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1

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

SciTech Connect

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

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

2010-03-19

2

Nuclear envelope protein MAN1 regulates clock through BMAL1  

PubMed Central

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

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

2014-01-01

3

Circadian Factor BMAL1 in Histaminergic Neurons Regulates Sleep Architecture  

PubMed Central

Summary Circadian clocks allow anticipation of daily environmental changes [1]. The suprachiasmatic nucleus (SCN) houses the master clock, but clocks are also widely expressed elsewhere in the body [1]. Although some peripheral clocks have established roles [1], it is unclear what local brain clocks do [2, 3]. We tested the contribution of one putative local clock in mouse histaminergic neurons in the tuberomamillary nucleus to the regulation of the sleep-wake cycle. Histaminergic neurons are silent during sleep, and start firing after wake onset [4–6]; the released histamine, made by the enzyme histidine decarboxylase (HDC), enhances wakefulness [7–11]. We found that hdc gene expression varies with time of day. Selectively deleting the Bmal1 (also known as Arntl or Mop3 [12]) clock gene from histaminergic cells removes this variation, producing higher HDC expression and brain histamine levels during the day. The consequences include more fragmented sleep, prolonged wake at night, shallower sleep depth (lower nonrapid eye movement [NREM] ? power), increased NREM-to-REM transitions, hindered recovery sleep after sleep deprivation, and impaired memory. Removing BMAL1 from histaminergic neurons does not, however, affect circadian rhythms. We propose that for mammals with polyphasic/nonwake consolidating sleep, the local BMAL1-dependent clock directs appropriately timed declines and increases in histamine biosynthesis to produce an appropriate balance of wake and sleep within the overall daily cycle of rest and activity specified by the SCN. PMID:25454592

Yu, Xiao; Zecharia, Anna; Zhang, Zhe; Yang, Qianzi; Yustos, Raquel; Jager, Polona; Vyssotski, Alexei L.; Maywood, Elizabeth S.; Chesham, Johanna E.; Ma, Ying; Brickley, Stephen G.; Hastings, Michael H.; Franks, Nicholas P.; Wisden, William

2014-01-01

4

BMAL1-dependent regulation of the mTOR signaling pathway delays aging  

PubMed Central

The circadian clock, an internal time-keeping system, has been linked with control of aging, but molecular mechanisms of regulation are not known. BMAL1 is a transcriptional factor and core component of the circadian clock; BMAL1 deficiency is associated with premature aging and reduced lifespan. Here we report that activity of mammalian Target of Rapamycin Complex 1 (mTORC1) is increased upon BMAL1 deficiency both in vivo and in cell culture. Increased mTOR signaling is associated with accelerated aging; in accordance with that, treatment with the mTORC1 inhibitor rapamycin increased lifespan of Bmal1?/? mice by 50%. Our data suggest that BMAL1 is a negative regulator of mTORC1 signaling. We propose that the circadian clock controls the activity of the mTOR pathway through BMAL1-dependent mechanisms and this regulation is important for control of aging and metabolism. PMID:24481314

Khapre, Rohini V.; Kondratova, Anna A.; Patel, Sonal; Dubrovsky, Yuliya; Wrobel, Michelle; Antoch, Marina P.; Kondratov, Roman V.

2014-01-01

5

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

PubMed

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

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

2015-01-15

6

Circadian gene Bmal1 regulates diurnal oscillations of Ly6Chi inflammatory monocytes  

PubMed Central

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 Ly6Chi 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 Ly6Chi 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 Ly6Chi monocyte numbers. PMID:23970558

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

2013-01-01

7

PPAR and liver circadian clock Reciprocal regulation of BMAL1 and PPAR defines a novel positive feedback loop in  

E-print Network

PPAR and liver circadian clock Reciprocal regulation of BMAL1 and PPAR defines a novel positive feedback loop in the rodent liver circadian clock. Laurence Canaple*¶ , Juliette Rambaud*, Ouria Dkhissi.laudet@ens-lyon.fr The authors have nothing to declare. Running Title: PPAR and liver circadian clock Key words: PPAR, BMAL1

Boyer, Edmond

8

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

9

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

10

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. PMID:22913986

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

2012-01-01

11

The E3 ubiquitin ligase UBE3A is an integral component of the molecular circadian clock through regulating the BMAL1 transcription factor  

PubMed Central

Post-translational modifications (such as ubiquitination) of clock proteins are critical in maintaining the precision and robustness of the evolutionarily conserved circadian clock. Ubiquitination of the core clock transcription factor BMAL1 (brain and muscle Arnt-like 1) has recently been reported. However, it remains unknown whether BMAL1 ubiquitination affects circadian pacemaking and what ubiquitin ligase(s) is involved. Here, we show that activating UBE3A (by expressing viral oncogenes E6/E7) disrupts circadian oscillations in mouse embryonic fibroblasts, measured using PER2::Luc dynamics, and rhythms in endogenous messenger ribonucleic acid and protein levels of BMAL1. Over-expression of E6/E7 reduced the level of BMAL1, increasing its ubiquitination and proteasomal degradation. UBE3A could bind to and degrade BMAL1 in a ubiquitin ligase-dependent manner. This occurred both in the presence and absence of E6/E7. We provide in vitro (knockdown/over-expression in mammalian cells) and in vivo (genetic manipulation in Drosophila) evidence for an endogenous role of UBE3A in regulating circadian dynamics and rhythmic locomotor behaviour. Together, our data reveal an essential and conserved role of UBE3A in the regulation of the circadian system in mammals and flies and identify a novel mechanistic link between oncogene E6/E7-mediated cell transformation and circadian (BMAL1) disruption. PMID:24728990

Gossan, Nicole C.; Zhang, Feng; Guo, Baoqiang; Jin, Ding; Yoshitane, Hikari; Yao, Aiyu; Glossop, Nick; Zhang, Yong Q.; Fukada, Yoshitaka; Meng, Qing-Jun

2014-01-01

12

The E3 ubiquitin ligase UBE3A is an integral component of the molecular circadian clock through regulating the BMAL1 transcription factor.  

PubMed

Post-translational modifications (such as ubiquitination) of clock proteins are critical in maintaining the precision and robustness of the evolutionarily conserved circadian clock. Ubiquitination of the core clock transcription factor BMAL1 (brain and muscle Arnt-like 1) has recently been reported. However, it remains unknown whether BMAL1 ubiquitination affects circadian pacemaking and what ubiquitin ligase(s) is involved. Here, we show that activating UBE3A (by expressing viral oncogenes E6/E7) disrupts circadian oscillations in mouse embryonic fibroblasts, measured using PER2::Luc dynamics, and rhythms in endogenous messenger ribonucleic acid and protein levels of BMAL1. Over-expression of E6/E7 reduced the level of BMAL1, increasing its ubiquitination and proteasomal degradation. UBE3A could bind to and degrade BMAL1 in a ubiquitin ligase-dependent manner. This occurred both in the presence and absence of E6/E7. We provide in vitro (knockdown/over-expression in mammalian cells) and in vivo (genetic manipulation in Drosophila) evidence for an endogenous role of UBE3A in regulating circadian dynamics and rhythmic locomotor behaviour. Together, our data reveal an essential and conserved role of UBE3A in the regulation of the circadian system in mammals and flies and identify a novel mechanistic link between oncogene E6/E7-mediated cell transformation and circadian (BMAL1) disruption. PMID:24728990

Gossan, Nicole C; Zhang, Feng; Guo, Baoqiang; Jin, Ding; Yoshitane, Hikari; Yao, Aiyu; Glossop, Nick; Zhang, Yong Q; Fukada, Yoshitaka; Meng, Qing-Jun

2014-05-01

13

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

PubMed

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

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

2013-01-01

14

WOUND-HEALING PROPERTIES OF TRANSFORMING GROWTH FACTOR ? (TGF-?) INDUCIBLE EARLY GENE 1 (TIEG1) KNOCKOUT MICE  

PubMed Central

Transforming growth factor beta (TGF-?) has a broad effect on wound healing, but many questions remain about the regulation of TGF-? during the healing process. TGF-? inducible early gene 1 (TIEG1) is a primary response gene for TGF-? that controls the activities of the TGF-?/Smad pathway, the primary TGF-? signaling pathway. The purpose of this study was to investigate the role of TIEG1 in cutaneous wound healing using TIEG1 knockout mice. The wound healing in TIEG1 knockout mice and wild-type controls was evaluated by wound breaking strength, Western blot, and histology at postoperative days 3, 7, and 14. Although re-epithelialization of both groups was similarly complete at day 7, the TIEG1 knockout mice had a significantly lower wound breaking strength than the controls at postoperative day 14. These results suggest that TIEG1 expression may be an important factor involved in the initiation and support of normal cutaneous wound healing. PMID:20016760

Taguchi, Manabu; Moran, Steven L.; Zobitz, Mark E.; Zhao, Chunfeng; Subramaniam, Malayannan; Spelsberg, Thomas C.; Amadio, Peter C.

2009-01-01

15

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

16

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. PMID:22025675

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

17

Liver clock protein BMAL1 promotes de novo lipogenesis through insulin-mTORC2-AKT signaling.  

PubMed

The clock protein BMAL1 (brain and muscle Arnt-like protein 1) participates in circadian regulation of lipid metabolism, but its contribution to insulin AKT-regulated hepatic lipid synthesis is unclear. Here we used both Bmal1(-/-) and acute liver-specific Bmal1-depleted mice to study the role of BMAL1 in refeeding-induced de novo lipogenesis in the liver. Both global deficiency and acute hepatic depletion of Bmal1 reduced lipogenic gene expression in the liver upon refeeding. Conversely, Bmal1 overexpression in mouse liver by adenovirus was sufficient to elevate the levels of mRNA of lipogenic enzymes. Bmal1(-/-) primary mouse hepatocytes displayed decreased levels of de novo lipogenesis and lipogenic enzymes, supporting the notion that BMAL1 regulates lipid synthesis in hepatocytes in a cell-autonomous manner. Both refed mouse liver and insulin-treated primary mouse hepatocytes showed impaired AKT activation in the case of either Bmal1 deficiency or Bmal1 depletion by adenoviral shRNA. Restoring AKT activity by a constitutively active mutant of AKT nearly normalized de novo lipogenesis in Bmal1(-/-) hepatocytes. Finally, Bmal1 deficiency or knockdown decreased the protein abundance of RICTOR, the key component of the mTORC2 complex, without affecting the gene expression of key factors of insulin signaling. Thus, our study uncovered a novel metabolic function of hepatic BMAL1 that promotes de novo lipogenesis via the insulin-mTORC2-AKT signaling during refeeding. PMID:25063808

Zhang, Deqiang; Tong, Xin; Arthurs, Blake; Guha, Anirvan; Rui, Liangyou; Kamath, Avani; Inoki, Ken; Yin, Lei

2014-09-12

18

The Circadian Clock Protein BMAL1 Is Necessary for Fertility and Proper Testosterone Production in Mice  

PubMed Central

Although it is well established that the circadian clock regulates mammalian reproductive physiology, the molecular mechanisms by which this regulation occurs are not clear. The authors investigated the reproductive capacity of mice lacking Bmal1 (Arntl, Mop3), one of the central circadian clock genes. They found that both male and female Bmal1 knockout (KO) mice are infertile. Gross and microscopic inspection of the reproductive anatomy of both sexes suggested deficiencies in steroidogenesis. Male Bmal1 KO mice had low testosterone and high luteinizing hormone serum concentrations, suggesting a defect in testicular Leydig cells. Importantly, Leydig cells rhythmically express BMAL1 protein, suggesting peripheral control of testosterone production by this clock protein. Expression of steroidogenic genes was reduced in testes and other steroidogenic tissues of Bmal1 KO mice. In particular, expression of the steroidogenic acute regulatory protein (StAR) gene and protein, which regulates the rate-limiting step of steroidogenesis, was decreased in testes from Bmal1 KO mice. A direct effect of BMAL1 on StAR expression in Leydig cells was indicated by in vitro experiments showing enhancement of StAR transcription by BMAL1. Other hormonal defects in male Bmal1 KO mice suggest that BMAL1 also has functions in reproductive physiology outside of the testis. These results enhance understanding of how the circadian clock regulates reproduction. PMID:18258755

Alvarez, J. D.; Hansen, Amanda; Ord, Teri; Bebas, Piotr; Chappell, Patrick E.; Giebultowicz, Jadwiga M.; Williams, Carmen; Moss, Stuart; Sehgal, Amita

2010-01-01

19

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

Microsoft Academic Search

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

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

2004-01-01

20

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. PMID:20658528

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

2010-01-01

21

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

PubMed

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

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

2014-09-30

22

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

PubMed Central

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

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

2014-01-01

23

Cardiomyocyte-specific BMAL1 Plays Critical Roles in Metabolism, Signaling, and Maintenance of Contractile Function of the Heart  

PubMed Central

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

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

2014-01-01

24

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. PMID:22707558

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

2012-01-01

25

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

PubMed Central

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

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

2014-01-01

26

Chronotype and stability of spontaneous locomotor activity rhythm in BMAL1-deficient mice.  

PubMed

Behavior, physiological functions and cognitive performance change over the time of the day. These daily rhythms are either externally driven by rhythmic environmental cues such as the light/dark cycle (masking) or controlled by an internal circadian clock, the suprachiasmatic nucleus (SCN), which can be entrained to the light/dark cycle. Within a given species, there is genetically determined variability in the temporal preference for the onset of the active phase, the chronotype. The chronotype is the phase of entrainment between external and internal time and is largely regulated by the circadian clock. Genetic variations in clock genes and environmental influences contribute to the distribution of chronotypes in a given population. However, little is known about the determination of the chronotype, the stability of the locomotor rhythm and the re-synchronization capacity to jet lag in an animal without a functional endogenous clock. Therefore, we analyzed the chronotype of BMAL1-deficient mice (BMAL1-/-) as well as the effects of repeated experimental jet lag on locomotor activity rhythms. Moreover, light-induced period expression in the retina was analyzed to assess the responsiveness of the circadian light input system. In contrast to wild-type mice, BMAL1-/- showed a significantly later chronotype, adapted more rapidly to both phase advance and delay but showed reduced robustness of rhythmic locomotor activity after repeated phase shifts. However, photic induction of Period in the retina was not different between the two genotypes. Our findings suggest that a disturbed clockwork is associated with a late chronotype, reduced rhythm stability and higher vulnerability to repeated external desynchronization. PMID:25216070

Pfeffer, Martina; Korf, Horst-Werner; von Gall, Charlotte

2015-02-01

27

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

PubMed Central

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

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

2011-01-01

28

Light and Glutamate-Induced Degradation of the Circadian Oscillating Protein BMAL1 during the Mammalian Clock Resetting  

Microsoft Academic Search

Recently discovered mammalian clock genes are believed to compose the core oscillator, which generates the circadian rhythm. BMAL1\\/CLOCK heterodimer is the essential positive element that drives clock-related transcription and self- sustaining oscillation by a negative feedback mechanism. We examined BMAL1 protein expression in the rat suprachiasmatic nuclei (SCN) by immunoblot analysis. Anti-BMAL1 antiserum raised against rBMAL1 recognized 70 kDa mBMAL1b

Teruya Tamaru; Yasushi Isojima; Takashi Yamada; Masato Okada; Katsuya Nagai; Ken Takamatsu

2000-01-01

29

Circadian Genes, xBmal1 and xNocturnin, Modulate the Timing and Differentiation of Somites in Xenopus laevis  

PubMed Central

We have been investigating whether xBmal1 and xNocturnin play a role in somitogenesis, a cyclic developmental process with an ultradian period. Previous work from our lab shows that circadian genes (xPeriod1, xPeriod2, xBmal1, and xNocturnin) are expressed in developing somites. Somites eventually form the vertebrae, muscles of the back, and dermis. In Xenopus, a pair of somites is formed about every 50 minutes from anterior to posterior. We were intrigued by the co-localization of circadian genes in an embryonic tissue known to be regulated by an ultradian clock. Cyclic expression of genes involved in Notch signaling has been implicated in the somite clock. Disruption of Notch signaling in humans has been linked to skeletal defects in the vertebral column. We found that both depletion (morpholino) and overexpression (mRNA) of xBMAL1 protein (bHLH transcription factor) or xNOCTURNIN protein (deadenylase) on one side of the developing embryo led to a significant decrease in somite number with respect to the untreated side (p<0.001). These manipulations also significantly affect expression of a somite clock component (xESR9; p<0.05). We observed opposing effects on somite size. Depletion of xBMAL1 or xNOCTURNIN caused a statistically significant decrease in somite area (quantified using NIH ImageJ; p<0.002), while overexpression of these proteins caused a significant dose dependent increase in somite area (p<0.02; p<0.001, respectively). We speculate that circadian genes may play two separate roles during somitogenesis. Depletion and overexpression of xBMAL1 and NOCTURNIN both decrease somite number and influence expression of a somite clock component, suggesting that these proteins may modulate the timing of the somite clock in the undifferentiated presomitic mesoderm. The dosage dependent effects on somite area suggest that xBMAL1 and xNOCTURNIN may also act during somite differentiation to promote myogenesis. PMID:25238599

Curran, Kristen L.; Allen, Latoya; Porter, Brittany Bronson; Dodge, Joseph; Lope, Chelsea; Willadsen, Gail; Fisher, Rachel; Johnson, Nicole; Campbell, Elizabeth; VonBergen, Brett; Winfrey, Devon; Hadley, Morgan; Kerndt, Thomas

2014-01-01

30

Antioxidant N-acetyl-L-cysteine ameliorates symptoms of premature aging associated with the deficiency of the circadian protein BMAL1.  

PubMed

Deficiency of the circadian clock protein BMAL1 leads to premature aging and increased levels of reactivate oxygen species in several tissues of mice. In order to investigate the role of oxidative stress in accelerated aging and development of age-related pathologies, we continuously administered the antioxidant N-acetyl-L-cysteine toBmal1-deficient mice through their entire lifespan by supplementing drinking water. We found that the life long treatment with antioxidant significantly increased average and maximal lifespan and reduced the rate of age-dependent weight loss and development of cataracts. At the same time, it had no effect on time of onset and severity of other age-related pathologies characteristic of Bmal1-/- mice, such as joint ossification, reduced hair regrowth and sarcopenia. We conclude that chronic oxidative stress affects longevity and contributes to the development of at least some age-associated pathology, although ROS-independent mechanisms may also play a role. Our bioinformatics analysis identified the presence of a conservative E box element in the promoter regions of several genes encoding major antioxidant enzymes. We speculate that BMAL1 controls antioxidant defense by regulating the expression of major antioxidant enzymes. PMID:20157581

Kondratov, Roman V; Vykhovanets, Olena; Kondratova, Anna A; Antoch, Marina P

2009-12-01

31

Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex.  

PubMed

The circadian clock in mammals is driven by an autoregulatory transcriptional feedback mechanism that takes approximately 24 hours to complete. A key component of this mechanism is a heterodimeric transcriptional activator consisting of two basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) domain protein subunits, CLOCK and BMAL1. Here, we report the crystal structure of a complex containing the mouse CLOCK:BMAL1 bHLH-PAS domains at 2.3 Å resolution. The structure reveals an unusual asymmetric heterodimer with the three domains in each of the two subunits--bHLH, PAS-A, and PAS-B--tightly intertwined and involved in dimerization interactions, resulting in three distinct protein interfaces. Mutations that perturb the observed heterodimer interfaces affect the stability and activity of the CLOCK:BMAL1 complex as well as the periodicity of the circadian oscillator. The structure of the CLOCK:BMAL1 complex is a starting point for understanding at an atomic level the mechanism driving the mammalian circadian clock. PMID:22653727

Huang, Nian; Chelliah, Yogarany; Shan, Yongli; Taylor, Clinton A; Yoo, Seung-Hee; Partch, Carrie; Green, Carla B; Zhang, Hong; Takahashi, Joseph S

2012-07-13

32

Bmal1 and ?-Cell Clock Are Required for Adaptation to Circadian Disruption, and Their Loss of Function Leads to Oxidative Stress-Induced ?-Cell Failure in Mice  

PubMed Central

Circadian disruption has deleterious effects on metabolism. Global deletion of Bmal1, a core clock gene, results in ?-cell dysfunction and diabetes. However, it is unknown if this is due to loss of cell-autonomous function of Bmal1 in ? cells. To address this, we generated mice with ?-cell clock disruption by deleting Bmal1 in ? cells (?-Bmal1?/?). ?-Bmal1?/? mice develop diabetes due to loss of glucose-stimulated insulin secretion (GSIS). This loss of GSIS is due to the accumulation of reactive oxygen species (ROS) and consequent mitochondrial uncoupling, as it is fully rescued by scavenging of the ROS or by inhibition of uncoupling protein 2. The expression of the master antioxidant regulatory factor Nrf2 (nuclear factor erythroid 2-related factor 2) and its targets, Sesn2, Prdx3, Gclc, and Gclm, was decreased in ?-Bmal1?/? islets, which may contribute to the observed increase in ROS accumulation. In addition, by chromatin immunoprecipitation experiments, we show that Nrf2 is a direct transcriptional target of Bmal1. Interestingly, simulation of shift work-induced circadian misalignment in mice recapitulates many of the defects seen in Bmal1-deficient islets. Thus, the cell-autonomous function of Bmal1 is required for normal ?-cell function by mitigating oxidative stress and serves to preserve ?-cell function in the face of circadian misalignment. PMID:23547261

Lee, Jeongkyung; Moulik, Mousumi; Fang, Zhe; Saha, Pradip; Zou, Fang; Xu, Yong; Nelson, David L.; Ma, Ke; Moore, David D.

2013-01-01

33

Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant.  

PubMed

In order to assess the contribution of a central clock in the hypothalamic suprachiasmatic nucleus (SCN) to circadian behavior and the organization of peripheral clocks, we generated forebrain/SCN-specific Bmal1 knockout mice by using floxed Bmal1 and pan-neuronal Cre lines. The forebrain knockout mice showed >90% deletion of BMAL1 in the SCN and exhibited an immediate and complete loss of circadian behavior in constant conditions. Circadian rhythms in peripheral tissues persisted but became desynchronized and damped in constant darkness. The loss of synchrony was rescued by light/dark cycles and partially by restricted feeding (only in the liver and kidney but not in the other tissues) in a distinct manner. These results suggest that the forebrain/SCN is essential for internal temporal order of robust circadian programs in peripheral clocks, and that individual peripheral clocks are affected differently by light and feeding in the absence of a functional oscillator in the forebrain. PMID:25525750

Izumo, Mariko; Pejchal, Martina; Schook, Andrew C; Lange, Ryan P; Walisser, Jacqueline A; Sato, Takashi R; Wang, Xiaozhong; Bradfield, Christopher A; Takahashi, Joseph S

2014-01-01

34

TGFbeta inducible early gene-1 (TIEG1) and cardiac hypertrophy: Discovery and characterization of a novel signaling pathway.  

PubMed

Cellular mechanisms causing cardiac hypertrophy are currently under intense investigation. We report a novel finding in the TGFbeta inducible early gene (TIEG) null mouse implicating TIEG1 in cardiac hypertrophy. The TIEG(-/-) knock-out mouse was studied. Male mice age 4-16 months were characterized (N = 86 total) using echocardiography, transcript profiling by gene microarray, and immunohistochemistry localized upregulated genes for determination of cellular mechanism. The female mice (N = 40) did not develop hypertrophy or fibrosis. The TIEG(-/-) knock-out mouse developed features of cardiac hypertrophy including asymmetric septal hypertrophy, an increase in ventricular size at age 16 months, an increase (214%) in mouse heart/weight body weight ratio TIEG(-/-), and an increase in wall thickness in TIEG(-/-) mice of (1.85 +/- 0.21 mm), compared to the control (1.13 +/- 0.15 mm, P < 0.04). Masson Trichrome staining demonstrated evidence of myocyte disarray and myofibroblast fibrosis. Microarray analysis of the left ventricles demonstrated that TIEG(-/-) heart tissues expressed a 13.81-fold increase in pituitary tumor-transforming gene-1 (Pttg1). An increase in Pttg1 and histone H3 protein levels were confirmed in the TIEG(-/-) mice hearts tissues. We present evidence implicating TIEG and possibly its target gene, Pttg1, in the development of cardiac hypertrophy in the TIEG null mouse. PMID:16888812

Rajamannan, Nalini M; Subramaniam, Malayannan; Abraham, Theodore P; Vasile, Vlad C; Ackerman, Michael J; Monroe, David G; Chew, Teng-Leong; Spelsberg, Thomas C

2007-02-01

35

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

PubMed

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

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

2014-03-01

36

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

37

Posttranslational Mechanisms Regulate the Mammalian Circadian Clock  

Microsoft Academic Search

We have examined posttranslational regulation of clock proteins in mouse liver in vivo. The mouse PERIOD proteins (mPER1 and mPER2), CLOCK, and BMAL1 undergo robust circadian changes in phosphorylation. These proteins, the cryptochromes (mCRY1 and mCRY2), and casein kinase I epsilon (CKI?) form multimeric complexes that are bound to DNA during negative transcriptional feedback. CLOCK:BMAL1 heterodimers remain bound to DNA

Choogon Lee; Jean-Pierre Etchegaray; Felino R. A. Cagampang; Andrew S. I. Loudon; Steven M. Reppert

2001-01-01

38

The peripheral clock regulates human pigmentation.  

PubMed

Although the regulation of pigmentation is well characterized, it remains unclear whether cell-autonomous controls regulate the cyclic on-off switching of pigmentation in the hair follicle (HF). As human HFs and epidermal melanocytes express clock genes and proteins, and given that core clock genes (PER1, BMAL1) modulate human HF cycling, we investigated whether peripheral clock activity influences human HF pigmentation. We found that silencing BMAL1 or PER1 in human HFs increased HF melanin content. Furthermore, tyrosinase expression and activity, as well as TYRP1 and TYRP2 mRNA levels, gp100 protein expression, melanocyte dendricity, and the number gp100+ HF melanocytes, were all significantly increased in BMAL1 and/or PER1-silenced HFs. BMAL1 or PER1 silencing also increased epidermal melanin content, gp100 protein expression, and tyrosinase activity in human skin. These effects reflect direct modulation of melanocytes, as BMAL1 and/or PER1 silencing in isolated melanocytes increased tyrosinase activity and TYRP1/2 expression. Mechanistically, BMAL1 knockdown reduces PER1 transcription, and PER1 silencing induces phosphorylation of the master regulator of melanogenesis, microphthalmia-associated transcription factor, thus stimulating human melanogenesis and melanocyte activity in situ and in vitro. Therefore, the molecular clock operates as a cell-autonomous modulator of human pigmentation and may be targeted for future therapeutic strategies. PMID:25310406

Hardman, Jonathan A; Tobin, Desmond J; Haslam, Iain S; Farjo, Nilofer; Farjo, Bessam; Al-Nuaimi, Yusur; Grimaldi, Benedetto; Paus, Ralf

2015-04-01

39

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

PubMed Central

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

2013-01-01

40

Inter-Individual Differences In Habitual Sleep Timing and Entrained Phase of Endogenous Circadian Rhythms of BMAL1, PER2 and PER3 mRNA in Human Leukocytes  

PubMed Central

Study Objectives: Individual sleep timing differs and is governed partly by circadian oscillators, which may be assessed by hormonal markers, or by clock gene expression. Clock gene expression oscillates in peripheral tissues, including leukocytes. The study objective was to determine whether the endogenous phase of these rhythms, assessed in the absence of the sleep-wake and light-dark cycle, correlates with habitual sleep-wake timing. Design: Observational, cross-sectional. Setting: Home environment and Clinical Research Center. Participants: 24 healthy subjects aged 25.0 ± 3.5 (SD) years. Measurements: Actigraphy and sleep diaries were used to characterize sleep timing. Circadian rhythm phase and amplitude of plasma melatonin, cortisol, and BMAL1, PER2, and PER3 expression were assessed during a constant routine. Results: Circadian oscillations were more robust for PER3 than for BMAL1 or PER2. Average peak timings were 6:05 for PER3, 8:06 for PER2, 15:06 for BMAL1, 4:20 for melatonin, and 10:49 for cortisol. Individual sleep-wake timing correlated with the phases of melatonin and cortisol. Individual PER3 rhythms correlated significantly with sleep-wake timing and the timing of melatonin and cortisol, but those of PER2 and BMAL1 did not reach significance. The correlation between sleep timing and PER3 expression was stronger in individuals homozygous for the variant of the PER3 polymorphism that is associated with morningness. Conclusions: Individual phase differences in PER3 expression during a constant routine correlate with sleep timing during entrainment. PER3 expression in leukocytes represents a useful molecular marker of the circadian processes governing sleep-wake timing. Citation: Archer SN; Viola AU; Kyriakopoulou V; von Schantz M; Dijk DJ. Inter-individual differences in habitual sleep timing and entrained phase of endogenous circadian rhythms of BMAL1, PER2 and PER3 mRNA in human leukocytes. SLEEP 2008;31(5):608-617. PMID:18517031

Archer, Simon N.; Viola, Antoine U.; Kyriakopoulou, Vanessa; von Schantz, Malcolm; Dijk, Derk-Jan

2008-01-01

41

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration  

PubMed Central

Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism. The genes encoding clock proteins are expressed throughout the brain, though it is unknown whether these proteins modulate brain homeostasis. We observed that deletion of circadian clock transcriptional activators aryl hydrocarbon receptor nuclear translocator–like (Bmal1) alone, or circadian locomotor output cycles kaput (Clock) in combination with neuronal PAS domain protein 2 (Npas2), induced severe age-dependent astrogliosis in the cortex and hippocampus. Mice lacking the clock gene repressors period circadian clock 1 (Per1) and period circadian clock 2 (Per2) had no observed astrogliosis. Bmal1 deletion caused the degeneration of synaptic terminals and impaired cortical functional connectivity, as well as neuronal oxidative damage and impaired expression of several redox defense genes. Targeted deletion of Bmal1 in neurons and glia caused similar neuropathology, despite the retention of intact circadian behavioral and sleep-wake rhythms. Reduction of Bmal1 expression promoted neuronal death in primary cultures and in mice treated with a chemical inducer of oxidative injury and striatal neurodegeneration. Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration. PMID:24270424

Musiek, Erik S.; Lim, Miranda M.; Yang, Guangrui; Bauer, Adam Q.; Qi, Laura; Lee, Yool; Roh, Jee Hoon; Ortiz-Gonzalez, Xilma; Dearborn, Joshua T.; Culver, Joseph P.; Herzog, Erik D.; Hogenesch, John B.; Wozniak, David F.; Dikranian, Krikor; Giasson, Benoit I.; Weaver, David R.; Holtzman, David M.; FitzGerald, Garret A.

2013-01-01

42

A Molecular Mechanism Regulating Rhythmic Output from the Suprachiasmatic Circadian Clock  

Microsoft Academic Search

We examined the transcriptional regulation of the clock-controlled arginine vasopressin gene in the suprachiasmatic nuclei (SCN). A core clock mechanism in mouse SCN appears to involve a transcriptional feedback loop in which CLOCK and BMAL1 are positive regulators and three mPeriod (mPer) genes are involved in negative feedback. We show that the RNA rhythm of each mPer gene is severely

Xiaowei Jin; Lauren P. Shearman; David R. Weaver; Mark J. Zylka; Geert J. De Vries; Steven M. Reppert

1999-01-01

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

2013-10-01

44

The De-Ubiquitinylating Enzyme, USP2, Is Associated with the Circadian Clockwork and Regulates Its Sensitivity to Light  

PubMed Central

We have identified a novel component of the circadian clock that regulates its sensitivity to light at the evening light to dark transition. USP2 (Ubiquitin Specific Protease 2), which de-ubiquitinylates and stabilizes target proteins, is rhythmically expressed in multiple tissues including the SCN. We have developed a knockout model of USP2 and found that exposure to low irradiance light at ZT12 increases phase delays of USP2?/? mice compared to wildtype. We additionally show that USP2b is in a complex with several clock components and regulates the stability and turnover of BMAL1, which in turn alters the expression of several CLOCK/BMAL1 controlled genes. Rhythmic expression of USP2 in the SCN and other tissues offers a new level of control of the clock machinery through de-ubiqutinylation and suggests a role for USP2 during circadian adaptation to environmental day length changes. PMID:21966515

Scoma, Heather Dehlin; Humby, Monica; Yadav, Geetha; Zhang, Qingjiong; Fogerty, Joseph; Besharse, Joseph C.

2011-01-01

45

Cellular Clocks in AVP Neurons of the SCN Are Critical for Interneuronal Coupling Regulating Circadian Behavior Rhythm.  

PubMed

The suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals, is a network structure composed of multiple types of neurons. Here, we report that mice with a Bmal1 deletion specific to arginine vasopressin (AVP)-producing neurons showed marked lengthening in the free-running period and activity time of behavior rhythms. When exposed to an abrupt 8-hr advance of the light/dark cycle, these mice reentrained faster than control mice did. In these mice, the circadian expression of genes involved in intercellular communications, including Avp, Prokineticin 2, and Rgs16, was drastically reduced in the dorsal SCN, where AVP neurons predominate. In slices, dorsal SCN cells showed attenuated PER2::LUC oscillation with highly variable and lengthened periods. Thus, Bmal1-dependent oscillators of AVP neurons may modulate the coupling of the SCN network, eventually coupling morning and evening behavioral rhythms, by regulating expression of multiple factors important for the network property of these neurons. PMID:25741730

Mieda, Michihiro; Ono, Daisuke; Hasegawa, Emi; Okamoto, Hitoshi; Honma, Ken-Ichi; Honma, Sato; Sakurai, Takeshi

2015-03-01

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

2013-03-01

47

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

PubMed Central

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

2013-01-01

48

Class IIa Histone Deacetylases Are Conserved Regulators of Circadian Function*  

PubMed Central

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

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

2014-01-01

49

The Circadian Clock Maintains Cardiac Function by Regulating Mitochondrial Metabolism in Mice  

PubMed Central

Cardiac function is highly dependent on oxidative energy, which is produced by mitochondrial respiration. Defects in mitochondrial function are associated with both structural and functional abnormalities in the heart. Here, we show that heart-specific ablation of the circadian clock gene Bmal1 results in cardiac mitochondrial defects that include morphological changes and functional abnormalities, such as reduced enzymatic activities within the respiratory complex. Mice without cardiac Bmal1 function show a significant decrease in the expression of genes associated with the fatty acid oxidative pathway, the tricarboxylic acid cycle, and the mitochondrial respiratory chain in the heart and develop severe progressive heart failure with age. Importantly, similar changes in gene expression related to mitochondrial oxidative metabolism are also observed in C57BL/6J mice subjected to chronic reversal of the light-dark cycle; thus, they show disrupted circadian rhythmicity. These findings indicate that the circadian clock system plays an important role in regulating mitochondrial metabolism and thereby maintains cardiac function. PMID:25389966

Kohsaka, Akira; Das, Partha; Hashimoto, Izumi; Nakao, Tomomi; Deguchi, Yoko; Gouraud, Sabine S.; Waki, Hidefumi; Muragaki, Yasuteru; Maeda, Masanobu

2014-01-01

50

Molecular characterization and chromosomal mapping of porcine brain and muscle Arnt-like protein-1 gene.  

PubMed

As a transcription factor regulating circadian rhythm, brain and muscle Arnt-like protein-1 (BMAL1) plays an important role in lipid homeostasis. The Chinese indigenous and western pig breeds show marked difference in fat deposition, the structure and function of porcine BMAL1 (pBMAL1) between them might be different. In present study, the molecular characteristics and chromosomal location of pBMAL1 were analyzed. The results indicated that pBMAL1 cDNA had a coding region of 1,878 bp and shared 94.36, 89.85 and 89.79% identity with human, mouse and rat BMAL1, respectively, and the pBMAL1 protein had 99.20, 98.24 and 97.92% identity to those of human BMAL1b, mouse BMAL1b and rat BMAL1b, respectively. Compared with other mammals, pBMAL1 was more closely related to human BMAL1. The expression of pBMAL1 was detected in kidney, stomach, spleen, bladder, gallbladder, lumbar spinal cord, medulla oblongata, heart, longissimus dorsi muscle, liver, small intestine, large intestine, lung and backfat tissues. In adipose tissues, it was detected in mesentery fat, leaf fat, caul fat, backfat and cardiac fat, however, the expression level was not significantly different. Alternative usage of exon 2 was revealed to result in two pBMAL1 transcripts. Finally, by using a whole genome porcine radiation hybrid (RH) panel (IMpRH), the pBMAL1 gene was mapped to SSC 2p11-q21. PMID:19247803

Xing, Jinyi; Xu, Qinying; Li, Kui; Wang, Jiying; Wu, Ying; Jiang, Yunliang

2009-11-01

51

Temporal Regulation of Cytokines by the Circadian Clock  

PubMed Central

Several parameters of the immune system exhibit oscillations with a period of approximately 24 hours that refers to “circadian rhythms.” Such daily variations in host immune system status might evolve to maximize immune reactions at times when encounters with pathogens are most likely to occur. However, the mechanisms behind circadian immunity have not been fully understood. Recent studies reveal that the internal time keeping system “circadian clock” plays a key role in driving the daily rhythms evident in the immune system. Importantly, several studies unveil molecular mechanisms of how certain clock proteins (e.g., BMAL1 and CLOCK) temporally regulate expression of cytokines. Since cytokines are crucial mediators for shaping immune responses, this review mainly summarizes the new knowledge that highlights an emerging role of the circadian clock as a novel regulator of cytokines. A greater understanding of circadian regulation of cytokines will be important to exploit new strategies to protect host against infection by efficient cytokine induction or to treat autoimmunity and allergy by ameliorating excessive activity of cytokines. PMID:24809063

Nakao, Atsuhito

2014-01-01

52

Regulation of period 1 expression in cultured rat pineal  

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

53

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

PubMed Central

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

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

2014-01-01

54

Bmal1 is a direct transcriptional target of the orphan nuclear receptor, NR2F1  

Technology Transfer Automated Retrieval System (TEKTRAN)

Orphan nuclear receptor NR2F1 (also known as COUP-TFI, Chicken Ovalbumin Upstream Promoter Transcription Factor I) is a highly conserved member of the nuclear receptor superfamily. NR2F1 plays a critical role during embryonic development, particularly in the central and peripheral nervous systems a...

55

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

56

Mistimed sleep disrupts circadian regulation of the human transcriptome.  

PubMed

Circadian organization of the mammalian transcriptome is achieved by rhythmic recruitment of key modifiers of chromatin structure and transcriptional and translational processes. These rhythmic processes, together with posttranslational modification, constitute circadian oscillators in the brain and peripheral tissues, which drive rhythms in physiology and behavior, including the sleep-wake cycle. In humans, sleep is normally timed to occur during the biological night, when body temperature is low and melatonin is synthesized. Desynchrony of sleep-wake timing and other circadian rhythms, such as occurs in shift work and jet lag, is associated with disruption of rhythmicity in physiology and endocrinology. However, to what extent mistimed sleep affects the molecular regulators of circadian rhythmicity remains to be established. Here, we show that mistimed sleep leads to a reduction of rhythmic transcripts in the human blood transcriptome from 6.4% at baseline to 1.0% during forced desynchrony of sleep and centrally driven circadian rhythms. Transcripts affected are key regulators of gene expression, including those associated with chromatin modification (methylases and acetylases), transcription (RNA polymerase II), translation (ribosomal proteins, initiation, and elongation factors), temperature-regulated transcription (cold inducible RNA-binding proteins), and core clock genes including CLOCK and ARNTL (BMAL1). We also estimated the separate contribution of sleep and circadian rhythmicity and found that the sleep-wake cycle coordinates the timing of transcription and translation in particular. The data show that mistimed sleep affects molecular processes at the core of circadian rhythm generation and imply that appropriate timing of sleep contributes significantly to the overall temporal organization of the human transcriptome. PMID:24449876

Archer, Simon N; Laing, Emma E; Möller-Levet, Carla S; van der Veen, Daan R; Bucca, Giselda; Lazar, Alpar S; Santhi, Nayantara; Slak, Ana; Kabiljo, Renata; von Schantz, Malcolm; Smith, Colin P; Dijk, Derk-Jan

2014-02-11

57

Bioinformatics analysis of transcriptional regulation of circadian genes in rat liver  

PubMed Central

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

2014-01-01

58

Mathematical model of the Drosophila circadian clock: loop regulation and transcriptional integration.  

PubMed

Eukaryotic circadian clocks include interconnected positive and negative feedback loops. The clock-cycle dimer (CLK-CYC) and its homolog, CLK-BMAL1, are key transcriptional activators of central components of the Drosophila and mammalian circadian networks, respectively. In Drosophila, negative loops include period-timeless and vrille; positive loops include par domain protein 1. Clockwork orange (CWO) is a recently discovered negative transcription factor with unusual effects on period, timeless, vrille, and par domain protein 1. To understand the actions of this protein, we introduced a new system of ordinary differential equations to model regulatory networks. The model is faithful in the sense that it replicates biological observations. CWO loop actions elevate CLK-CYC; the transcription of direct targets responds by integrating opposing signals from CWO and CLK-CYC. Loop regulation and integration of opposite transcriptional signals appear to be central mechanisms as they also explain paradoxical effects of period gain-of-function and null mutations. PMID:19883582

Fathallah-Shaykh, Hassan M; Bona, Jerry L; Kadener, Sebastian

2009-11-01

59

The PXDLS linear motif regulates circadian rhythmicity through protein–protein interactions  

PubMed Central

The circadian core clock circuitry relies on interlocked transcription-translation feedback loops that largely count on multiple protein interactions. The molecular mechanisms implicated in the assembly of these protein complexes are relatively unknown. Our bioinformatics analysis of short linear motifs, implicated in protein interactions, reveals an enrichment of the Pro-X-Asp-Leu-Ser (PXDLS) motif within circadian transcripts. We show that the PXDLS motif can bind to BMAL1/CLOCK and disrupt circadian oscillations in a cell-autonomous manner. Remarkably, the motif is evolutionary conserved in the core clock protein REV-ERB?, and additional proteins implicated in the clock's function (NRIP1, CBP). In this conjuncture, we uncover a novel cross talk between the two principal core clock feedback loops and show that BMAL/CLOCK and REV-ERB? interact and that the PXDLS motif of REV-ERB? participates in their binding. Furthermore, we demonstrate that the PXDLS motifs of NRIP1 and CBP are involved in circadian rhythmicity. Our findings suggest that the PXDLS motif plays an important role in circadian rhythmicity through regulation of protein interactions within the clock circuitry and that short linear motifs can be employed to modulate circadian oscillations. PMID:25260595

Shalev, Moran; Aviram, Rona; Adamovich, Yaarit; Kraut-Cohen, Judith; Shamia, Tal; Ben-Dor, Shifra; Golik, Marina; Asher, Gad

2014-01-01

60

Mathematical Model of the Drosophila Circadian Clock: Loop Regulation and Transcriptional Integration  

PubMed Central

Eukaryotic circadian clocks include interconnected positive and negative feedback loops. The clock-cycle dimer (CLK-CYC) and its homolog, CLK-BMAL1, are key transcriptional activators of central components of the Drosophila and mammalian circadian networks, respectively. In Drosophila, negative loops include period-timeless and vrille; positive loops include par domain protein 1. Clockwork orange (CWO) is a recently discovered negative transcription factor with unusual effects on period, timeless, vrille, and par domain protein 1. To understand the actions of this protein, we introduced a new system of ordinary differential equations to model regulatory networks. The model is faithful in the sense that it replicates biological observations. CWO loop actions elevate CLK-CYC; the transcription of direct targets responds by integrating opposing signals from CWO and CLK-CYC. Loop regulation and integration of opposite transcriptional signals appear to be central mechanisms as they also explain paradoxical effects of period gain-of-function and null mutations. PMID:19883582

Fathallah-Shaykh, Hassan M.; Bona, Jerry L.; Kadener, Sebastian

2009-01-01

61

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

PubMed

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

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

2015-02-01

62

Regulation of Retinal Inflammation by Rhythmic Expression of MiR-146a in Diabetic Retina  

PubMed Central

Purpose. Chronic inflammation and dysregulation of circadian rhythmicity are involved in the pathogenesis of diabetic retinopathy. MicroRNAs (miRNAs) can regulate inflammation and circadian clock machinery. We tested the hypothesis that altered daily rhythm of miR-146a expression in diabetes contributes to retinal inflammation. Methods. Nondiabetic and STZ-induced diabetic rats kept in 12/12 light/dark cycle were killed every 2 hours over a 72-hour period. Human retinal endothelial cells (HRECs) were synchronized with dexamethasone. Expression of miR-146a, IL-1 receptor-associated kinase 1 (IRAK1), IL-1?, VEGF and ICAM-1, as well as clock genes was examined by real-time PCR and Western blot. To modulate expression levels of miR-146a, mimics and inhibitors were used. Results. Diabetes inhibited amplitude of negative arm (per1) and enhanced amplitude of the positive arm (bmal1) of clock machinery in retina. In addition to clock genes, miR-146a and its target gene IRAK1 also exhibited daily oscillations in antiphase; however, these patterns were lost in diabetic retina. This loss of rhythmic pattern was associated with an increase in ICAM-1, IL-?, and VEGF expression. Human retinal endothelial cells had robust miR-146a expression that followed circadian oscillation pattern; however, HRECs isolated from diabetic donors had reduced miR-146a amplitude but increased amplitude of IRAK1 and ICAM-1. In HRECs, miR-146a mimic or inhibitor caused 1.6- and 1.7-fold decrease or 1.5- and 1.6-fold increase, respectively, in mRNA and protein expression levels of ICAM-1 after 48 hours. Conclusions. Diabetes-induced dysregulation of daily rhythms of miR-146a and inflammatory pathways under miR-146a control have potential implications for the development of diabetic retinopathy. PMID:24867582

Wang, Qi; Bozack, Svetlana N.; Yan, Yuanqing; Boulton, Michael E.; Grant, Maria B.; Busik, Julia V.

2014-01-01

63

Phosphorylation of clock protein PER1 regulates its circadian degradation in normal human fibroblasts.  

PubMed Central

Recent advances suggest that the molecular components of the circadian clock generate a self-sustaining transcriptional-translational feedback loop with a period of approx. 24 h. The precise expression profiles of human clock genes and their products have not been elucidated. We cloned human clock genes, including per1, per2, per3, cry2 and clock, and evaluated their circadian mRNA expression profiles in WI-38 fibroblasts stimulated with serum. Transcripts of hPer1, hPer2, hPer3, hBMAL1 and hCry2 (where h is human) underwent circadian oscillation. Serum-stimulation also caused daily oscillations of hPER1 protein and the apparent molecular mass of hPER1 changed. Inhibitor studies indicated that the CKI (casein kinase I) family, including CKIepsilon and CKIdelta, phosphorylated hPER1 and increased the apparent molecular mass of hPER1. The inhibition of hPER1 phosphorylation by CKI-7 [ N -(2-aminoethyl)-5-chloro-isoquinoline-8-sulphonamide], a CKI inhibitor, disturbed hPER1 degradation, delayed the nuclear entry of hPER1 and allowed it to persist for longer in the nucleus. Furthermore, proteasome inhibitors specifically blocked hPER1 degradation. However leptomycin B, an inhibitor of nuclear export, did not alter the degradation state of hPER1 protein. These findings indicate that circadian hPER1 degradation through a proteasomal pathway can be regulated through phosphorylation by CKI, but not by subcellular localization. PMID:14750904

Miyazaki, Koyomi; Nagase, Takahiro; Mesaki, Miho; Narukawa, Junko; Ohara, Osamu; Ishida, Norio

2004-01-01

64

When the circadian clock meets the melanin pigmentary system.  

PubMed

Silencing of BMAL1 and PER1 stimulates melanogenic activity of follicular and epidermal melanocytes, indicating a novel role for peripheral circadian clock processes in the regulation of melanin pigmentation. Linking the expression levels of BMAL1/PER1 with changes in melanogenesis opens exciting opportunities to study the role of the local molecular clock in modulation of melanocyte functions in the hair follicle and the epidermis with attendant effects on epidermal barrier functions in general. PMID:25785947

Slominski, Andrzej T; Hardeland, Rüdiger; Reiter, Russel J

2015-04-01

65

Inducible cAMP Early Repressor Regulates the Period 1 Gene of the Hepatic and Adrenal Clocks*  

PubMed Central

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

2013-01-01

66

Annual life history-dependent gene expression in the hypothalamus and liver of a migratory songbird: insights into the molecular regulation of seasonal metabolism.  

PubMed

Birds seasonally switch from one life history state (LHS) to another to maximize their fitness. Accordingly, they exhibit distinct differences in their physiological and behavioral phenotypes between seasons. Possible molecular mechanisms underlying changes through the seasons have scarcely been examined in migratory birds. The present study measured key genes suggested to be involved in the metabolic regulation of 4 photoperiodically induced seasonal LHSs in a long-distance migratory songbird, the blackheaded bunting (Emberiza melanocephala). Buntings were held under short days (8 h light:16 h darkness, 8L:16D), during which they maintained the winter nonmigratory phenotype. Then they were exposed for several weeks to long days (13L:11D). Differences in the activity-rest pattern, body fattening and weight gain, testis size, organ (heart, intestine) weights, and blood glucose and triglyceride levels confirmed that buntings sequentially exhibited spring migration-linked premigratory, migratory, and postmigratory LHSs under long days. The mRNA levels of circadian genes involved in metabolism (Bmal1, Clock, Npas2, Ror?, and Rev-erb?) and of genes that encode for proteins/enzymes involved in the regulation of glucose (Sirt1, FoxO1, Glut1, and Pygl) and lipids (Hmg-CoA; Ppar?, Ppar?; Fasn and Acaca) showed LHS-dependent changes in their light-dark expression patterns in the hypothalamus and liver. These initial results on genetic regulation of metabolism in a migratory species extend the idea that the transitions between LHSs in a seasonal species are accomplished by changes at multiple regulatory levels. Thus, these findings promise new insights into the mechanism(s) of adaptation to seasons in higher vertebrates. PMID:25252711

Trivedi, Amit K; Kumar, Jayant; Rani, Sangeeta; Kumar, Vinod

2014-10-01

67

Library Regulations Library Regulations  

E-print Network

Library Regulations 2012-13 Library Regulations UNIVERSITY OF BIRMINGHAM REGULATIONS LIBRARY REGULATIONS Preamble: The Library Regulations apply to all users of library facilities managed on behalf of the University by Library Services, and thus there are sections that apply also to non- members of the University

Birmingham, University of

68

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

SciTech Connect

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

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

2013-05-03

69

SUMO: regulating the regulator  

Microsoft Academic Search

Post-translational modifiers of the SUMO (Small Ubiquitin-related Modifier) family have emerged as key regulators of protein function and fate. While the past few years have seen an enormous increase in knowledge on SUMO enzymes, substrates, and consequences of modification, regulation of SUMO conjugation is far from being understood. This brief review will provide an overview on recent advances concerning (i)

Guillaume Bossis; Frauke Melchior

2006-01-01

70

Specificity in circadian clock feedback from targeted reconstitution of the NuRD corepressor.  

PubMed

Mammalian circadian rhythms are generated by a negative feedback loop in which PERIOD (PER) proteins accumulate, form a large nuclear complex (PER complex), and bind the transcription factor CLOCK-BMAL1, repressing their own expression. We found that mouse PER complexes include the Mi-2/nucleosome remodelling and deacetylase (NuRD) transcriptional corepressor. Unexpectedly, two NuRD subunits, CHD4 and MTA2, constitutively associate with CLOCK-BMAL1, with CHD4 functioning to promote CLOCK-BMAL1 transcriptional activity. At the onset of negative feedback, the PER complex delivers the remaining complementary NuRD subunits to DNA-bound CLOCK-BMAL1, thereby reconstituting a NuRD corepressor that is important for circadian transcriptional feedback and clock function. The PER complex thus acquires full repressor activity only upon successful targeting of CLOCK-BMAL1. Our results show how specificity is generated in the clock despite its dependence on generic transcriptional regulators and reveal the existence of active communication between the positive and negative limbs of the circadian feedback loop. PMID:25453762

Kim, Jin Young; Kwak, Pieter Bas; Weitz, Charles J

2014-12-18

71

Sleep and Circadian Rhythm Regulation in Early Parkinson Disease  

PubMed Central

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

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

2014-01-01

72

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. PMID:22936800

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

2012-01-01

73

Telomerase Regulation  

PubMed Central

The intimate connection between telomerase regulation and human disease is now well established. The molecular basis for telomerase regulation is highly complex and entails multiple layers of control. While the major target of enzyme regulation is the catalytic subunit TERT, the RNA subunit of telomerase is also implicated in telomerase control. In addition, alterations in gene dosage and alternative isoforms of core telomerase components have been described. Finally, telomerase localization, recruitment to the telomere and enzymology at the chromosome terminus are all subject to modulation. In this review we summarize recent advances in understanding fundamental mechanisms of telomerase regulation. PMID:22032831

Cifuentes-Rojas, Catherine; Shippen, Dorothy E.

2011-01-01

74

Thyroxine Differentially Modulates the Peripheral Clock: Lessons from the Human Hair Follicle  

PubMed Central

The human hair follicle (HF) exhibits peripheral clock activity, with knock-down of clock genes (BMAL1 and PER1) prolonging active hair growth (anagen) and increasing pigmentation. Similarly, thyroid hormones prolong anagen and stimulate pigmentation in cultured human HFs. In addition they are recognized as key regulators of the central clock that controls circadian rhythmicity. Therefore, we asked whether thyroxine (T4) also influences peripheral clock activity in the human HF. Over 24 hours we found a significant reduction in protein levels of BMAL1 and PER1, with their transcript levels also decreasing significantly. Furthermore, while all clock genes maintained their rhythmicity in both the control and T4 treated HFs, there was a significant reduction in the amplitude of BMAL1 and PER1 in T4 (100 nM) treated HFs. Accompanying this, cell-cycle progression marker Cyclin D1 was also assessed appearing to show an induced circadian rhythmicity by T4 however, this was not significant. Contrary to short term cultures, after 6 days, transcript and/or protein levels of all core clock genes (BMAL1, PER1, clock, CRY1, CRY2) were up-regulated in T4 treated HFs. BMAL1 and PER1 mRNA was also up-regulated in the HF bulge, the location of HF epithelial stem cells. Together this provides the first direct evidence that T4 modulates the expression of the peripheral molecular clock. Thus, patients with thyroid dysfunction may also show a disordered peripheral clock, which raises the possibility that short term, pulsatile treatment with T4 might permit one to modulate circadian activity in peripheral tissues as a target to treat clock-related disease. PMID:25822259

Hardman, Jonathan A.; Haslam, Iain S.; Farjo, Nilofer; Farjo, Bessam; Paus, Ralf

2015-01-01

75

Government Regulation  

E-print Network

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

Ashford, Nicholas

2005-01-01

76

Gene Regulation  

NSDL National Science Digital Library

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

Robert Frederick (AAAS; )

2008-03-28

77

Regulation 28: Library REGULATION 28: LIBRARY  

E-print Network

Regulation 28: Library 180 REGULATION 28: LIBRARY The purpose of this Regulation is to safeguard the common interests of all Library users. All persons are admitted on the understanding that they have read and agreed to observe the Library Regulations. Breach of this Regulation could result in membership being

Sussex, University of

78

PPARs Integrate the Mammalian Clock and Energy Metabolism  

PubMed Central

Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that function as transcription factors regulating the expression of numerous target genes. PPARs play an essential role in various physiological and pathological processes, especially in energy metabolism. It has long been known that metabolism and circadian clocks are tightly intertwined. However, the mechanism of how they influence each other is not fully understood. Recently, all three PPAR isoforms were found to be rhythmically expressed in given mouse tissues. Among them, PPAR? and PPAR? are direct regulators of core clock components, Bmal1 and Rev-erb?, and, conversely, PPAR? is also a direct Bmal1 target gene. More importantly, recent studies using knockout mice revealed that all PPARs exert given functions in a circadian manner. These findings demonstrated a novel role of PPARs as regulators in correlating circadian rhythm and metabolism. In this review, we summarize advances in our understanding of PPARs in circadian regulation. PMID:24693278

Chen, Lihong; Yang, Guangrui

2014-01-01

79

SIRTUIN 1: regulating the regulator.  

PubMed

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 importance in the development of innovative treatment strategies for cancer, neurodegenerative disorders and metabolic disease. Based on differences in their catalytic activities, SIRT1 and the sirtuins in general, are insensitive to the classical class I and II HDAC inhibitors which are increasingly becoming part of treatment regimens for solid tumors and hematological malignancies. In this review we outline recent research advances on the regulation of SIRT1 which may provide the basis for the development of therapeutic inhibitors with improved specificity. PMID:18774777

Zschoernig, Barbara; Mahlknecht, Ulrich

2008-11-14

80

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

81

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. PMID:22210883

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

2012-01-01

82

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

PubMed Central

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

2013-01-01

83

Survival of adult generated hippocampal neurons is altered in circadian arrhythmic mice.  

PubMed

The subgranular zone of the hippocampal formation gives rise to new neurons that populate the dentate gyrus throughout life. Cells in the hippocampus exhibit rhythmic clock gene expression and the circadian clock is known to regulate the cycle of cell division in other areas of the body. These facts suggest that the circadian clock may regulate adult neurogenesis in the hippocampus as well. In the present study, neurogenesis in the hippocampal subgranular zone was examined in arrhythmic Bmal1 knockout (-KO) mice and their rhythmic heterozygous and wildtype littermates. Proliferation and survival of newly generated subgranular zone cells were examined using bromodeoxyuridine labelling, while pyknosis (a measure of cell death) and hippocampal volume were examined in cresyl violet stained sections. There was no significant difference in cellular proliferation between any of the groups, yet survival of proliferating cells, 6 weeks after the bromodeoxyuridine injection, was significantly greater in the BMAL1-KO animals. The number of pyknotic cells was significantly decreased in Bmal1-KO animals, yet hippocampal volume remained the same across genotypes. These findings suggest that while a functional circadian clock is not necessary for normal proliferation of neuronal precursor cells, the normal pruning of newly generated neurons in the hippocampus may require a functional circadian clock. PMID:24941219

Rakai, Brooke D; Chrusch, Michael J; Spanswick, Simon C; Dyck, Richard H; Antle, Michael C

2014-01-01

84

Altered Stra13 and Dec2 circadian gene expression in hypoxic cells  

SciTech Connect

The circadian system regulates rhythmically most of the mammalian physiology in synchrony with the environmental light/dark cycle. Alteration of circadian clock gene expression has been associated with tumour progression but the molecular links between the two mechanisms remain poorly defined. Here we show that Stra13 and Dec2, two circadian transcriptional regulators which play a crucial role in cell proliferation and apoptosis are overexpressed and no longer rhythmic in serum shocked fibroblasts treated with CoCl{sub 2,} a substitute of hypoxia. This effect is associated with a loss of circadian expression of the clock genes Rev-erb{alpha} and Bmal1, and the clock-controlled gene Dbp. Consistently, cotransfection assays demonstrate that STRA13 and DEC2 both antagonize CLOCK:BMAL1 dependent transactivation of the Rev-erb{alpha} and Dbp promoters. Using a transplantable osteosarcoma tumour model, we show that hypoxia is associated with altered circadian expression of Stra13, Dec2, Rev-erb{alpha}, Bmal1 and Dbp in vivo. These observations collectively support the notion that overexpression of Stra13 and Dec2 links hypoxia signalling to altered circadian clock gene expression.

Guillaumond, Fabienne; Lacoche, Samuel; Dulong, Sandrine; Grechez-Cassiau, Aline [Universite de Nice-Sophia Antipolis, CNRS FRE3094, 28 Av. Valrose, 06108 Nice (France); Filipski, Elisabeth; Li, Xiao-Mei; Levi, Francis [Universite Paris-Sud, INSERM U776, Hopital Paul Brousse, 14 Av. P.V. Couturier, 94800 Villejuif (France); Berra, Edurne [Cell Biology and Stem Cells Unit, CIC BioGUNE, Technologic Park of Bizkaia, 48160-Derio (Spain); Delaunay, Franck [Universite de Nice-Sophia Antipolis, CNRS FRE3094, 28 Av. Valrose, 06108 Nice (France); Teboul, Michele [Universite de Nice-Sophia Antipolis, CNRS FRE3094, 28 Av. Valrose, 06108 Nice (France)], E-mail: teboulm@unice.fr

2008-05-16

85

Survival of Adult Generated Hippocampal Neurons Is Altered in Circadian Arrhythmic Mice  

PubMed Central

The subgranular zone of the hippocampal formation gives rise to new neurons that populate the dentate gyrus throughout life. Cells in the hippocampus exhibit rhythmic clock gene expression and the circadian clock is known to regulate the cycle of cell division in other areas of the body. These facts suggest that the circadian clock may regulate adult neurogenesis in the hippocampus as well. In the present study, neurogenesis in the hippocampal subgranular zone was examined in arrhythmic Bmal1 knockout (-KO) mice and their rhythmic heterozygous and wildtype littermates. Proliferation and survival of newly generated subgranular zone cells were examined using bromodeoxyuridine labelling, while pyknosis (a measure of cell death) and hippocampal volume were examined in cresyl violet stained sections. There was no significant difference in cellular proliferation between any of the groups, yet survival of proliferating cells, 6 weeks after the bromodeoxyuridine injection, was significantly greater in the BMAL1-KO animals. The number of pyknotic cells was significantly decreased in Bmal1-KO animals, yet hippocampal volume remained the same across genotypes. These findings suggest that while a functional circadian clock is not necessary for normal proliferation of neuronal precursor cells, the normal pruning of newly generated neurons in the hippocampus may require a functional circadian clock. PMID:24941219

Rakai, Brooke D.; Chrusch, Michael J.; Spanswick, Simon C.; Dyck, Richard H.; Antle, Michael C.

2014-01-01

86

MicroRNA 22 Regulates Cell Cycle Length in Cerebellar Granular Neuron Precursors  

PubMed Central

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

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

2013-01-01

87

Changes in the daily rhythm of lipid metabolism in the diabetic retina.  

PubMed

Disruption of circadian regulation was recently shown to cause diabetes and metabolic disease. We have previously demonstrated that retinal lipid metabolism contributed to the development of diabetic retinopathy. The goal of this study was to determine the effect of diabetes on circadian regulation of clock genes and lipid metabolism genes in the retina and retinal endothelial cells (REC). Diabetes had a pronounced inhibitory effect on the negative clock arm with lower amplitude of the period (per) 1 in the retina; lower amplitude and a phase shift of per2 in the liver; and a loss of cryptochrome (cry) 2 rhythmic pattern in suprachiasmatic nucleus (SCN). The positive clock arm was increased by diabetes with higher amplitude of circadian locomotor output cycles kaput (CLOCK) and brain and muscle aryl-hydrocarbon receptor nuclear translocator-like 1 (bmal1) and phase shift in bmal1 rhythmic oscillations in the retina; and higher bmal1 amplitude in the SCN. Peroxisome proliferator-activated receptor (PPAR) ? exhibited rhythmic oscillation in retina and liver; PPAR? had lower amplitude in diabetic liver; sterol regulatory element-binding protein (srebp) 1c had higher amplitude in the retina but lower in the liver in STZ- induced diabetic animals. Both of Elongase (Elovl) 2 and Elovl4 had a rhythmic oscillation pattern in the control retina. Diabetic retinas lost Elovl4 rhythmic oscillation and had lower amplitude of Elovl2 oscillations. In line with the in vivo data, circadian expression levels of CLOCK, bmal1 and srebp1c had higher amplitude in rat REC (rREC) isolated from diabetic rats compared with control rats, while PPAR? and Elovl2 had lower amplitude in diabetic rREC. In conclusion, diabetes causes dysregulation of circadian expression of clock genes and the genes controlling lipid metabolism in the retina with potential implications for the development of diabetic retinopathy. PMID:24736612

Wang, Qi; Tikhonenko, Maria; Bozack, Svetlana N; Lydic, Todd A; Yan, Lily; Panchy, Nicholas L; McSorley, Kelly M; Faber, Matthew S; Yan, Yuanqing; Boulton, Michael E; Grant, Maria B; Busik, Julia V

2014-01-01

88

Changes in the Daily Rhythm of Lipid Metabolism in the Diabetic Retina  

PubMed Central

Disruption of circadian regulation was recently shown to cause diabetes and metabolic disease. We have previously demonstrated that retinal lipid metabolism contributed to the development of diabetic retinopathy. The goal of this study was to determine the effect of diabetes on circadian regulation of clock genes and lipid metabolism genes in the retina and retinal endothelial cells (REC). Diabetes had a pronounced inhibitory effect on the negative clock arm with lower amplitude of the period (per) 1 in the retina; lower amplitude and a phase shift of per2 in the liver; and a loss of cryptochrome (cry) 2 rhythmic pattern in suprachiasmatic nucleus (SCN). The positive clock arm was increased by diabetes with higher amplitude of circadian locomotor output cycles kaput (CLOCK) and brain and muscle aryl-hydrocarbon receptor nuclear translocator-like 1 (bmal1) and phase shift in bmal1 rhythmic oscillations in the retina; and higher bmal1 amplitude in the SCN. Peroxisome proliferator-activated receptor (PPAR) ? exhibited rhythmic oscillation in retina and liver; PPAR? had lower amplitude in diabetic liver; sterol regulatory element-binding protein (srebp) 1c had higher amplitude in the retina but lower in the liver in STZ- induced diabetic animals. Both of Elongase (Elovl) 2 and Elovl4 had a rhythmic oscillation pattern in the control retina. Diabetic retinas lost Elovl4 rhythmic oscillation and had lower amplitude of Elovl2 oscillations. In line with the in vivo data, circadian expression levels of CLOCK, bmal1 and srebp1c had higher amplitude in rat REC (rREC) isolated from diabetic rats compared with control rats, while PPAR? and Elovl2 had lower amplitude in diabetic rREC. In conclusion, diabetes causes dysregulation of circadian expression of clock genes and the genes controlling lipid metabolism in the retina with potential implications for the development of diabetic retinopathy. PMID:24736612

Wang, Qi; Tikhonenko, Maria; Bozack, Svetlana N.; Lydic, Todd A.; Yan, Lily; Panchy, Nicholas L.; Mcsorley, Kelly M.; Faber, Matthew S.; Yan, Yuanqing; Boulton, Michael E.; Grant, Maria B.; Busik, Julia V.

2014-01-01

89

Regulations.gov  

NSDL National Science Digital Library

Locating information about U.S. government regulations just got much easier with the Regulations.gov website. Visitors can use the site to find regulations from almost 300 federal agencies, and they can also search for proposed rules, final rules, and also submit comments on pending regulations. First-time visitors can get a feel for the site by looking at the "What's Hot" area, which features some of the most visited regulations. Other sections include "Newly Posted Regulations", "Your Voice in Action", and "Regulations with Comment Periods Closing Soon". Searching for regulations and related materials is made quite easy by the simple keyword search tool and visitors are also welcome to browse everything from "Abandoned Mine Reclamation Programs" to "Zones". Visitors can also sign up for the site's RSS feed and they may also wish to share this site with others via a host of different social media networks.

90

Computer Use Regulation Introduction  

E-print Network

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

Liu, Paul

91

3 Library Regulations Definitions  

E-print Network

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

Mottram, Nigel

92

Emotion Regulation CONCEPTUAL FOUNDATIONS  

E-print Network

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

Gross, James J.

93

Regulation and the Macroeconomy  

Microsoft Academic Search

SUMMARYThis article uses the number of pages in the Code of Federal Regulations to investigate the empirical relationship between federal regulation and macroeconomic performance in the U.S. The analysis uses an aggregate production framework to study the co-movement of output and the factors of production that results from regulation. The use of cointegration methodology overcomes some shortcomings of traditional techniques.

John W. Dawson; John J. Seater

2007-01-01

94

A Novel Protein, CHRONO, Functions as a Core Component of the Mammalian Circadian Clock  

PubMed Central

Circadian rhythms are controlled by a system of negative and positive genetic feedback loops composed of clock genes. Although many genes have been implicated in these feedback loops, it is unclear whether our current list of clock genes is exhaustive. We have recently identified Chrono as a robustly cycling transcript through genome-wide profiling of BMAL1 binding on the E-box. Here, we explore the role of Chrono in cellular timekeeping. Remarkably, endogenous CHRONO occupancy around E-boxes shows a circadian oscillation antiphasic to BMAL1. Overexpression of Chrono leads to suppression of BMAL1–CLOCK activity in a histone deacetylase (HDAC) –dependent manner. In vivo loss-of-function studies of Chrono including Avp neuron-specific knockout (KO) mice display a longer circadian period of locomotor activity. Chrono KO also alters the expression of core clock genes and impairs the response of the circadian clock to stress. CHRONO forms a complex with the glucocorticoid receptor and mediates glucocorticoid response. Our comprehensive study spotlights a previously unrecognized clock component of an unsuspected negative circadian feedback loop that is independent of another negative regulator, Cry2, and that integrates behavioral stress and epigenetic control for efficient metabolic integration of the clock. PMID:24736997

Myung, Jihwan; Kim, Jae Kyoung; Yoritaka, Takashi; Tanoue, Shintaro; Abe, Takaya; Kiyonari, Hiroshi; Fujimoto, Katsumi; Kato, Yukio; Todo, Takashi; Matsubara, Akio; Forger, Daniel; Takumi, Toru

2014-01-01

95

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

96

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

97

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

PubMed

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

Vriend, Jerry; Reiter, Russel J

2015-01-01

98

Federal, State, and Local regulations  

Microsoft Academic Search

This article is a review of federal, state, and local regulations pertinent treatment of leachate from hazardous materials landfills in California. The topics covered include under federal regulations: pretreatment, whole-effluent toxicity, hazardous waste regulation; under state regulations: hazardous waste regulations, air toxics, environmental quality act; under local regulations: local limits, toxicity-regional water quality board, air emissions and district code.

J. M. Kelly; B. L. Brandenburg

1991-01-01

99

Oscillation of clock and clock controlled genes induced by serum shock in human breast epithelial and breast cancer cells: regulation by melatonin.  

PubMed

This study investigates differences in expression of clock and clock-controlled genes (CCGs) between human breast epithelial and breast cancer cells and breast tumor xenografts in circadian intact rats and examines if the pineal hormone melatonin influences clock gene and CCG expression. Oscillation of clock gene expression was not observed under standard growth conditions in vitro, however, serum shock (50% horse serum for 2 h) induced oscillation of clock gene and CCG expression in MCF-10A cells, which was repressed or disrupted in MCF-7 cells. Melatonin administration following serum shock differentially suppressed or induced clock gene (Bmal1 and Per2) and CCG expression in MCF10A and MCF-7 cells. These studies demonstrate the lack of rhythmic expression of clock genes and CCGs of cells in vitro and that transplantation of breast cancer cells as xenografts into circadian competent hosts re-establishes a circadian rhythm in the peripheral clock genes of tumor cells. PMID:23012497

Xiang, S; Mao, L; Duplessis, T; Yuan, L; Dauchy, R; Dauchy, E; Blask, D E; Frasch, T; Hill, S M

2012-01-01

100

Pressure reducing regulator  

DOEpatents

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

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

1995-01-01

101

Pressure reducing regulator  

DOEpatents

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

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

1995-10-10

102

Modular magnet current regulator  

SciTech Connect

A modular current regulation system is being developed to power the low current correction and focusing magnets used for beam transport. The system consists of numerous multi-channel assemblies, each housed in a standard relay rack. Each multi-channel assembly consists of common power supplies, CAMAC control modules, and Eurocard cages for the current regulators. These regulators are linear, bipolar modules capable of parallel connection for higher current output. 3 figs.

Dobeck, N.; Burtner, G.; Garza, O.; LaMora, R.

1989-01-01

103

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.

104

Novel regulators of spermatogenesis.  

PubMed

Spermatogenesis is a multistep process that supports the production of millions of sperm daily. Understanding of the molecular mechanisms that regulate spermatogenesis has been a major focus for decades. Yet, the regulators involved in different cellular processes of spermatogenesis remain largely unknown. Human diseases that result in defective spermatogenesis have provided hints on the molecular mechanisms regulating this process. In this review, we have summarized recent findings on the function and signaling mechanisms of several genes that are known to be associated with disease or pathological processes, including CFTR, CD147, YWK-II and CT genes, and discuss their potential roles in regulating different processes of spermatogenesis. PMID:24594193

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

2014-05-01

105

Regulation of University Teaching  

ERIC Educational Resources Information Center

The aims of the present study are twofold: firstly, to explore dimensions in the regulation of teaching in a multidisciplinary sample of university teachers, and secondly, to analyse factors related to the regulation of university teaching. Seventy-three university teachers representing several disciplines participated in the study. These teachers…

Lindblom-Ylanne, Sari; Nevgi, Anne; Trigwell, Keith

2011-01-01

106

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

107

Pressure regulating valve controller  

Microsoft Academic Search

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

1988-01-01

108

Fuel pressure regulator valve  

Microsoft Academic Search

This patent describes a fuel pressure regulator valve. It comprises: a housing containing a diaphragm assembly that divides the housing into two chambers, one chamber being a fuel chamber, and the other chamber being a control chamber, the fuel chamber having an inlet adapted to be communicated to a supply of pressurized fluid whose pressure is to be regulated and

Hornby

1990-01-01

109

Pressure regulating valve  

Microsoft Academic Search

This patent describes a pressure regulating valve for regulating a pressure of fuel to be supplied to a fuel injection device, comprising: a diaphragm chamber having a connecting portion for inducing an intake manifold vacuum in the vicinity of a nozzle hold of the fuel injection device; a fuel chamber having a connecting portion for inducing a fuel and located

Hayashi

1988-01-01

110

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

111

Child Care Center Regulations.  

ERIC Educational Resources Information Center

This guide enumerates regulations for anyone caring for four or more children, from families other than their own, for compensation and on a regular basis, in the state of Nebraska. The purpose of the regulations is to protect and promote the health and safety of children in child care facilities. The first section of the guide lists specific…

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

112

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

113

Pressure regulating valve controller  

SciTech Connect

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

Goodman, R.B.

1988-04-05

114

From Regulations to Reality:  

Cancer.gov

Phase 0 Imaging Studies From Regulations to Reality: Obtaining and Holding an IND at Your Institution Karen A. Kurdziel, MD Virginia Commonwealth University, Richmond, VA National Cancer Institute, Bethesda, MD www.molecularimaging.vcu.edu Phase 0 “First-in

115

Self-Regulated Learning  

NSDL National Science Digital Library

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

Gianluca Corsi

2010-10-01

116

International Regulation Database  

NSDL National Science Digital Library

Created and maintained by the Organisation for Economic Co-operation and Development (OECD), the International Regulation Database is a "comprehensive internationally-comparable set of information about the state of regulation and market structures in OECD countries." The contents of the database are derived primarily from an ad hoc questionnaire that was given to OECD member countries in 1998. The database contains over 1,100 variables for each country and includes both broad regulations dealing with product markets, such as "state control of business enterprises" and international trade and investment barriers, as well as sector-specific regulations for areas such as telecommunications, retail distribution, and electricity supply. The database must be downloaded to users's computers, and is offered in both Access and Excel versions. An eleven-page, detailed description of the database's contents, structure, and use is also available, as is a Users' Guide, which offers step-by-step instructions for manipulating the Access database.

117

R2 REGULATED FACILITIES  

EPA Science Inventory

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

118

Mercury: Laws and Regulations  

MedlinePLUS

... and uses of these compounds in products and processes. Exemptions to the Export Ban for Essential Uses ... to a rulemaking petition from the Department of Energy, EPA issued this regulation because the then-current ...

119

Proposed EEOC Regulations.  

ERIC Educational Resources Information Center

This article explains how proposed Equal Employment Opportunity Commission (EEOC) regulations attempt to circumvent the case of Weber vs Kaiser Aluminum Corp. by providing employers with backpay immunity in reverse discrimination suits. (Author)

Farrell, Michael

1978-01-01

120

Regulation and behavior  

NSDL National Science Digital Library

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

2010-01-01

121

SB 4 Well Stimulation Treatment Regulations Text of Proposed Regulations  

E-print Network

SB 4 Well Stimulation Treatment Regulations Text of Proposed Regulations Page 1 of 13 SB 4 WELL STIMULATION TREATMENT REGULATIONS TEXT OF PROPOSED REGULATIONS Added text is shown in underline to perform well stimulation treatments and/or notices of intent to drill or rework wells. (b) A request

122

Intrinsically Disordered Proteins: Regulation and Disease Regulation of IDPs  

E-print Network

shown that most IDPs are tightly regulated and dosage-sensitive genes tend to encode proteins31st Jan 2011 Intrinsically Disordered Proteins: Regulation and Disease Regulation of IDPs M. Madan.....................................................................................................................................2 3.1. IDPs are tightly regulated from transcript synthesis to protein degradation

Babu, M. Madan

123

The Impact of Regulating Social Science Research with Biomedical Regulations  

ERIC Educational Resources Information Center

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

Durosinmi, Brenda Braxton

2011-01-01

124

The Hippo pathway: regulators and regulations  

PubMed Central

Control of cell number is crucial in animal development and tissue homeostasis, and its dysregulation may result in tumor formation or organ degeneration. The Hippo pathway in both Drosophila and mammals regulates cell number by modulating cell proliferation, cell death, and cell differentiation. Recently, numerous upstream components involved in the Hippo pathway have been identified, such as cell polarity, mechanotransduction, and G-protein-coupled receptor (GPCR) signaling. Actin cytoskeleton or cellular tension appears to be the master mediator that integrates and transmits upstream signals to the core Hippo signaling cascade. Here, we review regulatory mechanisms of the Hippo pathway and discuss potential implications involved in different physiological and pathological conditions. PMID:23431053

Yu, Fa-Xing; Guan, Kun-Liang

2013-01-01

125

Endothelin-1 gene regulation  

PubMed Central

Over two decades of research have demonstrated that the peptide hormone endothelin-1 (ET-1) plays multiple, complex roles in cardiovascular, neural, pulmonary, reproductive, and renal physiology. Differential and tissue-specific production of ET-1 must be tightly regulated in order to preserve these biologically diverse actions. The primary mechanism thought to control ET-1 bioavailability is the rate of transcription from the ET-1 gene (edn1). Studies conducted on a variety of cell types have identified key transcription factors that govern edn1 expression. With few exceptions, the cis-acting elements bound by these factors have been mapped in the edn1 regulatory region. Recent evidence has revealed new roles for some factors originally believed to regulate edn1 in a tissue or hormone-specific manner. In addition, other mechanisms involved in epigenetic regulation and mRNA stability have emerged as important processes for regulated edn1 expression. The goal of this review is to provide a comprehensive overview of the specific factors and signaling systems that govern edn1 activity at the molecular level.—Stow, L. R., Jacobs, M. E., Wingo, C. S., Cain, B. D. Endothelin-1 gene regulation. PMID:20837776

Stow, Lisa R.; Jacobs, Mollie E.; Wingo, Charles S.; Cain, Brian D.

2011-01-01

126

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. PMID:23539007

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

2013-01-01

127

Androgen receptor genomic regulation  

PubMed Central

The transcriptional activity of the androgen receptor (AR) is not only critical for the normal development and function of the prostate but also pivotal to the onset and progression of prostate cancer (PCa). The studies of AR transcriptional regulation were previously limited to a handful of AR-target genes. Owing to the development of various high-throughput genomic technologies, significant advances have been made in recent years. Here we discuss the discoveries of genome-wide androgen-regulated genes in PCa cell lines, animal models and tissues using expression microarray and sequencing, the mapping of genomic landscapes of AR using Combining Chromatin Immunoprecipitation (ChIP)-on-chip and ChIP-seq assays, the interplay of transcriptional cofactors in defining AR binding profiles, and the genomic regulation and AR reprogramming in advanced PCa. PMID:25237629

Jin, Hong-Jian; Kim, Jung; Yu, Jindan

2014-01-01

128

Environmentally regulated aerospace coatings  

NASA Technical Reports Server (NTRS)

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

Morris, Virginia L.

1995-01-01

129

Cochlear blood flow regulation.  

PubMed

The regulation of cochlear blood flow is crucial for auditory function due to the sensitivity of this sensory organ to hypoxia. Part of the regulation of cochlear blood flow occurs in the spiral modiolar artery, which provides the main blood supply to the cochlea. Blood flow in general is most effectively regulated through the control of the vascular diameter. The vascular diameter is determined by the degree of constriction of the smooth muscle cells in the vascular wall. A constriction of the smooth muscle cells reduces the diameter of the vascular lumen and thereby decreases blood flow, whereas a relaxation of the smooth muscle cells increases blood flow. The degree of constriction of the smooth muscle cells in the spiral modiolar artery is carefully controlled and must be adjusted properly to the demands of the cochlear tissues. To achieve proper control, smooth muscle cells integrate information from various sources. Vasoconstrictors and dilators may originate from the innervation surrounding the vessel, from endothelial cells lining the vascular lumen or from the smooth muscle cells themselves. Recent advances revealed that smooth muscle cells from different arterioles differ widely in their endowment with mechanisms that regulate the degree of smooth muscle cell tone. Signal transduction mechanisms, which mediate these neurogenic, local and paracrine regulations of smooth muscle contractility are now beginning to be understood. This report reviews recently obtained evidence for adrenergic regulation of cochlear blood flow and then focuses on a novel vasodilation mechanism that involves ryanodine receptors, Ca2+ sparks and the activation of Ca2+-activated K+ channels. PMID:11885661

Wangemann, Philine

2002-01-01

130

Environmentally regulated aerospace coatings  

SciTech Connect

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

Morris, V.L.

1995-03-01

131

Study Regulations October 2005  

E-print Network

/Regulations Art. 1. In General The training provided by the Faculty is divided into three levels · a first cycle The three-year course consists of a period of foundation training, not directly aimed at professional; · an advanced, specialized cycle; · doctorates. Art. 2. Awards 1. The Faculty awards the following degrees

Krause, Rolf

132

Metabolic regulation of yeast  

NASA Astrophysics Data System (ADS)

Metabolic regulation which is based on endogeneous and exogeneous process variables which may act constantly or time dependently on the living cell is discussed. The observed phenomena of the regulation are the result of physical, chemical, and biological parameters. These parameters are identified. Ethanol is accumulated as an intermediate product and the synthesis of biomass is reduced. This regulatory effect of glucose is used for the aerobic production of ethanol. Very high production rates are thereby obtained. Understanding of the regulation mechanism of the glucose effect has improved. In addition to catabolite repression, several other mechanisms of enzyme regulation have been described, that are mostly governed by exogeneous factors. Glucose also affects the control of respiration in a third class of yeasts which are unable to make use of ethanol as a substrate for growth. This is due to the lack of any anaplerotic activity. As a consequence, diauxic growth behavior is reduced to a one-stage growth with a drastically reduced cell yield. The pulse chemostat technique, a systematic approach for medium design is developed and medium supplements that are essential for metabolic control are identified.

Fiechter, A.

1982-12-01

133

Regulating intraflagellar transport.  

PubMed

Kinesin-2 motors mediate anterograde intraflagellar transport (IFT) of IFT particles from the ciliary base to its tip, where particles are remodelled before retrograde transport by dynein 2 motors. Bardet-Biedl syndrome (BBS) and IFT-A proteins are now implicated in regulation of IFT assembly at the ciliary base and tip. PMID:22945257

Pedersen, Lotte B; Christensen, Søren T

2012-09-01

134

Shadow banking regulation  

Microsoft Academic Search

Shadow banks conduct credit intermediation without direct, explicit access to public sources of liquidity and credit guarantees. Shadow banks contributed to the credit boom in the early 2000s and collapsed during the financial crisis of 2007-09. We review the rapidly growing literature on shadow banking and provide a conceptual framework for its regulation. Since the financial crisis, regulatory reform efforts

Tobias Adrian; Adam B. Ashcraft

2012-01-01

135

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.

136

CODE OF FEDERAL REGULATIONS  

EPA Science Inventory

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

137

Precision voltage regulator  

NASA Technical Reports Server (NTRS)

Balanced positive and negative voltage output circuit, in which error voltage for control is developed from difference in absolute value of positive and negative voltages referenced to a common point, regulates voltage for use with inertial reference unit. Fast-acting, temperature-compensated, high-gain operational amplifier circuits maintain common point.

Hand, P. J.; Crawford, R. A.

1972-01-01

138

Regulation and behavior  

NSDL National Science Digital Library

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

Teachers Domain

2002-01-01

139

Gene Regulation by Methylation  

Microsoft Academic Search

Epigenetic gene regulation of specific genes strongly affects clinical outcome of malignant glioma. MGMT is the best studied gene for the connection of promoter methylation and clinical course in glioblastoma. While MGMT promoter methylation analysis currently does not alter treatment of glioblastoma patients, mainly because of a lack of convincing\\u000a therapy to radiotherapy and concomitant administration of alkylating drugs, there

Wolf C. Mueller; Andreas von Deimling

140

Neuroendocrine regulation of inflammation.  

PubMed

The interaction between the sympathetic nervous system and the immune system has been documented over the last several decades. In this review, the neuroanatomical, cellular, and molecular evidence for neuroimmune regulation in the maintenance of immune homeostasis will be discussed, as well as the potential impact of neuroimmune dysregulation in health and disease. PMID:24486056

Padro, Caroline J; Sanders, Virginia M

2014-10-01

141

Self-regulating valve  

Microsoft Academic Search

A variable, self-regulating valve having a hydraulic loss coefficient proportional to a positive exponential power of the flow rate. The device includes two objects in a flow channel and structure which assures that the distance between the two objects is an increasing function of the flow rate. The range of spacing between the objects is such that the hydraulic resistance

Humphreys

1982-01-01

142

[Intraovarian regulators of folliculogenesis].  

PubMed

The review summarizes information about the intraovarian modulators of folliculogenesis. Consistently described auto-and paracrine factors and mechanisms involved in the regulation of follicular development from the entry in the growth of primordial follicles before ovulation of the dominant follicle. PMID:20209891

Borovaia, T G; Shevliagina, N V; Didenko, L V

2010-01-01

143

Neurochemical regulation of sleep.  

PubMed

This review summarizes recent developments in the field of sleep regulation, particularly in the role of hormones, and of synthetic GABA(A) receptor agonists. Certain hormones play a specific role in sleep regulation. A reciprocal interaction of the neuropeptides growth hormone (GH)-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) plays a key role in sleep regulation. At least in males GHRH is a common stimulus of non-rapid-eye-movement sleep (NREMS) and GH and inhibits the hypothalamo-pituitary adrenocortical (HPA) hormones, whereas CRH exerts opposite effects. Furthermore CRH may enhance rapid-eye-movement sleep (REMS). Changes in the GHRH:CRH ratio in favor of CRH appear to contribute to sleep EEG and endocrine changes during depression and normal ageing. In women, however, CRH-like effects of GHRH were found. Besides CRH somatostatin impairs sleep, whereas ghrelin, galanin and neuropeptide Y promote sleep. Vasoactive intestinal polypeptide appears to be involved in the temporal organization of human sleep. Beside of peptides, steroids participate in sleep regulation. Cortisol appears to promote REMS. Various neuroactive steroids exert specific effects on sleep. The beneficial effect of estrogen replacement therapy in menopausal women suggests a role of estrogen in sleep regulation. The GABA(A) receptor or GABAergic neurons are involved in the action of many of these hormones. Recently synthetic GABA(A) agonists, particularly gaboxadol and the GABA reuptake inhibitor tiagabine were shown to differ distinctly in their action from allosteric modulators of the GABA(A) receptor like benzodiazepines as they promote slow-wave sleep, decrease wakefulness and do not affect REMS. PMID:16777143

Steiger, Axel

2007-10-01

144

Clock-controlled StAR's expression and corticosterone production contribute to the endotoxemia immune response.  

PubMed

Increased studies have revealed that core mammalian clock genes regulate immune functions. Previously, we reported Per2(m/m) mice displayed a down-regulated circadian immune response to lipopolysaccharide (LPS) challenge. However, the mediators between Per2 and immune function and their underlying mechanisms remain unclear. In this study, serum corticosterone (CORT), a hormone which played a crucial role in immune suppression, was found to be significantly increased in Per2(m/m) mice compared with the one in wild-type mice following LPS administration at ZT3 and ZT8. The elevated level of serum CORT was correlated with their higher survival rate, which could be further suppressed by glucocorticoid receptor antagonist. Expression of StAR, a rate-limiting enzyme in CORT synthesis, as well as the expression of core clock genes (Clock/Bmal1), was more strongly induced and longer lasting in Per2(m/m) mice in contrast to the ones in control mice after LPS injection. Additionally, the binding of CLOCK and BMAL1 to StAR's promoter was elevated after LPS administration, and the binding was higher in Per2(m/m) mice. Furthermore, loss of Clock function resulted in lower survival and failed to induce the serum CORT production and StAR expression in Clock(m/m) mice following LPS administration. Our results revealed that CORT, regulated by Bmal1/Clock transcriptional activation of StAR's expression, could function as a mediator between clock system and immune response and contribute to the endotoxemia resistance in Per2(m/m) mice. PMID:25421094

Wang, Jiesi; Luo, YongLun; Wang, KangLi; Wang, Yan; Zhang, Xiaolin; Teng, Huajing; Sun, Zhongsheng

2015-04-01

145

University Regulations and Resources (Summer Programs, Courses and University Regulations  

E-print Network

University Regulations and Resources (Summer Studies) Programs, Courses and University Regulations 2012 #12;#12;This PDF excerpt of Programs, Courses and University Regulations is an archived snapshot correcting errors, altering fees, schedules of admission, and credit requirements, and revising or cancelling

Fabry, Frederic

146

FDA 101: Regulating Biological Products  

MedlinePLUS

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

147

State Licensing and Regulation Information  

MedlinePLUS

... Licensing and Regulation Information State Licensing and Regulation Information States are contacted at least twice per year to verify the accuracy of regulatory information. Click on state below to view state information. ...

148

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...

149

Iron regulation by hepcidin  

PubMed Central

Hepcidin is a key hormone that is involved in the control of iron homeostasis in the body. Physiologically, hepcidin is controlled by iron stores, inflammation, hypoxia, and erythropoiesis. The regulation of hepcidin expression by iron is a complex process that requires the coordination of multiple proteins, including hemojuvelin, bone morphogenetic protein 6 (BMP6), hereditary hemochromatosis protein, transferrin receptor 2, matriptase-2, neogenin, BMP receptors, and transferrin. Misregulation of hepcidin is found in many disease states, such as the anemia of chronic disease, iron refractory iron deficiency anemia, cancer, hereditary hemochromatosis, and ineffective erythropoiesis, such as ?-thalassemia. Thus, the regulation of hepcidin is the subject of interest for the amelioration of the detrimental effects of either iron deficiency or overload. PMID:23722909

Zhao, Ningning; Zhang, An-Sheng; Enns, Caroline A.

2013-01-01

150

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

151

Redox regulated peroxisome homeostasis  

PubMed Central

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

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

2014-01-01

152

Regulation of Protein Translation  

NSDL National Science Digital Library

This Teaching Resource provides a summary and slides derived from a lecture on protein translation and is part of the course "Cell Signaling Systems: A Course for Graduate Students." The lecture begins with a discussion of the various components that perform the translation process and then proceeds to describe the initiation, scanning, and ribosomal entry processes. The lecture concludes with the signaling mechanisms underlying translation regulation.

Emmanuel M. Landau (Mount Sinai School; Departments of Psychiatry and Pharmacology and Biological Chemistry REV)

2006-03-07

153

Regulating financial conglomerates  

Microsoft Academic Search

We analyze the risk-taking incentives of a financial conglomerate that combines a bank and a non-bank financial intermediary. The conglomerate's risk-taking incentives depend on the level of market discipline it faces, which in turn is determined by the conglomerate's liability structure. We examine optimal capital regulation for standalone institutions, for integrated conglomerates and holding company conglomerates. We show that, when

Xavier Freixas; Gyöngyi Lóránth; Alan D. Morrison

2007-01-01

154

Temperature controlled high voltage regulator  

DOEpatents

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

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

2004-04-20

155

Mechanisms regulating airway nucleotides.  

PubMed

In the respiratory system, extracellular nucleotides and nucleosides serve as signaling molecules for a wide spectrum of biological functions regulating airway defenses against infection and toxic material. Their concentrations are controlled by a complex network of cell surface enzymes named ectonucleotidases. This highly integrated metabolic network combines the activities of three dephosphorylating ectonucleotidases, namely nucleoside triphosphate diphosphohydrolases (NTPDases), nucleotide pyrophosphatase/phosphodiesterases (NPPs) and alkaline phosphatases (APs). Extracellular nucleotides are also inter-converted by the transphosphorylating activities of ecto adenylate kinase (ectoAK) and nucleoside diphosphokinase (NDPK). Different cell types use specific combinations of ectonucleotidases to regulate local concentrations of P2 receptor agonists (ATP, UTP, ADP and UDP). In addition, they provide AMP for the activity of ecto 5'-nucleotidase (ecto 5'-NT; CD73), which produces the P1 receptor agonist: adenosine (ADO). Finally, mechanisms are in place to prevent the accumulation of airway ADO, namely adenosine deaminases and nucleoside transporters. This chapter reviews the properties of each enzyme and transporter, and the current knowledge on their distribution and regulation in the airways. PMID:21560043

Picher, Maryse

2011-01-01

156

Restructuring nuclear regulations.  

PubMed Central

Nuclear regulations are a subset of social regulations (laws to control activities that may negatively impact the environment, health, and safety) that concern control of ionizing radiation from radiation-producing equipment and from radioactive materials. The impressive safety record among nuclear technologies is due, in no small part, to the work of radiation safety professionals and to a protection system that has kept pace with the rapid technologic advancements in electric power generation, engineering, and medicine. The price of success, however, has led to a regulatory organization and philosophy characterized by complexity, confusion, public fear, and increasing economic costs. Over the past 20 years, regulatory costs in the nuclear sector have increased more than 250% in constant 1995 U.S. dollars. Costs of regulatory compliance can be reduced sharply, particularly when health and environmental benefits of risk reduction are questionable. Three key regulatory areas should be closely examined and modified to improve regulatory effectiveness and efficiency: a) radiation protection should be changed from a risk-based to dose-based system; b) the U.S. government should adopt the modern metric system (International System of Units), and radiation quantities and units should be simplified to facilitate international communication and public understanding; and c) a single, independent office is needed to coordinate nuclear regulations established by U.S. federal agencies and departments. PMID:12515683

Mossman, Kenneth L

2003-01-01

157

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

158

The regulation of public utilities  

SciTech Connect

The current edition of [open quotes]The Regulation of Public Utilities[close quotes] is divided into 17 chapters which provide an historical analysis of the economic and legal concepts of public utility regulation, rate of return, rate base, operating expenses, rate structure, the electric power and natural gas industries, as well as the telecommunications and water industries. The value of the third edition is limited by the changes that have taken place in public utility regulation since 1992; current topic such as cogeneration, independent power production, and the sea-change in oil pipeline regulations are not discussed. The volume does, however, provide a comprehensive historical background of utility regulation.

Phillips, C.F. Jr.

1992-01-01

159

15 CFR 922.44 - Emergency regulations.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 false Emergency regulations. 922.44 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Regulations of General...

2012-01-01

160

15 CFR 922.44 - Emergency regulations.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 false Emergency regulations. 922.44 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Regulations of General...

2013-01-01

161

15 CFR 922.44 - Emergency regulations.  

Code of Federal Regulations, 2014 CFR

...2014-01-01 false Emergency regulations. 922.44 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Regulations of General...

2014-01-01

162

Effective doses, guidelines & regulations.  

PubMed

A number of countries have developed regulations or guidelines for cyanotoxins and cyanobacteria in drinking water, and in some cases in water used for recreational activity and agriculture. The main focus internationally has been upon microcystin toxins, produced predominantly by Microcystis aeruginosa. This is because microcystins are widely regarded as the most significant potential source of human injury from cyanobacteria on a world-wide scale. Many international guidelines have taken their lead from the World Health Organization's (WHO) provisional guideline of 1 microg L(-1) for microcystin-LR in drinking-water released in 1998 (WHO 2004). The WHO guideline value is stated as being 'provisional', because it covers only microcystin-LR, for reasons that the toxicology is limited and new data for toxicity of cyanobacterial toxins are being generated. The derivation of this guideline is based upon data that there is reported human injury related to consumption of drinking water containing cyanobacteria, or from limited work with experimental animals. It was also recognised that at present the human evidence for microcystin tumor promotion is inadequate and animal evidence is limited. As a result the guideline is based upon the model of deriving a Tolerable Daily intake (TDI) from an animal study No Observed Adverse Effects Level (NOAEL), with the application of appropriate safety or uncertainty factors. The resultant WHO guideline by definition is the concentration of a toxin that does not result in any significant risk to health of the consumer over a lifetime of consumption. Following the release of this WHO provisional guideline many countries have either adopted it directly (e.g., Czech Republic, France, Japan, Korea, New Zealand, Norway, Poland, Brazil and Spain), or have adopted the same animal studies, TDI and derivation convention to arrive at slight variants based upon local requirements (e.g., Australia, Canada). Brazil currently has the most comprehensive federal legislation which includes a mandatory standard of 1 microg L-(1) for microcystins, and also recommendations for saxitoxins (3 microg L(-1)) and for cylindrospermopsin (15 microg L(-1)). Although guidelines for cyanotoxins and cyanobacterial cell numbers for recreational waters are in place in a number of countries, it is consid ered that there is currently insufficient information to derive sound guidelines for the use of water contaminated by cyanobacteria or toxins for agricultural production, fisheries and ecosystem protection. In relation to the need for specific regulations for toxins for the US, the surveys that have been carried out to date would indicate that the priority compounds for regulation, based upon their incidence and distribution, are microcystins, cylindrospermopsin and Anatoxin-a. Additional research is required to support guideline development, including whole-of-life animal studies with each of the known cyanotoxins. In view of the animal studies that indicate that microcystins may act as tumor promoters, and also some evidence of genotoxicity and carcinogenicity for cylindrospermopsin, it may be appropriate to carry out whole-of-life animal studies with both toxicity and carcinogenicity as end-points. In relation to microcystins, it is known that there a large number of congeners, and the toxico-dynamics and kinetics of these variants are not well understood. Further research is needed to consider the approach to take in formulating health advisories or regulations for toxin mixtures, i.e. multiple microcystins, or mixtures of toxin types. An important requirement for regulation is the availability of robust monitoring and analytical protocols for toxins. Currently rapid and economical screening or quantitative analytical methods are not available to the water industry or natural resource managers, and this is a priority before the release of guidelines and regulations. There is insufficient information available in a range of the categories usually required to satisfy comprehensive risk assessment process for the major tox

Burch, Michael D

2008-01-01

163

Self-regulating valve  

DOEpatents

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

Humphreys, D.A.

1982-07-20

164

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

165

Epigenetic regulation in plants.  

PubMed

The study of epigenetics in plants has a long and rich history, from initial descriptions of non-Mendelian gene behaviors to seminal discoveries of chromatin-modifying proteins and RNAs that mediate gene silencing in most eukaryotes, including humans. Genetic screens in the model plant Arabidopsis have been particularly rewarding, identifying more than 130 epigenetic regulators thus far. The diversity of epigenetic pathways in plants is remarkable, presumably contributing to the phenotypic plasticity of plant postembryonic development and the ability to survive and reproduce in unpredictable environments. PMID:25452385

Pikaard, Craig S; Mittelsten Scheid, Ortrun

2014-12-01

166

Quality Regulations and Standards  

NSDL National Science Digital Library

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

167

Branded prescription drug fee. Final regulations, temporary regulations, and removal of temporary regulations.  

PubMed

This document contains final regulations that provide guidance on the annual fee imposed on covered entities engaged in the business of manufacturing or importing branded prescription drugs. This fee was enacted by section 9008 of the Patient Protection and Affordable Care Act, as amended by section 1404 of the Health Care and Education Reconciliation Act of 2010. This document also withdraws the Branded Prescription Drug Fee temporary regulations and contains new temporary regulations regarding the definition of controlled group that apply beginning on January 1, 2015. The final regulations and the new temporary regulations affect persons engaged in the business of manufacturing or importing certain branded prescription drugs. The text of the temporary regulations in this document also serves as the text of proposed regulations set forth in a notice of proposed rulemaking (REG-123286-14) on this subject in the Proposed Rules section in this issue of the Federal Register. PMID:25118373

2014-07-28

168

Environmental regulation of flowering.  

PubMed

The timing of flower initiation is a highly plastic developmental process. To achieve reproductive success, plants must select the most favourable season to initiate reproductive development; this in turn requires continuous monitoring of environmental factors and a properly response. Environmental factors which change in a predictable fashion along the year, such as light and temperature, are the most relevant in terms of selection of the flowering season. In Arabidopsis and more recently in a few other species, molecular genetic analyses are providing a way to identify the genes involved in the regulation of flowering time. From gene sequences it is possible to develop hypotheses regarding molecular function and to infer some of the molecular mechanisms involved in the environmental regulation of flowering time. In this paper, we summarize recent discoveries concerning the mechanisms which plants use to perceive and respond to major environmental factors (light and temperature) and their different components. We focus mainly on annual plants and especially on Arabidopsis because most of the available molecular and functional data come from this species. However, additional information arising from other plant systems is also considered. PMID:16096975

Ausín, Israel; Alonso-Blanco, Carlos; Martínez-Zapater, José-Miguel

2005-01-01

169

[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

2008-12-01

170

Regulation of testicular descent.  

PubMed

Testicular descent occurs in two morphologically distinct phases, each under different hormonal control from the testis itself. The first phase occurs between 8 and 15 weeks when insulin-like hormone 3 (Insl3) from the Leydig cells stimulates the gubernaculum to swell, thereby anchoring the testis near the future inguinal canal as the foetus grows. Testosterone causes regression of the cranial suspensory ligament to augment the transabdominal phase. The second, or inguinoscrotal phase, occurs between 25 and 35 weeks, when the gubernaculum bulges out of the external ring and migrates to the scrotum, all under control of testosterone. However, androgen acts mostly indirectly via the genitofemoral nerve (GFN), which produces calcitonin gene-related peptide (CGRP) to control the direction of migration. In animal models the androgen receptors are in the inguinoscrotal fat pad, which probably produces a neurotrophin to masculinise the GFN sensory fibres that regulate gubernacular migration. There is little direct evidence that this same process occurs in humans, but CGRP can regulate closure of the processus vaginalis in inguinal hernia, confirming that the GFN probably mediates human testicular descent by a similar mechanism as seen in rodent models. Despite increased understanding about normal testicular descent, the common causes of cryptorchidism remain elusive. PMID:25690562

Hutson, John M; Li, Ruili; Southwell, Bridget R; Newgreen, Don; Cousinery, Mary

2015-04-01

171

Shame regulation in personality pathology.  

PubMed

Drawing on extant work on shame and emotion regulation, this article proposes that three broad forms of maladaptive shame regulation strategies are fundamental in much of personality pathology: Prevention (e.g., dependence, fantasy), used preemptively, lessens potential for shame; Escape (e.g., social withdrawal, misdirection) reduces current or imminent shame; Aggression, used after shame begins, refocuses shame into anger directed at the self (e.g., physical self-harm) or others (e.g., verbal aggression). This article focuses on the contributions of shame regulation to the development and maintenance of personality pathology, highlighting how various maladaptive shame regulation strategies may lead to personality pathology symptoms, associated features, and dimensions. Consideration is also given to the possible shame-related constructs necessitating emotion regulation (e.g., shame aversion and proneness) and the points in the emotion process when regulation can occur. PMID:21895346

Schoenleber, Michelle; Berenbaum, Howard

2012-05-01

172

Mechanisms for regulating deubiquitinating enzymes  

PubMed Central

Ubiquitination is a reversible post-translational modification that plays a dynamic role in regulating most eukaryotic processes. Deubiquitinating enzymes (DUBs), which hydrolyze the isopeptide or peptide linkages joining ubiquitin to substrate lysines or N-termini, therefore play a key role in ubiquitin signaling. Cells employ multiple mechanisms to regulate DUB activity and thus ensure the appropriate biological response. Recent structural studies have shed light on several different mechanisms by which DUB activity and specificity is regulated. PMID:24403057

Wolberger, Cynthia

2014-01-01

173

The regulation of public utilities  

SciTech Connect

This book includes discussions of the determinants of market structure, limitations on government regulation, federal-state jurisdictional controversies, the regulation of accounting practices, legal and economic concepts of property valuation, criteria of a sound rate structure, cost of capital standards, and rate structures in practice. In addition, the author examines regulation as a substitute for competition and explores the need for regulatory policy review.

Phillips, C.F.

1988-01-01

174

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. PMID:22434687

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

2012-01-01

175

Machine Learning Helps Identify CHRONO as a Circadian Clock Component  

PubMed Central

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

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

2014-01-01

176

Temporal gradient in the clock gene and cell-cycle checkpoint kinase Wee1 expression along the gut.  

PubMed

Circadian clocks were recently discovered in the rat and mouse colon as well as mouse stomach and jejunum. The aim of this study was to determine whether clocks in the upper part of the gut are synchronized with those in the lower part, or whether there is a difference in their circadian phases. Moreover, the profiles of core clock-gene expression were compared with the profiles of the clock-driven Wee1 gene expression in the upper and lower parts of the gut. Adult rats were transferred to constant darkness on the day of sampling. 24 h expression profiles of the clock genes Per1, Per2, Rev-erbalpha, and Bmal1 and the cell-cycle regulator Wee1 were examined by a reverse transcriptase-polymerase chain reaction within the epithelium of the rat duodenum, ileum, jejunum, and colon. In contrast to the duodenum, the rhythms in expression of all genes but Rev-erbalpha and Bmal1 in the colon exhibited non-sinusoidal profiles. Therefore, a detailed analysis of the gene expression every 1 h within the 12 h interval corresponding to the previous lights-on was performed. The data demonstrate that rhythmic profiles of the clock gene Per1, Per2, Bmal1, Rev-erbalpha, and clock-driven Wee1 expression within the epithelium from different parts of the rat gut exhibited a difference in phasing, such that the upper part of the gut, as represented by the duodenum, was phase-advanced to the lower part, as represented by the distal colon. Our data demonstrate that the circadian clocks within each part of the gut are mutually synchronized with a phase delay in the cranio-caudal axis. Moreover, they support the view that the individual circadian clocks may control the timing of cell cycle within different regions of the gut. PMID:19444744

Polidarová, Lenka; Soták, Matús; Sládek, Martin; Pacha, Jirí; Sumová, Alena

2009-05-01

177

Altered Dynamics in the Circadian Oscillation of Clock Genes in Dermal Fibroblasts of Patients Suffering from Idiopathic Hypersomnia  

PubMed Central

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

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

2014-01-01

178

Power-MOSFET Voltage Regulator  

NASA Technical Reports Server (NTRS)

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

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

1982-01-01

179

Insulin regulation of myocardial autophagy.  

PubMed

Autophagy is a conserved cellular process that plays an important role in cardiovascular homeostasis. Basal levels of autophagy are required for the maintenance of organellar quality control. Autophagy is dynamically regulated in the heart in the fasting to re-feeding transition. Insulin signaling plays an important role in the regulation of myocardial fuel metabolism, mitochondrial function and cellular growth. Recent studies have suggested an important role for insulin signaling in the regulation of myocardial autophagy. This dynamic regulation of autophagy induction during fasting may contribute to organellar homeostasis and if perturbed under conditions of hyperinsulinemia could contribute to accelerated cardiac aging. PMID:25327953

Riehle, Christian; Abel, E Dale

2014-01-01

180

Critical period regulation.  

PubMed

Neuronal circuits are shaped by experience during critical periods of early postnatal life. The ability to control the timing, duration, and closure of these heightened levels of brain plasticity has recently become experimentally accessible, especially in the developing visual system. This review summarizes our current understanding of known critical periods across several systems and species. It delineates a number of emerging principles: functional competition between inputs, role for electrical activity, structural consolidation, regulation by experience (not simply age), special role for inhibition in the CNS, potent influence of attention and motivation, unique timing and duration, as well as use of distinct molecular mechanisms across brain regions and the potential for reactivation in adulthood. A deeper understanding of critical periods will open new avenues to "nurture the brain"-from international efforts to link brain science and education to improving recovery from injury and devising new strategies for therapy and lifelong learning. PMID:15217343

Hensch, Takao K

2004-01-01

181

Magnetostrictive Pressure Regulating System  

NASA Technical Reports Server (NTRS)

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

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

2013-01-01

182

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. PMID:23630462

Kierdorf, Katrin; Prinz, Marco

2013-01-01

183

TFEB regulates lysosomal proteostasis.  

PubMed

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

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

2013-05-15

184

[Regulation of terpene metabolism  

SciTech Connect

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

Croteau, R.

1989-11-09

185

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.

186

Parking Services Rules and Regulations  

E-print Network

.4 Liability 3 2 Two Wheeled Vehicles 4 2.1 Motorcycles / Mopeds / Scooters 4 3 Parking Permits 4 3.1 General Immobilization 13 4.17 Suspension of Parking Privileges 13 5 Appeals 13 5.1 Submission of Appeals 13 5.2 Appeal. Exceptions to regulations, temporary regulations and enforcement suspensions are valid only for when and how

Moore, Paul A.

187

Gravity and body mass regulation  

NASA Technical Reports Server (NTRS)

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

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

1997-01-01

188

Splicing regulators: targets and drugs  

PubMed Central

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. PMID:16356274

Yeo, Gene Wei-Ming

2005-01-01

189

Exhaust gas recirculation regulating system  

Microsoft Academic Search

A system for controlling introduction of gas into a passage of an internal combustion engine employs a first control valve in a gas introduction passageway, a second control valve in an air conduit connecting the intake passage to atmosphere, and a regulating valve responsive to vacuum intensity in the intake passage. The regulating valve actuates vacuum responsive actuators for the

K. Ishii; T. Shioya

1980-01-01

190

Design for pressure regulating components  

NASA Technical Reports Server (NTRS)

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

Wichmann, H.

1973-01-01

191

Voltage regulation and battery condition  

Microsoft Academic Search

Charging of automotive lead--acid batteries and the related aspects of voltage regulators are reviewed. Operation and proper setting of voltage regulators for different conditions are discussed. Factors affecting battery counter voltage (cemf) are examined: these include purity of battery materials, state of charge, strength of electrolyte, gassing, maintenance, and temperature--the latter is considered at some length. (RWR)

Wesley

1977-01-01

192

Gene regulation by nucleosome positioning  

E-print Network

Gene regulation by nucleosome positioning Lu Bai1 and Alexandre V. Morozov2 1 The Rockefeller]. The histone genes and nucleosome structure are extremely well conserved among eukaryotic species. Importantly in gene regulation by affecting the transcriptional compe- tence of various chromatin regions

Morozov, Alexandre V.

193

77 FR 13155 - Waste Regulation  

Federal Register 2010, 2011, 2012, 2013, 2014

The National Science Foundation (NSF) is required to publish notice of requests to modify permits issued to conduct activities regulated under the Antarctic Conservation Act of 1978 (Pub. L. 95-541; Code of Federal Regulations Title 45, Part 670). This is the required...

2012-03-05

194

Regulation of GMOs in China.  

PubMed

Genetically modified organisms (GMOs) are created by biotechnology to serve people with much benefit while may impose risks to ecological environment and human health and therefore need careful regulation. During the past two decades, GMOs have been well developed in China and so has their corresponding regulation. This paper reviews and comments the multiple aspects of mainly the agricultural GMOs, including their safety assessment, control measures, trade activities, import, labels, and GM food, which have been prescribed by the corresponding laws, regulations and administrative measures. It is held that till present a framework for regulation of agricultural GMOs and GM food has been established basically in China, while a more comprehensive system for regulation of all kinds of GMOs and all kinds of related activities is still needed at present and in the future. PMID:19492727

Liu, Yinliang

2008-12-01

195

Mechanisms regulating glioma invasion.  

PubMed

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

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

2015-06-28

196

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. PMID:19400965

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

2009-01-01

197

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

PubMed

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

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

2015-03-18

198

Impact Assessment in the EU: A Tool for Better Regulation, Less Regulation or Less Bad Regulation?  

Microsoft Academic Search

Impact Assessments (IAs) were introduced at the EU level under the rhetorical facade of ‘better regulation’. The actual aim was to improve not only the quality but also the reputation of EU regulation before stakeholders. However, evidence brought forward by a number of evaluations pointed out that IAs are yet to achieve acceptable quality standards. The paper offers an overview

Jacopo Torriti

2007-01-01

199

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

Federal Register 2010, 2011, 2012, 2013, 2014

...225, et al. Defense Federal Acquisition Regulation Supplements; Proposed Rules...Regulations System; Defense Federal Acquisition Regulation Supplement; Balance of...to amend the Defense Federal Acquisition Regulation Supplement (DFARS)...

2010-06-08

200

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

201

18 CFR 415.30 - Regulations generally.  

Code of Federal Regulations, 2011 CFR

...generally. 415.30 Section 415.30 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Standards § 415.30 Regulations generally....

2011-04-01

202

18 CFR 415.30 - Regulations generally.  

Code of Federal Regulations, 2013 CFR

...generally. 415.30 Section 415.30 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Standards § 415.30 Regulations generally....

2013-04-01

203

18 CFR 415.30 - Regulations generally.  

Code of Federal Regulations, 2014 CFR

...generally. 415.30 Section 415.30 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Standards § 415.30 Regulations generally....

2014-04-01

204

18 CFR 415.30 - Regulations generally.  

Code of Federal Regulations, 2010 CFR

...generally. 415.30 Section 415.30 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Standards § 415.30 Regulations generally....

2010-04-01

205

18 CFR 415.30 - Regulations generally.  

Code of Federal Regulations, 2012 CFR

...generally. 415.30 Section 415.30 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Standards § 415.30 Regulations generally....

2012-04-01

206

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

207

78 FR 1597 - Semiannual Agenda of Regulations  

Federal Register 2010, 2011, 2012, 2013, 2014

...Regulation Sequence No. Title Identifier...Required of 1210-AB51 Multiple Employer Welfare Arrangements...Regulation Sequence No. Title Identifier...Regulation Sequence No. Title Identifier...Filings Required of Multiple Employer Welfare...

2013-01-08

208

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 ...

209

75 FR 67912 - North Korea Sanctions Regulations  

Federal Register 2010, 2011, 2012, 2013, 2014

...Assets Control 31 CFR Part 510 North Korea Sanctions Regulations AGENCY...issuing regulations with respect to North Korea to implement Executive Order 13466...Foreign Assets Control is issuing the North Korea Sanctions Regulations, 31...

2010-11-04

210

76 FR 35740 - North Korea Sanctions Regulations  

Federal Register 2010, 2011, 2012, 2013, 2014

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

2011-06-20

211

High-efficiency step-up regulator  

NASA Technical Reports Server (NTRS)

Single-ended step-up regulator-chopper power supply /employing conventional chopper circuitry/ combines the advantages of the chopper and switching regulator circuits. Schematic of the power supply incorporating the step-up regulator is shown.

Lister, L. R.

1968-01-01

212

Drosophila Cytokine Unpaired 2 Regulates Physiological Homeostasis  

E-print Network

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

Higgins, Darren

213

27 CFR 19.3 - Related regulations.  

Code of Federal Regulations, 2010 CFR

...DEPARTMENT OF THE TREASURY LIQUORS DISTILLED SPIRITS PLANTS Scope § 19.3 Related regulations. Regulations...and Miscellaneous Regulations. 27 CFR part 30—Gauging Manual. 27 CFR part 31—Alcohol Beverage Dealers. 27...

2010-04-01

214

15 CFR 922.185 - Emergency regulations.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 false Emergency regulations. 922.185 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Hawaiian Islands...

2012-01-01

215

15 CFR 922.196 - Emergency regulations.  

Code of Federal Regulations, 2014 CFR

...2014-01-01 false Emergency regulations. 922.196 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Thunder Bay National...

2014-01-01

216

15 CFR 922.185 - Emergency regulations.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 false Emergency regulations. 922.185 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Hawaiian Islands...

2013-01-01

217

15 CFR 922.165 - Emergency regulations.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Emergency regulations. 922.165 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Florida Keys National...

2010-01-01

218

15 CFR 922.185 - Emergency regulations.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Emergency regulations. 922.185 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Hawaiian Islands...

2010-01-01

219

15 CFR 922.165 - Emergency regulations.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 false Emergency regulations. 922.165 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Florida Keys National...

2011-01-01

220

15 CFR 922.196 - Emergency regulations.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 false Emergency regulations. 922.196 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Thunder Bay National...

2011-01-01

221

15 CFR 922.165 - Emergency regulations.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 false Emergency regulations. 922.165 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Florida Keys National...

2013-01-01

222

15 CFR 922.185 - Emergency regulations.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 false Emergency regulations. 922.185 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Hawaiian Islands...

2011-01-01

223

15 CFR 922.165 - Emergency regulations.  

Code of Federal Regulations, 2014 CFR

...2014-01-01 false Emergency regulations. 922.165 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Florida Keys National...

2014-01-01

224

15 CFR 922.196 - Emergency regulations.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 false Emergency regulations. 922.196 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Thunder Bay National...

2013-01-01

225

15 CFR 922.185 - Emergency regulations.  

Code of Federal Regulations, 2014 CFR

...2014-01-01 false Emergency regulations. 922.185 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Hawaiian Islands...

2014-01-01

226

15 CFR 922.165 - Emergency regulations.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 false Emergency regulations. 922.165 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Florida Keys National...

2012-01-01

227

15 CFR 922.196 - Emergency regulations.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 false Emergency regulations. 922.196 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Thunder Bay National...

2012-01-01

228

15 CFR 922.196 - Emergency regulations.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Emergency regulations. 922.196 Section 922...Commerce and Foreign Trade Regulations Relating to Commerce and...DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT...NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Thunder Bay National...

2010-01-01

229

Regulation of TGF-? Signal Transduction  

PubMed Central

Transforming growth factor-? (TGF-?) signaling regulates diverse cellular processes, including cell proliferation, differentiation, apoptosis, cell plasticity, and migration. TGF-? signaling can be mediated by Smad proteins or other signaling proteins such as MAP kinases and Akt. TGF-? signaling is tightly regulated at different levels along the pathways to ensure its proper physiological functions in different cells and tissues. Deregulation of TGF-? signaling has been associated with various kinds of diseases, such as cancer and tissue fibrosis. This paper focuses on our recent work on regulation of TGF-? signaling. PMID:25332839

Zhao, Bing; Chen, Ye-Guang

2014-01-01

230

Melatonin Signaling Modulates Clock Genes Expression in the Mouse Retina  

PubMed Central

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

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

2014-01-01

231

An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action  

PubMed Central

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

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

2014-01-01

232

Acute melatonin treatment alters dendritic morphology and circadian clock gene expression in the hippocampus of Siberian Hamsters.  

PubMed

In the hippocampus of Siberian hamsters, dendritic length and dendritic complexity increase in the CA1 region whereas dendritic spine density decreases in the dentate gyrus region at night. However, the underlying mechanism of the diurnal rhythmicity in hippocampal neuronal remodeling is unknown. In mammals, most daily rhythms in physiology and behaviors are regulated by a network of circadian clocks. The central clock, located in the hypothalamus, controls melatonin secretion at night and melatonin modifies peripheral clocks by altering expression of circadian clock genes. In this study, we examined the effects of acute melatonin treatment on the circadian clock system as well as on morphological changes of hippocampal neurons. Male Siberian hamsters were injected with melatonin in the afternoon; 4 h later, mRNA levels of hypothalamic and hippocampal circadian clock genes and hippocampal neuron dendritic morphology were assessed. In the hypothalamus, melatonin treatment did not alter Period1 and Bmal1 expression. However, melatonin treatment increased both Period1 and Bmal1 expression in the hippocampus, suggesting that melatonin affected molecular oscillations in the hippocampus. Melatonin treatment also induced rapid remodeling of hippocampal neurons; melatonin increased apical dendritic length and dendritic complexity in the CA1 region and reduced the dendritic spine density in the dentate gyrus region. These data suggest that structural changes in hippocampal neurons are regulated by a circadian clock and that melatonin functions as a nighttime signal to coordinate the diurnal rhythm in neuronal remodeling. PMID:25160468

Ikeno, Tomoko; Nelson, Randy J

2015-02-01

233

Gene regulation: From biophysics to evolutionary genetics  

E-print Network

Gene regulation: From biophysics to evolutionary genetics Michael Lässig Institute for Theoretical interactions Multiple binding sites allow for complex regulation of individual genes in higher organisms

Lässig, Michael

234

Private Regulation of Consumer Arbitration  

E-print Network

Arbitration providers, such as the American Arbitration Association (“AAA”) and JAMS, have promulgated due process protocols to regulate the fairness of consumer and employment arbitration agreements. A common criticism of these due process...

Drahozal, Christopher R.; Zyontz, Samantha

2012-01-01

235

Nicotinic Regulation of Energy Homeostasis  

PubMed Central

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

2012-01-01

236

Diacylglycerol kinase ?: regulation and stability.  

PubMed

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

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

2013-01-01

237

Mitochondrial Regulation of Neuronal Plasticity  

Microsoft Academic Search

The structure and function of neurons is dynamic during development and in adaptive responses of the adult nervous system\\u000a to environmental demands. The mechanisms that regulate neuronal plasticity are poorly understood, but are believed to involve\\u000a neurotransmitter and neurotrophic factor signaling pathways. In the present article, I review emerging evidence that mitochondria\\u000a play important roles in regulating developmental and adult

Mark P. Mattson

2007-01-01

238

Regulating DNA Replication in Bacteria  

PubMed Central

The replication origin and the initiator protein DnaA are the main targets for regulation of chromosome replication in bacteria. The origin bears multiple DnaA binding sites, while DnaA contains ATP/ADP-binding and DNA-binding domains. When enough ATP-DnaA has accumulated in the cell, an active initiation complex can be formed at the origin resulting in strand opening and recruitment of the replicative helicase. In Escherichia coli, oriC activity is directly regulated by DNA methylation and specific oriC-binding proteins. DnaA activity is regulated by proteins that stimulate ATP-DnaA hydrolysis, yielding inactive ADP-DnaA in a replication-coupled negative-feedback manner, and by DnaA-binding DNA elements that control the subcellular localization of DnaA or stimulate the ADP-to-ATP exchange of the DnaA-bound nucleotide. Regulation of dnaA gene expression is also important for initiation. The principle of replication-coupled negative regulation of DnaA found in E. coli is conserved in eukaryotes as well as in bacteria. Regulations by oriC-binding proteins and dnaA gene expression are also conserved in bacteria. PMID:23471435

Skarstad, Kirsten; Katayama, Tsutomu

2013-01-01

239

Thyroid Hormone Regulation of Metabolism  

PubMed Central

Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, ? and ?, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5?-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets. PMID:24692351

Mullur, Rashmi; Liu, Yan-Yun

2014-01-01

240

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. PMID:23282474

2011-01-01

241

EARLY CAREER AWARD Emotion regulation: Affective, cognitive,  

E-print Network

EARLY CAREER AWARD Emotion regulation: Affective, cognitive, and social consequences JAMES J. GROSS challenges is successfully regulating emotions. Do some emotion regulation strategies have more to recommend of emotion regulation, strategies that act early in the emotion-generative process should have a different

Gross, James J.

242

Using Plant regUlators on  

E-print Network

Using Plant growth regUlators on Containerized herbaCeoUs Perennials Using Plant growth regUlators on Containerized herbaCeoUs Perennials #12;Using Plant Growth Regulators on Containerized Herbaceous Perennials Professor, Herbaceous Perennials Program, Virginia Tech #12;Selecting and Using Plant Growth Regulators

Liskiewicz, Maciej

243

Neuronal regulation of tendon homoeostasis  

PubMed Central

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

2013-01-01

244

Regulation of Autophagy by Kinases  

PubMed Central

Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets. PMID:24212825

Sridharan, Savitha; Jain, Kirti; Basu, Alakananda

2011-01-01

245

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

NSDL National Science Digital Library

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.

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

2012-10-02

246

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

PubMed Central

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

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

2013-01-01

247

SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging.  

PubMed

SIRT1 is a NAD(+)-dependent protein deacetylase that governs many physiological pathways, including circadian rhythm in peripheral tissues. Here, we show that SIRT1 in the brain governs central circadian control by activating the transcription of the two major circadian regulators, BMAL1 and CLOCK. This activation comprises an amplifying circadian loop involving SIRT1, PGC-1?, and Nampt. In aged wild-type mice, SIRT1 levels in the suprachiasmatic nucleus are decreased, as are those of BMAL1 and PER2, giving rise to a longer intrinsic period, a more disrupted activity pattern, and an inability to adapt to changes in the light entrainment schedule. Young mice lacking brain SIRT1 phenocopy these aging-dependent circadian changes, whereas mice that overexpress SIRT1 in the brain are protected from the effects of aging. Our findings indicate that SIRT1 activates the central pacemaker to maintain robust circadian control in young animals, and a decay in this activity may play an important role in aging. PMID:23791176

Chang, Hung-Chun; Guarente, Leonard

2013-06-20

248

Effects of age on clock gene expression in the rhesus macaque pituitary gland  

PubMed Central

Recent studies have shown that circadian clock genes are expressed in various peripheral tissues, raising the possibility that multiple clocks regulate circadian physiology. To study clock gene expression in the rhesus macaque pituitary gland we used gene microarray data and found that the pituitary glands of young and old adult males express several components of the circadian clock (Per1, Per2, Cry1, Bmal1, Clock, Rev-erb? and Csnk1?). Semi-quantitative reverse-transcription polymerase chain reaction (sqRT-PCR) confirmed the presence of these core-clock genes and detected significant age-related differences in expression of Per2. sqRT-PCR also showed differential expression of core-clock genes at two opposing time-points over the 24 hour day, with greater expression of Per2 and Bmal1 (P<0.05) at 1300 h as compared to 0100 h. Immunohistochemistry revealed rhythmic expression of REV-ERB? in the pituitary glands of female macaques. These data provide evidence that the rhesus macaque pituitary gland expresses core-clock genes and their associated protein products in a 24-hour rhythmic pattern, and that their expression is moderately impacted by aging processes. PMID:18614257

Sitzmann, Brandon D.; Lemos, Dario R.; Ottinger, Mary Ann; Urbanski, Henryk F.

2009-01-01

249

Metabolic Mechanisms of Epigenetic Regulation  

PubMed Central

Chromatin modifications have been well-established to play a critical role in the regulation of genome function. Many of these modifications are introduced and removed by enzymes that utilize cofactors derived from primary metabolism. Recently, it has been shown that endogenous cofactors and metabolites can regulate the activity of chromatin-modifying enzymes, providing a direct link between the metabolic state of the cell and epigenetics. Here we review metabolic mechanisms of epigenetic regulation with an emphasis on their role in cancer. Focusing on three core mechanisms, we detail and draw parallels between metabolic and chemical strategies to modulate epigenetic signaling, and highlight opportunities for chemical biologists to help shape our knowledge of this emerging phenomenon. Continuing to integrate our understanding of metabolic and genomic regulatory mechanisms may help elucidate the role of nutrition in diseases such as cancer, while also providing a basis for new approaches to modulate epigenetic signaling for therapeutic benefit. PMID:24228614

Meier, Jordan L.

2014-01-01

250

Epigenetic regulation by nuclear receptors.  

PubMed

Nuclear receptors (NRs) represent a vital class of ligand-activated transcription factors responsible for coordinately regulating the expression of genes involved in numerous biological processes. Transcriptional regulation by NRs is conducted through interactions with multiple coactivator or corepressor complexes that modify the chromatin environment to facilitate or inhibit RNA polymerase II binding and transcription initiation. In recent years, studies have identified specific biological roles for cofactors mediating NR signaling through epigenetic modifications such as acetylation and methylation of histones. Intriguingly, genome-wide analysis of NR and cofactor localization has both confirmed findings from single-gene studies and revealed new insights into the relationships between NRs, cofactors and target genes in determining gene expression. Here, we review recent developments in the understanding of epigenetic regulation by NRs across the genome within the context of the well-established background of cofactor complexes and their roles in histone modification. PMID:22126153

Green, Christopher D; Han, Jing-Dong J

2011-02-01

251

Dealing with duplicate regulations and conflicting jurisdictions  

SciTech Connect

There are a number of situations where mixed wastes are regulated by dual regulations and regulators. This presentation attempts to show where such duplication exists and how it evolved historically through legislative actions. The presentation includes a discussion of strategies that have been used to deal with the problems that result from duplicate regulations and jurisdictional conflicts. The RCRA and AEA regulations are really more similar than dissimilar. There are significant issues that must be worked through with the regulators. It is most important to work with your regulators early in process. The following are suggestions for dealing with the regulators. (1) Know the regulations in advance of discussions. (2) Begin dialogue with the regulator(s) as early as possible and get to know the people you will be dealing with -- and let them know you. (3) Explain the technical/regulatory issues/problems that you face at your facility in sufficient detail that they are clearly understood, and work with the regulator(s) to reasonably address them in the language/requirements of the permit. (4) Always attempt to comply with the regulations first before going in with a variance request -- document your efforts, and be honest with your assessment of issues. (5) Don't be adversarial -- remember that the regulator has the same objectives as you do. 1 tab.

Aamodt, P.L.

1991-01-01

252

Positively regulated bacterial expression systems.  

PubMed

Regulated promoters are useful tools for many aspects related to recombinant gene expression in bacteria, including for high-level expression of heterologous proteins and for expression at physiological levels in metabolic engineering applications. In general, it is common to express the genes of interest from an inducible promoter controlled either by a positive regulator or by a repressor protein. In this review, we discuss established and potentially useful positively regulated bacterial promoter systems, with a particular emphasis on those that are controlled by the AraC-XylS family of transcriptional activators. The systems function in a wide range of microorganisms, including enterobacteria, soil bacteria, lactic bacteria and streptomycetes. The available systems that have been applied to express heterologous genes are regulated either by sugars (L-arabinose, L-rhamnose, xylose and sucrose), substituted benzenes, cyclohexanone-related compounds, ?-caprolactam, propionate, thiostrepton, alkanes or peptides. It is of applied interest that some of the inducers require the presence of transport systems, some are more prone than others to become metabolized by the host and some have been applied mainly in one or a limited number of species. Based on bioinformatics analyses, the AraC-XylS family of regulators contains a large number of different members (currently over 300), but only a small fraction of these, the XylS/Pm, AraC/P(BAD), RhaR-RhaS/rhaBAD, NitR/PnitA and ChnR/Pb regulator/promoter systems, have so far been explored for biotechnological applications. PMID:21261879

Brautaset, Trygve; Lale, Rahmi; Valla, Svein

2009-01-01

253

Positively regulated bacterial expression systems  

PubMed Central

Summary Regulated promoters are useful tools for many aspects related to recombinant gene expression in bacteria, including for high?level expression of heterologous proteins and for expression at physiological levels in metabolic engineering applications. In general, it is common to express the genes of interest from an inducible promoter controlled either by a positive regulator or by a repressor protein. In this review, we discuss established and potentially useful positively regulated bacterial promoter systems, with a particular emphasis on those that are controlled by the AraC?XylS family of transcriptional activators. The systems function in a wide range of microorganisms, including enterobacteria, soil bacteria, lactic bacteria and streptomycetes. The available systems that have been applied to express heterologous genes are regulated either by sugars (l?arabinose, l?rhamnose, xylose and sucrose), substituted benzenes, cyclohexanone?related compounds, ??caprolactam, propionate, thiostrepton, alkanes or peptides. It is of applied interest that some of the inducers require the presence of transport systems, some are more prone than others to become metabolized by the host and some have been applied mainly in one or a limited number of species. Based on bioinformatics analyses, the AraC?XylS family of regulators contains a large number of different members (currently over 300), but only a small fraction of these, the XylS/Pm, AraC/PBAD, RhaR?RhaS/rhaBAD, NitR/PnitA and ChnR/Pb regulator/promoter systems, have so far been explored for biotechnological applications. PMID:21261879

Brautaset, Trygve; Lale, Rahmi; Valla, Svein

2009-01-01

254

Medical device regulation for manufacturers.  

PubMed

Manufacturers of medical devices are held to a higher standard than manufacturers of many other products due to the potential severity of the consequences of introducing inferior or unsafe products to the market-place. In Canada, the medical device industry is regulated by Health Canada under the Medical Device Regulations of the Food and Drug Act. The Medical Device Regulations define requirements of medical device design, development and manufacture to ensure that products reaching the public are safe and effective. Health Canada also requires that medical device manufacturers maintain distribution records to ensure that devices can be traced to the source and consumers can be contacted successfully in the event that a device is recalled. Medical devices exported from Canada must be compliant with the regulations of the country of import. The Canadian Medical Device Regulations were based on the Medical Device Directives of the European Union thus facilitating approval of Canadian devices for the European market. The United States Food and Drug Administration has separate and distinct requirements for safety and quality of medical devices. While effort has been made to facilitate approval and trade of Canadian medical devices in the United States and the European Union, obtaining approval from multiple regulatory bodies can result in increased device development time and cost. The Global Harmonization Task Force is an organization composed of members from Japanese, Australian, European, Canadian and American medical device regulatory bodies. This organization was formed with the objective of harmonizing medical device regulations in an effort to facilitate international trade and standardize the quality of medical devices available to all countries. This paper discusses the requirements that must be met by manufacturers when designing and manufacturing medical devices. PMID:14702983

McAllister, P; Jeswiet, J

2003-01-01

255

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

256

Redox regulation of Janus kinase  

PubMed Central

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

Duhé, Roy J

2013-01-01

257

Improving Regulation Through Incremental Adjustment  

E-print Network

" in that the treatment required by the regulation is unnecessary to protect the resource in question. See. e.g., Robert W. Adler, Water Quality and Agriculture: Assessing Alternative Futures, 25 ENVIRONS L. & POL'y J. 77, 89 (2002); William L. Andreen, The Evolution... discuss these proposals further in Sidney A. Shapiro & Robert L. Glicksman, The APA and the Back-End ofRegulation: Procedures for Informal Adjudication. 56 ADMIN. L. REv. 1159 (2004). 9. See. e.g., STEPHEN BREYER, BREAKING mE VICIOUS CIRCLE: TOWARD EFFECI1...

Glicksman, Robert L.; Shapiro, Sidney A.

2004-03-01

258

CNS Regulation of Glucose Homeostasis  

NSDL National Science Digital Library

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

2009-06-01

259

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

Federal Register 2010, 2011, 2012, 2013, 2014

...DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety...R)] New Jersey Regulations on Transportation of Regulated Medical Waste AGENCY...whether Federal hazardous material transportation law preempts regulations of the...

2011-11-10

260

76 FR 43585 - Bank Secrecy Act Regulations; Definitions and Other Regulations Relating to Money Services...  

Federal Register 2010, 2011, 2012, 2013, 2014

...Parts 1010, 1021 and 1022 RIN 1506-AA97 Bank Secrecy Act Regulations; Definitions and...revising the regulations implementing the Bank Secrecy Act (``BSA'') regarding money...2010) (Transfer and Reorganization of Bank Secrecy Act Regulations Final...

2011-07-21

261

76 FR 50331 - Hazardous Materials Regulations; Compatibility With the Regulations of the International Atomic...  

Federal Register 2010, 2011, 2012, 2013, 2014

...the International Atomic Energy Agency (IAEA) publication ``Regulations for the Safe...of Radioactive Material, 2009 Edition, IAEA Safety Standards Series No. TS-R-1...regulations with international regulations of the IAEA in: Safety Series No. 6,...

2011-08-12

262

Regulating Constructed Wetlands in Scotland  

E-print Network

23/05/2012 1 Regulating Constructed Wetlands in Scotland Andy Hemingway Constructed wetlands for Industry & Commerce 21st May 2012 Content · Types of wetland from regulatory perspective · Main regulatory regimes · Regulatory considerations and case studies of constructed wetlands ­ Sewage ­ Industrial

Heal, Kate

263

Lasp-1 Regulates Podosome Function  

Microsoft Academic Search

Eukaryotic cells form a variety of adhesive structures to connect with their environment and to regulate cell motility. In contrast to classical focal adhesions, podosomes, highly dynamic structures of different cell types, are actively engaged in matrix remodelling and degradation. Podosomes are composed of an actin-rich core region surrounded by a ring-like structure containing signalling molecules, motor proteins as well

Miriam Stölting; Christiane Wiesner; Vanessa van Vliet; Elke Butt; Hermann Pavenstädt; Stefan Linder; Joachim Kremerskothen

2012-01-01

264

ALTERNATIVE APPROACHES TO PESTICIDE REGULATION  

Microsoft Academic Search

Pesticide regulation has become a topic of increas- ing interest in recent years, owing to rising public concerns about residues on foods, in drinking- water wells, and damage to wildlife. Public- opinion polls and political responses to incidents like the controversy over Alar suggest that demand for government intervention to protect public health and the environment from pesticides is high.

Erik Lichtenberg

1992-01-01

265

INVESTIGATION Nonclassical Regulation of Transcription  

E-print Network

"transvection" was first coined by E. B. Lewis (1954) to describe complementation and trans-interactions between are wide ranging, affecting gene regulation in many species and creating complex possibilities in gene) locus in Drosophila melanogaster that results in allele-specific, non-additive gene expression. Using

Merritt, Thomas J. S.

266

Challenges in Regulating Pesticide Mixtures  

Microsoft Academic Search

This paper introduces the field of mixture toxicity and the challenges in regulating pesticide mixtures. Even though pesticides are unique chemical stressors designed to have biological activity that can affect a number of nontarget species, they are intentionally placed into the environment in large quantities. Currently, methods and terminology for evaluating mixture toxicity are poorly established. The most common approach

Michael Lydy; Jason Belden; Craig Wheelock; Bruce Hammock; Debra Denton

2004-01-01

267

Gaseous mediators in temperature regulation.  

PubMed

Deep body temperature (Tb) is kept relatively constant despite a wide range of ambient temperature variation. Nevertheless, in particular situations it is beneficial to decrease or to increase Tb in a regulated manner. Under hypoxia for instance a regulated drop in Tb (anapyrexia) is key to reduce oxygen demand of tissues when oxygen availability is diminished, leading to an increased survival rate in a number of species when experiencing low levels of inspired oxygen. On the other hand, a regulated rise in Tb (fever) assists the healing process. These regulated changes in Tb are mediated by the brain, where afferent signals converge and the most important regions for the control of Tb are found. The brain (particularly some hypothalamic structures located in the preoptic area) modulates efferent activities that cause changes in heat production (modulating brown adipose tissue activity and perfusion, for instance) and heat loss (modulating tail skin vasculature blood flow, for instance). This review highlights key advances about the role of the gaseous neuromodulators nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) in thermoregulation, acting both on the brain and the periphery. PMID:25428845

Branco, Luiz G S; Soriano, Renato N; Steiner, Alexandre A

2014-10-01

268

REGULATION SCOPING Alternative and Renewable  

E-print Network

REGULATION SCOPING PAPER Alternative and Renewable Fuel and Vehicle Technology Program California Energy Commission Presented at: 1516 Ninth Street Sacramento, California July 8, 2008 DISCLAIMER This paper was prepared by a California Energy Commission staff person. It does not necessarily represent

269

Developing Self-Regulated Learners.  

ERIC Educational Resources Information Center

Principles of teaching students with special needs the processes for self-regulation of their behavior are offered, for the four components of self-instruction, goal setting, self-monitoring, and self-reinforcement. Forms of self-instruction are described, with examples, and sample recording systems are provided. (DB)

Graham, Steve; And Others

1992-01-01

270

Construction regulations along metro alignment  

Microsoft Academic Search

The purpose of the current study was to determine construction regulations along subway alignment.The study aims to expand the underground tunnelling technique, comparison of different tunnel excavation techniques, tunnelling machines. The aim of this study was to evaluate and validate construction hazards and mitigation measures, shafts sinking, tunnel, excavated material determination. In recent years, there has been an increasing interest

V Ghiasi; H Omar; J Rostami; B K Huat

2010-01-01

271

Nutritional regulation of epigenetic changes  

Technology Transfer Automated Retrieval System (TEKTRAN)

The "Nutritional Regulation of Epigenetic Changes" Symposium was held in San Diego on April 25 in conjunction with the 2012 Annual Meetings of the American Society of Nutrition. The symposium was co-chaired by Drs. Romagnoo and Ziegler. In his opening remarks, Dr. Zeigler highlighted salient aspec...

272

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...

273

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

274

Autogenous regulation of gene expression.  

PubMed

A new term, autogenous regulation, is used to describe a phenomenon that is not a new discovery but rather is newly appreciated as a mechanism common to a number of systems in both prokaryotic and eukaryotic organisms. In this mechanism the product of a structural gene regulates expression of the operon in which that structural gene resides. In many (perhaps all) cases, the regulatory gene product has several functions, since it may act not only as a regulatory protein but also as an enzyme, structural protein, or antibody, for example. In a few cases, this protein is the multimeric allosteric enzyme that catalyzes the first step of a metabolic pathway, gearing together the two most important mechanisms for controlling the biosynthesis of metabolites in bacterial cells-feedback inhibition and repression. Autogenous regulation may provide a mechanism for amplification of gene expression (84); for severe and prolonged inactivation of gene expression (85); for buffering the response of structural genes to changes in the environment (45, 52); and for maintaining a constant intracellular concentration of a protein, independent of cell size or growth rate (86). Thus, autogenous regulation provides the cell with means for accomplishing a number of different regulatory tasks, each suited to better satisfying the needs of the organism for its survival. PMID:4589900

Goldberger, R F

1974-03-01

275

Transcriptional Regulation by P53  

PubMed Central

Inactivation of p53 is critical for the formation of most tumors. Illumination of the key function(s) of p53 protein in protecting cells from becoming cancerous is therefore a worthy goal. Arguably p53’s most important function is to act as a transcription factor that directly regulates perhaps several hundred of the cell’s RNA polymerase II (RNAP II)-transcribed genes, and indirectly regulates thousands of others. Indeed p53 is the most well studied mammalian transcription factor. The p53 tetramer binds to its response element where it can recruit diverse transcriptional coregulators such as histone modifying enzymes, chromatin remodeling factors, subunits of the mediator complex, and components of general transcription machinery and preinitiation complex (PIC) to modulate RNAPII activity at target loci (Laptenko and Prives 2006). The p53 transcriptional program is regulated in a stimulus-specific fashion (Murray-Zmijewski et al. 2008; Vousden and Prives 2009), whereby distinct subsets of p53 target genes are induced in response to different p53-activating agents, likely allowing cells to tailor their response to different types of stress. How p53 is able to discriminate between these different loci is the subject of intense research. Here, we describe key aspects of the fundamentals of p53-mediated transcriptional regulation and target gene promoter selectivity. PMID:20679336

Beckerman, Rachel; Prives, Carol

2010-01-01

276

Indiana Aquaculture Regulations and Permits  

E-print Network

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

277

Illinois Aquaculture Regulations and Permits  

E-print Network

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

278

ACADEMIC REGULATIONS COMMITTEE MEDICAL FORM  

E-print Network

it be medically necessary for the student to reduce his or her course load during the affected term(s)? YES\\ ACADEMIC REGULATIONS COMMITTEE MEDICAL FORM INSTRUCTIONS The lower part of this form needs to be completed by the appropriate medical professional and the entire form should be returned in a SEALED

Meyers, Steven 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 organisms.

Clopton, Joe R.

2007-01-01

280

Safety Regulations of Food Enzymes  

Microsoft Academic Search

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

Armin Spök

281

DOT regulations, safety relief valves  

Microsoft Academic Search

This review of overpressure protective devices is based on the ASME guide for gas transmission and distribution piping systems of 1980. Analysis of overpressure protection methods in the industry has been increasing since 1970 to insure that provisions of Part. 192, Title 49, Code of Federal Regulations, ''Transportation of natural and other gas by pipelines: minimum federal safety standards'', are

1981-01-01

282

Pressure regulator valve by Bondgraph  

Microsoft Academic Search

The Bondgraph represents mechanical, hydraulic and electric components with their power flow in an unified manner and is used here for a three port regulator valve for pressure. It consists of a valve spool and a valve body or casing, and an electric solenoid. The valve assembly has three ports and two variable metering orifices, represented by modulated R-elements. They

Katsuya Suzuki; Ikuo Nakamura; Jean Thoma

1999-01-01

283

Modellering og regulering af affaldsforbrnding  

E-print Network

deals with the regulation of a Danish waste incineration plant. It is tested if the flame front can on the Waste Incineration Plant, Haderslev Kraftvar- meværk in Denmark. Concurrently the position of the flame front was estimated, using a camera in the oven, a framegrapper card and an algorithm designed

284

5____________________________________________________________________________ Gene Regulation in Spermatogenesis  

E-print Network

5____________________________________________________________________________ Gene Regulation Nuclear Receptors C. HeatShock Factors D. Sox E. Plzf F. Dmrt1 G. CAF1 H. Homeobox Genes I. Perspective IV. TestisSpecific Gene Expression and DNA Methylation A. Male Germ Cell­Specific Genes B. SomaticCell Testis

Wilkinson, Miles F.

285

Cattle transport regulations in the European Union.  

PubMed

The essential items of the relevant EU legislation are described and their effects are discussed. A brief survey of the four most important legal regulations in the EU relevant for cattle transport is given from the point of view of administration. These regulations are: The Directive 91/628/EEC 1991 (protection of animals during transport), Council Regulation (EC) No 1255/97 (criteria for staging points and route plan), Council Regulation (EC) No 411/98 (additional standards for road vehicles for long distance transport), Commission Regulation (EC) No 615/98 (export refund regulations). Some critical points of the objectives are pointed out. PMID:12731105

Grötzschel, J

2003-03-01

286

B7 family checkpoint regulators in immune regulation and disease  

PubMed Central

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

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

2013-01-01

287

Regulation of Drosophila metamorphosis by xenobiotic response regulators.  

PubMed

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 cncC(K6/K6) and dKeap1(EY5/EY5) loss of function mutations in embryos reduced ecdysone-biosynthetic gene transcription. In contrast, dKeap1 depletion and the dKeap1(EY5/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. PMID:23408904

Deng, Huai; Kerppola, Tom K

2013-01-01

288

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. PMID:17173929

Xie, Guo-xi; Palmer, Pamela Pierce

2007-01-01

289

Petroleum: The Petroleum (Production) (Amendment) Regulations, 1957   

E-print Network

These Regulations amend the Petroleum (Production) Regulations, 1935, which set out the requirements for applications for, and the model clauses to be incorporated in, prospecting and mining licences issued under the Petroleum (Production) Act, 1934...

Her Majesty's Stationary Office

1957-01-01

290

7 CFR 958.328 - Handling regulation.  

Code of Federal Regulations, 2013 CFR

...AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE ONIONS GROWN IN CERTAIN DESIGNATED COUNTIES IN IDAHO, AND MALHEUR COUNTY, OREGON Handling Regulations § 958.328 Handling regulation. No person shall handle...

2013-01-01

291

7 CFR 958.328 - Handling regulation.  

Code of Federal Regulations, 2012 CFR

...Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ONIONS GROWN IN CERTAIN DESIGNATED COUNTIES IN IDAHO, AND MALHEUR COUNTY, OREGON Handling Regulations § 958.328 Handling regulation. No person shall handle...

2012-01-01

292

36 CFR 34.5 - Applicable regulations.  

Code of Federal Regulations, 2013 CFR

... 34.5 Section 34.5 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR EL PORTAL ADMINISTRATIVE SITE REGULATIONS § 34.5 Applicable regulations. The following sections and paragraphs of this...

2013-07-01

293

36 CFR 34.5 - Applicable regulations.  

Code of Federal Regulations, 2012 CFR

... 34.5 Section 34.5 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR EL PORTAL ADMINISTRATIVE SITE REGULATIONS § 34.5 Applicable regulations. The following sections and paragraphs of this...

2012-07-01

294

36 CFR 34.5 - Applicable regulations.  

Code of Federal Regulations, 2011 CFR

... 34.5 Section 34.5 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR EL PORTAL ADMINISTRATIVE SITE REGULATIONS § 34.5 Applicable regulations. The following sections and paragraphs of this...

2011-07-01

295

36 CFR 34.5 - Applicable regulations.  

Code of Federal Regulations, 2014 CFR

... 34.5 Section 34.5 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR EL PORTAL ADMINISTRATIVE SITE REGULATIONS § 34.5 Applicable regulations. The following sections and paragraphs of this...

2014-07-01

296

Current Regulator For Sodium-Vapor Lamps  

NASA Technical Reports Server (NTRS)

Regulating circuit maintains nearly-constant alternating current in sodium-vapor lamp. Regulator part of dc-to-ac inverter circuit used to supply power to street lamp from battery charged by solar-cell array.

Mclyman, W. T.

1989-01-01

297

77 FR 16784 - General Bridge Regulation; Amendment  

Federal Register 2010, 2011, 2012, 2013, 2014

...USCG-2008-1188] RIN 1625-AB36 General Bridge Regulation; Amendment AGENCY: Coast...rulemaking concerning amendments to the general bridge regulations. The rulemaking was initiated...clarify the statutory responsibilities of bridge owners to remove their bridges from...

2012-03-22

298

7 CFR 948.386 - Handling regulation.  

Code of Federal Regulations, 2014 CFR

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

2014-01-01

299

7 CFR 948.386 - Handling regulation.  

Code of Federal Regulations, 2012 CFR

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

2012-01-01

300

7 CFR 948.386 - Handling regulation.  

Code of Federal Regulations, 2011 CFR

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

2011-01-01

301

7 CFR 948.386 - Handling regulation.  

Code of Federal Regulations, 2013 CFR

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

2013-01-01

302

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

303

32 CFR 770.3 - Fishing regulations.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 2012-07-01 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...

2012-07-01

304

32 CFR 770.3 - Fishing regulations.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 2011-07-01 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...

2011-07-01

305

32 CFR 770.3 - Fishing regulations.  

Code of Federal Regulations, 2014 CFR

...2014-07-01 2014-07-01 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...

2014-07-01

306

32 CFR 770.3 - Fishing regulations.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 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...

2010-07-01

307

INTERNATIONAL WOMEN'S HACKATHON OFFICIAL RULES AND REGULATIONS  

E-print Network

. Participants can form their teams, plan their application ahead of time but cannot code until the day & Regulations Page 2 of 11 o U.S. export regulations prohibit the export of goods and services to Cuba, Iran

Bernstein, Phil

308

78 FR 35195 - Acquisition Regulations: Export Control  

Federal Register 2010, 2011, 2012, 2013, 2014

...public health and safety, and other advantages; distributive impacts; and equity...laws, regulations and directives when exporting items, included but not limited to...laws, regulations and directives when exporting unclassified information,...

2013-06-12

309

Flexible Bureaucracies in Labor Market Regulation  

E-print Network

This paper compares and contrasts the U.S. and French systems of labor market regulation. The U.S. system is specialized: Regulating authority is dispersed among a host of different agencies each with a relatively narrow ...

Piore, Michael J.

310

43 CFR 431.9 - Future regulations.  

Code of Federal Regulations, 2010 CFR

... Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR GENERAL REGULATIONS FOR POWER GENERATION, OPERATION, MAINTENANCE, AND REPLACEMENT AT THE BOULDER CANYON PROJECT, ARIZONA/NEVADA § 431.9 Future...

2010-10-01

311

The Scientific Basis of Tobacco Product Regulation  

E-print Network

WHO Technical Report Series THE SCIENTIFIC BASIS OF TOBACCOscientific basis of tobacco product regulation. Geneva, World Health Organization (WHO Technical Reportscientific basis of tobacco product regulation: second report of a WHO study group. (WHO technical report

World Health Organization

2008-01-01

312

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

313

Renewable energy and utility regulation  

SciTech Connect

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

Not Available

1991-04-10

314

Renewable energy and utility regulation  

SciTech Connect

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

Not Available

1991-04-10

315

Battery voltage regulator for vehicles  

SciTech Connect

This patent describes a vehicle battery charging system having a battery for outputting a battery voltage, a series combination of a key switch and a large lamp, a current generator having stator windings for outputting a stator output voltage, a field winding and a full-wave rectifier, and a voltage regulator. The above mentioned components are arranged to control the field current through the field winding in accordance with a predetermined voltage. The voltage regulator comprises: a series combination including a semiconductor switch means and a resistor connected between the terminal and ground. The semiconductor switch means are activated at least when the key switch is opened in order to bypass leakage current therethrough.

Sada, T.; Kato, H.; Shibata, H.; Mori, K.; Mayumi, N.; Sato, H.; Akita, Y.; Tanaka, S.

1987-05-12

316

Cardiac myofilaments: mechanics and regulation  

NASA Technical Reports Server (NTRS)

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

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

2003-01-01

317

The grammar of transcriptional regulation.  

PubMed

Eukaryotes employ combinatorial strategies to generate a variety of expression patterns from a relatively small set of regulatory DNA elements. As in any other language, deciphering the mapping between DNA and expression requires an understanding of the set of rules that govern basic principles in transcriptional regulation, the functional elements involved, and the ways in which they combine to orchestrate a transcriptional output. Here, we review the current understanding of various grammatical rules, including the effect on expression of the number of transcription factor binding sites, their location, orientation, affinity and activity; co-association with different factors; and intrinsic nucleosome organization. We review different methods that are used to study the grammar of transcription regulation, highlight gaps in current understanding, and discuss how recent technological advances may be utilized to bridge them. PMID:24390306

Weingarten-Gabbay, Shira; Segal, Eran

2014-06-01

318

Epigenetic regulation of epidermal differentiation.  

PubMed

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

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

2014-02-01

319

Redox regulation of Ran GTPase.  

PubMed

Ran, a small Ras-like GTP-binding nuclear protein, plays a key role in modulation of various cellular signaling events including the cell cycle. This study shows that a cellular redox agent (nitrogen dioxide) facilitates Ran guanine nucleotide dissociation, and identifies a unique Ran redox architecture involved in that process. Sequence analysis suggests that Dexras1 and Rhes GTPases also possess the Ran redox architecture. As Ran releases an intact nucleotide, the redox regulation mechanism of Ran is likely to differ from the radical-based guanine nucleotide modification mechanism suggested for Ras and Rho GTPases. These results provide a mechanistic reason for the previously observed oxidative stress-induced perturbation of the Ran-mediated nuclear import, and suggest that oxidative stress could be a factor in the regulation of cell signal transduction pathways associated with Ran. PMID:18796295

Heo, Jongyun

2008-11-21

320

Redox regulation of Ran GTPase  

SciTech Connect

Ran, a small Ras-like GTP-binding nuclear protein, plays a key role in modulation of various cellular signaling events including the cell cycle. This study shows that a cellular redox agent (nitrogen dioxide) facilitates Ran guanine nucleotide dissociation, and identifies a unique Ran redox architecture involved in that process. Sequence analysis suggests that Dexras1 and Rhes GTPases also possess the Ran redox architecture. As Ran releases an intact nucleotide, the redox regulation mechanism of Ran is likely to differ from the radical-based guanine nucleotide modification mechanism suggested for Ras and Rho GTPases. These results provide a mechanistic reason for the previously observed oxidative stress-induced perturbation of the Ran-mediated nuclear import, and suggest that oxidative stress could be a factor in the regulation of cell signal transduction pathways associated with Ran.

Heo, Jongyun [Department of Chemistry and Biochemistry, University of Texas at Arlington, 700 Planetarium Place, Arlington, TX 76019 (United States)], E-mail: jheo@uta.edu

2008-11-21

321

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. PMID:23275931

Yu, Ji Hee

2012-01-01

322

Gene regulation by mechanical forces  

NASA Technical Reports Server (NTRS)

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

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

1997-01-01

323

Papillomavirus transcripts and posttranscriptional regulation.  

PubMed

Papillomavirus gene expression is strictly linked to the differentiation state of the infected cell and is highly regulated at the level of transcription and RNA processing. All papillomaviruses make extensive use of alternative mRNA polyadenylation and splicing to control gene expression. This chapter contains a compilation of all known alternatively spliced papillomavirus mRNAs and it summarizes our current knowledge of viral RNA elements, and viral and cellular factors that control papillomavirus mRNA processing. PMID:23706315

Schwartz, Stefan

2013-10-01

324

Equitable regulation of private forests  

Microsoft Academic Search

The sustainability of forested ecosystems often requires cross-boundary management at large spatial scales. This can be challenging,\\u000a however, in landscapes where forests are primarily under small-scale, private ownership. Consequently, in many areas of the\\u000a world private forest practices are governmentally regulated to promote more consistent cross-boundary outcomes and better\\u000a protection of large-scale ecological integrity. In this qualitative, ‘grounded theory’ study,

Roje S. Gootee; Keith A. Blatner; David M. Baumgartner; Matthew S. Carroll; Edward P. Weber

325

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

326

Phenotyping jasmonate regulation of senescence.  

PubMed

Osmotic stress induces several senescence-like processes in leaves, such as specific changes in gene expression and yellowing. These processes are dependent on the accumulation of jasmonates and on intact jasmonate signaling. This chapter describes the treatment of Arabidopsis thaliana leaves with sorbitol as an osmotic stress agent and the determination of the elicited phenotypes encompassing chlorophyll loss, degradation of plastidial membrane lipids, and induction of genes regulated by senescence and jasmonate. PMID:23615983

Seltmann, Martin A; Berger, Susanne

2013-01-01

327

MORC proteins and epigenetic regulation  

PubMed Central

Two recent studies in Arabidopsis implicated MORC proteins, which contain a GHKL ATPase domain, in transcriptional gene silencing. Here, these studies are compared and contrasted to discuss the roles of MORC proteins in epigenetic regulation. Although MORC proteins are likely to catalyze changes in chromatin structure in response to epigenetic signals, their precise mode of action and target site-specificity still remain unclear. PMID:23072987

Lorkovi?, Zdravko J.

2012-01-01

328

Frequency regulator for synchronous generators  

DOEpatents

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

Karlicek, R.F.

1982-08-10

329

78 FR 13543 - Defense Federal Acquisition Regulation Supplement; Technical Amendments  

Federal Register 2010, 2011, 2012, 2013, 2014

...242, 245, and 252 Defense Federal Acquisition Regulation Supplement; Technical Amendments AGENCY: Defense Acquisition Regulations...technical amendments to the Defense Federal Acquisition Regulation Supplement (DFARS) to...

2013-02-28

330

76 FR 76318 - Defense Federal Acquisition Regulation Supplement; Technical Amendments  

Federal Register 2010, 2011, 2012, 2013, 2014

...Appendix A to Chapter 2 Defense Federal Acquisition Regulation Supplement; Technical Amendments AGENCY: Defense Acquisition Regulations...technical amendments to the Defense Federal Acquisition Regulation Supplement (DFARS) to...

2011-12-07

331

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

Federal Register 2010, 2011, 2012, 2013, 2014

...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

332

75 FR 78619 - Defense Federal Acquisition Regulation Supplement; Technical Amendments  

Federal Register 2010, 2011, 2012, 2013, 2014

...DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 216 and 237 Defense Federal Acquisition Regulation Supplement; Technical Amendments AGENCY: Defense Acquisition Regulations System, Department of...

2010-12-16

333

Intelligent Control and Biological Regulation For Bioinformatics  

Microsoft Academic Search

Regulation and control in biological processes are the center of life. Living organisms grow and reproduce. They maintain their structures and respond to their environments. All these processes are done through regulation and control. This paper reports the study of regulation and the applicability of intelligent control to bioinformatics, particularly to biological systems. In addition to two previously-described phases of

Aboubekeur Hamdi-Cherif

2010-01-01

334

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

335

A Computational Model for Adaptive Emotion Regulation  

E-print Network

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

Treur, Jan

336

Self-Regulation in Online Learning  

ERIC Educational Resources Information Center

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

Cho, Moon-Heum; Shen, Demei

2013-01-01

337

Regulation of Hydraulic Fracturing in California  

E-print Network

APRIL 2013 Regulation of Hydraulic Fracturing in California: A WAsteWAteR And WAteR QuAlity Pe | Regulation of Hydraulic Fracturing in California Wheeler Institute for Water Law & Policy Center for Law #12;Regulation of Hydraulic Fracturing in California | 3Berkeley law | wheeler InstItute for water law

Kammen, Daniel M.

338

Toward Rational Regulation of Genetically Modified Food  

Microsoft Academic Search

The regulation of genetically modified food pursuant to statutes enacted decades prior to the advent of biotechnology has created a regulatory system that unnecessarily exposes society and the environment to adverse risks of biotechnology and introduces numerous inefficiencies into the regulatory system. These risks and inefficiencies include gaps in regulation, duplicative and inconsistent regulation, unnecessary regulatory expense, agencies acting outside

Gregory N. Mandel

2006-01-01

339

The Goals for Regulating College Tuition  

ERIC Educational Resources Information Center

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

Zeng, Xiaodong

2009-01-01

340

Auxin signaling and regulated protein degradation  

E-print Network

Auxin signaling and regulated protein degradation Nihal Dharmasiri and Mark Estelle Department of Biology, Indiana University, Bloomington, IN 47405, USA Auxin regulates many aspects of plant growth and development. Auxin is known to regulate gene expression through degradation of the AUX/IAA pro- teins, short

Estelle, Mark

341

Regulation of equine infectious anemia virus expression  

Microsoft Academic Search

Equine infectious anemia virus (EIAV) is an ungulate lentivirus that is related to human immunodeficiency virus (HIV). Much of the understanding of lentiviral gene regulation comes from studies using HIV. HIV studies have provided insights into molecular regulation of EIAV expression; however, much of the regulation of EIAV expression stands in stark contrast to that of HIV. This review provides

Wendy Maury; S. Dak

1998-01-01

342

Emotion Regulation and Depressive Symptoms in Preadolescence  

ERIC Educational Resources Information Center

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

Siener, Shannon; Kerns, Kathryn A.

2012-01-01

343

Learning Styles and Self-Regulation.  

ERIC Educational Resources Information Center

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

Vermunt, Jan D. H. M.

344

Issues in the Regulation of Annuities Markets  

Microsoft Academic Search

Annuities are a vital aspect of a growing number of reformed pension systems around the world, and will be of increasing relevance in Europe as reform of generous social security schemes gathers pace. This paper addresses the regulation of annuities, essential to ensure integrity of the system, from three sides; prudential regulation of insurance companies, conduct of business regulation of

E. Philip Davis

2002-01-01

345

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

346

Gene regulation, protein networks and disease  

E-print Network

1 Gene regulation, protein networks and disease ­ a computational perspective Ron Shamir School in cancer DEGAS 2 #12;Regulation of Transcription · A gene's ranscription regulation is mainly encoded binding sites (BSs) that are bound by specific proteins called transcription factors (TFs) TFTF Gene 5' 3

Lonardi, Stefano

347

Musical affect regulation in infancy.  

PubMed

Adolescents and adults commonly use music for various forms of affect regulation, including relaxation, revitalization, distraction, and elicitation of pleasant memories. Mothers throughout the world also sing to their infants, with affect regulation as the principal goal. To date, the study of maternal singing has focused largely on its acoustic features and its consequences for infant attention. We describe recent laboratory research that explores the consequences of singing for infant affect regulation. Such work reveals that listening to recordings of play songs can maintain 6- to 9-month-old infants in a relatively contented or neutral state considerably longer than recordings of infant-directed or adult-directed speech. When 10-month-old infants fuss or cry and are highly aroused, mothers' multimodal singing is more effective than maternal speech at inducing recovery from such distress. Moreover, play songs are more effective than lullabies at reducing arousal in Western infants. We explore the implications of these findings along with possible practical applications. PMID:25773634

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

2015-03-01

348

Gibberellin biosynthesis and its regulation.  

PubMed

The GAs (gibberellins) comprise a large group of diterpenoid carboxylic acids that are ubiquitous in higher plants, in which certain members function as endogenous growth regulators, promoting organ expansion and developmental changes. These compounds are also produced by some species of lower plants, fungi and bacteria, although, in contrast to higher plants, the function of GAs in these organisms has only recently been investigated and is still unclear. In higher plants, GAs are synthesized by the action of terpene cyclases, cytochrome P450 mono-oxygenases and 2-oxoglutarate-dependent dioxygenases localized, respectively, in plastids, the endomembrane system and the cytosol. The concentration of biologically active GAs at their sites of action is tightly regulated and is moderated by numerous developmental and environmental cues. Recent research has focused on regulatory mechanisms, acting primarily on expression of the genes that encode the dioxygenases involved in biosynthesis and deactivation. The present review discusses the current state of knowledge on GA metabolism with particular emphasis on regulation, including the complex mechanisms for the maintenance of GA homoeostasis. PMID:22533671

Hedden, Peter; Thomas, Stephen G

2012-05-15

349

Autophagy regulation by nutrient signaling  

PubMed Central

The ability of cells to respond to changes in nutrient availability is essential for the maintenance of metabolic homeostasis and viability. One of the key cellular responses to nutrient withdrawal is the upregulation of autophagy. Recently, there has been a rapid expansion in our knowledge of the molecular mechanisms involved in the regulation of mammalian autophagy induction in response to depletion of key nutrients. Intracellular amino acids, ATP, and oxygen levels are intimately tied to the cellular balance of anabolic and catabolic processes. Signaling from key nutrient-sensitive kinases mTORC1 and AMP-activated protein kinase (AMPK) is essential for the nutrient sensing of the autophagy pathway. Recent advances have shown that the nutrient status of the cell is largely passed on to the autophagic machinery through the coordinated regulation of the ULK and VPS34 kinase complexes. Identification of extensive crosstalk and feedback loops converging on the regulation of ULK and VPS34 can be attributed to the importance of these kinases in autophagy induction and maintaining cellular homeostasis. PMID:24343578

Russell, Ryan C; Yuan, Hai-Xin; Guan, Kun-Liang

2014-01-01

350

A closely regulated TWT converter.  

NASA Technical Reports Server (NTRS)

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

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

1971-01-01

351

Negative regulators of cell proliferation  

NASA Technical Reports Server (NTRS)

Cell proliferation is governed by the influence of both mitogens and inhibitors. Although cell contact has long been thought to play a fundamental role in cell cycling regulation, and negative regulators have long been suspected to exist, their isolation and purification has been complicated by a variety of technical difficulties. Nevertheless, over recent years an ever-expanding list of putative negative regulators have emerged. In many cases, their biological inhibitory activities are consistent with density-dependent growth inhibition. Most likely their interactions with mitogenic agents, at an intracellular level, are responsible for either mitotic arrest or continued cell cycling. A review of naturally occurring cell growth inhibitors is presented with an emphasis on those factors shown to be residents of the cell surface membrane. Particular attention is focused on a cell surface sialoglycopeptide, isolated from intact bovine cerebral cortex cells, which has been shown to inhibit the proliferation of an unusually wide range of target cells. The glycopeptide arrest cells obtained from diverse species, both fibroblasts and epithelial cells, and a broad variety of transformed cells. Signal transduction events and a limited spectrum of cells that are refractory to the sialoglycopeptide have provided insight into the molecular events mediated by this cell surface inhibitor.

Johnson, T. C.; Spooner, B. S. (Principal Investigator)

1994-01-01

352

Redox Regulation of Protein Kinases  

PubMed Central

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

Truong, Thu H.; Carroll, Kate S.

2015-01-01

353

Regulation of cerebral blood flow.  

PubMed

The control of cerebral blood flow is complex, and only beginning to be elucidated. Studies have identified three key regulatory paradigms. The first is cerebral pressure autoregulation, which maintains a constant flow in the face of changing cerebral perfusion pressure. Flow-metabolism coupling refers to the brains ability to vary blood flow to match metabolic activity. An extensive arborization of perivascular nerves also serves to modulate cerebral blood flow, so-called neurogenic regulation. Central to these three paradigms are two cell types: endothelium and astrocytes. The endothelium produces several vasoactive factors that are germane to the regulation of cerebral blood flow: nitric oxide, endothelium-dependent hyperpolarization factor, the eicosanoids, and the endothelins. Astrocytic foot processes directly abut the blood vessels, and play a key role in regulation of cerebral blood flow. Lastly, new research has been investigating cell-cell communication at the microvascular level. Several lines of evidence point to the ability of the larger proximal vessels to coordinate vasomotor responses downstream. PMID:21808738

Peterson, Eric C; Wang, Zhengfeng; Britz, Gavin

2011-01-01

354

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. PMID:395764

Forster, R. P.; Goldstein, L.

1979-01-01

355

Regulation of bacterial glycogen synthesis.  

PubMed

The formation of the alpha 1,4 glucosidic linkages of bacterial glycogen occurs first by synthesis of ADPglucose from ATP and alpha glucose 1-P and then transfer of the glucose moiety from the formed sugar nucleotide to a pre-existing glucan primer. Unlike mammalian glycogen synthesis, regulation occurs at the synthesis of the sugar nucleotide. Generally glycolytic intermediates activate ADPglucose synthesis while AMP, ADP and/or Pi inhibit ADPglucose synthesis. A variation of activator specificity is is seen when the enzyme is isolated from different bacteria and is thought to be related to the predominant type of carbon assimilation or dissimilation pathways present in the particular organism. Evidence indicating that the allosteric activation effects observed in vitro are physiologically pertinent for the regulation of glycogen synthesis is reviewed. The recent experiments in identifying the allosteric activator site of the Escherichia coli ADPglucose pyrophosphorylase as well as other chemical modification studies identifying amino acid residues essential for allosteric activation and for catalytic activity are discussed. Evidence is also presented for the covalent modification of the Rhodopseudomonas sphaeroides ADPglucose pyrophosphorylase by bromopyruvate at its allosteric activator site. Regulation of the biosynthesis of glycogen also occurs at the genetic level and the current evidence for the existence of a glycogen operon is presented. In addition the current studies concerning the cloning of the DNA region containing the Escherichia coli structural genes coding for the glycogen biosynthetic enzymes as well as the nucleotide sequence of the E. coli ADPglucose pyrophosphorylase are presented. PMID:6316123

Preiss, J; Yung, S G; Baecker, P A

1983-01-01

356

Modulation of the TGF{beta}/Smad signaling pathway in mesangial cells by CTGF/CCN2  

SciTech Connect

Transforming growth factor-beta (TGF{beta}) drives fibrosis in diseases such as diabetic nephropathy (DN). Connective tissue growth factor (CTGF; CCN2) has also been implicated in this, but the molecular mechanism is unknown. We show that CTGF enhances the TGF{beta}/Smad signaling pathway by transcriptional suppression of Smad 7 following rapid and sustained induction of the transcription factor TIEG-1. Smad 7 is a known antagonist of TGF{beta} signaling and TIEG-1 is a known repressor of Smad 7 transcription. CTGF enhanced TGF{beta}-induced phosphorylation and nuclear translocation of Smad 2 and Smad 3 in mesangial cells. Antisense oligonucleotides directed against TIEG-1 prevented CTGF-induced downregulation of Smad 7. CTGF enhanced TGF{beta}-stimulated transcription of the SBE4-Luc reporter gene and this was markedly reduced by TIEG-1 antisense oligonucleotides. Expression of the TGF{beta}-responsive genes PAI-1 and Col III over 48 h was maximally stimulated by TGF{beta} + CTGF compared to TGF{beta} alone, while CTGF alone had no significant effect. TGF{beta}-stimulated expression of these genes was markedly reduced by both CTGF and TIEG-1 antisense oligonucleotides, consistent with the endogenous induction of CTGF by TGF{beta}. We propose that under pathological conditions, where CTGF expression is elevated, CTGF blocks the negative feedback loop provided by Smad 7, allowing continued activation of the TGF{beta} signaling pathway.

Abdel Wahab, Nadia [Cell and Molecular Biology Section, Division of Biomedical Sciences, Imperial College London, Sir Alexander Fleming Building, South Kensington, London, SW7 2AZ (United Kingdom)]. E-mail: nadia.wahab@imperial.ac.uk; Weston, Benjamin S. [Cell and Molecular Biology Section, Division of Biomedical Sciences, Imperial College London, Sir Alexander Fleming Building, South Kensington, London, SW7 2AZ (United Kingdom); Mason, Roger M. [Cell and Molecular Biology Section, Division of Biomedical Sciences, Imperial College London, Sir Alexander Fleming Building, South Kensington, London, SW7 2AZ (United Kingdom)

2005-07-15

357

Regulation of somatic embryogenesis by plant growth regulators in sugarcane  

Microsoft Academic Search

Effect of plant growth regulators on morphogenesis was studied using callus derived from inflorescence segments of sugarcane\\u000a cv. Co-91010 and CoC-671 cultured on MS medium supplemented with 2,4-D, malt extract, L-glutamine, casein hydroly sate and\\u000a coconut water (CW). Comparison was made of different media combinations of CW (5,10%), kinetin (lmg\\/l), zeatin (0.5mg\\/l) andTDZ\\u000a (0.5mg\\/l) to study callus growth and regeneration.

P. Suprasanna; R. S. Choudhary; N. S. Desai; V. A. Bapat

2005-01-01

358

The evolutionary origins of gene regulation.  

PubMed

One way that organisms cope with constantly changing physical and biological conditions is by regulating the expression of genes and thereby altering protein production. Clearly, altering the protein production to match the environmental demands can be adaptive, but there may be evolutionary barriers to the transition from constitutive expression to regulated expression. In particular, down-regulating a gene when it is not needed means that there will necessarily be a delay in protein production when the protein is up-regulated in the future. We develop a model of simple gene regulation in response to randomly changing environmental conditions. We calculate the long-term behavior of gene expression and determine the fitness consequences of changes in the gene regulation. We then embed this model into a population genetic framework in order to determine the conditions that allow populations to evolve environment-specific transcription rates. The population genetic model follows the evolutionary transition from constitutive expression to regulated expression. There are three distinct possible evolutionary outcomes. The gene may be stuck in the always on position, the gene may first evolve to an intermediate constitutive expression level and then evolve regulation, or regulation can evolve directly from the ancestral state in a smooth fashion. Regulation is most likely to evolve when the costs of mis-expression are low and the transcript decay rate is high. This suggests that genes that have less severe reductions in fitness when mis-expressed are more likely to initially evolve regulation. PMID:20095005

Proulx, Stephen R; Smiley, Michael W

2010-06-15

359

Petroleum: The Petroleum-Spirit (conveyance by Road) Regulations, 1957   

E-print Network

These Regulations consolidate with amendments the regulations specified in Regulation 29. The principal amendment of substance is tbe inclusion of Regulation 16, tbe provisions of which are new and relate to the precautions ...

Her Majesty's Stationary Office

1957-01-01

360

50 CFR 216.4 - Other laws and regulations.  

Code of Federal Regulations, 2010 CFR

...2010-10-01 false Other laws and regulations. 216.4...ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS REGULATIONS...Introduction § 216.4 Other laws and regulations. (a) Federal...or customs. (b) State laws or regulations. See...

2010-10-01

361

Stability issues in IC Low Drop Out voltage regulators  

E-print Network

regulators, and improves transient response and noise performance. Test results from the prototype provide an evaluation of the most important parameters of the regulator: ground current, load regulation, line regulation, output noise and start-up time....

Chava, Krishna Chaitanya

2002-01-01

362

7 CFR 930.51 - Issuance of volume regulations.  

Code of Federal Regulations, 2011 CFR

... 8 2011-01-01 2011-01-01 false Issuance of volume regulations. 930.51 Section 930.51 Agriculture ...Regulating Handling Regulations § 930.51 Issuance of volume regulations. (a) Whenever the Secretary...

2011-01-01

363

7 CFR 930.51 - Issuance of volume regulations.  

Code of Federal Regulations, 2013 CFR

... 8 2013-01-01 2013-01-01 false Issuance of volume regulations. 930.51 Section 930.51 Agriculture ...Regulating Handling Regulations § 930.51 Issuance of volume regulations. (a) Whenever the Secretary...

2013-01-01

364

7 CFR 930.51 - Issuance of volume regulations.  

Code of Federal Regulations, 2012 CFR

... 8 2012-01-01 2012-01-01 false Issuance of volume regulations. 930.51 Section 930.51 Agriculture ...Regulating Handling Regulations § 930.51 Issuance of volume regulations. (a) Whenever the Secretary...

2012-01-01

365

48 CFR 2001.104-2 - Arrangement of the regulations.  

Code of Federal Regulations, 2010 CFR

...2010-10-01 true Arrangement of the regulations. 2001.104-2 Section 2001.104-2 Federal Acquisition Regulations System...REGULATION SYSTEM Purpose, Authority, Issuance 2001.104-2 Arrangement of the regulations....

2010-10-01

366

7 CFR 925.51 - Recommendation for regulation.  

Code of Federal Regulations, 2011 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....

2011-01-01

367

7 CFR 925.51 - Recommendation for regulation.  

Code of Federal Regulations, 2014 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....

2014-01-01

368

7 CFR 925.51 - Recommendation for regulation.  

Code of Federal Regulations, 2010 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....

2010-01-01

369

7 CFR 925.51 - Recommendation for regulation.  

Code of Federal Regulations, 2012 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....

2012-01-01

370

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

371

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

Federal Register 2010, 2011, 2012, 2013, 2014

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

2013-12-12

372

12 CFR 1206.4 - Increased costs of regulation.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Increased costs of regulation. 1206.4 Section 1206...ASSESSMENTS § 1206.4 Increased costs of regulation. (a) Increase for inadequate...to pay additional estimated costs of regulation of that Regulated...

2010-01-01

373

45 CFR 1.1 - Location of HHS regulations.  

Code of Federal Regulations, 2014 CFR

...2014-10-01 2014-10-01 false Location of HHS regulations. 1.1 Section 1.1 Public...Health and Human Services GENERAL ADMINISTRATION HHS'S REGULATIONS § 1.1 Location of HHS regulations. Regulations for HHS's...

2014-10-01

374

45 CFR 1.1 - Location of HHS regulations.  

Code of Federal Regulations, 2011 CFR

...2011-10-01 2011-10-01 false Location of HHS regulations. 1.1 Section 1.1 Public...HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION HHS'S REGULATIONS § 1.1 Location of HHS regulations. Regulations for HHS's...

2011-10-01

375

45 CFR 1.1 - Location of HHS regulations.  

Code of Federal Regulations, 2012 CFR

...2012-10-01 2012-10-01 false Location of HHS regulations. 1.1 Section 1.1 Public...HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION HHS'S REGULATIONS § 1.1 Location of HHS regulations. Regulations for HHS's...

2012-10-01

376

45 CFR 1.1 - Location of HHS regulations.  

Code of Federal Regulations, 2010 CFR

...2010-10-01 2010-10-01 false Location of HHS regulations. 1.1 Section 1.1 Public...HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION HHS'S REGULATIONS § 1.1 Location of HHS regulations. Regulations for HHS's...

2010-10-01

377

45 CFR 1.1 - Location of HHS regulations.  

Code of Federal Regulations, 2013 CFR

...2013-10-01 2013-10-01 false Location of HHS regulations. 1.1 Section 1.1 Public...HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION HHS'S REGULATIONS § 1.1 Location of HHS regulations. Regulations for HHS's...

2013-10-01

378

7 CFR 915.55 - Avocados not subject to regulations.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 2010-01-01 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....

2010-01-01

379

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

380

7 CFR 915.55 - Avocados not subject to regulations.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 2011-01-01 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....

2011-01-01

381

7 CFR 915.55 - Avocados not subject to regulations.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 2012-01-01 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....

2012-01-01

382

7 CFR 915.55 - Avocados not subject to regulations.  

Code of Federal Regulations, 2014 CFR

...2014-01-01 2014-01-01 false Avocados not subject to regulations. 915...NUTS), DEPARTMENT OF AGRICULTURE AVOCADOS GROWN IN SOUTH FLORIDA Order Regulating Handling Regulations § 915.55 Avocados not subject to regulations....

2014-01-01

383

Redox Regulation of Plant Development  

PubMed Central

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

Considine, Michael J.

2014-01-01

384

Regulation of airway mucosal hydration.  

PubMed

Ion channels control the hydration status of the airway epithelium through apical anion secretion and cation absorption, which is accompanied by osmotically obligated water. The key channels in this process are the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), which is principally responsible for Cl(-) secretion by airway epithelial cells, and the epithelial Na(+) channel (ENaC), which is responsible for the absorption of Na ions. In CF, defective CFTR-mediated Cl(-) secretion and an accompanying upregulation in ENaC-mediated Na absorption results in a reduction in airway surface liquid volume, leading to poorly hydrated mucus and impaired mucociliary clearance. Restoration of normal airway hydration by modulation of ion channel activity represents an important therapeutic strategy for CF. CFTR corrector and potentiator compounds are being developed with the aim of recovering normal Cl(-) secretion. Ca(2+)-activated Cl(-) channels (CaCCs) are expressed by the respiratory epithelia and are reported to be functionally upregulated in CF and offer a 'surrogate' pathway for Cl(-) secretion. TMEM16A has recently been described as a CaCC in the airway epithelium and, as such, represents an alternative target for restoring Cl(-) secretion in CF. An alternative therapeutic strategy for CF is to inhibit ENaC, thereby blocking excessive Na absorption. This can be achieved by direct blockade of ENaC or inhibition of the channel-activating proteases (CAPs), whose activity regulates ENaC function. This review will describe the regulation of airway mucosal hydration by ion channels and the efforts currently underway to restore normal mucosal hydration in disease patients by modulating the function of these channels. PMID:22111616

Paisley, Derek; Gosling, Martin; Danahay, Henry

2010-05-01

385

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

386

Regulation of xylem cell fate  

PubMed Central

The vascular system is organized throughout the plant body for transporting water, nutrients, and signaling molecules. During vascular development, xylem, phloem, and procambial/cambial cells are produced in a spatiotemporally organized manner. Several key regulators for xylem cell patterning and differentiation have been discovered, including auxin, cytokinin, CLE peptides, microRNAs, HD-ZIPIIIs, VNDs, and moving transcription factors SHR and AHLs. Recent studies are identifying functional interactions among these factors that ultimately determine xylem cell fate. This review focuses on regulatory networks underlying xylem cell fate determination in root vascular development. PMID:25071798

Kondo, Yuki; Tamaki, Takayuki; Fukuda, Hiroo

2014-01-01

387

Transglutaminase Regulation of Cell Function  

PubMed Central

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

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

2014-01-01

388

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

389

Comment On The TANF Regulation  

NSDL National Science Digital Library

On August 22, 1996, President Clinton signed the "Personal Responsibility and Work Opportunity Reconciliation Act," which established the "Temporary Assistance for Needy Families (TANF) program," designed to replace the longstanding Aid to Families with Dependent Children (AFDC) program. Proposed regulations for the TANF program were issued in the Federal Register on November 20, 1997, and are posted at this site by the US Department of Health and Human Services. There is an open period for public comment from November 20, 1997 through February 18, 1997.

1997-01-01

390

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

391

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

392

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

393

Customary Law in Investment Regulation  

E-print Network

(Article 2). None of these references clearly brings customary law to bear but they do highlight the importance of regulatory powers as well as of the need to develop the law on foreign investment regulation even when that requires disregarding a precedent...                                                                                                                13 Asian Agricultural Products Ltd. v. Republic of Sri Lanka, ICSID Case No. ARB/87/3, Award of 27 June 1990, para. 21 (presided by Dr. A.S. El-Kosheri, a member of the IDI) (“AAPL v. Sri Lanka”). J. E. Viñuales, ‘Customary Law in Investment...

Viñuales, Jorge E.

2014-01-01

394

Post-Transcriptional Regulators of microRNA Biogenesis Regulate Pathogenesis - Pavel Sumazin, TCGA Scientific Symposium 2011  

Cancer.gov

Home News and Events Multimedia Library Videos Post-Transcriptional Regulators of microRNA Biogenesis Regulate Pathogenesis - Pavel Sumazin Post-Transcriptional Regulators of microRNA Biogenesis Regulate Pathogenesis - Pavel Sumazin, TCGA Scientific

395

Regulating dynamin dynamics during endocytosis  

PubMed Central

Dynamin is a large GTPase that mediates plasma membrane fission during clathrin-mediated endocytosis. Dynamin assembles into polymers on the necks of budding membranes in cells and has been shown to undergo GTP-dependent conformational changes that lead to membrane fission in vitro. Recent efforts have shed new light on the mechanisms of dynamin-mediated fission, yet exactly how dynamin performs this function in vivo is still not fully understood. Dynamin interacts with a number of proteins during the endocytic process. These interactions are mediated by the C-terminal proline-rich domain (PRD) of dynamin binding to SH3 domain-containing proteins. Three of these dynamin-binding partners (intersectin, amphiphysin and endophilin) have been shown to play important roles in the clathrin-mediated endocytosis process. They promote dynamin-mediated plasma membrane fission by regulating three important sequential steps in the process: recruitment of dynamin to sites of endocytosis; assembly of dynamin into a functional fission complex at the necks of clathrin-coated pits (CCPs); and regulation of dynamin-stimulated GTPase activity, a key requirement for fission. PMID:25374663

Sundborger, Anna C.

2014-01-01

396

Purinergic regulation of epithelial transport  

PubMed Central

Purinergic receptors are a family of ubiquitous transmembrane receptors comprising two classes, P1 and P2 receptors, which are activated by adenosine and extracellular nucleotides (i.e. ATP, ADP, UTP and UDP), respectively. These receptors play a significant role in regulating ion transport in epithelial tissues through a variety of intracellular signalling pathways. Activation of these receptors is partially dependent on ATP (or UTP) release from cells and its subsequent metabolism, and this release can be triggered by a number of stimuli, often in the setting of cellular damage. The function of P2Y receptor stimulation is primarily via signalling through the Gq/PLC-? pathway and subsequent activation of Ca2+-dependent ion channels. P1 signalling is complex, with each of the four P1 receptors A1, A2A, A2B, and A3 having a unique role in different epithelial tissue types. In colonic epithelium the A2B receptor plays a prominent role in regulating Cl? and water secretion. In airway epithelium, A2B and A1 receptors are implicated in the control of Cl? and other currents. In the renal tubular epithelium, A1, A2A, and A3 receptors have all been identified as playing a role in controlling the ionic composition of the lumenal fluid. Here we discuss the intracellular signalling pathways for each of these receptors in various epithelial tissues and their roles in pathophysiological conditions such as cystic fibrosis. PMID:14694149

Bucheimer, R Elaine; Linden, Joel

2004-01-01

397

Transcriptional regulation of tenascin genes.  

PubMed

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

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

2015-01-01

398

Non-Circadian Expression Masking Clock-Driven Weak Transcription Rhythms in U2OS Cells  

PubMed Central

U2OS cells harbor a circadian clock but express only a few rhythmic genes in constant conditions. We identified 3040 binding sites of the circadian regulators BMAL1, CLOCK and CRY1 in the U2OS genome. Most binding sites even in promoters do not correlate with detectable rhythmic transcript levels. Luciferase fusions reveal that the circadian clock supports robust but low amplitude transcription rhythms of representative promoters. However, rhythmic transcription of these potentially clock-controlled genes is masked by non-circadian transcription that overwrites the weaker contribution of the clock in constant conditions. Our data suggest that U2OS cells harbor an intrinsically rather weak circadian oscillator. The oscillator has the potential to regulate a large number of genes. The contribution of circadian versus non-circadian transcription is dependent on the metabolic state of the cell and may determine the apparent complexity of the circadian transcriptome. PMID:25007071

Hoffmann, Julia; Symul, Laura; Shostak, Anton; Fischer, Tamás; Naef, Felix; Brunner, Michael

2014-01-01

399

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. PMID:24106689

Troxell, Bryan; Hassan, Hosni M.

2013-01-01

400

Hormonal regulation of the hypothalamic melanocortin system  

PubMed Central

Regulation of energy homeostasis is fundamental for life. In animal species and humans, the Central Nervous System (CNS) plays a critical role in such regulation by integrating peripheral signals and modulating behavior and the activity of peripheral organs. A precise interplay between CNS and peripheral signals is necessary for the regulation of food intake and energy expenditure in the maintenance of energy balance. Within the CNS, the hypothalamus is a critical center for monitoring, processing and responding to peripheral signals, including hormones such as ghrelin, leptin, and insulin. Once in the brain, peripheral signals regulate neuronal systems involved in the modulation of energy homeostasis. The main hypothalamic neuronal circuit in the regulation of energy metabolism is the melanocortin system. This review will give a summary of the most recent discoveries on the hormonal regulation of the hypothalamic melanocortin system in the control of energy homeostasis. PMID:25538630

Kim, Jung D.; Leyva, Stephanie; Diano, Sabrina

2014-01-01

401

Congestion control through input rate regulation  

Microsoft Academic Search

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

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

1989-01-01

402

Mothers' strategies for regulating their toddlers' distress  

Microsoft Academic Search

Though theories of emotion regulation acknowledge the important roles of caregivers, few studies have examined parents' strategies for helping children regulate distress. In this study, 140 mothers' strategies were coded during a situation in which their toddlers (12-, 18-, 24- and 32-month-olds) were required to wait (parent-active). Children were also observed in a delay situation in which they regulated distress

Lisa J. Bridges; Jannette M. McMenamy

1998-01-01

403

Circuit Regulates Speed Of dc Motor  

NASA Technical Reports Server (NTRS)

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

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

1990-01-01

404

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)

2012-07-31

405

Circadian Clock Proteins in Mood Regulation  

PubMed Central

Mood regulation is known to be affected by the change of seasons. Recent research findings have suggested that mood regulation may be influenced by the function of circadian clocks. In addition, the activity of brown adipocytes has been hypothesized to contribute to mood regulation. Here, the overarching link to mood disorders might be the circadian clock protein nuclear receptor subfamily 1, group D, member 1. PMID:25610405

Partonen, Timo

2015-01-01

406

Exporting licensing regulations affecting US geothermal firms  

SciTech Connect

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

Not Available

1988-08-01

407

Ultra-Low-Dropout Linear Regulator  

NASA Technical Reports Server (NTRS)

A radiation-tolerant, ultra-low-dropout linear regulator can operate between -150 and 150 C. Prototype components were demonstrated to be performing well after a total ionizing dose of 1 Mrad (Si). Unlike existing components, the linear regulator developed during this activity is unconditionally stable over all operating regimes without the need for an external compensation capacitor. The absence of an external capacitor reduces overall system mass/volume, increases reliability, and lowers cost. Linear regulators generate a precisely controlled voltage for electronic circuits regardless of fluctuations in the load current that the circuit draws from the regulator.

Thornton, Trevor; Lepkowski, William; Wilk, Seth

2011-01-01

408

Cognitive emotion regulation fails the stress test.  

PubMed

Cognitive emotion regulation has been widely shown in the laboratory to be an effective way to alter the nature of emotional responses. Despite its success in experimental contexts, however, we often fail to use these strategies in everyday life where stress is pervasive. The successful execution of cognitive regulation relies on intact executive functioning and engagement of the prefrontal cortex, both of which are rapidly impaired by the deleterious effects of stress. Because it is specifically under stressful conditions that we may benefit most from such deliberate forms of emotion regulation, we tested the efficacy of cognitive regulation after stress exposure. Participants first underwent fear-conditioning, where they learned that one stimulus (CS+) predicted an aversive outcome but another predicted a neutral outcome (CS-). Cognitive regulation training directly followed where participants were taught to regulate fear responses to the aversive stimulus. The next day, participants underwent an acute stress induction or a control task before repeating the fear-conditioning task using these newly acquired regulation skills. Skin conductance served as an index of fear arousal, and salivary ?-amylase and cortisol concentrations were assayed as neuroendocrine markers of stress response. Although groups showed no differences in fear arousal during initial fear learning, nonstressed participants demonstrated robust fear reduction following regulation training, whereas stressed participants showed no such reduction. Our results suggest that stress markedly impairs the cognitive regulation of emotion and highlights critical limitations of this technique to control affective responses under stress. PMID:23980142

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

2013-09-10

409

Mechanotransduction: a major regulator of homeostasis and  

E-print Network

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

Mofrad, Mohammad R. K.

410

Circadian regulation of cellular physiology.  

PubMed

The circadian clock synchronizes behavioral and physiological processes on a daily basis in anticipation of the light-dark cycle. In mammals, molecular clocks are present in both the central pacemaker neurons and in nearly all peripheral tissues. Clock transcription factors in metabolic tissues coordinate metabolic fuel utilization and storage with alternating periods of feeding and fasting corresponding to the rest-activity cycle. In vitro and in vivo biochemical approaches have led to the discovery of mechanisms underlying the interplay between the molecular clock and the metabolic networks. For example, recent studies have demonstrated that the circadian clock controls rhythmic synthesis of the cofactor nicotinamide adenine dinucleotide (NAD(+)) and activity of NAD(+)-dependent sirtuin deacetylase enzymes to regulate mitochondrial function across the circadian cycle. In this chapter, we review current state-of-the-art methods to analyze circadian cycles in mitochondrial bioenergetics, glycolysis, and nucleotide metabolism in both cell-based and animal models. PMID:25707277

Peek, C B; Ramsey, K M; Levine, D C; Marcheva, B; Perelis, M; Bass, J

2015-01-01

411

Metabolic Regulation of T Lymphocytes  

PubMed Central

T cell activation leads to dramatic shifts in cell metabolism to protect against pathogens and to orchestrate the action of other immune cells. Quiescent T cells require predominantly ATP-generating processes, whereas proliferating effector T cells require high metabolic flux through growth-promoting pathways. Further, functionally distinct T cell subsets require distinct energetic and biosynthetic pathways to support their specific functional needs. Pathways that control immune cell function and metabolism are intimately linked, and changes in cell metabolism at both the cell and system levels have been shown to enhance or suppress specific T cell functions. As a result of these findings, cell metabolism is now appreciated as a key regulator of T cell function specification and fate. This review discusses the role of cellular metabolism in T cell development, activation, differentiation, and function to highlight the clinical relevance and opportunities for therapeutic interventions that may be used to disrupt immune pathogenesis. PMID:23298210

MacIver, Nancie J.; Michalek, Ryan D.; Rathmell, Jeffrey C.

2013-01-01

412

Social bonding: regulation by neuropeptides  

PubMed Central

Affiliative social relationships (e.g., among spouses, family members, and friends) play an essential role in human society. These relationships affect psychological, physiological, and behavioral functions. As positive and enduring bonds are critical for the overall well-being of humans, it is not surprising that considerable effort has been made to study the neurobiological mechanisms that underlie social bonding behaviors. The present review details the involvement of the nonapeptides, oxytocin (OT), and arginine vasopressin (AVP), in the regulation of social bonding in mammals including humans. In particular, we will discuss the role of OT and AVP in the formation of social bonds between partners of a mating pair as well as between parents and their offspring. Furthermore, the role of OT and AVP in the formation of interpersonal bonding involving trust is also discussed. PMID:25009457

Lieberwirth, Claudia; Wang, Zuoxin

2014-01-01

413

Redox Regulation of Mitochondrial Function  

PubMed Central

Abstract Redox-dependent processes influence most cellular functions, such as differentiation, proliferation, and apoptosis. Mitochondria are at the center of these processes, as mitochondria both generate reactive oxygen species (ROS) that drive redox-sensitive events and respond to ROS-mediated changes in the cellular redox state. In this review, we examine the regulation of cellular ROS, their modes of production and removal, and the redox-sensitive targets that are modified by their flux. In particular, we focus on the actions of redox-sensitive targets that alter mitochondrial function and the role of these redox modifications on metabolism, mitochondrial biogenesis, receptor-mediated signaling, and apoptotic pathways. We also consider the role of mitochondria in modulating these pathways, and discuss how redox-dependent events may contribute to pathobiology by altering mitochondrial function. Antioxid. Redox Signal. 16, 1323–1367. PMID:22146081

Handy, Diane E.

2012-01-01

414

Epigenetic Regulation by Heritable RNA  

PubMed Central

Genomic concepts are based on the assumption that phenotypes arise from the expression of genetic variants. However, the presence of non-Mendelian inheritance patterns provides a direct challenge to this view and suggests an important role for alternative mechanisms of gene regulation and inheritance. Over the past few years, a highly complex and diverse network of noncoding RNAs has been discovered. Research in animal models has shown that RNAs can be inherited and that RNA methyltransferases can be important for the transmission and expression of modified phenotypes in the next generation. We discuss possible mechanisms of RNA-mediated inheritance and the role of these mechanisms for human health and disease. PMID:24743450

Liebers, Reinhard; Rassoulzadegan, Minoo; Lyko, Frank

2014-01-01

415

Transcriptional regulation of wound inflammation.  

PubMed

The attraction and activation of immune cells is an important response of the skin to injury and allows an efficient defense against invading pathogens. In addition, immune cells fulfill various functions that are important for the repair process. An exaggerated inflammatory response, however, is a hallmark of chronic, non-healing wounds. Therefore, it is essential to strictly control and coordinate the levels and activities of various immune cells in normal and wounded skin. Recent studies provided insight into the molecular mechanisms underlying the inflammatory response after wounding, and various transcriptional regulators involved in this process have been identified. This review summarizes our current knowledge on the function of different transcription factors in wound repair, with particular emphasis on proteins with a documented role in the control of wound inflammation. PMID:24556599

Haertel, Eric; Werner, Sabine; Schäfer, Matthias

2014-08-01

416

Implementing CITES regulations for timber.  

PubMed

Foresters are currently confronted with a new challenge. For the first time a commonly traded timber species has been listed on the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). At the 12th Conference of the Parties in November 2002, countries voted 68 to 30 to place the premier timber species of Latin America, big-leaf mahogany (Swietenia macrophylla King [Meliaceae]), on CITES Appendix II. Under Appendix II regulations, trade in mahogany requires that exporting countries verify that each shipment was legally obtained and that its harvest was non-detrimental to the survival of the species. Unfortunately, implementation has been weak, in part because countries have yet to develop a common, pragmatic, cost-effective system to make the legal and non-detriment findings. This paper recommends what such a system might include. PMID:17489241

Blundell, Arthur G

2007-03-01

417

Fibronectin regulates calvarial osteoblast differentiation  

NASA Technical Reports Server (NTRS)

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

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

1996-01-01

418

Environmental Statistics and Optimal Regulation  

NASA Astrophysics Data System (ADS)

Any organism is embedded in an environment that changes over time. The timescale for and statistics of environmental change, the precision with which the organism can detect its environment, and the costs and benefits of particular protein expression levels all will affect the suitability of different strategies-such as constitutive expression or graded response-for regulating protein levels in response to environmental inputs. We propose a general framework-here specifically applied to the enzymatic regulation of metabolism in response to changing concentrations of a basic nutrient-to predict the optimal regulatory strategy given the statistics of fluctuations in the environment and measurement apparatus, respectively, and the costs associated with enzyme production. We use this framework to address three fundamental questions: (i) when a cell should prefer thresholding to a graded response; (ii) when there is a fitness advantage to implementing a Bayesian decision rule; and (iii) when retaining memory of the past provides a selective advantage. We specifically find that: (i) relative convexity of enzyme expression cost and benefit influences the fitness of thresholding or graded responses; (ii) intermediate levels of measurement uncertainty call for a sophisticated Bayesian decision rule; and (iii) in dynamic contexts, intermediate levels of uncertainty call for retaining memory of the past. Statistical properties of the environment, such as variability and correlation times, set optimal biochemical parameters, such as thresholds and decay rates in signaling pathways. Our framework provides a theoretical basis for interpreting molecular signal processing algorithms and a classification scheme that organizes known regulatory strategies and may help conceptualize heretofore unknown ones.

Sivak, David A.; Thomson, Matt

2015-01-01

419

Cellular ADMA: regulation and action.  

PubMed

Asymmetric (N(G),N(G)) dimethylarginine (ADMA) is present in plasma and cells. It can inhibit nitric oxide synthase (NOS) that generates nitric oxide (NO) and cationic amino acid transporters (CATs) that supply intracellular NOS with its substrate, l-arginine, from the plasma. Therefore, ADMA and its transport mechanisms are strategically placed to regulate endothelial function. This could have considerable clinical impact since endothelial dysfunction has been detected at the origin of hypertension and chronic kidney disease (CKD) in human subjects and may be a harbinger of large vessel disease and cardiovascular disease (CVD). Indeed, plasma levels of ADMA are increased in many studies of patients at risk for, or with overt CKD or CVD. However, the levels of ADMA measured in plasma of about 0.5micromol.l(-1) may be below those required to inhibit NOS whose substrate, l-arginine, is present in concentrations many fold above the Km for NOS. However, NOS activity may be partially inhibited by cellular ADMA. Therefore, the cellular production of ADMA by protein arginine methyltransferase (PRMT) and protein hydrolysis, its degradation by N(G),N(G)-dimethylarginine dimethylaminohydrolase (DDAH) and its transmembrane transport by CAT that determines intracellular levels of ADMA may also determine the state of activation of NOS. This is the focus of the review. It is concluded that cellular levels of ADMA can be 5- to 20-fold above those in plasma and in a range that could tonically inhibit NOS. The relative importance of PRMT, DDAH and CAT for determining the intracellular NOS substrate:inhibitor ratio (l-arginine:ADMA) may vary according to the pathophysiologic circumstance. An understanding of this important balance requires knowledge of these three processes that regulate the intracellular levels of ADMA and arginine. PMID:19682580

Teerlink, Tom; Luo, Zaiming; Palm, Fredrik; Wilcox, Christopher S

2009-12-01

420

Fibronectin regulates calvarial osteoblast differentiation.  

PubMed

The secretion of fibronectin by differentiating osteoblasts and its accumulation at sites of osteogenesis suggest that fibronectin participates in bone formation. To test this directly, we determined whether fibronectin-cell interactions regulate progressive differentiation of cultured fetal rat calvarial osteoblasts. Spatial distributions of alpha 5 integrin subunit, fibronectin, osteopontin (bone sialoprotein I) and osteocalcin (bone Gla-protein) were similar in fetal rat calvaria and mineralized, bone-like nodules formed by cultured osteoblasts. Addition of anti-fibronectin antibodies to cultures at confluence reduced subsequent formation of nodules to less than 10% of control values, showing that fibronectin is required for normal nodule morphogenesis. Anti-fibronectin antibodies selectively inhibited steady-state expression of mRNA for genes associated with osteoblast differentiation; mRNA levels for alkaline phosphatase and osteocalcin were suppressed, whereas fibronectin, type I collagen and osteopontin were unaffected. To identify functionally relevant domains of fibronectin, we treated cells with soluble fibronectin fragments and peptides. Cell-binding fibronectin fragments (type III repeats 6-10) containing the Arg-Gly-Asp (RGD) sequence blocked both nodule initiation and maturation, whether or not they contained a functional synergy site. In contrast, addition of the RGD-containing peptide GRGDSPK alone did not inhibit nodule initiation, although it did block nodule maturation. Thus, in addition to the RGD sequence, other features of the large cell-binding fragments contribute to the full osteogenic effects of fibronectin. Nodule formation and osteoblast differentiation resumed after anti-fibronectin antibodies or GRGDSPK peptides were omitted from the media, showing that the inhibition was reversible and the treatments were not cytotoxic. Outside the central cell-binding domain, peptides from the IIICS region and antibodies to the N terminus did not inhibit nodule formation. We conclude that osteoblasts interact with the central cell-binding domain of endogenously produced fibronectin during early stages of differentiation, and that these interactions regulate both normal morphogenesis and gene expression. PMID:8799825

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

1996-06-01

421

Environmental Statistics and Optimal Regulation  

PubMed Central

Any organism is embedded in an environment that changes over time. The timescale for and statistics of environmental change, the precision with which the organism can detect its environment, and the costs and benefits of particular protein expression levels all will affect the suitability of different strategies–such as constitutive expression or graded response–for regulating protein levels in response to environmental inputs. We propose a general framework–here specifically applied to the enzymatic regulation of metabolism in response to changing concentrations of a basic nutrient–to predict the optimal regulatory strategy given the statistics of fluctuations in the environment and measurement apparatus, respectively, and the costs associated with enzyme production. We use this framework to address three fundamental questions: (i) when a cell should prefer thresholding to a graded response; (ii) when there is a fitness advantage to implementing a Bayesian decision rule; and (iii) when retaining memory of the past provides a selective advantage. We specifically find that: (i) relative convexity of enzyme expression cost and benefit influences the fitness of thresholding or graded responses; (ii) intermediate levels of measurement uncertainty call for a sophisticated Bayesian decision rule; and (iii) in dynamic contexts, intermediate levels of uncertainty call for retaining memory of the past. Statistical properties of the environment, such as variability and correlation times, set optimal biochemical parameters, such as thresholds and decay rates in signaling pathways. Our framework provides a theoretical basis for interpreting molecular signal processing algorithms and a classification scheme that organizes known regulatory strategies and may help conceptualize heretofore unknown ones. PMID:25254493

2014-01-01

422

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

Code of Federal Regulations, 2013 CFR

...Federal Property Management Regulations; Interim Rule D-1 Appendix to Subchapter D Public Contracts and Property Management Federal...REGULATIONS PUBLIC BUILDINGS AND SPACE Ch. 101, Subch. D, App. Appendix to Subchapter D—Temporary...

2013-07-01

423

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

Code of Federal Regulations, 2012 CFR

...Federal Property Management Regulations; Interim Rule D-1 Appendix to Subchapter D Public Contracts and Property Management Federal...REGULATIONS PUBLIC BUILDINGS AND SPACE Ch. 101, Subch. D, App. Appendix to Subchapter D—Temporary...

2012-07-01

424

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

Code of Federal Regulations, 2014 CFR

...Federal Property Management Regulations; Interim Rule D-1 Appendix to Subchapter D Public Contracts and Property Management Federal...REGULATIONS PUBLIC BUILDINGS AND SPACE Ch. 101, Subch. D, App. Appendix to Subchapter D—Temporary...

2014-07-01

425

Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice  

PubMed Central

The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study. PMID:25414776

Moon, Eunjung; Lee, Sung Ok; Kang, Tong Ho; Kim, Hye Ju; Choi, Sang Zin; Son, Mi-Won; Kim, Sun Yeou

2014-01-01

426

Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice.  

PubMed

The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study. PMID:25414776

Moon, Eunjung; Lee, Sung Ok; Kang, Tong Ho; Kim, Hye Ju; Choi, Sang Zin; Son, Mi-Won; Kim, Sun Yeou

2014-09-01

427

SRC-2 is an essential coactivator for orchastrating metabolism and circadian rhythm  

Technology Transfer Automated Retrieval System (TEKTRAN)

Synchrony of the mammalian circadian clock is achieved by complex transcriptional and translational feedback loops centered on the BMAL1:CLOCK heterodimer. Modulation of circadian feedback loops is essential for maintaining rhythmicity, yet the role of transcriptional coactivators in driving BMAL1:C...

428

Quantifying the relative importance of flow regulation and grain size regulation of suspended sediment transport and  

E-print Network

sediment can be the most important factor regulating sediment transport. It might be argued that the keyQuantifying the relative importance of flow regulation and grain size regulation of suspended sediment transport and tracking changes in grain size of bed sediment David M. Rubin U.S. Geological Survey

429

Executive Pay Regulation: What Regulators, Shareholders, and Managers Can Learn from Major Sports Leagues  

Microsoft Academic Search

Executive pay regulation is widely discussed as a measure to reduce financial mismanagement in corporations. We show that the professional team sports industry, the only industry with substantial experience in the regulation of compensation arrangements, provides valuable insights for the regulation of executive pay. Based on the experience from professional sports leagues, we develop implications for the corporate sector regarding

Helmut Dietl; Tobias Duschl; Markus Lang

2011-01-01

430

Executive Pay Regulation: What Regulators, Shareholders, and Managers Can Learn from Major Sports Leagues  

Microsoft Academic Search

Executive pay regulation is widely discussed as a measure to reduce financial mismanagement in corporations. We show that the professional team sports industry, the only industry with substantial experience in the regulation of compensation arrangements, provides valuable insights for the regulation of executive pay. Based on the experience from professional sports leagues, we develop implications for the corporate sector regarding

Helmut Dietl; Tobias Duschl; Markus Lang

2010-01-01

431

Better regulation and enterprise: the case of environmental health risk regulation in Britain  

Microsoft Academic Search

Proposals for ‘better regulation’ and the policy dynamics behind them are examined with respect to the implications for the regulation of environmental health risks in smaller enterprises in Britain. Although better regulation has involved a fluid and rapidly changing discourse across the European Union, the regulatory reform agenda has recently refocused on competitiveness, simplification of targets and the reduction of

Ian Vickers

2008-01-01

432

43 CFR 2568.21 - Do other regulations directly apply to these regulations?  

Code of Federal Regulations, 2012 CFR

...regulations directly apply to these regulations? Yes. The regulations implementing the Native Allotment Act of 1906, 43 CFR Subpart 2561, also apply to Alaska Native Veteran Allotments to the extent they are not inconsistent with section 41 of ANCSA or other...

2012-10-01

433

43 CFR 2568.21 - Do other regulations directly apply to these regulations?  

Code of Federal Regulations, 2014 CFR

...regulations directly apply to these regulations? Yes. The regulations implementing the Native Allotment Act of 1906, 43 CFR Subpart 2561, also apply to Alaska Native Veteran Allotments to the extent they are not inconsistent with section 41 of ANCSA or other...

2014-10-01

434

43 CFR 2568.21 - Do other regulations directly apply to these regulations?  

Code of Federal Regulations, 2013 CFR

...regulations directly apply to these regulations? Yes. The regulations implementing the Native Allotment Act of 1906, 43 CFR Subpart 2561, also apply to Alaska Native Veteran Allotments to the extent they are not inconsistent with section 41 of ANCSA or other...

2013-10-01

435

43 CFR 2568.21 - Do other regulations directly apply to these regulations?  

Code of Federal Regulations, 2011 CFR

...regulations directly apply to these regulations? Yes. The regulations implementing the Native Allotment Act of 1906, 43 CFR Subpart 2561, also apply to Alaska Native Veteran Allotments to the extent they are not inconsistent with section 41 of ANCSA or other...

2011-10-01

436

Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents  

Microsoft Academic Search

A B S T R AC T The cystic fibrosis transmembrane conductance regulator (CFTR) is a C1- channel that is regulated by cAMP-dependent phosphorylation and by intracel- lular ATP. Intracellular ATP also regulates a class of K + channels that have a distinct pharmacology: they are inhibited by sulfonylureas and activated by a novel class of drugs called K ÷

DAVID N. SHEPPARD; MICHAEL J. WEmH

1992-01-01

437

Erratic Black Hole Regulates Itself  

NASA Astrophysics Data System (ADS)

New results from NASA's Chandra X-ray Observatory have made a major advance in explaining how a special class of black holes may shut off the high-speed jets they produce. These results suggest that these black holes have a mechanism for regulating the rate at which they grow. Black holes come in many sizes: the supermassive ones, including those in quasars, which weigh in at millions to billions of times the mass of the Sun, and the much smaller stellar-mass black holes which have measured masses in the range of about 7 to 25 times the Sun's mass. Some stellar-mass black holes launch powerful jets of particles and radiation, like seen in quasars, and are called "micro-quasars". The new study looks at a famous micro-quasar in our own Galaxy, and regions close to its event horizon, or point of no return. This system, GRS 1915+105 (GRS 1915 for short), contains a black hole about 14 times the mass of the Sun that is feeding off material from a nearby companion star. As the material swirls toward the black hole, an accretion disk forms. This system shows remarkably unpredictable and complicated variability ranging from timescales of seconds to months, including 14 different patterns of variation. These variations are caused by a poorly understood connection between the disk and the radio jet seen in GRS 1915. Chandra, with its spectrograph, has observed GRS 1915 eleven times since its launch in 1999. These studies reveal that the jet in GRS 1915 may be periodically choked off when a hot wind, seen in X-rays, is driven off the accretion disk around the black hole. The wind is believed to shut down the jet by depriving it of matter that would have otherwise fueled it. Conversely, once the wind dies down, the jet can re-emerge. "We think the jet and wind around this black hole are in a sort of tug of war," said Joseph Neilsen, Harvard graduate student and lead author of the paper appearing in the journal Nature. "Sometimes one is winning and then, for reasons we don't entirely understand, the other one gets the upper hand." GRS 1915+105 Chandra X-ray Image of GRS 1915+105 The latest Chandra results also show that the wind and the jet carry about the same amount of matter away from the black hole. This is evidence that the black hole is somehow regulating its accretion rate, which may be related to the toggling between mass expulsion via either a jet or a wind from the accretion disk. Self-regulation is a common topic when discussing supermassive black holes, but this is the first clear evidence for it in stellar-mass black holes. "It is exciting that we may be on the track of explaining two mysteries at the same time: how black hole jets can be shut down and also how black holes regulate their growth," said co-author Julia Lee, assistant professor in the Astronomy department at the Harvard-Smithsonian Center for Astrophysics. "Maybe black holes can regulate themselves better than the financial markets!" Although micro-quasars and quasars differ in mass by factors of millions, they should show a similarity in behavior when their very different physical scales are taken into account. People Who Read This Also Read... Chandra Data Reveal Rapidly Whirling Black Holes Jet Power and Black Hole Assortment Revealed in New Chandra Image Celebrate the International Year of Astronomy Ghost Remains After Black Hole Eruption "If quasars and micro-quasars behave very differently, then we have a big problem to figure out why, because gravity treats them the same," said Neilsen. "So, our result is actually very reassuring, because it's one more link between these different types of black holes." The timescale for changes in behavior of a black hole should vary in proportion to the mass. For example, an hour-long timescale for changes in GRS 1915 would correspond to about 10,000 years for a supermassive black hole that weighs a billion times the mass of the Sun. "We cannot hope to explore at this level of detail in any single supermassive black hole system," said L

2009-03-01

438

Regulations which require employee training: An overview  

SciTech Connect

In order to identify the Occupational Safety and Health Administration (OSHA) regulations which apply to a certain plant or facility, one needs to find the reference materials that are needed and that can be trusted. An overview is presented of the following: Title 29 -- Labor, OSHA Training Requirements; Title 40, Environmental Protection Agency Training Requirements; and Title 49, Department of Transportation Training Regulations.

Gilfus, L.J.

1995-11-01

439

Animal Physiology Plasma Glucose Regulation Lab  

E-print Network

: The two assigned problems represent simplistic predictions of non ­regulation of plasma glucose levels (usually referred to as "blood glucose" or "bG" ­ not exactly correct because the concentrations are basedAnimal Physiology Plasma Glucose Regulation Lab General Description and Questions Introduction

Prestwich, Ken

440

Regulators and effectors of the ARF GTPases  

Microsoft Academic Search

The small G proteins of the ARF family are key regulators of membrane dynamics. Many functions of ARF proteins in cells are being revealed by studies of their regulators and effectors. Significant progress has been made over the past year, with the identification of a surprisingly large family of novel ARF GTPase-activating proteins. In addition, two new classes of effectors,

Julie G Donaldson; Catherine L Jackson

2000-01-01

441

Engineer Regulation 1110-2-1150  

E-print Network

CECW-EP Engineer Regulation 1110-2-1150 Department of the Army U.S. Army Corps of Engineers Washington, DC 20314-1000 ER 1110-2-1150 31 August 1999 Engineering and Design ENGINEERING AND DESIGN 1110-2-1150 U.S. Army Corps of Engineers CECW-EP Washington, D.C. 20314-1000 Regulation No. 1110

US Army Corps of Engineers

442

Self-Regulation and Academic Procrastination.  

ERIC Educational Resources Information Center

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

Senecal, Caroline; And Others

1995-01-01

443

REGULATION OF HONEY BEE HOARDING EFFICIENCY  

E-print Network

held a pollen substi- tute. After being stocked with bees, cages were placed in an incubator (35 °C; 50REGULATION OF HONEY BEE HOARDING EFFICIENCY Thomas E. RINDERER Bee Breeding and Stock Center.01). This supports the hypothesis that empty comb volatiles in honey bee nests regulate the acceptance of nectar

Boyer, Edmond

444

California Appliance Efficiency Regulations for Manufacturers  

E-print Network

California Appliance Efficiency Regulations for Manufacturers CEC-400-2012-FS-004-En Updated 3/6/2012 What Manufacturers Need to Know If you manufacture or distribute certain types of new products that use requires To verify that covered products meet the regulations, manufacturers must: · Testthe products using

445

Regulation of chromatin by histone modifications  

Microsoft Academic Search

Chromatin is not an inert structure, but rather an instructive DNA scaffold that can respond to external cues to regulate the many uses of DNA. A principle component of chromatin that plays a key role in this regulation is the modification of histones. There is an ever-growing list of these modifications and the complexity of their action is only just

Andrew J Bannister; Tony Kouzarides

2011-01-01

446

the benefits and costs of regulating benzene  

Microsoft Academic Search

In the area of chemical regulation, where twelve statutes authorize regulation by four agencies, the need for evaluation and review is particularly apparent. Benzene, which is of interest to three agencies, the Enviromental Protection Agency, the Consumer Product Safety Commission, and the Occupational Safety and Health Administration, is the subject of this case study.The proposed benzene standards (except for intentional

Ralph H. Luken; Stephen G. Miller

1981-01-01

447

INNOVATION AND REGULATION IN THE PESTICIDE INDUSTRY  

Microsoft Academic Search

This paper examines the impact of pesticide regulation on the number of new pesticide registrations and pesticide toxicity. Results suggest that regulation adversely affects new pesticide introductions but encourages the development of pesticides with fewer toxic side effects. The estimated regression model implies that a 10% increase in regulatory costs (about $1.5 million per pesticide) causes a 5% reduction in

Michael Ollinger; Jorge Fernandez-Cornejo

1998-01-01

448

REGULATIONS OF THE UNIVERSITY OF FLORIDA  

E-print Network

1 REGULATIONS OF THE UNIVERSITY OF FLORIDA 3.0421 Employee Debt Collection. (1) Purpose owed to the University by its current or former employees. These collection procedures do not apply if the student thereafter becomes an employee of the University. (2) For purposes of this regulation, employee

Pilyugin, Sergei S.

449

Regulation of withdrawals in individual account systems  

Microsoft Academic Search

Funded mandatory pension systems based on individual accounts are spreading around the world. With the maturation of those systems, regulating the withdrawal of retirement savings will become increasingly important. Government regulation of withdrawals should mandate the purchase of inflation-indexed life annuities exceeding income available from government welfare programs for the retiree and potential survivors. However, proper functioning of insurance markets

Jan Walliser

2000-01-01

450

Regulation of Withdrawals in Individual Account Systems  

Microsoft Academic Search

Funded mandatory pension systems based on individual accounts are spreading around the world. With the maturation of these systems, regulating the withdrawal of retirement savings will become increasingly important. Government regulation of withdrawals should mandate the purchase of inflation-indexed life annuities exceeding income available from government welfare programs for the retiree and potential survivors. Proper functioning of insurance markets does

Jan Walliser

1999-01-01

451

Molecular mechanisms of caspase regulation during apoptosis  

Microsoft Academic Search

Caspases, which are the executioners of apoptosis, comprise two distinct classes, the initiators and the effectors. Although general structural features are shared between the initiator and the effector caspases, their activation, inhibition and release of inhibition are differentially regulated. Biochemical and structural studies have led to important advances in understanding the underlying molecular mechanisms of caspase regulation. This article reviews

Stefan J. Riedl; Yigong Shi

2004-01-01

452

Higher Education Regulations Study: Preliminary Findings  

ERIC Educational Resources Information Center

In the "Higher Education Opportunity Act" of 2008, Congress charged the Advisory Committee on Student Financial Assistance with conducting a review and analysis of regulations affecting higher education, to determine the extent to which regulations are overly burdensome and need to be streamlined, improved, or eliminated. Specifically, Congress…

Advisory Committee on Student Financial Assistance, 2011

2011-01-01

453

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

454

ENVIRONMENTAL REGULATIONS AND TECHNOLOGY - THE ELECTROPLATING INDUSTRY  

EPA Science Inventory

This 44-page Technology Transfer Environmental Regulations and Technology publication is an update of a 1980 EPA publication that has been revised to reflect changes in the EPA regulations, as well as in the pollution control technologies that affect the electroplating industry. ...

455

MAPPING GASOLINE REQUIREMENTS, APPLICABLE REGULATIONS AND BANS  

EPA Science Inventory

Federal and State regulations play an important role in understanding gasoline composition around the United States. Multiple sources of information on these programs were used to develop reliable, up-to-date maps showing gasoline requirements imposed by various regulations. Th...

456

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

457

7 CFR 984.49 - Volume regulation.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 2010-01-01 false Volume regulation. 984.49 Section 984...Handling Marketing Policy § 984.49 Volume regulation. (a) Free, reserve...it finds that there is an insufficient volume of reserve walnuts available for...

2010-01-01

458

7 CFR 984.49 - Volume regulation.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 2012-01-01 false Volume regulation. 984.49 Section 984...Handling Marketing Policy § 984.49 Volume regulation. (a) Free, reserve...it finds that there is an insufficient volume of reserve walnuts available for...

2012-01-01

459

7 CFR 984.49 - Volume regulation.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 2013-01-01 false Volume regulation. 984.49 Section 984...Handling Marketing Policy § 984.49 Volume regulation. (a) Free, reserve...it finds that there is an insufficient volume of reserve walnuts available for...

2013-01-01

460

7 CFR 984.49 - Volume regulation.  

Code of Federal Regulations, 2014 CFR

...2014-01-01 2014-01-01 false Volume regulation. 984.49 Section 984...Handling Marketing Policy § 984.49 Volume regulation. (a) Free, reserve...it finds that there is an insufficient volume of reserve walnuts available for...

2014-01-01

461

7 CFR 984.49 - Volume regulation.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 2011-01-01 false Volume regulation. 984.49 Section 984...Handling Marketing Policy § 984.49 Volume regulation. (a) Free, reserve...it finds that there is an insufficient volume of reserve walnuts available for...

2011-01-01

462

Optimizing Web Service Composition While Enforcing Regulations  

E-print Network

Ilraith Department of Computer Science, University of Toronto, Toronto, Canada {shirin,sheila}@cs.toronto with enforcement of regulations, perhaps in the form of corpo- rate policies and/or government regulations including e-science (e.g., [1]), e-government (e.g., [2]), and Grid computing (e.g., [3]). A WSC template

McIlraith, Sheila

463

The Kidney and Acid-Base Regulation  

ERIC Educational Resources Information Center

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

Koeppen, Bruce M.

2009-01-01

464

Stress Hormones: Their Interaction and Regulation  

Microsoft Academic Search

Stress stimulates several adaptive hormonal responses. Prominent among these responses are the secretion of catecholamines from the adrenal medulla, corticosteroids from the adrenal cortex, and adrenocorticotropin from the anterior pituitary. A number of complex interactions are involved in the regulation of these hormones. Glucocorticoids regulate catecholamine biosynthesis in the adrenal medulla and catecholamines stimulate adrenocorticotropin release from the anterior pituitary.

Julius Axelrod; Terry D. Reisine

1984-01-01

465

Epigenetic regulation of aging stem cells  

Microsoft Academic Search

The function of adult tissue-specific stem cells declines with age, which may contribute to the physiological decline in tissue homeostasis and the increased risk of neoplasm during aging. Old stem cells can be ‘rejuvenated’ by environmental stimuli in some cases, raising the possibility that a subset of age-dependent stem cell changes is regulated by reversible mechanisms. Epigenetic regulators are good

E A Pollina; A Brunet

2011-01-01

466

Regulation of skin color in apples  

Microsoft Academic Search

The literature of the regulation of color in apple skin is reviewed and compared with current knowledge of the regulation of flower color.Color in apple skin is a blend of various amounts of chlorophyll, carotenoids, and anthocyanins\\/flavonols. A variety of red colors are produced by cyanidin glycosides copigmented with flavonols and other compounds. The concentration and identification of flavonols, proanthocyanidins,

J. E. Lancaster; Donald K. Dougall

1992-01-01

467

Higher Education Regulations Study: Final Report  

ERIC Educational Resources Information Center

In the "Higher Education Opportunity Act" of 2008, Congress charged the Advisory Committee on Student Financial Assistance with conducting a review and analysis of regulations affecting higher education to determine the extent to which regulations are overly burdensome and need to be streamlined, improved, or eliminated. Specifically, Congress…

Advisory Committee on Student Financial Assistance, 2011

2011-01-01

468

Self-Regulation: Calm, Alert, and Learning  

ERIC Educational Resources Information Center

There is a growing awareness among developmental scientists that the better a child can self-regulate, the better she can rise to the challenge of mastering ever more complex skills and concepts. In the simplest terms, self-regulation can be defined as the ability to stay calmly focused and alert, which often involves--but cannot be reduced…

Shanker, Stuart

2010-01-01

469

Emotion Regulation and Childhood Aggression: Longitudinal Associations  

ERIC Educational Resources Information Center

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

Roll, Judith; Koglin, Ute; Petermann, Franz

2012-01-01

470

Methylation: a regulator of HIV-1 replication?  

PubMed Central

Recent characterizations of methyl transferases as regulators of cellular processes have spurred investigations into how methylation events might influence the HIV-1 life cycle. Emerging evidence suggests that protein-methylation can positively and negatively regulate HIV-1 replication. How DNA- and RNA- methylation might impact HIV-1 is also discussed. PMID:17274823

Yedavalli, Venkat RK; Jeang, Kuan-Teh

2007-01-01

471

Designing Freedom, Regulating a Nation: Socialist Cybernetics  

E-print Network

in Chile during the socialist presidency of Salvador Allende (1970­1973) to regulate the growing social property area and manage the transition of Chile's economy from capitalism to socialism. Under the guidanceDesigning Freedom, Regulating a Nation: Socialist Cybernetics in Allende's Chile* EDEN MEDINA

Medina, Eden

472

Plasma Glucose Regulation, p. 1 Animal Physiology  

E-print Network

Plasma Glucose Regulation, p. 1 Animal Physiology Plasma Glucose Regulation How to Obtain Blood to not spill blood all over the place! (f) Now get a fresh piece of cotton and be ready. #12;Plasma Glucose for a dash in the middle and several seconds later your blood glucose value will be displayed in mg glucose

Prestwich, Ken

473

Cayne Dunnett Memorial Scholarship REGULATIONS FOR 2014  

E-print Network

Cayne Dunnett Memorial Scholarship REGULATIONS FOR 2014 BACKGROUND This Scholarship was established in Taxation, 1994 Ernst and Young Memorial Scholarship. He also represented Waikato in the NZ Universities. This Scholarship is offered by the BNZ in his name. REGULATIONS 1. This Scholarship is open for applications from

Waikato, University of

474

A Guide to Federal Reserve Regulations.  

ERIC Educational Resources Information Center

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

Federal Reserve Bank of New York, NY.

475

Regulation of force in vascular smooth muscle  

Microsoft Academic Search

Vascular smooth muscle contraction plays a defining role in the regulation and maintenance of blood pressure, and its deregulation is associated with many clinical syndromes including hypertension, coronary vasospasm and congestive heart failure. Over the past 20 years, there has been a growing understanding of the regulation of 20 kDa myosin light chain phosphorylation by myosin light chain kinase and

Ozgur Ogut; Frank V. Brozovich

2003-01-01

476

Transcriptional Regulation and its Misregulation in Disease  

PubMed Central

The gene expression programs that establish and maintain specific cell states in humans are controlled by thousands of transcription factors, cofactors and chromatin regulators. Misregulation of these gene expression programs can cause a broad range of diseases. Here we review recent advances in our understanding of transcriptional regulation and discuss how these have provided new insights into transcriptional misregulation in disease. PMID:23498934

Lee, Tong Ihn; Young, Richard A.

2013-01-01

477

Input filter compensation for switching regulators  

NASA Technical Reports Server (NTRS)

Problems caused by input filter interaction and conventional input filter design techniques are discussed. The concept of feedforward control is modeled with an input filter and a buck regulator. Experimental measurement and comparison to the analytical predictions is carried out. Transient response and the use of a feedforward loop to stabilize the regulator system is described. Other possible applications for feedforward control are included.

Lee, F. C.

1984-01-01

478

AUTONOMOUS REGULATION OF FREE CA2+ CONCENTRATIONS  

E-print Network

AUTONOMOUS REGULATION OF FREE CA2+ CONCENTRATIONS IN ISOLATED PLANT CELL NUCLEI: A MATHEMATICAL] or nuclei [5-7]. Nuclei are separated from the other cell compartments by a double membrane system and cytosolic calcium may be regulated independently. In nuclei of HepG2 cells, nuclear calcium signals may

Paris-Sud XI, Université de

479

Translational Control via Protein-Regulated Upstream  

E-print Network

Translational Control via Protein-Regulated Upstream Open Reading Frames Jan Medenbach,1 Markus of the regulation of msl-2 mRNA by Sex lethal (SXL), which is critical for dosage compensa- tion in Drosophila, has reading frames (uORFs), and interaction sites for RNA-binding proteins. We show that SXL binding

Bedwell, David M.

480

Cardiac Vagal Regulation and Early Peer Status  

ERIC Educational Resources Information Center

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

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

2007-01-01

481

Gas flow rate control regulator valve  

Microsoft Academic Search

An improved gas flow rate control regulator valve is described for a gas burning furnace for maintaining an optimum precombustion air to gas mass ratio over a wide range of air and gas flows within the combustion chamber of the furnace for efficient burning therewithin. The regulator valve consists of: a valve housing having a gas influent chamber; a gas

Belknap

1986-01-01

482

Pressure regulating and relief valve assembly  

Microsoft Academic Search

A pressure regulating and relief valve assembly, such as an assembly positionable in a lower portion of a well casing are disclosed. The valve assembly has a main relief valve assembly or back pressure regulator that is designed to open when the steam pressure exceeds a first predetermined value. A secondary relief valve assembly is provided to vent excess pressure

W. J. Nicholl; J. H. Leggett; J. R. Shychick

1984-01-01

483

Labor Regulations and European Private Equity  

Microsoft Academic Search

European nations substitute between employment protection regulations and labor market expenditures (e.g., unemployment insurance benefits) for providing worker insurance. Employment regulations more directly tax firms making frequent labor adjustments than other labor insurance mechanisms. Venture capital and private equity investors are especially sensitive to these labor adjustment costs. Nations favoring labor expenditures as the mechanism for providing worker insurance developed

Ant Bozkaya; William R. Kerr

2009-01-01

484

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

485

Insights from Experimental Economics for Market Regulation  

Microsoft Academic Search

We present selected results in experimental economics with relevance for market regulation and derive from them concrete insights that could be interesting for regulating authorities. For those readers that are new to experimental economics, the purposes and advantages of economic experiments are discussed and the experimental double-auction market is described in detail to serve as a benchmark example. The experimental

M. Krause; S. Kröger; J. J. M. Potters

2004-01-01

486

Design of allosterically regulated protein catalysts.  

PubMed

Activity of allosteric protein catalysts is regulated by an external stimulus, such as protein or small molecule binding, light activation, pH change, etc., at a location away from the active site of the enzyme. Since its original introduction in 1961, the concept of allosteric regulation has undergone substantial expansion, and many, if not most, enzymes have been shown to possess some degree of allosteric regulation. The ability to create new catalysts that can be turned on and off using allosteric interactions would greatly expand the chemical biology toolbox and will allow for detection of environmental pollutants and disease biomarkers and facilitate studies of cellular processes and metal homeostasis. Thus, design of allosterically regulated protein catalysts represents an actively growing area of research. In this paper, we describe various approaches to achieving regulation of catalysis. PMID:25642601

Makhlynets, Olga V; Raymond, Elizabeth A; Korendovych, Ivan V

2015-02-24

487

Shale gas development: a smart regulation framework.  

PubMed

Advances in directional drilling and hydraulic fracturing have sparked a natural gas boom from shale formations in the United States. Regulators face a rapidly changing industry comprised of hundreds of players, operating tens of thousands of wells across 30 states. They are often challenged to respond by budget cuts, a brain drain to industry, regulations designed for conventional gas developments, insufficient information, and deeply polarized debates about hydraulic fracturing and its regulation. As a result, shale gas governance remains a halting patchwork of rules, undermining opportunities to effectively characterize and mitigate development risk. The situation is dynamic, with research and incremental regulatory advances underway. Into this mix, we offer the CO/RE framework--characterization of risk, optimization of mitigation strategies, regulation, and enforcement--to design tailored governance strategies. We then apply CO/RE to three types of shale gas risks, to illustrate its potential utility to regulators. PMID:24564674

Konschnik, Katherine E; Boling, Mark K

2014-08-01

488

Regulation of Plasma Membrane Recycling by CFTR  

NASA Astrophysics Data System (ADS)

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

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