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1

PKC? participates in food entrainment by regulating BMAL1  

PubMed Central

Temporally restricted feeding (RF) can phase reset the circadian clocks in numerous tissues in mammals, contributing to altered timing of behavioral and physiological rhythms. However, little is known regarding the underlying molecular mechanism. Here we demonstrate a role for the gamma isotype of protein kinase C (PKC?) in food-mediated entrainment of behavior and the molecular clock. We found that daytime RF reduced late-night activity in wild-type mice but not mice homozygous for a null mutation of PKC? (PKC??/?). Molecular analysis revealed that PKC? exhibited RF-induced changes in activation patterns in the cerebral cortex and that RF failed to substantially phase shift the oscillation of clock gene transcripts in the absence of PKC?. PKC? exerts effects on the clock, at least in part, by stabilizing the core clock component brain and muscle aryl hydrocarbon receptor nuclear translocator like 1 (BMAL1) and reducing its ubiquitylation in a deubiquitination-dependent manner. Taken together, these results suggest that PKC? plays a role in food entrainment by regulating BMAL1 stability.

Zhang, Luoying; Abraham, Diya; Lin, Shu-Ting; Oster, Henrik; Eichele, Gregor; Fu, Ying-Hui; Ptacek, Louis J.

2012-01-01

2

Circadian gene Bmal1 regulates diurnal oscillations of Ly6C(hi) inflammatory monocytes.  

PubMed

Circadian clocks have evolved to regulate physiologic and behavioral rhythms in anticipation of changes in the environment. Although the molecular clock is present in innate immune cells, its role in monocyte homeostasis remains unknown. Here, we report that Ly6C(hi) inflammatory monocytes exhibit diurnal variation, which controls their trafficking to sites of inflammation. This cyclic pattern of trafficking confers protection against Listeria monocytogenes and is regulated by the repressive activity of the circadian gene Bmal1. Accordingly, myeloid cell-specific deletion of Bmal1 induces expression of monocyte-attracting chemokines and disrupts rhythmic cycling of Ly6C(hi) monocytes, predisposing mice to development of pathologies associated with acute and chronic inflammation. These findings have unveiled a critical role for BMAL1 in controlling the diurnal rhythms in Ly6C(hi) monocyte numbers. PMID:23970558

Nguyen, Khoa D; Fentress, Sarah J; Qiu, Yifu; Yun, Karen; Cox, Jeffery S; Chawla, Ajay

2013-08-22

3

Bidirectional CLOCK/BMAL1-dependent circadian gene regulation by retinoic acid in vitro.  

PubMed

A central circadian clock located in the suprachiasmatic nucleus (SCN) of the mammalian hypothalamus entrains peripheral clocks through both neural and humoral factors. Although candidates for entrainment factors have been described, their details remain obscure. Here, we screened ligands for nuclear receptors that affect CLOCK/BMAL1-dependent transactivation of the mouse Period1 (mPer1) gene in NIH3T3 cells. We found that retinoic acids (RAs) significantly up-regulate mPer1 expression in an E-box-dependent manner. We also found that RAs up-regulate the expression of other E-box-dependent circadian genes such as mPer2, arginine vasopressin (mAVP), and peroxisome proliferator-activated receptor alpha (mPPARalpha). Surprisingly, the effect of RAs on CLOCK/BMAL1 (E-box)-dependent mRNA expression was bidirectional and depended on the presence of exogenous retinoic acid receptor alpha (RARalpha). These results suggest that RAs regulate the CLOCK/BMAL1-dependent transcription of circadian genes in a complex manner. PMID:17069763

Shirai, Hidenori; Oishi, Katsutaka; Ishida, Norio

2006-10-27

4

Bidirectional CLOCK/BMAL1-dependent circadian gene regulation by retinoic acid in vitro  

SciTech Connect

A central circadian clock located in the suprachiasmatic nucleus (SCN) of the mammalian hypothalamus entrains peripheral clocks through both neural and humoral factors. Although candidates for entrainment factors have been described, their details remain obscure. Here, we screened ligands for nuclear receptors that affect CLOCK/BMAL1-dependent transactivation of the mouse Period1 (mPer1) gene in NIH3T3 cells. We found that retinoic acids (RAs) significantly up-regulate mPer1 expression in an E-box-dependent manner. We also found that RAs up-regulate the expression of other E-box-dependent circadian genes such as mPer2, arginine vasopressin (mAVP), and peroxisome proliferator-activated receptor {alpha} (mPPAR{alpha}). Surprisingly, the effect of RAs on CLOCK/BMAL1 (E-box)-dependent mRNA expression was bidirectional and depended on the presence of exogenous retinoic acid receptor {alpha} (RAR{alpha}). These results suggest that RAs regulate the CLOCK/BMAL1-dependent transcription of circadian genes in a complex manner.

Shirai, Hidenori [Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566 (Japan); Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8502 (Japan); Oishi, Katsutaka [Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566 (Japan); Ishida, Norio [Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566 (Japan) and Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8502 (Japan)]. E-mail: n.ishida@aist.go.jp

2006-12-15

5

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

SciTech Connect

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.

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

6

CLOCK and BMAL1 regulate MyoD and are necessary for maintenance of skeletal muscle phenotype and function  

PubMed Central

MyoD, a master regulator of myogenesis, exhibits a circadian rhythm in its mRNA and protein levels, suggesting a possible role in the daily maintenance of muscle phenotype and function. We report that MyoD is a direct target of the circadian transcriptional activators CLOCK and BMAL1, which bind in a rhythmic manner to the core enhancer of the MyoD promoter. Skeletal muscle of Clock?19 and Bmal1?/? mutant mice exhibited ?30% reductions in normalized maximal force. A similar reduction in force was observed at the single-fiber level. Electron microscopy (EM) showed that the myofilament architecture was disrupted in skeletal muscle of Clock?19, Bmal1?/?, and MyoD?/? mice. The alteration in myofilament organization was associated with decreased expression of actin, myosins, titin, and several MyoD target genes. EM analysis also demonstrated that muscle from both Clock?19 and Bmal1?/? mice had a 40% reduction in mitochondrial volume. The remaining mitochondria in these mutant mice displayed aberrant morphology and increased uncoupling of respiration. This mitochondrial pathology was not seen in muscle of MyoD?/? mice. We suggest that altered expression of both Pgc-1? and Pgc-1? in Clock?19 and Bmal1?/? mice may underlie this pathology. Taken together, our results demonstrate that disruption of CLOCK or BMAL1 leads to structural and functional alterations at the cellular level in skeletal muscle. The identification of MyoD as a clock-controlled gene provides a mechanism by which the circadian clock may generate a muscle-specific circadian transcriptome in an adaptive role for the daily maintenance of adult skeletal muscle.

Andrews, Jessica L.; Zhang, Xiping; McCarthy, John J.; McDearmon, Erin L.; Hornberger, Troy A.; Russell, Brenda; Campbell, Kenneth S.; Arbogast, Sandrine; Reid, Michael B.; Walker, John R.; Hogenesch, John B.; Takahashi, Joseph S.; Esser, Karyn A.

2010-01-01

7

TIEG1/KLF10 Modulates Runx2 Expression and Activity in Osteoblasts  

PubMed Central

Deletion of TIEG1/KLF10 in mice results in a gender specific osteopenic skeletal phenotype with significant defects in both cortical and trabecular bone, which are observed only in female animals. Calvarial osteoblasts isolated from TIEG1 knockout (KO) mice display reduced expression levels of multiple bone related genes, including Runx2, and exhibit significant delays in their mineralization rates relative to wildtype controls. These data suggest that TIEG1 plays an important role in regulating Runx2 expression in bone and that decreased Runx2 expression in TIEG1 KO mice is in part responsible for the observed osteopenic phenotype. In this manuscript, data is presented demonstrating that over-expression of TIEG1 results in increased expression of Runx2 while repression of TIEG1 results in suppression of Runx2. Transient transfection and chromatin immunoprecipitation assays reveal that TIEG1 directly binds to and activates the Runx2 promoter. The zinc finger containing domain of TIEG1 is necessary for this regulation supporting that activation occurs through direct DNA binding. A role for the ubiquitin/proteasome pathway in fine tuning the regulation of Runx2 expression by TIEG1 is also implicated in this study. Additionally, the regulation of Runx2 expression by cytokines such as TGF?1 and BMP2 is shown to be inhibited in the absence of TIEG1. Co-immunoprecipitation and co-localization assays indicate that TIEG1 protein associates with Runx2 protein resulting in co-activation of Runx2 transcriptional activity. Lastly, Runx2 adenoviral infection of TIEG1 KO calvarial osteoblasts leads to increased expression of Runx2 and enhancement of their ability to differentiate and mineralize in culture. Taken together, these data implicate an important role for TIEG1 in regulating the expression and activity of Runx2 in osteoblasts and suggest that decreased expression of Runx2 in TIEG1 KO mice contributes to the observed osteopenic bone phenotype.

Hawse, John R.; Cicek, Muzaffer; Grygo, Sarah B.; Bruinsma, Elizabeth S.; Rajamannan, Nalini M.; van Wijnen, Andre J.; Lian, Jane B.; Stein, Gary S.; Oursler, Merry Jo; Subramaniam, Malayannan; Spelsberg, Thomas C.

2011-01-01

8

Circadian regulation of low density lipoprotein receptor promoter activity by CLOCK/BMAL1, Hes1 and Hes6  

PubMed Central

Low density lipoprotein receptor (LDLR) plays an important role in the cholesterol homeostasis. We examined the possible circadian regulation of LDLR and mechanism(s) underlying it. In mice, blood glucose and plasma triglyceride, total and high density lipoprotein cholesterol varied distinctively throughout a day. In addition, LDLR mRNA oscillated in the liver in a functional clock-dependent manner. Accordingly, analysis of human LDLR promoter sequence revealed three putative E-boxes, raising the possible regulation of LDLR expression by E-box-binding transcription factors. To test this possibility, human LDLR promoter reporter constructs were transfected into HepG2 cells and the effects of CLOCK/BMAL1, Hes1, and Hes6 expression were analyzed. It was found that positive circadian transcription factor complex CLOCK/BMAL1 upregulated human LDLR promoter activity in a serum-independent manner, while Hes family members Hes1 and Hes6 downregulated it only under serum-depleted conditions. Both effects were mapped to proximal promoter region of human LDLR, where mutation or deletion of well-known sterol regulatory element (SRE) abolished only the repressive effect of Hes1. Interestingly, hes6 and hes1 mRNA oscillated in an anti-phasic manner in the wild-type but not in the per1-/-per2-/- mouse. Comparative analysis of mouse, rat and human hes6 genes revealed that three E-boxes are conserved among three species. Transfection and site-directed mutagenesis studies with hes6 reporter constructs confirmed that the third E-box in the exon IV is functionally induced by CLOCK/BMAL1. Taken together, these results suggest that LDLR expression is under circadian control involving CLOCK/BMAL1 and Hes family members Hes1 and Hes6.

Lee, Yeon-Ju; Han, Dong-Hee; Pak, Youngmi Kim

2012-01-01

9

Quantitative analyses of cryptochrome-mBMAL1 interactions: mechanistic insights into the transcriptional regulation of the mammalian circadian clock.  

PubMed

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-537(mBMAL1) 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

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

2011-04-25

10

Rhythmic SAF-A Binding Underlies Circadian Transcription of the Bmal1 Gene  

Microsoft Academic Search

Although Bmal1 is a key component of the mammalian clock system, little is understood about the actual mechanism of circadian Bmal1 gene transcription, particularly at the chromatin level. Here we discovered a unique chromatin structure within the Bmal1 promoter. The RORE region, which is a critical cis element for the circadian regulation of the Bmal1 gene, is comprised of GC-rich

Yoshiaki Onishi; Syuji Hanai; Tomoya Ohno; Yasuhiro Hara; Norio Ishida

2008-01-01

11

TIEG1 Inhibits Breast Cancer Invasion and Metastasis by Inhibition of Epidermal Growth Factor Receptor (EGFR) Transcription and the EGFR Signaling Pathway  

PubMed Central

TIEG1 can induce apoptosis of cancer cells, but its role in inhibiting invasion and metastasis has not been reported and is unclear. In this study, we find that decreased TIEG1 expression is associated with increased human epidermal growth factor receptor (EGFR) expression in breast cancer tissues and cell lines. TIEG1 plays an important role in suppressing transcription of EGFR by directly binding to the EGFR promoter. While overexpression of TIEG1 attenuates EGFR expression, knockdown of TIEG1 stimulates EGFR expression. Furthermore, TIEG1 and HDAC1 form a complex, which binds to Sp1 sites on the EGFR promoter and inhibits its transcription by suppressing histone acetylation. TIEG1 significantly inhibits breast cancer cell invasion, suppresses mammary tumorigenesis in xenografts in mice, and decreases lung metastasis by inhibition of EGFR gene transcription and the EGFR signaling pathway. Therefore, TIEG1 is an antimetastasis gene product; regulation of EGFR expression by TIEG1 may be part of an integral signaling pathway that determines and explains breast cancer invasion and metastasis.

Jin, Wei; Chen, Bo-bin; Li, Ji-yu; Zhu, Hua; Huang, Mark; Gu, Sheng-mei; Wang, Qiao-qiao; Chen, Jia-ying; Yu, Sanjian

2012-01-01

12

Disruption of CLOCK-BMAL1 transcriptional activity is responsible for aryl hydrocarbon receptor-mediated regulation of Period1 gene.  

PubMed

The aryl hydrocarbon receptor (AhR) is a period-aryl hydrocarbon receptor nuclear transporter-simple minded domain transcription factor that shares structural similarity with circadian clock genes and readily interacts with components of the molecular clock. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters behavioral circadian rhythms and represses the Period1 (Per1) gene in murine hematopoietic stem and progenitor cells. Per1 expression is driven by circadian locomotor activity cycles kaput-brain muscle ARNT-like (CLOCK-BMAL1)-dependent activation of Eboxes in the Per1 promoter. We hypothesized that the effects of AhR activation on the circadian clock are mediated by disruption of CLOCK-BMAL1 function and subsequent Per1 gene suppression. Effects of AhR activation on rhythmic Per1 transcripts were examined in livers of mice after treatment with the AhR agonist, TCDD; the molecular mechanisms of Per1 repression by AhR were determined in hepatoma cells using TCDD and beta-napthoflavone as AhR activators. This study reports, for the first time, that AhR activation by TCDD alters the Per1 rhythm in the mouse liver and that Per1 gene suppression depends upon the presence of AhR. Furthermore, AhR interaction with BMAL1 attenuates CLOCK-BMAL1 activity and decreases CLOCK binding at Ebox1 and Ebox3 in the Per1 promoter. Taken together, these data suggest that AhR activation represses Per1 through disrupting CLOCK-BMAL1 activity, producing dysregulation of rhythmic Per1 gene expression. These data define alteration of the Per1 rhythm as novel signaling events downstream of AhR activation. Downregulation of Per1 could contribute to metabolic disease, cancer, and other detrimental effects resulting from exposure to certain environmental pollutants. PMID:20106950

Xu, Can-Xin; Krager, Stacey L; Liao, Duan-Fang; Tischkau, Shelley A

2010-01-27

13

Deficient of a clock gene, brain and muscle Arnt-like protein-1 (BMAL1), induces dyslipidemia and ectopic fat formation.  

PubMed

A link between circadian rhythm and metabolism has long been discussed. Circadian rhythm is controlled by positive and negative transcriptional and translational feedback loops composed of several clock genes. Among clock genes, the brain and muscle Arnt-like protein-1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) play important roles in the regulation of the positive rhythmic transcription. In addition to control of circadian rhythm, we have previously shown that BMAL1 regulates adipogenesis. In metabolic syndrome patients, the function of BMAL1 is dysregulated in visceral adipose tissue. In addition, analysis of SNPs has revealed that BMAL1 is associated with susceptibility to hypertension and type II diabetes. Furthermore, the significant roles of BMAL1 in pancreatic ? cells proliferation and maturation were recently reported. These results suggest that BMAL1 regulates energy homeostasis. Therefore, in this study, we examined whether loss of BMAL1 function is capable of inducing metabolic syndrome. Deficient of the Bmal1 gene in mice resulted in elevation of the respiratory quotient value, indicating that BMAL1 is involved in the utilization of fat as an energy source. Indeed, lack of Bmal1 reduced the capacity of fat storage in adipose tissue, resulting in an increase in the levels of circulating fatty acids, including triglycerides, free fatty acids, and cholesterol. Elevation of the circulating fatty acids level induced the formation of ectopic fat in the liver and skeletal muscle in Bmal1 -/- mice. Interestingly, ectopic fat formation was not observed in tissue-specific (liver or skeletal muscle) Bmal1 -/- mice even under high fat diet feeding condition. Therefore, we were led to conclude that BMAL1 is a crucial factor in the regulation of energy homeostasis, and disorders of the functions of BMAL1 lead to the development of metabolic syndrome. PMID:21966465

Shimba, Shigeki; Ogawa, Tomohiro; Hitosugi, Shunsuke; Ichihashi, Yuya; Nakadaira, Yuki; Kobayashi, Munehiro; Tezuka, Masakatsu; Kosuge, Yasuhiro; Ishige, Kumiko; Ito, Yoshihisa; Komiyama, Kazuo; Okamatsu-Ogura, Yuko; Kimura, Kazuhiro; Saito, Masayuki

2011-09-22

14

Deficient of a Clock Gene, Brain and Muscle Arnt-Like Protein-1 (BMAL1), Induces Dyslipidemia and Ectopic Fat Formation  

PubMed Central

A link between circadian rhythm and metabolism has long been discussed. Circadian rhythm is controlled by positive and negative transcriptional and translational feedback loops composed of several clock genes. Among clock genes, the brain and muscle Arnt-like protein-1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) play important roles in the regulation of the positive rhythmic transcription. In addition to control of circadian rhythm, we have previously shown that BMAL1 regulates adipogenesis. In metabolic syndrome patients, the function of BMAL1 is dysregulated in visceral adipose tissue. In addition, analysis of SNPs has revealed that BMAL1 is associated with susceptibility to hypertension and type II diabetes. Furthermore, the significant roles of BMAL1 in pancreatic ? cells proliferation and maturation were recently reported. These results suggest that BMAL1 regulates energy homeostasis. Therefore, in this study, we examined whether loss of BMAL1 function is capable of inducing metabolic syndrome. Deficient of the Bmal1 gene in mice resulted in elevation of the respiratory quotient value, indicating that BMAL1 is involved in the utilization of fat as an energy source. Indeed, lack of Bmal1 reduced the capacity of fat storage in adipose tissue, resulting in an increase in the levels of circulating fatty acids, including triglycerides, free fatty acids, and cholesterol. Elevation of the circulating fatty acids level induced the formation of ectopic fat in the liver and skeletal muscle in Bmal1 -/- mice. Interestingly, ectopic fat formation was not observed in tissue-specific (liver or skeletal muscle) Bmal1 -/- mice even under high fat diet feeding condition. Therefore, we were led to conclude that BMAL1 is a crucial factor in the regulation of energy homeostasis, and disorders of the functions of BMAL1 lead to the development of metabolic syndrome.

Shimba, Shigeki; Ogawa, Tomohiro; Hitosugi, Shunsuke; Ichihashi, Yuya; Nakadaira, Yuki; Kobayashi, Munehiro; Tezuka, Masakatsu; Kosuge, Yasuhiro; Ishige, Kumiko; Ito, Yoshihisa; Komiyama, Kazuo; Okamatsu-Ogura, Yuko; Kimura, Kazuhiro; Saito, Masayuki

2011-01-01

15

Deficiency in Core Circadian Protein Bmal1 is Associated With a Prothrombotic and Vascular Phenotype  

PubMed Central

Aging is associated with both the disturbances of circadian rhythms and a prothrombotic phenotype. It remains poorly understood how the circadian system regulates thrombosis, a critical outcome of aging-related cardiovascular disease. Using multiple in vivo models, we now show that mice with genetic ablation of the core clock gene Bmal1, which display pre-mature aging, have a dramatic prothrombotic phenotype. This phenotype is mechanistically linked to changes in the regulation of key risk factors for cardiovascular disease. These include circulating vWF, fibrinogen, and PAI-1, all of which are significantly elevated in Bmal1?/? mice. We also show that major circadian transcriptional regulators CLOCK and Bmal1 directly regulate the activity of vWF promoter and that lack of Bmal1 results in upregulation of vWF both at mRNA and protein level. Here we report a direct regulation of vWF expression in endothelial cells by biological clock gene Bmal1. This study establishes a mechanistic connection between Bmal1 and cardiovascular phenotype.

SOMANATH, PAYANINGAL R.; PODREZ, EUGENE A.; CHEN, JUHUA; MA, YI; MARCHANT, KANDICE; ANTOCH, MARINA; BYZOVA, TATIANA V.

2010-01-01

16

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

PubMed Central

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 germ cell differentiation. The CB is also important for fertility determination since mutations of genes encoding its components cause infertility by spermatogenesis arrest. Targeted ablation of the Bmal1 and Clock genes, which encode central regulators of the circadian clock also result in fertility defects caused by problems other than spermatogenesis alterations. We show that the circadian proteins CLOCK and BMAL1 are localized in the CB in a stage-specific manner of germ cells. Both BMAL1 and CLOCK proteins physically interact with the ATP-dependent DEAD-box RNA helicase MVH (mouse VASA homolog), a hallmark component of the CB. BMAL1 is differentially expressed during the spermatogenic cycle of seminiferous tubules, and Bmal1 and Clock deficient mice display significant CB morphological alterations due to BMAL1 ablation or low expression. These findings suggest that both BMAL1 and CLOCK contribute to CB assembly and physiology, raising questions on the role of the circadian clock in reproduction and on the molecular function that CLOCK and BMAL1 could potentially have in the CB assembly and physiology.

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

2012-01-01

17

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

PubMed Central

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.

Onishi, Yoshiaki; Kawano, Yasuhiro

2012-01-01

18

Ketamine Influences CLOCK:BMAL1 Function Leading to Altered Circadian Gene Expression  

PubMed Central

Major mood disorders have been linked to abnormalities in circadian rhythms, leading to disturbances in sleep, mood, temperature, and hormonal levels. We provide evidence that ketamine, a drug with rapid antidepressant effects, influences the function of the circadian molecular machinery. Ketamine modulates CLOCK:BMAL1-mediated transcriptional activation when these regulators are ectopically expressed in NG108-15 neuronal cells. Inhibition occurs in a dose-dependent manner and is attenuated after treatment with the GSK3? antagonist SB21673. We analyzed the effect of ketamine on circadian gene expression and observed a dose-dependent reduction in the amplitude of circadian transcription of the Bmal1, Per2, and Cry1 genes. Finally, chromatin-immunoprecipitation analyses revealed that ketamine altered the recruitment of the CLOCK:BMAL1 complex on circadian promoters in a time-dependent manner. Our results reveal a yet unsuspected molecular mode of action of ketamine and thereby may suggest possible pharmacological antidepressant strategies.

Bellet, Marina M.; Vawter, Marquis P.; Bunney, Blynn G.; Bunney, William E.; Sassone-Corsi, Paolo

2011-01-01

19

Molecular structure of tail tendon fibers in TIEG1 knockout mice using synchrotron diffraction technology  

PubMed Central

The purpose of this study was to characterize the effect of TIEG1 on the molecular structure of collagen within tail tendon fibers using 3-mo-old female C57BL/6 wild-type (WT) and TIEG1 KO mice. Synchrotron X-ray microdiffraction experiments were carried out on single tendon fibers extracted from the WT and TIEG1 KO dorsal tail tendon. The fibers were scanned in the radial direction, and X-ray patterns were obtained. From these patterns, the meridional direction was analyzed through X-ray intensity profile. In addition, collagen content was investigated using hydroxyproline assays, and qualitative real-time PCR experiments were performed on RNA isolated from fibroblasts to examine specific gene expression changes. The results showed different X-ray diffraction patterns between WT and TIEG1 KO tendon fibers, indicating a disorganization of the collagen structure for the TIEG1 KO compared with WT mice. Furthermore, the analyses of the X-ray intensity profiles exhibited a higher (23 ?) period of collagen for the TIEG1 KO compared with the WT mice. The results of the hydroxyproline assays revealed a significant decrease in the TIEG1 KO compared with WT mice, leading to a decrease in the total amount of collagen present within the TIEG1 KO tendons. Moreover, qualitative real-time PCR results showed differences in the expression profiles of specific genes known to play important roles in tendon fiber development. These data further elucidate the role of TIEG1 on tendon structure and could explain the previous defects in the structure-function relationship found for TIEG1 KO tendon fibers.

Gumez, Laurie; Doucet, Jean; Haddad, Oualid; Hawse, John R.; Subramaniam, Malayannan; Spelsberg, Thomas C.; Pichon, Chantal

2010-01-01

20

The clock gene brain and muscle Arnt-like protein-1 (BMAL1) is involved in hair growth.  

PubMed

It is known that baldness caused by androgenetic alopecia is involved with androgen and the androgen receptor. Furthermore, it has been reported that testosterone secretion follows a circadian rhythm. Therefore, we hypothesized that a relationship exists between androgen-induced alopecia and biological rhythm. The mammalian circadian rhythm is controlled by several clock genes. Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1), one of the clock genes, is a transcription factor that plays central roles in the regulation of circadian rhythms. In this study, we investigated the influence of BMAL1 on hair follicle functions and hair growth. Mice deficient in BMAL1 expression exhibited a delay in hair regrowth after shaving. In hair follicles of mouse vibrissa, expression of Bmal1 and other clock genes was found to be rhythmic. Knockdown of BMAL1 in human follicle dermal papilla cells resulted in modulation of expression of several hair growth-related genes. Therefore, we concluded that expression of clock genes in hair follicles is linked to the circadian rhythm and that BMAL1 can regulate hair growth. PMID:23955654

Watabe, Yuichi; Tomioka, Miyuki; Watabe, Ai; Aihara, Masaki; Shimba, Shigeki; Inoue, Hajime

2013-08-18

21

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

Microsoft Academic Search

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

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

2009-01-01

22

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

PubMed Central

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.)

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

23

Intermolecular recognition revealed by the complex structure of human CLOCK-BMAL1 basic helix-loop-helix domains with E-box DNA.  

PubMed

CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain and muscle ARNT-like 1) are both transcription factors of the circadian core loop in mammals. Recently published mouse CLOCK-BMAL1 bHLH (basic helix-loop-helix)-PAS (period-ARNT-single-minded) complex structure sheds light on the mechanism for heterodimer formation, but the structural details of the protein-DNA recognition mechanisms remain elusive. Here we have elucidated the crystal structure of human CLOCK-BMAL1 bHLH domains bound to a canonical E-box DNA. We demonstrate that CLOCK and BMAL1 bHLH domains can be mutually selected, and that hydrogen-bonding networks mediate their E-box recognition. We identified a hydrophobic contact between BMAL1 Ile80 and a flanking thymine nucleotide, suggesting that CLOCK-BMAL1 actually reads 7-bp DNA and not the previously believed 6-bp DNA. To find potential non-canonical E-boxes that could be recognized by CLOCK-BMAL1, we constructed systematic single-nucleotide mutations on the E-box and measured their relevant affinities. We defined two non-canonical E-box patterns with high affinities, AACGTGA and CATGTGA, in which the flanking A7-T7' base pair is indispensable for recognition. These results will help us to identify functional CLOCK-BMAL1-binding sites in vivo and to search for clock-controlled genes. Furthermore, we assessed the inhibitory role of potential phosphorylation sites in bHLH regions. We found that the phospho-mimicking mutation on BMAL1 Ser78 could efficiently block DNA binding as well as abolish normal circadian oscillation in cells. We propose that BMAL1 Ser78 should be a key residue mediating input signal-regulated transcriptional inhibition for external cues to entrain the circadian clock by kinase cascade. PMID:23229515

Wang, Zixi; Wu, Yaling; Li, Lanfen; Su, Xiao-Dong

2012-12-11

24

The Transcriptional Repressor ID2 Can Interact with the Canonical Clock Components CLOCK and BMAL1 and Mediate Inhibitory Effects on mPer1 Expression*  

PubMed Central

ID2 is a rhythmically expressed HLH transcriptional repressor. Deletion of Id2 in mice results in circadian phenotypes, highlighted by disrupted locomotor activity rhythms and an enhanced photoentrainment response. ID2 can suppress the transactivation potential of the positive elements of the clock, CLOCK-BMAL1, on mPer1 and clock-controlled gene (CCG) activity. Misregulation of CCGs is observed in Id2?/? liver, and mutant mice exhibit associated alterations in lipid homeostasis. These data suggest that ID2 contributes to both input and output components of the clock and that this may be via interaction with the bHLH clock proteins CLOCK and BMAL1. The aim of the present study was to explore this potential interaction. Coimmunoprecipitation analysis revealed the capability of ID2 to complex with both CLOCK and BMAL1, and mammalian two-hybrid analysis revealed direct interactions of ID2, ID1 and ID3 with CLOCK and BMAL1. Deletion of the ID2 HLH domain rendered ID2 ineffective at inhibiting CLOCK-BMAL1 transactivation, suggesting that interaction between the proteins is via the HLH region. Immunofluorescence analysis revealed overlapping localization of ID2 with CLOCK and BMAL1 in the cytoplasm. Overexpression of CLOCK and BMAL1 in the presence of ID2 resulted in a significant reduction in their nuclear localization, revealing that ID2 can sequester CLOCK and BMAL1 to the cytoplasm. Serum stimulation of Id2?/? mouse embryonic fibroblasts resulted in an enhanced induction of mPer1 expression. These data provide the basis for a molecular mechanism through which ID2 could regulate aspects of both clock input and output through a time-of-day specific interaction with CLOCK and BMAL1.

Ward, Sarah M.; Fernando, Shanik J.; Hou, Tim Y.; Duffield, Giles E.

2010-01-01

25

Development of dilated cardiomyopathy in Bmal1-deficient mice  

PubMed Central

Circadian rhythms are approximate 24-h oscillations in physiology and behavior. Circadian rhythm disruption has been associated with increased incidence of hypertension, coronary artery disease, dyslipidemia, and other cardiovascular pathologies in both humans and animal models. Mice lacking the core circadian clock gene, brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like protein (Bmal1), are behaviorally arrhythmic, die prematurely, and display a wide range of organ pathologies. However, data are lacking on the role of Bmal1 on the structural and functional integrity of cardiac muscle. In the present study, we demonstrate that Bmal1?/? mice develop dilated cardiomyopathy with age, characterized by thinning of the myocardial walls, dilation of the left ventricle, and decreased cardiac performance. Shortly after birth the Bmal1?/? mice exhibit a transient increase in myocardial weight, followed by regression and later onset of dilation and failure. Ex vivo working heart preparations revealed systolic ventricular dysfunction at the onset of dilation and failure, preceded by downregulation of both myosin heavy chain isoform mRNAs. We observed structural disorganization at the level of the sarcomere with a shift in titin isoform composition toward the stiffer N2B isoform. However, passive tension generation in single cardiomyocytes was not increased. Collectively, these findings suggest that the loss of the circadian clock gene, Bmal1, gives rise to the development of an age-associated dilated cardiomyopathy, which is associated with shifts in titin isoform composition, altered myosin heavy chain gene expression, and disruption of sarcomere structure.

Lefta, Mellani; Campbell, Kenneth S.; Feng, Han-Zhong; Jin, Jian-Ping

2012-01-01

26

Ketamine influences CLOCK:BMAL1 function leading to altered circadian gene expression.  

PubMed

Major mood disorders have been linked to abnormalities in circadian rhythms, leading to disturbances in sleep, mood, temperature, and hormonal levels. We provide evidence that ketamine, a drug with rapid antidepressant effects, influences the function of the circadian molecular machinery. Ketamine modulates CLOCK:BMAL1-mediated transcriptional activation when these regulators are ectopically expressed in NG108-15 neuronal cells. Inhibition occurs in a dose-dependent manner and is attenuated after treatment with the GSK3? antagonist SB21673. We analyzed the effect of ketamine on circadian gene expression and observed a dose-dependent reduction in the amplitude of circadian transcription of the Bmal1, Per2, and Cry1 genes. Finally, chromatin-immunoprecipitation analyses revealed that ketamine altered the recruitment of the CLOCK:BMAL1 complex on circadian promoters in a time-dependent manner. Our results reveal a yet unsuspected molecular mode of action of ketamine and thereby may suggest possible pharmacological antidepressant strategies. PMID:21887357

Bellet, Marina M; Vawter, Marquis P; Bunney, Blynn G; Bunney, William E; Sassone-Corsi, Paolo

2011-08-24

27

Expression and Rhythmic Modulation of Circulating MicroRNAs Targeting the Clock Gene Bmal1 in Mice  

PubMed Central

MicroRNAs (miRNAs) interact with 3? untranslated region (UTR) elements of target genes to regulate mRNA stability or translation and thus play a role in regulating many different biological processes, including circadian rhythms. However, specific miRNAs mediating the regulation of essential clock genes remain largely unknown. Because vesicles containing membrane-bound miRNAs are present in the circulatory system, we examined miRNAs predicted to target the clock gene, Bmal1, for evidence of rhythmic fluctuations in circulating levels and modulatory effects on the 3? UTR activity of Bmal1. A number of miRNAs with Bmal1 as a predicted target were expressed in the serum of mice exposed to LD 12?12 and of these miRNAs, miR-152 and miR-494 but not miR-142-3p were marked by diurnal oscillations with bimodal peaks in expression occurring near the middle of the day and 8 or 12 hr later during the night. Co-transfection of pre-miR over-expression constructs for miR-494 and miR-142-3p in HEK293 cells had significant effects in repressing luciferase-reported Bmal1 3? UTR activity by as much as 60%, suggesting that these miRNAs may function as post-transcriptional modulators of Bmal1. In conjunction with previous studies implicating miRNAs as extracellular regulatory signals, our results suggest that circulating miRNAs may play a role in the regulation of the molecular clockworks in peripheral circadian oscillators.

Shende, Vikram R.; Goldrick, Marianna M.; Ramani, Suchitra; Earnest, David J.

2011-01-01

28

Transactivation of the TIEG1 confers growth inhibition of transforming growth factor-?-susceptible hepatocellular carcinoma cells  

PubMed Central

AIM: To investigate the role of transforming growth factor (TGF)-?-inducible early gene 1 (TIEG1) in TGF-?-induced growth inhibition in hepatocellular carcinoma (HCC) cells. METHODS: Human hepatocyte and HCC cell lines with varied susceptibilities to TGF-?1 were tested by methylthiazoletetrazolium (MTT) assay. The expression changes of Smad2, Smad3, Smad4, Smad7, TIEG1 and TIEG2 gene following treatment with TGF-?1 in a TGF-?-sensitive hepatocyte cell line (MIHA), a TGF-?-sensitive hepatoma cell line (Hep3B) and two TGF-?-insensitive hepatoma cell lines (HepG2 and Bel7404) were examined. SiRNA targeting TIEG1 was transfected into Hep3B cells and the sensitivity of cells to TGF-?1 was examined. Overexpression of TIEG1 was induced by lentiviral-mediated transduction in TGF-?1-resistant hepatoma cell lines (Bel7404 and HepG2). MTT assay and 4’,6-Diamidino-2-phenylindole staining were used to identify cell viability and apoptosis, respectively. The expression level of stathmin was measured by reverse transcriptase polymerase chain reaction and Western-blotting analysis, and stathmin promoter activity by TIEG1 was monitored by a luciferase reporter gene system. RESULTS: TIEG1 was significantly upregulated by TGF-?1 in the TGF-?1-sensitive HCC cell line, Hep3B, but not in the resistant cell lines. The suppression of TIEG1 by siRNAs decreased the sensitivity of Hep3B cells to TGF-?1, whereas the overexpression of TIEG1 mediated growth inhibition and apoptosis in TGF-?1-resistant HCC cell lines, which resembled those of TGF-?1-sensitive HCC cells treated with TGF-?1. Our data further suggested that stathmin was a direct target of TIEG1, as stathmin was significantly downregulated by TIEG1 overexpression, and stathmin promoter activity was inhibited by TIEG1 in a dose-dependent manner. CONCLUSION: Our data suggest that transactivation of TIEG1 conferred growth inhibition of TGF-?-susceptible human HCC cells.

Jiang, Lei; Lai, Yiu-Kay; Zhang, Jin-Fang; Chan, Chu-Yan; Lu, Gang; Lin, Marie CM; He, Ming-Liang; Li, Ji-Cheng; Kung, Hsiang-Fu

2012-01-01

29

Cistanches Herba aqueous extract affecting serum BGP and TRAP and bone marrow Smad1 mRNA, Smad5 mRNA, TGF-?1 mRNA and TIEG1 mRNA expression levels in osteoporosis disease.  

PubMed

We studied molecular mechanism of Cistanches Herba aqueous extract (CHAE) in ovariectomized (OVX) rats, as an experimental model of postmenopausal osteoporosis. Female rats were either sham-operated or bilaterally OVX; and at 60 days postoperatively. The OVX group (n = 8) received an ovariectomy and treatment with normal saline for 90 days commencing from 20th post ovariectomy day. The ovariectomized +CHAE (OVX + CHAE) group (n = 8) received an ovariectomy and were treated with Cistanches Herba aqueous extract of 100 mg/kg body weight daily for 90 days commencing from 22nd post ovariectomy day. The ovariectomy +CHAE (OVX + CHAE) group (n = 8) received an ovariectomy, and were treated with the of 200 mg/kg body weight daily for 90 days commencing from 20th post ovariectomy day. Serum BGP and TRAP, E2, FSH and LH level, bone marrow Smad1, Smad5, TGF-?1 and TIEG1 mRNA expression levels were examined. Results showed that serum BGP and TRAP, FSH and LH levels were significantly increased, whereas E2, Smad1, Smad5, TGF-?1 and TIEG1 mRNA and proteins expression levels were significantly decreased in OVX rats compared to sham rats. 90 days of CHAE treatment could significantly decrease serum BGP and TRAP, FSH and LH levels, and increase E2, Smad1, Smad5, TGF-?1 and TIEG1 mRNA and proteins expression levels in OVX rats. It can be concluded that CHAE play its protective effect against OVX-induced bone degeneration partly by regulating some bone metabolism related genes, e.g. Smad1, Smad5, TGF-?1 and TIEG1. PMID:23232713

Liang, Hai-Dong; Yu, Fang; Tong, Zhi-Hong; Zhang, Hong-Quan; Liang, Wu

2012-12-12

30

CLOCK, PER2 and BMAL1 DNA methylation: association with obesity and metabolic syndrome characteristics and monounsaturated fat intake.  

PubMed

The circadian clock system instructs 24-h rhythmicity on gene expression in essentially all cells, including adipocytes, and epigenetic mechanisms may participate in this regulation. The aim of this research was to investigate the influence of obesity and metabolic syndrome (MetS) features in clock gene methylation and the involvement of these epigenetic modifications in the outcomes. Sixty normal-weight, overweight and obese women followed a 16-weeks weight reduction program. DNA methylation levels at different CpG sites of CLOCK, BMAL1 and PER2 genes were analyzed by Sequenom's MassARRAY in white blood cells obtained before the treatment. Statistical differences between normal-weight and overweight + obese subjects were found in the methylation status of different CpG sites of CLOCK (CpGs 1, 5-6, 8 and 11-14) and, with lower statistical significance, in BMAL1 (CpGs 6-7, 8, 15 and 16-17). The methylation pattern of different CpG sites of the three genes showed significant associations with anthropometric parameters such as body mass index and adiposity, and with a MetS score. Moreover, the baseline methylation levels of CLOCK CpG 1 and PER2 CpGs 2-3 and 25 correlated with the magnitude of weight loss. Interestingly, the percentage of methylation of CLOCK CpGs 1 and 8 showed associations with the intake of monounsaturated and polyunsaturated fatty acids. This study demonstrates for the first time an association between methylation status of CpG sites located in clock genes (CLOCK, BMAL1 and PER2) with obesity, MetS and weight loss. Moreover, the methylation status of different CpG sites in CLOCK and PER2 could be used as biomarkers of weight-loss success, particularly CLOCK CPGs 5-6. PMID:23003921

Milagro, Fermín I; Gómez-Abellán, Purificación; Campión, Javier; Martínez, J Alfredo; Ordovás, Jose M; Garaulet, Marta

2012-09-24

31

TIEG1 Null Mouse-Derived Osteoblasts Are Defective in Mineralization and in Support of Osteoclast Differentiation In Vitro  

PubMed Central

Transforming growth factor ?-inducible early gene 1 (TIEG1) is a member of the Krüppel-like transcription factor family. To understand the physiological role of TIEG1, we generated TIEG?/? (null) mice and found that the TIEG?/? mice had increased osteoblast numbers with no increased bone formation parameters. However, when calvarial osteoblasts (OBs) were isolated from neonatal TIEG?/? and TIEG+/+ mice and cultured in vitro, the TIEG?/? cells displayed reduced expression of important OB differentiation markers. When the OBs were differentiated in vitro by treatment with bone morphogenic protein 2, the OBs from TIEG+/+ calvaria displayed several mineralized nodules in culture, whereas those from TIEG?/? mice showed no nodules. To characterize the OBs' ability to support osteoclast differentiation, the OBs from TIEG+/+ and TIEG?/? mice were cultured with marrow and spleen cells from TIEG+/+ mice. Significantly fewer osteoclasts developed when TIEG?/? OBs were used to support osteoclast differentiation than when TIEG+/+ OBs were used. Examination of gene expression in the TIEG?/? OBs revealed decreased RANKL and increased OPG expression compared to TIEG+/+ OBs. The addition of RANKL to these cocultures only partially restored the ability of TIEG?/? OBs to support osteoclast differentiation, whereas M-CSF alone or combined with RANKL had no additional effect on osteoclast differentiation. We conclude from these data that TIEG1 expression in OBs is critical for both osteoblast-mediated mineralization and osteoblast support of osteoclast differentiation.

Subramaniam, Malayannan; Gorny, Genevieve; Johnsen, Steven A.; Monroe, David G.; Evans, Glenda L.; Fraser, Daniel G.; Rickard, David J.; Rasmussen, Kay; van Deursen, Jan M. A.; Turner, Russell T.; Oursler, Merry Jo; Spelsberg, Thomas C.

2005-01-01

32

Sleep Loss Reduces the DNA-Binding of BMAL1, CLOCK, and NPAS2 to Specific Clock Genes in the Mouse Cerebral Cortex  

PubMed Central

We have previously demonstrated that clock genes contribute to the homeostatic aspect of sleep regulation. Indeed, mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock gene expression in the forebrain. Here, we investigate a possible mechanism by which sleep deprivation (SD) could alter clock gene expression by quantifying DNA-binding of the core-clock transcription factors CLOCK, NPAS2, and BMAL1 to the cis-regulatory sequences of target clock genes in mice. Using chromatin immunoprecipitation (ChIP), we first showed that, as reported for the liver, DNA-binding of CLOCK and BMAL1 to target clock genes changes in function of time-of-day in the cerebral cortex. Tissue extracts were collected at ZT0 (light onset), ?6, ?12, and ?18, and DNA enrichment of E-box or E'-box containing sequences was measured by qPCR. CLOCK and BMAL1 binding to Cry1, Dbp, Per1, and Per2 depended on time-of-day, with maximum values reached at around ZT6. We then observed that SD, performed between ZT0 and ?6, significantly decreased DNA-binding of CLOCK and BMAL1 to Dbp, consistent with the observed decrease in Dbp mRNA levels after SD. The DNA-binding of NPAS2 and BMAL1 to Per2 was also decreased by SD, although SD is known to increase Per2 expression in the cortex. DNA-binding to Per1 and Cry1 was not affected by SD. Our results show that the sleep-wake history can affect the clock molecular machinery directly at the level of chromatin binding thereby altering the cortical expression of Dbp and Per2 and likely other targets. Although the precise dynamics of the relationship between DNA-binding and mRNA expression, especially for Per2, remains elusive, the results also suggest that part of the reported circadian changes in DNA-binding of core clock components in tissues peripheral to the suprachiasmatic nuclei could, in fact, be sleep-wake driven.

Curie, Thomas; Franken, Paul

2011-01-01

33

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

PubMed Central

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.

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

2013-01-01

34

Functional CLOCK is not involved in the entrainment of peripheral clocks to the restricted feeding: entrainable expression of mPer2 and BMAL1 mRNAs in the heart of Clock mutant mice on Jcl:ICR background.  

PubMed

The mammalian circadian timing system consists of a central pacemaker in brain hypothalamus and damping oscillators in most peripheral tissues. To investigate the mechanism that controls circadian rhythms in the mammalian peripheral tissues, we examined the expression rhythm of mPer2, BMAL1, albumin D-site binding protein (DBP), and Rev-erbalpha mRNAs in the heart of homozygous Clock mutant mice on Jcl:ICR background under the temporal feeding restriction. Unexpectedly, the restricted feeding (RF) shifted the circadian phase of both mPer2 and BMAL1 mRNA expressions in the heart not only of wild-type mice but also of Clock mutant mice. Furthermore, in the Clock mutant mice, the amplitude of the circadian expression of mPer2 and BMAL1 mRNAs was dramatically increased by the RF. These data indicate that functional CLOCK is not required for an entrainment of peripheral clocks to RF. On the other hand, the expression levels of DBP and Rev-erbalpha mRNAs were blunted in Clock mutant mice not only under ad libitum but also under RF conditions. Thus, it seems that the rhythmic expression of Rev-erbalpha is not involved in the RF-induced circadian expression of BMAL1 mRNA, although REV-ERBalpha has been identified as a major regulator of BMAL1 transcription. Thus, the entraining mechanism of peripheral tissues to the RF seems to be different from that to the central clock in the suprachiasmatic nucleus. PMID:12387815

Oishi, Katsutaka; Miyazaki, Koyomi; Ishida, Norio

2002-10-25

35

Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes  

PubMed Central

Many aspects of physiology and behavior follow a circadian rhythm. Brain and muscle Arnt-like protein-1 (BMAL1) is a key component of the mammalian molecular clock, which controls circadian oscillations. In the rat, the gene encoding Bmal1 is located within hypertension susceptibility loci. We analyzed the SNP distribution pattern in a congenic interval associated with hypertension in the spontaneously hypertensive rat (SHR), and we show that Bmal1 maps close to a region genetically divergent between SHR and its normotensive (Wistar–Kyoto) counterpart. Bmal1 sequencing in rat strains identified 19 polymorphisms, including an SHR promoter variant that significantly affects Gata-4 activation of transcription in transient transfection experiments. A genetic association study designed to test the relevance of these findings in 1,304 individuals from 424 families primarily selected for type 2 diabetes showed that two BMAL1 haplotypes are associated with type 2 diabetes and hypertension. This comparative genetics finding translated from mouse and rat models to human provides evidence of a causative role of Bmal1 variants in pathological components of the metabolic syndrome.

Woon, Peng Y.; Kaisaki, Pamela J.; Braganca, Jose; Bihoreau, Marie-Therese; Levy, Jonathan C.; Farrall, Martin; Gauguier, Dominique

2007-01-01

36

Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis  

PubMed Central

The role of the circadian clock in skin and the identity of genes participating in its chronobiology remain largely unknown, leading us to define the circadian transcriptome of mouse skin at two different stages of the hair cycle, telogen and anagen. The circadian transcriptomes of telogen and anagen skin are largely distinct, with the former dominated by genes involved in cell proliferation and metabolism. The expression of many metabolic genes is antiphasic to cell cycle-related genes, the former peaking during the day and the latter at night. Consistently, accumulation of reactive oxygen species, a byproduct of oxidative phosphorylation, and S-phase are antiphasic to each other in telogen skin. Furthermore, the circadian variation in S-phase is controlled by BMAL1 intrinsic to keratinocytes, because keratinocyte-specific deletion of Bmal1 obliterates time-of-day–dependent synchronicity of cell division in the epidermis leading to a constitutively elevated cell proliferation. In agreement with higher cellular susceptibility to UV-induced DNA damage during S-phase, we found that mice are most sensitive to UVB-induced DNA damage in the epidermis at night. Because in the human epidermis maximum numbers of keratinocytes go through S-phase in the late afternoon, we speculate that in humans the circadian clock imposes regulation of epidermal cell proliferation so that skin is at a particularly vulnerable stage during times of maximum UV exposure, thus contributing to the high incidence of human skin cancers.

Geyfman, Mikhail; Kumar, Vivek; Liu, Qiang; Ruiz, Rolando; Gordon, William; Espitia, Francisco; Cam, Eric; Millar, Sarah E.; Smyth, Padhraic; Ihler, Alexander; Takahashi, Joseph S.; Andersen, Bogi

2012-01-01

37

Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice.  

PubMed

Genetic and molecular approaches have been critical for elucidating the mechanism of the mammalian circadian clock. Here, we demonstrate that the Clock?19 mutant behavioral phenotype is significantly modified by mouse strain genetic background. We map a suppressor of the Clock?19 mutation to a ?900 kb interval on mouse chromosome 1 and identify the transcription factor, Usf1, as the responsible gene. A SNP in the promoter of Usf1 causes elevation of its transcript and protein in strains that suppress the Clock mutant phenotype. USF1 competes with the CLOCK:BMAL1 complex for binding to E-box sites in target genes. Saturation binding experiments demonstrate reduced affinity of the CLOCK?19:BMAL1 complex for E-box sites, thereby permitting increased USF1 occupancy on a genome-wide basis. We propose that USF1 is an important modulator of molecular and behavioral circadian rhythms in mammals. DOI:http://dx.doi.org/10.7554/eLife.00426.001. PMID:23580255

Shimomura, Kazuhiro; Kumar, Vivek; Koike, Nobuya; Kim, Tae-Kyung; Chong, Jason; Buhr, Ethan D; Whiteley, Andrew R; Low, Sharon S; Omura, Chiaki; Fenner, Deborah; Owens, Joseph R; Richards, Marc; Yoo, Seung-Hee; Hong, Hee-Kyung; Vitaterna, Martha H; Bass, Joseph; Pletcher, Mathew T; Wiltshire, Tim; Hogenesch, John; Lowrey, Phillip L; Takahashi, Joseph S

2013-04-09

38

Expression and Rhythmic Modulation of Circulating MicroRNAs Targeting the Clock Gene Bmal1 in Mice  

Microsoft Academic Search

MicroRNAs (miRNAs) interact with 3? untranslated region (UTR) elements of target genes to regulate mRNA stability or translation and thus play a role in regulating many different biological processes, including circadian rhythms. However, specific miRNAs mediating the regulation of essential clock genes remain largely unknown. Because vesicles containing membrane-bound miRNAs are present in the circulatory system, we examined miRNAs predicted

Vikram R. Shende; Marianna M. Goldrick; Suchitra Ramani; David J. Earnest

2011-01-01

39

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

Microsoft Academic Search

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

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

2012-01-01

40

Diurnal expression of Dnmt3b mRNA in mouse liver is regulated by feeding and hepatic clockwork  

PubMed Central

DNA methyltransferase 3B (DNMT3B) is critically involved in de novo DNA methylation and genomic stability, while the regulatory mechanism in liver is largely unknown. We previously reported that diurnal variation occurs in the mRNA expression of Dnmt3b in adult mouse liver. The aim of this study was to determine the mechanism underlying the diurnal expression pattern. The highest level and the lowest level of Dnmt3b mRNA expression were confirmed to occur at dawn and in the afternoon, respectively, and the expression pattern of Dnmt3b closely coincided with that of Bmal1. Since the diurnal pattern of Dnmt3b mRNA expression developed at weaning and scheduled feeding to separate the feeding cycle from the light/dark cycle led to a phase-shift in the expression, it could be assumed that feeding plays a critical role as an entrainment signal. In liver-specific Bmal1 knockout (L-Bmal1 KO) mice, L-Bmal1 deficiency resulted in significantly higher levels of Dnmt3b at all measured time points, and the time when the expression was the lowest in wild-type mice was shifted to earlier. Investigation of global DNA methylation revealed a temporal decrease of 5-methyl-cytosine percentage in the genome of wild-type mice in late afternoon. By contrast, no such decrease in 5-methyl-cytosine percentage was detected in L-Bmal1 KO mice, suggesting that altered Dnmt3b expression affects the DNA methylation state. Taken together, the results suggest that the feeding and hepatic clockwork generated by the clock genes, including Bmal1, regulate the diurnal variation in Dnmt3b mRNA expression and the consequent dynamic changes in global DNA methylation.

Maekawa, Fumihiko; Shimba, Shigeki; Takumi, Shota; Sano, Tomoharu; Suzuki, Takehiro; Bao, Jinhua; Ohwada, Mika; Ehara, Tatsuya; Ogawa, Yoshihiro; Nohara, Keiko

2012-01-01

41

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

PubMed Central

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.

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

42

Identification of an estrogen-regulated circadian mechanism necessary for breast acinar morphogenesis  

PubMed Central

Altered estrogen receptor ? (ERA) signaling and altered circadian rhythms are both features of breast cancer. By using a method to entrain circadian oscillations in human cultured cells, we recently reported that the expression of key clock genes oscillates in a circadian fashion in ERA-positive breast epithelial cells but not in breast cancer cells, regardless of their ERA status. Moreover, we reported that ERA mRNA oscillates in a circadian fashion in ERA-positive breast epithelial cells, but not in ERA-positive breast cancer cells. By using ERA-positive HME1 breast epithelial cells, which can be both entrained in vitro and can form mammary gland-like acinar structures in three-dimensional (3D) culture, first we identified a circuit encompassing ERA and an estrogen-regulated loop consisting of two circadian clock genes, PER2 and BMAL1. Further, we demonstrated that this estrogen-regulated circuit is necessary for breast epithelial acinar morphogenesis. Disruption of this circuit due to ERA-knockdown, negatively affects the estrogen-sustained circadian PER2-BMAL1 mechanism as well as the formation of 3D HME1 acini. Conversely, knockdown of either PER2 or BMAL1, by hampering the PER2-BMAL1 loop of the circadian clock, negatively affects ERA circadian oscillations and 3D breast acinar morphogenesis. To our knowledge, this study provides the first evidence of the implication of an ERA-circadian clock mechanism in the breast acinar morphogenetic process.

Rossetti, Stefano; Corlazzoli, Francesca; Gregorski, Alex; Azmi, Nurul Hidayah A.; Sacchi, Nicoletta

2012-01-01

43

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

PubMed

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

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

2013-07-03

44

TGF-? Inducible Early Gene 1 Regulates Osteoclast Differentiation and Survival by Mediating the NFATc1, AKT, and MEK/ERK Signaling Pathways  

PubMed Central

TGF-? Inducible Early Gene-1 (TIEG1) is a Krüppel-like transcription factor (KLF10) that was originally cloned from human osteoblasts as an early response gene to TGF-? treatment. As reported previously, TIEG1?/? mice have decreased cortical bone thickness and vertebral bone volume and have increased spacing between the trabeculae in the femoral head relative to wildtype controls. Here, we have investigated the role of TIEG1 in osteoclasts to further determine their potential role in mediating this phenotype. We have found that TIEG1?/? osteoclast precursors differentiated more slowly compared to wildtype precursors in vitro and high RANKL doses are able to overcome this defect. We also discovered that TIEG1?/? precursors exhibit defective RANKL-induced phosphorylation and accumulation of NFATc1 and the NFATc1 target gene DC-STAMP. Higher RANKL concentrations reversed defective NFATc1 signaling and restored differentiation. After differentiation, wildtype osteoclasts underwent apoptosis more quickly than TIEG1?/? osteoclasts. We observed increased AKT and MEK/ERK signaling pathway activation in TIEG1?/? osteoclasts, consistent with the roles of these kinases in promoting osteoclast survival. Adenoviral delivery of TIEG1 (AdTIEG1) to TIEG1?/? cells reversed the RANKL-induced NFATc1 signaling defect in TIEG1?/? precursors and eliminated the differentiation and apoptosis defects. Suppression of TIEG1 with siRNA in wildtype cells reduced differentiation and NFATc1 activation. Together, these data provide evidence that TIEG1 controls osteoclast differentiation by reducing NFATc1 pathway activation and reduces osteoclast survival by suppressing AKT and MEK/ERK signaling.

Cicek, Muzaffer; Vrabel, Anne; Sturchio, Catherine; Pederson, Larry; Hawse, John R.; Subramaniam, Malayannan; Spelsberg, Thomas C.; Oursler, Merry Jo

2011-01-01

45

Liver X receptors (LXR? and LXR?) are potent regulators for hepatic Dec1 expression  

Microsoft Academic Search

DEC1 (BHLHB2\\/Stra13\\/Sharp2)—a basic helix-loop-helix transcription factor—is known to be involved in various biological phenomena including clock systems and metabolism. In the clock systems, Dec1 expression is dominantly up-regulated by CLOCK : BMAL1 heterodimer, and it exhibits circadian rhythm in the suprachiasmatic nucleus (SCN)—the central circadian pacemaker— and other peripheral tissues. Recent studies have shown that the strong circadian rhythmicity of

Mitsuhide Noshiro; Emiko Usui; Takeshi Kawamoto; Fuyuki Sato; Ayumu Nakashima; Taichi Ueshima; Kiyomasa Honda; Katsumi Fujimoto; Sato Honma; Ken-ichi Honma; Makoto Makishima; Yukio Kato

2009-01-01

46

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

PubMed

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

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

2013-03-21

47

p75 neurotrophin receptor is a clock gene that regulates oscillatory components of circadian and metabolic networks.  

PubMed

The p75 neurotrophin receptor (p75(NTR)) 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 p75(NTR) transcription in the nervous system and its expression in other tissues remain largely unknown. Here we show that p75(NTR) is an oscillating gene regulated by the helix-loop-helix transcription factors CLOCK and BMAL1. The p75(NTR) promoter contains evolutionarily conserved noncanonical E-box enhancers. Deletion mutagenesis of the p75(NTR)-luciferase reporter identified the -1039 conserved E-box necessary for the regulation of p75(NTR) by CLOCK and BMAL1. Accordingly, gel-shift assays confirmed the binding of CLOCK and BMAL1 to the p75(NTR-)1039 E-box. Studies in mice revealed that p75(NTR) transcription oscillates during dark and light cycles not only in the suprachiasmatic nucleus (SCN), but also in peripheral tissues including the liver. Oscillation of p75(NTR) 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, p75(NTR) is required for circadian clock oscillation, since loss of p75(NTR) alters the circadian oscillation of clock genes in the SCN, liver, and fibroblasts. Consistent with this, Per2::Luc/p75(NTR-/-) liver explants showed reduced circadian oscillation amplitude compared with those of Per2::Luc/p75(NTR+/+). Moreover, deletion of p75(NTR) also alters the circadian oscillation of glucose and lipid homeostasis genes. Overall, our findings reveal that the transcriptional activation of p75(NTR) 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

Baeza-Raja, Bernat; Eckel-Mahan, Kristin; Zhang, Luoying; Vagena, Eirini; Tsigelny, Igor F; Sassone-Corsi, Paolo; Ptácek, Louis J; Akassoglou, Katerina

2013-06-19

48

ROR? directly regulates the circadian expression of clock genes and downstream targets in vivo  

PubMed Central

In this study, we demonstrate that the lack of retinoic acid-related orphan receptor (ROR) ? or ? expression in mice significantly reduced the peak expression level of Cry1, Bmal1, E4bp4, Rev-Erb? and Per2 in an ROR isotype- and tissue-selective manner without affecting the phase of their rhythmic expression. Analysis of ROR?/ROR? double knockout mice indicated that in certain tissues ROR? and ROR? exhibited a certain degree of redundancy in regulating clock gene expression. Reporter gene analysis showed that ROR? was able to induce reporter gene activity through the RORE-containing regulatory regions of Cry1, Bmal1, Rev-Erb? and E4bp4. Co-expression of Rev-Erb? or addition of a novel ROR antagonist repressed this activation. ChIP-Seq and ChIP–Quantitative real-time polymerase chain reaction (QPCR) analysis demonstrated that in vivo ROR? regulate these genes directly and in a Zeitgeber time (ZT)-dependent manner through these ROREs. This transcriptional activation by RORs was associated with changes in histone acetylation and chromatin accessibility. The rhythmic expression of ROR?1 by clock proteins may lead to the rhythmic expression of ROR?1 target genes. The presence of ROR? binding sites and its down-regulation in ROR??/? liver suggest that the rhythmic expression of Avpr1a depends on ROR? consistent with the concept that ROR?1 provides a link between the clock machinery and its regulation of metabolic genes.

Takeda, Yukimasa; Jothi, Raja; Birault, Veronique; Jetten, Anton M.

2012-01-01

49

Circadian Clock Genes Contribute to the Regulation of Hair Follicle Cycling  

PubMed Central

Hair follicles undergo recurrent cycling of controlled growth (anagen), regression (catagen), and relative quiescence (telogen) with a defined periodicity. Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK–regulated genes are also modulated in phase with the hair growth cycle. During telogen and early anagen, circadian clock genes are prominently expressed in the secondary hair germ, which contains precursor cells for the growing follicle. Analysis of Clock and Bmal1 mutant mice reveals a delay in anagen progression, and the secondary hair germ cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock genes regulate anagen progression via their effect on the cell cycle. Consistent with a block at the G1 phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadian clock mechanisms have been implicated in a variety of diurnal biological processes, our findings indicate that circadian clock genes may be utilized to modulate the progression of non-diurnal cyclic processes.

Lin, Kevin K.; Kumar, Vivek; Geyfman, Mikhail; Chudova, Darya; Ihler, Alexander T.; Smyth, Padhraic; Paus, Ralf; Takahashi, Joseph S.; Andersen, Bogi

2009-01-01

50

An essential role for the circadian-regulated gene Nocturnin in osteogenesis: the importance of local timekeeping in skeletal homeostasis  

PubMed Central

The role of circadian proteins in regulating whole body metabolism and bone turnover has been studied in detail and has led to the discovery of an elemental system for timekeeping involving the core genes Clock, Bmal1, Per, and Cry. Nocturnin, a peripheral circadian-regulated gene has been shown to play a very important role in regulating adipogenesis by deadenylation of key mRNAs and intra-cytoplasmic transport of PPAR?. The role that it plays in osteogenesis has previously not been studied in detail. In this report we examined in vitro and in vivo osteogenesis in the presence and absence of Nocturnin and show that loss of Nocturnin enhances bone formation and can rescue Rosiglitazone induced bone loss in mice. The circadian rhythm of Nocturnin is likely to be an essential element of marrow stromal cell fate.

Guntur, Anyonya R.; Kawai, Masanobu; Le, Phuong; Bouxsein, Mary L.; Bornstein, Sheila; Green, Carla B.; Rosen, Clifford J.

2012-01-01

51

An essential role for the circadian-regulated gene nocturnin in osteogenesis: the importance of local timekeeping in skeletal homeostasis.  

PubMed

The role of circadian proteins in regulating whole-body metabolism and bone turnover has been studied in detail and has led to the discovery of an elemental system for timekeeping involving the core genes Clock, Bmal1, Per, and Cry. Nocturnin?(Noc; Ccrn4l), a peripheral circadian-regulated gene has been shown to play a very important role in regulating adipogenesis by deadenylation of key mRNAs and intracytoplasmic transport of PPAR?. The role that it plays in osteogenesis has previously not been studied in detail. In this report we examined in vitro and in vivo osteogenesis in the presence and absence of Noc and show that loss of Noc enhances bone formation and can rescue rosiglitazone-induced bone loss in mice. The circadian rhythm of Noc is likely to be an essential element of marrow stromal cell fate. PMID:22082366

Guntur, Anyonya R; Kawai, Masanobu; Le, Phuong; Bouxsein, Mary L; Bornstein, Sheila; Green, Carla B; Rosen, Clifford J

2011-11-01

52

The Orphan Nuclear Receptor REV-ERB? Controls Circadian Transcription within the Positive Limb of the Mammalian Circadian Oscillator  

Microsoft Academic Search

Mammalian circadian rhythms are generated by a feedback loop in which BMAL1 and CLOCK, players of the positive limb, activate transcription of the cryptochrome and period genes, components of the negative limb. Bmal1 and Per transcription cycles display nearly opposite phases and are thus governed by different mechanisms. Here, we identify the orphan nuclear receptor REV-ERB? as the major regulator

Nicolas Preitner; Francesca Damiola; Luis-Lopez-Molina; Joszef Zakany; Denis Duboule; Urs Albrecht; Ueli Schibler

2002-01-01

53

Photoperiod regulates clock gene rhythms in the ovine liver.  

PubMed

To investigate the photoperiodic entrainment of peripheral rhythms in ruminants, we studied the expression of clock genes in the liver in the highly seasonal Soay sheep. Animals were kept under long (LD 16:8) or short photoperiod (LD 8:16). Daily rhythms in locomotor activity were recorded, and blood concentrations of melatonin and cortisol were measured by RIA. Per2, Bmal1, and Cry1 gene expression was determined by Northern blot analyses using ovine RNA probes in liver collected every 4h for 24h. Liver Per2 and Bmal1, but not Cry1, expression was rhythmic in all treatments. Under long days, peak Per2 expression occurred at end of the night with a similar timing to Bmal1, whereas, under short days the Per2 maximum was in the early night with an inverse pattern to Bmal1. There was a photoperiodxtime interaction for only Per2 (P < 0.001). The 24-h pattern in plasma cortisol matched the observed phasing of Per2 expression, suggesting that it may act as an endocrine entraining factor. The clock gene rhythms in the peripheral tissues were different in timing compared with the ovine suprachiasmatic nucleus (SCN, central pacemaker) and pars tuberalis (melatonin target tissue), and the hepatic rhythms were of lower amplitude compared with photoperiodic rodents. Thus, there are likely to be important species differences in the way the central and peripheral clockwork encodes external photoperiod. PMID:15935162

Andersson, Håkan; Johnston, Jonathan D; Messager, Sophie; Hazlerigg, David; Lincoln, Gerald

2005-03-17

54

Regulation of Clock-Controlled Genes in Mammals  

PubMed Central

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.

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

2009-01-01

55

Inducible cAMP early repressor regulates the Period 1 gene of the hepatic and adrenal clocks.  

PubMed

Light, restricted feeding, and hormonal inputs may operate as time givers (zeitgebers) for the circadian clock within peripheral organs through the activation of tissue-specific signaling cascades. cAMP signaling through CREM (cAMP-responsive element modulator) and its variant ICER (inducible cAMP early repressor) is linked to the circadian regulation of pineal melatonin synthesis, although little is known about its influence in other organs. We performed experiments in the absence of light and feeding-time cues to test which core clock genes are controlled by CREM/ICER in the liver and adrenal gland. In vivo, Crem loss-of-function mutation resulted in fine-tuning of all measured adrenal clock genes (Per1/2/3, Cry1/2, Bmal1, and Rev-erb?), whereas only Per1 and Cry1 were affected in the liver. Icer expression was circadian in the adrenal gland, with peak gene expression at zeitgeber 12 and the highest protein levels at zeitgeber ?20. The expression of both Icer and Per1 genes responded to cAMP stimuli in an immediate-early fashion. In immortal cells, forskolin induced expression of Per1 after 2 h, and de novo protein synthesis led to Per1 attenuation. We show that the de novo synthesized protein responsible for Per1 attenuation is ICER. Indeed, Per1 expression is up-regulated in cells ectopically expressing antisense Icer, and mobility shift experiments identified ICER binding to cAMP-responsive elements of the Per1 promoter. We propose that ICER acts as a noise filter for different signals that could affect transcription in the adrenal gland. Because ICER is an immediate-early repressor, the circadian nature of adrenal Icer expression could serve a role in a time-dependent gating mechanism. PMID:23443664

Zmrzljak, Uršula Prosenc; Koren?i?, Anja; Košir, Rok; Goli?nik, Marko; Sassone-Corsi, Paolo; Rozman, Damjana

2013-02-25

56

Modeling an Evolutionary Conserved Circadian Cis-Element  

PubMed Central

Circadian oscillator networks rely on a transcriptional activator called CLOCK/CYCLE (CLK/CYC) in insects and CLOCK/BMAL1 or NPAS2/BMAL1 in mammals. Identifying the targets of this heterodimeric basic-helix-loop-helix (bHLH) transcription factor poses challenges and it has been difficult to decipher its specific sequence affinity beyond a canonical E-box motif, except perhaps for some flanking bases contributing weakly to the binding energy. Thus, no good computational model presently exists for predicting CLK/CYC, CLOCK/BMAL1, or NPAS2/BMAL1 targets. Here, we use a comparative genomics approach and first study the conservation properties of the best-known circadian enhancer: a 69-bp element upstream of the Drosophila melanogaster period gene. This fragment shows a signal involving the presence of two closely spaced E-box–like motifs, a configuration that we can also detect in the other four prominent CLK/CYC target genes in flies: timeless, vrille, Pdp1, and cwo. This allows for the training of a probabilistic sequence model that we test using functional genomics datasets. We find that the predicted sequences are overrepresented in promoters of genes induced in a recent study by a glucocorticoid receptor-CLK fusion protein. We then scanned the mouse genome with the fly model and found that many known CLOCK/BMAL1 targets harbor sequences matching our consensus. Moreover, the phase of predicted cyclers in liver agreed with known CLOCK/BMAL1 regulation. Taken together, we built a predictive model for CLK/CYC or CLOCK/BMAL1-bound cis-enhancers through the integration of comparative and functional genomics data. Finally, a deeper phylogenetic analysis reveals that the link between the CLOCK/BMAL1 complex and the circadian cis-element dates back to before insects and vertebrates diverged.

Paquet, Eric R; Rey, Guillaume; Naef, Felix

2008-01-01

57

Thyroid transcription factor 1, a homeodomain containing transcription factor, contributes to regulating periodic oscillations in GnRH gene expression.  

PubMed

Thyroid transcription factor 1 (TTF1), a member of the Nkx family of transcription factors required for basal forebrain morphogenesis, functions in the postnatal hypothalamus as a transcriptional regulator of genes encoding neuromodulators and hypophysiotrophic peptides. One of these peptides is gonadotrophin-releasing hormone (GnRH). In the present study, we show that Ttf1 mRNA abundance varies in a diurnal and melatonin-dependent fashion in the preoptic area of the rat, with maximal Ttf1 expression attained during the dark phase of the light/dark cycle, preceding the nocturnal peak in GnRH mRNA content. GnRH promoter activity oscillates in a circadian manner in GT1-7 cells, and this pattern is enhanced by TTF1 and blunted by small interfering RNA-mediated Ttf1 gene silencing. TTF1 transactivates GnRH transcription by binding to two sites in the GnRH promoter. Rat GnRH neurones in situ contain key proteins components of the positive (BMAL1, CLOCK) and negative (PER1) limbs of the circadian oscillator, and these proteins repress Ttf1 promoter activity in vitro. By contrast, Ttf1 transcription is activated by CRY1, a clock component required for circadian rhythmicity. In turn, TTF1 represses transcription of Rev-erb?, a heme receptor that controls circadian transcription within the positive limb of the circadian oscillator. These findings suggest that TTF1 is a component of the molecular machinery controlling circadian oscillations in GnRH gene transcription. PMID:22356123

Matagne, V; Kim, J G; Ryu, B J; Hur, M K; Kim, M S; Kim, K; Park, B S; Damante, G; Smiley, G; Lee, B J; Ojeda, S R

2012-06-01

58

Expression and functional analyses of circadian genes in mouse oocytes and preimplantation embryos: Cry1 is involved in the meiotic process independently of circadian clock regulation.  

PubMed

In mammals, circadian genes, Clock, Arntl (also known as Bmal1), Cry1, Cry2, Per1, Per2, and Per3, are rhythmically transcribed every 24 h in almost all organs and tissues to tick the circadian clock. However, their expression and function in oocytes and preimplantation embryos have not been investigated. In this study we found that the circadian clock may stop in mouse oocytes and preimplantation embryos. Real-time PCR analysis revealed the presence of transcripts of these genes in both oocytes and preimplantation embryos; however, their amounts did not oscillate every 24 h in one- to four-cell and blastocyst-stage embryos. Moreover, immunofluorescence analyses revealed that CLOCK, ARNTL, and CRY1 were localized similarly in the nuclei of germinal vesicle (GV) oocytes and one-cell- to four-cell-stage embryos. Because CRY1 is known to interact with the CLOCK-ARNTL complex to suppress transcription-promoting activity of the complex for genes such as Wee1, Cry2, Per1, Per2, and Per3 in cells having the ticking circadian clock, we hypothesized that if the circadian clock functions in GV oocytes and one-cell- to four-cell-stage embryos, CLOCK, ARNTL, and CRY1 might suppress the transcription of these genes in GV oocytes and one-cell- to 4-cell-stage embryos as well. As a result, knockdown of CRY1 in GV oocytes by RNA interference did not affect the transcription levels of Wee1, Cry2, Per1, Per2, and Per3, but it reduced maturation ability. Thus, it seems that circadian genes are not involved in circadian clock regulation in mouse oocytes and preimplantation embryos but are involved in physiologies, such as meiosis. PMID:19020302

Amano, Tomoko; Matsushita, Akinori; Hatanaka, Yuki; Watanabe, Tatsuya; Oishi, Katsutaka; Ishida, Norio; Anzai, Masayuki; Mitani, Tasuku; Kato, Hiromi; Kishigami, Satoshi; Saeki, Kazuhiro; Hosoi, Yoshihiko; Iritani, Akira; Matsumoto, Kazuya

2008-11-19

59

INSURANCE REGULATION  

Microsoft Academic Search

This chapter summarizes the economic understanding of insurance regulation with a focus on solvency regulation, underwriting regulation, contract regulation and competition law exemptions. Insurance industry solvency regulation is viewed as a solution to a collective action problem that might otherwise induce insurers to take excessive risk. The chapter analyzes the economics of regulations addressing adverse selection, including traditional doctrines of

Seth J. Chandler

60

Roles of CLOCK Phosphorylation in Suppression of E-Box-Dependent Transcription?  

PubMed Central

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?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.

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

2009-01-01

61

Clock genes influence gene expression in growth plate and endochondral ossification in mice.  

PubMed

We have previously shown transient promotion by parathyroid hormone of Period-1 (Per1) expression in cultured chondrocytes. Here we show the modulation by clock genes of chondrogenic differentiation through gene transactivation of the master regulator of chondrogenesis Indian hedgehog (IHH) in chondrocytes of the growth plate. Several clock genes were expressed with oscillatory rhythmicity in cultured chondrocytes and rib growth plate in mice, whereas chondrogenesis was markedly inhibited in stable transfectants of Per1 in chondrocytic ATDC5 cells and in rib growth plate chondrocytes from mice deficient of brain and muscle aryl hydrocarbon receptor nuclear translocator-like (BMAL1). Ihh promoter activity was regulated by different clock gene products, with clear circadian rhythmicity in expression profiles of Ihh in the growth plate. In BMAL1-null mice, a predominant decrease was seen in Ihh expression in the growth plate with a smaller body size than in wild-type mice. BMAL1 deficit led to disruption of the rhythmic expression profiles of both Per1 and Ihh in the growth plate. A clear rhythmicity was seen with Ihh expression in ATDC5 cells exposed to dexamethasone. In young mice defective of BMAL1 exclusively in chondrocytes, similar abnormalities were found in bone growth and Ihh expression. These results suggest that endochondral ossification is under the regulation of particular clock gene products expressed in chondrocytes during postnatal skeletogenesis through a mechanism relevant to the rhythmic Ihh expression. PMID:22936800

Takarada, Takeshi; Kodama, Ayumi; Hotta, Shogo; Mieda, Michihiro; Shimba, Shigeki; Hinoi, Eiichi; Yoneda, Yukio

2012-08-30

62

Clock Genes Influence Gene Expression in Growth Plate and Endochondral Ossification in Mice*  

PubMed Central

We have previously shown transient promotion by parathyroid hormone of Period-1 (Per1) expression in cultured chondrocytes. Here we show the modulation by clock genes of chondrogenic differentiation through gene transactivation of the master regulator of chondrogenesis Indian hedgehog (IHH) in chondrocytes of the growth plate. Several clock genes were expressed with oscillatory rhythmicity in cultured chondrocytes and rib growth plate in mice, whereas chondrogenesis was markedly inhibited in stable transfectants of Per1 in chondrocytic ATDC5 cells and in rib growth plate chondrocytes from mice deficient of brain and muscle aryl hydrocarbon receptor nuclear translocator-like (BMAL1). Ihh promoter activity was regulated by different clock gene products, with clear circadian rhythmicity in expression profiles of Ihh in the growth plate. In BMAL1-null mice, a predominant decrease was seen in Ihh expression in the growth plate with a smaller body size than in wild-type mice. BMAL1 deficit led to disruption of the rhythmic expression profiles of both Per1 and Ihh in the growth plate. A clear rhythmicity was seen with Ihh expression in ATDC5 cells exposed to dexamethasone. In young mice defective of BMAL1 exclusively in chondrocytes, similar abnormalities were found in bone growth and Ihh expression. These results suggest that endochondral ossification is under the regulation of particular clock gene products expressed in chondrocytes during postnatal skeletogenesis through a mechanism relevant to the rhythmic Ihh expression.

Takarada, Takeshi; Kodama, Ayumi; Hotta, Shogo; Mieda, Michihiro; Shimba, Shigeki; Hinoi, Eiichi; Yoneda, Yukio

2012-01-01

63

Regulating danger  

SciTech Connect

This book contains the following chapters: The Industrial Setting; Work in the Hand-Mining and Early Machines Era; Early Coal-Mining Legislation in the Rocky Mountain West; Safety and Regulation, 1884-1912; Legislation in the Progressive Era; Death and Rebellion, 1913-1933; Industry and Regulation, 1913-1933; Safety and Regulation in Depression and War; and Regulation since World War II: The Federal Takeover.

Whiteside, J.

1990-01-01

64

Regulating Contracts  

Microsoft Academic Search

Using an interdisciplinary approach involving economics, sociology and law, Regulating Contracts explores fundamental questions about the purposes and effects of legal regulation of contractual relationships. What kind of social relation do contracts create, or, more precisely, how do contracts govern social interaction. How are contractual relations, or more generally, markets constructed? Does the law play a significant role in particular

Hugh Collins

65

Preschool Regulations.  

ERIC Educational Resources Information Center

|Published by the Department of Health and Human Services, as required by Nebraska law, this guide details regulations for the physical well-being, safety, and protection of children and defines the minimum levels of acceptable services to be provided in Nebraska preschools. The first section of the guide lists specific preschool regulations,…

Nebraska State Dept. of Health and Human Services, Lincoln.

66

Circadian clock, cancer and lipid metabolism  

Microsoft Academic Search

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

Norio Ishida

2007-01-01

67

Regulator valve  

US Patent & Trademark Office Database

A regulator valve is structured such that hydraulic pressure to be output from a regulated pressure output port is regulated according to urging forces, i.e., line pressure to be regulated, throttle pressure, spring force from a compression coil spring, and operating force from a plunger, which are applied to a valve spool. The plunger has a small diameter portion and a large diameter portion having a diameter larger than the diameter of the small diameter portion, both of which are axially displaceably retained in a spring receiving sleeve. The small diameter portion is urged in one axial direction at one end of the plunger that protrudes into a spring chamber and faces the valve spool, while the large diameter portion is urged in the other axial direction by range pressure at the other end of the plunger which is isolated from the small diameter portion located in the spring chamber.

2012-12-11

68

Comparative genomic analysis of teleost fish bmal genes  

Microsoft Academic Search

Bmal1 (Brain and muscle ARNT\\u000a like 1) gene is a key circadian clock gene. Tetrapods also have the second Bmal gene, Bmal2. Fruit fly has only one bmal1\\/cycle gene. Interrogation of the five teleost fish genome sequences coupled with phylogenetic and splice site analyses found that\\u000a zebrafish have two bmal1 genes, bmal1a and bmal1b, and bmal2a; Japanese pufferfish (fugu), green

Han Wang

2009-01-01

69

Mop3 Is an Essential Component of the Master Circadian Pacemaker in Mammals  

Microsoft Academic Search

Circadian oscillations in mammalian physiology and behavior are regulated by an endogenous biological clock. Here we show that loss of the PAS protein MOP3 (also known as BMAL1) in mice results in immediate and complete loss of circadian rhythmicity in constant darkness. Additionally, locomotor activity in light–dark (LD) cycles is impaired and activity levels are reduced in Mop3?\\/? mice. Analysis

Maureen K. Bunger; Lisa D. Wilsbacher; Susan M. Moran; Cynthia Clendenin; Laurel A. Radcliffe; John B. Hogenesch; M. Celeste Simon; Joseph S. Takahashi; Christopher A. Bradfield

2000-01-01

70

A non-canonical E-box within the MyoD core enhancer is necessary for circadian expression in skeletal muscle.  

PubMed

The myogenic differentiation 1 (MyoD) gene is a master regulator of myogenesis. We previously reported that the expression of MyoD mRNA oscillates over 24?h in skeletal muscle and that the circadian clock transcription factors, BMAL1 (brain and muscle ARNT-like 1) and CLOCK (circadian locomotor output cycles kaput), were bound to the core enhancer (CE) of the MyoD gene in vivo. In this study, we provide in vivo and in vitro evidence that the CE is necessary for circadian expression of MyoD in adult muscle. Gel shift assays identified a conserved non-canonical E-box within the CE that is bound by CLOCK and BMAL1. Functional analysis revealed that this E-box was required for full activation by BMAL1/CLOCK and for in vitro circadian oscillation. Expression profiling of muscle of CE(loxP/loxP) mice found approximately 1300 genes mis-expressed relative to wild-type. Based on the informatics results, we analyzed the respiratory function of mitochondria isolated from wild-type and CE(loxP/loxP) mice. These assays determined that State 5 respiration was significantly reduced in CE(loxP/loxP) muscle. The results of this work identify a novel element in the MyoD enhancer that confers circadian regulation to MyoD in skeletal muscle and suggest that loss of circadian regulation leads to changes in myogenic expression and downstream mitochondrial function. PMID:22210883

Zhang, Xiping; Patel, Samir P; McCarthy, John J; Rabchevsky, Alexander G; Goldhamer, David J; Esser, Karyn A

2011-12-30

71

A non-canonical E-box within the MyoD core enhancer is necessary for circadian expression in skeletal muscle  

PubMed Central

The myogenic differentiation 1 (MyoD) gene is a master regulator of myogenesis. We previously reported that the expression of MyoD mRNA oscillates over 24?h in skeletal muscle and that the circadian clock transcription factors, BMAL1 (brain and muscle ARNT-like 1) and CLOCK (circadian locomotor output cycles kaput), were bound to the core enhancer (CE) of the MyoD gene in vivo. In this study, we provide in vivo and in vitro evidence that the CE is necessary for circadian expression of MyoD in adult muscle. Gel shift assays identified a conserved non-canonical E-box within the CE that is bound by CLOCK and BMAL1. Functional analysis revealed that this E-box was required for full activation by BMAL1/CLOCK and for in vitro circadian oscillation. Expression profiling of muscle of CEloxP/loxP mice found approximately 1300 genes mis-expressed relative to wild-type. Based on the informatics results, we analyzed the respiratory function of mitochondria isolated from wild-type and CEloxP/loxP mice. These assays determined that State 5 respiration was significantly reduced in CEloxP/loxP muscle. The results of this work identify a novel element in the MyoD enhancer that confers circadian regulation to MyoD in skeletal muscle and suggest that loss of circadian regulation leads to changes in myogenic expression and downstream mitochondrial function.

Zhang, Xiping; Patel, Samir P.; McCarthy, John J.; Rabchevsky, Alexander G.; Goldhamer, David J.; Esser, Karyn A.

2012-01-01

72

Profiling of circadian genes expressed in the uterus endometrial stromal cells of pregnant rats as revealed by DNA microarray coupled with RNA interference.  

PubMed

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

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

2013-07-08

73

SIRTUIN 1: Regulating the regulator  

Microsoft Academic Search

Earlier analyses on the sirtuin family of histone deacetylases and its well-known member SIRT1 had their primary focus mostly on the identification of cellular targets exploring molecular mechanisms and functional networks in the control of metabolic homeostasis, differentiation, apoptosis and cell survival. However, only little is known about the regulation of SIRT1 itself, so far. Presently, SIRT1 is gaining increasing

Barbara Zschoernig; Ulrich Mahlknecht

2008-01-01

74

Episodes of prolactin gene expression in GH3 cells are dependent on selective promoter binding of multiple circadian elements.  

PubMed

Prolactin (PRL) gene expression in mammotropes occurs in pulses, but the mechanism(s) underlying this dynamic process remains obscure. Recent findings from our laboratory of an E-box in the rat PRL promoter (E-box133) that can interact with the circadian factors, circadian locomoter output cycles kaput (CLOCK) and brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (BMAL)-1, and was necessary for pulse activity raised the intriguing possibility that the circadian system may be central to this oscillatory process. In this study, we used serum-shocked GH(3) cells, established previously to synchronize PRL pulses between cells in culture, to reveal that pulses of PRL mRNA are linked temporally to the expression of bmal1, cry1, per1, and per3 mRNA in these cells. Moreover, we found that each of these circadian factors binds to the rat PRL promoter by chromatin immunoprecipitation analysis. Using EMSA analysis, we observed that two sites present in the proximal promoter region, E-box133 and E-box10, bind circadian factors differentially (E-box133 interacted with BMAL1, cryptochrome-1, period (PER)-1, and PER3 but not PER2 and E-box10 bound BMAL1, cryptochrome-1, PER2, PER3 but not PER1). More importantly, down-regulation of any factor binding E-box133 significantly reduced PRL mRNA levels during pulse periods. Our results demonstrate clearly that certain circadian elements binding to the E-box133 site are required for episodes of PRL mRNA expression in serum-shocked GH(3) cultures. Moreover, our findings of binding-related differences between functionally distinct E-boxes demonstrate not only that E-boxes can bind different components but suggest that the number and type of circadian elements that bind to an E-box is central in dictating its function. PMID:20215567

Bose, Sudeep; Boockfor, Fredric R

2010-03-09

75

Modulation of Clock Gene Expression by the Transcriptional Coregulator Receptor Interacting Protein 140 (RIP140)  

PubMed Central

Circadian rhythms are generated in central and peripheral tissues by an intracellular oscillating timing mechanism known as the circadian clock. Several lines of evidence show a strong and bidirectional interplay between metabolism and circadian rhythms. Receptor interacting protein 140 (RIP140) is a coregulator for nuclear receptors and other transcription factors that represses catabolic pathways in metabolic tissues. Although RIP140 functions as a corepressor for most nuclear receptors, mounting evidence points to RIP140 as a dual coregulator that can repress or activate different sets of genes. Here, we demonstrate that RIP140 mRNA and protein levels are under circadian regulation and identify RIP140 as a modulator of clock gene expression, suggesting that RIP140 can participate in a feedback mechanism affecting the circadian clock. We show that the absence of RIP140 disturbs the basal levels of BMAL1 and other clock genes, reducing the amplitude of their oscillations. In addition, we demonstrate that RIP140 is recruited to retinoid-related orphan receptor (ROR) binding sites on the BMAL1 promoter, directly interacts with ROR?, and increases transcription from the BMAL1 promoter in a ROR?-dependent manner. These results indicate that RIP140 is not only involved in metabolic control but also acts as a coactivator for ROR?, influencing clock gene expression.

Poliandri, Ariel H. B.; Gamsby, Joshua J.; Christian, Mark; Spinella, Michael J.; Loros, Jennifer J.; Dunlap, Jay C.; Parker, Malcolm G.

2011-01-01

76

Glucocorticoid-mediated Period2 induction delays the phase of circadian rhythm.  

PubMed

Glucocorticoid (GC) signaling synchronizes the circadian rhythm of individual peripheral cells and induces the expression of circadian genes, including Period1 (Per1) and Period2 (Per2). However, no GC response element (GRE) has been reported in the Per2 promoter region. Here we report the molecular mechanisms of Per2 induction by GC signaling and its relevance to the regulation of circadian timing. We found that GC prominently induced Per2 expression and delayed the circadian phase. The overlapping GRE and E-box (GE2) region in the proximal Per2 promoter was responsible for GC-mediated Per2 induction. The GRE in the Per2 promoter was unique in that brain and muscle ARNT-like protein-1 (BMAL1) was essential for GC-induced Per2 expression, whereas other GRE-containing promoters, such as Per1 and mouse mammary tumor virus, responded to dexamethasone in the absence of BMAL1. This specialized regulatory mechanism was mediated by BMAL1-dependent binding of the GC receptor to GRE in Per2 promoter. When Per2 induction was abrogated by the mutation of the GRE or E-box, the circadian oscillation phase failed to be delayed compared with that of the wild-type. Therefore, the current study demonstrates that the rapid Per2 induction mediated by GC is crucial for delaying the circadian rhythm. PMID:23620290

Cheon, Solmi; Park, Noheon; Cho, Sehyung; Kim, Kyungjin

2013-04-24

77

Glucocorticoid-mediated Period2 induction delays the phase of circadian rhythm  

PubMed Central

Glucocorticoid (GC) signaling synchronizes the circadian rhythm of individual peripheral cells and induces the expression of circadian genes, including Period1 (Per1) and Period2 (Per2). However, no GC response element (GRE) has been reported in the Per2 promoter region. Here we report the molecular mechanisms of Per2 induction by GC signaling and its relevance to the regulation of circadian timing. We found that GC prominently induced Per2 expression and delayed the circadian phase. The overlapping GRE and E-box (GE2) region in the proximal Per2 promoter was responsible for GC-mediated Per2 induction. The GRE in the Per2 promoter was unique in that brain and muscle ARNT-like protein-1 (BMAL1) was essential for GC-induced Per2 expression, whereas other GRE-containing promoters, such as Per1 and mouse mammary tumor virus, responded to dexamethasone in the absence of BMAL1. This specialized regulatory mechanism was mediated by BMAL1-dependent binding of the GC receptor to GRE in Per2 promoter. When Per2 induction was abrogated by the mutation of the GRE or E-box, the circadian oscillation phase failed to be delayed compared with that of the wild-type. Therefore, the current study demonstrates that the rapid Per2 induction mediated by GC is crucial for delaying the circadian rhythm.

Cheon, Solmi; Park, Noheon; Cho, Sehyung; Kim, Kyungjin

2013-01-01

78

Nuclear regulation  

SciTech Connect

The Nuclear Regulatory Commission routinely waives its background investigation requirements for new hires. NRC security staff estimate that 99 percent of new employees are hired before they receive a security clearance. They say waivers are used because the Office of Personnel and Management takes too long to conduct the required background investigations. NRC policies do not require reinvestigation of the background of nearly 50 percent of its clearance holders. Therefore, NRC does not know whether circumstances in some employees' lifestyle have changed, making them security risks. Also, NRC does not have accurate clearance information to effectively manage its program. For example, its computerized system does not have all the data needed to determine when reinvestigations should be requested. This report proposes that, to enhance security and improve the effectiveness of its clearance program NRC should require periodic reinvestigations for all employees, validate and update the security clearance database, and expedite a decision to issue either a policy statement or a regulation regarding access to commercial nuclear power plants.

Not Available

1989-01-01

79

Banking Regulation versus Securities Market Regulation  

Microsoft Academic Search

There is a long tradition of regulating banks and securities markets in many countries. The primary justification for bank regulation that is usually given is the avoidance of systemic risk, or in other words, the avoidance of financial crises. With securities markets it is usually argued the main purposes of regulation are investor protection and enhancing the efficiency of markets.

Franklin Allen; Richard Herring

2001-01-01

80

Alterations of circadian clockworks during differentiation and apoptosis of rat ovarian cells.  

PubMed

Ovarian development is related to cell proliferation, differentiation, and apoptosis of granulosa cells and luteal cells under the control of various modulators, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), and growth factors. In the present study, the expression of clock genes and the related regulation mechanism were analyzed in different ovarian cell types during differentiation and apoptosis. The authors focused on the circadian expression of Per2 as a core clock gene for the maintenance of circadian rhythms. By using a real-time monitoring system of the Per2 promoter activity, the circadian oscillation was analyzed in the granulosa and luteal cells from preantral follicles, antral follicles, and corpora lutea of immature Per2 promoter-destabilized luciferase transgenic rats that were primed with diethylstilbestrol, equine chorionic gonadotropin (eCG), and/or human CG. In addition, transcript levels of Per2, Bmal1, Clock, and Nampt were quantified by quantitative polymerase chain reaction (qPCR). Immunohistochemical studies revealed strong circadian rhythmicity of PER2 protein in the luteal cells, but apparently little rhythmicity in granulosa cells of both preantral and antral follicles. In vitro monitoring of promoter activity showed generation of several oscillations in luteal cells after exposure to dexamethasone (DXM), whereas oscillatory amplitudes of immature and mature granulosa cells were rapidly attenuating. The circadian rhythm of the Bmal1 transcript levels, but not the Per2 transcript, was very weak in the granulosa cells, as compared with that in luteal cells. Granulosa cells gained a strong circadian rhythm ability of the Per2 promoter activity after stimulation with FSH for 3 days. In contrast, LH had little effect on the circadian rhythm before stimulation of granulosa cells with FSH, probably owing to lack of LH receptor. In luteal cells, induction of apoptosis by inhibiting progesterone synthesis resulted in deregulation of Per2 circadian oscillation. Transcript levels of Bmal1 and Clock, but not Per2 and Nampt, were significantly decreased in apoptotic luteal cells. The Bmal1 transcript level was particularly reduced. Consequently, these results strongly suggest the circadian clockwork alters in ovarian cells during follicular development, luteinization, and apoptosis, and expression of Bmal1 may be related to the switch-on and switch-off of the circadian oscillation. PMID:21797776

Chu, Guiyan; Yoshida, Kaoru; Narahara, Sayoko; Uchikawa, Miho; Kawamura, Madoka; Yamauchi, Nobuhiko; Xi, Yongmei; Shigeyoshi, Yasufumi; Hashimoto, Seiichi; Hattori, Masa-Aki

2011-07-01

81

Regulating the Automobile.  

National Technical Information Service (NTIS)

Five analyses aimed at clarifying the nature of the American system of automotive regulation, its impact, and the reasons for its structure, are presented in this report. (1) A comparative analysis of safety, fuel economy, and emissions regulation yields ...

J. B. Heywood H. D. Jacoby L. H. Linden H. Margolis D. Iverach

1977-01-01

82

Proposed Regulation: Vinyl Chloride.  

National Technical Information Service (NTIS)

OSHA proposes to regulate producers of vinyl chloride, polyvinyl chloride, and articles made from these substances by requiring that their employees not be exposed to vinyl chloride above specified levels. The major impact of the regulation is expected to...

1974-01-01

83

The Regulation of Labor  

Microsoft Academic Search

We investigate the regulation of labor markets through employment, collective relations, and social security laws in 85 countries. We find that the political power of the left is associated with more stringent labor regulations and more generous social security systems, and that socialist, French, and Scandinavian legal origin countries have sharply higher levels of labor regulation than do common law

JUAN C. BOTERO; Simeon Djankov; RAFAEL LA PORTA; Florencio C. Lopez-De-Silanes; ANDREI SHLEIFER

2004-01-01

84

Pressure Sensitive Regulation Valve.  

National Technical Information Service (NTIS)

The patent application relates to a pressure sensitive regulating valve formed of a spring mounted within a conduit in which fluid flow is to be regulated. The fluid flow is regulated by the pressure responsive expansion and contraction of the axially def...

E. A. Gallo

1975-01-01

85

Load regulating expansion fixture  

DOEpatents

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.

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

1998-12-15

86

Load regulating expansion fixture  

DOEpatents

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.

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

1998-01-01

87

Altered feeding differentially regulates circadian rhythms and energy metabolism in liver and muscle of rats.  

PubMed

Energy metabolism follows a diurnal pattern responding to the light/dark cycle and food availability. This study investigated the impact of restricting feeding to the daylight hours and feeding a high fat diet on circadian clock (bmal1, dbp, tef and e4bp4) and metabolic (pepck, fas, ucp3, pdk4) gene expression and markers of energy metabolism in muscle and liver of rats. The results show that in chow-fed rats switched to daylight feeding, the peak diurnal expression of genes in liver was shifted by 6-12h while expression of these genes in muscle remained in a similar phase to rats feeding ad libitum. High fat feeding during the daylight hours had limited effect on clock gene expression in liver or muscle but shifted the peak expression of metabolic genes (pepck, fas) in liver by 6-12h. The differential effects of daylight feeding on gene and protein expression in muscle and liver were accompanied by an 8% reduction in whole body energy expenditure, a 20-30% increased glycogen content during the light phase in muscle of day-fed rats and increased adipose tissue deposition per gram food consumed. These data demonstrate that a mismatch of feeding and light/dark cycle disrupts tissue metabolism in muscle with significant consequences for whole body energy homeostasis. PMID:22952003

Reznick, Jane; Preston, Elaine; Wilks, Donna L; Beale, Susan M; Turner, Nigel; Cooney, Gregory J

2012-08-19

88

Cytokines and Sleep Regulation  

Microsoft Academic Search

\\u000a There is substantial evidence implicating the brain cytokine network in sleep regulation; this network seems to be intimately\\u000a involved in the regulation of daily physiological sleep as well as sleep responses to perturbations such as sleep loss and\\u000a infectious challenge. Two cytokines are extensively studied for their involvement in sleep regulation; they are tumor necrosis\\u000a factor ? (TNF?) and interleukin-1?

James M. Krueger; Lynn Churchill

89

Regulated Software Application (RSA)  

Center for Biologics Evaluation and Research (CBER)

... Regulated Software Application (RSA). Applicant: Community Blood Centers of South Florida. 510(k) number: BK110048. ... More results from www.fda.gov/biologicsbloodvaccines/bloodbloodproducts/approvedproducts

90

Plant Growth Regulation  

NSDL National Science Digital Library

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.

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.

91

Private Global Business Regulation  

Microsoft Academic Search

Abstract Regulations that govern,the social and environmental,impacts,of global firms and markets,without state enforcement,are a relatively new,dimension,of global business regulation. The growth,of such voluntary,“civil regulations” reflects both the expansion,of legiti- mate,authority in the global economy,outside the state and the in- creasing use of alternative regulatory instruments to govern firms, including self-regulation, market-based instruments, and soft laws. In response to global social

David Vogel

2008-01-01

92

Robust regulation with performance  

Microsoft Academic Search

We consider the problem of minimizing the 9~'2 norm of a feedback system subject to the constraint that the controller robustly regulate against constants and sinusoids. We show that, for any e > 0, there exists a controller that both achieves robust regulation and renders the closed-loop .,~2 norm within e of the optimal norm (the norm achievable without the

J. Abedor; K. Nagpal; K. Poolla

1994-01-01

93

Plant Growth Regulators.  

ERIC Educational Resources Information Center

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

Nickell, Louis G.

1978-01-01

94

The Regulation of Entry  

Microsoft Academic Search

We present new data on the regulation of entry of start-up firms in 85 countries. The data covers the number of procedures, official time, and official cost that a start-up must bear before it can operate legally. The official costs of entry are extremely high in most countries. Countries with heavier regulation of entry have higher corruption and larger unofficial

Simeon Djankov; Rafael La Porta; Florencio López-de-Silanes

2001-01-01

95

The Regulation of Entry  

Microsoft Academic Search

We present new data on the regulation of entry of start-up firms in 75 countries. The data set contains information on the number of procedures, official time, and official cost that a start-up must bear before it can operate legally. The official costs of entry are extremely high in most countries. Countries with heavier regulation of entry have higher corruption

Simeon Djankov; Rafael La Porta; Florencio Lopez-de-Silanes; Andrei Shleifer

2000-01-01

96

The Regulation Of Entry  

Microsoft Academic Search

We present new data on the regulation of entry of start-up firms in 85 countries. The data cover the number of procedures, official time, and official cost that a start-up must bear before it can operate legally. The official costs of entry are extremely high in most countries. Countries with heavier regulation of entry have higher corruption and larger unofficial

Simeon Djankov; Rafael La Porta; Florencio Lopez-De-Silanes; Andrei Shleifer

2002-01-01

97

Health practitioner regulation  

Microsoft Academic Search

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

IAN FRECKELTON

98

Regulating Controversial Land Uses  

Microsoft Academic Search

While the definition of what may constitute a controversial land use differs from community to community, the bottom line is that land use controls have been attempting to regulate these uses since the advent of zoning (and through nuisance law before that). When regulating many types of controversial land uses, constitutional issues may come into play and federal and state

Patricia E. Salkin

2011-01-01

99

Plant Growth Regulators.  

ERIC Educational Resources Information Center

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

Nickell, Louis G.

1978-01-01

100

Positive Autoregulation Delays the Expression Phase of Mammalian Clock Gene Per2  

PubMed Central

In mammals, cellular circadian rhythms are generated by a transcriptional-translational autoregulatory network that consists of clock genes that encode transcriptional regulators. Of these clock genes, Period1 (Per1) and Period2 (Per2) are essential for sustainable circadian rhythmicity and photic entrainment. Intriguingly, Per1 and Per2 mRNAs exhibit circadian oscillations with a 4-hour phase difference, but they are similarly transactivated by CLOCK-BMAL1. In this study, we investigated the mechanism underlying the phase difference between Per1 and Per2 through a combination of mathematical simulations and molecular experiments. Mathematical analyses of a model for the mammalian circadian oscillator demonstrated that the slow synthesis and fast degradation of mRNA tend to advance the oscillation phase of mRNA expression. However, the phase difference between Per1 and Per2 was not reproduced by the model, which implemented a 1.1-fold difference in degradation rates and a 3-fold difference in CLOCK-BMAL1 mediated inductions of Per1 and Per2 as estimated in cultured mammalian cells. Thus, we hypothesized the existence of a novel transcriptional activation of Per2 by PER1/2 such that the Per2 oscillation phase was delayed. Indeed, only the Per2 promoter, but not Per1, was strongly induced by both PER1 and PER2 in the presence of CLOCK-BMAL1 in a luciferase reporter assay. Moreover, a 3-hour advance was observed in the transcriptional oscillation of the delta-Per2 reporter gene lacking cis-elements required for the induction by PER1/2. These results indicate that the Per2 positive feedback regulation is a significant factor responsible for generating the phase difference between Per1 and Per2 gene expression.

Ogawa, Yukino; Koike, Nobuya; Kurosawa, Gen; Soga, Tomoyoshi; Tomita, Masaru; Tei, Hajime

2011-01-01

101

Regulation of cholesterol homeostasis.  

PubMed

Cholesterol homeostasis is among the most intensely regulated processes in biology. Since its isolation from gallstones at the time of the French Revolution, cholesterol has been extensively studied. Insufficient or excessive cellular cholesterol results in pathological processes including atherosclerosis and metabolic syndrome. Mammalian cells obtain cholesterol from the circulation in the form of plasma lipoproteins or intracellularly, through the synthesis of cholesterol from acetyl coenzyme A (acetyl-CoA). This process is tightly regulated at multiple levels. In this review, we provide an overview of the multiple mechanisms by which cellular cholesterol metabolism is regulated. We also discuss the recent advances in the post-transcriptional regulation of cholesterol homeostasis, including the role of small non-coding RNAs (microRNAs). These novel findings may open new avenues for the treatment of dyslipidemias and cardiovascular diseases. PMID:22009455

Goedeke, Leigh; Fernández-Hernando, Carlos

2011-10-19

102

Subdivision Regulations: Englewood, Tennessee.  

National Technical Information Service (NTIS)

The subdivision regulations of Englewood, Tennessee, were prepared to give the planning commission a system of controls to be exercised in considering the formation of new subdivisions within the municipality. (Author)

1969-01-01

103

Clayton, Alabama: Subdivision Regulations.  

National Technical Information Service (NTIS)

The purpose of these regulations is to provide the Planning Commission of the Town of Clayton with a recommended regulatory measure designed to meet current and anticipated future needs for the promotion of the health, safety, morals, convenience, order, ...

1972-01-01

104

Regulation of RNA Synthesis.  

National Technical Information Service (NTIS)

Messenger RNA synthesis can take place during amino acid starvation and is thus not regulated by the stringent control. Transfer RNA and ribosomal RNA are coordinately controlled by the stringent control. Transfer RNA and ribosomal RNA vary independently ...

R. Lavalle

1968-01-01

105

Epigenetic Regulation in Drosophila  

Microsoft Academic Search

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

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

106

The regulation of appetite  

PubMed Central

The worsening global obesity epidemic, particularly the increase in childhood obesity, has prompted research into the mechanisms of appetite regulation. Complex pathways modulate energy balance, involving appetite centres in the hypothalamus and brain stem, and hormonal signals of energy status released by the gut and by the periphery. Better understanding of appetite regulation improves understanding of the aetiology of obesity. Manipulation of this homoeostatic system offers potentially useful treatments for obesity.

Druce, M; Bloom, S R

2006-01-01

107

CBER-Regulated Products: Discontinuations  

Center for Biologics Evaluation and Research (CBER)

... CBER-Regulated Products: Discontinuations. How does CBER Learn about the Discontinuation of the Products It Regulates? ... More results from www.fda.gov/biologicsbloodvaccines/safetyavailability/shortages

108

Interpersonal emotion regulation.  

PubMed

Contemporary emotion regulation research emphasizes intrapersonal processes such as cognitive reappraisal and expressive suppression, but people experiencing affect commonly choose not to go it alone. Instead, individuals often turn to others for help in shaping their affective lives. How and under what circumstances does such interpersonal regulation modulate emotional experience? Although scientists have examined allied phenomena such as social sharing, empathy, social support, and prosocial behavior for decades, there have been surprisingly few attempts to integrate these data into a single conceptual framework of interpersonal regulation. Here we propose such a framework. We first map a "space" differentiating classes of interpersonal regulation according to whether an individual uses an interpersonal regulatory episode to alter their own or another person's emotion. We then identify 2 types of processes-response-dependent and response-independent-that could support interpersonal regulation. This framework classifies an array of processes through which interpersonal contact fulfills regulatory goals. More broadly, it organizes diffuse, heretofore independent data on "pieces" of interpersonal regulation, and identifies growth points for this young and exciting research domain. (PsycINFO Database Record (c) 2013 APA, all rights reserved). PMID:24098929

Zaki, Jamil; Williams, W Craig

2013-10-01

109

TEMPORAL PATTERNS OF LIPOPEROXIDATION AND ANTIOXIDANT ENZYMES ARE MODIFIED IN THE HIPPOCAMPUS OF VITAMIN A-DEFICIENT RATS  

PubMed Central

Animals can adapt their behavior to predictable temporal fluctuations in the environment through both, memory-and-learning processes and an endogenous time-keeping mechanism. Hippocampus plays a key role in memory and learning and is especially susceptible to oxidative stress. In compensation, antioxidant enzymes activity, such as Catalase (CAT) and Glutathione peroxidase (GPx), has been detected in this brain region. Daily rhythms of antioxidant enzymes activitiy, as well as of glutathione and lipid peroxides levels, have been described in brain. Here, we investigate day/night variations in lipoperoxidation, CAT and GPx expression and activity, as well as the temporal fluctuations of two key components of the endogenous clock, BMAL1 and PER1, in the rat hippocampus and evaluate to which extent vitamin A deficiency may affect their amplitude or phase. Holtzman male rats from control, vitamin A-deficient and vitamin A-refed groups were sacrificed throughout a 24-h period. Daily levels of clock proteins, lipoperoxidation, CAT and GPx mRNA, protein, and activity, were determined in the rat hippocampus obtained every 4 or 5 h. Gene expression of RAR? and RXR? was also quantified in the hippocampus of the three groups of rats. Our results show significant daily variations of BMAL1 and PER1 protein expression. Rhythmic lipoperoxidation, CAT, and GPx, expression and activity, were also observed in the rat hippocampus. Vitamin A deficiency reduced RXR? mRNA level, as well as the amplitude of BMAL1 and PER1 daily oscillation, phase-shifted the daily peak of lipoperoxidation, and had a differential effect on the oscillating CAT and GPx mRNA, protein, and activity. Learning how vitamin A deficiency affects the circadian gene expression in the hippocampus may have an impact on the neurobiology, nutritional and chronobiology fields, emphasizing for the first time the importance of nutritional factors, such as dietary micronutrients, in the regulation of circadian parameters in this brain memory-and-learning-related region.

Navigatore Fonzo, Lorena S.; Golini, Rebeca S.; Delgado, Silvia M.; Ponce, Ivana T.; Bonomi, Myrta R.; Rezza, Irma G.; Gimenez, Maria S.; Anzulovich, Ana C.

2011-01-01

110

DAILY PATTERNS OF CLOCK AND COGNITION-RELATED FACTORS ARE MODIFIED IN THE HIPPOCAMPUS OF VITAMIN A-DEFICIENT RATS  

PubMed Central

The circadian expression of clock and clock-controlled cognition-related genes in the hippocampus would be essential to achieve an optimal daily cognitive performance. There is some evidence that retinoid nuclear receptors (RARs and RXRs) can regulate circadian gene expression in different tissues. In this study, Holtzman male rats from control and vitamin A-deficient groups were sacrificed throughout a 24-h period and hippocampus samples were isolated every 4 or 5 h. RAR? and RXR? expression level was quantified and daily expression patterns of clock BMAL1, PER1, ROR? and REVERB genes, ROR? and REVERB proteins, as well as temporal expression of cognition-related RC3 and BDNF genes were determined in the hippocampus of the two groups of rats. Our results show significant daily variations of BMAL1, PER1, ROR? and REVERB genes, ROR? and REVERB proteins and, consequently, daily oscillating expression of RC3 and BDNF genes in the rat hippocampus. Vitamin A deficiency reduced RXR? mRNA level as well as the amplitude of PER1, REVERB gene and REVERB protein rhythms, and phase-shifted the daily peaks of BMAL1 and ROR? mRNA, ROR? protein and RC3 and BDNF mRNA levels. Thus, nutritional factors, such as vitamin A and its derivatives the retinoids, might modulate daily patterns of BDNF and RC3 expression in the hippocampus and they could be essential to maintain an optimal daily performance at molecular level in this learning-and-memory-related brain area.

Golini, Rebeca S.; Delgado, Silvia M.; Navigatore Fonzo, Lorena S.; Ponce, Ivana T.; Lacoste, Maria G.; Anzulovich, Ana C.

2012-01-01

111

On regulating perceived risk.  

PubMed

Modern society increasingly depends on government regulation to manage risks. Until recently, evaluation of risks of technology was primarily considered a technical problem. However, public controversy has politicized the issue of risk, raising questions about the role of experts. This paper briefly explores the nature of technical risks of aircraft, nuclear energy and medicines. It is contended that in the case of aircraft intensive regulation has led to a measurable improvement of its safety record. The constant call for more regulation in the areas of medicines and nuclear energy on the other hand seems more the result of public controversy, since the actual effect of regulatory measures on safety is too difficult to show. This stresses the important role of the media, a theme, which is elaborated by reviewing a number of cases. The general conclusion is concerned with the notion that public pressure is the only rationale which makes regulators step in. Regulatory decision-making about risk, then, is more anecdotal than systematic, because public controversy is unpredictable. As a consequence regulators can no longer seek to minimize harm, but must now move towards the aim of minimizing perceived harm. Finally, in the light of this assumption, some thought is given to costs and benefits of medicines and nuclear energy. It is appropriate to make a strong case for medicines in this context, for, as opposed to nuclear energy, alternatives are usually not available. PMID:10271778

van Andel, F G

1985-01-01

112

Distribution Feeder Voltage Regulation Control  

Microsoft Academic Search

Step voltage regulators are the workhorse of distribution feeders for maintaining the voltage at every customer's meter to be within the ANSI standards. A step voltage regulator can be viewed as a tap-changing autotransformer. This paper will apply a model of the step voltage regulator. The IEEE 13 Node Test Feeders will be used to demonstrate how the regulator is

W. H. Kersting

2010-01-01

113

Mechanisms regulating melanogenesis*  

PubMed Central

Skin pigmentation is an important human phenotypic trait whose regulation, in spite of recent advances, has not yet been fully understood. The pigment melanin is produced in melanosomes by melanocytes in a complex process called melanogenesis. The melanocyte interacts with endocrine, immune, inflammatory and central nervous systems, and its activity is also regulated by extrinsic factors such as ultraviolet radiation and drugs. We have carried out a review of the current understanding of intrinsic and extrinsic factors regulating skin pigmentation, the melanogenesis stages and related gene defects. We focused on melanocyte-keratinocyte interaction, activation of melanocortin type 1 receptor (MC1-R) by peptides (melanocyte-stimulating hormone and adrenocorticotropic hormone) resulting from proopiomelanocortin (POMC) cleavage, and mechanisms of ultraviolet-induced skin pigmentation. The identification and comprehension of the melanogenesis mechanism facilitate the understanding of the pathogenesis of pigmentation disorders and the development of potential therapeutic options.

Videira, Ines Ferreira dos Santos; Moura, Daniel Filipe Lima; Magina, Sofia

2013-01-01

114

Regulating the unregistered.  

PubMed

A high proportion of health services is provided by complementary health practitioners who are not subject to formal regulation via a statutory registration scheme. The risk is that such practitioners are not subject to effective forms of professional accountability in relation to services which have the potential to be seriously counter-therapeutic for their clients if they breach fundamental norms of propriety generally accepted within their professions and expected by their clients. Consideration has been given in both South Australia and Victoria to increasing the oversight over complementary health professionals. New South Wales and New Zealand have gone further, bringing such practitioners within the rubric of regulation. The operation of these schemes is reviewed and it is argued that there is a need to ensure that all health practitioners are subject to effective regulation in relation to their adherence to fundamental ethical obligations. PMID:19205304

Freckelton, Ian

2008-12-01

115

Mechanogenetic regulation of transcription.  

PubMed

In many biological systems mechanical forces regulate gene expression: in bacteria changes in turgor pressure cause a deformation of the membrane and induce the expression of osmoregulatory genes; in plants gravity regulates cell growth ('geotropism'); in mammals stretching a muscle induces hypertrophy which is accompanied by qualitative changes in protein synthesis. Consequently, the term 'mechanogenetic control' seems to be a suitable common name for all these processes. The mechanism by which mechanical factors modulate transcriptional activity is still unknown. The purpose of this review is to bring together data from different fields in order to obtain a better understanding of the mechanogenetic control of cell growth. PMID:1747387

Erdos, T; Butler-Browne, G S; Rappaport, L

1991-09-01

116

A Furnace Temperature Regulator  

Microsoft Academic Search

Synopsis.-By making the heating coil of an electric furnace one arm of a wheatstone bridge, and combining this with a galvanometer regulator, thus keeping constant the resistance of the coil, we can, regardless of variations in the current supply, and with no attention, maintain constant the temperature of furnaces not too directly influenced by the temperature of the room, or

Walter P. White; Leason H. Adams

1919-01-01

117

Introducing Franchising Regulation  

Microsoft Academic Search

The mandatory Franchising Code of Conduct was introduced in Australia in 1998 to regulate the franchising sector. This paper examines the effect of the Code on the sector and on franchising relationships in the 12 months following its implementation.A two-stage methodology was used in this research. Stage one involved a mail survey of the population of Australian franchisors and results

Jolene Lim; Lorelle Frazer

2003-01-01

118

METABOLIC PATHWAY REGULATION  

Technology Transfer Automated Retrieval System (TEKTRAN)

Research efforts in the past two decades have revealed the complex mechanisms employed by fungi to control gene activity. The tremendous expansion in our knowledge of the regulation of nitrogen metabolism and carbon metabolism, due largely to the powerful combination of genetics, biochemistry, and ...

119

Regulation of Television advertising  

Microsoft Academic Search

Regulation of television advertising typically covers both the time devoted to commercials and restrictions on the commodities or services that can be publicized to various audiences (stricter laws often apply to children’s programming). Time restrictions (advertising caps) may improve welfare when advertising is overprovided in the market system. Even then, such caps may reduce the diversity of programming by curtailing

Simon P. Anderson

2005-01-01

120

Airport regulation and competition  

Microsoft Academic Search

In the airports industry, there is a trade off between imperfect (or monopolistic) competition and economic regulation (with the latter introducing separate economic distortions). The nature of the imperfectly competitive market in the supply of airport services is examined and it is suggested that market power is the consequence of the problems of gaining access to competing sites rather than

David Starkie

2002-01-01

121

Meniscus Regulator System.  

National Technical Information Service (NTIS)

A method and system is provided for regulating the meniscus of a water droplet in a high velocity water droplet apparatus in which a large pulse of energy is applied to the water droplet to propel the water droplet at high velocity. In this method the sha...

M. F. Thomas

1994-01-01

122

Orexins and appetite regulation  

Microsoft Academic Search

Initial research on the functional significance of two novel hypothalamic neuropeptides, orexin-A and orexin-B, suggested an important role in appetite regulation. Since then, however, these peptides have also been shown to influence a wide range of other physiological and behavioural processes. In this paper, we review the now quite extensive literature on orexins and appetite control, and consider their additional

R. J. Rodgers; Y. Ishii; J. C. G. Halford; J. E. Blundell

2002-01-01

123

Gene regulation by riboswitches  

Microsoft Academic Search

Riboswitches are complex folded RNA domains that serve as receptors for specific metabolites. These domains are found in the non-coding portions of various mRNAs, where they control gene expression by harnessing allosteric structural changes that are brought about by metabolite binding. New findings indicate that riboswitches are robust genetic elements that are involved in regulating fundamental metabolic processes in many

Maumita Mandal; Ronald R. Breaker

2004-01-01

124

Migratory Bird Hunting Regulations  

NSDL National Science Digital Library

The US Fish and Wildlife Service has placed online this collection of documents (.pdf format) on the regulations associated with hunting of migratory birds. Several dozen documents are posted here, with new documents (e.g., Federal Register releases) added periodically.

125

Aptamers for allosteric regulation  

Microsoft Academic Search

Aptamers are useful for allosteric regulation because they are nucleic acid–based structures in which ligand binding induces conformational changes that may alter the function of a connected oligonucleotide at a distant site. Through this approach, a specific input is efficiently converted into an altered output. This property makes these biomolecules ideally suited to function as sensors or switches in biochemical

Jan L Vinkenborg; Nora Karnowski; Michael Famulok

2011-01-01

126

REGULATIONS AND SYLLABUSES 1966.  

ERIC Educational Resources Information Center

|DESCRIBED IN THIS MANUAL ARE EXAMINATIONS USED IN 1966 IN AWARDING EDUCATIONAL CERTIFICATES TO STUDENTS IN ENGLISH SECONDARY SCHOOLS AND ESTABLISHMENTS FOR FURTHER EDUCATION. IT IS WRITTEN PRIMARILY FOR HEADS OF COLLEGES AND SCHOOLS AND DESCRIBES IN DETAIL THE PROCEDURES AND REGULATIONS FOR THE ADMINISTRATION OF EXAMINATIONS IN ALL SUBJECT AREAS.…

JOHNSON, ARTHUR L.; AND OTHERS

127

REGULATIONS AND SYLLABUSES, 1968.  

ERIC Educational Resources Information Center

|EXAMINATIONS USED IN AWARDING EDUCATIONAL CERTIFICATES TO STUDENTS IN ENGLISH SECONDARY SCHOOLS IN 1968 ARE DESCRIBED IN THIS MANUAL. IT IS WRITTEN PRIMARILY FOR HEADS OF COLLEGES AND SCHOOLS AND DESCRIBES IN DETAIL THE PROCEDURES AND REGULATIONS FOR THE ADMINISTRATION OF EXAMINATIONS IN ALL SUBJECT AREAS. EXAMINATIONS MAY BE TAKEN AT THE…

Associated Examining Board, Aldershot, Hampshire (England).

128

REGULATIONS AND SYLLABUSES 1967.  

ERIC Educational Resources Information Center

|DESCRIBED IN THIS MANUAL ARE EXAMINATIONS USED IN 1967 IN AWARDING EDUCATIONAL CERTIFICATES TO STUDENTS IN ENGLISH SECONDARY SCHOOLS AND ESTABLISHMENTS FOR FURTHER EDUCATION. IT IS WRITTEN PRIMARILY FOR HEADS OF COLLEGES AND SCHOOLS AND DESCRIBES IN DETAIL THE PROCEDURES AND REGULATIONS FOR THE ADMINISTRATION OF EXAMINATIONS IN ALL SUBJECT AREAS.…

Associated Examining Board, Aldershot, Hampshire (England).

129

Regulation of Cadherin Trafficking  

PubMed Central

Cadherins are a large family of cell-cell adhesion molecules that tether cytoskeletal networks of actin and intermediate filaments to the plasma membrane. This function of cadherins promotes tissue organization and integrity, as demonstrated by numerous disease states that are characterized by the loss of cadherin-based adhesion. However, plasticity in cell adhesion is often required in cellular processes such as tissue patterning during development and epithelial migration during wound healing. Recent work has revealed a pivotal role for various membrane trafficking pathways in regulating cellular transitions between quiescent adhesive states and more dynamic phenotypes. The regulation of cadherins by membrane trafficking is emerging as a key player in this balancing act and studies are beginning to reveal how this process goes awry in the context of disease. This review summarizes the current understanding of how cadherins are routed and how the interface between cadherins and membrane trafficking pathways regulates cell surface adhesive potential. Particular emphasis is placed on the regulation of cadherin trafficking by catenins and the interplay between growth factor signaling pathways and cadherin endocytosis.

Delva, Emmanuella; Kowalczyk, Andrew P.

2010-01-01

130

Regulating the New Governance  

ERIC Educational Resources Information Center

|This article arises out of a research project that sought to assess the development of regulation within the public sector. It examines the forms and impact of the regulatory systems that now operate within the public sector focusing on the further education sector. The research project developed out of an awareness that the increase in various…

Cope, Stephen; Goodship, Jo; Holloway, David

2003-01-01

131

Regulation of Chloroplast Translation  

Microsoft Academic Search

During the evolution of chloroplasts from cyanobacterial endosymbionts, many genes encoding components necessary for protein synthesis and photosynthesis have been transferred to the nucleus. Assembly of the machinery for both processes now relies on the concerted expression of genes in the nuclear and plastid genomes. Evidence accumulating in C. reinhardtii indicates that the expression and regulation of chloroplast genes probably

Charles R. Hauser; Nicholas W. Gillham; John E. Boynton

132

Transcriptional regulation in lymphocytes  

Microsoft Academic Search

Lymphocytes have been used to investigate many cellular processes, including lineage commitment, differentiation, proliferation and apoptosis. The transcription factors that mediate these processes are often expressed broadly in many cell types. The emerging theme is one of cell-type-specific regulation, affecting not only the functional activation of transcription factors but also their access to appropriate regions of DNA.

Heidi Okamura; Anjana Rao

2001-01-01

133

International Regulations on Halocarbons  

Microsoft Academic Search

The Montreal Protocol on Substances that Deplete the Ozone Layer was a landmark in international environmental regulation. This chapter describes the development of understanding of atmospheric science that led to the initial Protocol, agreed in 1987, and the subsequent developments that shaped its revisions. Eleven years later, both industrial statistics and, perhaps more significantly, atmospheric measurements clearly show compliance with

P. M. Midgley; A. McCulloch

134

Metabolic Regulation in Fungi  

Microsoft Academic Search

Metabolic Pathways in the fungi are subject to a high degree of regulation which frequently occurs at the level of transcription. Expression of structural genes within a control circuit is achieved by a network of interactions between metabolic repressors and inducers with both global-acting regulatory factors and pathway-specific factors. These sophisticated regulatory circuits operate in such a way to allow

G. A. Marzluf

2001-01-01

135

Glucose regulation in birds  

Microsoft Academic Search

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

Eldon J. Braun; Karen L. Sweazea

2008-01-01

136

Serial Regulation of Transcriptional Regulators in the Yeast Cell Cycle  

Microsoft Academic Search

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

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

137

Regulating the regulator: post-translational modification of RAS  

Microsoft Academic Search

RAS proteins are monomeric GTPases that act as binary molecular switches to regulate a wide range of cellular processes. The exchange of GTP for GDP on RAS is regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), which regulate the activation state of RAS without covalently modifying it. By contrast, post-translational modifications (PTMs) of RAS proteins direct them

Ian M. Ahearn; Kevin Haigis; Dafna Bar-Sagi; Mark R. Philips

2011-01-01

138

Regulation of RAG transposition.  

PubMed

V(D)J recombination is initiated by the lymphoid specific proteins RAG1 and RAG2, which together constitute the V(D)J recombinase. However, the RAG 1/2 complex can also act as a transposase, inserting the broken DNA molecules generated during V(D)J recombination into an unrelated piece of DNA. This process, termed RAG transposition, can potentially cause insertional mutagenesis, chromosomal translocations and genomic instability. This review focuses on the mechanism and regulation of RAG transposition. We first provide a brief overview of the biochemistry of V(D)J recombination. We then discuss the discovery of RAG transposition and present an overview of the RAG transposition pathway. Using this pathway as a framework, we discuss the factors and forces that regulate RAG transposition. PMID:19731798

Matthews, Adam G W; Oettinger, Marjorie A

2009-01-01

139

CNS regulation of appetite.  

PubMed

This article reviews the regulation of appetite from a biopsychological perspective. It considers psychological experiences and peripheral nutritional systems (both episodic and tonic) and addresses their relationship with the CNS networks that process and integrate their input. Whilst such regulatory aspects of obesity focus on homeostatic control mechanisms, in the modern environment hedonic aspects of appetite are also critical. Enhanced knowledge of the complexity of appetite regulation and the mechanisms that sustain obesity indicate the challenge presented by management of the obesity epidemic. Nonetheless, effective control of appetite expression remains a critical therapeutic target for weight management. Currently, strategies which utilise a combination of agents to target both homeostatic and hedonic control mechanisms represent the most promising approaches. This article is part of a Special Issue entitled 'Central Control of Food Intake'. PMID:22313528

Harrold, Joanne A; Dovey, Terry M; Blundell, John E; Halford, Jason C G

2012-01-30

140

Regulating secretory lysosomes.  

PubMed

Secretory lysosomes are lysosomes which are capable of undergoing regulated secretion in response to external stimuli. Many cells of the immune system use secretory lysosomes to release proteins involved in their specialised effector mechanisms. Precisely how lysosomal secretion is regulated in each of these cell types is now the study of much research as these mechanisms control the ability of each of these cells to function. Studies on a number of human genetic diseases have identified some key proteins in controlling secretory lysosome release, and now many interacting partners have been identified. The different regulatory components seem to vary from one cell type to another, providing a multitude of ways for fine tuning the release of secretory lysosomes. PMID:16877763

Holt, Oliver J; Gallo, Federico; Griffiths, Gillian M

2006-07-01

141

Siglecs and Immune Regulation  

PubMed Central

Sialic acid binding Ig-like lectins or Siglecs vary in their specificity for sialic acid containing ligands and are mainly expressed by cells of the immune system. Many siglecs are inhibitory receptors expressed in innate immune cells that regulate inflammation mediated by DAMPs and PAMPs. This family also includes molecules involved in adhesion and phagocytosis and receptors that can associate with the ITAM containing DAP12 adaptor. Siglecs contribute to the inhibition of immune cells both by binding to cis-ligands (expressed in the same cells) as well as by responding to pathogen derived sialoglycoconjugates. They can help maintain tolerance in B lymphocytes, modulate the activation of conventional and plasmacytoid dendritic cells, and contribute to the regulation of T cell function both directly and indirectly. Siglecs modulate immune responses influencing almost every cell in the immune system, and are of relevance both in health and disease.

Pillai, Shiv; Netravali, Ilka Arun; Cariappa, Annaiah; Mattoo, Hamid

2013-01-01

142

Regulation of inflammasome signaling  

PubMed Central

Innate immune responses have the ability to both combat infectious microbes and drive pathological inflammation. Inflammasome complexes are a central component of these processes through their regulation of interleukin 1? (IL-1?), IL-18 and pyroptosis. Inflammasomes recognize microbial products or endogenous molecules released from damaged or dying cells both through direct binding of ligands and indirect mechanisms. The potential of the IL-1 family of cytokines to cause tissue damage and chronic inflammation emphasizes the importance of regulating inflammasomes. Many regulatory mechanisms have been identified that act as checkpoints for attenuating inflammasome signaling at multiple steps. Here we discuss the various regulatory mechanisms that have evolved to keep inflammasome signaling in check to maintain immunological balance.

Rathinam, Vijay A K; Vanaja, Sivapriya Kailasan; Fitzgerald, Katherine A

2012-01-01

143

Beyond Emotion Regulation  

PubMed Central

Recent research indicates that emotionality, emotion information processing, emotion knowledge, and discrete emotion experiences may influence and interact with emotion utilization, that is, the effective use of the inherently adaptive and motivational functions of emotions. Strategies individuals learn for emotion modulation and emotion utilization become stabilized in emerging affective-cognitive structures, or emotion schemas. In these emotion schemas, the feeling/motivational component of emotion and perceptual and cognitive processes interact dynamically and continually. The concepts and techniques that promote emotion knowledge, emotion regulation, and emotion utilization have proved effective in promoting favorable behavioral outcomes in both emotion-based and cognitive-behavioral interventions. In this paper, we suggest that current conceptualizations of emotion regulation need to be extended to take these interactions into account.

Izard, Carroll; Stark, Kevin; Trentacosta, Christopher; Schultz, David

2009-01-01

144

Cholinergic regulation of bone.  

PubMed

Bone remodeling is regulated by the two branches of the autonomic nervous system: the adrenergic and the cholinergic branches. Adrenergic activity favors bone loss, whereas cholinergic activity has been recently shown to favor bone mass accrual. In vitro studies have reported that cholinergic activity induces proliferation and differentiation of bone cells. In vivo studies have shown that the inhibition of cholinergic activity favors bone loss, whereas its stimulation favors bone mass accrual. Clinical studies have shown that bone density is associated with the function of many cholinergic-regulated tissues such as the hypothalamus, salivary glands, lacrimal glands and langerhans cells, suggesting a common mechanism of control. Altogether, these observations and linked findings are of great significance since they improve our understanding of bone physiology. These discoveries have been successfully used recently to investigate new promising therapies for bone diseases based on cholinergic stimulation. Here, we review the current understanding of the cholinergic activity and its association with bone health. PMID:23728099

Eimar, H; Tamimi, I; Murshed, M; Tamimi, F

2013-06-01

145

Regulation of Meiotic Recombination  

SciTech Connect

Meiotic recombination results in the heritable rearrangement of DNA, primarily through reciprocal exchange between homologous chromosome or gene conversion. In plants these events are critical for ensuring proper chromosome segregation, facilitating DNA repair and providing a basis for genetic diversity. Understanding this fundamental biological mechanism will directly facilitate trait mapping, conventional plant breeding, and development of genetic engineering techniques that will help support the responsible production and conversion of renewable resources for fuels, chemicals, and the conservation of energy (1-3). Substantial progress has been made in understanding the basal recombination machinery, much of which is conserved in organisms as diverse as yeast, plants and mammals (4, 5). Significantly less is known about the factors that regulate how often and where that basal machinery acts on higher eukaryotic chromosomes. One important mechanism for regulating the frequency and distribution of meiotic recombination is crossover interference - or the ability of one recombination event to influence nearby events. The MUS81 gene is thought to play an important role in regulating the influence of interference on crossing over. The immediate goals of this project are to use reverse genetics to identify mutants in two putative MUS81 homologs in the model plant Arabidopsis thaliana, characterize those mutants and initiate a novel forward genetic screen for additional regulators of meiotic recombination. The long-term goal of the project is to understand how meiotic recombination is regulated in higher eukaryotes with an emphasis on the molecular basis of crossover interference. The ability to monitor recombination in all four meiotic products (tetrad analysis) has been a powerful tool in the arsenal of yeast geneticists. Previously, the qrt mutant of Arabidopsis, which causes the four pollen products of male meiosis to remain attached, was developed as a facile system for assaying recombination using tetrad analysis in a higher eukaryotic system (6). This system enabled the measurement of the frequency and distribution of recombination events at a genome wide level in wild type Arabidopsis (7), construction of genetic linkage maps which include positions for each centromere (8), and modeling of the strength and pattern of interference (9). This proposal extends the use of tetrad analysis in Arabidopsis by using it as the basis for assessing the phenotypes of mutants in genes important for recombination and the regulation of crossover interference and performing a novel genetic screen. In addition to broadening our knowledge of a classic genetic problem - the regulation of recombination by crossover interference - this proposal also provides broader impact by: generating pedagogical tools for use in hands-on classroom experience with genetics, building interdisciplinary collegial partnerships, and creating a platform for participation by junior scientists from underrepresented groups. There are three specific aims: (1) Isolate mutants in Arabidopsis MUS81 homologs using T-DNA and TILLING (2) Characterize recombination levels and interference in mus81 mutants (3) Execute a novel genetic screen, based on tetrad analysis, for genes that regulate meiotic recombination

Gregory p. Copenhaver

2011-11-09

146

Regulation of Apoptosis by Caspases.  

National Technical Information Service (NTIS)

Caspases are a family of cysteine proteases that play important roles in regulating apoptosis, a genetically encoded cellular suicide mechanism. To determine the mechanism by which caspases regulate apoptosis. We carried out a screen to identify substrate...

J. Yuan

1999-01-01

147

Federal Regulation of Methadone Treatment.  

National Technical Information Service (NTIS)

The charge to the Committee on Federal Regulation of Methadone Treatment was to study current Department of Health and Human Services (DHHS) standards for narcotic addiction treatment and the regulation of methadone treatment programs pursuant to those st...

R. A. Rettig A. Yarmolinsky

1995-01-01

148

Commercially Available IDI Scuba Regulators.  

National Technical Information Service (NTIS)

Evaluations were conducted to determine which commercially available open-circuit SCUBA regulators were capable of meeting performance goal standards for Navy use. Bench testing of all candidate regulators was conducted to establish flow patterns and air ...

J. A. Noe

1993-01-01

149

REGULATION OF VASCULOGENESIS AND ANGIOGENESIS  

EPA Science Inventory

Regulation of vasculogenesis and angiogenesis. B.D. Abbott Reproductive Toxicology Division, Environmental Protection Agency, Research Triangle Park, North Carolina, USA Vasculogenesis and angiogenesis are regulated by a complex, interactive family of receptors and lig...

150

Effects of NAD(P)H and its derivatives on the DNA-binding activity of NPAS2, a mammalian circadian transcription factor.  

PubMed

NPAS2 is a transcription factor that regulates mammalian circadian rhythms. It has been suggested that NPAS2 DNA-binding activity is regulated by the intracellular redox state of NAD(P)H, although the mechanism remains unclear. To investigate the NAD(P)H interaction site of murine NPAS2, we performed electrophoretic mobility shift assays using several truncation mutants of the NPAS2 bHLH domain. Among the mutants, NPAS2 containing the N-terminal 61 residues formed a heterodimer with BMAL1 to bind DNA, and NAD(P)H enhanced the binding activity, while NAD(P)H inhibited the DNA-binding activity of the BMAL1 homodimer in a dose-dependent manner. NAD(P)H derivatives such as 2',5'-ADP, nicotinamide, nicotinic acid and nicotinic acid adenine dinucleotide (NAAD) did not affect the DNA-binding activity. Interestingly, NAD(P)(+), previously reported as an inhibitor, did not affect NPAS2 binding activity in the presence or absence of NAD(P)H in our system. These results suggest that NPAS2 DNA-binding activity is specifically enhanced by NAD(P)H independently of NAD(P)(+) and that the N-terminal 1-61 amino acids of NPAS2 are sufficient to sense NAD(P)H. PMID:23831463

Yoshii, Katsuhiro; Ishijima, Sumio; Sagami, Ikuko

2013-07-02

151

Transcriptional Regulation of Angiogenesis  

Microsoft Academic Search

Until recently, the transcription factors necessary for regulating vascular development were largely unknown. This is in sharp\\u000a contrast with other developmental processes, such as hematopoiesis and myogenesis, in which several cell- or tissue-specific\\u000a transcription factors have been identified. Vascular development requires the differentiation of endothelial cells from pluripotent\\u000a stem cells. Progress in identifying the molecular mechanisms underlying vascular development has

Peter Oettgen

152

Regulation of biomedical products.  

PubMed

Two recent decisions, one from Australia and one from Canada, should cause us to examine the ethical issues surrounding the regulation of biomedical products. The protection of vulnerable consumers from variable quality and poorly prepared drugs with uncertain parameters of safety and efficacy is a priority for any community and should not have to be weighed against possible costs based on restrictions of trade. However, the possibility of an environment in which the multinational biomedical industry edges out any other players in the treatment of various illnesses has its own dangers. Not least is the apparent collusion between regulators and industry that ramps up the costs and intensity of licensing and risk management so that only an industry-type budget can sustain the costs of compliance. This has the untoward effect of delivering contemporary health care into the hands of those who make immense fortunes out of it. An approach to regulation that tempers bureaucratic mechanisms with a dose of common sense and realistic evidence-based risk assessment could go a long way in avoiding the Scylla and Charybdis awaiting the clinical world in these troubled waters. PMID:20552933

Gillett, Grant; Saville-Cook, Donald

2010-05-01

153

Improving CS regulations.  

SciTech Connect

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)

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

1980-10-01

154

Regulation reform slows down  

SciTech Connect

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.

NONE

1995-03-29

155

Financial Private Regulation and Enforcement  

Microsoft Academic Search

This paper considers the topic of private regulation and enforcement for internationally active financial services firms. The paper documents the following types of regulation and enforcement that involve significant private input: house rules, contracts, internal compliance, management-based regulation, private standard-setting bodies, cartels, and private litigation. The paper assesses these systems or modalities along the dimensions of effectiveness, legitimacy, quality, and

Geoffrey Miller

2011-01-01

156

The Theory of Economic Regulation  

Microsoft Academic Search

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.

George J. Stigler

1971-01-01

157

THE REGULATION OF PUBLIC GOODS  

Microsoft Academic Search

The paper examines the complex ways in which public goods are regulated. The provision and distribution of public goods is deeply affected by the degree of excludability of those goods and the regulatory context of that excludability. Using a decentered conception of regulation, the paper shows through various examples how state and non-state actors regulate each other's capacities to provide,

Peter Drahos

2004-01-01

158

Distribution feeder voltage regulation control  

Microsoft Academic Search

Step voltage regulators are the work horse of distribution feeders for maintaining the voltage at every customer's meter to be within the ANSI standards. A step voltage regulator can be viewed as a tap changing autotransformer. This paper will apply a model of the step voltage regulator. The IEEE 13 Node Test Feeders will be used to demonstrate how the

W. H. Kersting

2009-01-01

159

Impact DG on voltage regulation  

Microsoft Academic Search

This paper includes the technical impact of distributed generation (DG) on voltage regulation when integrated into a typical distribution system. To study the interaction of DG with voltage regulators and capacitors, computer models were developed and control systems simulated and implemented. Test cases are presented that demonstrate and visualize the impact of DG on voltage regulation and the interaction of

Ljubomir Kojovic

2002-01-01

160

DO FINANCIAL MARKETS NEED REGULATION?  

Microsoft Academic Search

Do Financial Markets Need Regulations? In this article, the arguments in favor of the need for regulation is justified by the function per- formed by Financial Intermediaries in an asymmetric information environment. The need of some forms of Regulation is proposed, even though the latter constitue a second-best compared with the ideal perfectly functioning financial markets. The case in favor

Rodrigo Cárcamo Díaz

2000-01-01

161

Self-Regulating Mathematics Skills.  

ERIC Educational Resources Information Center

|Explores self-regulated learning (SRL) theory in light of the reform vision of mathematics education depicted with "Principles and Standards for School Mathematics," asserting that implementation of mathematics reform makes possible the development of self-regulated learners while also necessitating developing self-regulated learners. The paper…

Pape, Stephen J.; Smith, Cynthia

2002-01-01

162

78 FR 1689 - Semiannual Agenda of Regulations  

Federal Register 2010, 2011, 2012, 2013

...Semiannual Agenda of Regulations AGENCY: Federal Deposit Insurance Corporation...Federal Deposit Insurance Corporation (``FDIC'') regulations to prohibit...Federal Deposit Insurance Corporation...Regulation Sequence...

2013-01-08

163

Trust-based environmental regulation.  

PubMed

Within this paper, we examine the contribution that trust-based relationships can make to achieving better-and particularly more effective, efficient and equitable-environmental regulation. While levels of trust in regulators, regulatory processes and outcomes are often discussed, the influence of trust on different actors and on different measures of regulatory performance is poorly understood. Within this paper, we define trust-based environmental regulation as a specific regulatory style that involves openness and cooperation in interaction between regulated, regulators and third-party stakeholders in order to achieve environmental protection objectives. We then discuss the pros and cons of trust relationships between regulators, regulated businesses and citizens for achieving behavioural change towards greater environmental protection. To illustrate the significance of these issues, we then examine three forms of contractual regulatory style where trust relationships are critically important: responsive regulation, self-regulation and environmental agreements. Based on this analysis, we highlight the importance of trust-based relationships, and we argue that one of the greatest contributions of trust-based environmental regulation is to challenge how we think about regulation. Trust is often understood as enabling existing regulatory relationships or in the case of self-regulation as a complement to regulation. However, we argue that the real potential of trust is to open up new ways for participants in regulatory regimes to engage in collective action, to go beyond a perception of regulation as driven by the competing interests of individual actors, and thus, to open up new channels of influence for behavioural change towards greater environmental protection. Our analysis therefore has great relevance for future research and for on-going debates on the future of regulation. PMID:20797772

Lange, Bettina; Gouldson, Andy

2010-08-24

164

Emotion Regulation and Anxiety Disorders  

PubMed Central

A growing body of research suggests that the construct of emotion regulation is important for understanding the onset, maintenance, and treatment of anxiety disorders. In this review, we provide a selective overview of this emerging field and highlight the major sources of evidence. First, evidence suggests that the construct of emotion regulation can be differentiated from the construct of emotion. Second, there is a large and consistent body of research demonstrating that emotion regulation strategies can modulate emotional responding, and this finding is observed in both behavioral and neuroimaging studies. Third, measures of emotion regulation explain incremental variance in measures of anxiety disorder symptoms not accounted for by measures of negative affect. Although the research implicating emotion regulation in the anxiety disorders is promising, future research will be necessary to further clarify causal mechanisms explaining how emotion regulation confers vulnerability for anxiety disorders and to improve the clarity and consistency of definitions of emotion regulation.

Cisler, Josh M.; Olatunji, Bunmi O.

2013-01-01

165

Charge regulation circuit  

SciTech Connect

This patent describes a charge regulation circuit. It comprises: an unregulated power supply having a first unregulated voltage value during a first charge cycle and a second unregulated voltage value during a second charge cycle, an inductor and capacitor connected in series with one another, wherein a charge voltage exists across the capacitor; a diode connected in parallel with the inductor and capacitor; a switch, and means for closing the switch at a first time for permitting the unregulated power supply to be connected to the capacitor through the inductor when the switch is in a closed position; means for opening the switch during the first charge cycle.

Ball, D.G.

1992-06-23

166

Phospholipid - Driven gene regulation  

PubMed Central

Phospholipids (PLs), well known for their fundamental role in cellular structure, play critical signaling roles via their derivatives and cleavage products acting as second messengers in signaling cascades. Recent work has shown that intact PLs act as signaling molecules in their own right by modulating the activity of nuclear hormone transcription factors responsible for tuning genes involved in metabolism, lipid flux, steroid synthesis and inflammation. As such, PLs have been classified as novel hormones. This review highlights recent work in PL-driven gene regulation with a focus on the unique structural features of phospholipid-sensing transcription factors and what sets them apart from well known soluble phospholipid transporters.

Musille, Paul M.; Kohn, Jeffrey A.; Ortlund, Eric A.

2013-01-01

167

Growth regulation by macrophages  

SciTech Connect

The evidence reviewed here indicates that macrophages, either acting alone or in concert with other cells, influence the proliferation of multiple types of cells. Most of the data indicate that these effects are mediated by soluble macrophage-elaborated products (probably proteins) although the role of direct cell-to-cell contacts cannot be ruled out in all cases. A degree of success has been achieved on the biochemical characterization of these factors, due mainly to their low specific activity in conditioned medium and the lack of rapid, specific assays. Understanding the growth-regulating potential of macrophages is an important and needed area of research.

Wharton, W.; Walker, E.; Stewart, C.C.

1982-01-01

168

Rapamycin regulates biochemical metabolites.  

PubMed

The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth, and deregulation of this pathway is associated with tumorigenesis. p53, and its less investigated family member p73, have been shown to interact closely with mTOR pathways through the transcriptional regulation of different target genes. To investigate the metabolic changes that occur upon inhibition of the mTOR pathway and the role of p73 in this response primary mouse embryonic fibroblast from control and TAp73(-/-) were treated with the macrocyclic lactone rapamycin. Extensive gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS) analysis were used to obtain a rapamycin-dependent global metabolome profile from control or TAp73(-/-) cells. In total 289 metabolites involved in selective pathways were identified; 39 biochemical metabolites were found to be significantly altered, many of which are known to be associated with the cellular stress response. PMID:23839040

Tucci, Paola; Porta, Giovanni; Agostini, Massimiliano; Antonov, Alexey; Garabadgiu, Alexander Vasilievich; Melino, Gerry; Willis, Anne E

2013-06-28

169

Regulation of myoglobin expression  

PubMed Central

Myoglobin is a well-characterized, cytoplasmic hemoprotein that is expressed primarily in cardiomyocytes and oxidative skeletal muscle fibers. However, recent studies also suggest low-level myoglobin expression in various non-muscle tissues. Prior studies incorporating molecular, pharmacological, physiological and transgenic technologies have demonstrated that myoglobin is an essential oxygen-storage hemoprotein capable of facilitating oxygen transport and modulating nitric oxide homeostasis within cardiac and skeletal myocytes. Concomitant with these studies, scientific investigations into the transcriptional regulation of myoglobin expression have been undertaken. These studies have indicated that activation of key transcription factors (MEF2, NFAT and Sp1) and co-activators (PGC-1?) by locomotor activity, differential intracellular calcium fluxes and low intracellular oxygen tension collectively regulate myoglobin expression. Future studies focused on tissue-specific transcriptional regulatory pathways and post-translational modifications governing myoglobin expression will need to be undertaken. Finally, further studies investigating the modulation of myoglobin expression under various myopathic processes may identify myoglobin as a novel therapeutic target for the treatment of various cardiac and skeletal myopathies.

Kanatous, Shane B.; Mammen, Pradeep P. A.

2010-01-01

170

Sleep and endocrine regulation.  

PubMed

A bidirectional interaction exists between sleep electroencephalogram (EEG) and endocrine activity in various species including humans. Various hormones (peptides, steroids) were shown to participate in sleep regulation. A keyrole was shown for the reciprocal interaction between sleep-promoting growth hormone-releasing hormone (GHRH) and sleep-impairing corticotropin-releasing hormone (CRH). Changes in the GHRH:CRH ratio result in changes of sleep-endocrine activity. There is good evidence that the change of this ratio in favor of CRH contributes to aberrances of sleep during aging and depression. Besides of GHRH ghrelin and galanin promote SWS, whereas somatostatin is another sleep-impairing factor. NPY acts as a CRH antagonist and induces sleep onset. Prolactin enhances rapid eve-movement sleep (REMS) in rats. SWS is enhanced in patients with prolactinoma. Other studies on the influence of prolactin of human sleep are lacking. There is a controversy whether CRH promotes REMS. In humans vasocactive intestinal polypeptide (VIP) appears to play a role in the temporal organization of sleep, since after VIP administration the NREMS-REMS cycle decelerated. Several neuroactive steroids (pregnenolone, progesterone, allopregnanolone, dehydroepiandrosterone) exert specific effects on sleep EEG via GABAA receptors. Cortisol appears to enhance REMS. Finally gonadal hormones participate in sleep regulation. Estrogen replacement therapy and CRH-1 receptor antagonism in depression are beneficial clinical applications of the basic research presented here. PMID:12700062

Steiger, Axel

2003-05-01

171

[Regulation for contractual practice].  

PubMed

The use of contractualisation has greatly developed over the last years in the field of health care, with results that are often promising, but also with failures and sometime virulent criticism. Thus it has become more and more necessary to regulate contractual practices. In the framework of its mission of general administration, that is to say, protection of the general interest, it falls to the Ministry of Health to put in place this regulation. Several tools are available. Certain, such as standard contracts and master agreements, although useful, do not remain specific and ad hoc. On the other hand, the politics of contractualisation, fitting well in the general politics of Health Care, form, without doubt, the most globalised tool, since they allow contractualisation to be replaced in the management of the total health case system, and thus to be seen as a potential contribution in the framework of performance improvement. The conditions for success are not, however, automatically united. One must ensure that the mechanisms exist which bring about regulatory tools, and which ensure that the participants use correctly the framework defined by the Ministry of Health. PMID:19027694

Perrot, Jean

2008-09-25

172

Regulating the regulators: posttranslational modifications of RNA silencing factors.  

PubMed

Every regulator should be regulated, and this holds true for small RNAs and their associated proteins. Knowledge has begun to emerge of the various mechanisms that impose specificity on the expression and function of RNA silencing factors. Recent papers, including one in this issue of Cell (Paroo et al., 2009), now reveal the posttranslational modifications that take part in the regulation of the core RNA silencing factors, Ago, Piwi, and TRBP. PMID:19804751

Heo, Inha; Kim, V Narry

2009-10-01

173

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

PubMed Central

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.

Kino, Tomoshige

2013-01-01

174

[Molecular mechanisms of circadian clock functioning].  

PubMed

Most physiological processes of all organisms are rhythmic with a period of about 24 h and are generated by an endogenous biological CLOCK present in all cells. However, there is also a central CLOCK--the primary circadian pacemaker which is localized in the suprachiasmatic nuclei of the mammalian hypothalamus. Factors of groups Period (PER1, PER2 and PER3), BMAL (BMAL1 and BMAL2), CRYptochromes (CRY1 and CRY2) as well as some other factors are the components of this circadian CLOCK system. Some of these genes contain E-box sequences and their expression is regulated by a transcription factor complex CLOCK-BMAL1. The enzymes responsible for the post-translational modification of circadian gene products are also the components of circadian CLOCK system. These enzymes define CLOCK's work and determine the duration of circadian biorhythm and functional state of the whole organism. The most important of these enzymes are casein kinase-1epsilon and -1delta. We have analysed data about the interconnection between the circadian CLOCK system, cell cycle, and cancerogenesis as well as about the sensitivity of circadian gene expression to the action of toxic agents and nanomaterials. PMID:21888051

Karbovsky?, L L; Minchenko, D O; Garmash, Ia A; Minchenko, O G

175

Imaging of heme/hemeproteins in nucleus of the living cells expressing heme-binding nuclear receptors.  

PubMed

Several factors involved in the core circadian rhythm are PAS domain proteins, one of which, neuronal PAS2 (NPAS2), contains a heme-binding motif. It is thought that heme controls the transcriptional activity of core circadian factors BMAL1-NPAS2, and that the heme-binding nuclear receptor REV-erb? negatively regulates the expression of BMAL1. To examine the role of heme in the nucleus, we expressed nuclear hemeproteins including the nuclear localization signal-added cytoglobin, NPAS2 and REV-erb?. Then, the living cells expressing these proteins were treated with 2',7'-dichlorodihydrofluorescin diacetate (DCFH-DA). The fluorescent signal derived from DCFH-DA was observed in the nucleus. When the cells were cultured with hemin, the signal of heme in the nucleus increased. Considering that DCFH-DA reacted with heme, we propose that the use of DCFH-DA could be useful in detection of the heme moiety of hemeprotein in vivo. PMID:23735699

Itoh, Ryuhei; Fujita, Ken-ichi; Mu, Anfeng; Kim, Dao Hoang Thien; Tai, Tran Tien; Sagami, Ikuko; Taketani, Shigeru

2013-06-02

176

Strategic Automation of Emotion Regulation  

Microsoft Academic Search

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,

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

2009-01-01

177

Regulation of cholesterol homeostasis.  

PubMed

Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-coding RNA's. The last two decades insight into underlying mechanisms has increased vastly but there are still a lot of unknowns, particularly regarding intracellular cholesterol transport. After decades of concentration on the liver, in recent years the intestine has come into focus as an important control point in cholesterol homeostasis. This review will discuss current knowledge of cholesterol physiology, with emphasis on cholesterol absorption, cholesterol synthesis and fecal excretion, and new (possible) therapeutic options for hypercholesterolemia. PMID:22721653

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

2012-06-19

178

Orbit utilization - Current regulations  

NASA Astrophysics Data System (ADS)

It is pointed out that an increasingly efficient use of the geostationary satellite orbit and spectrum is necessary to accommodate the growing number of planned U.S. domestic satellites, as well as those of other countries. Technical efficiency can be maximized by designing satellites in a homogeneous manner which minimizes transmission differences between satellites. However, flexibility is also needed to design domestic satellite facilities to respond to the diverse demands in a competitive market. The Federal Communication Commission (FCC) seeks to achieve a balance between these goals in their domestic satellite policies and regulations. In December 1980, the FCC authorized the construction of some 22 new domestic satellites and the launch of 18 satellites. Attention is given to orbit use policies and reduced orbital spacings.

Lepkowski, R. J.

179

Steamlined nuclear regulation  

SciTech Connect

Whatever form is taken by the power reactor of the future, it will be subject to government regulation. That is a certainty. It seems equally clear that if nuclear power is to approach its maximum potential cost effectiveness while fully protecting public health and safety and the environment, the applicable nuclear regulatory process must be both effective and efficient. This paper outlines the major constraints and requirements involved in the development of an effective, streamlined nuclear regulatory process. It then suggests a general approach to the development of more efficient regulatory processes based upon the experience gained in the adaptation of classic system engineering techniques to the definition and implemention of such a process for a high-level radioactive waste geologic repository.

Romine, D.T.

1993-06-01

180

Factors regulating microglia activation  

PubMed Central

Microglia are resident macrophages of the central nervous system (CNS) that display high functional similarities to other tissue macrophages. However, it is especially important to create and maintain an intact tissue homeostasis to support the neuronal cells, which are very sensitive even to minor changes in their environment. The transition from the “resting” but surveying microglial phenotype to an activated stage is tightly regulated by several intrinsic (e.g., Runx-1, Irf8, and Pu.1) and extrinsic factors (e.g., CD200, CX3CR1, and TREM2). Under physiological conditions, minor changes of those factors are sufficient to cause fatal dysregulation of microglial cell homeostasis and result in severe CNS pathologies. In this review, we discuss recent achievements that gave new insights into mechanisms that ensure microglia quiescence.

Kierdorf, Katrin; Prinz, Marco

2013-01-01

181

Regulation of Terpene Metabolism  

SciTech Connect

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.

Rodney Croteau

2004-03-14

182

Factors regulating microglia activation.  

PubMed

Microglia are resident macrophages of the central nervous system (CNS) that display high functional similarities to other tissue macrophages. However, it is especially important to create and maintain an intact tissue homeostasis to support the neuronal cells, which are very sensitive even to minor changes in their environment. The transition from the "resting" but surveying microglial phenotype to an activated stage is tightly regulated by several intrinsic (e.g., Runx-1, Irf8, and Pu.1) and extrinsic factors (e.g., CD200, CX3CR1, and TREM2). Under physiological conditions, minor changes of those factors are sufficient to cause fatal dysregulation of microglial cell homeostasis and result in severe CNS pathologies. In this review, we discuss recent achievements that gave new insights into mechanisms that ensure microglia quiescence. PMID:23630462

Kierdorf, Katrin; Prinz, Marco

2013-04-23

183

Low pressure gas regulator  

SciTech Connect

This patent describes a low pressure gas regulator. It comprises: a body member, an inlet opening formed in the body member, an outlet opening formed in the body member, a partition in the body member which separates the inlet and outlet opening and formed with an opening which is surrounded with a valve seat, a moveable diaphragm mounted in the body member so as to have atmospheric pressure on one side thereof and the pressure of the outlet opening on the other side, a valve stem connected to the diaphragm and extending through the opening in the partition, a ball valve mounted on the valve stem in the inlet opening, and a relatively thick soft resilient cover mounted over the ball valve and engageable with the valve seat. Wherein the cover has a first thicker portion which engages the valve seat and a second portion which does not engage the valve seat which is thinner than the first portion.

Wallace, E.E.

1990-02-06

184

Centrosomes in cellular regulation.  

PubMed

Centrosomes, spindle pole bodies, and related structures in other organisms are a morphologically diverse group of organelles that share a common ability to nucleate and organize microtubules and are thus referred to as microtubule organizing centers or MTOCs. Features associated with MTOCs include organization of mitotic spindles, formation of primary cilia, progression through cytokinesis, and self-duplication once per cell cycle. Centrosomes bind more than 100 regulatory proteins, whose identities suggest roles in a multitude of cellular functions. In fact, recent work has shown that MTOCs are required for several regulatory functions including cell cycle transitions, cellular responses to stress, and organization of signal transduction pathways. These new liaisons between MTOCs and cellular regulation are the focus of this review. Elucidation of these and other previously unappreciated centrosome functions promises to yield exciting scientific discovery for some time to come. PMID:16212501

Doxsey, Stephen; McCollum, Dannel; Theurkauf, William

2005-01-01

185

Comparative genomic analysis of teleost fish bmal genes.  

PubMed

Bmal1 (Brain and muscle ARNT like 1) gene is a key circadian clock gene. Tetrapods also have the second Bmal gene, Bmal2. Fruit fly has only one bmal1/cycle gene. Interrogation of the five teleost fish genome sequences coupled with phylogenetic and splice site analyses found that zebrafish have two bmal1 genes, bmal1a and bmal1b, and bmal2a; Japanese pufferfish (fugu), green spotted pufferfish (tetraodon) and Japanese medaka fish each have two bmal2 genes, bmal2a and bmal2b, and bmal1a; and three-spine stickleback have bmal1a and bmal2b. Syntenic analysis further indicated that zebrafish bmal1a/bmal1b, and fugu, tetraodon and medaka bmal2a/bmal2b are ancient duplicates. Although the dN/dS ratios of these four fish bmal duplicates are all <1, implicating they have been under purifying selection, the Tajima relative rate test showed that fugu, tetraodon and medaka bmal2a/bmal2b have asymmetric evolutionary rates, suggesting that one of these duplicates have been subject to positive selection or relaxed functional constraint. These results support the notion that teleost fish bmal genes were derived from the fish-specific genome duplication (FSGD), divergent resolution following the duplication led to retaining different ancient bmal duplicates in different fishes, which could have shaped the evolution of the complex teleost fish timekeeping mechanisms. PMID:18850331

Wang, Han

2008-10-14

186

Risking Regulation, Regulating Risk: Lessons from the Transatlantic Biotech Dispute  

Microsoft Academic Search

Debates over the future of new technologies frequently implicate governmental policies and regulation, the purpose of which has traditionally been to mitigate the dangers of new technologies through promotion of conditions of safe use. It is increasingly recognized, however, that regulation is predicated on a particular conception of the nature of risk which may or may not correspond to the

Noah Zerbe

2007-01-01

187

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

Microsoft Academic Search

This paper uses plant-level data from the Census of Manufactures and the variation in toxic air pollution regulations across states to measure the effects of laws that are more stringent for new sources of pollution than for existing sources (so-called ‘grandfather’ regulations). Of particular interest is the resulting ‘new source bias’ and its effects on capital vintage and investment. Two

Arik Levinson

1999-01-01

188

[Epigenetic regulation in depression].  

PubMed

Recent research has raised the notion that epigenetic mechanisms (e.g., DNA methylation and histone modifications), which exert lasting control over gene expression without altering the genetic code, could mediate stable changes in brain function. However, the role of environmental factors along with genetic factors in the epigenetic regulation of the pathogenesis of depression is largely unknown. Two genetically distinct mice strains, BALB/c (BALB) and C57BL/6 (B6), exhibit different behavioral responses to chronic stress. With chronic stress, BALB mice showed depressive-like behaviors, but not B6 mice, and glial cell-derived neurotrophic factor (GDNF) expression level was decreased in the ventral striatum of BALB mice but increased in B6 mice. In BALB mice, depressive-like behaviors and decreased GDNF expression were recovered by chronic antidepressant treatment. Therefore, we used these two mice strains to investigate how the epigenetic status of the GDNF gene in the ventral striatum modulates stress vulnerability. Both mice strains showed increased DNA methylation levels and MeCP2 recruitment in the GDNF promoter region. However, histone H3 acetylation level was decreased in BALB mice, but increased in B6 mice. Furthermore, BALB mice showed increased histone deacetylase2 (HDAC2) expression level and Re-ChIP assay revealed HDAC2-MeCP2 complex in BALB mice. Our results indicate the crucial role of histone modification by HDAC2 and MeCP2 complex for the control of GDNF expression and subsequent behavioral responses to chronic stress, in other words, the susceptibility to stress. In addition, we investigated the effect of antidepressants on the epigenetic regulation of GDNF expression. We found a reduced level of HDAC4 recruitment at the GDNF promoter region with antidepressants. Thus, our data suggest that antidepressants increase transcriptional activity of the GDNF gene through the modulation of histone acetylation by HDAC4. Finally, we examined the expressions of GDNF and epigenetic-related molecules mRNAs with major depressive and bipolar disorder patients by using quantitative real-time PCR. We found the aberrant expression of GDNF and epigenetic-related genes including HDAC2 and HDAC4 in mood disorder patients. Thus, our data provide novel insights suggesting that epigenetic mechanisms of GDNF expression are involved in the pathogenesis or pathophysiology of depression. PMID:23012885

Otsuki, Koji; Uchida, Shusaku; Hobara, Teruyuki; Yamagata, Hirotaka; Watanabe, Yoshifumi

2012-08-01

189

Deceptive Business Practices: Federal Regulations.  

ERIC Educational Resources Information Center

|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,…

Rohrer, Daniel Morgan

190

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. ...

191

Regulation vs. Competition in Telecommunications  

Microsoft Academic Search

Standard microeconomics tells us that enforcing competition raises social welfare. Second we know form the theory of natural monopoly regulation that Ramsey-pricing will maximize your welfare function. This article tries to analyze a multiproduct enterprise producing in both, markets with competition and markets without competition. The latter ones are considered to be subject to regulation. The article starts with a

Leopold Sgner

192

Technological Change in Regulated Industries.  

ERIC Educational Resources Information Center

|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…

Capron, William M., Ed.

193

Automated regulation of hemodynamic variables  

Microsoft Academic Search

Experimental studies of two control methodologies for regulating multiple variables in critical care patients are described. The control strategies for the regulation of mean arterial pressure and cardiac output use vasoactive and inotropic drugs. Corresponding experimental results from the evaluation of the controllers with canines are presented.

Ramesh R. Rao; Cesar C. Palerm; Brian Aufderheide; B. Wayne Bequette

2001-01-01

194

Bank Regulation, Compliance and Enforcement  

Microsoft Academic Search

A model is presented where the question of bank regulation is developed under a principal-agent scenario in a regime where the regulator has limited resources and banks may have an incentive to act ultra virus the regulatory standards. If banks are subject to random audit, then compliance is achieved through a system of fines determined according to the extent of

Rupinder Singh

2000-01-01

195

Regulated secretion of conventional lysosomes  

Microsoft Academic Search

Regulated secretion has been traditionally regarded as a specialized process present in only a few cell types. Similarly, the secretory lysosomes of hematopoietic cells have been viewed as ‘modified’ organelles that acquired the machinery for regulated exocytosis. However, there is evidence that conventional lysosomes can, in many cell types, respond to rises in the intracellular free Ca2+ concentration by fusing

Norma W Andrews

2000-01-01

196

Manual for Regulating Water Systems.  

National Technical Information Service (NTIS)

Practical aspects of regulation are detailed as a guide to commissioning engineers and designers. Regulation is defined as a process during which the flow of water through a distribution system is measured and adjusted to achieve the design flows within a...

1979-01-01

197

Regulating Pornography: A Public Dilemma.  

ERIC Educational Resources Information Center

|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)|

Thompson, Margaret E.; And Others

1990-01-01

198

PLANT CHITINASES - REGULATION AND FUNCTION  

Microsoft Academic Search

The aim of this review is to present the current state of knowledge on plant chitinases and their regulation and function. Chitinases are up-regulated by a variety of stress conditions, both biotic and abiotic, and by such phytohormones as ethylene, jasmonic acid, and salicylic acid. Like other PR proteins, chitinases play a role in plant resistance against distinct pathogens. Moreover,

ANNA KASPRZEWSKA

2003-01-01

199

Public Perception' of Government Regulation  

Microsoft Academic Search

Conventional wisdom has it that people view current levels of government regulation of business activities as excessive and inefficient. This study was designed to investigate people's perception of government regulation. The study was conducted through personal interviews with 579 males, 1849 years old, in seven major metropolitan areas across the nation. Individuals were asked about their feelings as to 1)

Bernard J. Cunningham; S. Prakash Sethi; Thomas Turicchi

1982-01-01

200

Affect and Self-Regulation  

ERIC Educational Resources Information Center

|This paper presents affect as an essential aspect of students' self-reflection and self-regulation. The introduced concepts of self-system and self-system process stress the importance of self-appraisals of personal competence and agency in affective responses and self-regulation in problem solving. Students are viewed as agents who constantly…

Malmivuori, Marja-Liisa

2006-01-01

201

Splicing regulators: targets and drugs  

Microsoft Academic Search

Silencing of splicing regulators by RNA interference, combined with splicing-specific microarrays, has revealed a complex network of distinct alternative splicing events in Drosophila, while a high-throughput screen of more than 6,000 compounds has identified drugs that interfere specifically and directly with one class of splicing regulators in human cells.

Gene Wei-Ming Yeo

2005-01-01

202

75 FR 32635 - Defense Acquisition Regulations System; Defense Federal Acquisition Regulation Supplement...  

Federal Register 2010, 2011, 2012, 2013

...Defense Acquisition Regulations System...217, 225, et al. Defense Federal Acquisition Regulation Supplements; Proposed Rules...DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 252...

2010-06-08

203

Gene regulation of steroidogenesis.  

PubMed

The biosynthesis of various steroid hormones in animal tissues are catalyzed by six forms of cytochrome P450 and two hydroxysteroid dehydrogenases. The tissue-specific expression of these enzymes, which are under the control of the pituitary gland and mainly regulated at the transcriptional level, determines the steroidogenesis of animal tissues. Analysis of the promoter regions of the steroidogenic P450 genes revealed various cis-acting elements, including cAMP-responsive sequences (CRS), Ad4, and GC-rich sequences, which were needed for the tissue-specific and cAMP-dependent expression of the genes. Some of the nuclear protein factors binding to the cis-acting elements were isolated and characterized. A zinc-finger protein binding to Ad4, which was termed Ad4BP or SF-1, seems to be of particular importance in steroidogenesis. Ad4BP was expressed in the cells of the steroidogenic tissues, adrenal gland and gonadal tissues, in the rat fetus prior to the expression of steroidogenic P450s, and remained expressed only in steroidogenic cells in adult animals. Close investigation of the temporal and spacial expression of Ad4BP in the fetal tissues suggested its role in the differentiation of the steroidogenic tissues and the sex determination of the gonadal tissues. PMID:7626452

Omura, T; Morohashi, K

1995-06-01

204

Visibility: science and regulation.  

PubMed

The 1999 Regional Haze Rule provides a context for this review of visibility, the science that describes it, and the use of that science in regulatory guidance. The scientific basis for the 1999 regulation is adequate. The deciview metric that tracks progress is an imperfect but objective measure of what people see near the prevailing visual range. The definition of natural visibility conditions is adequate for current planning, but it will need to be refined as visibility improves. Emissions from other countries will set achievable levels above those produced by natural sources. Some natural events, notably dust storms and wildfires, are episodic and cannot be represented by annual average background values or emission estimates. Sulfur dioxide (SO2) emission reductions correspond with lower sulfate (SO4(2-)) concentrations and visibility improvements in the regions where these have occurred. Non-road emissions have been growing more rapidly than emissions from other sources, which have remained stable or decreased since 1970. Simpler models representing transport, limiting precursor pollutants, and gas-to-particle equilibrium should be used to understand where and when emission reductions will be effective, rather than large complex models that have insufficient input and validation measurements. Examples of model-based source attribution show large differences among estimates from various modeling systems and with ambient measurements. PMID:12074426

Watson, John G

2002-06-01

205

Regulation of Chk1  

PubMed Central

Chk1 is a serine/threonine protein kinase that is the effector of the G2 DNA damage checkpoint. Chk1 homologs have a highly conserved N-terminal kinase domain, and a less conserved C-terminal regulatory domain of ~200 residues. In response to a variety of genomic lesions, a number of proteins collaborate to activate Chk1, which in turn ensures that the mitotic cyclin-dependent kinase Cdc2 remains in an inactive state until DNA repair is completed. Chk1 activation requires the phosphorylation of residues in the C-terminal domain, and this is catalyzed by the ATR protein kinase. How phosphorylation of the C-terminal regulatory domain activates the N-terminal kinase domain has not been elucidated, though some studies have suggested that this phosphorylation relieves an inhibitory intramolecular interaction between the N- and C-termini. However, recent studies in the fission yeast Schizosaccharomyces pombe have revealed that there is more to Chk1 regulation than this auto-inhibition model, and we review these findings and their implication to the biology of this genome integrity determinant.

Tapia-Alveal, Claudia; Calonge, Teresa M; O'Connell, Matthew J

2009-01-01

206

Fuel pressure regulator  

SciTech Connect

This patent describes a fuel pressure regulator for internal combustion of automobiles and the like. It comprises a body including first, second and third chambers; a resilient impervious diaphragm separating the second and third chambers; a fuel inlet communicating with the first chamber; a fuel outlet communicating with the second chamber; a passageway for permitting fluid communication between the first and second chambers; a ball valve means adjacent one end of the passageway ball valve means comprising a movable ball and a movable valve seat; first biasing means for biasing the ball valve means at one end of the passageway; actuating means for actuating the ball valve means at the one end of the passageway, the actuating comprising a piston positioned in the second chamber in abutment with one side of the resilient impervious diaphragm and a stem extending from the piston with its distal end adapted to bear against the ball of the valve means; second biasing means in the third chamber in abutment with the other side of the resilient impervious diaphragm for biasing the resilient diaphragm to move the piston toward the first chamber; stem guide means positioned between the first and second chambers along the length of the stem and intermediate the ends of the stem for guiding the stem to limit the motion of the stem to a substantially linear, reciprocating motion while in contact with the ball of the ball valve means.

Grant, B.

1992-05-19

207

Regulation of cholangiocyte proliferation.  

PubMed

Intrahepatic bile duct epithelial cells (i.e., cholangiocytes) are the target cells of chronic cholestatic liver diseases (i.e., cholangiopathies), which makes these cells of great interest to clinical hepatologists. This review will focus on "typical" cholangiocyte proliferation, whereas "atypical" (extension of cholangiocyte proliferation into parenchyma), and premalignant "oval" cell proliferation are reviewed elsewhere. The bile duct ligated (BDL) rat model, where most of the known mechanisms of cholangiocyte proliferation have been illustrated, was the first and remains the prototype animal model for "typical" cholangiocyte proliferation. Following a short overview of cholangiocyte functions, we briefly discuss the: (i) in vivo models [i.e., BDL (Fig. 1 and 4), chronic alpha-naphthylisothiocyanate (ANIT) or bile acid feeding (Fig. 2), acute carbon tetrachloride (CCl4) feeding and partial hepatectomy; and (ii) in vitro experimental tools [e.g., purified cholangiocytes and isolated intrahepatic bile duct units (IBDU)] that are key to the understanding of the mechanisms of "typical" cholangiocyte growth. In the second part of the review, we discuss a number of potential factors or conditions [e.g., gastrointestinal hormones, nerves, estrogens, blood supply, and growth factors] as well as the intracellular mechanisms [e.g., adenosine 3',5'-monophosphate (cAMP), and protein kinase C (PKC)] that may regulate "typical" cholangiocyte hyperplasia. PMID:11318975

LeSage, G; Glaser, S; Alpini, G

2001-04-01

208

Outsourcing self-regulation.  

PubMed

Three studies demonstrate a novel phenomenon--self-regulatory outsourcing--in which thinking about how other people can be instrumental (i.e., helpful) for a given goal undermines motivation to expend effort on that goal. In Experiment 1, participants who thought about how their partner helped them with health goals (as opposed to career goals) planned to spend less time and effort on health goals in the upcoming week. This pattern was stronger for depleted participants than for nondepleted participants. In Experiment 2, participants who thought about how their partner helped them with academic-achievement goals procrastinated more, leaving themselves less time for an academic task, than did participants in two control conditions. This pattern was stronger for participants who were told that procrastinating would drain their resources for the academic task than for participants who were told that procrastinating would not drain their resources for that task. In Experiment 3, participants who decreased their effort after thinking of an instrumental significant other reported higher relationship commitment to that individual than did participants who did not decrease their effort. The possibility for shared (or transactive) self-regulation is discussed. PMID:21303992

Fitzsimons, Gráinne M; Finkel, Eli J

2011-02-08

209

A framework for insurance regulation of China  

Microsoft Academic Search

On the base of comparative analysis for a main part of current western insurance regulation theories, a framework of our national insurance regulation theories is provided. The framework encompasses the public interest theory of regulation at the prior place, supplemented with the capture theory of regulation and the economic theory of regulation.

Shi Lei; Huang Yanmin; Zhang Yangui

2010-01-01

210

Assessing Academic Self-Regulated Learning  

Microsoft Academic Search

Abstract Self-regulated learning concerns the application of general models of regulation and self- regulation to issues of learning especially within academic contexts. Self-regulated learning is an active, constructive process whereby learners set goals for their learning and then attempt to monitor, regulate, and control their cognition, motivation, and behavior, guided and constrained

Christopher A. Wolters; Paul R. Pintrich; Stuart A. Karabenick

211

Ball valve regulator reduces noise at regulating stations  

SciTech Connect

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, control capabilities, rangeability, and dependability makes the below grade ball valve regulator the preferred method for controlling natural gas flow. Its long-term reliability makes the below grade ball valve regulator the ideal method of, not only maintaining superior flow characteristics, but also of greatly reducing noise created in the station facilities.

Hogan, M.P.

1998-10-01

212

77 FR 43082 - Federal Acquisition Regulation; Information Collection; Commerce Patent Regulations  

Federal Register 2010, 2011, 2012, 2013

...Regulation; Information Collection; Commerce Patent Regulations AGENCIES: Department...requirement concerning Department of Commerce patent regulations. Public comments...Information Collection 9000- 0095, Commerce Patent Regulations, by any of the...

2012-07-23

213

78 FR 31551 - Federal Acquisition Regulation; Submission for OMB Review; Commerce Patent Regulations  

Federal Register 2010, 2011, 2012, 2013

...Regulation; Submission for OMB Review; Commerce Patent Regulations AGENCIES: Department...requirement concerning Department of Commerce patent regulations. A notice was published...Information Collection 9000- 0095, Commerce Patent Regulations, by any of the...

2013-05-24

214

New EU regulations in endoscopy.  

PubMed

As a result of European unification, new regulations valid within the territory of the European Union (EU) have been negotiated and published. As in other medical fields, the Medical Device Directive (MDD) is the most important new regulation and also effects endoscopy. In a transition period until June 1998, the MDD will be transposed into national law by the member states of the EU. Compliance with the MDD and other European regulations is indicated by the CE mark affixed to the product. PMID:8565892

Wächter, M; Diekjobst, T

1995-09-01

215

76 FR 35740 - North Korea Sanctions Regulations  

Federal Register 2010, 2011, 2012, 2013

...Foreign Assets Control 31 CFR Part 510 North Korea Sanctions Regulations AGENCY: Office of...OFAC'') is amending the North Korea Sanctions Regulations to implement Executive...Foreign Assets Control published the North Korea Sanctions Regulations, 31 CFR part...

2011-06-20

216

78 FR 44393 - Semiannual Agenda of Regulations  

Federal Register 2010, 2011, 2012, 2013

...records.'' Deposit Insurance Regulations; Deposits in Foreign Branches...proposing to amend its deposit insurance regulations, with respect to deposits...definitions used in the deposit insurance assessment regulations and those used within...

2013-07-23

217

75 FR 5169 - Insurance Cost Information Regulation  

Federal Register 2010, 2011, 2012, 2013

...NHTSA 2008-0032] Insurance Cost Information Regulation AGENCY: National...CFR Part 582, Insurance Cost Information Regulation, to require all...On the Laws/Regulations page, the Comparison of Insurance Costs is...

2010-02-01

218

18 CFR 415.30 - Regulations generally.  

Code of Federal Regulations, 2013 CFR

...Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Standards § 415.30 Regulations generally. The uses of land within a flood hazard area shall be...

2013-04-01

219

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 ...

220

7 CFR 983.50 - Aflatoxin regulations.  

Code of Federal Regulations, 2010 CFR

...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...

2010-01-01

221

7 CFR 983.50 - Aflatoxin regulations.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 2013-01-01 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...

2013-01-01

222

7 CFR 983.150 - Aflatoxin regulations.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 2010-01-01 false Aflatoxin regulations. 983.150 Section 983...Rules and Regulations § 983.150 Aflatoxin regulations. (a) Maximum level...consumption, pistachios that exceed an aflatoxin level of 15 ppb; Provided,...

2010-01-01

223

Post regulation circuit with energy storage  

DOEpatents

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.

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

1992-01-01

224

Self-regulated reionization  

NASA Astrophysics Data System (ADS)

Recently, we have presented the first, truly large-scale radiative transfer simulations of inhomogeneous cosmic reionization which resolve all the possible halo sources down to the dwarf galaxy mass range, M >~ 109Msolar, in a comoving volume (100h-1 Mpc)3. This is large enough to sample the global mean history, geometry and statistical properties of reionization fairly and accurately for the first time. Here we present new simulations which extend the source halo mass range downward to 108Msolar, to capture the full range of halo masses thought to be primarily responsible for reionization by their star formation following atomic hydrogen radiative cooling and gravitational collapse. Haloes below about 109Msolar, however, are subject to Jeans-mass filtering in the ionized regions, which suppresses their baryonic content and their ability to release ionizing radiation. By including these smaller mass haloes but accounting for their suppression, too, we find that reionization is `self-regulating', as follows. As the mean ionized fraction rises, so does the fraction of the volume within which suppression occurs. Hence, the degree of suppression is related to the mean ionized fraction. Since low-mass haloes with high efficiency (i.e. high emissivity) achieve a given mean ionized fraction earlier than do those with low efficiency, Jeans-mass filtering compensates for the difference in the emissivity of the suppressible haloes in these two cases. As a result, in the presence of lower mass source haloes, reionization begins earlier, but the later stages of reionization and the time of overlap are dictated by the efficiency of the higher mass haloes, independent of the efficiency of the suppressible, lower mass haloes. Hence, while the lower mass haloes do not alter the overlap redshift, zov, they serve to boost the electron-scattering optical depth of the universe, ?es. This may explain why observations of quasar absorption spectra at high redshift find that reionization ended late (zov < 7), while cosmic microwave background polarization measurements report a large enough ?es that reionization must have begun much earlier (z > 11). We present results for the Lambda cold dark matter universe with cosmological parameters from both 1- and 3-yr data releases of Wilkinson Microwave Anisotropy Probe. Reionization histories consistent with current constraints on zov and ?es are shown to be achievable with standard stellar sources in haloes above 108Msolar. Neither minihaloes nor exotic sources are required, and the phenomenon of `double reionization' previously suggested does not occur.

Iliev, Ilian T.; Mellema, Garrelt; Shapiro, Paul R.; Pen, Ue-Li

2007-04-01

225

Regulation of Repressor Expression in ?*  

PubMed Central

A new gene in bacteriophage ? is described. The product of this gene cro prevents expression of immunity and regulates the expression of those genes to the left of the immunity region. cro- mutants have been isolated and characterized.

Eisen, H.; Brachet, P.; Silva, L. Pereira da; Jacob, F.

1970-01-01

226

Turgor regulation in hyphal organisms.  

PubMed

Turgor regulation in two saprophytic hyphal organisms was examined directly with the pressure probe technique. The ascomycete Neurospora crassa, a terrestrial fungi, regulates turgor after hyperosmotic treatments when growing in a minimal medium containing K(+), Mg(2+), Ca(2+), Cl(-), and sucrose. Turgor recovery by N. crassa after hyperosmotic treatment is concurrent with changes in ion transport: hyperpolarization of the plasma membrane potential and a decline in transmembrane ion conductance. In contrast the oomycete Achlya bisexualis, a freshwater hyphal organism, does not regulate turgor after hyperosmotic treatment, although small transient increases in turgor were occasionally observed. We also monitored turgor in both organisms during hypoosmotic treatment and did not observe a turgor increase, possibly due to turgor regulation. Both hyphal organisms grow with similar morphologies, cellular expansion rates and turgor (0.4-0.7 MPa), yet respond differently to osmotic stress. The results do not support the assumption of a universal mechanism of tip growth driven by cell turgor. PMID:15465389

Lew, Roger R; Levina, Natalia N; Walker, Sophie K; Garrill, Ashley

2004-11-01

227

Cell Biology: Growth Regulation, Differentiation.  

National Technical Information Service (NTIS)

The scope of this Cancergram includes factors which have significant effects on growth and differentiation of normal and neoplastic cells in vivo and in vitro. The scope centers on the production, physical characteristics, and action of these growth regul...

1980-01-01

228

Cell Biology: Growth Regulation, Differentiation.  

National Technical Information Service (NTIS)

The scope of this Cancergram includes factors which have significant effects on growth and differentiation of normal and neoplastic cells in vivo and in vitro. The scope centers on the production, physical characteristics, and action of these growth regul...

1984-01-01

229

Cell Biology: Growth Regulation, Differentiation.  

National Technical Information Service (NTIS)

The scope of this Cancergram includes factors which have significant effects on growth and differentiation of normal and neoplastic cells in vivo and in vitro. The scope centers on the production, physical characteristics, and action of these growth regul...

1983-01-01

230

Cell Biology: Growth Regulation, Differentiation.  

National Technical Information Service (NTIS)

The scope of this Cancergram includes factors which have significant effects on growth and differentiation of normal and neoplastic cells in vivo and in vitro. The scope centers on the production, physical characteristics, and action of these growth regul...

1981-01-01

231

Cell Biology: Growth Regulation, Differentiation.  

National Technical Information Service (NTIS)

The scope of this Cancergram includes factors which have significant effects on growth and differentiation of normal and neoplastic cells in vivo and in vitro. The scope centers on the production, physical characteristics, and action of these growth regul...

1982-01-01

232

Regulation of the Blood Supply  

Center for Biologics Evaluation and Research (CBER)

... Vaccines, Blood & Biologics. ... Regulation of the Blood Supply. FDA/CBER is responsible for regulatory oversight of the US blood supply. ... More results from www.fda.gov/biologicsbloodvaccines/bloodbloodproducts/regulationofthebloodsupply

233

Method of regulating plant growth  

US Patent & Trademark Office Database

A method for producing a growth regulating effect in a plant which comprises applying to the plant an effective amount, with respect to the plant being treated, of cinchoninic acid or a derivative thereof.

Starke; George Robert (Perkasie, PA); Cooke; Anson Richard (Hatfield, PA)

1977-02-22

234

Federal Regulations for Clinical Investigators  

Center for Drug Evaluation (CDER)

... food and drugs. The regulations document all actions of all drug sponsors that are required under Federal law. Part 54 ... More results from www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved

235

Physiological Mechanisms Impacting Weight Regulation  

Microsoft Academic Search

Within the framework of body weight regulation, the first law of thermodynamics (i.e., the Law of Conservation of Energy -\\u000a “Energy cannot be created nor destroyed, it simply is transferred from one form to another”) concisely and eloquently identifies\\u000a the basic paradigm of body weight regulation, and is described by the equation below: Energy intake + Energy expenditure =\\u000a ±

David Fields; Higgins Paul

236

RAGs and Regulation of Autoantibodies  

Microsoft Academic Search

? Abstract Autoreactive antibodies are etiologic agents in a number,of autoim- mune,diseases. Like all other antibodies these antibodies are produced,in developing,B cells by V(D)J recombination,in the bone marrow. Three mechanisms,regulate autore- active B cells: deletion, receptor editing, and anergy. Here we review the prevalence of autoantibodies in the initial antibody repertoire, their regulation by receptor editing, and the role of

Mila Jankovic; Rafael Casellas; Nikos Yannoutsos; Hedda Wardemann; Michel C. Nussenzweig

2004-01-01

237

Modulating Transcription with Artificial Regulators  

Microsoft Academic Search

\\u000a Many human diseases are characterized by altered gene expression patterns caused by malfunctioning transcriptional regulators.\\u000a This has inspired intense interest in the development of artificial transcription factors that regulate the expression of\\u000a specific genes either positively or negatively. Particular success has been achieved through the use of DNA-binding molecules\\u000a such as triplex-forming oligonucleotides, peptide nucleic acids, and polyamides that upregulate

A. K. Mapp; A. Z. Ansari; Z. Wu; Z. Lu

238

Metabolic regulation by p53  

Microsoft Academic Search

We are increasingly aware that cellular metabolism plays a vital role in diseases such as cancer, and that p53 is an important\\u000a regulator of metabolic pathways. By transcriptional activation and other means, p53 is able to contribute to the regulation\\u000a of glycolysis, oxidative phosphorylation, glutaminolysis, insulin sensitivity, nucleotide biosynthesis, mitochondrial integrity,\\u000a fatty acid oxidation, antioxidant response, autophagy and mTOR signalling.

Oliver D. K. Maddocks; Karen H. Vousden

2011-01-01

239

Appendix 2: Regulation Concept Paper Template  

Center for Biologics Evaluation and Research (CBER)

Text VersionPage 1. Appendix 2: Regulation Concept Paper Template Regulation Concept Paper Template Instructions: Document ... More results from www.fda.gov/downloads/biologicsbloodvaccines/guidancecomplianceregulatoryinformation

240

7 CFR 29.29 - Regulations.  

Code of Federal Regulations, 2013 CFR

...29 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT...AND STANDARD CONTAINER REGULATIONS TOBACCO INSPECTION...

2013-01-01

241

32 CFR 770.7 - Violations and environmental regulations.  

Code of Federal Regulations, 2010 CFR

...PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps...regulations. Violations of hunting regulations, fishing regulations, safety regulations, or principles...administrative restriction of hunting or fishing privileges...

2010-07-01

242

32 CFR 770.7 - Violations and environmental regulations.  

Code of Federal Regulations, 2010 CFR

...PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps...regulations. Violations of hunting regulations, fishing regulations, safety regulations, or principles...administrative restriction of hunting or fishing privileges...

2009-07-01

243

76 FR 35739 - Foreign Assets Control Regulations; Transaction Control Regulations (Regulations Prohibiting...  

Federal Register 2010, 2011, 2012, 2013

...DEPARTMENT OF THE TREASURY Office of Foreign Assets Control 31 CFR Parts 500 and 505 Foreign Assets Control Regulations; Transaction Control...Foreign Countries) AGENCY: Office of Foreign Assets Control, Treasury. ACTION: Final...

2011-06-20

244

Regulating the regulator: post-translational modification of RAS.  

PubMed

RAS proteins are monomeric GTPases that act as binary molecular switches to regulate a wide range of cellular processes. The exchange of GTP for GDP on RAS is regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), which regulate the activation state of RAS without covalently modifying it. By contrast, post-translational modifications (PTMs) of RAS proteins direct them to various cellular membranes and, in some cases, modulate GTP-GDP exchange. Important RAS PTMs include the constitutive and irreversible remodelling of its carboxy-terminal CAAX motif by farnesylation, proteolysis and methylation, reversible palmitoylation, and conditional modifications, including phosphorylation, peptidyl-prolyl isomerisation, monoubiquitylation, diubiquitylation, nitrosylation, ADP ribosylation and glucosylation. PMID:22189424

Ahearn, Ian M; Haigis, Kevin; Bar-Sagi, Dafna; Philips, Mark R

2011-12-22

245

Regulating the Regulators: microRNA and Asthma  

PubMed Central

One obstacle to developing an effective therapeutic strategy to treat or prevent asthma is that the fundamental causes of asthma are not totally understood. Asthma is thought to be a chronic TH2 immune-mediated inflammatory disease. Epigenetic changes are recognized to play a role in the initiation and maintenance of a TH2 response. MicroRNAs (miRNAs) are key epigenetic regulators of gene expression, and their expression is highly regulated, therefore, deregulation of miRNAs may play an important role in the pathogenesis of asthma. Profiling circulating miRNA might provide the highest specificity and sensitivity to diagnose asthma; similarly, correcting potential defects in the miRNA regulation network may lead to new therapeutic modalities to treat this disease.

2011-01-01

246

How Europe regulates its genes  

SciTech Connect

As Europe moves toward unification in 1992, more than two dozen regulations and directives that will affect biotech are working their way through the complex European legislative system. The result could mean tough scrutiny for genetically engineered products. One reason is that the European Community (EC) has chosen to examine genetically engineered products as a special category - an approach the FDA has rejected. Another is that the EC is considering enacting regulations that would mandate consideration of the socioeconomic effects of biotech products in addition to their safety. In addition, some - particularly in industry - fear a nightmare of overlapping and contradictory regulations. It's too soon to tell how well the European system will work, or how stifling the regulations might be. In all likelihood the regulations emerging in Europe won't be demonstrably superior - or inferior - to the American ones, just different, with different strengths and weaknesses. But since many US biotech companies are looking to the huge market that a unified Europe represents, the specifics of those strengths and weaknesses will ultimately be of more than passing interest.

Balter, M.

1991-06-07

247

Neuronal regulation of tendon homoeostasis.  

PubMed

The regulation of tendon homoeostasis, including adaptation to loading, is still not fully understood. Accumulating data, however, demonstrates that in addition to afferent (sensory) functions, the nervous system, via efferent pathways which are associated with through specific neuronal mediators plays an active role in regulating pain, inflammation and tendon homeostasis. This neuronal regulation of intact-, healing- and tendinopathic tendons has been shown to be mediated by three major groups of molecules including opioid, autonomic and excitatory glutamatergic neuroregulators. In intact healthy tendons the neuromediators are found in the surrounding structures: paratenon, endotenon and epitenon, whereas the proper tendon itself is practically devoid of neurovascular supply. This neuroanatomy reflects that normal tendon homoeostasis is regulated from the tendon surroundings. After injury and during tendon repair, however, there is extensive nerve ingrowth into the tendon proper, followed by a time-dependent emergence of sensory, autonomic and glutamatergic mediators, which amplify and fine-tune inflammation and regulate tendon regeneration. In tendinopathic condition, excessive and protracted presence of sensory and glutamatergic neuromediators has been identified, suggesting involvement in inflammatory, nociceptive and hypertrophic (degenerative) tissue responses. Under experimental and clinical conditions of impaired (e.g. diabetes) as well as excessive (e.g. tendinopathy) neuromediator release, dysfunctional tendon homoeostasis develops resulting in chronic pain and gradual degeneration. Thus there is a prospect that in the future pharmacotherapy and tissue engineering approaches targeting neuronal mediators and their receptors may prove to be effective therapies for painful, degenerative and traumatic tendon disorders. PMID:23718724

Ackermann, Paul W

2013-05-30

248

Epigenetic regulation during mammalian oogenesis.  

PubMed

The advent of the epigenetic era has sparked a new frontier in molecular research and the understanding of how development can be regulated beyond direct alterations of the genome. Thus far, the focal point of epigenetic regulation during development has been chromatin modifications that control differential gene expression by DNA methylation and histone alterations. But what of events that alter gene expression without direct influence on the DNA itself? The present review focuses on epigenetic pathways regulating development from oogenesis to organogenesis and back that do not involve methylation of cytosine in DNA. We discuss target components of epigenetic modification such as organelle development, compartmentalisation of maternal factors and molecular mediators in the oocyte and how these factors acting during oogenesis impact on later development. Epigenetic regulation of development, be it via cytosine methylation or not, has wide-ranging effects on the subsequent success of a pregnancy and the intrinsic health of offspring. Perturbations in epigenetic regulation have been clearly associated with disease states in adult offspring, including Type II diabetes, hypertension, cancers and infertility. A clear understanding of all epigenetic mechanisms is paramount when considering the increased use of assisted reproductive techniques and the risks associated with their use. PMID:18154701

Bromfield, John; Messamore, Will; Albertini, David F

2008-01-01

249

Law and regulation of benzene.  

PubMed Central

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.

Feitshans, I L

1989-01-01

250

Government regulations: two sides to the story  

Microsoft Academic Search

Critics who blame regulatory costs for US economic problems fail to consider the benefits of the regulations and fail to distinguish the small contribution that new social regulation makes to the budget. It is important to separate the economic regulations designed to keep the economy running smoothly from the social goals of health, safety, and environment. Social regulation seeks to

Tabb

1980-01-01

251

Adaptive Emotion Regulation among Low-Income  

Microsoft Academic Search

This study examined early childhood predictors of adaptive emotion regulation among economically disadvantaged urban African American children. Vagal tone (VNA), attachment, and regulation capacities were assessed among 69 preschoolers. Two years later, additional indices of child regulation were obtained for 56 of the children. Emotion regulation was assessed through observation, child self-report, parent report, and teacher report. As expected, attachment

Shari L. Kidwell

2007-01-01

252

Automatic emotion regulation during anger provocation  

Microsoft Academic Search

Individuals frequently have to regulate their emotions, especially negative ones, to function successfully. However, deliberate emotion regulation can have significant costs for the individual. Are there less costly ways to achieve emotion regulatory goals? In two studies, we test the hypothesis that more automatic types of emotion regulation might provide the benefits of deliberate emotion regulation without the costs. Study

Iris B. Mauss; Crystal L. Cook; James J. Gross

2007-01-01

253

Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1.  

PubMed

Many metabolic and physiological processes display circadian oscillations. We have shown that the core circadian regulator, CLOCK, is a histone acetyltransferase whose activity is counterbalanced by the nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase SIRT1. Here we show that intracellular NAD+ levels cycle with a 24-hour rhythm, an oscillation driven by the circadian clock. CLOCK:BMAL1 regulates the circadian expression of NAMPT (nicotinamide phosphoribosyltransferase), an enzyme that provides a rate-limiting step in the NAD+ salvage pathway. SIRT1 is recruited to the Nampt promoter and contributes to the circadian synthesis of its own coenzyme. Using the specific inhibitor FK866, we demonstrated that NAMPT is required to modulate circadian gene expression. Our findings in mouse embryo fibroblasts reveal an interlocked transcriptional-enzymatic feedback loop that governs the molecular interplay between cellular metabolism and circadian rhythms. PMID:19286518

Nakahata, Yasukazu; Sahar, Saurabh; Astarita, Giuseppe; Kaluzova, Milota; Sassone-Corsi, Paolo

2009-03-12

254

Planned and proposed pipeline regulations  

SciTech Connect

The Research and Special Programs Administration administers the Natural Gas Pipeline Safety Act of 1968 (NGPSA) and the Hazardous Liquid Pipeline Safety Act of 1979 (HLPSA). The RSPA issues and enforces design, construction, operation and maintenance regulations for natural gas pipelines and hazardous liquid pipelines. This paper discusses a number of proposed and pending safety regulations and legislative initiatives currently being considered by the RSPA and the US Congress. Some new regulations have been enacted. The next few years will see a great deal of regulatory activity regarding natural gas and hazardous liquid pipelines, much of it resulting from legislative requirements. The office of Pipeline Safety is currently conducting a study to streamline its operations. This study is analyzing the office's business, social and technical operations with the goal of improving overall efficiency, effectiveness, productivity and job satisfaction to meet the challenges of the future.

De Leon, C. (U.S. Dept. of Transportation, Research and Special Programs Administration, Washington, DC (US))

1992-04-01

255

Cellular regulation by protein phosphorylation.  

PubMed

A historical account of the discovery of reversible protein phosphorylation is presented. This process was uncovered in the mid 1950s in a study undertaken with Edwin G. Krebs to elucidate the complex hormonal regulation of skeletal muscle glycogen phosphorylase. Contrary to the known activation of this enzyme by AMP which serves as an allosteric effector, its hormonal regulation results from a phosphorylation of the protein by phosphorylase kinase following the activation of the latter by Ca(2+) and ATP. The study led to the establishment of the first hormonal cascade of successive enzymatic reactions, kinases acting on kinases, initiated by cAMP discovered by Earl Sutherland. It also showed how two different physiological processes, carbohydrate metabolism and muscle contraction, could be regulated in concert. PMID:23058924

Fischer, Edmond H

2012-10-09

256

ISOs: The new antitrust regulators?  

SciTech Connect

Fear of seller market power in emerging electricity markets has led regulators to sanction use of independent system operators as private market police. A more restrained approach is likely to yield better results without the chilling effects of private regulation. This new industry regulatory paradigm has received little critical attention to date. This is unfortunate because ISO antitrust regulation raises serious legal and policy concerns. The California and New England Power Pool (NEPOOL) plans are quite intrusive. They require the ISO to make difficult distinctions between acceptable and unacceptable market behavior. They create considerable risk that desirable competitive behavior will be chilled and that market participants will incur significant explicit and implicit costs to meet regulatory requirements.

Raskin, D.B. [Steptoe and Johnson LLP, Washington, DC (United States)

1998-04-01

257

REGULATION OF FATTY ACID SYNTHESIS.  

PubMed

All plant cells produce fatty acids from acetyl-CoA by a common pathway localized in plastids. Although the biochemistry of this pathway is now well understood, much less is known about how plants control the very different amounts and types of lipids produced in different tissues. Thus, a central challenge for plant lipid research is to provide a molecular understanding of how plants regulate the major differences in lipid metabolism found, for example, in mesophyll, epidermal, or developing seed cells. Acetyl-CoA carboxylase (ACCase) is one control point that regulates rates of fatty acid synthesis. However, the biochemical modulators that act on ACCase and the factors that in turn control these modulators are poorly understood. In addition, little is known about how the expression of genes involved in fatty acid synthesis is controlled. This review evaluates current knowledge of regulation of plant fatty metabolism and attempts to identify the major unanswered questions. PMID:15012259

Ohlrogge, John B.; Jaworski, Jan G.

1997-06-01

258

Calcium regulation of keratinocyte differentiation  

PubMed Central

Calcium is the major regulator of keratinocyte differentiation in vivo and in vitro. A calcium gradient within the epidermis promotes the sequential differentiation of keratinocytes as they traverse the different layers of the epidermis to form the permeability barrier of the stratum corneum. Calcium promotes differentiation by both outside–in and inside–out signaling. A number of signaling pathways involved with differentiation are regulated by calcium, including the formation of desmosomes, adherens junctions and tight junctions, which maintain cell–cell adhesion and play an important intracellular signaling role through their activation of various kinases and phospholipases that produce second messengers that regulate intracellular free calcium and PKC activity, critical for the differentiation process. The calcium receptor plays a central role by initiating the intracellular signaling events that drive differentiation in response to extracellular calcium. This review will discuss these mechanisms.

Bikle, Daniel D; Xie, Zhongjian; Tu, Chia-Ling

2012-01-01

259

miRNA regulation of cytokine genes  

PubMed Central

In this review we discuss specific examples of regulation of cytokine genes and focus on a new mechanism involving post-transcriptional regulation via miRNAs. The post-transcriptional regulation of cytokine genes via the destabilizing activity of AU-rich elements [AREs] and miRNAs is a pre-requisite for regulating the half-life of many cytokines and achieving the temporal and spatial distributions required for regulation of these genes.

Asirvatham, Ananthi J.; Magner, William J.; Tomasi, Thomas B.

2011-01-01

260

Natural regulation of herbivorous forest insect populations  

Microsoft Academic Search

From basic principles of positive\\/negative feedback control and classical density-dependent\\/independent population theory we outline a general explanation for the regulation of herbivore populations in forested ecosystems. We identify three fundamental patterns of behavior; (i) populations regulated close to equilibrium (“tight” regulation) by fast-acting negative feedback processes, (ii) populations regulated by delayed negative feedback processes (“loose” regulation) which often exhibit wide-amplitude

A. A. Berryman; N. Chr. Stenseth; A. S. Isaev

1987-01-01

261

Self-regulation in securities markets  

Microsoft Academic Search

This paper canvasses the trends in self-regulation and the role of self-regulation in securities markets in different parts of the world. The paper also describes the conditions in which self-regulation might be an effective element of securities markets regulation, particularly in emerging markets. Use of self-regulation and self-regulatory organizations is often recommended in emerging markets as part of a broader

John Carson

2011-01-01

262

Cell Regulation by a Novel Estrogen Regulated Gene.  

National Technical Information Service (NTIS)

This report describes the work conducted in the first year of a two year IDEA. Our original proposal was funded to study a human estrogen regulated transcript, HEM45, that encodes a novel protein of 181 amino-acid residues (M, 20,300). The HEM45 protein h...

B. T. Pentacost

1997-01-01

263

Regulations against the human nature  

NASA Astrophysics Data System (ADS)

The discussion around the concept of the addiction to noise has evidenced the importance of noise for the human being and explains why in some cases the regulations fail to control the noise in cities. In this presentation the different uses, consciously or unconsciously, of the noise will be analyzed, uses that go from habits to maybe addictions. Also discussed are the implications of establishing regulations against the human nature as well as the importance of education to manage the noise and design acoustically instead of trying to ban the noise in some social circumstances.

Elizondo-Garza, Fernando J.

2001-05-01

264

Regulation of Inflammation by Adenosine  

PubMed Central

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.

Hasko, Gyorgy; Cronstein, Bruce

2013-01-01

265

Calcium regulation in protozoan parasites  

Microsoft Academic Search

The calcium ion (Ca2+) is used as a major signaling molecule in a diverse range of eukaryotic cells including several human parasitic protozoa, such as Trypanosoma cruzi, Trypanosoma brucei, Leishmania spp, Plasmodium spp, Toxoplasma gondii, Cryptosporidium parvum, Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis. Ca2+ is critical for invasion of intracellular parasites, and its cytosolic concentration is regulated by the

Silvia NJ Moreno; Roberto Docampo

2003-01-01

266

Mitofusins: mighty regulators of metabolism.  

PubMed

Mitochondria are central regulators of cellular metabolism but how their function in a subset of cells affects whole-body energy balance is less understood. Two studies in this issue of Cell identify how diet-dependent modulation of mitochondrial fusion in specific neuronal circuits impact the metabolic status of an animal. PMID:24074856

Ozcan, Umut

2013-09-26

267

Domestic Technology Transfer Program Regulation.  

National Technical Information Service (NTIS)

The Regulation authorizes the DoD Domestic Technology Transfer Program and responds to the requirements of Public Law 96-480, the Federal Technology Transfer Act of 1986, and Executive Order 12591. Its purpose is to ensure the full use of the nation's fed...

D. Appler

1988-01-01

268

Regulation of International Information Flows.  

ERIC Educational Resources Information Center

Describes the current status of developments concerning the regulation of information flow across national borders. Similarities and trends in various privacy laws from European countries are discussed, as are the business position on data protection and efforts to harmonize national laws. (SW)

Maisonrouge, J. G.

1981-01-01

269

Signalling networks regulating dental development  

Microsoft Academic Search

There has been rapid progress recently in the identification of signalling pathways regulating tooth development. It has become apparent that signalling networks involved in Drosophila development and development of mammalian organs such as the limb are also used in tooth development. Teeth are epithelial appendages formed in the oral region of vertebrates and their early developmental anatomy resembles that of

Irma Thesleff; Paul Sharpe

1997-01-01

270

Posttranslational modifications regulate microtubule function  

Microsoft Academic Search

The ??-tubulin heterodimer, the building block of microtubules, is subject to a large number of post-translational modifications, comparable in diversity to the intensively studied histone modifications. Although these unusual modifications are conserved throughout evolution, their functions have remained almost completely elusive. Recently, however, important advances in the understanding of how tubulin modifications regulate function and organization have been made.

Klaus Weber; Stefan Westermann

2003-01-01

271

Isometric Force Regulation in Children.  

ERIC Educational Resources Information Center

Isometric pinch force regulation was investigated in children and adults using a visuo-motor tracking paradigm. Younger children aged 5-7 years performed significantly worse than older children aged 9-11 years and adults in terms of an overall error score as well as a correlation score, which is believed to reflect the ability to predict the…

Lazarus, Jo-Anne C.; And Others

1995-01-01

272

State Regulations versus Private Foundations.  

ERIC Educational Resources Information Center

|State governments recognize higher education's need to reach out aggressively to industry and other private donors for financial support, but may also closely regulate the activities of private foundations that seek and manage funds for public institutions of higher education. Both private and public higher education institutions should be…

Sansbury, Olin B., Jr.

1984-01-01

273

Re-Regulating Offshore Finance?  

Microsoft Academic Search

This article explores global efforts to regulate offshore finance in the wake of international concern about the effects of so-called harmful tax competition, as well as money laundering and terrorist financing (the latter a relatively new category since September 11, 2001). In the mid-1990s, a number of multilateral organizations, from the Organization for Economic Cooperation and Development (OECD) to the

B. Maurer

2008-01-01

274

In Brief: Coal mining regulations  

Microsoft Academic Search

The U.S. Department of the Interior (DOI) announced on 18 November measures to strengthen the oversight of state surface coal mining programs and to promulgate federal regulations to protect streams affected by surface coal mining operations. DOI's Office of Surface Mining Reclamation and Enforcement (OSM) is publishing an advance notice of a proposed rule about protecting streams from adverse impacts

Randy Showstack

2009-01-01

275

Health Claims Regulation and Welfare  

Microsoft Academic Search

Regulation (EC) No 1924\\/2006, 20 December 2006, requires functional foods manufacturers operating in Europe to provide evidence that the health claims reported on the packaging are truthful. However, most applications reviewed by the European Food Safety Authority (EFSA) have been rejected, leaving food manufacturers with the option of either selling products deprived of their claims or discontinuing their production. This

Rui Huang; Alessandro Bonanno

2011-01-01

276

Regulated Childhood: Equivalence with Variation  

ERIC Educational Resources Information Center

|The overriding aim of this article is to make a contribution to the discussion on individual development plans (IDPs) in Sweden as an expression of a regulated childhood and institutional practice. Individual development plans are seen as a phenomenon linked to the emergence of an auditing society. In sum, children are studied as subjects in…

Vallberg Roth, Ann-Christine; Mansson, Annika

2009-01-01

277

Regulation of Growth Hormone Secretion  

Microsoft Academic Search

The regulation of growth hormone (GH) secretion is complex, depending on the interaction of a wide array of central and peripheral feedback signals. In this brief review we will build up a picture of the current understanding of GH control mechanisms, highlighting areas of particular clinical relevance.Copyright © 1996 S. Karger AG, Basel

Maurice F. Scanlon; Basil G. Issa; Carlos Dieguez

1996-01-01

278

The Politics of Broadcast Regulation.  

ERIC Educational Resources Information Center

The thesis of this book is that the Federal Communications Commission (FCC) is but one party in the development of broadcast regulations--it feels pressure from not only the industry and Congress but also the White House, citizen groups and the courts. Four major commission actions are analyzed in terms of those pressures. These actions are: the…

Krasnow, Erwin G.; Longley, Lawrence D.

279

Temperature: Human Regulating, Ants Conforming  

ERIC Educational Resources Information Center

|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…

Clopton, Joe R.

2007-01-01

280

Gene expression regulating blastocyst formation  

Microsoft Academic Search

Development of embryos to the blastocyst stage is a critical event in the early lives of all eutherian mammalian species. Blastocyst formation is essential for implantation and is the principal morphological determinant of embryo quality prior to embryo transfer. The physiological events and roles of specific gene families that regulate blastocyst formation are subjects of intense research. Recent findings have

A. J Watson; M. E Westhusin; P. A De Sousa; D. H Betts; L. C Barcroft

1999-01-01

281

Telomerase Regulation of Myofibroblast Differentiation  

Microsoft Academic Search

Telomerase activity, which has wide expression in cancerous cells, is induced in lung proliferating fibroblasts. It is preferentially ex- pressed in fibroblasts versus myofibroblasts. It is unknown whether regulation of telomerase expression is related to the process of fibroblast differentiation into myofibroblasts. The objective of this studywastoclarifysuchapotentiallinkbetweentelomeraseexpres- sion and myofibroblast differentiation. Telomerase inhibitor, 3- azido-2,3-dideoxythymidine, or antisense oligonucleotide to the

Tianju Liu; Biao Hu; Myoung Ja Chung; Matt Ullenbruch; Hong Jin; Sem H. Phan

2006-01-01

282

Regulating Railways in Logistics Chains  

Microsoft Academic Search

ailways contain natural monopoly components in their track infrastructure. Hence, like most infrastructure industries in Australia, they are subject to economic regulation to prevent abuses of monopoly power. Railways also form part of logistics chains and, as such, their ability to abuse market power depends upon the characteristics of those chains. Third party access regimes presently apply to the whole

Nick Wills-Johnson

2007-01-01

283

Regulation of vesicular neurotransmitter transporters  

Microsoft Academic Search

Neurotransmitters are key molecules of neurotransmission. They are concentrated first in the cytosol and then in small synaptic vesicles of presynaptic terminals by the activity of specific neurotransmitter transporters of the plasma and the vesicular membrane, respectively. It has been shown that postsynaptic responses to single neurotransmitter packets vary over a wide range, which may be due to a regulation

G. Ahnert-Hilger; M. Höltje; I. Pahner; S. Winter; I. Brunk

2003-01-01

284

Internal regulation of iron absorption  

Microsoft Academic Search

MCCANCE and Widdowson1 concluded that body iron content is regulated by variation in the amount absorbed and not by variation in excretion, and many workers have since attempted to define the factors which relate iron absorption to the needs of the body. Although there is a large body of data on the intracellular mechanisms of absorption2 this has not advanced

I. Cavill; M. Worwood; A. Jacobs

1975-01-01

285

Deceptive Business Practices: State Regulations.  

ERIC Educational Resources Information Center

|Although much has been done at the federal level to control deceptive advertising practices, many states have no criminal laws designed to regulate advertising, and several states recently repealed such laws. This paper examines states' efforts to balance the advertiser's freedom of speech with the consumer's need for information about products…

Rohrer, Daniel Morgan

286

Angiostatic Regulators in Ovarian Cancer  

Microsoft Academic Search

Angiogenesis by either normal or neoplastic cells involves a delicate balance of both angiogenic and angiostatic regulators. In the ovary, normal physiological angiogenesis occurs around the developing follicle and corpus luteum in response to hormonal shifts. Interestingly, carcinomas arising from the ovary are usually highly vascularized and are commonly clinically observed to produce cyst fluids or ascites which contain both

Christina Diane Drenberg

2010-01-01

287

Regulated Antigen Delivery System (RADS).  

National Technical Information Service (NTIS)

We describe a regulated antigen delivery system (RADS) that has (a) a vector that includes (1) a gene encoding a desired gene product operably linked to a control sequence, (2) an origin of replication conferring vector replication using DNA polymerase II...

R. Curtis S. A. Tinge

2004-01-01

288

Regulation of Involucrin Gene Expression  

Microsoft Academic Search

The epidermis is a dynamic renewing structure that provides life-sustaining protection from the environment. The major cell type of the epidermis, the epidermal keratinocyte, undergoes a carefully choreographed program of differentiation. Alteration of these events results in a variety of debilitating and life-threatening diseases. Understanding how this process is regulated is an important current goal in biology. In this review,

Richard L. Eckert; James F. Crish; Tatiana Efimova; Shervin R. Dashti; Anne Deucher; Frederic Bone; Gautam Adhikary; Guosheng Huang; Ramamurthy Gopalakrishnan; Sivaprakasam Balasubramanian

2004-01-01

289

Amended Zoning Regulations, Surfside, Florida.  

National Technical Information Service (NTIS)

The draft contains recommendations for the content of zoning regulations designed to insure sound land use controls and a desirable character of development in the town of Surfside in accordance with a comprehensive plan. The draft has been developed by t...

1969-01-01

290

Endocytic regulation of TGF-? signaling  

Microsoft Academic Search

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

Ye-Guang Chen

2009-01-01

291

Phosphoprotein Regulation of Behavioral Reactivity.  

National Technical Information Service (NTIS)

The regulation of synaptic reactivity by protein kinase C and its substrates has been studied using the long-term potentation paradigm (LTP). We have studied the effects of protein kinase C activators and inhibitors on the durability of synaptic reactivit...

A. Routtenberg

1990-01-01

292

Sweden's regulation of consumer affairs  

Microsoft Academic Search

Within the sociology of law, empirical research from Sweden has repeatedly shown the advantages of a soft approach to legal regulation. A soft approach, that is, an approach based on voluntary compliance and cooperation with a governmental regulatory agency, cannot be successful, however, unless certain conditions are met. Firstly, there must exist possible recourse to a governing body composed of

Antoinette Hetzler

1984-01-01

293

Endocrine Disorders of Sodium Regulation  

Microsoft Academic Search

Salt and water homoeostasis is tightly regulated by a variety of control mechanisms with the adrenal steroid hormone aldosterone playing a central role. Defects or disturbances in these systems lead to either salt loss, which is life threatening in the neonatal period, or sodium retention causing hypertension. Rapid and accurate diagnosis is required to avoid severe complications. During the last

Ursula Kuhnle; Sabina Lewicka; Peter J. Fuller

2004-01-01

294

Regulated childhood: equivalence with variation  

Microsoft Academic Search

The overriding aim of this article is to make a contribution to the discussion on individual development plans (IDPs) in Sweden as an expression of a regulated childhood and institutional practice. Individual development plans are seen as a phenomenon linked to the emergence of an auditing society. In sum, children are studied as subjects in relation to content, form and

Annika Månsson

2009-01-01

295

Calcium regulates podocyte actin dynamics.  

PubMed

Ca(2+)-mediated remodeling of the actin cytoskeleton is a dynamic process that regulates cell motility through the modulation of rho guanosine triphosphatase (GTPase) signaling. Kidney podocytes are unique, pericyte-like cells with a complex cellular organization consisting of a cell body, major processes, and foot processes (FPs). The FPs form a characteristic interdigitating pattern with FPs of neighboring podocytes, leaving in between filtration slits that are covered by the slit diaphragm (SD). The actin-based FP and the SD form the final barrier to proteinuria. Mutations affecting several podocyte proteins cause disruption of the filtration barrier and rearrangement of the highly dynamic podocyte actin cytoskeleton. Proteins regulating the plasticity of the podocyte actin cytoskeleton are therefore of critical importance for sustained kidney barrier function. Dynamic regulation of the actin-based contractile apparatus in podocyte FPs is essential for sustained kidney filter function. Thus, the podocyte represents an excellent model system to study calcium signaling and actin dynamics in a physiologic context. Here, we discuss the regulation of podocyte actin dynamics by angiotensin or bradykinin-mediated calcium influx and downstream Rho GTPase signaling pathways and how these pathways are operative in other cells including fibroblasts and cancer cells. PMID:22958486

Greka, Anna; Mundel, Peter

2012-07-01

296

Phytochrome-regulated Gene Expression  

Technology Transfer Automated Retrieval System (TEKTRAN)

Identification of all genes involved in the phytochrome (phy)- mediated responses of plants to their light environment is an important goal in providing an overall understanding of light-regulated growth and development. This article highlights and integrates the central findings of two recent compr...

297

Regulating the Shadow Banking System  

Microsoft Academic Search

The shadow banking system played a major role in the recent financial crisis but remains largely unregulated. We propose principles for its regulation and describe a specific proposal to implement those principles. We document how the rise of shadow banking was helped by regulatory and legal changes that gave advantages to three main institutions: money-market mutual funds (MMMFs) to capture

Gary Gorton; Andrew Metrick

2011-01-01

298

Regulating the Shadow Banking System  

Microsoft Academic Search

:The shadow banking system played a major role in the recent financial crisis but remains largely unregulated. We propose principles for its regulation and describe a specific proposal to implement those principles. We document how the rise of shadow banking was helped by regulatory and legal changes that gave advantages to three main institutions: money-market mutual funds (MMMFs) to capture

Gary Gorton; Andrew Metrick

2011-01-01

299

Calcineurin regulation of neuronal plasticity  

Microsoft Academic Search

From the most basic of nervous systems to the intricate circuits found within the human brain, a fundamental requirement of neuronal function is that it be malleable, altering its output based upon experience. A host of cellular proteins are recruited for this purpose, which themselves are regulated by protein phosphorylation. Over the past several decades, research has demonstrated that the

Rachel D Groth; Robert L Dunbar; Paul G Mermelstein

2003-01-01

300

Government regulations: two sides to the story  

SciTech Connect

Critics who blame regulatory costs for US economic problems fail to consider the benefits of the regulations and fail to distinguish the small contribution that new social regulation makes to the budget. It is important to separate the economic regulations designed to keep the economy running smoothly from the social goals of health, safety, and environment. Social regulation seeks to correct a market failure by including social costs in the price and reflecting the true cost of production. In contrast to Murray L. Weidenbaum's theory, social regulation needs to be reorganized into four categories: new social regulation, older social regulation, economic regulation, and miscellaneous regulation in assessing regulatory costs. The monetary benefit estimates that are available show positive net contributions in reduced morbidity and improved environmental quality. 5 tables. (DCK)

Tabb, W.K.

1980-11-01

301

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

Federal Register 2010, 2011, 2012, 2013

...10, 2009. The rule modified the import regulations for Irish potatoes and made minor administrative changes to the potato, onion, and tomato import regulations to update informational references. This document corrects two Code of Federal Regulation...

2010-01-11

302

77 FR 39125 - Defense Acquisition Regulations System; Defense Federal Acquisition Regulation Supplement; Only...  

Federal Register 2010, 2011, 2012, 2013

...Defense Federal Acquisition Regulation Supplement; Only One Offer (DFARS Case 2011-D013...Defense Federal Acquisition Regulation Supplement: Shipping Instructions (DFARS Case...Defense Federal Acquisition Regulation Supplement: Applicability of Hexavalent...

2012-06-29

303

Least cost planning regulation; Restructuring the roles of utility management and regulators  

SciTech Connect

This purpose of this paper is to examine the roles of regulators in long-range utility resource planning. Summary of major points include: Three regulatory options exist today with respect to integrated resource planning: Command and Control Regulation; Incentive Regulation; and Flexible Regulation. If deregulation is likely in the end, flexible regulation today offers the greatest promise of long-run success. Flexible regulation requires commissions and companies to agree on underlying principles and for utility management to exercise defensible judgment.

Donovan, D.J.; Goldfield, S.R. (Richard Metzler and Associates, Northbrook, IL (US))

1992-01-01

304

Regulation of Drosophila Metamorphosis by Xenobiotic Response Regulators  

PubMed Central

Mammalian Nrf2-Keap1 and the homologous Drosophila CncC-dKeap1 protein complexes regulate both transcriptional responses to xenobiotic compounds as well as native cellular and developmental processes. The relationships between the functions of these proteins in xenobiotic responses and in development were unknown. We investigated the genes regulated by CncC and dKeap1 during development and the signal transduction pathways that modulate their functions. CncC and dKeap1 were enriched within the nuclei in many tissues, in contrast to the reported cytoplasmic localization of Keap1 and Nrf2 in cultured mammalian cells. CncC and dKeap1 occupied ecdysone-regulated early puffs on polytene chromosomes. Depletion of either CncC or dKeap1 in salivary glands selectively reduced early puff gene transcription. CncC and dKeap1 depletion in the prothoracic gland as well as cncCK6/K6 and dKeap1EY5/EY5 loss of function mutations in embryos reduced ecdysone-biosynthetic gene transcription. In contrast, dKeap1 depletion and the dKeap1EY5/EY5 loss of function mutation enhanced xenobiotic response gene transcription in larvae and embryos, respectively. Depletion of CncC or dKeap1 in the prothoracic gland delayed pupation by decreasing larval ecdysteroid levels. CncC depletion suppressed the premature pupation and developmental arrest caused by constitutive Ras signaling in the prothoracic gland; conversely, constitutive Ras signaling altered the loci occupied by CncC on polytene chromosomes and activated transcription of genes at these loci. The effects of CncC and dKeap1 on both ecdysone-biosynthetic and ecdysone-regulated gene transcription, and the roles of CncC in Ras signaling in the prothoracic gland, establish the functions of these proteins in the neuroendocrine axis that coordinates insect metamorphosis.

Deng, Huai; Kerppola, Tom K.

2013-01-01

305

How regulators of G protein signaling achieve selective regulation  

PubMed Central

Summary The regulators of G protein signaling (RGS) are a family of cellular proteins that play an essential regulatory role in G protein-mediated signal transduction. There are multiple RGS subfamilies consisting of over twenty different RGS proteins. They are basically the guanosine triphosphatase (GTPase)-accelerating proteins that specifically interact with G protein ? subunits. RGS proteins display remarkable selectivity and specificity in their regulation of receptors, ion channels, and other G protein-mediated physiological events. The molecular and cellular mechanisms underlying such selectivity are complex and cooperate at many different levels. Recent research data have provided strong evidence that the spatiotemporal-specific expression of RGS proteins and their target components, as well as the specific protein-protein recognition and interaction through their characteristic structural domains and functional motifs, are determinants for RGS selectivity and specificity. Other molecular mechanisms, such as alternative splicing and scaffold proteins, also significantly contribute to RGS selectivity. To pursue a thorough understanding of the mechanisms of RGS selective regulation will be of great significance for the advancement of our knowledge of molecular and cellular signal transduction.

Xie, Guo-xi; Palmer, Pamela Pierce

2007-01-01

306

O-GlcNAcylation, Novel Post-Translational Modification Linking Myocardial Metabolism and Cardiomyocyte Circadian Clock*  

PubMed Central

The cardiomyocyte circadian clock directly regulates multiple myocardial functions in a time-of-day-dependent manner, including gene expression, metabolism, contractility, and ischemic tolerance. These same biological processes are also directly influenced by modification of proteins by monosaccharides of O-linked ?-N-acetylglucosamine (O-GlcNAc). Because the circadian clock and protein O-GlcNAcylation have common regulatory roles in the heart, we hypothesized that a relationship exists between the two. We report that total cardiac protein O-GlcNAc levels exhibit a diurnal variation in mouse hearts, peaking during the active/awake phase. Genetic ablation of the circadian clock specifically in cardiomyocytes in vivo abolishes diurnal variations in cardiac O-GlcNAc levels. These time-of-day-dependent variations appear to be mediated by clock-dependent regulation of O-GlcNAc transferase and O-GlcNAcase protein levels, glucose metabolism/uptake, and glutamine synthesis in an NAD-independent manner. We also identify the clock component Bmal1 as an O-GlcNAc-modified protein. Increasing protein O-GlcNAcylation (through pharmacological inhibition of O-GlcNAcase) results in diminished Per2 protein levels, time-of-day-dependent induction of bmal1 gene expression, and phase advances in the suprachiasmatic nucleus clock. Collectively, these data suggest that the cardiomyocyte circadian clock increases protein O-GlcNAcylation in the heart during the active/awake phase through coordinated regulation of the hexosamine biosynthetic pathway and that protein O-GlcNAcylation in turn influences the timing of the circadian clock.

Durgan, David J.; Pat, Betty M.; Laczy, Boglarka; Bradley, Jerry A.; Tsai, Ju-Yun; Grenett, Maximiliano H.; Ratcliffe, William F.; Brewer, Rachel A.; Nagendran, Jeevan; Villegas-Montoya, Carolina; Zou, Chenhang; Zou, Luyun; Johnson, Russell L.; Dyck, Jason R. B.; Bray, Molly S.; Gamble, Karen L.; Chatham, John C.; Young, Martin E.

2011-01-01

307

Culture, emotion regulation, and adjustment.  

PubMed

This article reports differences across 23 countries on 2 processes of emotion regulation--reappraisal and suppression. Cultural dimensions were correlated with country means on both and the relationship between them. Cultures that emphasized the maintenance of social order--that is, those that were long-term oriented and valued embeddedness and hierarchy--tended to have higher scores on suppression, and reappraisal and suppression tended to be positively correlated. In contrast, cultures that minimized the maintenance of social order and valued individual Affective Autonomy and Egalitarianism tended to have lower scores on Suppression, and Reappraisal and Suppression tended to be negatively correlated. Moreover, country-level emotion regulation was significantly correlated with country-level indices of both positive and negative adjustment. PMID:18505309

Matsumoto, David; Yoo, Seung Hee; Nakagawa, Sanae

2008-06-01

308

Molecular Mechanisms of Appetite Regulation  

PubMed Central

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

Yu, Ji Hee

2012-01-01

309

Genetic Regulation of Prostate Development  

PubMed Central

Prostatic development is a dynamic process in which basic mechanisms of epithelial outgrowth and epithelial-mesenchymal interaction are initiated by androgens and androgen receptor signaling. Even in adulthood, the prostate's function remains tightly regulated by androgens--without them, pathologic diseases including hyperplastic and malignant growth which together plague nearly 50% of aging males does not occur. Unraveling the etiology of these pathologic processes is a complex and important goal. In fact, many insights into these processes have come from an intimate understanding of the complex signaling networks that regulate physiologic prostatic growth in development. This review aims to highlight important key molecules such as Nkx3.1, sonic hedgehog and Sox9 as well as key signaling pathways including the Fibroblast growth factor and Wnt pathways. These molecules and pathways are critical for prostate development with both know and postulated roles in prostatic pathology.

Meeks, Joshua; Schaeffer, Edward M

2011-01-01

310

Regulation of an Actin Spring  

NASA Astrophysics Data System (ADS)

To produce motion, cells rely on the conversion of potential energy into mechanical work. One such example is the dramatic process involving the acrosome reaction of Limulus sperm, whereby a 60 ?m-long bundle of actin filaments straightens from a coiled conformation to extend out of the cell in five seconds. This cellular engine and the motion it produces represent a third type of actin-based motility fundamentally different from polymerization or myosin-driven processes. The motive force for this extension originates from stored elastic energy in the overtwisted, pre-formed coil---much like a compressed mechanical spring. When the actin bundle untwists, this energy is converted to mechanical work powering the extension. We report on experiments probing the regulation of this actin spring by extracellular calcium. We find that extracellular calcium needs to be present for the spring to activate, and that calcium regulates the velocity of the extension.

Tam, Barney; Shin, Jennifer; Brau, Ricardo; Lang, Matthew; Mahadevan, L.; Matsudaira, Paul

2006-03-01

311

Natural gas cavern storage regulation  

SciTech Connect

Investigation of an incident at an LPG storage facility in Texas by U.S. Department of Transportation resulted in recommendation that state regulation of natural gas cavern storage might be improved. Interstate Oil & Gas Compact Commission has established a subcommittee to analyze the benefits and risks associated with natural gas cavern storage, and to draft a regulation model which will suggest engineering and performance specifications. The resulting analysis and regulatory language will be reviewed by I.O.G.C.C., and if approved, distributed to member states (including New York) for consideration. Should the states desire assistance in modifying the language to reflect local variables, such as policy and geology, I.O.G.C.C. may offer assistance. The proposed presentation will review the I.O.G.C.C. product (if published at that date), and discuss implications of its application in New York.

Heneman, H.

1995-09-01

312

Mitochondrial regulation of cell death.  

PubMed

Although required for life, paradoxically, mitochondria are often essential for initiating apoptotic cell death. Mitochondria regulate caspase activation and cell death through an event termed mitochondrial outer membrane permeabilization (MOMP); this leads to the release of various mitochondrial intermembrane space proteins that activate caspases, resulting in apoptosis. MOMP is often considered a point of no return because it typically leads to cell death, even in the absence of caspase activity. Because of this pivotal role in deciding cell fate, deregulation of MOMP impacts on many diseases and represents a fruitful site for therapeutic intervention. Here we discuss the mechanisms underlying mitochondrial permeabilization and how this key event leads to cell death through caspase-dependent and -independent means. We then proceed to explore how the release of mitochondrial proteins may be regulated following MOMP. Finally, we discuss mechanisms that enable cells sometimes to survive MOMP, allowing them, in essence, to return from the point of no return. PMID:24003207

Tait, Stephen W G; Green, Douglas R

2013-09-01

313

77 FR 4887 - DOE Patent Licensing Regulations  

Federal Register 2010, 2011, 2012, 2013

...inventions covered by patents or patent applications vested in the...the codification of the DOE patent licensing regulations. Also...original codification of the patent licensing regulations at 10...initial regulatory flexibility analysis for any rule that by law...

2012-02-01

314

43 CFR 431.9 - Future regulations.  

Code of Federal Regulations, 2012 CFR

...INTERIOR GENERAL REGULATIONS FOR POWER GENERATION, OPERATION, MAINTENANCE, AND REPLACEMENT AT THE BOULDER CANYON PROJECT, ARIZONA/NEVADA § 431.9 Future regulations. (a) Reclamation may from time to time promulgate additional or...

2012-10-01

315

43 CFR 431.9 - Future regulations.  

Code of Federal Regulations, 2011 CFR

...INTERIOR GENERAL REGULATIONS FOR POWER GENERATION, OPERATION, MAINTENANCE, AND REPLACEMENT AT THE BOULDER CANYON PROJECT, ARIZONA/NEVADA § 431.9 Future regulations. (a) Reclamation may from time to time promulgate additional or...

2011-10-01

316

47 CFR 32.14 - Regulated accounts.  

Code of Federal Regulations, 2012 CFR

... 2012-10-01 false Regulated accounts. 32.14 Section 32.14 Telecommunication...CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES General Instructions § 32.14 Regulated accounts. (a) In the context of this...

2012-10-01

317

78 FR 35195 - Acquisition Regulations: Export Control  

Federal Register 2010, 2011, 2012, 2013

...COMPLIANCE WITH EXPORT CONTROL LAWS, REGULATIONS AND DIRECTIVES (XXX 20XX) (a) The Contractor shall comply with applicable laws...COMPLIANCE WITH EXPORT CONTROL LAWS, REGULATIONS AND DIRECTIVES (XXX 20XX) (a) The Contractor shall comply with applicable...

2013-06-12

318

Prokaryotic genome regulation: A revolutionary paradigm  

PubMed Central

After determination of the whole genome sequence, the research frontier of bacterial molecular genetics has shifted to reveal the genome regulation under stressful conditions in nature. The gene selectivity of RNA polymerase is modulated after interaction with two groups of regulatory proteins, 7 sigma factors and 300 transcription factors. For identification of regulation targets of transcription factors in Escherichia coli, we have developed Genomic SELEX system and subjected to screening the binding sites of these factors on the genome. The number of regulation targets by a single transcription factor was more than those hitherto recognized, ranging up to hundreds of promoters. The number of transcription factors involved in regulation of a single promoter also increased to as many as 30 regulators. The multi-target transcription factors and the multi-factor promoters were assembled into complex networks of transcription regulation. The most complex network was identified in the regulation cascades of transcription of two master regulators for planktonic growth and biofilm formation.

ISHIHAMA, Akira

2012-01-01

319

76 FR 6516 - Insurance Cost Information Regulation  

Federal Register 2010, 2011, 2012, 2013

...NHTSA 2011-0009] Insurance Cost Information Regulation AGENCY: National Highway...amended 49 CFR part 582, Insurance Cost Information Regulation, to require all dealers...compares differences in insurance costs of different...

2011-02-04

320

77 FR 11191 - Insurance Cost Information Regulation  

Federal Register 2010, 2011, 2012, 2013

...NHTSA 2012-0015] Insurance Cost Information Regulation AGENCY: National Highway...amended 49 CFR part 582, Insurance Cost Information Regulation, to require all dealers...compares differences in insurance costs of different...

2012-02-24

321

32 CFR 770.5 - Safety regulations.  

Code of Federal Regulations, 2010 CFR

...2009-07-01 2009-07-01 false Safety regulations. 770.5 Section...TO PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps...Quantico, Virginia § 770.5 Safety regulations. (a) Hunting is not permitted...

2009-07-01

322

32 CFR 770.5 - Safety regulations.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false Safety regulations. 770.5 Section...TO PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps...Quantico, Virginia § 770.5 Safety regulations. (a) Hunting is not permitted...

2010-07-01

323

32 CFR 770.3 - Fishing regulations.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Fishing regulations. 770.3 Section 770...PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps Base, Quantico, Virginia § 770.3 Fishing regulations. (a) All persons...

2013-07-01

324

The new EMTALA regulations--introduction.  

PubMed

This Introduction provides a broad overview of the new Emergency Medical Treatment and Labor Act (EMTALA) regulations and the changes they effected. The three Articles that follow discuss various aspects of the regulations in much greater detail. Health Lawyers Teleconference: EMTALA Update provides a commentary on the regulations from the perspective of representatives of the Centers for Medicare & Medicaid Services and the Department of Health and Human Services, followed by a critique of the regulations from a practitioner's standpoint. EMTALA: Dedicating an Emergency Department Near You analyzes the provisions of the regulations in detail and discusses their implications for hospitals and their counsel. Finally, The New EMTALA Regulations and the On-Call Physician Shortage: In Defense of the Regulations analyzes the on-call provisions of the regulations in light of the current shortage of on-call physicians. PMID:15191233

2004-01-01

325

43 CFR 417.6 - General regulations.  

Code of Federal Regulations, 2012 CFR

...regulations. In addition to the recommendations and determinations formulated according to the procedures set out above, the right is reserved to issue regulations of general applicability to the topics dealt with...

2012-10-01

326

43 CFR 417.6 - General regulations.  

Code of Federal Regulations, 2011 CFR

...regulations. In addition to the recommendations and determinations formulated according to the procedures set out above, the right is reserved to issue regulations of general applicability to the topics dealt with...

2011-10-01

327

7 CFR 948.387 - Handling regulation.  

Code of Federal Regulations, 2013 CFR

...SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN COLORADO Handling Regulations § 948.387 Handling regulation. On and after August 1, 1982, no person shall handle...

2013-01-01

328

7 CFR 3.87 - Agency regulations.  

Code of Federal Regulations, 2012 CFR

...Office of the Secretary of Agriculture DEBT MANAGEMENT Federal Salary Offset § 3.87 Agency regulations. USDA agencies may...regulations in this subpart governing the collection of a debt by salary...

2012-01-01

329

Regulation of GE Animals at FDA  

Center for Biologics Evaluation and Research (CBER)

Text Version... Page 2. Regulation of GE Animals at FDA Larisa Rudenko, PhD, DABT ... Page 6. Regulation of GE Animals at FDA • FFDCA/NEPA • Guidance 187 ... More results from www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials

330

Guidance for Industry: The Juice HACCP Regulation ...  

Center for Food Safety and Applied Nutrition (CFSAN)

... 3. Is juice used in alcoholic beverages (eg, wines, alcoholic cider) covered under the regulation? It depends. The regulation ... More results from www.fda.gov/food/guidanceregulation/guidancedocumentsregulatoryinformation

331

32 CFR 770.4 - Hunting regulations.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false Hunting regulations. 770.4 Section 770...ACCESS TO PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps Base, Quantico, Virginia § 770.4 Hunting regulations. All persons...

2010-07-01

332

50 CFR 20.153 - Regulations committee.  

Code of Federal Regulations, 2012 CFR

...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....

2012-10-01

333

32 CFR 770.4 - Hunting regulations.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Hunting regulations. 770.4 Section 770...ACCESS TO PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps Base, Quantico, Virginia § 770.4 Hunting regulations. All persons...

2013-07-01

334

50 CFR 20.153 - Regulations committee.  

Code of Federal Regulations, 2011 CFR

...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....

2011-10-01

335

Drinking Water Standards and Regulations. Volume 2.  

National Technical Information Service (NTIS)

The following 11 important documents are compiled for Drinking Water Standards and Regulations: (1) U.S. Environmental Agency Water Programs, National Interim Primary Drinking Water Regulations; (2) New Jersey Safe Drinking Water Act; (3) Summary of New J...

L. K. Wang M. H. S. Wang

1988-01-01

336

Drinking Water Standards and Regulations. Volume 3.  

National Technical Information Service (NTIS)

The following 12 important documents are compiled for a manual entitled 'Drinking Water Standards and Regulations': (1) Rules and Regulations for Public Water Systems; (2) Drinking Water Standards Governing Drinking Water Quality and Reporting Requirement...

L. K. Wang M. H. S. Wang

1988-01-01

337

Recommended Subdivision Regulations, Bamberg, South Carolina.  

National Technical Information Service (NTIS)

The document contains an ordinance regulating the subdivision of land in the town of Bamberg, South Carolina, requiring and regulating the preparation and presentation of preliminary and final plats for such purpose; establishing minimum subdivision desig...

S. Carter

1969-01-01

338

47 CFR 32.14 - Regulated accounts.  

Code of Federal Regulations, 2011 CFR

... 2011-10-01 false Regulated accounts. 32.14 Section 32.14 Telecommunication...CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES General Instructions § 32.14 Regulated accounts. (a) In the context of this...

2011-10-01

339

Home-Based Business and Government Regulation.  

National Technical Information Service (NTIS)

Government regulations typically have a disproportionately large impact on very small businesses. Studies using various methodologies have found that unit costs of complying with regulations are consistently higher for businesses with fewer than 20 employ...

H. B. R. Beale

2004-01-01

340

Media Attention, Insurance Regulation and Liability Insurance  

Microsoft Academic Search

The goal of this paper id to test whether the threat of regulating (or more stringent regulation of) automobile liability insurance as portrayed in the population and industry press induces insurers to change the way they price their policies.

M. Boyer

1999-01-01

341

46 CFR 197.535 - Regulated areas.  

Code of Federal Regulations, 2011 CFR

...percent larger than the other words) must be posted at each access to the regulated areas: DANGERâBENZENE REGULATED AREA CANCER CAUSING AGENT FLAMMABLEâNO SMOKING AUTHORIZED PERSONNEL ONLY RESPIRATOR...

2011-10-01

342

46 CFR 197.535 - Regulated areas.  

Code of Federal Regulations, 2012 CFR

...percent larger than the other words) must be posted at each access to the regulated areas: DANGERâBENZENE REGULATED AREA CANCER CAUSING AGENT FLAMMABLEâNO SMOKING AUTHORIZED PERSONNEL ONLY RESPIRATOR...

2012-10-01

343

[The regulation of medical practice in Mexico].  

PubMed

The recent evolution and present situation of the regulation of medical practice in Mexico is discussed. In part one the regulation function is defined in the context of the main functions of a health system. In part two, sanitary regulation and health care regulation are distinguished and discussed. Finally, the present situation of the regulation of medical practice in Mexico is discussed in detail in part three, more specifically, two of the most developed forms of regulation: i) legal regulation and ii) regulation through licensing and certification of general practitioners and medical specialists, respectively. A set of measures to develop a mixed and participatory regulatory system is presented in the section on conclusions. PMID:10546506

Gómez Dantés, O

344

Regulating proliferation during retinal development  

Microsoft Academic Search

Recent studies have shown that components of the cell-cycle machinery can have diverse and unexpected roles in the retina. Cyclin-kinase inhibitors, for example, have been implicated as regulators of cell-fate decisions during histogenesis and reactive gliosis in the adult tissue after injury. Also, various mechanisms have been identified that can compensate for extra rounds of cell division when the normal

Michael A. Dyer; Constance L. Cepko

2001-01-01

345

Catabolite regulation of antibiotic biosynthesis  

Microsoft Academic Search

Conclusion  In view of the possible mediation of carbon catabolite repression of antibiotic biosynthesis by phosphorylated substances,\\u000a the concept of the role of phosphorus in the regulation of secondary metabolism should be re-evaluated. Many conclusions are\\u000a based on an analogy with the effect of phosphorus in animal or plant cells (for review cf. Martin 1977). However, in contrast\\u000a with plant and

Z. Hoš?álek

1980-01-01

346

Phospholipids as Plant Growth Regulators  

Microsoft Academic Search

In this paper the potential to use phospholipids and lysophospholipids as plant growth regulators is discussed. Recent evidence shows that phospholipids and phospholipases play an\\u000a important signalling role in the normal course of plant development and in the response of plants to abiotic and biotic stress.\\u000a It is apparent that phospholipase A (PLA), C (PLC) and D (PLD), lysophospholipids, and

A. Keith Cowan

2006-01-01

347

Regulation of vesicular neurotreansmitter transporters  

Microsoft Academic Search

Neurotransmitters are key molecules of neurotransmission. They are concentrated first in the cytosol and then in small synaptic\\u000a vesicles of presynaptic terminals by the activity of specific neurotransmitter transporters of the plasma and the vesicular\\u000a membrane, respectively. It has been shown that postsynaptic responses to single neurotransmitter packets vary over a wide\\u000a range, which may be due to a regulation

G. Ahnert-Hilger; M. Höltje; I. Pahner; S. Winter; I. Brunk

348

Regulation of Genes by Light  

Microsoft Academic Search

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

Gabriele Klug; Shinji Masuda

349

Redox regulation of intercellular transport  

Microsoft Academic Search

Plant cells communicate with each other via plasmodesmata (PDs) in order to orchestrate specific responses to environmental\\u000a and developmental cues. At the same time, environmental signals regulate this communication by promoting changes in PD structure\\u000a that modify symplastic permeability and, in extreme cases, isolate damaged cells. Reactive oxygen species (ROS) are key messengers\\u000a in plant responses to a range of

Yoselin Benitez-Alfonso; David Jackson; Andy Maule

2011-01-01

350

Photomultiplier tube gain regulating system  

DOEpatents

This invention relates to an improved system for regulating the gain of a photomultiplier tube, and was designed for use with the photomultiplier tubes of a GeMSAEC fast analyzers. It has the following advantages over the prior system: noise is virtually eliminated; sample analysis can begin after 3 to 4 revolutions of the rotor; fluorescent and light scattering solutions can be used as a reference; and the reference solution can be in any cuvette on the rotor.

Johnson, Wayne F. (Loudon, TN)

1976-01-01

351

Actin cytoskeleton regulates hippo signaling.  

PubMed

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

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

2013-09-11

352

Mechanosensitive mechanisms in transcriptional regulation.  

PubMed

Transcriptional regulation contributes to the maintenance of pluripotency, self-renewal and differentiation in embryonic cells and in stem cells. Therefore, control of gene expression at the level of transcription is crucial for embryonic development, as well as for organogenesis, functional adaptation, and regeneration in adult tissues and organs. In the past, most work has focused on how transcriptional regulation results from the complex interplay between chemical cues, adhesion signals, transcription factors and their co-regulators during development. However, chemical signaling alone is not sufficient to explain how three-dimensional (3D) tissues and organs are constructed and maintained through the spatiotemporal control of transcriptional activities. Accumulated evidence indicates that mechanical cues, which include physical forces (e.g. tension, compression or shear stress), alterations in extracellular matrix (ECM) mechanics and changes in cell shape, are transmitted to the nucleus directly or indirectly to orchestrate transcriptional activities that are crucial for embryogenesis and organogenesis. In this Commentary, we review how the mechanical control of gene transcription contributes to the maintenance of pluripotency, determination of cell fate, pattern formation and organogenesis, as well as how it is involved in the control of cell and tissue function throughout embryogenesis and adult life. A deeper understanding of these mechanosensitive transcriptional control mechanisms should lead to new approaches to tissue engineering and regenerative medicine. PMID:22797927

Mammoto, Akiko; Mammoto, Tadanori; Ingber, Donald E

2012-07-13

353

Mechanosensitive mechanisms in transcriptional regulation  

PubMed Central

Summary Transcriptional regulation contributes to the maintenance of pluripotency, self-renewal and differentiation in embryonic cells and in stem cells. Therefore, control of gene expression at the level of transcription is crucial for embryonic development, as well as for organogenesis, functional adaptation, and regeneration in adult tissues and organs. In the past, most work has focused on how transcriptional regulation results from the complex interplay between chemical cues, adhesion signals, transcription factors and their co-regulators during development. However, chemical signaling alone is not sufficient to explain how three-dimensional (3D) tissues and organs are constructed and maintained through the spatiotemporal control of transcriptional activities. Accumulated evidence indicates that mechanical cues, which include physical forces (e.g. tension, compression or shear stress), alterations in extracellular matrix (ECM) mechanics and changes in cell shape, are transmitted to the nucleus directly or indirectly to orchestrate transcriptional activities that are crucial for embryogenesis and organogenesis. In this Commentary, we review how the mechanical control of gene transcription contributes to the maintenance of pluripotency, determination of cell fate, pattern formation and organogenesis, as well as how it is involved in the control of cell and tissue function throughout embryogenesis and adult life. A deeper understanding of these mechanosensitive transcriptional control mechanisms should lead to new approaches to tissue engineering and regenerative medicine.

Mammoto, Akiko; Mammoto, Tadanori; Ingber, Donald E.

2012-01-01

354

Rethinking regulations for disposal criticality  

SciTech Connect

This paper provides the basis for the position that the current U.S. Nuclear Regulatory Commission (NRC) criticality regulation is in need of revision to address problems in implementing it for the postclosure period in a geologic high-level waste repository. The authors believe that the applicant for such a facility should be able to demonstrate that postulated postclosure criticality events will not cause unacceptable risk of deleterious effects on public health and safety. In addition, the applicant should be expected to take practical and feasible measures to reduce the probability of a criticality occurring, even if (as expected) the consequences of such a criticality for repository performance and public health and safety would be negligible. This approach, while recognizing the probabilistic nature of analyses of events and conditions in the distant future, is also arguably consistent with the defense in depth concept that has been successfully applied to nuclear reactor regulation. The authors believe regulations for postclosure criticality control should support this dual approach, rather than require a deterministic prohibition of criticality as does the current rule. The existing rule seems appropriate for the preclosure period, as long as it is clearly specified to apply only to that period.

Scott, M. [Duke Engineering and Services, Inc., Las Vegas, NV (United States); Doering, T. [Framatome Cogema Fuels, Las Vegas, NV (United States)

1997-08-01

355

Amino acids and cell regulation.  

PubMed Central

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.

Forster, R. P.; Goldstein, L.

1979-01-01

356

Oxygen regulation in Salmonella typhimurium.  

PubMed Central

Regulation by oxygen of the peptidase T (pepT) locus of Salmonella typhimurium was studied by measuring beta-galactosidase levels in strains containing a pepT::Mu d1(Apr lac) operon fusion. beta-Galactosidase was induced in anaerobic cultures and late-exponential and stationary-phase aerated cultures. Peptidase T activity also was induced under these growth conditions. pepT+ but not pepT strains will utilize as amino acid sources the tripeptides Leu-Leu-Leu and Leu-Gly-Gly only when grown anaerobically. Mutations at two loci, oxrA and oxrB (oxygen regulation) prevent induction of the pepT locus. The oxrA locus is homologous to the fnr locus of Escherichia coli. We have isolated 12 independent Mu d1 insertions (oxd::Mu d1, oxygen dependent) that show induction of beta-galactosidase in anaerobic cultures and stationary-phase aerated cultures. These insertions fall into nine classes based on map location. All of the oxd::Mu d1 insertions are regulated by oxrA and oxrB and therefore define a global regulon that responds to oxygen limitation.

Strauch, K L; Lenk, J B; Gamble, B L; Miller, C G

1985-01-01

357

Auricular Acupuncture and Vagal Regulation  

PubMed Central

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.

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

2012-01-01

358

NRC - regulator of nuclear safety  

SciTech Connect

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.

NONE

1997-05-01

359

Drug regulation and policy formulation.  

PubMed

Reviews the legislative basis of the regulation of clinical investigation and the approval of new drugs as a foundation for examination of some current policy issues facing the FDA. Intentions and stipulations of the major legislation passed by Congress, including the Pure Food and Drug Act of 1906, the Food, Drug, and Cosmetic Act of 1938, and the New Drug amendments of 1962 are described, and their basic policies outlined. The major regulations rooted in that legislation and other guidelines representing FDA implementation are identified and discussed, including new drug regulations, guidelines for clinical investigations, and other aspects of the drug approval process. Proposed legislation affecting new drug development and clinical investigations, and FDA administrative proposals affecting revised new drug applications, monitoring of research, institutional review boards, informed consent, clinical investigations, and obligations of the sponsor or monitor are examined. Current problems and proposals involving larger societal issues are also discussed, such as the therapeutic use of investigational drugs, state drug legislation on marijuana and laetrile, the alleged drug lag, orphan drugs, and international cooperation in drug development. The paper focuses throughout on concern about human subject protection and validation of research data. PMID:7024847

Nightingale, S L

1981-01-01

360

An executioner caspase regulates autophagy  

PubMed Central

The relationships between autophagy and cell death are complex and still not well understood. To advance our understanding of the molecular connections between autophagy and apoptosis, we performed an RNAi-based screen of Drosophila melanogaster apoptosis-related genes for their ability to enhance or suppress starvation-induced autophagy. We discovered that six apoptosis-related genes, Dcp-1, hid, Bruce, buffy, debcl and p53 as well as Ras/ Raf/MAPK signaling pathway components play a role in autophagy regulation in Drosophila cultured cells. Our study also provides the first in vivo evidence that the effector caspase Dcp-1 and IAP protein Bruce regulate both autophagy and starvation-induced cell death at two nutrient status checkpoints, germarium and mid-oogenesis, in the Drosophila ovary. Analysis of degenerating mid-stage egg chambers in DmAtg1 and DmAtg7 mutants reveal a reduction in TUNEL staining though DNA condensation appears unaffected. Based on these and previous findings, we propose here a putative molecular pathway that might regulate the sensitivity threshold of apoptotic and autophagic responses. We also discuss multiple interpretations of the Atg mutant egg chamber TUNEL phenotype that are consistent with a possible role for autophagy in either suppressing or enhancing the efficiency of cell degradation and/or promoting cell clearance associated with the death process.

Hou, Y.C. Claire; Hannigan, Adrienne M.; Gorski, Sharon M.

2011-01-01

361

Investment and regulation: the Dutch experience  

SciTech Connect

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)

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

2010-06-15

362

The Temporal Dynamics of Voluntary Emotion Regulation  

Microsoft Academic Search

BackgroundNeuroimaging has demonstrated that voluntary emotion regulation is effective in reducing amygdala activation to aversive stimuli during regulation. However, to date little is known about the sustainability of these neural effects once active emotion regulation has been terminated.Methodology\\/Principal FindingsWe addressed this issue by means of functional magnetic resonance imaging (fMRI) in healthy female subjects. We performed an active emotion regulation

Henrik Walter; Alexander von Kalckreuth; Dina Schardt; Achim Stephan; Thomas Goschke; Susanne Erk; André Aleman

2009-01-01

363

End-use regulation: beginning the debate  

Microsoft Academic Search

Four papers are presented from the proceedings of the seminar, End-Use Regulation: Beginning the Debate. These are National Energy Conservation and End-Use Regulation, What Can End-Use Regulation Accomplish for Minnesota, National Energy Policy and the Rocky Mountain West, and Tasks for the Participants. An extensive panel discussion on Perspectives on End-Use Regulation was conducted. Informal summaries of workshop summaries are

G. Vermilye; W. A. Blanpied

1976-01-01

364

Conscious Regulation of Sexual Arousal in Men  

Microsoft Academic Search

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

Jason Winters; Kalina Christoff; Boris B. Gorzalka

2009-01-01

365

Specificity of age differences in emotion regulation  

Microsoft Academic Search

Objectives: The present study attempts to extend previous research examining differences between young and older adults in emotion regulation, by investigating age differences across a great range of facets of emotion regulation.Method: Young (n = 40) and older adults (n = 40) completed the Difficulties in Emotion Regulation Scale (DERS) and self-report measures of anxiety and depression.Results: Whereas young and

Vasiliki Orgeta

2009-01-01

366

FCC Regulation: Indecency by Interest Groups  

Microsoft Academic Search

FCC regulations are among the most controversial administrative law regulations because of their impact on broadcast television. This iBrief analyzes the history of FCC regulation and highlights the problems associated with the current model. Applying theories of economics, this iBrief proposes solutions to the current problems of selective enforcement and vagueness in enforcement. While the Supreme Court recognized that FCC

Patricia Daza

2008-01-01

367

International Radio Regulations Resulting from WARC 1979.  

ERIC Educational Resources Information Center

|The main features of international regulations on radio communications of the International Telecommunication Union are summarized and the possible effects on these regulations of the World Administrative Radio Conference of 1979 (WARC-79) are discussed in this paper. It is noted that while the international radio regulations are regarded as…

Berrada, Abderrazak

368

Regulation of Motivation: Contextual and Social Aspects  

ERIC Educational Resources Information Center

|Background: Models of self-regulated learning have been used extensively as a way of understanding how students understand, monitor, and manage their own academic functioning. The regulation of motivation is a facet of self-regulated learning that describes students' efforts to control their own motivation or motivational processing. The…

Wolters, Christopher A.

2011-01-01

369

The Truth About Regulation in America  

Microsoft Academic Search

The special interests leading the accelerating crusade against regulation have re-ignited a potent coalition of industry lobbyists, traditional conservatives, and grassroots Tea Party activists. The politicians speak in generic terms for public consumption: “the nation is broke,” “big government is bad,” “regulation costs trillions.” Behind the scenes, industry lobbyists target for repeal dozens of regulations that are designed to control

Rena I. Steinzor

2011-01-01

370

Development of insurance regulation in Ireland  

Microsoft Academic Search

Purpose – The purpose of this paper is to chart the chronology of insurance regulation in Ireland and evaluate the integration within European Union directives. Design\\/methodology\\/approach – The approach used was to chart the development of insurance regulation in Ireland and establish the stakeholders in the insurance industry that are affected by regulation. The various aspects of the EU involvement

Richard Brophy

2012-01-01

371

Bureaucrats and Brainpower: Government Regulation of Universities.  

ERIC Educational Resources Information Center

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.…

Seabury, Paul, Ed.

372

Regulation probability method for gene selection  

Microsoft Academic Search

This paper proposes a novel method for gene selection. In the method, the gene regulation, an important mechanism of gene activities, is first introduced, and then the probabilities of gene regulation are estimated. These probabilities can be seen as the gene regulation information and can be used for gene selection. The applications to the leukemia dataset and the colon dataset

Hong-qiang Wang; De-shuang Huang

2006-01-01

373

Plasma protein regulation by thyroid hormone  

Microsoft Academic Search

Thyroid hormones (THs) regulate growth, development, differentiation and metabolic processes by interacting and activating thyroid hormone receptors (TRs). Although much progress has been made in our understanding of the transcriptional regulation of many TR target genes, little is known of the regulation of plasma protein gene expression by TRs. To investigate the role of TRs in plasma protein expression we

K-H Lin; H-Y Lee; C-H Shih; C-C Yen; S-L Chen; R-C Yang; C-S Wang

2003-01-01

374

How does Public Regulation affect Growth?  

Microsoft Academic Search

Public regulations can increase economic growth by correcting market faults and decrease growth by consuming resources and reducing incentives. A simple theoretical framework is developed to represent commonly held views on the relationship between growth an regulation. The relationship is possibly non-linear with some level of regulation being optimal. We estimate the relation by a fixed effect non-linear panel data

Tue Goergens; Martin Paldam; Allan Würtz

375

Competition, Capital Regulation and Bank Risk Taking  

Microsoft Academic Search

This paper discusses the efiect of capital regulation on the risk taking be- havior of commercial banks. We flrst develop a simple model, which shows that capital regulation works difierently in difierent market structures of bank- ing sectors. In high competitive markets, capital regulation is efiective in mit- igating excessive risk taking behavior because banks' franchise values are low. If

Patrick Behr; Reinhard H. Schmidt; Ru Xie

2008-01-01

376

Land use regulation and new construction  

Microsoft Academic Search

This paper describes the relationship between land use regulation and residential construction. We characterize regulations as either adding explicit costs, uncertainty, or delays to the development process. The theoretical framework suggests that the effects on new construction vary by the type of regulation. Using quarterly data from a panel of 44 U.S. metropolitan areas between 1985 and 1996, we find

Christopher J. Mayer; C. Tsuriel Somerville

2000-01-01

377

Data considerations for regulation of water contaminants  

Microsoft Academic Search

There are several pieces of legislation based on human health assessment that set the framework for U.S. EPA's regulation of water contaminants, such as bromate. The Safe Drinking Water Act, for example, specifies that the best available science be used in support of regulation of drinking water contaminants, and highlights that regulations must provide protection to sensitive human populations. Recent

Rita Schoeny; Lynne Haber; Michael Dourson

2006-01-01

378

Diving second\\/stage demand regulator  

Microsoft Academic Search

The purpose of this study was to establish and analyze a controlling equation in a second stage demand regulator. The feasibility of optimizing the regulator design according to a controlling equation was evaluated. Equivalent flow constants to be used in testing the regulator capability at depth were also analytically determined. All these goals were achieved, As a result this study

S. Hilal; S. de Soto

1977-01-01

379

Disambiguating the Components of Emotion Regulation  

ERIC Educational Resources Information Center

|Affective neuroscience and cognitive science approaches are useful for understanding the components of emotion regulation; several examples from current research are provided. Individual differences in emotion regulation and a focus on the context of emotion experience and expression provide additional tools to study emotion regulation, and its…

Goldsmith, H. H.; Davidson, Richard J.

2004-01-01

380

Fast Voltage Regulator for Multilevel Flash Memories  

Microsoft Academic Search

This paper presents a very fast recovery voltage regulator for large capacitive loads in multilevel (ML) Flash memories. A suitable low-power structure limits positive output overshoots during transients, thereby allowing the basic regulation loop to be designed for very high recovery speed. The circuit is therefore able to quickly restore the output voltage to its regulated value when a previously

Osama Khouri; Rino Micheloni; Stefano Gregori; Guido Torelli

2000-01-01

381

48 CFR 2001.104-2 - Arrangement of the regulations.  

Code of Federal Regulations, 2011 CFR

...regulations. 2001.104-2 Section 2001.104-2 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Purpose, Authority, Issuance...

2011-10-01

382

48 CFR 2001.104-2 - Arrangement of the regulations.  

Code of Federal Regulations, 2012 CFR

...regulations. 2001.104-2 Section 2001.104-2 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION GENERAL NUCLEAR REGULATORY COMMISSION ACQUISITION REGULATION SYSTEM Purpose, Authority, Issuance...

2012-10-01

383

76 FR 13297 - Defense Federal Acquisition Regulation Supplement; Technical Amendments  

Federal Register 2010, 2011, 2012, 2013

...DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 215 Defense Federal Acquisition Regulation Supplement; Technical Amendments AGENCY: Defense Acquisition Regulations System, Department of Defense...

2011-03-11

384

76 FR 25 - Defense Federal Acquisition Regulation Supplement; Technical Amendments  

Federal Register 2010, 2011, 2012, 2013

...DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 252 Defense Federal Acquisition Regulation Supplement; Technical Amendments AGENCY: Defense Acquisition Regulations System, Department of Defense...

2011-01-03

385

Socially Constructed Self-Regulated Learning and Motivation Regulation in Collaborative Learning Groups  

ERIC Educational Resources Information Center

|Background/Context: Most of the earlier empirical findings deal with motivation regulation in individual learning situations. This study identifies higher education students' socially constructed motivation regulation in collaborative learning and stresses that regulation of motivation is crucial in socially self-regulated learning because…

Jarvela, Sanna; Jarvenoja, Hanna

2011-01-01

386

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

ERIC Educational Resources Information Center

|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…

Kaplan, Avi

2008-01-01

387

Regulation and insurer competition: Did insurers use rate regulation to reduce competition?  

Microsoft Academic Search

This article examines rate regulation and the market share of insurers using exclusive agents, known as direct writers. Direct writers have lower market share in rate regulation states; however, the effect is observed in both the regulated automobile lines and the less regulated homeowners' insurance. This suggests that statute implementation and not the statue itself affects insurers' market shares. Including

Anne Gron

1995-01-01

388

Removal of Regulations. Final Regulations. Federal Register, Department of Education, 34 CFR Part 345  

ERIC Educational Resources Information Center

|The Secretary amends the Code of Federal Regulations (CFR) to remove obsolete regulations. As a result of the enactment of the Assistive Technology Act of 1998, these regulations are no longer needed. The Secretary therefore takes this action to remove the regulations. Part 345 is removed effective March 25, 2004.|

National Archives and Records Administration, 2004

2004-01-01

389

Information Economics and New Forms of Regulation  

Microsoft Academic Search

\\u000a The regulation of public utilities is currently undergoing some major changes. These are particularly in evidence in telecommunications,\\u000a where technological change, competition, and entry are bringing about drastic rethinking in the way telecommunications are\\u000a regulated. For AT&T Communications, price-cap regulation has now replaced traditional rate-of-return regulation in their interstate\\u000a long-distance telecommunications business. Price-cap regulation is currently under active consideration for

A Michael Crew; Michael R. Frierman

390

Implementing HIPAA privacy regulations in pharmacy practice.  

PubMed

A worthy goal of HIPAA is to protect the privacy of patient health information. Final regulations for achieving this goal have been issued, and all covered entities, including all pharmacies that transmit health information electronically, must comply with these regulations by April 14, 2003. Pharmacists are strongly advised to begin educating themselves about the HIPAA privacy regulations and taking steps toward implementation as soon as possible. Because of the complexity of the privacy rule and the lingering ambiguities about how to implement the regulations, pharmacies also are encouraged to obtain expert guidance and stay up-to-date with the regulations and implementation recommendations posted by OCR. PMID:12482006

Bishop, Susan K; Winckler, Susan C

391

Hospital rate regulation: American and foreign comparisons.  

PubMed

Rate regulation in the United States usually is inspired by widespread indignant pressures to protect the public against venal exploitation. Rate regulation of American hospitals does not ride such a wave of outrage but is motivated by the need to restrain Medicaid spending and insurance premium increases in some states. Hospital rate regulation in America lacks strong political support, makes many politically prudent concessions to hospitals, and is often threatened by repeal. Since Americans distrust regulators and since individual scrutiny of so many hospitals is burdensome and contentious, they often seek automatic formulae that will produce equitable results by rational calculation. In contrast, rate regulation in Europe is a method of refereeing between hospitals and alert third parties. Hospitals' prospective budgets are always scrutinized by regulators. Guidelines are transmitted by government to link public policy to hospital payment, and the regulators apply the guidelines to each hospital's individual situation. The system results in less contention and more stability in European than in American regulation. Certain features of European hospital practice have kept hospital costs high, but the regulators are now reducing annual increases in costs below America's. In order to reduce cost increases further, Europe is moving toward global budgeting and public grants of hospitals' operating costs, instead of regulation of unit rates. However, regulators may still be essential to scrutinize hospital prospective budgets and to investigate the merits of the claims by individual establishments. PMID:6421923

Glaser, W A

1984-01-01

392

A New Synchronous Current Regulator and an Analysis of Current-Regulated PWM Inverters  

Microsoft Academic Search

Detailed models are presented for the stationary and synchronous sine-triangle current regulators. Analytical and test results are compared for purposes of model verification and regulator evaluation. The results demonstrate the limitations of the two most often used current regulators and the robustness of the synchronous current regulator. The stationary sine-triangle and hysteretic current regulators are shown to have steady-state characteristics

Timothy M. Rowan; Russel J. Kerkman

1986-01-01

393

Replica Compensated Linear Regulators for Supply-Regulated Phase-Locked Loops  

Microsoft Academic Search

Supply-regulated phase-locked loops rely upon the VCO voltage regulator to maintain a low sensitivity to supply noise and hence low overall jitter. By analyzing regulator supply rejection, we show that in order to simultaneously meet the bandwidth and low dropout requirements, previous regulator implementations used in supply-regulated PLLs suffer from unfavorable tradeoffs between power supply rejection and power consumption. We

Elad Alon; Jaeha Kim; Sudhakar Pamarti; Ken Chang; Mark Horowitz

2006-01-01

394

Oxygen Regulates Tissue Nitrite Metabolism  

PubMed Central

Abstract Aims: Once dismissed as an inert byproduct of nitric oxide (NO) auto-oxidation, nitrite (NO2-) is now accepted as an endocrine reservoir of NO that elicits biological responses in major organs. While it is known that tissue nitrite is derived from NO oxidation and the diet, little is known about how nitrite is metabolized by tissue, particularly at intermediate oxygen tensions. We investigated the rates and mechanisms of tissue nitrite metabolism over a range of oxygen concentrations. Results: We show that the rate of nitrite consumption differs in each organ. Further, oxygen regulates the rate and products of nitrite metabolism. In anoxia, nitrite is reduced to NO, with significant formation of iron–nitrosyl proteins and S-nitrosothiols. This hypoxic nitrite metabolism is mediated by different nitrite reductases in each tissue. In contrast, low concentrations (?3.5??M) of oxygen increase the rate of nitrite consumption by shifting nitrite metabolism to oxidative pathways, yielding nitrate. While cytochrome P450 and myoglobin contribute in the liver and heart, respectively, mitochondrial cytochrome c oxidase plays a significant role in nitrite oxidation, which is inhibited by cyanide. Using cyanide to prevent artifactual nitrite decay, we measure metabolism of oral and intraperitoneally administered nitrite in mice. Innovation: These data provide insight into the fate of nitrite in tissue, the enzymes involved in nitrite metabolism, and the role of oxygen in regulating these processes. Conclusion: We demonstrate that even at low concentrations, oxygen is a potent regulator of the rate and products of tissue nitrite metabolism. Antioxid. Redox Signal. 17, 951–961.

Curtis, Erin; Hsu, Lewis L.; Noguchi, Audrey C.; Geary, Lisa

2012-01-01

395

Tonic regulation of vascular permeability.  

PubMed

Our major theme is that the layered structure of the endothelial barrier requires continuous activation of signalling pathways regulated by sphingosine-1-phosphate (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 signalling 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 re-establishing 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

Curry, F-R E; Adamson, R H

2013-02-25

396

[Ultraviolet: a regulator of immunity].  

PubMed

Humans establish acquired immune systems during the growth, which can sufficiently eliminate pathogen avoiding immune responses to self, such as allergy and autoimmunity. An imbalance of the acquired immune system leads up to immune-mediated disorders. Ultraviolet (UV) exposure helps to establish the normal peripheral tolerance to contact allergen avoiding excessive immune responses. By contrast, UV develops kinds of autoimmune diseases on rare occasions, suggesting that abnormality in the process of UV-induced peripheral tolerance may induce these diseases. To elucidate the mechanism of UV-induced tolerance is possible to provide a new approach for the management of immune diseases. In the current review, focus is on the suggested players of UV-induced tolerance, blocking mechanisms on the elicitation phase of contact hypersensitivity, and the association between UV and autoimmunity. The major impact in basic immunology in this area is the discovery of cell surface marker of regulatory T cells. Therefore, we first discuss about the association of regulatory/suppressor T cells with UV-induced tolerance. Since the elicitation phase depends on cellular influx into the inflammatory sites, which is tightly regulated by adhesion molecules, we also focused on the role of adhesion molecules. Finally, this paper also includes statistical findings concerning the association between UV-radiation and the prevalence of a myositis specific autoantibody. Thus, UV is one of the nice regulators of an immune network and the knowledge of UV-mediated immune regulation will be translated into new therapeutic strategies to human immune-mediated disorders. PMID:18587222

Komura, Kazuhiro

2008-06-01

397

The regulation of cell size.  

PubMed

An adult animal consists of cells of vastly different size and activity, but the regulation of cell size remains poorly understood. Recent studies uncovering some of the signaling pathways important for size/growth control, together with the identification of diseases resulting from aberrations in these pathways, have renewed interest in this field. This Review will discuss our current understanding of how a cell sets its size, how it can adapt its size to a changing environment, and how these processes are relevant to human disease. PMID:24034244

Lloyd, Alison C

2013-09-12

398

QB1 - Stochastic Gene Regulation  

SciTech Connect

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.

Munsky, Brian [Los Alamos National Laboratory

2012-07-23

399

Energy Regulation in Young People  

PubMed Central

Obesity in young people is now realised as a worldwide crisis of epidemic proportion. The aetiology of this disease suggests a disruption in regulation of energy at the population level, leading to a positive energy balance and excess adiposity. The relative contribution of food intake and physical inactivity remains to be elucidated. Treatment interventions have aimed to create a deficit in energy balance through manipulation of physical activity, behavioural components or, to a lesser extent, dietary modification. Whether such intervention is maintained in the long-term is as yet unclear, however it seems a combination of therapies is optimal. Mindful of a mismatch between energy intake and expenditure, recent work has begun to examine the acute relationship between physical activity and food intake in children. Initial findings suggest a short-term delay in compensation through energy intake for exercise- induced energy expenditure. The overarching study of energy regulation in children and adolescents is clearly multifaceted in nature and variables to be assessed or manipulated require careful consideration. The collection of paediatric physical activity, energy expenditure and food intake data is a time-consuming process, fraught with potential sources of error. Investigators should consider the validity and reliability of these and other issues, alongside the logistics of any proposed study. Despite these areas of concern, recent advances in the field should provide exciting opportunities for future research in paediatric energy regulation on a variety of levels. Key pointsPhysical activity appears to be an effective intervention in paediatric weight-management, however future studies need to be extended over the longer-term employing consistent protocols to aid comparison.In the short-term, exercise-induced energy expenditure and subsequent energy intake do not appear to be tightly regulated in young people; this acute imbalance is similar to the ‘loose coupling’ of energy described for adults.The relationship between energy expenditure and food intake in young people requires further examination in longer-term interventions. A rigorous protocol is necessary to study parameters under free-living conditions.

Dodd, Caroline J.

2007-01-01

400

Inositol pyrophosphates regulate endocytic trafficking  

PubMed Central

The high energy potential and rapid turnover of the recently discovered inositol pyrophosphates, such as diphosphoinositol-pentakisphosphate and bis-diphosphoinositol-tetrakisphosphate, suggest a dynamic cellular role, but no specific functions have yet been established. Using several yeast mutants with defects in inositol phosphate metabolism, we identify dramatic membrane defects selectively associated with deficient formation of inositol pyrophosphates. We show that this phenotype reflects specific abnormalities in endocytic pathways and not other components of membrane trafficking. Thus, inositol pyrophosphates are major regulators of endocytosis.

Saiardi, Adolfo; Sciambi, Catherine; McCaffery, J. Michael; Wendland, Beverly; Snyder, Solomon H.

2002-01-01

401

Circadian regulation of adipose function.  

PubMed

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

Shostak, Anton; Husse, Jana; Oster, Henrik

2013-08-13

402

Returning common sense to regulations  

SciTech Connect

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

Fox, M.R.

1995-10-01

403

Environmental justice regulations draw fire  

NASA Astrophysics Data System (ADS)

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

Showstack, Randy

404

Environmental justice regulations draw fire  

NASA Astrophysics Data System (ADS)

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

Showstack, Randy

405

Modeling Auxin-regulated Development  

PubMed Central

The phytohormone auxin plays an essential role in many aspects of plant growth and development. Its patterning, intercellular transport, and means of signaling have been extensively studied both in experiments and computational models. Here, we present a review of models of auxin-regulated development in different plant tissues. This includes models of organ initiation in the shoot apical meristem, development of vascular strands in leafs and stems, and auxin-related functioning in roots. The examples show how mathematical modeling can help to examine expected and unexpected behavior of the system, challenge our knowledge and hypotheses, obtain quantitative results, or suggest new experiments and ways to approach a problem.

Krupinski, Pawel; Jonsson, Henrik

2010-01-01

406

Circadian regulation of adipose function  

PubMed Central

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.

Shostak, Anton; Husse, Jana; Oster, Henrik

2013-01-01

407

Frequency Regulation Basics and Trends  

SciTech Connect

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.

Kirby, BJ

2005-05-06

408

Endocytic regulation of Notch signaling  

PubMed Central

Endocytosis and endosomal trafficking have emerged as important cell biological steps in the Notch developmental signaling pathway. Ligand endocytosis helps generate the physical forces needed to dissociate and activate the receptor, and activated receptors enter endosomes to signal productively. Endosomal trafficking is also responsible for down-regulating Notch receptors that have not been activated by ligand. Recent studies have provided new insights into these Notch trafficking steps, and have uncovered additional endosomal mechanisms that contribute to asymmetric Notch activation and ligand-independent Notch signaling.

Fortini, Mark E.; Bilder, David

2009-01-01

409

Safe harbor regulations for GPOs.  

PubMed

At one time, GPOs were placed under the umbrella of those who receive "kickbacks". Now, they have regulations that specifically exempt them from legal repercussions when accepting fees for recommending to its member hospitals that they do business with particular healthcare vendors. In short, for a GPO to legally accept fees from vendors, the GPO needs a written agreement with each hospital that permits the GPO to accept fees and it must report in writing to the hospitals at least annually the amount of the fees collected from each vendor. PMID:10117776

Thomas, H

1992-05-01

410

7 CFR 925.51 - Recommendation for regulation.  

Code of Federal Regulations, 2013 CFR

...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....

2013-01-01

411

7 CFR 915.55 - Avocados not subject to regulations.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 2013-01-01 false Avocados not subject to regulations. 915...NUTS), DEPARTMENT OF AGRICULTURE AVOCADOS GROWN IN SOUTH FLORIDA Order Regulating Handling Regulations § 915.55 Avocados not subject to regulations....

2013-01-01

412

Agouti regulates adipocyte transcription factors.  

PubMed

Agouti is a secreted paracrine factor that regulates pigmentation in hair follicle melanocytes. Several dominant mutations cause ectopic expression of agouti, resulting in a phenotype characterized by yellow fur, adult-onset obesity and diabetes, increased linear growth and skeletal mass, and increased susceptibility to tumors. Humans also produce agouti protein, but the highest levels of agouti in humans are found in adipose tissue. To mimic the human agouti expression pattern in mice, transgenic mice (aP2-agouti) that express agouti in adipose tissue were generated. The transgenic mice develop a mild form of obesity, and they are sensitized to the action of insulin. We correlated the levels of specific regulators of insulin signaling and adipocyte differentiation with these phenotypic changes in adipose tissue. Signal transducers and activators of transcription (STAT)1, STAT3, and peroxisome proliferator-activated receptor (PPAR)-gamma protein levels were elevated in the transgenic mice. Treatment of mature 3T3-L1 adipocytes recapitulated these effects. These data demonstrate that agouti has potent effects on adipose tissue. We hypothesize that agouti increases adiposity and promotes insulin sensitivity by acting directly on adipocytes via PPAR-gamma. PMID:11245612

Mynatt, R L; Stephens, J M

2001-04-01

413

NRC regulation of DOE facilities  

SciTech Connect

The US Department of Energy (DOE), its contractors, and the Nuclear Regulatory Commission (NRC) are in for major changes if the DOE follows through on its intentions announced December 20, 1996. The DOE is seeking legislation to establish the NRC as the regulatory agency with jurisdiction over nuclear health, safety, and security at a wide range of DOE facilities. At this stage, it appears that as many as 200 (though not all) DOE facilities would be affected. On March 28, 1997, the NRC officially endorsed taking over the responsibility for regulatory oversight of DOE nuclear facilities as the DOE had proposed, contingent upon adequate funding, staffing resources, and a clear delineation of NRC authority. This article first contrasts the ways in which the NRC and the DOE carry out their basic regulatory functions. Next, it describes the NRC`s current authority over DOE facilities and the status of the DOE`s initiative to expand that authority. Then, it discusses the basic changes and impacts that can be expected in the regulation of DOE facilities. The article next describes key lessons learned from the recent transition of the GDPs from DOE oversight to NRC regulation and the major regulatory issues that arose in that transition. Finally, some general strategies are suggested for resolving issues likely to arise as the NRC assumes regulatory authority over DOE facilities.

Buhl, A.R. [Kaiser-Hill, Golden, CO (United States); Edgar, G.; Silverman, D. [Morgan, Lewis and Bockius, Washington, DC (United States); Murley, T.

1997-08-01

414

Gene expression regulation in trypanosomatids.  

PubMed

Trypanosomatids are protozoan micro-organisms that cause serious health problems in humans and domestic animals. In addition to their medical relevance, these pathogens have novel biological structures and processes. From nuclear DNA transcription to mRNA translation, trypanosomes use unusual mechanisms to control gene expression. For example, transcription by RNAPII (RNA polymerase II) is polycistronic, and only a few transcription initiation sites have been identified so far. The sequences present in the polycistronic units code for proteins having unrelated functions, that is, not involved in a similar metabolic pathway. Owing to these biological constraints, these micro-organisms regulate gene expression mostly by post-transcriptional events. Consequently, the function of proteins that recognize RNA elements preferentially at the 3' UTR (untranslated region) of transcripts is central. It was recently shown that mRNP (messenger ribonucleoprotein) complexes are organized within post-transcriptional operons to co-ordinately regulate gene expression of functionally linked transcripts. In the present chapter we will focus on particular characteristics of gene expression in the so-called TriTryp parasites: Trypanosoma cruzi, Trypanosoma brucei and Leishmania major. PMID:22023440

De Gaudenzi, Javier G; Noé, Griselda; Campo, Vanina A; Frasch, Alberto C; Cassola, Alejandro

2011-01-01

415

Microbial regulation in gorgonian corals.  

PubMed

Gorgonian corals possess many novel natural products that could potentially mediate coral-bacterial interactions. Since many bacteria use quorum sensing (QS) signals to facilitate colonization of host organisms, regulation of prokaryotic cell-to-cell communication may represent an important bacterial control mechanism. In the present study, we examined extracts of twelve species of Caribbean gorgonian corals, for mechanisms that regulate microbial colonization, such as antibacterial activity and QS regulatory activity. Ethanol extracts of gorgonians collected from Puerto Rico and the Florida Keys showed a range of both antibacterial and QS activities using a specific Pseudomonas aeruginosa QS reporter, sensitive to long chain AHLs and a short chain N-acylhomoserine lactones (AHL) biosensor, Chromobacterium violaceium. Overall, the gorgonian corals had higher antimicrobial activity against non-marine strains when compared to marine strains. Pseudopterogorgia americana, Pseusopterogorgia acerosa, and Pseudoplexuara flexuosa had the highest QS inhibitory effect. Interestingly, Pseudoplexuara porosa extracts stimulated QS activity with a striking 17-fold increase in signal. The stimulation of QS by P. porosa or other elements of the holobiont may encourage colonization or recruitment of specific microbial species. Overall, these results suggest the presence of novel stimulatory QS, inhibitory QS and bactericidal compounds in gorgonian corals. A better understanding of these compounds may reveal insight into coral-microbial ecology and whether a therapeutic potential exists. PMID:22822369

Hunt, Laura R; Smith, Stephanie M; Downum, Kelsey R; Mydlarz, Laura D

2012-06-04

416

Microbial Regulation in Gorgonian Corals  

PubMed Central

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

Hunt, Laura R.; Smith, Stephanie M.; Downum, Kelsey R.; Mydlarz, Laura D.

2012-01-01

417

Understanding regulations affecting pet foods.  

PubMed

In the United States, pet foods are subject to regulation at both the federal and the state levels. The US Food and Drug Administration has jurisdiction over all animal feeds (including pet foods, treats, chews, supplements, and ingredients) in interstate commerce, which includes imported products. Many states adopt and enforce at least in part the Association of American Feed Control Officials Model Bill and Model Regulations for Pet Food and Specialty Pet Food. Thus, all pet foods in multi-state distribution are subject to a host of labeling requirements covering aspects such as product names, ingredient lists, nutrient content guarantees, and nutritional adequacy statements. Ingredients must be GRAS (generally recognized as safe) substances, approved food additives, or defined by Association of American Feed Control Officials for their intended use. Pet food labels may not bear claims that are false or misleading or that state or imply use for the treatment or prevention of disease. Pet foods that are found to be adulterated or misbranded may be subject to seizure or other enforcement actions. PMID:18656837

Dzanis, David A

2008-08-01

418

Connexin40 regulates platelet function  

PubMed Central

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.

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

419

Voltage regulates adrenergic receptor function  

PubMed Central

The present study demonstrates that agonist-mediated activation of ?2A adrenergic receptors (?2AAR) is voltage-dependent. By resolving the kinetics of conformational changes of ?2AAR at defined membrane potentials, we show that negative membrane potentials in the physiological range promote agonist-mediated activation of ?2AAR. We discovered that the conformational change of ?2AAR by voltage is independent from receptor-G protein docking and regulates receptor signaling, including ?-arrestin binding, activation of G proteins, and G protein-activated inwardly rectifying K+ currents. Comparison of the dynamics of voltage-dependence of clonidine- vs. norepinephrine-activated receptors uncovers interesting mechanistic insights. For norepinephrine, the time course of voltage-dependent deactivation reflected the deactivation kinetics of the receptor after agonist withdrawal and was strongly attenuated at saturating concentrations. In contrast, clonidine-activated ?2AAR were switched by voltage even under fully saturating concentrations, and the kinetics of this switch was notably faster than dissociation of clonidine from ?2AAR, indicating voltage-dependent regulation of the efficacy. We conclude that adrenergic receptors exhibit a unique, agonist-dependent mechanism of voltage-sensitivity that modulates downstream receptor signaling.

Rinne, Andreas; Birk, Alexandra; Bunemann, Moritz

2013-01-01

420

Phosphorylation regulates human OCT4  

PubMed Central

The transcription factor OCT4 is fundamental to maintaining pluripotency and self-renewal. To better understand protein-level regulation of OCT4, we applied liquid chromatography–MS to identify 14 localized sites of phosphorylation, 11 of which were previously unknown. Functional analysis of two sites, T234 and S235, suggested that phosphorylation within the homeobox region of OCT4 negatively regulates its activity by interrupting sequence-specific DNA binding. Mutating T234 and S235 to mimic constitutive phosphorylation at these sites reduces transcriptional activation from an OCT4-responsive reporter and decreases reprogramming efficiency. We also cataloged 144 unique phosphopeptides on known OCT4 interacting partners, including SOX2 and SALL4, that copurified during immunoprecipitation. These proteins were enriched for phosphorylation at motifs associated with ERK signaling. Likewise, OCT4 harbored several putative ERK phosphorylation sites. Kinase assays confirmed that ERK2 phosphorylated these sites in vitro, providing a direct link between ERK signaling and the transcriptional machinery that governs pluripotency.

Brumbaugh, Justin; Russell, Jason D.; Howden, Sara E.; Yu, Pengzhi; Ledvina, Aaron R.; Coon, Joshua J.; Thomson, James A.

2012-01-01

421

How cholesterol regulates endothelial biomechanics  

PubMed Central

As endothelial cells form the barrier between blood flow and surrounding tissue, many of their functions depend on mechanical integrity, in particular those of the plasma membrane. As component and organizer of the plasma membrane, cholesterol is a regulator of cellular mechanical properties. Disruption of cholesterol balance leads to impairment of endothelial functions and eventually to disease. The mechanical properties of the membrane are strongly affected by the cytoskeleton. As Phosphatidylinositol-4,5-bisphosphate (PIP2) is a key mediator between the membrane and cytoskeleton, it also affects cellular biomechanical properties. Typically, PIP2 is concentrated in cholesterol-rich microdomains, such as caveolae and lipid rafts, which are particularly abundant in the endothelial plasma membrane. We investigated the connection between cholesterol and PIP2 by extracting membrane tethers from bovine aortic endothelial cells (BAEC) at different cholesterol levels and PIP2 conditions. Our results suggest that in BAEC the role of PIP2, as a mediator of membrane-cytoskeleton adhesion, is regulated by cholesterol. Our findings confirm the specific role of cholesterol in endothelial cells and may have implications for cholesterol-dependent vascular pathologies.

Hong, Zhongkui; Staiculescu, Marius C.; Hampel, Paul; Levitan, Irena; Forgacs, Gabor

2012-01-01

422

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

PubMed Central

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.

Troxell, Bryan; Hassan, Hosni M.

2013-01-01

423

Dynamic Voltage Regulation Using Distributed Energy Resources  

SciTech Connect

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.

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

2007-01-01

424

Perfectionism and Deficits in Cognitive Emotion Regulation  

Microsoft Academic Search

The current study investigated the general hypothesis that perfectionists have deficits in cognitive emotion regulation. A\\u000a sample of 100 students completed the Perfectionism Cognitions Inventory, the Multidimensional Perfectionism Scale, the Cognitive\\u000a Emotion Regulation Questionnaire (CERQ), and a measure of depression. Correlational analyses revealed that frequent thoughts\\u000a involving perfectionism were associated with maladaptive cognitive emotion regulation tendencies, including catastrophization,\\u000a self-blame, rumination,

Susan G. Rudolph; Gordon L. Flett; Paul L. Hewitt

2007-01-01

425

Global virulence regulation networks in phytopathogenic bacteria  

Microsoft Academic Search

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

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

2007-01-01

426

Regulation of phospholipid synthesis in yeast  

PubMed Central

Phospholipid synthesis in the yeast Saccharomyces cerevisiae is a complex process that involves regulation by both genetic and biochemical mechanisms. The activity levels of phospholipid synthesis enzymes are controlled by gene expression (e.g., transcription) and by factors (lipids, water-soluble phospholipid precursors and products, and covalent modification of phosphorylation) that modulate catalysis. Phosphatidic acid, whose levels are controlled by the biochemical regulation of key phospholipid synthesis enzymes, plays a central role in the regulation of phospholipid synthesis gene expression.

Carman, George M.; Han, Gil-Soo

2009-01-01

427

Rho as a regulator of the cytoskeleton  

Microsoft Academic Search

Many cell functions, including maintenance of morphology, aggregation, motility, membrane ruffling, smooth-muscle contraction, cytokinesis in mammals and bud formation in yeast, are regulated through the dynamic reorganization of actin filaments. Although it has long been known that Ca2+ is a key regulator of the cytoskeleton, evidence is now accumulating that Rho, a Ras-related small GTP-binding protein, is another important regulator

Yoshimi Takai; Takuya Sasaki; Kazuma Tanaka; Hiroyuki Nakanishi

1995-01-01

428

Focus Issue: Regulation of Lymphocyte Function  

NSDL National Science Digital Library

During the month of July, Science Signaling has highlighted mechanisms by which lymphocytes of the innate and adaptive immune responses are regulated to promote effective immunity and prevent inappropriate and damaging responses. Research Articles and Perspectives in this series and the Archives focus on the mechanisms by which the functions of T cells, B cells, and natural killer cells are regulated and the therapeutic implications of understanding the regulation of these cells.

Ernesto Andrianantoandro (American Association for the Advancement of Science;Science Signaling REV); John F. Foley (American Association for the Advancement of Science;Science Signaling REV)

2012-07-31

429

Regulation of Plant Protection in Organic Farming  

Microsoft Academic Search

\\u000a Organic farming is a system approach aiming at a sustainable ecosystem, safe food, good nutrition, animal welfare and social\\u000a justice. Quantitatively, organic farming is still of minor importance, but it is one of the most rapidly growing agricultural\\u000a sectors worldwide. The new EU ‘organic regulation’ consists of a framework regulation, complemented by implementation rules\\u000a and guidelines. Other important regulations\\/standards are

Bernhard Speiser; Lucius Tamm

430

MicroRNA Regulation of Cardiovascular Development  

Microsoft Academic Search

The transcriptional regulation of cardiovascular development requires precise spatiotemporal control of gene expression, and heterozygous mutations of transcription factors have frequently been implicated in human cardiovas- cular malformations. A novel mechanism involving posttranscriptional regulation by small, noncoding microRNAs (miRNAs) has emerged as a central regulator of many cardiogenic processes. We are beginning to understand the functions that miRNAs play during

Eric Olson; Kimberly R. Cordes; Deepak Srivastava

2009-01-01

431

Epigenetics of ?-globin gene regulation  

PubMed Central

It is widely recognized that the next great challenge in the post-genomic period is to understand how the genome establishes the cell and tissue specific patterns of gene expression that underlie development. The ?-globin genes are among the most extensively studied tissue specific and developmentally regulated genes. The onset of erythropoiesis in precursor cells and the progressive expression of different members of the ?-globin family during development are accompanied by dramatic epigenetic changes in the locus. In this review, we will consider the relationship between histone and DNA modifications and the transcriptional activity of the ?-globin genes, the dynamic changes in epigenetic modifications observed during erythroid development, and the potential these changes hold as new targets for therapy in human disease.

Kiefer, Christine M.; Hou, Chunhui; Little, Jane; Dean, Ann

2008-01-01

432

Robustness in Glyoxylate Bypass Regulation  

PubMed Central

The glyoxylate bypass allows Escherichia coli to grow on carbon sources with only two carbons by bypassing the loss of carbons as CO2 in the tricarboxylic acid cycle. The flux toward this bypass is regulated by the phosphorylation of the enzyme isocitrate dehydrogenase (IDH) by a bifunctional kinase–phosphatase called IDHKP. In this system, IDH activity has been found to be remarkably robust with respect to wide variations in the total IDH protein concentration. Here, we examine possible mechanisms to explain this robustness. Explanations in which IDHKP works simultaneously as a first-order kinase and as a zero-order phosphatase with a single IDH binding site are found to be inconsistent with robustness. Instead, we suggest a robust mechanism where both substrates bind the bifunctional enzyme to form a ternary complex.

Shinar, Guy; Rabinowitz, Joshua D.; Alon, Uri

2009-01-01

433

Molecular regulation of fruit ripening.  

PubMed

Fruit ripening is a highly coordinated developmental process that coincides with seed maturation. The ripening process is regulated by thousands of genes that control progressive softening and/or lignification of pericarp layers, accumulation of sugars, acids, pigments, and release of volatiles. Key to crop improvement is a deeper understanding of the processes underlying fruit ripening. In tomato, mutations blocking the transition to ripe fruits have provided insights into the role of ethylene and its associated molecular networks involved in the control of ripening. However, the role of other plant hormones is still poorly understood. In this review, we describe how plant hormones, transcription factors, and epigenetic changes are intimately related to provide a tight control of the ripening process. Recent findings from comparative genomics and system biology approaches are discussed. PMID:23785378

Osorio, Sonia; Scossa, Federico; Fernie, Alisdair R

2013-06-14

434

Wetlands: their use and regulation  

SciTech Connect

Although destruction of United States wetlands has slowed, their continued conversion, especially in certain inland regions of the country, may pose adverse ecological effects over the next few decades. The Army Corps of Engineers' regulatory program (Section 404 of the Clean Water Act) protects most coastal wetlands, but provides no protection for 95% of the country's wetlands which remain inland. These inland, freshwater wetlands, converted for agricultural purposes, comprise 80% of the wetland losses over the past 30 years. This report outlines options for more effective federal management, such as the mapping and categorizing of wetlands to determine relative values. In effect, agencies can focus protection programs on higher-value wetlands, especially those threatened by agricultural conversion. The report also discusses the contradictory federal policies aimed at wetlands; for example, the tax code encourages the development and draining of wetlands at the same time that federal regulations discourage their destruction.

Not Available

1984-01-01

435

Neurohormones regulate T cell function  

PubMed Central

In this communication we show that T cell locomotion is affected by direct interaction with neurohormones. Opioid peptides, including beta- END, MET-ENK, LEU-ENK, and related enkephalin analogues enhanced migration of human peripheral blood T lymphocytes. Activity was dependent on the peptide NH2-terminal sequence, stimulated by enkephalin analogues with specificity for classical delta or mu types of opiate receptor, and inhibited by the opiate receptor antagonist naloxone. Our studies suggest that such neuropeptides stimulate T cell chemotaxis by interaction with sites analogues to classical opiate receptors. We propose that the endogenous opioids beta-END, MET-ENK, and LEU-ENK are potent immunomodulating signals that regulate the trafficking of immune response cells.

1990-01-01

436

Physicochemical regulation of biofilm formation  

PubMed Central

This article reviews the physical and chemical constraints of environments on biofilm formation. We provide a perspective on how materials science and engineering can address fundamental questions and unmet technological challenges in this area of microbiology, such as biofilm prevention. Specifically, we discuss three factors that impact the development and organization of bacterial communities. (1) Physical properties of surfaces regulate cell attachment and physiology and affect early stages of biofilm formation. (2) Chemical properties influence the adhesion of cells to surfaces and their development into biofilms and communities. (3) Chemical communication between cells attenuates growth and influences the organization of communities. Mechanisms of spatial and temporal confinement control the dimensions of communities and the diffusion path length for chemical communication between biofilms, which, in turn, influences biofilm phenotypes. Armed with a detailed understanding of biofilm formation, researchers are applying the tools and techniques of materials science and engineering to revolutionize the study and control of bacterial communities growing at interfaces.

Renner, Lars D.; Weibel, Douglas B.

2011-01-01

437

["Medical devices and European regulations"].  

PubMed

In order to put on the European Market, the medical devices shall be in conformity with two European Directives transcribed in national regulation: Directive 90/385/CEE--20 June 1990: concerning the implantable active medical devices, mandatory since the 1/01/95; Directive 93/42/CEE--13 June 1993: concerning the medical devices, applicable since the 1/01/95 and mandatory the 14/06/98. Both impose the conformity to essential requirements which can be proved by different procedures of evaluation verified by notify bodies. Then, the CE mark, technical passport, can be apposed. To demonstrate this conformity, the manufacturers can use harmonized european standards without obligation. The "Safety clause" allows to follow the "well-founded" of the CE marking and the national systems of vigilance to register and evaluate the incidents and to define corrective actions. PMID:9181704

Fleur, F

1997-01-01

438

Transcriptional Regulation: a Genomic Overview  

PubMed Central

The availability of the Arabidopsis thaliana genome sequence allows a comprehensive analysis of transcriptional regulation in plants using novel genomic approaches and methodologies. Such a genomic view of transcription first necessitates the compilation of lists of elements. Transcription factors are the most numerous of the different types of proteins involved in transcription in eukaryotes, and the Arabidopsis genome codes for more than 1,500 of them, or approximately 6% of its total number of genes. A genome-wide comparison of transcription factors across the three eukaryotic kingdoms reveals the evolutionary generation of diversity in the components of the regulatory machinery of transcription. However, as illustrated by Arabidopsis, transcription in plants follows similar basic principles and logic to those in animals and fungi. A global view and understanding of transcription at a cellular and organismal level requires the characterization of the Arabidopsis transcriptome and promoterome, as well as of the interactome, the localizome, and the phenome of the proteins involved in transcription.

Riechmann, Jose Luis

2002-01-01

439

Extracellular Matrix Regulation of Autophagy  

PubMed Central

Summary Integrin-mediated attachment of epithelial cells to extracellular matrix (ECM) is critical for proper growth and survival. Although detachment leads to apoptosis, termed anoikis, recent work demonstrates that ECM detachment also robustly induces autophagy, a tightly regulated lysosomal self-digestion process that actually promotes survival. Autophagy presumably protects epithelial cells from the stresses of ECM detachment, allowing them to survive provided they reattach in a timely manner. Currently, the intracellular signals linking integrin engagement to autophagy remain unclear, but certain growth factor, energy-sensing, and stress response pathways represent attractive candidates. Moreover, autophagy may be a previously unrecognized mechanism utilized by detached cancer cells to survive anoikis, which may facilitate tumor cell dormancy, dissemination, and metastasis.

Lock, Rebecca; Debnath, Jayanta

2008-01-01

440

Regulation of Lrp6 phosphorylation.  

PubMed

The Wnt/beta-catenin signaling pathway plays important roles in embryonic development and tissue homeostasis, and is implicated in human disease. Wnts transduce signals via transmembrane receptors of the Frizzled (Fzd/Fz) family and the low density lipoprotein receptor-related protein 5/6 (Lrp5/6). A key mechanism in their signal transduction is that Wnts induce Lrp6 signalosomes, which become phosphorylated at multiple conserved sites, notably at PPSPXS motifs. Lrp6 phosphorylation is crucial to beta-catenin stabilization and pathway activation by promoting Axin and Gsk3 recruitment to phosphorylated sites. Here, we summarize how proline-directed kinases (Gsk3, PKA, Pftk1, Grk5/6) and non-proline-directed kinases (CK1 family) act upon Lrp6, how the phosphorylation is regulated by ligand binding and mitosis, and how Lrp6 phosphorylation leads to beta-catenin stabilization. PMID:20229235

Niehrs, Christof; Shen, Jinlong

2010-03-14

441

Astroglial regulation of sleep homeostasis.  

PubMed

Mammalian sleep is regulated by two distinct mechanisms. A circadian oscillator provides timing signals that organize sleep and wake across the 24hour day. A homeostatic mechanism increases sleep drive and sleep amounts (or intensity) as a function of prior time awake. The cellular mechanisms of sleep homeostasis are poorly defined, but are thought to be primarily neuronal. According to one view, sleep homeostasis arises from interactions between subcortical neurons that register sleep pressure and other neurons that promote either sleep or wakefulness. Alternatively, sleep drive may arise independently among neurons throughout the brain in a use-dependent fashion. Implicit in both views is the idea that sleep homeostasis is solely the product of neurons. In this article, I discuss an emerging view that glial astrocytes may play an essential role in sleep homeostasis. PMID:23518138

Frank, Marcos G

2013-03-18

442

Homologous recombination and its regulation  

PubMed Central

Homologous recombination (HR) is critical both for repairing DNA lesions in mitosis and for chromosomal pairing and exchange during meiosis. However, some forms of HR can also lead to undesirable DNA rearrangements. Multiple regulatory mechanisms have evolved to ensure that HR takes place at the right time, place and manner. Several of these impinge on the control of Rad51 nucleofilaments that play a central role in HR. Some factors promote the formation of these structures while others lead to their disassembly or the use of alternative repair pathways. In this article, we review these mechanisms in both mitotic and meiotic environments and in different eukaryotic taxa, with an emphasis on yeast and mammal systems. Since mutations in several proteins that regulate Rad51 nucleofilaments are associated with cancer and cancer-prone syndromes, we discuss how understanding their functions can lead to the development of better tools for cancer diagnosis and therapy.

Krejci, Lumir; Altmannova, Veronika; Spirek, Mario; Zhao, Xiaolan

2012-01-01

443

Long noncoding RNAs regulate adipogenesis  

PubMed Central

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

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

2013-01-01

444

Regulation of leptin by agouti.  

PubMed

Dominant mutations at the mouse Agouti locus lead to ectopic expression of the Agouti gene and exhibit diabetes, obesity, and yellow coat color. Obese yellow mice are hyperinsulinemic and hyperleptinemic, and we hypothesized that Agouti directly induces leptin secretion. Accordingly, we used transgenic mice expressing agouti in adipocytes (under the control of aP2 promoter, aP212) to examine changes in leptin levels. Agouti expression in adipose tissue did not significantly alter food intake, weight gain, fat pad weight, or insulinemia; however, the transgenic mice were hyperglycemic. We demonstrated that plasma leptin levels are approximately twofold higher in aP212 transgenic mice compared with their respective controls, whereas ubiquitous expression of agouti (under the control of beta-actin promoter, BAP20) led to a sixfold increase in leptin. Insulin treatment of aP212 mice increased adipocyte leptin content without affecting plasma leptin levels. These findings were further confirmed in vitro in 3T3-L1 adipocytes treated with recombinant Agouti protein and/or insulin. Agouti but not insulin significantly increased leptin secretion, indicating that insulin enhances leptin synthesis but not secretion while Agouti increases both leptin synthesis and secretion. This increased leptin synthesis and secretion was due to increased leptin mRNA levels by Agouti. Interestingly, agouti regulation of leptin was not mediated by melanocortin receptor 4, previously implicated in agouti regulation of food intake. These results suggest that increased leptin secretion by agouti may serve to limit agouti-induced obesity, independent of melanocortin receptor antagonism, and indicate that interaction between obesity genes may play a key role in obesity. PMID:11015588

Claycombe, K J; Xue, B Z; Mynatt, R L; Zemel, M B; Moustaid-Moussa, N

2000-04-27

445

Air/fuel ratio regulator  

SciTech Connect

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.

Simko, A.

1980-07-22

446

State regulators see Federal preemption; more intervention  

SciTech Connect

The possibility that Federal regulators will preempt state public service commissions is seen as a valid threat unless state commissions can demonstrate that they perform more than a rubber-stamp function. Others view the Public Utility Regulatory Policies Act of 1978 more as a vehicle for strengthening the states' role in utility regulation, with Federal preemption a possible penalty for poor performance. Now that consumer groups are demonstrating an increasing impact on utility planning and regulation, regulators are asked to grant these groups as much consideration as is given to the case for utility stockholders. (DCK)

Utroska, D.

1980-02-01

447

Endothelial Cell Regulation by Phospholipid Oxidation Products  

PubMed Central

Oxidized phospholipids accumulate in atherosclerotic lesions, on lipoproteins, in other states of chronic inflammation, on apoptotic cells, necrotic cells and cells exposed to oxidative stress. These lipids regulate the transcription of over 1000 gene, regulating many endothelial functions, by activating several different cell surface receptors and multiple signaling pathways. These lipids also have important effects not involving transcription that regulate cell junctions and leukocyte binding. Thus these lipids are potent regulators of endothelial cell function with broad effects comparable in extent but differing from those of cytokines.

Berliner, Judith A; Gharavi, Nima M

2010-01-01

448

Biochemical analysis of the canonical model for the mammalian circadian clock.  

PubMed

The current consensus model for the circadian clock in mammals is based on a transcription-translation feedback loop. In this model, CRY and PER proteins repress their own transcription by suppressing the transactivator function of the CLOCK:BMAL1 heterodimer directly (physical model) and by facilitating post-translational modifications (chemical model). Most of the data for this model come from genetic and cell biological experiments. Here, we have purified all of the core clock proteins and performed in vitro and in vivo biochemical experiments to test the physical model. We find that CLOCK:BMAL1 binds to an E-box sequence in DNA and that CRY binds stably to the CLOCK:BMAL1:E-box ternary complex independently of PER. Both CRY and PER bind to CLOCK and BMAL1 off DNA but, in contrast to CRY, PER does not bind to the CLOCK:BMAL1:E-box complex. Unexpectedly, PER actually interferes with the binding of CRY to the CLOCK:BMAL1:E-box ternary complex. CRY likely destabilizes the CLOCK:BMAL1 heterodimer on DNA by a post-translational mechanism after binding to the complex. These findings support some aspects of the canonical model, but also suggest that some key features of the model need to be revised. PMID:21613214

Ye, Rui; Selby, Christopher P; Ozturk, Nuri; Annayev, Yunus; Sancar, Aziz

2011-05-25

449

Multiple effects of melatonin on rhythmic clock gene expression in the mammalian pars tuberalis.  

PubMed

In mammals, changing day length modulates endocrine rhythms via nocturnal melatonin secretion. Studies of the pituitary pars tuberalis (PT) suggest that melatonin-regulated clock gene expression is critical to this process. Here, we considered whether clock gene rhythms continue in the PT in the absence of melatonin and whether the effects of melatonin on the expression of these genes are temporally gated. Soay sheep acclimated to long photoperiod (LP) were transferred to constant light for 24 h, suppressing endogenous melatonin secretion. Animals were infused with melatonin at 4-h intervals across the final 24 h, and killed 3 h after infusion. The expression of five clock genes (Per1, Per2, Cry1, Rev-erbalpha, and Bmal1) was measured by in situ hybridization. In sham-treated animals, PT expression of Per1, Per2, and Rev-erbalpha showed pronounced temporal variation despite the absence of melatonin, with peak times occurring earlier than predicted under LP. The time of peak Bmal1 expression remained LP-like, whereas Cry1 expression was continually low. Melatonin infusion induced Cry1 expression at all times and suppressed other genes, but only when they showed high expression in sham-treated animals. Hence, 3 h after melatonin treatment, clock gene profiles were driven to a similar state, irrespective of infusion time. In contrast to the PT, melatonin infusions had no clear effect on clock gene expression in the suprachiasmatic nuclei. Our results provide the first example of acute sensitivity of multiple clock genes to one endocrine stimulus and suggest that rising melatonin levels may reset circadian rhythms in the PT, independently of previous phase. PMID:16269454

Johnston, Jonathan D; Tournier, Benjamin B; Andersson, Hakan; Masson-Pévet, Mireille; Lincoln, Gerald A; Hazlerigg, David G

2005-11-03

450

Low-carbohydrate, high-protein diet affects rhythmic expression of gluconeogenic regulatory and circadian clock genes in mouse peripheral tissues.  

PubMed

Recent studies have demonstrated that metabolic changes in mammals induce feedback regulation of the circadian clock. The present study evaluates the effects of a low-carbohydrate high-protein diet (HPD) on circadian behavior and peripheral circadian clocks in mice. Circadian rhythms of locomotor activity and core body temperature remained normal in mice fed with the HPD diet (HPD mice), suggesting that it did not affect the central clock in the hypothalamus. Two weeks of HPD feeding induced mild hypoglycemia without affecting body weight, although these mice consumed more calories than mice fed with a normal diet (ND mice). Plasma insulin levels were increased during the inactive phase in HPD mice, but increased twice, beginning and end of the active phase, in ND mice. Expression levels of the key gluconeogenic regulatory genes PEPCK and G6Pase were significantly induced in the liver and kidneys of HPD mice. The HPD appeared to induce peroxisome proliferator-activated receptor ? (PPAR?) activation, since mRNA expression levels of PPAR? and its typical target genes, such as PDK4 and Cyp4A10, were significantly increased in the liver and kidneys. Circadian mRNA expression of clock genes, such as BMAL1, Cry1, NPAS2, and Rev-erb?, but not Per2, was significantly phase-advanced, and mean expression levels of BMAL1 and Cry1 mRNAs were significantly elevated, in the liver and kidneys of HPD mice. These findings suggest that a HPD not only affects glucose homeostasis, but that it also advances the molecular circadian clock in peripheral tissues. PMID:22823864

Oishi, Katsutaka; Uchida, Daisuke; Itoh, Nanako

2012-08-01

451

Lithium differentially affects clock gene expression in serum-shocked NIH-3T3 cells.  

PubMed

Bipolar disorder has been associated with disturbances in circadian rhythms. Lithium is frequently used in the long-term treatment of bipolar disorder, and has been shown to prolong such rhythms in animals and humans. To examine whether lithium affects the expression of genes regulating the circadian clock, cultured NIH-3T3 cells were synchronized by serum-shocking, and the relative expression of the clock genes Period1 (Per1), Period2 (Per2), Period3 (Per3), Cryptochrome1 (Cry1), Cryptochrome2 (Cry2), Brain and muscle aryl hydrocarbon nuclear translocator-like 1 (Bmal1), Circadian locomotor output cycles kaput (Clock), Rev-Erb-? (Nr1d1), RAR-related orphan receptor ? (Ror-?), Glycogen synthase kinase-3? (Gsk-3?), Casein kinase 1-? (CK1-?; Csnk1?), E4 binding protein 4 (E4BP4; Nfil-3) and albumin D-binding protein (Dbp) was examined for three consecutive days in the presence of lithium (20?mM) or vehicle (20?mM NaCl). We found that lithium significantly increased the expression of Per2 and Cry1, whereas Per3, Cry2, Bmal1, E4BP4 and Rev-Erb-? expression was reduced. We also found that lithium prolonged the period of Per2. Taken together, these effects on clock gene expression may be relevant for the effects of lithium on biological rhythms and could also give new leads to further explore its mood-stabilizing actions in the treatment of bipolar disorder. PMID:20837565

Osland, Teresa M; Fernø, Johan; Håvik, Bjarte; Heuch, Ivar; Ruoff, Peter; Lærum, Ole Didrik; Steen, Vidar M

2010-09-13

452

41 CFR Appendix to Subchapter D - Temporary Regulations Federal Property Management Regulations; Interim Rule D-1  

Code of Federal Regulations, 2011 CFR

...Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS PUBLIC BUILDINGS AND SPACE Ch. 101, Subch. D, App...chapter 102 parts 1 through 220). For information on location of space, see FMR...

2011-07-01

453

41 CFR Appendix to Subchapter D - Temporary Regulations Federal Property Management Regulations; Interim Rule D-1  

Code of Federal Regulations, 2012 CFR

41 Public Contracts and Property Management 2 2012-07-01 2012-07-01...Temporary Regulations Federal Property Management Regulations; Interim Rule D-1 Appendix...Subchapter D Public Contracts and Property Management Federal Property Management...

2012-07-01

454

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

Microsoft Academic Search

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-

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

2004-01-01

455

NewSART automatic voltage and reactive power regulator for secondary voltage regulation: Design and application  

Microsoft Academic Search

Secondary Voltage Regulation (SVR) is part of the hierarchical control system of EHV transmission network, currently operated by the Italian Independent System Operator. SVR is being actuated using automatic voltage and reactive power regulators, named SART, in power stations rated more than 100 MVA. Each SART receives from the Regional Voltage Regulator a reactive level signal and implements it by

G. Sulligoi; M. Chiandone; V. Arcidiacono

2011-01-01

456

Medical regulation in India: an outsider's perspective.  

PubMed

This personal comment briefly describes the working of the General Medical Council, the medical regulator in the United Kingdom, with the aim of informing the discussion on how to regulate medical education and doctors' practice in India. Given that the ministry of health and family welfare is still debating the final constitution of the Medical Council of India, this paper is timely. PMID:24152354

Madhok, Rajan

457

REGULATION OF MUSCLE MASS BY MYOSTATIN  

Microsoft Academic Search

? Abstract Myostatin is a secreted protein that acts as a negative regulator of skeletal muscle mass. During embryogenesis, myostatin is expressed by cells in the myotome and in developing skeletal muscle and acts to regulate the final number of muscle fibers that are formed. During adult life, myostatin protein is produced by skeletal muscle, circulates in the blood, and

Se-Jin Lee

2004-01-01

458

Emotion Regulation in Children with Anxiety Disorders  

ERIC Educational Resources Information Center

|This study examined emotion management skills in addition to the role of emotional intensity and self-efficacy in emotion regulation in 26 children with anxiety disorders (ADs) ages 8 to 12 years and their counterparts without any form of psychopathology. Children completed the Children's Emotion Management Scales (CEMS) and Emotion Regulation

Suveg, Cynthia; Zeman, Janice

2004-01-01

459

Money Laundering: the Economics of Regulation  

Microsoft Academic Search

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.

DONATO MASCIANDARO

1999-01-01

460

Regulation with non-price discrimination  

Microsoft Academic Search

This paper considers the optimal regulation of access charges, and the effect such regulation has on incentives for non-price discrimination. I show that when a vertically integrated firm is able to discriminate against rivals by means of non-price measures, optimal access charges must be set higher than in the case when no discrimination is possible since the level of the

Jan Y. Sand

2004-01-01

461

Advertising Regulations in Sub-Saharan Africa  

Microsoft Academic Search

This paper examines the status and outlook of advertising regulations in sub-Saharan Africa. It begins with a synoptic overview of the region's advertising industry, which is used as a backdrop. Advertising regulations pertaining to tobacco, alcohol, pharmaceuticals, children, and politics are examined, and seven regulatory forces (consumer protection; growth of service industry; fairness and vulnerable groups; new media technologies; civil

William K. Darley

2002-01-01

462

The Development of Self-Regulated Learning.  

ERIC Educational Resources Information Center

|Examines the tendency for the development of self-regulated learning according to grade level. Sets up three competing causal models of self-regulated learning and then tests validity of each to determine most suitable for South Korean students. Selects model where motivational variables, such as self-efficacy and intrinsic value, indirectly…

Chung, Mi-Kyung

2000-01-01

463

The Political Economy of Japanese Pollution Regulation  

Microsoft Academic Search

Japan has long been commended for its quick and decisive action to clean up pollution and to impose strict anti -pollution regulations in the late 1960s and early 1970s. But recent reports indicate that Japan's pollution problem is worse than previously thought, and even worse than in most advanced industrial countries. Highly visible and relatively easily regulated air pollution has

Frances Rosenbluth; Michael F. Thies

1999-01-01

464

Controlling illegal stimulants: a regulated market model  

Microsoft Academic Search

Prohibition of illegal drugs is a failed social policy and new models of regulation of these substances are needed. This paper explores a proposal for a post-prohibition, public health based model for the regulation of the most problematic drugs, the smokable and injectable stimulants. The literature on stimulant maintenance is explored. Seven foundational principles are suggested that could support this

Mark Haden

2008-01-01

465

Self-Regulation and Learning Strategies  

ERIC Educational Resources Information Center

|Learning strategies are a bit difficult to define since the nomenclatures used in cognitive educational psychology as well as in strategic and self-regulated learning have not yet been standardized across and within these fields of study. The self-regulated use of learning strategies helps enable students to take more responsibility for their own…

Weinstein, Claire Ellen; Acee, Taylor W.; Jung, JaeHak

2011-01-01

466

Multistage dual priority regulator for photovoltaic systems  

Microsoft Academic Search

The design and application are investigated of an array shedding voltage regulator for use in photovoltaic (PV) systems with two separate loads of different priority. The multistage dual-priority regulator charges two separate battery systems for high- and low-priority loads. This controller switches the array modules from the main battery to the auxiliary battery as the main battery nears full charge,

Ziyad M. Salameh; William A. Lynch

1989-01-01

467

Growth with regulation in random environment  

Microsoft Academic Search

The diffusion model for a population subject to Malthusian growth is generalized to include regulation effects. This is done by incorporating a logarithmic term in the regulation function in a way to obtain, in the absence of noise, an S-shaped growth law retaining the qualitative features of the logistic growth curve. The growth phenomenon is modeled as a diffusion process

R. M. Capocelli; L. M. Ricciardi

1974-01-01

468

REGULATION AND CONTROL VS. DEREGULATION AND DECONTROL  

Microsoft Academic Search

In this century, governments increased the scope of their regulations and controls to market a great deal. In the late 1970's, economists began to argue that regulations and controls into the market ›mpose some important costs to the society. They argued that deregulation and decontrol policies should be implemented. In this study, I shall try to make an analysis of

Can Aktan

469

The epigenetic regulation of mammalian telomeres  

Microsoft Academic Search

Increasing evidence indicates that chromatin modifications are important regulators of mammalian telomeres. Telomeres provide well studied paradigms of heterochromatin formation in yeast and flies, and recent studies have shown that mammalian telomeres and subtelomeric regions are also enriched in epigenetic marks that are characteristic of heterochromatin. Furthermore, the abrogation of master epigenetic regulators, such as histone methyltransferases and DNA methyltransferases,

María A. Blasco

2007-01-01

470

Neglected risk regulation: The institutional attenuation phenomenon  

Microsoft Academic Search

This paper considers the institutional factors that shape regulatory officials' perceptions of risks to human health and safety and their attitudes towards associated regulation. In particular, the paper considers the extent to which the perceptions of risk and regulation of officials responsible for monitoring and enforcement are aligned with regulatory requirements, and, if not, what factors explain those perceptions. Moreover,

Henry Rothstein

2003-01-01

471

Groundwater monitoring regulations for solid waste landfills  

Microsoft Academic Search

The subtitle D groundwater monitoring regulations are even more complex than the Resource Conservation and Recovery Act (RCRA) hazardous waste groundwater monitoring regulations, requiring statistical comparison of data after each sampling event in detection monitoring after background is established. Beginning Oct. 1994, municipal solid waste landfills located within one mile of a drinking water intake must comply with Subtitle D

1994-01-01

472

Liability Insurance and the Regulation of Firearms  

Microsoft Academic Search

Prepared for an edited volume on gun litigation (Suing the Firearms Industry, T. Lytton, ed.), this working paper examines the topic of gun risks as a case study of liability insurance as a form of regulation. The paper identifies the following broad categories of 'regulation by insurance': loss spreading, gate keeping, loss prevention, management of loss costs, research and education,

Tom Baker; Thomas O. Farrish

2004-01-01

473

Rackets, Regulation and the Rule of Law  

Microsoft Academic Search

Governments that levy predatory regulation and provide few weak legal institutions draw businesses into the unofficial economy and compel them to hire private protection organizations. Based on a survey of shopkeepers in three cities in Russia, we find that retail shops face very high levels of predatory regulation and have frequent contacts with private protection rackets. In addition, we show

Timothy Frye; Ekaterina Zhuravskaya

2000-01-01