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Sample records for tieg1 regulates bmal1

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

    SciTech Connect

    Miyake, Masato; Hayashi, Shinichiro; Iwasaki, Shunsuke; Chao, Guozheng; Takahashi, Hideyuki; Watanabe, Kouichi; Ohwada, Shyuichi; Aso, Hisashi; Yamaguchi, Takahiro

    2010-03-19

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Shirai, Hidenori; Oishi, Katsutaka; Ishida, Norio . E-mail: n.ishida@aist.go.jp

    2006-12-15

    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.

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

    SciTech Connect

    Oiwa, Ako; Kakizawa, Tomoko . E-mail: tkaki@hsp.md.shinshu-u.ac.jp; Miyamoto, Takahide; Yamashita, Koh; Jiang, Wei; Takeda, Teiji; Suzuki, Satoru; Hashizume, Kiyoshi

    2007-02-23

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

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

    SciTech Connect

    Haddad, Oualid; Gumez, Laurie; Hawse, John R.; Subramaniam, Malayannan; Spelsberg, Thomas C.; Bensamoun, Sabine F.

    2011-07-15

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

  6. Role of the clock gene Bmal1 and the gastric ghrelin-secreting cell in the circadian regulation of the ghrelin-GOAT system

    PubMed Central

    Laermans, J.; Vancleef, L.; Tack, J.; Depoortere, I.

    2015-01-01

    As adequate food intake is crucial to survival, organisms have evolved endogenous circadian clocks to generate optimal temporal patterns of food-related behavior and physiology. The gastric ghrelin-secreting cell is thought to be part of this network of peripheral food-entrainable oscillators (FEOs), regulating the circadian release of this orexigenic peptide. This study aimed to determine the role of the core clock gene Bmal1 and the gastric ghrelin-secreting cell as an FEO in the circadian rhythmicity of ghrelin expression and secretion in vivo and in vitro. Bmal1-deficient mice not only lacked circadian rhythmicity in plasma ghrelin levels and food intake, but also showed decreased gastric mRNA expression of ghrelin and ghrelin O-acyltransferase (GOAT), the ghrelin activating enzyme. Furthermore, in the absence of the hypothalamic master clock, food-related stimuli entrained the molecular clock of gastric ghrelinoma cells to regulate the rhythmic release of ghrelin. Divergent responses in octanoyl and total ghrelin release towards different food cues were observed, suggesting that the FEO also regulates the circadian rhythmicity of GOAT. Collectively, these findings indicate that circadian rhythmicity of ghrelin signaling requires Bmal1 and is driven by a food-responsive clock in the gastric ghrelin-secreting cell that not only regulates ghrelin, but also GOAT activity. PMID:26576661

  7. Role of the clock gene Bmal1 and the gastric ghrelin-secreting cell in the circadian regulation of the ghrelin-GOAT system.

    PubMed

    Laermans, J; Vancleef, L; Tack, J; Depoortere, I

    2015-01-01

    As adequate food intake is crucial to survival, organisms have evolved endogenous circadian clocks to generate optimal temporal patterns of food-related behavior and physiology. The gastric ghrelin-secreting cell is thought to be part of this network of peripheral food-entrainable oscillators (FEOs), regulating the circadian release of this orexigenic peptide. This study aimed to determine the role of the core clock gene Bmal1 and the gastric ghrelin-secreting cell as an FEO in the circadian rhythmicity of ghrelin expression and secretion in vivo and in vitro. Bmal1-deficient mice not only lacked circadian rhythmicity in plasma ghrelin levels and food intake, but also showed decreased gastric mRNA expression of ghrelin and ghrelin O-acyltransferase (GOAT), the ghrelin activating enzyme. Furthermore, in the absence of the hypothalamic master clock, food-related stimuli entrained the molecular clock of gastric ghrelinoma cells to regulate the rhythmic release of ghrelin. Divergent responses in octanoyl and total ghrelin release towards different food cues were observed, suggesting that the FEO also regulates the circadian rhythmicity of GOAT. Collectively, these findings indicate that circadian rhythmicity of ghrelin signaling requires Bmal1 and is driven by a food-responsive clock in the gastric ghrelin-secreting cell that not only regulates ghrelin, but also GOAT activity. PMID:26576661

  8. A Novel Bmal1 Mutant Mouse Reveals Essential Roles of the C-Terminal Domain on Circadian Rhythms

    PubMed Central

    Cheon, Solmi; Row, Hansang; Lee, Jiyeon; Han, Dong-Hee; Cho, Sehyung; Kim, Kyungjin

    2015-01-01

    The mammalian circadian clock is an endogenous biological timer comprised of transcriptional/translational feedback loops of clock genes. Bmal1 encodes an indispensable transcription factor for the generation of circadian rhythms. Here, we report a new circadian mutant mouse from gene-trapped embryonic stem cells harboring a C-terminus truncated Bmal1 (Bmal1GT?C) allele. The homozygous mutant (Bmal1GT?C/GT?C) mice immediately lost circadian behavioral rhythms under constant darkness. The heterozygous (Bmal1+/GT?C) mice displayed a gradual loss of rhythms, in contrast to Bmal1+/- mice where rhythms were sustained. Bmal1GT?C/GT?C mice also showed arrhythmic mRNA and protein expression in the SCN and liver. Lack of circadian reporter oscillation was also observed in cultured fibroblast cells, indicating that the arrhythmicity of Bmal1GT?C/GT?C mice resulted from impaired molecular clock machinery. Expression of clock genes exhibited distinct responses to the mutant allele in Bmal1+/GT?C and Bmal1GT?C/GT?C mice. Despite normal cellular localization and heterodimerization with CLOCK, overexpressed BMAL1GT?C was unable to activate transcription of Per1 promoter and BMAL1-dependent CLOCK degradation. These results indicate that the C-terminal region of Bmal1 has pivotal roles in the regulation of circadian rhythms and the Bmal1GT?C mice constitute a novel model system to evaluate circadian functional mechanism of BMAL1. PMID:26394143

  9. CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Control the Mammalian Circadian Clock

    PubMed Central

    Tamaru, Teruya; Hattori, Mitsuru; Honda, Kousuke; Nakahata, Yasukazu; Sassone-Corsi, Paolo; van der Horst, Gijsbertus T. J.; Ozawa, Takeaki; Takamatsu, Ken

    2015-01-01

    Intracellular circadian clocks, composed of clock genes that act in transcription-translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we established a pivotal role for casein kinase (CK)-2-mediated circadian BMAL1-Ser90 phosphorylation (BMAL1-P) in regulating central and peripheral core clocks. Subsequent analysis of the underlying mechanism showed a novel role of CRY as a repressor for protein kinase. Co-immunoprecipitation experiments and real-time monitoring of protein–protein interactions revealed that CRY-mediated periodic binding of CK2? to BMAL1 inhibits BMAL1-Ser90 phosphorylation by CK2?. The FAD binding domain of CRY1, two C-terminal BMAL1 domains, and particularly BMAL1-Lys537 acetylation/deacetylation by CLOCK/SIRT1, were shown to be critical for CRY-mediated BMAL1–CK2? binding. Reciprocally, BMAL1-Ser90 phosphorylation is prerequisite for BMAL1-Lys537 acetylation. We propose a dual negative-feedback model in which a CRY-dependent CK2-driven posttranslational BMAL1–P-BMAL1 loop is an integral part of the core clock oscillator. PMID:26562092

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

    PubMed

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

    2014-09-12

    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

  11. Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway

    PubMed Central

    JUNG, CHAN-HUN; KIM, EUN MI; PARK, JONG KUK; HWANG, SANG-GU; MOON, SUNG-KWON; KIM, WUN-JAE; UM, HONG-DUCK

    2013-01-01

    Bmal1 is a core factor in the regulation of circadian rhythms. Previous studies have shown that Bmal1 suppresses tumor growth in cell culture and animal models and is down-regulated in certain types of cancer. The aim of the present study was to investigated whether Bmal1 influences the invasiveness of cancer cells. We demonstrated that knockdown of Bmal1 by RNA interference promoted cancer cell invasion, whereas its overexpression reduced cellular invasiveness. These effects were observed in lung cancer and glioma cells, and occurred regardless of p53 status. Therefore, it appears that Bmal1 suppresses the invasion of multiple cancer types in a p53-independent manner. Bmal1 knockdown-induced cancer cell invasion was accompanied by activation of the PI3K-Akt-MMP-2 pathway, and was prevented by inhibitors of PI3K, Akt or MMP-2. This suggests that Bmal1 suppresses cell invasion by blocking the PI3K-Akt-MMP-2 pathway. Since this invasion pathway is activated by the oncogene Bcl-w, we investigated whether Bmal1 affects the activity of Bcl-w. As expected, Bmal1 attenuated the ability of Bcl-w to promote MMP-2 accumulation and cell invasion, supporting the idea that Bmal1 antagonizes Bcl-w activity. Collectively, our data suggest that Bmal1 is a tumor suppressor, capable of suppressing cancer cell growth and invasiveness, and support the recent proposal that there is a tight molecular link between circadian rhythms and tumor formation/progression. PMID:23563360

  12. OVEREXPRESSION OF BOTH CLOCK AND BMAL1 INHIBITS ENTRY TO S PHASE IN HUMAN COLON CANCER CELLS.

    PubMed

    Sakamoto, Wataru; Takenoshita, Seiichi

    2015-12-19

    Many physiological, biochemical and behavioral processes operate under the circadian rhythm, which is generated by an internal time-keeping mechanism commonly referred to as the biological clock, in almost all organisms from bacteria to mammals. The core circadian oscillator is composed of an autoregulatory transcription-translation feedback loop, in which CLOCK and BMAL1 are positive regulators. A cell has two mechanisms, "cell cycle" and "cell rhythm", the relationship between which remains controversial. Therefore, the aim of this study was to explore the effect of Clock and Bmal1 on cell cycle, especially on the G1 phase, using vectors with the tetracycline operator-repressor system. The present study revealed that simultaneous induction of Bmal1 and Clock had an influential effect on the cell cycle in SW480/T-REx/Clock/Bmal1 cells, in which both Clock and Bmal1 could be induced by tetracycline. The observation that induction of both Clock and Bmal1 inhibited cell growth and the significant increase of the G1 phase proportion of in SW480/T-REx/Clock/Bmal1 cells indicated that entry from the G1 to S phase was inhibited by the induction of Clock and Bmal1. Furthermore, overexpression of Clock and Bmal1 prevented the cells from entering into the G2/M phase induced by Paclitaxel, and made the cells more resistant to the agent. In conclusion, we found that overexpression of both Clock and Bmal1 suppressed cell growth. In addition, the present study raised the possibility that Clock and Bmal1 may in part play a role in preventing the cells from entering G1 to S phase of cell cycle via suppression of CyclinD1 expression, and thus acquiring resistance to Paclitaxel. PMID:26370682

  13. Premature aging of the hippocampal neurogenic niche in adult Bmal1? deficient mice

    PubMed Central

    Ali, Amira A. H.; Schwarz?Herzke, Beryl; Stahr, Anna; Prozorovski, Timour; Aktas, Orhan; von Gall, Charlotte

    2015-01-01

    Hippocampal neurogenesis undergoes dramatic age?related changes. Mice with targeted deletion of the clock gene Bmal1 (Bmal1?/?) show disrupted regulation of reactive oxygen species homeostasis, accelerated aging, neurodegeneration and cognitive deficits. As proliferation of neuronal progenitor/precursor cells (NPCs) is enhanced in young Bmal1?/? mice, we tested the hypothesis that this results in premature aging of hippocampal neurogenic niche in adult Bmal1?/? mice as compared to wildtype littermates. We found significantly reduced pool of hippocampal NPCs, scattered distribution, enhanced survival of NPCs and an increased differentiation of NPCs into the astroglial lineage at the expense of the neuronal lineage. Immunoreaction of the redox sensitive histone deacetylase Sirtuine 1, peroxisomal membrane protein at 70kDa and expression of the cell cycle inhibitor p21 Waf1/CIP1 were increased in adult Bmal1?/? mice. In conclusion, genetic disruption of the molecular clockwork leads to accelerated age?dependent decline in adult neurogenesis presumably as a consequence of oxidative stress. PMID:26142744

  14. Vascular PPARgamma controls circadian variation in blood pressure and heart rate through Bmal1.

    PubMed

    Wang, Ningning; Yang, Guangrui; Jia, Zhanjun; Zhang, Hui; Aoyagi, Toshinori; Soodvilai, Sunhapas; Symons, J David; Schnermann, Jurgen B; Gonzalez, Frank J; Litwin, Sheldon E; Yang, Tianxin

    2008-12-01

    Thiazolidinediones (TZDs) are PPARgamma activators that exhibit vasculoprotective properties. To determine the vascular function of PPARgamma, we analyzed Tie2Cre/flox and SM22Cre/flox mice. Unexpectedly, both knockout strains exhibited a significant reduction of circadian variations in blood pressure and heart rate in parallel with diminished variations in urinary norepinephrine/epinephrine excretion and impaired rhythmicity of the canonical clock genes, including Bmal1. PPARgamma expression in the aorta exhibited a robust rhythmicity with a more than 20-fold change during the light/dark cycle. Rosiglitazone treatment induced aortic expression of Bmal1 mRNA, and ChIP and promoter assays revealed that Bmal1 is a direct PPARgamma target gene. These studies have uncovered a role for vascular PPARgamma as a peripheral factor participating in regulation of cardiovascular rhythms. PMID:19041764

  15. Dual attenuation of proteasomal and autophagic BMAL1 degradation in Clock?19/+ mice contributes to improved glucose homeostasis

    PubMed Central

    Jeong, Kwon; He, Baokun; Nohara, Kazunari; Park, Noheon; Shin, Youngmin; Kim, Seonghwa; Shimomura, Kazuhiro; Koike, Nobuya; Yoo, Seung-Hee; Chen, Zheng

    2015-01-01

    Circadian clocks orchestrate essential physiology in response to various cues, yet their mechanistic and functional plasticity remains unclear. Here, we investigated Clock?19/+ heterozygous (Clk/+) mice, known to display lengthened periodicity and dampened amplitude, as a model of partially perturbed clocks. Interestingly, Clk/+ mice exhibited improved glycemic control and resistance to circadian period lengthening under high-fat diet (HFD). Furthermore, BMAL1 protein levels in Clk/+ mouse liver were upregulated compared with wild-type (WT) mice under HFD. Pharmacological and molecular studies showed that BMAL1 turnover entailed proteasomal and autophagic activities, and CLOCK?19 attenuated both processes. Consistent with an important role of BMAL1 in glycemic control, enhanced activation of insulin signaling was observed in Clk/+ mice relative to WT in HFD. Finally, transcriptome analysis revealed reprogramming of clock-controlled metabolic genes in Clk/+ mice. Our results demonstrate a novel role of autophagy in circadian regulation and reveal an unforeseen plasticity of circadian and metabolic networks. PMID:26228022

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-02-01

    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

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

    PubMed Central

    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

    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

  19. Progressive Arthropathy in Mice With a Targeted Disruption of the Mop3/Bmal-1 Locus

    E-print Network

    Bradfield, Christopher A.

    ARTICLE Progressive Arthropathy in Mice With a Targeted Disruption of the Mop3/Bmal-1 Locus Maureen 2004 Summary: Disruption of the murine Mop3 (also known as Bmal1 or Arntl) locus results in a loss of behavioral and molecular circadian rhythms. Although Mop3 null mice do not display anomalies in early

  20. The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity.

    PubMed

    Dudek, Michal; Gossan, Nicole; Yang, Nan; Im, Hee-Jeong; Ruckshanthi, Jayalath P D; Yoshitane, Hikari; Li, Xin; Jin, Ding; Wang, Ping; Boudiffa, Maya; Bellantuono, Ilaria; Fukada, Yoshitaka; Boot-Handford, Ray P; Meng, Qing-Jun

    2016-01-01

    Osteoarthritis (OA) is the most prevalent and debilitating joint disease, and there are currently no effective disease-modifying treatments available. Multiple risk factors for OA, such as aging, result in progressive damage and loss of articular cartilage. Autonomous circadian clocks have been identified in mouse cartilage, and environmental disruption of circadian rhythms in mice predisposes animals to OA-like damage. However, the contribution of the cartilage clock mechanisms to the maintenance of tissue homeostasis is still unclear. Here, we have shown that expression of the core clock transcription factor BMAL1 is disrupted in human OA cartilage and in aged mouse cartilage. Furthermore, targeted Bmal1 ablation in mouse chondrocytes abolished their circadian rhythm and caused progressive degeneration of articular cartilage. We determined that BMAL1 directs the circadian expression of many genes implicated in cartilage homeostasis, including those involved in catabolic, anabolic, and apoptotic pathways. Loss of BMAL1 reduced the levels of phosphorylated SMAD2/3 (p-SMAD2/3) and NFATC2 and decreased expression of the major matrix-related genes Sox9, Acan, and Col2a1, but increased p-SMAD1/5 levels. Together, these results define a regulatory mechanism that links chondrocyte BMAL1 to the maintenance and repair of cartilage and suggest that circadian rhythm disruption is a risk factor for joint diseases such as OA. PMID:26657859

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    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

    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

  4. Cardiomyocyte-specific Bmal1 deletion in mice triggers diastolic dysfunction, extracellular matrix response, and impaired resolution of inflammation.

    PubMed

    Ingle, Kevin A; Kain, Vasundhara; Goel, Mehak; Prabhu, Sumanth D; Young, Martin E; Halade, Ganesh V

    2015-12-01

    The mammalian circadian clock consists of multiple transcriptional regulators that coordinate biological processes in a time-of-day-dependent manner. Cardiomyocyte-specific deletion of the circadian clock component, Bmal1 (aryl hydrocarbon receptor nuclear translocator-like protein 1), leads to age-dependent dilated cardiomyopathy and decreased lifespan in mice. We investigated whether cardiomyocyte-specific Bmal1 knockout (CBK) mice display early alterations in cardiac diastolic function, extracellular matrix (ECM) remodeling, and inflammation modulators by investigating CBK mice and littermate controls at 8 and 28 wk of age (i.e., prior to overt systolic dysfunction). Left ventricles of CBK mice exhibited (P < 0.05): 1) progressive abnormal diastolic septal annular wall motion and reduced pulmonary venous flow only at 28 wk of age; 2) progressive worsening of fibrosis in the interstitial and endocardial regions from 8 to 28 wk of age; 3) increased (>1.5 fold) expression of collagen I and III, as well as the matrix metalloproteinases MMP-9, MMP-13, and MMP-14 at 28 wk of age; 4) increased transcript levels of neutrophil chemotaxis and leukocyte migration genes (Ccl2, Ccl8, Cxcl2, Cxcl1, Cxcr2, Il1?) with no change in Il-10 and Il-13 genes expression; and 5) decreased levels of 5-LOX, HO-1 and COX-2, enzymes indicating impaired resolution of inflammation. In conclusion, genetic disruption of the cardiomyocyte circadian clock results in diastolic dysfunction, adverse ECM remodeling, and proinflammatory gene expression profiles in the mouse heart, indicating signs of early cardiac aging in CBK mice. PMID:26432841

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

    PubMed

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

    2013-01-23

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-09-15

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

  8. Histone monoubiquitination by Clock-Bmal1 complex marks Per1 and Per2 genes for circadian feedback.

    PubMed

    Tamayo, Alfred G; Duong, Hao A; Robles, Maria S; Mann, Matthias; Weitz, Charles J

    2015-10-01

    Circadian rhythms in mammals are driven by a feedback loop in which the transcription factor Clock-Bmal1 activates expression of Per and Cry proteins, which together form a large nuclear complex (Per complex) that represses Clock-Bmal1 activity. We found that mouse Clock-Bmal1 recruits the Ddb1-Cullin-4 ubiquitin ligase to Per (Per1 and Per2), Cry (Cry1 and Cry2) and other circadian target genes. Histone H2B monoubiquitination at Per genes was rhythmic and depended on Bmal1, Ddb1 and Cullin-4a. Depletion of Ddb1-Cullin-4a or an independent decrease in H2B monoubiquitination caused defective circadian feedback and decreased the association of the Per complex with DNA-bound Clock-Bmal1. Clock-Bmal1 thus covalently marks Per genes for subsequent recruitment of the Per complex. Our results reveal a chromatin-mediated signal from the positive to the negative limb of the clock that provides a licensing mechanism for circadian feedback. PMID:26323038

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

    NASA Astrophysics Data System (ADS)

    Li, Ying; Liu, Zengrong

    2015-07-01

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

  10. The harmala alkaloid harmine is a modulator of circadian Bmal1 transcription.

    PubMed

    Onishi, Yoshiaki; Oishi, Katsutaka; Kawano, Yasuhiro; Yamazaki, Yoshimitsu

    2012-02-01

    Biological rhythms are orchestrated by a cell-autonomous clock system that drives the rhythmic cascade of clock genes. We established an assay system using NIH 3T3 cells stably expressing the Bmal1 promoter-driven luciferase reporter gene and used it to analyse circadian oscillation of the gene. Modulators of PKC (protein kinase C) revealed that an activator and an inhibitor represented short- and long-period phenotypes respectively which were consistent with reported effects of PKC on the circadian clock and validated the assay system. We examined the effects of the alkaloid harmine, contained in Hoasca, which has a wide spectrum of pharmacological actions, on circadian rhythms using the validated assay system. Harmine dose dependently elongated the period. Furthermore, EMSA (electrophoretic mobility-shift assay) and Western-blot analysis showed that harmine enhanced the transactivating function of ROR? (retinoid-related orphan receptor ?), probably by increasing its nuclear translocation. Exogenous expression of ROR? also caused a long period, confirming the phenotype indicated by harmine. These results suggest that harmine extends the circadian period by enhancing ROR? function and that harmine is a new candidate that contributes to the control of period length in mammalian cells. PMID:21401525

  11. Histone mono-ubiquitination by a Clock–Bmal1 complex marks Per1 and Per2 genes for circadian feedback

    PubMed Central

    Tamayo, Alfred G.; Duong, Hao A.; Robles, Maria S.; Mann, Matthias; Weitz, Charles J.

    2015-01-01

    Circadian rhythms in mammals are driven by a feedback loop in which the transcription factor Clock–Bmal1 activates expression of Per and Cry proteins, which together form a large nuclear complex (Per complex) that represses Clock–Bmal1 activity. We found that mouse Clock–Bmal1 recruits the Ddb1–Cullin-4 ubiquitin ligase to Per, Cry, and other circadian target genes. Histone 2B mono-ubiquitination at Per genes was rhythmic and depended on Bmal1, Ddb1, and Cullin-4a. Depletion of Ddb1–Cullin-4a or independent reduction of Histone 2B mono-ubiquitination caused defective circadian feedback and reduced the association of the Per complex with DNA-bound Clock–Bmal1. Clock–Bmal1 thus covalently marks Per genes for subsequent recruitment of the Per complex. Our results reveal a chromatin-mediated signal from the positive to the negative limb of the clock that provides a licensing mechanism for circadian feedback. PMID:26323038

  12. 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 ...

  13. The peripheral clock regulates human pigmentation.

    PubMed

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

    2015-04-01

    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

  14. Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

    PubMed Central

    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

    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

  15. Circadian regulation of myocardial sarcomeric Titin-cap (Tcap, telethonin): identification of cardiac clock-controlled genes using open access bioinformatics data.

    PubMed

    Podobed, Peter S; Alibhai, Faisal J; Chow, Chi-Wing; Martino, Tami A

    2014-01-01

    Circadian rhythms are important for healthy cardiovascular physiology and are regulated at the molecular level by a circadian clock mechanism. We and others previously demonstrated that 9-13% of the cardiac transcriptome is rhythmic over 24 h daily cycles; the heart is genetically a different organ day versus night. However, which rhythmic mRNAs are regulated by the circadian mechanism is not known. Here, we used open access bioinformatics databases to identify 94 transcripts with expression profiles characteristic of CLOCK and BMAL1 targeted genes, using the CircaDB website and JTK_Cycle. Moreover, 22 were highly expressed in the heart as determined by the BioGPS website. Furthermore, 5 heart-enriched genes had human/mouse conserved CLOCK:BMAL1 promoter binding sites (E-boxes), as determined by UCSC table browser, circadian mammalian promoter/enhancer database PEDB, and the European Bioinformatics Institute alignment tool (EMBOSS). Lastly, we validated findings by demonstrating that Titin cap (Tcap, telethonin) was targeted by transcriptional activators CLOCK and BMAL1 by showing 1) Tcap mRNA and TCAP protein had a diurnal rhythm in murine heart; 2) cardiac Tcap mRNA was rhythmic in animals kept in constant darkness; 3) Tcap and control Per2 mRNA expression and cyclic amplitude were blunted in Clock(?19/?19) hearts; 4) BMAL1 bound to the Tcap promoter by ChIP assay; 5) BMAL1 bound to Tcap promoter E-boxes by biotinylated oligonucleotide assay; and 6) CLOCK and BMAL1 induced tcap expression by luciferase reporter assay. Thus this study identifies circadian regulated genes in silico, with validation of Tcap, a critical regulator of cardiac Z-disc sarcomeric structure and function. PMID:25121604

  16. Circadian Clock Genes Contribute to the Regulation of Hair Follicle Cycling

    E-print Network

    Ihler, Alexander

    cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadianCircadian Clock Genes Contribute to the Regulation of Hair Follicle Cycling Kevin K. Lin1

  17. Circadian Rhythms Regulate Amelogenesis

    PubMed Central

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

    2013-01-01

    Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24h) intervals both at RNA and protein levels. This study also reveals that two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stage of amelogenesis might be under circadian control. Changes in clock genes expression patterns might result in significant alterations of enamel apposition and mineralization. PMID:23486183

  18. Pancreatic ? cell enhancers regulate rhythmic transcription of genes controlling insulin secretion.

    PubMed

    Perelis, Mark; Marcheva, Biliana; Ramsey, Kathryn Moynihan; Schipma, Matthew J; Hutchison, Alan L; Taguchi, Akihiko; Peek, Clara Bien; Hong, Heekyung; Huang, Wenyu; Omura, Chiaki; Allred, Amanda L; Bradfield, Christopher A; Dinner, Aaron R; Barish, Grant D; Bass, Joseph

    2015-11-01

    The mammalian transcription factors CLOCK and BMAL1 are essential components of the molecular clock that coordinate behavior and metabolism with the solar cycle. Genetic or environmental perturbation of circadian cycles contributes to metabolic disorders including type 2 diabetes. To study the impact of the cell-autonomous clock on pancreatic ? cell function, we examined pancreatic islets from mice with either intact or disrupted BMAL1 expression both throughout life and limited to adulthood. We found pronounced oscillation of insulin secretion that was synchronized with the expression of genes encoding secretory machinery and signaling factors that regulate insulin release. CLOCK/BMAL1 colocalized with the pancreatic transcription factor PDX1 within active enhancers distinct from those controlling rhythmic metabolic gene networks in liver. We also found that ? cell clock ablation in adult mice caused severe glucose intolerance. Thus, cell type-specific enhancers underlie the circadian control of peripheral metabolism throughout life and may help to explain its dysregulation in diabetes. PMID:26542580

  19. TGF? Inducible Early Gene-1 Plays an Important Role in Mediating Estrogen Signaling in the Skeleton

    PubMed Central

    Hawse, John R.; Pitel, Kevin S.; Cicek, Muzaffer; Philbrick, Kenneth A.; Gingery, Anne; Peters, Kenneth D.; Syed, Farhan A.; Ingle, James N.; Suman, Vera J.; Iwaniec, Urszula T.; Turner, Russell T.; Spelsberg, Thomas C.; Subramaniam, Malayannan

    2014-01-01

    TGF? Inducible Early Gene-1 (TIEG1) knockout (KO) mice display a gender specific osteopenic phenotype characterized by low bone mineral density, bone mineral content and overall loss of bone strength in female mice. We therefore speculated that loss of TIEG1 expression would impair the actions of estrogen on bone in female mice. In order to test this hypothesis, we employed an ovariectomy (OVX) and estrogen replacement model system to comprehensively analyze the role of TIEG1 in mediating estrogen signaling in bone at the tissue, cell and biochemical level. DXA, pQCT and micro-CT analyses revealed that loss of TIEG1 expression diminished the effects of estrogen throughout the skeleton and within multiple bone compartments. Estrogen exposure also led to reductions in bone formation rates and mineralizing perimeter in wild-type mice with little to no effects on these parameters in TIEG1 KO mice. Osteoclast perimeter per bone perimeter, and resorptive activity as determined by serum levels of CTX-1, were differentially regulated following estrogen treatment in TIEG1 KO mice compared to wild-type littermates. No significant differences were detected in serum levels of P1NP between wild-type and TIEG1 KO mice. Taken together, these data implicate an important role for TIEG1 in mediating estrogen signaling throughout the mouse skeleton and suggest that defects in this pathway are likely to contribute to the gender specific osteopenic phenotype observed in female TIEG1 KO mice. PMID:24190163

  20. EGR1 regulates hepatic clock gene amplitude by activating Per1 transcription

    PubMed Central

    Tao, Weiwei; Wu, Jing; Zhang, Qian; Lai, Shan-Shan; Jiang, Shan; Jiang, Chen; Xu, Ying; Xue, Bin; Du, Jie; Li, Chao-Jun

    2015-01-01

    The mammalian clock system is composed of a master clock and peripheral clocks. At the molecular level, the rhythm-generating mechanism is controlled by a molecular clock composed of positive and negative feedback loops. However, the underlying mechanisms for molecular clock regulation that affect circadian clock function remain unclear. Here, we show that Egr1 (early growth response 1), an early growth response gene, is expressed in mouse liver in a circadian manner. Consistently, Egr1 is transactivated by the CLOCK/BMAL1 heterodimer through a conserved E-box response element. In hepatocytes, EGR1 regulates the transcription of several core clock genes, including Bmal1, Per1, Per2, Rev-erb? and Rev-erb?, and the rhythm amplitude of their expression is dependent on EGR1’s transcriptional function. Further mechanistic studies indicated that EGR1 binds to the proximal region of the Per1 promoter to activate its transcription directly. When the peripheral clock is altered by light or feeding behavior transposition in Egr1-deficient mice, the expression phase of hepatic clock genes shifts normally, but the amplitude is also altered. Our data reveal a critical role for EGR1 in the regulation of hepatic clock circuitry, which may contribute to the rhythm stability of peripheral clock oscillators. PMID:26471974

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

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

    2012-01-01

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

  3. Regulation of period 1 expression in cultured rat pineal

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  4. 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...

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

    E-print Network

    Bradfield, Christopher A.

    Liua,b , Brian P. Johnsona,b , Anna L. Shena,b , Jacqueline A. Wallissera,b , Kathy J. Krentza the interlocking and synergistic network of the circadian clock and reproductive systems. ovary | circadian rhythm | fertility | steroidogenesis Disruption of circadian rhythms has been implicated in a va- riety of human

  6. The Liver Clock Controls Cholesterol Homeostasis through Trib1 Protein-mediated Regulation of PCSK9/Low Density Lipoprotein Receptor (LDLR) Axis.

    PubMed

    Ma, Di; Liu, Tongyu; Chang, Lin; Rui, Crystal; Xiao, Yuanyuan; Li, Siming; Hogenesch, John B; Chen, Y Eugene; Lin, Jiandie D

    2015-12-25

    Disruption of the body clock has been recognized as a risk factor for cardiovascular disease. How the circadian pacemaker interacts with the genetic factors associated with plasma lipid traits remains poorly understood. Recent genome-wide association studies have identified an expanding list of genetic variants that influence plasma cholesterol and triglyceride levels. Here we analyzed circadian regulation of lipid-associated candidate genes in the liver and identified two distinct groups exhibiting rhythmic and non-rhythmic patterns of expression during light-dark cycles. Liver-specific inactivation of Bmal1 led to elevated plasma LDL/VLDL cholesterol levels as a consequence of the disruption of the PCSK9/LDL receptor regulatory axis. Ablation of the liver clock perturbed diurnal regulation of lipid-associated genes in the liver and markedly reduced the expression of the non-rhythmically expressed gene Trib1. Adenovirus-mediated rescue of Trib1 expression lowered plasma PCSK9 levels, increased LDL receptor protein expression, and restored plasma cholesterol homeostasis in mice lacking a functional liver clock. These results illustrate an unexpected mechanism through which the biological clock regulates cholesterol homeostasis through its regulation of non-rhythmic genes in the liver. PMID:26547624

  7. Regulation of Clock-Controlled Genes in Mammals

    PubMed Central

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

    2009-01-01

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

  8. Involvement of 5-HT? and 5-HT? receptors in the regulation of circadian clock gene expression in mouse small intestine.

    PubMed

    Aoki, Natsumi; Watanabe, Hiroyuki; Okada, Kazuya; Aoki, Kazuyuki; Imanishi, Takuma; Yoshida, Daisuke; Ishikawa, Ryosuke; Shibata, Shigenobu

    2014-01-01

    Several lines of evidence suggest that 5-HT receptors play a critical role in the expression of clock genes in the suprachiasmatic nucleus, the main circadian oscillator in hamsters. The contributions of 5-HT-receptor subtypes in the intestine, where they are expressed at high concentrations, are however not yet clarified. The 5-HT synthesis inhibitor, p-chlorophenylalanine, attenuated the daily rhythm of Per1 and Per2 gene expression in the intestine. Injection of 5-HT and agonists of the 5-HT3 and 5-HT4 receptors increased Per1/Per2 expression and decreased Bmal1 expression in a dose-dependent manner. Although treatment with antagonists of 5-HT3 and 5-HT4 alone did not affect clock gene expression, co-injection of these antagonists with 5-HT blocked the 5-HT-induced changes in clock gene expression. Increased tissue levels of 5-HT due to treatment with the antidepressants clomipramine and fluvoxamine did not affect clock gene expression. The present results suggest that the 5-HT system in the small intestine may play a critical role in regulating circadian rhythms through 5-HT3/5-HT4-receptor activation. PMID:24492464

  9. Clock-Controlled Regulation of the Acute Effects of Norepinephrine on Chick Pineal Melatonin Rhythms.

    PubMed

    Li, Ye; Cassone, Vincent M

    2015-12-01

    The chicken pineal gland synthesizes and releases melatonin rhythmically in light/dark (LD) cycles, with high melatonin levels during the dark phase, and in constant darkness (DD) for several cycles before it gradually damps to arrhythmicity in DD. Daily administration of norepinephrine (NE) in vivo and in vitro prevents the damping and restores the melatonin rhythm. To investigate the role of the circadian clock on melatonin rhythm damping and of its restoration by NE, the effects of NE administration at different phases of the melatonin cycle revealed a robust rhythm in NE sensitivity in which NE efficacy in increasing melatonin amplitude peaked in late subjective night and early subjective day, suggesting a clock underlying NE sensitivity. However, NE itself had no effect on circadian phase or period of the melatonin rhythms. Transcriptional analyses indicated that even though the rhythm of melatonin output damped to arrhythmicity, messenger RNA (mRNA) encoding clock genes gper2, gper3, gBmal1, gclock, gcry1, and gcry2; enzymes associated with melatonin biosynthesis; and enzymes involved in cyclic nucleotide signaling remained robustly rhythmic. Of these, only gADCY1 (adenylate cyclase 1) and gPDE4D (cAMP-specific 3',5'-cyclic phosphodiesterase 4D) were affected by NE administration at the mRNA levels, and only ADCY1 was affected at the protein level. The data strongly suggest that damping of the melatonin rhythm in the chick pineal gland occurs at the posttranscriptional level and that a major role of the clock is to regulate pinealocytes' sensitivity to neuronal input from the brain. PMID:26446873

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

    PubMed

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

    2014-10-01

    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

  11. Library Regulations Library Regulations

    E-print Network

    Birmingham, University of

    -13 Library Regulations `Service' is deemed to include any system whereby Library Services provides accessLibrary 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

  12. SRC-2 is an essential coactivator for orchestrating metabolism and circadian rhythm.

    PubMed

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

    2014-02-27

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

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

    SciTech Connect

    Nakabayashi, Hiroko; Ohta, Yasuharu Yamamoto, Masayoshi; Susuki, Yosuke; Taguchi, Akihiko; Tanabe, Katsuya; Kondo, Manabu; Hatanaka, Masayuki; Nagao, Yuko; Tanizawa, Yukio

    2013-05-03

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

  14. Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock

    PubMed Central

    Liang, Xue; Bushman, Frederic D.; FitzGerald, Garret A.

    2015-01-01

    In mammals, multiple physiological, metabolic, and behavioral processes are subject to circadian rhythms, adapting to changing light in the environment. Here we analyzed circadian rhythms in the fecal microbiota of mice using deep sequencing, and found that the absolute amount of fecal bacteria and the abundance of Bacteroidetes exhibited circadian rhythmicity, which was more pronounced in female mice. Disruption of the host circadian clock by deletion of Bmal1, a gene encoding a core molecular clock component, abolished rhythmicity in the fecal microbiota composition in both genders. Bmal1 deletion also induced alterations in bacterial abundances in feces, with differential effects based on sex. Thus, although host behavior, such as time of feeding, is of recognized importance, here we show that sex interacts with the host circadian clock, and they collectively shape the circadian rhythmicity and composition of the fecal microbiota in mice. PMID:26240359

  15. Regulation and Synchronization of the Master Circadian Clock by Purinergic Signaling from Suprachiasmatic Nucleus Astrocytes 

    E-print Network

    Womac, Alisa Diane

    2012-10-19

    accumulation did not persist in mouse SCN cells containing targeted disruption of Per1 and Per2............................................................. 50 Figure 8 ATP-evoked calcium responses were rhythmic............................... 54... of oscillators throughout the SCN produces a coordinated, ensemble rhythm. 6 Several genes are core components of the mammalian canonical clock machinery: Period (Per) 1, Per2, Per3, Cryptochrome (Cry) 1, Cry2, Bmal1, Clock, & Rev...

  16. Sleep and Circadian Rhythm Regulation in Early Parkinson Disease

    PubMed Central

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

    2014-01-01

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

  17. Cell, Vol. 110, 251260, July 26, 2002, Copyright 2002 by Cell Press The Orphan Nuclear Receptor REV-ERB Controls

    E-print Network

    Halazonetis, Thanos

    REV-ERB Controls Circadian Transcription within the Positive Limb of the Mammalian Circadian REV-ERB as the major regulator of Whereas a large body of genetic and biochemicalcyclic Bmal1 transcription. Circadian Rev-erb ex- evidence has been collected on the regulation of Crypression is controlled

  18. Optimal Design for Minimizing Uncertainty in Dynamic Equilibrium H.T. Banks, Robert Baraldi, Kevin Flores

    E-print Network

    the circadian rhythm and intertwined positive and negative regulatory loops of Per, Cry, Bmal1, and Clock genes calculation, complex-step method, circadian rhythms. 1 #12;1 Introduction Current efforts in modeling the host analyzed a mathematical model describing the regulation of genes involved in mammalian circadian rhythms

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. A role for Id2 in regulating photic entrainment of the mammalian circadian system.

    PubMed

    Duffield, Giles E; Watson, Nathan P; Mantani, Akio; Peirson, Stuart N; Robles-Murguia, Maricela; Loros, Jennifer J; Israel, Mark A; Dunlap, Jay C

    2009-02-24

    Inhibitor of DNA binding genes (Id1-Id4) encode helix-loop-helix (HLH) transcriptional repressors associated with development and tumorigenesis [1, 2], but little is known concerning the function(s) of these genes in normal adult animals. Id2 was identified in DNA microarray screens for rhythmically expressed genes [3-5], and further analysis revealed a circadian pattern of expression of all four Id genes in multiple tissues including the suprachiasmatic nucleus. To explore an in vivo function, we generated and characterized deletion mutations of Id2 and of Id4. Id2(-/-) mice exhibit abnormally rapid entrainment and an increase in the magnitude of the phase shift of the pacemaker. A significant proportion of mice also exhibit disrupted rhythms when maintained under constant darkness. Conversely, Id4(-/-) mice did not exhibit a noticeable circadian phenotype. In vitro studies using an mPer1 and an AVP promoter reporter revealed the potential for ID1, ID2, and ID3 proteins to interact with the canonical basic HLH clock proteins BMAL1 and CLOCK. These data suggest that the Id genes may be important for entrainment and operation of the mammalian circadian system, potentially acting through BMAL1 and CLOCK targets. PMID:19217292

  1. Preschool Regulations.

    ERIC Educational Resources Information Center

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

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

  2. Government Regulation

    E-print Network

    Ashford, Nicholas

    2005-01-01

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

  3. Microgravity influences circadian clock oscillation in human keratinocytes

    PubMed Central

    Ranieri, Danilo; Cucina, Alessandra; Bizzarri, Mariano; Alimandi, Maurizio; Torrisi, Maria Rosaria

    2015-01-01

    Microgravity and sudden changes of gravitational forces exert numerous effects on tissues, organs and apparatus. Responses to these forces variably applied to cells indicate the existence of mechanotransduction pathways able to modulate transcription. Oscillation of circadian clocks similarly influences many cellular and metabolic processes. Here we hypothesized that signals derived from changes of gravitational forces applied to epidermal cells might influence their physiology in harmony with the oscillation of the molecular clock. In this study, we describe amplified oscillations of Bmal1 circadian clock gene in human keratinocytes exposed to short simulated microgravity and to rapid variation of gravitational forces. We found that exposure to microgravity enhances the amplitude of the Bmal1 feedback loop sustained by an apparently lower variability of Rev-erb? transcription, while recovery from microgravity is characterized by increased amplitude of Bmal1 expression and elongation of the oscillatory periods of Bmal1 and Rev-erb?. These data highlight the existence of integrated signaling network connecting mechanosensitive pathways to circadian gene regulation. PMID:26448904

  4. Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver.

    PubMed

    Atger, Florian; Gobet, Cédric; Marquis, Julien; Martin, Eva; Wang, Jingkui; Weger, Benjamin; Lefebvre, Grégory; Descombes, Patrick; Naef, Felix; Gachon, Frédéric

    2015-11-24

    Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5'-Terminal Oligo Pyrimidine tract (5'-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5'-UTR (TISU) motif. The increased translation efficiency of 5'-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. PMID:26554015

  5. Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

    PubMed Central

    Atger, Florian; Gobet, Cédric; Marquis, Julien; Martin, Eva; Wang, Jingkui; Weger, Benjamin; Lefebvre, Grégory; Descombes, Patrick; Naef, Felix; Gachon, Frédéric

    2015-01-01

    Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light–dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5?-Terminal Oligo Pyrimidine tract (5?-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5?-UTR (TISU) motif. The increased translation efficiency of 5?-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. PMID:26554015

  6. Suprachiasmatic regulation of circadian rhythms of gene expression in hamster peripheral organs: effects of transplanting the pacemaker.

    PubMed

    Guo, Hongnian; Guo, Hongian; Brewer, Judy McKinley; Lehman, Michael N; Bittman, Eric L

    2006-06-14

    Neurotransplantation of the suprachiasmatic nucleus (SCN) was used to assess communication between the central circadian pacemaker and peripheral oscillators in Syrian hamsters. Free-running rhythms of haPer1, haPer2, and Bmal1 expression were documented in liver, kidney, spleen, heart, skeletal muscle, and adrenal medulla after 3 d or 11 weeks of exposure to constant darkness. Ablation of the SCN of heterozygote tau mutants eliminated not only rhythms of locomotor activity but also rhythmic expression of these genes in all peripheral organs studied. The Per:Bmal ratio suggests that this effect was attributable not to asynchronous rhythmicity between SCN-lesioned individuals but to arrhythmicity within individuals. Grafts of wild-type SCN to heterozygous, SCN-lesioned tau mutant hamsters not only restored locomotor rhythms with the period of the donor but also led to recovery of rhythmic expression of haPer1, haPer2, and haBmal1 in liver and kidney. The phase of these rhythms most closely resembled that of intact wild-type hamsters. Rhythmic gene expression was also restored in skeletal muscle, but the phase was altered. Behaviorally effective SCN transplants failed to reinstate rhythms of clock gene expression in heart, spleen, or adrenal medulla. These findings confirm that peripheral organs differ in their response to SCN-dependent cues. Furthermore, the results indicate that conventional models of internal entrainment may need to be revised to explain control of the periphery by the pacemaker. PMID:16775127

  7. Regulation Theory

    E-print Network

    Bouvet, F

    2015-01-01

    This paper reviews the design of regulation loops for power converters. Power converter control being a vast domain, it does not aim to be exhaustive. The objective is to give a rapid overview of the main synthesis methods in both continuous- and discrete-time domains.

  8. Analysis of Circadian Rhythm Gene Expression With Reference to Diurnal Pattern of Intraocular Pressure in Mice

    PubMed Central

    Dalvin, Lauren A.; Fautsch, Michael P.

    2015-01-01

    Purpose. To determine the expression of circadian rhythm clock genes in the iris–ciliary body complex of mice and their association with the diurnal pattern of intraocular pressure (IOP). Methods. Thirty wild-type C57BL/6 mice were acclimated to a 12-hour light–dark cycle. Intraocular pressure was measured with a rebound tonometer at six time points daily (circadian time [CT] 2, 6, 10, 14, 18, and 22 hours) for five consecutive days. On day 6, mice were euthanized at CT 2, 6, 10, 14, 18, and 22. Eyes were flash-frozen or fixed in 4% phosphate-buffered paraformaldehyde. Total RNA was extracted from the iris–ciliary body complex, and RNA expression of circadian rhythm genes Bmal1, Clock, Cry1, Cry2, Per1, and Per2 was assessed by quantitative real-time PCR. Fixed eyes were paraffin embedded, and immunohistochemistry was performed to localize corresponding proteins (BMAL1, CLOCK, CRY1, CRY2, PER1, and PER2). Linear regression analysis was performed to correlate gene expression with IOP. Results. Intraocular pressure demonstrated a consistent circadian pattern. The clock genes Bmal1, Clock, Cry1, Cry2, Per1, and Per2 showed a circadian pattern of expression in the iris–ciliary body complex of mice. Bmal1, Clock, Cry1, Per1, and Per2 gene expression demonstrated statistically significant correlations with diurnal variations of IOP. BMAL1, CLOCK, CRY1, CRY2, PER1, and PER2 proteins were found to be expressed locally in the nonpigmented epithelium of the ciliary body. Conclusions. Expression patterns of candidate circadian rhythm genes correlates with the diurnal pattern variation of IOP in mouse eyes, indicating a possible mechanism of IOP regulation through these genes. PMID:25813988

  9. Epigenetic Regulation.

    PubMed

    Minarovits, Janos; Banati, Ferenc; Szenthe, Kalman; Niller, Hans Helmut

    2016-01-01

    Some of the key epigenetic regulatory mechanisms appeared early during evolution, and the acquisition of novel epigenetic regulators apparently facilitated certain evolutionary transitions. In this short review we focus mainly on the major epigenetic mechanisms that control chromatin structure and accessibility in mammalian cells. The enzymes methylating CpG dinucleotides and those involved in the active demethylation of 5-metylcytosine (5mC) are outlined together with the members of the methyl binding protein (MBP) family that bind to and "interpret" the 5mC mark. The enzymes involved in reversible, covalent modifications of core histone proteins that affect chromatin structure are also described briefly. Proteins that build up Polycomb group (PcG) and Trithorax group (TrxG) protein complexes may also modify histones. By establishing heritable chromatin states, PcG and TrxG complexes contribute - similarly to cytosine methylation - to the transmission of cell type-specific gene expression patterns from cell generation to cell generation. Novel players involved in epigenetic regulation, including variant histones, pioneer transcription factors, long noncoding RNA molecules and the regulators of long-distance chromatin interactions are introduced as well, followed by the characterization of various chromatin types. PMID:26659261

  10. All-encomPASsing regulation of ?-cells: PAS domain proteins in ?-cell dysfunction and diabetes.

    PubMed

    Sabatini, Paul V; Lynn, Francis C

    2015-01-01

    As a sensory micro-organ, pancreatic ?-cells continually respond to nutritional signals and neuroendocrine input from other glucoregulatory organs. This sensory ability is essential for normal ?-cell function and systemic glucose homeostasis. Period circadian protein (Per)-aryl hydrocarbon receptor nuclear translocator protein (Arnt)-single-minded protein (Sim) (PAS) domain proteins have a conserved role as sensory proteins, critical in adaptation to changes in voltage, oxygen potential, and xenobiotics. Within ?-cells, PAS domain proteins such as hypoxia inducible factor 1? (Hif1?), Arnt, PAS kinase, Bmal1, and Clock respond to disparate stimuli, but act in concert to maintain proper ?-cell function. Elucidating the function of these factors in islets offers a unique insight into the sensing capacity of ?-cells, the consequences of impaired sensory function, and the potential to develop novel therapeutic targets for preserving ?-cell function in diabetes. PMID:25500169

  11. On the Role of Histamine Receptors in the Regulation of Circadian Rhythms

    PubMed Central

    Rozov, Stanislav V.; Porkka-Heiskanen, Tarja; Panula, Pertti

    2015-01-01

    Several lines of evidence suggest a regulatory role of histamine in circadian rhythms, but little is known about signaling pathways that would be involved in such a putative role. The aim of this study was to examine whether histamine mediates its effects on the circadian system through Hrh1 or Hrh3 receptors. We assessed both diurnal and free-running locomotor activity rhythms of Hrh1-/- and Hrh3-/- mice. We also determined the expression of Per1, Per2 and Bmal1 genes in the suprachiasmatic nuclei, several areas of the cerebral cortex and striatum under symmetric 24 h light-dark cycle at zeitgeber times 14 and 6 by using radioactive in situ hybridization. We found no differences between Hrh1-/- and wild type mice in the length, amplitude and mesor of diurnal and free-running activity rhythms as well as in expression of Per1, Per2 and Bmal1 genes in any of the examined brain structures. The amplitude of free-running activity rhythm of the Hrh3-/- mice was significantly flattened, whereas the expression of the clock genes in Hrh3-/- mice was similar to the wild type animals in all of the assessed brain structures. Therefore, the knockout of Hrh1 receptor had no effects on the circadian rhythm of spontaneous locomotion, and a knockout of Hrh3 receptor caused a substantial reduction of free-running activity rhythm amplitude, but none of these knockout models affected the expression patterns of the core clock genes in any of the studied brain structures. PMID:26660098

  12. Future trends in regulation

    SciTech Connect

    Remick, F.J.

    1993-12-31

    This report presents a discussion on the future of nuclear regulations and what regulators should strive for. The following 6 trends are described: the regulatory presence around the world will grow; there is a trend towards giving the regulator greater independence; there is a trend toward greater self-regulation by the industry; less prescriptive regulation; regulators may be converging no a quantitative risk goal; increasing recognition of the importance of stability in the regulator.

  13. CLOCK and NPAS2 have overlapping roles in the circadian oscillation of arylalkylamine N-acetyltransferase (Aanat) mRNA in chicken cone photoreceptors

    PubMed Central

    Haque, Rashidul; Ali, Fatima G.; Biscoglia, Rebecca; Abey, Jane; Weller, Joan; Klein, David; Iuvone, P. Michael

    2010-01-01

    Circadian clocks in vertebrates are thought to be composed of transcriptional-translational feedback loops involving a highly conversed set of “clock genes”: namely, period (Per1–3) and cryptochrome (Cry1–2), which encode negative transcriptional regulators; and Bmal1, Clock, and Npas2, which encode positive regulators. Aanat, which encodes arylalkylamine N-acetyltransferase (AANAT), the key regulatory enzyme that drives the circadian rhythm of melatonin synthesis, contains a circadian E-box element (CACGTG) in its proximal promoter that is potentially capable of binding CLOCK: BMAL1 and NPAS2: BMAL1 heterodimers. The present study was conducted to investigate whether CLOCK and/or NPAS2 regulates Aanat expression in photoreceptor cells. Npas2 and Clock are both expressed in photoreceptor cells in vivo and in vitro. To assess the roles of CLOCK and NPAS2 in Aanat expression, gene specific microRNA (miR) vectors were used to knock down expression of these clock genes in photoreceptor-enriched cell cultures. The knockdown of CLOCK protein significantly reduced the circadian expression of Npas2, Per2, and Aanat transcripts but had no effect on the circadian rhythm of Bmal1 transcript level. The knockdown of NPAS2 significantly damped the circadian rhythm of Aanat mRNAs but had no effect on circadian expression of any of clock genes examined, except Npas2 itself. Chromatin immunoprecipitation studies indicated that both CLOCK and NPAS2 bound to the Aanat promoter in situ. Thus, CLOCK and NPAS2 have overlapping roles in the clock output pathway that regulates the rhythmic expression of Aanat in photoreceptors. However, CLOCK plays the predominant role in the chicken photoreceptor circadian clockwork mechanism, including the regulation of NPAS2 expression. PMID:20345751

  14. Molecular components of the circadian clock in mammals.

    PubMed

    Takahashi, J S

    2015-09-01

    The circadian clock mechanism in animals involves a transcriptional feedback loop in which the bHLH-PAS proteins CLOCK and BMAL1 form a transcriptional activator complex to activate the transcription of the Period and Cryptochrome genes, which in turn feed back to repress their own transcription. In the mouse liver, CLOCK and BMAL1 interact with the regulatory regions of thousands of genes, which are both cyclically and constitutively expressed. The circadian transcription in the liver is clustered in phase and this is accompanied by circadian occupancy of RNA polymerase II recruitment and initiation. These changes also lead to circadian fluctuations in histone H3 lysine4 trimethylation (H3K4me3) as well as H3 lysine9 acetylation (H3K9ac) and H3 lysine27 acetylation (H3K27ac). Thus, the circadian clock regulates global transcriptional poise and chromatin state by regulation of RNA polymerase II. PMID:26332962

  15. Housing under abnormal light-dark cycles attenuates day/night expression rhythms of the clock genes Per1, Per2, and Bmal1 in the amygdala and hippocampus of mice.

    PubMed

    Moriya, Shunpei; Tahara, Yu; Sasaki, Hiroyuki; Ishigooka, Jun; Shibata, Shigenobu

    2015-10-01

    Although the results of previous studies have suggested that disruptions in circadian rhythms are involved in the pathogenesis of depression, no studies have examined the interaction of clock gene expression deficit and depression state. In this study, we examined clock gene expression levels and depressive-like behavior in mice housed under 3.5h light, 3.5h dark (T = 7) conditions to investigate the association between clock gene expression and depressive state. C57BL/6J mice were housed under a T = 24 cycle (12h light, 12h dark) or a T = 7 cycle and clock gene expression levels in the hippocampus and the amygdala were measured by real-time RT-PCR. Depressive state was evaluated by the forced swim test (FST). Although circadian rhythms of Per1 and Per2 clock gene expression in the hippocampus and amygdala were still detected under T = 7 conditions, rhythmicity and expression levels of both significantly decreased. Mice housed with a T = 7 cycle showed increased immobile time in the FST than those with a T = 24 cycle. The present results suggest that the presence of a depressive state around the early active phase of activity may be related to impairment of rhythmicity and expression levels of Per1 and Per2 genes under abnormal light-dark conditions. PMID:26026603

  16. Facilitated physiological adaptation to prolonged circadian disruption through dietary supplementation with essence of chicken.

    PubMed

    Wu, Tao; Yao, Cencen; Tsang, Fai; Huang, Liangfeng; Zhang, Wanjing; Jiang, Jianguo; Mao, Youxiang; Shao, Yujian; Kong, Boda; Singh, Paramjeet; Fu, Zhengwei

    2015-12-01

    Synchrony between circadian and metabolic processes is critical to the maintenance of energy homeostasis. Studies on essence of chicken (EC), a chicken meat extract rich in proteins, amino acids and peptides, showed its effectiveness in alleviating fatigue and promoting metabolism. A recent study revealed that it facilitated the re-entrainment of clock genes (Bmal1, Cry1, Dec1, Per1 and Per2) in the pineal gland and liver in a rat model of circadian disruption. Here, we investigated the role of EC-facilitated circadian synchrony in the maintenance of the energy homeostasis using a mouse model of prolonged circadian disruption. Prolonged circadian disruption (12 weeks) resulted in hepatic maladaptation, manifested by a mild but significant (p?regulators (e.g. mTOR and AMPK) and hepatic clock genes (Per1, Cry1, Dec1, Bmal1). Further, we showed that the loss of circadian synchrony between the master and hepatic clock genes (Per1, Cry1, Dec1, Bmal1) could be the underlying cause of the maladaptation. When supplemented with EC, the functional impairment and inflammation were abolished. The protective effects could be linked to its effectiveness in maintaining the synchrony between the master and hepatic clocks, and the resultant improved coupling of the circadian oscillators (Per1, Cry1, Dec1, Bmal1) and metabolic regulators (mTOR, AMPK). Overall, EC supplementation promoted the physiological adaptation to the prolonged circadian disruption through facilitation of endogenous circadian synchrony and the coupling of circadian oscillators and metabolic regulators. This forms an important basis for further elucidation of the physiological benefits of EC-facilitated circadian synchrony. PMID:26595385

  17. Altered Stra13 and Dec2 circadian gene expression in hypoxic cells

    SciTech Connect

    Guillaumond, Fabienne; Lacoche, Samuel; Dulong, Sandrine; Grechez-Cassiau, Aline; Filipski, Elisabeth; Li, Xiao-Mei; Levi, Francis; Berra, Edurne; Delaunay, Franck; Teboul, Michele

    2008-05-16

    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.

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

    PubMed Central

    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

    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

  19. Emerging Models for the Molecular Basis of Mammalian Circadian Timing

    PubMed Central

    2015-01-01

    Mammalian circadian timekeeping arises from a transcription-based feedback loop driven by a set of dedicated clock proteins. At its core, the heterodimeric transcription factor CLOCK:BMAL1 activates expression of Period, Cryptochrome, and Rev-Erb genes, which feed back to repress transcription and create oscillations in gene expression that confer circadian timing cues to cellular processes. The formation of different clock protein complexes throughout this transcriptional cycle helps to establish the intrinsic ?24 h periodicity of the clock; however, current models of circadian timekeeping lack the explanatory power to fully describe this process. Recent studies confirm the presence of at least three distinct regulatory complexes: a transcriptionally active state comprising the CLOCK:BMAL1 heterodimer with its coactivator CBP/p300, an early repressive state containing PER:CRY complexes, and a late repressive state marked by a poised but inactive, DNA-bound CLOCK:BMAL1:CRY1 complex. In this review, we analyze high-resolution structures of core circadian transcriptional regulators and integrate biochemical data to suggest how remodeling of clock protein complexes may be achieved throughout the 24 h cycle. Defining these detailed mechanisms will provide a foundation for understanding the molecular basis of circadian timing and help to establish new platforms for the discovery of therapeutics to manipulate the clock. PMID:25303119

  20. Hepcidin: regulation of the master iron regulator

    PubMed Central

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

    2015-01-01

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

  1. Load regulating expansion fixture

    DOEpatents

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

    1998-01-01

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

  2. Load regulating expansion fixture

    DOEpatents

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

    1998-12-15

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

  3. TOWARD MORE EFFECTIVE REGULATION

    SciTech Connect

    J. GRAF

    2000-06-01

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

  4. Pressure reducing regulator

    DOEpatents

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

    1995-10-10

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

  5. Pressure reducing regulator

    DOEpatents

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

    1995-01-01

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

  6. Regulation of natural monopolies

    E-print Network

    Joskow, Paul L.

    2005-01-01

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

  7. GENES REGULATING CHOLESTEROL METABOLISM

    E-print Network

    Brutlag, Doug

    GENES REGULATING CHOLESTEROL METABOLISM Chau Vu Bio 118 #12;FUNCTIONS OF CHOLESTEROL Maintain atherosclerosis #12;SYNTHESIS OF CHOLESTEROL Occurs in cytoplasm and microsomes acetyl-CoA ­ starting material OF CHOLESTEROL #12;REGULATION OF CHOLESTEROL Synthesis and dietary intake: Normal Adult: produce1g/day; consume

  8. Plant Growth Regulators.

    ERIC Educational Resources Information Center

    Nickell, Louis G.

    1978-01-01

    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)

  9. Bioethics regulations in Turkey.

    PubMed Central

    Aydin, E

    1999-01-01

    Although modern technical and scientific developments in medicine are followed closely in Turkey, it cannot be claimed that the same is true in the field of bioethics. Yet, more and more attention is now being paid to bioethics and ethics training in health sciences. In addition, there are also legal regulations in bioethics, some of which are not so new. The objective of these regulations is to provide technical and administrative control. Ethical concerns are rather few. What attracts our attention most in these regulations is the presence of the idea of "consent". PMID:10536766

  10. 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...

  11. Regulation of Genetic Tests

    MedlinePLUS

    ... are not regulated, meaning that they go to market without any independent analysis to verify the claims ... test is determined by how it comes to market. A test may be marketed as a commercial ...

  12. 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

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

    ERIC Educational Resources Information Center

    Durosinmi, Brenda Braxton

    2011-01-01

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

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

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

    PubMed

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

    2015-07-01

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

  16. Extracellular regulation of metalloproteinases.

    PubMed

    Yamamoto, Kazuhiro; Murphy, Gillian; Troeberg, Linda

    2015-01-01

    Matrix metalloproteinases (MMPs) and adamalysin-like metalloproteinase with thrombospondin motifs (ADAMTSs) belong to the metzincin superfamily of metalloproteinases and they play key roles in extracellular matrix catabolism, activation and inactivation of cytokines, chemokines, growth factors, and other proteinases at the cell surface and within the extracellular matrix. Their activities are tightly regulated in a number of ways, such as transcriptional regulation, proteolytic activation and interaction with tissue inhibitors of metalloproteinases (TIMPs). Here, we highlight recent studies that have illustrated novel mechanisms regulating the extracellular activity of these enzymes. These include allosteric activation of metalloproteinases by molecules that bind outside the active site, modulation of location and activity by interaction with cell surface and extracellular matrix molecules, and endocytic clearance from the extracellular milieu by low-density lipoprotein receptor-related protein 1 (LRP1). PMID:25701651

  17. Reviving regulation - and antitrust

    SciTech Connect

    Shepherd, W.G.

    1994-06-01

    The ills of utility regulation have been overstated by interested players and at least some academics. One can have the best features of both competition and regulation by a paradigm that combines some regulation with stronger antitrust enforcement. It is now obvious that the success of deregulation actually depends crucially on whether antitrust policy is effective in preventing monopoly. In fact, antitrust policies have been extremely weak since 1980, under a deliberate Reagan administration withdrawal of enforcement. Where deregulation has led to market dominance, which antitrust cannot well cure, the policy changes of the 1980`s may have created costly and irreversible mistakes in a number of major sectors. Yet fast-paced events are currently creating a frenzy of even more deregulation, supposedly to fit new {open_quotes}revolutions{close_quotes} in technology and the impacts of large mergers. Instead it is time for particular caution in electricity.

  18. Consolidation and translation regulation.

    PubMed

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

    2012-09-01

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

  19. Environmentally regulated aerospace coatings

    NASA Technical Reports Server (NTRS)

    Morris, Virginia L.

    1995-01-01

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

  20. What Price Government Regulations?

    PubMed Central

    McGill, Clinton S.

    1980-01-01

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

  1. Design of Optimal Regulators

    E-print Network

    Alexander Bolonkin; Robert Sierakowski

    2007-01-19

    Current research suggests the use of a liner quadratic performance index for optimal control of regulators in various applications. Some examples include correcting the trajectory of rocket and air vehicles, vibration suppression of flexible structures, and airplane stability. In all these cases, the focus is in suppressing/decreasing system deviations rapidly. However, if one compares the Linear Quadratic Regulator (LQR) solution with optimal solutions (minimum time), it is seen that the LQR solution is less than optimal in some cases indeed (3-6) times that obtained using a minimum time solution. Moreover, the LQR solution is sometimes unacceptable in practice due to the fact that values of control extend beyond admissible limits and thus the designer must choose coefficients in the linear quadratic form, which are unknown. The authors suggest methods which allow finding a quasi-optimal LQR solution with bounded control which is closed to the minimum time solution. They also remand the process of the minimum time decision. Keywords: Optimal regulator, minimum time controller, Linear Quadratic Regulator (LQR). -- This paper is declared a work of the U.S. Government and not subject to copyright protection in the USA. The manuscript is accepted as paper AIAA-2003-6638 by 2nd AIAA Unmanned Unlimited Systems, Technologies, and Operations-Aerospace, Land, and See Conference and Workshop - Exhibit, San Diego, California, USA, 15-18 Sep. 2003.

  2. Federal Regulation of Education.

    ERIC Educational Resources Information Center

    Shapiro, Martin

    Fresh light might be shed on problems of federal education policy by treating them not only as problems of intergovernmental relations but of government regulation of enterprise, given that they involve the attempts of a central government to influence the conduct of enterprises that it does not own nor directly operate. Using well-established…

  3. Regulated Gene Therapy.

    PubMed

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

    2016-01-01

    Gene therapy represents a promising approach for the treatment of monogenic and multifactorial neurological disorders. It can be used to replace a missing gene and mutated gene or downregulate a causal gene. Despite the versatility of gene therapy, one of the main limitations lies in the irreversibility of the process: once delivered to target cells, the gene of interest is constitutively expressed and cannot be removed. Therefore, efficient, safe and long-term gene modification requires a system allowing fine control of transgene expression.Different systems have been developed over the past decades to regulate transgene expression after in vivo delivery, either at transcriptional or post-translational levels. The purpose of this chapter is to give an overview on current regulatory system used in the context of gene therapy for neurological disorders. Systems using external regulation of transgenes using antibiotics are commonly used to control either gene expression using tetracycline-controlled transcription or protein levels using destabilizing domain technology. Alternatively, specific promoters of genes that are regulated by disease mechanisms, increasing expression as the disease progresses or decreasing expression as disease regresses, are also examined. Overall, this chapter discusses advantages and drawbacks of current molecular methods for regulated gene therapy in the central nervous system. PMID:26611578

  4. Focus on PTEN Regulation

    PubMed Central

    Bermúdez Brito, Miriam; Goulielmaki, Evangelia; Papakonstanti, Evangelia A.

    2015-01-01

    The role of phosphatase and tensin homolog on chromosome 10 (PTEN) as a tumor suppressor has been for a long time attributed to its lipid phosphatase activity against PI(3,4,5)P3, the phospholipid product of the class I PI3Ks. Besides its traditional role as a lipid phosphatase at the plasma membrane, a wealth of data has shown that PTEN can function independently of its phosphatase activity and that PTEN also exists and plays a role in the nucleus, in cytoplasmic organelles, and extracellularly. Accumulating evidence has shed light on diverse physiological functions of PTEN, which are accompanied by a complex regulation of its expression and activity. PTEN levels and function are regulated transcriptionally, post-transcriptionally, and post-translationally. PTEN is also sensitive to regulation by its interacting proteins and its localization. Herein, we summarize the current knowledge on mechanisms that regulate the expression and enzymatic activity of PTEN and its role in human diseases. PMID:26284192

  5. Metabolic regulation of yeast

    NASA Astrophysics Data System (ADS)

    Fiechter, A.

    1982-12-01

    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.

  6. Introduction..............................................................................................................................4 Academic Regulations ..............................................................................................

    E-print Network

    Stuart, Steven J.

    .........................................................................................18 Ordering of Equipment and Supplies Office Supplies Work Orders Building Access, Keys and Security..........................................................................................................................21 Income Tax Driver's License and Automobile Registration Academic Regulations Appendix and academic experience. This manual has been prepared to acquaint students with the basic policies

  7. Lysosomal Trafficking Regulator (LYST).

    PubMed

    Ji, Xiaojie; Chang, Bo; Naggert, Jürgen K; Nishina, Patsy M

    2016-01-01

    Regulation of vesicle trafficking to lysosomes and lysosome-related organelles (LROs) as well as regulation of the size of these organelles are critical to maintain their functions. Disruption of the lysosomal trafficking regulator (LYST) results in Chediak-Higashi syndrome (CHS), a rare autosomal recessive disorder characterized by oculocutaneous albinism, prolonged bleeding, severe immunodeficiency, recurrent bacterial infection, neurologic dysfunction and hemophagocytic lympohistiocytosis (HLH). The classic diagnostic feature of the syndrome is enlarged LROs in all cell types, including lysosomes, melanosomes, cytolytic granules and platelet dense bodies. The most striking CHS ocular pathology observed is an enlargement of melanosomes in the retinal pigment epithelium (RPE), which leads to aberrant distribution of eye pigmentation, and results in photophobia and decreased visual acuity. Understanding the molecular function of LYST and identification of its interacting partners may provide therapeutic targets for CHS and other diseases associated with the regulation of LRO size and/or vesicle trafficking, such as asthma, urticaria and Leishmania amazonensis infections. PMID:26427484

  8. METABOLIC PATHWAY REGULATION

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  9. REGULATIONS AND SYLLABUSES 1967.

    ERIC Educational Resources Information Center

    Associated Examining Board, Aldershot, Hampshire (England).

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

  10. REGULATIONS AND SYLLABUSES, 1968.

    ERIC Educational Resources Information Center

    Associated Examining Board, Aldershot, Hampshire (England).

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

  11. REGULATIONS AND SYLLABUSES 1966.

    ERIC Educational Resources Information Center

    JOHNSON, ARTHUR L.; AND OTHERS

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

  12. Regulated exocytosis per partes.

    PubMed

    Coorssen, Jens R; Zorec, Robert

    2012-01-01

    This Special Issue (SI) of Cell Calcium focuses on regulated exocytosis, a recent evolutionary invention of eukaryotic cells. This essential cellular process consists of several stages: (i) the delivery of membrane bound vesicles to specific plasma membrane sites, (ii) where the merger between the vesicle and the plasma membranes occurs, (iii) leading to the formation of an aqueous channel through which vesicle content starts to be discharged to the cell exterior, (iv) after the full incorporation of the vesicle membrane into the plasma membrane, the added vesicle membrane is retrieved back into the cytoplasm by endocytosis. (v) When a fusion pore opens it may close again, a process known as transient fusion pore opening (also kiss-and-run exocytosis). In some cell types these stages are extremely shortlived, as in some neurons, and thus relatively inaccessible to experimentation. In other cell types the transition between these stages is orders of magnitude slower and can be studied in more detail. However, despite the intense investigations of this critical biological process over the last decades, the molecular mechanisms underlying regulated exocytosis have yet to be fully resolved. We thus still lack a comprehensive physiological insight into the nature of the progressive and coupled stages of exocytosis. Such a molecular-level understanding would help to fully reconstruct this process in vitro, as well as identify potential therapeutic targets for a range of diseases and dysfunctions. There are 18 papers in this SI which have been organized into three sections: Rapid regulated exocytosis and calcium homeostasis with an introduction by Erwin Neher, Molecular mechanisms of regulated exocytosis, and Cell models for regulated exocytosis. Here we briefly outline and integrate the messages of these sections. PMID:22784668

  13. Disruption of Sirtuin 1-Mediated Control of Circadian Molecular Clock and Inflammation in Chronic Obstructive Pulmonary Disease.

    PubMed

    Yao, Hongwei; Sundar, Isaac K; Huang, Yadi; Gerloff, Janice; Sellix, Michael T; Sime, Patricia J; Rahman, Irfan

    2015-12-01

    Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death, and it is characterized by abnormal inflammation and lung function decline. Although the circadian molecular clock regulates inflammatory responses, there is no information available regarding the impact of COPD on lung molecular clock function and its regulation by sirtuin 1 (SIRT1). We hypothesize that the molecular clock in the lungs is disrupted, leading to increased inflammatory responses in smokers and patients with COPD and its regulation by SIRT1. Lung tissues, peripheral blood mononuclear cells (PBMCs), and sputum cells were obtained from nonsmokers, smokers, and patients with COPD for measurement of core molecular clock proteins (BMAL1, CLOCK, PER1, PER2, and CRY1), clock-associated nuclear receptors (REV-ERB?, REV-ERB?, and ROR?), and SIRT1 by immunohistochemistry, immunofluorescence, and immunoblot. PBMCs were treated with the SIRT1 activator SRT1720 followed by LPS treatment, and supernatant was collected at 6-hour intervals. Levels of IL-8, IL-6, and TNF-? released from PBMCs were determined by ELISA. Expression of BMAL1, PER2, CRY1, and REV-ERB? was reduced in PBMCs, sputum cells, and lung tissues from smokers and patients with COPD when compared with nonsmokers. SRT1720 treatment attenuated LPS-mediated reduction of BMAL1 and REV-ERB? in PBMCs from nonsmokers. Additionally, LPS differentially affected the timing and amplitude of cytokine (IL-8, IL-6, and TNF-?) release from PBMCs in nonsmokers, smokers, and patients with COPD. Moreover, SRT1720 was able to inhibit LPS-induced cytokine release from cultured PBMCs. In conclusion, disruption of the molecular clock due to SIRT1 reduction contributes to abnormal inflammatory response in smokers and patients with COPD. PMID:25905433

  14. Regulation of Meiotic Recombination

    SciTech Connect

    Gregory p. Copenhaver

    2011-11-09

    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

  15. Epigenetic regulation in obesity.

    PubMed

    Lavebratt, C; Almgren, M; Ekström, T J

    2012-06-01

    The availability to the DNA strand and the activity of the transcription machinery is crucial for the cell to use the information in the DNA. The epigenetic mechanisms DNA methylation, modification of histone tails, other chromatin-modifying processes and interference by small RNAs regulate the cell-type-specific DNA expression. Epigenetic marks can be more or less plastic perpetuating responses to various molecular signals and environmental stimuli, but in addition apparently stochastic epigenetic marks have been found. There is substantial evidence from animal and man demonstrating that both transient and more long-term epigenetic mechanisms have a role in the regulation of the molecular events governing adipogenesis and glucose homeostasis. Intrauterine exposure such as poor maternal nutrition has consistently been demonstrated to contribute to a particular epigenotype and thereby developmental metabolic priming of the exposed offspring in animal and man. Epigenetic modifications can be passed not only from one cell generation to the next, but metabolic disease-related epigenotypes have been proposed to also be transmitted germ-line. Future more comprehensive knowledge on epigenetic regulation will complement genome sequence data for the understanding of the complex etiology of obesity and related disorder. PMID:21912396

  16. Flow compensating pressure regulator

    NASA Technical Reports Server (NTRS)

    Baehr, E. F. (inventor)

    1978-01-01

    An apparatus for regulating pressure of treatment fluid during ophthalmic procedures is described. Flow sensing and pressure regulating diaphragms are used to modulate a flow control valve. The pressure regulating diaphragm is connected to the flow control valve to urge the valve to an open position due to pressure being applied to the diaphragm by bias means such as a spring. The flow sensing diaphragm is mechanically connected to the flow control valve and urges it to an opened position because of the differential pressure on the diaphragm generated by a flow of incoming treatment fluid through an orifice in the diaphragm. A bypass connection with a variable restriction is connected in parallel relationship to the orifice to provide for adjusting the sensitivity of the flow sensing diaphragm. A multiple lever linkage system is utilized between the center of the second diaphragm and the flow control valve to multiply the force applied to the valve by the other diaphragm and reverse the direction of the force.

  17. FDA 101: Regulating Biological Products

    MedlinePLUS

    ... Home For Consumers Consumer Updates FDA 101: Regulating Biological Products Share Tweet Linkedin Pin it More sharing ... and highly important field. back to top What biological products does FDA regulate? The Center for Biologics ...

  18. 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...

  19. Trust-based environmental regulation.

    PubMed

    Lange, Bettina; Gouldson, Andy

    2010-10-15

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

  20. Effective doses, guidelines & regulations.

    PubMed

    Burch, Michael D

    2008-01-01

    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

  1. Regulation of adipocyte lipolysis.

    PubMed

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

    2014-06-01

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

  2. Self-regulating valve

    DOEpatents

    Humphreys, D.A.

    1982-07-20

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

  3. Regulators of nucleolar functions.

    PubMed

    Hernandez-Verdun, Danièle; Roussel, Pascal

    2003-01-01

    The nucleolus is the ribosome factory and also a multifunctional domain that plays an important role in nuclear organization and function. Interestingly, ribosome biogenesis appears directly related to cell growth and proliferation. The nucleolus corresponds to a very dynamic nuclear domain resulting from an equilibrium between the level of ribosomal RNA synthesis and the efficiency of ribosomal RNA processing. Ribosome biogenesis is regulated throughout interphase and stops during mitosis. The mitotic silencing of transcription, the distribution of the processing machinery, as well as the link between transcription and processing were found to be dependent on cyclin-dependent kinase(s). PMID:14593725

  4. Epigenetic regulation in plants.

    PubMed

    Pikaard, Craig S; Mittelsten Scheid, Ortrun

    2014-12-01

    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

  5. Growth regulation by macrophages

    SciTech Connect

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

    1982-01-01

    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.

  6. Phospholipid – Driven gene regulation

    PubMed Central

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

    2013-01-01

    Phospholipids (PLs), well known for their fundamental role in cellular structure, play critical signaling roles via their derivatives and cleavage products acting as second messengers in signaling cascades. Recent work has shown that intact PLs act as signaling molecules in their own right by modulating the activity of nuclear hormone transcription factors responsible for tuning genes involved in metabolism, lipid flux, steroid synthesis and inflammation. As such, PLs have been classified as novel hormones. This review highlights recent work in PL-driven gene regulation with a focus on the unique structural features of phospholipid-sensing transcription factors and what sets them apart from well known soluble phospholipid transporters. PMID:23333623

  7. Abortion and fertility regulation.

    PubMed

    Kulczycki, A; Potts, M; Rosenfield, A

    1996-06-15

    To achieve their desired fertility, women use a combination of contraception and abortion, and some societies also place constraints on marriage and sexual activity. The degree to which these means are adopted varies considerably, but for the foreseeable future abortion will remain an important element of fertility regulation. Globally, complications of unsafe abortion affect hundreds of thousands of women each year, and account for as many as 100,000 deaths annually (about two in ten maternal deaths), mainly in poor countries, where abortion typically remains illegal. Access to safe abortion is both essential and technically feasible and should be provided in combination with good quality family planning services. PMID:8642962

  8. Gastrointestinal hormones regulating appetite

    PubMed Central

    Chaudhri, Owais; Small, Caroline; Bloom, Steve

    2006-01-01

    The role of gastrointestinal hormones in the regulation of appetite is reviewed. The gastrointestinal tract is the largest endocrine organ in the body. Gut hormones function to optimize the process of digestion and absorption of nutrients by the gut. In this capacity, their local effects on gastrointestinal motility and secretion have been well characterized. By altering the rate at which nutrients are delivered to compartments of the alimentary canal, the control of food intake arguably constitutes another point at which intervention may promote efficient digestion and nutrient uptake. In recent decades, gut hormones have come to occupy a central place in the complex neuroendocrine interactions that underlie the regulation of energy balance. Many gut peptides have been shown to influence energy intake. The most well studied in this regard are cholecystokinin (CCK), pancreatic polypeptide, peptide YY, glucagon-like peptide-1 (GLP-1), oxyntomodulin and ghrelin. With the exception of ghrelin, these hormones act to increase satiety and decrease food intake. The mechanisms by which gut hormones modify feeding are the subject of ongoing investigation. Local effects such as the inhibition of gastric emptying might contribute to the decrease in energy intake. Activation of mechanoreceptors as a result of gastric distension may inhibit further food intake via neural reflex arcs. Circulating gut hormones have also been shown to act directly on neurons in hypothalamic and brainstem centres of appetite control. The median eminence and area postrema are characterized by a deficiency of the blood–brain barrier. Some investigators argue that this renders neighbouring structures, such as the arcuate nucleus of the hypothalamus and the nucleus of the tractus solitarius in the brainstem, susceptible to influence by circulating factors. Extensive reciprocal connections exist between these areas and the hypothalamic paraventricular nucleus and other energy-regulating centres of the central nervous system. In this way, hormonal signals from the gut may be translated into the subjective sensation of satiety. Moreover, the importance of the brain–gut axis in the control of food intake is reflected in the dual role exhibited by many gut peptides as both hormones and neurotransmitters. Peptides such as CCK and GLP-1 are expressed in neurons projecting both into and out of areas of the central nervous system critical to energy balance. The global increase in the incidence of obesity and the associated burden of morbidity has imparted greater urgency to understanding the processes of appetite control. Appetite regulation offers an integrated model of a brain–gut axis comprising both endocrine and neurological systems. As physiological mediators of satiety, gut hormones offer an attractive therapeutic target in the treatment of obesity. PMID:16815798

  9. [Regulation of terpene metabolism

    SciTech Connect

    Croteau, R.

    1992-01-01

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

  10. Bidirectional Pressure-Regulator System

    NASA Technical Reports Server (NTRS)

    Burke, Kenneth; Miller, John R.

    2008-01-01

    A bidirectional pressure-regulator system has been devised for use in a regenerative fuel cell system. The bidirectional pressure-regulator acts as a back-pressure regulator as gas flows through the bidirectional pressure-regulator in one direction. Later, the flow of gas goes through the regulator in the opposite direction and the bidirectional pressure-regulator operates as a pressure- reducing pressure regulator. In the regenerative fuel cell system, there are two such bidirectional regulators, one for the hydrogen gas and another for the oxygen gas. The flow of gases goes from the regenerative fuel cell system to the gas storage tanks when energy is being stored, and reverses direction, flowing from the storage tanks to the regenerative fuel cell system when the stored energy is being withdrawn from the regenerative fuel cell system. Having a single bidirectional regulator replaces two unidirectional regulators, plumbing, and multiple valves needed to reverse the flow direction. The term "bidirectional" refers to both the bidirectional nature of the gas flows and capability of each pressure regulator to control the pressure on either its upstream or downstream side, regardless of the direction of flow.

  11. Buck/boost regulator

    NASA Astrophysics Data System (ADS)

    Paulkovich, J.; Rodriguez, G. E.

    1981-01-01

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

  12. [Regulation of terpene metabolism

    SciTech Connect

    Croteau, R.

    1991-01-01

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

  13. Environmental regulations on chlorofluorocarbons

    SciTech Connect

    Hoffman, J.S.; Wells, J.B. )

    1989-05-01

    In August 1988, the US Environmental Protection Agency issued final regulations that implement the Montreal Protocol on Substances that Deplete the Ozone Layer. The regulations require a 50% reduction in consumption of fully halogenated chlorofluorocarbons (CFCs) within 10 years and a freeze on consumption of halons within 4 years. The Montreal Protocol provisions were designed in September 1987 based on the results of a 2-year international series of scientific, technical, and economic workshops. As would be expected, scientific investigations continued during this period. While these investigations suggested that significant global depletion had already occurred, these preliminary findings were not taken into account during negotiations or rulemaking. In March 1988, however, the international Ozone Trends Panel confirmed the findings. Depletion greater than that projected under the Montreal Protocol has already occurred. An early reassessment of the Protocol provisions appears to be inevitable. Restrictions on CFCs will affect the refrigeration and air-conditioning industries. Emerging alternatives to CFCs include newly developed refrigerants, innovative designs, and engineering controls. Key issues in evaluating these alternatives include energy efficiency, capital costs, service to consumers, and compatibility with existing designs.

  14. 12 CFR 335.801 - Inapplicable SEC regulations; FDIC substituted regulations; additional information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 2011-01-01 false Inapplicable SEC regulations; FDIC substituted regulations...INSURED BANKS § 335.801 Inapplicable SEC regulations; FDIC substituted regulations...the cross reference to regulations of the SEC issued under sections 10A(m),...

  15. 12 CFR 335.801 - Inapplicable SEC regulations; FDIC substituted regulations; additional information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 2014-01-01 false Inapplicable SEC regulations; FDIC substituted regulations...INSURED BANKS § 335.801 Inapplicable SEC regulations; FDIC substituted regulations...the cross reference to regulations of the SEC issued under sections 10A(m),...

  16. 12 CFR 335.801 - Inapplicable SEC regulations; FDIC substituted regulations; additional information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 2013-01-01 false Inapplicable SEC regulations; FDIC substituted regulations...INSURED BANKS § 335.801 Inapplicable SEC regulations; FDIC substituted regulations...the cross reference to regulations of the SEC issued under sections 10A(m),...

  17. 12 CFR 335.801 - Inapplicable SEC regulations; FDIC substituted regulations; additional information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 2010-01-01 false Inapplicable SEC regulations; FDIC substituted regulations...INSURED BANKS § 335.801 Inapplicable SEC regulations; FDIC substituted regulations...the cross reference to regulations of the SEC issued under sections 10A(m),...

  18. 12 CFR 335.801 - Inapplicable SEC regulations; FDIC substituted regulations; additional information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 2012-01-01 false Inapplicable SEC regulations; FDIC substituted regulations...INSURED BANKS § 335.801 Inapplicable SEC regulations; FDIC substituted regulations...the cross reference to regulations of the SEC issued under sections 10A(m),...

  19. Regulation of Transcript Elongation.

    PubMed

    Belogurov, Georgiy A; Artsimovitch, Irina

    2015-10-15

    Bacteria lack subcellular compartments and harbor a single RNA polymerase that synthesizes both structural and protein-coding RNAs, which are cotranscriptionally processed by distinct pathways. Nascent rRNAs fold into elaborate secondary structures and associate with ribosomal proteins, whereas nascent mRNAs are translated by ribosomes. During elongation, nucleic acid signals and regulatory proteins modulate concurrent RNA-processing events, instruct RNA polymerase where to pause and terminate transcription, or act as roadblocks to the moving enzyme. Communications among complexes that carry out transcription, translation, repair, and other cellular processes ensure timely execution of the gene expression program and survival under conditions of stress. This network is maintained by auxiliary proteins that act as bridges between RNA polymerase, ribosome, and repair enzymes, blurring boundaries between separate information-processing steps and making assignments of unique regulatory functions meaningless. Understanding the regulation of transcript elongation thus requires genome-wide approaches, which confirm known and reveal new regulatory connections. PMID:26132790

  20. Regulation of Terpene Metabolism

    SciTech Connect

    Rodney Croteau

    2004-03-14

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

  1. Magnetostrictive Pressure Regulating System

    NASA Technical Reports Server (NTRS)

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

    2013-01-01

    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.

  2. Regulation of CDK4

    PubMed Central

    Bockstaele, Laurence; Coulonval, Katia; Kooken, Hugues; Paternot, Sabine; Roger, Pierre P

    2006-01-01

    Cyclin-dependent kinase (CDK)4 is a master integrator that couples mitogenic and antimitogenic extracellular signals with the cell cycle. It is also crucial for many oncogenic transformation processes. In this overview, we address various molecular features of CDK4 activation that are critical but remain poorly known or debated, including the regulation of its association with D-type cyclins, its subcellular location, its activating Thr172-phosphorylation and the roles of Cip/Kip CDK "inhibitors" in these processes. We have recently identified the T-loop phosphorylation of CDK4, but not of CDK6, as a determining target for cell cycle control by extracellular factors, indicating that CDK4-activating kinase(s) might have to be reconsidered. PMID:17092340

  3. Factors regulating microglia activation

    PubMed Central

    Kierdorf, Katrin; Prinz, Marco

    2013-01-01

    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

  4. Regulation of Vascular Integrity

    PubMed Central

    Murakami, Masahiro; Simons, Michael

    2010-01-01

    The integrity of blood vessels is critical to vascular homeostasis. Maintenance of vascular integrity has been conventionally regarded as a passive process that is largely dependent on continuous blood flow. Recent studies, however, have begun unveiling molecular processes essential for maintenance of vascular integrity and homeostasis under physiological conditions, leading to the notion that maintenance of the vasculature is an active biological process that requires continuous, basal cellular signaling. Failure of this system results in serious consequences such as hemorrhage, edema, inflammation and tissue ischemia. In this review, we will discuss the emerging concepts in regulation of vascular integrity with the emphasis on structural components of blood vessels that are essential for vascular maintenance. PMID:19337719

  5. [Regulation of terpene metabolism

    SciTech Connect

    Croteau, R.

    1989-11-09

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

  6. TFEB regulates lysosomal proteostasis.

    PubMed

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

    2013-05-15

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

  7. Circadian clock and output genes are rhythmically expressed in extratesticular ducts and accessory organs of mice

    PubMed Central

    Bebas, Piotr; Goodall, Cheri P.; Majewska, Magda; Neumann, Adam; Giebultowicz, Jadwiga M.; Chappell, Patrick E.

    2009-01-01

    Circadian clocks regulate multiple rhythms in mammalian tissues. In most organs core clock gene expression is oscillatory, with negative components Per and Cry peaking in antiphase to Bmal1. A notable exception is the testis, where clock genes seem nonrhythmic. Earlier mammalian studies, however, did not examine clock expression patterns in accessory ductal tissue required for sperm maturation and transport. Previous studies in insects demonstrated control of sperm maturation in vas deferens by a local circadian system. Sperm ducts express clock genes and display circadian pH changes controlled by vacuolar-type H+-ATPase and carbonic anhydrase (CA-II). It is unknown whether sperm-processing rhythms are conserved beyond insects. To address this question in mice housed in a light-dark environment, we examined temporal patterns of mPer1 and Bmal1 gene expression and protein abundance in epididymis, vas deferens, seminal vesicles, and prostate. Results demonstrate variable tissue-specific patterns of expression of the two genes, with variations in levels of clock proteins and their nucleo-cytoplasmic cycling observed among examined tissues. Strikingly, mPer1 and Bmal1 mRNA and proteins oscillate in antiphase in the prostate, with similar peak-trough patterns as observed in the suprachiasmatic nuclei, the brain’s central clock. Genes encoding CA and a V-ATPase subunit, which are rhythmically expressed in sperm ducts of moths, are also rhythmic in some segments of murine sperm ducts. Our data suggest that some sperm duct segments may contain peripheral circadian systems whereas others may express clock genes in a pleiotropic manner.—Bebas, P., Goodall, C. P., Majewska, M., Neumann, A., Giebultowicz, J. M., Chappell, P. E. Circadian clock and output genes are rhythmically expressed in extratesticular ducts and accessory organs of mice. PMID:18945877

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

    PubMed Central

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

    2012-01-01

    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

  9. Environmental Regulation, Globalization, and Innovation

    E-print Network

    Ashford, Nicholas

    2009-01-01

    This essay explores the complex relationship between environmental regulation, innovation, and sustainable development within the context of an increasingly globalizing economy. It will be argued that industrial policy, ...

  10. Power-MOSFET Voltage Regulator

    NASA Technical Reports Server (NTRS)

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

    1982-01-01

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

  11. T cells in helminth infection: the regulators and the regulated

    E-print Network

    T cells in helminth infection: the regulators and the regulated Matthew D. Taylor, Nienke van der Werf and Rick M. Maizels Institute of Immunology and Infection Research, University of Edinburgh, Ashworth Laboratories, West Mains Road, Edinburgh EH9 3JT, UK Helminth parasites survive through

  12. RUG Philosophy PhD Regulations, page 1 Regulations

    E-print Network

    Zaroubi, Saleem

    RUG Philosophy PhD Regulations, page 1 Regulations PhD programmes in Philosophy Faculty of Philosophy Contents 1. General provisions 2. Structure of the PhD programme (training and research) 3D programme in Philosophy. 1.1.2. The PhD programmes are organized by the Philosophy Graduate School

  13. Regulation of TGF-? Receptors.

    PubMed

    Budi, Erine H; Xu, Jian; Derynck, Rik

    2016-01-01

    In cells responding to extracellular polypeptide ligands, regulatory mechanisms at the level of cell surface receptors are increasingly seen to define the nature of the ligand-induced signaling responses. Processes that govern the levels of receptors at the plasma membrane, including posttranslational modifications, are crucial to ensure receptor function and specify the downstream signals. Indeed, extracellular posttranslational modifications of the receptors help define stability and ligand binding, while intracellular modifications mediate interactions with signaling mediators and accessory proteins that help define the nature of the signaling response. The use of various molecular biology and biochemistry techniques, based on chemical crosslinking, e.g., biotin or radioactive labeling, immunofluorescence to label membrane receptors and flow cytometry, allows for quantification of changes of cell surface receptor presentation. Here, we discuss recent progress in our understanding of the regulation of TGF-? receptors, i.e., the type I (T?RI) and type II (T?RII) TGF-? receptors, and describe basic methods to identify and quantify TGF-? cell surface receptors. PMID:26520115

  14. Redox regulation in cancer

    PubMed Central

    Das, Ila; Chandhok, Des

    2010-01-01

    Oxidative stress, implicated in the etiology of cancer, results from an imbalance in the production of reactive oxygen species (ROS) and cell’s own antioxidant defenses. ROS deregulate the redox homeostasis and promote tumor formation by initiating an aberrant induction of signaling networks that cause tumorigenesis. Ultraviolet (UV) exposures, ?-radiation and other environmental carcinogens generate ROS in the cells, which can exert apoptosis in the tumors, thereby killing the malignant cells or induce the progression of the cancer growth by blocking cellular defense system. Cancer stem cells take the advantage of the aberrant redox system and spontaneously proliferate. Oxidative stress and gene-environment interactions play a significant role in the development of breast, prostate, pancreatic and colon cancer. Prolonged lifetime exposure to estrogen is associated with several kinds of DNA damage. Oxidative stress and estrogen receptor-associated proliferative changes are suggested to play important roles in estrogen-induced breast carcinogenesis. BRCA1, a tumor suppressor against hormone responsive cancers such as breast and prostate cancer, plays a significant role in inhibiting ROS and estrogen mediated DNA damage; thereby regulate the redox homeostasis of the cells. Several transcription factors and tumor suppressors are involved during stress response such as Nrf2, NF?B and BRCA1. A promising strategy for targeting redox status of the cells is to use readily available natural substances from vegetables, fruits, herbs and spices. Many of the phytochemicals have already been identified to have chemopreventive potential, capable of intervening in carcinogenesis. PMID:20716925

  15. Lighting and Dark Sky Regulations

    E-print Network

    Radcliffe, David

    Lighting and Dark Sky Regulations Marjorie Palmer Spring 2008 #12;The UGA Land Use Clinic provides Road, Room 101 Athens, GA 30602-1510 (706) 583-0373 · Fax (706) 583-0612 jroskie@uga.edu #12;Lighting and Dark Sky Regulations Author:MarjoriePalmer Editor:JamieBakerRoskie Universityof

  16. Street sweeping and stormwater regulations

    SciTech Connect

    Not Available

    1993-10-01

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

  17. Design for pressure regulating components

    NASA Technical Reports Server (NTRS)

    Wichmann, H.

    1973-01-01

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

  18. Gravity and body mass regulation

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

  19. The Universities and Federal Regulation.

    ERIC Educational Resources Information Center

    Crowley, John C.

    The impact of increasing federal regulation on American universities is discussed based on an informal survey of senior academic and administrative officials in 13 public and private universities. As government regulation is becoming more intensive and compliance more resource- and time-consuming, government is perceived as having little…

  20. SIK2 regulates insulin secretion.

    PubMed

    Belgardt, Bengt-Frederik; Stoffel, Markus

    2014-03-01

    Correct regulation of insulin secretion by the pancreas is crucial for organismal function and survival. The AMPK-related kinase SIK2 (salt-inducible kinase 2) is now shown to be stabilized in pancreatic ?-cells following glucose stimulation, leading to improved systemic glucose homeostasis by regulating cellular calcium flux and insulin secretion. PMID:24576898

  1. Mental fatigue impairs emotion regulation.

    PubMed

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

    2015-06-01

    Because healthy physical and mental functioning depends on the ability to regulate emotions, it is important to identify moderators of such regulations. Whether mental fatigue, subsequent to the depletion of cognitive resources, impairs explicit emotion regulation to negative stimuli is currently unknown. This study explored this possibility. In a within-subject design over 2 separate sessions, healthy individuals performed easy (control session) or difficult (depletion session) cognitive tasks. Subsequently, they were presented with neutral and negative pictures, with instructions to either maintain or regulate (i.e., reduce) the emotions evoked by the pictures. Emotional reactivity was probed with the startle reflex. The negative pictures evoked a similar aversive state in the control and depletion sessions as measured by startle potentiation. However, subjects were able to down-regulate their aversive state only in the control session, not in the depletion session. These results indicate that mental fatigue following performance of cognitive tasks impairs emotion regulation without affecting emotional reactivity. These findings suggest that mental fatigue needs to be incorporated into models of emotion regulation. PMID:25706833

  2. Mental fatigue impairs emotion regulation

    PubMed Central

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

    2015-01-01

    As healthy physical and mental functioning depends on the ability to regulate emotions, it is important to identify moderators of such regulations. Whether mental fatigue, subsequent to the depletion of cognitive resources, impairs explicit emotion regulation to negative stimuli is currently unknown. This study explored this possibility. In a within-subject design over two separate sessions, healthy individuals performed easy (control session) or difficult (depletion session) cognitive tasks. Subsequently, they were presented neutral and negative pictures, with the instructions to either maintain or regulate (i.e., reduce) the emotions evoked by the pictures. Emotional reactivity was probed with the startle reflex. The negative pictures evoked a similar aversive state in the control and depletion sessions as measured by startle potentiation. However, subjects were able to down-regulate their aversive state only in the control session, but not in the depletion session. These results indicate that mental fatigue following performance of cognitive tasks impairs emotion regulation without affecting emotion reactivity. These findings suggest that mental fatigue needs to be incorporated into models of emotion regulation. PMID:25706833

  3. Regulation of TGF-? Signal Transduction

    PubMed Central

    Zhao, Bing; Chen, Ye-Guang

    2014-01-01

    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

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

    PubMed

    Ikeno, Tomoko; Nelson, Randy J

    2015-02-01

    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

  5. DEC2–E4BP4 Heterodimer Represses the Transcriptional Enhancer Activity of the EE Element in the Per2 Promoter

    PubMed Central

    Tanoue, Shintaro; Fujimoto, Katsumi; Myung, Jihwan; Hatanaka, Fumiyuki; Kato, Yukio; Takumi, Toru

    2015-01-01

    The circadian oscillation of clock gene expression in mammals is based on the interconnected transcriptional/translational feedback loops of Period (Per) and Bmal1. The Per feedback loop initiates transcription through direct binding of the BMAL1–CLOCK (NPAS2) heterodimer to the E-box of the Per2 promoter region. Negative feedback of PER protein on this promoter subsequently represses transcription. Other circadian transcription regulators, particularly E4BP4 and DEC2, regulate the amplitude and phase of Per2 expression rhythms. Moreover, a direct repeat of E-box-like (EE) elements in the Per2 promoter is required for its cell-autonomous circadian rhythm. However, the detailed mechanism for repression of the two core sequences of the EE element in the Per2 promoter region is unknown. Here, we show that E4BP4 binds to the Per2 EE element with DEC2 to repress transcription and identify the DEC2–E4BP4 heterodimer as a key repressor of the tightly interlocked Per2 feedback loop in the mammalian circadian oscillator. Our results suggest an additional modulatory mechanism for tuning of the phase of cell-autonomous Per2 gene expression cycling. PMID:26257703

  6. ROS Stress Resets Circadian Clocks to Coordinate Pro-Survival Signals

    PubMed Central

    Tamaru, Teruya; Kawamura, Genki; Varès, Guillaume; Honda, Kousuke; Mishra, Durga Prasad; Wang, Bing; Benjamin, Ivor; Sassone-Corsi, Paolo; Ozawa, Takeaki; Takamatsu, Ken

    2013-01-01

    Dysfunction of circadian clocks exacerbates various diseases, in part likely due to impaired stress resistance. It is unclear how circadian clock system responds toward critical stresses, to evoke life-protective adaptation. We identified a reactive oxygen species (ROS), H2O2 -responsive circadian pathway in mammals. Near-lethal doses of ROS-induced critical oxidative stress (cOS) at the branch point of life and death resets circadian clocks, synergistically evoking protective responses for cell survival. The cOS-triggered clock resetting and pro-survival responses are mediated by transcription factor, central clock-regulatory BMAL1 and heat shock stress-responsive (HSR) HSF1. Casein kinase II (CK2) –mediated phosphorylation regulates dimerization and function of BMAL1 and HSF1 to control the cOS-evoked responses. The core cOS-responsive transcriptome includes CK2-regulated crosstalk between the circadian, HSR, NF-kappa-B-mediated anti-apoptotic, and Nrf2-mediated anti-oxidant pathways. This novel circadian-adaptive signaling system likely plays fundamental protective roles in various ROS-inducible disorders, diseases, and death. PMID:24312621

  7. 77 FR 43082 - Federal Acquisition Regulation; Information Collection; Commerce Patent Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-23

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

  8. Targeting epigenetic regulations in cancer.

    PubMed

    Ning, Bo; Li, Wenyuan; Zhao, Wei; Wang, Rongfu

    2016-01-01

    Epigenetic regulation of gene expression is a dynamic and reversible process with DNA methylation, histone modifications, and chromatin remodeling. Recently, groundbreaking studies have demonstrated the importance of DNA and chromatin regulatory proteins from different aspects, including stem cell, development, and tumor genesis. Abnormal epigenetic regulation is frequently associated with diseases and drugs targeting DNA methylation and histone acetylation have been approved for cancer therapy. Although the network of epigenetic regulation is more complex than people expect, new potential druggable chromatin-associated proteins are being discovered and tested for clinical application. Here we review the key proteins that mediate epigenetic regulations through DNA methylation, the acetylation and methylation of histones, and the reader proteins that bind to modified histones. We also discuss cancer associations and recent progress of pharmacological development of these proteins. PMID:26508480

  9. State Regulation of Private Education.

    ERIC Educational Resources Information Center

    Lines, Patricia M.

    1982-01-01

    Examines state laws and the actions of various courts on home instruction and unauthorized educational programs. Suggests reforming the regulation of private education through legislative action that requires periodic testing as an alternative to compulsory school attendance. (Author/MLF)

  10. Feedback regulation in gene networks

    E-print Network

    Acar, Murat

    2007-01-01

    Cellular genetic information is encoded in DNA. The passage of this information from DNA to proteins is regulated at multiple levels and each level gives cells the chance to control the structure and function of their ...

  11. Flow-compensating pressure regulator

    NASA Technical Reports Server (NTRS)

    Baehr, E. F.

    1979-01-01

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

  12. Themes in ion pump regulation.

    PubMed

    Cornelius, F; Mahmmoud, Y A

    2003-04-01

    The Na,K-ATPase is an ion pump present in the plasma membrane. It is of vital importance for cell and body homeostasis and as such is under strict hormonal control. The molecular basis for the acute regulation of Na,K-ATPase is multisite phosphorylation by protein kinases that can alter its behavior. This includes direct effects on the Na,K-ATPase activity, regulation by membrane trafficking, and even dynamic regulation of interaction with regulatory proteins. In shark Na,K-ATPase, the latter includes functional interaction with a small hydrophobic protein of the FXYD protein family, phospholemman-like protein from shark, PLMS. This article summarizes our recent work on the mechanisms involved in the acute regulation of the Na,K-ATPase studied using a plasma membrane preparation from shark salt glands as an epithelial transport model. PMID:12763892

  13. 77 FR 13155 - Waste Regulation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-05

    ... From the Federal Register Online via the Government Printing Office NATIONAL SCIENCE FOUNDATION Waste Regulation AGENCY: National Science Foundation. ACTION: Notice of permit modification request... Martin personnel will be assuming responsibility for waste management activities. Those activities...

  14. 7 CFR 983.50 - Aflatoxin regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  15. 7 CFR 983.150 - Aflatoxin regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  16. 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 ...

  17. Petroleum: The Gas Cylinders (conveyance) Regulations, 1959 

    E-print Network

    Butler, R.A.

    1959-01-01

    These Regulations make various amendments to the Gas Cylinders (Conveyance) Regulations, 1931, as amended by ,the Gas Cylinders (Conveyance) Regulations, 1947. In particular, they make provision for conveyance of hydrogen ...

  18. Post regulation circuit with energy storage

    DOEpatents

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

    1992-01-01

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

  19. Drosophila Cytokine Unpaired 2 Regulates Physiological Homeostasis

    E-print Network

    Higgins, Darren

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

  20. 76 FR 15901 - Acquisition Regulation Miscellaneous Changes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-22

    ...Parts 1401, 1402, 1415, 1417, 1419, 1436, and 1452 RIN 1093-AA13 Acquisition Regulation Miscellaneous Changes AGENCY...regulations.gov. Please use the Regulation Identifier Number (RIN) 1093-AA13 in your message. Follow the instructions on the Web...

  1. Molecular determinants of regulated exocytosis.

    PubMed

    Gerber, Stefan H; Südhof, Thomas C

    2002-02-01

    Regulated exocytosis forms the basis for many intercellular signaling processes, for example, in hormone secretion or neurotransmitter release. During regulated exocytosis, the membrane of a secretory vesicle fuses with the plasma membrane in a tightly controlled reaction that is most often triggered by calcium. Recent advances have allowed major insights into the molecular mechanisms that mediate regulated exocytosis. In the present review, we will briefly discuss two key features of regulated exocytosis that have been particularly well studied recently. First, we will examine the current understanding of the membrane fusion reaction that underlies regulated exocytosis and that is effected by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) and munc18-like proteins similar to other membrane fusion reactions. Second, we will describe the role of the major candidates for the calcium sensors that trigger exocytosis, a protein family called synaptotagmins. Although our understanding of regulated exocytosis is as yet incomplete, the results from the studies of SNAREs, munc18s, and synaptotagmins have provided a molecular anchor for a more complete future description. PMID:11815450

  2. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart regulations....

  3. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart regulations....

  4. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart regulations....

  5. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart regulations....

  6. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart regulations....

  7. Thyroid Hormone Regulation of Metabolism

    PubMed Central

    Mullur, Rashmi; Liu, Yan-Yun

    2014-01-01

    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

  8. Cosmetic Regulations: A Comparative Study.

    PubMed

    Suhag, Jyoti; Dureja, Harish

    2015-01-01

    The regulatory framework, compliance requirement, efficacy, safety, and marketing of cosmetic products are considered the most important factors for growth of the cosmetic industry. There are different regulatory bodies across the globe that have their own insights for regulation; moreover, governments such as the United States, European Union, and Japan follow a stringent regulatory framework, whereas cosmetics are not so much strictly regulated in countries such as India, Brazil, and China. The alignment of a regulatory framework will play a significant role in the removal of barriers to trade, growth of market at an international level, innovation in the development and presentation of new products, and most importantly safety and efficacy of the marketed products. The present contribution gives insight into the important cosmetic regulations in areas of premarket approval, ingredient control, and labeling and warnings, with a special focus on the cosmetic regulatory environments in the United States, European Union, Japan, and India. Most importantly, the authors highlight the dark side of cosmetics associated with allergic reactions and even skin cancer. The importance of cosmetic regulations has been highlighted by dint of which the society can be healthier, accomplished by more stringent and harmonized regulations. PMID:26380505

  9. Neuronal regulation of tendon homoeostasis

    PubMed Central

    Ackermann, Paul W

    2013-01-01

    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

  10. How Europe regulates its genes

    SciTech Connect

    Balter, M.

    1991-06-07

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

  11. PTEN regulates cilia through Dishevelled

    PubMed Central

    Shnitsar, Iryna; Bashkurov, Mikhail; Masson, Glenn R.; Ogunjimi, Abiodun A.; Mosessian, Sherly; Cabeza, Eduardo Aguiar; Hirsch, Calley L.; Trcka, Daniel; Gish, Gerald; Jiao, Jing; Wu, Hong; Winklbauer, Rudolf; Williams, Roger L.; Pelletier, Laurence; Wrana, Jeffrey L.; Barrios-Rodiles, Miriam

    2015-01-01

    Cilia are hair-like cellular protrusions important in many aspects of eukaryotic biology. For instance, motile cilia enable fluid movement over epithelial surfaces, while primary (sensory) cilia play roles in cellular signalling. The molecular events underlying cilia dynamics, and particularly their disassembly, are not well understood. Phosphatase and tensin homologue (PTEN) is an extensively studied tumour suppressor, thought to primarily act by antagonizing PI3-kinase signalling. Here we demonstrate that PTEN plays an important role in multicilia formation and cilia disassembly by controlling the phosphorylation of Dishevelled (DVL), another ciliogenesis regulator. DVL is a central component of WNT signalling that plays a role during convergent extension movements, which we show here are also regulated by PTEN. Our studies identify a novel protein substrate for PTEN that couples PTEN to regulation of cilia dynamics and WNT signalling, thus advancing our understanding of potential underlying molecular etiologies of PTEN-related pathologies. PMID:26399523

  12. Beat regulation in twisted axonemes

    E-print Network

    Sartori, Pablo; Howard, Jonathon; Jülicher, Frank

    2015-01-01

    Cilia and flagella are hairlike organelles that propel cells through fluid. The active motion of the axoneme, the motile structure inside cilia and flagella, is powered by molecular motors of the dynein family. These motors generate forces and torques that slide and bend the microtubule doublets within the axoneme. To create regular waveforms the activities of the dyneins must be coordinated. It is thought that coordination is mediated by stresses due to radial, transverse, or sliding deformations, that build up within the moving axoneme. However, which particular component of the stress regulates the motors to produce the observed flagellar waveforms remains an open question. To address this question, we describe the axoneme as a three-dimensional bundle of filaments and characterize its mechanics. We show that regulation of the motors by radial and transverse stresses can lead to a coordinated flagellar motion only in the presence of twist. By comparison, regulation by shear stress is possible without twist...

  13. NETs and cell cycle regulation.

    PubMed

    Robson, Michael I; Le Thanh, Phu; Schirmer, Eric C

    2014-01-01

    There are many ways that the nuclear envelope can influence the cell cycle. In addition to roles of lamins in regulating the master cell cycle regulator pRb and nuclear envelope breakdown in mitosis, many other nuclear envelope proteins influence the cell cycle through regulatory or structural functions. Of particular note among these are the nuclear envelope transmembrane proteins (NETs) that appear to influence cell cycle regulation through multiple separate mechanisms. Some NETs and other nuclear envelope proteins accumulate on the mitotic spindle, suggesting functional or structural roles in the cell cycle. In interphase exogenous overexpression of some NETs promotes an increase in G1 populations, while others promote an increase in G2/M populations, sometimes associated with the induction of senescence. Intriguingly, most of the NETs linked to the cell cycle are highly restricted in their tissue expression; thus, their misregulation in cancer could contribute to the many tissue-specific types of cancer. PMID:24563348

  14. Circadian Regulation of Macronutrient Absorption.

    PubMed

    Hussain, M Mahmood; Pan, Xiaoyue

    2015-12-01

    Various intestinal functions exhibit circadian rhythmicity. Disruptions in these rhythms as in shift workers and transcontinental travelers are associated with intestinal discomfort. Circadian rhythms are controlled at the molecular level by core clock and clock-controlled genes. These clock genes are expressed in intestinal cells, suggesting that they might participate in the circadian regulation of intestinal functions. A major function of the intestine is nutrient absorption. Here, we will review absorption of proteins, carbohydrates, and lipids and circadian regulation of various transporters involved in their absorption. A better understanding of circadian regulation of intestinal absorption might help control several metabolic disorders and attenuate intestinal discomfort associated with disruptions in sleep-wake cycles. PMID:26269217

  15. 18 CFR 415.30 - Regulations generally.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Regulations 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....

  16. Interaction of circadian clock proteins CRY1 and PER2 is modulated by zinc binding and disulfide bond formation.

    PubMed

    Schmalen, Ira; Reischl, Silke; Wallach, Thomas; Klemz, Roman; Grudziecki, Astrid; Prabu, J Rajan; Benda, Christian; Kramer, Achim; Wolf, Eva

    2014-05-22

    Period (PER) proteins are essential components of the mammalian circadian clock. They form complexes with cryptochromes (CRY), which negatively regulate CLOCK/BMAL1-dependent transactivation of clock and clock-controlled genes. To define the roles of mammalian CRY/PER complexes in the circadian clock, we have determined the crystal structure of a complex comprising the photolyase homology region of mouse CRY1 (mCRY1) and a C-terminal mouse PER2 (mPER2) fragment. mPER2 winds around the helical mCRY1 domain covering the binding sites of FBXL3 and CLOCK/BMAL1, but not the FAD binding pocket. Our structure revealed an unexpected zinc ion in one interface, which stabilizes mCRY1-mPER2 interactions in vivo. We provide evidence that mCRY1/mPER2 complex formation is modulated by an interplay of zinc binding and mCRY1 disulfide bond formation, which may be influenced by the redox state of the cell. Our studies may allow for the development of circadian and metabolic modulators. PMID:24855952

  17. Calcium regulation of muscle contraction.

    PubMed Central

    Szent-Györgyi, A G

    1975-01-01

    Calcium triggers contraction by reaction with regulatory proteins that in the absence of calcium prevent interaction of actin and myosin. Two different regulatory systems are found in different muscles. In actin-linked regulation troponin and tropomyosin regulate actin by blocking sites on actin required for complex formation with myosin; in myosin-linked regulation sites on myosin are blocked in the absence of calcium. The major features of actin control are as follows: there is a requirement for tropomyosin and for a troponin complex having three different subunits with different functions; the actin displays a cooperative behavior; and a movement of tropomyosin occurs controlled by the calcium binding on troponin. Myosin regulation is controlled by a regulatory subunit that can be dissociated in scallop myosin reversibly by removing divalent cations with EDTA. Myosin control can function with pure actin in the absence of tropomyosin. Calcium binding and regulation of molluscan myosins depend on the presence of regulatory light chains. It is proposed that the light chains function by sterically blocking myosin sites in the absence of calcium, and that the "off" state of myosin requires cooperation between the two myosin heads. Both myosin control and actin control are widely distributed in different organisms. Many invertebrates have muscles with both types of regulation. Actin control is absent in the muscles of molluscs and in several minor phyla that lack troponin. Myosin control is not found in striated vertebrate muscles and in the fast muscles of crustacean decapods, although regulatory light chains are present. While in vivo myosin control may not be excluded from vertebrate striated muscles, myosin control may be absent as a result of mutations of the myosin heavy chain. PMID:806311

  18. Vasopressin and the Regulation of Aquaporin-2

    PubMed Central

    Wilson, Justin L.L.; Miranda, Carlos A.; Knepper, Mark A.

    2013-01-01

    Water excretion is regulated in large part through the regulation of the osmotic water permeability of the renal collecting duct epithelium. The water permeability is controlled by vasopressin through regulation of the water channel, aquaporin-2 (AQP2). Two processes contribute: 1) regulation of AQP2 trafficking to the apical plasma membrane; and 2) regulation of the total amount of the AQP2 protein in the cells. Regulation of AQP2 abundance is defective in several water balance disorders including many polyuric disorders and the syndrome of inappropriate antidiuresis (SIADH). Here we review vasopressin signaling in the renal collecting duct that is relevant to the two modes of water permeability regulation. PMID:23584881

  19. 75 FR 32719 - Acquisition Regulation: Agency Supplementary Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-09

    ... ``significant regulatory action'' under Executive Order 12866, ``Regulatory Planning and Review,'' (58 FR 51735... new regulations, section 3(a) of Executive Order 12988, ``Civil Justice Reform,'' 61 FR 4729 (February... 13132 Executive Order 13132, 64 FR 43255 (August 4, 1999), imposes certain requirements on...

  20. Regulation of Francisella Tularensis Virulence

    PubMed Central

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

    2011-01-01

    Francisella tularensis is one of the most virulent bacteria known and a Centers for Disease Control and Prevention Category A select agent. It is able to infect a variety of animals and insects and can persist in the environment, thus Francisella spp. must be able to survive in diverse environmental niches. However, F. tularensis has a surprising dearth of sensory and regulatory factors. Recent advancements in the field have identified new functions of encoded transcription factors and greatly expanded our understanding of virulence gene regulation. Here we review the current knowledge of environmental adaptation by F. tularensis, its transcriptional regulators and their relationship to animal virulence. PMID:21687801

  1. Regulations against the human nature

    NASA Astrophysics Data System (ADS)

    Elizondo-Garza, Fernando J.

    2001-05-01

    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.

  2. Epigenetic regulation in cardiac fibrosis

    PubMed Central

    Yu, Li-Ming; Xu, Yong

    2015-01-01

    Cardiac fibrosis represents an adoptive response in the heart exposed to various stress cues. While resolution of the fibrogenic response heralds normalization of heart function, persistent fibrogenesis is usually associated with progressive loss of heart function and eventually heart failure. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix proteins, a process the epigenetic machinery plays a pivotal role. In this mini-review, we summarize recent advances regarding the epigenetic regulation of cardiac fibrosis focusing on the role of histone and DNA modifications and non-coding RNAs. PMID:26635926

  3. Dealing with duplicate regulations and conflicting jurisdictions

    SciTech Connect

    Aamodt, P.L.

    1991-01-01

    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.

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

    SciTech Connect

    Abdel Wahab, Nadia . E-mail: nadia.wahab@imperial.ac.uk; Weston, Benjamin S.; Mason, Roger M.

    2005-07-15

    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.

  5. 76 FR 43585 - Bank Secrecy Act Regulations; Definitions and Other Regulations Relating to Money Services...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ... Bank Secrecy Act Regulations--Definitions and Other Regulations Relating to Prepaid Access, 75 FR 36589... 31 of the Code of Federal Regulations for the BSA regulations. See 75 FR 65806 (October 26, 2010... Proposed Rulemaking, Definitions and Other Regulations Relating to Money Services Businesses, 74 FR...

  6. 9 CFR 83.4 - VHS-regulated fish and VHS-regulated areas.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 false VHS-regulated fish and VHS-regulated areas. 83.4 ...SEPTICEMIA § 83.4 VHS-regulated fish and VHS-regulated areas. (a)(1) APHIS will list as a VHS-regulated fish any fish species found in...

  7. 9 CFR 83.4 - VHS-regulated fish and VHS-regulated areas.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false VHS-regulated fish and VHS-regulated... HEMORRHAGIC SEPTICEMIA § 83.4 VHS-regulated fish and VHS-regulated areas. (a)(1) APHIS will list as a VHS-regulated fish any fish species found in freshwater to be susceptible to the North American (type IV)...

  8. 9 CFR 83.4 - VHS-regulated fish and VHS-regulated areas.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false VHS-regulated fish and VHS-regulated... HEMORRHAGIC SEPTICEMIA § 83.4 VHS-regulated fish and VHS-regulated areas. (a)(1) APHIS will list as a VHS-regulated fish any fish species found in freshwater to be susceptible to the North American (type IV)...

  9. 9 CFR 83.4 - VHS-regulated fish and VHS-regulated areas.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false VHS-regulated fish and VHS-regulated... HEMORRHAGIC SEPTICEMIA § 83.4 VHS-regulated fish and VHS-regulated areas. (a)(1) APHIS will list as a VHS-regulated fish any fish species found in freshwater to be susceptible to the North American (type IV)...

  10. 9 CFR 83.4 - VHS-regulated fish and VHS-regulated areas.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false VHS-regulated fish and VHS-regulated... HEMORRHAGIC SEPTICEMIA § 83.4 VHS-regulated fish and VHS-regulated areas. (a)(1) APHIS will list as a VHS-regulated fish any fish species found in freshwater to be susceptible to the North American (type IV)...

  11. 9 CFR 83.4 - VHS-regulated fish and VHS-regulated areas.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false VHS-regulated fish and VHS-regulated... HEMORRHAGIC SEPTICEMIA § 83.4 VHS-regulated fish and VHS-regulated areas. (a)(1) APHIS will list as a VHS-regulated fish any fish species found in freshwater to be susceptible to the North American (type IV)...

  12. The Regulation of Carcinogenic Hazards.

    ERIC Educational Resources Information Center

    Gori, Gio Batta

    1980-01-01

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

  13. Microbial Metabolism Production and Regulation

    E-print Network

    Huang, Ching-Tsan

    1 Microbial Metabolism Production and Regulation of Primary and Secondary Metabolites Ching antibiotics and toxins #12;5 Primary metabolic pathway for the synthesis of aromatic amino acids The secondary metabolite antibiotics containing aromatic rings. Relation between 1o and 2o metabolic pathway #12

  14. Adrenocortical Activity and Emotion Regulation.

    ERIC Educational Resources Information Center

    Stansbury, Kathy; Gunnar, Megan R.

    1994-01-01

    This essay argues that the activity of the hypothalamic-pituitary-adrenocortical (HPA) system does not appear to be related to emotion regulation processes in children, although individual differences in emotion processes related to negative emotion temperaments appear to be associated with individual differences in HPA reactivity among normally…

  15. Parking Regulations PARKING POLICY STATEMENT

    E-print Network

    Aazhang, Behnaam

    1 Parking Regulations PARKING POLICY STATEMENT: 1. All employees and students of Rice University. CAMPUS PARKING REGISTRATION · A valid Rice permit must be permanently affixed to the rear window will be assessed when issuing a new card. · The purchase of contract parking in a lot or the garage does

  16. REGULATIONS OF UNIVERSITY OF FLORIDA

    E-print Network

    Sin, Peter

    REGULATIONS OF UNIVERSITY OF FLORIDA 6C1-3.0051 Lost or Abandoned Property. (1) For the purposes lands located in the City of Gainesville, Florida, occupied or controlled by the University of Florida as the date on which an identified owner of lost or abandoned property is notified by the Property Custodian

  17. Student Travel: Policies - Regulations - Exhibits.

    ERIC Educational Resources Information Center

    Trujillo, Lorenzo A.; And Others

    The Jefferson County (Colorado) Public Schools' regulations and policies concerning student travel covers these forms of travel: student activity travel, extended student travel, district sponsored student travel, district authorized student travel, student exchange, and bonus learning trips. Issues and items addressed include: (1) authorization…

  18. Electropneumatic rheostat regulates high current

    NASA Technical Reports Server (NTRS)

    Haacker, J. F.; Jedlicka, J. R.; Wagoner, C. B.

    1965-01-01

    Electropneumatic rheostat maintains a constant direct current in each of several high-power parallel loads, of variable resistance, across a single source. It provides current regulation at any preset value by dissipating the proper amount of energy thermally, and uses a column of mercury to vary the effective length of a resistance element.

  19. 77 FR 14571 - Waste Regulation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-12

    ... From the Federal Register Online via the Government Printing Office NATIONAL SCIENCE FOUNDATION Waste Regulation AGENCY: National Science Foundation. ACTION: Correction to notice of permit modification request received under the Antarctic Conservation Act of 1978, Public Law 95-541. SUMMARY:...

  20. Autophagy proteins regulate ERK phosphorylation.

    PubMed

    Martinez-Lopez, Nuria; Athonvarangkul, Diana; Mishall, Priti; Sahu, Srabani; Singh, Rajat

    2013-01-01

    Autophagy is a conserved pathway that maintains cellular quality control. Extracellular signal-regulated kinase (ERK) controls various aspects of cell physiology including proliferation. Multiple signalling cascades, including ERK, have been shown to regulate autophagy, however whether autophagy proteins (ATG) regulate cell signalling is unknown. Here we show that growth factor exposure increases the interaction of ERK cascade components with ATG proteins in the cytosol and nucleus. ERK and its upstream kinase MEK localize to the extra-luminal face of autophagosomes. ERK2 interacts with ATG proteins via its substrate-binding domains. Deleting Atg7 or Atg5 or blocking LC3 lipidation or ATG5-ATG12 conjugation decreases ERK phosphorylation. Conversely, increasing LC3-II availability by silencing the cysteine protease ATG4B or acute trehalose exposure increases ERK phosphorylation. Decreased ERK phosphorylation in Atg5?/? cells does not occur from overactive phosphatases. Our findings thus reveal an unconventional function of ATG proteins as cellular scaffolds in the regulation of ERK phosphorylation. PMID:24240988

  1. Beat regulation in twisted axonemes

    E-print Network

    Pablo Sartori; Veikko Geyer; Jonathon Howard; Frank Jülicher

    2015-11-24

    Cilia and flagella are hairlike organelles that propel cells through fluid. The active motion of the axoneme, the motile structure inside cilia and flagella, is powered by molecular motors of the dynein family. These motors generate forces and torques that slide and bend the microtubule doublets within the axoneme. To create regular waveforms the activities of the dyneins must be coordinated. It is thought that coordination is mediated by stresses due to radial, transverse, or sliding deformations, that build up within the moving axoneme. However, which particular component of the stress regulates the motors to produce the observed flagellar waveforms remains an open question. To address this question, we describe the axoneme as a three-dimensional bundle of filaments and characterize its mechanics. We show that regulation of the motors by radial and transverse stresses can lead to a coordinated flagellar motion only in the presence of twist. By comparison, regulation by shear stress is possible without twist. We calculate emergent beating patterns in twisted axonemes resulting from regulation by transverse stresses. The waveforms are similar to those observed in flagella of Chlamydomonas and sperm. Due to the twist, the waveform has non-planar components, which result in swimming trajectories such as twisted ribbons and helices that agree with observations.

  2. Transcriptional regulation of hepatic lipogenesis.

    PubMed

    Wang, Yuhui; Viscarra, Jose; Kim, Sun-Joong; Sul, Hei Sook

    2015-10-22

    Fatty acid and fat synthesis in the liver is a highly regulated metabolic pathway that is important for very low-density lipoprotein (VLDL) production and thus energy distribution to other tissues. Having common features at their promoter regions, lipogenic genes are coordinately regulated at the transcriptional level. Transcription factors, such as upstream stimulatory factors (USFs), sterol regulatory element-binding protein 1C (SREBP1C), liver X receptors (LXRs) and carbohydrate-responsive element-binding protein (ChREBP) have crucial roles in this process. Recently, insights have been gained into the signalling pathways that regulate these transcription factors. After feeding, high blood glucose and insulin levels activate lipogenic genes through several pathways, including the DNA-dependent protein kinase (DNA-PK), atypical protein kinase C (aPKC) and AKT-mTOR pathways. These pathways control the post-translational modifications of transcription factors and co-regulators, such as phosphorylation, acetylation or ubiquitylation, that affect their function, stability and/or localization. Dysregulation of lipogenesis can contribute to hepatosteatosis, which is associated with obesity and insulin resistance. PMID:26490400

  3. Temperature: Human Regulating, Ants Conforming

    ERIC Educational Resources Information Center

    Clopton, Joe R.

    2007-01-01

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

  4. Regulating Knowledge: Intellectual Property and

    E-print Network

    Raina, Ramesh

    Professor of Law, University of Pittsburgh School of Law February 6, 2015 Syracuse University Topics expression / free use/ the public domain, and regulating fair competition practices (via accurate use of matter," or, in general, applications of science, technology, and engineering. The Supreme Court

  5. Army Regulation 2001 Environmental Quality

    E-print Network

    US Army Corps of Engineers

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

  6. Army Regulation 69012 Civilian Personnel

    E-print Network

    US Army Corps of Engineers

    Army Regulation 690­12 Civilian Personnel Equal Employment Opportunity and Affirmative Action Headquarters Department of the Army Washington, DC 4 March 1988 Unclassified #12;SUMMARY of CHANGE AR 690 opportunity management at Headquarters, Department of the Army (para 1-4); and implements DODD 1440.1. #12

  7. Army Regulation 690600 Civilian Personnel

    E-print Network

    US Army Corps of Engineers

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

  8. 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...

  9. Essential infrastructure: national nuclear regulation.

    PubMed

    Paperiello, Carl J

    2011-01-01

    In order for nuclear power to expand to many countries that do not currently have it, it will be essential for these countries to have laws, regulations, guidance and organizations that can license or permit nuclear power plants and support nuclear facilities, ensure compliance by inspection, and enforce nuclear regulations. The viability of nuclear power worldwide depends on an extremely high level of safety everywhere, and compliance with a number of international treaties is required before supplier nations will provide the material, both hardware and software, to build and operate nuclear power plants. While infrastructure support can be obtained from the IAEA and other countries, an essential core of expertise must exist in the country seeking to establish domestic nuclear power generation. While some reliance can be placed on the safety reviews of standard reactor designs by the nuclear regulators in supplier nations, the certification of fuel design, the quality of instruments, and the matching of a new reactor to a proposed site in the importing nation will require site-specific reviews. National arrangements are also needed for emergency preparedness, environmental protection, fuel transportation and the storage, transportation and disposal of radioactive waste. If foreign contractors and consultants are engaged to perform much of the technical work for the regulatory body(s) that has to be performed by the importing nation, that nation must have a core cadre of technically knowledgeable regulators and an organization to provide management and oversight of the contractors and consultants. Consistency in national nuclear regulations, the deployment of standardized nuclear power plant designs and standardized supporting material infrastructure can promote the safe and secure worldwide growth in nuclear power. PMID:21399415

  10. 48 CFR Appendix - Federal Acquisition Regulation (FAR) Index

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Federal Acquisition Regulation (FAR) Index Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT... (IFMS) Contract clause. FAR Index Federal Acquisition Regulation (FAR) Index Editorial Note:...

  11. 77 FR 54863 - Polychlorinated Biphenyls (PCBs): Revisions to Manifesting Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-06

    ...sections of the Polychlorinated Biphenyl (PCB) regulations associated with the manifesting...Federal Regulations (CFR) part 761 of the PCB regulations. In the ``Rules and Regulations...the existing regulations for manifesting PCB wastes to match the existing Uniform...

  12. Swiss regulations for controlling clinical trials.

    PubMed

    Zanini, G M

    1998-04-01

    Switzerland has recently issued regulations designed to control all trials with drugs in human subjects, namely the 'Regolamento dell'Ufficio Intercantonale per il controllo dei medicamenti in fase di studio clinico' (Intercantonal Regulations Controlling Drugs used in Clinical Trials), which have been operating since 1st January 1995. These new regulations are generally consistent with other international regulations and have introduced the concept of good clinical practice (GCP) into Switzerland. There are other regulations in Switzerland, such as Federal regulations on immunobiological products, special rules governing the administration of radiolabelled drugs to humans, drugs of abuse and medical devices. Any gap in the central regulations must be filled by cantonal regulations, where they exist. This is a comprehensive review of the regulations governing clinical trials in Switzerland, with special attention being devoted to trials with therapeutic compounds and to compatibility between Swiss and international procedures. PMID:9634649

  13. Regulation of Drosophila Metamorphosis by Xenobiotic Response Regulators

    PubMed Central

    Deng, Huai; Kerppola, Tom K.

    2013-01-01

    Mammalian Nrf2-Keap1 and the homologous Drosophila CncC-dKeap1 protein complexes regulate both transcriptional responses to xenobiotic compounds as well as native cellular and developmental processes. The relationships between the functions of these proteins in xenobiotic responses and in development were unknown. We investigated the genes regulated by CncC and dKeap1 during development and the signal transduction pathways that modulate their functions. CncC and dKeap1 were enriched within the nuclei in many tissues, in contrast to the reported cytoplasmic localization of Keap1 and Nrf2 in cultured mammalian cells. CncC and dKeap1 occupied ecdysone-regulated early puffs on polytene chromosomes. Depletion of either CncC or dKeap1 in salivary glands selectively reduced early puff gene transcription. CncC and dKeap1 depletion in the prothoracic gland as well as cncCK6/K6 and dKeap1EY5/EY5 loss of function mutations in embryos reduced ecdysone-biosynthetic gene transcription. In contrast, dKeap1 depletion and the dKeap1EY5/EY5 loss of function mutation enhanced xenobiotic response gene transcription in larvae and embryos, respectively. Depletion of CncC or dKeap1 in the prothoracic gland delayed pupation by decreasing larval ecdysteroid levels. CncC depletion suppressed the premature pupation and developmental arrest caused by constitutive Ras signaling in the prothoracic gland; conversely, constitutive Ras signaling altered the loci occupied by CncC on polytene chromosomes and activated transcription of genes at these loci. The effects of CncC and dKeap1 on both ecdysone-biosynthetic and ecdysone-regulated gene transcription, and the roles of CncC in Ras signaling in the prothoracic gland, establish the functions of these proteins in the neuroendocrine axis that coordinates insect metamorphosis. PMID:23408904

  14. 78 FR 59902 - Regulated Navigation Area; Special Buzzards Bay Vessel Regulation, Buzzards Bay, MA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-30

    ...USCG-2011-0322] RIN 1625-AA11 Regulated Navigation Area; Special Buzzards Bay Vessel Regulation, Buzzards Bay, MA AGENCY: Coast Guard, DHS. ACTION...Proposed Rulemaking for the Special Buzzards Bay regulation published in the Federal...

  15. 75 FR 1269 - Vegetable Import Regulations; Modification of Potato Import Regulations; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

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

  16. Redox regulation of Ran GTPase.

    PubMed

    Heo, Jongyun

    2008-11-21

    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

  17. Gene regulation by mechanical forces

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

  18. Hawking Radiation and Ultraviolet Regulators

    E-print Network

    N. Hambli; C. P. Burgess

    1995-10-24

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

  19. Epigenetic pathways regulating bone homeostasis.

    PubMed

    Lian, Jane B

    2015-12-01

    Epigenetic control of the genome involves a complex series of unique, physiologically responsive and integrated pathways, each with distinct mechanisms. Insight into epigenetic regulation has transformed understanding of inheritance, development and a broad spectrum of biological processes as well as advances in mechanistic and clinical characterization of tissues and disease states. The dynamics of bone tissue undergoing continuous remodeling during growth and turnover in the adult skeleton, involves epigenetic mechanisms that have emerged as an important component to maintaining skeletal homeostasis. A series of four reviews are presented in the journal BONE covering different aspects of epigenetic control mechanisms that have impacted on the skeleton. Authorship on each of the reviews is shared by investigators from different institutions to present a consensus of emerging concepts and future directions for understanding regulation of the bone epigenome and skeletal pathologies. PMID:26036171

  20. Regulating health: transcending disciplinary boundaries.

    PubMed

    Seddon, Toby

    2013-03-01

    Health and health care problems can be addressed from multiple disciplinary perspectives. This raises challenges for how to do cross-disciplinary scholarship in ways that are still robust, rigorous and coherent. This paper sets out one particular approach to cross-cutting research--regulation--which has proved extremely fertile for scholars working in diverse fields, from coal mine safety to tax compliance. The first part of the paper considers how regulatory ideas might be applied to health and health care research in general. The second part goes on to sketch out how a regulation perspective on one specific area, illicit drug policy, can open up new directions for research. In conclusion, a future research agenda is outlined for regulatory scholarship on health and health care. PMID:23070460

  1. Complex Dynamics of Transcription Regulation

    PubMed Central

    Stavreva, Diana A; Varticovski, Lyuba; Hager, Gordon L.

    2012-01-01

    Transcription is a tightly regulated cellular function which can be triggered by endogenous (intrinsic) or exogenous (extrinsic) signals. The development of novel techniques to examine the dynamic behavior of transcription factors and the analysis of transcriptional activity at the single cell level with increased temporal resolution has revealed unexpected elements of stochasticity and dynamics of this process. Emerging research reveals a complex picture, wherein a wide range of time scales and temporal transcription patterns overlap to generate transcriptional programs. The challenge now is to develop a perspective that can guide us to common underlying mechanisms, and consolidate these findings. Here we review the recent literature on temporal dynamic and stochastic gene regulation patterns governed by intrinsic or extrinsic signals, utilizing the glucocorticoid receptor (GR)-mediated transcriptional model to illustrate commonality of these emerging concepts. PMID:22484099

  2. Cardiac myofilaments: mechanics and regulation

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  3. Redox regulation of Ran GTPase

    SciTech Connect

    Heo, Jongyun

    2008-11-21

    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.

  4. Frequency regulator for synchronous generators

    DOEpatents

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

    1982-01-01

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

  5. Strategic Behaviour under Regulation Benchmarking

    E-print Network

    Jamasb, Tooraj; Nillesen, Paul; Pollitt, Michael G.

    2004-06-16

    returns to scale models can affect the long-term structure of the sector. The Dutch regulator has used a constant returns to scale DEA model and assumes that firms can freely adjust their scale of operations through mergers and acquisitions. Other... , University of Cambridge 10 the model. In DEA-based models increasing the discriminatory power of models generally results in improving efficiency scores of firms.11 3.3 Mergers and acquisitions The result of unbundling vertically integrated...

  6. Frequency regulator for synchronous generators

    DOEpatents

    Karlicek, R.F.

    1982-08-10

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

  7. Regulation of eucaryotic gene expression

    SciTech Connect

    Brent, R.; Ptashne, M.S

    1989-05-23

    This patent describes a method of regulating the expression of a gene in a eucaryotic cell. The method consists of: providing in the eucaryotic cell, a peptide, derived from or substantially similar to a peptide of a procaryotic cell able to bind to DNA upstream from or within the gene, the amount of the peptide being sufficient to bind to the gene and thereby control expression of the gene.

  8. Redox Regulation of Protein Kinases

    PubMed Central

    Truong, Thu H.; Carroll, Kate S.

    2015-01-01

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

  9. Actin Cytoskeleton Regulates Hippo Signaling

    PubMed Central

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

    2013-01-01

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

  10. Auricular Acupuncture and Vagal Regulation

    PubMed Central

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

    2012-01-01

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

  11. Optical regulation of cell chain

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  12. Package warehouse upgrades and regulations

    SciTech Connect

    Hester, J.F.

    1994-12-31

    Many regulations have been written by states and the EPA about bulk chemical storage since its introduction in the late 1970`s. However, until this year the National Fire Protection Association, through their NFPA guidelines, and the Uniform Fire Code have been the only significant work written concerning package ag chemical storage. These codes have been adopted by many states and are enforced at the local (city) level on both US coasts and larger cities around the midwest and south. Several catastrophic fires at package locations during the last few years have resulted in discussions by regulators and industry to provide not only insurance and guidance but also regulations to retailers and distributors in order to upgrade facilities to reduce the risk of large spills and fires. The Midwest Ag Chemical Association began the task of providing guidance regarding package warehouses three years ago and after twelve months of input from EPA, suppliers and retail dealers, has published the Fundamental Principles of Agricultural Chemical Storage in August of 1993.

  13. Optical regulation of cell chain

    PubMed Central

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

    2015-01-01

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

  14. Rethinking regulations for disposal criticality

    SciTech Connect

    Scott, M.; Doering, T.

    1997-08-01

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

  15. NRC - regulator of nuclear safety

    SciTech Connect

    1997-05-01

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

  16. Regulation of distribution network business

    SciTech Connect

    Roman, J.; Gomez, T.; Munoz, A.; Peco, J.

    1999-04-01

    The traditional distribution function actually comprises two separate activities: distribution network and retailing. Retailing, which is also termed supply, consists of trading electricity at the wholesale level and selling it to the end users. The distribution network business, or merely distribution, is a natural monopoly and it must be regulated. Increasing attention is presently being paid to the regulation of distribution pricing. Distribution pricing, comprises two major tasks: global remuneration of the distribution utility and tariff setting by allocation of the total costs among all the users of the network services. In this paper, the basic concepts for establishing the global remuneration of a distribution utility are presented. A remuneration scheme which recognizes adequate investment and operation costs, promotes losses reduction and incentivates the control of the quality of service level is proposed. Efficient investment and operation costs are calculated by using different types of strategic planning and regression analysis models. Application examples that have been used during the distribution regulation process in Spain are also presented.

  17. Musical affect regulation in infancy.

    PubMed

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

    2015-03-01

    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

  18. Revision of Suggested State Regulations.

    PubMed

    Winston, John P

    2016-02-01

    It is the mission of the Conference of Radiation Control Program Directors (CRCPD) to promote radiological health in all aspects and phases of implementation and to create a seamless and coherent regulatory structure across the United States. CRCPD currently has 25 committees charged with the development of Suggested State Regulations (SSRs) for everything from transportation and waste disposal to tanning and medical therapy. The SR-F Committee is responsible for the suggested regulations of the equipment and processes used in medical diagnostic and interventional x-ray procedures. Several states are required by law to adopt the SSR verbatim, making it vital that they are kept current. The current revision of SR-F brought together representatives from the state radiation control programs, the Food and Drug Administration, the American Association of Physicists in Medicine, American College of Radiology, and industry. Through the course of two meetings and multiple conference calls, the Committee finalized an updated draft. The CRCPD process for the development of SSR is well established and includes internal and external peer review, review by the state Director Members, approval by the Board of Directors, and concurrence from relevant federal agencies. Once final, an SSR allows a state radiation control program to proceed through the state's own regulatory process with a vetted set of regulations, making this difficult process more efficient and effective. PMID:26717174

  19. 75 FR 59611 - Iranian Transactions Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ...Regulations in the Code of Federal Regulations to remove general licenses authorizing the importation into the United States of, and dealings in, certain foodstuffs and carpets of Iranian origin and related services, and to implement the import and export...

  20. 15 CFR 922.165 - Emergency regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Florida Keys National Marine Sanctuary § 922.165 Emergency regulations. Where necessary to prevent or minimize the destruction...

  1. 15 CFR 922.165 - Emergency regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Florida Keys National Marine Sanctuary § 922.165 Emergency regulations. Where necessary to prevent or minimize the destruction...

  2. 15 CFR 2.7 - Supplementary regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...THE FEDERAL TORT CLAIMS ACT § 2.7 Supplementary regulations...mentioned in paragraph (a) of § 2.3 may issue regulations or instructions covering his/her area of responsibility hereunder...amended at 63 FR 29945, June 2,...

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

    E-print Network

    Her Majesty's Stationary Office

    1957-01-01

    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 ...

  4. 50 CFR 26.33 - Special regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...public use, access, and recreation within certain individual national wildlife refuges where there is a need to amend, modify, relax or make more stringent the regulations contained in this subchapter C. The issued special regulations will supplement the...

  5. 7 CFR 932.52 - Outgoing regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...Vegetables, Nuts), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order Regulating Handling...regulations. (a) Minimum standards for packaged olives. No handler shall use processed olives in the production of packaged olives or...

  6. 7 CFR 932.52 - Outgoing regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order Regulating Handling...regulations. (a) Minimum standards for packaged olives. No handler shall use processed olives in the production of packaged olives or...

  7. 7 CFR 932.52 - Outgoing regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order Regulating Handling...regulations. (a) Minimum standards for packaged olives. No handler shall use processed olives in the production of packaged olives or...

  8. 15 CFR 922.185 - Emergency regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Hawaiian Islands Humpback Whale National Marine Sanctuary § 922.185 Emergency regulations. Where necessary to prevent or minimize the destruction...

  9. 15 CFR 922.185 - Emergency regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Hawaiian Islands Humpback Whale National Marine Sanctuary § 922.185 Emergency regulations. Where necessary to prevent or minimize the destruction...

  10. 50 CFR 20.153 - Regulations committee.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  11. 50 CFR 20.153 - Regulations committee.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  12. 50 CFR 20.153 - Regulations committee.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  13. 50 CFR 20.153 - Regulations committee.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  14. 32 CFR 770.4 - Hunting regulations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  15. 50 CFR 20.153 - Regulations committee.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  16. 32 CFR 770.4 - Hunting regulations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2014-07-01 2014-07-01 false Hunting regulations. 770.4 Section 770...ACCESS TO PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps Base, Quantico, Virginia § 770.4 Hunting regulations. All persons...

  17. 32 CFR 770.4 - Hunting regulations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2012-07-01 2012-07-01 false Hunting regulations. 770.4 Section 770...ACCESS TO PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps Base, Quantico, Virginia § 770.4 Hunting regulations. All persons...

  18. 43 CFR 431.9 - Future regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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...

  19. Factories: The Cinematograph Film Stripping Regulations, 1939 

    E-print Network

    Her Majesty's Stationary Office

    1941-01-01

    In pursuance of Section 60 of the Factories Act, 1937, and, as respects Part II of these Regulations, in pursuance of Section 35 of the said Act, I hereby make the following Regulations and direct that they shall apply ...

  20. 46 CFR 310.67 - Academy regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 8 2010-10-01 2010-10-01 false Academy regulations. 310.67 Section 310.67 Shipping...of Midshipmen at the United States Merchant Marine Academy § 310.67 Academy regulations. The Superintendent of the...

  1. 75 FR 10567 - Commerce Acquisition Regulation (CAR)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-08

    ...Chapter 13 Commerce Acquisition Regulation (CAR); Final Rule Federal Register / Vol...0605-AA26 Commerce Acquisition Regulation (CAR) AGENCY: Department of Commerce (DOC...guidance. This final rule updates the entire CAR through FAC 2005- 21. DATES: This...

  2. 32 CFR 770.3 - Fishing regulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...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...

  3. 32 CFR 770.3 - Fishing regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...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...

  4. POWERSTRUCTURES : the urban form of regulations

    E-print Network

    Noyman, Ariel

    2015-01-01

    This thesis aims to explore the relationship between urban form and law, regulation and policy in the built environment. It depicts the roots, the necessity and exponential growth of regulations across the urbanized world ...

  5. Flexible Bureaucracies in Labor Market Regulation

    E-print Network

    Piore, Michael J.

    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 ...

  6. 76 FR 62630 - Information Security Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-11

    ... From the Federal Register Online via the Government Printing Office CENTRAL INTELLIGENCE AGENCY 32 CFR Part 1902 Information Security Regulations AGENCY: Central Intelligence Agency. ACTION: Final rule. SUMMARY: The Central Intelligence agency is removing certain information security regulations which...

  7. Liechtenstein: New Regulation for the Gymnasium.

    ERIC Educational Resources Information Center

    Western European Education, 1984

    1984-01-01

    In 1981 the Liechtenstein government issued a regulation concerning the gymnasium or secondary school. The educational objectives and administrative structure of and teacher obligations to the gymnasium under the new regulation are described. (RM)

  8. Emotion Regulation and Depressive Symptoms in Preadolescence

    ERIC Educational Resources Information Center

    Siener, Shannon; Kerns, Kathryn A.

    2012-01-01

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

  9. 7 CFR 959.322 - Handling regulation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Handling regulation. 959.322 Section 959.322 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE ONIONS GROWN IN SOUTH TEXAS Handling Regulations § 959.322...

  10. Regulation of Motivation: Contextual and Social Aspects

    ERIC Educational Resources Information Center

    Wolters, Christopher A.

    2011-01-01

    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…

  11. Self-Regulation in Online Learning

    ERIC Educational Resources Information Center

    Cho, Moon-Heum; Shen, Demei

    2013-01-01

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

  12. 43 CFR 424.1 - Regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Regulations. 424.1 Section 424.1 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR REGULATIONS PERTAINING TO STANDARDS FOR THE PREVENTION, CONTROL, AND ABATEMENT OF ENVIRONMENTAL POLLUTION...

  13. 43 CFR 424.1 - Regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Regulations. 424.1 Section 424.1 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR REGULATIONS PERTAINING TO STANDARDS FOR THE PREVENTION, CONTROL, AND ABATEMENT OF ENVIRONMENTAL POLLUTION...

  14. 43 CFR 424.1 - Regulations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Regulations. 424.1 Section 424.1 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR REGULATIONS PERTAINING TO STANDARDS FOR THE PREVENTION, CONTROL, AND ABATEMENT OF ENVIRONMENTAL POLLUTION...

  15. 43 CFR 424.1 - Regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Regulations. 424.1 Section 424.1 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR REGULATIONS PERTAINING TO STANDARDS FOR THE PREVENTION, CONTROL, AND ABATEMENT OF ENVIRONMENTAL POLLUTION...

  16. 43 CFR 424.1 - Regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Regulations. 424.1 Section 424.1 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR REGULATIONS PERTAINING TO STANDARDS FOR THE PREVENTION, CONTROL, AND ABATEMENT OF ENVIRONMENTAL POLLUTION...

  17. 43 CFR 431.9 - Future regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Future regulations. 431.9 Section 431.9 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE... CANYON PROJECT, ARIZONA/NEVADA § 431.9 Future regulations. (a) Reclamation may from time to...

  18. 10 CFR 904.14 - Future regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Future regulations. 904.14 Section 904.14 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.14 Future regulations. (a) Western may from time to time promulgate...

  19. 10 CFR 904.14 - Future regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Future regulations. 904.14 Section 904.14 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.14 Future regulations. (a) Western may from time to time promulgate...

  20. 43 CFR 431.9 - Future regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Future regulations. 431.9 Section 431.9 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE... CANYON PROJECT, ARIZONA/NEVADA § 431.9 Future regulations. (a) Reclamation may from time to...

  1. 43 CFR 431.9 - Future regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Future regulations. 431.9 Section 431.9 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE... CANYON PROJECT, ARIZONA/NEVADA § 431.9 Future regulations. (a) Reclamation may from time to...

  2. 43 CFR 431.9 - Future regulations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Future regulations. 431.9 Section 431.9 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE... CANYON PROJECT, ARIZONA/NEVADA § 431.9 Future regulations. (a) Reclamation may from time to...

  3. 10 CFR 904.14 - Future regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Future regulations. 904.14 Section 904.14 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.14 Future regulations. (a) Western may from time to time promulgate...

  4. 10 CFR 904.14 - Future regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Future regulations. 904.14 Section 904.14 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.14 Future regulations. (a) Western may from time to time promulgate...

  5. 10 CFR 904.14 - Future regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Future regulations. 904.14 Section 904.14 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.14 Future regulations. (a) Western may from time to time promulgate...

  6. 43 CFR 431.9 - Future regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Future regulations. 431.9 Section 431.9 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE... CANYON PROJECT, ARIZONA/NEVADA § 431.9 Future regulations. (a) Reclamation may from time to...

  7. [Consideration of Mobile Medical Device Regulation].

    PubMed

    Peng, Liang; Yang, Pengfei; He, Weigang

    2015-07-01

    The regulation of mobile medical devices is one of the hot topics in the industry now. The definition, regulation scope and requirements, potential risks of mobile medical devices were analyzed and discussed based on mobile computing techniques and the FDA guidance of mobile medical applications. The regulation work of mobile medical devices in China needs to adopt the risk-based method. PMID:26665948

  8. Bureaucrats and Brainpower: Government Regulation of Universities.

    ERIC Educational Resources Information Center

    Seabury, Paul, Ed.

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

  9. 50 CFR 216.105 - Specific regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Specific regulations. 216.105 Section 216.105 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS REGULATIONS GOVERNING THE TAKING AND IMPORTING OF MARINE MAMMALS General Regulations Governing...

  10. 50 CFR 26.33 - Special regulations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false Special regulations. 26.33 Section 26.33 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM PUBLIC ENTRY AND USE Public Use and Recreation § 26.33 Special regulations. (a) Special regulations shall...

  11. 50 CFR 26.33 - Special regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Special regulations. 26.33 Section 26.33 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM PUBLIC ENTRY AND USE Public Use and Recreation § 26.33 Special regulations. (a) Special regulations shall...

  12. 36 CFR 34.5 - Applicable regulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Applicable regulations. 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...

  13. 36 CFR 34.5 - Applicable regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Applicable regulations. 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...

  14. International Radio Regulations Resulting from WARC 1979.

    ERIC Educational Resources Information Center

    Berrada, Abderrazak

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

  15. 7 CFR 953.322 - Handling regulation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Potatoes as amended (7 CFR 2851.1540-2851.1566), including the tolerances set forth in it. The term other... “Import regulations” (7 CFR 980.1), Irish potatoes of the round white type imported during the effective... Federal Regulations. For Federal Register citations affecting these regulations, see the List of...

  16. 21 CFR 868.2700 - Pressure regulator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Pressure regulator. 868.2700 Section 868.2700 Food... DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2700 Pressure regulator. (a) Identification. A pressure regulator is a device, often called a pressure-reducing valve, that is intended for...

  17. 21 CFR 868.2700 - Pressure regulator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pressure regulator. 868.2700 Section 868.2700 Food... DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2700 Pressure regulator. (a) Identification. A pressure regulator is a device, often called a pressure-reducing valve, that is intended for...

  18. 21 CFR 868.2700 - Pressure regulator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pressure regulator. 868.2700 Section 868.2700 Food... DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2700 Pressure regulator. (a) Identification. A pressure regulator is a device, often called a pressure-reducing valve, that is intended for...

  19. 21 CFR 868.2700 - Pressure regulator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pressure regulator. 868.2700 Section 868.2700 Food... DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2700 Pressure regulator. (a) Identification. A pressure regulator is a device, often called a pressure-reducing valve, that is intended for...

  20. 21 CFR 868.2700 - Pressure regulator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pressure regulator. 868.2700 Section 868.2700 Food... DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2700 Pressure regulator. (a) Identification. A pressure regulator is a device, often called a pressure-reducing valve, that is intended for...

  1. 27 CFR 22.3 - Related regulations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Spirits, Wines and Beer. 27 CFR Part 29—Stills and Miscellaneous Regulations. 27 CFR Part 30—Gauging... OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Scope § 22.3 Related regulations. Regulations related to this part are listed below: 27 CFR Part 19—Distilled Spirits Plants. 27 CFR Part...

  2. 27 CFR 22.3 - Related regulations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Spirits, Wines and Beer. 27 CFR Part 29—Stills and Miscellaneous Regulations. 27 CFR Part 30—Gauging... OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Scope § 22.3 Related regulations. Regulations related to this part are listed below: 27 CFR Part 19—Distilled Spirits Plants. 27 CFR Part...

  3. Conserved mechanisms regulate outgrowth in zebrafish fins

    E-print Network

    Mullen, Sean P.

    Conserved mechanisms regulate outgrowth in zebrafish fins M Kathryn Iovine Regulation of size the zebrafish fin, genetic, cellular and molecular strategies have also been employed to follow both normal regulation of the outgrowth and patterning of the zebrafish caudal fin during regeneration

  4. Gene regulation by transmembrane signaling.

    PubMed

    Braun, Volkmar; Mahren, Susanne; Sauter, Annette

    2006-04-01

    Studies of the ferric citrate transport genes in Escherichia coli K-12 have revealed a novel type of transcriptional regulation. The inducer, ferric citrate, binds to an outer membrane protein and must not be transported into the cells to initiate transcription of the ferric citrate transport genes. Rather, a signaling cascade from the cell surface across the outer membrane, the periplasm, and the cytoplasmic membrane into the cytoplasm transmits information on the presence of the inducer in the culture medium into the cytoplasm, where gene transcription occurs. The outer membrane protein FecA serves as a signal receiver and as a signal transmitter across the outer membrane. The FecR protein serves as a signal receiver in the periplasm and as a signal transmitter across the cytoplasmic membrane into the cytoplasm, where the FecI sigma factor is activated to bind RNA polymerase and specifically initiate transcription of the fecABCDE transport genes by binding to the promoter upstream of the fecA gene. Transcription of the fecI fecR regulatory genes is repressed by Fe2+ bound to the Fur repressor protein. Under iron-limiting conditions, Fur is not loaded with Fe2+, the fecI and fecR genes are transcribed, and the FecI and FecR proteins are synthesized and respond to the presence of ferric citrate in the medium when ferric citrate binds to the FecA protein. Regulation of the fec genes represents the paradigm of a growing number of gene regulation systems involving transmembrane signaling across three cellular compartments. PMID:16718597

  5. Gene regulation by transmembrane signaling.

    PubMed

    Braun, Volkmar; Mahren, Susanne; Sauter, Annette

    2005-10-01

    Studies of the ferric citrate transport genes in Escherichia coli K-12 have revealed a novel type of transcriptional regulation. The inducer, ferric citrate, binds to an outer membrane protein and must not be transported into the cells to initiate transcription of the ferric citrate transport genes. Rather, a signaling cascade from the cell surface across the outer membrane, the periplasm, and the cytoplasmic membrane into the cytoplasm transmits information on the presence of the inducer in the culture medium into the cytoplasm, where gene transcription occurs. The outer membrane protein FecA serves as a signal receiver and as a signal transmitter across the outer membrane. The FecR protein serves as a signal receiver in the periplasm and as a signal transmitter across the cytoplasmic membrane into the cytoplasm, where the FecI sigma factor is activated to bind RNA polymerase and specifically initiate transcription of the fecABCDE transport genes by binding to the promoter upstream of the fecA gene. Transcription of the fecI fecR regulatory genes is repressed by Fe(2+) bound to the Fur repressor protein. Under iron-limiting conditions, Fur is not loaded with Fe(2+), the fecI and fecR genes are transcribed, and the FecI and FecR proteins are synthesized and respond to the presence of ferric citrate in the medium when ferric citrate binds to the FecA protein. Regulation of the fec genes represents the paradigm of a growing number of gene regulation systems involving transmembrane signaling across three cellular compartments. PMID:16333751

  6. Redox Regulation of Plant Development

    PubMed Central

    Considine, Michael J.

    2014-01-01

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

  7. Transglutaminase Regulation of Cell Function

    PubMed Central

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

    2014-01-01

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

  8. Endocrine regulation of placental phenotype

    E-print Network

    Fowden, A. L.; Forhead, A. J.; Sferruzzi-Perri, A. N.; Burton, G. J.; Vaughan, O. R.

    2014-12-03

    as for lactation. Indeed, in mares, preterm changes in placental 312 progestagen production induced by stress or more direct glucocorticoid administration are 313 associated with prepartum running of milk, poor colostrum production at birth and failure 314... , Tuchscherer M, Grabner M, Brussow K-P, Rehfeldt C, Metges CC. 419 High and low protein: carbohydrate dietary ratios during gestation alter maternal-fetal 420 cortisol regulation in pigs. PLoS One 2012; 7:e52748. 421 13 Waddell BJ, Benediktsson R, Brown RW...

  9. Circadian regulation of adipose function

    PubMed Central

    Shostak, Anton; Husse, Jana; Oster, Henrik

    2013-01-01

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

  10. QB1 - Stochastic Gene Regulation

    SciTech Connect

    Munsky, Brian

    2012-07-23

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

  11. Returning common sense to regulations

    SciTech Connect

    Fox, M.R.

    1995-10-01

    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.

  12. Regulation possibilities of biomass combustion

    NASA Astrophysics Data System (ADS)

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

    2012-11-01

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

  13. Doing justice to allosteric regulation.

    PubMed

    Keller, Evelyn Fox

    2015-06-01

    Jacques Monod gave us not only our first regulatory system, but also our first smart molecules - i.e., he gave us allosteric proteins. But both of these contributions hung in a certain tension with his primary commitments. In particular, I focus here on the ways in which his ontological commitments constrained his thinking about the power of allostery. Although he wrote that "so far as regulation through allosteric interaction is concerned, everything is possible", for him, not everything was conceivable. In particular, what was not conceivable was a challenge to the primacy of DNA. PMID:25908117

  14. Neurobiology of Circadian Rhythm Regulation.

    PubMed

    Rosenwasser, Alan M; Turek, Fred W

    2015-12-01

    Over the past few decades, multilevel research has elucidated the basic neuroanatomy, neurochemistry, and molecular neurobiology of the master circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). The circadian timing system is composed of a large number of cellular oscillators located in the SCN, in non-SCN brain structures, and throughout the body. Cellular-level oscillations are generated by a molecular feedback loop in which circadian clock genes rhythmically regulate their own transcription, as well as that of hundreds of clock-controlled genes. The maintenance of proper coordination within this network of cellular- and tissue-level clocks is essential for health and well-being. PMID:26568118

  15. Optimized regulator for the quantized anharmonic oscillator

    NASA Astrophysics Data System (ADS)

    Kovacs, J.; Nagy, S.; Sailer, K.

    2015-04-01

    The energy gap between the first excited state and the ground state is calculated for the quantized anharmonic oscillator in the framework of the functional renormalization group method. The compactly supported smooth regulator is used which includes various types of regulators as limiting cases. It was found that the value of the energy gap depends on the regulator parameters. We argue that the optimization based on the disappearance of the false, broken symmetric phase of the model leads to the Litim's regulator. The least sensitivity on the regulator parameters leads, however, to an IR regulator being somewhat different of the Litim's one, but it can be described as a perturbatively improved, or generalized Litim's regulator and provides analytic evolution equations, too.

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

    PubMed Central

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

    2014-01-01

    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

  17. Mechanisms regulating chemokine receptor activity

    PubMed Central

    Bennett, Laura D; Fox, James M; Signoret, Nathalie

    2011-01-01

    Co-ordinated movement and controlled positioning of leucocytes is key to the development, maintenance and proper functioning of the immune system. Chemokines and their receptors play an essential role in these events by mediating directed cell migration, often referred to as chemotaxis. The chemotactic property of these molecules is also thought to contribute to an array of pathologies where inappropriate recruitment of specific chemokine receptor-expressing leucocytes is observed, including cancer and inflammatory diseases. As a result, chemokine receptors have become major targets for therapeutic intervention, and during the past 15 years much research has been devoted to understanding the regulation of their biological activity. From these studies, processes which govern the availability of functional chemokine receptors at the cell surface have emerged as playing a central role. In this review, we summarize and discuss current knowledge on the molecular mechanisms contributing to the regulation of chemokine receptor surface expression, from gene transcription and protein degradation to post-translational modifications, multimerization, intracellular transport and cross-talk. PMID:21977995

  18. Regulated cell death in AKI.

    PubMed

    Linkermann, Andreas; Chen, Guochun; Dong, Guie; Kunzendorf, Ulrich; Krautwald, Stefan; Dong, Zheng

    2014-12-01

    AKI is pathologically characterized by sublethal and lethal damage of renal tubules. Under these conditions, renal tubular cell death may occur by regulated necrosis (RN) or apoptosis. In the last two decades, tubular apoptosis has been shown in preclinical models and some clinical samples from patients with AKI. Mechanistically, apoptotic cell death in AKI may result from well described extrinsic and intrinsic pathways as well as ER stress. Central converging nodes of these pathways are mitochondria, which become fragmented and sensitized to membrane permeabilization in response to cellular stress, resulting in the release of cell death-inducing factors. Whereas apoptosis is known to be regulated, tubular necrosis was thought to occur by accident until recent work unveiled several RN subroutines, most prominently receptor-interacting protein kinase-dependent necroptosis and RN induced by mitochondrial permeability transition. Additionally, other cell death pathways, like pyroptosis and ferroptosis, may also be of pathophysiologic relevance in AKI. Combination therapy targeting multiple cell-death pathways may, therefore, provide maximal therapeutic benefits. PMID:24925726

  19. Regulated Cell Death in AKI

    PubMed Central

    Chen, Guochun; Dong, Guie; Kunzendorf, Ulrich; Krautwald, Stefan

    2014-01-01

    AKI is pathologically characterized by sublethal and lethal damage of renal tubules. Under these conditions, renal tubular cell death may occur by regulated necrosis (RN) or apoptosis. In the last two decades, tubular apoptosis has been shown in preclinical models and some clinical samples from patients with AKI. Mechanistically, apoptotic cell death in AKI may result from well described extrinsic and intrinsic pathways as well as ER stress. Central converging nodes of these pathways are mitochondria, which become fragmented and sensitized to membrane permeabilization in response to cellular stress, resulting in the release of cell death–inducing factors. Whereas apoptosis is known to be regulated, tubular necrosis was thought to occur by accident until recent work unveiled several RN subroutines, most prominently receptor-interacting protein kinase–dependent necroptosis and RN induced by mitochondrial permeability transition. Additionally, other cell death pathways, like pyroptosis and ferroptosis, may also be of pathophysiologic relevance in AKI. Combination therapy targeting multiple cell-death pathways may, therefore, provide maximal therapeutic benefits. PMID:24925726

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

    PubMed Central

    Troxell, Bryan; Hassan, Hosni M.

    2013-01-01

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

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

    E-print Network

    Her Majesty's Stationary Office

    1957-01-01

    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 ...

  2. 7 CFR 925.51 - Recommendation for regulation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  3. 7 CFR 925.51 - Recommendation for regulation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

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

  4. 7 CFR 925.51 - Recommendation for regulation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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

  5. 7 CFR 925.51 - Recommendation for regulation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

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

    E-print Network

    Her Majesty's Stationary Office

    1933-02-08

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

  7. Stability issues in IC Low Drop Out voltage regulators 

    E-print Network

    Chava, Krishna Chaitanya

    2002-01-01

    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....

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

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...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....

  9. 7 CFR 915.55 - Avocados not subject to regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...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....

  10. 7 CFR 915.55 - Avocados not subject to regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...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....

  11. 7 CFR 915.55 - Avocados not subject to regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...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....

  12. 7 CFR 915.55 - Avocados not subject to regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...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....

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

    PubMed Central

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

    2014-01-01

    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

  14. Shunt regulation electric power system

    NASA Technical Reports Server (NTRS)

    Wright, W. H.; Bless, J. J. (inventors)

    1971-01-01

    A regulated electric power system having load and return bus lines is described. A plurality of solar cells interconnected in a power supplying relationship and having a power shunt tap point electrically spaced from the bus lines is provided. A power dissipator is connected to the shunt tap point and provides for a controllable dissipation of excess energy supplied by the solar cells. A dissipation driver is coupled to the power dissipator and controls its conductance and dissipation and is also connected to the solar cells in a power taping relationship to derive operating power therefrom. An error signal generator is coupled to the load bus and to a reference signal generator to provide an error output signal which is representative of the difference between the electric parameters existing at the load bus and the reference signal generator. An error amplifier is coupled to the error signal generator and the dissipation driver to provide the driver with controlling signals.

  15. Regulating anxiety with extrasynaptic inhibition.

    PubMed

    Botta, Paolo; Demmou, Lynda; Kasugai, Yu; Markovic, Milica; Xu, Chun; Fadok, Jonathan P; Lu, Tingjia; Poe, Michael M; Xu, Li; Cook, James M; Rudolph, Uwe; Sah, Pankaj; Ferraguti, Francesco; Lüthi, Andreas

    2015-10-01

    Aversive experiences can lead to complex behavioral adaptations including increased levels of anxiety and fear generalization. The neuronal mechanisms underlying such maladaptive behavioral changes, however, are poorly understood. Here, using a combination of behavioral, physiological and optogenetic approaches in mouse, we identify a specific subpopulation of central amygdala neurons expressing protein kinase C ? (PKC?) as key elements of the neuronal circuitry controlling anxiety. Moreover, we show that aversive experiences induce anxiety and fear generalization by regulating the activity of PKC?(+) neurons via extrasynaptic inhibition mediated by ?5 subunit-containing GABAA receptors. Our findings reveal that the neuronal circuits that mediate fear and anxiety overlap at the level of defined subpopulations of central amygdala neurons and demonstrate that persistent changes in the excitability of a single cell type can orchestrate complex behavioral changes. PMID:26322928

  16. Menstrual regulation in Ibadan, Nigeria.

    PubMed

    Ladipo, O A; Ojo, O A; James, S; Stewart, K R

    1978-01-01

    Menstrual regulation (MR) (i.e., vacuum aspiration of the uterus with a small diameter, flexible cannula before pregnancy can be determined by a conventional pregnancy test) has been proven safe and effective in many clinics around the world. The present study, which we believe is the first such study of MR in Subsaharan Africa, shows that, for women in an urban African setting, MR is an acceptable backup for other contraceptive methods. Data on 507 MR patients treated at the University College Hospital in Ibadan, Nigeria, between January 1974 and April 1976, showed that the procedure was both safe and effective for 93.4% of the study subjects: there was an overall complication rate of 3.4% and MR failed in seven cases (3.2%). Data also showed that MR is an effective method of recruiting new contraceptive acceptors, as well as an effective back-up procedure in case of contraceptive failure. PMID:28977

  17. Epigenetic Regulation by Heritable RNA

    PubMed Central

    Liebers, Reinhard; Rassoulzadegan, Minoo; Lyko, Frank

    2014-01-01

    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

  18. Circadian Regulation of Cellular Physiology

    PubMed Central

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

    2015-01-01

    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

  19. RGS Protein Regulation of Phototransduction

    PubMed Central

    Chen, Ching-Kang Jason

    2015-01-01

    First identified in yeast and worm and later in other species, the physiological importance of regulators of G-protein signaling (RGS) in mammals was first demonstrated at the turn of the century in mouse retinal photoreceptors, in which RGS9 is needed for timely recovery of rod phototransduction. The role of RGS in vision has been established a synapse away in retinal depolarizing bipolar cells (DBCs), where RGS7 and RGS11 work redundantly and in a complex with G?5-S as GAPs for Go? in the metabotropic glutamate receptor 6 pathway at DBC dendritic tips. Much less is known on how RGS protein subserves vision in the rest of the visual system. The research into the roles of RGS proteins in vision holds great potential for many exciting new discoveries. PMID:26123301

  20. Social bonding: regulation by neuropeptides

    PubMed Central

    Lieberwirth, Claudia; Wang, Zuoxin

    2014-01-01

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

  1. Dynamics of bacterial gene regulation

    NASA Astrophysics Data System (ADS)

    Narang, Atul

    2009-03-01

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

  2. Fibronectin regulates calvarial osteoblast differentiation

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

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

  3. 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

  4. Regulation and the empowerment of nursing.

    PubMed

    Ralph, C

    1993-01-01

    The International Council of Nurses (ICN) has been a vanguard for the regulation of nursing standards worldwide. In the European region ICN has organized three workshops at which nurses representing 14 countries* critically examined their national legislations and, with their respective nurses' associations, devised concrete plans to change the regulations where necessary in their respective countries. Compared with developing countries, the structures in the European countries are more established and resistant to change, thus making it more difficult for European nurses to break the hard-fast regulatory encasement. An area that has received special attention has been the regulation of nursing specialties, particularly issues relating to their identity and control. An active participant in ICN's European regulation workshops and chief executive of the UK's regulatory body for nursing and midwifery, Colin Ralph takes a stand for empowering the nursing profession through regulation and offers assistance to those who need help in developing nursing regulations, not only in Europe but worldwide. PMID:8463059

  5. Dynamic Voltage Regulation Using Distributed Energy Resources

    SciTech Connect

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

    2007-01-01

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

  6. Self-regulated profiles and academic achievement.

    PubMed

    Valle, Antonio; Núñez, José Carlos; Cabanach, Ramón G; González-Pienda, Julio Antonio; Rodríguez, Susana; Rosário, Pedro; Cerezo, Rebeca; Muñoz-Cadavid, María A

    2008-11-01

    To date, research on the relation between learning self-regulation and academic achievement has generally show disparate results. This work intends to look into this relation from a new perspective, which consists in classifying the students as more or less self-regulated depending on diverse indicators and using cluster analysis. The aim of this work was to identify the possible self-regulated learning profiles in a sample of university students. By means of stepwise linear regression analysis, we determined which of the selected variables better predicted metacognitive self-regulation. Then, three significantly different self-regulated learning profiles were obtained by two-step cluster analysis with those variables. Lastly, ANOVA was used to analyse the relation between the self-regulated learning profiles and academic achievement. The implications of these data for the educational practice at university are discussed. PMID:18940075

  7. Exporting licensing regulations affecting US geothermal firms

    SciTech Connect

    Not Available

    1988-08-01

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

  8. 7 CFR 993.48 - Regulation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DRIED PRUNES PRODUCED IN CALIFORNIA Order Regulating Handling Prohibition on Handling §...

  9. Brief Report Self-Regulation of Negative

    E-print Network

    reactivity), and with temperament-based parental ratings of orient- ing/regulation. Looking and cardiac behavior, parental reports of temperament dimensions, and changes in psychophysi- ological response

  10. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart...

  11. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart...

  12. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart...

  13. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart...

  14. 50 CFR 402.04 - Counterpart regulations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED General § 402.04 Counterpart...

  15. Ultra-Low-Dropout Linear Regulator

    NASA Technical Reports Server (NTRS)

    Thornton, Trevor; Lepkowski, William; Wilk, Seth

    2011-01-01

    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.

  16. Molecular Cell Circadian Dbp Transcription Relies on

    E-print Network

    Halazonetis, Thanos

    with E Boxes and Requires the Proteasome Markus Stratmann,1,3 David Michael Suter,1,3,4 Nacho Molina,2 tandem arrays of Dbp repeats and monitored the binding of a fluorescent BMAL1 fusion protein (Bunger et al., 2000). However, BMAL1 and CLOCK levels display only shallow daily oscillations (Asher et

  17. 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...

  18. Erratic Black Hole Regulates Itself

    NASA Astrophysics Data System (ADS)

    2009-03-01

    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

  19. 41 CFR Appendix to Subchapter D - Temporary Regulations Federal Property Management Regulations; Interim Rule D-1

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...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...

  20. 41 CFR Appendix to Subchapter D - Temporary Regulations Federal Property Management Regulations; Interim Rule D-1

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...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...

  1. Immunological approaches to fertility regulation.

    PubMed

    Stevens, V C

    1978-01-01

    Strong evidence that specific immunogenic components of the reproductive system exist that are not represented in other body systems has led to efforts to develop an acceptable vaccine for fertility regulation. The aim is to create a vaccine administered infrequently by trained technicians outside the clinical environment. For safety and practical reasons, an approach using active immunization with a vaccine is preferred to passive immunization with antibodies. In current research with sperm antigens, a lactate dehydrogenase isoenzyme (LDH-X), an enzyme normally present on the sperm surface, reduced fertility in mice and rabbits. However, significant embryo mortality occurred. Other sperm antigens have been tested and rejected. Most of the research on ovum antigens is directed toward the zona pellucida, and work is in progress to isolate experimental quantities of specific zona pellucida antigens. Antibodies to human zona are reported to react with pig zona and vice versa, providing a model system. Antibodies to whole-placenta homogenates reportedly disrupt pregnancy in several laboratory animal species, and 2 placenta-specific proteins are potential antigens since antibodies to them do not react with any other tissue so far tested. Of 3 protein hormones isolated from placental tissue, 2 are potential antigens. The possible hazards of antifertility vaccines can be divided into 2 categories: problems related to immunization and problems caused by antibodies produced. PMID:307451

  2. Multiple pathways regulate shoot branching

    PubMed Central

    Rameau, Catherine; Bertheloot, Jessica; Leduc, Nathalie; Andrieu, Bruno; Foucher, Fabrice; Sakr, Soulaiman

    2015-01-01

    Shoot branching patterns result from the spatio-temporal regulation of axillary bud outgrowth. Numerous endogenous, developmental and environmental factors are integrated at the bud and plant levels to determine numbers of growing shoots. Multiple pathways that converge to common integrators are most probably involved. We propose several pathways involving not only the classical hormones auxin, cytokinins and strigolactones, but also other signals with a strong influence on shoot branching such as gibberellins, sugars or molecular actors of plant phase transition. We also deal with recent findings about the molecular mechanisms and the pathway involved in the response to shade as an example of an environmental signal controlling branching. We propose the TEOSINTE BRANCHED1, CYCLOIDEA, PCF transcription factor TB1/BRC1 and the polar auxin transport stream in the stem as possible integrators of these pathways. We finally discuss how modeling can help to represent this highly dynamic system by articulating knowledges and hypothesis and calculating the phenotype properties they imply. PMID:25628627

  3. Physiological regulation of lipoprotein lipase.

    PubMed

    Kersten, Sander

    2014-07-01

    The enzyme lipoprotein lipase (LPL), originally identified as the clearing factor lipase, hydrolyzes triglycerides present in the triglyceride-rich lipoproteins VLDL and chylomicrons. LPL is primarily expressed in tissues that oxidize or store fatty acids in large quantities such as the heart, skeletal muscle, brown adipose tissue and white adipose tissue. Upon production by the underlying parenchymal cells, LPL is transported and attached to the capillary endothelium by the protein GPIHBP1. Because LPL is rate limiting for plasma triglyceride clearance and tissue uptake of fatty acids, the activity of LPL is carefully controlled to adjust fatty acid uptake to the requirements of the underlying tissue via multiple mechanisms at the transcriptional and post-translational level. Although various stimuli influence LPL gene transcription, it is now evident that most of the physiological variation in LPL activity, such as during fasting and exercise, appears to be driven via post-translational mechanisms by extracellular proteins. These proteins can be divided into two main groups: the liver-derived apolipoproteins APOC1, APOC2, APOC3, APOA5, and APOE, and the angiopoietin-like proteins ANGPTL3, ANGPTL4 and ANGPTL8, which have a broader expression profile. This review will summarize the available literature on the regulation of LPL activity in various tissues, with an emphasis on the response to diverse physiological stimuli. PMID:24721265

  4. Conformational flexibility in biochemical regulation

    SciTech Connect

    Trewhella, J.

    1993-09-01

    Small-angle X-ray and neutron scattering have proven extremely useful for studying the evolutionarily related dumbbell-shaped Ca {sup 2+} -binding proteins calmodulin and troponin C and their interactions with the target proteins whose activity they regulate. Calmodulin contracts about target enzyme binding domains with the common characteristic of having a high propensity for forming a basic, amphipathic a-helix. The contraction is achieved via flexibility in the interconnecting helix region of the molecule that links its two globular domains. This flexibility allows calmodulin to optimize its binding to different arrangements of hydrophobic and charged residues important in forming these complexes. In contrast calmodulin remains extended in its interaction with the catalytic subunit of phosphorylase kinase. There are structural and functional similarities between this interaction and that of troponin C and troponin I. Our most recent neutron scattering experiments confirm our prediction that troponin C also remains extended in this complex. The ability of the dumbbell-shaped Ca {sup 2+} -binding proteins to modulate their conformations via flexibility in the interconnecting helix region in order to accommodate different target binding domains is a remarkable example nature building functional diversity as well as specificity into a compact and unusual shape.

  5. Electronically Variable Pressure Regulator (EVPR)

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

    A new programmable electronically variable pressure regulator (EVPR) concept accurately controls the local outlet or remote system pressure. It uses an integral pulse width modulated rare earth permanent magnet motor operating in response to redundant pressure transducer feedback signals. The EVPR is a simple single stage device that does not use dynamic seals or pilot valving. Conversion of partial revolution motor torque to poppet lifting force is accomplished by pure flexure action to avoid using bearings. The flexure drive (called the ROTAX) has a variable lead to minimize motor weight and power consumption. Breadboard tests were completed successfully on two critical design elements of the EVPR: the ROTAX and the motor. The ROTAX cable system was tested for 250,000 cycles without failure. The breadboard motor met the basic design requirements including the design torque and power consumption. Prototype parts were fabricated, and testing of the prototype EVPR has started. It is PC computer controlled to facilitate programming, data acquisition and analysis. A lightweight dedicated microprocessor is planned for the flightweight EVPR.

  6. The Regulation of Energy Medicine

    NASA Astrophysics Data System (ADS)

    Kosovich, Judy; Esq

    This paper describes the laws and regulations that affect the practice of energy medicine. State law often has more impact on a health care practice than federal law, but federal law provides a common denominator among states. Device law is emphasized here because practitioners of energy medicine are more likely to use devices than drugs. For purposes of this paper, energy medicine is defined as practices that measure or benefit energy flow and overall energy in the body. This broad definition encompasses things as diverse as certain forms of exercise, measurement of meridian resistance, the use of electrical current or magnetic pulses to relieve pain, and the use of light, sound, scent, touch, position, or movement to stimulate the body's own electrical systems. What is of greatest importance in determining legal implications of a practice is whether there are any health-related claims. Two federal entities are pivotal. The Food and Drug Administration ("FDA") is authorized to protect health and safety and the Federal Trade Commission ("FTC") is authorized to protect consumers from false or misleading advertising. There are 5 things that FDA looks at: 1) intended use, 2) claims made in advertising and in labeling, 3) substantial equivalence to a predicate, 4) safety, and 5) effectiveness. A concern regarding any one of these can be the basis for denying clearance to market a device. The FTC looks at whether statements are true and substantiated and whether they might be misleading. The FTC often consults with the FDA on the interpretation of technical information.

  7. Asbestos products, hazards, and regulation.

    PubMed

    Castleman, Barry

    2006-01-01

    Asbestos is present in the United States in a multitude of products used in past decades, and in some products that continue to be imported and domestically produced. We have limited information on the hazards posed by some of these individual products and no information at all on most of them. Legal discovery of corporate documents has shed some light on the use of asbestos in some products and exposures from asbestos in others, sometimes adding considerably to what was in the published literature. But liability concerns have motivated corporate efforts to curtail governmental public health guidance on long-recognized hazards to workers. Liability considerations have also evidently led, in the case of asbestos brake linings, to the support of publication in the scientific literature of review articles denying in the 21st century what had been widely accepted and established in health policy in the 20th century. This report is an effort to illustrate the suppression and emergence of scientific knowledge in a climate of regulation and liability. Examples discussed are vinyl-asbestos flooring, feminine hygiene products, automotive friction materials, and asbestos contamination of other minerals such as talc and vermiculite. Global efforts to deal with the hazards of continuing marketing of asbestos products are also discussed. PMID:16878394

  8. Type XIV Collagen Regulates Fibrillogenesis

    PubMed Central

    Ansorge, Heather L.; Meng, Xianmin; Zhang, Guiyun; Veit, Guido; Sun, Mei; Klement, John F.; Beason, David P.; Soslowsky, Louis J.; Koch, Manuel; Birk, David E.

    2009-01-01

    Type XIV collagen is a fibril-associated collagen with an interrupted triple helix. This collagen interacts with the fibril surface and has been implicated as a regulator of fibrillogenesis; however, a specific role has not been elucidated. Functional roles for type XIV collagen were defined utilizing a new type XIV collagen-deficient mouse line. This line was produced using a conventional targeted knock-out approach. Col14a1(–/–) mice were devoid of type XIV collagen, whereas heterozygous mice had reduced synthesis. Both mutant Col14a1 genotypes were viable with a grossly normal phenotype; however, mature skin exhibited altered mechanical properties. Prior to evaluating tendon fibrillogenesis in type XIV collagen-deficient mice, the developmental expression patterns were analyzed in wild-type flexor digitorum longus (FDL) tendons. Analyses of mRNA and protein expression indicated tissue-specific temporal expression that was associated with the early stages in fibrillogenesis. Ultrastructural analyses of wild-type and null tendons demonstrated premature fibril growth and larger fibril diameters in tendons from null mice at postnatal day 4 (P4). However, fibril structure in mature tendons was normal. Biomechanical studies established a direct structure/function relationship with reduced strength in P7-null tendons. However, the biomechanical properties in P60 tendons were comparable in null and wild-type mice. Our results indicate a regulatory function for type XIV collagen in early stages of collagen fibrillogenesis with tissue differences. PMID:19136672

  9. Regulation of pulpal blood flow

    SciTech Connect

    Kim, S.

    1985-04-01

    The regulation of blood flow of the dental pulp was investigated in dogs and rats anesthetized with sodium pentobarbital. Pulpal blood flow was altered by variations of local and systemic hemodynamics. Macrocirculatory blood flow (ml/min/100 g) in the dental pulp was measured with both the /sup 133/Xe washout and the 15-microns radioisotope-labeled microsphere injection methods on the canine teeth of dogs, to provide a comparison of the two methods in the same tooth. Microcirculatory studies were conducted in the rat incisor tooth with microscopic determination of the vascular pattern, RBC velocity, and intravascular volumetric flow distribution. Pulpal resistance vessels have alpha- and beta-adrenergic receptors. Activation of alpha-receptors by intra-arterial injection of norepinephrine (NE) caused both a reduction in macrocirculatory Qp in dogs and decreases in arteriolar and venular diameters and intravascular volumetric flow (Qi) in rats. These responses were blocked by the alpha-antagonist PBZ. Activation of beta-receptors by intra-arterial injection of isoproterenal (ISO) caused a paradoxical reduction of Qp in dogs. In rats, ISO caused a transient increase in arteriolar Qi followed by a flow reduction; arteriolar dilation was accompanied by venular constriction. These macrocirculatory and microcirculatory responses to ISO were blocked by the alpha-antagonist propranolol.

  10. Molecular mechanisms of regulated necrosis.

    PubMed

    Galluzzi, Lorenzo; Kepp, Oliver; Krautwald, Stefan; Kroemer, Guido; Linkermann, Andreas

    2014-11-01

    It is now clear that apoptosis does not constitute the sole genetically encoded form of cell death. Rather, cells can spontaneously undertake or exogenously be driven into a cell death subroutine that manifests with necrotic features, yet can be inhibited by pharmacological and genetic interventions. As regulated necrosis (RN) plays a major role in both physiological scenarios (e.g., embryonic development) and pathological settings (e.g., ischemic disorders), consistent efforts have been made throughout the last decade toward the characterization of the molecular mechanisms that underlie this cell death modality. Contrarily to initial beliefs, RN does not invariably result from the activation of a receptor interacting protein kinase 3 (RIPK3)-dependent signaling pathway, but may be ignited by distinct molecular networks. Nowadays, various types of RN have been characterized, including (but not limited to) necroptosis, mitochondrial permeability transition (MPT)-dependent RN and parthanatos. Of note, the inhibition of only one of these modules generally exerts limited cytoprotective effects in vivo, underscoring the degree of interconnectivity that characterizes RN. Here, we review the signaling pathways, pathophysiological relevance and therapeutic implications of the major molecular cascades that underlie RN. PMID:24582829

  11. REGULATIONS Academic Regulations is an annual publication of the Office of the Provost.

    E-print Network

    Massachusetts at Amherst, University of

    ACADEMIC REGULATIONS 2014-2015 #12;Page 2 Academic Regulations is an annual publication _________________________________________________________________________________ Academic Regulations 5 Academic Honesty 6 Enrollment Categories 6 Academic Status 8 Graduation Requirements 36 Evaluation of the Pre-Matriculation Record 37 Academic Grievance Procedure 38 Introduction 38

  12. Not legally binding translation of the "Regulations for Doctoral Studies" Regulations for Doctoral Degree Studies

    E-print Network

    Potsdam, Universität

    Not legally binding translation of the "Regulations for Doctoral Studies" Regulations for Doctoral;Not legally binding translation of the "Regulations for Doctoral Studies" (2) Professors and lecturers Degree Studies in the Faculty of Science at the University of Potsdam As of 18 September 2013 The Faculty

  13. The academic regulations for the Master's degree in Italian The framework provisions of the academic regulations

    E-print Network

    Bataillon, Thomas

    The academic regulations for the Master's degree in Italian The framework provisions of the academic regulations The academic regulations for the Master's degree in Italian (2007) were prepared's degree in Italian gives the right to use the title Master of Arts in Italian The academic direction

  14. 78 FR 31551 - Federal Acquisition Regulation; Submission for OMB Review; Commerce Patent Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-24

    ... approved information collection requirement concerning Department of Commerce patent regulations. A notice was published in Federal Register at 77 FR 43082, on July 23, 2012. One respondent submitted comments... Regulation; Submission for OMB Review; Commerce Patent Regulations AGENCIES: Department of Defense...

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

    E-print Network

    Stuart, Steven J.

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

  16. Self-Regulation and Learning Strategies

    ERIC Educational Resources Information Center

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

    2011-01-01

    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…

  17. The Kidney and Acid-Base Regulation

    ERIC Educational Resources Information Center

    Koeppen, Bruce M.

    2009-01-01

    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…

  18. Test Review: Anger Regulation and Expression Scale

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  19. Focus on Preschool Aquatics: Child Care Regulations.

    ERIC Educational Resources Information Center

    Sayre, Nancy E.

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

  20. A Guide to Federal Reserve Regulations.

    ERIC Educational Resources Information Center

    Federal Reserve Bank of New York, NY.

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

  1. REGULATIONS OF THE UNIVERSITY OF FLORIDA

    E-print Network

    Sin, Peter

    by the University based on the happening of a future event, such as a change in the Consumer Price Index or other safety, life safety and disabled access standards, applicable to University buildings. (b1 REGULATIONS OF THE UNIVERSITY OF FLORIDA 3.025 Lease of Space (1) Purpose. This regulation

  2. Regulations.gov Federal Regulatory Portal

    ERIC Educational Resources Information Center

    Ashlin, John; Davis, Richard; Dalecky, Selene; Grasso, Richard; LaPlant, Lisa; Morales, Oscar; Nelson, Jennifer; White, Michael; Whitt, Sharon A.

    2004-01-01

    The Regulations.gov Online Rulemaking Project is 1 of the 24 e-Government Initiatives on the President's Management Agenda (PMA), which was announced by the White House in 2001. The Regulations.gov Web site is the central electronic rulemaking portal for the federal government. Through a single Web site, citizens can search, view, and comment on…

  3. REGULATIONS OF THE UNIVERSITY OF FLORIDA

    E-print Network

    Sin, Peter

    1 REGULATIONS OF THE UNIVERSITY OF FLORIDA 2.019 Alcoholic Beverages. (1) The sale of alcoholic the conditions set forth in this regulation. (a) Functions at which alcoholic beverages are sold shall include any function at which alcoholic beverages are served and for which an admission fee is charged, cups

  4. 77 FR 73523 - HUD Acquisition Regulations (HUDAR)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-10

    ... September 19, 1983 (48 FR 42102). The FAR is codified in title 48, chapter 1, of the Code of Federal Regulations. HUD promulgated its regulation to implement the FAR on March 1, 1984 (49 FR 7696). The HUDAR... final rule published on January 13, 2006 (71 FR 2432). II. Public Comments The proposed rule...

  5. 47 CFR 32.14 - Regulated accounts.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Regulated accounts. 32.14 Section 32.14 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES General Instructions § 32.14 Regulated accounts. (a) In the...

  6. 47 CFR 32.14 - Regulated accounts.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Regulated accounts. 32.14 Section 32.14 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES General Instructions § 32.14 Regulated accounts. (a) In the...

  7. Self-Regulation and Academic Procrastination.

    ERIC Educational Resources Information Center

    Senecal, Caroline; And Others

    1995-01-01

    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)

  8. High power solar array switching regulation

    SciTech Connect

    Decker, D.K.; Cassinelli, J.; Valgora, M.

    1981-01-01

    Military and NASA power requirements for missions of the 1980s are imposing new problems for spacecraft power subsystems because of increased heat dissipations and severe system weight constraints. Solar array switching regulation is proposed as a replacement for conventional regulation techniques to reduce weight, thermal dissipation, and power system complexity for large power spacecraft and for advanced space missions.

  9. 7 CFR 932.152 - Outgoing regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Rules and Regulations § 932.152 Outgoing regulations. (a) Inspection stations. Processed olives shall be sampled and inspected only at an inspection station which shall be any olive processing plant...

  10. 7 CFR 932.152 - Outgoing regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Rules and Regulations § 932.152 Outgoing regulations. (a) Inspection stations. Processed olives shall be sampled and inspected only at an inspection station which shall be any olive processing plant...

  11. 7 CFR 932.151 - Incoming regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Rules and Regulations § 932.151 Incoming regulations. (a) Inspection stations. Natural condition olives... other place having facilities for sampling and size-grading such olives: Provided, That such...

  12. 7 CFR 932.152 - Outgoing regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Rules and Regulations § 932.152 Outgoing regulations. (a) Inspection stations. Processed olives shall be sampled and inspected only at an inspection station which shall be any olive processing plant...

  13. 7 CFR 932.151 - Incoming regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Rules and Regulations § 932.151 Incoming regulations. (a) Inspection stations. Natural condition olives... other place having facilities for sampling and size-grading such olives: Provided, That such...

  14. 7 CFR 932.152 - Outgoing regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Rules and Regulations § 932.152 Outgoing regulations. (a) Inspection stations. Processed olives shall be sampled and inspected only at an inspection station which shall be any olive processing plant...

  15. Regulations which require employee training: An overview

    SciTech Connect

    Gilfus, L.J.

    1995-11-01

    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.

  16. 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...

  17. Transcriptional Regulation and its Misregulation in Disease

    PubMed Central

    Lee, Tong Ihn; Young, Richard A.

    2013-01-01

    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

  18. 76 FR 64868 - Orphan Drug Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-19

    ... (56 FR 3338), section II.E, paragraph 8, ``even a drug considered the `same' drug structurally could... preamble to the final rule, ``Orphan Drug Regulations'' (57 FR 62076 at 62084), FDA reiterated that it... Regulations in the Federal Register of December 29, 1992 (57 FR 62076), FDA has reviewed over 3,350...

  19. Emotion Regulation and Childhood Aggression: Longitudinal Associations

    ERIC Educational Resources Information Center

    Roll, Judith; Koglin, Ute; Petermann, Franz

    2012-01-01

    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…

  20. SWITCHED-CAPACITOR VOLTAGE CONVERTERS WITH REGULATORS

    E-print Network

    Berns, Hans-Gerd

    LT1054 SWITCHED-CAPACITOR VOLTAGE CONVERTERS WITH REGULATORS SLVS033E ­ FEBRUARY 1990 ­ REVISED-to-Pin Compatible With the LTC1044/7660 description The LT1054 is a bipolar, switched-capacitor voltage converter regulation, a feature not previously available in switched-capacitor voltage converters. By adding

  1. 50 CFR 26.33 - Special regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... individual national wildlife refuges where there is a need to amend, modify, relax or make more stringent the... NATIONAL WILDLIFE REFUGE SYSTEM PUBLIC ENTRY AND USE Public Use and Recreation § 26.33 Special regulations... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false Special regulations. 26.33 Section...

  2. 50 CFR 26.33 - Special regulations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... individual national wildlife refuges where there is a need to amend, modify, relax or make more stringent the... NATIONAL WILDLIFE REFUGE SYSTEM PUBLIC ENTRY AND USE Public Use and Recreation § 26.33 Special regulations... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false Special regulations. 26.33 Section...

  3. 50 CFR 26.33 - Special regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... individual national wildlife refuges where there is a need to amend, modify, relax or make more stringent the... NATIONAL WILDLIFE REFUGE SYSTEM PUBLIC ENTRY AND USE Public Use and Recreation § 26.33 Special regulations... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Special regulations. 26.33 Section...

  4. 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. ...

  5. Self-Regulation: Calm, Alert, and Learning

    ERIC Educational Resources Information Center

    Shanker, Stuart

    2010-01-01

    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…

  6. Emotion Regulation in Children with Anxiety Disorders

    ERIC Educational Resources Information Center

    Suveg, Cynthia; Zeman, Janice

    2004-01-01

    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

  7. 50 CFR 404.7 - Regulated activities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Regulated activities. 404.7 Section 404.7 Wildlife and Fisheries JOINT REGULATIONS (UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR AND NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED...

  8. 77 FR 69735 - Consumer Leasing (Regulation M)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-21

    ... Dodd-Frank Act, and the Board's Regulation M continues to apply to those entities.\\4\\ \\3\\ 76 FR 78500... the Bureau of Labor Statistics. In April 2011, the Board issued a final rule amending Regulation M...-203 Sec. 1100E, 124 Stat. 1376 (2010). \\2\\ 76 FR 18349 (Apr. 4, 2011). Title X of the Dodd-Frank...

  9. 78 FR 70193 - Consumer Leasing (Regulation M)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-25

    ... Dodd-Frank Act, and the Board's Regulation M continues to apply to those entities.\\4\\ \\3\\ 76 FR 78500... the Bureau of Labor Statistics. In April 2011, the Board issued a final rule amending Regulation M...-203 Sec. 1100E, 124 Stat. 1376 (2010). \\2\\ 76 FR 18349 (Apr. 4, 2011). Title X of the Dodd-Frank...

  10. Federal Regulations at Franklin and Marshall College.

    ERIC Educational Resources Information Center

    Karlesky, Joseph J.

    Administrators were interviewed at Franklin and Marshall College, a small private liberal arts college in Pennsylvania, to learn the impact of federal regulation on the institution. These issues were discussed: (1) what federal regulations affect the interviewee's responsibilities and which are of greatest concern; (2) how the interviewee assesses…

  11. Fostering Self-Regulation in Distributed Learning

    ERIC Educational Resources Information Center

    Terry, Krista P.; Doolittle, Peter

    2006-01-01

    Although much has been written about fostering self-regulated learning in traditional classroom settings, there has been little that addresses how to facilitate self-regulated learning skills in distributed and online environments. This article will examine some such strategies by specifically focusing on time management. Specific principles for…

  12. 47 CFR 32.14 - Regulated accounts.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Regulated accounts. 32.14 Section 32.14 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES General Instructions § 32.14 Regulated accounts. (a) In the...

  13. 47 CFR 32.14 - Regulated accounts.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Regulated accounts. 32.14 Section 32.14 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES General Instructions § 32.14 Regulated accounts. (a) In the...

  14. 47 CFR 32.14 - Regulated accounts.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Regulated accounts. 32.14 Section 32.14 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES General Instructions § 32.14 Regulated accounts. (a) In the...

  15. 32 CFR 770.4 - Hunting regulations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 5 2014-07-01 2014-07-01 false Hunting regulations. 770.4 Section 770.4... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps Base, Quantico, Virginia § 770.4 Hunting regulations. All persons possessing the proper State, Federal and Base...

  16. 32 CFR 770.4 - Hunting regulations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Hunting regulations. 770.4 Section 770.4... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps Base, Quantico, Virginia § 770.4 Hunting regulations. All persons possessing the proper State, Federal and Base...

  17. 32 CFR 770.4 - Hunting regulations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 5 2012-07-01 2012-07-01 false Hunting regulations. 770.4 Section 770.4... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps Base, Quantico, Virginia § 770.4 Hunting regulations. All persons possessing the proper State, Federal and Base...

  18. 32 CFR 770.4 - Hunting regulations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 5 2011-07-01 2011-07-01 false Hunting regulations. 770.4 Section 770.4... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps Base, Quantico, Virginia § 770.4 Hunting regulations. All persons possessing the proper State, Federal and Base...

  19. 32 CFR 770.4 - Hunting regulations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 5 2013-07-01 2013-07-01 false Hunting regulations. 770.4 Section 770.4... LIMITING PUBLIC ACCESS TO PARTICULAR INSTALLATIONS Hunting and Fishing at Marine Corps Base, Quantico, Virginia § 770.4 Hunting regulations. All persons possessing the proper State, Federal and Base...

  20. Ways for regulators to use performance measures

    SciTech Connect

    Costello, Ken

    2010-12-15

    The core challenge for regulators is to determine what constitutes a well-performing utility. The question of what is considered acceptable performance needs to be addressed by regulators if they are to exploit fully the information contained in performance measures for regulatory actions such as prudence determination, further inquiry, and rate setting. (author)

  1. Parent-Child Attachment and Emotion Regulation.

    PubMed

    Brumariu, Laura E

    2015-01-01

    Given the centrality of both parent-child attachment and emotion regulation in children's development and adjustment, it is important to evaluate the relations between these constructs. This article discusses conceptual and empirical links between attachment and emotion regulation in middle childhood, highlights progress and challenges in the literature, and outlines future inquiries. Studies have established that securely attached children internalize effective emotion regulation strategies within the attachment relationship and are able to successfully employ adaptive emotion regulation strategies outside the attachment relationship, when the attachment figure is not present. There are not enough studies to conclude yet that the insecure attachment patterns (ambivalent, avoidant, and disorganized) may relate differentially with emotion regulation processes. Studies investigating whether there are unique links between the four attachment patterns and the various emotion regulation processes will advance the field considerably. Studies evaluating the associations between attachment and emotion regulation will benefit from a multimethod approach in measuring these constructs. Embedding the relation between parent-child attachment and emotion regulation within broader developmental models will further advance the research on this topic. PMID:26086126

  2. Cardiac Vagal Regulation and Early Peer Status

    ERIC Educational Resources Information Center

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

    2007-01-01

    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…

  3. REGULATIONS OF THE UNIVERSITY OF FLORIDA

    E-print Network

    Sin, Peter

    1 REGULATIONS OF THE UNIVERSITY OF FLORIDA 2.001 Possession and Use of Firearms. (1) The possession of firearms on the University campus or any land or property occupied by the University of Florida) The term "firearm" is defined for the purposes of this regulation to have the same meaning set forth

  4. 77 FR 8066 - Semiannual Agenda of Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-13

    ... Federal Banking Agencies Legal Authority: Not Yet Determined Abstract: The regulations of the Office of... prohibitions and restrictions on the ability of banking entities and nonbank financial companies supervised by...-Based Capital Guidelines of the Federal Banking Agencies (AD62): The regulations of the Office of...

  5. 76 FR 38562 - Libyan Sanctions Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-01

    ...The Department of the Treasury's Office of Foreign Assets Control (``OFAC'') is issuing regulations with respect to Libya to implement Executive Order 13566 of February 25, 2011. OFAC intends to supplement this part 570 with a more comprehensive set of regulations, which may include additional interpretive and definitional guidance and additional general licenses and statements of licensing......

  6. Advanced Clean Cars Zero Emission Vehicle Regulation

    E-print Network

    California at Davis, University of

    Advanced Clean Cars Zero Emission Vehicle Regulation ZEV #12;Advanced Clean Cars ZEV Program.4% of Annual Sales in 2025 Projected: ZEVs #12;Advanced Clean Cars Hydrogen Infrastructure · Without infrastructure, the cars won't come · Complementary Policies to support ZEV regulation ­ Clean Fuels Outlet

  7. 77 FR 16784 - General Bridge Regulation; Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-22

    ... SECURITY Coast Guard 33 CFR Part 114, 116, 118 RIN 1625-AB36 General Bridge Regulation; Amendment AGENCY... rulemaking concerning amendments to the general bridge regulations. The rulemaking was initiated to clarify the statutory responsibilities of bridge owners to remove their bridges from navigable waterways...

  8. Higher Education Regulations Study: Final Report

    ERIC Educational Resources Information Center

    Advisory Committee on Student Financial Assistance, 2011

    2011-01-01

    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…

  9. 75 FR 52213 - Cold Treatment Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-25

    ...We are adopting as a final rule, with changes, an interim rule that amended the phytosanitary treatment regulations for cold treatment enclosures and procedures, including regulations for precooling temperatures and temperature recording devices. The interim rule as amended by this document requires articles destined for cold treatment to be precooled at or below the highest temperature listed......

  10. 10 CFR 850.26 - Regulated areas.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Regulated areas. 850.26 Section 850.26 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.26 Regulated areas. (a) If airborne concentrations of beryllium in areas in DOE facilities are measured at...

  11. 10 CFR 850.26 - Regulated areas.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Regulated areas. 850.26 Section 850.26 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.26 Regulated areas. (a) If airborne concentrations of beryllium in areas in DOE facilities are measured at...

  12. 10 CFR 850.26 - Regulated areas.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Regulated areas. 850.26 Section 850.26 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.26 Regulated areas. (a) If airborne concentrations of beryllium in areas in DOE facilities are measured at...

  13. 10 CFR 850.26 - Regulated areas.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Regulated areas. 850.26 Section 850.26 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.26 Regulated areas. (a) If airborne concentrations of beryllium in areas in DOE facilities are measured at...

  14. 10 CFR 850.26 - Regulated areas.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Regulated areas. 850.26 Section 850.26 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.26 Regulated areas. (a) If airborne concentrations of beryllium in areas in DOE facilities are measured at...

  15. Parent-Child Attachment and Emotion Regulation

    ERIC Educational Resources Information Center

    Brumariu, Laura E.

    2015-01-01

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

  16. Higher Education Regulations Study: Preliminary Findings

    ERIC Educational Resources Information Center

    Advisory Committee on Student Financial Assistance, 2011

    2011-01-01

    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…

  17. 50 CFR 229.9 - Emergency regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Emergency regulations. 229.9 Section 229.9 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... PROTECTION ACT OF 1972 General Provisions § 229.9 Emergency regulations. (a) If the Assistant...

  18. 50 CFR 229.9 - Emergency regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Emergency regulations. 229.9 Section 229.9 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... PROTECTION ACT OF 1972 General Provisions § 229.9 Emergency regulations. (a) If the Assistant...

  19. Shale gas development: a smart regulation framework.

    PubMed

    Konschnik, Katherine E; Boling, Mark K

    2014-01-01

    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

  20. The art of regulation and the regulation of ART: the impact of regulation on research and clinical practice.

    PubMed

    Johnson, Martin H

    2002-05-01

    How a society regulates Assisted Reproduction Technologies (ART) depends on cultural context. The challenge for the regulatory regime is to balance protection for patients and society with freedom for medico-scientific creativity. Neither an exclusively market-regulated nor a peer-regulated approach is realistic politically, or desirable socially, ethically and legally. Legitimate social issues that go beyond the exclusive expertise of doctors and scientists or market choice by patients need to be accommodated within the regulatory regime. Within this context, four key issues are discussed: the lack of a shared social ethic that helps the needs of the community to be balanced against those of its individual members; the negative impact of intrusive external regulation on scientists and doctors; the requirement for doctors and scientists to review their professional structures reflectively and critically if they are to be entrusted with peer-regulation; and the desirability of constructive dialogue between regulators and regulated rather than the use of coercion and criminal sanctions. PMID:12194472

  1. Bacteriophage lysis: mechanism and regulation.

    PubMed Central

    Young, R

    1992-01-01

    Bacteriophage lysis involves at least two fundamentally different strategies. Most phages elaborate at least two proteins, one of which is a murein hydrolase, or lysin, and the other is a membrane protein, which is given the designation holin in this review. The function of the holin is to create a lesion in the cytoplasmic membrane through which the murein hydrolase passes to gain access to the murein layer. This is necessary because phage-encoded lysins never have secretory signal sequences and are thus incapable of unassisted escape from the cytoplasm. The holins, whose prototype is the lambda S protein, share a common organization in terms of the arrangement of charged and hydrophobic residues, and they may all contain at least two transmembrane helical domains. The available evidence suggests that holins oligomerize to form nonspecific holes and that this hole-forming step is the regulated step in phage lysis. The correct scheduling of the lysis event is as much an essential feature of holin function as is the hole formation itself. In the second strategy of lysis, used by the small single-stranded DNA phage phi X174 and the single-stranded RNA phage MS2, no murein hydrolase activity is synthesized. Instead, there is a single species of small membrane protein, unlike the holins in primary structure, which somehow causes disruption of the envelope. These lysis proteins function by activation of cellular autolysins. A host locus is required for the lytic function of the phi X174 lysis gene E. Images PMID:1406491

  2. Peripheral Leptin Regulates Bone Formation

    PubMed Central

    Turner, Russell T.; Kalra, Satya P.; Wong, Carmen P.; Philbrick, Kenneth A.; Lindenmaier, Laurence B.; Boghossian, Stephane; Iwaniec, Urszula T.

    2012-01-01

    Substantial evidence does not support the prevailing view that leptin, acting through a hypothalamic relay, decreases bone accrual by inhibiting bone formation. To clarify the mechanisms underlying regulation of bone architecture by leptin, we evaluated bone growth and turnover in wild type (WT) mice, leptin receptor-deficient db/db mice, leptin-deficient ob/ob mice and ob/ob mice treated with leptin. We also performed hypothalamic leptin gene therapy to determine the effect of elevated hypothalamic leptin levels on osteoblasts. Finally, to determine the effects of loss of peripheral leptin signaling on bone formation and energy metabolism, we used bone marrow (BM) from WT or db/db donor mice to reconstitute the hematopoietic and mesenchymal stem cell compartments in lethally irradiated WT recipient mice. Decreases in bone growth, osteoblast-lined bone perimeter and bone formation rate were observed in ob/ob mice and greatly increased in ob/ob mice following subcutaneous administration of leptin. Similarly, hypothalamic leptin gene therapy increased osteoblast-lined bone perimeter in ob/ob mice. In spite of normal osteoclast-lined bone perimeter, db/db mice exhibited a mild but generalized osteopetrotic-like (calcified cartilage encased by bone) skeletal phenotype and greatly reduced serum markers of bone turnover. Tracking studies and histology revealed quantitative replacement of BM cells following BM transplantation. WT mice engrafted with db/db BM did not differ in energy homeostasis from untreated WT mice or WT mice engrafted with WT BM. Bone formation in WT mice engrafted with WT BM did not differ from WT mice, whereas bone formation in WT mice engrafted with db/db cells did not differ from the low rates observed in untreated db/db mice. In summary, our results indicate that leptin, acting primarily through peripheral pathways, increases osteoblast number and activity. PMID:22887758

  3. Regulation and policy working group

    SciTech Connect

    1997-03-01

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

  4. Unity power factor switching regulator

    NASA Technical Reports Server (NTRS)

    Rippel, Wally E. (Inventor)

    1983-01-01

    A single or multiphase boost chopper regulator operating with unity power factor, for use such as to charge a battery is comprised of a power section for converting single or multiphase line energy into recharge energy including a rectifier (10), one inductor (L.sub.1) and one chopper (Q.sub.1) for each chopper phase for presenting a load (battery) with a current output, and duty cycle control means (16) for each chopper to control the average inductor current over each period of the chopper, and a sensing and control section including means (20) for sensing at least one load parameter, means (22) for producing a current command signal as a function of said parameter, means (26) for producing a feedback signal as a function of said current command signal and the average rectifier voltage output over each period of the chopper, means (28) for sensing current through said inductor, means (18) for comparing said feedback signal with said sensed current to produce, in response to a difference, a control signal applied to the duty cycle control means, whereby the average inductor current is proportionate to the average rectifier voltage output over each period of the chopper, and instantaneous line current is thereby maintained proportionate to the instantaneous line voltage, thus achieving a unity power factor. The boost chopper is comprised of a plurality of converters connected in parallel and operated in staggered phase. For optimal harmonic suppression, the duty cycles of the switching converters are evenly spaced, and by negative coupling between pairs 180.degree. out-of-phase, peak currents through the switches can be reduced while reducing the inductor size and mass.

  5. Neurotrophin-regulated signalling pathways

    PubMed Central

    Reichardt, Louis F

    2006-01-01

    Neurotrophins are a family of closely related proteins that were identified initially as survival factors for sensory and sympathetic neurons, and have since been shown to control many aspects of survival, development and function of neurons in both the peripheral and the central nervous systems. Each of the four mammalian neurotrophins has been shown to activate one or more of the three members of the tropomyosin-related kinase (Trk) family of receptor tyrosine kinases (TrkA, TrkB and TrkC). In addition, each neurotrophin activates p75 neurotrophin receptor (p75NTR), a member of the tumour necrosis factor receptor superfamily. Through Trk receptors, neurotrophins activate Ras, phosphatidyl inositol-3 (PI3)-kinase, phospholipase C-?1 and signalling pathways controlled through these proteins, such as the MAP kinases. Activation of p75NTR results in activation of the nuclear factor-?B (NF-?B) and Jun kinase as well as other signalling pathways. Limiting quantities of neurotrophins during development control the number of surviving neurons to ensure a match between neurons and the requirement for a suitable density of target innervation. The neurotrophins also regulate cell fate decisions, axon growth, dendrite growth and pruning and the expression of proteins, such as ion channels, transmitter biosynthetic enzymes and neuropeptide transmitters that are essential for normal neuronal function. Continued presence of the neurotrophins is required in the adult nervous system, where they control synaptic function and plasticity, and sustain neuronal survival, morphology and differentiation. They also have additional, subtler roles outside the nervous system. In recent years, three rare human genetic disorders, which result in deleterious effects on sensory perception, cognition and a variety of behaviours, have been shown to be attributable to mutations in brain-derived neurotrophic factor and two of the Trk receptors. PMID:16939974

  6. Rainwater harvesting state regulations and technical resources

    SciTech Connect

    Loper, Susan A.

    2015-06-01

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

  7. Patterns of emotion regulation and psychopathology

    PubMed Central

    Eftekhari, Afsoon; Zoellner, Lori A.; Vigil, Shree A.

    2011-01-01

    Emotion regulatory strategies such as higher expressive suppression and lower cognitive reappraisal may be associated with increased psychopathology (Gross & John, 2003). Yet, it is unclear whether these strategies represent distinct cognitive styles associated with psychopathology, such that there are individuals who are predominantly “suppressors” or “reappraisers.” Using cluster analysis, we examined whether women with and without exposure to potentially traumatic events evidence distinct patterns of emotion regulation frequency, capacity, suppression, and cognitive reappraisal. Four patterns emerged: high regulators; high reappraisers/low suppressors; moderate reappraisers/low suppressors; and low regulators. Individuals who reported infrequently and ineffectively regulating their emotions (low regulators) also reported higher depression, anxiety, and posttraumatic stress disorder (PTSD). In contrast, individuals who reported frequently and effectively using reappraisal and low levels of suppression (high reappraisers/low suppressors) reported the lowest levels of these symptoms, suggesting that this specific combination of emotion regulation may be most adaptive. Our findings highlight that the capacity to regulate emotions and the ability to flexibly apply different strategies based on the context and timing may be associated with reduced psychopathology and more adaptive functioning. PMID:19381989

  8. Social regulation of emotion: messy layers.

    PubMed

    Kappas, Arvid

    2013-01-01

    Emotions are evolved systems of intra- and interpersonal processes that are regulatory in nature, dealing mostly with issues of personal or social concern. They regulate social interaction and in extension, the social sphere. In turn, processes in the social sphere regulate emotions of individuals and groups. In other words, intrapersonal processes project in the interpersonal space, and inversely, interpersonal experiences deeply influence intrapersonal processes. Thus, I argue that the concepts of emotion generation and regulation should not be artificially separated. Similarly, interpersonal emotions should not be reduced to interacting systems of intraindividual processes. Instead, we can consider emotions at different social levels, ranging from dyads to large scale e-communities. The interaction between these levels is complex and does not only involve influences from one level to the next. In this sense the levels of emotion/regulation are messy and a challenge for empirical study. In this article, I discuss the concepts of emotions and regulation at different intra- and interpersonal levels. I extend the concept of auto-regulation of emotions (Kappas, 2008, 2011a,b) to social processes. Furthermore, I argue for the necessity of including mediated communication, particularly in cyberspace in contemporary models of emotion/regulation. Lastly, I suggest the use of concepts from systems dynamics and complex systems to tackle the challenge of the "messy layers." PMID:23424049

  9. Social regulation of emotion: messy layers

    PubMed Central

    Kappas, Arvid

    2013-01-01

    Emotions are evolved systems of intra- and interpersonal processes that are regulatory in nature, dealing mostly with issues of personal or social concern. They regulate social interaction and in extension, the social sphere. In turn, processes in the social sphere regulate emotions of individuals and groups. In other words, intrapersonal processes project in the interpersonal space, and inversely, interpersonal experiences deeply influence intrapersonal processes. Thus, I argue that the concepts of emotion generation and regulation should not be artificially separated. Similarly, interpersonal emotions should not be reduced to interacting systems of intraindividual processes. Instead, we can consider emotions at different social levels, ranging from dyads to large scale e-communities. The interaction between these levels is complex and does not only involve influences from one level to the next. In this sense the levels of emotion/regulation are messy and a challenge for empirical study. In this article, I discuss the concepts of emotions and regulation at different intra- and interpersonal levels. I extend the concept of auto-regulation of emotions (Kappas, 2008, 2011a,b) to social processes. Furthermore, I argue for the necessity of including mediated communication, particularly in cyberspace in contemporary models of emotion/regulation. Lastly, I suggest the use of concepts from systems dynamics and complex systems to tackle the challenge of the “messy layers.” PMID:23424049

  10. 7 CFR 915.51 - Issuance of regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Issuance of regulations. 915.51 Section 915.51... Order Regulating Handling Regulations § 915.51 Issuance of regulations. (a) The Secretary shall regulate... production area and for the handling of avocados between the production area and any point outside...

  11. 7 CFR 915.51 - Issuance of regulations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Issuance of regulations. 915.51 Section 915.51... Order Regulating Handling Regulations § 915.51 Issuance of regulations. (a) The Secretary shall regulate... production area and for the handling of avocados between the production area and any point outside...

  12. Cycles in spatial and temporal chromosomal organization driven by the circadian clock

    PubMed Central

    Aguilar-Arnal, Lorena; Hakim, Ofir; Patel, Vishal R.; Baldi, Pierre; Hager, Gordon L.; Sassone-Corsi, Paolo

    2013-01-01

    Dynamic transitions in the epigenome have been associated with regulated patterns of nuclear organization. The accumulating evidence that chromatin remodeling is implicated in circadian function prompted us to explore whether the clock may control nuclear architecture. We applied the 3C-derived 4C technology (Chromosome Conformation Capture on Chip) in mouse embryonic fibroblasts (MEFs) to demonstrate the presence of circadian long-range interactions, using the clock-controlled Dbp gene as bait. The circadian genomic interactions with Dbp are highly specific and are absent in MEFs whose clock is disrupted by ablation of the Bmal1 gene. We establish that the Dbp circadian interactome contains a wide variety of genes and clock-related DNA elements. These findings reveal a previously unappreciated circadian and clock-dependent shaping of the nuclear landscape. PMID:24056944

  13. Fluorescent probes for monitoring regulated secretion

    PubMed Central

    Li, Wen-hong; Li, Daliang

    2013-01-01

    Numerous secretory cells use the regulated secretory pathway to release signaling molecules. Regulated secretion is an essential component of the intercellular communication network of a multicellular organism and serves diverse functions in neurobiology, endocrinology, and many other aspects of animal physiology. Probes that can monitor a specific exocytotic event with high temporal and spatial resolution would be invaluable tools for studying the molecular and cellular mechanisms underlying stimulus-secretion coupling, and for characterizing secretion defects that are found in different human diseases. This review summarizes different strategies and recent progress in developing fluorescent sensors for imaging regulated cell secretion. PMID:23711436

  14. Regulation of phospholipid synthesis in yeast

    PubMed Central

    Carman, George M.; Han, Gil-Soo

    2009-01-01

    Phospholipid synthesis in the yeast Saccharomyces cerevisiae is a complex process that involves regulation by both genetic and biochemical mechanisms. The activity levels of phospholipid synthesis enzymes are controlled by gene expression (e.g., transcription) and by factors (lipids, water-soluble phospholipid precursors and products, and covalent modification of phosphorylation) that modulate catalysis. Phosphatidic acid, whose levels are controlled by the biochemical regulation of key phospholipid synthesis enzymes, plays a central role in the regulation of phospholipid synthesis gene expression. PMID:18955729

  15. Can visitor regulations enhance recreational experiences?

    NASA Astrophysics Data System (ADS)

    Frost, Jeffrey E.; McCool, Stephen F.

    1988-01-01

    Regulations at recreation sites have been described as anathema to recreation itself. Many recent authors have suggested that managers use more “light-handed” techniques, such as information and education, before attempting regulatory and intrusive actions. This study of visitors to Glacier National Park in Montana, USA, during the fall bald eagle migration season demonstrates that, under certain conditions, recreationists will view regulations as a way to enhance the opportunity rather than detract from it. The results reinforce previous suggestions in the literature that managers carefully examine the objectives and consequences of regulations prior to their use.

  16. EPA revs up to regulate biotechnology.

    PubMed

    Sun, Marjorie

    1983-11-18

    The Environmental Protection Agency is preparing to regulate products of genetic engineering. Unlike the Recombinant DNA Advisory Committee of the National Institutes of Health, which oversees federally funded researchers, the EPA has the power to regulate industry and to concern itself with the health risks and environmental impact of commercial ventures. Claiming authority to regulate geneticaly engineered pesticides and organisms under the Federal Insecticide, Fungicide and Rodenticide Act, and under the Toxic Substances Control Act, EPA officials expect industry to contest in court the agency's controversial extension of its regulatory powers. PMID:11644077

  17. 9 CFR 83.3 - Interstate movement of live VHS-regulated fish species from VHS-regulated areas.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...Interstate movement of live VHS-regulated fish species from VHS-regulated areas. ...Interstate movement of live VHS-regulated fish species from VHS-regulated areas. ...of this section, live VHS-regulated fish, including fish moved to live fish...

  18. 9 CFR 83.3 - Interstate movement of live VHS-regulated fish species from VHS-regulated areas.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...Interstate movement of live VHS-regulated fish species from VHS-regulated areas. ...Interstate movement of live VHS-regulated fish species from VHS-regulated areas. ...of this section, live VHS-regulated fish, including fish moved to live fish...

  19. 9 CFR 83.3 - Interstate movement of live VHS-regulated fish species from VHS-regulated areas.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...Interstate movement of live VHS-regulated fish species from VHS-regulated areas. ...Interstate movement of live VHS-regulated fish species from VHS-regulated areas. ...of this section, live VHS-regulated fish, including fish moved to live fish...

  20. 9 CFR 83.3 - Interstate movement of live VHS-regulated fish species from VHS-regulated areas.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...Interstate movement of live VHS-regulated fish species from VHS-regulated areas. ...Interstate movement of live VHS-regulated fish species from VHS-regulated areas. ...of this section, live VHS-regulated fish, including fish moved to live fish...

  1. 9 CFR 83.3 - Interstate movement of live VHS-regulated fish species from VHS-regulated areas.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...-regulated fish species from VHS-regulated areas. 83.3 Section 83.3 Animals and Animal Products ANIMAL AND...-regulated fish species from VHS-regulated areas. (a) Except as provided in paragraphs (b) through (e) of this section, live VHS-regulated fish, including fish moved to live fish markets, may only be...

  2. 9 CFR 83.3 - Interstate movement of live VHS-regulated fish species from VHS-regulated areas.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...-regulated fish species from VHS-regulated areas. 83.3 Section 83.3 Animals and Animal Products ANIMAL AND...-regulated fish species from VHS-regulated areas. (a) Except as provided in paragraphs (b) through (e) of this section, live VHS-regulated fish, including fish moved to live fish markets, may only be...

  3. 9 CFR 83.3 - Interstate movement of live VHS-regulated fish species from VHS-regulated areas.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...-regulated fish species from VHS-regulated areas. 83.3 Section 83.3 Animals and Animal Products ANIMAL AND...-regulated fish species from VHS-regulated areas. (a) Except as provided in paragraphs (b) through (e) of this section, live VHS-regulated fish, including fish moved to live fish markets, may only be...

  4. 9 CFR 83.3 - Interstate movement of live VHS-regulated fish species from VHS-regulated areas.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...-regulated fish species from VHS-regulated areas. 83.3 Section 83.3 Animals and Animal Products ANIMAL AND...-regulated fish species from VHS-regulated areas. (a) Except as provided in paragraphs (b) through (e) of this section, live VHS-regulated fish, including fish moved to live fish markets, may only be...

  5. 9 CFR 83.3 - Interstate movement of live VHS-regulated fish species from VHS-regulated areas.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...-regulated fish species from VHS-regulated areas. 83.3 Section 83.3 Animals and Animal Products ANIMAL AND...-regulated fish species from VHS-regulated areas. (a) Except as provided in paragraphs (b) through (e) of this section, live VHS-regulated fish, including fish moved to live fish markets, may only be...

  6. FDA-Proposed Lab Practice Regulations Scored

    ERIC Educational Resources Information Center

    Murray, Chris

    1977-01-01

    Discusses the negative reactions to the Food & Drug Administration's proposed good laboratory practices for nonclinical laboratory practices. Industry representatives protest the inflexibility and excessive detail in the regulations. (MLH)

  7. 78 FR 2319 - Relocation of Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-11

    ...FEDERAL HOUSING FINANCE BOARD 12 CFR Subchapters D and F Through L FEDERAL HOUSING FINANCE AGENCY 12 CFR Parts 1201, 1225, 1228...of Regulations AGENCY: Federal Housing Finance Agency and Federal Housing Finance...

  8. 76 FR 74648 - Repeal of Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-01

    ...FEDERAL HOUSING FINANCE AGENCY FEDERAL HOUSING FINANCE BOARD 12 CFR Parts 912 and 997 DEPARTMENT OF HOUSING...Repeal of Regulations AGENCIES: Federal Housing Finance Agency; Federal Housing Finance Board; and...

  9. 50 CFR 665.964 - Regulated activities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES IN THE WESTERN PACIFIC Rose Atoll Marine National Monument § 665.964 Regulated activities. (a) Commercial fishing is prohibited in the...

  10. 50 CFR 665.964 - Regulated activities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES IN THE WESTERN PACIFIC Rose Atoll Marine National Monument § 665.964 Regulated activities. (a) Commercial fishing is prohibited in the...

  11. Menstrual regulation in family planning services.

    PubMed Central

    Kessel, E; Brenner, W E; Stathes, G H

    1975-01-01

    Menstrual regulation is a safe, effective, and economical method of fertility control. Its increased safety compared to first trimester abortion establishes menstrual regulation by vacuum aspiration for treatment of up to 14 days missed menstrual period as probably better medical practice than waiting to confirm the presence of a pregnancy. Because it is a postcontraceptive method, menstrual regulation has potential in family planning services both as a recruitment service and for the treatment of contraceptive failures. Its use as an only method of fertility control is being studied. The acceptance of this new family planning service will primarily depend on its availability, dissemination of information about the service, and the ability of women freely to avail themselves of the service without delay. Although long term effects of single and repeated use of menstrual regulation are not known, its immediate complications are few and it can be recommended as a useful addition to present fertility control methods in family planning programs. PMID:1147115

  12. 7 CFR 984.49 - Volume regulation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...Nuts), DEPARTMENT OF AGRICULTURE WALNUTS GROWN IN CALIFORNIA Order Regulating...information, that limiting the quantity of walnuts that may be handled in domestic markets for merchantable free walnuts during a marketing year will tend...

  13. 7 CFR 984.49 - Volume regulation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...Nuts), DEPARTMENT OF AGRICULTURE WALNUTS GROWN IN CALIFORNIA Order Regulating...information, that limiting the quantity of walnuts that may be handled in domestic markets for merchantable free walnuts during a marketing year will tend...

  14. 7 CFR 984.49 - Volume regulation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...Nuts), DEPARTMENT OF AGRICULTURE WALNUTS GROWN IN CALIFORNIA Order Regulating...information, that limiting the quantity of walnuts that may be handled in domestic markets for merchantable free walnuts during a marketing year will tend...

  15. 7 CFR 984.49 - Volume regulation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...NUTS), DEPARTMENT OF AGRICULTURE WALNUTS GROWN IN CALIFORNIA Order Regulating...information, that limiting the quantity of walnuts that may be handled in domestic markets for merchantable free walnuts during a marketing year will tend...

  16. 7 CFR 984.49 - Volume regulation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...NUTS), DEPARTMENT OF AGRICULTURE WALNUTS GROWN IN CALIFORNIA Order Regulating...information, that limiting the quantity of walnuts that may be handled in domestic markets for merchantable free walnuts during a marketing year will tend...

  17. Gene Regulation Networks for Modeling Drosophila Development

    NASA Technical Reports Server (NTRS)

    Mjolsness, E.

    1999-01-01

    This chapter will very briefly introduce and review some computational experiments in using trainable gene regulation network models to simulate and understand selected episodes in the development of the fruit fly, Drosophila Melanogaster.

  18. 10 CFR 850.26 - Regulated areas.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...Section 850.26 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements... Regulated areas. (a) If airborne concentrations of beryllium in areas in DOE facilities are measured at or above...

  19. 10 CFR 850.26 - Regulated areas.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...Section 850.26 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements... Regulated areas. (a) If airborne concentrations of beryllium in areas in DOE facilities are measured at or above...

  20. 10 CFR 850.26 - Regulated areas.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...Section 850.26 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements... Regulated areas. (a) If airborne concentrations of beryllium in areas in DOE facilities are measured at or above...