011 K&L Gates LLP, 1601 K Street, NW, Washington, DC Viable, The Brattle Group, "Smart Grid/Smart Regulation" John Caldwell, EEI, "Economic Efficiency and the Smart Grid

  7. Health practitioner regulation

    Microsoft Academic Search

    IAN FRECKELTON

    A number of patterns in the regulation of health practitioners can be identified internationally since the early 1990s. This period of time has seen a significant homogenization and globalization in regulation but it has also seen the emergence of complex new trends and difficulties. Significant changes in “consumer culture” and the emergence of the “information age” have engendered new attitudes

  8. Workshop in Regulation &

    E-print Network

    Lin, Xiaodong

    ;10/1/13 ADVANCED WORKSHOP IN REGULATION AND COMPETITION Networking Industries­telecommunications, electricity, gas INDUSTRIES November 30, 2001 The Role of Trading and Financial Instruments in Network Industries (to be held Regulation and Network Industries April 19, 2002 Lessons of Deregulation and Restructuring 21st Annual

  9. Molecular Cell Gene Regulation

    E-print Network

    Collins, James J.

    Molecular Cell Previews Gene Regulation: Hacking the Network on a Sugar High Tom Ellis,1,2 Xiao. The resulting input-function map reveals that gene network regulation follows non-Boolean, and often how its individual parts behave in response to different conditions. In the case of gene networks

  10. The Right to Regulate

    NASA Technical Reports Server (NTRS)

    Vittek, J. F.

    1972-01-01

    An introduction to the historical and constitutional framework of industry regulation by local and Federal Governments is presented. Problems of the confiscation of private property without due process, government control and the rights and duties of the regulated industry are discussed.

  11. Dynamics of price regulation

    Microsoft Academic Search

    Gary Biglaiser; Michael Riordan

    1998-01-01

    We study the dynamics of price regulation for an industry adjusting to exogenous technological progress. First, we characterize the optimal capacity path and replace- ment cycles in a neoclassical investment model. Second, we show that naive rate-of- return regulation, which ignores components of economic depreciation, eventually results in a deficient level of capacity due to excessively high retail prices burdened

  12. Dynamics of Price Regulation

    Microsoft Academic Search

    Gary Biglaiser; Michael Riordan

    2000-01-01

    We study the dynamics of price regulation for an industry adjusting to exogenous technological progress. First, we characterize the optimal capacity path and replacement cycles in a neoclassical investment model. Second, we show that naive rate-of-return regulation, which ignores components of economic depreciation, eventually results in a deficient level of capacity due to excessively high retail prices burdened by the

  13. Pressure regulating valve controller

    Microsoft Academic Search

    1988-01-01

    In an aircraft cabin air conditioning system comprising a pair of air cycle refrigeration systems which provide chilled air to the cabin, airflow through the air cycle refrigeration systems being controllable by a pair of pressure regulating valves, each of the pressure regulating valves being disposed in a corresponding main airflow conduit and operated by a corresponding pneumatic valve actuator,

  14. Regulation XXV: REGULATIONS RELATING TO INTELLECTUAL PROPERTY

    E-print Network

    's programme of study or research. For the avoidance of any doubt, if the student is also an employee for the purposes of education and/or quality assurance. The University will use reasonable endeavours to seek in the University pursuant to these Regulations, the University may exploit it, or any part of it, using reasonable

  15. Melatonin feedback on clock genes: a theory involving the proteasome.

    PubMed

    Vriend, Jerry; Reiter, Russel J

    2015-01-01

    The expression of 'clock' genes occurs in all tissues, but especially in the suprachiasmatic nuclei (SCN) of the hypothalamus, groups of neurons in the brain that regulate circadian rhythms. Melatonin is secreted by the pineal gland in a circadian manner as influenced by the SCN. There is also considerable evidence that melatonin, in turn, acts on the SCN directly influencing the circadian 'clock' mechanisms. The most direct route by which melatonin could reach the SCN would be via the cerebrospinal fluid of the third ventricle. Melatonin could also reach the pars tuberalis (PT) of the pituitary, another melatonin-sensitive tissue, via this route. The major 'clock' genes include the period genes, Per1 and Per2, the cryptochrome genes, Cry1 and Cry2, the clock (circadian locomotor output cycles kaput) gene, and the Bmal1 (aryl hydrocarbon receptor nuclear translocator-like) gene. Clock and Bmal1 heterodimers act on E-box components of the promoters of the Per and Cry genes to stimulate transcription. A negative feedback loop between the cryptochrome proteins and the nucleus allows the Cry and Per proteins to regulate their own transcription. A cycle of ubiquitination and deubiquitination controls the levels of CRY protein degraded by the proteasome and, hence, the amount of protein available for feedback. Thus, it provides a post-translational component to the circadian clock mechanism. BMAL1 also stimulates transcription of REV-ERB? and, in turn, is also partially regulated by negative feedback by REV-ERB?. In the 'black widow' model of transcription, proteasomes destroy transcription factors that are needed only for a particular period of time. In the model proposed herein, the interaction of melatonin and the proteasome is required to adjust the SCN clock to changes in the environmental photoperiod. In particular, we predict that melatonin inhibition of the proteasome interferes with negative feedback loops (CRY/PER and REV-ERB?) on Bmal1 transcription genes in both the SCN and PT. Melatonin inhibition of the proteasome would also tend to stabilize BMAL1 protein itself in the SCN, particularly at night when melatonin is naturally elevated. Melatonin inhibition of the proteasome could account for the effects of melatonin on circadian rhythms associated with molecular timing genes. The interaction of melatonin with the proteasome in the hypothalamus also provides a model for explaining the dramatic 'time of day' effect of melatonin injections on reproductive status of seasonal breeders. Finally, the model predicts that a proteasome inhibitor such as bortezomib would modify circadian rhythms in a manner similar to melatonin. PMID:25369242

  16. Pressure regulating valve controller

    SciTech Connect

    Goodman, R.B.

    1988-04-05

    In an aircraft cabin air conditioning system comprising a pair of air cycle refrigeration systems which provide chilled air to the cabin, airflow through the air cycle refrigeration systems being controllable by a pair of pressure regulating valves, each of the pressure regulating valves being disposed in a corresponding main airflow conduit and operated by a corresponding pneumatic valve actuator, the improvement is described by: one of the pneumatic valve actuators associated with one of the pressure regulating valves being operated by a controller comprising: a main servo conduit communicating with one of the main airflow conduits and the pneumatic valve actuator for channeling pneumatic pressure thereto from the main airflow; a first pressure regulator communicating with the main servo conduit for continuously adjusting pneumatic pressure therewithin in response to ram air temperature; a second pressure regulator communicating with the main servo conduit for providing step function adjustment in pneumatic pressure; and means communicating with the main servo conduit for overriding the second pressure regulator to effect partial closing of the one pressure regulating valve despite the deactivation of the air cycle system.

  17. Module Regulations 2013 These regulations must be read in conjunction with the Student Regulations. The Student

    E-print Network

    Bandara, Arosha

    Module Regulations 2013 These regulations must be read in conjunction with the Student Regulations. The Student Regulations set out the University's rules about registration as a student. These Module Regulations set out the rules that apply if you have: · registered for a module which you are not studying

  18. California Energy Commission PROPOSED REGULATIONS

    E-print Network

    California Energy Commission PROPOSED REGULATIONS MARCH 2012 CEC-400-2010-004-SD3 NONRESIDENTIAL BUILDING ENERGY USE DISCLOSURE PROGRAM Proposed Regulations Title 20, Division 2, Chapter 4 PREFACE The California Energy Commission is releasing proposed regulations for implementing Assembly

  19. California Energy Commission PROPOSED REGULATIONS

    E-print Network

    California Energy Commission PROPOSED REGULATIONS ENFORCEMENT PROCEDURES FOR THE RENEWABLES PORTFOLIO STANDARD FOR LOCAL PUBLICLY OWNED ELECTRIC UTILITIES Proposed Regulations Title 20 regulations specifying rules and procedures for enforcement of the Renewables Portfolio Standard ("RPS

  20. Workshop in Regulation &

    E-print Network

    Lin, Xiaodong

    Industries November 16, 2012 Rutgers Business School, 1 Washington Park Newark, NJ Regulation, Smart Grid, Smart Grid and Reliability Location: Rutgers Business School, 1 Washington Park, Newark, NJ 07102, "Local Distribution Reliability Policies" Victor Glass, National Exchange Carrier Association, Inc

  1. California Energy Commission REGULATIONS

    E-print Network

    California Energy Commission REGULATIONS NONRESIDENTIAL BUILDING ENERGY Efficiency and Renewable Energy Division Robert Oglesby Executive Director DISCLAIMER or adequacy of the information in this report. #12; 1 Nonresidential Building Energy Use

  2. R2 REGULATED FACILITIES

    EPA Science Inventory

    The Facility Registry System (FRS) is a centrally managed database that identifies facilities, sites or places subject to environmental regulations or of environmental interest. FRS creates high-quality, accurate, and authoritative facility identification records through rigorous...

  3. Self-Regulated Learning

    NSDL National Science Digital Library

    Gianluca Corsi

    2010-10-01

    Self-regulated learning (SRL) encourages students to learn using metacognition, strategic action, and motivation. This nontraditional approach to education relies on the student's active role in learning and the instructor's facilitatory role in teaching.

  4. Stable hydraulic pressure regulator

    NASA Technical Reports Server (NTRS)

    Gold, H.

    1979-01-01

    Neither sensing line restrictors nor frictional dampers are required for stability. Analysis presents method by which stability margin, response, and droop magnitude can be incorporated during design of direct-acting hydraulic pressure regulators.

  5. Introduction..............................................................................................................................4 Academic Regulations ..............................................................................................

    E-print Network

    Duchowski, Andrew T.

    ..........................................................................................................................17 Assistantships Other Financial Assistance Fringe Benefits and Medical Care General Department Safety Mail Email Telephone Desk Assignment Traffic and Parking Regulations #12;3 Contents (continued from other departments whose interests are closely allied to bioengineering also participate actively

  6. Epigenetic Regulation in Drosophila

    Microsoft Academic Search

    F. Lyko; C. Beisel; J. Marhold; R. Paro

    Epigenetic regulation of gene transcription relies on molecular marks like DNA methylation or histone modifications. Here\\u000a we review recent advances in our understanding of epigenetic regulation in the fruit fly Drosophila melanogaster. In the past, DNA methylation research has primarily utilized mammalian model systems. However, several recent landmark discoveries\\u000a have been made in other organisms. For example, the interaction between

  7. Regulation and behavior

    NSDL National Science Digital Library

    2010-01-01

    Regulation and Behavior is a graduate-level professional development course designed to enhance your understanding and teaching of life science. You will explore how organisms get what they need in order to survive and thrive. You will investigate regulation and behavior using hands-on activities and online resources including video segments, interactive activities, readings, and other multimedia materials. These resources are drawn from Teachers' Domain, WGBH's digital library service.

  8. Trigger Price Regulation

    Microsoft Academic Search

    David J. Salant; Glenn A. Woroch

    1992-01-01

    We consider the difficulty of achieving efficient prices and investments when returns on a public utility's projects are vulnerable to opportunistic ratemaking. We model the long-term relationship between a firm and its regulator as a time-dependent supergame in which the regulator sets price ceilings to maximize surplus and the firm invests to maximize profit. We find history-dependent strategies that support

  9. The Impact of Regulating Social Science Research with Biomedical Regulations

    ERIC Educational Resources Information Center

    Durosinmi, Brenda Braxton

    2011-01-01

    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…

  10. Regulation 2: Student Discipline REGULATION 2: STUDENT DISCIPLINE

    E-print Network

    Sussex, University of

    Regulation 2: Student Discipline 6 REGULATION 2: STUDENT DISCIPLINE 1. Definitions In this Regulation: The University means the University of Sussex. Council means Council of the University. Senate to the regulations of the affiliated institution, and excluding students in attendance at the Brighton and Sussex

  11. Other-Regulation in Collaborative Groups: Implications for Regulation Quality

    ERIC Educational Resources Information Center

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

    2014-01-01

    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…

  12. Economic Regulation of Water Companies

    Microsoft Academic Search

    Michael Klein

    1999-01-01

    September 1996The key to effective regulation of water companies is to generate information that allows the regulator to make good rules and allows the interest groups to watch out for improprieties by the regulator.Both public and private water companies need regulation (of water price and quality) when real competition is not feasible. Piped water systems tend to be monopolies or

  13. The 2003 Money Laundering Regulations

    Microsoft Academic Search

    Richard Alexander

    2004-01-01

    Considers first the 1993 Money Laundering Regulations, which were introduced to implement the European Union’s 1991 Money Laundering Directive and were addressed specifically to the financial sector; they were amended by the Second Money Laundering Regulations 2001 [sic] to include money transmission offices and bureaux de change, and the 2003 Regulations followed. Details the types of business which the Regulations

  14. Environmentally regulated aerospace coatings

    NASA Technical Reports Server (NTRS)

    Morris, Virginia L.

    1995-01-01

    Aerospace coatings represent a complex technology which must meet stringent performance requirements in the protection of aerospace vehicles. Topcoats and primers are used, primarily, to protect the structural elements of the air vehicle from exposure to and subsequent degradation by environmental elements. There are also many coatings which perform special functions, i.e., chafing resistance, rain erosion resistance, radiation and electric effects, fuel tank coatings, maskants, wire and fastener coatings. The scheduled promulgation of federal environmental regulations for aerospace manufacture and rework materials and processes will regulate the emissions of photochemically reactive precursors to smog and air toxics. Aerospace organizations will be required to identify, qualify and implement less polluting materials. The elimination of ozone depleting chemicals (ODC's) and implementation of pollution prevention requirements are added constraints which must be addressed concurrently. The broad categories of operations affected are the manufacture, operation, maintenance, and repair of military, commercial, general aviation, and space vehicles. The federal aerospace regulations were developed around the precept that technology had to be available to support the reduction of organic and air toxic emissions, i.e., the regulations cannot be technology forcing. In many cases, the regulations which are currently in effect in the South Coast Air Quality Management District (SCAQMD), located in Southern California, were used as the baseline for the federal regulations. This paper addresses strategies used by Southern California aerospace organizations to cope with these regulatory impacts on aerospace productions programs. All of these regulatory changes are scheduled for implementation in 1993 and 1994, with varying compliance dates established.

  15. Consolidation and translation regulation

    PubMed Central

    Gal-Ben-Ari, Shunit; Kenney, Justin W.; Ounalla-Saad, Hadile; Taha, Elham; David, Orit; Levitan, David; Gildish, Iness; Panja, Debabrata; Pai, Balagopal; Wibrand, Karin; Simpson, T. Ian; Proud, Christopher G.; Bramham, Clive R.; Armstrong, J. Douglas; Rosenblum, Kobi

    2012-01-01

    mRNA translation, or protein synthesis, is a major component of the transformation of the genetic code into any cellular activity. This complicated, multistep process is divided into three phases: initiation, elongation, and termination. Initiation is the step at which the ribosome is recruited to the mRNA, and is regarded as the major rate-limiting step in translation, while elongation consists of the elongation of the polypeptide chain; both steps are frequent targets for regulation, which is defined as a change in the rate of translation of an mRNA per unit time. In the normal brain, control of translation is a key mechanism for regulation of memory and synaptic plasticity consolidation, i.e., the off-line processing of acquired information. These regulation processes may differ between different brain structures or neuronal populations. Moreover, dysregulation of translation leads to pathological brain function such as memory impairment. Both normal and abnormal function of the translation machinery is believed to lead to translational up-regulation or down-regulation of a subset of mRNAs. However, the identification of these newly synthesized proteins and determination of the rates of protein synthesis or degradation taking place in different neuronal types and compartments at different time points in the brain demand new proteomic methods and system biology approaches. Here, we discuss in detail the relationship between translation regulation and memory or synaptic plasticity consolidation while focusing on a model of cortical-dependent taste learning task and hippocampal-dependent plasticity. In addition, we describe a novel systems biology perspective to better describe consolidation. PMID:22904372

  16. What Price Government Regulations?

    PubMed Central

    McGill, Clinton S.

    1980-01-01

    Cost containment in health care will be a major target for governmental regulation in the coming decade. A number of potential economies in health care exist, among them a reduction of the heavy burden of government regulation. It is important to review pending congressional action as related to health cost, as well as congressional proposals for reform of the regulatory agencies. Organized medicine is involved in cost containment and the private sector has made some progress. However, there is much that individual practitioners can do. PMID:7385851

  17. Telecommunications Regulation: An Introduction

    Microsoft Academic Search

    Nicholas Economides

    2003-01-01

    This paper examines the justifications, history, and practice of regulation in the US telecommunications sector. We examine the impact of technological and regulatory change on market structure and business strategy. Among others, we discuss the emergence and decline of the telecom bubble, the impact on pricing of digitization and the emergence of Internet telephony (VOIP). We also examine the impact

  18. Lysosomal calcium regulates autophagy.

    PubMed

    Medina, Diego L; Ballabio, Andrea

    2015-06-01

    Recent evidence has indicated that the lysosome is able to act as a signaling organelle that senses nutrient availability and generates an adaptive response that is important for cellular homeostasis. We recently discovered another example of lysosomal signaling where lysosomal calcium release activates the master autophagy regulator TFEB via the phosphatase calcineurin. PMID:26000950

  19. Battery voltage regulation system

    Microsoft Academic Search

    N. Mayumi; H. Kato; H. Matsuhashi

    1986-01-01

    A battery voltage regulating system is described for an automotive vehicle having a battery, an alternator driven by an internal combustion engine mounted on the vehicle and generating an alternating current, and a full-wave rectifier for rectifying the alternating current to charge the battery. The system consists of: an operational amplifier connected to the battery for comparing a battery voltage

  20. Water Regulation I. Osmoregulation

    E-print Network

    Dever, Jennifer A.

    1 Water Regulation I. Osmoregulation II. Water Gain III. Water loss IV. Extreme Environments Animal matched over time, or else!!! I. Osmoregulation ­ water balance l Different problems with osmoregulation depending on the habitat the organism lives in A. Freshwater: B. Salt water: C. Terrestrial: Excessive

  1. Water Regulation I. Osmoregulation

    E-print Network

    Dever, Jennifer A.

    1 Water Regulation I. Osmoregulation II. Water Gain III. Water loss IV. Extreme Environments I. Osmoregulation ­ water balance Animal = open system that exchanges materials & energy w/environment. Different is hyperosmotic B. Salt water: the animal is hypoosmotic C. Terrestrial: evaporation main problem Excessive

  2. Water Regulation I. Osmoregulation

    E-print Network

    Dever, Jennifer A.

    1 Water Regulation I. Osmoregulation II. Water Gain III. Water loss IV. Extreme Environments I. Osmoregulation ­ water balance Animal = open system that exchanges materials & energy w/environment. Rates depending on the habitat the organism lives in A. Freshwater: the animal is hyperosmotic B. Salt water

  3. Water Regulation I. Osmoregulation

    E-print Network

    Dever, Jennifer A.

    1 Water Regulation I. Osmoregulation II. Water Gain III. Water loss IV. Extreme Environments I. Osmoregulation ­ water balance l Different problems with osmoregulation depending on the habitat the organism lives in #12;2 Nitrogenous Wastes 1) Ammonia 2) Urea 3) Uric Acid II. Water Gain 1. Drinking (reptiles

  4. Army Regulation 38510 Headquarters

    E-print Network

    US Army Corps of Engineers

    Army Regulation 385­10 Safety The Army Safety Program Headquarters Department of the Army Washington, DC 27 November 2013 UNCLASSIFIED #12;SUMMARY of CHANGE AR 385­10 The Army Safety Program This major revision, dated 27 November 2013-- o Adds responsibility for U.S. Army Technical Center

  5. Regulation and behavior

    NSDL National Science Digital Library

    Teachers Domain

    2002-01-01

    How can animals and plants exist in every biome on Earth: blazing hot or freezing cold, sopping wet or bone dry? How does homeostasis help organisms survive changes in their environment? How do animals, including humans, sense change in their environment, and how do they respond? Explore these questions and more in this collection of Regulation and Behavior resources.

  6. CODE OF FEDERAL REGULATIONS

    EPA Science Inventory

    The Code of Federal Regulations (CFR) is an annually revised codification of the general and permanent rules published in the Federal Register by the executive departments and agencies of the Federal Government. The CFR is divided into 50 titles which represent broad areas subje...

  7. Regulating the Internet

    ERIC Educational Resources Information Center

    Anderson, Byron

    2007-01-01

    The Internet's breakthrough to primetime usage beginning in the mid-1990s evolved in an era of openness. Unfettered access seemed key to Internet development. An important foundation for the 1996 Telecommunications Act was the theory that the telecom industry would work best if it were free of government regulation, a guiding principle that has…

  8. Glucose regulation in birds

    Microsoft Academic Search

    Eldon J. Braun; Karen L. Sweazea

    2008-01-01

    Birds maintain higher plasma glucose concentrations (PGlu) than other vertebrates of similar body mass and, in most cases, appear to store comparatively very little glucose intracellularly as glycogen. In general, birds are insensitive to the regulation of PGlu by insulin. However, there appears to be no phylogenetic or dietary pattern in the avian response to exogenous insulin. Moreover, the high

  9. Parking and Traffic Regulations

    E-print Network

    Tufts University

    Parking and Traffic Regulations July 2001 Edition Department of Public Safety Parking and Traffic Services 419 Boston Avenue Medford, MA 02155 (617) 627-3692 parking @tufts.edu Visit http and to operate a motor vehicle on the streets, drive- ways and parking lots of the campus. 4. DEFINITIONS A

  10. Advice & Regulations for parking

    E-print Network

    Davies, Christopher

    Advice & Regulations for parking 2009-2010 C A M P U S PA RK I N G P L A N PARKING ZONES Pay and display, and permit zones are depicted on the Parking Plan overleaf. Westwood has Pay and Display parking of staff, other persons employed on campus, students resident off campus or visitors may park in the Pay

  11. [Regulation of terpene metabolism

    Microsoft Academic Search

    Croteau

    1989-01-01

    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

  12. Regulation 8: Responsibility for Creation and Amendment of Regulations: REGULATION 8: RESPONSIBILITY FOR CREATION AND AMENDMENT OF

    E-print Network

    Sussex, University of

    Regulation 8: Responsibility for Creation and Amendment of Regulations: 36 REGULATION 8: RESPONSIBILITY FOR CREATION AND AMENDMENT OF REGULATIONS This Regulation may only be amended at a meeting and revoke Regulations. Regulations may be created, amended and revoked at any meeting of Council. 2

  13. Novel Targets for the Transcription Factors MEF2 in MA-10 Leydig Cells.

    PubMed

    Di-Luoffo, Mickaël; Daems, Caroline; Bergeron, Francis; Tremblay, Jacques J

    2015-07-01

    Testosterone production by Leydig cells is a tightly regulated process requiring synchronized expression of several steroidogenic genes by numerous transcription factors. Myocyte enhancer factor 2 (MEF2) are transcription factors recently identified in somatic cells of the male gonad. In other tissues, MEF2 factors are essential regulators of organogenesis and cell differentiation. So far in the testis, MEF2 factors were found to regulate Leydig cell steroidogenesis by controlling Nr4a1 and Star gene expression. To expand our understanding of the role of MEF2 in Leydig cells, we performed microarray analyses of MEF2-depleted MA-10 Leydig cells, and the results were analyzed using Partek and Ingenuity Pathway Analysis software. Several genes were differentially expressed in MEF2-depleted Leydig cells, and 16 were validated by quantitative RT-PCR. A large number of these genes are known to be involved in fertility, gonad morphology, and steroidogenesis. These include Ahr, Bmal1, Cyp1b1, Hsd3b1, Hsd17b7, Map2k1, Nr0b2, Pde8a, Por, Smad4, Star, and Tsc22d3, which were all downregulated in the absence of MEF2. In silico analyses revealed the presence of MEF2-binding sites within the first 2 kb upstream of the transcription start site of the Por, Bmal1, and Nr0b2 promoters, suggesting direct regulation by MEF2. Using transient transfections in MA-10 Leydig cells, small interfering RNA knockdown, and a MEF2-Engrailed dominant negative, we found that MEF2 activates the Por, Bmal1, and Nr0b2 promoters and that this requires an intact MEF2 element. Our results identify novel target genes for MEF2 and define MEF2 as an important regulator of Leydig cell function and male reproduction. PMID:26019261

  14. Serial Regulation of Transcriptional Regulators in the Yeast Cell Cycle

    Microsoft Academic Search

    Itamar Simon; John Barnett; Nancy Hannett; Christopher T Harbison; Nicola J Rinaldi; Thomas L Volkert; John J Wyrick; Julia Zeitlinger; David K Gifford; Tommi S Jaakkola; Richard A Young

    2001-01-01

    Genome-wide location analysis was used to determine how the yeast cell cycle gene expression program is regulated by each of the nine known cell cycle transcriptional activators. We found that cell cycle transcriptional activators that function during one stage of the cell cycle regulate transcriptional activators that function during the next stage. This serial regulation of transcriptional activators forms a

  15. FDA 101: Regulating Biological Products

    MedlinePLUS

    ... mail Consumer Updates RSS Feed FDA 101: Regulating Biological Products Search the Consumer Updates Section Consumer Update ... friendly PDF (196 KB) On this page: What biological products does FDA regulate? How do biologics differ ...

  16. Corporate governance and banking regulation

    E-print Network

    Alexander, Kern

    The globalisation of banking markets has raised important issues regarding corporate governance regulation for banking institutions. This research paper addresses some of the major issues of corporate governance as it relates to banking regulation...

  17. ACADEMIC REGULATIONS BACHELOR OF ARTS IN INTERNATIONAL

    E-print Network

    ACADEMIC REGULATIONS BACHELOR OF ARTS IN INTERNATIONAL COMMUNICATION AND MULTIMEDIA 2013 #12;[2] Table of Contents 1. The outline provisions of the academic regulations................................................................................................................................................5 Transitional regulations

  18. Neuropilin regulation of angiogenesis.

    PubMed

    Lampropoulou, Anastasia; Ruhrberg, Christiana

    2014-12-01

    Blood vessel formation during vertebrate development relies on a process called angiogenesis and is essential for organ growth and tissue viability. In addition, angiogenesis leads to pathological blood vessel growth in diseases with tissue ischaemia, such as neovascular eye disease and cancer. Neuropilin 1 (NRP1) is a transmembrane protein that serves as a receptor for the VEGF??? isoform of the vascular endothelial growth factor (VEGF) to enhance cell migration during angiogenesis via VEGF receptor 2 (VEGFR2), and it is also essential for VEGF-induced vascular permeability and arteriogenesis. In addition, NRP1 activation affects angiogenesis independently of VEGF signalling by activating the intracellular kinase ABL1. NRP1 also acts as a receptor for the class 3 semaphorin (SEMA3A) to regulate vessel maturation during tumour angiogenesis and vascular permeability in eye disease. In the present paper, we review current knowledge of NRP1 regulation during angiogenesis and vascular pathology. PMID:25399580

  19. Effectiveness of price regulation

    SciTech Connect

    Meyer, R.A.; Leland, H.E.

    1980-11-01

    That it is easier to measure the costs of price regulation than the benefits is evident in the conflicting results of studies made to determine welfare gains. An econometric study based on a simple theory of demand by customer class concludes that: (1) the effectiveness of regulation across states is irregular, which suggests that state regulatory agencies confront firms with highly variable political climates and may serve customers with an uneven quality of benefits; (2) the pattern of cross-subsidization of prices that penalized residential customers in 1969 was gone or shifted to favor residential customers by 1974; (3) a more-detailed re-evaluation of the presumed benefits and costs of nonuniform pricing may be warranted; and (4) welfare improvements appear to be possible. The dominant question that emerges is how to explain what underlying forces contribute to the substantial state-to-state and between-customer variations in regulatory impact. 13 references, 6 tables.

  20. Optimal Price-Cap Regulation

    Microsoft Academic Search

    Gerhard Clemenz

    1991-01-01

    The author considers the problem of a regulator who cannot observe the R&D expenditures of a firm devoted to reductions in the costs of production. It is shown, for a finite horizon model, that price-cap regulation does not only provide stronger incentives for cost reductions than does rate of return regulation, but that it is also capable of achieving a

  1. Temperature controlled high voltage regulator

    DOEpatents

    Chiaro, Jr., Peter J. (Clinton, TN); Schulze, Gerald K. (Knoxville, TN)

    2004-04-20

    A temperature controlled high voltage regulator for automatically adjusting the high voltage applied to a radiation detector is described. The regulator is a solid state device that is independent of the attached radiation detector, enabling the regulator to be used by various models of radiation detectors, such as gas flow proportional radiation detectors.

  2. The Theory of Economic Regulation

    Microsoft Academic Search

    George J. Stigler

    1971-01-01

    The potential uses of public resources and powers to improve the economic status of economic groups (such as industries and occupations) are analyzed to provide a scheme of the demand for regulation. The characteristics of the political process which allow relatively small groups to obtain such regulation is then sketched to provide elements of a theory of supply of regulation.

  3. Grantiau a Rheoliadau Grants & Regulations

    E-print Network

    Grantiau a Rheoliadau Grants & Regulations Forestry Commission Wales policy position on development under Part 2 of the Forestry Act (1967), under the FC Wales Head of Grants and Regulation · As Statutory of Grants and Regulation · As Agent for the Welsh Assembly Government under Section 83 of the Government

  4. Emotion Regulation JAMES J. GROSS

    E-print Network

    Gross, James J.

    CHAPTER 31 ·Emotion Regulation JAMES J. GROSS Have you ever gotten so angry that you've done). Although the topic of emotion regulation is a relatively late addition to the field of emotion, a concern with emotion regulation is anything but new. Emotion regu lation has been a focus in the study of psycho

  5. REGULATION AND DISTRUST Philippe AGHION

    E-print Network

    Paris-Sud XI, Université de

    REGULATION AND DISTRUST Philippe AGHION Yann ALGAN Pierre CAHUC Andrei SHLEIFER January 2009 Cahier://www.enseignement.polytechnique.fr/economie/ mailto:chantal.poujouly@polytechnique.edu hal-00396268,version1-17Jun2009 #12;REGULATION AND DISTRUST1: In a cross-section of countries, government regulation is strongly negatively correlated with social capital

  6. Mining regulation: procedures versus standards

    Microsoft Academic Search

    1979-01-01

    Regulations pertaining to coal mining and development are serving as a model for non-fuel minerals policy. The regulatory framework, however, is designed to constrain domestic mineral extraction. Five key problems - advancing technology, cost of environmental studies, changing regulations, cycles in state and Federal regulations, and inconsistent administrations - relate to the long lead times required for mineral development. Two

  7. Understanding Self-Regulated Learning.

    ERIC Educational Resources Information Center

    Pintrich, Paul R.

    1995-01-01

    Self-regulated learning is an important component of learning for college students. Students must have greater awareness of their own behavior, motivation, and cognition and of positive motivational beliefs, and must practice self-regulated learning strategies. Faculty can model self-regulated learning and provide appropriate classroom tasks. (MSE)

  8. Redox regulated peroxisome homeostasis.

    PubMed

    Wang, Xiaofeng; Li, Shuo; Liu, Yu; Ma, Changle

    2015-01-01

    Peroxisomes are ubiquitous organelles present in nearly all eukaryotic cells. Conserved functions of peroxisomes encompass beta-oxidation of fatty acids and scavenging of reactive oxygen species generated from diverse peroxisomal metabolic pathways. Peroxisome content, number, and size can change quickly in response to environmental and/or developmental cues. To achieve efficient peroxisome homeostasis, peroxisome biogenesis and degradation must be orchestrated. We review the current knowledge on redox regulated peroxisome biogenesis and degradation with an emphasis on yeasts and plants. PMID:25545794

  9. Regulating Telecommunications in Europe

    NASA Astrophysics Data System (ADS)

    Cave, Martin

    This chapter describes and assesses the new regime for regulating electronic communications services, which came into force in Europe in July 2003. The first two sections describe, respectively, the previous regime (the 1998 package) and the new regime. The third section discusses experience of the new system up to the end of 2007,1 whereas the fourth evaluates its operation and the plans, already in place, to reform it.

  10. Regulation reform slows down

    SciTech Connect

    NONE

    1995-03-29

    Regulatory reformers in Congress are easing off the accelerator as they recognize that some of their more far-reaching proposals lack sufficient support to win passage. Last week the proposed one-year moratorium on new regulations was set back in the Senate by it main sponsor, Sen. Non Nickles (R., OK), who now seeks to replace it with a more moderate bill. Nickel`s substitute bill would give Congress 45 days after a regulation is issued to decide whether to reject it. It also retroactively allows for review of 80 regulations issued since last November 9, 1994. Asked how his new proposal is superior to a moratorium, which is sharply opposed by the Clinton Administration, Nickles says he thinks it is better because its permanent. The Chemical Manufacturer`s Association (CMA) has not publicly made a regulatory moratorium a top priority, but has quietly supported it by joining with other industry groups lobbying on the issue. A moratorium would halt EPA expansion of the Toxics Release Inventory (TRI) and alloys the delisting of several TRI chemicals.

  11. Improving CS regulations.

    SciTech Connect

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

    1980-10-01

    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)

  12. USF Graduate Catalog 20142015 Section 7 Academic Policies and Regulations Academic Policies and Regulations

    E-print Network

    Meyers, Steven D.

    USF Graduate Catalog 20142015 Section 7 Academic Policies and Regulations 34 Section 7 Academic Policies and Regulations Academic Policy and Regulation Information For USF Regulations refer to http://generalcounsel.usf.edu/regulations/currentregulations.asp For USF Policies refer

  13. 8 CFR 100.5 - Regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...2011-01-01 2011-01-01 false Regulations. 100.5 Section 100.5 Aliens...DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS STATEMENT OF ORGANIZATION § 100.5 Regulations. The regulations of the...

  14. 7 CFR 987.48 - Container regulation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 2010-01-01 false Container regulation. 987.48 Section 987.48 Agriculture Regulations of the Department of Agriculture (Continued...Order Regulating Handling Container Regulation § 987.48 Container...

  15. 7 CFR 987.48 - Container regulation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 2014-01-01 false Container regulation. 987.48 Section 987.48 Agriculture Regulations of the Department of Agriculture (Continued...Order Regulating Handling Container Regulation § 987.48 Container...

  16. 7 CFR 29.29 - Regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 2013-01-01 false Regulations. 29.29 Section 29.29 Agriculture Regulations of the Department of Agriculture...COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS TOBACCO INSPECTION Regulations...

  17. 7 CFR 29.29 - Regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 2010-01-01 false Regulations. 29.29 Section 29.29 Agriculture Regulations of the Department of Agriculture...COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS TOBACCO INSPECTION Regulations...

  18. 8 CFR 100.5 - Regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 2014-01-01 false Regulations. 100.5 Section 100.5 Aliens...DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS STATEMENT OF ORGANIZATION § 100.5 Regulations. The regulations of the...

  19. 7 CFR 29.29 - Regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 2014-01-01 false Regulations. 29.29 Section 29.29 Agriculture Regulations of the Department of Agriculture...COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS TOBACCO INSPECTION Regulations...

  20. General Qualification Regulations 2014 (Registered Undergraduate Qualifications)

    E-print Network

    Bandara, Arosha

    General Qualification Regulations 2014 (Registered Undergraduate Qualifications) The General Qualification Regulations should not be read in isolation. It is important that you read them in conjunction with the following documents. · The Module Regulations · The specific regulations governing your qualification

  1. 15 CFR 922.44 - Emergency regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 false Emergency regulations. 922.44 Section 922.44 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Regulations of General...

  2. MILLERSVILLE UNIVERSITY PARKING REGULATIONS AND PROCEDURES

    E-print Network

    Hardy, Christopher R.

    MILLERSVILLE UNIVERSITY PARKING REGULATIONS AND PROCEDURES 2012-2013 CONTENTS 1. General Regulations ­ Driving and Parking 10. Handicapped Parking 11. Motorcycle Regulations 12. Reserved Spaces 13. Specific Parking Regulations 14. Parking Violations Penalties, Fines and Fees 15. Appeals of Parking

  3. 7 CFR 993.49 - Incoming regulation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 2014-01-01 false Incoming regulation. 993.49 Section 993.49 Agriculture Regulations of the Department of Agriculture (Continued...Regulating Handling Grade and Size Regulations § 993.49 Incoming...

  4. Regulation of adipocyte lipolysis.

    PubMed

    Frühbeck, Gema; Méndez-Giménez, Leire; Fernández-Formoso, José-Antonio; Fernández, Secundino; Rodríguez, Amaia

    2014-06-01

    In adipocytes the hydrolysis of TAG to produce fatty acids and glycerol under fasting conditions or times of elevated energy demands is tightly regulated by neuroendocrine signals, resulting in the activation of lipolytic enzymes. Among the classic regulators of lipolysis, adrenergic stimulation and the insulin-mediated control of lipid mobilisation are the best known. Initially, hormone-sensitive lipase (HSL) was thought to be the rate-limiting enzyme of the first lipolytic step, while we now know that adipocyte TAG lipase is the key enzyme for lipolysis initiation. Pivotal, previously unsuspected components have also been identified at the protective interface of the lipid droplet surface and in the signalling pathways that control lipolysis. Perilipin, comparative gene identification-58 (CGI-58) and other proteins of the lipid droplet surface are currently known to be key regulators of the lipolytic machinery, protecting or exposing the TAG core of the droplet to lipases. The neuroendocrine control of lipolysis is prototypically exerted by catecholaminergic stimulation and insulin-induced suppression, both of which affect cyclic AMP levels and hence the protein kinase A-mediated phosphorylation of HSL and perilipin. Interestingly, in recent decades adipose tissue has been shown to secrete a large number of adipokines, which exert direct effects on lipolysis, while adipocytes reportedly express a wide range of receptors for signals involved in lipid mobilisation. Recently recognised mediators of lipolysis include some adipokines, structural membrane proteins, atrial natriuretic peptides, AMP-activated protein kinase and mitogen-activated protein kinase. Lipolysis needs to be reanalysed from the broader perspective of its specific physiological or pathological context since basal or stimulated lipolytic rates occur under diverse conditions and by different mechanisms. PMID:24872083

  5. Quality Regulations and Standards

    NSDL National Science Digital Library

    This "Course-in-a-Box" from Bio-Link is a good starting point for instructors to develop a course on quality regulations and standards. Quality products mean those "that are suitable for their intended use and are free of defects and variability." This is especially important in the biotechnology field as many products have medical or food applications. This page contains two example courses as this is a "vast and complex field" so courses may cover a variety of topics. Furthermore, links to an Outline, Additional Instructional Resources, Quality Courses and Programs, and Careers in Quality Control are included.

  6. Regulations, 30 January 1987.

    PubMed

    1987-01-01

    Regulations adopted by the All-Union Women's Committee give recently established women's councils greater scope to initiate legislation and provide that laws and statutory instruments affecting women's interests cannot be discussed without their participation. The Councils are also to play an active role in representing the interests of the female workforce at the enterprise level through participation in formulating and monitoring collective agreements, planning the allocation of resources on the social and day-to-day needs of the staff, and supervising the work of medical, pre-school and educational institutions, commercial and public catering enterprises, and day-to-day services. PMID:12346611

  7. Self-regulating valve

    DOEpatents

    Humphreys, D.A.

    1982-07-20

    A variable, self-regulating valve having a hydraulic loss coefficient proportional to a positive exponential power of the flow rate. The device includes two objects in a flow channel and structure which assures that the distance between the two objects is an increasing function of the flow rate. The range of spacing between the objects is such that the hydraulic resistance of the valve is an increasing function of the distance between the two objects so that the desired hydraulic loss coefficient as a function of flow rate is obtained without variation in the flow area.

  8. Emotion Regulation and Anxiety Disorders

    PubMed Central

    Amstadter, Ananda B.

    2009-01-01

    Recent attention has been given to the role of emotion regulation in the development and maintenance of psychopathology. Gross (1998) provided a framework from which to understand emotion regulation processes, and it is within this framework that the literature on emotion regulation/dysregulation in the anxiety disorder population is reviewed, with a focus on possible deficiencies that lead to or maintain the disorders. The present paper aims to (1) briefly introduce emotion regulation strategies of suppression and reappraisal; (2) summarize the empirical studies of emotion regulation within anxiety disorders; (3) discuss the neurobiological markers of emotion regulation within these disorders; (4) provide future directions for research; and (5) summarize possible treatment implications resulting from this important area of research. PMID:17349775

  9. Strategic Automation of Emotion Regulation

    Microsoft Academic Search

    Inge Schweiger Gallo; Andreas Keil; Kathleen C. McCulloch; Brigitte Rockstroh; Peter M. Gollwitzer

    2009-01-01

    As implementation intentions are a powerful self-regulation tool for thought and action (meta-analysis by P. M. Gollwitzer & P. Sheeran, 2006), the present studies were conducted to address their effectiveness in regulating emotional reactivity. Disgust- (Study 1) and fear- (Study 2) eliciting stimuli were viewed under 3 different self-regulation instructions: the goal intention to not get disgusted or frightened, respectively,

  10. Power-MOSFET Voltage Regulator

    NASA Technical Reports Server (NTRS)

    Miller, W. N.; Gray, O. E.

    1982-01-01

    Ninety-six parallel MOSFET devices with two-stage feedback circuit form a high-current dc voltage regulator that also acts as fully-on solid-state switch when fuel-cell out-put falls below regulated voltage. Ripple voltage is less than 20 mV, transient recovery time is less than 50 ms. Parallel MOSFET's act as high-current dc regulator and switch. Regulator can be used wherever large direct currents must be controlled. Can be applied to inverters, industrial furnaces photovoltaic solar generators, dc motors, and electric autos.

  11. Dimerizer-regulated gene expression.

    PubMed

    Pollock, Roy; Clackson, Tim

    2002-10-01

    Control of gene expression using small molecules is a powerful research tool and has clinical utility in the context of regulated gene therapy. Use of chemical inducers of dimerization, or dimerizers, for this purpose has several advantages, including tight regulation, modularity to facilitate iterative improvements, and assembly from human proteins to minimize immune responses in clinical applications. Recent developments include the use of the rapamycin-based dimerizer system to regulate the expression of endogenous genes, the generation of new chemical dimerizers based on FK506, dexamethasone and methotrexate, and progress towards the clinical use of adeno-associated virus and adenovirus vectors regulated by rapamycin analogs. PMID:12459338

  12. REGULATION POLITIQUE ET REGULATION D'USAGE DANS LE TEMPS DE TRAVAIL1

    E-print Network

    Paris-Sud XI, Université de

    1 REGULATION POLITIQUE ET REGULATION D'USAGE DANS LE TEMPS DE TRAVAIL1 : par G. de Terssac, J REGULATION AND REGULATION OF USE OVER WORKING TIME In this paper we discuss « social regulations » as defined by Reynaud (1999). These regulations, in our case (working)-time regulations, are multiple. Their combination

  13. Regulation of Terpene Metabolism

    SciTech Connect

    Rodney Croteau

    2004-03-14

    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.

  14. Regulation by mitophagy.

    PubMed

    Hattori, Nobutaka; Saiki, Shinji; Imai, Yuzuru

    2014-08-01

    Eukaryotes employ elaborate mitochondrial quality control to maintain the function of the power-generating organelle. Mitochondrial quality control is particularly important for the maintenance of neural and muscular tissues. Mitophagy is specialized version of the autophagy pathway. Mitophagy delivers damaged mitochondria to lysosomes for degradation. Recently, a series of elegant studies have demonstrated that two Parkinson's disease-associated genes PINK1 and parkin are involved in the maintenance of healthy mitochondria as mitophagy. Parkin in co-operation with PINK1 specifically recognizes damaged mitochondria with reduced mitochondrial membrane potential (??m), rapidly isolates them from the mitochondrial network and eliminates them through the ubiquitin-proteasome and autophagy pathways. Here we introduce and review recent studies that contribute to understanding the molecular mechanisms of mitophagy such as PINK1 and Parkin-mediated mitochondrial regulation. We also discuss how defects in the PINK1-Parkin pathway may cause neurodegeneration in Parkinson's disease. PMID:24842103

  15. Regulation 3: Students' Union REGULATION 3: THE STUDENTS' UNION

    E-print Network

    Sussex, University of

    Regulation 3: Students' Union 15 REGULATION 3: THE STUDENTS' UNION 1. Pursuant to Article 9 of the Charter, there shall be a students' union of the University. The name of the union shall be 'THE UNIVERSITY OF SUSSEX STUDENTS' UNION' (hereinafter called the 'Union'). 2. The aims of the Union shall

  16. Ball valve regulator reduces noise at regulating stations

    Microsoft Academic Search

    Hogan

    1998-01-01

    In recent years, there has been growing concern within the natural gas industry regarding the effect regulating stations have on their surrounding environments. To reduce excessive noise and pollution, many gas distribution and transmission companies have begun utilizing equipment which reduces environmental impact. The below grade ball valve regulator is a prime example of this environment-friendly equipment. Its high capacity,

  17. [Regulation of terpene metabolism

    SciTech Connect

    Croteau, R.

    1989-11-09

    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.

  18. TFEB regulates lysosomal proteostasis.

    PubMed

    Song, Wensi; Wang, Fan; Savini, Marzia; Ake, Ashley; di Ronza, Alberto; Sardiello, Marco; Segatori, Laura

    2013-05-15

    Loss-of-function diseases are often caused by destabilizing mutations that lead to protein misfolding and degradation. Modulating the innate protein homeostasis (proteostasis) capacity may lead to rescue of native folding of the mutated variants, thereby ameliorating the disease phenotype. In lysosomal storage disorders (LSDs), a number of highly prevalent alleles have missense mutations that do not impair the enzyme's catalytic activity but destabilize its native structure, resulting in the degradation of the misfolded protein. Enhancing the cellular folding capacity enables rescuing the native, biologically functional structure of these unstable mutated enzymes. However, proteostasis modulators specific for the lysosomal system are currently unknown. Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs. We show that TFEB activation results in enhanced folding, trafficking and lysosomal activity of a severely destabilized glucocerebrosidase (GC) variant associated with the development of Gaucher disease (GD), the most common LSD. TFEB specifically induces the expression of GC and of key genes involved in folding and lysosomal trafficking, thereby enhancing both the pool of mutated enzyme and its processing through the secretory pathway. TFEB activation also rescues the activity of a ?-hexosaminidase mutant associated with the development of another LSD, Tay-Sachs disease, thus suggesting general applicability of TFEB-mediated proteostasis modulation to rescue destabilizing mutations in LSDs. In summary, our findings identify TFEB as a specific regulator of lysosomal proteostasis and suggest that TFEB may be used as a therapeutic target to rescue enzyme homeostasis in LSDs. PMID:23393155

  19. EPA REGULATIONS RELATED TO DIOXIN

    EPA Science Inventory

    EPA currently has regulations relating to release of dioxin-like compounds from air sources and from pulp and paper mills into water bodies. Information on these regulations for dioxin-like compounds and other pollutants can be found at these sites. ...

  20. UNIVERSITY OF SUSSEX Financial Regulations

    E-print Network

    Sussex, University of

    Laundering 8 2.6. Risk management 8 2.7. Accounting records and annual financial statements 9 2.8. PrivateUNIVERSITY OF SUSSEX Financial Regulations Issued April 2012 #12;If you need part or all Office on +44 (0)1273 678305 #12;Financial Regulations 2012 v1 Contents 1. Introduction Page 1.1. Purpose

  1. BIOTECHNOLOGY REGULATIONS AND THE WTO

    Microsoft Academic Search

    Ian M. Sheldon; Timothy E. Josling

    2002-01-01

    This paper examines the regulation of trade in genetically modified organisms (GMOs) by the World Trade Organization (WTO). Despite rapid adoption of GMOs by a few exporters, many importers have developed relatively restrictive procedures for pre-market approval of GMOs, and are introducing mandatory labeling. While exporters have yet to seek a ruling from the WTO on these regulations, a trade

  2. Regulating Pornography: A Public Dilemma.

    ERIC Educational Resources Information Center

    Thompson, Margaret E.; And Others

    1990-01-01

    Examines attitudes toward sex and pornography by means of a telephone survey of Dane County, Wisconsin, adults. Describes survey questions about sexual attitudes, perceived effects of pornography, and pornography regulation. Concludes that adults who feel more strongly that pornography has negative effects are more opposed to its regulation. (SG)

  3. Deceptive Business Practices: Federal Regulations.

    ERIC Educational Resources Information Center

    Rohrer, Daniel Morgan

    Federal regulations to prevent deceptive advertising seek to balance the advertiser's freedom of speech with protection of the consumer. This paper discusses what the Federal Trade Commission (FTC) has done to regulate advertising and evaluates the adequacy of its controls. The commission uses cease-and-desist orders, affirmative disclosure,…

  4. The Effectiveness of Price Regulation

    Microsoft Academic Search

    Robert A Meyer; Hayne E. Leland

    1980-01-01

    That it is easier to measure the costs of price regulation than the benefits is evident in the conflicting results of studies made to determine welfare gains. An econometric study based on a simple theory of demand by customer class concludes that: (1) the effectiveness of regulation across states is irregular, which suggests that state regulatory agencies confront firms with

  5. Technological Change in Regulated Industries.

    ERIC Educational Resources Information Center

    Capron, William M., Ed.

    The articles in this volume discuss how well industries operating under government regulation respond to technical innovation: do the effects of regulations vary among industries, and if so, does this result from variations in the regulatory approach, the organization of the firms, or the nature of the technology? Industries considered include…

  6. Street sweeping and stormwater regulations

    SciTech Connect

    Not Available

    1993-10-01

    This article examines the role of street sweeping in meeting the requirements of the Clean Water Act stormwater regulations. The article identifies those industrial and municipal activities which are covered by the regulations and cites frequent sweeping of site surfaces for industry and street sweeping for municipalities as an integral part of compliance plans.

  7. Team Regulation, Regulation of Social Activities or Co-Regulation: Different Labels for Effective Regulation of Learning in CSCL

    ERIC Educational Resources Information Center

    Saab, Nadira

    2012-01-01

    Computer-supported collaborative learning (CSCL) is an approach to learning in which learners can actively and collaboratively construct knowledge by means of interaction and joint problem solving. Regulation of learning is especially important in the domain of CSCL. Next to the regulation of task performance, the interaction between learners who…

  8. Brain circuits regulating energy homeostasis

    Microsoft Academic Search

    Alfonso Abizaid; Tamas L. Horvath

    2008-01-01

    Recent years have seen an impetus in the study for central mechanisms regulating energy balance, and caloric intake possibly as a response to the obesity pandemic. This renewed interest as well as drastic improvements in the tools that are now currently available to neuroscientists, has yielded a great deal of insight into the mechanisms by which the brain regulates metabolic

  9. Gravity and body mass regulation

    NASA Technical Reports Server (NTRS)

    Warren, L. E.; Horwitz, B. A.; Fuller, C. A.

    1997-01-01

    The effects of altered gravity on body mass, food intake, energy expenditure, and body composition are examined. Metabolic adjustments are reviewed in maintenance of energy balance, neural regulation, and humoral regulation are discussed. Experiments with rats indicate that genetically obese rats respond differently to hypergravity than lean rats.

  10. Web Regulation Battles Heat Up.

    ERIC Educational Resources Information Center

    Newcombe, Pat

    1999-01-01

    Considers issues involving deregulation and freedom of speech on the Internet versus government regulation and licensing. Discusses a case in Texas that challenged a software program offering legal advice; and a federal regulatory agency's attempt to regulate the opinions and content of newsletters, Web site publishers, and related software. (LRW)

  11. Design for pressure regulating components

    NASA Technical Reports Server (NTRS)

    Wichmann, H.

    1973-01-01

    The design development for Pressure Regulating Components included a regulator component trade-off study with analog computer performance verification to arrive at a final optimized regulator configuration for the Space Storable Propulsion Module, under development for a Jupiter Orbiter mission. This application requires the pressure regulator to be capable of long-term fluorine exposure. In addition, individual but basically identical (for purposes of commonality) units are required for separate oxidizer and fuel pressurization. The need for dual units requires improvement in the regulation accuracy over present designs. An advanced regulator concept was prepared featuring redundant bellows, all metallic/ceramic construction, friction-free guidance of moving parts, gas damping, and the elimination of coil springs normally used for reference forces. The activities included testing of actual size seat/poppet components to determine actual discharge coefficients and flow forces. The resulting data was inserted into the computer model of the regulator. Computer simulation of the propulsion module performance over two mission profiles indicated satisfactory minimization of propellant residual requirements imposed by regulator performance uncertainties.

  12. Oxygen, Homeostasis, and Metabolic Regulation

    Microsoft Academic Search

    Peter W. Hochachka

    Even a cursory review of the literature today indicates that two views dominate experimental approaches to metabolic regulation. Model I assumes that cell behavior is quite similar to that expected for a bag of enzymes. Model II assumes that 3-D order and structure constrain metabolite behavior and that metabolic regulation theory has to incorporate structure to ever come close to

  13. Strategic automation of emotion regulation.

    PubMed

    Gallo, Inge Schweiger; Keil, Andreas; McCulloch, Kathleen C; Rockstroh, Brigitte; Gollwitzer, Peter M

    2009-01-01

    As implementation intentions are a powerful self-regulation tool for thought and action (meta-analysis by P. M. Gollwitzer & P. Sheeran, 2006), the present studies were conducted to address their effectiveness in regulating emotional reactivity. Disgust- (Study 1) and fear- (Study 2) eliciting stimuli were viewed under 3 different self-regulation instructions: the goal intention to not get disgusted or frightened, respectively, this goal intention furnished with an implementation intention (i.e., an if-then plan), and a no-self-regulation control group. Only implementation-intention participants succeeded in reducing their disgust and fear reactions as compared to goal-intention and control participants. In Study 3, electrocortical correlates (using dense-array electroencephalography) revealed differential early visual activity in response to spider slides in ignore implementation-intention participants, as reflected in a smaller P1. Theoretical and applied implications of the present findings for emotion regulation via implementation intentions are discussed. PMID:19210061

  14. Competitive niche: Way of population regulation

    E-print Network

    Meszéna, Géza

    1 / 27 Competitive niche: Way of population regulation G´eza Mesz´ena1, Andr´as Szil´agyi1, Kalle of coexistence Theory Regulating loop Results Examples Spatial segregation Functional & spatial segregation Regulating loop y Results Examples Conclusions 7 / 27 #12;Regulating loop Introduction Theory y Regulating

  15. University of St Andrews SENATE REGULATIONS

    E-print Network

    Brierley, Andrew

    University of St Andrews SENATE REGULATIONS CHANGES TO TAKE EFFECT FROM 2009-10 Undergraduate Regulations General Regulation 27: amendment to the Regulation to clarify the categories of grades necessary. The Regulation was approved for implementation for all students who enter the MA General programme from the start

  16. Regulating chemicals: law, science, and the unbearable burdens of regulation.

    PubMed

    Silbergeld, Ellen K; Mandrioli, Daniele; Cranor, Carl F

    2015-03-18

    The challenges of regulating industrial chemicals remain unresolved in the United States. The Toxic Substances Control Act (TSCA) of 1976 was the first legislation to extend coverage to the regulation of industrial chemicals, both existing and newly registered. However, decisions related to both law and science that were made in passing this law inevitably rendered it ineffectual. Attempts to fix these shortcomings have not been successful. In light of the European Union's passage of innovative principles and requirements for chemical regulation, it is no longer possible to deny the opportunity and need for reform in US law and practice. PMID:25785889

  17. 75 FR 1269 - Vegetable Import Regulations; Modification of Potato Import Regulations; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

    ...Vegetable Import Regulations; Modification of Potato Import Regulations; Correction AGENCY...modified the import regulations for Irish potatoes and made minor administrative changes to the potato, onion, and tomato import regulations...

  18. Mechanisms regulating glioma invasion.

    PubMed

    Paw, Ivy; Carpenter, Richard C; Watabe, Kounosuke; Debinski, Waldemar; Lo, Hui-Wen

    2015-06-28

    Glioblastoma (GBM) is the most aggressive, deadliest, and most common brain malignancy in adults. Despite the advances made in surgical techniques, radiotherapy and chemotherapy, the median survival for GBM patients has remained at a mere 14 months. GBM poses several unique challenges to currently available treatments for the disease. For example, GBM cells have the propensity to aggressively infiltrate/invade into the normal brain tissues and along the vascular tracks, which prevents complete resection of all malignant cells and limits the effect of localized radiotherapy while sparing normal tissue. Although anti-angiogenic treatment exerts anti-edematic effect in GBM, unfortunately, tumors progress with acquired increased invasiveness. Therefore, it is an important task to gain a deeper understanding of the intrinsic and post-treatment invasive phenotypes of GBM in hopes that the gained knowledge would lead to novel GBM treatments that are more effective and less toxic. This review will give an overview of some of the signaling pathways that have been shown to positively and negatively regulate GBM invasion, including, the PI3K/Akt, Wnt, sonic hedgehog-GLI1, and microRNAs. The review will also discuss several approaches to cancer therapies potentially altering GBM invasiveness. PMID:25796440

  19. Mental fatigue impairs emotion regulation

    PubMed Central

    Grillon, C; Quispe-Escudero, D; Mathur, A; Ernst, M

    2015-01-01

    As 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 two separate sessions, healthy individuals performed easy (control session) or difficult (depletion session) cognitive tasks. Subsequently, they were presented neutral and negative pictures, with the 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, but not in the depletion session. These results indicate that mental fatigue following performance of cognitive tasks impairs emotion regulation without affecting emotion reactivity. These findings suggest that mental fatigue needs to be incorporated into models of emotion regulation. PMID:25706833

  20. Mental fatigue impairs emotion regulation.

    PubMed

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

    2015-06-01

    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. (PsycINFO Database Record PMID:25706833

  1. 75 FR 73958 - Belarus Sanctions Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ...Foreign Assets Control 31 CFR Part 548 Belarus Sanctions Regulations AGENCY: Office...Control (``OFAC'') is amending the Belarus Sanctions Regulations (``BSR...202/622-0077. Background The Belarus Sanctions Regulations, 31 CFR part...

  2. MEMBRANE SUMMARY: PERFORMANCE, CONCERNS, AND REGULATIONS

    EPA Science Inventory

    Several Federal regulations have been promulgated and many more are expected for limiting the concentrations of contaminants in drinking water. s these regulations are developed, Best Available Technology (BAT) has to be stipulated for meeting these regulations. arious treatment ...

  3. Post regulation circuit with energy storage

    DOEpatents

    Ball, Don G. (Livermore, CA); Birx, Daniel L. (Oakley, CA); Cook, Edward G. (Livermore, CA)

    1992-01-01

    A charge regulation circuit provides regulation of an unregulated voltage supply and provides energy storage. The charge regulation circuit according to the present invention provides energy storage without unnecessary dissipation of energy through a resistor as in prior art approaches.

  4. Drosophila Cytokine Unpaired 2 Regulates Physiological Homeostasis

    E-print Network

    Higgins, Darren

    Erratum Drosophila Cytokine Unpaired 2 Regulates Physiological Homeostasis by Remotely Controlling in press as: Rajan and Perrimon, Drosophila Cytokine Unpaired 2 Regulates Physiological Homeostasis Cytokine Unpaired 2 Regulates Physiological Homeostasis by Remotely Controlling Insulin Secretion, Cell

  5. 31 CFR 332.3 - Governing regulations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 2013-07-01 false Governing regulations. 332.3 Section 332.3 Money and Finance: Treasury Regulations Relating...OFFERING OF UNITED STATES SAVINGS BONDS, SERIES H § 332.3 Governing regulations. Series H bonds are...

  6. 5 CFR 550.1104 - Agency regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...2012-01-01 2012-01-01 false Agency regulations. 550.1104 Section 550.1104...PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) ...Government Employees § 550.1104 Agency regulations. Under this subpart and 5...

  7. MANEUVER REGULATION, TRANSVERSE FEEDBACK LINEARIZATION, AND ZERO

    E-print Network

    Maggiore, Manfredi

    MANEUVER REGULATION, TRANSVERSE FEEDBACK LINEARIZATION, AND ZERO DYNAMICS Chris Nielsen,1 Manfredi focus is on output maneuver regulation where stabilizing transverse dynamics is a key requirement. Keywords: Maneuver regulation, path following, feedback linearization, zero dynamics, non-square systems

  8. 34 CFR 303.3 - Applicable regulations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 2013-07-01 false Applicable regulations. 303.3 Section 303.3 Education Regulations of the Offices of the Department of...DISABILITIES General Purpose and Applicable Regulations § 303.3 Applicable...

  9. 5 CFR 550.1104 - Agency regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 2014-01-01 false Agency regulations. 550.1104 Section 550.1104...PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) ...Government Employees § 550.1104 Agency regulations. Under this subpart and 5...

  10. 5 CFR 550.1104 - Agency regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 2010-01-01 false Agency regulations. 550.1104 Section 550.1104...PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) ...Government Employees § 550.1104 Agency regulations. Under this subpart and 5...

  11. 5 CFR 550.1104 - Agency regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 2013-01-01 false Agency regulations. 550.1104 Section 550.1104...PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) ...Government Employees § 550.1104 Agency regulations. Under this subpart and 5...

  12. 15 CFR 922.165 - Emergency regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...2012-01-01 false Emergency regulations. 922.165 Section 922.165 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Florida Keys National Marine...

  13. 50 CFR 216.105 - Specific regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...2012-10-01 false Specific regulations. 216.105 Section 216.105...DEPARTMENT OF COMMERCE MARINE MAMMALS REGULATIONS GOVERNING THE TAKING AND IMPORTING OF MARINE MAMMALS General Regulations Governing Small Takes of...

  14. 5 CFR 550.1104 - Agency regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...2011-01-01 2011-01-01 false Agency regulations. 550.1104 Section 550.1104...PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) ...Government Employees § 550.1104 Agency regulations. Under this subpart and 5...

  15. General Qualification Regulations (Registered Undergraduate Qualifications)

    E-print Network

    Bandara, Arosha

    General Qualification Regulations (Registered Undergraduate Qualifications) Revised March 2013, effective from 1 March 2013 The General Qualification Regulations should not be read in isolation. It is important that you read them in conjunction with the following documents. · Module Regulations

  16. 7 CFR 983.50 - Aflatoxin regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 2010-01-01 false Aflatoxin regulations. 983.50 Section 983...NEW MEXICO Regulations § 983.50 Aflatoxin regulations. The committee shall...with the approval of the Secretary, such aflatoxin sampling, analysis, and...

  17. Machine Learning Helps Identify CHRONO as a Circadian Clock Component

    PubMed Central

    Venkataraman, Anand; Ramanathan, Chidambaram; Kavakli, Ibrahim H.; Hughes, Michael E.; Baggs, Julie E.; Growe, Jacqueline; Liu, Andrew C.; Kim, Junhyong; Hogenesch, John B.

    2014-01-01

    Over the last decades, researchers have characterized a set of “clock genes” that drive daily rhythms in physiology and behavior. This arduous work has yielded results with far-reaching consequences in metabolic, psychiatric, and neoplastic disorders. Recent attempts to expand our understanding of circadian regulation have moved beyond the mutagenesis screens that identified the first clock components, employing higher throughput genomic and proteomic techniques. In order to further accelerate clock gene discovery, we utilized a computer-assisted approach to identify and prioritize candidate clock components. We used a simple form of probabilistic machine learning to integrate biologically relevant, genome-scale data and ranked genes on their similarity to known clock components. We then used a secondary experimental screen to characterize the top candidates. We found that several physically interact with known clock components in a mammalian two-hybrid screen and modulate in vitro cellular rhythms in an immortalized mouse fibroblast line (NIH 3T3). One candidate, Gene Model 129, interacts with BMAL1 and functionally represses the key driver of molecular rhythms, the BMAL1/CLOCK transcriptional complex. Given these results, we have renamed the gene CHRONO (computationally highlighted repressor of the network oscillator). Bi-molecular fluorescence complementation and co-immunoprecipitation demonstrate that CHRONO represses by abrogating the binding of BMAL1 to its transcriptional co-activator CBP. Most importantly, CHRONO knockout mice display a prolonged free-running circadian period similar to, or more drastic than, six other clock components. We conclude that CHRONO is a functional clock component providing a new layer of control on circadian molecular dynamics. PMID:24737000

  18. Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia.

    PubMed

    Lippert, Julian; Halfter, Hartmut; Heidbreder, Anna; Röhr, Dominik; Gess, Burkhard; Boentert, Mathias; Osada, Nani; Young, Peter

    2014-01-01

    From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH. PMID:24454829

  19. A Regulator's View of Cogeneration

    E-print Network

    Shanaman, S. M.

    1982-01-01

    The Pennsylvania Public Utility Commission regulates essentially all types of public utilities and has the authority to investigate issues of public interest. To establish a point of reference, Pennsylvania's utilities contribute about 5 percent...

  20. California Energy Commission PROPOSED REGULATIONS

    E-print Network

    resources will reduce the amount of electricity generated and procured from nonrenewable energy sources renewable energy sources that is procured for California retail customers. An eligible renewable energyCalifornia Energy Commission PROPOSED REGULATIONS INITIAL STATEMENT OF REASONS FOR ENFORCEMENT

  1. Regulations and the air ambulance.

    PubMed

    Gibbons, H L

    1984-03-01

    The recent biopolitical history of air ambulance development and the need for regulations is reviewed. There has been significant interaction between Aerospace Medical Association committees, the Federal Aviation Administration, and the Civil Aeronautics Board. The Federal Aviation Administration's Advanced Notice and Withdrawal of Proposed Rulemaking, the latter based on the FAA supposition that the "majority" of states had enacted regulations and guidelines, is compared to actual data that only seven states have regulations and two have guidelines. The precedence for FAA to act on regulations is established. The Aerospace Medical Association and the National Highway Traffic Safety Administration - not the FAA - have established and documented excellent guidelines. The FAA is providing a valuable service to aviation in general and air ambulance operations specifically through physiological training at military facilities which can provide information to promote patient protection in air ambulance operations. PMID:6721812

  2. Nicotinic Regulation of Energy Homeostasis

    PubMed Central

    2012-01-01

    Introduction: The ability of nicotine, the primary psychoactive substance in tobacco smoke, to regulate appetite and body weight is one of the factors cited by smokers that prevents them from quitting and is the primary reason for smoking initiation in teenage girls. The regulation of feeding and metabolism by nicotine is complex, and recent studies have begun to identify nicotinic acetylcholine receptor (nAChR) subtypes and circuits or cell types involved in this regulation. Discussion: We will briefly describe the primary anatomical and functional features of the input, output, and central integration structures of the neuroendocrine systems that regulate energy homeostasis. Then, we will describe the nAChR subtypes expressed in these structures in mammals to identify the possible molecular targets for nicotine. Finally, we will review the effects of nicotine and its withdrawal on feeding and energy metabolism and attribute them to potential central and peripheral cellular targets. PMID:22990212

  3. Flow-compensating pressure regulator

    NASA Technical Reports Server (NTRS)

    Baehr, E. F.

    1979-01-01

    Pressure regulator developed for use with cataract-surgery instrument controls intraocular pressure during substantial variations in flow rate of infusion fluid. Device may be applicable to variety of eye-surgery instruments.

  4. Indiana Aquaculture Regulations and Permits

    E-print Network

    Indiana Aquaculture Regulations and Permits Jennifer Strasser, DVM Aquaculture Coordinator Indiana in public waters ­ Diseases of concern to wild fish ­ Invasive species · BOAH ­ Aquaculture operations ­ Listed regulatory diseases #12;Farm Permits · DNR Aquaculture Permit ­ Raise "non-approved" species

  5. Illinois Aquaculture Regulations and Permits

    E-print Network

    Illinois Aquaculture Regulations and Permits Steven Shults Aquaculture and AIS Program Manager ­ Fish diseases ­ Invasive species · IDAg ­ Marketing and Promotions #12;Aquaculture Permits · IDNR Aquaculture Permit ­ Breed, Hatch, Propagate or Raise aquatic life ­ Applies to both "approved

  6. Clock genes: their role in colorectal cancer.

    PubMed

    Karantanos, Theodoros; Theodoropoulos, George; Pektasides, Dimitrios; Gazouli, Maria

    2014-02-28

    Clock genes create a complicated molecular time-keeping system consisting of multiple positive and negative feedback loops at transcriptional and translational levels. This circadian system coordinates and regulates multiple cellular procedures implicated in cancer development such as metabolism, cell cycle and DNA damage response. Recent data support that molecules such as CLOCK1, BMAL1 and PER and CRY proteins have various effects on c-Myc/p21 and Wnt/?-catenin pathways and influence multiple steps of DNA damage response playing a critical role in the preservation of genomic integrity in normal and cancer cells. Notably, all these events have already been related to the development and progression of colorectal cancer (CRC). Recent data highlight critical correlations between clock genes' expression and pathogenesis, progression, aggressiveness and prognosis of CRC. Increased expression of positive regulators of this circadian system such as BMAL1 has been related to decrease overall survival while decreased expression of negative regulators such as PER2 and PER3 is connected with poorer differentiation, increased aggressiveness and worse prognosis. The implications of these molecules in DNA repair systems explain their involvement in the development of CRC but at the same time provide us with novel targets for modern therapeutic approaches for patients with advanced CRC. PMID:24587674

  7. Regulated Genes in Transgenic Plants

    Microsoft Academic Search

    Philip N. Benfey; Nam-Hai Chua

    1989-01-01

    Transgenic plants are an effective system for the study of regulated gene expression. Developmental control of expression can be monitored by assaying different tissues or by assaying a plant at different developmental stages. Analysis of the petunia 5-enolpyruvylshikimate-3-phosphate synthase gene, which is highly expressed in flowers, allowed identification of an upstream region that confers tissue-specific and developmentally regulated expression. The

  8. Does diacylglycerol regulate KCNQ channels?

    Microsoft Academic Search

    Byung-Chang Suh; Bertil Hille

    2006-01-01

    Some ion channels are regulated by inositol phospholipids and by the products of cleavage by phospholipase C (PLC). KCNQ channels\\u000a (Kv7) require membrane phosphatidylinositol 4,5-bisphosphate (PIP2) and are turned off when muscarinic receptors stimulate cleavage of PIP2 by PLC. We test whether diacylglycerols are also important in the regulation of KCNQ2\\/KCNQ3 channels using electrophysiology\\u000a and fluorescent translocation probes as indicators

  9. Diacylglycerol kinase ?: Regulation and stability

    PubMed Central

    Tu-Sekine, Becky; Goldschmidt, Hana; Petro, Elizabeth; Raben, Daniel M.

    2014-01-01

    Given the well-established roles of diacylglycerol (DAG) and phosphatidic acid (PtdOH) in a variety of signaling cascades, it is not surprising that there is an increasing interest in understanding their physiological roles and mechanisms that regulate their cellular levels. One class of enzymes capable of coordinately regulating the levels of these two lipids is the diacylglycerol kinases (DGKs). These enzymes catalyze the transfer of the ?-phosphate of ATP to the hydroxyl group of DAG, which generates PtdOH while reducing DAG. As these enzymes reciprocally modulate the relative levels of these two signaling lipids, it is essential to understand the regulation and roles of these enzymes in various tissues. One system where these enzymes play important roles is the nervous system. Of the ten mammalian DGKs, eight of them are readily detected in the mammalian central nervous system (CNS): DGK-?, DGK-?, DGK-?, DGK-?, DGK-?, DGK-?, DGK-?, and DGK-?. Despite the increasing interest in DGKs, little is known about their regulation. We have focused some attention on understanding the enzymology and regulation of one of these DGK isoforms, DGK-?. We recently showed that DGK-? is regulated by an accessory protein containing polybasic regions. We now report that this accessory protein is required for the previously reported broadening of the pH profile observed in cell lysates in response to phosphatidylserine (PtdSer). Our data further reveal DGK-? is regulated by magnesium and zinc, and sensitive to the known DGK inhibitor R599022. These data outline new parameters involved in regulating DGK-?. PMID:23266086

  10. Emotion regulation and sport performance.

    PubMed

    Wagstaff, Christopher R D

    2014-08-01

    This study used a single-blind, within-participant, counterbalanced, repeated-measures design to examine the relationship between emotional self-regulation and sport performance. Twenty competitive athletes completed four laboratory-based conditions; familiarization, control, emotion suppression, and nonsuppression. In each condition participants completed a 10-km cycling time trial requiring self-regulation. In the experimental conditions participants watched an upsetting video before performing the cycle task. When participants suppressed their emotional reactions to the video (suppression condition) they completed the cycling task slower, generated lower mean power outputs, and reached a lower maximum heart rate and perceived greater physical exertion than when they were given no self-regulation instructions during the video (nonsuppression condition) and received no video treatment (control condition). The findings suggest that emotional self-regulation resource impairment affects perceived exertion, pacing and sport performance and extends previous research examining the regulation of persistence on physical tasks. The results are discussed in line with relevant psychophysiological theories of self-regulation and fatigue and pertinent potential implications for practice regarding performance and well-being are suggested. PMID:25226609

  11. The Political Economy of Price Cap Regulation

    Microsoft Academic Search

    Dale E. Lehman; Dennis L. Weisman

    2000-01-01

    The last decade has witnessed a dramatic substitutionof price cap regulation for rate-of-return regulationin the telecommunications industry. The 1996Telecommunications Act empowers state regulators toset the terms of competitive entry in local telephonemarkets. We investigate whether the form of regulationendogenously affects the regulator's behavior withrespect to competitive entry. The evidence revealsthat regulators in price cap jurisdictions tend to setmore liberal terms

  12. Risk, price regulation, and irreversible investment

    Microsoft Academic Search

    Lewis T. Evans; Graeme A. Guthrie

    2005-01-01

    We show that regulators' price-setting, rate base, and allowed rate of return decisions are inextricably linked if prices are set so that regulated firms just break even whenever they are forced to invest. Breaking even ex ante is a necessary condition for Ramsey pricing to be sustainable over time. Unless regulators adopt traditional rate of return regulation, the irreversibility of

  13. OUTPUT REGULATION OF NONLINEAR NEUTRAL SYSTEMS

    E-print Network

    Fridman, Emilia

    OUTPUT REGULATION OF NONLINEAR NEUTRAL SYSTEMS Emilia Fridman1 Department of Electrical Engineering, Tel-Aviv University Ramat-Aviv, Tel-Aviv 69978, Israel emilia@eng.tau.ac.il Summary. Output regulation regulation, regulator equations, center manifold 1 Introduction One of the most important problems in control

  14. University of St Andrews Undergraduate Senate Regulations

    E-print Network

    Brierley, Andrew

    University of St Andrews Undergraduate Senate Regulations Amendments taking effect from 2011-2012 Faculty of Arts Senate Regulations 1. Trailing Credits into Honours Reason for amendment: In Divinity of Arts and needs to be reflected in the Senate Regulations. II ARTS REGULATIONS, D. Honours 4. A student

  15. University of St Andrews POSTGRADUATE SENATE REGULATIONS

    E-print Network

    Brierley, Andrew

    University of St Andrews POSTGRADUATE SENATE REGULATIONS CHANGES TO TAKE EFFECT FROM 2010-11 Postgraduate regulations all amended per TLAC 19 May 2010: A. REGULATIONS FOR RESEARCH STUDENTS AND APPOINTMENT OF PHILOSOPHY (Ph.D.) IV Duration and Place of Study New Regulation 4. 4. Where a supervisor joins the staff

  16. NOTICE OF REGULATION REPEAL Date: May 24, 2010

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: May 24, 2010 REGULATION TITLE: REGULATION NO.: Conflict of Interest 6C7-3.008 SUMMARY OF REGULATION REPEAL: This regulation is proposed for repeal, because the material contained in this regulation has been moved to regulation UCF-3.018 AUTHORITY: BOG Regulation 1

  17. NOTICE OF REGULATION REPEAL Date: June 9, 2014

    E-print Network

    Pattanaik, Sumanta N.

    NOTICE OF REGULATION REPEAL Date: June 9, 2014 REGULATION TITLE: REGULATION NO.: Tenure UCF-3.011 SUMMARY OF REGULATION REPEAL: This regulation is proposed for repeal because the material contained in this regulation has been moved to regulation UCF-3.015. AUTHORITY: BOG Regulations 1.001 NAME OF PERSON WHO

  18. NOTICE OF REGULATION REPEAL Date: August 6, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: August 6, 2009 REGULATION TITLE: REGULATION NO.: Purchase and Sale of Real Property 6C7-7.202 SUMMARY OF REGULATION REPEAL: This regulation is not necessary and does REGULATION REPEAL: Regulations Administrator COMMENTS CONCERNING THE REGULATION REPEAL SHOULD BE SUBMITTED

  19. Bile Acids Regulate Cardiovascular Function

    PubMed Central

    Khurana, Sandeep; Raufman, Jean-Pierre; Pallone, Thomas L.

    2011-01-01

    Research over the last decade has uncovered roles for bile acids (BAs) that extend beyond their traditional functions in regulating lipid digestion and cholesterol metabolism. BAs are now recognized as signaling molecules that interact with both plasma membrane and nuclear receptors. Emerging evidence indicates that by interacting with these receptors BAs regulate their own synthesis, glucose and energy homeostasis, and other important physiological events. Herein, we provide a comprehensive review of the actions of BAs on cardiovascular function. In the heart and the systemic circulation, BAs interact with plasma membrane G-protein coupled receptors, e.g. TGR5 and muscarinic receptors, and nuclear receptors, e.g. the farnesoid (FXR) and pregnane (PXR) xenobiotic receptors. BA receptors are expressed in cardiovascular tissue, however, the mechanisms underlying BA-mediated regulation of cardiovascular function remain poorly understood. BAs reduce heart rate by regulating channel conductance and calcium dynamics in sino-atrial and ventricular cardiomyocytes, and regulate vascular tone via both endothelium-dependent and -independent mechanisms. End-stage-liver disease, obstructive jaundice and intrahepatic cholestasis of pregnancy are prominent conditions in which elevated serum BAs alter vascular dynamics. This review focuses on BAs as newly-recognized signaling molecules that modulate cardiovascular function. PMID:21707953

  20. Law and regulation of benzene.

    PubMed Central

    Feitshans, I L

    1989-01-01

    OSHA has created final benzene regulations after extensive rulemakings on two occasions, 1978 and 1987. These standards have been the subject of extensive litigation for nearly 20 years. This article examines in detail the conceptual underpinnings of the Benzene Case, (which was decided by the U.S. Supreme Court in 1980) in light of U.S. administrative law precedents that have set limits upon administrative discretion under the test for "substantial evidence" and the "hard look doctrine." This article also addresses recent developments in the wake of the Benzene Case and their implications for benzene regulations following the "significant risk" doctrine in that case. This article briefly describes other national, regional, and international laws governing the use of benzene. This article concludes that the revisions of the benzene regulation and subsequent rulemaking provide substantial evidence of scientific underpinnings for regulatory action and that laws from other nations reflect an international consensus that occupational exposure to benzene is a proper subject of regulation. Such regulations and policies are therefore likely to withstand scrutiny and remain enforceable as widely accepted norms. PMID:2792048

  1. Endocrine regulation of HOX genes.

    PubMed

    Daftary, Gaurang S; Taylor, Hugh S

    2006-06-01

    Hox genes have a well-characterized role in embryonic development, where they determine identity along the anteroposterior body axis. Hox genes are expressed not only during embryogenesis but also in the adult, where they are necessary for functional differentiation. Despite the known function of these genes as transcription factors, few regulatory mechanisms that drive Hox expression are known. Recently, several hormones and their cognate receptors have been shown to regulate Hox gene expression and thereby mediate development in the embryo as well as functional differentiation in the adult organism. Estradiol, progesterone, testosterone, retinoic acid, and vitamin D have been shown to regulate Hox gene expression. In the embryo, the endocrine system directs axial Hox gene expression; aberrant Hox gene expression due to exposure to endocrine disruptors contributes to the teratogenicity of these compounds. In the adult, endocrine regulation of Hox genes is necessary to enable such diverse functions as hematopoiesis and reproduction; endocrinopathies can result in dysregulated HOX gene expression affecting physiology. By regulating HOX genes, hormonal signals utilize a conserved mechanism that allows generation of structural and functional diversity in both developing and adult tissues. This review discusses endocrine Hox regulation and its impact on physiology and human pathology. PMID:16632680

  2. An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action

    PubMed Central

    Gibbs, Julie; Ince, Louise; Matthews, Laura; Mei, Junjie; Bell, Thomas; Yang, Nan; Saer, Ben; Begley, Nicola; Poolman, Toryn; Pariollaud, Marie; Farrow, Stuart; Demayo, Francesco; Hussell, Tracy; Worthen, G Scott; Ray, David; Loudon, Andrew

    2014-01-01

    The circadian system is as an important regulator of immune function. Human inflammatory lung diseases frequently show time-of-day variation in symptom severity and lung function, but the mechanisms and cell types that are underlying these effects remain unclear. We show that pulmonary antibacterial responses are modulated by a circadian clock within epithelial club (Clara) cells. These drive circadian neutrophil recruitment to the lung via the chemokine CXCL5. Genetic ablation of the clock gene Bmal1 (also called Arntl or MOP3) in bronchiolar cells disrupts rhythmic Cxcl5 expression, resulting in exaggerated inflammatory responses to lipopolysaccharide and bacterial infection. Adrenalectomy blocks rhythmic inflammatory responses and the circadian regulation of CXCL5, suggesting a key role for the adrenal axis in driving CXCL5 expression and pulmonary neutrophil recruitment. Glucocorticoid receptor occupancy at the Cxcl5 locus shows circadian oscillations, but this is disrupted in mice with bronchiole-specific ablation of Bmal1, leading to enhanced CXCL5 expression despite normal corticosteroid secretion. In clock-gene disrupted mice the synthetic glucocorticoid dexamethasone loses anti-inflammatory efficacy. We now define a regulatory mechanism that links the circadian clock and glucocorticoid hormones to control both time-of-day variation and also the magnitude of pulmonary inflammation and responses to bacterial infection. PMID:25064128

  3. Melatonin Signaling Modulates Clock Genes Expression in the Mouse Retina

    PubMed Central

    Coulson, Elise; Kunst, Stefanie; Spessert, Rainer; Tosini, Gianluca

    2014-01-01

    Previous studies have shown that retinal melatonin plays an important role in the regulation of retinal daily and circadian rhythms. Melatonin exerts its influence by binding to G-protein coupled receptors named melatonin receptor type 1 and type 2 and both receptors are present in the mouse retina. Earlier studies have shown that clock genes are rhythmically expressed in the mouse retina and melatonin signaling may be implicated in the modulation of clock gene expression in this tissue. In this study we determined the daily and circadian expression patterns of Per1, Per2, Bmal1, Dbp, Nampt and c-fos in the retina and in the photoreceptor layer (using laser capture microdissection) in C3H-f+/+ and in melatonin receptors of knockout (MT1 and MT2) of the same genetic background using real-time quantitative RT-PCR. Our data indicated that clock and clock-controlled genes are rhythmically expressed in the retina and in the photoreceptor layer. Removal of melatonin signaling significantly affected the pattern of expression in the retina whereas in the photoreceptor layer only the Bmal1 circadian pattern of expression was affected by melatonin signaling removal. In conclusion, our data further support the notion that melatonin signaling may be important for the regulation of clock gene expression in the inner or ganglion cells layer, but not in photoreceptors. PMID:25203735

  4. Administrative Regulation 9:1 Page 1 of 6 Administrative Regulation 9:1

    E-print Network

    MacAdam, Keith

    Administrative Regulation 9:1 Page 1 of 6 Administrative Regulation 9:1 Responsible Office: Vice/3/1985 Regulations Governing Time, Place, and Manner of Meetings, Demonstrations, and Other Assemblies Regulation of their exercise and the rights of others in the effective use of University facilities, the following regulations

  5. Regulations on the Conduct of Research 1 REGULATION ON THE CONDUCT OF RESEARCH

    E-print Network

    Fabry, Frederic

    Regulations on the Conduct of Research 1 REGULATION ON THE CONDUCT OF RESEARCH This Regulation replaces the following: Policy on Research Ethics Regulations on Research Policy PREAMBLE Research in place. This Regulation, therefore, establishes a general framework for the conduct of research

  6. SB 4 Interim Well Stimulation Treatment Regulations Text of Proposed Regulations

    E-print Network

    SB 4 Interim Well Stimulation Treatment Regulations Text of Proposed Regulations Page 1 of 12 SB 4 INTERIM WELL STIMULATION TREATMENT REGULATIONS TEXT OF PROPOSED REGULATIONS Added text is shown in underline. CHAPTER 4. DEVELOPMENT, REGULATION, AND CONSERVATION OF OIL AND GAS RESOURCES Subchapter 2

  7. Human Telomerase and Its Regulation

    PubMed Central

    Cong, Yu-Sheng; Wright, Woodring E.; Shay, Jerry W.

    2002-01-01

    The telomere is a special functional complex at the end of linear eukaryotic chromosomes, consisting of tandem repeat DNA sequences and associated proteins. It is essential for maintaining the integrity and stability of linear eukaryotic genomes. Telomere length regulation and maintenance contribute to normal human cellular aging and human diseases. The synthesis of telomeres is mainly achieved by the cellular reverse transcriptase telomerase, an RNA-dependent DNA polymerase that adds telomeric DNA to telomeres. Expression of telomerase is usually required for cell immortalization and long-term tumor growth. In humans, telomerase activity is tightly regulated during development and oncogenesis. The modulation of telomerase activity may therefore have important implications in antiaging and anticancer therapy. This review describes the currently known components of the telomerase complex and attempts to provide an update on the molecular mechanisms of human telomerase regulation. PMID:12208997

  8. [Regulation of brain microvessel function].

    PubMed

    Kobayashi, Hideyuki; Yokoo, Hiroki; Yanagita, Toshihiko; Wada, Akihiko

    2002-05-01

    The brain microvessels are formed by a specialized endothelium and regulate the movement of solutes between blood and brain. The endothelial cells are sealed together by tight junctions and play a role as the blood-brain barrier. The brain microvessels express GLUT1 as the major form of glucose transporter, aquaporin-4 as a water channel, and p-glycoprotein as a xenobiotic transporter. Occludin and claudin-5 have been identified as the components of tight junction. Increasing evidence suggests that the activities of the transporters are regulated by adrenergic nerve activity as well as by bioactive peptides such as adrenomedullin. The regulation of the activity as well as expression of these transporters may become a strategy for prophylaxis and treatment of not only cerebral vascular diseases but also neurodegenerative disorders, developmental abnormalities and aging of the brain. PMID:12061139

  9. Redox regulation of Janus kinase

    PubMed Central

    Duhé, Roy J

    2013-01-01

    The redox regulation of Janus kinases (JAKs) is a complex subject. Due to other redox-sensitive kinases in the kinome, redox-sensitive phosphatases, and cellular antioxidant systems and reactive oxygen species (ROS) production systems, the net biological outcomes of oxidative stress on JAK-dependent signal transduction vary according to the specific biological system examined. This review begins with a discussion of the biochemical evidence for a cysteine-based redox switch in the catalytic domain of JAKs, proceeds to consider direct and indirect regulatory mechanisms involved in biological experiments, and ends with a discussion of the role(s) of redox regulation of JAKs in various diseases. PMID:24416654

  10. Regulation of Inflammation by Adenosine

    PubMed Central

    Haskó, György; Cronstein, Bruce

    2013-01-01

    Adenosine, a purine nucleoside generated by the dephosphorylation of adenine nucleotides, is a potent endogenous physiologic and pharmacologic regulator of many functions. Adenosine was first reported to inhibit the inflammatory actions of neutrophils nearly 30?years ago and since then the role of adenosine and its receptors as feedback regulators of inflammation has been well established. Here we review the effects of adenosine, acting at its receptors, on neutrophil and monocyte/macrophage function in inflammation. Moreover, we review the role of adenosine in mediating the anti-inflammatory effects of methotrexate, the anchor drug in the treatment of Rheumatoid Arthritis and other inflammatory disorders. PMID:23580000

  11. Transcriptional regulation in wood formation.

    PubMed

    Demura, Taku; Fukuda, Hiroo

    2007-02-01

    Wood (i.e. xylem tissue) in trees is mainly composed of two types of cells, fibres and tracheary elements. Recent molecular studies of various trees, as well as the non-tree species Arabidopsis thaliana and Zinnia elegans, have revealed coordinated gene expression during differentiation of these cells in wood and the presence of several transcription factors that might govern the complex networks of transcriptional regulation. This article reviews recent findings concerning the regulation of genes by transcription factors involved in wood formation such as AUXIN RESPONSE FACTOR (ARF), CLASS III HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIPIII), KANADI (KAN), MYB and NAM/ATAF/CUC (NAC). PMID:17224301

  12. Politics of public utility regulation

    SciTech Connect

    Gormley, W.T. Jr.

    1983-01-01

    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.

  13. CNS Regulation of Glucose Homeostasis

    NSDL National Science Digital Library

    2009-06-01

    The past decade has hosted a remarkable surge in research dedicated to the central control of homeostatic mechanisms. Evidence indicates that the brain, in particular the hypothalamus, directly senses hormones and nutrients to initiate behavioral and metabolic responses to control energy and nutrient homeostasis. Diabetes is chiefly characterized by hyperglycemia due to impaired glucose homeostatic regulation, and a primary therapeutic goal is to lower plasma glucose levels. As such, in this review, we highlight the role of the hypothalamus in the regulation of glucose homeostasis in particular and discuss the cellular and molecular mechanisms by which this neural pathway is orchestrated.

  14. Regulation of Francisella Tularensis Virulence

    PubMed Central

    Dai, Shipan; Mohapatra, Nrusingh P.; Schlesinger, Larry S.; Gunn, John S.

    2011-01-01

    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. PMID:21687801

  15. Implementation Regulations MSc programme CE 2014 2015 THE IMPLEMENTATION REGULATIONS

    E-print Network

    part) completes the master programme. The student may opt for: - Research and Development (Industrial-2015 MASTER OF SCIENCE CHEMICAL ENGINEERING DELFT UNIVERSITY OF TECHNOLOGY #12;Implementation Regulations MSc Chemical Engineering 2014-2015 2 LIST OF CONTENTS Article 1 ­ The study load

  16. SB 4 Well Stimulation Treatment Regulations Text of Proposed Regulations

    E-print Network

    . CHAPTER 4. DEVELOPMENT, REGULATION, AND CONSERVATION OF OIL AND GAS RESOURCES Subchapter 2. Environmental to perform well stimulation treatments and/or notices of intent to drill or rework wells. (b) A request: (1) "Well stimulation treatment" means a treatment of a well designed to enhance oil and gas

  17. Regulation XXI: GENERAL REGULATIONS AS TO PROGRESS OF STUDENTS8

    E-print Network

    by the Faculty under the following Regulations or by the Faculty Student Review Committee to which the Faculty into consideration. 3. The Pro-Vice-Chancellor or another Officer of the Faculty will offer any student whose affecting the case. 4. The Faculty or the Committee will have power: (a) to exclude or suspend the student

  18. Implementation Regulations, supplementing LS&T Teaching and Examination Regulations (Delft Master's degree programme) 2014-15

    E-print Network

    Implementation Regulations, supplementing LS&T Teaching and Examination Regulations (Delft Master Regulations relating to the Teaching and Examination Regulations for the Master's degree programme Life Science & Technology, Delft 2014-2015 #12;Implementation Regulations, supplementing LS&T Teaching

  19. 76 FR 70220 - New Jersey Regulations on Transportation of Regulated Medical Waste

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-10

    ...on Transportation of Regulated Medical Waste AGENCY: Pipeline and Hazardous...the transportation of regulated medical waste in commerce, including the packaging of regulated medical waste for transportation; marking...

  20. 75 FR 75904 - Global Terrorism Sanctions Regulations; Terrorism Sanctions Regulations; Foreign Terrorist...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-07

    ...Control 31 CFR Parts 594, 595, and 597 Global Terrorism Sanctions Regulations; Terrorism Sanctions Regulations; Foreign Terrorist Organizations...Department of the Treasury is amending the Global Terrorism Sanctions Regulations (``GTSR'') and...

  1. 43 CFR 1821.13 - What if the specific program regulations conflict with these regulations?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...2012-10-01 2012-10-01 false What if the specific program regulations conflict with these regulations? 1821.13 Section 1821.13 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND...

  2. The Regulation of Carcinogenic Hazards.

    ERIC Educational Resources Information Center

    Gori, Gio Batta

    1980-01-01

    It is suggested that a system of relative standards be formulated which would compare utility of substances to their relative risk as carcinogens. This would define a range of use restrictions. Substances intended for specific uses would then be regulated according to these standards. (Author/RE)

  3. Beyond population regulation and limitation

    Microsoft Academic Search

    Charles J. Krebs

    2002-01-01

    The study of population dynamics addresses three questions that are not always separated in discussions with empirical data. Two questions address population regulation. What stabilises population density is the first question, and, in spite of much theory, little progress has been made in answering this question empirically. The assumption of an equilibrium density is impossible to test and direct experimental

  4. ACADEMIC REGULATIONS COMMITTEE MEDICAL FORM

    E-print Network

    Meyers, Steven D.

    \\ ACADEMIC REGULATIONS COMMITTEE MEDICAL FORM INSTRUCTIONS The lower part of this form needs to be completed by the appropriate medical professional and the entire form should be returned in a SEALED: ______________________ Affected Semester (s): __________________ Medical problem pertains to: _____ Student _____ Family Member

  5. Electronically Variable Pressure Regulator (EVPR)

    Microsoft Academic Search

    R. H. Reinicke; R. O. Nelson; E. Hurlbert

    1989-01-01

    A new programmable electronically variable pressure regulator (EVPR) concept accurately controls the local outlet or remote system pressure. It uses an integral pulse width modulated rare earth permanent magnet motor operating in response to redundant pressure transducer feedback signals. The EVPR is a simple single stage device that does not use dynamic seals or pilot valving. Conversion of partial revolution

  6. California Energy Commission PROPOSED REGULATIONS

    E-print Network

    the amount of electricity generated and procured from nonrenewable energy sources, such as fossil fuelbased the amount of electricity generated from eligible renewable energy sources3 that is procured for CaliforniaCalifornia Energy Commission PROPOSED REGULATIONS SUPPORTING MATERIAL FOR THE ECONOMIC

  7. Army Regulation 690600 Civilian Personnel

    E-print Network

    US Army Corps of Engineers

    Army Regulation 690­600 Civilian Personnel Equal Employment Opportunity Discrimination Complaints Headquarters Department of the Army Washington, DC 9 February 2004 UNCLASSIFIED #12;SUMMARY of CHANGE AR 690 discrimination complaints. o Requires Army activities to establish an alternative dispute resolution program

  8. Army Regulation 2001 Environmental Quality

    E-print Network

    US Army Corps of Engineers

    Army Regulation 200­1 Environmental Quality Environmental Protection and Enhancement Headquarters Department of the Army Washington, DC 13 December 2007 UNCLASSIFIED #12;SUMMARY of CHANGE AR 200 the policy regarding Army Program Guidance Memorandum (para 15-1). o Corrects typographical errors throughout

  9. Temperature: Human Regulating, Ants Conforming

    ERIC Educational Resources Information Center

    Clopton, Joe R.

    2007-01-01

    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.

  10. Molecular regulation of vessel maturation

    Microsoft Academic Search

    Rakesh K Jain

    2003-01-01

    The maturation of nascent vasculature, formed by vasculogenesis or angiogenesis, requires recruitment of mural cells, generation of an extracellular matrix and specialization of the vessel wall for structural support and regulation of vessel function. In addition, the vascular network must be organized so that all the parenchymal cells receive adequate nutrients. All of these processes are orchestrated by physical forces

  11. Pricing Regulation Under Bypass Competition

    Microsoft Academic Search

    Nicolas Curien; Bruno Jullien; Patrick Rey

    1998-01-01

    We analyze optimal pricing policies in local telecommunications subject to bypass for the access of long-distance carriers. We first consider the case of a regulated monopoly that operates the local network and has access to an additional technology (bypass) more efficient for large customers. We then study how competition in bypass affects the optimal nonlinear pricing policy and the resulting

  12. Safety Regulations of Food Enzymes

    Microsoft Academic Search

    Armin Spök

    Summary The majority of industrial enzymes available at present is used in food industry. Safe- ty regulations of food enzymes differ among countries, including fundamental aspects, whether a pre-market approval is needed and on the level of details, e.g. what particular information manufacturers have to provide in the course of safety evaluation. Occupa- tional safety concerns focus on allergenic properties

  13. Grantiau a Rheoliadau Grants & Regulations

    E-print Network

    Grantiau a Rheoliadau Grants & Regulations Information Note 13 Transitional Arrangements for BWW July 2010 Background Forestry Commission Wales (FCW) currently provides grant aid via the Better reviewed how the woodland grants should be delivered in future. The aim of the review was to reposition

  14. Cytokine regulation of chemical sensitization

    Microsoft Academic Search

    Ian Kimber; Mark R. Holliday; Rebecca J. Dearman

    1995-01-01

    The skin is an immunologically active tissue. Epidermal cells, both keratinocytes and Langerhans cells (LC), produce constitutively or can be stimulated to produce a variety of cytokines, many of which play important roles in the induction and regulation of allergic responses to sensitizing chemicals. Tumor necrosis factor a (TNF-?) provides the signal for LC migration from the skin and granulocyte\\/macrophage

  15. Posttranscriptional Gene Regulation by Spatial

    E-print Network

    Bedwell, David M.

    Posttranscriptional Gene Regulation by Spatial Rearrangement of the 3 Untranslated Region Andrea B for Posttranscriptional Gene Regualtion by spatial Rearrangement of 3'UTR #12;A Competition between Stimulators Intron Enhances NMD PABC1 Antagonizes the interaction between eRF3 and hUpf1 in vitro #12;A Competition

  16. SAFETY REGULATION GROUP FLIGHT OPERATIONS

    E-print Network

    Ladkin, Peter B.

    SAFETY REGULATION GROUP FLIGHT OPERATIONS DEPARTMENT COMMUNICATION Flight Operations Department the technical investigation continues, it is considered prudent to remind operators and their flight crews was transmitting an erroneous signal that the aircraft may have used to update the Flight Management Guidance

  17. Promoting Floriculture Using VAT Regulation

    Microsoft Academic Search

    Frank H. J. Bunte; J. van der Lugt; W. Erno Kuiper

    2008-01-01

    In twelve EU countries, the lower VAT-tariff is applied to flowers and plants in order to promote the production and employment in floriculture. This paper assesses whether the VAT-regulation for flowers and plants achieves the goals set – promoting consumer demand and production and employment in the ornamental supply chain - (effectiveness) and at what cost (efficiency). The empirical results

  18. Endocytic regulation of TGF-? signaling

    Microsoft Academic Search

    Ye-Guang Chen

    2009-01-01

    Transforming growth factor-? (TGF-?) signaling is tightly regulated to ensure its proper physiological functions in different cells and tissues. Like other cell surface receptors, TGF-? receptors are internalized into the cell, and this process plays an important regulatory role in TGF-? signaling. It is well documented that TGF-? receptors are endocytosed via clathrin-coated vesicles as TGF-? endocytosis can be blocked

  19. Cadherin Regulates Dendritic Spine Morphogenesis

    Microsoft Academic Search

    Hideru Togashi; Kentaro Abe; Akira Mizoguchi; Kanna Takaoka; Osamu Chisaka; Masatoshi Takeichi

    2002-01-01

    Synaptic remodeling has been postulated as a mechanism underlying synaptic plasticity, and cadherin adhesion molecules are thought to be a regulator of such a process. We examined the effects of cadherin blockage on synaptogenesis in cultured hippocampal neurons. This blockade resulted in alterations of dendritic spine morphology, such as filopodia-like elongation of the spine and bifurcation of its head structure,

  20. REGULATIONS OF UNIVERSITY OF FLORIDA

    E-print Network

    Pilyugin, Sergei S.

    -resident tuition costs as set forth in Regulation 6C1-3.0375, for the audited course. (19) Off-campus educational to the University of Florida shall pay a non-refundable application fee in the amount of $30.00. This fee is waived as determined by the College Board or the American College Testing Program. (3) Library overdue fines

  1. Regulation of protein kinase C

    Microsoft Academic Search

    Alexandra C Newton

    1997-01-01

    Protein kinase C has been in the spotlight since the discovery two decades ago that is activated by the lipid second messenger diacylglycerol. Despite protein kinase C's enduring stage presence, the regulation and specific roles of its isozymes in defined cellular processes are still under intense investigation. Elucidation of the structures of protein kinase C's regulatory modules, the discovery that

  2. Regulation of Cranial Suture Morphogenesis

    Microsoft Academic Search

    Roy C. Ogle; Sunil S. Tholpady; Kathryn A. McGlynn; Rebecca A. Ogle

    2004-01-01

    The cranial sutures are the primary sites of bone formation during skull growth. Morphogenesis and phenotypic maintenance of the cranial sutures are regulated by tissue interactions, especially those with the underlying dura mater. Removal of the dura mater in fetuses causes abnormal suture development and premature suture obliteration. The dura mater interacts with overlying tissues of the cranial vault by

  3. Parking Services Rules and Regulations

    E-print Network

    Moore, Paul A.

    Parking Services Rules and Regulations 2013 ­ 2014 Academic Year / Summer #12;Table of Contents 1 Authority 3 1.1 Manager of Parking Services 3 1.2 Discretion and Authority 3 1.3 Authorization 3 1.4 Liability 3 2 Two Wheeled Vehicles 4 2.1 Motorcycles / Mopeds / Scooters 4 3 Parking Permits 4 3.1 General

  4. Parking Regulations PARKING POLICY STATEMENT

    E-print Network

    Richards-Kortum, Rebecca

    1 Parking Regulations PARKING POLICY STATEMENT: 1. All employees and students of Rice University who park on campus are required to register their motor vehicles with the Rice Parking Office or park in designated *paid visitor parking facilities. 2. All visitors park in *visitor parking. 3. Only areas marked

  5. Minireview: Gut Peptides Regulating Satiety

    Microsoft Academic Search

    MARALYN R. DRUCE; CAROLINE J. SMALL; STEPHEN R. BLOOM

    2004-01-01

    The gastrointestinal tract and the pancreas release hormones regulating satiety and body weight. Ghrelin stimulates appe- tite, and glucagon-like peptide-1, oxyntomodulin, peptide YY, cholecystokinin, and pancreatic polypeptide inhibit appetite. These gut hormones act to markedly alter food intake in hu- mans and rodents. Obesity is the current major cause of pre- mature death in the United Kingdom, killing almost 1000

  6. B7 family checkpoint regulators in immune regulation and disease

    PubMed Central

    Ceeraz, Sabrina; Nowak, Elizabeth C; Noelle, Randolph J

    2013-01-01

    Fine-tuning the immune response and maintaining tolerance to self antigens involves a complex network of co-stimulatory and co-inhibitory molecules. The recent FDA approval of ipilimumab, a monoclonal antibody blocking CTLA-4, demonstrates the impact of checkpoint regulators in disease. This is reinforced by ongoing clinical trials targeting not only CTLA-4, but also the PD-1 and B7-H4 pathways in various disease states. Recently two new B7 family inhibitory ligands, VISTA and B7-H6 were identified. Here we review recent understanding of B7 family members and their concerted regulation of the immune response to either self or foreign pathogens. We also discuss clinical developments in targeting these pathways in different disease settings, and introduce VISTA as a putative therapeutic target. PMID:23954143

  7. NOTICE OF REGULATION REPEAL Date: June 9, 2014

    E-print Network

    Pattanaik, Sumanta N.

    NOTICE OF REGULATION REPEAL Date: June 9, 2014 REGULATION TITLE: REGULATION NO.: Promotion of Tenured and Tenure-earning faculty UCF-3.017 SUMMARY OF REGULATION REPEAL: This regulation is proposed for repeal because the material contained in this regulation has been moved to regulation UCF-3

  8. NOTICE OF REGULATION REPEAL Date: May 5, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: May 5, 2009 REGULATION TITLE: REGULATION NO.: Student Rights and Responsibilities 6C7-5.003 SUMMARY OF REGULATION REPEAL: This regulation is being repealed. New regulations OF PERSON WHO INITIATED REGULATION REPEAL: Patricia MacKown, Director, Office of Student Rights

  9. NOTICE OF REGULATION REPEAL Date: August 6, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: August 6, 2009 REGULATION TITLE: REGULATION NO.: Rental Rates 6C7-7.219 SUMMARY OF REGULATION REPEAL: This regulation is noticed for repeal because the subject matter of the regulation is not needed and is out of date. Florida Board of Governors Regulation 17.001 requires

  10. General Regulations 1 2011/12 General Regulations -Page 1 of 15 GENERAL REGULATIONS 1

    E-print Network

    Jones, Graeme A.

    Statement on the provision of education Section A · Enrolment 1-3 · Tuition Fees 4-6 · Withdrawal/Cut-off partnership arrangements with colleges in the United Kingdom or abroad, you will also be enrolled by the partner college and required to comply with its regulations and codes of conduct when on its premises

  11. 7 CFR 948.386 - Handling regulation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...Nuts), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN COLORADO Handling Regulations...regulation. No person shall handle any lot of potatoes grown in Area No. 2 unless such potatoes meet the requirements of paragraphs...

  12. 32 CFR 9.7 - Regulations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...DEFENSE MILITARY COMMISSIONS PROCEDURES FOR TRIALS BY MILITARY COMMISSIONS OF CERTAIN NON-UNITED STATES CITIZENS IN THE WAR AGAINST TERRORISM § 9.7 Regulations. (a) Supplementary regulations and instructions. The...

  13. 32 CFR 9.7 - Regulations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...DEFENSE MILITARY COMMISSIONS PROCEDURES FOR TRIALS BY MILITARY COMMISSIONS OF CERTAIN NON-UNITED STATES CITIZENS IN THE WAR AGAINST TERRORISM § 9.7 Regulations. (a) Supplementary regulations and instructions. The...

  14. 32 CFR 9.7 - Regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...MILITARY COMMISSIONS PROCEDURES FOR TRIALS BY MILITARY COMMISSIONS OF CERTAIN NON-UNITED STATES CITIZENS IN THE WAR AGAINST TERRORISM § 9.7 Regulations. (a) Supplementary regulations and instructions. The Appointing Authority...

  15. Feedback regulation between autophagy and PKA.

    PubMed

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

    2015-07-01

    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

  16. Tertium Datur: Pricing, Regulating and Intrinsic Motivation

    Microsoft Academic Search

    Bruno S. Frey

    1992-01-01

    Beyond prices and regulations, a third motivation influences human behavior: intrinsic motivation. Under identifiable conditions, rational individuals replace their intrinsic by extrinsic motivation when prices and regulations are imposed from the outside (\\

  17. 50 CFR 20.153 - Regulations committee.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Special Procedures for Issuance of Annual Hunting Regulations § 20.153 Regulations committee. (a) Notice of meetings....

  18. The goals for regulating college tuition

    Microsoft Academic Search

    Xiaodong Zeng

    2009-01-01

    Regulation refers to governmental restrictions over enterprise in order to protect public interest. Research on governmental\\u000a regulation in China primarily focuses on public utility, and inadequate attention has been paid to regulating college tuition.\\u000a Currently, although the educational administrative agencies have successfully kept college tuition at the level of the year\\u000a 2000, the governmental regulation on tuition has not achieved

  19. Investment and regulation: the Dutch experience

    SciTech Connect

    Haffner, Robert; Helmer, Dorine; van Til, Harry

    2010-06-15

    Theoretical studies on the relationship between incentive regulation and investment in network industries generally point out that incentive regulation has a negative impact on investment. However, empirical evidence in this area is scarce. An analysis suggests that in the Dutch electricity and gas networks since 2001, incentive regulation has ensured a more rational and professional approach towards investments, with investment levels coming down somewhat at the start of the regulation but picking up later on. (author)

  20. Analog simulation of a gas pressure regulator.

    NASA Technical Reports Server (NTRS)

    Dustin, M. O.

    1972-01-01

    The behavior characteristics of direct-acting gas pressure regulators are discussed in terms of spring force, flow force, and friction force. The dynamics of the metering valve and bellows assembly are described by equating all forces on the valve to zero. Continuity equations for the regulator are derived. Simulations are carried out to determine effects of sensing orifice diameter, poppet stem friction, output volume, and supply pressure on regulator behavior. Several regulator configurations are studied.

  1. 76 FR 44225 - Alternative Mortgage Transaction Parity (Regulation D)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-22

    ...transactions ``notwithstanding any State constitution, law, or regulation.'' \\9...transactions ``notwithstanding any State constitution, law, or regulation.'' Section...transactions ``notwithstanding any State constitution, law, or regulation that...

  2. 21 CFR 870.5900 - Thermal regulating system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...Thermal regulating system. 870.5900 ...MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Therapeutic Devices...Thermal regulating system. (a) Identification...thermal regulating system is an...

  3. Admission Regulations Queen's University, Faculty of Arts and Science

    E-print Network

    Abolmaesumi, Purang

    Admission Regulations Queen's University, Faculty of Arts and Science TABLE .................................................................................................................................................... 3 ADMISSION REGULATION 1: ENGLISH LANGUAGE PROFICIENCY ........................................................................ 4 ADMISSION REGULATION 2: ADMISSION WITH AN ONTARIO SECONDARY SCHOOL DIPLOMA

  4. Statistical significance of combinatorial regulations

    PubMed Central

    Terada, Aika; Okada-Hatakeyama, Mariko; Tsuda, Koji; Sese, Jun

    2013-01-01

    More than three transcription factors often work together to enable cells to respond to various signals. The detection of combinatorial regulation by multiple transcription factors, however, is not only computationally nontrivial but also extremely unlikely because of multiple testing correction. The exponential growth in the number of tests forces us to set a strict limit on the maximum arity. Here, we propose an efficient branch-and-bound algorithm called the “limitless arity multiple-testing procedure” (LAMP) to count the exact number of testable combinations and calibrate the Bonferroni factor to the smallest possible value. LAMP lists significant combinations without any limit, whereas the family-wise error rate is rigorously controlled under the threshold. In the human breast cancer transcriptome, LAMP discovered statistically significant combinations of as many as eight binding motifs. This method may contribute to uncover pathways regulated in a coordinated fashion and find hidden associations in heterogeneous data. PMID:23882073

  5. Regulation: how much is enough

    SciTech Connect

    Crickmer, B.

    1980-03-01

    Typically, Federal regulation begins when single-interest pressure groups identify real or alleged hazards. This article reviews briefly such areas as transportation (National Highway Traffic Safety Administration), industry (Occupational Safety and Health Administration), drugs (Food and Drug Administration), and the environment (Environmental Protection Agency) outlining the failures of the agencies to improve historical downward trends accidents, deaths, hazards, etc. In many cases the hazards (deaths, accidents, pollution, etc.) had shown marked decline until Federal regulatory agencies began to influence the various industries. Without a basis for making trade-off decision, regulations could continue to be a jumble of cost-ineffective measures to achieve ill-defined objectives. Three accompanying articles discuss Congressional regulatory reform, the dollar value of a human life, and market incentives to accomplish regulatory objectives. 2 figures. (SAC)

  6. Ethics, regulation, and biomedical research.

    PubMed

    Weed, Matthew

    2004-12-01

    Controversy has surrounded the institutions that facilitate discussion and regulation of American biomedical research for years. Recent challenges to the legitimacy of the President's Council on Bioethics have been focused on stem cell research. These arguments represent an opportunity to reconsider the legislation under which stem cell research is regulated, as well as to consider preexisting bodies like the Recombinant DNA Advisory Committee and National Bioethics Advisory Commission. This paper proposes a Federal Life Sciences Policy Commission, a novel commission with advisory and regulatory powers that would benefit from the positive and negative lessons learned under the legislation that currently shapes the formation and institutional characteristics of advisory bodies in the United States. The Federal Life Sciences Policy Commission would have institutional independence not present in previous advisory bodies, while maintaining the tradition of broad societal representation and thoughtful discourse that has developed in the United States. PMID:15812984

  7. Gene regulation by mechanical forces

    NASA Technical Reports Server (NTRS)

    Oluwole, B. O.; Du, W.; Mills, I.; Sumpio, B. E.

    1997-01-01

    Endothelial cells are subjected to various mechanical forces in vivo from the flow of blood across the luminal surface of the blood vessel. The purpose of this review was to examine the data available on how these mechanical forces, in particular cyclic strain, affect the expression and regulation of endothelial cell function. Studies from various investigators using models of cyclic strain in vitro have shown that various vasoactive mediators such as nitric oxide and prostacyclin are induced by the effect of mechanical deformation, and that the expression of these mediators may be regulated at the transcription level by mechanical forces. There also seems to be emerging evidence that endothelial cells may also act as mechanotransducers, whereby the transmission of external forces induces various cytoskeletal changes and second messenger cascades. Furthermore, it seems these forces may act on specific response elements of promoter genes.

  8. Regulating health: transcending disciplinary boundaries.

    PubMed

    Seddon, Toby

    2013-03-01

    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. PMID:23070460

  9. Epigenetic regulation of epidermal differentiation.

    PubMed

    Perdigoto, Carolina N; Valdes, Victor J; Bardot, Evan S; Ezhkova, Elena

    2014-02-01

    In a cell, the chromatin state is controlled by the highly regulated interplay of epigenetic mechanisms ranging from DNA methylation and incorporation of different histone variants to posttranslational modification of histones and ATP-dependent chromatin remodeling. These changes alter the structure of the chromatin to either facilitate or restrict the access of transcription machinery to DNA. These epigenetic modifications function to exquisitely orchestrate the expression of different genes, and together constitute the epigenome of a cell. In the skin, different epigenetic regulators form a regulatory network that operates to guarantee skin stem cell maintenance while controlling differentiation to multiple skin structures. In this review, we will discuss recent findings on epigenetic mechanisms of skin control and their relationship to skin pathologies. PMID:24492849

  10. Epigenetic Regulation of Epidermal Differentiation

    PubMed Central

    Bardot, Evan S.; Ezhkova, Elena

    2015-01-01

    In a cell, the chromatin state is controlled by the highly regulated interplay of epigenetic mechanisms ranging from DNA methylation and incorporation of different histone variants to posttranslational modification of histones and ATP-dependent chromatin remodeling. These changes alter the structure of the chromatin to either facilitate or restrict the access of transcription machinery to DNA. These epigenetic modifications function to exquisitely orchestrate the expression of different genes, and together constitute the epigenome of a cell. In the skin, different epigenetic regulators form a regulatory network that operates to guarantee skin stem cell maintenance while controlling differentiation to multiple skin structures. In this review, we will discuss recent findings on epigenetic mechanisms of skin control and their relationship to skin pathologies. PMID:22314499

  11. Cardiac myofilaments: mechanics and regulation

    NASA Technical Reports Server (NTRS)

    de Tombe, Pieter P.; Bers, D. M. (Principal Investigator)

    2003-01-01

    The mechanical properties of the cardiac myofilament are an important determinant of pump function of the heart. This report is focused on the regulation of myofilament function in cardiac muscle. Calcium ions form the trigger that induces activation of the thin filament which, in turn, allows for cross-bridge formation, ATP hydrolysis, and force development. The structure and protein-protein interactions of the cardiac sarcomere that are responsible for these processes will be reviewed. The molecular mechanism that underlies myofilament activation is incompletely understood. Recent experimental approaches have been employed to unravel the mechanism and regulation of myofilament mechanics and energetics by activator calcium and sarcomere length, as well as contractile protein phosphorylation mediated by protein kinase A. Central to these studies is the question whether such factors impact on muscle function simply by altering thin filament activation state, or whether modulation of cross-bridge cycling also plays a part in the responses of muscle to these stimuli.

  12. Renewable energy and utility regulation

    SciTech Connect

    Not Available

    1991-04-10

    This report summarizes the results of a joint project on renewable energy of the National Association of Regulatory Utility Commissioners (NARUC) and the US DOE. NARUC'S Task Force on Renewable Energy conducted a review of the current state of renewable energy technologies to evaluate their potential and extract key policy lessons from experience already gained in deployment of these technologies in numerous states. The main focus of this effort has been to clarify how utility regulators affect the development of renewable energy resources. The goal of the project was twofold: (1) identify the factors that have led to success or failure or renewable energy technologies in various energy markets, and (2) to develop an agenda on renewable energy and utility regulation for NARUC and the DOE. This report consists of three sections: renewable energy contributions, costs and potential; factors affecting development of renewable energy resources; and a renewable energy agenda for NARUC.

  13. Renewable energy and utility regulation

    SciTech Connect

    Not Available

    1991-04-10

    This report summarizes the results of a joint project on renewable energy of the National Association of Regulatory Utility Commissioners (NARUC) and the US DOE. NARUC`S Task Force on Renewable Energy conducted a review of the current state of renewable energy technologies to evaluate their potential and extract key policy lessons from experience already gained in deployment of these technologies in numerous states. The main focus of this effort has been to clarify how utility regulators affect the development of renewable energy resources. The goal of the project was twofold: (1) identify the factors that have led to success or failure or renewable energy technologies in various energy markets, and (2) to develop an agenda on renewable energy and utility regulation for NARUC and the DOE. This report consists of three sections: renewable energy contributions, costs and potential; factors affecting development of renewable energy resources; and a renewable energy agenda for NARUC.

  14. Temporal dynamics of mouse hippocampal clock gene expression support memory processing.

    PubMed

    Jilg, Antje; Lesny, Sandra; Peruzki, Natalie; Schwegler, Herbert; Selbach, Oliver; Dehghani, Faramarz; Stehle, Jörg H

    2010-03-01

    Hippocampal plasticity and mnemonic processing exhibit a striking time-of-day dependence and likely implicate a temporally structured replay of memory traces. Molecular mechanisms fulfilling the requirements of sensing time and capturing time-related information are coded in dynamics of so-called clock genes and their protein products, first discovered and described in the hypothalamic suprachiasmatic nucleus. Using real-time PCR and immunohistochemical analyses, we show that in wildtype mice core clock components (mPer1/PER1, mPer2/PER2, mCry1/CRY1, mCry2/CRY2, mClock/CLOCK, mBmal1/BMAL1) are expressed in neurons of all subregions of the hippocampus in a time-locked fashion over a 24-h (diurnal) day/night cycle. Temporal profiling of these transcriptional regulators reveals distinct and parallel peaks, at times when memory traces are usually formed and/or consolidated. The coordinated rhythmic expression of hippocampal clock gene expression is greatly disordered in mice deficient for the clock gene mPer1, a key player implicated in both, maintenance and adaptative plasticity of circadian clocks. Moreover, Per1-knockout animals are severely handicapped in a hippocampus-dependent long-term spatial learning paradigm. We propose that the dynamics of hippocampal clock gene expression imprint a temporal structure on memory processing and shape at the same time the efficacy of behavioral learning. PMID:19437502

  15. Dynamic Circadian Protein–Protein Interaction Networks Predict Temporal Organization of Cellular Functions

    PubMed Central

    Wallach, Thomas; Schellenberg, Katja; Maier, Bert; Kalathur, Ravi Kiran Reddy; Porras, Pablo; Wanker, Erich E.; Futschik, Matthias E.; Kramer, Achim

    2013-01-01

    Essentially all biological processes depend on protein–protein interactions (PPIs). Timing of such interactions is crucial for regulatory function. Although circadian (?24-hour) clocks constitute fundamental cellular timing mechanisms regulating important physiological processes, PPI dynamics on this timescale are largely unknown. Here, we identified 109 novel PPIs among circadian clock proteins via a yeast-two-hybrid approach. Among them, the interaction of protein phosphatase 1 and CLOCK/BMAL1 was found to result in BMAL1 destabilization. We constructed a dynamic circadian PPI network predicting the PPI timing using circadian expression data. Systematic circadian phenotyping (RNAi and overexpression) suggests a crucial role for components involved in dynamic interactions. Systems analysis of a global dynamic network in liver revealed that interacting proteins are expressed at similar times likely to restrict regulatory interactions to specific phases. Moreover, we predict that circadian PPIs dynamically connect many important cellular processes (signal transduction, cell cycle, etc.) contributing to temporal organization of cellular physiology in an unprecedented manner. PMID:23555304

  16. Circadian Rhythms of Glucocorticoid Hormone Actions in Target Tissues: Potential Clinical Implications

    NSDL National Science Digital Library

    Tomoshige Kino (NIH; Eunice Kennedy Shriver National Institute of Child Health and Human Development REV)

    2012-10-02

    Organisms face unforeseen short- and long-term changes in the environment (stressors). To defend against these changes, organisms have developed a stress system that includes the hypothalamic-pituitary-adrenal (HPA) axis, which employs glucocorticoids and the glucocorticoid receptor (GR) for signal transduction. In addition, organisms live under the strong influence of day-night cycles and, hence, have also developed a highly conserved circadian clock system for adjusting their activities to recurring environmental changes. This regulatory system creates and maintains internal circadian rhythmicity by employing a self-oscillating molecular pacemaker composed of the Clock-Bmal1 heterodimer and other transcription factors. The circadian clock consists of a central master clock in the suprachiasmatic nucleus of the brain hypothalamus and peripheral slave clocks in virtually all organs and tissues. The HPA axis and the circadian clock system communicate with each other at multiple levels. The central clock controls the HPA axis, creating the diurnal oscillation of circulating adrenocorticotropic hormone and cortisol, and the HPA axis adjusts the circadian rhythmicity of the peripheral clocks in response to various stressors through the GR. Further, Clock-Bmal1 regulates the response to glucocorticoids in peripheral tissues through acetylation of the GR, possibly antagonizing the biologic actions of diurnally fluctuating circulating cortisol. Importantly, dysregulation in the clock system and the HPA axis may cause similar pathologic manifestations—including obesity, metabolic syndrome, and cardiovascular disease—by uncoupling circulating cortisol concentrations from tissue sensitivity to glucocorticoids.

  17. Bureaucrats and Brainpower: Government Regulation of Universities.

    ERIC Educational Resources Information Center

    Seabury, Paul, Ed.

    The exploration of the growth and cost benefit effectiveness of governmental regulation of higher education is examined in this book. An introductory article by Robert Hatfield examines university regulation from a businessman's perspective. Hatfield concludes that business and higher education must work together to curb the stream of regulation.…

  18. 77 FR 4887 - DOE Patent Licensing Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-01

    ...OF ENERGY 10 CFR Part 781 RIN 1990-AA41 DOE Patent Licensing Regulations AGENCY: Office...SUMMARY: The Department of Energy (DOE) is amending its patent licensing regulations...Board. Under the new regulations, the DOE Deputy General Counsel for Technology...

  19. 25 CFR 167.2 - General regulations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...THE INTERIOR LAND AND WATER NAVAJO GRAZING REGULATIONS § 167.2 General regulations...Commissioner of Indian Affairs to regulate the grazing of livestock on Indian lands under...the Navajo Tribal Council, the Central Grazing Committee and the District Grazing...

  20. The Goals for Regulating College Tuition

    ERIC Educational Resources Information Center

    Zeng, Xiaodong

    2009-01-01

    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…

  1. Nuclear regulation: an historical perspective. [Monograph

    Microsoft Academic Search

    J. Quirk; K. Terasawa

    1982-01-01

    The California Institute of Technology has compiled an historical review of nuclear regulation that begins with the Atomic Energy Act of 1954 and follows changes in regulation as the nuclear industry matured. The paper highlights nuclear licensing regulation under the Atomic Energy Commission (AEC) - Nuclear Regulatory Commission (NRC) to show how procedural changes have lengthened the licensing process and

  2. FULL REPORT Regulation and biomedical research

    E-print Network

    Rambaut, Andrew

    Regulation of medical research is necessary. It is important to protect the public against the risks and scientists' interests, and to protect participants in research and the researchers themselves. But regulation and consumer risk, and many stakeholders making competing demands on regulators. There is potential

  3. Issues at Stake in Occupational Regulation.

    ERIC Educational Resources Information Center

    Shimberg, Benjamin

    State regulation of occupational licensing is becoming the subject of nationwide debate. The issues being questioned and suggestions for their solutions include the following: (1) Is it necessary to regulate occupations, and, if it is, to what extent? Regulation is required only if its need is well-documented, and it should be kept to the minimum…

  4. Conscious Regulation of Sexual Arousal in Men

    Microsoft Academic Search

    Jason Winters; Kalina Christoff; Boris B. Gorzalka

    2009-01-01

    The goals of this study were to examine the effectiveness of emotional reappraisal in regulating male sexual arousal and to investigate a set of variables theoretically linked to sexual arousal regulation success. Participants first completed a series of online sexuality questionnaires. Subsequently, they were assessed for their success in regulating sexual arousal in the laboratory. Results showed that the ability

  5. Multiplexing Regulated Traffic Streams: Design and Performance

    E-print Network

    Boucherie, Richard J.

    developed Intserv (individual flows regulated) and Diffserv (only ag- gregates regulated). The regulator, Internet, Intserv, Diffserv. I. INTRODUCTION We are currently faced with important changes in the nature: Diffserv [2]. In Diffserv no micro-flows are identified, hence solving the scalability problems; instead

  6. A Computational Model for Adaptive Emotion Regulation

    E-print Network

    Treur, Jan

    A Computational Model for Adaptive Emotion Regulation Tibor Bosse, Matthijs Pontier, and Jan Treur} Abstract. Emotion regulation describes how a subject can use certain strategies to affect emotion response levels. Usually, models for emotion regulation as- sume mechanisms based on feedback loops that indicate

  7. 2013-2014 Case Summaries Regulation 1

    E-print Network

    Royer, Dana

    2013-2014 Case Summaries Regulation 1 Disturbance of the Peace ­ the infringement upon the right that repeated violation of this regulation could result in administrative reassignment to another residential violated Section II, Regulations 1 and 14 of the Code of Non-Academic Conduct. The board found the group

  8. Learning Styles and Self-Regulation.

    ERIC Educational Resources Information Center

    Vermunt, Jan D. H. M.

    Data from 211 adult students (ages 20 to 75) at the Open University, The Netherlands, were used to construct and test an instrument to measure learning styles and regulation processes. Test development was guided by a three-tiered model of self-regulation encompassing: (1) cognitive learning processes (deep, surface, elaborative); (2) regulation

  9. Identifying differentially regulated subnetworks from phosphoproteomic data

    Microsoft Academic Search

    Martin Klammer; Klaus Godl; Andreas Tebbe; Christoph Schaab

    2010-01-01

    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

  10. Regulation theories in retrospect and prospect

    Microsoft Academic Search

    Jessop Bob

    1990-01-01

    This paper presents a detailed methodological critique of the regulation research programme and its application to capitalist economies and the state. It defines four common methodological and substantive properties of the regulation approach and shows how different school or tendencies in regulation theory share these properties. It is this context that the foundations of the regulationist approach in realist ontology,

  11. Ordinances and Resolutions ORDINANCES, RESOLUTIONS AND REGULATIONS

    E-print Network

    Brierley, Andrew

    Page 2.1 Ordinances and Resolutions ORDINANCES, RESOLUTIONS AND REGULATIONS 1. ORDINANCES AND RESOLUTIONS I. REGULATIONS FOR RESEARCH STUDENTS AND APPOINTMENT OF RESEARCH FELLOWS Ordinance 350, and Supplementary Regulations by the Senatus Academicus 1. Ordinance No. 61 (General No. 23) of the Commissioners

  12. NOTES TO ACCOMPANY FLOWCHARTS PROGRESSION REGULATIONS

    E-print Network

    Wirosoetisno, Djoko

    NOTES TO ACCOMPANY FLOWCHARTS OF PROGRESSION REGULATIONS 1. These flowcharts are intended to help students and staff understand the implications of the progression regulations. Inevitably they use a form of `short-hand' and do not illustrate all the details of the progression regulations

  13. California Energy Commission REVISED DRAFT REGULATIONS

    E-print Network

    California Energy Commission REVISED DRAFT REGULATIONS AUGUST, 2011 CEC-400-2010-004-SD2 Nonresidential Building Energy Use Disclosure Program Draft Regulations Title 20, Division 2, Chapter 4 of the California Energy Commission is releasing draft regulations for implementing Assembly Bill (AB) 1103 (Saldaña

  14. University of St Andrews Postgraduate Senate Regulations

    E-print Network

    Brierley, Andrew

    University of St Andrews Postgraduate Senate Regulations Amendments taking effect from 2011-2012 Postgraduate Senate Regulations 1. Staff Fees Reason for amendment: Amend point of contact for approval concessionary staff rate from Academic Registrar to University Fees Officer. 2. A. REGULATIONS FOR RESEARCH

  15. Scoping Report Northern Fur Seal Harvest Regulations

    E-print Network

    Scoping Report for Northern Fur Seal Harvest Regulations Environmental Assessment April 2012 #12; #12;NATIONAL MARINE FISHERIES SERVICE NORTHERN FUR SEAL SUBSISTENCE HARVEST REGULATIONS SCOPING REPORT Regulations FSA Fur Seal Act MMPA Marine Mammal Protection Act NEPA National Environmental Policy Act NMFS

  16. Self-Regulation in Online Learning

    ERIC Educational Resources Information Center

    Cho, Moon-Heum; Shen, Demei

    2013-01-01

    The purpose of this study was to examine the role of goal orientation and academic self-efficacy in student achievement mediated by effort regulation, metacognitive regulation, and interaction regulation in an online course. The results show that intrinsic goal orientation and academic self-efficacy predicted students' metacognitive…

  17. Emotion Regulation and Depressive Symptoms in Preadolescence

    ERIC Educational Resources Information Center

    Siener, Shannon; Kerns, Kathryn A.

    2012-01-01

    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…

  18. Regulating competition: Transition or travesty?

    SciTech Connect

    Cicchetti, C.J.; Sepetys, K.M.

    1996-05-01

    The coming of competition in California and elsewhere will not mean less regulation but more - at least in the short run. The acid test of the transition will be whether the responsible political officials can define and impose {open_quotes}competitive transition charge{close_quotes} on a basis that is fair to all parties, and then hold fast against customer pressures to avoid it.

  19. Regulation of Genes by Light

    Microsoft Academic Search

    Gabriele Klug; Shinji Masuda

    Our current understanding of light-dependent regulation of gene expression in purple bacteria is summarized. Most of the regulatory\\u000a systems utilize photoreceptor proteins that transmit a light-dependent signal to different downstream components to control\\u000a a wide variety of physiological responses. The photoreceptors identified so far are (bacterio)phytochrome, sensory rhodopsin,\\u000a phototropin-related proteins, BLUF domain proteins, cryptochrome, and photoactive yellow protein. They use

  20. Autonomic cardiovascular regulation in obesity

    Microsoft Academic Search

    K Laederach-Hofmann; L Mussgay

    2000-01-01

    Obese persons suffer from an increased mortality risk supposedly due to cardiovascular disorders related to either continuously lowered parasympathetic or altered sympa- thetic activation. Our cross-sectional correlation study establishes the relationship between obesity and autonomic regulation as well as salivary cortisol levels. Three patient cohorts were sampled, covering ranges of body mass index (BMI) of 27-32 (n=17), 33-39 (n=13) and

  1. [Chronobiological viewpoints of respiratory regulation].

    PubMed

    Raschke, F

    1995-01-01

    Control of breathing is ruled by autonomous and behavioural necessities as well. These adaptive functions are realized by temporally structured processes, which are described, analyzed, and functionally estimated by means of the methods of chronobiology. Chronobiological labels like circadian/ultradian, internal clock, Zeitgeber, coordination, entrainment, and resetting are given as examples from sleep, wake, physical strain, and pathophysiology. They are compared to their corresponding functions in respiratory control. Disturbances in chronobiological indicators reveal functional and sleep regulating disorders. PMID:8588359

  2. Frequency regulator for synchronous generators

    DOEpatents

    Karlicek, R.F.

    1982-08-10

    The present invention is directed to a novel frequency regulator which controls a generator output frequency for variations in both the input power to the generator and the power supplied to an uncontrolled external load. The present invention further includes over current and current balance protection devices which are relatively inexpensive to manufacture, which may be encapsulated to provide protection from the operating environment and which respond more quickly than previously known electromechanical devices. 11 figs.

  3. Frequency regulator for synchronous generators

    DOEpatents

    Karlicek, Robert F. (1920 Camino Centroloma, Fullerton, CA 92633)

    1982-01-01

    The present invention is directed to a novel frequency regulator which controls a generator output frequency for variations in both the input power to the generator and the power supplied to an uncontrolled external load. The present invention further includes over current and current balance protection devices which are relatively inexpensive to manufacture, which may be encapsulated to provide protection from the operating environment and which respond more quickly than previously known electromechanical devices.

  4. A closely regulated TWT converter.

    NASA Technical Reports Server (NTRS)

    Hopper, D. J.; Andryczyk, R. W.

    1971-01-01

    The design concept for the TWT amplifier converter for possible use in the Thermoelectric Outer Planet Spacecraft (TOPS) is presented. An unusual combination of semiconductors and magnetics was utilized to achieve very stable voltage regulation on a number of separate outputs to satisfy the requirements of a high-power TWT, and at the same time operate at an efficiency of better than 90% from a 30-V source. The circuitry consists of an output filter, an auxiliary Jensen oscillator driving a high-reactance transformer to provide current limiting to the heater, a variable time delay, a main Jensen oscillator driving the power transformer with a maximum step-up ratio of 120 to 1, and series transistorized post regulators to provide precise voltage adjustment and low output impedance. This paper discusses the design of the high-reactance transformer and the high step-up ratio transformer, as well as the high-voltage series regulators that are limited in range and operate at the top of the unregulated output voltage. Test data are presented, and details of current transients caused by charging the filter circuits, input current ripple, and output voltage ripples are considered.

  5. Does diacylglycerol regulate KCNQ channels?

    PubMed

    Suh, Byung-Chang; Hille, Bertil

    2006-12-01

    Some ion channels are regulated by inositol phospholipids and by the products of cleavage by phospholipase C (PLC). KCNQ channels (Kv7) require membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)) and are turned off when muscarinic receptors stimulate cleavage of PIP(2) by PLC. We test whether diacylglycerols are also important in the regulation of KCNQ2/KCNQ3 channels using electrophysiology and fluorescent translocation probes as indicators for PIP(2) and diacylglycerol in tsA cells. The cells are transfected with M(1) muscarinic receptors, channel subunits, and translocation probes. Although they cause translocation of a fluorescent probe with a diacylglycerol-binding C1 domain, exogenously applied diacylglycerol (oleoyl-acetyl-glycerol and dioctanoyl glycerol) and phorbol ester do not mimic or occlude the suppression of KCNQ current by muscarinic agonist. Blocking the metabolism of endogenous diacylglycerol by inhibiting diacylglycerol kinase with R59022 or R59949 slows the decay of diacylglycerol twofold but does not mimic or occlude muscarinic regulation and recovery of current. Blocking diacylglycerol lipase with RHC-80267 also does not occlude muscarinic modulation of current. We conclude that the diacylglycerol produced during activation of PLC, any activation of protein kinase C that it may stimulate, and downstream products of its metabolism are not essential players in the acute muscarinic modulation of KCNQ channels. PMID:16721610

  6. Actin Cytoskeleton Regulates Hippo Signaling

    PubMed Central

    Reddy, Pradeep; Deguchi, Masashi; Cheng, Yuan; Hsueh, Aaron J. W.

    2013-01-01

    Hippo pathway controls the organ size by modulating cell proliferation and apoptosis. However, the upstream regulation of hippo signaling by actin cytoskeleton is not clear. To elucidate the role of actin as an upstream regulator of Hippo signaling, the levels of F (filamentous)-actin in cells were elevated using jasplakinolide, an actin-stabilizing drug. Induction of F-actin formation in HeLa cells resulted in decreased phosphorylation of YAP, a key effector molecule for Hippo signaling. The activated YAP is localized to the cell nucleus and YAP increase was associated with increased expression of downstream CCN growth factors CCN1/CYR61 and CCN2/CTGF. The effect of the actin-stabilizing drug was blocked when YAP levels were suppressed in YAP “knock-down” cells. In summary, using an actin-stabilizing drug we show that actin cytoskeleton is one of the upstream regulators of Hippo signaling capable of activating YAP and increasing its downstream CCN growth factors. PMID:24040060

  7. NRC - regulator of nuclear safety

    SciTech Connect

    NONE

    1997-05-01

    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.

  8. Redox Regulation of Protein Kinases

    PubMed Central

    Truong, Thu H.; Carroll, Kate S.

    2015-01-01

    Protein kinases represent one of the largest families of genes found in eukaryotes. Kinases mediate distinct cellular processes ranging from proliferation, differentiation, survival, and apoptosis. Ligand-mediated activation of receptor kinases can lead to the production of endogenous H2O2 by membrane-bound NADPH oxidases. In turn, H2O2 can be utilized as a secondary messenger in signal transduction pathways. This review presents an overview of the molecular mechanisms involved in redox regulation of protein kinases and its effects on signaling cascades. In the first half, we will focus primarily on receptor tyrosine kinases (RTKs), whereas the latter will concentrate on downstream non-receptor kinases involved in relaying stimulant response. Select examples from the literature are used to highlight the functional role of H2O2 regarding kinase activity, as well as the components involved in H2O2 production and regulation during cellular signaling. In addition, studies demonstrating direct modulation of protein kinases by H2O2 through cysteine oxidation will be emphasized. Identification of these redox-sensitive residues may help uncover signaling mechanisms conserved within kinase subfamilies. In some cases, these residues can even be exploited as targets for the development of new therapeutics. Continued efforts in this field will further basic understanding of kinase redox regulation, and delineate the mechanisms involved in physiologic and pathological H2O2 responses. PMID:23639002

  9. Optical regulation of cell chain

    PubMed Central

    Liu, Xiaoshuai; Huang, Jianbin; Zhang, Yao; Li, Baojun

    2015-01-01

    Formation of cell chains is a straightforward and efficient method to study the cell interaction. By regulating the contact sequence and interaction distance, the influence of different extracellular cues on the cell interaction can be investigated. However, it faces great challenges in stable retaining and precise regulation of cell chain, especially in cell culture with relatively low cell concentration. Here we demonstrated an optical method to realize the precise regulation of cell chain, including removing or adding a single cell, adjusting interaction distance, and changing cell contact sequence. After injecting a 980-nm wavelength laser beam into a tapered optical fiber probe (FP), a cell chain of Escherichia colis (E. colis) is formed under the optical gradient force. By manipulating another FP close to the cell chain, a targeted E. coli cell can be trapped by the FP and removed from the chain. Further, the targeted cell can be added back to the chain at different positions to change the cell contact sequence. The experiments were interpreted by numerical simulations and the impact of cell sizes and shapes on this method was analyzed. PMID:26098707

  10. Amino acids and cell regulation.

    PubMed Central

    Forster, R. P.; Goldstein, L.

    1979-01-01

    Free amino play an important role in regulating cell volume in fishes. Four tissues/cells (skeletal muscle, RBC, brain, and myocardium) of the little skate, Raja erinacea, were selected for detailed study because of their special importance or unique advantage as experimental models. Three particular amino acids, beta-alanine, taurine, and sarcosine play a predominant role in all four tissues. As in higher vertebrates, amino acid uptake in skate brain, heart, and RBC is mediated via a Na+-dependent process. Amino acids leave the skate brain rapidly in response to a sudden decrease in plasma osmolality and/or to a simultaneous drop in extracellular Na+ concentration. However, although amino acids are important for volume regulation in normal brain cells, they do not appear to be likely candidates for the unidentified "idiogenic" osmolytes in mammalian brain cells. The high concentration of taurine in skate myocardium is of special interest because of the special role of this amino acid in myocardial contractility. Thus, unlike beta-alanine and sarcosine, taurine may play a dual role in regulating both cell volume and contractility of myocardial cells. The isolated skate atrium is well suited for in vitro studies of these two processes. PMID:395764

  11. Optical regulation of cell chain.

    PubMed

    Liu, Xiaoshuai; Huang, Jianbin; Zhang, Yao; Li, Baojun

    2015-01-01

    Formation of cell chains is a straightforward and efficient method to study the cell interaction. By regulating the contact sequence and interaction distance, the influence of different extracellular cues on the cell interaction can be investigated. However, it faces great challenges in stable retaining and precise regulation of cell chain, especially in cell culture with relatively low cell concentration. Here we demonstrated an optical method to realize the precise regulation of cell chain, including removing or adding a single cell, adjusting interaction distance, and changing cell contact sequence. After injecting a 980-nm wavelength laser beam into a tapered optical fiber probe (FP), a cell chain of Escherichia colis (E. colis) is formed under the optical gradient force. By manipulating another FP close to the cell chain, a targeted E. coli cell can be trapped by the FP and removed from the chain. Further, the targeted cell can be added back to the chain at different positions to change the cell contact sequence. The experiments were interpreted by numerical simulations and the impact of cell sizes and shapes on this method was analyzed. PMID:26098707

  12. Auricular Acupuncture and Vagal Regulation

    PubMed Central

    He, Wei; Wang, Xiaoyu; Shi, Hong; Shang, Hongyan; Li, Liang; Jing, Xianghong; Zhu, Bing

    2012-01-01

    Auricular acupuncture has been utilized in the treatment of diseases for thousands of years. Dr. Paul Nogier firstly originated the concept of an inverted fetus map on the external ear. In the present study, the relationship between the auricular acupuncture and the vagal regulation has been reviewed. It has been shown that auricular acupuncture plays a role in vagal activity of autonomic functions of cardiovascular, respiratory, and gastrointestinal systems. Mechanism studies suggested that afferent projections from especially the auricular branch of the vagus nerve (ABVN) to the nucleus of the solitary tract (NTS) form the anatomical basis for the vagal regulation of auricular acupuncture. Therefore, we proposed the “auriculovagal afferent pathway” (AVAP): both the autonomic and the central nervous system could be modified by auricular vagal stimulation via projections from the ABVN to the NTS. Auricular acupuncture is also proposed to prevent neurodegenerative diseases via vagal regulation. There is a controversy on the specificity and the efficacy of auricular acupoints for treating diseases. More clinical RCT trials on auricular acupuncture and experimental studies on the mechanism of auricular acupuncture should be further investigated. PMID:23304215

  13. Price and Profit Regulation in Developing and Transition Economies: A Survey of the Regulators

    Microsoft Academic Search

    Colin Kirkpatrick; David Parker; Yin-Fang Zhang

    2005-01-01

    Rate of return or cost of service regulation was the traditional means by which governments, especially in the USA, regulated profitability and prices in privately-owned public utility businesses. However, rate of return regulation was associated with efficiency disincentives. Hence, in 1983 a price cap was proposed to regulate British Telecom when it was privatized. Price caps were later introduced for

  14. Emotion Regulation as Situated Conceptualizations 1 RUNNING HEAD: EMOTION REGULATION AS SITUATED CONCEPTUALIZATIONS

    E-print Network

    Barsalou, Lawrence W.

    Emotion Regulation as Situated Conceptualizations 1 RUNNING HEAD: EMOTION REGULATION AS SITUATED CONCEPTUALIZATIONS TITLE: A psychological construction account of emotion regulation and dysregulation: The role Boston, MA 02115 Phone: 617-373-2044 Fax: 617-373-8714 Email: l.barrett@neu.edu #12;Emotion Regulation

  15. IMPLICIT EVALUATION OF EMOTION REGULATION 1 Running Head: IMPLICIT EVALUATION OF EMOTION REGULATION

    E-print Network

    Gross, James J.

    IMPLICIT EVALUATION OF EMOTION REGULATION 1 Running Head: IMPLICIT EVALUATION OF EMOTION REGULATION How to Bite Your Tongue without Blowing Your Top: Implicit Evaluation of Emotion Regulation Predicts EVALUATION OF EMOTION REGULATION 2 Abstract People frequently have to control their emotions to function

  16. Clarifying Metacognition, Self-Regulation, and Self-Regulated Learning: What's the Purpose?

    ERIC Educational Resources Information Center

    Kaplan, Avi

    2008-01-01

    In this commentary on the special issue, I join the authors in searching for a conceptual framework that would clarify the concepts of metacognition, self-regulation, and self-regulated learning. Building on the insights of the different articles, I suggest that metacognition, self-regulation, and self-regulated learning should be considered as…

  17. Postgraduate Regulations -2006/07 August 2006 ORDINANCES, RESOLUTIONS AND REGULATIONS

    E-print Network

    Brierley, Andrew

    Postgraduate Regulations - 2006/07 ­ August 2006 Page 2.1 ORDINANCES, RESOLUTIONS AND REGULATIONS 1. ORDINANCES AND RESOLUTIONS I. REGULATIONS FOR RESEARCH STUDENTS AND APPOINTMENT OF RESEARCH FELLOWS Ordinance, and Supplementary Regulations by the Senatus Academicus 1. Ordinance No. 61 (General No. 23) of the Commissioners

  18. Postgraduate Resolutions and Regulations 2008/09 -August 2008 ORDINANCES, RESOLUTIONS AND REGULATIONS

    E-print Network

    Brierley, Andrew

    Postgraduate Resolutions and Regulations 2008/09 - August 2008 ORDINANCES, RESOLUTIONS AND REGULATIONS 1. ORDINANCES AND RESOLUTIONS I. REGULATIONS FOR RESEARCH STUDENTS AND APPOINTMENT OF RESEARCH October 1960, and Supplementary Regulations by the Senatus Academicus 1. Ordinance No. 61 (General No. 23

  19. Postgraduate Resolutions and Regulations 2007/08 ORDINANCES, RESOLUTIONS AND REGULATIONS

    E-print Network

    Brierley, Andrew

    Postgraduate Resolutions and Regulations 2007/08 Page 2.1 ORDINANCES, RESOLUTIONS AND REGULATIONS 1. ORDINANCES AND RESOLUTIONS I. REGULATIONS FOR RESEARCH STUDENTS AND APPOINTMENT OF RESEARCH FELLOWS Ordinance, and Supplementary Regulations by the Senatus Academicus 1. Ordinance No. 61 (General No. 23) of the Commissioners

  20. Student Regulations 2014 The Student Regulations (including the Code of Practice for Student Assessment and

    E-print Network

    Bandara, Arosha

    Student Regulations 2014 The Student Regulations (including the Code of Practice for Student University. These regulations define the basis of the registration agreement between you and us. Students who are also governed by our Qualification Regulations which deal with registering for or declaring

  1. University Computing Regulations The University of Edinburgh has adopted a set of Regulations to cover the

    E-print Network

    Edinburgh, University of

    University Computing Regulations The University of Edinburgh has adopted a set of Regulations authorised to use them. Regulations covering the use of Computing Facilities 18th Edition August 2010 (Reprinted September 2011) Introduction and Definitions These Regulations cover the use by users of all

  2. University Computing Regulations The University of Edinburgh has adopted a set of Regulations to cover the

    E-print Network

    Koehn, Philipp

    University Computing Regulations The University of Edinburgh has adopted a set of Regulations authorised to use them. Regulations covering the use of Computing Facilities 19th Edition August 2013 Introduction and Definitions These Regulations cover the use by users of all computing facilities administered

  3. Postgraduate Resolutions and Regulations 2009/10 ORDINANCES, RESOLUTIONS AND REGULATIONS

    E-print Network

    Brierley, Andrew

    Postgraduate Resolutions and Regulations 2009/10 Page 2.1 ORDINANCES, RESOLUTIONS AND REGULATIONS 1. ORDINANCES AND RESOLUTIONS I. REGULATIONS FOR RESEARCH STUDENTS AND APPOINTMENT OF RESEARCH FELLOWS Ordinance, and Supplementary Regulations by the Senatus Academicus 1. Ordinance No. 61 (General No. 23) of the Commissioners

  4. PA Nutrient Management Regulations: Act 38 of 2005 Summary of Regulations

    E-print Network

    Guiltinan, Mark

    PA Nutrient Management Regulations: Act 38 of 2005 Summary of Regulations Effective October 1, 2006 Who is regulated under this law (see Fact Sheet 54, from PSU): o Must be high animal density AND must of animals/4 acres = 2,500 lbs per acre (this is a regulated farm) o Also must have over 8,000 lbs of animals

  5. Postgraduate Resolutions and Regulations 2010/11 ORDINANCES, RESOLUTIONS AND REGULATIONS

    E-print Network

    Brierley, Andrew

    Postgraduate Resolutions and Regulations 2010/11 Page 2.1 ORDINANCES, RESOLUTIONS AND REGULATIONS 1. ORDINANCES AND RESOLUTIONS I. REGULATIONS FOR RESEARCH STUDENTS AND APPOINTMENT OF RESEARCH FELLOWS Ordinance, and Supplementary Regulations by the Senatus Academicus 1. Ordinance No. 61 (General No. 23) of the Commissioners

  6. Over- and under-regulating hazardous waste

    SciTech Connect

    Loranger, T.; Delistraty, D. [Washington State Dept. of Ecology, Spokane, WA (United States)] [Washington State Dept. of Ecology, Spokane, WA (United States)

    1999-01-01

    Hazardous waste regulations in the United States tend to over-regulate certain wastes and under-regulate others. Over-regulation is related to the listing strategy, whereas under-regulation is primarily a result of failing to assess waste toxicity directly. Hazardous waste regulations in individual states are required to be at least as stringent as federal rules. As such, the state of Washington has added several waste criteria, including acute toxicity, persistence, and carcinogenicity. Recently, the acute toxicity threshold for the fish bioassay has been lowered and the carcinogenicity criterion has been deleted to avoid over-regulating waste. Approximately 36% of the total hazardous waste reported annually in Washington state is designated as state-only waste, with 93% of this state-only fraction classified by acute toxicity. Thus, a significant portion of hazardous waste in Washington state is captured by state criteria. This waste is removed from the environment, enhancing protection of human and ecological receptors.

  7. 7 CFR 987.40 - Additional grade or size regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 2010-01-01 false Additional grade or size regulations. 987.40 Section 987...COUNTY, CALIFORNIA Order Regulating Handling Grade Regulation § 987.40 Additional grade or size regulations. Whenever the...

  8. 7 CFR 987.40 - Additional grade or size regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...2011-01-01 2011-01-01 false Additional grade or size regulations. 987.40 Section 987...COUNTY, CALIFORNIA Order Regulating Handling Grade Regulation § 987.40 Additional grade or size regulations. Whenever the...

  9. 78 FR 75484 - Federal Management Regulation (FMR); Shipping Household Goods

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-12

    ...RIN 3090-AJ38 Federal Management Regulation (FMR); Shipping...GSA is amending the Federal Management Regulation (FMR) to update...Professional Books, Paper and Equipment, and temporary storage...regulations in the Federal Management Regulation (FMR) part...

  10. 7 CFR 948.22 - Issuance of regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...2011-01-01 false Issuance of regulations. 948.22 Section 948.22 Agriculture Regulations of the Department of Agriculture (Continued...COLORADO Order Regulating Handling Regulation § 948.22 Issuance of...

  11. 7 CFR 905.51 - Recommendations for regulation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 false Recommendations for regulation. 905.51 Section 905.51 Agriculture Regulations of the Department of Agriculture (Continued...FLORIDA Order Regulating Handling Regulations § 905.51 Recommendations for...

  12. 7 CFR 958.51 - Recommendations for regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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  13. 7 CFR 906.40 - Issuance of regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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  14. 7 CFR 905.52 - Issuance of regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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  15. 7 CFR 948.22 - Issuance of regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 false Issuance of regulations. 948.22 Section 948.22 Agriculture Regulations of the Department of Agriculture (Continued...COLORADO Order Regulating Handling Regulation § 948.22 Issuance of...

  16. 7 CFR 905.51 - Recommendations for regulation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...2011-01-01 false Recommendations for regulation. 905.51 Section 905.51 Agriculture Regulations of the Department of Agriculture (Continued...FLORIDA Order Regulating Handling Regulations § 905.51 Recommendations for...

  17. 7 CFR 948.22 - Issuance of regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 false Issuance of regulations. 948.22 Section 948.22 Agriculture Regulations of the Department of Agriculture (Continued...COLORADO Order Regulating Handling Regulation § 948.22 Issuance of...

  18. 34 CFR 100.2 - Application of this regulation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2011-07-01 false Application of this regulation. 100.2 Section 100.2 Education Regulations of the Offices of the Department of Education...1964 § 100.2 Application of this regulation. This regulation applies...

  19. 7 CFR 948.22 - Issuance of regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 false Issuance of regulations. 948.22 Section 948.22 Agriculture Regulations of the Department of Agriculture (Continued...COLORADO Order Regulating Handling Regulation § 948.22 Issuance of...

  20. 7 CFR 905.52 - Issuance of regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 false Issuance of regulations. 905.52 Section 905.52 Agriculture Regulations of the Department of Agriculture (Continued...FLORIDA Order Regulating Handling Regulations § 905.52 Issuance of...

  1. 34 CFR 100.2 - Application of this regulation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2013-07-01 false Application of this regulation. 100.2 Section 100.2 Education Regulations of the Offices of the Department of Education...1964 § 100.2 Application of this regulation. This regulation applies...

  2. 7 CFR 905.52 - Issuance of regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 false Issuance of regulations. 905.52 Section 905.52 Agriculture Regulations of the Department of Agriculture (Continued...FLORIDA Order Regulating Handling Regulations § 905.52 Issuance of...

  3. 7 CFR 948.22 - Issuance of regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...2012-01-01 false Issuance of regulations. 948.22 Section 948.22 Agriculture Regulations of the Department of Agriculture (Continued...COLORADO Order Regulating Handling Regulation § 948.22 Issuance of...

  4. 7 CFR 905.52 - Issuance of regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...2012-01-01 false Issuance of regulations. 905.52 Section 905.52 Agriculture Regulations of the Department of Agriculture (Continued...FLORIDA Order Regulating Handling Regulations § 905.52 Issuance of...

  5. 7 CFR 946.51 - Recommendation for regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 false Recommendation for regulations. 946.51 Section 946.51 Agriculture Regulations of the Department of Agriculture (Continued...WASHINGTON Order Regulating Handling Regulation § 946.51 Recommendation for...

  6. 7 CFR 905.52 - Issuance of regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...2011-01-01 false Issuance of regulations. 905.52 Section 905.52 Agriculture Regulations of the Department of Agriculture (Continued...FLORIDA Order Regulating Handling Regulations § 905.52 Issuance of...

  7. 7 CFR 953.42 - Issuance of regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...2011-01-01 false Issuance of regulations. 953.42 Section 953.42 Agriculture Regulations of the Department of Agriculture (Continued...STATES Order Regulating Handling Regulations § 953.42 Issuance of...

  8. 7 CFR 915.55 - Avocados not subject to regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 false Avocados not subject to regulations. 915.55 Section 915.55 Agriculture Regulations of the Department of Agriculture (Continued...FLORIDA Order Regulating Handling Regulations § 915.55 Avocados not...

  9. 7 CFR 915.51 - Issuance of regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 false Issuance of regulations. 915.51 Section 915.51 Agriculture Regulations of the Department of Agriculture (Continued...FLORIDA Order Regulating Handling Regulations § 915.51 Issuance of...

  10. Forms Supplement page -1 Export Administration Regulations January 2001

    E-print Network

    Bernstein, Daniel

    Forms Supplement page - 1 Export Administration Regulations January 2001 #12;Forms Supplement page - 2 Export Administration Regulations January 2001 #12;Forms Supplement page - 3 Export Administration Regulations January 2001 #12;Forms Supplement page - 4 Export Administration Regulations January 2001 #12

  11. Mapping Regulations to Industry-Specific Taxonomies Chin Pang Cheng

    E-print Network

    Stanford University

    Mapping Regulations to Industry-Specific Taxonomies Chin Pang Cheng Stanford University Dept multiple sources of regulations from different government agencies. Industry practitioners, unlike legal organization systems. To help browsing of regulations by industry practitioners, we propose to map regulations

  12. 7 CFR 946.51 - Recommendation for regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 false Recommendation for regulations. 946.51 Section 946.51 Agriculture Regulations of the Department of Agriculture (Continued...WASHINGTON Order Regulating Handling Regulation § 946.51 Recommendation for...

  13. 7 CFR 924.51 - Recommendations for regulation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...2011-01-01 false Recommendations for regulation. 924.51 Section 924.51 Agriculture Regulations of the Department of Agriculture (Continued...OREGON Order Regulating Handling Regulations § 924.51 Recommendations for...

  14. 7 CFR 917.40 - Recommendations for regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 false Recommendations for regulations. 917.40 Section 917.40 Agriculture Regulations of the Department of Agriculture (Continued...CALIFORNIA Order Regulating Handling Regulations § 917.40 Recommendations for...

  15. 7 CFR 958.51 - Recommendations for regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 false Recommendations for regulations. 958.51 Section 958.51 Agriculture Regulations of the Department of Agriculture (Continued...OREGON Order Regulating Handling Regulation § 958.51 Recommendations for...

  16. Exerpt: Examination Regulations MSc Economics Excerpt from the

    E-print Network

    Mannheim, Universität

    Exerpt: Examination Regulations MSc Economics - 1 - Excerpt from the Examination Regulations is based on the German version of the Examination Regulations for the Master's Program in Economics the translation of the original shall be excluded. Contents General Regulations

  17. 7 CFR 946.51 - Recommendation for regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...2011-01-01 false Recommendation for regulations. 946.51 Section 946.51 Agriculture Regulations of the Department of Agriculture (Continued...WASHINGTON Order Regulating Handling Regulation § 946.51 Recommendation for...

  18. The Furniture and Furnishings (Fire) (Safety) (Amendment) Regulations 1993 

    E-print Network

    Her Majesty's Stationary Office

    1933-02-08

    These Regulations amend the Furnilure and Furnishings (Fire) (Safely) Regulations ("the 1988 Regulations") so as to disapply the provisions of the 1988 Regulations in so far as they impose requirements in relation to ...

  19. 7 CFR 925.51 - Recommendation for regulation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...Recommendation for regulation. 925.51 Section 925.51 Agriculture Regulations of the Department...AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF SOUTHEASTERN CALIFORNIA Regulations § 925.51 Recommendation for regulation....

  20. 7 CFR 925.51 - Recommendation for regulation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...Recommendation for regulation. 925.51 Section 925.51 Agriculture Regulations of the Department...AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF SOUTHEASTERN CALIFORNIA Regulations § 925.51 Recommendation for regulation....

  1. 7 CFR 925.51 - Recommendation for regulation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...Recommendation for regulation. 925.51 Section 925.51 Agriculture Regulations of the Department...AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF SOUTHEASTERN CALIFORNIA Regulations § 925.51 Recommendation for regulation....

  2. 7 CFR 925.51 - Recommendation for regulation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...Recommendation for regulation. 925.51 Section 925.51 Agriculture Regulations of the Department...AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF SOUTHEASTERN CALIFORNIA Regulations § 925.51 Recommendation for regulation....

  3. 7 CFR 925.51 - Recommendation for regulation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...Recommendation for regulation. 925.51 Section 925.51 Agriculture Regulations of the Department...AGRICULTURE GRAPES GROWN IN A DESIGNATED AREA OF SOUTHEASTERN CALIFORNIA Regulations § 925.51 Recommendation for regulation....

  4. Redox Regulation of Plant Development

    PubMed Central

    Considine, Michael J.

    2014-01-01

    Abstract Significance: We provide a conceptual framework for the interactions between the cellular redox signaling hub and the phytohormone signaling network that controls plant growth and development to maximize plant productivity under stress-free situations, while limiting growth and altering development on exposure to stress. Recent Advances: Enhanced cellular oxidation plays a key role in the regulation of plant growth and stress responses. Oxidative signals or cycles of oxidation and reduction are crucial for the alleviation of dormancy and quiescence, activating the cell cycle and triggering genetic and epigenetic control that underpin growth and differentiation responses to changing environmental conditions. Critical Issues: The redox signaling hub interfaces directly with the phytohormone network in the synergistic control of growth and its modulation in response to environmental stress, but a few components have been identified. Accumulating evidence points to a complex interplay of phytohormone and redox controls that operate at multiple levels. For simplicity, we focus here on redox-dependent processes that control root growth and development and bud burst. Future Directions: The multiple roles of reactive oxygen species in the control of plant growth and development have been identified, but increasing emphasis should now be placed on the functions of redox-regulated proteins, along with the central roles of reductants such as NAD(P)H, thioredoxins, glutathione, glutaredoxins, peroxiredoxins, ascorbate, and reduced ferredoxin in the regulation of the genetic and epigenetic factors that modulate the growth and vigor of crop plants, particularly within an agricultural context. Antioxid. Redox Signal. 21, 1305–1326. PMID:24180689

  5. Tonic regulation of vascular permeability

    PubMed Central

    Curry, Fitz-Roy E.; Adamson, Roger H.

    2014-01-01

    Our major theme is that the layered structure of the endothelial barrier requires continuous activation of signaling pathways regulated by S1P and intracellular cAMP. These pathways modulate the adherens junction, continuity of tight junction strands, and the balance of synthesis and degradation of glycocalyx components. We evaluate recent evidence that baseline permeability is maintained by constant activity of mechanisms involving the small GTPases Rap1 and Rac1. In the basal state, the barrier is compromised when activities of the small GTPases are reduced by low S1P supply or delivery. With inflammatory stimulus, increased permeability can be understood in part as the action of signaling to reduce Rap1 and Rac1 activation. With the hypothesis that microvessel permeability and selectivity under both normal and inflammatory conditions are regulated by mechanisms that are continuously active it follows that when S1P or intracellular cAMP are elevated at the time of inflammatory stimulus, they can buffer changes induced by inflammatory agents and maintain normal barrier stability. When endothelium is exposed to inflammatory conditions and subsequently exposed to elevated S1P or intracellular cAMP, the same processes restore the functional barrier by first reestablishing the adherens junction, then modulating tight junctions and glycocalyx. In more extreme inflammatory conditions, loss of the inhibitory actions of Rac1 dependent mechanisms may promote expression of more inflammatory endothelial phenotypes by contributing to the up-regulation of RhoA dependent contractile mechanisms and the sustained loss of surface glycocalyx allowing access of inflammatory cells to the endothelium. PMID:23374222

  6. Chemosensory Receptor Specificity and Regulation.

    PubMed

    Dalton, Ryan P; Lomvardas, Stavros

    2015-07-01

    The senses provide a means by which data on the physical and chemical properties of the environment may be collected and meaningfully interpreted. Sensation begins at the periphery, where a multitude of different sensory cell types are activated by environmental stimuli as different as photons and odorant molecules. Stimulus sensitivity is due to expression of different cell surface sensory receptors, and therefore the receptive field of each sense is defined by the aggregate of expressed receptors in each sensory tissue. Here, we review current understanding on patterns of expression and modes of regulation of sensory receptors. PMID:25938729

  7. Transglutaminase Regulation of Cell Function

    PubMed Central

    Kaartinen, Mari T.; Nurminskaya, Maria; Belkin, Alexey M.; Colak, Gozde; Johnson, Gail V. W.; Mehta, Kapil

    2014-01-01

    Transglutaminases (TGs) are multifunctional proteins having enzymatic and scaffolding functions that participate in regulation of cell fate in a wide range of cellular systems and are implicated to have roles in development of disease. This review highlights the mechanism of action of these proteins with respect to their structure, impact on cell differentiation and survival, role in cancer development and progression, and function in signal transduction. We also discuss the mechanisms whereby TG level is controlled and how TGs control downstream targets. The studies described herein begin to clarify the physiological roles of TGs in both normal biology and disease states. PMID:24692352

  8. Frequency Regulation Basics and Trends

    SciTech Connect

    Kirby, BJ

    2005-05-06

    The electric power system must address two unique requirements: the need to maintain a near real-time balance between generation and load, and the need to adjust generation (or load) to manage power flows through individual transmission facilities. These requirements are not new: vertically integrated utilities have been meeting them for a century as a normal part of conducting business. With restructuring, however, the services needed to meet these requirements, now called ''ancillary services'', are being more clearly defined. Ancillary services are those functions performed by the equipment and people that generate, control, and transmit electricity in support of the basic services of generating capacity, energy supply, and power delivery. The Federal Energy Regulatory Commission (FERC) has defined such services as those ''necessary to support the transmission of electric power from seller to purchaser given the obligations of control areas and transmitting utilities within those control areas to maintain reliable operations of the interconnected transmission system''. This statement recognizes the importance of ancillary services for both bulk-power reliability and support of commercial transactions. Balancing generation and load instantaneously and continuously is difficult because loads and generators are constantly fluctuating. Minute-to-minute load variability results from the random turning on and off of millions of individual loads. Longer-term variability results from predictable factors such as the daily and seasonal load patterns as well as more random events like shifting weather patterns. Generators also introduce unexpected fluctuations because they do not follow their generation schedules exactly and they trip unexpectedly due to a range of equipment failures. The output from wind generators varies with the wind. Storage technologies should be ideal suppliers of several ancillary services, including regulation, contingency reserves (spinning reserve, supplemental reserve, replacement reserve), and voltage support. These services are not free; in regions with energy markets, generators are paid to supply these services. In vertically integrated utilities (without energy markets) the utility incurs significant costs to supply these services. Supplying these services may be a significant business opportunity for emerging storage technologies. This report briefly explores the various ancillary services that may be of interest to storage. It then focuses on regulation, the most expensive ancillary service. It also examines the impact that increasing amounts of wind generation may have on regulation requirements, decreasing conventional regulation supplies, and the implications for energy storage.

  9. Epigenetic regulation of photoperiodic flowering

    PubMed Central

    2010-01-01

    The cytidine analogue 5-azacytidine, which causes DNA demethylation, induced flowering in the non-vernalization-requiring plants Perilla frutescens var. crispa, Silene armeria and Pharbitis nil (synonym Ipomoea nil) under non-inductive photoperiodic conditions, suggesting that the expression of photoperiodic flowering-related genes is regulated epigenetically by DNA methylation. The flowering state induced by DNA demethylation was not heritable. Changes in the genome-wide methylation state were examined by methylation-sensitive amplified fragment length polymorphism analysis. This analysis indicated that the DNA methylation state was altered by the photoperiodic condition. DNA demethylation also induced dwarfism, and the induced dwarfism of P. frutescens was heritable. PMID:20448475

  10. QB1 - Stochastic Gene Regulation

    SciTech Connect

    Munsky, Brian [Los Alamos National Laboratory

    2012-07-23

    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.

  11. Circadian regulation of adipose function

    PubMed Central

    Shostak, Anton; Husse, Jana; Oster, Henrik

    2013-01-01

    Adipose physiology shows prominent variation over the course of the day, responding to changing demands in energy metabolism. In the last years the tight interaction between the endogenous circadian timing system and metabolic function has been increasingly acknowledged. Recent work suggests that clock and adipose function go hand in hand, regulating each other to ensure optimal adaptation to environmental changes over the 24-h cycle. In this review we describe the current knowledge on the mechanistic basis of this interaction and summarize recent findings on the impact of clock dysfunction on adipose physiology and energy homeostasis. PMID:24052895

  12. Oxygen, homeostasis, and metabolic regulation.

    PubMed

    Hochachka, P W

    2000-01-01

    Even a cursory review of the literature today indicates that two views dominate experimental approaches to metabolic regulation. Model I assumes that cell behavior is quite similar to that expected for a bag of enzymes. Model II assumes that 3-D order and structure constrain metabolite behavior and that metabolic regulation theory has to incorporate structure to ever come close to describing reality. The phosphagen system may be used to illustrate that both approaches lead to very productive experimentation and significant advances are being made within both theoretical frameworks. However, communication between the two approaches or the two 'groups' is essentially nonexistent and in many cases (our own for example) some experiments are done in one framework and some in the other (implying some potential schizophrenia in the field). In our view, the primary paradox and problem which no one has solved so far is that essentially all metabolite concentrations are remarkably stable (are homeostatic) over large changes in pathway fluxes. For muscle cells O2 is one of the most perfectly homeostatic of all even though O2 delivery and metabolic rate usually correlate in a 1:1 fashion. Four explanations for this behavior are given by traditional metabolic regulation models. Additionally, there is some evidence for universal O2 sensors which could help to get us out of the paradox. In contrast, proponents of an ultrastructurally dominated view of the cell assume intracellular perfusion or convection as the main means for accelerating enzyme-substrate encounter and as a way to account for the data which have been most perplexing so far: the striking lack of correlation between changes in pathway reaction rates and changes in concentrations of pathway substrates and intermediates, including oxygen. The polarization illustrated by these two views of living cells extends throughout the metabolic regulation field (and has caused the field to progress along two surprisingly independent paths with minimal communication between them). The time may have come when cross talk between the two fields may be useful. PMID:10849672

  13. NOTICE OF REGULATION REPEAL Date: July 1, 2010

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: July 1, 2010 REGULATION TITLE: REGULATION NO.: Fees for Testing, Certification, Inspection and UCF-8.004 Services SUMMARY OF REGULATION REPEAL: This regulation is proposed for repeal because the material contained in this regulation has been updated and adopted as rule 6C7

  14. NOTICE OF REGULATION REPEAL Date: July 31, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: July 31, 2009 REGULATION TITLE: REGULATION NO.: Evaluation of Lease Proposals 6C7-7.212 SUMMARY OF REGULATION REPEAL: This regulation is noticed for repeal due to the inclusion of the relevant information in the proposed amendment to regulation UCF-7.209. AUTHORITY: BOG

  15. NOTICE OF REGULATION REPEAL Date: August 6, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: August 6, 2009 REGULATION TITLE: REGULATION NO.: Definitions 6C7-7.204 SUMMARY OF REGULATION REPEAL: This regulation is noticed for repeal due to the inclusion of the relevant information in the proposed amendment to regulation UCF-7.203. AUTHORITY: BOG Resolution dated January 7, 2003

  16. NOTICE OF REGULATION REPEAL Date: July 31, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: July 31, 2009 REGULATION TITLE: REGULATION NO.: Exception to Competitive Bidding for Leased Space 6C7-7.220 SUMMARY OF REGULATION REPEAL: This regulation is noticed for repeal due to the inclusion of the relevant information in the proposed amendment to regulation UCF-7

  17. NOTICE OF REGULATION REPEAL Date: July 1, 2010

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: July 1, 2010 REGULATION TITLE: REGULATION NO.: Solar Thermal and Photovoltaic System UCF-8.005 Standards and Certification SUMMARY OF REGULATION REPEAL: This regulation is proposed for repeal because the material contained in this regulation has been updated and adopted as rule

  18. NOTICE OF REGULATION REPEAL Date: May 8, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: May 8, 2009 REGULATION TITLE: REGULATION NO.: Confidential Information Policy for Faculty 6C73.030 SUMMARY OF REGULATION REPEAL: This regulation is being repealed NAME OF PERSON WHO INITIATED REGULATION REPEAL: Mark Roberts, Director, Human Resources COMMENTS

  19. NOTICE OF REGULATION REPEAL Date: August 6, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: August 6, 2009 REGULATION TITLE: REGULATION NO.: Code Compliance in Lease Space 6C7-7.207 SUMMARY OF REGULATION REPEAL: This regulation is noticed for repeal due to the inclusion of the relevant information in the proposed amendment to regulation UCF-7.203. AUTHORITY: BOG

  20. NOTICE OF REGULATION REPEAL Date: July 1, 2010

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: July 1, 2010 REGULATION TITLE: REGULATION NO.: Florida Solar Energy Center Operations UCF-8.001 SUMMARY OF REGULATION REPEAL: This regulation is proposed for repeal, because the material contained in this regulation has been updated and adopted as rule 6C7-8.006, F

  1. NOTICE OF REGULATION REPEAL Date: February 26, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: February 26, 2009 REGULATION TITLE: REGULATION NO.: Space Allocation 6C7-7.218 SUMMARY OF REGULATION REPEAL: This regulation is being repealed. The subject matter of regulation 6C7-7.218 is addressed by the Board of Governors. AUTHORITY: BOG Resolution dated January 7, 2003

  2. NOTICE OF REGULATION REPEAL Date: July 31, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: July 31, 2009 REGULATION TITLE: REGULATION NO.: Proposals to Lease 6C7-7.211 SUMMARY OF REGULATION REPEAL: This regulation is noticed for repeal due to the inclusion of the relevant information in the proposed amendment to regulation UCF-7.209. AUTHORITY: BOG Resolution dated

  3. NOTICE OF REGULATION REPEAL Date: August 6, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: August 6, 2009 REGULATION TITLE: REGULATION NO.: Certification of Compliance - Leases 6C7-7.216 SUMMARY OF REGULATION REPEAL: This regulation is noticed for repeal because the subject matter of the regulation is not needed and is out of date. AUTHORITY: BOG Resolution dated January

  4. NOTICE OF REGULATION REPEAL Date: August 6, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: August 6, 2009 REGULATION TITLE: REGULATION NO.: Space Measurement 6C7-7.217 SUMMARY OF REGULATION REPEAL: This regulation is noticed for repeal due to the inclusion of the relevant information in the proposed amendment to regulation UCF-7.203. AUTHORITY: BOG Resolution dated

  5. NOTICE OF REGULATION REPEAL Date: August 6, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: August 6, 2009 REGULATION TITLE: REGULATION NO.: Standard Lease Agreement Form 6C7-7.206 SUMMARY OF REGULATION REPEAL: This regulation is noticed for repeal due to the inclusion of the relevant information in the proposed amendment to regulation UCF-7.203. AUTHORITY: BOG

  6. NOTICE OF REGULATION REPEAL Date: August 6, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: August 6, 2009 REGULATION TITLE: REGULATION NO.: Approval of Real Property Leases 6C7-7.205 SUMMARY OF REGULATION REPEAL: This regulation is noticed for repeal due to the inclusion of the relevant information in the proposed amendment to regulation UCF-7.203. AUTHORITY: BOG

  7. NOTICE OF REGULATION REPEAL Date: July 9, 2009

    E-print Network

    Wu, Shin-Tson

    NOTICE OF REGULATION REPEAL Date: July 9, 2009 REGULATION TITLE: REGULATION NO.: Grievance Procedures for Non-unit Faculty and UCF-3.0132 A&P Staff Members SUMMARY OF REGULATION REPEAL: This regulation is being repealed. New regulations are being adopted that will cover the subject matter. AUTHORITY

  8. Transcriptional regulation of tenascin genes.

    PubMed

    Chiovaro, Francesca; Chiquet-Ehrismann, Ruth; Chiquet, Matthias

    2015-01-01

    Extracellular matrix proteins of the tenascin family resemble each other in their domain structure, and also share functions in modulating cell adhesion and cellular responses to growth factors. Despite these common features, the 4 vertebrate tenascins exhibit vastly different expression patterns. Tenascin-R is specific to the central nervous system. Tenascin-C is an "oncofetal" protein controlled by many stimuli (growth factors, cytokines, mechanical stress), but with restricted occurrence in space and time. In contrast, tenascin-X is a constituitive component of connective tissues, and its level is barely affected by external factors. Finally, the expression of tenascin-W is similar to that of tenascin-C but even more limited. In accordance with their highly regulated expression, the promoters of the tenascin-C and -W genes contain TATA boxes, whereas those of the other 2 tenascins do not. This article summarizes what is currently known about the complex transcriptional regulation of the 4 tenascin genes in development and disease. PMID:25793574

  9. Connexin40 regulates platelet function

    PubMed Central

    Vaiyapuri, Sakthivel; Moraes, Leonardo A.; Sage, Tanya; Ali, Marfoua S.; Lewis, Kirsty R.; Mahaut-Smith, Martyn P.; Oviedo-Orta, Ernesto; Simon, Alexander M.; Gibbins, Jonathan M.

    2013-01-01

    The presence of multiple connexins was recently demonstrated in platelets, with notable expression of Cx37. Studies with Cx37-deficient mice and connexin inhibitors established roles for hemichannels and gap junctions in platelet function. It was uncertain, however, whether Cx37 functions alone or in collaboration with other family members through heteromeric interactions in regulation of platelet function. Here we report the presence and functions of an additional platelet connexin, Cx40. Inhibition of Cx40 in human platelets or its deletion in mice reduces platelet aggregation, fibrinogen binding, granule secretion and clot retraction. The effects of the Cx37 inhibitor 37,43Gap27 on Cx40?/? mouse platelets and of the Cx40 inhibitor 40Gap27 on Cx37?/? mouse platelets revealed that each connexin is able to function independently. Inhibition or deletion of Cx40 reduces haemostatic responses in mice, indicating the physiological importance of this protein in platelets. We conclude that multiple connexins are involved in regulating platelet function, thereby contributing to haemostasis and thrombosis. PMID:24096827

  10. Transcriptional regulation by Ferric Uptake Regulator (Fur) in pathogenic bacteria

    PubMed Central

    Troxell, Bryan; Hassan, Hosni M.

    2013-01-01

    In the ancient anaerobic environment, ferrous iron (Fe2+) was one of the first metal cofactors. Oxygenation of the ancient world challenged bacteria to acquire the insoluble ferric iron (Fe3+) and later to defend against reactive oxygen species (ROS) generated by the Fenton chemistry. To acquire Fe3+, bacteria produce low-molecular weight compounds, known as siderophores, which have extremely high affinity for Fe3+. However, during infection the host restricts iron from pathogens by producing iron- and siderophore-chelating proteins, by exporting iron from intracellular pathogen-containing compartments, and by limiting absorption of dietary iron. Ferric Uptake Regulator (Fur) is a transcription factor which utilizes Fe2+ as a corepressor and represses siderophore synthesis in pathogens. Fur, directly or indirectly, controls expression of enzymes that protect against ROS damage. Thus, the challenges of iron homeostasis and defense against ROS are addressed via Fur. Although the role of Fur as a repressor is well-documented, emerging evidence demonstrates that Fur can function as an activator. Fur activation can occur through three distinct mechanisms (1) indirectly via small RNAs, (2) binding at cis regulatory elements that enhance recruitment of the RNA polymerase holoenzyme (RNAP), and (3) functioning as an antirepressor by removing or blocking DNA binding of a repressor of transcription. In addition, Fur homologs control defense against peroxide stress (PerR) and control uptake of other metals such as zinc (Zur) and manganese (Mur) in pathogenic bacteria. Fur family members are important for virulence within bacterial pathogens since mutants of fur, perR, or zur exhibit reduced virulence within numerous animal and plant models of infection. This review focuses on the breadth of Fur regulation in pathogenic bacteria. PMID:24106689

  11. Dynamic Voltage Regulation Using Distributed Energy Resources

    SciTech Connect

    Xu, Yan [ORNL; Rizy, D Tom [ORNL; Li, Fangxing [ORNL; Kueck, John D [ORNL

    2007-01-01

    Many distributed energy resources (DE) are near load centres and equipped with power electronics converters to interface with the grid, therefore it is feasible for DE to provide ancillary services such as voltage regulation, nonactive power compensation, and power factor correction. A synchronous condenser and a microturbine with an inverter interface are implemented in parallel in a distribution system to regulate the local voltage. Voltage control schemes of the inverter and the synchronous condenser are developed. The experimental results show that both the inverter and the synchronous condenser can regulate the local voltage instantaneously, while the dynamic response of the inverter is faster than the synchronous condenser; and that integrated voltage regulation (multiple DE perform voltage regulation) can increase the voltage regulation capability, increase the lifetime of the equipment, and reduce the capital and operation costs.

  12. Regulation of IGFBP-1 in Metabolic Diseases

    PubMed Central

    Bae, Jae-Hoon; Song, Dae-Kyu; Im, Seung-Soon

    2013-01-01

    Insulin-like growth factor binding proteins (IGFBPs) play a key role in insulin and insulin growth factor signaling and are known to be expressed in several tissues. Studies on the transcriptional regulation of IGFBP genes in various cell types have suggested that IGFBPs control both systemic hormones and regulators. Also, the complex regulatory mechanisms involved in both transcription and translation of IGFBPs provide evidence for molecular mechanisms by which growth factor- and hormone-mediated gene expression are regulated. In particular, IGFBP-1 is known to be an important regulator of IGF activity and mainly regulates metabolism in mammals. In this review, we focus on recent progress in elucidating the transcriptional regulation of IGFBP-1 among IGFBP isoforms.

  13. Global virulence regulation networks in phytopathogenic bacteria

    Microsoft Academic Search

    Beth M. Mole; David A. Baltrus; Jeffery L. Dangl; Sarah R. Grant

    2007-01-01

    Phytopathogens coordinate multifaceted life histories and deploy stratified virulence determinants via com- plex, global regulation networks. We dissect the global regulation of four distantly related model phytopatho- gens to evaluate large-scale events and mechanisms that determine successful pathogenesis. Overarching themes include dependence on centralized cell-to-cell communication systems, pervasive two-component sig- nal-transduction systems, post-transcriptional regula- tion systems, AraC-like regulators and sigma

  14. 70 FR 15553 - Karnal Bunt; Regulated Areas

    Federal Register 2010, 2011, 2012, 2013, 2014

    2005-03-28

    We are amending the Karnal bunt regulations to make changes to the list of areas or fields regulated because of Karnal bunt, a fungal disease of wheat. We are adding certain areas in La Paz, Maricopa, and Pinal Counties, AZ, and Riverside County, CA, to the list of regulated areas either because they were found during surveys to contain a bunted wheat kernel, or because they are within the......

  15. 69 FR 21039 - Golden Nematode; Regulated Area

    Federal Register 2010, 2011, 2012, 2013, 2014

    2004-04-20

    We are adopting as a final rule, with one change, an interim rule that amended the golden nematode regulations by adding a field in Steuben County, NY, to the list of generally infested regulated areas. In this document, we are making an editorial change in order to correct a reference in the regulations. The interim rule was necessary to prevent the artificial spread of golden nematode to......

  16. Congestion control through input rate regulation

    Microsoft Academic Search

    Moshe Sidi; Wen-zu Liu; Israel Cidon; Inder Gopal

    1989-01-01

    Input-rate-regulation schemes are extensively studied from the viewpoint of smoothing and regulating effects of the incoming traffic. The smoothing effect is characterized by the variance of the interdeparture time of the packet-departure process from the input-rate-regulation mechanism. Under the assumption of Poisson arrivals, the characteristics of this departure process are explicitly derived in terms of the scheme's parameters, and the

  17. Circuit Regulates Speed Of dc Motor

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

    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.

  18. Redox regulation in the lens.

    PubMed

    Lou, Marjorie F

    2003-09-01

    The high content of glutathione (GSH) in the lens is believed to protect thiols in structural proteins and enzymes for proper biological functions. The lens has both biosynthetic and regenerating systems for GSH to maintain its large pool size. However, ageing lenses or lenses under oxidative stress show an extensively diminished size of GSH pool with some protein thiols being S-thiolated by oxidized non-protein thiols to form protein-thiol mixed disulfides, either as protein-S-S-glutathione (PSSG) or protein-S-S-cysteine (PSSC) or protein-S-S-gamma-glutamylcysteine. It was shown in an H(2)O(2)-induced cataract model that PSSG formation precedes a cascade of events before cataract formation, starting with protein disulfide crosslinks, protein solubility loss and high molecular weight aggregation. Furthermore, this early oxidative damage in protein thiols can be spontaneously reversed in H(2)O(2) pretreated lenses if the oxidant is removed in time. This dethiolation process appears to have mediated through a redox-regulating enzyme, thioltransferase (TTase), which is ubiquitously present in microbial, plant and animal tissues, including the lens. The GSH-dependent, low molecular weight (11.8 kDa) cytosolic enzyme plays an important role in oxidative defense and can modulate key metabolic enzymes in the glycolytic pathway. The enzyme repairs oxidatively damaged proteins/enzymes through its unique catalytic site with a vicinal cysteine moiety, which can specifically dethiolate protein-S-S-glutathione and restore protein free SH groups for proper enzymatic or protein functions. Most importantly, it has been demonstrated that thioltransferase has a remarkable resistance to oxidation (H(2)O(2)) in cultured human and rabbit lens epithelial cells under oxidative stress conditions when other oxidation defense systems of GSH peroxidase and GSH reductase are severely inactivated. A second repair enzyme, thioredoxin (TRx), which is NADPH-dependent, is widely found in many lower and higher life forms of life. It can dethiolate protein disulfides and thus is an extremely important regulator for redox homeostasis in the cells. Thioredoxin has been recently found in the lens and has been shown to participate in the repair process of oxidatively damaged lens proteins/enzymes. These two enzymes may work synergistically to regulate and repair thiols in lens proteins and enzymes, keeping a balanced redox potential to maintain the function of the lens. PMID:12892645

  19. Designing Freedom, Regulating a Nation: Socialist Cybernetics

    E-print Network

    Medina, Eden

    Designing Freedom, Regulating a Nation: Socialist Cybernetics in Allende's Chile* EDEN MEDINA principles of Allende's presidency. The project, later referred to as `Cybersyn' in English and Eden Medina

  20. Mechanotransduction: a major regulator of homeostasis and

    E-print Network

    Mofrad, Mohammad R. K.

    Overview Mechanotransduction: a major regulator of homeostasis and development Kevin S. Kolahi. Studies illustrate the diversity of mechanotransduction, and the major role it has on organism homeostasis

  1. Regulation of the photosynthetic electron transport chain.

    PubMed

    Ott; Clarke; Birks; Johnson

    1999-08-12

    The regulation of electron transport between photosystems II and I was investigated in the plant Silene dioica L. by means of measurement of the kinetics of reduction of P(700) following a light-to-dark transition. It was found that, in this species, the rate constant for P(700) reduction is sensitive to light intensity and to the availability of CO(2). The results indicated that at 25 degrees C the rate of electron transport is down-regulated by approximately 40-50% relative to the maximum rate achievable in saturating CO(2) and that this down-regulation can be explained by regulation of the electron transport chain itself. Measurements of the temperature sensitivity of this rate constant indicated that there is a switch in the rate-limiting step that controls electron transport at around 20 degrees C: at higher temperatures, CO(2) availability is limiting; at lower temperatures some other process regulates electron transport, possibly a diffusion step within the electron transport chain itself. Regulation of electron transport also occurred in response to drought stress and sucrose feeding. Measurements of non-photochemical quenching of chlorophyll fluorescence did not support the idea that electron transport is regulated by the pH gradient across the thylakoid membrane, and the possibility is discussed that the redox potential of a stromal component may regulate electron transport.Keywords: DeltapH. Electron transport. Photosynthesis. Photosynthetic control. Redox regulation. Silene (photosynthesis) PMID:10436228

  2. Exporting licensing regulations affecting US geothermal firms

    SciTech Connect

    Not Available

    1988-08-01

    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.

  3. Chromatin Regulators of Genomic Imprinting

    PubMed Central

    Weaver, Jamie R.; Bartolomei, Marisa S.

    2013-01-01

    Genomic imprinting is an epigenetic phenomenon in which genes are expressed monoallelically in a parent-of-origin-specific manner. Each chromosome is imprinted with its parental identity. Here we will discuss the nature of this imprinting mark. DNA methylation has a well-established central role in imprinting, and the details of DNA methylation dynamics and the mechanisms that target it to imprinted loci are areas of active investigation. However, there is increasing evidence that DNA methylation is not solely responsible for imprinted expression. At the same time, there is growing appreciation for the contributions of post-translational histone modifications to the regulation of imprinting. The integration of our understanding of these two mechanisms is an important goal for the future of the imprinting field. PMID:24345612

  4. Glutaminolysis and Transferrin Regulate Ferroptosis.

    PubMed

    Gao, Minghui; Monian, Prashant; Quadri, Nosirudeen; Ramasamy, Ravichandran; Jiang, Xuejun

    2015-07-16

    Ferroptosis has emerged as a new form of regulated necrosis that is implicated in various human diseases. However, the mechanisms of ferroptosis are not well defined. This study reports the discovery of multiple molecular components of ferroptosis and its intimate interplay with cellular metabolism and redox machinery. Nutrient starvation often leads to sporadic apoptosis. Strikingly, we found that upon deprivation of amino acids, a more rapid and potent necrosis process can be induced in a serum-dependent manner, which was subsequently determined to be ferroptosis. Two serum factors, the iron-carrier protein transferrin and amino acid glutamine, were identified as the inducers of ferroptosis. We further found that the cell surface transferrin receptor and the glutamine-fueled intracellular metabolic pathway, glutaminolysis, played crucial roles in the death process. Inhibition of glutaminolysis, the essential component of ferroptosis, can reduce heart injury triggered by ischemia/reperfusion, suggesting a potential therapeutic approach for treating related diseases. PMID:26166707

  5. Social bonding: regulation by neuropeptides

    PubMed Central

    Lieberwirth, Claudia; Wang, Zuoxin

    2014-01-01

    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. PMID:25009457

  6. Biomechanics of Fundamental Frequency Regulation

    PubMed Central

    Chan, Roger W.; Siegmund, Thomas; Zhang, Kai

    2009-01-01

    Accurate characterization of biomechanical characteristics of the vocal fold is critical for understanding the regulation of vocal fundamental frequency (F0), which depends on the active control of the intrinsic laryngeal muscles as well as the passive biomechanical response of the vocal fold lamina propria. Specifically, the tissue stress-strain response and viscoelastic properties under cyclic tensile deformation are relevant, when the vocal folds are subjected to length and tension changes due to posturing. This paper describes a constitutive modeling approach quantifying the relationship between vocal fold stress and strain (or stretch), and establishes predictions of F0 with the string model of phonation based on the constitutive parameters. Results indicated that transient and time-dependent changes in F0, including global declinations in declarative sentences, as well as local F0 overshoots and undershoots, can be partially attributed to the time-dependent viscoplastic response of the vocal fold cover. PMID:19415568

  7. Regulation of keratin network organization.

    PubMed

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

    2015-02-01

    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. PMID:25594948

  8. OSHA regulation of ergonomic health.

    PubMed

    Hansen, J A

    1993-01-01

    The occupational illnesses most frequently reported to the Occupational Safety and Health Administration (OSHA) are "disorders associated with repeated trauma," a category including noise-induced hearing loss and illnesses caused by ergonomic exposure. In response, OSHA has begun "rule-making" for a standard to control ergonomic exposures. This paper defines ergonomic illness as any diagnosis of gradual onset for which ergonomic exposure increases relative risk. The "Red Meat Guidelines," the model for OSHA's proposed "Ergonomic Safety and Health Program standard," are critically reviewed in terms of basic clinical and epidemiologic concepts. The OSHA 200 log is a cohort study which reaches its entire target population. The use of selected case definitions with the OSHA 200 log is recommended as a powerful, comparable, and cost-effective epidemiologic basis for ergonomic regulation. PMID:8423502

  9. Genomic neighbourhood and the regulation of gene expression Genomic neighbourhood and transcriptional regulation

    E-print Network

    Babu, M. Madan

    Genomic neighbourhood and the regulation of gene expression Genomic neighbourhood..................................................................................................................................................................................1 2. Genomic neighbourhood and its influence on gene regulation ..................................................................................................1 2.1 The eukaryotic genome is organised into genomic neighbourhoods

  10. Epigenetic regulation in drug addiction.

    PubMed

    Bili?ski, Przemys?aw; Wojty?a, Andrzej; Kapka-Skrzypczak, Lucyna; Chwedorowicz, Roman; Cyranka, Ma?gorzata; Studzi?ski, Tadeusz

    2012-01-01

    The interaction between environmental signals and genes has now taken on a clear molecular form as demonstrated by stable changes in chromatin structure. These changes occur through activation or repression of specific gene programmes by a combination of chromatin remodelling, activation and enzymatic modification of DNA and histones as well as nucleosomal subunit exchange. Recent research investigating the molecular mechanisms controlling drug-induced transcriptional, behavioural and synaptic activity has shown a direct role for chromatin remodelling--termed as epigenetic regulation--of neuronal gene programmes and subsequent addictive behaviour arising from it. Recent data suggest that repeated exposure to certain drugs promotes changes in levels of histone acetylation, phosphorylation and methylation, together with alterations in DNA methylation levels in the neurons of the brain reward centre, localised in the Nucleus Accumbens (NAc) region of the limbic system. The combination of acetylating, phosphorylating and methylating H3 and H4 histone tails alter chromatin compaction thereby promoting altered levels of cellular gene expression. Histone modifications, which weaken histone interaction with DNA or that promote recruitment of transcriptional activating complexes, correlate with permissive gene expression. Histone deacetylation, (which strengthen histone: DNA contacts), or histone methylation, (which recruits repressive complexes to chromatin), promote a state of transcriptional repression. Using animal models, acute cocaine treatment increases H4 acetylation at acutely regulated gene promoters, whereas H3 acetylation appears to predominate at chronically induced promoters. Chronic cocaine and alcohol treatment activate and repress many genes such as FosB, Cdk5, and Bdnf, where their dysregulation, at the chromatin level, contribute to the development and maintenance of addiction. Following drug exposure, it is still unknown, howver, how long these changes in chromatin structure persist in affecting neuronal function, but some do so for life. PMID:23020045

  11. Air/fuel ratio regulator

    SciTech Connect

    Simko, A.

    1980-07-22

    A description is given of an air/fuel ratio regulator for use with the fuel injection control system of an internal combustion engine of the spark ignition type having an air and exhaust gas (gas) induction passage open at one end to air at ambient pressure level and connected at its other end to the engine combustion chamber to be subject to manifold vacuum changes therein, a throttle valve rotatably mounted for movement across the passage to control the gas flow therethrough, exhaust gas recirculation (egr) passage means connecting engine exhaust gases to the induction passage above the closed position of the throttle valve, an egr flow control valve mounted in the egr passage means for movement between open and closed postions to control the volume of egr gas flow, an engine speed responsive positive displacement type fuel injection pump having a fuel flow output to the engine that varies in direct proportion to changes in engines speed to match fuel flow and mass airflow through the induction system of the engine over the entire speed and load range of the engine to maintain the intake mixture ratio of air to fuel constant, the pump having a fuel flow control lever movable to vary the fuel rate of flow, the regulator being characterized by engine manifold vacuum responsive first servo means operably connected to the fuel control lever for maintaining a constant air/fuel (A/F) ratio by changing fuel output as a function of changing manifold vacuum and air flow upon opening of the throttle valve, a fuel enrichment control lever operably connected to the pump control lever and movable to modify the position of the pump lever dictated by the first servo means to change the A/F ratio, and further means responsive to engine operating conditions for moving the fuel enrichment control lever to provide the changed A/F ratio.

  12. Fibronectin regulates calvarial osteoblast differentiation

    NASA Technical Reports Server (NTRS)

    Moursi, A. M.; Damsky, C. H.; Lull, J.; Zimmerman, D.; Doty, S. B.; Aota, S.; Globus, R. K.

    1996-01-01

    The secretion of fibronectin by differentiating osteoblasts and its accumulation at sites of osteogenesis suggest that fibronectin participates in bone formation. To test this directly, we determined whether fibronectin-cell interactions regulate progressive differentiation of cultured fetal rat calvarial osteoblasts. Spatial distributions of alpha 5 integrin subunit, fibronectin, osteopontin (bone sialoprotein I) and osteocalcin (bone Gla-protein) were similar in fetal rat calvaria and mineralized, bone-like nodules formed by cultured osteoblasts. Addition of anti-fibronectin antibodies to cultures at confluence reduced subsequent formation of nodules to less than 10% of control values, showing that fibronectin is required for normal nodule morphogenesis. Anti-fibronectin antibodies selectively inhibited steady-state expression of mRNA for genes associated with osteoblast differentiation; mRNA levels for alkaline phosphatase and osteocalcin were suppressed, whereas fibronectin, type I collagen and osteopontin were unaffected. To identify functionally relevant domains of fibronectin, we treated cells with soluble fibronectin fragments and peptides. Cell-binding fibronectin fragments (type III repeats 6-10) containing the Arg-Gly-Asp (RGD) sequence blocked both nodule initiation and maturation, whether or not they contained a functional synergy site. In contrast, addition of the RGD-containing peptide GRGDSPK alone did not inhibit nodule initiation, although it did block nodule maturation. Thus, in addition to the RGD sequence, other features of the large cell-binding fragments contribute to the full osteogenic effects of fibronectin. Nodule formation and osteoblast differentiation resumed after anti-fibronectin antibodies or GRGDSPK peptides were omitted from the media, showing that the inhibition was reversible and the treatments were not cytotoxic. Outside the central cell-binding domain, peptides from the IIICS region and antibodies to the N terminus did not inhibit nodule formation. We conclude that osteoblasts interact with the central cell-binding domain of endogenously produced fibronectin during early stages of differentiation, and that these interactions regulate both normal morphogenesis and gene expression.

  13. Local Regulation of Cystic Fibrosis Transmembrane Regulator and Epithelial Sodium Channel in Airway Epithelium

    Microsoft Academic Search

    Pingbo Huang; Elaine Gilmore; Patricia Kultgen; Paul Barnes; Sharon Milgram; M. Jackson

    2004-01-01

    Regulation of cystic fibrosis transmembrane regulator (CFTR) and epithelial sodium channel (ENaC) in airway epithelia strongly influ- ences the rate of mucociliary clearance (MCC) by determining the volume of airway surface liquid. MCC increases in response to stimuli originating on the airway surface, and CFTR and ENaC in airway epithelia appear to be regulated by local rather than systemic signal-

  14. Regulation 9: Procedure for Written and Email Resolutions REGULATION 9 : PROCEDURE FOR WRITTEN AND EMAIL RESOLUTIONS

    E-print Network

    Sussex, University of

    Regulation 9: Procedure for Written and Email Resolutions 39 REGULATION 9 : PROCEDURE FOR WRITTEN AND EMAIL RESOLUTIONS Regulation 9.5 and this paragraph may only be amended at a meeting of Council. In accordance with Statute IV.6, a written or email resolution of Council passed in accordance

  15. DEPARTMENT OF PESTICIDE REGULATION http://www.clemson.edu/public/regulatory/pesticide_regulation/

    E-print Network

    Stuart, Steven J.

    DEPARTMENT OF PESTICIDE REGULATION http://www.clemson.edu/public/regulatory/pesticide_regulation/ The Department of Pesticide Regulation (DPR) is the South Carolina regulatory and investigative agency for pesticides. The DPR enforces the South Carolina Pesticide Control Act (SCPCA), the South Carolina Chemigation

  16. Running header: SUPPORTING SELF-REGULATED SCIENCE 1 Supporting Self-Regulated Science Learning in

    E-print Network

    Young, R. Michael

    #12;SUPPORTING SELF-REGULATED SCIENCE 2 Abstract Narrative-centered learning environments and self-regulation for science learning. Connections are drawn between the salient characteristics of narrative-centered learning environments and principles for promoting self-regulation in science education

  17. Local dissipative Hamiltonian realization by feedback regulation

    Microsoft Academic Search

    Nicolas Hudon; Martin Guay

    2010-01-01

    This paper considers the design of smooth feedback regulators for control affine nonlinear systems. The reference dynamics to track is generated by a dissipative Hamiltonian system. The objective of the paper is to show that damping assignment can be achieved by regulation, thus avoiding the solution of the matching equations when the expression of an energy function is unknown. The

  18. Money Laundering: the Economics of Regulation

    Microsoft Academic Search

    DONATO MASCIANDARO

    1999-01-01

    The paper undertakes an economic analysis of money laundering and of anti-money laundering regulation within a theoretical and normative framework. The model is then applied to the development of the Italian anti-money laundering regulation in recent years.

  19. Focus on Preschool Aquatics: Child Care Regulations.

    ERIC Educational Resources Information Center

    Sayre, Nancy E.

    This paper proposes state regulations for the training of child care staff members in developmentally appropriate safe aquatic practices, outlines required features of any pools that children visit, and suggests safe practices for water-related activities at child care centers and swimming pools. The staff training regulation suggestions include…

  20. Regulation and innovation in the telecommunications industry

    Microsoft Academic Search

    Marc Bourreau; Pinar Do?an

    2001-01-01

    This paper aims to introduce issues that relate regulation and innovation in the telecommunications industry. We try to address the following question: which types of regulatory schemes are likely to promote innovation in a fast-growing telecommunications industry? Section 2 analyses ex ante control by sector-specific regulation and ex post control by competition policies. Section 3 deals with the importance of